The endocrine glands include the pituitary, thy-  roid, parathyroids, adrenals, thymus, pancreas,  pineal, ovaries (in the female), and testes (in the  male) (Figure 1.2e). The endocrine glands are not  connected anatomically in the same way that the  parts of other organ systems are. What they have in  common is that they all secrete hormones, which  regulate other structures. The body functions    controlled by hormones are many and varied, involv-  ing every cell in the body. Growth, reproduction, and  the use of nutrients by cells are all controlled (at  least in part) by hormones.    The primary organs of the cardiovascular system  are the heart and blood vessels (Figure 1.2f). Using  blood as a carrier, the cardiovascular system delivers  oxygen, nutrients, hormones, and other substances  to, and picks up wastes such as carbon dioxide from,  cells near sites of exchange. White blood cells and  chemicals in the blood help to protect the body  from such foreign invaders as bacteria, viruses, and  tumor cells. The heart propels blood out of its cham-  bers into blood vessels to be transported to all body  tissues.   The role of the lymphatic system complements  that of the cardiovascular system. Its organs include  lymphatic vessels, lymph nodes, and other lymphoid  organs such as the spleen and tonsils (Figure 1.2g).  When fluid is leaked into tissues from the blood,  lymphatic vessels return it to the bloodstream so  that there is enough blood to continuously circulate  through the body. The lymph nodes and other lym-  phoid organs help to cleanse the blood and house  white blood cells involved in immunity.    The job of the respiratory system is to keep the  body supplied with oxygen and to remove carbon  dioxide. The respiratory system consists of the nasal  passages, pharynx, larynx, trachea, bronchi, and  lungs (Figure 1.2h). Within the lungs are tiny air  sacs, called alveoli. Gases are exchanged with the  blood through the thin walls of these alveoli.    The digestive system is basically a tube running  through the body from mouth to anus. The organs of  the digestive system include the oral cavity (mouth),  esophagus, stomach, small and large intestines, and  rectum plus a number of accessory organs (liver, sal-  ivary glands, pancreas, and others) (Figure 1.21).  Their role is to break down food and deliver the  resulting nutrients to the blood for dispersal to body  cells. The breakdown activities that begin in the  mouth are completed in the small intestine. From  that point on, the major function of the digestive sys-  tem is to absorb nutrients and reabsorb water. The    Forms the external body covering;  protects deeper tissue from injury;  synthesizes vitamin D; location of  sensory receptors (pain, pressure,  etc.) and sweat and oil glands.    Fast-acting control system of the  body; responds to internal and  external changes by activating  appropriate muscles and glands.    Protects and supports body organs;  provides a framework the muscles  use to cause movement; blood cells  are formed within bones; stores  minerals.    Glands secrete hormones that  regulate processes such as growth,  reproduction, and nutrient use by  body cells.    Allows manipulation of the  environment, locomotion, and facial  expression; maintains posture;  produces heat.    Blood vessels transport blood, which  carries oxygen, nutrients, hormones,  carbon dioxide, wastes, etc.; the heart  pumps blood.    Picks up fluid leaked from blood  vessels and returns it to blood;  disposes of debris in the lymphatic  stream; houses white blood cells  involved in immunity.    Eliminates nitrogen-containing  wastes from the body; regulates  water, electrolyte, and acid-base  balance of the blood.    Keeps blood constantly supplied  with oxygen and removes carbon  dioxide; gas exchange occurs  through the walls of the air sacs of  the lungs.    Breaks food down into absorbable  nutrients that enter the blood for  distribution to body cells; indigestible  foodstuffs are eliminated as feces.    Overall function of the reproductive system is production of offspring. Testes  produce sperm and male sex hormone; ducts and glands aid in delivery of viable  sperm to the female reproductive tract. Ovaries produce eggs and female sex  hormones; remaining structures serve as sites for fertilization and development of  the fetus. Mammary glands of female breasts produce milk to nourish the newborn.    undigested food that remains in the tract leaves the  body through the anus as feces. The liver is consid-  ered a digestive organ because the bile it produces  helps to break down fats. The pancreas, which deliv-  ers digestive enzymes to the small intestine, has both  endocrine and digestive functions.    A normal part of healthy body function is the produc-  tion of waste by-products, which must be disposed  of. One type of waste contains nitrogen (examples  are urea and uric acid), which results when the body  cells break down proteins and nucleic acids, which  are genetic information molecules. The urinary  system removes the nitrogen-containing wastes  from the blood and flushes them from the body in  urine. This system, often called the excretory system, is  composed of the kidneys, ureters, bladder, and ure-  thra (Figure 1.2j). Other important functions of this  system include maintaining the body’s water and salt  (electrolyte) balance, regulating the acid-base bal-  ance of the blood, and helping to regulate normal  blood pressure.    The role of the reproductive system is to pro-  duce offspring. The male testes produce sperm.  Other male reproductive system structures are the  scrotum, penis, accessory glands, and the duct sys-  tem, which carries sperm to the outside of the body  (Figure 1.2k). The female ovaries produce eggs, or  ova; the female duct system consists of the uterine  tubes, uterus, and vagina (Figure 1.21). The uterus  provides the site for the development of the fetus  (immature infant) once fertilization has occurred.    3. At which level of structural organization is the  stomach? At which level is a glucose molecule?  4. Which organ system includes the trachea, lungs,  nasal cavity, and bronchi?  5. Which system functions to remove wastes and help  regulate blood pressure?  For answers, see Appendix A.    Now that we have introduced the structural levels  composing the human body, a question naturally  follows: What does this highly organized human  body do? Like all complex animals, human beings  maintain their boundaries, move, respond to envi-  ronmental changes, take in and digest nutrients,  carry out metabolism, dispose of wastes, reproduce  themselves, and grow.   Organ systems do not work in isolation; instead,  they work together to promote the well-being of the  entire body (Figure 1.3, p. 30). Because this theme is  emphasized throughout this text, it is worthwhile to  identify the most important organ systems contrib-  uting to each of the necessary life functions. Also, as  you study this figure, you may want to refer to the  more detailed descriptions of the organ systems just  provided (pp. 26-29 and in Figure 1.2).    Every living organism must be able to maintain its  boundaries so that its “inside” remains distinct from  its “outside.” Every cell of the human body is sur-  rounded by an external membrane that separates  its contents from the outside interstitial fluid (fluid  between cells) and allows entry of needed substances  while generally preventing entry of potentially dam-  aging or unnecessary substances. The body as a  whole is also enclosed by the integumentary system,  or skin. The integumentary system protects internal  organs from drying out (which would be fatal), from  pathogens, and from the damaging effects of heat,  sunlight, and an unbelievable number of chemical  substances in the external environment.    Movement includes all the activities promoted by  the muscular system, such as propelling ourselves  from one place to another (by walking, swimming,  and so forth) and manipulating the external envi-  ronment with our fingers. The skeletal system pro-  vides the bones that the muscles pull on as they work.  Movement also occurs when substances such as blood,  foodstuffs, air, and urine are propelled through the  internal organs of the cardiovascular, digestive, respi-  ratory, and urinary systems, respectively.   Responsiveness, or irritability, is the ability to  sense changes (stimuli) in the environment and then  to react to them. For example, if you accidentally   Takes in nutrients, digests them  (part of metabolism), and excretes  unabsorbed matter (feces)    Cardiovascular system  Via the blood, distributes oxygen and  nutrients to all body cells and delivers  wastes and carbon dioxide to    Integumentary system  Protects the body as a whole  from the external environment  by maintaining boundaries   Takes in oxygen, which is  required for metabolism, and  excretes carbon dioxide    touch a hot pan, you involuntarily pull your hand  away from the painful stimulus (the pan). You do  not need to think about it—it just happens! Likewise,  when the amount of carbon dioxide in your blood  rises to a dangerously high level, your breathing rate  speeds up to blow off the excess carbon dioxide.  Because nerve cells are highly irritable and can  communicate rapidly with each other via electrical    impulses, the nervous system bears the major respon-  sibility for responsiveness. However, all body cells  are responsive to some extent.   Digestion is the process of breaking down ingested  food into simple molecules that can then be  absorbed into the blood. The nutrient-rich blood is    then distributed to all body cells by the cardiovascu-  lar system, where body cells use these simple mole-  cules for energy and raw materials.    Metabolism is a broad term that refers to all chemi-  cal reactions that occur within the body and all of its  cells. It includes breaking down complex substances  into simpler building blocks (as in digestion), making  larger structures from smaller ones, and using nutrients  and oxygen to produce molecules of adenosine triphos-  phate (ATP), the energy-rich molecules that power cel-  lular activities. Metabolism depends on the digestive  and respiratory systems to make nutrients and oxygen  available to the blood and on the cardiovascular sys-  tem to distribute these needed substances throughout  the body. Metabolism is regulated chiefly by hormones  secreted by the glands of the endocrine system.    Excretion is the process of removing excreta (ek-  skre’tah), or wastes, from the body. Several organ  systems participate in excretion. For example, the  digestive system rids the body of indigestible food  residues in feces, the urinary system disposes of  nitrogen-containing metabolic wastes in urine, and  the skin disposes of various waste products as com-  ponents of sweat.    Reproduction, the production of offspring, can  occur on the cellular or organismal level. In cellu-  lar reproduction, the original cell divides, producing  two identical daughter cells that may then be used for  body growth or repair. Reproduction of the human  organism is the task of the organs of the reproduc-  tive system, which produce sperm and eggs. When a  sperm unites with an egg, a fertilized egg forms, which  then develops into a baby within the mother’s body.  The function of the reproductive system is regulated  very precisely by hormones of the endocrine system.    Growth can be an increase in cell size or an increase  in body size that is usually accomplished by an  increase in the number of cells. For growth to occur,  cell-constructing activities must occur at a faster rate  than cell-destroying ones. Hormones released by  the endocrine system play a major role in directing  growth.    The goal of nearly all body systems is to maintain life.  However, life is extraordinarily fragile and requires  that several factors be available. These factors, which  we will call survival needs, include nutrients (food),  oxygen, water, and appropriate temperature and  atmospheric pressure.   Nutrients, which the body takes in through  food, contain the chemicals used for energy and cell  building. Carbohydrates are the major energy-  providing fuel for body cells. Proteins and, to a lesser  extent, fats are essential for building cell structures.  Fats also cushion body organs and provide reserve  fuel. Minerals and vitamins are required for the chem-  ical reactions that go on in cells and for oxygen  transport in the blood.   All the nutrients in the world are useless unless  oxygen is also available. Because the chemical reac-  tions that release energy from foods require oxygen,  human cells can survive for only a few minutes with-  out it. It is made available to the blood and body  cells by the cooperative efforts of the respiratory and  cardiovascular systems.   Water accounts for 60 to 80 percent of body  weight, depending on the age of the individual. It  is the single most abundant chemical substance in  the body and provides the fluid base for body  secretions and excretions. We obtain water chiefly  from ingested foods or liquids, and we lose it  by evaporation from the lungs and skin and in  body excretions.   If chemical reactions are to continue at life-  sustaining levels, normal body temperature must  be maintained. If body temperature drops below  37°C (98.6°F), metabolic reactions become slower  and slower and finally stop. If body temperature is  too high, chemical reactions proceed too rapidly,  and body proteins begin to break down. At either  extreme, death occurs. Most body heat is generated  by the activity of the skeletal muscles and dissipated  via blood circulating close to the skin surface or by  the evaporation of sweat.   The force exerted on the surface of the body by  the weight of air is referred to as atmospheric  pressure. Breathing and the exchange of oxygen  and carbon dioxide in the lungs depend on appro-  priate atmospheric pressure. At high altitudes, where  the air is thin and atmospheric pressure is lower, gas  exchange may be too slow to support cellular  metabolism.   diagnostic tools that are either mini-  mally invasive or not invasive at all. By  bombarding the body with different  forms of energy, medical imaging  techniques can reveal the structure of  internal organs, show blood flow in  real time, and even determine the  density of bone.   Until about 60 years ago, the magi-  cal but murky X-ray was the only  means of peering into a living body  without performing surgery.   Two examples of low-dose X-ray  procedures are mammography and  bone densitometry. A mammogram  is used to identify changes in breast  tissue, including dense masses or  calcifications; see photo (a). Bone  densitometry detects the amount of  calcium and minerals stored in bone  and is the major diagnostic test for  osteoporosis.    which has some distinct advantages  over other imaging techniques. The  equipment employs high-frequency  sound waves (ultrasound) as its energy  source. The body is probed with pulses  of sound waves, which cause echoes  when reflected and scattered by body  tissues. The echoes are analyzed by  computer to construct visual images  of body organs, much like sonar is  used to map the ocean floor. Even  though ultrasound is the safest imag-  ing technique available, health care  providers should limit patients’ expo-  sure to the lowest level that will be  effective. The long-term effects of  ultrasound exposure are not known.  Perhaps the best known of these  newer imaging devices is computed  tomography (CT), a refined version  of X-ray that eliminates the confusion  resulting from images of overlapping  structures. A CT scanner takes “pic-  tures” of a thin slice of the body. Dif-  ferent tissues absorb the radiation in    varying amounts. The device’s com-  puter translates this information into a  detailed image of the body region  scanned; see photo (b). CT scans are  at the forefront in evaluating most  problems that affect the brain and  abdomen, and their clarity has all but  eliminated exploratory surgery. Special  ultrafast CT scanners have produced a  technique called dynamic spatial  reconstruction (DSR), which pro-  vides three-dimensional images of  body organs from any angle. It also  allows organ movements and changes  in internal volumes to be observed at  normal speed, in slow motion, and at  a specific moment in time. The great-  est value of DSR has been to visualize  the heart beating and blood flowing  through blood vessels.   Positron emission tomography  (PET) requires an injection of short-  lived radioisotopes that have been  tagged to biological molecules (such  as glucose) in order to view metabolic    The mere presence of these survival factors is not  sufficient to maintain life. They must be present in  appropriate amounts as well; excesses and deficits  may be equally harmful. For example, the food  ingested must be of high quality and in proper  amounts; otherwise, nutritional disease, obesity, or  starvation is likely.    6. In addition to being able to metabolize, grow,  digest food, and excrete wastes, what other  functions must an organism perform if it is to  survive?   7. Oxygen is a survival need. Why is it so important?  In which life function does oxygen participate  directly?   yz Use proper anatomical terminology to describe  body directions, surfaces, and body planes.    v# Locate the major body cavities, and list the chief  organs in each cavity.    Learning about the body is exciting, but it can be  difficult to maintain our interest when we are faced  with all the new terminology of anatomy and phys-  iology. Let’s face it: You can’t just pick up an anat-  omy and physiology book and read it as if it were a  novel. Unfortunately, confusion is inevitable with-  out specialized terminology. For example, if you are  looking at a ball, “above” always means the area over  the top of the ball. Other directional terms can also  be used consistently because the ball is a sphere. All    processes. As the radio-  isotopes are absorbed  by the most active   brain cells, high-energy  gamma rays are pro-  duced, which a com-  puter then analyzes to  generate a picture of the    ity in vivid colors. PET's  greatest clinical value  has been its ability to  provide insights into  brain activity in real  time, particularly in peo-  ple affected by mental  illness, Alzheimer's dis-  ease, and epilepsy.    Learn more at Mastering A&P > Study Area > | _  Additional Study Tools > A Closer Look    ence of radio waves.  When the radio waves  are turned off, energy is  released and translated  by a computer into a  visual image (see  Figure 1.5, p. 37). MRI is  immensely popular  because it can do many  things a CT scan cannot.  Dense structures do not  show up in MRI, so  bones of the skull and/or  vertebral column do not  impair the view of soft  tissues, such as the brain  or intervertebral discs,  the cartilage pads  between vertebrae.    isotopes, fMRI provides a less invasive  alternative. Despite its advantages, the  powerful magnets of the MRI can  pose risks. For example, metal objects,  such as implanted pacemakers and  loose tooth fillings, can be “sucked”  through the body. Also, the long-term  health risks of exposure to strong  magnetic fields are not clear.   e The most common imaging  techniques include X-ray, CT,  MRI, and ultrasound.   e All of these except ultrasound  expose patients to ionizing radi-  ation in some form.   up to 60,000 times  stronger than Earth’s to  pry information from  body tissues. Hydrogen molecules spin  like tops in the magnetic field, and  their energy is enhanced by the pres-    sides and surfaces are equal. The human body, of  course, has many protrusions and bends. Thus, the  question becomes: Above what? To prevent misun-  derstanding, anatomists use a set of terms that allow  body structures to be located and identified clearly  with just a few words. We present and explain this  language of anatomy next.    To accurately describe body parts and position,  we must have an initial reference point and use  directional terms. To avoid confusion, we always  assume that the body is in a standard position called  anatomical position. It is important to under-  stand this position because most body terminol-  ogy used in this text refers to this body positioning  regardless of the position the body happens to be  in. In anatomical position, the body is erect with  the feet parallel and the arms hanging at the sides  with the palms facing forward. Stand up now, and    magnetic resonance  imaging (fMRI) allows  tracking of blood flow  into the brain in real  time. Before 1992, PET was the only  way to match brain activity to disease.  With no need for injections of radio-    computer software to build and  manipulate three-dimensional  images for better visualization of  body structures and irregularities.    assume the anatomical position. Notice that it is  similar to “standing at attention” but is less comfort-  able because the palms are held unnaturally forward  (with thumbs pointing away from the body) rather  than hanging cupped toward the thighs.   Directional terms allow medical personnel and  anatomists to explain exactly where one body struc-  ture is in relation to another. For example, we can  describe the relationship between the ears and the  nose informally by saying, “The ears are located on  each side of the head to the right and left of the nose.”  In anatomical terminology, this condenses to, “The  ears are lateral to the nose.” Using anatomical ter-  minology saves words and, once learned, is much  clearer. Commonly used directional terms are defined  and illustrated in Table 1.1. Although many of these  terms are also used in everyday conversation, keep in  mind that their anatomical meanings are very precise.    Definition  Toward the head end or upper part  of a structure or the body; above    Away from the head end or toward  the lower part of a structure or the  body; below    Toward or at the front of the body;  in front of    Toward or at the midline of the body  on the inner side of    Away from the midline of the body;  on the outer side of    Close to the origin of the body part  or the point of attachment of a limb  to the body trunk    Farther from the origin of a body  part or the point of attachment of a  limb to the body trunk    *The term caudal, literally “toward the tail,” is synonymous with inferior only to the inferior end of the spine.  tAnterior and ventral are synonymous in humans, but not in four-legged animals. Ventral refers to an animal's “belly,” making it the inferior surface.  Likewise, posterior and dorsal surfaces are the same in humans, but dorsal refers to an animal's back, making it the superior surface.    The elbow is proximal to the  wrist (meaning that the elbow  is closer to the shoulder or  attachment point of the arm  than the wrist is).    Study this figure for a moment to answer these two questions. Where would you  hurt if you (1) pulled a groin muscle or (2) cracked a bone in your olecranal area?    J €g _ Popliteal -R  Crural (leg)  Sural (calf)  E| Thorax Fibular  E| Abdomen Pedal (foot)  Œ| Back (Dorsum) E (ankle)  A  e ooa  Plantar    Figure 1.4 The anatomical position and regional terms. This figure shows terms used  to designate specific body areas. (a) Anterior view. (b) Posterior view. The heels are raised  slightly to show the inferior plantar surface (sole) of the foot, which is actually on the  inferior surface of the body.    f : There are many visible landmarks on the surface of  following statements with the correct anatomical term.    The wrist is to the hand. names, you can be specific in referring to different  The breastbone is to the spine. regions of the body.  The brain is to the spinal cord.   Look at Figure 1.4a to find the following body  regions. Once you have identified all the anterior  body landmarks, cover the labels that describe what    The thumb is to the fingers. (Be  careful here. Remember the anatomical position.)    the structures are. Then go through the list again,  pointing out these areas on your own body.    e thoracic (tho-ras’ik): area between the neck  and abdomen, supported by the ribs, sternum  and costal cartilages; chest    Identify the following body regions in Figure 1.4b,  and then locate them on yourself without referring  to this text.    e occipital (ok-sip'i-tal): posterior surface of head  or base of skull    The plantar region, or the sole of the foot, actu-  ally on the inferior body surface, is illustrated with  the posterior body landmarks (see Figure 1.4b).    8. What is the anatomical position, and why is it  important that an anatomy student understand it?   9. The axillary and the acromial areas are both in the  general area of the shoulder. To what specific body  area does each of these terms apply?   10. Use anatomical language to describe the location  of a cut to the back of your left forearm.  For answers, see Appendix A.   When preparing to look at the internal structures  of the body, medical students make a section, or  cut. When the section is made through the body  wall or through an organ, it is made along an imag-  inary line called a plane. Because the body is three-  dimensional, we can refer to three types of planes  or sections that lie at right angles to one another  (Figure 1.5).    (a) Median (midsagittal) (b) Frontal (coronal) plane (c) Transverse plane  Vertebral Right Left  column lung Heart lung Liver Aorta Pancreas Spleen    Figure 1.5 The planes of the body—median, frontal, and transverse—with  corresponding MRI scans. Note that the planes are shown on a body in  anatomical position.    A sagittal (saj'i-tal) section is a cut along the down the median plane of the body and the right  lengthwise, or longitudinal, plane of the body, divid- and left parts are equal In size, It 1s called a median  ing the body into right and left parts. If the cut is (midsagittal) section. All other sagittal sections    A frontal section is a cut along a lengthwise  plane that divides the body (or an organ) into ante-  rior and posterior parts. It is also called a coronal  (ko-ro’nal, “crown”) section.   A transverse section is a cut along a horizontal  plane, dividing the body or organ into superior and  inferior parts. It is also called a cross section.   Sectioning a body or one of its organs along dif-  ferent planes often results in very different views. For  example, a transverse section of the body trunk at the  level of the kidneys would show kidney structure in  cross section very nicely; a frontal section of the  body trunk would show a different view of kidney  anatomy; and a midsagittal section would miss the  kidneys completely. Information on body organ  positioning can be gained by taking magnetic reso-  nance imaging (MRI) scans along different body  planes (see Figure 1.5). MRI scans are described fur-  ther in “A Closer Look” (pp. 32-33).    Anatomy and physiology textbooks typically  describe two sets of internal body cavities, called the  dorsal and ventral body cavities, that provide differ-  ent degrees of protection to the organs within them  (Figure 1.6). Because these cavities differ in their  mode of embryological development and in their  lining membranes, many anatomy reference books  do not identify the dorsal, or neural, body cavity as  an internal body cavity. However, the idea of two  major sets of internal body cavities is a useful learn-  ing concept, so we will continue to use it here.    The dorsal body cavity has two subdivisions,  which are continuous with each other. The cranial  cavity is the space inside the bony skull. The brain is  well protected because it occupies the cranial cavity.  The spinal cavity extends from the cranial cavity to  the end of the spinal cord. The spinal cord, which is  a continuation of the brain, is protected by the bony  vertebrae, which surround the spinal cavity and form  the spine.    The ventral body cavity is much larger than the  dorsal cavity. It contains all the structures within  the chest and abdomen, that is, the organs in those  regions. Like the dorsal cavity, the ventral body cav-  ity is subdivided. The superior thoracic cavity is  separated from the rest of the ventral cavity by a    Figure 1.6 Body cavities. Notice the angular  relationship between the abdominal and pelvic cavities.    dome-shaped muscle, the diaphragm (di’ah-fram).  The organs in the thoracic cavity (lungs, heart, and  others) are protected by the rib cage. A central region  called the mediastinum (me"de-as-ti’num) sepa-  rates the lungs into right and left cavities in the tho-  racic cavity. The mediastinum itself houses the heart,  trachea, and several other visceral organs.   The cavity inferior to the diaphragm is the  abdominopelvic (ab-dom"i-no-pel’vik) cavity.  Some prefer to subdivide it into a superior abdominal  cavity containing the stomach, liver, intestines, and  other organs, and an inferior pelvic cavity containing  the reproductive organs, bladder, and rectum.  However, there is no actual physical structure dividing  the abdominopelvic cavity. The pelvic cavity is not  immediately inferior to the abdominal cavity, but  rather tips away from the abdominal cavity in the  posterior direction (see Figure 1.6).    When the body is subjected to physical trauma  (as often happens in an automobile accident, for  example), the most vulnerable abdominopelvic  organs are those within the abdominal cavity. The  reason is that the abdominal cavity walls are formed  only of trunk muscles and are not reinforced by  bone. The pelvic organs receive some protection  from the bony pelvis in which they reside.   Because the abdominopelvic cavity is quite large  and contains many organs, it helps to divide it up    etree fa ate into smaller areas for study. A scheme commonly  used by medical personnel divides the abdomino-  (RUQ) (LUQ) y  pelvic cavity into four more or less equal regions  called quadrants. The quadrants are named according  Right lower Left lower to their relative locations with respect to anatomical  ao u position—that is, right upper quadrant (RUQ), right    lower quadrant (RLQ), left upper quadrant (LUQ),  and left lower quadrant (LLQ) (Figure 1.7).   Another system, used mainly by anatomists,  Figure 1.7 The four abdominopelvic quadrants. divides the abdominopelvic cavity into nine separate  In this scheme used by medical personnel, the regions by four planes (Figure 1.8a). As you locate these    abdominopelvic cavity is divided into four quadrants regions, notice the organs they contain (Figure 1.8b).  by two planes.    e The umbilical region is the centermost region,  deep to and surrounding the umbilicus (navel).    région region region | Small intestine  . l  Right iliac |Hypogastric| Leftiliac ,  (ifiguinal) (pubic) (inguinal) Appendix Urinary  feoi - i9  egion region region bladder  (a) Nine regions delineated by four planes (b) Anterior view of the nine regions  showing the superficial organs  Figure 1.8 The nine scheme used mostly by anatomists. the hip bones; and the parasagittal  abdominopelvic regions. The In (a), the superior transverse plane is planes lie just medial to the nipples.    abdominopelvic cavity is divided into just superior to the ribs; the inferior  nine regions by four planes in this transverse plane is just superior to   e The hypogastric (pubic) region is inferior to  the umbilical region (hypo = below).   e The right iliac (inguinal) region and left iliac  (inguinal) region are lateral to the hypogastric  region (iliac = superior part of the hip bone).   e The right lumbar region and left lumbar  region lie lateral to the umbilical region  (lumbus = loins) and spinal column between the  bottom ribs and the hip bones; see Figure 1.4b).    e The right hypochondriac (hi"po-kon’dre-ak)  region and left hypochondriac region are  lateral to the epigastric region and contain the  lower ribs (chondro = cartilage).    In addition to the large closed body cavities, there  are several smaller body cavities. Most are in the  head and open to the body exterior.    e Oral cavity and digestive cavity. The oral cav-  ity, or the mouth, contains the teeth and tongue.  This cavity is part of and continuous with the  digestive organs, which open to the exterior at  the anus.    e Nasal cavity. Located within and posterior to  the nose, the nasal cavity is part of the respira-  tory system.    e Orbital cavities. The orbital cavities (orbits) in  the skull house the eyes and present them in an  anterior position.    e Middle ear cavities. The middle ear cavities  carved into the skull lie just medial to the ear-  drums. These cavities contain tiny bones that  transmit sound vibrations to the hearing recep-  tors in the inner ears.    11. If you were dissecting a cadaver and wanted to  separate the thoracic cavity from the abdominal  cavity, which type of section would you make?   12. Which of the following organs are in the abdomino-  pelvic cavity: spinal cord, small intestine, uterus,  heart?   13. Joe went to the emergency room, where he com-  plained of severe pains in the lower right quadrant  of his abdomen. What might be his problem?   When you really think about the fact that your body  contains trillions of cells in nearly constant activity,  and that remarkably little usually goes wrong with it,  you begin to appreciate what a marvelous organism  your body really is. The word homeostasis (ho’me-  o-sta’sis) describes the body’s ability to maintain rel-  atively stable internal conditions even though the  outside world is continuously changing. Although  the literal translation of homeostasis is “unchanging”  (homeo = the same; stasis = standing still), the term  does not really mean an unchanging state. Instead,  it indicates a dynamic state of equilibrium, or a bal-  ance in which internal conditions change and vary  but always within relatively narrow limits.   In general, the body demonstrates homeostasis  when its needs are being adequately met and it is  functioning smoothly. Virtually every organ system  plays a role in maintaining the constancy of the inter-  nal environment. Adequate blood levels of vital nutri-  ents must be continuously present, and heart activity  and blood pressure must be constantly monitored  and adjusted so that the blood is propelled with ade-  quate force to reach all body tissues. Additionally,  wastes must not be allowed to accumulate, and body  temperature must be precisely controlled.   Communication within the body is essential for  homeostasis and is accomplished chiefly by the ner-  vous and endocrine systems, which use electrical sig-  nals delivered by nerves or bloodborne hormones,  respectively, as information carriers. The details of  how these two regulating systems operate are the  subjects of later chapters, but we explain the basic  characteristics of the neural and hormonal control  systems that promote homeostasis here.   Regardless of the factor or event being regulated (this  is called the variable), all homeostatic control mech-  anisms have at least three components: a receptor,  control center, and effector (Figure 1.9). The receptor  is a type of sensor that monitors and responds to  changes in the environment. It responds to such  changes, called stimuli, by sending information  (input) to the second component, the control center.    (3) Input: Information  is sent along afferent  pathway to control  center.    Information flows from the receptor to the control  center along the afferent pathway. (It may help to  remember that information traveling along the affer-  ent pathway approaches the control center.)   The control center determines the level (set  point) at which a variable is to be maintained. This  component analyzes the information it receives and  then determines the appropriate response or course  of action.   The third component, the effector, provides the  means for the control center's response (output) to  the stimulus. Information flows from the control  center to the effector along the efferent pathway.  (Efferent information exits the control center.) The  results of the response then feed back to influence the  stimulus (the original change), either by reducing  the amount of change (negative feedback), so that  the whole control mechanism is shut off; or by  increasing the amount of change (positive feedback),  so that the reaction continues at an even faster rate.    Figure 1.9 The elements of a homeostatic control system. Interaction between the  receptor, control center, and effector is essential for normal operation of the system. This    Most homeostatic control mechanisms are negative  feedback mechanisms, as indicated in Figure 1.9. In  such systems, the net effect of the response to the stim-  ulus is to either shut off the original stimulus or reduce  its intensity. A good example of a nonbiological neg-  ative feedback system is a home heating system con-  nected to a thermostat. In this situation, the thermostat  contains both the receptor and the control center. If  the thermostat is set at 20°C (68°F), the heating system  (effector) will be triggered ON when the house tem-  perature drops below that setting. As the furnace pro-  duces heat, the air is warmed. When the temperature  reaches 20°C or slightly higher, the thermostat sends a  signal to shut off the furnace. Your body “thermostat”  operates in a similar way to regulate body temperature.  Other negative feedback mechanisms regulate heart  rate, blood pressure, breathing rate, the release of hor-  mones, and blood levels of glucose (blood sugar), oxy-  gen, carbon dioxide, and minerals.   Positive feedback mechanisms are rare in the  body because they tend to increase the original dis-  turbance (stimulus) and to push the variable farther  from its original value. Typically these mechanisms    control infrequent events that occur explosively and  do not require continuous adjustments. Blood clot-  ting and the birth of a baby are the most familiar  examples of positive feedback mechanisms.    Homeostasis is so important that most disease can  be regarded as being the result of its disturbance, a  condition called homeostatic imbalance. As we  age, our body organs become less efficient, and our  internal conditions become less and less stable.  These events place us at an increasing risk for illness  and produce the changes we associate with aging.    1.2a. Six levels of structural organization: atoms  and molecules, cells, tissues, organs, organ  systems, and the organism    1.2b. Eleven organ systems: integumentary  system, skeletal system, muscular system,  nervous system, endocrine system,  cardiovascular system, lymphatic system,  respiratory system, digestive system, urinary  system, and reproductive system    1.3 Maintaining Life (pp. 29-32)  1.3a. Necessary life functions: maintaining  boundaries, movement, responsiveness, digestion,  metabolism, excretion, reproduction, and growth  1.3b. Items required for survival: nutrients,    We provide examples of homeostatic imbalances  throughout this text to enhance your understanding  of normal physiological mechanisms.    14. When we say that the body demonstrates homeo-  stasis, do we mean that conditions in the body are  unchanging? Explain your answer.   15. When we begin to become dehydrated, we usually  get thirsty, which causes us to drink liquids. Is the  thirst sensation part of a negative or a positive  feedback control system? Defend your choice.    a) Listen to the story of this chapter in a brief summary at Mastering A&P >  ot Study Area > Author Narrated Audio Summaries   e Anterior (toward the front of the body):  posterior (toward the rear or back of the body)   e Medial (toward the midline of the body): lateral  (away from the midline of the body)   e Proximal (closer to the trunk): distal (farther  from the trunk)    è Superficial (at or close to the body surface):  deep (below or away from the body surface)    e A sagittal section separates the body into right  and left parts    o A midsagittal section separates the body into  equal right and left parts    e A frontal section separates the body into  anterior and posterior parts    e A transverse section separates the body into  superior and inferior parts    e Dorsal body cavity: well protected by bone;  includes cranial cavity (brain) and spinal cavity  (spinal cord)   e Ventral body cavity: protected only by trunk  muscles; includes thoracic cavity (heart and  lungs) and abdominopelvic cavity (digestive,  urinary, and reproductive organs)    e Other small body cavities: oral cavity, nasal  cavity, orbital cavity, and middle ear cavity   e All homeostatic control mechanisms include a  receptor, which responds to environmental    Which level of organization consists of groups of cells  with similar structures and functions?    . Using the terms listed below, fill in the blank with the    changes (stimuli); a control center, which  assesses changes and stimulates an effector,  which produces a response to the environmental  change    e Negative feedback systems act to reduce or stop  the initial stimulus    The gluteal region is located on the  surface of the body.    5. Anatomical terms that apply to the backside of the  body in the anatomical position include    6. A neurosurgeon orders a spinal tap for a patient. Into  what body cavity will the needle be inserted?    7. Which of the following body regions are subdivisions  of the abdominopelvic cavity?    8. Which component of homeostatic control is respon-  sible for the following? See the figure.    10. List the 11 organ systems of the body, briefly describe  the function of each, and then name two organs in  each system.    11. Which regions of the body do the following body  landmarks refer to—acromial, crural, inguinal, popli-  teal, and sural?    12. Which of the following organ systems—digestive,  respiratory, reproductive, circulatory, urinary, or  muscular—are found in both subdivisions of the  ventral body cavity? Which are found in the thoracic  cavity only? In the abdominopelvic cavity only?    13. Explain the meaning of homeostasis as applied to the  living organism.    14. What is the consequence of loss of homeostasis, or  homeostatic imbalance?    15. A diagnostic radiographer told John that she was  going to take an image of his calcaneal region. What  part of his body was she referring to? Later, a nurse  told him that she was going to give him an injection  containing pain killers in his gluteal region. Did he  take off his shirt or his pants to get the injection?  When John next saw a physiotherapist, the therapist  noticed John had tenderness and swelling in the tar-  sal region. What part of his body was tender and  swollen?    16. Jennifer fell off her motorcycle and tore a nerve in her  axillary region. She also tore ligaments in her cervical  and scapular regions and broke the only bone of her  right brachial region. Explain where each of her inju-  ries is located.    17. Students of an anatomy class are preparing to dissect  a body to reach the heart. In which cavity is the heart  located, and how can they gain access to it?    18. Parathyroid hormone (PTH) is secreted in response to  a drop in the calcium level in the blood. The secretion  of PTH is regulated by a negative feedback mecha-  nism. What can you expect to happen to the calcium  blood level as increased amounts of PTH are secreted,  and why?    19. Tom likes to discuss medical matters with his doctor.  Since Tom has fever quite often, he wants to know  what might happen if a person’s body temperature  deviates grossly from the normal. What would be the  doctor's response?    Chemistry is the  basis for how the body  transforms and uses energy and  for how our cells use molecules  such as carbohydrates, lipids,  proteins, and nucleic acids.   interactions store energy, such as  in fat, and other interactions  release energy, such as when   a topic. So why include it here? The answer  is simple: Your entire body is made up of chemicals—  thousands of them—continuously interacting with  one another at an incredible pace.   Chemical reactions underlie all body processes—  movement, digestion, the pumping of your heart,  and even your thoughts. In this chapter we present  the basics of chemistry and biochemistry (the  chemistry of living systems), providing the back-  ground you will need to understand body functions    Everything that happens  in the body, from signaling  and communication to energy  metabolism requires the movement  or participation of chemicals such as  ions, carbohydrates, lipids, and  proteins.    4# List four major energy forms, and provide one  example of how each is used in the body.   Matter is the “stuff” of the universe. With some  exceptions, it can be seen, smelled, and felt. More  precisely, matter is anything that occupies space and  has mass. Weight is a measure of gravity pulling on   Matter exists in solid, liquid, and gaseous states,  all of which are found in the human body. Solids,  such as bones and teeth, have a definite shape and  volume. Liquids have a definite volume, but they  conform to the shape of their container. Examples of  body liquids are blood plasma and the interstitial  fluid that bathes all body cells. Gases have neither a  definite shape nor a definite volume. The air we  breathe is a mixture of gases.   Matter may be changed both physically and  chemically. Physical changes do not alter the basic  nature of a substance. Examples include changes in  state, such as ice melting to water and food being cut  into smaller pieces. Chemical changes do alter the  composition of the substance—often substantially.  Fermenting grapes to make wine and the digestion  of food in the body are examples of chemical  changes.    In contrast to matter, energy has no mass and does  not take up space. It can be measured only by its  effects on matter. We commonly define energy  as the ability to do work or to put matter into  motion. When energy is actually doing work (mov-  ing objects), we refer to it as kinetic (ki-neh’'tik)  energy. Kinetic energy is displayed in the constant  movement of the tiniest particles of matter (atoms)  as well as in larger objects, such as a bouncing ball.  When energy is inactive or stored (as in the batteries  of an unused toy), we call it potential energy. All  forms of energy exhibit both kinetic and potential  work capacities.   All living things are built of matter, and to grow  and function they require a continuous supply of  energy. Thus, matter is the substance, and energy is  the mover of the substance. Because this is so, let's  take a brief detour to introduce the forms of energy  the body uses as it does its work.    e Chemical energy is stored in the bonds of  chemical substances. When the bonds are bro-  ken, the (potential) stored energy is unleashed  and becomes kinetic energy (energy in action).  For example, when gasoline molecules are bro-  ken apart in your automobile engine, the energy  released powers your car. Similarly, the chemical    e Electrical energy results from the movement of  charged particles. In your house, electrical  energy is the flow of subatomic particles called  electrons along the wiring. In your body, an elec-  trical current is generated when charged particles  (called ions) move across cell membranes. The  nervous system uses electrical currents called  nerve impulses to transmit messages from one  part of the body to another.    e Mechanical energy is energy directly involved  in moving matter. When you pedal a bicycle,  your legs provide the mechanical energy that  turns the wheels. We can take this example one  step further back: As the muscles in your legs  shorten (contract), they pull on your bones,  causing your limbs to move (so that you can  pedal the bike).    e Radiant energy travels in waves; that is, it is the  energy of the electromagnetic spectrum, which  includes X rays, infrared radiation (heat energy),  visible light, radio, and ultraviolet (UV) waves.  Light energy, which stimulates the retinas of  your eyes, is important in vision. UV waves cause  sunburn, but they also stimulate our bodies to  make vitamin D.    With a few exceptions, energy is easily converted  from one form to another. For example, chemical  energy (from gasoline) that powers the motor of a  speedboat is converted into the mechanical energy  of the whirling propeller that allows the boat to skim  across the water. In the body, chemical energy from  food is trapped in the bonds of a high-energy chem-  ical called ATP (adenosine triphosphate), and  ATP’s energy may ultimately be transformed into the  electrical energy of a nerve impulse or the mechani-  cal energy of contracting muscles.   Energy conversions are not very efficient, and  some of the initial energy supply is always “lost” to  the environment as heat (thermal energy). It is not  really lost, because energy cannot be created or  destroyed, but the part given off as heat is unusable.  You can easily demonstrate this principle by putting  your finger close to a lightbulb that has been lit for  an hour or so. Notice that some of the electrical  energy reaching the bulb is producing heat instead  of light. Likewise, all energy conversions in the body    liberate heat. This heat makes us warm-blooded ani-  mals and contributes to our relatively high body  temperature, which has an important influence on  body function. For example, when matter is heated,  its particles begin to move more quickly; that is, their  kinetic energy (energy of motion) increases. This is  important to the chemical reactions that occur in the  body because, up to a point, the higher the tempera-  ture, the faster those reactions occur.   2. What form of energy is used to transmit messages  from one part of the body to another? What form  of energy fuels cellular processes?   3. What type of energy is available when we are still?  When we are exercising?   4. What does it mean when we say that some energy  is “lost” every time energy changes from one form  to another in the body?    2.2a Elements and Atoms  Learning Objectives  1# Define element, and list the four elements that  form the bulk of body matter.  v Explain how elements and atoms are related.    All matter is composed of a limited number of sub-  stances called elements, unique substances that  cannot be broken down into simpler substances by  ordinary chemical methods. Examples of elements  include many commonly known substances, such as  oxygen, silver, gold, copper, and iron.   So far, 118 elements have been identified with  certainty. Ninety-two of these occur in nature; the  rest are made artificially in accelerator devices. A  complete listing of the elements appears in the  periodic table, an odd-shaped checkerboard (see  Appendix C) that appears in chemistry classrooms  the world over. Four of these elements—carbon, oxy-  gen, hydrogen, and nitrogen—make up about 96  percent of the weight of the human body. Besides  these four elements, several others are present in  small or trace amounts. The most abundant ele-  ments found in the body and their major roles are  listed in Table 2.1, p. 48.    Each element is composed of very similar parti-  cles, or building blocks, called atoms. Because all  elements are unique, the atoms of each element dif-  fer from those of all other elements. We designate  each element by a one- or two-letter shorthand  name called an atomic symbol. In most cases, the  atomic symbol is simply the first or first two letters  of the element's name. For example, C stands for car-  bon, O for oxygen, and Ca for calcium. In a few  cases, the atomic symbol is taken from the Latin  name for the element. For instance, Na (from the  Latin word natrium) indicates sodium, and K (from  kalium) potassium.    4 List the subatomic particles, and describe their rel-  ative masses, charges, and positions in the atom.    The word atom comes from the Greek word meaning  “incapable of being divided,” and historically this  idea of an atom was accepted as a scientific truth.  According to this notion, you could theoretically  divide a pure element, such as a block of gold, into  smaller and smaller particles until you got down  to the individual atoms, at which point you could  subdivide no further. We now know that atoms,  although indescribably small, are clusters of even  smaller components called subatomic particles,  which include protons, neutrons, and electrons. Even  so, the old idea of atomic indivisibility is still very  useful because an atom loses the unique properties  of its element when it is split into its component  particles.   An atom’s subatomic particles differ in their  mass, electrical charge, and position within the atom  (Table 2.2, p. 49). Protons (p*) have a positive  charge, whereas neutrons (n°) are uncharged, or  neutral. Protons and neutrons are heavy particles  and have approximately the same mass (1 atomic  mass unit, or amu). The tiny electrons (e`) beara  negative charge equal in strength to the positive  charge of the protons, but their mass is so small that  it is usually designated as 0 amu.   The electrical charge of a particle is a measure  of its ability to attract or repel other charged parti-  cles. Particles with the same type of charge (+ to +  or — to —) repel each other, but particles with    A major component of both organic and inorganic molecules; as a gas,    essential to the oxidation of glucose and other food fuels, during which  cellular energy (ATP) is produced.    A component of all organic molecules; as an ion (a charged atom), it    Found as a salt in bones and teeth; in ionic form, required for muscle    Present as a Salt, in combination with calcium, in bones and teeth; also    present in nucleic acids and many proteins; forms part of the high-energy    In its ionic form, the major intracellular cation; necessary for the    As an ion, the major extracellular cation; important for water balance,    Present in bone; also an important cofactor for enzyme activity in a    Chromium (Cr), Cobalt (Co), Copper (Cu), Fluorine (F), Manganese (Mn), Molybdenum (Mo), Selenium (Se), Silicon (Si),    *Referred to as the trace elements because they are required in very small amounts; many are found as part of enzymes or are required for enzyme activation.    opposite charges (+ to —) attract each other.  Neutral particles are neither attracted to nor  repelled by charged particles.   Because all atoms are electrically neutral, the  number of protons an atom has must be balanced by  its number of electrons (the + and — charges will    then cancel the effect of each other). Thus, helium has  two protons and two electrons, and iron has 26 pro-  tons and 26 electrons. For any atom, the number of  protons and electrons is always equal. Atoms that  have gained or lost electrons are called ions and no  longer have equal numbers of protons and electrons.    *The mass of an electron is so small, that we will ignore it and assume a mass of 0 amu.    The planetary model of an atom portrays the atom  as a miniature solar system (Figure 2.1a) in which  the protons and neutrons are clustered at the center  of the atom in the atomic nucleus. Because the  nucleus contains all the heavy particles, it is fantas-  tically dense and positively charged. The tiny elec-  trons orbit around the nucleus in fixed, generally  circular orbits, like planets around the sun. But we  can never determine the exact location of electrons  at a particular time because they jump around fol-  lowing unknown paths. So, instead of speaking of  specific orbits, chemists talk about orbitals—regions  around the nucleus in which electrons are likely to    Figure 2.1 The structure of an atom. The dense  central nucleus contains the protons and neutrons.  (a) In the planetary model of an atom, the electrons  move around the nucleus in fixed orbits. (b) In the  orbital model, electrons are shown as a cloud of  negative charge.    be found. The orbital model depicts the general  location of electrons outside the nucleus as a haze  of negative charge referred to as the electron cloud  (Figure 2.1b). Regions where electrons are most  likely to be found are shown by denser shading  rather than by orbit lines.   Notice that in both models, the electrons have  the run of nearly the entire volume of the atom.  Electrons also determine an atom’s chemical behav-  ior (that is, its ability to bond with other atoms).  Though now considered outdated, the planetary  model is simple and easy to understand and use.  Most of the descriptions of atomic structure in this  text use that model.   Hydrogen is the simplest atom, with just one  proton and one electron. You can visualize the  hydrogen atom by imagining it as a sphere with its  diameter equal to the length of a football field. The  nucleus could then be represented by a lead ball the  size of a gumdrop in the exact center of the sphere  and the lone electron pictured as a fly buzzing about  unpredictably within the sphere. This mental picture  should remind you that most of the volume of an  atom is empty space, and most of the mass is in the  central nucleus.    5. Which four elements make up the bulk of living  matter?  6. How is an atom related to an element?  For answers, see Appendix A.    4 Define radioisotope, and describe briefly how  radioisotopes are used in diagnosing and treating  disease.    All protons are alike, regardless of the atom being  considered. The same is true of all neutrons and all    electrons. So what determines the unique properties  of each element? The answer is that atoms of differ-  ent elements are composed of different numbers of  protons, neutrons, and electrons.   The simplest and smallest atom, hydrogen, has  one proton, one electron, and no neutrons  (Figure 2.2). Next is the helium atom, with two pro-  tons, two neutrons, and two orbiting electrons.  Lithium follows with three protons, four neutrons,  and three electrons. If we continue this step-by-step  listing of subatomic particles, we could describe all  known atoms by adding one proton and one elec-  tron at each step. The number of neutrons is not as  easy to pin down, but light atoms tend to have equal  numbers of protons and neutrons, whereas in larger  atoms neutrons outnumber protons. However, all we  really need to know to identify a particular element  is its atomic number, atomic mass number, and atomic  weight. Taken together, these indicators provide a  fairly complete picture of each element.    Each element is given a number, called its atomic  number, that is equal to the number of protons  its atoms contain. Atoms of each element contain a  different number of protons from the atoms of any  other element; hence, its atomic number is unique.  Because the number of protons is always equal to the  number of electrons, the atomic number indirectly  also tells us the number of electrons that atom  contains.    The atomic mass number (or just mass number)  of any atom is the sum of the masses of all the    protons and neutrons contained in its nucleus.  (Remember, the mass of an electron is so small that  we ignore it.) Because hydrogen has one proton and  no neutrons in its nucleus, its atomic number and  mass number are the same: 1. Helium, with two pro-  tons and two neutrons, has a mass number of 4. The  mass number is written as a superscript to the left of  the atomic symbol (see the examples in Figure 2.3).    At first glance, it seems that the atomic weight of an  atom should be equal to its atomic mass. This would  be so if there were only one type of atom represent-  ing each element. However, the atoms of almost  all elements exhibit two or more structural varia-  tions; these varieties are called isotopes (i's0-tops).  Isotopes have the same number of protons and elec-  trons but vary in the number of neutrons they con-  tain. Thus, the isotopes of an element have the same  atomic number but different atomic masses. Because  all of an element's isotopes have the same num-  ber of electrons (and electrons determine bonding  properties), their chemical properties are exactly the  same. As a general rule, the atomic weight of any ele-  ment is approximately equal to the mass number of  its most abundant isotope. For example, as we said  before, hydrogen has an atomic number of 1, but it  also has isotopes with atomic masses of 1, 2 (called  deuterium), and 3 (called tritium) (see Figure 2.3). Its  atomic weight is 1.008, which reveals that its lightest  isotope is present in much greater amounts in our  world than its °H or °H forms. (The atomic num-  bers, mass numbers, and atomic weights for ele-  ments commonly found in the body are provided in  Table 2.3).    The heavier isotopes of certain atoms are unsta-  ble and tend to release energy in order to become  more stable; such isotopes are called radioisotopes.  Why this process occurs is very complex, but appar-  ently the “glue” that holds the atomic nuclei  together is weaker in the heavier isotopes. This pro-  cess of spontaneous atomic decay, which is called    Figure 2.3 Isotopes of hydrogen. Isotopes differ in their numbers of neutrons.    radioactivity, can be compared to a tiny sustained  explosion. All types of radioactive decay involve the  ejection of particles (alpha or beta particles) or elec-  tromagnetic energy (gamma rays) from the atom’s  nucleus and are damaging to living cells. Emission of  alpha particles has the least penetrating power;  gamma radiation has the most. Contrary to what    Table 2.3 Atomic Structures of the Most Abundant Elements in the Body    some believe, ionizing radiation does not damage  the atoms in its path directly. Instead, it sends elec-  trons flying, like a bowling ball through pins, all  along its path. It is these electrons that do the  damage.   Radioisotopes are used in minute amounts to tag  biological molecules so that they can be followed, or  traced, through the body and are valuable tools for  medical diagnosis and treatment. For example, PET  scans, which use radioisotopes, are discussed in “A  Closer Look” (pp. 32-33). A radioisotope of iodine  can be used to scan the thyroid gland of a patient  suspected of having a thyroid tumor. Additionally,  radium, cobalt, and certain other radioisotopes are  used to destroy localized cancers.    7. An atom has five neutrons, four protons, and four  electrons. What is its atomic number? What is its  atomic mass number?   8. What name is given to an unstable atom that has  either more or fewer neutrons than its typical  number?    v# Define molecule, and explain how molecules are  related to compounds.    When two or more atoms combine chemically,  molecules are formed. If two or more atoms of the  same element bond, or become chemically linked  together, a molecule of that element is produced. For    example, when two hydrogen atoms bond, a mole-  cule of hydrogen gas is formed:    In this example of a chemical reaction, the reac-  tants (the atoms taking part in the reaction) are indi-  cated by their atomic symbols, and the product (the  molecule formed) is indicated by a molecular formula  that shows its atomic makeup. The chemical reaction  is shown as a chemical equation.   When two or more different atoms bind together  to form a molecule, the molecule is more specifically  referred to as a molecule of a compound. For exam-  ple, four hydrogen atoms and one carbon atom can  interact chemically to form methane:    Thus, a molecule of methane is a compound,  but a molecule of hydrogen gas is not—it is instead  called molecular hydrogen.   Compounds always have properties quite differ-  ent from those of the atoms making them up, and it  would be next to impossible to determine the atoms  making up a compound without analyzing it chem-  ically. Sodium chloride is an excellent example of  the difference in properties between a compound  and its constituent atoms (Figure 2.4). Sodium is a  silvery white metal, and chlorine in its molecular  state is a poisonous green gas used to make bleach.  However, sodium chloride is table salt, a white    *Notice that when the number of atoms is written as a  subscript, it indicates that the atoms are joined by a chemical  bond. Thus, 2H represents two separate atoms, but H,  indicates that the two hydrogen atoms are bound together to  form a molecule. The atomic symbol by itself represents    Figure 2.4 Properties of a compound differ from those of its atoms.    crystalline solid that we sprinkle on our food. Notice  that just as an atom is the smallest particle of an ele-  ment that still retains that element’s properties, a  molecule is the smallest particle of a compound that  still retains the properties of that compound. If you  break the bonds between the atoms of the com-  pound, properties of the atoms, rather than those of  the compound, will be exhibited.    9. What is the meaning of the term molecule?  10. How does a molecular substance differ from a  molecule of a compound?  For answers, see Appendix A.    w@ Recognize that chemical reactions involve the  interaction of electrons to make and break  chemical bonds.    vy Differentiate between ionic, polar covalent, and  nonpolar covalent bonds, and describe the  importance of hydrogen bonds.    Chemical reactions occur whenever atoms com-  bine with or dissociate from other atoms. When  atoms unite chemically, chemical bonds are formed.   A chemical bond is not an actual physical structure,  like a pair of handcuffs linking two people together.  Instead, it is an energy relationship that involves  interactions between the electrons of the reacting  atoms. Let's consider the role electrons play in form-  ing bonds.    The orbits, or generally fixed regions of space that  electrons occupy around the nucleus (see Figure 2.2),  are called electron shells, or energy levels. The  maximum number of electron shells in any atom  known so far is seven, and these are numbered 1  to 7 from the nucleus outward. The electrons clos-  est to the nucleus are those most strongly attracted  to its positive charge, and those farther away are less    securely held. As a result, the more distant electrons  are likely to interact with other atoms. Put more sim-  ply, the electron shell furthest from the nucleus is  also the first part of the atom any other atom will  come into contact with prior to reacting or bonding.   There is an upper limit to the number of elec-  trons that each electron shell can hold. Shell 1, clos-  est to the nucleus, is small and can accommodate  only 2 electrons. Shell 2 holds a maximum of 8.  Shell 3 can accommodate up to 18 electrons.  Subsequent shells hold larger and larger numbers of  electrons. In most (but not all) cases, the shells tend  to be filled consecutively.   The only electrons that are important to bonding  behavior are those in the atom’s outermost shell.  This shell is called the valence shell, and its valence  electrons determine the chemical behavior of the  atom. As a general rule, the electrons of inner shells  do not take part in bonding.   The key to chemical reactivity is referred to as the  rule of eights: In the absence of a full valence shell,  atoms interact in such a way that they will have eight  electrons in their valence shell. The first electron shell  represents an exception to this rule, because it is “full”  when it has two electrons. When the valence shell of  an atom contains eight electrons, the atom is com-  pletely stable and is chemically inactive (inert). When  the valence shell contains fewer than eight electrons,  an atom will tend to gain, lose, or share electrons  with other atoms to reach a stable state. When any of  these events occurs, chemical bonds are formed.  (Examples of chemically inert and reactive elements  are shown in Figure 2.5, p. 54). As you might guess,  atoms must approach each other very closely for their  electrons to interact in a chemical bond—in fact, their  outermost electron shells must overlap.    lonic Bonds Ionic (i-on’ik) bonds form when  electrons are completely transferred from one atom  to another. Atoms are electrically neutral, but when  they gain or lose electrons during bonding, their pos-  itive and negative charges are no longer balanced,  and charged particles, called ions, result. When an  atom gains an electron, it acquires a net negative  charge because it now has more electrons than pro-  tons. Negatively charged ions are more specifically  called anions, and they are indicated by a minus sign  after the atomic symbol, such as Cl for the chloride  ion. When atoms lose an electron, they become    Figure 2.5 Chemically inert and reactive elements.  To simplify the diagrams, each atomic nucleus is shown  as a circle with the atom’s symbol in it; protons and  neutrons are not shown.    positively charged ions, cations, because they now  possess more protons than electrons. Cations are  represented by their atomic symbol with a plus sign,  such as H* for the hydrogen ion (it may help you to  remember that a cation is positively charged by  thinking of its “t” as a plus  sign). Both anions  and cations result when an ionic bond is formed.    Because opposite charges attract, the newly created  ions tend to stay close together.   The formation of sodium chloride (NaCl), com-  mon table salt, provides a good example of ionic  bonding. Sodium’s valence shell contains only one  electron and so is incomplete (Figure 2.6). However,  if this single electron is “lost” to another atom, shell  2, which contains eight electrons, becomes the  valence shell; thus sodium becomes a cation (Na”)  and achieves stability. Chlorine needs only one elec-  tron to fill its valence shell, and it is much easier to  gain one electron (forming Cl) than it is to “give  away” seven. Thus, the ideal situation is for sodium  to donate its valence electron to chlorine, which is  exactly what happens. Sodium chloride and most  other compounds formed by ionic bonding fall  into the general category of inorganic chemicals  called salts.    Covalent Bonds Electrons do not have to be com-  pletely lost or gained for atoms to become stable.  Instead, they can be shared in such a way that each  atom is able to fill its valence shell at least part of  the time.   Molecules in which atoms share valence elec-  trons are called covalent molecules, and their bonds  are covalent bonds (co = with; valent = having  power). For example, hydrogen, with its single elec-  tron, can become stable if it fills its valence shell  (energy level 1) by sharing a pair of electrons—its  own and one from another atom. A hydrogen atom  can share an electron pair with another hydrogen  atom to form a molecule of hydrogen gas  (Figure 2.7a, p. 56). The shared electron pair orbits  the whole molecule and satisfies the stability needs  of both hydrogen atoms. Likewise, two oxygen  atoms, each with six valence electrons, can share two  pairs of electrons (form double bonds) with each  other (Figure 2.7b) to form a molecule of oxygen  gas (O2).   A hydrogen atom may also share its electron  with an atom of a different element. Carbon has four  valence electrons but needs eight to achieve stability.  When methane gas (CH,) is formed, carbon shares  four electrons with four hydrogen atoms (each bond  includes one electron from each atom to form a pair  of electrons; Figure 2.7c). Because the shared elec-  trons orbit and “belong to” the whole molecule,  each atom has a full valence shell enough of the time  to satisfy its stability needs.    Figure 2.6 Formation of an ionic bond. Both sodium and chlorine atoms are  chemically reactive because their valence shells are incompletely filled. Sodium gains  stability by losing one electron, whereas chlorine becomes stable by gaining one  electron. After electron transfer, sodium becomes a sodium ion (Na*), and chlorine  becomes a chloride ion (CI”). The oppositely charged ions attract each other.    In the covalent molecules described thus far,  electrons have been shared equally between the  atoms of the molecule. Such molecules are called  nonpolar covalent molecules. However, electrons are  not shared equally in all cases. When covalent bonds  are made, the molecule formed always has a definite  three-dimensional shape. A molecule’s shape plays a  major role in determining just what other molecules  (or atoms) it can interact with; the shape may also  result in unequal electron-pair sharing. The follow-  ing two examples illustrate this principle.   Carbon dioxide (CO,) is formed when a carbon  atom shares its four valence electrons with two oxy-  gen atoms. Oxygen is a very “electron-hungry” atom,  so it attracts the shared electrons much more strongly  than does carbon. However, because the carbon  dioxide molecule is linear (O—=C=O), the  electron-pulling power of one oxygen atom is offset  by that of the other, like a tug-of-war at a standoff  between equally strong teams (Figure 2.8a, p. 57). As  a result, the electron pairs are shared equally and  orbit the entire molecule, and carbon dioxide is a  nonpolar molecule.   A water molecule (H,O) is formed when two  hydrogen atoms bind covalently to a single oxygen  atom. Each hydrogen atom shares an electron pair  with the oxygen atom, and again the oxygen has the  stronger electron-attracting ability. But in this case,  the molecule formed is V-shaped (AY 7H). The    two hydrogen atoms are located at one end of the  molecule, and the oxygen atom is at the other  (Figure 2.8b); consequently, the electron pairs are  not shared equally. This arrangement allows them to  spend more time in the vicinity of the oxygen atom.  Because electrons are negatively charged, that end of  the molecule becomes slightly more negative (indi-  cated by ò`, the Greek letter delta with a minus sign)  and the hydrogen end becomes slightly more posi-  tive (indicated by 8°). In other words, a polar mole-  cule, a molecule with two charged poles, is formed.   Polar molecules orient themselves toward other  polar molecules or charged particles (ions, proteins,  and others), and they play an important role in  chemical reactions that occur in body cells. Because  different types of body tissues can consist of up to  80 percent water, the fact that water is a polar mole-  cule is particularly significant.    Hydrogen Bonds Hydrogen bonds are extremely  weak bonds formed when a hydrogen atom bound  to one “electron-hungry” nitrogen or oxygen atom is  attracted by another such atom, and the hydrogen  atom forms a “bridge” between them. Electrons are  not involved in hydrogen bonds, as they are in ionic  and covalent bonds. Hydrogen bonding is common  between water molecules (Figure 2.9a, p. 57) and is  reflected in water's surface tension. The surface ten-  sion of water causes it to “ball up,” or form spheres  at the surface. This tension allows some insects, such    — or O=0  Oxygen atom Oxygen atom Molecule of oxygen gas (Oz)  (b) Formation of a double covalent bond  i  2 F or a  (0)    bonds. (a) Formation of a single its partner; thus, a double covalent the far right, each pair of shared  covalent bond* between two bond is formed. (c) Formation of a electrons is indicated by a single line  hydrogen atoms forms a molecule of molecule of methane. A carbon atom connecting the sharing atoms.  hydrogen gas. (b) Formation of a shares four electron pairs with four    *Note that in each covalent bond formed, each participating atom donates one electron to the partnership. Thus, each individual covalent bond includes  a pair of electrons (2) being shared by both atoms.    Figure 2.8 Molecular models illustrating the  three-dimensional structure of carbon dioxide and    Figure 2.9 Hydrogen bonding  between polar water molecules.  (a) The slightly positive ends of the  water molecules (indicated by è*)    become aligned with the slightly  negative ends (indicated by è`) of  other water molecules. (b) Water's  high surface tension, a result of the    as water striders, to walk on water as long as they 2   Hydrogen bonds are also important intramolecu-  lar bonds; that is, they help to bind different parts of  the same molecule together into a special three-  dimensional shape. These rather fragile bonds are  very important in helping to maintain the structure  of both protein molecules, which are essential func-  tional molecules and body-building materials, and  DNA, the genetic information molecule.    Chemical reactions involve the making or breaking  of bonds between atoms. The total number of atoms  remains the same, but the atoms appear in new com-  binations. Most chemical reactions have one of the  three recognizable patterns we describe next.    Synthesis reactions occur when two or more  atoms or molecules combine to form a larger,    combined strength of its hydrogen  bonds, allows a water strider to walk  on a pond without breaking the  surface.    Smaller particles are  bonded together to form  larger, more complex  molecules.    Bonds are broken in larger  molecules, resulting in  smaller, less complex    Example  ATP transfers its terminal phosphate  group to glucose to form glucose-    Synthesis reactions always involve bond forma-  tion. Because energy must be absorbed to make  bonds, synthesis reactions are energy-storing  reactions.   Synthesis reactions underlie all anabolic  (building) activities that occur in body cells. They are  particularly important for growth and for repair of  worn-out or damaged tissues. The formation of a  protein molecule by the joining of amino acids (pro-  tein building blocks) into long chains is a synthesis  reaction (Figure 2.10a).    Decomposition reactions occur when a molecule  is broken down into smaller molecules, atoms, or  ions and can be indicated by    Essentially, decomposition reactions are synthe-  sis reactions in reverse. Bonds are always broken, and  the products of these reactions are smaller and sim-  pler than the original molecules. As bonds are bro-  ken, chemical energy is released.   Decomposition reactions underlie all catabolic  (destructive) processes that occur in body cells; that  is, they are reactions that break down molecules.  Examples include the digestion of foods into their  building blocks and the breakdown of glycogen (a  large carbohydrate molecule stored in the liver) to  release glucose (Figure 2.10b) when the blood sugar  level starts to decline.    Exchange reactions involve simultaneous synthe-  sis and decomposition reactions; in other words,  bonds are both made and broken. During exchange  reactions, a switch is made between molecule parts  (changing partners, so to speak), and different    ft the kinetic energy of the molecules, which in turn move more rapidly and  collide more forcefully.    T the number of collisions because reacting particles are crowded together.    Smaller particles have more kinetic energy and move faster than larger ones,    { the amount of energy the molecules need to interact by holding the reactants    molecules are made. Thus, an exchange reaction can  be generally indicated as    An exchange reaction occurs, for example, when  ATP reacts with glucose and transfers its end phos-  phate group (its full name is adenosine triphosphate;  tri- = three) to glucose, forming glucose-phosphate  (Figure 2.10c). At the same time, the ATP becomes  ADP, adenosine diphosphate (di- = two). This impor-  tant reaction, which occurs whenever glucose enters a  body cell, traps glucose inside the cell.   Most chemical reactions are reversible. If chemi-  cal bonds can be made, they can be broken, and vice  versa. Reversibility is indicated by a double arrow in  a chemical equation. When the arrows differ in  length, the longer arrow indicates the more rapid  reaction or the major direction in which the reaction  is proceeding. For example, in the reaction    the reaction going to the right is occurring more  rapidly, so over time AB will accumulate while A  and B will decrease in amount. If the arrows are of  equal length, the reaction is at chemical equilibrium.  Thus, in    for each molecule of AB made, a molecule of AB is  breaking down to release A and B.    As mentioned earlier, for the atoms forming mole-  cules to react chemically, their outermost electron  shells must overlap. In fact, for them to get close  enough for this to happen, the particles must collide    forcefully. Remember also that atoms move con-  stantly because of their kinetic energy—this is what  drives collisions between particles. Several factors,  including temperature, concentration of the parti-  cles, and size of the particles, influence the kinetic  energy and, hence, the speed of the particles and the  force of collisions (Table 2.4).   13. Which reaction type (see Figure 2.10) occurs when  fats are digested in your small intestine?   14. How can you indicate that a chemical reaction is  reversible?    All chemicals found in the body fall into one of  two major classes of molecules: either inorganic or  organic compounds. The class of the compound  is determined solely by the presence or absence  of carbon. Except for a few so far unexplainable  exceptions (such as carbon dioxide gas [CO,] and  carbon monoxide [CO]), inorganic compounds  lack carbon and tend to be small, simple mole-  cules. Examples of inorganic compounds found in  the body are water, salts, and many (but not all)    acids and bases. Organic compounds contain car-  bon. The important organic compounds in the body  are carbohydrates, lipids, proteins, and nucleic acids. All  organic compounds are fairly (or very) large cova-  lent molecules.   Inorganic and organic compounds are equally  essential for life. Trying to determine which is more  valuable can be compared to trying to decide  whether the ignition system or the engine is more  essential to the operation of a car.    y Explain the importance of water to body  homeostasis, and provide several examples of  the roles of water.    4 List several salts (or their ions) vitally important to  body functioning.  vy Differentiate a salt, an acid, and a base.    v Explain the concept of pH, and state the pH of  blood.    Water is the most abundant inorganic compound in  the body. It accounts for about two-thirds of body  weight. Among the properties that make water so  vital are the following:    e High heat capacity. Water has a high heat capac-  ity; that is, it absorbs and releases large amounts  of heat before its temperature changes. Thus, it  prevents the sudden changes in body tempera-  ture that might otherwise result from intense  sun exposure, chilling winter winds, or internal  events (such as vigorous muscle activity) that  liberate large amounts of heat.    e Polarity/solvent properties. Water is an excel-  lent solvent because of its polarity; indeed, it is  often called the “universal solvent.” A solvent is a  liquid or gas in which smaller amounts of other  substances, called solutes (which may be gases,  liquids, or solids), can be dissolved or sus-  pended. The resulting mixture is called a solution  when the solute particles are exceedingly tiny,  and a suspension when the solute particles are  fairly large. Translucent mixtures with solute  particles of intermediate size are called colloids.   Small reactive chemicals—such as salts, acids,  and bases—dissolve easily in water and become  evenly distributed. Molecules cannot react chem-  ically unless they are in solution, so virtually all    chemical reactions that occur in the body depend  on water's solvent properties.   Because nutrients, respiratory gases (oxygen  and carbon dioxide), and wastes can dissolve in  water, water can act as a transport and exchange  medium in the body. For example, all these sub-  stances are carried around the body in blood  plasma (the liquid part of blood that is mostly  made up of water) and are exchanged between  the blood and body cells by passing through the  water-based interstitial fluid that bathes cells.  Specialized molecules that lubricate the body,  such as mucus and synovial fluid, also use water  as their solvent. Synovial fluid “oils” the ends of  bones as they move within joint cavities.    e Chemical reactivity. Water is an important reac-  tant in some types of chemical reactions. For  example, to digest foods or break down biologi-  cal molecules, water molecules are added to the  bonds of the larger molecules in order to break  them. Such reactions are called hydrolysis reac-  tions, a term that specifically recognizes this role  of water (hydro = water; lys = splitting).  Cushioning. Water also serves a protective func-  tion. In cerebrospinal fluid, water forms a cush-  ion around the brain that helps to protect it  from physical trauma. Amniotic fluid, which  surrounds a developing fetus within the  mother’s body, plays a similar role in protect-  ing the fetus.    A salt is an ionic compound containing cations  other than the hydrogen ion (H*) and anions other  than the hydroxide ion (OH). Salts of many metal  elements are commonly found in the body, but the  most plentiful salts are those containing calcium and  phosphorus, found chiefly in bones and teeth. When  dissolved in body fluids, salts easily separate into  their ions. This process, called dissociation, occurs  rather easily because the ions have already been  formed. All that remains is for the ions to “spread  out.” This is accomplished by the polar water mol-  ecules, which orient themselves with their slightly  negative ends toward the cations and their slightly  positive ends toward the anions, thereby overcoming  the attraction between them (Figure 2.11).   Salts, both in their ionic forms and in combina-  tion with other elements, are vital to body function-  ing. For example, sodium and potassium ions are    Figure 2.11 Dissociation of salt in water. The slightly  negative ends of the water molecules (8~) are attracted  to Na‘, whereas the slightly positive ends of water  molecules (8*) orient toward CI”, causing the ions of  the salt crystal to be pulled apart.    essential for nerve impulses, and iron forms part of  the hemoglobin molecule that transports oxygen  within red blood cells.   Because ions are charged particles, all salts are  electrolytes—substances that conduct an electrical  current in solution. When electrolyte balance is  severely disturbed, virtually nothing in the body  works. (The functions of the elements found in body  salts are summarized in Table 2.1 on p. 48.)    Like salts, acids and bases are electrolytes. That is,  they ionize, dissociate in water, and can then con-  duct an electrical current.    Characteristics of Acids Acids have a sour taste  and can dissolve many metals or “burn” a hole in  your rug. Acids can have a devastating effect; for  example, consider the damage to sea life, trees, and  famous historical monuments caused by the    of an acid is that it is a substance that can release  hydrogen ions (H™ ) in detectable amounts. Because a  hydrogen ion is a hydrogen nucleus (a “naked pro-  ton”), acids are also defined as proton (H*)  donors. You may find it useful to think of acids as  putting protons “in the game.” As free protons,  hydrogen ions can influence the acidity of body  fluids.   When acids are dissolved in water, they release  hydrogen ions and some anions. The anions are  unimportant; it is the release of protons that deter-  mines an acid’s effects on the environment. The ion-  ization of hydrochloric acid (an acid produced by  stomach cells that aids digestion) is shown in the  following equation:    Other acids found or produced in the body include  acetic acid (the acidic component of vinegar) and  carbonic acid.   Acids that ionize completely and liberate all  their protons are called strong acids; an example is  hydrochloric acid. Acids that ionize incompletely, as  do acetic and carbonic acid, are called weak acids. For  example, when carbonic acid dissolves in water, only  some of its molecules ionize to liberate H”.    2H CO; > H” + HCO; + H,CO;  (carbonic (proton) (anion) (carbonic  acid) acid)    Characteristics of Bases Bases have a bitter taste,  feel slippery, and are proton (H+) acceptors. (You  can also think of them as taking protons “out of the  game”; when protons are bound to a molecule, they  are unable to affect the acidity of body fluids.)  Hydroxides are common inorganic bases. Like acids,  the hydroxides ionize and dissociate in water; but in  this case, the hydroxide ion (OH) and some cations  are released. The ionization of sodium hydroxide  (NaOH), commonly known as lye, is shown as    The hydroxide ion is an avid proton (H*) seeker,  and any base containing this ion is considered a    strong base. By contrast, bicarbonate ion (HCO; ), an  important base in blood, is a fairly weak base.    Acids, Bases, and Neutralization When acids and  bases are mixed, they react with each other (in an  exchange reaction) to form water and a salt:    HCl + NaOH + H,O + NaCl  (acid) (base) (water) (salt)    This type of exchange reaction, in which an acid  and a base interact, is more specifically called a  neutralization reaction.    pH: Acid-Base Concentrations ‘The relative con-  centration of hydrogen (and hydroxide) ions in var-  ious body fluids is measured in concentration units  called pH (pe-ach) units. The pH scale, which was  devised in 1909 by a Danish biochemist (and part-  time beer brewer) named Sørensen, is based on the  number of protons in solution.   The pH scale runs from 0 to 14 (Figure 2.12), and  each successive change of 1 pH unit represents a ten-  fold change in hydrogen ion concentration. At a pH  of 7, the number of hydrogen ions exactly equals the  number of hydroxide ions, and the solution is neu-  tral; that is, neither acidic nor basic. Solutions with a  PH lower than 7 are acidic: The hydrogen ions out-  number the hydroxide ions. A solution with a pH of  6 has 10 times as many hydrogen ions as a solution  with a pH of 7, and a pH of 3 indicates a 10,000-fold  (10 x 10 X 10 X 10) increase in hydrogen ion con-  centration from pH 7. Solutions with a pH number  higher than 7 are basic, or alkaline, and solutions  with a pH of 8 and 12 have 1/10 and 1/100,000  (respectively) the number of hydrogen ions present  in a solution with a pH of 7.   Living cells are extraordinarily sensitive to even  slight changes in pH. Acid-base balance is carefully  regulated by the kidneys, lungs, and a number of  chemicals called buffers that are present in body  fluids. Weak acids and weak bases are important  components of the body's buffer systems, which act  to maintain pH stability by taking up excess hydro-  gen or hydroxide ions (see Chapter 15).    Figure 2.12 The pH scale and pH values of  representative substances. The pH scale is based on  the number of hydrogen ions in solution. At a pH of 7,  the number of H* = the number of OH”, and the  solution is neutral. A solution with a pH below 7 is  acidic (more H* than OH); above 7, basic, or alkaline  (less H+ than OH").    Monomers are joined by removal of OH from one monomer  and removal of H from the other at the site of bond formation.    A bond between monomers is broken by the addition of a water molecule,  adding OH “i one monomer and H to the other.    Figure 2.13 Dehydration synthesis and hydrolysis of biological molecules.  Biological molecules are formed from their monomers (units) by dehydration    Because blood comes into close contact with  nearly every body cell, regulation of blood pH is  especially critical. Normally, blood pH varies in a  narrow range, from 7.35 to 7.45. When blood pH  changes more than a few tenths of a pH unit from  these limits, death becomes a distinct possibility.  Although we could give hundreds of examples to  illustrate this point, we will provide just one very  important one: When blood pH begins to dip into  the acid range, the amount of life-sustaining oxygen  that the hemoglobin in blood can carry to body cells  decreases rapidly to dangerously low levels.    15. What property of water prevents rapid changes in  body temperature?   17. Is a pH of 11 acidic or basic? What is the difference  in pH between a solution at pH 11 and a solution  at pH 5?    v Explain the role of dehydration synthesis and  hydrolysis in formation and breakdown of organic  molecules.    ı# Compare and contrast carbohydrates and lipids in  terms of their building blocks, structures, and  functions in the body.    Most organic compounds are very large molecules,  but their interactions with other molecules typically  involve only small, reactive parts of their structure  called functional groups (acid groups, amines, and  others).   Many organic compounds (carbohydrates and  proteins, for example) are polymers. Polymers are  chainlike molecules made of many similar or repeat-  ing units (monomers), which are joined together  by dehydration synthesis (Figure 2.13a). During  dehydration synthesis, a hydrogen atom is removed  from one monomer and a hydroxyl group (—OH) is  removed from the monomer it is to be joined with.  A covalent bond then forms, uniting the monomers,  and a water molecule is released. This removal of a  water molecule (dehydration) at the bond site occurs    Figure 2.14 Carbohydrates. (a) The generalized structure of a monosaccharide.  (b) and (d) The basic structures of a disaccharide and a polysaccharide, respectively.  (c) Formation and breakdown of the disaccharide sucrose by dehydration synthesis    each time a monomer is added to the growing poly-  mer chain (synthesis).   When polymers must be broken down or  digested to their monomers, the reverse process,  called hydrolysis, occurs (Figure 2.13b). As a water  molecule is added to each bond, the bond is broken,  releasing the monomers. All organic molecules cov-  ered in this chapter—carbohydrates, lipids, proteins,  and nucleic acids—are formed by dehydration syn-  thesis and broken down by hydrolysis.    Carbohydrates, which include sugars and starches,  contain carbon, hydrogen, and oxygen. With slight  variations, the hydrogen and oxygen atoms appear  in the same ratio as in water; that is, two hydrogen  atoms to one oxygen atom. This is reflected in the  word carbohydrate, which means “hydrated carbon,”  and in the molecular formulas of sugars. For exam-  ple, glucose is C6H1206, and ribose is CsH100s5.    Carbohydrates are classified according to size  and solubility in water as monosaccharides, disac-  charides, or polysaccharides. Because monosaccha-  rides are joined to form the molecules of the other  two groups, they are the structural units, or building  blocks, of carbohydrates.    Monosaccharides Monosaccharide means one  (mono) sugar (saccharide), and thus monosaccharides  are also referred to as simple sugars. They are single-  chain or single-ring structures (meaning the carbon  backbone forms either a line or a circle), containing  from three to seven carbon atoms (Figure 2.14a).   The most important monosaccharides in the  body are glucose, fructose, galactose, ribose, and  deoxyribose. Glucose, also called blood sugar, is the  universal cellular fuel. Fructose and galactose are con-  verted to glucose for use by body cells. Ribose and  deoxyribose form part of the structure of nucleic acids,  another group of organic molecules responsible for  genetic information.    Disaccharides Disaccharides, or double sugars  (Figure 2.14b), are formed when two simple sugars  are joined by dehydration synthesis. In this reaction,  as noted earlier, a water molecule is lost as the bond  forms (Figure 2.14c).   Some of the important disaccharides in the diet  are sucrose (glucose-fructose), which is cane sugar;  lactose (glucose-galactose), found in milk; and malt-  ose (glucose-glucose), or malt sugar. Because the  double sugars are too large to pass through cell  membranes, they must be broken down (digested)  to their monosaccharide units to be absorbed from  the digestive tract into the blood; this is accom-  plished by hydrolysis (see Figures 2.14b and 2.13b).    Polysaccharides Long, branching chains of linked  simple sugars are called polysaccharides (literally,  “many sugars”) (Figure 2.14d). Because they are  large, insoluble molecules, they are ideal storage  products. Another consequence of their large size is  that they lack the sweetness of simple and double  sugars.   Only two polysaccharides, starch and glycogen,  are of major importance to the body. Starch is the  storage polysaccharide formed by plants. We ingest it  in the form of “starchy” foods, such as grain prod-  ucts (corn, rice) and root vegetables (potatoes and  carrots, for example). Glycogen is a slightly smaller,  but similar, polysaccharide found in animal tissues  (largely in the muscles and the liver). Like starch, it  is a polymer of linked glucose units.   Carbohydrates provide a ready, easily used  source of fuel for cells, and glucose is at the top of  the “cellular menu.” When glucose is oxidized  (“burned” by combining with oxygen) in a complex  set of chemical reactions, it is broken down into car-  bon dioxide and water. Some of the energy released  as the glucose bonds are broken is trapped in the  bonds of high-energy ATP molecules, the energy  “currency” of all body cells. If not immediately  needed for ATP synthesis, dietary carbohydrates are  converted to glycogen or fat and stored. Those of us  who have gained weight from eating too many  carbohydrate-rich snacks have firsthand experience  of this conversion process!   Small amounts of carbohydrates are used for  structural purposes and represent 1 to 2 percent of  cell mass. Some sugars are found in our genes, and  others are attached to outer surfaces of cell    membranes (boundaries), where they act as road  signs to guide cellular interactions.   Lipids, or fats, are a large and diverse group of  organic compounds (Table 2.5, p. 68). They enter the  body in the form of meats, egg yolks, dairy products,  and oils. The most abundant lipids in the body are  triglycerides, phospholipids, and steroids. Like carbohy-  drates, all lipids contain carbon, hydrogen, and oxy-  gen atoms, but in lipids, carbon and hydrogen atoms  far outnumber oxygen atoms, as illustrated by the  formula for a typical fat named tristearin, which is  C57Hy9O¢. Lipids are insoluble in water but readily  dissolve in other lipids and in organic solvents such  as alcohol and acetone.    Triglycerides The triglycerides (tri-glis’ er-idz), or  neutral fats, are composed of two types of building  blocks, fatty acids and glycerol. Their synthesis  involves the attachment of three fatty acids to a sin-  gle glycerol molecule. The result is an E-shaped mol-  ecule that resembles the tines of a fork (Figure 2.15a,  p. 66). Although the glycerol backbone is the same in  all neutral fats, the fatty acid chains vary; this varia-  tion results in different kinds of neutral fats.   The length of a triglyceride’s fatty acid chains  and their type of C=C bonds determine how solid  the molecule is at a given temperature. Fatty acid  chains with only single covalent bonds between car-  bon atoms are referred to as saturated fats. Their  fatty acid chains are straight (Figure 2.16a, p. 67),  and, at room temperature, the molecules of a satu-  rated fat pack closely together, forming a solid; but-  ter is an example. Fatty acids that contain one or  more double bonds between carbon atoms are said  to be unsaturated fats (monounsaturated and  polyunsaturated, respectively). The double and tri-  ple bonds cause the fatty acid chains to kink  (Figure 2.16b) so that they cannot pack closely  enough to solidify. Hence, triglycerides with short  fatty acid chains or unsaturated fatty acids are oils  (liquid at room temperature). Plant lipids are typi-  cally oils. Examples include olive oil (rich in mono-  unsaturated fats) and soybean and safflower oils,  which contain a high percentage of polyunsaturated  fatty acids. Longer fatty acid chains and more satu-  rated fatty acids are common in animal fats, such as  butterfat and the fat of meats, which are solid at    Triglycerides and phospholipids are similar. What is  the major structural difference between them?    Glycerol 3 fatty acid chains Triglyceride, or neutral fat 3 water  , _ molecules  (a) Formation of a triglyceride. Fatty acid chains are bound to glycerol by dehydration synthesis.    Phosphorus-containing Glycerol 2 fatty acid chains  group (polar head) backbone (nonpolar tail)    (b) Typical structure of a phospholipid molecule (phosphatidylcholine). Two fatty acid chains and a  phosphorous-containing group are attached to a glycerol backbone.    (c) Cholesterol. Simplified structure of cholesterol, a steroid, formed by four interlocking carbon rings.    Figure 2.15 Lipids. (a) Triglycerides, (b) Structure of a typical phospho- (c) The generalized structure of   or neutral fats, are synthesized by lipid molecule. Notice that one fatty cholesterol (the basis for all steroids  dehydration synthesis, and a water acid chain in (b) is unsaturated (has made in the body).   molecule is lost at each bond site. one or more C=C [double] bonds).    (a) Saturated fat. At room temperature, the  molecules of a saturated fat such as this butter  are packed closely together, forming a solid.    (b) Unsaturated fat. At room temperature, the  molecules of an unsaturated fat such as this olive  oil cannot pack together closely enough to solidify  because of the kinks in some of their fatty acid  chains.    Figure 2.16 Examples of saturated and  unsaturated fats and fatty acids.    room temperature. Of the two types of fatty acids,  the unsaturated variety, especially olive oil, is more  “heart healthy.”   Trans fats, common in many margarines and  baked products, are oils that have been solidified by  the addition of hydrogen atoms at sites of double  carbon bonds, which reduces those bonds to single  carbon bonds. They increase the risk of heart disease  by raising “bad” cholesterol and decreasing “good”  cholesterol. In contrast, the omega-3 fatty acids,  found naturally in cold-water fish, appear to decrease   Triglycerides represent the body's most abundant  and concentrated source of usable energy. When  they are oxidized, they yield large amounts of energy.  They are stored chiefly in fat deposits beneath the  skin and around body organs, where they help insu-  late the body and protect deeper body tissues from  heat loss and injury.    Phospholipids Phospholipids (fos’fo-lip"idz) are  similar to triglycerides. The major difference is that a  phosphorus-containing group is always part of the  molecule and takes the place of one of the fatty acid  chains. Thus, phospholipids have two instead of  three attached fatty acids (see Figure 2.15b).   Because the phosphorus-containing portion (the  “head”) bears a negative charge, phospholipids have  special chemical properties and polarity. For exam-  ple, the charged region is hydrophilic (“water lov-  ing”), meaning it attracts and interacts with water  and ions. The fatty acid chains (the nonpolar “tail”)  are hydrophobic (“water fearing”) and do not  interact with polar or charged molecules. The pres-  ence of phospholipids in cell membranes allows cells  to be selective about what may enter or leave.    Steroids Steroids are basically flat molecules  formed of four interlocking carbon rings (see  Figure 2.15c); thus, their structure differs quite a bit  from that of other lipids. However, like fats, steroids  are made largely of hydrogen and carbon atoms and  are fat-soluble. The single most important steroid  molecule is cholesterol. We ingest cholesterol in  animal products such as meat, eggs, and cheese, and  some is made by the liver, regardless of dietary  intake.   Cholesterol has earned bad press because of its  role in arteriosclerosis, but it is essential for human  life. Cholesterol is found in cell membranes and is  the raw material used to make vitamin D, steroid  hormones (chemical signaling molecules in the  body), and bile salts (which help emulsify fats dur-  ing digestion). Although steroid hormones are pres-  ent in the body in only small quantities, they are  vital to homeostasis. Without sex hormones, repro-  duction would be impossible; and without the corti-  costeroids produced by the adrenal glands, the body  would not survive.    Found in fat deposits (subcutaneous tissue and around organs); protect and  insulate the body organs; the major source of stored energy in the body.    Found in cell membranes; participate in the transport of lipids in plasma; abundant  in the brain and the nervous tissue in general, where they help to form insulating  white matter.    A breakdown product of cholesterol; released by the liver into the digestive tract,  where they aid in fat digestion and absorption.    A fat-soluble vitamin produced in the skin on exposure to UV (ultraviolet) radiation  (sunshine); necessary for calcium absorption and normal bone growth and  function.    Estrogen and progesterone (female hormones) and testosterone (a male hormone)  produced from cholesterol; necessary for normal reproductive function; deficits  result in sterility.    Cortisol, a glucocorticoid, is a long-term antistress hormone that is necessary for  life; aldosterone helps regulate salt and water balance in body fluids by targeting  the kidneys.    Found in orange-pigmented vegetables (carrots) and fruits (tomatoes); part of the  photoreceptor pigment involved in vision.    Taken in via plant products such as wheat germ and green leafy vegetables; may  promote wound healing and contribute to fertility, but not proven in humans; an  antioxidant; may help to neutralize free radicals (highly reactive particles believed to  be involved in triggering some types of cancers).    Made available largely by the action of intestinal bacteria; also prevalent in a wide  variety of foods; required to make clotting proteins.    Derivatives of fatty acids found in cell membranes; various functions depending   on the specific class, including stimulation of uterine contractions (thus inducing  labor and miscarriages), regulation of blood pressure, and control of motility of the  gastrointestinal tract; involved in inflammation.    Lipoid and protein-based substances that transport fatty acids and cholesterol in  the bloodstream; major varieties are high-density lipoproteins (HDLs) and low-  density lipoproteins (LDLs).    Component of cell membranes. Lipids associated with carbohydrate molecules that  determine blood type, play a role in cell recognition or in recognition of foreign  substances by immune cells.    (c) Aspartic acid  (an acidic amino  acid) has an acid  group (—COOH)  in the R group.    (d) Lysine (abasic (e) Cysteine (a  amino acid) basic amino  has an amine acid) has a  group (—NHb») sulfhydryl (—SH)  in the R group. group in the    Figure 2.17 Amino acid structures. (a) Generalized structure of amino acids. All  amino acids have both an amine (NH,) group and an acid (COOH) group; they differ  only in the atomic makeup of their R-groups (green). (b-e) Specific structures of    20. What are the structural units, or building blocks, of  carbohydrates? Of lipids?  21. Which type(s) of lipid(s) is/are found in cellular  membranes?  22. Is the formation of glycogen from glucose an  example of hydrolysis or dehydration synthesis?  For answers, see Appendix A.    Proteins account for over 50 percent of the organic  matter in the body, and they have the most varied  functions of all organic molecules. Some are con-  struction materials; others play vital roles in cell  function. Like carbohydrates and lipids, all proteins    contain carbon, oxygen, and hydrogen. In addition,  they contain nitrogen and sometimes sulfur atoms  as well.   The building blocks of proteins are small mole-  cules called amino (ah-me’no) acids. Twenty variet-  ies of amino acids are found in human proteins. All  amino acids have an amine group (—NH;), which  gives them basic properties, and an acid group  (—COOR), which allows them to act as acids. In fact,  all amino acids are identical except for a single group  of atoms called their R-group (Figure 2.17). Differences  in the R-groups make each amino acid chemically  unique. For example, an extra acid group (—COOH)  in the R-group (such as in aspartic acid) makes the  amino acid more acidic, and a sulfhydryl group (—SH)  in the R-group (such as in cysteine) is often involved  in stabilizing protein structure by binding to another  amino acid within the same protein.   Amino acids are joined together in chains to  form polypeptides (fewer than 50 amino acids); pro-  teins (more than 50 amino acids); and large, com-  plex proteins (50 to thousands of amino acids).  Because each type of amino acid has distinct proper-  ties, the sequence in which they are bound together  produces proteins that vary widely both in structure    and function. To understand this more easily, think  of the 20 amino acids as a 20-letter alphabet. The let-  ters (amino acids) are used in specific combinations  to form words (a protein). Just as a change in one  letter of any word can produce a word with an  entirely different meaning (flour — floor) or one  that is nonsensical (flour — fluur), changes in amino  acids (letters) or in their positions in the protein  allow literally thousands of different protein mole-  cules to be made.    Structural Levels of Proteins Proteins can be  described in terms of four structural levels. The  sequence of amino acids composing each amino    (a) Primary structure. A  protein’s primary structure  is the unique sequence of  amino acids in the  polypeptide chain.    (b) Secondary structure.  Two types of secondary  structure are the alpha-  helix and beta-pleated  sheet. Secondary  structure is reinforced  by hydrogen bonds,  represented by dashed  lines in this figure.    overall three-dimensional  shape of the polypeptide  or protein is called tertiary  structure. It is reinforced  by chemical bonds  between the R-groups of  amino acids in different  regions of the protein  chain.    Protein (if > 50  amino acids) or  polypeptide (if < 50  amino acids)    (d) Quaternary structure.  Some proteins consist of  two or more polypeptide  chains. For example, four  polypeptides construct  the protein hemoglobin, a  blood protein.    acid chain is called the primary structure. This struc-  ture, which resembles a strand of amino acid  “beads,” is the backbone of a protein molecule in  which the chemical properties of each amino acid  will affect how the protein folds (Figure 2.18a).   Most proteins do not function as simple, linear  chains of amino acids. Instead, they twist or bend  upon themselves to form a more complex secondary  structure. The most common secondary structure is  the alpha (a)-helix, which resembles a metal spring  (Figure 2.18b). The a-helix is formed by coiling of  the primary chain and is stabilized by hydrogen  bonds. Hydrogen bonds in a-helices always link dif-  ferent parts of the same chain together.    (b) Hemoglobin molecule composed of the  protein globin and attached heme groups.  (Globin is a globular, or functional, protein.)    In another type of secondary structure, the beta  (B)-pleated sheet, the primary polypeptide chains  do not coil, but are linked side by side by hydrogen  bonds to form a pleated, ribbonlike structure that  resembles the pleats of a skirt or a sheet of paper  folded into a fan (see Figure 2.18b). In this type of  secondary structure, the hydrogen bonds may link  together different polypeptide chains as well as different  parts of the same chain that has folded back on itself.   Many proteins have tertiary structure (ter'she-  are), the next higher level of complexity. Tertiary  structure is achieved when a-helical or B-pleated  regions of the amino acid chain fold upon one  another to produce a compact ball-like, or globular,  protein (Figure 2.18c). The unique structure is main-  tained by covalent and hydrogen bonds between  amino acids that are often far apart in the primary  chain. Finally, when two or more amino acid chains  (polypeptide chains) combine in a regular manner  to form a complex protein, the protein has quater-  nary (kwah’‘ter-na"re) structure (Figure 2.18d).   Although a protein with tertiary or quaternary  structure looks a bit like a crumpled ball of tin foil,  the final structure of any protein is very specific and  is dictated by its primary structure. In other words,  the types and positions of amino acids in the protein  backbone determine where hydrogen bonds can  form to keep water-loving (hydrophilic) amino acids  near the surface and water-fearing (hydrophobic)  amino acids buried in the protein’s core so the pro-  tein remains water-soluble.    Fibrous and Globular Proteins Based on their  overall shape and structure, proteins are classed as  either fibrous or globular proteins (Figure 2.19). The  strandlike fibrous proteins, also called structural  proteins, appear most often in body structures.  Some exhibit only secondary structure, but most  have tertiary or even quaternary structure. They are  very important in binding structures together and  providing strength in certain body tissues. For exam-  ple, collagen (kol’ah-jen) is found in bones, cartilage,  and tendons and is the most abundant protein in the  body (Figure 2.19a). Keratin (ker’ah-tin) is the struc-  tural protein of hair and nails and the material that  makes skin tough.   Globular proteins are mobile, generally com-  pact, spherical molecules that have at least tertiary  structure. These water-soluble proteins play crucial  roles in virtually all biological processes. Because they  do things rather than just form structures, they are also  called functional proteins; the scope of their  activities is remarkable (Table 2.6). For example, some  proteins called antibodies help to provide immunity;  others (hormones) help to regulate growth and devel-  opment. Still others, called enzymes (en'zimz), regu-  late essentially every chemical reaction that goes on  within the body. The oxygen-carrying protein  hemoglobin is an example of a globular protein with  quaternary structure (Figure 2.19b).   The fibrous structural proteins are exceptionally  stable, but the globular functional proteins are quite    Highly specialized proteins that recognize, bind with, and inactivate bacteria, toxins,    Hemoglobin transports oxygen in the blood; other transport proteins in the blood carry    Essential to virtually every biochemical reaction in the body; increase the rates    of chemical reactions by at least a millionfold; in their absence (or destruction),    the opposite. Hydrogen bonds are critically impor-  tant in maintaining their structure, but hydrogen  bonds are fragile and are easily broken by heat and  excesses of pH. When their three-dimensional struc-  tures are destroyed, the proteins are said to be dena-  tured and can no longer perform their physiological  roles. Why? Their function depends on their specific  three-dimensional shapes. Hemoglobin becomes  totally unable to bind and transport oxygen when  blood pH becomes too acidic, as we stated earlier.  Pepsin, a protein-digesting enzyme that acts in the  stomach, is inactivated by alkaline pH. In each case,  the improper pH has destroyed the structure required  for function.   Because enzymes are important in the function-  ing of all body cells, we consider these incredibly  complex molecules here.    Enzymes and Enzyme Activity Enzymes are  functional proteins that act as biological catalysts. A  catalyst is a substance that increases the rate of a  chemical reaction without becoming part of the  product or being changed itself. Enzymes can accom-  plish this feat because they have unique regions  called active sites on their surfaces. These sites “fit”  and interact chemically with other molecules of  complementary shape and charge called substrates  (Figure 2.20). While the substrates are bound to the  enzyme’s active site, producing a structure called an  enzyme-substrate complex, they undergo structural    changes that result in a new product. Whereas some  enzymes build larger molecules, others break things  into smaller pieces or simply modify a substrate.  Once the reaction has occurred, the enzyme releases  the product. Because enzymes are not changed dur-  ing the reaction, they are reusable, and the cells need  only small amounts of each enzyme. Think of scis-  sors cutting paper. The scissors (the enzyme) are  unchanged while the paper (the substrate) is “cut” to  become the product. The scissors are reusable and go  on to “cut” other paper.   Enzymes are capable of catalyzing millions of  reactions each minute. However, they do more than  just increase the speed of chemical reactions; they  also determine just which reactions are possible at a  particular time. No enzyme, no reaction! Enzymes  can be compared to a bellows used to fan a sluggish  fire into flaming activity. Without enzymes, bio-  chemical reactions would occur far too slowly to sus-  tain life.   Although there are hundreds of different kinds  of enzymes in body cells, they are very specific in  their activities, each controlling only one (or a small  group of) chemical reaction(s) and acting only on  specific substrates. Most enzymes are named accord-  ing to the specific type of reaction they catalyze. For  example, hydrolases add water, and oxidases cause oxi-  dation. (In most cases, you can recognize an enzyme  by the suffix -ase in its name.)    Enzyme-substrate  complex (E-S)  (4) Substrates bind at active  site, temporarily forming an  enzyme-substrate complex.    The activity of different enzymes is controlled in  different ways. Many enzymes are produced in an  inactive form and must be activated in some way  before they can function. In other cases, enzymes are  inactivated immediately after they have performed  their catalytic function. Both events are true of  enzymes that promote blood clotting when a blood  vessel has been damaged. If this were not so, large  numbers of unneeded and potentially lethal blood  clots would be formed.    23. What is the primary structure of proteins?  24. Which is more important for building body  structures, fibrous or globular proteins?  25. How does an enzyme recognize its substrate(s)?  For answers, see Appendix A.    ı# Compare and contrast the structures and  functions of DNA and RNA.    The role of nucleic (nu-kle’ik) acids is fundamental:  They make up your genes, which provide the basic    (2) The E-S complex Enzyme (E)  undergoes structural  changes that form the (3) The enzyme    releases the product of  the reaction and is free  to bind more substrates.    blueprint of life. They not only determined what  type of organism you would be, but also directed  your growth and development—and they did this  largely by dictating protein structure. (Remember  that enzymes, which catalyze all the chemical reac-  tions that occur in the body, are proteins.)   Nucleic acids, composed of carbon, oxygen,  hydrogen, nitrogen, and phosphorus atoms, are the  largest biological molecules in the body. Their build-  ing blocks, nucleotides (nu’kle-o-tidz), are quite  complex. Each consists of three basic parts: (1) a  nitrogen-containing base, (2) a pentose (5-carbon)  sugar, and (3) a phosphate group (Figure 2.21a  and b, p. 74).   The bases come in five varieties: adenine (A), gua-  nine (G), cytosine (C), thymine (T), and uracil (U). A  and G are large, nitrogen-containing bases made up  of two carbon rings, whereas C, T and U are smaller,  single-ring structures. The nucleotides are named  according to the base they contain: A-containing  bases are adenine nucleotides, C-containing bases  are cytosine nucleotides, and so on.   The two major kinds of nucleic acids are deoxy-  ribonucleic (de-ok’si-ri"bo-nu-kle’ik) acid (DNA)  and ribonucleic acid (RNA). DNA and RNA differ  in many respects. DNA is the genetic material found  within the cell nucleus (the control center of the cell).    sugar  Phosphate  Sugar-phosphate  backbone  (c) Computer-generated image of a DNA molecule (d) Diagram of a DNA molecule  KEY:  = Thymine (T) D) Cytosine (C)  WHE Adenine (A) (QR Guanine (G)  Figure 2.21 Structure of DNA. and (b) diagrammatic structures, alternating sugar and phosphate  (a) The subunit of DNA, the nucleo- contains the base adenine. molecules. The “rungs” are formed  tide, is composed of a deoxyribose (c) Computer-generated image of by complementary bases (A to T, G to  sugar molecule linked to a phosphate DNA. (d) Diagrammatic structure of C) bound by two or three hydrogen  group. A nitrogen-containing base is a DNA molecule—two nucleotide bonds, respectively.    attached to the sugar. The nucleotide  illustrated, both in its (a) chemical    Learn more at Mastering A&P > Study Area >  Additional Study Tools > Focus on Careers   ication, they open up the pack-  age and toss out the little pamphlet  that describes how the medication  works. Not Chris Green. “| love reading  the package inserts,” says Green, the  lead pharmacy technician at a CVS  drugstore in Birmingham, Alabama.   legally prohibited from talking with  patients about their symptoms, they  can translate medical jargon and dis-  cuss a medications side effects and    Pharmacy technicians work in retail  and mail-order pharmacies, hospitals,  nursing homes, assisted living facilities,  and anywhere else patients have high  needs for medication. As the Baby  Boomers age and the number of senior  citizens grows, so does the demand for  pharmacists and pharmacy technicians.   Requirements to be a pharmacy  technician vary from state to state,  though many require specific training  and may include an internship at a  pharmacy.   A busy retail pharmacy has various  stations: data entry, where the patient's  record is updated with a new prescrip-  tion; production, where the prescrip-  tion is filled; and verification, where the  pharmacist reviews the prescription and  makes sure it is filled and labeled cor-  rectly. Green's job is to make sure the  process flows smoothly from station to  station.    pharmacy technicians must have a  good grasp of the sciences, especially  basic chemistry and anatomy and phys-  iology, to help them understand each  drug's chemical makeup and  properties.   “When all the data is entered, we  see what potential side effects there  are,” he says. “It's important to know  how the medications work, how they  interact with each other, how they  interact with the body. | might see  something and bring it to the pharma-  cist's attention.”    e Pharmacy technicians assist with  dispensing, labeling, and taking  inventory of medications.    e Knowledge of anatomy and  physiology helps pharmacy tech-  nicians understand drug interac-  tions and side effects so that they  can explain this information to  patients.    It has two fundamental roles: (1) It replicates itself  exactly before a cell can divide, thus ensuring that  every body cell gets an identical copy of the genetic  information; and (2) it provides the instructions for  building every protein in the body. For the most part,  RNA functions outside the nucleus and can be con-  sidered the “molecular assistant” of DNA; that is,  RNA carries out the orders for protein synthesis  issued by DNA.   Although both DNA and RNA are formed when  nucleotides join together, their final structures are  different. DNA is a long double chain of nucleotides  (Figure 2.21c and d). Its bases are A, G, T, and C, and  its sugar is deoxyribose. Its two nucleotide chains are  held together by hydrogen bonds between the bases,    forming a ladderlike molecule. Alternating sugar and  phosphate molecules form the “uprights” of the lad-  der, called the sugar-phosphate backbone, and each  “rung” is formed by two joined bases (one base pair).  Binding between the bases is very specific: A always  binds to T, and G always binds to C. Thus, A and T  are said to be complementary bases, as are C and G.  Therefore, a sequence of ACTGA on one nucleotide  chain would be bound to the complementary  sequence TGACT on the other nucleotide strand. The  whole molecule is then coiled into a spiral-staircase-  like structure called a double helix.   Whereas DNA is double-stranded, RNA mole-  cules are single nucleotide strands. The RNA bases  are A, G, C, and U (U replaces the T found in DNA),    and its sugar is ribose instead of deoxyribose. Three  major varieties of RNA exist—messenger, transfer, and  ribosomal RNA—and each has a specific role to play  in carrying out DNA’s instructions for building pro-  teins. Messenger RNA (mRNA) carries the informa-  tion for building the protein from the DNA to the  ribosomes, the protein-synthesizing sites outside the  nucleus. Transfer RNA (tRNA) ferries amino acids to  the ribosomes. Ribosomal RNA (rRNA) forms part of  the ribosomes, where it oversees the translation of  the message and the binding together of amino acids  to form the proteins. (We describe protein synthesis  in greater detail in Chapter 3.)    The synthesis of adenosine triphosphate (ah-  den’o-sén tri-fos’fat), or ATP, is all-important  because it provides a form of chemical energy that  all body cells can use. Without ATP, molecules can-  not be made or broken down, cells cannot maintain  their membrane boundaries, and all life processes  grind to a halt.   Although glucose is the most important fuel for  body cells, none of the chemical energy contained    Figure 2.22 ATP—structure and hydrolysis.  (a) The structure of ATP (adenosine triphosphate).  (b) Hydrolysis of ATP to yield ADP (adenosine  diphosphate) and inorganic phosphate (P). High-  energy bonds are indicated by a red ~.    in its bonds can be used directly to power cellular  work. Instead, energy is released as glucose is oxi-  dized, and it is captured and stored in the bonds of  ATP molecules as small packets of energy. Compare  glucose and ATP to crude oil and gasoline: While oil  stores lots of energy, it cannot be used directly to  power a car without first being refined into  gasoline.   Structurally, ATP is a modified RNA nucleotide;  it consists of an adenine base, ribose sugar, and  three phosphate groups instead of one (Figure 2.22a).  The phosphate groups are attached by unique chem-  ical bonds called high-energy phosphate bonds. These  bonds are high energy because the phosphate  groups are negatively charged and the like charges  repel one another, generating tension at these sites.  As ATP is used to provide cellular energy, adenosine  diphosphate (ADP) accumulates (Figure 2.22b),  and ATP supplies are replenished by oxidation of  food fuels. Essentially, the same amount of energy  must be captured and used to reattach a phosphate  group to ADP (that is, to reverse the reaction) as is  liberated when the terminal phosphate is removed  from ATP.    (a) Chemical work. ATP provides the  energy needed to drive  energy-absorbing chemical  reactions.    (b) Transport work. ATP drives the  transport of certain solutes (amino  acids, for example) across cell    (c) Mechanical work. ATP activates  contractile proteins in muscle cells  so that the cells can shorten and  perform mechanical work.   e Chemical energy, electrical energy, mechani-  cal energy, and radiant energy are important  for body function    When the high-energy bonds of ATP are broken  by hydrolysis, energy is liberated and can be used  immediately by the cell to do work or power a partic-  ular activity—such as driving chemical reactions,  transporting solutes across the membrane, or, in the  case of muscle cells, contracting (Figure 2.23). ATP  can be compared to a tightly coiled spring that is  ready to uncoil with tremendous energy when the  “catch” is released. The consequence of breaking its  terminal phosphate bond can be represented as  follows:    ATP == ADP + @) + E  (adenosine (adenosine (inorganic (energy)  triphosphate) diphosphate) phosphate)    26. How do DNA and RNA differ from each other in  the kinds of bases and sugars they contain?  27. What is the vital importance of ATP to body cells?  For answers, see Appendix A.    Figure 2.23 Three examples of how ATP drives  cellular work. The high-energy bonds of ATP release  energy for use by the cell when they are broken. ATP is  regenerated (phosphate is again bound to ADP) as  energy is released by the oxidation of food fuels and  captured in the third high-energy bond.    a) Listen to the story of this chapter in a brief summary at Mastering A&P >  ue Study Area > Author Narrated Audio Summaries    e Energy conversions from one form to another are  inefficient; some energy is lost as heat    e Elements—made of atoms; cannot be broken  down into simpler substances and remain the  same element; the 118 elements have different  chemical and physical properties.   e Carbon, hydrogen, oxygen, and nitrogen make up  96 percent of living matter; other elements are  present in trace amounts   e Atoms—made of protons , electrons ,  and neutrons (no charge)   e An atom can be identified by its atomic number  (equal to the number of protons in the nucleus)    e Atoms are electrically neutral; number of protons  in any atom equals its number of electrons    e The sum of the protons and neutrons is the atomic  mass number    e Isotopes—different forms of the same element  that differ in number of neutrons; heavier iso-  topes are often unstable and release energy as  radioactivity    e Bonding of two or more atoms of the same ele-  ment forms a molecule of a molecular substance  (such as H3, O2)    e Bonding of two or more atoms from different ele-  ments forms a molecule of a compound (such as  H,O, CH4)    o Compounds have different properties than the  individual atoms they contain    e Chemical bonds involve electrons in the outer-  most energy level (valence shell)  o Reactive atoms (incomplete valence shell) inter-  act by losing, gaining, or sharing electrons  o Atoms with a stable (full or meets the rule of 8)  valence shell are chemically non-reactive  e Valence electrons—completely transferred from  one atom to another to form ions  o Ions with opposite charges attract each other to  form an ionic bond  e Valence electron pairs shared between atoms form  covalent bonds  ° Electrons shared equally form nonpolar covalent  molecules    e Fragile bonds involving hydrogen on one mole-  cule and oxygen or nitrogen on another molecule  are hydrogen bonds    o Hydrogen bonds help stabilize large organic  molecules such as proteins and nucleic acids    e Synthesis reactions store energy in newly  formed bonds and result in larger, more complex  molecules    e Decomposition reactions release energy by  breaking bonds and result in simpler molecules  or individual atoms    e Temperature, concentration of the reactants,  particle size, and catalysts (enzymes) affect the  number and force of collisions    e Inorganic compounds do not contain carbon  (exceptions include CO, and CO)    ° Inorganic compounds include water, salts, and  some acids and bases    e Water is the most abundant compound in the  body, is a universal solvent, and is a reactant in  hydrolysis reactions    o Water is the vehicle for chemical reactions, trans-  portation around the body, and lubricating  fluids    o Water helps maintain body temperature by  slowly absorbing and releasing heat    o Water forms a watery cushion to protect certain  body structures (such as the brain)    è Salts in ionic form (electrolytes) are necessary  for nerve transmission, muscle contraction,  blood clotting, transport of oxygen by  hemoglobin, metabolism, and many other  reactions    o Strong acids dissociate completely in water;  weak acids partially dissociate    o Acids and bases react in a neutralization reac-  tion to form a salt and water    e The pH scale measures the relative concentrations  of hydrogen ions in various body fluids    ° One pH unit represents a tenfold change in  hydrogen ion concentration    ° pH 7 is neutral; the concentrations of hydrogen  and hydroxide ions are equal    ° A pH below 7 is acidic; a pH above 7 is alkaline  (basic)  e Normal blood pH ranges from 7.35 to 7.45.  2.5b. Organic compounds  e Organic compounds contain carbon    ° Carbohydrates, lipids, proteins, and nucleic  acids all contain carbon, oxygen, and hydrogen    ° Proteins and nucleic acids also contain nitrogen  o Nucleic acids also contain phosphorus    e Carbohydrates, lipids, proteins, and nucleic acids  are all degraded by hydrolysis and synthesized by  dehydration synthesis reactions    e Carbohydrates contain carbon, hydrogen, and  oxygen in the general relationship of one carbon  atom to two hydrogen atoms to one oxygen atom  (such as C,H, 0.)   ° Carbohydrate building blocks are monosaccha-  rides such as glucose, fructose, galactose    = Disaccharides have two monomers cova-  lently linked, such as sucrose, maltose, and  lactose    = Polysaccharides (many sugars) include  starch and glycogen  o Carbohydrates are ingested as sugars and starches  ° Glucose—maijor energy source for making ATP  e Lipids include triglycerides, phospholipids,  and steroids (the most important of which is  cholesterol)  ° Triglycerides (glycerol plus three fatty acid  chains) provide insulation in fat tissue and  reserve body fuel    o Cholesterol forms the basis of some hormones,  bile salts, and vitamin D    Proteins are polymers of amino acids  ° 20 amino acids are found in body proteins    Levels of protein structure include the amino acid  sequence (primary); the alpha-helix and  beta-pleated sheet (secondary); a three-  dimensional structure formed by secondary  structures folding on one another (tertiary); and a  globular structure formed by two or more  polypeptide chains (quaternary)    ° Different amino acid sequences result in differ-  ent proteins with different shapes and functions    Globular proteins are functional proteins such  as enzymes, peptide hormones, and hemoglobin    ° Functional proteins unfold (denature and inac-  tivate) when their hydrogen bonds are disrupted  by heat or pH changes    Enzymes speed the rates of chemical reactions by  binding temporarily and specifically with reac-  tants and holding them in the proper position to  interact    Nucleic acids include deoxyribonucleic acid  (DNA) and ribonucleic acid (RNA)  ° The monomer of nucleic acids is the nucleotide  ° Each nucleotide consists of a nitrogen-  containing base, a sugar (ribose or deoxyribose),  and a phosphate group  = DNA has nucleotides adenine, cytosine, gua-  nine, and thymine  = RNA has nucleotides adenine, cytosine, gua-  nine, and uracil  ° DNA (genes) maintains genetic heritage by rep-  licating itself before cell division and specifying  protein structure  o RNA executes instructions from DNA during  protein synthesis    ° Some liberated energy is lost as heat during ATP  production    2. Pick out the correct match(es) of element and num-  ber of valence electrons. Draw a planetary model of  each atom to help you choose the best answer.    a Carbon—6  b. Calcium—2  c. Iodine—7  d. Oxygen—6  e. Sodium—2  3. Important functions of water include which of the  following?  a Provides cushioning  b. Acts as a transport medium  c. Participates in chemical reactions  d. Acts as a solvent for sugars, salts, and other solutes  e. Reduces temperature fluctuations    4. Acidic substances include which of the following?  a Blood  b. Water  c. Gastric juice  d. Egg white  e. Lye  5. Glucose is to starch as  a asteroid is to a lipid.  b. a nucleotide is to a nucleic acid.  c. an amino acid is to a protein.  d. a polypeptide is to an amino acid.  6. Which of the following is an acidic amino acid?  a Glycine  b. Aspartic acid   Which of the following molecules is (are) present in  RNA but not in DNA?   13. Name and provide the atomic symbols of the four ele-  ments that make up the bulk of all living matter.  Which of these is found primarily in proteins and  nucleic acids?    which of them (the lightest, the one with an interme-  diate mass, or the heaviest) is most likely to be a  radioisotope, and why?    Describe how the two “generic” atoms shown below  would form an ionic bond. Include in your answer  where electrons come from, where they go, and why.    What are hydrogen bonds, and how are they impor-  tant in the body?    Identify each of the following reactions as a synthesis,  decomposition, or exchange reaction:    2H, + O, > 2H,O0  MgCl, > Mg?* + Cl,  Zn** + CuCl, > ZnCl, + Cu?*  Li,CO;— LipO + CO,    Distinguish inorganic from organic compounds, and  list the major categories of each in the body.    Define pH. The pH range of blood is from 7.35 to  7.45. Circle the correct answer to complete the sen-  tence: This is slightly (acidic / basic).    Several antibiotics act by binding to certain essential  enzymes in the target bacteria. How might these anti-  biotics influence the chemical reaction controlled by  the enzyme? What might be the effect on the bacteria?  On the person taking the antibiotic prescription?    Mrs. Roberts, who is in a diabetic coma, has just been  admitted to Noble Hospital. Her blood pH indicates  that she is in severe acidosis (blood pH in the acid  range), and the medical staff quickly institute mea-  sures to bring her blood pH back within normal lim-  its. Note the normal pH of blood, and discuss why  severe acidosis is a problem.    Stephen wants to bring some changes in his diet in  order to make it more heart healthy. His friend advises  him to choose the fats in his diet correctly. How can  he improve his intake of fats? Why are some fats good  for the heart and some are not?    Pediatricians become concerned about the potential for  brain damage when an infant's temperature approaches  105°F. Which class of organic molecules is most likely  to be damaged by high temperature? Explain why.    The cell is the  structural and functional  unit of the human body,    The many types of  tissues formed by cells  allow for the division of  labor among the body  systems.    Just as bricks and lumber are used to build a  house, cells are the structural units of all living  things, from one-celled organisms such as amoe-  bas to complex multicellular organisms such as  humans, dogs, and trees. The human body con-  tains 50 to 100 trillion of these tiny building  blocks.   In this chapter, we focus on structures and  functions shared by all cells. We consider special-  ized cells and their unique functions in later  chapters.    Cells carry out  the metabolic activities needed  to sustain life, and they divide  to form or repair tissues.    vz Name and describe the four concepts of the cell  theory.    y List four elements that make up the bulk of living  matter.    In the late 1600s, Robert Hooke was look-  ing through a crude microscope at some plant  tissue—cork. He saw some cubelike structures that    reminded him of the long rows of monk's rooms  (or cells) at the monastery, so he named these  structures “cells.” The living cells that had formed  the cork were long since dead; only the plant cell  walls remained. However, the name stuck and is  still used to describe the smallest unit of all living  things.   Since the late 1800s, cell research has been  exceptionally fruitful and has provided us with the  following four concepts collectively known as the  cell theory:    e Acell is the basic structural and functional unit  of living organisms. So, when you define cell  properties, you are in fact defining the properties  of life.    e The activity of an organism depends on the col-  lective activities of its cells.    e According to the principle of complementarity,  the activities of cells are dictated by their struc-  ture (anatomy), which determines function  (physiology).   e Continuity of life has a cellular basis. In other  words, cells come from cells.    We will expand on all of these concepts as we go  along. Let’s begin with the idea that the cell is the  smallest living unit. Whatever its form, however it  behaves, the cell contains all the parts necessary to  survive in a changing world. It follows, then, that  loss of cell homeostasis underlies virtually every  disease.   Perhaps the most striking thing about a cell is its  organization. Yet if we chemically analyze cells, we  find that they are made up primarily of the same  four elements—carbon, oxygen, hydrogen, and  nitrogen—plus much smaller amounts of several  other elements. (A detailed account of body chemis-  try appears in Chapter 2.)   Strange as it may seem, especially when we feel  our firm muscles, living cells are about 60 percent  water, which is one of the reasons water is essential  for life.    1. Define cell.  2. According to the cell theory, what the organism can  do depends on . (Fill in the blank.)  For answers, see Appendix A.    # Identify on a cell model or diagram the three  major cell regions (nucleus, cytoplasm, and  plasma membrane).    List the structures of the nucleus, and explain the  function of chromatin and nucleoli.    Although no one cell type is exactly like all others,  cells do have the same basic parts, and there are cer-  tain functions common to all cells. Here we will talk  about the generalized cell, which demonstrates  most of these typical features.   In general, all cells have three main regions or  parts—a plasma membrane, a nucleus (nu'kle-us), and  the cytoplasm (si'to-plazm”). The nucleus is usually  located near the center of the cell. It is surrounded by  the semifluid cytoplasm, which in turn is enclosed  by the plasma membrane, which forms the outer cell  boundary. (If you look ahead to Figure 3.4 on p. 88,  you can see a more detailed illustration of general-  ized cell structure.)    3.2a The Plasma Membrane  Learning Objectives  Describe the chemical composition of the plasma  membrane, and relate it to membrane functions.    vz Compare the structure and function of tight  junctions, desmosomes, and gap junctions.    The flexible plasma membrane is a fragile, transpar-  ent barrier that contains the cell contents and separates  them from the surrounding environment. (The terms  cell membrane or cytoplasmic membrane are sometimes  used instead, but because nearly all cellular organ-  elles are composed of membranes, in this text we will  always refer to the cell’s surface or outer limiting mem-  brane as the plasma membrane.) Although the plasma  membrane is important in defining the limits of the  cell, itis much more than a passive envelope, or “bag-  gie.” As you will see, its unique structure allows it to  play a dynamic role in many cellular activities.    The structure of the plasma membrane consists of  two phospholipid (fat) layers arranged “tail to tail,”  with cholesterol and floating proteins scattered among  them (Figure 3.1, p. 84). Some phospholipids may    also have sugar groups attached, forming glycolipids.  The proteins, some of which are free to move and  bob in the lipid layer, form a constantly changing  pattern or mosaic, hence the name fluid mosaic model.    charged end interacts with water, and the fatty acid  chains do not (see Chapter 2, p. 67). It is this property  of polarity that makes phospholipids a good foundation  for cell membranes.    The phospholipid bilayer forms the basic “fabric”  of the membrane. The polar “heads” of the lollipop-  shaped phospholipid molecules are hydrophilic  (“water loving”) and are attracted to water, the main  component of both the intracellular and extracellular  fluids, and so they lie on both the inner and outer  surfaces of the membrane. Their nonpolar fatty acid  “tails,” being hydrophobic (“water fearing”), avoid  water and line up in the center (interior) of the  membrane. The self-orienting property of the    Some proteins float freely in the lipid bilayer of the membrane, whereas others are  anchored in specific locations. What structure(s) could anchor the stationary proteins?    phospholipids allows biological membranes to reseal  themselves quickly when torn. The hydrophobic  makeup of the membrane interior makes the plasma  membrane relatively impermeable to most water-  soluble molecules. The cholesterol helps to both  stabilize the membrane and keep it flexible.   The proteins scattered in the lipid bilayer are  responsible for most of the specialized functions of  the membrane. Some proteins are enzymes. Many of  the proteins protruding from the cell exterior are  receptors for hormones or other chemical messen-  gers or are binding sites for anchoring the cell to  fibers or to other structures inside or outside the cell.  Most proteins that span the membrane are involved  in transport. For example, some cluster together to  form protein channels (tiny pores) through which  water and small water-soluble molecules or ions can  move; others act as carriers that bind to a substance  and move it through the membrane. Branching  sugar groups are attached to most of the proteins  abutting the extracellular space. Such “sugar-  proteins” are called glycoproteins, and because of their  presence, the cell surface is a fuzzy, sticky, sugar-rich  area called the glycocalyx (gli-ko-ka'liks). (You can  think of your cells as being sugar coated.) Among  other things, these glycoproteins determine your  blood type, act as receptors that certain bacteria,    Figure 3.2 Cell junctions. An epithelial cell is shown  joined to adjacent cells by the three common types of  cell junctions: tight junctions, desmosomes, and gap  junctions. Also illustrated are microvilli, which increase  the cell's surface area for absorption (seen projecting  from the free cell surface).    viruses, or toxins can bind to, and play a role in cell-  to-cell recognition and interactions. Definite changes  in glycoproteins occur in cells that are being trans-  formed into cancer cells. (We discuss cancer in “A  Closer Look” on p. 123.)    Although certain cell types—blood cells, sperm cells,  and some phagocytic cells (which ingest bacteria  and foreign debris)—are “footloose” in the body,  many other types, particularly epithelial cells, are  knit into tight communities. Typically, cells are  bound together in three ways:    e Glycoproteins in the glycocalyx act as an adhe-  sive or cellular glue.    e Wavy contours of the membranes of adjacent  cells fit together in a tongue-and-groove fashion.  e Special cell membrane junctions are formed    Because this last factor is the most important, let us  look more closely at the main types of junctions:  tight junctions, desmosomes, and gap junctions.    e Tight junctions are impermeable junctions that  encircle the cells and bind them together into leak-  proof sheets. In tight junctions, adjacent plasma  membranes fuse together tightly like a zipper and  prevent substances from passing through the extra-  cellular space between cells. In the small intestine,  for example, these junctions prevent digestive  enzymes from seeping into the bloodstream.    e Desmosomes (dez’mo-somz) are anchoring  junctions scattered like rivets along the sides of  adjacent cells. They prevent cells subjected to  mechanical stress (such as heart muscle cells and  skin cells) from being pulled apart. Structurally,  these junctions are buttonlike thickenings of adja-  cent plasma membranes (plaques) that are con-  nected by fine protein filaments. Thicker protein  filaments extend from the plaques inside the cells  to the plaques on the cells’ opposite sides, thus  forming an internal system of strong “guy wires.”    e Gap junctions function mainly to allow com-  munication. These junctions are commonly  found in the heart and between embryonic cells.  In gap junctions, the neighboring cells are con-  nected by hollow cylinders composed of proteins  (called connexons) that span the entire width of  the abutting membranes, much like adjoining  hotel rooms are directly connected by a door  inside the rooms. Because they span both mem-  branes, these connexons are called transmembrane  proteins. Chemical molecules, such as nutrients or  ions, can pass directly through the water-filled  connexon channels from one cell to another.    3. Why do phospholipids (which form the bulk of  plasma membranes) organize into a bilayer, tail to  tail, in a watery environment?   4. The external faces of some membrane proteins have  sugar groups attached to them. What are three roles  these sugar-coated proteins play in the life of a cell?   5. What is the special function of gap junctions? Of  tight junctions?    Figure 3.3 Anatomy of the generalized animal  cell nucleus. (a) Orientation diagram: the three  main regions of the generalized cell. (b) Structure  of the nucleus surrounded by rough ER.    center, is the nucleus (nucle = kernel). The genetic  material, or deoxyribonucleic acid (DNA), is a blue-  print that contains all the instructions needed for  building the whole body; so, as you might expect,  human DNA differs from frog DNA. More specif-  ically, DNA has genes, which carry the instructions  for building proteins. DNA is also absolutely nec-  essary for cell reproduction. A cell that has lost or  ejected its nucleus (for whatever reason) is destined  to “self-destruct.”   Although the nucleus is most often oval or spher-  ical, its shape usually conforms to the shape of the  cell. For example, if the cell is elongated, the nucleus  is usually elongated as well. The nucleus has three  recognizable regions or structures: the nuclear enve-  lope, nucleolus, and chromatin.    The nuclear boundary is a double membrane bar-  rier called the nuclear envelope, or nuclear  membrane (Figure 3.3). Between the two mem-  branes is a fluid-filled “moat,” or space. At vari-  ous points, the two layers of the nuclear envelope  fuse, generating openings called nuclear pores.  Like other cellular membranes, the nuclear envelope  allows some but not all substances to pass through  it, but substances pass through it much more freely  than elsewhere because of its relatively large pores.  The nuclear membrane encloses a jellylike fluid  called nucleoplasm (nu’kle-o-plazm”) in which other  nuclear elements are suspended.    The nucleus contains one or more small, dark-  staining, essentially round bodies called nucleoli  (nu-kle’o-li; “little nuclei”). Nucleoli (plural for  nucleolus) are sites where cell structures called ribo-  somes are assembled. Most ribosomes eventually  migrate into the cytoplasm, where they serve as the  actual sites of protein synthesis.    When a cell is not dividing, its DNA is carefully  wound around proteins called histones to form  a loose network of “beads on a string” called  chromatin (kro’mah-tin) that is scattered through-  out the nucleus. When a cell is dividing to form  two daughter cells, the chromatin threads coil and  condense to form dense, rodlike bodies called  chromosomes (chromo = colored, soma = body)—  much the way a stretched spring becomes shorter  and thicker when allowed to relax. We discuss the  functions of DNA and the events of cell division in  the Cell Physiology section (beginning on p. 96).    6. Name the three basic parts of a cell, and give  the location of each.  7. How would you explain the meaning of a  “generalized cell” to a classmate?  8. What is the general function of nucleoli?  For answers, see Appendix A.    4# Identify the organelles on a cell model or describe  them, and indicate the major function of each.    The cytoplasm is the cellular material outside the  nucleus and inside the plasma membrane. It is the  site of most cellular activities, so you might think  of the cytoplasm as the “factory floor” of the cell.  Although early scientists believed that the cytoplasm  was a structureless gel, the electron microscope has  revealed that it has three major components: the  cytosol, inclusions, and organelles. Let's take a look at  each of these.    The cytosol is semitransparent fluid that suspends  the other elements. Dissolved in the cytosol, which  is largely water, are nutrients and a variety of other  solutes (sol’yutz; dissolved substances).   Inclusions are chemical substances that may or  may not be present, depending on the specific cell  type. Most inclusions are stored nutrients or cell  products floating in the cytosol. They include the  lipid droplets common in fat cells, glycogen granules  abundant in liver and muscle cells, pigments such as  melanin in skin and hair cells, mucus and other  secretory products, and various kinds of crystals. It  may help to think of an inclusion as a cellular “pan-  try” where items are kept on hand until needed.    The organelles (or’gah-nelz’; “little organs”) are  specialized cellular compartments (Figure 3.4, p. 88)  that are the metabolic machinery of the cell. Each  type of organelle is specialized to carry out a specific  function for the cell as a whole, much like the organs  carry out specialized functions for the whole body.  Some synthesize proteins, others package those pro-  teins, and so on.   Many organelles are bounded by a membrane  similar to the plasma membrane. These membrane  boundaries allow organelles to maintain an internal  environment quite different from that of the sur-  rounding cytosol. This compartmentalization is cru-  cial to their ability to perform their specialized  functions for the cell. Let’s consider what goes on in  each of these workshops of our cellular factory.    tiny, beanlike or sausage-shaped organelles (see  Figure 3.4), but in living cells they lengthen and  change shape almost continuously. The mitochon-  drial wall consists of a double membrane, equal to  two plasma membranes placed side by side. The  outer membrane is smooth and featureless, but the  inner membrane has shelflike protrusions called cris-  tae (kris’te; “crests”). Enzymes dissolved in the fluid  within the mitochondria, as well as enzymes that  form part of the cristae membranes, carry out the  reactions in which oxygen is used to break down  foods. As the foods are broken down, energy is  released. Much of this energy escapes as heat, but  some is captured and used to form ATP molecules.   ATP provides the energy for all cellular work, and  every living cell requires a constant supply of ATP for  its many activities. Because the mitochondria supply  most of this ATP, they are the “powerhouses” of the  cell. Metabolically “busy” cells, such as liver and  muscle cells, use huge amounts of ATP and have  hundreds of mitochondria, which replicate them-  selves by pinching in half. By contrast, cells that are  relatively inactive (an unfertilized egg, for instance)  have fewer.    Ribosomes Ribosomes (ri’bo-sOmz) are tiny,  bilobed, dark bodies made of proteins and one vari-  ety of RNA called ribosomal RNA. Ribosomes are the  actual sites of protein synthesis in the cell. Ribosomes  that float freely in the cytoplasm manufacture pro-  teins that function inside the cell, while others attach  to membranes such as the rough ER, which produces  proteins that function outside the cell or on the exte-  rior cell surface.    Endoplasmic Reticulum The endoplasmic re-  ticulum (en”do-plas’mik ré-tik’u-lum; “network  within the cytoplasm”), or ER, is a system of fluid-  filled tunnels (or canals) that coil and twist through  the cytoplasm. It is continuous with the nuclear  envelope and accounts for about half of a cell's  membranes. It serves as a mini circulatory system for  the cell because it provides a network of channels for  carrying substances (primarily proteins) from one  part of the cell to another. There are two forms of ER,  rough and smooth (see Figure 3.4); a particular cell  may have both forms or only one, depending on its  specific functions.   The rough endoplasmic reticulum is so called  because it is studded with ribosomes. Because es-  sentially all of the building materials of cellular    Figure 3.4 Structure of the generalized cell. No cell is exactly like this one, but  this generalized cell drawing illustrates features common to many human cells.    membranes are formed either in it or on it, you can  think of the rough ER as the cell’s membrane factory.  The proteins made on its ribosomes migrate into the  rough ER tunnels, where they fold into their  functional three-dimensional shapes. These proteins  are then dispatched to other areas of the cell in small  “sacs” of membrane called transport vesicles  (Figure 3.5) that carry substances around the cell.  Rough ER is especially abundant in cells that make    (synthesize) and export (secrete) proteins—for  example, pancreatic cells, which produce digestive  enzymes to be delivered to the small intestine. The  enzymes that catalyze the synthesis of membrane  lipids reside on the external (cytoplasmic) face of the  rough ER, where the needed building blocks are  readily available.   Although the smooth endoplasmic reticulum  communicates with the rough variety, it plays no  role in protein synthesis, because it lacks ribosomes.  Instead it functions in lipid metabolism (cholesterol  and phospholipid synthesis and breakdown) and  detoxification of drugs and pesticides. Hence it is not    OLS the protein is synthesized on the ribosome,  it migrates into the rough ER tunnel system.    Figure 3.5 Synthesis and export of a protein by the rough ER.    surprising that the liver cells are chock-full of smooth  ER. So too are body cells that produce steroid-based  hormones—for instance, cells of the male testes that  manufacture testosterone.    Golgi Apparatus The Golgi (gol’je) apparatus  appears as a stack of flattened membranous sacs that  are associated with swarms of tiny vesicles. It is gen-  erally found close to the ER and is the principal “traf-  fic director” for cellular proteins. Its major function  is to modify, package, and ship proteins (sent to it by  the rough ER via transport vesicles) in specific ways,  depending on their final destination (Figure 3.6,  p 68). Initially, all proteins leaving the Golgi appara-  tus accumulate in sacs called Golgi vesicles.   As proteins “tagged” for export accumulate in  the Golgi apparatus, the sacs swell. Then their swol-  len ends, filled with protein, pinch off and form  secretory vesicles (ves’i-kulz), which travel to the  plasma membrane. When the vesicles reach the  plasma membrane, they fuse with it, and the con-  tents of the sac are ejected to the outside of the cell  (pathway 1 in Figure 3.6). Mucus is packaged this  way, as are digestive enzymes made by pancreatic  cells.   In addition to its packaging-for-release func-  tions, the Golgi apparatus pinches off sacs contain-  ing proteins and phospholipids destined for a    “home” in the plasma membrane (pathway 2 in  Figure 3.6) or other cellular membranes. It also  packages hydrolytic enzymes into membrane-bound  organelles called lysosomes that remain in the cell  (pathway 3 in Figure 3.6 and discussed next).    Lysosomes_ Lysosomes (li’so-somz; “breakdown  bodies”), which appear in different sizes, are mem-  branous “bags” containing powerful digestive  enzymes. Because lysosomal enzymes are capable of  digesting worn-out or nonusable cell structures and  most foreign substances that enter the cell, lyso-  somes function as cellular “stomachs.” Lysosomes  are especially abundant in white blood cells called  phagocytes, the cells that dispose of bacteria and cell  debris. As we mentioned, the enzymes they contain  are formed by ribosomes on the rough ER and pack-   Homeostatic J  £ Imbalance 3.1  The lysosomal membrane is ordinarily quite stable,  but it becomes fragile when the cell is injured or  deprived of oxygen and when excessive amounts of    Figure 3.6 Role of the Golgi  apparatus in packaging the  products of the rough ER.  Protein-containing transport vesicles  pinch off the rough ER and migrate    Peroxisomes Peroxisomes (per-ok’sih-somz) are  membranous sacs containing powerful oxidase  (ok'si-daz) enzymes that use molecular oxygen (O2)  to detoxify a number of harmful or poisonous sub-  stances, including alcohol and formaldehyde.  However, their most important function is to “dis-  arm” dangerous free radicals. Free radicals are  highly reactive chemicals with unpaired electrons  that can damage the structure of proteins and nucleic  acids. Free radicals are normal by-products of cellu-  lar metabolism, but if allowed to accumulate, they  can have devastating effects on cells. Peroxisomes  convert free radicals to hydrogen peroxide (H,O;), a  function indicated in their naming (peroxisomes =  peroxide bodies). The enzyme catalase (kat'ah-las)  then converts excess hydrogen peroxide to water.  Peroxisomes are especially numerous in liver and  kidney cells, which are very active in detoxification.  Although peroxisomes look like small lysosomes  (see Figure 3.4), they do not arise by budding from  the Golgi apparatus. Instead, one way they replicate  themselves is by simply pinching in half, like    to fuse with the Golgi apparatus. As  the proteins travel through the Golgi  apparatus, they are sorted (and  slightly modified if necessary), then  packaged within vesicles. These    Golgi vesicle containing  membrane components  fuses with the plasma  membrane and is  incorporated into it.    vesicles then leave the Golgi  apparatus and head for various  destinations (pathways 1-3), as  shown.    mitochondria, but most peroxisomes appear to bud  directly from the ER.    9. How do the cytosol and the cytoplasm differ?  10. Which two organelles are sacs of enzymes, and  what is the function of each of these organelles?  11. Which organelle is the major site of ATP synthesis?  Which packages proteins?  For answers, see Appendix A.    Cytoskeleton An elaborate network of protein  structures extends throughout the cytoplasm. This  network, or cytoskeleton, acts as a cell’s “bones and  muscles” by furnishing an internal framework that  determines cell shape, supports other organelles, and  provides the machinery for intracellular transport and  various types of cellular movements. From its small-  est to its largest elements, the cytoskeleton is made up  of microfilaments, intermediate filaments, and  microtubules (Figure 3.7). Although there is some    Figure 3.7 Cytoskeletal elements support the cell and help to generate  movement. Diagrammatic views (above) and photos (below). The photos are of  cells with the structure of interest “tagged” by fluorescent molecules.    overlap in roles, generally speaking microfilaments  (such as actin) are most involved in cell motility and  in producing changes in cell shape. (You could say  that cells move when they get their act(in) together.)  The strong, stable, ropelike intermediate filaments  are made up of fibrous subunits. They help form des-  mosomes (see Figure 3.2) and provide internal guy  wires to resist pulling forces on the cell. The tubelike  microtubules are made up of repeating subunits of  the protein tubulin. They determine the overall shape  of a cell and the distribution of organelles. They are  very important during cell division (see pp. 102-105).    Centrioles The paired centrioles (sen'tre-ōlz),  collectively called the centrosome, lie close to the  nucleus (see Figure 3.4). They are rod-shaped bodies  that lie at right angles to each other; internally they  are made up of a pinwheel array of nine triplets of  fine microtubules. Centrioles are best known for  their role in generating microtubules and also for  directing the formation of the mitotic spindle during  cell division (look ahead to Figure 3.15, p. 104).   Cell parts and their structures and functions are  summarized in Table 3.1 (pp. 92-94).    In addition to the cell structures described previ-  ously, some cells have obvious surface extensions.  These come in two major “flavors,” or varieties,  depending on whether they have a core of microtu-  bules or actin microfilaments.    Cilia (sil'e-ah; “eyelashes”) are whiplike cellular  extensions that move substances along the cell sur-  face. For example, mucus is carried up and away from  the lungs by “crowd surfing” on the ciliated cells  lining the respiratory system. Where cilia appear,  there are usually many of them projecting from the  exposed cell surface.   When a cell is about to make cilia, its centrioles  multiply and then line up beneath the plasma mem-  brane at the free cell surface. Microtubules then  begin to “sprout” from the centrioles and put pres-  sure on the membrane, forming the projections.   If the projections formed by the centrioles are  substantially longer, they are called flagella (flah-  jel’ah). The only example of a flagellated cell in the    Membrane made of a double layer of Serves as an external cell barrier and acts    Sugar group a z. i '  lipids (phospholipids and cholesterol) in transport of substances into or out of  with proteins embedded within. Most the cell. Maintains an electrical condition  externally facing proteins and some (membrane potential) that is essential for  lipids have attached sugar groups. the function of excitable cells. Externally    facing proteins act as receptors (for  hormones, neurotransmitters, and so  on), transport proteins, and in cell-to-cell   Cytoplasm Cellular region between the nuclear and plasma membranes. Consists of fluid cytosol  containing dissolved solutes, organelles (the metabolic machinery of the cytoplasm),  and inclusions (stored nutrients, secretory products, pigment granules).   e Ribosomes (Figures 3.4, 3.5) Dense particles consisting of two The sites of protein synthesis.    subunits, each composed of ribosomal  J = RNA and protein. Free or attached to    e Rough endoplasmic Membranous system enclosing a Sugar groups are attached to proteins  reticulum (Figures 3.4, 3.5) cavity, the tunnel, and coiling through within the tunnels. Proteins are bound in  7 the cytoplasm. Externally studded with vesicles for transport to the Golgi apparatus  ribosomes. and other sites. External face synthesizes    e Smooth endoplasmic Membranous system of tunnels and Site of lipid and steroid (cholesterol)  reticulum (Figure 3.4) sacs; free of ribosomes. synthesis, lipid metabolism, and drug  detoxification.  e Golgi apparatus (Figures 3.4, A stack of flattened membranes and Packages, modifies, and segregates proteins  3.6) associated vesicles close to the ER. for secretion from the cell, inclusion in  lysosomes, or incorporation into the plasma  membrane.    Table 3.1 (continued) 3  Cell part* Structure Functions  e Peroxisomes ( (not shown) Membranous sacs of oxidase and The enzymes detoxify a number of toxic  catalase enzymes. substances such as free radicals. The most  o J important enzyme, catalase, breaks down  hydrogen peroxide.    e Lysosomes (Figures 3.4, 3.6) | Membranous sacs containing acid Sites of intracellular digestion. The    e Microtubules (Figure 3.7) Cylindrical structures made of tubulin Support the cell and give it shape. Involved  es protein. in intracellular and cellular movements.   e Microfilaments (Figure 3.7) Fine filaments composed of the protein Involved in muscle contraction and other    Largest organelle. Surrounded by Control center of the cell; responsible  the nuclear envelope; contains fluid for transmitting genetic information and  nucleoplasm, nucleoli, and chromatin. providing the instructions for protein  synthesis.  e Nuclear envelope (Figure 3.3) Double-membrane structure pierced Separates the nucleoplasm from the    human body is the sperm, which has a single pro-  pulsive flagellum called its tail (look ahead to  Figure 3.8g). Notice that cilia propel other sub-  stances across a cell’s surface, whereas a flagellum  propels the cell itself.   Microvilli (mi"kro-vil’i; “little shaggy hairs”) are  tiny, fingerlike extensions of the plasma mem-  brane that project from an exposed cell surface (see  Figure 3.2). They increase the cell’s surface area tre-  mendously and so are usually found on the surface  of cells active in absorption such as intestinal and  kidney tubule cells. Microvilli have a core of actin fil-  aments that extend into the internal cytoskeleton of  the cell and stiffen the microvillus. Note that micro-  villi are “alcoves” projecting off one cell surface and  do not involve microtubules.    12. Which two types of cytoskeletal elements are  involved in cell mobility?   13. Which of the cytoskeletal elements is the basis of  centrioles? Of microvilli?   14. The major function of cilia is to move substances  across the free cell surface. What is the major role  of microvilli?    Apply the principle of complementarity to  different cell types by comparing overall shapes,  internal structures, and special functions.    Dense spherical (non-membrane-  ay bounded) bodies, composed of  k ribosomal RNA and proteins.    Granular, threadlike material  composed of DNA and histone  proteins. “Beads on a string.”    DNA constitutes the genes, which  carry instructions for building proteins.  The structure of chromatin keeps DNA  organized and prevents breakage.    So far in this chapter, we have focused on a gener-  alized human cell. However, the trillions of cells  in the human body include over 200 different cell  types that vary greatly in size, shape, and function.  They include sphere-shaped fat cells, disc-shaped red  blood cells, branching nerve cells, and cube-shaped  cells of the kidney tubules.   Depending on type, cells also vary greatly in  length—ranging from 1/12,000 of an inch in the  smallest cells to over a yard in the nerve cells that  cause you to wiggle your toes. A cell's shape reflects  its function. For example, the flat, tilelike epithelial  cells that line the inside of your cheek fit closely  together, forming a living barrier that protects under-  lying tissues from bacterial invasion.   The shapes of cells and the relative numbers of  the various organelles they contain relate to special-  ized cell functions (Figure 3.8). Let's take a look at  some examples of specialized cells.    e Fibroblast. This cell has an elongated shape,  like the cable-like fibers that it secretes. It  has an abundant rough ER and a large Golgi  apparatus to make and secrete the protein  building blocks of these fibers.    e Erythrocyte (red blood cell). This cell carries  oxygen in the blood. Its biconcave disc shape  provides extra surface area for the uptake of  oxygen and streamlines the cell so it flows  easily through the bloodstream. So much  oxygen-carrying pigment is packed in eryth-  rocytes that all other organelles have been  ejected to make room.    e Epithelial cell. The hexagonal shape of this  cell is exactly like a “cell” in a honeycomb of  a beehive. This shape allows epithelial cells  to pack together in sheets. An epithelial cell = ZS  has abundant intermediate filaments and _ ai i Nucleus  desmosomes that resist tearing when the #  epithelium is rubbed or pulled.    (a) Cells that connect body parts  e Cells that move organs and body parts    e Skeletal, cardiac, and smooth muscle cells.  These cells are elongated and filled with  abundant contractile microfilaments, so they  can shorten forcefully and move the bones,  pump blood, or change the size of internal  organs to move substances around the body.    e White blood cells such as the macrophage  (a phagocytic cell). This cell extends long  pseudopods (“false feet”) to crawl through tissue Lysosomes  to reach infection sites. The many lysosomes  within the cell digest the infectious microor-  ganisms (such as bacteria) that it “eats.”    o Cell that gathers information and controls  body functions (Figure 3.8f)   o Nerve cell (neuron). This cell has long pro-  cesses (extensions) for receiving messages (d) Cell that stores (e) Cell that fights  and transmitting them to other structures nutrients disease  in the body. The processes are covered with  an extensive plasma membrane, and a  plentiful rough ER synthesizes membrane  components and signaling molecules called  neurotransmitters.    Nucleus Flagellum  Figure 3.8 Cell diversity. The shape of human cells  and the relative abundances of their various organelles D N  determine their function in the body. (Note that these perm  cells are not drawn to the same scale.) (g) Cell of reproduction    the daughter cells that arise when the fertil-  ized egg divides to become an embryo.    e Sperm (male). This cell is long and stream-  lined, built for swimming to the egg for  fertilization. Its flagellum acts as a motile  whip to propel the sperm.    15. Name the two cell types involved in connecting  body parts or regions.  16. What is the main function of a neuron?  For answers, see Appendix A.    Each of the cell’s internal parts is designed to per-  form a specific function for the cell. As mentioned  earlier, most cells have the ability to metabolize (use  nutrients to build new cell material, break down  substances, and make ATP), digest foods, dispose of  wastes, reproduce, grow, move, and respond to a stim-  ulus (irritability). We consider most of these func-  tions in detail in later chapters. (For example, we  cover metabolism in Chapter 14, and the ability to  react to a stimulus in Chapter 7). In this chapter, we  consider only the functions of membrane transport  (the means by which substances get through plasma  membranes), protein synthesis, and cell reproduc-  tion (cell division).    4 Define selective permeability, diffusion (including  simple and facilitated diffusion and osmosis),  active transport, passive transport, solute  pumping, exocytosis, endocytosis, phagocytosis,  pinocytosis, hypertonic, hypotonic, and isotonic.   v Describe plasma membrane structure, and explain  how the various transport processes account for  the directional movements of specific substances  across the plasma membrane.    The fluid environment on both sides of the plasma  membrane is an example of a solution. It is important  that you really understand solutions before we dive  into an explanation of membrane transport. In the  most basic sense, a solution is a homogeneous mix-  ture of two or more components. Examples include  the air we breathe (a mixture of gases), seawater (a  mixture of water and salts), and rubbing alcohol (a  mixture of water and alcohol). The substance present    in the largest amount in a solution is called the  solvent (or dissolving medium). Water is the body’s  chief solvent. Components or substances present in  smaller amounts are called solutes. The solutes in  a solution are so tiny that the molecules cannot be  seen with the naked eye and do not settle out.   Intracellular fluid (collectively, the nucleo-  plasm and the cytosol) is a solution containing small  amounts of gases (oxygen and carbon dioxide),  nutrients, and salts, dissolved in water. So too is  extracellular fluid, or interstitial fluid, the fluid  that continuously bathes the exterior of our cells.  You can think of interstitial fluid as a rich, nutritious,  and rather unusual “soup.” It contains thousands of  ingredients, including nutrients (amino acids, sug-  ars, fatty acids, vitamins), regulatory substances such  as hormones and neurotransmitters, salts, and waste  products. To remain healthy, each cell must extract  from this soup the exact amounts of the substances  it needs at specific times and reject the rest.   The plasma membrane is a selectively permeable  barrier. Selective permeability means that a barrier  allows some substances to pass through it while  excluding others. Thus, it allows nutrients to enter  the cell but keeps many undesirable or unnecessary  substances out. At the same time, valuable cell pro-  teins and other substances are kept within the cell,  and wastes are allowed to pass out of it.    Homeostatic J  £ Imbalance 3.2  The property of selective permeability is typical only  of healthy, unharmed cells. When a cell dies or is  badly damaged, its plasma membrane can no longer  be selective and becomes permeable to nearly every-  thing. We see this problem when someone has been  severely burned. Precious fluids, proteins, and ions  “weep” (leak out) from the dead and damaged cells  at the burn site.    Substances move through the plasma membrane  in basically two ways—passively or actively. In pas-  sive processes, substances are transported across the  membrane without any energy input from the cell.  In active processes, the cell provides the metabolic  energy (AIP) that drives the transport process.    Passive Processes: Diffusion and Filtration  Diffusion (di-fu’zhun) is an important means of pas-  sive membrane transport for every cell of the body.    The other passive transport process, filtration, gener-  ally occurs only across capillary walls. Let's examine  how these two types of passive transport differ.    Diffusion Diffusion is the process by which mol-  ecules (and ions) move away from areas where they  are more concentrated (more numerous) to areas  where they are less concentrated (with fewer of  them). All molecules possess kinetic energy, or energy  of motion (as described in Chapter 2), and as the  molecules move about randomly at high speeds,  they collide and change direction with each colli-  sion. The overall effect of this erratic movement is  that molecules move down their concentration  gradient (spread out). The greater the difference in  concentration between the two areas, the faster diffu-  sion occurs. Because the driving force (source of  energy) is the kinetic energy of the molecules them-  selves, the speed of diffusion is affected by the size of  the molecules (the smaller the faster) and tempera-  ture (the warmer the faster).   An example should help you understand diffu-  sion. Picture yourself dropping a tea bag into a cup  of boiling water, but not stirring the cup. The bag  itself represents the semipermeable cell membrane,  which lets only some molecules leave the tea bag. As  the tea molecules dissolve in the hot water and col-  lide repeatedly, they begin to “spread out” from the  tea bag even though it was never stirred. Eventually,  as a result of their activity, the entire cup will have  the same concentration of tea molecules and will  appear uniform in color. (A laboratory example that  might be familiar to some students is illustrated  Figure 3.9).   The hydrophobic core of the plasma membrane  is a physical barrier to diffusion. However, molecules  will diffuse through the plasma membrane if any of  the following are true:    e The molecules are small enough to pass through  the membrane’s pores (channels formed by  membrane proteins).    The unassisted diffusion of solutes through  the plasma membrane (or any selectively perme-  able membrane) is called simple diffusion  (Figure 3.10a, p. 98). Solutes transported this way  are lipid-soluble (such as fats, fat-soluble vitamins,  oxygen, carbon dioxide).    Figure 3.9 Diffusion. Particles in solution move  continuously and collide constantly with other particles.  As a result, particles tend to move away from areas  where they are most highly concentrated to become  evenly distributed, as illustrated by the diffusion of dye  molecules in a beaker of water.    Diffusion of water through a selectively perme-  able membrane such as the plasma membrane is  specifically called osmosis (oz-mo'sis). Because  water is highly polar, it is repelled by the (nonpolar)  lipid core of the plasma membrane, but it can and  does pass easily through special pores called aqua-  porins (“water pores”) created by proteins in the  membrane (Figure 3.10b). Osmosis into and out of  cells is occurring all the time as water moves down  its concentration gradient. The movement of water  across the membrane occurs quickly. Anyone admin-  istering an IV (intravenous, into the vein) solution  must use the correct solution to protect the patient's  cells from life-threatening dehydration or rupture  (see “A Closer Look” on p. 99).   Still another example of diffusion is facilitated  diffusion. Facilitated diffusion provides passage for  certain needed substances (notably glucose) that are  both lipid-insoluble and too large to pass through  the membrane pores, or charged, as in the case of  chloride ions passing through a membrane protein  channel. Although facilitated diffusion follows the  laws of diffusion—that is, the substances move down  their own concentration gradients—a membrane  protein channel is used (Figure 3.10c), or a mem-  brane protein that acts as a carrier (Figure 3.10d) is  needed to move glucose and certain other solutes  passively across the membrane into the cell without  requiring ATP.   Substances that pass into and out of cells by dif-  fusion save the cell a great deal of energy. When you  consider how vitally important water, glucose, and    oxygen are to cells, you can understand just how nec-  essary these passive transport processes really are.  Glucose and oxygen continually move into the cells  (where they are in lower concentration because the  cells keep using them up), and carbon dioxide (a  waste product of cellular activity) continually moves  out of the cells into the blood (where it is in lower  concentration).    Filtration Filtration is the process by which water  and solutes are forced through a membrane (or cap-  illary wall) by fluid, or hydrostatic, pressure. In the  body, hydrostatic pressure is usually exerted by the  blood. Like diffusion, filtration is a passive process,  and a gradient is involved. In filtration, however, the  gradient is a pressure gradient that actually pushes  solute-containing fluid (filtrate) from the higher-  pressure area through the filter to the lower-pressure  area. In the kidneys, water and small solutes filter out  of the capillaries into the kidney tubules because the    blood pressure in the capillaries is greater than the  fluid pressure in the tubules. Part of the filtrate  formed in this way eventually becomes urine.  Filtration is not very selective. For the most part, only  blood cells and protein molecules too large to pass  through the membrane pores are held back.   17. What is the energy source for all types of  diffusion?   19. What are the two ways that facilitated diffusion is  carried out, and how do they differ?    When a cell uses ATP to move substances across the  membrane, the process is active. Substances moved  actively are usually unable to pass in the desired  direction by diffusion. They may be too large to pass    J% Learn more at Mastering A&P > Study Area > A   personnel give only the proper  intravenous (IV), or into-the-vein, solu-  tions to patients?   The tendency of a solution to hold  water or “pull” water into it is called  osmotic pressure. Osmotic pressure is  directly related to the concentration of  solutes in the solution. The higher the  solute concentration, the greater the  osmotic pressure and the greater  the tendency of water to move into  the solution. Many molecules, particu-  larly proteins and some ions, are pre-  vented from diffusing through the  plasma membrane. Consequently, any  change in their concentration on one  side of the membrane forces water to  move from one side of the membrane  to the other, causing cells to lose or  gain water. The ability of a solution to  change the size and shape of cells by  altering the amount of water they  contain is called tonicity (ton-is’i-te;  ton = strength).   A hypertonic (hi’per-ton’ik) solu-  tion is a solution that contains more  solutes, or dissolved substances, than  there are inside the cells. Hypertonic  solutions are sometimes given to  patients who have edema (swelling    through membrane channels, the membrane may  lack special protein carriers for their transport, they  may not be able to dissolve in the fat core, or they  may have to move “uphill” against their concentra-  tion gradients. The two most important active pro-  cesses are active transport and vesicular transport.    Active Transport Sometimes called solute pumping,  active transport is similar to facilitated diffusion in    due to fluid retention). Such solutions  draw water out of the tissue spaces  into the bloodstream so that the kid-  neys can eliminate excess fluid.   When a solution contains fewer  solutes (and therefore more water)  than the cell does, it is hypotonic  (hipo-ton'ik) to the cell. Hypotonic  solutions are sometimes infused intra-  venously to rehydrate extremely dehy-  drated patients. This must be done  slowly to avoid cell /ysis, or rupture,  caused by too much fluid flowing into  the cells.    e |V solutions are delivered intra-  venously, or directly into a vein.    e Cells in hypertonic solution have  fewer solutes and more water  compared to the solution out-  side, and thus water is drawn  out of the cells toward the  higher solute concentration.    e Cells in hypotonic solution have  more solutes and less water  compared to the solution out-  side, and thus water is drawn  into the cell toward the higher  solute concentration.    e Cells in isotonic solutions gain  and lose water at the same rate.    that both processes require protein carriers that  interact specifically and reversibly with the sub-  stances to be transported across the membrane.  However, facilitated diffusion is driven by the kinetic  energy of the diffusing molecules, whereas active  transport uses AIP to energize its protein carriers,  which are called solute pumps. Amino acids, some  sugars, and most ions are transported by solute  pumps, and in most cases these substances move    (4) Binding of cytoplasmic Nat  to the pump protein stimulates  phosphorylation by ATP, which    (2) The shape change expels  Nat to the outside. Extracellular  K* binds, causing release of the    (3) Loss of phosphate restores  the original shape of the pump  protein. Kt is released to the    Figure 3.11 Operation of the  sodium-potassium pump, a solute  pump. ATP provides the energy for a  “pump” protein to move three  sodium ions out of the cell and two    against concentration (or electrical) gradients. This is  opposite to the direction in which substances would  naturally flow by diffusion, which explains the need  for energy in the form of ATP; they are essentially  moving “uphill.”   The sodium-potassium (Na*-K*) pump alter-  nately carries sodium ions (Na*) out of and potas-  sium ions (K*) into the cell (Figure 3.11). This  process is absolutely necessary for normal transmis-  sion of nerve impulses. There are more sodium ions  outside the cells than inside, so those inside tend to  remain in the cell unless the cell uses ATP to force, or  “pump,” them out. ATP is split into ADP and P;  (inorganic phosphate), and the phosphate is then  attached to the sodium-potassium pump in a    pump moves both ions against their  concentration gradients. The num-  bered steps indicate the sequence of  ion and phosphate binding a pump  protein goes through as it expels Nat    process called phosphorylation. Likewise, there are  more potassium ions inside cells than in the extra-  cellular fluid, and potassium ions that leak out of  cells must be actively pumped back inside. Because  each of the pumps in the plasma membrane trans-  ports only specific substances, active transport pro-  vides a way for the cell to be very selective in cases  where substances cannot pass by diffusion. (No  pump—no transport.)    Vesicular Transport Some substances cannot get  through the plasma membrane by active or passive  transport. Vesicular transport, which involves help  from ATP to fuse or separate membrane vesicles and  the cell membrane, moves substances into or out of   Exocytosis (ek’so-si-to’sis; “out of the cell”)  (Figure 3.12) is the mechanism that cells use to  actively secrete hormones, mucus, and other cell  products or to eject certain cellular wastes. The prod-  uct to be released is first “packaged” (typically by the  Golgi apparatus) into a secretory vesicle. The vesicle  migrates to the plasma membrane, fuses with it, and  then ruptures, spilling its contents out of the cell  (also look back at pathway 1 of Figure 3.6).  Exocytosis involves a “docking” process in which  docking proteins on the vesicles recognize plasma  membrane docking proteins and bind with them.  This binding causes the membranes to “corkscrew”  together and fuse (see Figure 3.12).   Endocytosis (en"do-si-to’sis; “into the cell”)  includes those ATP-requiring processes that take up,  or engulf, extracellular substances by enclosing  them in a vesicle (Figure 3.13a, p. 102). Once the  vesicle is formed, it detaches from the plasma  membrane and moves into the cytoplasm, where it  typically fuses with a lysosome and its contents are  digested (by lysosomal enzymes). However, in  some cases, the vesicle travels to the opposite side  of the cell and releases its contents by exocytosis  there.   If the engulfed substances are relatively large  particles, such as bacteria or dead body cells, and the  cell separates them from the external environment  by pseudopods, the endocytosis process is more  specifically called phagocytosis (fag’o-si-to’sis), a  term that means “cell eating” (Figure 3.13b).  Certain white blood cells, such as the macrophage,  and other “professional” phagocytes of the body act  as scavenger cells that police and protect the body  by ingesting bacteria and other foreign debris.  Hence, phagocytosis is a protective mechanism—a  way to “clean house”—not a means of getting  nutrients.   Cells eat by phagocytosis and drink by a form of  endocytosis called pinocytosis (pi’no-si-to’sis;  “cell drinking”), during which the cell “gulps” drop-  lets of extracellular fluid. (It may help you to  remember the name of this process to think of your  mother drinking a glass of pinot noir wine.) The  plasma membrane indents to form a tiny pit, or  “cup,” and then its edges fuse around the droplet of  extracellular fluid containing dissolved proteins or    ° : a  @  @  ° ve =)  r Pseudopod  A (b) Phagocytosis  @  4  @  @  @ -  ofo a  Target molecule  o o TES  @  @  (a) Endocytosis (pinocytosis) (c) Receptor-mediated  endocytosis  Figure 3.13 Events and types of may be digested within a lysosome membrane components and recep-  endocytosis. (a) Sequence of events and then released to the cytosol. tors are recycled to the plasma  in endocytosis. A vesicle forms by Alternatively, the vesicle may be membrane @). The type illustrated  forming a pit in the membrane Q). transported across the cell intact and is pinocytosis. (b) Phagocytosis.  Once the vesicle detaches from the then released to the cell exterior by (c) Receptor-mediated endocytosis.  plasma membrane, its contents exocytosis @B). If present, its    fats (see Figure 3.13a). Unlike phagocytosis, pinocy-  tosis is a routine activity of most cells. It is especially   include enzymes, some hormones, cholesterol, and The cell life cycle is the series of changes a cell goes    The cycle has two major periods: interphase, in  which the cell grows and carries on its usual meta-  bolic activities, and cell division, during which it  reproduces itself. Although the term interphase might  lead you to believe that it is merely a resting time  between the phases of cell division, this is not the  case. During interphase, which is by far the longer  phase of the cell cycle, the cell is very active and is  preparing for cell division. A more accurate name for  interphase would be metabolic phase.    The function of cell division is to produce more cells  for growth and repair processes. Because it is essen-  tial that all body cells have the same genetic mate-  rial, an important event always precedes cell division:  The DNA molecule (the genetic material) is dupli-  cated exactly in a process called DNA replication.  This occurs toward the end of interphase.    Chapter 2, p. 74). It is composed of building blocks  called nucleotides, each consisting of a deoxyribose  sugar, a phosphate group, and a nitrogen-containing  base. Essentially, DNA is a double helix, a ladderlike  molecule that is coiled into a spiral staircase shape. The  upright parts of the DNA “ladder,” or backbone, are  alternating phosphate and sugar units, and the rungs of  the ladder are made of pairs of nitrogen-containing  bases.    The precise trigger for DNA synthesis is  unknown, but once it starts, it continues until all the  DNA has been replicated. The process begins as the  DNA helix “unzips,” gradually separating into its  two nucleotide chains (Figure 3.14). Each nucleotide  strand then serves as a template, or set of instructions,  for building a new nucleotide strand.   Remember that nucleotides join in a complemen-  tary way: Adenine (A) always bonds to thymine (T),  and guanine (G) always bonds to cytosine (C).  Hence, the order of the nucleotides on the template  strand also determines the order on the new strand.  For example, a TACTGC sequence on a template  strand would generate a new strand with the order  ATGACG. The end result is two DNA molecules that  are identical to the original DNA helix, each consist-  ing of one old and one newly assembled nucleotide  strand.    Figure 3.14 Replication of the DNA molecule at the  end of interphase. In a process controlled by enzymes,  the DNA helix unwinds (center), and its nucleotide strands  are separated. Each strand then acts as a template for  building a new complementary strand. As a result, two  helices, each identical to the original DNA helix, are formed.    In all cells other than bacteria and some cells of the  reproductive system, cell division consists of two  events. Mitosis (mi-to’sis), or division of the nucleus,  occurs first. The second event is division of the cy-  toplasm, cytokinesis (si"to-ki-ne’sis), which begins  when mitosis is nearly completed.    Mitosis Mitosis is the process of dividing a nucleus  into two daughter nuclei with exactly the same genes  as the “mother” nucleus. As explained previously,  DNA replication precedes mitosis, so that for a short    time the cell nucleus contains a double dose of  genes. When the nucleus divides, each daughter  nucleus ends up with exactly the same genetic infor-  mation as the original mother cell.    e Prophase (pro’faz). As cell division begins,  the chromatin threads coil and shorten so that  the barlike chromosomes become visible under  a microscope. Because DNA has already been  replicated, each chromosome is actually made  up of two identical strands called sister    chromatids (kro’mah-tidz), held together by a  small buttonlike body called a centromere  (sen’tro-mér) (see Figure 3.15). The centrioles  separate from each other and begin to move  toward opposite sides of the cell, directing the  assembly of a mitotic spindle (composed of  microtubules) between them as they move. The  spindle provides scaffolding for the attachment  and movement of the chromosomes during the  later mitotic stages. By the end of prophase, the  nuclear envelope and the nucleoli have broken  down and temporarily disappeared, and the  chromosomes have attached randomly to the  spindle fibers by their centromeres.    e Metaphase (met’ah-faz). In this short stage,  the chromosomes line up at the metaphase plate  (the center of the spindle midway between the  centrioles) so that a straight line of chromo-  somes is seen.    e Anaphase (an'ah-faz). During anaphase, the  centromeres that have held the chromatids  together split. The chromatids (now called chro-  mosomes again) begin to move slowly apart,  drawn toward opposite ends of the cell. The  chromosomes seem to be pulled by their half-  centromeres, with their “arms” dangling behind  them. This careful division of sister chromatids  ensures that each daughter cell gets one copy of  every chromosome. Anaphase is over when the  chromosomes stop moving.    e Telophase (tel’o-faz). Telophase is essentially  prophase in reverse. The chromosomes at oppo-  site ends of the cell uncoil to become threadlike  chromatin again. The spindle breaks down and  disappears, a nuclear envelope forms around  each chromatin mass, and nucleoli appear in  each of the daughter nuclei.    Mitosis is basically the same in all animal cells.  Depending on the type of tissue, it takes from 5 min-  utes to several hours to complete, but typically it  lasts about 2 hours. Centriole replication is deferred  until late interphase of the next cell cycle, when DNA  replication begins before the onset of mitosis.    Cytokinesis Cytokinesis, or the division of the  cytoplasm, usually begins during late anaphase and  completes during telophase. A contractile ring made  of microfilaments forms a cleavage furrow over the  midline of the spindle, and it eventually squeezes, or  pinches, the original cytoplasmic mass into two    parts. Thus, at the end of cell division, two daughter  cells exist. Each is smaller with less cytoplasm than  the mother cell had but is genetically identical to the  mother cell. The daughter cells grow and carry out  normal cell activities (interphase) until it is their  turn to divide.   Mitosis and cytokinesis usually go hand in hand,  but in some cases the cytoplasm is not divided. This  condition leads to the formation of binucleate (two  nuclei) or multinucleate cells. This is fairly common  in the liver and in the formation of skeletal muscle.    Proteins are key substances for all aspects of cell life.  Fibrous (structural) proteins are the major building  materials for cells (see Chapter 2). Other proteins,  the globular (functional) proteins, perform functional  roles in the body. For example, all enzymes, bio-  logical catalysts that speed up every chemical reac-  tion that occurs in cells, are functional proteins. It  follows, then, that every cell needs to produce pro-  teins, a process called protein synthesis. This is accom-  plished at ribosomes with information in the DNA  genes and with the help of the nucleic acid RNA.  Let's look at this process and its components more  closely.    In addition to replicating itself for cell division, DNA  serves as the master blueprint for protein synthe-  sis. Traditionally, a gene is defined as a DNA seg-  ment that carries the information for building one  protein.   DNA’s information is encoded in the sequence  of bases. Each sequence of three bases (a triplet)  encodes a particular amino acid. (Amino acids are the  building blocks of proteins and are joined during  protein synthesis; see Chapter 2.) For example, a  DNA base sequence of AAA specifies an amino acid  called phenylalanine, and CCT encodes glycine. Just  as different arrangements of notes on sheet music  are played as different chords, variations in the  arrangements of A, C, T, and G in each gene allow  cells to make all the different kinds of proteins  needed. A single gene can contain an estimated 300  to 2 million base pairs in sequence. The human  genome contains 20,000 to 25,000 genes.    By itself, DNA is rather like a coded message;  its information is not useful until it is decoded.    Furthermore, most ribosomes—the manufacturing  sites for proteins—are in the cytoplasm, but DNA  never leaves the nucleus during interphase. Thus,  DNA requires not only a decoder but also a trusted  messenger to carry the instructions for building pro-  teins to the ribosomes. These messenger and decoder  functions are carried out by a second type of nucleic  acid, called ribonucleic (ri’bo-nu-kle’ik) acid,  or RNA.   RNA differs from DNA in being single-stranded,  in having ribose sugar instead of deoxyribose, and in  having a uracil (U) base instead of thymine (T)  (recall what you learned in Chapter 2). Three variet-  ies of RNA play a special role in protein synthesis.  Ribosomal RNA (rRNA) helps form the ribosomes,  where proteins are built. Messenger RNA (mRNA)  molecules are long, single nucleotide strands that  resemble half of a DNA molecule. They carry the  “message” containing instructions for protein syn-  thesis from the DNA (gene) in the nucleus to the  ribosomes in the cytoplasm. Transfer RNA (tRNA)  molecules are small, cloverleaf-shaped molecules  that escort amino acids to the ribosome.    Protein synthesis involves two major phases: tran-  scription, when complementary mRNA (the messen-  ger) is made using the information in the DNA  gene, and translation, when the information carried  in mRNA molecules is “decoded” and translated  from nucleic acids into proteins (Figure 3.16).    Transcription You may have heard the word tran-  scription used to describe the process of converting  oral conversation to a written record, like the job  done by a court reporter. The language is the same;  the only difference is the form (oral versus written).  In the context of protein synthesis, transcription also  refers to converting the same information, in the  same language, from one form to another—but in  this context, the “language” is nucleic acids. In  cells, transcription involves the transfer of infor-  mation from the sequence of bases in a DNA gene  into the complementary sequence of mRNA by an  enzyme (see Figure 3.16, step @). DNA is the tem-  plate for transcription, and mRNA is the product.  Each three-base sequence specifying a particular  amino acid on the DNA gene is called a triplet,  and the corresponding three-base sequences on  mRNA are called codons. The form is different, but  the same information is being conveyed. Thus, if    the (partial) sequence of DNA triplets is AAT-CGT-  TCG, RNA base-pairing rules (A:U, G:C) tell us that  the corresponding codons on mRNA would be  UUA-GCA-AGC.    Translation A translator takes words in one lan-  guage and restates them in another language. In the  translation phase of protein synthesis, the language  of nucleic acids (base sequence) is “translated” into  the language of proteins (amino acid sequence).  Translation occurs in the cytoplasm and involves all  three major varieties of RNA. Translation consists of  the following series of events (see Figure 3.16,  steps 2-5). Once the mRNA attaches to the ribosome  (®©), tRNA transfers, or delivers, amino acids to  the ribosome, where they are linked together by  peptide bonds (formed by dehydration synthesis; see  Chapter 2) in the exact sequence specified by the  gene (and its mRNA). There are about 45 common  types of tRNAs, each capable of carrying one of the  20 types of amino acids. But that is not the only job  of the tRNAs. They also have to recognize the mRNA  codons to “double check” that the amino acid they are  toting will be added in the correct order. They can do  this because they have a special three-base sequence  called an anticodon on their “head” that can tempo-  rarily bind to the complementary codons .   Once the first tRNA delivers its amino acid in the  correct position at the beginning of the mRNA mes-  sage, the ribosome moves the mRNA strand along,  bringing the next codon into position to be read by  another tRNA. As amino acids are brought to their  proper positions along the length of mRNA, they are  joined together with peptide bonds catalyzed by the  large ribosomal subunit , and begin folding into  the final protein structure.    into peptide bonds is the result of dehydration synthe-  sis reactions (Chapter 2, p. 63). To make room for the  new peptide bond, water (H,O) must be removed. A  hydrogen atom is removed from one amino acid, and a  hydroxyl group (OH) is removed from the other.    As each amino acid is added to the chain, its  tRNA is released and moves away from the ribosome  to pick up another amino acid (©). When the last  codon (the termination, or “stop,” codon) is read,  the protein is released.    Nucleus TSn fi Cytoplasm  (site of transcription) Is / (site of translation)    (1)mRNA specifying one  polypeptide is made from  the DNA template (a  gene) by an enzyme (not  o shown).    (3) Incoming tRNA  recognizes a complementary  mRNA codon encoding its  amino acid by temporarily  binding its anticodon to the  codon.    (4)As the ribosome moves along  the mRNA, a new amino acid is  added to the growing protein  chain.   reenters the cytoplasmic  pool, ready to attach toa  new amino acid.    Figure 3.16 Protein synthesis. Q) Transcription. @-G) Translation. Step 3 ensures  that the correct amino acid is added at the correct location in the growing protein.   25. What is cytokinesis? What results if cytokinesis  does not happen?   26. What is the role of mRNA in protein synthesis?  What about tRNA?   27. What are the two stages of protein synthesis, and  in which stage are proteins actually synthesized?  What occurs in the other stage?    v@ Name the four major tissue types and their chief  subcategories. Explain how the four major tissue  types differ structurally and functionally.   # Give the chief locations of the various tissue types  in the body.    The human body, complex as it is, starts out as a sin-  gle cell, the fertilized egg, which divides almost end-  lessly. The trillions of cells that result become  specialized for particular functions. Some become  muscle cells, others the transparent lens of the eye,  still others skin cells, and so on. Thus, there is a divi-  sion of labor in the body.   Cell specialization carries with it certain hazards.  When a small group of cells is indispensable, its loss  can disable or even destroy the body. For example,  the action of the heart depends on a very specialized  cell group in the heart muscle that controls its con-  tractions. If those particular cells are damaged or  stop functioning, the heart will no longer work prop-  erly, and the whole body will suffer or die from lack  of oxygen.   Groups of cells that are similar in structure and  function are called tissues and represent the next  level of structural organization (look back at  Figure 1.1). The four primary tissue types—epithelial,  connective, nervous, and muscle tissues—interweave to  form the fabric of the body. If we had to assign a sin-  gle term to each primary tissue type that would best  describe its overall role, the terms would most likely  be covering (epithelium), support (connective), move-  ment (muscle), and control (nervous). However, these  terms reflect only a tiny fraction of the functions that  each of these tissues performs.    Tissues are organized into organs such as the  heart, kidneys, and lungs. Most organs contain sev-  eral tissue types, and the arrangement of the tissues  determines each organ’s structure and what it is  able to do. Thus, a study of tissues will be helpful  in your later study of the body’s organs and how  they work.   For now, we want to become familiar with the  major similarities and differences in the primary tis-  sues. Because epithelium and some types of connec-  tive tissue will not be considered again, they are  emphasized more in this section than are muscle,  nervous tissues, and bone (a connective tissue),  which we cover in more depth in later chapters.   A description of the various tissue types follows,  and a helpful summary of the major functions and  body locations of the four primary tissue types  appears later (look ahead to Figure 3.22 on p. 121).    Epithelial tissue, or epithelium (ep’i-the’le-um;  epithe = laid on, covering; plural epithelia), is the  lining, covering, and glandular tissue of the body.  Covering and lining epithelium covers all free body  surfaces, both inside and out, and contains versatile  cells. Because epithelium forms the boundaries that  separate us from the outside world, nearly all sub-  stances that the body gives off or receives must pass  through epithelium.   Epithelial functions include protection, absorption,  filtration, and secretion. For example, the epithelium  of the skin protects against bacterial and chemical  damage, and the epithelium lining the respiratory  tract has cilia, which sweep dust and other debris  away from the lungs. Epithelium specialized to  absorb substances lines some digestive system organs  such as the stomach and small intestine, which  absorb nutrients from food into the body. In the kid-  neys, epithelium both absorbs and filters.   Glandular epithelium forms various glands in  the body. Secretion is a specialty of the glands, which  produce such substances as sweat, oil, digestive en-  zymes, and mucus.    3.4a Hallmarks of Epithelium  Epithelium generally has the unique characteristics  listed below:  e Except for glandular epithelium (described on    form continuous sheets. Neighboring cells are  bound together at many points by specialized  cell junctions, including desmosomes and tight  junctions (see p. 85).   e The membranes always have one free (unat-  tached) surface or edge. This apical surface is  exposed to the body’s exterior or to the cavity  of an internal organ. The exposed surfaces of  some epithelia are slick and smooth, but others  exhibit cell surface modifications, such as micro-  villi or cilia.   e The anchored (basal) surface of epithelium  rests on a basement membrane, a structureless  material secreted by both the epithelial cells and  the connective tissue cells deep to the epithe-  lium. Think of the basement membrane as the  “glue” holding the epithelium in place.    e Epithelial tissues are avascular, meaning they  have no blood supply of their own and depend  on diffusion from the capillaries in the underly-  ing connective tissue for food and oxygen.    Each epithelium is given two names. The first indi-  cates the number of cell layers it has (Figure 3.17a).  The classifications by cell arrangement (layers) are  simple epithelium (one layer of cells) and strati-  fied epithelium (more than one cell layer). The sec-  ond describes the shape of its cells (Figure 3.17b).  There are squamous (skwa'mus) cells, flattened like  fish scales (squam = scale), cuboidal (ku-boi'dal)  cells, which are cube-shaped like dice, and colum-  nar cells, shaped like columns. The terms describing  the shape and arrangement are then combined to  describe the epithelium fully. Stratified epithelia are  named for the cells at the free surface of the epithelial  membrane, not those resting on the basement mem-  brane, which can appear “squished” and variable in  shape. Figure 3.17c shows the relationship between  the structure of these tissues and their functions, a  topic we will cover more as we look at each type.   The simple epithelia are most concerned with  absorption, secretion, and filtration. Because simple  epithelia are usually very thin, protection is not one  of their specialties.    Figure 3.17 Classification and functions of epithelia. (a) Classification on the  basis of arrangement (layers). (b) Classification on the basis of cell shape; for each  category, a whole cell is shown on the left, and a longitudinal section is shown on    Simple Squamous Epithelium Simple squamous  epithelium is a single layer of thin squamous cells  resting on a basement membrane. The cells fit closely  together, much like floor tiles. This type of epithe-  lium usually forms membranes where filtration or  exchange of substances by rapid diffusion occurs.  Simple squamous epithelium is in the air sacs of the  lungs (called alveoli), where oxygen and carbon  dioxide are exchanged (Figure 3.18a), and it forms  the walls of capillaries, where nutrients and gases  pass between the blood in the capillaries and the  interstitial fluid. Simple squamous epithelium also  forms serous membranes, or serosae (se-ro’se),  the slick membranes that line the ventral body cavity  and cover the organs in that cavity. (We describe the  serous membranes in more detail in Chapter 4.)    Simple Cuboidal Epithelium Simple cuboidal  epithelium, which is one layer of cuboidal cells rest-  ing on a basement membrane, is common in glands  and their associated small tubes called ducts (for  example, the salivary glands and pancreas). It also  forms the walls of the kidney tubules (Figure 3.18b)  and covers the surface of the ovaries.    Simple Columnar Epithelium Simple columnar  epithelium is made up of a single layer of tall cells  that fit closely together and whose nuclei appear to  form a straight line. Goblet cells, which produce a  lubricating mucus, are often seen in this type of epi-  thelium. Simple columnar epithelium lines the  entire length of the digestive tract from the stomach    to the anus (Figure 3.18c). Epithelial membranes  that line body cavities open to the body exterior  are called mucosae (mu-ko’se), or mucous  membranes.    Pseudostratified Columnar Epithelium All of  the cells of pseudostratified (soo’do-stra’ti-fid)  columnar epithelium rest on a basement mem-  brane. However, some of its cells are shorter than  others, and their nuclei appear at different heights  above the basement membrane. As a result, this epi-  thelium gives the false (pseudo) impression that it is  stratified; hence its name. Like simple columnar epi-  thelium, this variety mainly functions in absorption  and secretion. A ciliated variety (more precisely  called pseudostratified ciliated columnar epithelium)  lines most of the respiratory tract (Figure 3.18d). The  mucus produced by the goblet cells in this epithe-  lium acts as a “sticky trap” to catch dust and other  debris, and the cilia propel the mucus upward and  away from the lungs.    Stratified epithelia consist of two or more cell lay-  ers. Being considerably more durable than the sim-  ple epithelia, these epithelia function primarily in  protection.    Stratified Squamous Epithelium Stratified  squamous epithelium is the most common strati-  fied epithelium in the body. It usually consists of  many cell layers. The cells at the free edge are    Basement : -  membrane Photomicrograph: Simple squamous  epithelium forming part of the alveolar  (a) Diagram: Simple squamous (air sac) walls (275x).    Simple  cuboidal  epithelial  cells  Nucleus of  simple i Basement  cuboida membrane  epithelial  pell Connective  ti  Basement ae  membrane  Photomicrograph: Simple cuboidal  epithelium in kidney tubules (250x).  Mucus of a  Nuclei of simple goblet cell    Figure 3.18 Types of epithelia and examples of common  locations in the body. (Figure continues on page 112.)    Photomicrograph: Transitional epithelium lining of the  bladder, relaxed state (270x); surface rounded cells  flatten and elongate when the bladder fills with urine.    squamous cells, whereas those close to the basement  membrane are cuboidal or columnar. Stratified squa-  mous epithelium is found in sites that receive a good  deal of abuse or friction, such as the surface of the  skin, the mouth, and the esophagus (Figure 3.18e).    Stratified Cuboidal and Stratified Columnar  Epithelia Stratified cuboidal epithelium typi-  cally has just two cell layers with (at least) the surface  cells being cuboidal in shape. The surface cells of  stratified columnar epithelium are columnar cells,  but its basal cells vary in size and shape. Both  of these epithelia are fairly rare in the body, found  mainly in the ducts of large glands. (Because the dis-  tribution of these two epithelia is extremely limited,  they are not illustrated in Figure 3.18. We mention  them here only to provide a complete listing of the  epithelial tissues.)    Transitional Epithelium Transitional epithe-  lium is a highly modified, stratified squamous epi-  thelium that forms the lining of only a few  organs—the urinary bladder, the ureters, and part of  the urethra. As part of the urinary system, all of these  organs are subject to considerable stretching  (Figure 3.18f). Cells of the basal layer are cuboidal or  columnar; those at the free surface vary in appear-  ance. When the organ is not stretched, the mem-  brane is many-layered, and the superficial cells are  rounded and domelike. When the organ is distended  with urine, the epithelium thins like a rubber band  being stretched, and the surface cells flatten and  become squamouslike. This ability of transitional  cells to slide past one another and change their  shape (undergo “transitions” ) allows the ureter wall  to stretch as a greater volume of urine flows through  that tubelike organ. In the bladder, the ability of  transitional epithelium to stretch allows more urine  to be stored without increasing pressure in the  bladder.    A gland consists of one or more cells that make  and secrete a particular product. This product, a  secretion, typically contains protein molecules in  an aqueous (water-based) fluid. The term secretion  also indicates an active process in which the glandu-  lar cells obtain needed materials from the blood and  use them to make their products, which they then  discharge by exocytosis.    Two major types of glands develop from epithe-  lial sheets: endocrine and exocrine. Endocrine  (en'do-krin) glands lose their ducts; thus they are  often called ductless glands. Their secretions (all  hormones) diffuse directly into the blood vessels  that weave through the glands. Examples of endo-  crine glands include the thyroid, adrenals, and  pituitary.   Exocrine (ek’so-krin) glands retain their ducts,  and their secretions exit through the ducts to the  epithelial surface. Exocrine glands, which include  the sweat and oil glands, liver, and pancreas, are  both internal and external. We discuss them with  the organ systems to which their products are  related.   29. How do endocrine and exocrine glands differ in  structure and function?   30. Which of the following properties apply to  epithelial tissues: has blood vessels; can repair  itself; cells have specialized cell junctions?    Connective tissue, as its name suggests, connects  body parts. It is found everywhere in the body. It is  the most abundant and widely distributed of the tis-  sue types. Connective tissues perform many func-  tions, but they are primarily involved in protecting,  supporting, cushioning, and insulating other body  tissues.    e Variations in blood supply. Many connective  tissues are well vascularized (that is, they have a  good blood supply), but there are exceptions.  Tendons and ligaments, for example, have a  poor blood supply, and cartilages are avascular.  Consequently, all these structures heal very  slowly when injured. (This is why some people  say that, given a choice, they would rather have a  broken bone than a torn ligament.)    e Extracellular matrix. Connective tissues are  made up of many different types of cells plus  varying amounts of a nonliving substance found  outside the cells, called the extracellular matrix.    The extracellular matrix deserves a bit more expla-  nation because it is what makes connective tissue so  different from the other tissue types. The matrix,  which is produced by the connective tissue cells and  then secreted to their exterior, has two main ele-  ments, a structureless ground substance and fibers.  The ground substance of the matrix is composed  largely of water plus some cell adhesion proteins  and large, charged polysaccharide molecules. The  cell adhesion proteins serve as a glue that allows  the connective tissue cells to attach themselves to  the matrix fibers embedded in the ground sub-  stance. The charged polysaccharide molecules trap  water as they intertwine. As these polysaccharides  become more abundant, they cause the matrix to  vary from fluid to gel-like to firm in its consistency.   Depending on the connective tissue type, various  types and amounts of fibers contribute to the matrix.  These include collagen fibers distinguished by their  high tensile strength; elastic fibers, which have the  ability to stretch and recoil; and reticular fibers,  which are fine collagen fibers that form the internal  “skeleton” of soft organs such as the spleen. The  building blocks, or monomers, of these fibers are made  by the connective tissue cells and secreted into the  ground substance in the extracellular space, where  they join together to form the various fiber types.   Because of the variations in extracellular matrix,  connective tissues are able to form soft packing tis-  sues around other organs, to bear weight, and to  withstand stretching and other abuses, such as abra-  sion, that no other tissue could endure.    As noted previously, all connective tissues con-  sist of living cells surrounded by extracellular  matrix. Their major differences reflect specific cell  types, fiber types, and the number of fibers in the  matrix. At one extreme, bone and cartilage have  very few cells and large amounts of hard matrix,  which makes them extremely strong. At the oppo-  site extreme, fat tissue is composed mostly of cells,  and the matrix is soft. From most rigid to softest or  most fluid, the major connective tissue classes are  bone, cartilage, dense connective tissue, loose connective    tissue, and blood. Find the various types of connec-  tive tissues in Figure 3.19 as you read the following  descriptions.    Bone, sometimes called osseous (os’e-us) tissue, is  composed of osteocytes (os'te-o-sitz; bone cells) sit-  ting in cavities called lacunae (lah-ku'ne; “pits”).  These pits are surrounded by layers of a very hard  matrix that contains calcium salts in addition to  large numbers of collagen fibers (Figure 3.19a).  Because of its rocklike hardness, bone has an excep-  tional ability to protect and support other body  organs (for example, the skull protects the brain).  (We consider bone in detail in Chapter 5.)    Cartilage is less hard and more flexible than bone.  Its major cell type is chondrocytes (cartilage cells). It  is found in only a few places in the body. Most wide-  spread is hyaline (hi’ah-lin) cartilage, which has  abundant collagen fibers hidden by a rubbery matrix  with a glassy (hyalin = glass), blue-white appearance  (Figure 3.19b). It forms the trachea, or windpipe,  attaches the ribs to the breastbone, and covers bone  ends at joints. The skeleton of a fetus is made largely  of hyaline cartilage; but by the time the baby is born,  most of that cartilage has been replaced by bone. The  exceptions include the epiphyseal, or growth, plates in  long bones, which allow the bones to grow in length.   Although hyaline cartilage is the most abundant  type of cartilage in the body, there are others. Highly  compressible fibrocartilage forms the cushionlike  disks between the vertebrae of the spinal column  (Figure 3.19c). Elastic cartilage is found in struc-  tures with elasticity, such as the external ear. (Elastic  cartilage is not illustrated in Figure 3.19.)    In dense connective tissue, also called dense  regular fibrous tissue, collagen fibers are the main  matrix element (Figure 3.19d). Crowded between the  collagen fibers are rows of fibroblasts (fiber-forming  cells) that manufacture the building blocks of the  fibers. Dense regular connective tissue forms strong,  ropelike structures such as tendons and ligaments  that withstand tension in one direction. Tendons  attach skeletal muscles to bones; ligaments connect  bones to bones at joints. Ligaments are more stretchy  and contain more elastic fibers than do tendons.  Another dense connective tissue, dense irregular    Lacunae  (a) Diagram: Bone Photomicrograph: Cross-sectional view  of bone (165x).  Chondrocyte  (cartilage cell)  Chondrocyte  in lacuna  Lacunae Matrix  (b) Diagram: Hyaline cartilage Photomicrograph: Hyaline cartilage  from the trachea (400x).  Chondrocytes  in lacunae    Figure 3.19 Connective tissues and their common body locations. (Figure continues on page 116.)    fibers  Collagen  fibers  . L = — 3 Nuclei of  Nuclei of n n ~ fibroblasts  fibroblasts —  (d) Diagram: Dense regular Photomicrograph: Dense regular fibrous  fibrous connective tissue from a tendon (475x).  Mucosal  epithelium  Lamina Elastic  propria fibers  Collagen  fibers  Elastic Fibroblast  fibers of nuclei  matrix  Nuclei of  fibroblasts  Collagen  fibers `  (e) Diagram: Areolar Photomicrograph: Areolar connective tissue, a    (f) Diagram: Adipose Photomicrograph: Adipose tissue from the  subcutaneous layer beneath the skin (570x).    Figure 3.19 (continued) Connective tissues and their common body locations.  (e) and (f) are subclasses of loose connective tissues.    Figure 3.19 (continued) (g) is a subclass of loose connective tissue.    connective tissue, makes up the lower layers of the  skin (dermis), where it is arranged in sheets and  withstands tension in many directions (not shown).    Relatively speaking, loose connective tissues are  softer and have more cells and fewer fibers than any  other connective tissue type except blood. There are  three main types of loose connective tissue: areolar,  adipose, and reticular.    Areolar Connective Tissue Areolar (ah-re'o-lar)  connective tissue, the most widely distributed    connective tissue variety in the body, is a soft, pli-  able, “cobwebby” tissue that cushions and protects  the body organs it wraps (Figure 3.19e). It functions  as a universal packing tissue and connective tissue  “glue” because it helps to hold the internal organs  together and in their proper positions. A soft layer of  areolar connective tissue called the lamina propria  (l4'mï-nah pro'pre-ah) underlies all mucous mem-  branes. Its fluid matrix contains all types of fibers,  which form a loose network. In fact, when viewed  through a microscope, most of the matrix appears to  be empty space, which explains the name of this tis-  sue type (areola = small open space). Because of its    loose and fluid nature, areolar connective tissue pro-  vides a reservoir of water and salts for the surround-  ing tissues, and essentially all body cells obtain their  nutrients from and release their wastes into this “tis-  sue fluid.” When a body region is inflamed, the local  areolar tissue soaks up the excess fluid like a sponge,  and the area swells and becomes puffy, a condition  called edema (eh-de’mah). Many types of phago-  cytes wander through this tissue, scavenging for bac-  teria, dead cells, and other debris, which they destroy.    Adipose Connective Tissue Adipose (ad'i-pos)  tissue is commonly called fat. Basically, it is an are-  olar tissue in which adipose (fat) cells predominate  (Figure 3.19f). A glistening droplet of oil occupies  most of a fat cell’s volume and compresses the  nucleus, displacing it to one side.   Adipose tissue forms the subcutaneous tissue  beneath the skin, where it insulates the body and  protects it from bumps and extremes of both heat  and cold. Adipose tissue also protects some organs  individually—the kidneys are surrounded by a cap-  sule of fat, and adipose tissue cushions the eyeballs  in their sockets. There are also fat “depots” in the  body, such as the hips, breasts, and belly, where fat is  stored and available for fuel if needed.    Reticular Connective Tissue Reticular connec-  tive tissue consists of a delicate network of interwo-  ven reticular fibers associated with reticular cells,  which resemble fibroblasts (Figure 3.19g). Reticular  tissue is limited to certain sites: It forms the stroma  (literally, “bed” or “mattress”), or internal frame-  work of an organ. The stroma can support many free  blood cells (largely white blood cells called lympho-  cytes) in lymphoid organs such as lymph nodes, the  spleen, and bone marrow. It may help to think of  reticular tissue as “cellular bleachers” where other  cells can observe their surroundings.    Blood, or vascular tissue, is considered a connective  tissue because it consists of blood cells surrounded  by a nonliving, fluid matrix called blood plasma  (Figure 3.19h). The “fibers” of blood are soluble pro-  teins that become visible only during blood clotting.  Still, blood is quite atypical as connective tissues  go. Blood is the transport vehicle for the cardiovas-  cular system, carrying nutrients, wastes, respiratory  gases, white blood cells, and many other substances  throughout the body. (We consider blood in detail  in Chapter 10.)    32. What are the two hallmarks of connective tissue?  33. Which fiber type contributes strength to connec-  tive tissues?  For answers, see Appendix A.    Muscle tissues are highly specialized to contract, or  shorten, which generates the force required to pro-  duce movement. In order to contract, muscle must  also be irritable, that is, able to respond to stim-  uli. There are three types of muscle tissue: skeletal,  cardiac, and smooth (Figure 3.20). Notice their sim-  ilarities and differences as you read through the fol-  lowing descriptions.    Skeletal muscle tissue is packaged by connective  tissue sheets into organs called skeletal muscles, which  are attached to the skeleton. These muscles, which  can be controlled voluntarily (or consciously), form  the flesh of the body, the so-called muscular sys-  tem (see Chapter 6). When the skeletal muscles con-  tract, they pull on bones or skin. As a result, gross  body movements or changes in our facial expres-  sions occur.   The cells of skeletal muscle are long, cylindrical,  and multinucleate, and they have obvious striations  (stripes). Because skeletal muscle cells are elongated  to provide a long axis for contraction, they are often  called muscle fibers.    Cardiac muscle (covered in more detail in Chapter 11)  is found only in the heart wall. As it contracts, the heart  acts as a pump to propel blood through the blood ves-  sels. Like skeletal muscle, cardiac muscle has striations,  but cardiac cells have only a single nucleus and are rel-  atively short, branching cells that fit tightly together  (like clasped fingers) at junctions called intercalated  discs. These intercalated discs contain gap junctions  that allow ions to pass freely from cell to cell. This ties  the cardiac cells into a functional syncytium (syn =  together, cyt = cell), resulting in rapid conduction of  the electrical signal to contract across the heart. Cardiac  muscle is under involuntary control, which means that  we cannot consciously control the activity of the heart.  Can you imagine having to “tell” your heart to beat  like you “tell” your legs to walk?    > a SS Multiple nuclei  Mi per fiber  omy) ` Wit  Part of muscle  fiber  (a) Diagram: Skeletal muscle Photomicrograph: Skeletal muscle (195).  Intercalated  discs  Nucleus  (b) Diagram: Cardiac muscle Photomicrograph: Cardiac muscle (475X).    Figure 3.20 Types of muscle tissue and their common locations in the body.    Figure 3.21 Nervous tissue. Neurons and supporting cells form the brain, spinal    Smooth (visceral) muscle is so called because no  striations are visible. The individual cells have a sin-  gle nucleus and are tapered at both ends. Smooth  muscle is found in the walls of hollow organs  such as the stomach, uterus, and blood vessels. As  smooth muscle in its walls contracts, the cavity of  an organ alternately becomes smaller (constricts  when smooth muscle contracts) or enlarges (dilates  when smooth muscle relaxes) so that substances are  mixed and/or propelled through the organ along  a specific pathway. Contractions of smooth mus-  cle are longer and slower than the other two muscle  types. Peristalsis (per’I-stal’sis), a wavelike motion  that keeps food moving through the small intestine,  is typical of its activity.    When we think of nervous tissue, we think of cells  called neurons. All neurons receive and send elec-  trochemical impulses from one part of the body to  another; thus, irritability and conductivity are their  two major functional characteristics. The structure  of neurons is unique (Figure 3.21). Their cytoplasm  is drawn out into long processes (extensions), as    long as 3 feet or more in the leg, which allows a sin-  gle neuron to conduct an impulse to distant body  locations.   However, the nervous system is more than just  neurons. A special group of supporting cells called  neuroglia insulate, support, and protect the delicate  neurons in the structures of the nervous system—the  brain, spinal cord, and nerves. (We consider nervous  tissue in detail in Chapter 7.)   Figure 3.22 summarizes the tissue types, includ-  ing their hallmarks and functions in the body.    The body has many techniques for protecting itself  from uninvited guests or injury. Intact physical bar-  riers such as the skin and mucous membranes, cilia,  and the strong acid produced by stomach glands are  just a few examples of body defenses exerted at the tis-  sue level. When tissue injury does occur, it stimulates  the body’s inflammatory and immune responses,  and the healing process begins almost immediately.  Inflammation is a general (nonspecific) body response  that attempts to prevent further injury. The immune  response, in contrast, is extremely specific and mounts    Nervous tissue: Internal communication and control  Hallmarks: irritable, conductive  e Brain, spinal cord, and nerves    Epithelial tissue: Forms boundaries between different  environments, covers and lines structures, protects,  secretes, absorbs, filters    Figure 3.22 Summary of the major functions, characteristics, and body  locations of the four tissue types: epithelial, connective, muscle, and    a vigorous attack against recognized invaders, includ-  ing bacteria, viruses, and toxins. (We consider these  protective responses in detail in Chapter 12.) Here we  will concentrate on the process of tissue repair itself.  Tissue repair, or wound healing, occurs in two  major ways: by regeneration and by fibrosis.  Regeneration is the replacement of destroyed tissue  by the same kind of cells, whereas fibrosis involves  repair by dense (fibrous) connective tissue, that is, by  the formation of scar tissue. Which occurs depends    on (1) the type of tissue damaged and (2) the  severity of the injury. Generally speaking, clean cuts  (incisions) heal much more successfully than ragged  tears of the tissue.  Tissue injury sets the following series of events  into motion:  e Inflammation sets the stage. Injured tissue  cells and others release inflammatory chemicals  that make the capillaries very permeable. This    allows fluid rich in clotting proteins and other  substances to seep into the injured area from the  bloodstream. The leaked clotting proteins con-  struct a clot, which “plugs the hole” to stop  blood loss and hold the edges of the wound  together. The injured area becomes walled off,  preventing bacteria or other harmful substances  from spreading to surrounding tissues. Where  the clot is exposed to air, it quickly dries and  hardens, forming a scab.    e Granulation tissue forms. Granulation tissue is  delicate pink tissue composed largely of new  capillaries that grow into the damaged area from  undamaged blood vessels nearby. These capillar-  ies are fragile and bleed freely, as when a scab is  picked away from a skin wound. Granulation  tissue also contains phagocytes, which eventu-  ally dispose of the blood clot, and connective  tissue cells (fibroblasts), which produce the  building blocks of collagen fibers (scar tissue) to  permanently bridge the gap.    e Regeneration and fibrosis effect permanent  repair. As the surface epithelium begins to regen-  erate, it makes its way between the granulation tis-  sue and the scab. The scab soon detaches, and the  final result is a fully regenerated surface epithe-  lium that covers an underlying area of fibrosis (the  scar). The scar is composed of dense connective  tissue and is invisible, or visible as a thin white  line, depending on the severity of the wound.    The ability of the different tissue types to regen-  erate varies widely. Epithelial tissues such as the skin  epidermis and mucous membranes regenerate beau-  tifully. So, too, do most of the fibrous connective tis-  sues and bone. Skeletal muscle regenerates poorly,  and cardiac muscle and nervous tissue within the    brain and spinal cord are replaced largely by scar tis-  sue. If wounds are deep or very large, damaged tis-  sues may be completely replaced by scar tissue.    Scar tissue is strong, but it lacks the flexibility of  most normal tissues. Perhaps even more important  is its inability to perform the normal functions of the  tissue it replaces. Thus, if scar tissue forms in the wall  of the bladder, heart, or another muscular organ, it  may severely hamper the functioning of that organ.  A contracture is a permanent tightening of the  skin affecting the underlying tendons or muscles.  Contractures develop during the healing process as  inelastic fibrous tissue replaces the normal elastic con-  nective tissues. Because fibrous tissue resists stretch-  ing, movement of the affected area may be limited.    Besides the tissue changes associated with repair or  scar formation, other modifications of cells and tissues  may occur at any time. For example, when cells fail to  honor normal controls on cell division and multiply  wildly, an abnormal mass of proliferating cells, known  as a neoplasm (ne’o-plazm”; “new growth”), results.  Neoplasms may be benign or malignant (cancerous).  (See “A Closer Look”.)   However, not all increases in cell number involve  neoplasms. Certain body tissues (or organs) may  enlarge because there is some local irritant or condi-  tion that stimulates the cells. This response is called  hyperplasia (hi’per-pla’ze-ah). For example, a wom-  an’s breasts enlarge during pregnancy in response to  increased hormones; this is a normal but temporary  situation that doesn’t have to be treated. In contrast,  atrophy (at’ro-fe), or decrease in size, can occur in  an organ or body area that loses its normal stimula-  tion. For example, the muscles of a broken leg atro-  phy while in a cast during the healing period.    34. Which muscle type(s) is(are) injured when you pull  a muscle while exercising?  35. How does the extended length of a neuron’s  processes aid its function in the body?  36. Nervous tissue is irritable. What does this mean?  37. Which tissue type is the basis for scar tissue?  38. What cellular error allows a neoplasm to form?  For answers, see Appendix A.    Learn more at Mastering A&P > Study Area >  Additional Study Tools > A Closer Look   malfunction, an abnormal cell  mass called a neoplasm (“new  growth”) or tumor develops. Not all  neoplasms are cancerous. Benign  (be-nin’; “kindly”) neoplasms are usu-  ally surrounded by a capsule, grow  slowly, and seldom kill their hosts. In  contrast, malignant (“bad”) neo-  plasms (cancers) are not encapsulated.  They grow more relentlessly and may  become killers. Normal cells die when  they lose contact with the surrounding  matrix, but malignant cells tend to  break away from the parent mass and  spread via the blood to distant parts  of the body. The formation of new  masses at other body sites is called  metastasis (mé-tas’td-sis).   What causes transformation—the  changes that convert a normal cell into  a cancerous one? Radiation, mechanical  trauma, certain viral infections, and  many chemicals (tobacco tars, organic  solvents such as mineral spirits) can all  act as carcinogens (cancer-causers).  What all of these factors have in com-  mon is that they cause mutations—  changes in DNA that alter the  expression of certain genes. Transforma-  tion requires several genetic changes.   Proto-oncogenes code for proteins  that are needed for normal cell division  and growth. However, many have frag-  ile sites that break when they are  exposed to carcinogens, which converts  them into oncogenes. Another group of  genes, the tumor-suppressor genes  (such as p53 and p76) put the “brakes”  on cell division, so inactivation of these  genes leads to uncontrolled growth,  allowing oncogenes to “do their thing.”   Consider colorectal cancer (see the  figure). One of its first signs is a polyp (a  small, benign growth of apparently nor-    mal mucosa cells. As cell division con-  tinues, the polyp enlarges and may  become a malignant neoplasm. In most  cases, these changes parallel cellular  changes at the DNA level and include  the activation of oncogenes and the  inactivation of tumor-suppressor genes.  The seeds of cancer appear to be in our  own genes—an intimate enemy indeed.  Screening procedures aid early  detection. Unfortunately, most cancers  are diagnosed after symptoms have  already appeared. Increasingly, diagno-  sis includes genetic or chemical analy-  sis of tissue samples to determine  which genes are switched on or off,  and which drugs may be most effec-  tive. MRI and CT scans can detect large  cancers or the degree of metastasis.  Most neoplasms are removed surgi-  cally if possible. Radiation and drugs  (chemotherapy) may also be used.  Current cancer treatments—" cut,  burn, and poison”—are recognized as  crude and painful. Promising new  treatments include:  e Delivering radiation or antican-  cer drugs precisely to the cancer.  e Strengthening the immune sys-  tem by using “hand-picked”  immune cells from the patient.   e Testing the tumor for genetic  markers to customize treatment  plans.    e Tumors are the result of uncon-  trolled cell growth and can be  benign or malignant. Malignant  tumors are cancerous and can  spread, or metastasize, to other  areas of the body.    e Tumor-suppressor genes  turned off by exposure to DNA-  damaging agents no longer  regulate cell division, and un-  controlled growth results.    e Oncogenes turned on by expo-  sure to DNA-damaging agents,  such as carcinogens, allow  uncontrolled growth and metas-  tasis to occur.    e Cell theory says:  o Cells are the structural and functional unit of life  ° An organism’s activities depend on its cells’  activities  ° A cell's structure determines its function (prin-  ciple of complementarity)    e Four most common elements in a cell: carbon,  hydrogen, oxygen, and nitrogen    ° Living matter is over 60 percent water  ° Protein is the major building material in a cell  o Cells vary in shape and size    e The membrane is a phospholipid bilayer contain-  ing proteins, sugars, and cholesterol    o Membrane proteins can act as enzymes, trans-  port proteins, channel proteins; serve as recep-  tors for hormones and other cell-to-cell  communication molecules    ° Special membrane junctions: microvilli  (increase surface area) and cell junctions  (desmosomes— anchor; tight junctions—  seal the membrane; gap junctions—  communication)    3.2c. Cytoplasm contains cytosol, inclusions,  stored or inactive materials in the cytoplasm (fat  globules, water vacuoles, crystals), and organelles    e Major organelles and their functions include mito-  chondria (ATP synthesis), ribosomes (protein  synthesis), endoplasmic reticulum (tunnel sys-  tem involved in fat and protein synthesis), Golgi  apparatus (modifies and packages proteins for  export), lysosomes (intracellular digestion), per-    i» Listen to the story of this chapter in a brief summary at Mastering A&P >  pt Study Area > Author Narrated Audio Summaries    oxisomes (detoxify free radicals), cytoskeleton  (cellular support and motion), centrioles (cell  division and form the bases of cilia and flagella)    e Cilia project from the cell surface and aid in mov-  ing substances (for example, mucus) across the cell  surface; composed of microtubules    e Flagella are longer projections made of microtu-  bules that propel the cell    e Microvilli, structures to increase surface area, are  composed of actin filaments    e Cells differ in their sizes, shapes, and number of  organelles; structure determines function    e All cells respond to stimuli (irritable), digest foods,  excrete wastes, and are able to grow, move, and  metabolize; most can reproduce by mitosis    ° Diffusion is the movement of a substance from  higher concentration to an area of lower concen-  tration due to the kinetic energy of the mole-  cules themselves  = Diffusion of dissolved solutes through the  plasma membrane is simple diffusion   = Diffusion of water across the plasma mem-  brane is osmosis   = Diffusion that requires a protein channel or  carrier is facilitated diffusion   = Filtration is passive transport that requires a  pressure gradient across a membrane    e Active transport requires both ATP and a carrier  protein and can move items against their gradient    o Vesicular transport includes endocytosis and  exocytosis, the movement of bulk substances  into or out of the cell, respectively    3.3b. Cell division—two phases: mitosis (division  of the nucleus) and cytokinesis (division of the  cytoplasm); provides cells for growth and repair    e Mitosis—four phases: prophase, metaphase,  anaphase, and telophase; results in two daugh-  ter nuclei that are identical to the mother nucleus    e Cytokinesis overlaps anaphase and telophase,  progressively pinches cytoplasm and cell mem-  brane in half    o Cytokinesis does not always occur; in such cases,  binucleate or multinucleate cells result    e Genes (DNA) carry instructions for building pro-  teins; each three-base sequence (triplet) encodes  one amino acid    e Messenger RNA (mRNA) carries the DNA  instructions for protein synthesis to the ribosome,  transfer RNA (tRNA) transports amino acids to  the ribosome, ribosomal RNA (rRNA) forms  part of the ribosomal structure    o mRNA—three base-pair codons are read by the  ribosome; tRNA has anticodons; codons and  anticodons temporarily bind to ensure that the  correct amino acid is added in the correct posi-  tion in growing protein    3.4b. Classification of epithelia—named according  to number of layers (simple epithelium, stratified  epithelium) and cell shape (squamous, cuboidal,  columnar)    e Types of epithelium: simple squamous epithe-  lium, simple cuboidal epithelium, simple  columnar epithelium, pseudostratified colum-  nar epithelium, stratified squamous epithe-  lium, stratified cuboidal epithelium, stratified  columnar epithelium, transitional epithelium,  glandular epithelium    outside cells that secrete it (ground substance plus  fibers); varies in amount and consistency    3.5c. Types of connective tissue: bone, cartilage  (hyaline cartilage, elastic cartilage,  fibrocartilage), dense regular fibrous tissue  (ligaments and tendons), dense irregular fibrous  tissue (dermis), loose connective tissue (areolar  connective tissue, adipose tissue, reticular  connective tissue), blood    e Neurons are irritable and conductive, and they are  specialized to receive and transmit nerve impulses;  neuroglia (support cells)    e Make up the fast control center of the body;  found in brain, nerves, and spinal cord    e Wound healing: regeneration, fibrosis, or both  ° Regeneration—injured tissue is replaced by same  type of cells  ° Fibrosis—wound is repaired with scar tissue    ° Epithelium, connective tissues regenerate well;  cardiac muscle and nervous tissue are repaired  by fibrosis    e Neoplasms—abnormal cell growths (benign or  cancerous); result from lack of control of cell  division    1. Which of the following would you expect to find in or  on cells whose main function is absorption?    2. Which of the following cell types would not have  tight junctions, desmosomes, or connexons?    3. Which element of the plasma membrane contributes  to its hydrophobic characteristics?    a. Polar heads of phospholipid molecules  b. Nonpolar tails of phospholipid molecules    A cell stimulated to increase its steroid production  will have abundant    In which of the following tissue types might you  expect to find goblet cells?   a. Simple cuboidal d. Stratified squamous  b. Simple columnar e. Transitional   What kind of connective tissue acts as a sponge, soak-  ing up fluid when edema occurs?   What type of connective tissue prevents muscles from  pulling away from bones during contraction?   b. Areolar d. Hyaline cartilage  Which of the following is (are) not true of skeletal  muscles?    Short Answer Essay 15.  13. Although cells have differences that reflect their spe-  cial functions in the body, what functional abilities 16.  do all cells exhibit?  14. Describe the four structural components of the 17.    Name the cellular organelles, and explain the func-  tion of each.    Describe the relative roles of DNA and RNA in pro-  tein synthesis.    Describe the general characteristics of epithelial tis-  sue. List the most important functions of epithelial  tissues, and give examples of each.    What are the general structural characteristics of con-  nective tissues? What are the functions of connective  tissues? How are their functions reflected in their  structures?    Tell where each of the three types of muscle tissue  would be found in the body. What is meant by the  statement, “Smooth muscles are involuntary in  action”?    thicker and thicker from years of continual irritation.  Michael’s dentist noticed his greatly thickened lip,  then told him to have it checked to see if the thicken-  ing was a tumor. A biopsy revealed hyperplasia, but  no evidence of neoplasia. What do these terms mean?  Did Michael have cancer of the mouth?    Think carefully about the chemistry of the plasma  membrane, and then answer this question: Why is  minor damage to the membrane usually not a  problem?    Lisa, an elderly lady, is overweight and has a sedentary  lifestyle. She has recently developed puffy ankles.  What is this condition called, and how do you think  this has developed?    The integument f  includes body membranes, 4  skin, hair, fingernails, and    The skin is the first  barrier to keep good things  such as water in, and bad things  such as harmful bacteria out.   cating) sheets around organs. They fall into  two major groups: (1) epithelial membranes, which  include the cutaneous, mucous, and serous mem-  branes; and (2) connective tissue membranes, repre-  sented by synovial membranes. The cutaneous  membrane, generally called the skin or integumentary  system, is the outer covering that we all rely on for  protection. In this chapter, the skin will receive most  of our attention, but first we will consider the other  body membranes.    The skin has  multiple layers that protect the  body, help regulate body  temperature, and help excrete  wastes via sweat.    1# List the general functions of each membrane  type—cutaneous, mucous, serous, and synovial—  and give its location in the body.    vz Compare the structure (tissue makeup) of the  major membrane types.    The two major categories of body membranes—  epithelial and connective tissue—are classified ac-  cording to their tissue makeup.   The epithelial membranes, also called covering and  lining membranes, include the cutaneous membrane  (skin), the mucous membranes, and the serous mem-  branes (Figure 4.1, p. 130). However, calling these  membranes “epithelial” is misleading because it is  not the whole story. Although they all do contain an  epithelial layer, it is always combined with an under-  lying layer of connective tissue. Hence these mem-  branes are actually simple organs. Because we will  discuss the skin in detail shortly, we will list it here  solely as a subcategory of the epithelial membranes.    The cutaneous (ku-ta’ne-us) membrane is com-  posed of two layers, the superficial epidermis and the  underlying dermis. The epidermis is composed of  stratified squamous epithelium, whereas the dermis  is mostly dense irregular (fibrous) connective tissue.  Unlike other epithelial membranes, the cutaneous  membrane is exposed to air and is a dry membrane  (Figure 4.1a).    A mucous (myu’kus) membrane (mucosa) is  composed of epithelium (the type varies with the  site) resting on a loose (areolar) connective tissue  membrane called a lamina propria (Figure 4.1b). This  membrane type lines all body cavities that open to  the exterior, such as those of the hollow organs of  the respiratory, digestive, urinary, and reproductive  tracts. Notice that the term mucosa refers only to the  location of the epithelial membranes, not their cellu-  lar makeup, which varies. However, most mucosae  contain either stratified squamous epithelium (as  in the mouth and esophagus) or simple columnar  epithelium (as in the rest of the digestive tract). In  all cases, they are moist membranes that are almost  continuously bathed in secretions or, in the case of  the urinary mucosae, urine.   The epithelium of mucosae is often adapted for  absorption or secretion. Although many mucosae  secrete mucus, not all do. The mucosae of the respi-  ratory and digestive tracts secrete large amounts of  protective, lubricating mucus; that of the urinary  tract does not.   A serous membrane, or serosa, is composed of  a layer of simple squamous epithelium resting on  a thin layer of areolar connective tissue. In contrast    to mucous membranes, which line open body cav-  ities, serous membranes line compartments in the  ventral body cavity that are closed to the exterior.   Serous membranes occur in pairs (Figure 4.1c).  The parietal (pah-ri’é-tal: parie = wall) layer lines a  specific portion of the wall of the ventral body cavity.  It folds in on itself to form the visceral (vis'er-al)  layer, which covers the outside of the organ(s) in that  cavity.   You can visualize the relationship between the  serosal layers by pushing your fist into a limp bal-  loon only partially filled with air (Figure 4.1d). The  part of the balloon that clings to your fist can be  compared to the visceral serosa clinging to the  organ’s external surface. The outer wall of the bal-  loon represents the parietal serosa that lines the  walls of the cavity and that, unlike the balloon, is  never exposed but is always fused to the cavity wall.   In the body, the serous layers are separated not  by air but by a scanty amount of thin, clear fluid,  called serous fluid, which is secreted by both mem-  branes. Although there is a potential space between  the two membranes, they tend to lie very close to  each other. The lubricating serous fluid allows the  organs to slide easily across the cavity walls and one  another without friction or pain as they carry out  their routine functions. This is extremely important  when mobile organs such as the pumping heart and  expanding lungs are involved.   The specific names of the serous membranes  depend on their locations. The serosa lining the  abdominal cavity and covering its organs is the  peritoneum (per’i-to-ne’um). In the thorax, serous  membranes isolate the lungs and heart from one  another. The membranes surrounding the lungs are  the pleurae (ploo’re); those around the heart are the  pericardia (per’i-kar’de-ah).    4.1b Connective Tissue Membranes  Synovial (si-no've-al) membranes are composed  of loose areolar connective tissue and contain no epi-  thelial cells at all. These membranes line the fibrous  capsules surrounding joints (Figure 4.2, p. 131),  where they provide a smooth surface and secrete a  lubricating fluid. They also line small sacs of con-  nective tissue called bursae (ber’se) and the tubelike  tendon sheaths. Both of these structures cushion organs  moving against each other during muscle activity—  such as the movement of a tendon across a bone’s  surface. (Bursae and tendon sheaths will be discussed  in more detail in Chapter 5.)    (d) A fist thrust into a limp balloon demonstrates the relationship  between the parietal and visceral serous membrane layers.    1. How do the body locations of serous and mucous  membranes differ?   2. A scalpel penetrates the left lung and enters the  heart. Name the six serous membrane layers the  blade passes through as it moves from the body  surface into the heart.    4# List several important functions of the integumen-  tary system, and explain how these functions are  accomplished.    vz When provided with a model or diagram of the  skin, recognize and name the following skin  structures: epidermis, dermis (papillary and  reticular layers), hair and hair follicle, sebaceous  gland, and sweat gland.    vw Name the layers of the epidermis, and describe  the characteristics of each.    Would you be enticed by an advertisement for a  coat that is waterproof, stretchable, and washable;  that invisibly repairs small cuts, rips, and burns;  and that is guaranteed to last a lifetime with rea-  sonable care? Sounds too good to be true, but you  already have such a coat—your cutaneous mem-  brane, or skin.   Skin is absolutely essential because it maintains  your body’s boundary. It keeps water and other pre-  cious molecules in the body and keeps excess water  (and other things) out. (This is why you can swim  for hours without becoming waterlogged.)  Structurally, the skin is a marvel. It is pliable yet  tough, which allows it to take constant punishment  from external agents. Without our skin, we would  quickly fall prey to bacteria and perish from water  and heat loss.   The skin and its appendages (sweat and oil  glands, hair, and nails) are collectively called the  integumentary (in-teg’u-men’tuh-re) system. Let's  take a look at the structure and function of this often  underappreciated body system.   The integumentary system, also called the  integument (in-teg’u-ment), which simply means  “covering,” performs a variety of functions; most, but  not all, of which are protective (Table 4.1, p. 132).  It insulates and cushions the deeper body organs  and protects the entire body from mechanical dam-  age (bumps and cuts), chemical damage (such as  from acids and bases), thermal damage (heat and  cold), ultraviolet (UV) radiation (in sunlight),  and microbes. The uppermost layer of the skin is  hardened, to help prevent water loss from the body  surface.   The skin’s rich capillary network and sweat  glands (both controlled by the nervous system)  play an important role in regulating heat loss from  the body surface. The skin acts as a mini-excretory  system; urea, salts, and water are lost when we  sweat. The skin is also a chemical plant; it manufac-  tures several proteins important to immunity and  synthesizes vitamin D. (Modified cholesterol mole-  cules in the skin are converted to vitamin D by sun-  light.) The skin also produces acidic secretions,  called the acid mantle, that protect against bacterial  invasion.    and pain receptors, which alert the nervous system to possible damage. Fat  deep to skin cushions deeper structures.    thus inhibit microbes, such as bacteria and yeast). Phagocytes ingest foreign  substances and pathogens, preventing them from penetrating into deeper    body tissues.  e Ultraviolet (UV) radiation  (damaging effects of sunlight or  tanning beds)  e Thermal (heat or cold) damage  e Desiccation (drying out)    Heat loss: By activating sweat glands and by allowing blood to flush into skin  capillary beds so that heat can radiate from the skin surface.    Heat retention: By not allowing blood to flush into skin capillary beds.    Modified cholesterol molecules in skin converted to vitamin D in the    4. Explain the relationships between the words  skin, cutaneous membrane, integument, and  integumentary system.  5. What are three important functions of the  integumentary system?  For answers, see Appendix A.    As we mentioned, the skin is composed of two  kinds of tissue (Figure 4.3). The outer epidermis  (ep’i-der’ mis) is made up of stratified squamous epi-  thelium that is capable of becoming hard and tough.  The underlying dermis is made up mostly of dense  irregular connective tissue. The epidermis and der-  mis are firmly connected and the dermis is fairly tear  resistant. However, a burn or friction (such as the  rubbing of a poorly fitting shoe) may cause them to  separate, allowing interstitial fluid to accumulate in  the cavity between the layers, which results in a blister.   Deep to the dermis is the subcutaneous tissue,  or hypodermis, which essentially is adipose (fat)    tissue. It is not considered part of the skin, but it does  anchor the skin to underlying organs and provides a  site for nutrient storage. Subcutaneous tissue serves  as a shock absorber and insulates the deeper tissues  from extreme temperature changes occurring outside  the body. It is also responsible for the curves that are  more a part of a woman’s anatomy than a man’s.   Most cells of the epidermis are keratinocytes (ker-  atin cells), which produce keratin, the fibrous pro-  tein that makes the epidermis a tough protective  layer in a process called keratinization. These kerat-  inocytes are connected by desmosomes throughout  the epidermis (refer to Figure 3.3, p. 86).   Like all epithelial tissues, the epidermis is  avascular; that is, it has no blood supply of its own.  This explains why a man can shave daily and not  bleed even though he cuts off many cell layers each  time he shaves.   The epidermis is composed of up to five layers,  or strata (strah'tah), each with multiple layers of  cells. From the inside out these are the stratum basale,    Nervous structures  e Sensory nerve fiber  e Lamellar corpuscle  e Hair follicle receptor  (root hair plexus)    spinosum, granulosum, lucidum, and corneum, illus-  trated in (Figure 4.4, p. 134) (except the stratum  lucidum, which is found only in thick skin).   The deepest cell layer of the epidermis, the  stratum basale (stra’tum ba-sah'le), lies closest to  the dermis and is connected to it along a wavy bor-  der that resembles corrugated cardboard. This basal  layer contains the most adequately nourished of the  epidermal cells because nutrients diffusing from the  dermis reach them first. Stem cells in this layer are  constantly dividing, and millions of new cells are  produced daily; hence its alternate name, stratum ger-  minativum (jer"min-ah-tiv’um; “germinating layer”).  Of the new cells produced, some become epidermal  cells, and others maintain the population of stem  cells by continuing to divide. The daughter cells des-  tined to become epidermal cells are pushed upward,  away from the source of nutrition, to become part of  the epidermal layers closer to the skin surface. As  they move away from the dermis and become part of  the more superficial layers, the stratum spinosum    and then the stratum granulosum, they become  flatter and increasingly keratinized.   As these cells leave the stratum granulosum, they  die, forming the clear stratum lucidum (lu’sid-um).  This latter epidermal layer is not present in all skin  regions. It occurs only where the skin is hairless and  extra thick, that is, on the palms of the hands and  soles of the feet. The combination of accumulating  keratin inside them, secreting a water-repellent  glycolipid into the extracellular space, and their  increasing distance from the blood supply (in the  dermis) effectively dooms the stratum lucidum cells  and the more superficial epidermal cells because  they are unable to get adequate nutrients and  oxygen.   The outermost layer, the stratum corneum  (kor’ne-um), is 20 to 30 cell layers thick, but it  accounts for about three-quarters of the epidermal  thickness. The shinglelike dead cells, completely  filled with keratin, are referred to as cornified, or  horny, cells (cornu = horn). The common saying    Figure 4.4 The main structural  features of the epidermis.  Keratinocytes (tan), connected by  many desmosomes, form most of the    “Beauty is only skin deep” is especially interesting  in light of the fact that nearly everything we see  when we look at someone is dead! The abundance  of the tough keratin protein in the stratum cor-  neum allows that layer to provide a durable “over-  coat” for the body, which protects deeper cells  from the hostile external environment and from  water loss, and helps the body resist biological,  chemical, and physical assaults. The stratum cor-  neum rubs and flakes off slowly and steadily as  dandruff. The average person sheds about 18 kg  (40 lb) of these flakes in a lifetime, providing a  food source for the dust mites that inhabit our  homes and bed linens. This layer is replaced by  cells produced by the division of the deeper    epidermis. Melanocytes (gray) make  the pigment melanin, and star-  shaped epidermal dendritic cells  (blue) are protective immune cells.    Stratum corneum. Cells are dead, flat  membranous sacs filled with keratin.  Glycolipids in extracellular space make  skin water resistant.    Stratum spinosum. Cells contain thick  bundles of intermediate filaments made  of pre-keratin.    dividing; some newly formed cells  become part of the more superficial  layers.    Occasional Merkel cells (purple), each  associated with a nerve ending, act  as touch receptors. (Only part of the  stratum corneum is illustrated.)   Melanin (mel’ah-nin), a pigment that ranges in  color from yellow to brown to black, is produced by  special spider-shaped cells called melanocytes  (mel’ah-no-sitz), found chiefly in the stratum  basale. Freckles and moles are seen where melanin is  concentrated in one spot.   Scattered in the epidermis are epidermal  dendritic cells, which are important “sentries” that  alert and activate immune system cells to a threat  such as bacterial or viral invasion. Seen here and  there at the epidermal-dermal junction are Merkel  cells, which are associated with sensory nerve end-  ings and serve as touch receptors called Merkel discs.    Homeostatic B  —S Imbalance 4.1  Despite melanin’s protective effects, excessive  exposure to UV light (via sunlight or tanning beds)  eventually damages the skin, leading to a leathery  appearance. It also depresses the immune system.  This may help to explain why people infected with  the human herpesvirus 1, which causes cold sores,  are more likely to have an eruption after sunbath-  ing. Overexposure to the sun can also alter the DNA  of skin cells, leading to skin cancer. People with  naturally dark skin seldom have skin cancer, attest-  ing to melanin’s amazing effectiveness as a natural  sunscreen.   7. Which layer of the epidermis produces new epider-  mal cells?   8. Excess shedding of dead cells from the superficial  layer of the skin of the scalp causes dandruff. What  is the name of that skin layer?    The dermis is your “hide.” It is a strong, stretchy  envelope that helps to bind the body together. When  you purchase leather goods (bags, belts, shoes), you  are buying the treated dermis of animals.   The connective tissue making up the dermis con-  sists of two major regions—the papillary and the retic-  ular areas (Figure 4.5), which are composed of areolar  and dense irregular connective tissue, respectively.  Like the epidermis, the dermis varies in thickness.  For example, it is particularly thick on the palms of  the hands and soles of the feet but is quite thin on  the eyelids.   The papillary layer is the superficial dermal  region. It is uneven and has peglike projections from  its superficial surface, called dermal papillae (pah-  pil'e; papill = nipple), which indent the epidermis  above. Many of the dermal papillae contain capillary  loops, which furnish nutrients to the epidermis.  Others house pain receptors (free nerve endings) and  touch receptors. On the palms of the hands and soles  of the feet, the papillae are arranged in definite pat-  terns that form looped and whorled ridges on the  epidermal surface that increase friction and enhance    Figure 4.5 Light micrograph of the two layers of  the dermis (100x). The dermal papillae are extensions  of the superficial papillary layer, which consists of  areolar connective tissue. The deeper reticular layer is  dense irregular fibrous connective tissue.    the gripping ability of the fingers and feet. Papillary  patterns are genetically determined. The ridges of the  fingertips are well provided with sweat pores and  leave unique, identifying films of sweat called finger-  prints on almost anything they touch.   The reticular layer is the deepest skin layer. It  contains dense irregular connective tissue, as well as  blood vessels, sweat and oil glands, and deep pres-  sure receptors called lamellar corpuscles.   Other cutaneous sensory receptors, which are actu-  ally part of the nervous system, are also located in  the skin. These tiny sensors, which include touch,  pressure, temperature, and pain receptors, provide us  with a great deal of information about our external  environment. They alert us to sources of heat or cold,  or the tickle of a bug exploring our skin. In addition  to detecting stimuli from our environment, phago-  cytes found here (and, in fact, throughout the der-  mis) act to prevent microbes that have managed to  get through the epidermis from penetrating any  deeper into the body.   Both collagen and elastic fibers are found through-  out the dermis. Collagen fibers are responsible for    genes, to not smoke, to use a  good sunscreen, and to  think pleasant  thoughts. But even   are bothered by the  appearance of frown  lines, furrowed brows, or   Botulinum toxin type A, more  familiarly called Botox®, is a neuro-  toxin produced by the bacterium that  causes botulism, a deadly form of  food poisoning. Injected in extremely  small doses, the purified toxin blocks  acetylcholine (ACh) release by nerve  cells (ACh is a chemical signal from  nerves telling muscles to contract),    ." Learn more at Mastering A&P > Study Area > |  Additional Study Tools > A Closer Look    thus inhibiting the muscle’s ability to  contract. This “induced paralysis”  smooths lines in about a week.  Botulinum toxin type A  was approved in 1989 to  treat two eye muscle  disorders—uncontrol-  lable blinking (bleph-  arospasm) and  misaligned eyes (stra-  bismus). Its ability to  relax wrinkles was dis-  covered as a side effect  and quickly became its most  common application. In addition to  smoothing wrinkles, Botox® is rou-  tinely used to treat chronic migraines,  excessive axillary sweating, overactive  bladder, and severe neck spasms. Clin-  ical trials are currently exploring the  use of botulinum toxin type A to treat  premature ejaculation and depression.  The process has some risks. If too  much toxin is injected, a person can  end up with droopy eyelid muscles or  temporary muscle weakness for    weeks (the effects of Botox® last 3 to  6 months), and the toxin can spread  to nearby tissues. So, something the  person did not want to paralyze could  become paralyzed. Other side effects  include allergic reaction, nausea, pain,  dizziness, and difficulty breathing.    e Use of botulinum toxin type A  causes “induced paralysis” by  inhibiting the ability of muscle  to contract.    e Smoothing wrinkles is the most  common use for botulinum  toxin type A.    e Botox® is approved for treating  migraines, misaligned eyes,  excessive underarm sweating,  overactive bladder, uncontrolla-  ble blinking, and neck spasms.   e Studies and clinical trials are  under way for further applica-  tions of botulinum toxin type A.    the toughness of the dermis; they also attract and  bind water and thus help to keep the skin hydrated.  Elastic fibers give the skin its elasticity when we are  young. As we age, the number of collagen and elastic  fibers decreases, and the subcutaneous tissue loses  fat. As a result, the skin loses its elasticity and begins  to sag and wrinkle.   The dermis is abundantly supplied with blood  vessels that play a role in maintaining body temper-  ature homeostasis. When body temperature is high,  the capillaries of the dermis become engorged, or  swollen, with heated blood, and the skin becomes  reddened and warm. This allows body heat to radi-  ate from the skin surface. If the environment is cool  and body heat must be conserved, blood bypasses  the dermis capillaries temporarily, allowing internal  body temperature to remain high.    Homeostatic J  £ Imbalance 4.2  Any restriction of the normal blood supply to the  skin results in cell death and, if severe or prolonged  enough, skin ulcers. Decubitus (de-ku’bi-tus)  ulcers (bedsores) occur in bedridden patients who  are not turned regularly or who are dragged or pulled  across the bed repeatedly. The weight of the body  puts pressure on the skin, especially over bony pro-  jections. Because this pressure restricts the blood  supply, the skin becomes pale or blanched at pres-  sure points. At first, the skin reddens when pressure  is released, but if the situation is not corrected, the  cells begin to die, and small cracks or breaks in the  skin appear at compressed sites. Permanent damage  to the superficial blood vessels and tissue eventually    results in degeneration and ulceration of the skin  (see the photos).    The dermis also has a rich nerve supply. As men-  tioned earlier, many of the nerve endings are designed  to detect different types of stimuli (pressure, temper-  ature, pain, etc.), then send messages to the central  nervous system for interpretation. (We discuss these  cutaneous receptors in more detail in Chapter 7.)    vw Name the factors that determine skin color, and  describe the function of melanin.    e The amount and kind (yellow, reddish brown,  or black) of melanin in the epidermis. Skin  exposure to sunlight stimulates melanocytes to  produce more melanin pigment, resulting in  tanning of the skin. As the melanocytes  produce melanin, it accumulates in their  cytoplasm in membrane-bound granules called  melanosomes. These granules then move to the  ends of the melanocytes’ spidery arms, where  they are taken up by nearby keratinocytes.  Inside the keratinocytes, the melanin forms a  pigment umbrella over the superficial, or  “sunny,” side of their nuclei and shields their  genetic material (DNA) from the damaging  effects of UV radiation in sunlight (see  Figure 4.4). People who produce a lot of  melanin have brown-toned skin, whereas  people with less melanin are light skinned.   e The amount of carotene deposited in the stratum  corneum and subcutaneous tissue. (Carotene is  an orange-yellow pigment plentiful in carrots    and other orange, deep yellow, or leafy green  vegetables.) In people who eat large amounts of  carotene-rich foods, the skin tends to take on a  yellow-orange cast.    e The amount of oxygen-rich hemoglobin (pigment  in red blood cells) in the dermal blood vessels.  In light-skinned people, the crimson color of  oxygen-rich hemoglobin in the dermal blood  supply flushes through the transparent cell lay-  ers above and gives the skin a rosy glow.    Homeostatic J  £ Imbalance 4.3  When hemoglobin is poorly oxygenated, both the  blood and the skin of light-skinned people appear  blue, a condition called cyanosis (si’ah-no’sis).  Cyanosis is common during heart failure and severe  breathing disorders. In dark-skinned people, the skin  does not appear cyanotic in the same situations  because of the masking effects of melanin, but cya-  nosis is apparent in their mucous membranes and  nail beds.    Emotions also influence skin color, and many  alterations in skin color signal certain disease  states:    e Redness, or erythema (er’i-the'mah). Reddened  skin may indicate embarrassment (blushing),  fever, hypertension, inflammation, or allergy.    e Pallor, or blanching. Under certain types of  emotional stress (fear, anger, and others), some  people become pale. Pale skin may also signify  anemia, low blood pressure, or impaired blood  flow into the area.    e Jaundice (jon'dis), or a yellow cast. An abnormal  yellow skin tone usually signifies a liver disorder  in which excess bile pigments accumulate in the  blood, circulate throughout the body, and  become deposited in body tissues.    e Bruises. The black-and-blue marks of bruising  reveal sites where blood has escaped from the  circulation and has clotted in the tissue spaces.  Such clotted blood masses are called hematomas.  An unusual tendency to bruise may signify a  deficiency of vitamin C in the diet or hemo-  philia (bleeder’s disease).    10. Which structure(s) are responsible for fingerprints?  11. You have just gotten a paper cut, but it doesn't  bleed. Which layer(s) of the skin has/have the cut  penetrated?  12. What pigments determine skin color?  For answers, see Appendix A.    v# Describe the distribution and function of the  epidermal appendages—sebaceous glands,  sweat glands, hair, and nails.    The skin appendages include cutaneous glands,  hair and hair follicles, and nails (see Figure 4.3).  Despite being physically located in the dermis, each  of these appendages is produced by cells that origi-  nate in the epidermal layer and plays a unique role  in maintaining body homeostasis.    The cutaneous glands are all exocrine glands that  release their secretions to the skin surface via ducts.  They fall into two groups: sebaceous glands and sweat  glands. As these glands are formed by the cells of  the stratum basale, they push into the deeper skin  regions and ultimately reside almost entirely in the  dermis.    Sebaceous (Oil) Glands The sebaceous (se-ba’shus)  glands, or oil glands, are found all over the skin,  except on the palms of the hands and the soles of the  feet. Their ducts usually empty into a hair follicle  (Figure 4.6a), but some open directly onto the skin  surface.   The product of the sebaceous glands, sebum  (se’bum; seb = grease), is a mixture of oily sub-  stances and fragmented cells. Sebum is a lubricant  that keeps the skin soft and moist and prevents the  hair from becoming brittle. Sebum also contains  chemicals that kill bacteria, so it is important in  preventing bacterial infection of the skin. The seba-  ceous glands become very active when androgens  (male sex hormones) are produced in increased  amounts (in both sexes) during adolescence. Thus,  the skin tends to become oilier during this period  of life.    Homeostatic B  £ Imbalance 4.4  When sebaceous gland ducts are blocked by sebum,  acne appears on the skin surface. Acne is an active  infection of the sebaceous glands. If the accumulated  material oxidizes and dries, it darkens, forming a  blackhead. If the material does not dry or darken, a  whitehead forms. Acne can be mild or extremely  severe, leading to permanent scarring.   Seborrhea (seb”o-re'ah; “fast-flowing sebum”),  known as “cradle cap” in infants, is caused by over-  activity of the sebaceous glands. It begins on the  scalp as pink, raised lesions that gradually form a  yellow-to-brown crust that sloughs off oily scales  and dandruff. Careful washing to remove the exces-  sive oil often helps cradle cap in a newborn baby.    Sweat Glands Sweat glands, also called sudorif-  erous (su’do-rif’er-us; sudor = sweat) glands, are  widely distributed in the skin. Their number is  staggering—more than 2.5 million per person. There  are two types of sweat glands, eccrine and apocrine.  The eccrine (ek’rin) glands are far more numer-  ous and are found all over the body. They produce  sweat, a clear secretion that is primarily water plus  some salts (sodium chloride), vitamin C, traces of  metabolic wastes (ammonia, urea, uric acid), and  lactic acid (a chemical that accumulates during  vigorous muscle activity). Sweat is acidic (pH from 4  to 6), a characteristic that inhibits the growth of    certain bacteria, which are always present on the skin  surface. Typically, sweat reaches the skin surface via a  duct that opens externally as a funnel-shaped sweat  pore (Figure 4.6b). Notice, however, that the facial  “pores” commonly referred to when we talk about  our complexion are the external outlets of hair  follicles where sebaceous ducts empty, not these  sweat pores.   The eccrine sweat glands are an important and  highly efficient part of the body's heat-regulating  equipment. They are supplied with nerve endings  that cause them to secrete sweat when the external  temperature or body temperature is too high. When  sweat evaporates off the skin surface, it carries large  amounts of body heat with it. On a hot day, it is    possible to lose up to 7 liters of body water in this  way. The heat-regulating functions of the body are  important—if internal temperature changes more  than a few degrees from the normal 37°C (98.6°F),  life-threatening changes occur in the body. (We dis-  cuss body temperature regulation in more detail in  Chapter 14.)   Apocrine (ap’o-krin) glands are largely con-  fined to the axillary (armpit) and genital areas of the  body. They are usually larger than eccrine glands,  and their ducts empty into hair follicles. Their secre-  tion contains fatty acids and proteins in addition to  all the substances present in eccrine sweat; conse-  quently, it may have a milky or yellowish color. The  secretion is odorless, but when bacteria that live on    the skin use its proteins and fats as a source of nutri-  ents, it can take on a musky, unpleasant odor.   Apocrine glands begin to function during  puberty under the influence of androgens. Although  they produce their secretions almost continuously,  apocrine glands play a minimal role in thermoregu-  lation. Their precise function is not yet known, but  they are activated by nerve fibers during pain and  stress and during sexual arousal.    Hair is an important part of our body image.  Consider, for example, the spiky hair style of punk  rockers and the flowing locks of high-fashion mod-  els. Millions of hairs, produced by hair follicles, are  found all over the body surface except on the palms  of the hands, soles of the feet, nipples, and lips.  Humans are born with as many hair follicles as they  will ever have, and hairs are among the fastest grow-  ing tissues in the body. Hair serves a few minor pro-  tective functions, such as guarding the head against  bumps, shielding the eyes (via eyelashes), and help-  ing to keep foreign particles out of the respiratory  tract (via nose hairs). Hormones account for the  development of hairy regions—the scalp and, in  the adult, the pubic and axillary areas. Despite these  functions, however, our body hair has lost much of  its usefulness. Hair served early humans (and still  serves hairy animals) by providing insulation in  cold weather, but now we have other means of keep-  ing warm.    Hairs A hair is a flexible epithelial structure. The  part of the hair enclosed in the hair follicle is called  the root, and the part projecting from the surface of  the scalp or skin is called the shaft (Figure 4.7a). A  hair forms by division of the well-nourished stratum  basale epithelial cells in the matrix (growth zone)  of the hair bulb at the deep end of the follicle. As the  daughter cells are pushed farther away from the  growing region, they become keratinized and die.  Thus the bulk of the hair shaft, like the bulk of the  epidermis, is dead material and almost entirely  protein.   Each hair is made up of a central core called the  medulla (mé-dul'ah), consisting of large cells and air  spaces, surrounded by a bulky cortex layer composed  of several layers of flattened cells (Figure 4.7b). The  cortex is, in turn, enclosed by an outermost cuticle  formed by a single layer of cells that overlap one  another like shingles on a roof. This arrangement of    the cuticle cells helps to keep the hairs apart and  keeps them from matting (Figure 4.7c). The cuticle is  the most heavily keratinized region; it provides  strength and helps keep the inner hair layers tightly  compacted. Because it is most subject to abrasion,  the cuticle tends to wear away at the tip of the shaft,  allowing the keratin fibrils in the inner hair regions  to frizz out, a phenomenon called “split ends.” Hair  pigment is made by melanocytes in the hair bulb,  and varying amounts of different types of melanin  (yellow, rust, brown, and black) combine to produce  all varieties of hair color from pale blond to red to  pitch black.   Hairs come in a variety of sizes and shapes.  They are short and stiff in the eyebrows, long and  flexible on the head, and usually nearly invisible  almost everywhere else. When the hair shaft is oval,  hair is smooth, silky, and wavy. When the shaft is  flat and ribbonlike, the hair is curly or kinky. If it  is perfectly round, the hair is straight and tends to  be coarse.    Hair Follicles Hair follicles (folli = bag) are actu-  ally compound structures. The inner epithelial root  sheath is composed of epithelial tissue and forms the  hair. The outer fibrous sheath is actually dermal con-  nective tissue (Figure 4.7d). This dermal region sup-  plies blood vessels to the epidermal portion and  reinforces it. Its nipplelike hair papilla provides the  blood supply to the matrix in the hair bulb (the  deepest part of the follicle).   If you look carefully at the structure of the hair  follicle, you will notice that it is slightly slanted (see  Figure 4.7a). Small bands of smooth muscle cells—  arrector pili (ah-rek’tor pi'li; “raiser of hair”)—  connect each side of the hair follicle to the dermal  tissue. When these muscles contract (as when we are  cold or frightened), the hair is pulled upright, dim-  pling the skin surface with “goose bumps.”    A nail is a scalelike modification of the epider-  mis that corresponds to the hoof or claw of other  animals. Each nail has a free edge, a body (visible  attached portion), and a root (embedded in the  skin) (Figure 4.8, p. 142). The borders of the nail  are overlapped by folds of skin called nail folds. The  edge of the thick proximal nail fold is commonly  called the cuticle.   The stratum basale of the epidermis extends  beneath the nail as the nail bed. Its thickened    gland  Hair follicle  Hair root  (b) Hair (c) Scanning electron micrograph  Hair bulb of hair shaft emerging from  in follicle follicle (435X)    Figure 4.7 Structure of a hair hair. (c) Scanning electron micro- expanded hair bulb in the follicle  root and follicle. (a) Longitudinal graph showing a hair shaft emerging showing the root and matrix, the  section of a hair within its follicle. from a follicle at the skin surface. region of actively dividing epithelial    (b) Enlarged longitudinal section ofa (d) Enlarged longitudinal view of the cells that produces the hair.    proximal area, called the nail matrix, is responsible the underlying dermis. The exception to this is the  for nail growth. As the matrix produces nail cells, region over the thickened nail matrix that appears as  they become heavily keratinized and die. Thus, nails, a white crescent and is called the lunule (loo'nyul;  like hairs, are mostly nonliving material. lunul = crescent). As noted earlier, when the supply   Nails are transparent and nearly colorless, but of oxygen in the blood is low, the nail beds take on a    they look pink because of the rich blood supply in cyanotic (blue) cast.    13. Which of the cutaneous gland types can make  some people's hair limp and oily?   14. How do secretions of apocrine glands differ from  those of the eccrine sweat glands?   15. When a factory worker caught his finger in a machine,  the entire nail, plus the nail matrix and bed, was torn  off. Will his nail grow back? Why or why not?    vz Summarize the characteristics of basal cell  carcinoma, squamous cell carcinoma, and  malignant melanoma.    The most common skin disorders are infections with  pathogens (path'o-jenz) such as bacteria, viruses, or  fungi. Allergies, which are caused by abnormally strong  immune responses, are also commonly seen in the  skin. Less common, but far more damaging to body  well-being, are burns and skin cancers. We briefly sum-  marize these homeostatic imbalances of the skin here.    Infections and allergies cause the following com-  monly occurring skin disorders:    Athlete's foot. An itchy, red, peeling condition  of the skin between the toes, resulting from an  infection with the fungus Tinea pedis.    Boils (furuncles) and carbuncles (kar'bun-kulz).  Boils are caused by inflammation of hair follicles  and surrounding tissues, commonly on the dor-  sal neck. Carbuncles are clusters of boils often  caused by the bacterium Staphylococcus aureus.    Cold sores (fever blisters). Small fluid-filled  blisters that itch and sting, caused by human  herpesvirus 1 infection. The virus localizes in a  cutaneous nerve, where it remains dormant until  activated by emotional upset, fever, or UV radia-  tion. Cold sores usually occur around the lips  and in the mucosa of the mouth and nose  (Figure 4.9a).    Contact dermatitis. Itching, redness, and swelling  of the skin, progressing to blistering. It is caused  by exposure of the skin to chemicals (such as  those in poison ivy) that provoke allergic re-  sponses in sensitive individuals.   Impetigo (im-peh-ti’go; impet = an attack). Pink,  fluid-filled, raised lesions (commonly around the  mouth and nose) that develop a yellow crust and  eventually rupture and weep fluid (Figure 4.9b).  Caused by highly contagious staphylococcus or  streptococcus infections, impetigo is common in  elementary school-aged children.    Psoriasis (so-ri'ah-sis). Characterized by red-  dened epidermal lesions covered with dry, sil-  very scales that itch, burn, crack, and sometimes  bleed (Figure 4.9c). A chronic condition, psoria-  sis is believed to be an autoimmune disorder in  which the immune system attacks a person's  own tissues, leading to the rapid overproduc-    Loss of homeostasis in body cells and organs reveals  itself on the skin, sometimes in startling ways. The  skin can develop more than 1,000 different ailments.    tion of skin cells. Attacks are often triggered by  trauma, infection, hormonal changes, or stress.  When severe, psoriasis may be disfiguring.    There are few threats to life more serious than burns.  A burn is tissue damage and cell death caused by  intense heat, electricity, UV radiation (sunburn), or  certain chemicals (such as acids), which denature  proteins and cause cell death in the affected areas.   When the skin is burned and its cells are  destroyed, two life-threatening problems result.  First, without an intact boundary, the body loses its  precious supply of fluids containing proteins and  electrolytes as these seep from the burned surfaces.  Dehydration and electrolyte imbalance follow and  can lead to a shutdown of the kidneys and circula-  tory shock (inadequate circulation of blood caused  by low blood volume). To save the patient, lost flu-  ids must be replaced immediately. The volume of  fluid lost can be estimated indirectly by determin-  ing how much of the body surface is burned, using  the rule of nines. This method divides the body  into 11 areas, each accounting for 9 percent of the  total body surface area, plus an additional area sur-  rounding the genitals (the perineum) representing  1 percent of body surface area (Figure 4.10a, p. 144).   Later, infection becomes the most important threat  and is the leading cause of death in burn victims.  Burned skin is sterile for about 24 hours. But after that,  pathogens easily invade areas where the skin has been  destroyed and multiply rapidly in the nutrient-rich  environment of dead tissues. To make matters worse,  the patients immune system becomes depressed  within one to two days after severe burn injury.   Burns are classified according to their severity  (depth) as first-degree (superficial), second-degree  (superficial partial-thickness burns), third-degree  (full-thickness burns), or fourth-degree (full-  thickness burns with deep-tissue involvement)    (Figure 4.10b). In first-degree burns, only the  superficial epidermis is damaged. The area becomes  red and swollen. Except for temporary discomfort,  first-degree burns are not usually serious and gener-  ally heal in two to three days. Sunburn without blis-  tering is a first-degree burn.   Second-degree burns involve injury to the epi-  dermis and the superficial part of the dermis. The  skin is red, painful, and blistered. Because sufficient  numbers of epithelial cells are still present, regrowth  (regeneration) of the epithelium can occur. Or-  dinarily, no permanent scars result if care is taken to  prevent infection. Third-degree burns destroy  both the epidermis and the dermis and often extend  into the subcutaneous tissue, reflecting their catego-  rization as full thickness burns. Blisters are usually  present, and the burned area appears blanched (gray-  white) or blackened. Because the nerve endings in  the area are destroyed, the burned area is not pain-  ful. In third-degree burns, regeneration is not possi-  ble, and skin grafting must be done to cover the  underlying exposed tissues.   Fourth-degree burns are also full-thickness  burns, but they extend into deeper tissues such as  bone, muscle, or tendons. These burns appear dry  and leathery, and they require surgery and grafting to  cover exposed tissue. In severe cases, amputation  may be required to save the patient's life.   In general, burns are considered critical if any of  the following conditions exists:   e Over 10 percent of the body has third- or fourth-  degree burns.    e There are third- or fourth-degree burns of the  face, hands, feet, or genitals.    Would you expect to see hair regeneration in an area  that suffers third-degree burns? Why or why not?    Figure 4.10 Burns. (a) Estimating  the extent of burns using the rule of  nines. The surface areas for the  anterior body surface are indicated    Facial burns are particularly dangerous because  of the possibility of burns in respiratory passageways,  which can swell and cause suffocation. Joint injuries  are troublesome because the scar tissue that even-  tually forms can severely limit joint mobility.  Circumferential burns can restrict movement, and  depending on location, can interfere with normal  breathing.    on the human figure. Total surface  area (anterior and posterior body  surfaces) is tabulated to the right of  the figure. (b) Burns of increasing    severity, from top to bottom: first-  degree, second-degree, and third-  degree.    Numerous types of neoplasms (tumors) arise in the  skin. Most skin neoplasms are benign and do not  spread (metastasize) to other body areas. For exam-  ple, warts are caused by human papillomaviruses  but are benign and do not spread. However, some  skin neoplasms are malignant, or cancerous, and they  tend to invade other body areas.    (Chapter 3, pp. 104-105). These cells lack normal control  of cell division and divide quickly, resulting in errors dur-  ing DNA replication, mitosis, or both. Cells experiencing  rapid, uncontrolled growth become cancerous and can  metastasize (spread) to other parts of the body.    Which of these cancers arises from the most superficial  epidermal cells?    Skin cancer is the single most common type of  cancer in humans. The incidence rate of skin cancer  is increasing worldwide. White skin, aging, and male  sex contribute as risk factors. The most important  risk factor is overexposure to UV radiation in sun-  light and tanning beds. Frequent irritation of the  skin by infections, chemicals, or physical trauma also  seems to be a predisposing factor. Let's look in a bit  more detail at the three most common types of skin  cancer: basal cell carcinoma, squamous cell carci-  noma, and malignant melanoma.    Basal Cell Carcinoma Basal cell carcinoma (kar"si-  no’mah) is the least malignant and most common  skin cancer. Cells of the stratum basale, altered so  that they cannot form keratin, no longer honor the  boundary between epidermis and dermis. They pro-  liferate, invading the dermis and subcutaneous  tissue. The cancerous lesions occur most often on  sun-exposed areas of the face and often appear  as shiny, dome-shaped nodules that later develop  a central ulcer with a “pearly” beaded edge  (Figure 4.11a). Basal cell carcinoma is relatively slow-  growing, and metastasis seldom occurs before the  lesion is noticed. When the lesion is removed surgi-  cally, 99 percent of cases are completely cured.    Squamous Cell Carcinoma Squamous cell carci-  noma arises from the cells of the stratum spinosum.  The lesions appear as scaly, reddened papules (small,  rounded swellings) that gradually form shallow  ulcers with firm, raised borders (Figure 4.11b). This  variety of skin cancer appears most often on the    scalp, ears, back of the hands, and lower lip, but can  appear anywhere on the skin. It grows rapidly and  metastasizes to adjacent lymph nodes if not  removed. This epidermal cancer is also believed to  be induced by UV exposure. If it is caught early and  removed surgically or by radiation therapy, the  chance of complete cure is good.    Malignant Melanoma Malignant melanoma (mel"ah-  no’mah) is a cancer of melanocytes. It accounts for  only about 5 percent of skin cancers, but it is often  deadly. Melanoma can begin wherever there is pig-  ment; most such cancers appear spontaneously, but  some develop from pigmented moles. It arises from  accumulated DNA damage in a skin cell and usually  appears as a spreading brown to black patch (Figure  4.11c) that metastasizes rapidly to surrounding lymph  and blood vessels. The chance for survival is about 50  percent, and early detection helps. The American  Cancer Society suggests that people who sunbathe  frequently or use tanning beds examine their skin  periodically for new moles or pigmented spots and  apply the ABCDE rule for recognizing melanoma:    (A) Asymmetry. Any two sides of the pigmented  spot or mole do not match.    (B) Border irregularity. The borders of the lesion  are not smooth but exhibit indentations.    (C) Color. The pigmented spot contains areas of  different colors (black, brown, tan, and some-  times blue or red).   (D) Diameter. The lesion is larger than 6 milli-  meters (mm) in diameter (the size of a pencil  eraser).   (E) Evolution. One or more of these characteris-  tics (ABCD) is evolving, or changing.    Learn more at Mastering A&P > Study Area >  Additional Study Tools > Focus on Careers    FY time you consult a doctor or  are hospitalized, your medical  record gets longer. Medical transcrip-  tionists play a key role in creating and  maintaining these vital documents.   A medical transcriptionist is a medi-  cal language specialist who interprets  and transcribes notes dictated by physi-  cians and other healthcare profession-  als. These reports, which cover all    spelling, and punctuation skills are cru-  cial. Physicians often dictate these  records on the go, and a good tran-  scriptionist must be able to edit the dic-  tated material for grammar and  clarity.”   Knowledge of anatomy and physiol-  ogy, however, is even more important.  Notes Shull, “If you understand anat-  omy and medical terminology, you will   Classes for medical transcription  vary in length from several months to  two years. Accreditation procedures  vary from state to state. The Asso-  ciation for Healthcare Documen-  tation Integrity (AHDI) evaluates  medical transcription programs and  posts a list of recommended programs    be much more accurate at interpreting on its website.  and transcribing what you hear.  Accurate transcription is vital    aspects of a patient's assessment, di-  agnosis, treatment, and outcome,  become part of the person’s confiden-  tial medical record.  What does it take  to be a transcrip-  tionist? “Certainly,  you need a good    The usual therapy for malignant melanoma is  wide surgical excision along with immunotherapy, a  treatment that involves the patient’s immune system.  Large lesions may also require radiation or chemo-  therapy after surgical removal.    During the fifth and sixth months of development,  a fetus is covered with a downy type of hair called  lanugo (lah-noo’go). By the time the infant is born,  it has usually shed this hairy cloak, and instead its  skin is covered with an oily coating called the vernix  caseosa (ver'niks kah-se-o'sah). This white, cheesy-  looking substance, produced by the sebaceous  glands, protects the baby’s skin while it is floating  in its water-filled sac inside the mother. The new-  born’s skin is very thin, and blood vessels are easily  seen through it. As the baby grows, its skin becomes  thicker, and more subcutaneous fat is deposited.    16. What are the two life-threatening consequences of  a severe burn?   17. What are the criteria for classifying burns as first-,  second-, third-, or fourth-degree?   18. What name is given to the rule for recognizing the  signs of melanoma?   19. What is the single most common risk factor for  skin cancer?   20. Why do no skin cancers develop from stratum  corneum cells?   e Nervous system regulates  diameter of blood vessels in skin;  activates sweat glands  (contributing to thermoregulation);  interprets cutaneous sensation;  activates arrector pili muscles   e Androgens produced by the  endocrine system activate  sebaceous glands and help  regulate hair growth; estrogen  helps maintain skin hydration   e Lymphatic system prevents  edema by picking up excessive  leaked fluid; immune system  protects skin cells    e Respiratory system furnishes  oxygen to skin cells and removes  carbon dioxide via gas exchange  with blood    e Skin protects cardiovascular  organs; prevents fluid loss from  body surface; serves as blood  reservoir   removes wastes from skin;  provides substances needed by  skin glands to make their  secretions    e Skin protects urinary organs;  excretes salts and some  nitrogen-containing wastes in sweat   e Urinary system activates vitamin D  made by keratinocytes; disposes  of nitrogen-containing wastes of  skin metabolism    e Skin protects bones; skin  synthesizes vitamin D that bones  need for normal calcium    During adolescence, the skin and hair become  oilier as sebaceous glands are activated, and acne may  appear. Acne usually subsides in early adulthood, and  the skin reaches its optimal appearance when we are  in our twenties and thirties. Then visible changes in  the skin begin to appear, as it is continually assaulted  by abrasion, chemicals, wind, sun, and other irritants  and as its pores become clogged with air pollutants  and bacteria. As a result, pimples, scales, and various  kinds of dermatitis (der’mah-ti'tis), or skin inflamma-  tion, become more common.   As we continue to age, the amount of subcutane-  ous tissue decreases, leading to sensitivity to cold.  The skin also becomes drier (because of decreased  oil production), and as a result, it may become itchy  and bothersome. Thinning of the skin, another result  of the aging process, makes it more susceptible to  bruising and other types of injuries. The decreasing  elasticity of the skin, along with the loss of subcuta-  neous fat, allows bags to form under our eyes, and  our jowls begin to sag. Smoking and sunlight speed  up this loss of elasticity, so three of the best things  you can do for your skin are to avoid smoking,  shield your skin from the sun, and do not go to tan-  ning beds. There is no way to avoid aging skin, but  good nutrition, plenty of fluids, and cleanliness help  delay the process.   Hair loses its luster as we age, and by age 50 the  number of hair follicles has dropped by one-third  and continues to decline, resulting in hair thin-  ning and some degree of baldness, or alopecia  (al”o-pe’she-ah), in most people. Many men become  bald as they age, a phenomenon called male pattern    e Cutaneous membranes (the skin): superficial  epidermis (stratified squamous epithelium) and  deep dermis (dense connective tissue); protects  body surface   e Mucous membranes: epithelial sheet connected  to a lamina propria (areolar connective tissue);  lines body cavities open to the exterior    baldness. A bald man is not really hairless—he does  have hairs in the bald area. But, because those hair  follicles have begun to degenerate, the vellus (vell =  wool) hairs are colorless and very tiny (and may not  even emerge from the follicle). Another phenome-  non of aging is graying hair. Like balding, this is usu-  ally genetically controlled by a “delayed-action”  gene. Once the gene takes effect, the amount of mel-  anin deposited in the hair decreases or becomes  entirely absent, which results in gray-to-white hair.    Certain events can cause hair to gray or fall out pre-  maturely. For example, many people have claimed  that they turned gray nearly overnight because of  some emotional crisis in their life. In addition, we  know that anxiety, protein-deficient diets, therapy  with certain chemicals (chemotherapy), radiation,  excessive vitamin A, and certain fungal diseases  (ringworm) can cause both graying and hair loss.  However, when the cause of these conditions is not  genetic, hair loss is usually not permanent.    21. What change in aging skin accounts for wrinkles  and cold intolerance in older adults?  22. What is the source of the vernix caseosa that  covers the skin of the newborn baby?  For answers, see Appendix A.    A Listen to the story of this chapter in a brief summary at Mastering A&P >  E Study Area > Author Narrated Audio Summaries    e Serous membranes: simple squamous epithe-  lium resting on a thin connective tissue layer;  occurs in pairs of parietal and visceral layers  separated by serous fluid; lines the ventral body  cavity (closed to the exterior)    4.2a. Skin functions: protect deeper tissue from  chemicals, bacteria, bumps, and drying; regulating    o Layers from superficial to deep: stratum  corneum, stratum lucidum (in thick skin  only), stratum granulosum, stratum  spinosum, and stratum basale    o Cells at its surface are dead and continually  flake off; they are replaced by dividing cells    o As the cells are displaced toward the skin sur-  face, they accumulate keratin and die    e Dermis is dense connective tissue and contains  blood vessels, nerves, and epidermal appendages    o Reticular layer is dense irregular connective  tissue; houses deep pressure receptors, sweat  and oil glands, and hair follicles    e Melanin, a pigment produced by melanocytes,  protects the nuclei of epithelial cells from the  damaging rays of the sun    e Carotene is deposited in skin and subcutaneous  tissue; it is an orange-yellow pigment found in  vegetables such as carrots    4.2d. Skin appendages are formed by the  epidermis but reside in the dermis    ° Sebum keeps the skin and hair soft and  contains chemicals that kill bacteria    e Sweat glands (sudoriferous glands)—produce  sweat and release it at the epithelial surface; help  regulate body temperature   ° Apocrine glands—found in axillary and ingui-  nal areas; include fatty acids and proteins in  addition to the regular components found in  eccrine sweat    e A hair is primarily dead keratinized cells and is  produced by the matrix in the root of the hair  bulb; the root is enclosed in a sheath called the  hair follicle    e Nails are hooflike derivatives of epidermis; simi-  lar to hair, nails are primarily dead keratinized  cells    4.2e. Homeostatic imbalances of skin often result  from infections or allergic responses; more serious  are burns and skin cancer    e Burn—an area of tissue damage involving cell  death due to excessive heat, chemicals, electricity,  or UV radiation    e Burns interfere with skin's protective functions  and represent major infection and dehydration  threats    ° The extent of burns is assessed by the rule of  nines; the severity (depth) of burns includes  first-degree burns (epidermal damage only),  second-degree burns (epidermal and some  dermal injury), third-degree burns (epidermis  and dermis totally destroyed; may involve some  subcutaneous tissue), and fourth-degree  burns (all of skin and involves deeper tissue  such as bone or muscle)  = Third- and fourth-degree burns require skin   grafting  e The most common cause of skin cancer is  exposure to ultraviolet (UV) radiation    o Basal cell carcinoma (stratum basale) and  squamous cell carcinoma (stratum spinosum)  are easily cured if they are caught early and  removed before metastasis    o Malignant melanoma, a cancer of melanocytes,  is still fairly rare but metastasizes quickly and is  often fatal  = Assess moles or pigmented spots using the    e The skin is thick, resilient, and well hydrated in  youth but loses elasticity and thins as we age; skin  cancer is a major threat to skin exposed to exces-  sive sunlight   e Balding and/or graying occurs with aging; both  are genetically determined but can also be caused  by other factors (drugs, emotional stress, and  so on)    a. The epithelial type is the same in all serous  membranes, but there are different epithelial types  in different mucous membranes.   b. Serous membranes line closed body cavities,  whereas mucous membranes line body cavities  open to the outside.   c. Serous membranes always produce serous fluid,  and mucous membranes always secrete mucus.   d. Both membranes contain an epithelium plus a  layer of loose connective tissue.    . have a connective tissue layer called the lamina  propria.  e. secrete a lubricating fluid.    7. Which one of the following is not associated with the    9. Match the appropriate structure with the proper description and/or function.    What is the name of the connective tissue membrane  found lining the joint cavities?    From what types of damage does the skin protect the  body?    Name two different categories of skin secretions and  the glands that manufacture them.    How does the skin help to regulate body temperature?  What are arrector pili? What do they do?   What kind of a disorder is psoriasis? What triggers it?  Contrast the secretions of eccrine and apocrine glands.    Explain the difference between a blackhead, whitehead,  boil, and carbuncle. Which is most serious? Why?    Jane’s newborn baby’s scalp is covered with a brown-  ish crust that is full of scales and dandruff. What is the  likely cause?    Roger, a 40-year-old man who loves spending time on the  beach, is complaining to you that his suntan made him  popular when he was young—but now his face is all wrin-  kled, and he has several darkly pigmented moles that are  growing rapidly and are as big as large coins. He shows  you the moles, and immediately you think “ABCDE.”  What does that mean, and why should he be concerned?    Fred's new cycling shorts have got special silicone grip  strips on the inside of the material to hold the shorts    in place. After a day on the saddle, Fred notices that  he has got more than just a tan line. Two bright red  circles appeared on his thighs a few hours after he  changed out of his gear. Explain what type of skin  condition Fred might be experiencing.    Mr. Grayson is receiving a drug treatment transder-  mally (through the skin). Explain why drugs delivered  by this route are fat-soluble rather than water-soluble.    A burn victim exhibits a red and swollen arm with blis-  tering; a hand that has been charred black, exposing  bone; and a cheek that appears blanched. How serious  is each burn, and is this patient critical? Explain.    The skeletal system is  the internal frame of the  body and includes bones,    The skeleton is essential  for protecting organs, producing  blood cells, storing essential  minerals, and anchoring skeletal  muscles so that their contractions  cause body movements.    lthough the word skeleton comes from the  A Greek word meaning “dried-up body,” our  internal framework is beautifully formed and  proportioned. Strong yet light, it is perfectly adapted  for its functions of protecting the body and allowing  motion. No other animal has such long legs (com-  pared to the arms or forelimbs) or such a strange foot,  and few have grasping hands with opposable thumbs.  The bones of the skeleton are part of the skeletal  system, which also includes joints, cartilages, and  ligaments (fibrous cords that bind the bones together  at joints). The skeleton is divided into two parts: the  axial skeleton, the bones that form the longitudinal  axis of the body, and the appendicular skeleton,    In addition to  providing structure,  bones articulate, or come  together, at joints to allow  body movement.    the bones of the limbs and girdles that attach them  to the axial skeleton. Joints give these parts of the  skeleton flexibility and allow movement to occur.    1# \dentify the subdivisions of the skeleton as axial or  appendicular.    bones”—pretty unflattering and inaccurate images  of some of our most phenomenal organs. Our  brains, not our bones, convey feelings of fatigue, and  living bones are far from dry. As for “bag of bones,”  they are indeed more obvious in some of us, but  without bones to form our internal skeleton, we  would creep along the ground like slugs, lacking any  definite shape or form. Let's examine how our bones  contribute to overall body homeostasis.    Besides contributing to body structure, our bones  perform several important body functions:    e Support. Bones, the “steel frame” of the body,  form the internal framework that supports the  body and cradles its soft organs. The bones of  the legs act as pillars to support the body trunk  when we stand, and the rib cage reinforces the  thoracic wall.    e Protection. Bones protect soft body organs. For  example, the fused bones of the skull provide a  snug enclosure for the brain, allowing someone  to juggle a soccer ball with their head without  worrying about injuring the brain. The vertebrae  surround the spinal cord, and the rib cage helps  protect the vital organs in the thorax.    e Allow movement. Skeletal muscles, attached to  bones by tendons, use the bones as levers to  move the body and its parts. As a result, we can  breathe, walk, swim, and throw a ball. Before  continuing, take a moment to imagine that your  bones have turned to putty. What if you were  running when this change took place? Now  imagine your bones forming a rigid metal frame-  work inside your body (without joints). What  problems could you envision with this arrange-  ment? These images should help you understand  how well our skeletal system provides support  and protection while allowing movement.    e Storage. Fat is stored in the internal (marrow)  cavities of bones. Bone itself serves as a store-  house for minerals, the most important of  which are calcium and phosphorus. Most of the  body’s calcium is deposited in the bones as cal-  cium salts, but a small amount of calcium in its  ionic form (Ca?*) must be present in the blood  at all times for the nervous system to transmit  messages, for muscles to contract, and for blood  to clot. Problems occur not only when there is  too little calcium in the blood, but also when  there is too much. Hormones control the    Figure 5.1 Flat bones consist of a layer of spongy  bone sandwiched between two thin layers of  compact bone.    movement of calcium to and from the bones  and blood according to the needs of the body.  Indeed, “deposits” and “withdrawals” of cal-  cium (and other minerals) to and from bones  go on almost all the time.    e Blood cell formation. Blood cell formation,  or hematopoiesis (hem”ah-to-poi-e'sis), occurs  within the marrow cavities of certain bones.   The adult skeleton is composed of 206 bones. There  are two basic types of osseous, or bone, tissue:  Compact bone is dense and looks smooth and  homogeneous, whereas spongy bone has a spiky,  open appearance like a sponge (Figure 5.1).   Additionally, bones come in many sizes and  shapes. For example, the tiny pisiform bone of the  wrist is the size and shape of a pea, whereas the  femur, or thigh bone, is nearly 2 feet long and has a  large, ball-shaped head. The unique shape of each  bone fulfills a particular need. Bones are classified  according to shape into four groups: long, short, flat,  and irregular (Figure 5.2, p. 154).   As their name suggests, long bones are typically  longer than they are wide. As a rule, they have a shaft  with enlarged ends. Long bones are mostly compact  bone but also contain spongy bone at the ends. All    the bones of the limbs, except the patella (kneecap)  and the wrist and ankle bones, are long bones.   Flat bones are thin, flattened, and usually  curved. They have two thin layers of compact bone  sandwiching a layer of spongy bone between them  (see Figure 5.1). Most bones of the skull, the ribs,  and the sternum (breastbone) are flat bones.   Short bones are generally cube-shaped and  contain mostly spongy bone with an outer layer of  compact bone. The bones of the wrist and ankle are  short bones. Sesamoid (ses'ah-moyd) bones, which  form within tendons, are a special type of short  bone. The best-known example is the patella.   Bones that do not fit one of the preceding cate-  gories are called irregular bones. The vertebrae,  which make up the spinal column, fall into this  group. Like short bones, they are mainly spongy  bone with an outer layer of compact bone.    1. What is the relationship between muscle function  and bones?  2. What are two possible functions of a bone’s marrow  cavity?  3. Where are most long bones found in the body?  For answers, see Appendix A.    v Explain the role of bone salts and the organic  matrix in making bone both hard and flexible.    bones, remember the levels of structural organization  (Figure 1.1, p. 25). Bones are organs, so they contain not  only osseous tissue but also other connective tissues:  fibrous tissue, cartilage, adipose tissue, and blood.    In a long bone, the diaphysis (di-af'i-sis), or shaft,  makes up most of the bone’s length and is composed  of compact bone (Figure 5.3). The diaphysis is cov-  ered and protected by a fibrous connective tissue  membrane, the periosteum  (per-e-os’te-um).  Hundreds of connective tissue fibers, called  perforating fibers, or Sharpey’s fibers, secure the  periosteum to the underlying bone.   The epiphyses (¢-pif’i-séz) are the ends of long  bones. Each epiphysis consists of a thin layer of com-  pact bone enclosing an area filled with spongy bone.  Instead of a periosteum, articular cartilage covers  its external surface. Because the articular cartilage is  glassy hyaline cartilage, it provides a smooth surface  that decreases friction at the joint when covered by  lubricating fluid. Imagine how slick a marble floor  (the articular cartilage) is when wet; this is analo-  gous to the lubrication of a joint.   In adult bones, there is a thin line of bony tissue  spanning the epiphysis that looks a bit different  from the rest of the bone in that area. This is the  epiphyseal line. The epiphyseal line is a remnant of  the epiphyseal plate (a flat plate of hyaline carti-  lage) seen in a young, growing bone. Epiphyseal  plates cause the lengthwise growth of a long bone.  By the end of puberty, when hormones inhibit long  bone growth, epiphyseal plates have been com-  pletely replaced by bone, leaving only the epiphyseal  lines to mark their previous location.   The inner bony surface of the shaft is covered by  a delicate connective tissue called endosteum. In    Figure 5.3 The structure of a  long bone (humerus of arm).  (a) Anterior view with longitudinal  section cut away. (b) Pie-shaped,    infants, the cavity of the shaft, called the medullary  cavity, is a storage area for red marrow, which pro-  duces blood cells. Children’s bones contain red mar-  row until the age of 6 or 7, when it is gradually  replaced by yellow marrow, which stores adipose  (fat) tissue. In adult bones, red marrow is confined  to cavities in the spongy bone of the axial skeleton,  the hip bones, and the epiphyses of long bones such  as the humerus and femur.    three-dimensional view of spongy  bone and compact bone of the  epiphysis. (c) Cross section of the shaft  (diaphysis). Note that the external    surface of the diaphysis is covered by  a periosteum but that the articular  surface of the epiphysis (see a and b)  is covered with hyaline cartilage.    Even when looking casually at bones, you can  see that their surfaces are not smooth but scarred  with bumps, holes, and ridges. These bone  markings (described and illustrated in Table 5.1 on  p. 156) reveal where muscles, tendons, and liga-  ments attach and where blood vessels and nerves  pass. There are two categories of bone markings:  (a) projections, or processes, which grow out from the  bone surface, and (b) depressions, or cavities, which    Very large, blunt,  irregularly shaped  process (the only  examples are on the  femur)    Furrow  Narrow, slitlike opening  Round or oval opening through a bone    Cavity within a bone, filled with air and  lined with mucous membrane    Shallow, basinlike depression in a bone,  often serving as an articular surface    are indentations in the bone. There is a little trick for  remembering some of the bone markings listed in  the table: All the terms beginning with T are  projections, and the terms beginning with F (except  facet) are depressions.    The appearance of spongy bone and compact bone  to the naked eye only hints at their underlying  complexity. Under a microscope, you can see that  spongy bone is composed of small needlelike pieces  of bone called trabeculae and lots of “open” space  filled by marrow, blood vessels and nerves  (Figure 5.4a, p. 158).   In compact bone, the mature bone cells,  osteocytes (os’te-o-sitz”), are found within the  bone matrix in tiny cavities called lacunae  (lah-ku'ne). The lacunae are arranged in concentric  circles called lamellae (lah-mel’e) around central  canals (also called Haversian canals). Each com-  plex consisting of a central canal and matrix rings is  called an osteon, or Haversian system, and is the  structural and functional unit of compact bone.  Central canals run lengthwise through the bony  matrix, carrying blood vessels and nerves to all areas  of the bone. Tiny canals, canaliculi (kan"ah-lik’u-li),  radiate outward from the central canals to all lacu-  nae. The canaliculi form a transportation system that  connects all the bone cells to the nutrient supply and  waste removal services through the hard bone  matrix. Because of this elaborate network of canals,  bone cells are well nourished in spite of the hardness  of the matrix, and bone injuries heal quickly. The  communication pathway from the outside of the  bone to its interior (and the central canals) is com-  pleted by perforating canals (also called  Volkmann’s canals), which run in the compact  bone at right angles to the shaft (diaphysis) and cen-  tral canals.   Bone is one of the hardest materials in the body,  and although relatively light in weight, it has a  remarkable ability to resist tension and other forces  acting on it. Nature has given us an extremely  strong and exceptionally simple supporting system  that also allows mobility. The calcium salts depos-  ited in the matrix give bone its hardness, which  resists compression. The organic parts (especially  the collagen fibers) provide for bone’s flexibility  and great tensile strength (ability to be stretched  without breaking).    4. What is the anatomical name for the shaft of a long  bone? For its ends?  5. How does the structure of compact bone differ from  the structure of spongy bone?  6. What is the importance of canaliculi?  For answers, see Appendix A.    v Describe briefly the process of bone formation  in the fetus, and summarize the events of bone  remodeling throughout life.    The skeleton is formed from two of the strongest and  most supportive tissues in the body—cartilage and  bone. In embryos, the skeleton is primarily made of  hyaline cartilage, but in young children, most of the  cartilage has been replaced by bone. Cartilage  remains only in isolated areas such as the bridge of  the nose, parts of the ribs, and the joints.   Except for flat bones, which form on fibrous  membranes, most bones develop using hyaline carti-  lage structures as their “models.” This process of  bone formation, or ossification (os"I-fi-ka’shun),  involves two major phases (Figure 5.5, p. 159). First,  the hyaline cartilage model is completely covered  with bone matrix (a bone “collar”) by bone-building  cells called osteoblasts. So, as the embryo develops  into a fetus, for a short period it has cartilage “bones”  enclosed by actual bone matrix. Then, in the fetus,  the enclosed hyaline cartilage model is replaced by  bone, and the center is digested away, opening up a  medullary cavity within the newly formed bone.   By birth or shortly after, most hyaline cartilage  models have been converted to bone except for two  regions—the articular cartilages (that cover the bone  ends) and the epiphyseal plates. In order for bones to  increase in length as the infant grows into a child,  new cartilage is formed continuously on the external  face (joint side) of the articular cartilage and on the  epiphyseal plate surface that faces the bone end (is  farther away from the medullary cavity). At the same  time, the old cartilage abutting the internal face of  the articular cartilage and the medullary cavity is bro-  ken down and replaced by bony matrix (Figure 5.6,  p. 159).   (b) (c)  Figure 5.4 Microscopic structure structural units (osteons) and osteocytes in lacunae (cavities in the  of bone. (a) Diagram of a pie- trabeculae, respectively. (b) Higher matrix). (c) Photo of a cross-sectional  shaped segment of compact and magnification view of part of one view of an osteon.    Figure 5.6 Growth and  remodeling of long bones. The  events on the left depict before  (a) and after (b) the process of    articular cartilages and epiphyseal  plates as the bone grows in length.  The events on the right show bone    before (c) and after (d) long-bone  growth to maintain proper bone  proportions.    Growing bones also widen as they lengthen to  maintain proper proportion. How do they widen?  Simply, osteoblasts in the periosteum add bone  matrix to the outside of the diaphysis as cells called  osteoclasts in the endosteum remove bone from the  inner face of the diaphysis wall, enlarging the med-  ullary cavity (see Figure 5.6). Because these two pro-  cesses occur at about the same rate, the circumference  of the long bone expands, and the bone widens. This  process by which bones increase in diameter is called  appositional growth, and like growth in length, is con-  trolled by hormones. The most important hormones  are growth hormone and, during puberty, the sex hor-  mones. It ends during adolescence, when the epiphy-  seal plates are completely converted to bone.    Many people mistakenly think that bones are lifeless  structures that never change once long-bone growth  has ended. Nothing could be further from the truth;  bone is a dynamic and active tissue. Bones are re-  modeled continually in response to changes in two  factors: (1) the calcium ion level in the blood and  (2) the pull of gravity and muscles on the skeleton.   When the blood calcium ion level drops below  its homeostatic level, the parathyroid glands (located  in the throat) are stimulated to release parathyroid  hormone (PTH) into the blood. PTH activates  osteoclasts, giant bone-destroying cells in bones, to  break down bone matrix and release calcium ions  into the blood. When the blood calcium ion level is  too high (hypercalcemia [hi'per-kal-se’me-ah]), cal-  cium is deposited in bone matrix as hard calcium  salts by osteoblasts.   Bone remodeling is essential if bones are to  retain normal proportions and strength during long-  bone growth as the body increases in size and weight.  It also accounts for the fact that bones become  thicker and form large projections to increase their  strength in areas where bulky muscles are attached.  At such sites, osteoblasts lay down new matrix and  become trapped within it. (Once they are trapped,  they become osteocytes, or mature bone cells.) In con-  trast, the bones of bedridden or physically inactive  people tend to lose mass and to atrophy because  they are no longer subjected to stress.   These two controlling mechanisms—calcium  uptake and release as well as bone remodeling—  work together. PTH determines when bone is to be  broken down or formed in response to the need for  more or fewer calcium ions in the blood. The stresses    of muscle pull and gravity acting on the skeleton  determine where bone matrix is to be broken down  or formed so that the skeleton can remain as strong  and vital as possible.    Homeostatic J  K Imbalance 5.1  Rickets is a disease of children in which the bones  fail to calcify. As a result, the bones soften, and the  weight-bearing bones of the legs become bowed.  Rickets is usually due to a lack of calcium in the diet  or lack of vitamin D, which is needed to absorb cal-  cium into the bloodstream. Rickets is not seen very  often in the United States. Milk, bread, and other  foods are fortified with vitamin D, and most chil-  dren drink enough calcium-rich milk. However, it  can happen in infants nursed by mothers who  become vitamin D deficient, and it remains a prob-  lem in some other parts of the world.    This child suffering from rickets is a member of the el-Molo  tribe in Kenya, whose diet consists primarily of fish.   8. Which stimulus—PTH (a hormone) or mechanical  forces acting on the skeleton—is more important in  maintaining levels of calcium ions in the blood than  in maintaining bone strength?   9. If osteoclasts in a long bone are more active than  osteoblasts, what change in bone mass is likely to  occur?    must be prepared to spend a lot of  time on their feet and to think  quickly. Regalado described one case  when a two-car accident sent five   and her coworkers  operate X-ray equip-  ment and must be  ready to do every-  thing from preparing  patients for chest  X-ray exams to MRIs.   Fortunately for  Regalado, anatomy  was her favorite  class, because it’s an  important one for  radiologic technolo-  gists. After getting  her associate's  degree in diagnostic  imaging, she com-  pleted both state  and national  certifications.    Homeostatic B  —S Imbalance 5.2  For their relatively low mass, bones are amazingly  strong. Consider, for example, the forces endured in  football and professional hockey. Despite their  remarkable strength, bones are susceptible to  fractures, or breaks, throughout life. During youth,  most fractures result from exceptional trauma that  twists or smashes the bones. Sports activities such as  football, skating, and skiing jeopardize the bones,  and automobile accidents certainly take their toll. In    Learn more at Mastering A&P > Study Area >  Additional Study Tools > Focus on Careers    In a hospital setting, radiologic  technologists are needed 24 hours a  day and often are required to be on-  call in addition to their regular shifts.  Technologists who work in clinics  usually have a more traditional  9-to-5 schedule. Depending on the  clinic, these technologists may also  specialize in areas such as ultra-  sound, mammography, magnetic reso-  nance imaging (MRI), or computed    children to the  trauma unit. The  radiologic tech-  nologists had to  work quickly to  help the doctors  see what injuries    up anyone's  X-ray exams. e Radiologic technologists operate  “You don’t X-ray, MRI, CT, ultrasound, and    closely with patients from many  different departments in a hospi-  tal setting.    old age, bones thin and weaken, and fractures occur  more often.   A fracture in which the bone breaks cleanly but  does not penetrate the skin is a closed (or simple) frac-  ture. When the broken bone ends penetrate through  the skin, the fracture is open (or compound). Some of  the many common types of fractures are illustrated  and described in Table 5.2, p. 162.    A fracture is treated by reduction, which is the  realignment of the broken bone ends, followed by  immobilization. In a closed reduction, the bone ends  are coaxed back into their normal position by the  physician’s hands. In an open reduction, surgery is  performed, and the bone ends are secured together   with pins or wires. After the broken bone is reduced, external masses of repair tissue, which collec-   ple fracture is 6 to 8 weeks but is much longer for luses, originate from cells of the endosteum and   large bones and for the bones of older people periosteum, respectively, and contain several   © A fibrocartilage callus forms. Two early events weeks to months, depending on the bone’s size  of tissue repair are the growth of new capillaries and site of the break, the bony callus is remod-  (granulation tissue) into the clotted blood at the eled in response to the mechanical stresses  site of the damage and disposal of dead tissue placed on it, so that it forms a strong, perma-  by phagocytes. As this goes on, connective nent “patch” at the fracture site.    Did You Get It?  10. What is a fracture? What two fracture types are  particularly common in older people?  For the answer, see Appendix A.    As noted earlier, the skeleton is divided into two  parts, the axial and appendicular skeletons. The axial  skeleton forms the longitudinal axis of the body (it  is shown as the green portion of Figure 5.8). It can be  divided into three parts—the skull, the vertebral col-  umn, and the thoracic cage.    (look back at Figure 1.4, p. 35). Many of these terms  can be associated with a bone name or group of bones.  For example, the carpal region is the location of the car-  pals, or wrist bones.    vw On a skull or diagram, identify and name the  bones of the skull and the four major skull  sutures.    The skull is formed by two sets of bones. The  cranium encloses and protects the fragile brain  tissue. The facial bones form a cradle for the eyes    that is open to the anterior and allow the facial mus-  cles to show our feelings through smiles or frowns.  All but one of the bones of the skull are joined  together by sutures, which are interlocking, immov-  able joints. Only the mandible (jawbone) is attached  to the rest of the skull by a freely movable joint.    The boxlike cranium is composed of eight large flat  bones. Except for two sets of paired bones (the  parietal and temporal), they are all single bones.    E Frontal Bone The frontal bone forms the fore-  head, the bony projections under the eyebrows, and  the superior part of each eye’s orbit (Figure 5.9, p. 166).    | Parietal Bones The paired parietal bones form  most of the superior and lateral walls of the cra-  nium (see Figure 5.9). The sagittal suture is formed  at the midline where the two parietal bones  meet (shown in Figure 5.12, p. 169), and the  coronal suture is formed where the paired parietal  bones meet the frontal bone.   e The external acoustic meatus is a canal that  leads to the eardrum and the middle ear. It is the  route by which sound enters the ear.    Figure 5.8 The human skeleton. The bones of the axial skeleton are colored  green. Bones of the appendicular skeleton are gold.    e The styloid process, a sharp, needlelike pro-  jection, is just inferior to the external auditory  meatus. Many neck muscles use the styloid pro-  cess as an attachment point.   e The zygomatic (zi’go-mat’ik) process is a thin  bridge of bone that joins with the cheekbone  (zygomatic bone) anteriorly.    e The mastoid (mas’toid) process, which is full  of air cavities (the mastoid sinuses), is a rough  projection posterior and inferior to the external  acoustic meatus. It provides an attachment site  for some muscles of the neck.   The mastoid sinuses are so close to the mid-  dle ear—a high-risk spot for infections—that  they may become infected too, a condition  called mastoiditis. Also, this area is so close to the  brain that mastoiditis may spread to the brain.    e The jugular foramen, at the junction of the  occipital and temporal bones (Figure 5.10),  allows passage of the jugular vein, the largest vein  of the head, which drains blood from the brain.  Just anterior to it in the cranial cavity is the  internal acoustic meatus (see Figure 5.10),  which transmits cranial nerves VII and VIII (the    facial and vestibulocochlear nerves). Anterior to  the jugular foramen on the skull’s inferior aspect  is the carotid canal (see Figure 5.11), through  which the internal carotid artery runs, supplying  blood to most of the brain.    a Occipital Bone The occipital (ok-sip’i-tal) bone  is the most posterior bone of the cranium  (Figure 5.11). It forms the base and back wall of the  skull. The occipital bone joins the parietal bones  anteriorly at the lambdoid (lam'doyd) suture (see  Figure 5.9). In the base of the occipital bone is a  large opening, the foramen magnum (literally,  “large hole”). The foramen magnum surrounds the  lower part of the brain and allows the spinal cord to  connect with the brain. Lateral to the foramen mag-  num on each side are the rockerlike occipital  condyles (see Figure 5.11), which rest on the first  vertebra of the spinal column.    |_| Sphenoid Bone The butterfly-shaped sphenoid  (sfe’noid) bone spans the width of the skull and  forms part of the floor of the cranial cavity (see  Figure 5.10). In the midline of the sphenoid is a    small depression, the sella turcica (sel’ah tur’si-kah),  or Turk’s saddle, which forms a snug enclosure for the  pituitary gland. The foramen ovale, a large oval  opening in line with the posterior end of the sella  turcica (see Figure 5.10), allows fibers of cranial  nerve V (the trigeminal nerve) to pass to the chewing  muscles of the lower jaw (mandible). Parts of the  sphenoid bone, seen exteriorly forming part of the  eye orbits (Figure 5.12), have two important open-  ings, the optic canal, which allows the optic nerve to  pass to the eye, and the slitlike superior orbital fis-  sure, through which the cranial nerves controlling  eye movements (III, IV, and VI) pass (see Figure  5.12). The central part of the sphenoid bone is rid-  dled with air cavities, the sphenoidal sinuses  (Figure 5.13, p. 170).    |_| Ethmoid Bone The ethmoid (eth’moid) bone  is very irregularly shaped and lies anterior to the  sphenoid (see Figure 5.10). It forms the roof of  the nasal cavity and part of the medial walls of the  orbits. Projecting from its superior surface is the  crista galli (kris’tah gah'le), literally “cock's comb”  (see Figure 5.10). The outermost covering of the  brain attaches to this projection. On each side of  the crista galli are many small holes. These holey  areas, the cribriform (krib’ri-form) plates, allow  nerve fibers carrying impulses from the olfactory  (smell) receptors of the nose to reach the brain.  Extensions of the ethmoid bone, the superior  nasal conchae (kong’ke) and middle nasal con-  chae, form part of the lateral walls of the nasal cav-  ity (see Figure 5.12).    Fourteen bones make up the face. Twelve are paired;  only the mandible and vomer are single. (Figures 5.9  and 5.12 show most of the facial bones.)    E maxillae The two maxillae (mak-si'le), or  maxillary bones, fuse to form the upper jaw. All  facial bones except the mandible join the maxillae;  thus they are the main, or “keystone,” bones of  the face. The maxillae carry the upper teeth in the  alveolar process.   Extensions of the maxillae called the palatine  (pal’ah-tin) processes form the anterior part of the  hard palate of the mouth (see Figure 5.11). Like  many other facial bones, the maxillae contain  sinuses, which drain into the nasal passages (see    Figure 5.13). These paranasal sinuses, whose nam-  ing reveals their position surrounding the nasal cav-  ity, lighten the skull bones and amplify the sounds  we make as we speak.    Homeostatic J  —S Imbalance 5.3  The paranasal sinuses cause many people a great  deal of misery. Because the mucosa lining these  sinuses is continuous with that in the nose and  throat, infections in these areas tend to migrate into  the sinuses, causing sinusitis. Depending on which  sinuses are infected, a headache or upper jaw pain is  the usual result.    Palatine Bones The paired palatine bones lie  posterior to the palatine processes of the maxillae.  They form the posterior part of the hard palate (see  Figure 5.11). Failure of these or the palatine pro-  cesses to fuse medially results in cleft palate.    (| Zygomatic Bones The zygomatic bones are  commonly referred to as the cheekbones. They also  form a good-sized portion of the lateral walls of the  orbits.    Wi tacrimal Bones The lacrimal (lak’ri-mal) bones  are fingernail-sized bones forming part of the medial  wall of each orbit. Each lacrimal bone has a groove  that serves as a passageway for tears (lacrima = tear).    E vasal Bones The small rectangular bones form-  ing the bridge of the nose are the nasal bones. (The  lower part of the skeleton of the nose is made up of  hyaline cartilage.)    m Vomer Bone The single bone in the median  line of the nasal cavity is the vomer. (Vomer means  “plow,” which refers to the bone’s shape.) The vomer  forms the inferior part of the bony nasal septum,  which separates the two nostrils.    E inferior Nasal Conchae The inferior nasal con-  chae (kon’ke) are thin, curved bones projecting  medially from the lateral walls of the nasal cavity.  (As mentioned earlier, the superior and middle con-  chae are similar but are parts of the ethmoid bone.)    Figure 5.14 Anatomical location and structure of  the hyoid bone. Anterior view.    a) Anterior view  (a) mandible with the temporal bone. The lower teeth    lie in alveoli (sockets) in the alveolar process at the  superior edge of the mandibular body. The mental  foramen in the mandibular body allows blood ves-  sels and nerves to pass.    Though not really part of the skull, the hyoid  (hi’oid) bone (Figure 5.14) is closely related to the  mandible and temporal bones. The hyoid bone is  unique in that it is the only bone of the body that  does not articulate (form a joint) with any other  bone. Instead, it is suspended in the midneck region  about 2 cm (1 inch) above the larynx (voicebox),  where it is anchored by ligaments to the styloid pro-  cesses of the temporal bones. Horseshoe-shaped,  with a body and two pairs of horns, the hyoid bone  serves as a movable base for the tongue and as an  attachment point for neck muscles that raise and  lower the larynx when we swallow and speak.    Figure 5.13 Paranasal sinuses. Did You Get It?  11. What are the three main parts of the axial  skeleton?  || Mandible The mandible, or lower jaw, is the 12. Johnny was vigorously exercising the only joints in    largest and strongest bone of the face. It joins the guess he was doing?   temporal bones on each side of the face, forming 13. Which skull bone(s) form the “keystone of the  the only freely movable joints in the skull. You can face"?   find these joints on yourself by placing your fingers 14. Which bone has the cribriform plate and crista  just anterior to your ears and opening and closing galli?    15. Which bones are connected by the coronal suture?  By the sagittal suture?  For answers, see Appendix A.    your mouth. The horizontal part of the mandible  (the body) forms the chin. Two upright bars of bone  (the rami) extend from the body to connect the    v@ Name the parts of a typical vertebra, and explain  in general how the cervical, thoracic, and lumbar  vertebrae differ from one another.    1# Explain how the abnormal spinal curvatures (scoliosis,  lordosis, and kyphosis) differ from one another.    Serving as the axial support of the body, the vertebral  column, or spine, extends from the skull, which it  supports, to the pelvis, where it transmits the weight of  the body to the lower limbs. Some people think of the  vertebral column as a rigid supporting rod, but that  picture is inaccurate. Instead, the spine is formed from  26 irregular bones connected and reinforced by liga-  ments in such a way that a flexible, curved structure  results (Figure 5.15). Running through the central cav-  ity of the vertebral column is the delicate spinal cord,  which the vertebral column surrounds and protects.   Before birth, the spine consists of 33 separate  bones called vertebrae, but 9 of these eventually fuse  to form the two composite bones, the sacrum and  the coccyx, that construct the inferior portion of the  vertebral column. Of the 24 single bones, the 7 verte-  brae of the neck are cervical vertebrae, the next 12 are  the thoracic vertebrae, and the remaining 5 supporting  the lower back are lumbar vertebrae. Remembering  common meal times, 7 a.m., 12 noon, and 5 p.m.,  may help you to recall the number of bones in these  three regions of the vertebral column.   The individual vertebrae are separated by pads of  flexible fibrocartilage—intervertebral discs—that  cushion the vertebrae and absorb shock while allow-  ing the spine flexibility. In a young person, the discs  have a high water content (about 90 percent) and are  spongy and compressible. But as a person ages, the  water content of the discs decreases (as it does in  other tissues throughout the body), and the discs  become harder and less compressible.    Homeostatic J  £ Imbalance 5.4  Drying of the discs, along with a weakening of the  ligaments of the vertebral column, predisposes older  people to herniated (“slipped”) discs. However,  herniation also may result when the vertebral col-  umn is subjected to exceptional twisting forces. If the  protruding disc presses on the spinal cord or the spi-  nal nerves exiting from the cord, numbness and  excruciating pain can result.    Figure 5.15 The vertebral column. Thin discs  between the thoracic vertebrae allow great flexibility in  the thoracic region; thick discs between the lumbar  vertebrae reduce flexibility. Notice that the terms convex  and concave refer to the curvature of the posterior  aspect of the vertebral column.    The discs and the S-shaped structure of the verte-  bral column work together to prevent shock to the  head when we walk or run. They also make the body    trunk flexible. The spinal curvatures in the thoracic  and sacral regions are referred to as primary  curvatures because they are present when we are  born. Together the two primary curvatures produce  the C-shaped spine of the newborn baby (Figure 5.16).  The curvatures in the cervical and lumbar regions are  referred to as secondary curvatures because they  develop some time after birth. In adults, the second-  ary curvatures allow us to center our body weight on  our lower limbs with minimum effort. The cervical  curvature appears when a baby begins to raise its  head, and the lumbar curvature develops when the  baby begins to walk.    Homeostatic J  —S~ Imbalance 5.5  Were you ever given a “spine check” in middle  school? There are several types of abnormal spinal  curvatures that can be identified by simple observa-  tion. Three of these are scoliosis (sko”le-o’sis),  kyphosis (ki-fo’sis), and lordosis (lor-do’sis).  These spinal abnormalities may be congenital  (present at birth) or may result from disease, poor  posture, unequal muscle pull on the spine, or  injury. Generally, unless there is a congenital  problem, young healthy people have no skeletal  problems, assuming that their diet is nutritious and  they stay reasonably active. As you look at these  photos, try to pinpoint how each of these condi-  tions differs from a normal healthy spine. The usual  treatments for these abnormal curvatures are braces,  casts, or surgery.    All vertebrae have a similar structural pattern  (Figure 5.17). The common features of vertebrae  include the following:    e Body, or centrum: disclike, weight-bearing part  of the vertebra facing anteriorly in the vertebral  column.    e Vertebral arch: arch formed from the joining  of all posterior extensions, the laminae and  pedicles, from the vertebral body.   e Spinous process: single projection arising from  the posterior aspect of the vertebral arch (actu-  ally the fused laminae).    e Superior articular process and inferior  articular process: paired projections lateral to  the vertebral foramen, allowing a vertebra to  form joints with adjacent vertebrae.    In addition to these common features, vertebrae  in the different regions of the spine have very specific  structural characteristics, which we describe next.    The seven cervical vertebrae (identified as C, to C7)  form the neck region of the spine. The first two verte-  brae (atlas and axis) are different because they per-  form functions not shared by the other cervical  vertebrae. As you can see in Figure 5.18a on p. 174,  the atlas (C,) has no body. The superior surfaces of    Figure 5.17 A typical vertebra, superior view.  (Inferior articulating surfaces are not shown.)    its transverse processes contain large depressions that  receive the occipital condyles of the skull. This joint  allows you to nod “yes.” The axis (C,) acts as a pivot  for the rotation of the atlas (and skull) above. It has a  large upright process, the dens, which acts as the  pivot point. The joint between C, and C, allows you  to rotate your head from side to side to indicate “no.”  The “typical” cervical vertebrae are C3 through  C; (Figure 5.18b). They are the smallest, lightest ver-  tebrae, and most often their spinous processes are  short and divided into two branches. The transverse  processes of the cervical vertebrae contain foramina  (openings) through which the vertebral arteries pass  on their way to the brain above. Any time you see  these foramina in a vertebra, you should know  immediately that it is a cervical vertebra.    The 12 thoracic vertebrae (T; to T,,) are all typical.  They are larger than the cervical vertebrae and are  distinguished by the fact that they are the only verte-  brae to articulate with the ribs. The body is some-  what heart-shaped (dotted line in Figure 5.18c) and  has two costal facets (articulating surfaces) on each  side, which receive the heads of the ribs. The trans-  verse processes of each thoracic vertebra articulate  with the knoblike tubercles of the ribs. The spinous  process is long and hooks sharply downward,    causing the vertebra to look like a giraffe’s head  viewed from the side.    The five lumbar vertebrae (L, to L;) have massive,  blocklike bodies that are shaped somewhat like a  kidney bean (dotted line in Figure 5.18d). Their  short, hatchet-shaped spinous processes make them  look like a moose head from the lateral aspect.  Because most of the stress on the vertebral column  occurs in the lumbar region, these are the sturdiest of  the vertebrae.    The sacrum (sa’krum) is formed by the fusion of five  vertebrae (Figure 5.19, p. 175). Superiorly it articu-  lates with L;, and inferiorly it connects with the coc-  cyx. Each winglike ala articulates laterally (at the  auricular surface) with the hip bone, forming a sacro-  iliac joint. The sacrum forms the posterior wall of the  pelvis. Its posterior midline surface is roughened by  the median sacral crest, the fused spinous processes  of the sacral vertebrae. This is flanked laterally by the  posterior sacral foramina. The vertebral canal continues  inside the sacrum as the sacral canal and terminates  in a large inferior opening called the sacral hiatus.    The coccyx is formed from the fusion of three to five  tiny, irregularly shaped vertebrae (see Figure 5.19). It  is the human “tailbone,” a remnant of the tail that  other vertebrate animals have.    5.2c Thoracic Cage  Learning Objectives  vz Name the components of the thoracic cage.  1# Describe how a true rib differs from a false rib.    The sternum, ribs, and thoracic vertebrae make up the  bony thorax (Figure 5.20, p. 176). The bony thorax  is routinely called the thoracic cage because it forms  a protective cage of slender bones and cartilages  around the organs of the thoracic cavity (heart,  lungs, and major blood vessels).    The sternum (breastbone) is a typical flat bone  and the result of the fusion of three bones—the  manubrium (mah-nu’bre-um), body, and xiphoid  (zif’oid) process. It is attached directly to the first  seven pairs of ribs via costal cartilages.    Figure 5.18 Regional characteristics of vertebrae. (The types of vertebrae are  not shown to scale with respect to one another.)    The sternum has three important bony land-  marks—the jugular notch, the sternal angle, and the  xiphisternal joint.    e The jugular notch (concave upper border  of the manubrium) can be palpated easily;  generally it is at the level of the third thoracic  vertebra.    e The sternal angle results where the manubrium  and body meet at a slight angle to each other, so  that a transverse ridge is formed at the level of the  second ribs. It provides a handy reference point  for counting ribs to locate the second intercostal  space for listening to certain heart valves. To clar-  ify the location of these structures, you can pal-  pate your own sternal angle and jugular notch.    e The xiphisternal (zi'fe-ster’nal) joint, the point  where the sternal body and xiphoid process fuse,  lies at the level of the ninth thoracic vertebra.    Because the sternum is so close to the body sur-  face, it is easy to obtain samples from it of blood-  forming (hematopoietic) tissue for the diagnosis of  suspected blood diseases. A needle is inserted into the  marrow of the sternum, and the sample is withdrawn;  this procedure is called a sternal puncture. Because the  heart lies immediately posterior to the sternum, the  physician must take extreme care not to penetrate  beyond the sternum during this procedure.   Twelve pairs of ribs form the walls of the bony thorax.  All the ribs articulate with the vertebral column poste-  riorly and then curve downward and toward the ante-  rior body surface. The true ribs, the first seven pairs,  attach directly to the sternum by costal cartilages.  False ribs, the next five pairs, either attach indirectly  to the sternum or are not attached to the sternum at  all. The last two pairs of false ribs lack the sternal  attachments, so they are also called floating ribs.   The intercostal spaces (spaces between the ribs)  are filled with the intercostal muscles, which aid in  breathing.    16. What are the five major regions of the vertebral  column?   17. How can you distinguish a lumbar vertebra from a  cervical vertebra?   19. Besides the ribs and sternum, there is a third group  of bones forming the thoracic cage. What is it?   22. How does the shape of a newborn baby’s spine  differ from that of an adult?    Learning Objectives  4# Identify on a skeleton or diagram the bones of the  shoulder and pelvic girdles and their attached limbs.    v@ Describe important differences between a male  and a female pelvis.    The appendicular skeleton (shaded gold in Figure 5.8)  is composed of 126 bones of the limbs (appendages)  and the pectoral and pelvic girdles, which attach the  limbs to the axial skeleton.    ribs (11, 12)  (a)  Figure 5.20 The bony thorax (thoracic cage).    Each pectoral girdle, or shoulder girdle, consists  of two bones—a clavicle and a scapula (Figure 5.21a).   The paired clavicles (klav'ï-kulz), or collarbones,  are slender, doubly curved bones (Figure 5.21b).  Each clavicle attaches to the manubrium of the ster-  num medially (at its sternal end) and to the scapula  laterally, where it helps to form the shoulder joint.  The clavicle acts as a brace to hold the arm away  from the top of the thorax and helps prevent shoul-  der dislocation. When the clavicle is broken, the  whole shoulder region caves in medially, which  shows how important its bracing function is.   The paired scapulae (skap’u-le), or shoulder  blades, are commonly called “wings” because they  flare when we move our arms posteriorly. The scap-  ulae are not directly attached to the axial skeleton  (see Figure 5.21a); they are loosely held in place by  trunk muscles. Each triangular scapula has a flat-  tened body with three borders—superior, medial    (vertebral), and lateral (axillary) (Figure 5.21c). It  also has three angles—superior, inferior, and lat-  eral. The glenoid cavity, a shallow socket that  receives the head of the arm bone, is in the lateral  angle (Figure 5.21d). The scapula has two impor-  tant processes—the acromion (ah-kro’me-on),  which is the enlarged lateral end of the spine of the  scapula, and the beaklike coracoid (kor'ah-koid)  process. The acromion connects with the clavicle  laterally at the acromioclavicular joint. The cora-  coid process points laterally over the top of the  shoulder and anchors some of the muscles of  the arm. Just medial to the coracoid process is the  large suprascapular notch, which is a nerve  passageway.   The shoulder girdle is very light and allows the  upper limb exceptionally free movement. This is due  to the following factors:    , , , Coracoid  (a) Articulated right shoulder (pectoral) girdle process    (c) Right scapula, posterior aspect Figure 5.21 Bones of the shoulder girdle.    e The loose attachment of the scapula allows it  to slide back and forth against the thorax as  muscles act.    e The glenoid cavity is shallow, and the shoulder  joint is poorly reinforced by ligaments.    However, this exceptional flexibility also has a draw-  back; the shoulder girdle is very easily dislocated.    The arm is formed by a single bone, the humerus  (hu’mer-us), which is a typical long bone  (Figure 5.22a and b). At its proximal end is a  rounded head that fits into the shallow glenoid cav-  ity of the scapula. Immediately inferior to the head  is a slight constriction called the anatomical neck.  Anterolateral to the head are two bony projections  separated by the intertubercular sulcus—the  greater tubercle and lesser tubercle, which are  sites of muscle attachment. Just distal to the tuber-  cles is the surgical neck, so named because it is the  most frequently fractured part of the humerus. In  the midpoint of the shaft is a roughened area called  the deltoid tuberosity, where the large, fleshy del-  toid muscle of the shoulder attaches. Nearby, the  radial groove runs obliquely down the posterior  aspect of the shaft. This groove marks the course of  the radial nerve, an important nerve of the upper  limb. At the distal end of the humerus is the medial  trochlea (trok’le-ah), which looks somewhat like  a spool, and the lateral ball-like capitulum  (kah-pit’u-lum), which can be “outlined” with a  “C” from the anterior view. Both of these processes  articulate with bones of the forearm. Above the  trochlea anteriorly is a depression, the coronoid  fossa; on the posterior surface is the olecranon  (o-lek’rah-non) fossa. These two depressions,  which are flanked by the medial epicondyle and  lateral epicondyle, allow the corresponding pro-  cesses of the ulna to move freely when the elbow is  bent and extended.    Two bones, the radius and the ulna, form the skeleton  of the forearm (Figure 5.22c). When the body is in  the anatomical position, the radius is the lateral    bone; that is, it is on the thumb side of the forearm.  When the hand is rotated so that the palm faces  backward, the distal end of the radius crosses over  and ends up medial to the ulna. Both proximally  and distally the radius and ulna articulate at small  radioulnar joints, and the two bones are connected  along their entire length by the flexible interosseous  membrane. Both the ulna and the radius have a  styloid process at their distal end.   The disc-shaped head of the radius also forms a  joint with the capitulum of the humerus. Just below  the head is the radial tuberosity, where the tendon  of the biceps muscle attaches.   When the upper limb is in the anatomical posi-  tion, the ulna is the medial bone (on the little-finger  side) of the forearm. On its proximal end are the ante-  rior coronoid process and the posterior olecranon,  which are separated by the trochlear notch. Together  these two processes grip the trochlea of the humerus  in a curved “tongue-in-groove” -like joint.    The skeleton of the hand consists of the carpals,  the metacarpals, and the phalanges (fah-lan’jéz)  (Figure 5.23, p. 180). The eight carpal bones,  arranged in two irregular rows of four bones each,  form the part of the hand called the carpus, or the  wrist. The carpals are bound together by ligaments  that restrict movements between them.   The palm of the hand consists of the  metacarpals. The metacarpals are numbered 1 to 5  from the thumb side of the hand toward the little  finger. When the fist is clenched, the heads of the  metacarpals become obvious as the “knuckles.” The  phalanges are the bones of the fingers. Each hand  contains 14 phalanges. There are three in each finger  (proximal, middle, and distal), except in the thumb,  which has only two (proximal and distal).    23. Contrast the general function of the axial skeleton  to that of the appendicular skeleton.   24. What is the single point of attachment of the  shoulder girdle to the axial skeleton?   26. Where are the carpals found, and what type (long,  short, irregular, or flat) of bone are they?   27. Which bones of the upper limb have a styloid  process?    Figure 5.22 Bones of the right arm and forearm. (a) Humerus, anterior view.  (b) Humerus, posterior view. (c) Anterior view of the bones of the forearm: the   The pelvic girdle is formed by two coxal (kok’sal)  bones, commonly called hip bones, and the sacrum  (described on p. 173). Together with the coccyx, the  pelvic girdle forms the pelvis (Figure 5.24a, p. 181).  Note that the terms pelvic girdle (the coxal bones and  the sacrum) and pelvis (the coxal bones, sacrum, and  coccyx) have slightly different meanings.    The bones of the pelvic girdle are large and heavy,  and they are attached securely to the axial skeleton via  the sacral attachment to the L; lumbar vertebra. The  sockets, which receive the thigh bones, are deep and  heavily reinforced by ligaments that attach the limbs  firmly to the girdle. Bearing weight is the most impor-  tant function of this girdle because the total weight of  the upper body rests on the pelvis. The reproductive    organs, urinary bladder, and part of the large intestine  lie within and are protected by the pelvis.   Each hip bone is formed by the fusion of three  bones: the ilium, ischium, and pubis (Figure 5.24b).  The ilium (il’e-um), which connects posteriorly with  the sacrum at the sacroiliac (sak"ro-il’e-ac) joint, is  a large, flaring bone that forms most of the hip bone  (imagine a peacock’s fanned tail feathers). When you  put your hands on your hips, they are resting over the  alae, or winglike portions, of the ilia. The upper edge  of an ala, the iliac crest, is an important anatomical  landmark that is always kept in mind by those who  give intramuscular injections. The iliac crest ends  anteriorly in the anterior superior iliac spine and  posteriorly in the posterior superior iliac spine.  Small inferior spines are located below these.   Another important structural feature of the  ilium is the greater sciatic notch, which allows  blood vessels and the large sciatic nerve to pass from  the pelvis posteriorly into the thigh. Injections in the  buttock should always be given well away from this  area to avoid possible nerve damage.   The ischium (is’ke-um) is the “sit-down bone,” so  called because it forms the most inferior part of the  coxal bone. The ischial tuberosity is a roughened  area that receives body weight when you are sitting.  The ischial spine, superior to the tuberosity, is another  important anatomical landmark, particularly in the  pregnant woman, because it narrows the outlet of the  pelvis through which the baby must pass during birth.    The pubis (pu’bis) is the most anterior and infe-  rior part of a coxal bone. Fusion of the rami of the pubis  anteriorly and the ischium posteriorly forms a bar of  bone enclosing the obturator (ob’tu-ra’tor) foramen,  an opening that allows blood vessels and nerves to pass  into the anterior part of the thigh. The pubic bones of  each hip bone articulate anteriorly to form a cartilagi-  nous joint, the pubic symphysis (pu’bik sim’ fi-sis).   The ilium, ischium, and pubis fuse at the deep  socket called the acetabulum (as’é-tab’u-lum),  which means “vinegar cup.” The acetabulum receives  the head of the thigh bone.   Before we discuss pelvic features, we want to  acknowledge that while our understanding of genders  is evolving, for the purposes of this discussion of pelvis  anatomy, we will refer to his and her pelves. The bony  pelvis is divided into two regions. The false pelvis is  superior to the true pelvis; it is the area medial to the  flaring portions of the ilia. The true pelvis is sur-  rounded by bone and lies inferior to the flaring parts of  the ilia and the pelvic brim (Figure 5.24c). The dimen-  sions of the true pelvis for women who want to bear  children are very important because they must be large  enough to allow the infant's head (the largest part of  the infant) to pass during childbirth. The dimensions  of the cavity, particularly the outlet (the inferior open-  ing of the pelvis measured between the ischial spines)  and the inlet (superior opening between the right and  left sides of the pelvic brim), are critical, and they are  carefully measured by the obstetrician.   Of course, individual pelvic structures vary, but  there are fairly consistent differences between a male  and a female pelvis, including the following charac-  teristics (see Figure 5.24c):   e The female pelvis as a whole is shallower, and  the bones are lighter and thinner.   e The female ischial spines are shorter and farther  apart; thus, the outlet is larger.    e The female pubic arch is more rounded because  the angle of the pubic arch is greater.    28. What three bones form the hip bone? What bones  form each pelvic girdle?  29. Describe three ways the bony pelvis of a woman  differs from that of a man.  For answers, see Appendix A.    Coxal bone  (or nippone) Pelvic brim  Pubis >; 7 Ischial spine  = Acetabulum  f eal l= í .  Ischium > 4 k Pubic symphysis  : | |  Pubic arch  (a)  Ilium Inlet of  true  , pelvis  Posterior Iliac crest  superior j dD L  iliac Anterior superior "ij Pelvic brim  spine iliac spine i  Posterior Se eee Du pii arch  inferior Anterior inferior Male pelvis (less than 90°)  iliac spine iliac spine  Greater sciatic Acetabulum False pelvis  notch —  Ischial body :  Body of pubis  Ischial spine Inlet of  Pubis be  Ischial \ : F. pelvis  tuberosity Inferior pubic A aaa T~ Pelvic brim  ischi ramus = 2 s  schium  Obturator bomas Pubic arch  Ischial ramus foramen Female pelvis (more than 90°)    Figure 5.24 The bony pelvis. (a) Articulated pelvis. (b) Coxal (hip) bone, showing  the point of fusion of the ilium, ischium, and pubic bones at the acetabulum.  (c) Comparison of the pelves of the male (above) and female (below).    Figure 5.25 Bones of the right thigh and leg. Anterior view of femur (a).    The lower limbs carry our total body weight when we  are erect. Hence, it is not surprising that the bones  forming the three segments of the lower limbs  (thigh, leg, and foot) are much thicker and stronger  than the comparable bones of the upper limb.   The femur (fe’mur), or thigh bone, is the only bone  in the thigh (Figure 5.25a and b). It is the heaviest,  strongest, and longest bone in the body. Its proximal  end has a ball-like head, a neck, and a greater  trochanter and lesser trochanter (separated ante-  riorly by the intertrochanteric line and posteriorly  by the intertrochanteric crest). These markings    and the gluteal tuberosity, located on the proximal  end of the shaft, all serve as sites for muscle attach-  ment. The head of the femur articulates with the  deep, secure socket of the acetabulum of the hip  bone. However, the surgical neck of the femur is still  a common fracture site, especially in old age.   The femur slants medially as it runs downward  to join with the leg bones; this brings the knees in  line with the body’s center of gravity. The medial  course of the femur is more noticeable in women  because the female pelvis is typically wider than that  of the male. Distally on the femur are the lateral  condyle and medial condyle, which articulate with  the tibia below. Posteriorly these condyles are sepa-  rated by the deep intercondylar fossa. Anteriorly    on the distal femur is the smooth patellar surface,  which forms a joint with the patella, or kneecap.   Connected along their length by an interosseous  membrane, two bones, the tibia and fibula, form the  skeleton of the leg (Figure 5.25c). The tibia, or shin-  bone, is larger and more medial. At the proximal end,  the medial condyle and lateral condyle (separated  by the intercondylar eminence) articulate with the  distal end of the femur to form the knee joint.  The patellar (kneecap) ligament, which encloses the  patella, a sesamoid bone (look ahead to Figure 6.20c  and d on p. 229), attaches to the tibial tuberosity, a  roughened area on the anterior tibial surface.  Distally, a process called the medial malleolus  (mal-le’o-lus) forms the inner bulge of the ankle.  The anterior surface of the tibia is a sharp ridge, the  anterior border, that is unprotected by muscles;  thus, it is easily felt beneath the skin.   The fibula, which lies laterally alongside the  tibia, forms joints with it both proximally and dis-  tally, and is thin and sticklike. The fibula has no part  in forming the knee joint. Its distal end, the lateral  malleolus, forms the outer part of the ankle.    The foot, composed of the tarsals, metatarsals, and  phalanges, has two important functions. It supports  our body weight and serves as a lever that allows us  to propel our bodies forward when we walk and run.   The tarsus, forming the posterior half of  the foot, is composed of seven tarsal bones  (Figure 5.26). Body weight is carried mostly by the  two largest tarsals, the calcaneus (kal-ka’ne-us), or  heel bone, and the talus (ta’lus; “ankle”). The talus  lies superior to the calcaneus, articulates with  the tibia, and allows pointing of the toes. Five  metatarsals form the sole, and 14 phalanges form  the toes. Like the fingers of the hand, each toe has  three phalanges, except the great toe, which has two.   The bones in the foot are arranged to form three  strong arches: two longitudinal (medial and lateral)  and one transverse (Figure 5.27). Ligaments, which  bind the foot bones together, and tendons of the foot  muscles help to hold the bones firmly in the arched  position but still allow a certain amount of give, or  springiness. Weak arches are referred to as “fallen  arches,” or “flat feet.”    30. What two bones form the skeleton of the leg?  31. Which bone allows us to “point our toes”?  32. Which bone of the lower limb has an intertrochan-  teric line and crest and an intercondylar fossa?  For answers, see Appendix A.    Oz 1 million knee and hip joint  replacement surgeries are per-  formed each year, mostly because of  the destructive effects of osteoar-  thritis or rheumatoid arthritis.   The production of durable, mobile  joints requires a substance that is  strong, nontoxic, and resistant to the  corrosive effects of organic acids in  blood and that will not cause an  immune response. The first total hip  replacement using a modern pros-  thetic, was performed in 1963, and  revolutionized the therapy of arthritic  hips. The device consisted of a metal  ball on a stem (the femoral head) and  a cup-shaped polyethylene plastic  socket (the acetabulum) anchored to  the pelvis by bone cement. This  cement proved to be exceptionally  strong and relatively problem free.  Hip prostheses were followed by knee  prostheses (see photos a and b), and  replacements are now available for  most other joints, including shoul-  ders, wrists, fingers, elbows, and  ankles.   Total joint replacements last for  more than 20 years in patients who  do not excessively stress the joint but  may not last as long in younger (age  45 to 60), more active people. Most  such operations are done to reduce  pain and restore joint function.   To overcome the problem of the  prostheses working loose over time,  robot-assisted surgery uses the  information from a CT scan to pre-  cisely drill better-fitting holes.    (b) X-ray image of right knee  showing total knee replacement  prosthesis    Computer-aided design and  manufacturing techniques have  revolutionized the production of  individual joints. The computer draws  from a database of hundreds of healthy  joints, generates possible designs, and  directs the machines that shape them.    J% Learn more at Mastering A&P > Study Area >  Additional Study Tools > A Closer Look    Equally exciting are techniques that  call on the patient's own tissues to  regenerate, such as these three:   e Osteochondral grafting: Healthy  bone and cartilage are removed  from one part of the body and  transplanted to the injured joint.    e Autologous chondrocyte  implantation: Healthy chondro-  cytes are removed from the  body, cultivated in the lab, and  implanted at the damaged joint.    e Stem cell regeneration: Undiffer-  entiated stem cells are removed  from bone marrow and placed  in a gel, which is packed into an  area of eroded cartilage.    These techniques offer hope for  younger patients because they could  stave off the need for a joint  prosthesis.    e Artificial joints are available  to replace most joints of the  limbs.    e Joint prostheses must be  designed carefully to persist in  the body without corrosion or  toxic effects.    e Computer-assisted design and  manufacturing reduce the time  and expense to make artificial  joints.    vz Name the three major structural categories of  joints, and compare the amount of movement  allowed by each.    With one exception (the hyoid bone of the neck),  every bone in the body forms a joint with at least  one other bone. Joints, also called articulations,  are the sites where two or more bones meet. They  have two functions: They hold the bones together  securely but also allow the rigid skeleton to move.   The graceful movements of a ballet dancer and  the rough-and-tumble grapplings of a football player  illustrate the great variety of motion that joints  allow. With fewer joints, we would move like robots.  Nevertheless, the bone-binding function of joints is  just as important as their role in mobility. The  immovable joints of the skull, for instance, form a  snug enclosure for the vital brain.   Joints are classified in two ways—functionally  and structurally. The functional classification focuses  on the amount of movement the joint allows. On this  basis, there are synarthroses (sin’ar-thro’séz), or  immovable joints; amphiarthroses (am’fe-ar-  thro’séz), or slightly movable joints; and diarthroses  (di’ar-thro’séz), or freely movable joints. Immovable  and slightly movable joints are restricted mainly to  the axial skeleton, where firm attachments and pro-  tection of internal organs are priorities. Freely mov-  able joints predominate in the limbs, where mobility  is important.   Structurally, there are fibrous, cartilaginous, and  synovial joints. These classifications are based on  whether fibrous tissue, cartilage, or a joint cavity sep-  arates the bony regions at the joint. As a general rule,  fibrous joints are immovable, and synovial joints are  freely movable. Although cartilaginous joints have  both immovable and slightly movable examples,  most are amphiarthrotic. Because the structural clas-  sification is more clear-cut, we will focus on that  classification scheme here. The joint types are shown  in Figure 5.28 on p. 186 and described next.    clearly, recall the properties of tissues that form the  joints. Fibrous connective tissue contains many collagen    fibers for strength. The three types of cartilage (hyaline,  fibrocartilage, elastic) provide structure with some  degree of flexibility, and fibrocartilage also has the ability  to absorb compressive shock (Chapter 3, pp. 114-115).  Synovial membranes contain areolar connective tissue  and line the joint cavities of synovial joints (Chapter 4,  pp. 129, 131).   In fibrous joints, the bones are united by fibrous  tissue. The best examples of this type of joint are the  sutures of the skull (Figure 5.28a). In sutures, the  irregular edges of the bones interlock and are bound  tightly together by connective tissue fibers, allowing  no movement. Gomphoses (gom-fo'séz), are “peg-in-  socket” fibrous joints that are found where the teeth  meet the facial bones (Figure 5.28b). In another type  of fibrous joint, syndesmoses (sin-dez-mo'séz), the  connecting fibers are longer than those of sutures;  thus the joint has more “give.” The joint connecting  the distal ends of the tibia and fibula is a syndesmo-  sis (Figure 5.28c).   Cartilaginous joints come in two varieties, which  differ in the type of cartilage involved. Synchondroses  are immoveable (synarthrotic) joints linked by  hyaline cartilage. Examples include the epiphyseal  plates of growing long bones and the joints between  ribs 1-7 and the sternum (Figure 5.28d). Symphyses  are amphiarthrotic (slightly moveable) joints linked  by discs of fibrocartilage. Examples include the inter-  vertebral discs of the spinal column and the pubic sym-  physis of the pelvis (Figure 5.28e).    5.4c Synovial Joints  Synovial joints are joints in which the articulating  bone ends are separated by a joint cavity containing  synovial fluid (Figure 5.28f-h). All joints of the  limbs are synovial joints.    e Articular cartilage. Articular (hyaline) carti-  lage covers the ends of the bones forming the  joint.   e Articular capsule. The joint surfaces are  enclosed by a sleeve, or layer, of fibrous con-  nective tissue, which is lined with a smooth  synovial membrane (the reason these joints  are called synovial joints).    Figure 5.28 Types of joints. Joints to the left of the skeleton are fibrous joints  (a-c); joints in the center, above and below the skeleton, are cartilaginous joints  (d-e); and joints to the right of the skeleton are synovial joints (f-h).    = Articular  i capsule  a  Articular  (hyaline)  cartilage  Humerus  (f) Multiaxial joint  (shoulder joint)  Humerus  Articular  (hyaline)  cartilage    How does this joint type differ structurally from  cartilaginous and fibrous joints?    e Joint cavity. The articular capsule encloses a  cavity, called the joint cavity, which contains  lubricating synovial fluid secreted by the  synovial membrane (look back at Chapter 4,  pp. 129, 131).    e Reinforcing ligaments. The fibrous layer of  the capsule is usually reinforced with ligaments.    Bursae and tendon sheaths are not strictly part of  synovial joints, but they are often found closely asso-  ciated with them (see Figure 5.29). Essentially bags  of lubricant, they help cushion and act like ball bear-  ings to reduce friction between adjacent structures  during joint activity. Bursae (ber’se; “purses”) are  flattened fibrous sacs lined with synovial membrane  and containing a thin film of synovial fluid. They are  common where ligaments, muscles, skin, tendons,  or bones rub together. A tendon sheath is essen-  tially an elongated bursa that wraps completely    around a tendon subjected to friction, like a bun  around a hot dog.   The structural joint types are summarized in  Table 5.3, p. 188.    Homeostatic J  —S~ Imbalance 5.6  A dislocation happens when a bone is forced out of  its normal position in the joint cavity. The process of  returning the bone to its proper position, called  reduction, should be done only by a physician.  Attempts by an untrained person to “snap the bone  back into its socket” are usually more harmful than  helpful.   The shapes of the articulating bone surfaces deter-  mine what movements are allowed at a joint. Based  on such shapes, our synovial joints can be classified  as plane, hinge, pivot, condylar (kon'di-ler), saddle, or  ball-and-socket joints. Examples of these types of joints    Bone ends/parts covered  with articular cartilage and  enclosed within an articular  capsule lined with synovial  membrane    are shown in Figure 5.30; the arrows indicate move-  ment around one or more axes in each type.    In a plane joint (Figure 5.30a), the articular  surfaces are essentially flat, and only short  slipping or gliding movements are allowed.  The movements of plane joints are nonaxial;  that is, gliding back and forth does not involve  rotation around any axis. The intercarpal joints  of the wrist are the best examples of plane  joints.   In a hinge joint (Figure 5.30b), the cylindrical  end of one bone fits into a trough-shaped sur-  face on another bone. Angular movement is  allowed in just one plane, like a door hinge.  Examples are the elbow joint, ankle joint, and  the joints between the phalanges of the fin-   In a pivot joint (Figure 5.30c), the rounded end  of one bone fits into a sleeve or ring of bone  (and possibly ligaments). Because the rotating  bone can turn only around its long axis, pivot  joints are also uniaxial joints. To understand the  motion of this type of joint, think about a bas-  ketball player pivoting around one foot that  stays planted in one spot. The proximal radioul-  nar joint and the joint between the atlas and the  dens of the axis are examples.    In a condylar joint (“knucklelike”), the egg-  shaped articular surface of one bone fits into an  oval concavity in another (Figure 5.30d). Both  of these articular surfaces are oval. Condylar  joints allow the moving bone to travel (1) from  side to side and (2) back and forth, but the bone  cannot rotate around its long axis. Movement  occurs around two axes; hence, these joints are  biaxial (bi = two), as in knuckle (metacarpopha-  langeal) joints.   In saddle joints, each articular surface has  both convex and concave areas, like a saddle  for a horse (Figure 5.30e). These biaxial joints  allow essentially the same movements as  condylar joints. The best example of a saddle  joint is the carpometacarpal joint in the  thumb, which is responsible for our oppos-  able thumb.    In a ball-and-socket joint (Figure 5.30f), the  spherical head of one bone fits into the concave  socket in another. These multiaxial joints allow  movement in all axes, including rotation, and  are the most freely moving synovial joints. The  shoulder and hip are examples.    discuss the various types of movements that occur at  synovial joints in detail in the chapter covering the  muscular system (Chapter 6).   (a) Plane joint (intercarpal and intertarsal joints).  (b) Hinge joint (elbow and interphalangeal  joints). (c) Pivot joint (proximal joint between   the radius and the ulna). (d) Condylar joint  (knuckles). (e) Saddle joint (carpometacarpal joint  of the thumb). (f) Ball-and-socket joint (shoulder  and hip joints).    Homeostatic B  £ Imbalance 5.7  Few of us pay attention to our joints unless we expe-  rience joint pain or inflammation. For example, fall-  ing on one’s knee can cause painful bursitis, called  “water on the knee,” due to inflammation of bursae  or a synovial membrane. Sprains and dislocations    are other types of joint problems that result in swell-  ing and pain. A sprain results when the ligaments or  tendons reinforcing a joint are damaged by excessive  stretching or are torn away from the bone. Both ten-  dons and ligaments are cords of dense fibrous con-  nective tissue with a poor blood supply; thus, sprains  heal slowly and can be extremely painful.    Few inflammatory joint disorders cause more  pain and suffering than arthritis. The term arthritis  (arth = joint, itis = inflammation) describes over 100  different inflammatory or degenerative diseases that  damage joints. Globally, in all its forms, arthritis is a  widespread crippling disease. All forms of arthritis  have the same initial symptoms: pain, stiffness, and  swelling of the joint. Then, depending on the spe-  cific form, certain changes in the joint structure  occur.   Acute forms of arthritis usually result from bac-  terial invasion and are treated with antibiotic drugs.  During such an infection, the synovial membrane  thickens and fluid production decreases, leading to  increased friction and pain. Chronic forms of arthri-  tis include osteoarthritis, rheumatoid arthritis, and  gouty arthritis, which differ substantially in their later  symptoms and consequences. We will focus on these  forms here.   Osteoarthritis (OA), the most common form  of arthritis, is a chronic degenerative condition that  typically affects the aged: Thirty six percent of people  aged 75 and over in Australia develop this condition.  OA, also called degenerative joint disease (DJD) or  “wear-and-tear arthritis,” affects the articular carti-  lages. Over the years, the cartilage softens, frays, and  eventually breaks down. As the disease progresses,  the exposed bone thickens, and extra bone tissue,  called bone spurs, grows around the margins of the  eroded cartilage and restricts joint movement.  Patients complain of stiffness on arising that lessens  with activity, and the affected joints may make a  crunching noise (crepitus) when moved. The joints  most commonly affected are those of the fingers, the  cervical and lumbar joints of the spine, and the large,  weight-bearing joints of the lower limbs (knees  and hips).   The course of osteoarthritis is usually slow and  irreversible, but it is rarely crippling. In most cases,  its symptoms are controllable with a mild analgesic  such as aspirin, moderate activity to maintain joint  mobility, and rest when the joint becomes very pain-  ful. Some people with OA claim that rubbing capsa-  icin (hot pepper extract) on the skin over painful  joints provides relief. Others swear by the pain-  reducing ability of glucosamine sulfate, a nutritional  supplement.   Rheumatoid (1roo’ mah-toid) arthritis (RA) is a  chronic inflammatory disorder. Its onset is insidious  and usually occurs between the ages of 40 and 50,  but it may occur at any age. It affects three times as    many women as men. Many joints, particularly those  of the fingers, wrists, ankles, and feet, are affected at  the same time and usually in a symmetrical manner.  For example, if the right elbow is affected, most  likely the left elbow will be affected also. The course  of RA varies and is marked by remissions and flare-  ups (rheumat = susceptible to change or flux).   RA is an autoimmune disease—a disorder in  which the body’s immune system mistakenly  attempts to destroy its own tissues. The initial trigger  for this reaction is unknown but could involve  genetic factors, certain bacterial or viral infections,  hormones of the normal stress response, or a combi-  nation of these.   RA begins with inflammation of the synovial  membranes. The membranes thicken and the joints  swell as synovial fluid accumulates. Inflammatory  cells (white blood cells and others) enter the joint  cavity from the blood and inappropriately release a  deluge of inflammatory chemicals that lead to the  destruction of body tissues. In time, the inflamed  synovial membrane thickens into a pannus (“rag”),  an abnormal tissue that clings to and erodes articu-  lar cartilages. As the cartilage is destroyed, scar tissue  forms and connects the bone ends. The scar tissue  eventually ossifies, and the bone ends become firmly  fused (ankylosis) and often deformed. Not all cases  of RA progress to the severely crippling ankylosis  stage, but all cases involve restricted joint movement  and extreme pain.   Current therapy for RA involves many different  kinds of drugs. Some, such as methotrexate, are immu-  nosuppressants. Others, such as etanercept, neutralize  the inflammatory chemicals in the joint space and  (hopefully) prevent joint deformity. However, drug  therapy often begins with aspirin or ibuprofen, which  in large doses are effective anti-inflammatory agents.  Exercise is recommended to maintain as much joint  mobility as possible. Cold packs are used to relieve the  swelling and pain, and heat helps to relieve morning  stiffness. Replacement joints or bone removal are the  last resort for severely crippled RA patients.   Gouty (gow ’te) arthritis, or gout, is a disease in  which uric acid (a normal waste product of nucleic  acid metabolism) accumulates in the blood and may  be deposited as needle-shaped crystals in the soft tis-  sues of joints. This leads to an agonizingly painful  attack that typically affects a single joint, often in the  great toe. Gout is most common in men and rarely  appears before the age of 30. It tends to run in fami-  lies, so genetic factors are definitely implicated.    Untreated gout can be very destructive; the bone  ends fuse, and the joint becomes immobilized.  Fortunately, several drugs (colchicine, ibuprofen,  and others) are successful in preventing acute gout one  attacks. Patients are advised to lose weight if obese; of skull Occipital  to avoid foods such as liver, kidneys, and sardines, bone  which are high in nucleic acids; and to avoid Mandible  alcohol, which inhibits excretion of uric acid by the  kidneys.    Figure 5.31 Ossification centers in the skeleton of  a 12-week-old fetus are indicated by the darker    Did You Get It? areas. Lighter regions are still fibrous or cartilaginous.    34. What is the major difference between a fibrous look in more detail at the times when it changes  joint and a cartilaginous joint? the most.   35. Where is synovial membrane found, and what is  its role? 5.5a Birth to Adulthood    36. What two joints of the body are ball-and-socket  joints? What is the best example of a saddle joint?  For answers, see Appendix A.    As we described earlier, the first “long bones” in the  very young fetus are formed of hyaline cartilage, and  the earliest “flat bones” of the skull are actually  fibrous membranes. As the fetus develops and grows,   of the Skeleton that have yet to be converted to bone. These fibrous    1# Describe how the skull of a newborn infant (or ; : ,  fetus) differs from that of an adult, and explain because they are flexible, they allow the infant's    the function of fontanels. brain to grow during the latter part of pregnancy and  early infancy. This would not be possible if the cra-  As we have seen, the skeleton goes through many nial bones were fused by sutures. The fontanels usu-    The skeleton changes throughout life, but the  changes in childhood are most dramatic. At birth  and in infancy, the baby’s cranium is huge relative to  its face (Figure 5.33a). This is why some young kids  resemble “bobble head” dolls, because their heads  are quite large compared to their body size. The  rapid growth of the cranium before and after birth is  related to the growth of the brain. By 2 years, the  skull is three-quarters of its adult size; and, by 8 to  9 years, the skull is almost adult in size and propor-  tion. Between the ages of 6 and 11, the head appears  to enlarge substantially as the face literally grows out  from the skull. The jaw increases in size, and the  cheekbones and nose become more prominent as  respiratory passages expand and the permanent  teeth develop. During youth, growth of the skeleton  not only increases overall body height and size but  also changes body proportions (Figure 5.33b). At  birth, the head and trunk are proportionately much  longer than the lower limbs. The lower limbs grow    Figure 5.33 Differences in the growth rates for  some parts of the body compared to others  determine body proportions. (a) Differential growth  transforms the rounded, foreshortened skull of a new-  born to the sloping skull of an adult. (b) During growth  of a human, the arms and legs grow faster than the  head and trunk, as shown in this conceptualization of  different-aged individuals all drawn at the same height.    more rapidly than the trunk from this time on, and  by the age of 10, the head and trunk are approxi-  mately the same height as the lower limbs and  change little thereafter. During puberty, the female  pelvis broadens, and the entire male skeleton  becomes more robust. By the end of adolescence, the  epiphyseal plates of long bones that provide for lon-  gitudinal growth have become fully ossified, and  long-bone growth ends. Once adult height is  reached, a healthy skeleton changes very little until  late middle age. In old age, losses in bone mass  become obvious.   Bones have to be physically stressed to remain  healthy. When we remain active physically and mus-  cles and gravity pull on the skeleton, the bones    Figure 5.34 Osteoporosis. The architecture of normal  bone (a) is contrasted with that of osteoportic bone (b).    respond by becoming stronger. By contrast, if we are  totally inactive, they become thin and fragile.  Osteoporosis is a bone-thinning disease that afflicts  half of women over 65 and some 20 percent of men  over the age of 70. The ratio of bone formation to  bone breakdown decreases as osteoblast activity  becomes sluggish. Osteoporosis can make the bones  so fragile that even a hug or a sneeze can cause bones  to fracture (Figure 5.34). The bones of the spine and  the neck of the femur are particularly susceptible.  Vertebral collapse frequently results in a hunched-  over posture (kyphosis) known as dowager’s hump  (Figure 5.35).   Estrogen helps to maintain the health and nor-  mal density of a woman’s skeleton, and the estrogen  deficiency that occurs after a woman goes through  menopause (when menstruation ceases) is strongly    Figure 5.35 Vertebral collapse due to osteoporosis.  Women with postmenopausal osteoporosis are at risk  for vertebral fractures. Eventually these vertebrae  collapse, producing spinal curvature that causes loss    implicated as a cause of osteoporosis. Other factors  that may contribute to osteoporosis are a diet poor  in calcium and protein, lack of vitamin D, smoking,  and insufficient weight-bearing exercise to stress the  bones. Sadly, many older people feel that they are  helping themselves by “saving their strength” and  not doing anything too physical. Their reward for  this is pathologic fractures (breaks that occur sponta-  neously without apparent injury), which increase  dramatically with age and are the single most com-  mon skeletal problem for this age group.   Advancing years also take their toll on joints.  Weight-bearing joints in particular begin to degener-  ate, and osteoarthritis is common. Such degenerative  joint changes lead to the complaint often heard from  an aging person: “My joints are getting so stiff.”    37. Ninety-year-old Mrs. Pelky is groaning in pain.  Her grandson has just given her a bear hug.  What do you think might have happened to her  spine, and what bone condition may she be  suffering from?   38. Which two regions of the skeleton grow most  rapidly during childhood?    e Skeletal system protects brain  and spinal cord; provides a  depot for calcium ions needed  for neural function   e Nerves innervate bone and  articular capsules, providing  for pain and joint sense   e Hormones regulate uptake and  release of calcium from bone;  hormones promote long-bone  growth and maturation    e Skeletal system provides  some protection to lymphoid  organs; lymphocytes involved  in immune response originate  in bone marrow   e Lymphatic system drains leaked  interstitial fluid; immune cells  protect against pathogens    e Bone marrow cavities provide  site for blood cell formation;  matrix stores calcium needed  for muscle, nerve, and blood-  clotting activities    e Skeletal system provides  some bony protection to  intestines, pelvic  organs, and liver    A N Listen to the story of this chapter in a brief summary at Mastering A&P >  I Study Area > Author Narrated Audio Summaries    5.1a. Bone functions: support; protect; serve as  levers for the muscles to pull on to cause movement  at joints; store calcium, fats, and other substances;  some contain red marrow (the site of blood cell  production)    5.1b. Bones are classified as long bones, short  bones, flat bones, or irregular bones based on  shape and amount of compact bone or spongy  bone    e The epiphyses are covered with hyaline cartilage;  they contain spongy bone (with red marrow)    e The organic extracellular matrix makes bone flexi-  ble; calcium salts deposited in the matrix make  bone hard    Osteon (Haversian system)—the building block  of compact bone; contains a central canal  (Haversian canal), perpendicular perforating  canals (Volkmann's canals), rings of matrix  called lamellae with lacunae between the rings  containing osteocytes; lacunae are linked by  canaliculi   e Osteoblasts build new bone matrix; osteoclasts  release calcium from the matrix    e Bones change shape during bone remodeling,  which occurs in response to hormones (for exam-  ple, PTH, which regulates blood calcium levels)  and mechanical stresses acting on the skeleton    5.1e. A fracture is a break in a bone. Common  types include simple, compound, compression,  comminuted, depressed, impacted, spiral, and  greenstick; bone fractures are treated by reduction  and immobilization    5.2a. The skull is made up of cranial and facial  bones    e There are eight cranial bones: frontal, occipital,  ethmoid, sphenoid, and the paired parietal and  temporal bones    e There are 14 facial bones, all paired (maxillae,  zygomatics, palatines, nasals, lacrimals, and infe-  rior nasal conchae), except for the vomer and  mandible    e The hyoid bone, from the neck, is supported by  ligaments and does not articulate with any other  bones    5.2b. The vertebral column contains 24 vertebrae,  the sacrum, and the coccyx    e There are 7 cervical vertebrae, 12 thoracic  vertebrae, and 5 lumbar vertebrae, which have  common and unique features    e Vertebrae are separated by intervertebral discs  made of fibrocartilage; these allow the vertebral  column to be flexible    e Vertebral column—C-shaped at birth, primary  curvatures (thoracic and sacral) are present    ° Secondary curvatures (cervical and lumbar)  form when the baby begins to lift its head and  walk    o After infancy, the vertebral column is S-shaped  to allow for upright posture    5.2c. The bony thorax includes the sternum and  12 pairs of ribs    e All ribs attach posteriorly to thoracic vertebrae;  anteriorly the first 7 pairs attach directly to the ster-  num (true ribs) via costal cartilages; the last  5 pairs attach indirectly or not at all (false ribs)   a scapula and a clavicle—and attach the upper  limbs to the axial skeleton; they are light, poorly  reinforced girdles that allow the upper limbs a great  deal of freedom of movement    5.3b. The bones of the upper limb: the humerus  of the arm, the radius and ulna of the forearm, and  the carpal bones, metacarpals, and phalanges of  the hand    5.3c. The pelvic girdle is formed by the two coxal  bones (hip bones) and the sacrum    e Each hip bone is a fusion of the ilium, ischium,  and pubis bones    e The pelvic girdle is securely attached to the verte-  bral column, and the socket (acetabulum) for the  thigh bone is deep and heavily reinforced   e The pelvic girdle carries the weight of the upper  body and transfers it to the lower limbs   e The female pelvis is lighter and broader than the  male’s; its inlet and outlet are larger, reflecting  the childbearing function    5.3d. The lower limb bones: the femur of the  thigh; the tibia and fibula of the leg; and the tarsal  bones, metatarsals, and phalanges of the foot    e Joints (articulations) hold bones together and  allow movement of the skeleton    e Functional joint categories: synarthroses  (immovable), amphiarthroses (slightly mov-  able), and diarthroses (freely movable)    è Structural joint categories: fibrous, cartilaginous,  or synovial joints, depending on the substance  separating the articulating bones    5.4a. Most fibrous joints are synarthrotic; fibrous  joints occur mainly in the axial skeleton    5.4b. Most cartilaginous joints are amphi-  arthrotic; cartilaginous joints occur mainly in  the axial skeleton    5.4c. All joints in the limbs are synovial joints; all  synovial joints are diarthroses    e Articulating bone surfaces are covered with  articular cartilage, enclosed within the joint  cavity by a fibrous capsule lined with a synovial  membrane; the synovial membrane secretes lubri-  cating synovial fluid   e The most common joint problem is arthritis, or  inflammation of the joints    ° Osteoarthritis, or degenerative arthritis, is a  result of the “wear and tear” on joints over  many years and is a common affliction of the  aged   ° Rheumatoid arthritis occurs in both young  and older adults; it is believed to be an autoim-  mune disease    e Gouty arthritis, caused by the deposit of uric  acid crystals in joints, typically affects a single  joint in the great toe   Growth of the cranium after birth is related to  brain growth   The increase in size of the facial skeleton follows  tooth development and enlargement of the respi-  ratory passageways    Long bones continue to grow in length until late  adolescence; by age 10, the head and trunk are  approximately the same height as the lower limbs  and change little thereafter   e Osteoporosis, a condition of bone wasting that  results mainly from hormone deficit or inactivity,  is also common in older individuals    2. Match the appropriate name with the structure on the  figure.    . Which of the following are the elements of an osteon?  a. Haversian canals c. Lacunae   meatus.  . Bones that articulate with the sphenoid include which  of the following?  a. Parietal e. Ethmoid   . Which parts of the thoracic vertebrae articulate with  the ribs?    Which of the following bones are found in the feet?  a. Lunate d. Metatarsal  b. Talus    The shoulder joint is an example of a  a. plane joint. d. pivot joint.  b. condylar joint. e. hinge joint.   At what stage of life do the lower limbs attain the  same height as the head and trunk?   Match the types of joints to the descriptions that  apply to them. (More than one description might  apply.)   7. The most common type of joint in the body  8. Nearly all are synarthrotic    Match the joints on the right with the movement  types on the left.    What is yellow marrow? How do spongy and compact  bone look different?    Which of the facial bones bear teeth? What are the  teeth-bearing parts called?    Where is the jugular foramen located, and which  structure passes through it?    Which tarsals carry most of the body weight? Which  tarsal articulates with the tibia? How many phalanges  build up each toe?    Compare the amount of movement possible in  synarthrotic, amphiarthrotic, and diarthrotic joints.  Relate these terms to the structural classification of  joints—that is, to fibrous, cartilaginous, and synovial  joints.    Deborah, a 75-year-old woman, stumbled slightly  while walking, then felt a terrible pain in her left hip.  At the hospital, X-ray images revealed that the hip was  broken. Also, the compact bone and spongy bone  throughout her spine were very thin. What was her  probable condition?    At work, a box fell from a shelf onto Ella’s acromial  region. In the emergency room, the physician felt that  the head of her humerus had moved into the axilla.  What had happened to Ella?    Bone X-ray studies are sometimes used to determine  whether a person has reached his or her final height.  What are the clinicians checking out?    Anna, a 65-year-old woman, is experiencing discom-  forting lower back pain. She jokes to her doctor that  she must be shrinking because her body height has  somewhat diminished over the last few years. What  can be the case?    Mary, a 70-year-old woman, has been experiencing  severe pain, swelling, and stiffness in her hip joint.  Tests reveal Mary has osteoarthritis in her hip joint.  Which treatment can help her?    Muscles are  responsible for body  movements, stabilizing joints,  and generating heat.    In addition to whole body  movements, muscles are needed to  move substances inside our bodies: for  example, air into and out of our lungs,  food through our digestive tracts, and   ago dubbed them muscles, from the Latin  word mus, meaning “little mouse.” Indeed, the rip-  pling muscles of professional athletes often come to  mind when we hear the word muscle. But muscle is  also the dominant tissue in the heart and in the walls  of other hollow organs of the body such as the intes-  tines and blood vessels, and it makes up nearly half  the body’s mass.   The essential function of muscle is to contract, or  shorten—a unique characteristic that sets it apart  from other body tissues. As a result of this ability,  muscles are responsible for all body movements and  can be viewed as the “machines” of the body.    Muscles generate the  force required to cause  movement by contracting, a  process in which proteins inside  the muscle fibers overlap  more than when they  are at rest.    v@ Describe similarities and differences in the structure  and function of the three types of muscle tissue,  and indicate where they are found in the body.    vy Define and explain the role of the following:  endomysium, perimysium, epimysium, tendon,  and aponeurosis.    There are three types of muscle tissue—skeletal,  smooth, and cardiac (Table 6.1, p. 200). These differ    Cellshape and Single, very long, cylindrical, Branching chains of cells; Single, fusiform, uninucleate;  appearance multinucleate cells with very uninucleate, striations; no striations  obvious striations intercalated discs    Connective Epimysium, perimysium, and Endomysium attached to the Endomysium  tissue endomysium fibrous skeleton of the heart  components    in their cell structure, body location, and how they  are stimulated to contract. But before we explore  their differences, let’s look at how they are similar.   First, skeletal and smooth muscle cells are elon-  gated. For this reason, these types of muscle cells  (but not cardiac muscle cells) are called muscle  fibers. Second, the ability of muscle to shorten, or  contract, depends on two types of myofilaments, the  muscle cell equivalents of the microfilaments of the  cytoskeleton (studied in Chapter 3). A third similar-  ity has to do with terminology. Whenever you see the  prefixes myo- or mys- (“muscle”) or sarco- (“flesh”),  you will know that muscle is being referred to. For  example, in muscle cells, the cytoplasm is called sar-  coplasm (sar’ko-plaz”um).    Skeletal muscle fibers are packaged into organs  called skeletal muscles that attach to the skeleton. As  the skeletal muscles cover our bone and cartilage  framework, they help form the smooth contours of  the body. Skeletal muscle fibers are large, cigar-  shaped, multinucleate cells. They are the largest mus-  cle fibers—some ranging up to 30 cm (nearly 1 foot)  in length. Indeed, the fibers of large, hardworking  muscles, such as the antigravity muscles of the hip,  are so big and coarse that they can be seen with the  naked eye.   Skeletal muscle is also known as striated  muscle (because its fibers have obvious stripes) and  as voluntary muscle (because it is the only muscle  type subject to conscious control). However, it is  important to recognize that skeletal muscles can be  activated by reflexes (without our “willed com-  mand”) as well. Skeletal muscle tissue can contract  rapidly and with great force, but it tires easily and  must rest after short periods of activity. When you  think of skeletal muscle tissue, the key words to  remember are skeletal, striated, and voluntary.   Skeletal muscle fibers are soft and surprisingly  fragile. Yet skeletal muscles can exert tremendous  power—indeed, the force they generate while lifting  a weight is often much greater than that required to  lift the weight. The reason they are not ripped apart  as they exert force is that connective tissue bundles  thousands of their fibers together, which strengthens  and supports the muscle as a whole (Figure 6.1).   Each muscle fiber is enclosed in a delicate  connective tissue sheath called endomysium  (en"do-mis’e-um). Several sheathed muscle fibers  are then wrapped by a coarser fibrous membrane    What is the meaning of epi? Of mys? How do these word  roots relate to the role and position of the epimysium?    called perimysium to form a bundle of fibers called  a fascicle (fas’i-kul). Many fascicles are bound  together by an even tougher “overcoat” of connective  tissue called an epimysium, which covers the entire  muscle. The ends of the epimysium that extend  beyond the muscle (like the wrapper on a piece of  candy) blend either into a strong, cordlike tendon  or a sheetlike aponeurosis (ap”o-nu-ro’sis), which  indirectly attaches the muscle to bone, cartilage, or  another connective tissue covering.   In addition to anchoring muscles, tendons per-  form several other functions. The most important are  providing durability and conserving space. Tendons  are mostly tough collagen fibers, so they can cross  rough bony projections, which would tear the more  delicate muscle tissues. Because of their relatively  small size, more tendons than fleshy muscles can  Pass over a joint.   Many people think of muscles as always having  an enlarged “belly” that tapers down to a tendon at  each end. However, muscles vary considerably in the    way their fibers are arranged. Many are spindle-  shaped as just described, but in others, the fibers are  arranged in a fan shape, a circle, or a featherlike  pattern (as described on pp. 220-221).    Smooth muscle has no striations and is involuntary,  which means that we cannot consciously control it.  Found mainly in the walls of hollow (tubelike)  organs such as the stomach, urinary bladder, and  respiratory passages, smooth muscle propels sub-  stances along a pathway. Think of smooth muscle as  visceral, nonstriated, and involuntary.   Smooth muscle fibers are spindle-shaped, uni-  nucleate, and surrounded by scant endomysium (see  Table 6.1). They are arranged in layers, and most  often there are two such layers, one running circu-  larly and the other longitudinally (Figure 6.2a). As  the two layers alternately contract and relax, they  change the size and shape of the organ. Moving food  through the digestive tract and emptying the bowels  and bladder are examples of “housekeeping” activi-  ties normally handled by smooth muscles. Smooth  muscle contraction is slow and sustained. To use a  running analogy, if skeletal muscle is like a sprinter,  who runs fast but tires quickly, then smooth muscle  is like a marathoner, who runs more slowly but  keeps up the pace for many miles.    Cardiac muscle is found in only one place in the  body—the heart, where it forms the bulk of the heart  walls. The heart serves as a pump, propelling blood  through blood vessels to all body tissues. Like skele-  tal muscle, cardiac muscle is striated, and like  smooth muscle, it is uninucleate and under involun-  tary control. Important key words for this muscle  type are cardiac, striated, and involuntary.   The cardiac cells are cushioned by small amounts  of endomysium and are arranged in spiral or figure  8-shaped bundles (Figure 6.2b). When the heart  contracts, its internal chambers become smaller,  forcing blood on a one-way path through the cham-  bers and into the large arteries leaving the heart.  Cardiac muscle fibers are branching cells joined by  special gap junctions called intercalated discs (see  Figure 3.20 on p. 119 and Chapter 3, p. 118). These  two structural features and the spiral arrangement of  the muscle bundles in the heart allow heart activity  to be closely coordinated.    Figure 6.2 Arrangement of smooth and cardiac  muscle cells. (a) Diagrammatic view of a cross section  of the intestine. (b) Longitudinal view of the heart  showing the spiral arrangement of the cardiac muscle  cells in its walls.    Cardiac muscle usually contracts at a fairly  steady rate set by the heart's “in-house” pacemaker.  However, the nervous system can also stimulate the  heart to shift into “high gear” for short periods, as  when you run to catch a bus.   As you can see, each of the three muscle types  has a structure and function well suited for its job in  the body. But because the term muscular system  applies specifically to skeletal muscle, we will con-  centrate on this muscle type for the rest of this  chapter.    All muscle types produce movement, but skeletal  muscle plays three other important roles in the body  as well: it maintains posture and body position, stabilizes  joints, and generates heat. Let's take a look.    Skeletal muscles are responsible for our body's  mobility, including all locomotion (walking, swim-  ming, and cross-country skiing, for instance) and  manipulating things with your agile upper limbs.  They enable us to respond quickly to changes in the  external environment. For example, their speed and  power enable us to jump out of the way of a runaway  car and then follow its flight with our eyes. They also  allow us to express our emotions with the silent lan-  guage of facial expressions.   They are distinct from the smooth muscle of  blood vessel walls and cardiac muscle of the heart,  which work together to circulate blood and main-  tain blood pressure, and the smooth muscle of other  hollow organs, which forces fluids (urine, bile) and  other substances (food, a baby) through internal  body channels.    We are rarely aware of the workings of the skeletal  muscles that maintain body posture. Yet they func-  tion almost continuously, making one tiny adjust-  ment after another so that we maintain an erect or  seated posture, even when we slouch, despite the  never-ending downward pull of gravity.    As skeletal muscles pull on bones to cause move-  ments, they also stabilize the joints of the skeleton.  Muscles and tendons are extremely important in  reinforcing and stabilizing joints that have poorly  articulating surfaces, such as the shoulder and knee    joints. In fact, physical therapy for knee injuries  includes exercise to strengthen thigh muscles because  they support the knee.    Muscle activity generates body heat as a by-product  of contraction. As ATP is used to power muscle con-  traction, nearly three-quarters of its energy escapes as  heat. This heat is vital in maintaining normal body  temperature. Skeletal muscle accounts for at least 40  percent of body mass, so it is the muscle type most  responsible for generating heat.    Muscles perform other important functions as well.  Smooth muscles form valves that regulate the pas-  sage of substances through internal body openings,  dilate and constrict the pupils of our eyes, and make  up the arrector pili muscles that cause our hairs to  stand on end. Skeletal muscles form valves that are  under voluntary control, and they enclose and pro-  tect fragile internal organs.    1. How do cells of the three types of muscle tissues  differ from one another anatomically?   2. Which muscle type has the most elaborate connec-  tive tissue wrappings?   4. How do the movements promoted by skeletal  muscle differ from those promoted by smooth or  cardiac muscle?    1# Describe the microscopic structure of skeletal  muscle, and explain the role of actin- and myosin-  containing myofilaments.    As mentioned previously, skeletal muscle fibers  (cells) are multinucleate (Figure 6.3a, p. 204). Many  oval nuclei can be seen just beneath the plasma  membrane, which is called the sarcolemma  (sar”ko-lem’ah; “muscle husk”) in muscle fibers. The  nuclei are pushed aside by long ribbonlike organ-  elles, the myofibrils (mi"o-fi’brilz), which nearly fill    Figure 6.3 Anatomy of a skeletal muscle fiber (cell). (a) A portion of a muscle  fiber. One myofibril has been extended. (b) Enlarged view of a section of a myofibril  showing its banding pattern. (c) Enlarged view of one sarcomere (contractile unit) of    the cytoplasm. Alternating light (I) bands and dark  (A) bands along the length of the perfectly aligned  myofibrils give the muscle fiber its striated (banded)  appearance. (Think of the second letter of light, I,  and the second letter of dark, A, to help you remem-  ber which band is which.) A closer look at the band-  ing pattern reveals that the light I band has a midline  interruption, a darker area called the Z disc, and the    dark A band has a lighter central area called the H  zone (Figure 6.3b). The M line in the center of the H  zone contains tiny protein rods that hold adjacent  thick filaments together.    chains of tiny contractile units called sarcomeres  (sar’ko-mérz), which are the structural and func-  tional units of skeletal muscle. The sarcomeres are  aligned end to end like boxcars in a train along the  length of the myofibrils. Second, it is the precise  arrangement of even smaller structures (myofila-  ments) within sarcomeres that produces the stria-  tions in skeletal muscle fibers.   Let's examine how the arrangement of the myo-  filaments leads to the banding pattern. There are two  types of threadlike protein myofilaments within  each sarcomere (Figure 6.3c). The thick filaments  are made mostly of bundled molecules of the pro-  tein myosin. Notice that the thick filaments extend  the entire length of the dark A band. Also, notice that  the midparts of the thick filaments are smooth but  that their ends are studded with small projections  (Figure 6.3c). These projections, or myosin heads,  contain ATPase enzyme activity and split ATP to  release the energy used for muscle contraction. The  myosin heads also form cross bridges when they  bind to the thin myofilaments during contraction.  Myosin filaments are attached to the Z discs by titin,  elastic filaments that run through the core of the  thick filaments.   The thin filaments are composed of the con-  tractile protein called actin, plus some regulatory  proteins that play a role in allowing (or preventing)  binding of myosin heads to actin. The thin fila-  ments are anchored to the Z disc (a disclike mem-  brane). Notice that the light I band includes parts of  two adjacent sarcomeres and contains only the thin  filaments. Although they overlap the ends of the  thick filaments, the thin filaments do not extend  into the middle of a relaxed sarcomere, and thus the  central region (the H zone) looks a bit lighter.  When the actin-containing thin filaments slide  toward each other during contraction, the H zones  disappear because the actin and myosin filaments  completely overlap.   Another very important muscle fiber organelle—  the sarcoplasmic reticulum (SR)—is a specialized  smooth endoplasmic reticulum (not shown in  Figure 6.3). The interconnecting tubules and sacs of  the SR surround every myofibril just as the sleeve of  a loosely crocheted sweater surrounds your arm. The  major role of this elaborate system is to store cal-  cium and to release it on demand when the muscle  fiber is stimulated to contract. As you will see, cal-  cium provides the final “go” signal for contraction.    Did You Get It?  5. Specifically, what structure(s) is/are responsible for  the banding pattern in skeletal muscle cells?  For the answer, see Appendix A.    y“ Describe how an action potential is initiated in a  muscle cell.    Muscle fibers have several special functional prop-  erties that enable them to perform their duties.  The first of these is irritability, also called respon-  siveness, which is the ability to receive and respond  to a stimulus. The second, contractility, is the abil-  ity to forcibly shorten when adequately stimu-  lated. This property sets muscle apart from all  other tissue types. Extensibility is the ability of  muscle fibers to stretch, whereas elasticity is their  ability to recoil and resume their resting length  after being stretched.    To contract, skeletal muscle fibers must be stimu-  lated by nerve impulses. One motor neuron (nerve  cell) may stimulate a few muscle fibers or hun-  dreds of them, depending on the particular muscle  and the work it does. A motor unit consists of one  neuron and all the skeletal muscle fibers it stimu-  lates (Figure 6.4, p. 206). When the long, thread-  like extension of a neuron, called the axon, reaches  the muscle, it branches into a number of axon  terminals, each of which forms junctions with the  sarcolemma of a different muscle fiber (Figure 6.5,  p. 207). These junctions, called neuromuscular  (literally, “nerve-muscle”) junctions, contain syn-  aptic vesicles filled with a chemical referred to as a  neurotransmitter. The specific neurotransmit-  ter that stimulates skeletal muscle fibers is  acetylcholine (as”e-til-ko’len), or ACh. Although  the nerve endings and the muscle fiber membranes  are very close, they never touch. The gap between  them, the synaptic cleft, is filled with interstitial  fluid.    Figure 6.4 Motor units. Each  motor unit consists of a motor  neuron and all the muscle fibers it  activates. (a) Portions of two motor    Homeostatic B  £ Imbalance 6.1  In some cases, a motor nerve impulse is unable to  reach the muscle. In ALS, or amyotrophic lateral  sclerosis (also called Lou Gehrig's disease), motor neu-  rons degenerate over time, resulting in paralysis that  gradually worsens. The cause of ALS is unknown,  though some cases are hereditary. Common character-  istics include malfunctioning mitochondria, inflam-  mation, and the generation of free radicals that damage  DNA and tissue much like intense UV light. The prog-  nosis for patients with ALS is generally death within  three to five years because the breathing muscles will  eventually be affected, resulting in suffocation.    Now that we have described the structure of the  neuromuscular junction, refer to the numbered steps  in Figure 6.5 as we examine what happens there.  When a nerve impulse reaches the axon terminals @,  calcium channels open, and calcium (Ca?*) enters  the terminal ®©. Calcium entry causes some of the  synaptic vesicles in the axon terminal to fuse with the    units are shown. The motor neurons  reside in the spinal cord, and their  axons extend to the muscle. Within  the muscle, each axon divides into a    number of axon terminals distributed  to muscle fibers scattered throughout  the muscle. (b) Photo of a portion of  a motor unit (1150x).    cell membrane and release acetylcholine @), which  then diffuses across the synaptic cleft and attaches to  membrane receptors in highly folded regions of the  sarcolemma @). If enough acetylcholine is released,  the sarcolemma at that point becomes temporarily  even more permeable to sodium ions (Na+), which  rush into the muscle fiber, and to potassium ions  (K*), which diffuse out of the muscle fiber. However,  more Na* enters than K* leaves. This imbalance  gives the cell interior an excess of positive ions,  which reverses the resting electrical conditions of the  sarcolemma. This event, called depolarization, opens  more channels that only allow Na* entry ©. This  movement of ions generates an electrical current  called an action potential. Once begun, the action  potential is unstoppable; it travels over the entire sur-  face of the sarcolemma, conducting the electrical  impulse from one end of the cell to the other. The  result is contraction of the muscle fiber.   Note that while the action potential is occurring,  the enzyme acetylcholinesterase (AChE), present on  the sarcolemma and in the synaptic cleft, breaks  down acetylcholine to acetic acid and choline © to    Axon terminal of motor neuron  Mitochondrion  (2)In response to a nerve impulse;    (3) Cca% entry causes some  synaptic vesicles to release their  contents (the neurotransmitter  acetylcholine) by exocytosis.    (4) Acetylcholine diffuses across  the synaptic cleft and binds to  receptors in the sarcolemma.    ACh binds and opens channels  that allow simultaneous passage  of Na* into the muscle fiber and  K* out of the muscle fiber. More  Nat ions enter than Kt ions leave,  producing a local change in the  electrical conditions of the  membrane (depolarization). This  eventually leads to an action    ©The enzyme acetylcholinesterase  breaks down ACh in the synaptic  cleft, ending the stimulation of the  muscle fiber.    Figure 6.6 Comparing the action  potential to a flame consuming a  dry twig. (a) The first event in  igniting a dry twig is holding the  match flame under one area of the  twig. The second event is the twig’s    bursting into flame when it has been  heated enough and spreading of the  flame to burn the entire twig.  (b) The first event in exciting a  muscle fiber is the rapid diffusion of  sodium ions (Na*) into the cell when    the permeability of the sarcolemma  changes. The second event is the  spreading of the action potential  along the sarcolemma when enough  sodium ions have entered to upset  the electrical conditions in the cell.    prevent continued contraction of the muscle fiber in  the absence of additional nerve impulses. The mus-  cle fiber relaxes until stimulated by the next round of  acetylcholine release, so a single nerve impulse pro-  duces only one contraction.   Let's compare this series of events to lighting a  match under a small dry twig (Figure 6.6). The char-  ring of the twig by the flame can be compared to the  change in membrane permeability that allows  sodium ions into the cell. When that part of the twig  becomes hot enough (when enough sodium ions  have entered the cell), the twig will suddenly burst  into flame, and the flame will move along the twig  (the action potential will be conducted along the  entire length of the sarcolemma). We explain this  series of events more fully in the discussion of nerve  physiology (Chapter 7, pp. 251-253).   The events that return the cell to its resting state  include (1) diffusion of potassium ions (K*) out of  the cell and (2) operation of the sodium-potassium  pump, the active transport mechanism that moves  the sodium and potassium ions back to their initial  positions.    6. What two structures are closely associated at a  neuromuscular junction?  7. Which ions enter the muscle cell during the  generation of an action potential?  8. What is the role of calcium ions in muscle  contraction?  For answers, see Appendix A.    We have just described the events at the neuromus-  cular junction that lead to an action potential. Now  we'll describe excitation-contraction coupling (that  is, combining what just happened with what's about  to happen), and the cross-bridge cycle, during which  myofilaments overlap to a greater degree and sarco-  meres (and the whole muscle) shorten.   What causes the filaments to slide? This question  brings us back to the myosin heads that protrude all  around the ends of the thick filaments.   The formation of cross bridges—when the myo-  sin heads attach to actin—requires calcium ions  (Ca**) and ATP (to “energize” the myosin heads).  So where does the calcium come from? Action  potentials pass deep into the muscle fiber along  membranous tubules that fold inward from the  sarcolemma. Inside the cell, in a process called  excitation-contraction coupling, the action potential  stimulates the sarcoplasmic reticulum to release cal-  cium ions into the cytoplasm. The calcium ions trig-  ger the binding of myosin to actin, initiating filament  sliding (Figure 6.7). When the action potential ends,  calcium ions are immediately returned to the SR  storage areas, the regulatory proteins return to their  resting shape and block myosin-binding sites, and  the muscle fiber relaxes and settles back to its origi-  nal length. This whole series of events takes a few  thousandths of a second.    When the nervous system activates muscle fibers  as just described, the myosin heads attach to binding  sites on the thin filaments, and the sliding begins.  Each cross bridge attaches and detaches several times  during a contraction, generating tension that helps  pull the thin (actin) filaments toward the center of  the sarcomere. This “walking” of the myosin heads  along the thin filaments during muscle shortening is  much like a centipede’s gait. Some myosin heads  (“legs”) are always in contact with actin (“the  ground”), so that the thin filaments cannot slide  backward, and this cycle repeats again and again  during contraction. As this event occurs simultane-  ously in sarcomeres throughout the muscle fiber, it    In a relaxed muscle fiber, the regulatory proteins  forming part of the actin myofilaments block and  prevent myosin binding (see a). When an action  potential (AP) sweeps along its sarcolemma and a  muscle fiber is excited, calcium ions (Ca?) are  released from intracellular storage areas (the sacs of  the sarcoplasmic reticulum).    The flood of calcium acts as the final trigger for  contraction, because as calcium binds to the  regulatory proteins on the actin filaments, the proteins  undergo a change in both their shape and their  position on the thin filaments. This action exposes  myosin-binding sites on the actin, to which the myosin  heads can attach (see b), and the myosin heads  immediately begin seeking out binding sites. The  binding of myosin to actin constitutes cross bridge  formation.    Using energy from ATP, free myosin heads are  “cocked,” much like an oar ready to be pulled on for  rowing. Myosin attachment to actin causes the myosin  heads to snap (pivot) toward the center of the  sarcomere in a rowing motion. When this happens,  the thin filaments are pulled slightly toward the center  of the sarcomere (see c). ATP provides the energy  needed to release and recock each myosin head so  that it is ready to attach to a binding site farther along  the thin filament.    shortens (Figure 6.8, p. 210). Notice that the myofil-  aments themselves do not shorten during contrac-  tion; they simply slide past each other and overlap  more than in the relaxed state.    9. Which chemical—ATP or Ca?*—triggers sliding of  the muscle filaments?  10. Which is a cross-bridge attachment more similar  to: a synchronized rowing team or a person pulling  a bucket on a rope out of a well?  For answers, see Appendix A.    Figure 6.8 Diagrammatic views of a sarcomere.  Notice that in the contracted sarcomere (b), as a result  of increased myofilament overlap, the light H zone in  the center of the A band has disappeared, the Z discs  are closer to the thick filaments, and the | bands have  nearly disappeared. The A bands of adjacent sarcomeres  move closer together but do not change in length.    v# Define graded response, tetanus, isotonic and  isometric contractions, and muscle tone as these  terms apply to a skeletal muscle.    In skeletal muscles, the “all-or-none” law of muscle  physiology applies to the muscle fiber, not to the  whole muscle. It states that a muscle fiber will con-  tract to its fullest extent when it is stimulated ade-  quately; it never partially contracts. However, the  whole muscle reacts to stimuli with graded  responses, or different degrees of shortening, which  generate different amounts of force. In general,  graded muscle contractions can be produced two    ways: (1) by changing the frequency of muscle stimu-  lation and (2) by changing the number of muscle  fibers being stimulated at one time. Next, let's  describe a muscle’s response to each of these.    Muscle Response to Increasingly Rapid Stimulation  Although muscle twitches (single, brief, jerky con-  tractions) sometimes result from certain nervous sys-  tem problems, this is not the way our muscles  normally operate. In most types of muscle activity,  nerve impulses are delivered to the muscle at a very  rapid rate—so rapid that the muscle does not get a  chance to relax completely between stimuli. As a  result, the effects of the successive contractions are  “summed” (added) together, and the contractions  of the muscle get stronger and smoother. The mus-  cle exhibits unfused tetanus (tet’ah-nus), or  incomplete tetanus. When the muscle is stimulated  so rapidly that no evidence of relaxation is seen and  the contractions are completely smooth and sus-  tained, the muscle is in fused tetanus, or complete  tetanus, or in tetanic contraction* (Figure 6.9).    Muscle Response to Stronger Stimuli Tetanus pro-  duces stronger (more forceful) muscle contractions,  but its primary role is to produce smooth and pro-  longed muscle contractions. How forcefully a muscle  contracts depends to a large extent on how many of its  cells are stimulated. When only a few fibers are stim-  ulated, the muscle as a whole contracts only slightly.  When all the motor units are active and all the muscle  fibers are stimulated, the muscle contraction is as  strong as it can get. Thus, muscle contractions can  range from slight to vigorous depending on the work  to be done. The same hand that lifts a single sheet of  paper can also lift a heavy backpack full of books!    As a muscle contracts, the bonds of ATP molecules  are hydrolyzed to release the needed energy.    *Tetanic contraction is normal and desirable. It is quite differ-  ent from the pathological condition of tetanus (commonly  called lockjaw), which is caused by a toxin made by bacteria.  Lockjaw causes muscles to go into uncontrollable spasms,  finally causing respiratory arrest.    Figure 6.9 A whole muscle’s  response to different stimulation  rates. A single stimulus (a) causes  muscle contraction and relaxation (a  twitch). As stimuli are delivered more  frequently (b), the muscle does not  have time to completely relax before  the next stimulus; contraction force    Surprisingly, muscles store very limited supplies of  ATP—only a few seconds’ worth, just enough to get you  going. Because ATP is the only energy source that can be  used directly to power muscle activity, ATP must be  regenerated continuously if contraction is to continue.    e Direct phosphorylation of ADP by creatine  phosphate (Figure 6.10a, p. 212). The unique  high-energy molecule creatine phosphate  (CP) is found in muscle fibers but not other cell  types. As ATP is depleted, interactions between  CP and ADP result in transfers of a high-energy  phosphate group from CP to ADP, thus regen-  erating more AIP in a fraction of a second.  Although muscle fibers store perhaps five times  as much CP as ATP, the CP supplies are also  soon exhausted (in less than 15 seconds).    e Aerobic pathway (Figure 6.10b). At rest and dur-  ing light to moderate exercise, some 95 percent of  the ATP used for muscle activity comes from aero-  bic respiration. Aerobic respiration occurs in the    increases because effects of the  individual twitches are summed  (added). Further fusion (c) of the  twitches (unfused tetanus) occurs as  stimuli are delivered at a still faster  rate. Fused tetanus (d), a smooth  continuous contraction without any  evidence of relaxation, results from a    very rapid rate of stimulation. (Points  at which stimuli are delivered are  indicated by red arrows. Tension  [measured in grams] on the vertical  axis refers to the relative force of  muscle contraction.)    mitochondria and involves a series of metabolic  pathways that use oxygen. These pathways are col-  lectively referred to as oxidative phosphorylation.  During aerobic respiration, glucose is broken  down completely to carbon dioxide and water,  and some of the energy released as the bonds are  broken is captured in the bonds of ATP molecules.  Although aerobic respiration provides a rich ATP  harvest (about 32 ATP per 1 glucose), it is fairly  slow and requires continuous delivery of oxygen  and nutrient fuels to the muscle to keep it going.    Anaerobic glycolysis and lactic acid  formation (Figure 6.10c). The initial steps of  glucose breakdown occur via a pathway called  glycolysis, which does not use oxygen and hence  is anaerobic (literally “without oxygen”). During  glycolysis, which occurs in the cytosol, glucose  is broken down to pyruvic acid, and small  amounts of energy are captured in ATP bonds  (2 ATP per 1 glucose molecule). As long as  enough oxygen is present, the pyruvic acid then  enters the oxygen-requiring aerobic pathways  that occur within the mitochondria to produce  more ATP as described above. However, when  muscle activity is intense, or oxygen and glucose  delivery is temporarily inadequate to meet the  needs of working muscles, the sluggish aerobic  pathways cannot keep up with the demands for  ATP. Under these conditions, the pyruvic acid  generated during glycolysis is converted to lactic  acid, and the overall process is referred to as  anaerobic glycolysis.    acid; free fatty acids from adipose  tissue; amino acids from protein    Figure 6.10 Methods of regenerating ATP during muscle activity.  The fastest mechanism is (a) direct phosphorylation; the slowest is    Anaerobic glycolysis produces only about 5 per-  cent as much ATP from each glucose molecule as  aerobic respiration. However, it is some 2⁄2 times  faster, and it can provide most of the ATP needed for  30 to 40 seconds of strenuous muscle activity.  Anaerobic glycolysis has two main shortcomings: it  uses huge amounts of glucose for a small ATP har-  vest, and the accumulating lactic acid promotes  muscle soreness.    11. What are the three processes used to generate  energy for skeletal muscle contraction?  12. What is the direct source of energy used by muscle  fibers for contraction?  For answers, see Appendix A.    1# Define oxygen deficit and muscle fatigue, and list  possible causes of muscle fatigue.    If we exercise our muscles strenuously for a long  time, muscle fatigue occurs. A muscle is fatigued  when it is unable to contract even though it is still  being stimulated. Without rest, a working muscle  begins to tire and contracts more weakly until it  finally ceases reacting and stops contracting.   Factors that contribute to muscle fatigue are not  fully known. Suspected causes are imbalances in  ions (Ca**, K*) and problems at the neuromuscular  junction. However, many agree that the major factor  is the oxygen deficit that occurs during prolonged  muscle activity. Oxygen deficit is not a total lack of  oxygen; rather, it happens when a person is not able    to take in oxygen fast enough to keep the muscles  supplied with all the oxygen they need to continue  aerobic ATP production when they are working vig-  orously. Obviously, then, the work that a muscle can  do and how long it can work without becoming  fatigued depend on how good its blood supply is.  When muscles lack sufficient oxygen for aerobic res-  piration, lactic acid begins to accumulate in the mus-  cle via the anaerobic pathway. We can recognize this  event by the burning sensation we experience. In  addition, the muscle’s ATP supply starts to run low,  and ionic imbalances tend to occur. Together these  factors cause the muscle to contract less and less  effectively and finally to stop contracting altogether.  True muscle fatigue, in which the muscle quits  entirely, rarely occurs in most of us because we feel  tired long before it happens and we simply slow down  or stop our activity. It does happen in marathon run-  ners. Many of them have literally collapsed when their  muscles became fatigued and could no longer work.  Oxygen deficit, which always occurs to some  extent during vigorous muscle activity, is like a loan  that must be “paid back” whether fatigue occurs or  not. During the recovery period after activity, the indi-  vidual breathes rapidly and deeply. This continues  until the muscles have received the amount of oxygen  needed to get rid of the accumulated lactic acid and  replenish ATP and creatine phosphate reserves.    Until now, we have been discussing contraction in  terms of shortening, but muscles do not always shorten  when they contract. (I can hear you saying, “What kind  of double-talk is that?” —but pay attention.) The event  that is common to all muscle contractions is that ten-  sion (force) develops in the muscle as the myosin cross  bridges attempt to slide the thin actin-containing fila-  ments past the thick myosin filaments.   Isotonic contractions (literally, “same tone” or  tension) are familiar to most of us. In isotonic con-  tractions, the myofilaments are successful in their  sliding movements, the muscle shortens, and move-  ment occurs. Bending the knee, lifting weights, and  smiling are all examples of isotonic contractions.   Contractions in which the muscles do not  shorten are called isometric contractions (literally,  “same measurement” or length). In isometric con-  tractions, the myosin filaments are “spinning their  wheels,” and the tension in the muscle keeps increas-  ing. They are trying to slide, but the muscle is pitted    against some more or less immovable object. For  example, when you push the palms of your hands  together in front of you, your arms and chest mus-  cles are contracting isometrically.    One aspect of skeletal muscle activity cannot be con-  sciously controlled. Even when a muscle is volun-  tarily relaxed, some of its fibers are contracting—first  one group and then another. These contractions are  not visible, but thanks to them, the muscle remains  firm, healthy, and constantly ready for action. This  state of continuous partial contractions is called  muscle tone. Muscle tone is the result of different  motor units, which are scattered through the muscle,  being stimulated by the nervous system in a system-  atic way. Think of these motor units as being “on  duty” in case action is required.    Homeostatic J  K Imbalance 6.2  If the nerve supply to a muscle is destroyed (as in an  accident), the muscle is no longer stimulated in this  manner, and it loses tone. Soon after, it becomes  flaccid (fla’sid), or soft and flabby, and begins to  atrophy (waste away). This is called flaccid paralysis.  Compare this with a condition that increases muscle  tone until the muscle is no longer controllable—for  example, the disease tetanus, which is caused by a  bacterial toxin. This is called spastic paralysis.    v Describe the effects of aerobic and resistance  exercise on skeletal muscles and other body organs.    The amount of work a muscle does changes the mus-  cle. Muscle inactivity (due to a loss of nerve supply,  immobilization, or whatever the cause) always leads  to muscle weakness and wasting. Muscles are no  exception to the saying “Use it or lose it!” Conversely,  regular exercise increases muscle size, strength, and  endurance. However, not all types of exercise pro-  duce these effects—in fact, there are important dif-  ferences in the benefits of exercise.   Aerobic exercise, or endurance exercise, such  as participating in an aerobics class, jogging, or bik-  ing (Figure 6.11a, p. 214), results in stronger, more  flexible muscles with greater resistance to fatigue.    Figure 6.11 The effects of aerobic training versus  strength training. (a) A marathon runner. (b) A  weight lifter.    These changes come about, at least partly, because  the blood supply to the muscles increases, and the  individual muscle fibers form more mitochondria  and store more oxygen. Aerobic exercise helps us  reach a steady rate of ATP production and improves  the efficiency of aerobic respiration.   However, aerobic exercise benefits much more  than the skeletal muscles. It makes overall body  metabolism more efficient, improves digestion (and  elimination), enhances neuromuscular coordina-  tion, and strengthens the skeleton. The heart enlarges  (hypertrophies) and pumps out more blood with each  beat, helping to clear more fat deposits from the  blood vessel walls. The lungs become more efficient  in gas exchange. These benefits may be permanent or  temporary, depending on how often and how vigor-  ously a person exercises.   Aerobic exercise does not cause the muscles to  increase much in size, even though the exercise may  go on for hours. The bulging muscles of a profes-  sional bodybuilder result mainly from resistance  exercise, or isometric exercise (Figure 6.11b),  which pit the muscles against an immovable (or dif-  ficult to move) object.   Resistance exercises require very little time and  little or no special equipment. A few minutes every  other day is usually sufficient. You can push against  a wall, and you can strongly contract buttock mus-  cles even while standing in line at the grocery store.  The key is forcing your muscles to contract with as    much force as possible. The increased muscle size  and strength that result are due mainly to enlarge-  ment of individual muscle fibers (they make more  contractile myofilaments) rather than to an increase  in their number. The amount of connective tissue  that reinforces the muscle also increases.   Because endurance and resistance exercises pro-  duce different patterns of muscle response, it is  important to know what your exercise goals are.  Lifting weights will not improve your endurance for  a marathon. By the same token, jogging will not  make you stronger for lifting furniture. Obviously,  the best exercise program for most people includes  both types of exercise.    13. Gary is trying with all his might to pull a tree  stump out of the ground. It does not budge.  Which type of contraction are his muscles  performing?   15. To develop big skeletal muscles, you should focus  on which type of exercise: aerobic or resistance  exercise?    Learning Objectives  v Define origin, insertion, prime mover, antagonist,  synergist, and fixator as they relate to muscles.  vz Demonstrate or identify the different types of  body movements.  There are five basic guidelines for understanding  gross muscle activity. We refer to these as the Five  Golden Rules of skeletal muscle activity because they  make it easier to understand muscle movements and  appreciate muscle interactions (Table 6.2).    Every one of our 600-odd skeletal muscles is attached  to bone, or to other connective tissue structures, at  no fewer than two points. One of these points, the  origin, is attached to the immovable or less movable  bone (Figure 6.12). Think of the origin as the anchor,  or leverage, point. Another point, the insertion, is  attached to the movable bone. When the muscle  contracts, the insertion moves toward the origin.    Table 6.2 The Five Golden Rules of  Skeletal Muscle Activity  1. With few exceptions, all skeletal muscles cross at    2. Typically, the bulk of a skeletal muscle lies proximal to  the joint crossed.    3. All skeletal muscles have at least two attachments:  the origin and the insertion.    . During contraction, a skeletal muscle insertion moves  toward the origin.    Some muscles have interchangeable origins and  insertions, depending on the action being performed.  For example, the rectus femoris muscle of the ante-  rior thigh crosses both the hip and knee joints. Its  most common action is to extend the knee, in which  case the proximal pelvic attachment is the origin.  However, when the knee bends (by other muscles),  the rectus femoris can flex the hip, and then its distal  attachment on the leg is considered the origin.   Generally speaking, body movement occurs  when muscles contract across joints. The type of  movement depends on the mobility of the joint and  the location of the muscle in relation to the joint.  The most obvious examples of the action of muscles  on bones are the movements that occur at the joints  of the limbs. However, less freely movable bones are  also tugged into motion by the muscles, such as the  vertebrae’s movements when we bend to one side.   Next we describe the most common types of  body movements (Figure 6.13, pp. 216-217). Try to  act out each movement as you read the following  descriptions:    e Flexion. Flexion is a movement, generally in  the sagittal plane, that decreases the angle of  the joint and brings two bones closer together  (Figures 6.13a and 6.13b). Flexion is typical of  hinge joints (bending the knee or elbow), but it  is also common at ball-and-socket joints (for  example, bending forward at the hip).    e Extension. Extension is the opposite of flex-  ion, so it is a movement that increases the angle,  or distance, between two bones or parts of  the body (straightening the knee or elbow).  Extension that is greater than 180° (as when  you move your arm posteriorly beyond its  normal anatomical position, or tip your head    Figure 6.12 Muscle attachments (origin and  insertion). When a skeletal muscle contracts, its  insertion moves toward its origin.    so that your chin points toward the ceiling) is  called hyperextension (Figures 6.13a and 6.13b).    e Rotation. Rotation is movement of a bone  around its longitudinal axis (Figure 6.13c).  Rotation is a common movement of ball-and-  socket joints and describes the movement of the  atlas around the dens of the axis (as in shaking  your head “no”    e Abduction. Abduction is moving a limb  away (generally in the frontal plane) from the  midline, or median plane, of the body (Fig-  ure 6.13d). The terminology also applies to the  fanning movement of your fingers or toes when  they are spread apart.    e Adduction. Adduction is the opposite of  abduction, so it is the movement of a limb  toward the body midline (Figure 6.13d). Think  of adduction as “adding” a body part by  bringing it closer to the trunk.    e Circumduction. Circumduction is a combina-  tion of flexion, extension, abduction, and  adduction commonly seen in ball-and-socket  joints, such as the shoulder. The proximal end of  the limb is stationary, and its distal end moves  in a circle. The limb as a whole outlines a cone  (Figure 6.13d), as when you do big arm circles.    Pronation Supination  (radius rotates (radius and ulna  over ulna) are parallel)    Certain movements do not fit into any of the previ-  ous categories and occur at only a few joints.    e Dorsiflexion and plantar flexion. Up-and-  down movements of the foot at the ankle are  given special names. Lifting the foot so that its  superior surface approaches the shin (point-  ing your toe toward your head) is dorsiflexion,  whereas pointing the toes away from your head  is plantar flexion (Figure 6.13e). Dorsiflexion of  the foot corresponds to extension and hyperex-  tension of the hand at the wrist, whereas plantar  flexion of the foot corresponds to flexion of  the hand.    e Inversion and eversion. Inversion and ever-  sion are also special movements of the foot  (Figure 6.13f). To invert the foot, turn the sole  medially, as if you were looking at the bottom  of your foot. To evert the foot, turn the sole  laterally.    e Supination and pronation. The terms  supination (soo"pi-na’shun; “turning back-  ward”) and pronation (pro-na’shun; “turning  forward”) refer to movements of the radius  around the ulna (Figure 6.13g). Supination  occurs when the forearm rotates laterally so  that the palm faces anteriorly (or up) and the  radius and ulna are parallel, as in anatomical  position. Pronation occurs when the forearm  rotates medially so that the palm faces posteri-  orly (or down). Pronation brings the radius  across the ulna so that the two bones form an  X. A helpful memory trick: If you lift a cup of  soup up to your mouth on your palm, you are  supinating (“soup”-inating).   e Opposition. In the palm of the hand, the sad-  dle joint between metacarpal 1 and the carpals  allows opposition of the thumb (Figure 6.13h).  This is the action by which you move your  thumb to touch the tips of the other fingers on  the same hand. This unique action makes the  human hand a fine tool for grasping and manip-  ulating objects.    each other. Muscles are arranged so that whatever  one muscle (or group of muscles) can do, other mus-  cles can reverse. In general, groups of muscles that  produce opposite movements lie on opposite sides  of a joint (Figure 6.14). Because of this arrangement,  muscles are able to bring about an immense variety  of movements.   The muscle that has the major responsibility for  causing a particular movement is called the prime  mover. Muscles that oppose or reverse a movement  are antagonists (an-tag’o-nists). When a prime  mover is active, its antagonist is stretched and  relaxed. Antagonists can be prime movers in their  own right, but for different actions. For example, the  biceps brachii and brachialis muscles of the arm  (prime movers of elbow flexion) are antagonized  by the triceps brachii (a prime mover of elbow  extension).   Synergists (sin’er-jists; syn = together, erg =  work) help prime movers by producing the same  movement or by reducing undesirable movements.  When a muscle crosses two or more joints, its con-  traction will cause movement in all the joints crossed  unless synergists are there to stabilize them. For  example, the flexor muscles of the fingers cross both  the wrist and the finger joints. You can make a fist  without bending your wrist because synergist mus-  cles stabilize the wrist joints and allow the prime  mover to act on your finger joints.   Fixators are specialized synergists. They hold a  bone still or stabilize the origin of a prime mover so  all the tension can be used to move the insertion  bone. The postural muscles that stabilize the verte-  bral column are fixators, as are the muscles that  anchor the scapulae to the thorax.   In summary, although prime movers seem to get  all the credit for causing certain movements, the  actions of antagonistic and synergistic muscles are  also important in producing smooth, coordinated,  and precise movements.    16. What action is being performed by a person who  sticks out his thumb to hitch a ride?  17. What actions take place at the neck when you nod  your head up and down as if saying “yes”?  18. In what way are fixator and synergist muscles  important?  For answers, see Appendix A.    (a) A muscle that crosses on the anterior side of a joint produces flexion*   Teres major  (posterolateral view)  The teres major is  the antagonist of  the deltoid.    * These generalities are reversed for the knee and ankle because the lower limb is rotated during development.  The muscles that cross these joints posteriorly produce flexion, and those that cross anteriorly produce extension.    Figure 6.14 Muscle action. The action of a muscle can be inferred by the    Like bones, muscles come in many shapes and sizes  to suit their particular tasks in the body. Muscles are  named on the basis of several criteria, each of which  focuses on a particular structural or functional char-  acteristic. Paying close attention to these cues can  greatly simplify your task of learning muscle names  and actions:    e Direction of the muscle fibers. Some mus-  cles are named in reference to some imaginary  line, usually the midline of the body or the long  axis of a limb bone. When a muscle’s name  includes the term rectus (straight), its fibers or  whole structure run parallel to that imaginary  line. For example, the rectus femoris is the  straight muscle of the thigh. Similarly, the term  oblique in a muscle’s name tells you that the  muscle fibers run obliquely (at a slant) to the  imaginary line.   e Relative size of the muscle. Such terms as  maximus (largest), minimus (smallest), and longus  (long) are sometimes used in the names of  muscles—for example, the gluteus maximus is  the largest muscle of the gluteus muscle group.    e Location of the muscle. Some muscles are  named for the bone with which they are associ-  ated. For example, the temporalis and frontalis  muscles overlie the temporal and frontal bones  of the skull, respectively. Note the spellings!    e Number of origins. When the term biceps,  triceps, or quadriceps forms part of a muscle  name, you can assume that the muscle has two,  three, or four origins, respectively. For example,  the biceps muscle of the arm has two heads, or  origins, and the triceps muscle has three.    e Location of the muscle’s origin and inser-  tion. Occasionally, muscles are named for their  attachment sites. For example, the sternocleido-  mastoid muscle has its origin on the sternum  (sterno) and clavicle (cleido) and inserts on the  mastoid process of the temporal bone.    e Shape of the muscle. Some muscles have a  distinctive shape that helps to identify them. For  example, the deltoid muscle is roughly triangu-  lar (deltoid means “triangular” ), like the Greek  letter delta (A).    e Action of the muscle. When muscles are  named for their actions, terms such as flexor,  extensor, and adductor appear in their names. For  example, the adductor muscles of the thigh all  bring about its adduction, and the extensor  muscles of the wrist all extend the wrist.    Skeletal muscles consist of fascicles (refer to Fig-  ure 6.1), but fascicle arrangements vary, producing  muscles with different structures and functional prop-  erties. Next, let's look at the most common patterns of  fascicle arrangement: circular, convergent, fusiform,  parallel, multipennate, bipennate, and unipennate.   In a circular pattern, the fascicles are arranged in  concentric rings (Figure 6.15a). Circular muscles are  typically found surrounding external body openings  which they close by contracting, creating a valve.  A general term for such muscles is sphincters  (“squeezers”). Examples are the orbicularis muscles  surrounding the eyes and mouth.   In a convergent muscle, the fascicles converge  toward a single insertion tendon. A convergent mus-  cle is triangular or fan-shaped, such as the pectoralis  major muscle of the anterior thorax (Figure 6.15b).   In a parallel arrangement, the length of the fas-  cicles run parallel to the long axis of the muscle, as in  the sartorius of the anterior thigh. These muscles  are straplike (Figure 6.15d). A modification of the  parallel arrangement, called fusiform, results in a  spindle-shaped muscle with an expanded belly  (midsection) and tapered ends. An example is the  biceps brachii muscle of the arm (Figure 6.15c).   In a pennate (pen’at; “feather”) pattern, short fas-  cicles attach obliquely to a central tendon. In the  extensor digitorum muscle of the leg, the fascicles  insert into only one side of the tendon, and the muscle  is unipennate (Figure 6.15g). If the fascicles insert into  opposite sides of the tendon, the muscle is bipennate  (Figure 6.15f). If the fascicles insert from several differ-  ent sides, the muscle is multipennate (Figure 6.15e).   A muscle’s fascicle arrangement determines its  range of motion and power. The longer and the  more nearly parallel the fascicles are to a muscle’s  long axis, the more the muscle can shorten, but such  muscles are not usually very powerful. Muscle power  depends more on the total number of muscle fibers  in the muscle. The stocky bipennate and multipen-  nate muscles, which pack in the most fibers, shorten  very little but are very powerful, like the rectus femo-  ris of the anterior thigh.    19. Based on their names, deduce some characteristics of  the following muscles: tibialis anterior, erector spinae,  rectus abdominis, extensor carpi radialis longus.   20. What is the fascicle arrangement of the orbicularis  oris muscle?    v@ Name and locate the major muscles of the  human body (on a torso model, muscle chart,  or diagram), and state the action of each.    It is beyond the scope of this book to describe the  hundreds of skeletal muscles of the human body. We  describe only the most important muscles here. All  the superficial muscles we consider are summarized  in Tables 6.3 and 6.4 (pp. 234-235) and illustrated  in the overall body views shown later in the chapter  (Figures 6.22 and 6.23, pp. 232-233).    are usually grouped into two large categories—facial  muscles and chewing muscles. Facial muscles are  unique because they insert into soft tissues, such as  other muscles or skin. When they pull on the skin of  the face, they permit us to express ourselves by frown-  ing, smiling, and so forth. The chewing muscles  begin to break down food for the body. All head and  neck muscles we describe are paired except for the  platysma, orbicularis oris, frontalis, and occipitalis.    Frontalis and Occipitalis The frontalis, which cov-  ers the frontal bone, runs from the cranial aponeuro-  sis to the skin of the eyebrows, where it inserts. This  muscle allows you to raise your eyebrows, as in sur-  prise, and to wrinkle your forehead. At the posterior  end of the cranial aponeurosis is the small occipita-  lis muscle, which covers the posterior aspect of the  skull and pulls the scalp posteriorly. *    Orbicularis Oculi The fibers of the orbicularis oculi  (or-bik”u-la’ris ok’u-li) run in circles around the    *Although the current references on anatomic terminology  refer to the frontalis and occipitalis as the frontal and occipital  bellies of the epicranius (“over the cranium”) muscle, we will  continue to use the terms frontalis and occipitalis here.    eyes. It allows you to close your eyes, squint, blink,  and wink.    Orbicularis Oris The orbicularis oris is the circular  muscle of the lips. Often called the “kissing” muscle,  it closes the mouth and protrudes the lips.    Buccinator The fleshy buccinator (buck’si-na”tor)  muscle runs horizontally across the cheek and inserts  into the orbicularis oris. It flattens the cheek (as in  whistling or blowing a trumpet). It is also listed as a  chewing muscle because it compresses the cheek to  hold food between the teeth during chewing.    Zygomaticus The zygomaticus (zi"go-mat'i-kus)  extends from the corner of the mouth to the cheek-  bone. It is often referred to as the “smiling” muscle  because it raises the corners of the mouth.    Masseter As it runs from the zygomatic process of  the temporal bone to the mandible, the masseter  (mă-se'ter) covers the angle of the lower jaw. This  muscle elevates the mandible to close the jaw.    Temporalis The temporalis is a fan-shaped muscle  overlying the temporal bone. It inserts into the man-  dible and acts as a synergist of the masseter in clos-  ing the jaw.    For the most part, the neck muscles, which move the  head and shoulder girdle, are small and straplike. We  consider only two neck muscles here (Figure 6.16).    Platysma The platysma is a single sheetlike muscle  that covers the anterolateral neck (see Figure 6.16). It  originates from the connective tissue covering of the  chest muscles and inserts into the area around the  mouth. Its action is to pull the corners of the mouth  inferiorly, producing a downward sag of the mouth  (the “sad clown” face).    Sternocleidomastoid The paired sternocleidomas-  toid (ster"no-kli"do-mas'toid) muscles are two-  headed muscles, one found on each side of the neck.  Of the two heads of each muscle, one arises from the  sternum, and the other arises from the clavicle (see    Learn more at Mastering A&P > Study Area > A  ty Additional Study Tools > A Closer Look    So" people who feel the pressure  to look and perform their best turn  to performance-enhancing drugs. Ana-  bolic steroids are variants of testoster-   changes during puberty that usher boys  into manhood. The most notable effect   Do the claimed slight advantages  conferred by steroids outweigh their  risks? Absolutely not! Side effects  from steroid use vary but include  increased risk of heart attack and    facial hair but lose scalp hair, develop  a deeper voice, become infertile, and  have an increased risk of osteoporosis.  It is also increasingly clear that steroids  can be addictive and lead to serious  psychological issues such as depres-  sion, delusions, paranoia, and aggres-    e Anabolic steroids are versions  of the male sex hormone  testosterone.    is the increase in bone and muscle  mass. Anabolic steroids were introduced  in the 1950s to treat certain muscle-  wasting diseases, anemia, and muscle  atrophy in patients immobilized after  surgery, and they  became available to  the general public  during the 1980s.  Although most  international athletic  competitions and  leagues have banned  anabolic steroids,  some athletes still  claim they increase    stroke, high blood pressure, an  enlarged heart, dangerous changes in  cholesterol levels, fluid retention, and  acne. Adolescents can experience  stunted growth and early onset of  puberty. Gender-  specific side effects  can also occur:  Men may experi- e Serious side effects of steroid  ence baldness, use include increased risk of  breast enlarge- heart attack and stroke.    ment, and shrink- e Gender-specific risks include  ing testicles, with shrinking testicles in men and    The trunk muscles include (1) muscles that move the  vertebral column (most of which are posterior anti-  gravity muscles); (2) anterior thorax muscles, which  move the ribs, head, and arms; and (3) muscles of  the abdominal wall, which “hold your guts in” by  forming a natural girdle and help to move the verte-  bral column.    Figure 6.22, p. 232). The heads fuse before inserting  into the mastoid process of the temporal bone.  When both sternocleidomastoid muscles contract  together, they flex your neck. (It is this action of bow-  ing the head that has led some people to call these  muscles the “prayer” muscles.) If just one muscle  contracts, the face is rotated toward the shoulder on  the opposite side and tilts the head to its own side.    Pectoralis Major The pectoralis (pek’to-ra’lis) major  is a large fan-shaped muscle covering the upper part of  the chest. Its origin is from the sternum, shoulder    baby injured in this way has torticollis (tor’ti-kol’is),  or wryneck, and the neck remains rotated toward one  side.   22. Which two muscles are synergists in closing your jaw?  For answers, see Appendix A.    girdle, and the first six ribs. It inserts on the proximal  end of the humerus. This muscle forms the anterior  wall of the axilla (armpit) and acts to adduct and flex  the arm.    muscles found between the ribs. (Although they are  not shown in Figure 6.17, which shows only    Figure 6.17 Muscles of the anterior trunk, shoulder, and arm. (a) Muscles  crossing the shoulder joint, causing movements of the arm. The platysma of the  neck is removed. (b) Muscles of the abdominal wall. Portions of the superficial  muscles of the right side of the abdomen are cut away to reveal the deeper muscles.    superficial muscles, they are illustrated in Figure 6.22,  p. 232.) The external intercostals, which lie toward the  lateral edge of the rib cage, are important in breathing  because they help to raise the rib cage when you  inhale. The internal intercostals, which lie deep and  medial to the external intercostals, depress the rib cage,  helping to move air out of the lungs when you exhale  forcibly.    Muscles of the Abdominal Girdle The anterior ab-  dominal muscles (rectus abdominis, external and  internal obliques, and transversus abdominis) form  a natural “girdle” that reinforces the body trunk.  Taken together, they resemble the structure of ply-  wood because the fibers of each muscle or muscle  pair run in a different direction. Just as plywood is  exceptionally strong for its thickness, the abdominal  muscles form a muscular wall that is well suited for  its job of containing and protecting the abdominal  contents.    Rectus abdominis. The paired straplike rectus  abdominis muscles are the most superficial  muscles of the abdomen. They run from the  pubis to the rib cage, enclosed in an aponeuro-  sis. Their main function is to flex the vertebral  column. They also compress the abdominal con-  tents during defecation and childbirth (they  help you “push”) and are involved in forced  breathing.    External oblique. The external oblique muscles  are paired superficial muscles that make up the  lateral walls of the abdomen. Their fibers run  downward and medially from the last eight ribs  and insert into the ilium. Like the rectus abdomi-  nis, together they flex the vertebral column, but  individually they also rotate the trunk and bend  it laterally.    Internal oblique. The internal oblique muscles  are paired muscles deep to the external obliques.  Their fibers run at right angles to those of the    Figure 6.18 Muscles of the posterior neck, trunk, and arm. (a) Superficial  muscles. (b) The erector spinae muscles (longissimus, iliocostalis, and spinalis), deep    external obliques. They arise from the iliac crest  and insert into the last three ribs. Their functions  are the same as those of the external obliques.    e Transversus abdominis. The deepest muscle  of the abdominal wall, the transversus abdominis  has fibers that run horizontally across the abdo-  men. It arises from the lower ribs and iliac crest  and inserts into the pubis. This muscle com-  presses the abdominal contents like a wide belt.    Trapezius The trapezius (trah-pe’ze-us) muscles  are the most superficial muscles of the posterior  neck and upper trunk. When seen together, they  form a diamond- or kite-shaped muscle mass. Their  origin is very broad. Each muscle runs from the  occipital bone of the skull down the vertebral col-  umn to the end of the thoracic vertebrae. They then  flare laterally to insert on the scapular spine and  clavicle. The trapezius muscles extend the head (thus  they are antagonists of the sternocleidomastoids).  They also can elevate, depress, adduct, and stabilize  the scapula.    Latissimus Dorsi The latissimus (lah-tis’i-mus) dorsi  muscles are the two large, flat muscles that cover the  lower back. They originate on the lower spine and  ilium and then sweep superiorly to insert into the  proximal end of the humerus. Each latissimus dorsi  extends and adducts the humerus. These are very  important muscles when the arm must be brought  down in a power stroke, as when swimming or striking  a blow.    Erector Spinae The erector spinae (e-rek'tor spi’ne)  group is the prime mover of back extension. These  paired muscles are deep muscles of the back  (Figure 6.18b). Each erector spinae is a composite  muscle consisting of three muscle columns (longis-  simus, iliocostalis, and spinalis) that collectively  span the entire length of the vertebral column.  These muscles not only act as powerful back exten-  sors (“erectors”) but also provide resistance that  helps control the action of bending over at the  waist. Following injury to back structures, these  muscles go into spasms, a common source of lower  back pain.    Figure 6.19 The fleshy deltoid muscle is a favored  site for administering intramuscular injections.    Quadratus Lumborum The fleshy quadratus lum-  borum (qwad-ra’tus lum-bor'um) muscles form  part of the posterior abdominal wall. Acting sepa-  rately, each muscle of the pair flexes the spine later-  ally. Acting together, they extend the lumbar spine.  These muscles arise from the iliac crests and insert  into the upper lumbar vertebrae (Figure 6.18b).    Deltoid The deltoids are fleshy, triangle-shaped  muscles that form the rounded shape of your shoul-  ders. Because they are so bulky, they are a favorite  injection site (Figure 6.19) when relatively small  amounts of medication (less than 5 ml) must be  given intramuscularly (into muscle). The origin of  each deltoid winds across the shoulder girdle from  the spine of the scapula to the clavicle. It inserts into  the proximal humerus. The deltoids are the prime  movers of arm abduction.    23. Which muscle group is the prime mover of back  extension?   24. What structural feature makes the abdominal  musculature especially strong for its thickness?   25. Which muscle of the posterior trunk is the  synergist of the pectoralis major muscle in  arm adduction?    The upper limb muscles fall into three groups. The  first group includes muscles that arise from the  shoulder girdle and cross the shoulder joint to insert  into the humerus (see Figures 6.17 and 6.18a). We  have already considered these muscles, which move  the arm—they are the pectoralis major, latissimus  dorsi, and deltoid.   The second group causes movement at the elbow  joint. These muscles enclose the humerus and insert  on the forearm bones. In this section we will focus  on the muscles of this second group.   The third group of upper limb muscles includes  the muscles of the forearm, which insert on the hand  bones and cause their movement. The muscles of  this last group are thin and spindle-shaped, and  there are many of them. We will not consider them  here except to mention their general naming and  function. As a rule, the forearm muscles have names  that reflect their activities. For example, the flexor  carpi and flexor digitorum muscles, found on the  anterior aspect of the forearm, flex the wrist and fin-  gers, respectively. The extensor carpi and extensor  digitorum muscles, found on the lateral and poste-  rior aspect of the forearm, extend the same struc-  tures. (Table 6.4 and Figure 6.23 briefly describe  some of these muscles; see pp. 233, 235).    All anterior muscles of the humerus cause elbow flex-  ion. In order of decreasing strength these are the bra-  chialis, biceps brachii, and brachioradialis (Figures  6.17a and 6.22, p. 232).    Biceps Brachii The biceps brachii (bra’ke-i) is the  most familiar muscle of the arm because it bulges  when you flex your elbow (see Figure 6.17a). It  originates by two heads from the shoulder girdle  and inserts into the radial tuberosity. This muscle is  a powerful prime mover for flexion of the forearm  and acts to supinate the forearm. The best way to  remember its actions is to think of opening a bot-  tle of wine. The biceps supinates the forearm to  turn the corkscrew and then flexes the elbow to pull  the cork.    Brachialis The brachialis lies deep to the biceps  brachii and, like the biceps, is a prime mover in  elbow flexion. The brachialis lifts the ulna as the  biceps lifts the radius.    Brachioradialis The brachioradialis is a fairly weak  muscle that arises on the humerus and inserts into the  distal forearm (see Figure 6.22, p. 232). Hence, it  resides mainly in the forearm and aids elbow flexion.    Triceps Brachii The triceps brachii is the only mus-  cle fleshing out the posterior humerus (see Fig-  ure 6.18a). Its three heads arise from the shoulder  girdle and proximal humerus, and it inserts into the  olecranon process of the ulna. Being the powerful  prime mover of elbow extension, it is the antagonist  of the biceps brachii and brachialis. This muscle  straightens the arm—for instance, to deliver a strong  jab in boxing.    Muscles that act on the lower limb cause movement  at the hip, knee, ankle, and foot joints. They are  among the largest, strongest muscles in the body and  are specialized for walking and balancing the body.  Because the pelvic girdle is composed of heavy, fused  bones that allow little movement, no special group  of muscles is necessary to stabilize it. This is very dif-  ferent from the shoulder girdle, which requires sev-  eral fixator muscles.   Many muscles of the lower limb span two joints  and can cause movement at both of them. Therefore,  in reference to these muscles, the terms origin and  insertion are often interchangeable depending on the  action being performed.   Muscles acting on the thigh are massive mus-  cles that help hold the body upright against the  pull of gravity and cause various movements at the  hip joint. Muscles acting on the leg form the flesh  of the thigh. (Remember, anatomically the term  leg refers only to that part between the knee and  the ankle.) The thigh muscles cross the knee and  cause its flexion or extension. Because many of the  thigh muscles also have attachments on the pelvic  girdle, they can cause movement at the hip joint  as well.   Muscles originating on the leg cause assorted  movements of the ankle and foot. We will consider  only three muscles of this group, but there are many  others that extend and flex the ankle and toe joints.    Muscles Causing Movement at the Hip Joint  (Figure 6.20, pp. 228-229)    Gluteus Maximus The gluteus maximus (gloo’te-  us max'i-mus) is a superficial muscle of the hip    that forms most of the flesh of the buttock  (Figure 6.20a). It is a powerful hip extensor that  acts to bring the thigh in a straight line with the  pelvis. Although it is not very important in walk-  ing, it is probably the most important muscle for  extending the hip when power is needed, as when  climbing stairs or jumping. It originates from the  sacrum and iliac bones and inserts on the gluteal  tuberosity of the femur and into the large tendi-  nous iliotibial tract.    Gluteus Medius The gluteus medius runs from the  ilium to the femur, beneath the gluteus maximus for  most of its length. The gluteus medius is a hip abduc-  tor and is important in steadying the pelvis during  walking. It is also an important site for giving intra-  muscular injections, particularly when administering  more than 5 ml (Figure 6.20b). Although it might  appear that the large, fleshy gluteus maximus that  forms the bulk of the buttock mass would be a better  choice, note that the medial part of each buttock over-  lies the large sciatic nerve; hence this area must be care-  fully avoided to prevent nerve damage. This can be  accomplished by imagining the buttock is divided  into four equal quadrants (shown by the division  lines on Figure 6.20b). The superolateral quadrant  then overlies the gluteus medius muscle, which is usu-  ally a very safe site for an intramuscular injection.  Injections at or near the sciatic nerve can result in  physical trauma from the needle or degeneration of  the nerve itself.    Iliopsoas The iliopsoas (il”e-o-so'as; the p is silent)  is a fused muscle composed of two muscles, the ilia-  cus and the psoas major (Figure 6.20c). It runs from  the iliac bone and lower vertebrae deep inside the  pelvis to insert on the lesser trochanter of the femur.  It is a prime mover of hip flexion. It also acts to keep  the upper body from falling backward when we are  standing erect.    Adductor Muscles The muscles of the adductor  group form the muscle mass at the medial side of  each thigh (Figure 6.20c). As their name indicates,  they adduct, or press, the thighs together. However,  because gravity does most of the work for them, they  tend to become flabby very easily. Special exercises  are usually needed to keep them toned. The adduc-  tors have their origin on the pelvis and insert on the  proximal aspect of the femur.    Figure 6.20 Pelvic, hip, and thigh muscles of the right side of the body.  (a) Posterior view of hip and thigh muscles. (b) Diagram showing deep structures of  the gluteal region and the proper site for administering an injection into the gluteus    Hamstring Group The muscles forming the mus-  cle mass of the posterior thigh are the hamstrings  (Figure 6.20a). The group consists of three muscles—  the biceps femoris, semimembranosus, and semitendino-  sus—which originate on the ischial tuberosity and  run down the thigh to insert on both sides of the  proximal tibia. They are prime movers of thigh  extension and knee flexion. Their name comes from    the fact that butchers use their tendons to hang hams  (consisting of thigh and hip muscles) for smoking.  You can feel these tendons at the back of your knee.    Sartorius Compared with other thigh muscles  described here, the thin, straplike sartorius (sar-to’re-  us) muscle is not too important. However, it is the  most superficial muscle of the thigh and so is rather  hard to miss (Figure 6.20c). It runs obliquely across  the thigh from the anterior iliac crest to the medial    What is the insertion for the rectus femoris during hip flexion: the pelvis or the  tibial tuberosity? Which is the insertion during knee extension?    pelvic and thigh muscles. (d) Diagram showing  the proper site for administering an injection into  the lateral thigh (vastus lateralis muscle). *Note  that the fourth quadriceps muscle, the vastus    Figure 6.21 Superficial muscles of the right leg. (a) Anterior view.    side of the tibia. It is a weak thigh flexor. The sarto-  rius is commonly referred to as the “tailor's” muscle  because it acts as a synergist to help tailors sit with    Quadriceps Group The quadriceps (kwod'ri-seps)  group consists of four muscles—the rectus femoris  and three vastus muscles—that flesh out the anterior  thigh. (Only two vastus muscles are visible in  Figure 6.20c. The third, the vastus intermedius, is  obscured by the rectus femoris muscle, which lies  over it.) The vastus muscles originate from the  femur; the rectus femoris originates on the pelvis. All  four muscles insert into the tibial tuberosity via the    patellar ligament. The group as a whole acts to  extend the knee powerfully, as when kicking a soccer  ball. Because the rectus femoris crosses two joints,  the hip and knee, it can also help to flex the hip. The  vastus lateralis and rectus femoris are sometimes  used as intramuscular injection sites (Figure 6.20d),  particularly in infants, who have poorly developed  gluteus muscles.    Tibialis Anterior The tibialis anterior is a superfi-  cial muscle on the anterior leg. It arises from the  proximal tibia and then parallels the anterior crest as    it runs to the tarsal bones, where it inserts by a long  tendon. It acts to dorsiflex and invert the foot.    Extensor Digitorum Longus Lateral to the tibialis  anterior, the extensor digitorum longus muscle arises  from the lateral tibial condyle and proximal three-  quarters of the fibula and inserts into the phalanges  of toes 2 to 5. It is a prime mover of toe extension.    Fibularis Muscles The three fibularis muscles—  longus, brevis, and tertius—are found on the lateral  part of the leg. They arise from the fibula and insert  into the metatarsal bones of the foot. The group as a  whole plantar flexes and everts the foot, which is  antagonistic to the tibialis anterior.    Gastrocnemius The gastrocnemius (gas”trok-  ne’me-us) muscle is a two-bellied muscle that forms  the curved calf of the posterior leg. It arises by two  heads, one from each side of the distal femur, and  inserts through the large calcaneal (Achilles) tendon  into the heel of the foot. It is a prime mover for plan-  tar flexion of the foot; for this reason it is often  called the “toe dancer's” muscle. If the calcaneal ten-  don is severely damaged or cut, walking is very diffi-  cult. The foot drags because it is not able to “push  off” the toe (raise the heel).    Soleus Deep to the gastrocnemius is the fleshy  soleus muscle. Because it arises on the tibia and fib-  ula (rather than the femur), it does not affect knee  movement, but like the gastrocnemius, it inserts into  the calcaneal tendon and is a strong plantar flexor of  the foot.   Figure 6.22 (p. 232) and Figure 6.23 (p. 233)  show anterior and posterior views of the whole body,  including most of the superficial muscles we have  described. Table 6.3 (p. 234) and Table 6.4 (p. 235)  summarize these muscles. Take time to review these  muscles again before continuing with this chapter.    26. Which muscle is the antagonist of the biceps  brachii when the biceps flexes the elbow?   27. Which muscle group is the antagonist of the  hamstring muscles?   28. What are two good sites for intramuscular  injections in adults?   29. Which two muscles insert into the calcaneal  tendon? What movement do they effect?    v@ Explain the importance of a nerve supply and  exercise in keeping muscles healthy.    laid down in segments, and then each segment is  invaded by nerves. The muscles of the thoracic and  lumbar regions become very extensive because they  must cover and move the bones of the limbs. The  muscles and their control by the nervous system  develop rather early in pregnancy. The expectant  mother is often astonished by the first movements  (called the quickening) of the fetus, which usually  occur by the 16th week of pregnancy.    Homeostatic J  —S Imbalance 6.4  Very few congenital muscular problems occur. The  exception to this is muscular dystrophy—a group  of inherited muscle-destroying diseases that affect  specific muscle groups. The muscles appear to  enlarge because of fat and connective tissue deposits,  but the muscle fibers degenerate and atrophy.   The most common and serious form is  Duchenne’s muscular dystrophy, which is  expressed almost exclusively in boys. This tragic dis-  ease is usually diagnosed between the ages of 2 and  7 years. Active, normal-appearing children become  clumsy and fall frequently as their muscles weaken.  The disease progresses from the extremities upward,  finally affecting the head and chest muscles. Children  with this disease rarely live beyond their early twen-  ties and generally die of respiratory failure. Although  researchers have identified the cause of muscular  dystrophy—the diseased muscle fibers lack a protein  (called dystrophin) that helps maintain the sarco-  lemma—a cure is still elusive.    After birth, a baby’s movements are all gross  reflex types of movements. Because the nervous sys-  tem must mature before the baby can control mus-  cles, we can track nervous system function by  observing a baby’s development of muscle control.  This development proceeds in a superior/inferior    Facial l e Orbicularis oculi  e Temporalis e Zygomaticus  e Masseter    Neck  Shoulder e Platysma  e Trapezius e Sternocleidomastoid  Thorax  e Deltoid e Pectoralis minor  e Pectoralis major  Arm    Figure 6.23 Major superficial muscles  of the posterior surface of the body.    e Flexor carpi ulnaris  e Extensor carpi ulnaris  e Extensor digitorum    lliotibial tract  i e Adductor muscle  W e Hamstrings:  V Biceps femoris  \ Semitendinosus  Semimembranosus  Leg    Quadriceps group (vastus  medialis, intermedius, and  lateralis; and the rectus  femoris)    Table 6.4 Superficial Posterior Muscles of the Body (Some Forearm Muscles Also Shown)    Triceps brachii  Flexor carpi radialis  Flexor carpi ulnaris  Flexor digitorum  superficialis’    Lower spine and iliac crest  lliac crests, ribs 3-12, and  vertebrae    Proximal tibia (head of  fibula in the case of biceps  femoris)    *Erector spinae and quadratus lumborum are deep muscles (they are not shown in Figure 6.23; see Figure 6.18b).  tAlthough its name indicates that it is a superficial muscle, the flexor digitorum superficialis lies deep to the flexor carpi radialis and is not visible in a    direction, and gross muscular movements precede  fine ones. Babies can raise their heads before they  can sit up and can sit up before they can walk.  Muscular control also proceeds in a proximal/distal  direction; that is, babies can perform the gross move-  ments like waving “bye-bye” and pulling objects to  themselves before they can use the pincer grasp to  pick up a pin. By midadolescence, we have reached  the peak level of development of this natural control  and can simply accept it or bring it to a fine edge by  athletic training.   Because of its rich blood supply, skeletal muscle  is amazingly resistant to infection throughout life,  and given good nutrition, relatively few problems  afflict skeletal muscles. We repeat, however, that  muscles, like bones, will atrophy, even with normal  tone, if they are not used continually. A lifelong pro-  gram of regular exercise keeps the whole body oper-  ating at its best possible level.    Homeostatic B  £ Imbalance 6.5  One rare autoimmune disease that can affect mus-  cles during adulthood is myasthenia gravis  (mi’as-the’ne-ah gra'vis; asthen = weakness; gravi =  heavy), a disease characterized by drooping upper  eyelids, difficulty in swallowing and talking, and  generalized muscle weakness and fatigability. The  disease results when there are too few acetylcholine  receptors at neuromuscular junctions because anti-  bodies specific for acetylcholine receptors have  attacked them. Antibodies are immune molecules—  in this case, made by a person’s own immune  system—that will mark the receptors for destruc-  tion. Because the muscle fibers are not stimulated  properly, they get progressively weaker. Death  usually occurs when the respiratory muscles can  no longer function, which leads to respiratory  failure.    A female patient with myasthenia gravis. Notice the effect on  the patient's eyelid muscles.    As we age, the amount of connective tissue in  muscles increases, and the amount of muscle tissue  decreases; thus the muscles become stringier, or  more sinewy. Because skeletal muscles represent so  much of our body mass, body weight begins to  decline in older adults as this natural loss in muscle  mass occurs. Muscle strength also decreases by about  50 percent by age 80. Regular exercise can help offset  the effects of aging on the muscular system, and frail  older people who begin to “pump iron” (use leg and  hand weights) can rebuild muscle mass and dramat-  ically increase their strength.    30. What must happen before babies can control their  muscles?  31. How does lifelong exercise affect our skeletal  muscles and muscle mass in old age?  For answers, see Appendix A.    e Growth hormone and androgens  influence skeletal muscle strength  and mass    e Physical exercise may enhance  or depress immunity depending  on its intensity    e Skeletal muscle activity increases  efficiency of cardiovascular  functioning; helps prevent  atherosclerosis and causes  cardiac hypertrophy   e Cardiovascular system delivers  oxygen and nutrients to muscles;  carries away wastes    e Skeletal muscle helps support  pelvic organs (e.g., uterus in  females); assists erection of  penis and clitoris    e Physical activity promotes normal  voiding behavior; skeletal muscle  forms the voluntary sphincter of  the urethra Integumentary System    e Urinary system disposes of | e Muscular exercise enhances  nitrogen-containing wastes circulation to skin and improves  skin health; exercise also  increases body heat, which the  | skin helps dissipate  y e Skin protects the muscles by    (aN Listen to the story of this chapter in a brief summary at Mastering A&P >  S umma ry J Study Area > Author Narrated Audio Summaries    6.1 Overview of Muscle Tissues (pp. 199-203) 6.3 Skeletal Muscle Activity (pp. 205-214)  6.1a. The three types of muscle differ in structure, 6.3a. Skeletal muscle fibers are stimulated by a  location, and how they are controlled motor neuron at a neuromuscular junction  è Skeletal muscle—forms muscles attached to the e A motor neuron and all muscle fibers it inner-    ° Skeletal muscle fibers (cells) are long and  multinucleate; skeletal muscle also known as  striated muscle and voluntary muscle    o Connective tissue coverings (endomysium,  perimysium, and epimysium) enclose and  protect the muscle fibers and increase the  strength of skeletal muscles    e As a nerve impulse reaches the axon terminal,  the neuron releases a neurotransmitter  (acetylcholine), causing sarcolemma  permeability to change    ° Sodium ions enter the muscle fiber, causing  an action potential to flows across the entire  sarcolemma, resulting in release of calcium ions  (Ca?*) from the SR    = Epimysium ends blend to form tendons or e Calcium binds to regulatory proteins on the thin  aponeuroses that attach the muscle to the filaments, exposing myosin-binding sites  body . ; .  o Myosin heads attach to actin, forming cross  e Smooth muscle—uninucleate, spindle-shaped, bridges; contraction occurs when the attached  arranged in opposing layers in the walls of hollow heads pivot, sliding the thin filaments toward  organs the center of the sarcomere  ° Move substances (food, urine, a baby) along ° ATP provides the energy for the sliding process,  internal pathways, under involuntary control which continues as long as ionic calcium is  e Cardiac muscle—striated, branching cells that fit present   movement, maintaining posture, stabilizing joints, of stimulation or the number of motor units   arranged end-to-end = Fused tetanus—no relaxation between  = Sarcomere—the structural and functional stimuli; results in smooth, sustained  unit of skeletal muscle contraction  o Striations in myofibrils reflect the arrangement ° The strength of whole muscle contraction  of thin filaments (actin) and thick filaments reflects the relative number of muscle fibers  (myosin) within the sarcomeres contracting (more = stronger)   e Each myofibril is loosely enclosed by sarcoplas- e ATP provides energy for muscle contraction and is  mic reticulum (SR) (specialized ER)—plays an stored in muscle fibers in small amounts  important role in storing and releasing calcium e ATP is regenerated three ways (fastest to slowest)  ve o Creatine phosphate (CP) donates a phos-    o Aerobic respiration, which requires oxygen  and produces the most ATP    e Prolonged, strenuous activity results in muscle  fatigue  o Caused by ionic imbalances, lactic acid accu-  mulation, decreased ATP supply    o After exercise, oxygen deficit is repaid by rapid,  deep breathing    e Muscle contractions are isotonic contractions  (muscle shortens, movement occurs) or isomet-  ric contractions (muscle does not shorten, ten-  sion increases)    o No nerve supply; muscle loses tone, becomes  paralyzed, and atrophies    o Resistance exercise causes muscles to increase  in size and strength    ° Endurance exercise causes muscles to be more  efficient, stronger, and fatigue resistant; other  body systems also benefit    e Body movements include flexion, extension,  abduction, adduction, circumduction, rotation,  pronation, supination, inversion, eversion,  dorsiflexion, plantar flexion, and opposition    6.4b. On the basis of functions, muscles are  classified as prime movers, antagonists,  synergists, and fixators    6.4c. Muscles names can be derived from several  functional and structural characteristics, including  size, shape, number and location of origins, asso-  ciated bones, and action    6.4d. Fascicle arrangements influence the force and  degree of shortening a muscle can produce    e Fascicle arrangements include: circular,  convergent, fusiform, parallel, and pennate  (multipennate, bipennate, unipennate)    6.5b. Muscles of the trunk and neck move the  head, shoulder girdle, and trunk; and form the  abdominal girdle    e Anterior neck and trunk muscles—sternoclei-  domastoid, platysma, pectoralis major, external  and internal intercostals, rectus abdominis,  external and internal obliques, transversus  abdominis    e Posterior neck and trunk muscles—trapezius,  latissimus dorsi, deltoid, quadratus lumborum    e Muscles moving the hip—iliopsoas, gluteus maxi-  mus, gluteus medius, adductors   e Muscles moving the ankle and foot—gastrocne-  mius, tibialis anterior, fibularis muscles, soleus,  extensor digitorum longus   e Muscles will atrophy without regular exercise;  with vigorous exercise, they hypertrophy    1. Compare these images of a relaxed skeletal muscle  fiber and a fully contracted muscle fiber. Which  would you see only in the relaxed fiber?   2. After ACh attaches to its receptors at the neuromuscu-  lar junction, what is the next step?  a. Sodium channels open.    6. Which of the following muscles attach to the hip  bones?    7. Which of these muscles is found on the posterior sur-  face of the leg?    8. Which of the following is (are) true concerning the  pectoralis major?  a. It raises the clavicle. c. It abducts the arm.    9. Compare skeletal, smooth, and cardiac muscles in  regard to their microscopic anatomy, location and  arrangement in body organs, and function in the body.    10. Why are the connective tissue wrappings of skeletal  muscles important? Name these connective tissue  coverings, beginning with the finest and ending with  the coarsest.    11. Define neuromuscular junction, motor unit, tetanus,  graded response, aerobic respiration, anaerobic glycolysis,  muscle fatigue, and neurotransmitter.    12. Describe the events that occur from the time calcium  ions enter the axon terminal at the neuromuscular  junction until muscle cell contraction occurs.    13. How does muscle activity contribute to the mainte-  nance of body temperature? Explain how significant  this contribution is.    14. In addition to acting to flex the spine and compress    the abdominal contents, the abdominal muscles are  extremely important in protecting and containing the  abdominal viscera. What is it about the arrangement  of these muscles that makes them so well suited for  their job?    The hamstring and quadriceps muscle groups are  antagonists of each other, and each group is a prime  mover in its own right. What action does each muscle  group perform?    Explain the general relationship between the muscles  that flex and extend the wrist, including their location  on the body.    17. Name three muscles or muscle groups used as sites for    18. While jogging, Mr. Ahmadi was forced to jump out of    the way of a speeding car. He heard a snapping sound  that was immediately followed by pain in his right  lower calf. A gap was visible between his swollen calf  and his heel, and he was unable to plantar flex that  foot. What do you think happened?    heavily and sweating profusely, and he complained  that his legs ached and felt weak. On the basis of what    you have learned about muscle energy metabolism,  respond to the following questions:    c. What metabolic product(s) might account for his  sore muscles and his feeling of muscle weakness?    Chemical A binds and blocks acetylcholine receptors  of muscle cells. Chemical B floods the cytoplasm of  muscle cells with calcium ions. Which chemical  would make the best muscle relaxant, and why?    As the primary control  system of the body, the nervous  system provides for higher mental  function and emotional expression,  maintains homeostasis, and  regulates the activities of  muscles and glands.    All body systems are  influenced by the nervous  system in some way. If the nervous  systems stops functioning, the body  can stay alive only with the  A   You are with a group of friends but are not pay-  ing attention to any particular conversation, yet when  you hear your name, you immediately focus in. What  do these events have in common? They are everyday  examples of nervous system function, which has your  body cells humming with activity all the time.   The nervous system is the master control and  communication system of the body. Every thought,  action, and emotion reflects its activity. It communi-  cates with body cells using electrical impulses, which  are rapid and specific and cause almost immediate  responses.    Communication by  the nervous system involves  a combination of electrcial  and chemical signals.    The nervous system does not work alone to reg-  ulate and maintain body homeostasis; the endocrine  system is a second important regulating system.  Whereas the nervous system controls with rapid  electrical nerve impulses, the endocrine system pro-  duces hormones that are released into the blood.  Thus, the endocrine system acts in a more leisurely  way. We will discuss the endocrine system in detail  in Chapter 9.   To carry out its normal role, the nervous system  has three overlapping functions (Figure 7.1): (1) It  uses its millions of sensory receptors to monitor  changes occurring both inside and outside the body.  These changes are called stimuli, and the gathered    information is called sensory input. (2) It processes  and interprets the sensory input and decides what  should be done at each moment—a process called  integration. (3) It then causes a response, or effect, by  activating muscles or glands (effectors) via motor  output.    very similar to a feedback loop (Chapter 1, p. 41). Recall  that in a feedback loop, a receptor receives sensory  input, which it sends to the brain (control center) for  processing (integration); the brain then analyzes the  information and determines the appropriate output,  which leads to a motor response.    An example will illustrate how these functions  work together. When you are driving and see a red  light just ahead (sensory input), your nervous system  integrates this information (red light means “stop”)  and sends motor output to the muscles of your right  leg and foot. Your foot goes for the brake pedal (the  response).   v Explain the structural and functional classifications  of the nervous system.   1# Define central nervous system and peripheral  nervous system, and list the major parts of each.    We have only one nervous system, but because of its  complexity, it is difficult to consider all its parts at  the same time. So, to simplify its study, we divide it  in terms of its structures (structural classification) or  in terms of its activities (functional classification).  We briefly describe each of these classification  schemes next, and Figure 7.2 illustrates their rela-  tionships. You do not need to memorize this whole  scheme now, but as you are reading the descriptions,  try to get a “feel” for the major parts and how they fit  together. This will make learning easier as you make    Figure 7.2 Organization of the nervous system.  As the flowchart shows, the central nervous system  receives input via sensory fibers and issues commands  via motor fibers. The sensory and motor fibers together  form the nerves that constitute the peripheral nervous  system.    your way through this chapter. Later you will see all  these terms and concepts again in more detail.    The structural classification, which includes all ner-  vous system organs, has two subdivisions—the cen-  tral nervous system and the peripheral nervous  system (see Figure 7.2).   The central nervous system (CNS) consists of  the brain and spinal cord, which occupy the dorsal  body cavity and act as the integrating and command  centers of the nervous system. They interpret incom-  ing sensory information and issue instructions based  on past experience and current conditions.   The peripheral (pé-rif’er-al) nervous system  (PNS) includes all parts of the nervous system out-  side the CNS. It consists mainly of the nerves that  extend from the spinal cord and brain. Spinal nerves  carry impulses to and from the spinal cord. Cranial  (kra’ne-al) nerves carry impulses to and from the  brain. These nerves serve as communication lines.  They link all parts of the body by carrying impulses  from the sensory receptors to the CNS and from the  CNS to the appropriate glands or muscles.   The functional classification scheme is concerned  only with PNS structures. It divides them into two  principal subdivisions (see Figure 7.2).   The sensory division, or afferent (af’ er-ent; lit-  erally “to go toward”) division, consists of nerves  (composed of many individual nerve fibers) that  convey impulses to the central nervous system from  sensory receptors located in various parts of the  body. The sensory division keeps the CNS constantly  informed of events going on both inside and outside  the body. Sensory fibers delivering impulses from  the skin, skeletal muscles, and joints are called  somatic (soma = body) sensory (afferent) fibers,  whereas those transmitting impulses from the vis-  ceral organs are called visceral sensory (afferent) fibers.   The motor division, or efferent (ef'er-rent)  division (think: efferent exits the CNS), carries impulses  from the CNS to effector organs, the muscles and glands.  These impulses activate muscles and glands; that is,  they effect (bring about or cause) a motor response.   The motor division in turn has two subdivisions  (see Figure 7.2):    this subdivision as the voluntary nervous system.  However, not all skeletal muscle activity con-  trolled by this motor division is voluntary.  Skeletal muscle reflexes, such as the stretch reflex  (described later in the chapter), are involuntary.    e The autonomic (aw’to-nom'ik) nervous sys-  tem (ANS) regulates events that are involuntary  (no conscious control), such as the activity of  smooth muscle, cardiac muscle, and glands. This  subdivision, commonly called the involuntary  nervous system, itself has two parts, the sympa-  thetic and parasympathetic, which typically bring  about opposite effects. What one stimulates, the  other inhibits. We will describe these later.    Although it is simpler to study the nervous sys-  tem in terms of its subdivisions, remember that these  subdivisions are made for the sake of convenience  only. Remember that the nervous system acts as a  coordinated unit, both structurally and functionally.    Did You Get It?  1. Name the structures that make up the CNS and  those that make up the PNS.  For the answer, see Appendix A.    Even though it is complex, nervous tissue is made up  of just two principal types of cells—supporting cells  and neurons.   Supporting cells in the CNS are “lumped together”  as neuroglia (nu-rog’le-ah), literally, “nerve glue,”  also called glial cells or glia. Neuroglia include many  types of cells that support, insulate, and protect the  delicate neurons (Figure 7.3). In addition, each of  the different types of neuroglia has special functions.  CNS neuroglia include the following:    e Astrocytes: abundant star-shaped cells  that account for nearly half of neural tissue  (Figure 7.3a). Their numerous projections have  swollen ends that cling to neurons, bracing them  and anchoring them to their nutrient supply    (a) Astrocytes are the most abundant (d) Oligodendrocytes have processes that form  and versatile neuroglia. myelin sheaths around CNS nerve fibers.    (b) Microglial cells are phagocytes that (e) Satellite cells and Schwann cells (which form  defend CNS cells. myelin) surround neurons in the PNS.    lines, the blood capillaries. Astrocytes form a liv- e Microglia (mi-kro’'-gle-ah): spiderlike phago-  ing barrier between capillaries and neurons, help cytes that monitor the health of nearby neurons  determine capillary permeability, and play a role and dispose of debris, such as dead brain cells  in making exchanges between the two. In this and bacteria (Figure 7.3b).    Ependymal (é-pen’'di-mal) cells: neuroglia that  line the central cavities of the brain and the spi-  nal cord (Figure 7.3c). They participate in the  production of cerebrospinal fluid (CSF) and the  beating of their cilia helps to circulate the cere-  brospinal fluid that fills those cavities and forms  a protective watery cushion around the CNS.    substances that might be in the blood. Astrocytes  also help control the chemical environment in  the brain by “mopping up” leaked potassium  ions, which are involved in generating a nerve  impulse, and recapturing chemicals released for  communication purposes.    e Oligodendrocytes (ol’i-go-den’dro-sitz): neu-  roglia that wrap their flat extensions (processes)  tightly around CNS nerve fibers, producing fatty  insulating coverings called myelin sheaths  (Figure 7.3d).   Although neuroglia somewhat resemble neurons  structurally (both cell types have cell extensions),  they are not able to transmit nerve impulses, a func-  tion that is highly developed in neurons. Another  important difference is that neuroglia never lose  their ability to divide, whereas most neurons do.  Consequently, most brain tumors are gliomas, or  tumors formed by neuroglia.   Supporting cells in the PNS come in two major  varieties—Schwann cells and satellite cells  (Figure 7.3e). Schwann cells form the myelin  sheaths around nerve fibers in the PNS. Satellite  cells act as protective, cushioning cells for peripheral  neuron cell bodies.    2. Which neuroglia are most abundant in the body?  Which produce the insulating material called myelin?  3. Why is a brain tumor more likely to be formed from  neuroglia than from neurons?  For answers, see Appendix A.    Learning Objectives  v Describe the general structure of a neuron, and  name its important anatomical regions.    Neurons, also called nerve cells, are highly special-  ized to transmit messages (nerve impulses) from one  part of the body to another. Although neurons differ  structurally from one another, they have many com-  mon features (Figure 7.4). All have a cell body, which  contains the nucleus and one or more slender pro-  cesses extending from the cell body.    Cell Body The cell body is the metabolic center of  the neuron. Its transparent nucleus contains a large  nucleolus. The cytoplasm surrounding the nucleus  contains the usual organelles, except that it lacks  centrioles (which confirms the amitotic nature of  most neurons). The rough ER, called Nissl (nis’1)    bodies, and neurofibrils (intermediate filaments  that are important in maintaining cell shape) are  particularly abundant in the cell body.    Processes The armlike processes, or fibers, vary in  length from microscopic to over 3 feet long, reaching  from the lumbar region of the spine to the great toe.  Neuron processes that convey incoming messages  (electrical signals) toward the cell body are dendrites  (den’dritz), whereas those that generate nerve  impulses and typically conduct them away from the  cell body are axons (ak’sonz). Neurons may have  hundreds of branching dendrites (dendr = tree),  depending on the structural type. However, each neu-  ron has only one axon, which arises from a conelike  region of the cell body called the axon hillock.   An occasional axon gives off a collateral branch  along its length, but all axons branch profusely at  their terminal end, forming hundreds to thousands  of axon terminals. These terminals contain hun-  dreds of tiny vesicles, or membranous sacs, that con-  tain chemicals called neurotransmitters (review our  discussion of events at the neuromuscular junction in  Chapter 6). As we said, axons transmit nerve impulses  away from the cell body. When these impulses reach  the axon terminals, they stimulate the release of neu-  rotransmitters into the extracellular space between  neurons, or between a neuron and its target cell.   Each axon terminal is separated from the next  neuron or its target by a tiny gap called the synaptic  (si-nap’tik) cleft. Such a functional junction, where  an impulse is transmitted from one neuron to another,  is called a synapse (syn = to clasp or join). Although  they are close, neurons never actually touch other neu-  rons or target cells. You will learn more about syn-  apses and the events that occur there a bit later.    Myelin Sheaths Most long nerve fibers are covered  with a whitish, fatty material called myelin (mi’é-  lin), which has a waxy appearance. Myelin protects  and insulates the fibers and increases the speed of  nerve impulse transmission. Compare myelin  sheaths to the many layers of insulation that cover  the wires in an electrical cord; the layers keep the  electricity flowing along the desired path just as  myelin does for nerve fibers. Axons outside the CNS  are myelinated by Schwann cells, as previously  noted. Many of these cells wrap themselves around  the axon in a jelly-roll fashion (Figure 7.5, p. 248).  Initially, the membrane coil is loose, but the  Schwann cell cytoplasm is gradually squeezed from    Figure 7.4 Structure of a typical  motor neuron. (a) Diagrammatic  view. (b) Scanning electron micro-  graph showing the cell body and  (b) dendrites (615X).    Why does the myelin sheath that is produced by  Schwann cells have gaps in it?    Figure 7.5 Relationship of Schwann cells to axons  in the peripheral nervous system. (a-c) As illustrated  (top to bottom), a Schwann cell envelops part of an axon  in a trough and then rotates around the axon. Most of  the Schwann cell cytoplasm comes to lie just beneath  the exposed part of its plasma membrane. The tight coil  of plasma membrane material surrounding the axon is  the myelin sheath. The Schwann cell cytoplasm and  exposed membrane are referred to as the neurilemma.    between the membrane layers. When the wrapping  process is done, a tight coil of wrapped membranes,  the myelin sheath, encloses the axon. Most of the  Schwann cell cytoplasm ends up just beneath the  outermost part of its plasma membrane. This part of  the Schwann cell, external to the myelin sheath, is  called the neurilemma (nu"ri-lem’mah, “neuron    husk”). Because the myelin sheath is formed by  many individual Schwann cells, it has gaps, or inden-  tations, called nodes of Ranvier (rahn-vér), at regu-  lar intervals (see Figure 7.4).   As mentioned previously, myelinated fibers are  also found in the central nervous system. Oli-  godendrocytes form CNS myelin sheaths (see Fig-  ure 7.3d). In the PNS, it takes many Schwann cells  to make a single myelin sheath; but in the CNS, the  oligodendrocytes with their many flat extensions can  coil around as many as 60 different fibers at the  same time. Thus, in the CNS, one oligodendrocyte  can form many myelin sheaths. Although the myelin  sheaths formed by oligodendrocytes and those  formed by Schwann cells are similar, the CNS sheaths  lack a neurilemma. Because the neurilemma remains  intact (for the most part) when a peripheral nerve  fiber is damaged, it plays an important role in fiber  regeneration, an ability that is largely lacking in the  central nervous system.    Homeostatic J  —S~ Imbalance 7.1  The importance of myelin insulation is best illus-  trated by observing what happens when myelin is  not there. The disease multiple sclerosis (MS) grad-  ually destroys the myelin sheaths around CNS fibers  by converting them to hardened sheaths called  scleroses. As this happens, the electrical current is  short-circuited and may “jump” to another demye-  linated neuron. In other words, nerve signals do not  always reach the intended target. The affected person  may have visual and speech disturbances, lose the  ability to control his or her muscles, and become  increasingly disabled. Multiple sclerosis is an auto-  immune disease in which the person’s own immune  system attacks a protein component of the sheath. As  yet there is no cure, but injections of beta interferon  (a hormonelike substance released by some immune  cells) appear to hold the symptoms at bay and pro-  vide some relief. Other drugs aimed at slowing the  autoimmune response are also being used, though  further research is needed to determine their long-  term effects.    Terminology Clusters of neuron cell bodies and  collections of nerve fibers are named differently in  the CNS and in the PNS. For the most part, cell bod-  ies are found in the CNS in clusters called nuclei.  This well-protected location within the bony skull or    Figure 7.6 Neurons classified by  function. Sensory (afferent) neurons  conduct impulses from sensory  receptors (in the skin, viscera,  muscles) to the central nervous    vertebral column is essential to the well-being of the  nervous system—remember that neurons do not  routinely undergo cell division after birth. The cell  body carries out most of the metabolic functions of  a neuron, so if it is damaged, the cell dies and is not  replaced. Small collections of cell bodies called  ganglia (gang’le-ah; ganglion, singular) are found in  a few sites outside the CNS in the PNS.   Bundles of nerve fibers (neuron processes) run-  ning through the CNS are called tracts, whereas in  the PNS they are called nerves. The terms white mat-  ter and gray matter refer respectively to myelinated  versus unmyelinated regions of the CNS. As a general  tule, the white matter consists of dense collections  of myelinated fibers (tracts), and gray matter con-  tains mostly unmyelinated fibers and cell bodies.    1# List the types of general sensory receptors and  describe their functions.    system; most cell bodies are in  ganglia in the PNS. Motor (efferent)  neurons transmit impulses from   the CNS (brain or spinal cord) to  effectors in the body periphery.    Interneurons (association neurons)  complete the communication  pathway between sensory and motor  neurons; their cell bodies reside in  the CNS.    Neurons may be classified based on their function or  their structure.    Functional Classification Functionally, neurons are  grouped according to the direction the nerve impulse  travels relative to the CNS. On this basis, there are  sensory, motor, and association neurons (interneu-  rons) (Figure 7.6). Neurons carrying impulses from  sensory receptors (in the internal organs or the skin)  to the CNS are sensory neurons, or afferent  neurons. (Recall that afferent means “to go toward.”)  The cell bodies of sensory neurons are always found  in a ganglion outside the CNS. Sensory neurons keep  us informed about what is happening both inside  and outside the body.   The dendrite endings of the sensory neurons are  usually associated with specialized receptors that  are activated by specific changes occurring nearby.  (We cover the very complex receptors of the special  senses—vision, hearing, equilibrium, taste, and  smell—separately in Chapter 8). The simpler types of  sensory receptors in the skin are cutaneous sense  organs, and those in the muscles and tendons are    Figure 7.7 Types of sensory receptors. Parts (d) and (e) represent two types of    proprioceptors (pro”pre-o-sep'torz) (shown in  Figure 4.3 and Figure 7.7). The pain receptors (actu-  ally bare nerve endings) are the least specialized of  the cutaneous receptors. They are also the most  numerous, because pain warns us that some type of  body damage is occurring or is about to occur.  However, strong stimulation of any of the cutaneous  receptors (for example, by searing heat, extreme cold,  or excessive pressure) is also interpreted as pain.   The proprioceptors detect the amount of stretch,  or tension, in skeletal muscles, their tendons, and  joints. They send this information to the brain so  that the proper adjustments can be made to main-  tain balance and normal posture. Propria comes  from the Latin word meaning “one’s own,” and the   Neurons carrying impulses from the CNS to the  viscera and/or muscles and glands are motor  neurons, or efferent neurons (see Figure 7.6). The  cell bodies of motor neurons are usually located in  the CNS.   The third category of neurons consists of the  interneurons, or association neurons. They  connect the motor and sensory neurons in neural  pathways. Their cell bodies are typically located in  the CNS.    Structural Classification The structural classification  of neurons is based on the number of processes,    including both dendrites and axons, extending from  the cell body (Figure 7.8). If there are several, the neu-  ron is a multipolar neuron. Because all motor and  association neurons are multipolar, this is the most  common structural type. Neurons with two pro-  cesses—one axon and one dendrite—are bipolar neu-  rons. Bipolar neurons are rare in adults, found only in  some special sense organs (eye, nose), where they act  in sensory processing as receptor cells. Unipolar neu-  rons have a single process emerging from the cell body  as if the cell body were on a “cul-de-sac” off the “main  road” that is the axon. However, the process is very  short and divides almost immediately into proximal  (central) and distal (peripheral) processes. Unipolar  neurons are unique in that only the small branches at  the end of the peripheral process are dendrites. The  remainder of the peripheral process and the central  process function as the axon; thus, in this case, the  axon actually conducts nerve impulses both toward  and away from the cell body. Sensory neurons found in  PNS ganglia are unipolar. (Refer back to Figure 7.6.)   6. Which part of a neuron conducts impulses toward  the cell body in multipolar and bipolar neurons?  Which part releases neurotransmitters?   7. Your professor tells you that one neuron transmits a  nerve impulse at the rate of 1 meter per second and  another neuron conducts at the rate of 40 meters  per second. Which neuron has the myelinated axon?    v@ Describe the events that lead to the generation of  a nerve impulse and its conduction from one  neuron to another.    Neurons have two major functional properties:  irritability, the ability to respond to a stimulus by pro-  ducing a nerve impulse, and conductivity, the ability  to transmit the impulse to other neurons, muscles, or  glands.    Electrical Conditions of a Resting Neuron’s Mem-  brane The plasma membrane of a resting, or  inactive, neuron is polarized, which means that  there are fewer positive ions sitting on the inner face  of the neuron’s plasma membrane than there are on  its outer face (Figure 7.9 @), p. 252). The major pos-  itive ions inside the cell are potassium (K~), whereas  the major positive ions outside the cell are sodium  (Na+). The polarized membrane is more permeable  to K” than to Na” at rest, maintaining a more nega-  tive inside (fewer positive ions) compared to outside,  as K” ions exit the cell. This maintains the inactive,  resting state of the neuron.    Action Potential Initiation and Generation Many  different types of stimuli excite neurons to become  active and generate an impulse. For example, light  excites the eye receptors, sound excites some of the  ear receptors, and pressure excites some cutaneous  receptors of the skin. However, most neurons in the  body are excited by neurotransmitter chemicals re-  leased by other neurons, as we will describe shortly.   Regardless of the stimulus, the result is always  the same—the permeability properties of the cell’s  plasma membrane change for a very brief period.  Normally, sodium ions cannot diffuse through the    © Resting membrane is polarized. In the resting state, the  external face of the membrane is slightly positive; its internal  face is slightly negative. The chief extracellular ion is sodium  (Nat), whereas the chief intracellular ion is potassium (K*).  The membrane is more permeable to K* ions (which exit the  cell resulting in fewer positive ions inside) at rest.    © Stimulus initiates local depolarization. A stimulus  changes the permeability of a local "patch" of the membrane,  and sodium ions diffuse rapidly into the cell. This changes the  polarity of the membrane (the inside becomes more positive;  the outside becomes more negative) at that site.    ©) Depolarization and generation of an action potential.  If the stimulus is strong enough, depolarization causes  membrane polarity to be completely reversed, and an action  potential is initiated. (If the stimulus is not strong enough, the  cell returns to a resting membrane state and no action  potential occurs.)    (4) Propagation of the action potential. Depolarization of  the first membrane patch causes permeability changes in the  adjacent membrane, and the events described in step (2) are  repeated. Thus, the action potential propagates rapidly along  the entire length of the membrane like dominoes falling one  after another, or a crowd doing the "wave".    6) Repolarization. Potassium ions diffuse out of the cell as  the membrane permeability changes again, restoring the  negative charge on the inside of the membrane and the  positive charge on the outside surface. Repolarization occurs  in the same direction as depolarization.    © Initial ionic conditions restored. The ionic conditions  of the resting state are restored later by the activity of the  sodium-potassium pump. Three sodium ions are ejected for  every two potassium ions carried back into the cell. The  neuron is now ready to "fire" again.    plasma membrane to any great extent, but when  the neuron is adequately stimulated, the “gates” of  sodium channels in the membrane open. Because  sodium is in much higher concentration outside the  cell, it then “floods” (by diffusion) into the neuron.  This inward rush of sodium ions changes the polar-  ity of the neuron’s membrane at that site, an event  called depolarization (Figure 7.9 @). Locally, the  inside is now more positive, and the outside is less  positive, a local electrical situation called a graded  potential. However, if the stimulus is strong enough  and the sodium influx is great enough, the local depo-  larization (graded potential) activates the neuron to  initiate and transmit a long-distance signal called an  action potential, or a nerve impulse. @) The nerve  impulse is an all-or-nothing response, like starting a  car. It is either propagated (conducted, or sent) over  the entire axon @, or it doesn’t happen at all. The  nerve impulse never goes partway along an axon’s  length, nor does it die out with distance, as do  graded potentials.   Almost immediately after the sodium ions rush  into the neuron, the membrane permeability  changes again, becoming impermeable to sodium  ions but permeable to potassium ions. So potas-  sium ions are allowed to rapidly diffuse out of the  neuron into the interstitial fluid. This outflow of  positive ions from the cell restores the electrical  conditions at the membrane to the polarized, or  resting, state, an event called repolarization  (Figure 7.9 ©). After repolarization of the electrical  conditions, the sodium-potassium pump restores  ionic conditions, the initial concentrations of the  sodium and potassium ions inside and outside the  neuron ©). This pump uses ATP (cellular energy) to  pump excess sodium ions back out of the cell and to  bring potassium ions back into it. Until repolariza-  tion occurs, and resting ionic conditions are restored, a  neuron cannot conduct another impulse. Once begun,  these sequential events spread along the entire neu-  ronal membrane.   The events just described explain propagation of  a nerve impulse along unmyelinated fibers. Fibers  that have myelin sheaths conduct impulses much  faster because the nerve impulse literally jumps, or  leaps, from node to node along the length of the  fiber. This occurs because no electrical current can  flow across the axon membrane where there is fatty  myelin insulation. This faster type of electrical  impulse propagation is called saltatory (sal'tah-to’re)  conduction (saltare = to dance or leap).    Homeostatic J  £ Imbalance 7.2  A number of factors can impair the conduction of  impulses. For example, sedatives and anesthetics  block nerve impulses by altering membrane perme-  ability to ions, mainly sodium ions. As we have seen,  no sodium entry = no action potential.   Cold and continuous pressure hinder impulse  conduction because they interrupt blood circulation  (and hence the delivery of oxygen and nutrients) to  the neurons. For example, your fingers get numb  when you hold an ice cube for more than a few sec-  onds. Likewise, when you sit on your foot, it “goes to  sleep.” When you warm your fingers or remove the  pressure from your foot, the impulses begin to be  transmitted again, leading to an unpleasant prickly  feeling.    Transmission of the Signal at Synapses So far we  have explained only the irritability aspect of neuro-  nal function. What about conductivity—how does  the electrical impulse traveling along one neuron get  across the synapse to the next neuron (or effector  cell) to influence its activity?   The answer is that the impulse doesn’t! Instead, a  neurotransmitter chemical crosses the synapse to  transmit the signal from one neuron to the next, or to  the target cell (as occurred at the neuromuscular junc-  tion; see Chapter 6). When the action potential  reaches an axon terminal (Figure 7.10 @, p. 254), the  electrical change opens calcium channels. Calcium  ions, in turn, cause the tiny vesicles containing neu-  rotransmitter to fuse with the axonal membrane @),  releasing the neurotransmitter into the synaptic cleft  by exocytosis @). The neurotransmitter molecules dif-  fuse across the synaptic cleft* and bind to receptors on  the membrane of the next neuron @). If enough neu-  rotransmitter is released, the whole series of events  described above (sodium entry ©, depolarization,  etc.) will occur, generating a graded potential and  eventually a nerve impulse in the receiving neuron  beyond the synapse. The electrical changes prompted  by neurotransmitter binding are very brief because  the neurotransmitter is quickly removed from the   type of synapse described above, there are some examples of  electrical synapses, in which the neurons are physically joined  by gap junctions and electrical currents actually flow from  one neuron to the next.    Figure 7.10 How neurons communicate at  chemical synapses. The events occurring at the  synapse are numbered in order.    synaptic cleft ©, either by diffusing away, by reuptake  into the axon terminal, or by enzymatic breakdown.  This limits the effect of each nerve impulse to a period  shorter than the blink of an eye.    CONCEPT LINK  Recall what you learned about the events at the neuro-    muscular junction between a neuron and a muscle  fiber (Figure 6.5, p. 207). Events at synapses are very  similar, except that the "target" is another neuron, and  in some locations of the body, neurotransmitters other  than acetylcholine are released.    Notice that the transmission of an impulse is an  electrochemical event. Transmission down the length  of the neuron’s axon is basically electrical, but the  next neuron is stimulated by a neurotransmitter,  which is a chemical. Because each neuron both  receives signals from and sends signals to scores of  other neurons, it carries on “conversations” with  many different neurons at the same time. Also, dif-  ferent neurotransmitters are released in different  parts of the body, depending on “who” is talking  (which neurons) and “what” they are trying to  express (usually stimulation or inhibition).    7.2d Physiology: Reflexes  Although there are many types of communication  between neurons, much of what the body must do  every day is programmed as reflexes. Reflexes are  rapid, predictable, and involuntary responses to stimuli.  They are much like one-way streets—once a reflex  begins, it always goes in the same direction. Reflexes  occur over neural pathways called reflex arcs and  involve both CNS and PNS structures. Think of a reflex  as a preprogrammed response to a given stimulus.   The types of reflexes that occur in the body are  classed as either somatic or autonomic. Somatic  reflexes stimulate the skeletal muscles; these are still  involuntary reflexes even though skeletal muscle  normally is under voluntary control. When you  quickly pull your hand away from a hot object, a  somatic reflex is working. Autonomic reflexes regu-  late the activity of smooth muscles, the heart, and  glands. Secretion of saliva (salivary reflex) and  changes in the size of the eye pupils (pupillary  reflex) are two such reflexes. Autonomic reflexes reg-  ulate such body functions as digestion, elimination,  blood pressure, and sweating.   All reflex arcs have a minimum of five elements  (Figure 7.11a): a receptor (which reacts to a stimulus),    an effector (the muscle or gland eventually stimu-  lated), and sensory and motor neurons to connect the  two. The synapse or interneurons between the  sensory and motor neurons represents the fifth  element—the CNS integration center.   The simple patellar (pah-tel’ar), or knee-jerk,  reflex is an example of a two-neuron reflex arc, the  simplest type in humans (Figure 7.11b). The patellar  reflex (in which the quadriceps muscle attached to  the hit tendon is stretched) is familiar to most of us.  It is usually tested during a physical exam to deter-  mine the general health of the motor portion of our  nervous system.   Most reflexes are much more complex than the  two-neuron reflex, involving synapses between one  or more interneurons in the CNS (integration cen-  ter). The flexor, or withdrawal, reflex is a three-neuron  reflex arc in which the limb is withdrawn from a  painful stimulus (see Figure 7.11c). A three-neuron  reflex arc also consists of five elements—receptor,  sensory neuron, interneuron, motor neuron, and  effector. Because there is always a delay at synapses  (it takes time for neurotransmitter to diffuse through  the synaptic cleft), the more synapses there are in a  reflex pathway, the longer the reflex takes to happen.   Many spinal reflexes involve only spinal cord neu-  rons and occur without brain involvement. As long as  the spinal cord is functional, spinal reflexes, such as  the flexor reflex, will work. By contrast, some reflexes  require that the brain become involved because many  different types of information have to be evaluated to  arrive at the “right” response. The response of the  pupils of the eyes to light is a reflex of this type.   As noted earlier, reflex testing is an important  tool in evaluating the condition of the nervous sys-  tem. Reflexes that are exaggerated, distorted, or  absent indicate damage or disease in the nervous sys-  tem. Reflex changes often occur before a pathologi-  cal condition becomes obvious in other ways.    8. What is the difference between a graded potential  and an action potential?   9. Explain the difference between a synaptic cleft and  a synapse. How is a stimulus transmitted across a  synapse?   10. Which portion(s) of a neuron is (are) likely to be  associated with a sensory receptor or a sensory  organ?    4# identify and indicate the functions of the major  regions of the cerebral hemispheres, diencephalon,  brain stem, and cerebellum on a human brain  model or diagram.    The adult brain’s unimpressive appearance gives  few hints of its remarkable abilities. It is about two  good fistfuls of pinkish gray tissue, wrinkled like a  walnut and with the texture of cold oatmeal. It  weighs a little over 3 pounds. Because the brain is  the largest and most complex mass of nervous  tissue in the body, we commonly discuss it in terms  of its four major regions—cerebral hemispheres,  diencephalon (di"en-sef'ah-lon), brain stem, and cere-  bellum (Figure 7.12, and Table 7.1, p. 258).    The paired cerebral (suh re’bral) hemispheres, col-  lectively called the cerebrum, are the most superior  part of the brain and together are a good deal larger  than the other three brain regions combined. In fact,  as the cerebral hemispheres develop and grow, they  enclose and obscure most of the brain stem, so many  brain stem structures cannot normally be seen unless  a Sagittal section is made. Picture how a mushroom  cap covers the top of its stalk, and you have an idea  of how the cerebral hemispheres cover the dienceph-  alon and the superior part of the brain stem (see  Figure 7.12).   The entire surface of the cerebrum exhibits ele-  vated ridges of tissue called gyri (ji're; gyrus, singular;  “twisters” ), separated by shallow grooves called sulci  (sul’ki; sulcus, singular; “furrows”). Less numerous  are the deeper grooves called fissures (Figure 7.13a,  p. 259), which separate large regions of the brain.  Many of the fissures and gyri are important anatom-  ical landmarks. The cerebral hemispheres are sepa-  rated by a single deep fissure, the longitudinal fissure.  Other fissures or sulci divide each cerebral hemi-  sphere into a number of lobes, named for the cranial  bones that lie over them (see Figure 7.13a and b).   Each cerebral hemisphere has three basic regions:  a superficial cortex of gray matter, which looks gray  in fresh brain tissue; an internal area of white matter;  and the basal nuclei, islands of gray matter situated  deep within the white matter. We consider these  regions next.    Figure 7.12 Development and  regions of the human brain.  The brain can be considered in  terms of four main parts: cerebral  hemispheres, diencephalon, brain  stem, and cerebellum. (a) In the  developing brain, the cerebral    Cerebral Cortex Speech, memory, logical and emo-  tional responses, consciousness, the interpretation  of sensation, and voluntary movement are all func-  tions of the cerebral cortex. Many of the functional  areas of the cerebral hemispheres have been  identified (Figure 7.13c). The primary somatic  sensory area is located in the parietal lobe posteri-  or to the central sulcus. Impulses traveling from the  body’s sensory receptors (except for the special  senses) are localized and interpreted in this area of  the brain. The primary somatic sensory area allows  you to recognize pain, differences in temperature, or  a light touch.   A spatial map, the sensory homunculus  (ho-mung’ku-lus; “little man”), has been devel-  oped to show how much tissue in the primary  somatic sensory area is devoted to various sensory  functions. (Figure 7.14, p. 260; note that the body is  represented in an upside-down manner). Body  regions with the most sensory receptors—the lips  and fingertips—send impulses to neurons that  make up a large part of the sensory area.  Furthermore, the sensory pathways are crossed path-  ways—meaning that the left side of the primary  somatic sensory area receives impulses from the  right side of the body, and vice versa.   Impulses from the special sense organs are inter-  preted in other cortical areas (see Figure 7.13b and c).   and laterally over the other brain  regions by the bones of the skull.   (b) In the adult brain, the cerebral  hemispheres, now highly convoluted,  enclose the diencephalon and the    superior part of the brain stem. The  left cerebral hemisphere is drawn so  that it looks transparent, to reveal  the location of the deeply situated  diencephalon and superior part of  the brain stem.    For example, the visual area is located in the posterior  part of the occipital lobe, the auditory area is in the  temporal lobe bordering the lateral sulcus, and the  olfactory area is deep inside the temporal lobe.   The primary motor area, which allows us to  consciously move our skeletal muscles, is anterior to  the central sulcus in the frontal lobe. The axons of  these motor neurons form the major voluntary  motor tract—the pyramidal tract, or corticospinal  (kor’ti-ko-spi'nal) tract, which descends to the spi-  nal cord. As in the primary somatic sensory cortex, the  body is represented upside-down, and the pathways  are crossed. Most of the neurons in the primary motor  area control body areas having the finest motor  control; that is, the face, mouth, and hands (see  Figure 7.14). The body map on the motor cortex, as  you might guess, is called the motor homunculus.   A specialized cortical area that is very involved in  our ability to speak is Broca’s (bro’kahz) area. Also  called the motor speech area (see Figure 7.13c), it helps  us speak by sending the motor signals that allow us to  form words with our mouths. It is found at the base of  the precentral gyrus (the gyrus anterior to the central  sulcus). Damage to this area, which is located in only  one cerebral hemisphere (usually the left), causes the  inability to say words properly. You know what you  want to say, but you can’t vocalize the words.    = Cortex: Gray matter:  e Localizes and interprets sensory inputs  e Controls voluntary and skilled skeletal muscle activity  e Acts in intellectual and emotional processing  Basal nuclei:  e Subcortical motor centers help control skeletal muscle movements (see Figure 7.15)    E Thalamus:  e Relays sensory impulses to cerebral cortex  e Relays impulses between cerebral motor cortex and lower motor centers  e Involved in memory  E Hypothalamus:  e Chief integration center of autonomic (involuntary) nervous system  e Regulates body temperature, food intake, water balance, and thirst  e Regulates hormonal output of anterior pituitary gland and acts as an endocrine organ (producing  ADH and oxytocin)  E Limbic system—A functional system:  e Includes cerebral and diencephalon structures (e.g., hypothalamus and anterior thalamic nuclei)  e Mediates emotional response; involved in memory processing    E Midbrain:  e Contains visual and auditory reflex centers  e Contains subcortical motor centers  e Contains nuclei for cranial nerves Ill and IV; contains projection fibers (e.g., fibers of the  pyramidal tracts)  Pons:  e Relays information from the cerebrum to the cerebellum  e Cooperates with the medullary centers to control respiratory rate and depth  e Contains nuclei of cranial nerves V-VII; contains projection fibers  E Medulla oblongata:  e Relays ascending sensory pathway impulses from skin and proprioceptors  e Contains nuclei controlling heart rate, blood vessel diameter, respiratory rate, vomiting, etc.  e Relays sensory information to the cerebellum  e Contains nuclei of cranial nerves VIII-XII; contains projection fibers  e Site of crossover of pyramids  E Reticular formation—A functional system:  e Maintains cerebral cortical alertness; filters out repetitive stimuli  e Helps regulate skeletal and visceral muscle activity    e Processes information from cerebral motor cortex, proprioceptors, and visual and equilibrium  pathways    Precentral Central sulcus Figure 7.13 Left lateral view of the  Postcentral gyrus brain. (a) Diagrammatic view of major  Parietal lobe structural areas. (b) Photograph of a brain.  (c) Functional areas of the cerebral  hemisphere, diagrammatic view. More  intense colors (red and blue) indicate  primary cortical areas (motor and sensory  Lateral sulcus areas). Pastel colors (pink and pale blue)    Figure 7.14 Sensory and motor  areas of the cerebral cortex. The  relative amount of cortical tissue  devoted to each function is indicated    Areas involved in higher intellectual reasoning  and socially acceptable behavior are believed to be  in the anterior part of the frontal lobes, the anterior  association area. The frontal lobes also house areas  involved with language comprehension. Complex  memories appear to be stored in the temporal and  frontal lobes.   The posterior association area encompasses  part of the posterior cortex. This area plays a role in  recognizing patterns and faces, and blending several  different inputs into an understanding of the whole  situation. Within this area is the speech area, located  at the junction of the temporal, parietal, and occipi-  tal lobes. The speech area allows you to sound out  words. This area (like Broca’s area) is usually in only  one cerebral hemisphere.    by the amount of the gyrus occu-  pied by the body area diagrams  (homunculi). The primary motor  cortex is shown on the left side of    the diagram, and the somatic sensory  cortex is on the right.    Cerebral White Matter Most of the remaining cere-  bral hemisphere tissue—the deeper cerebral white  matter (see Figures 7.13a and 7.15)—is composed of  fiber tracts carrying impulses to, from, or within the  cortex. One very large fiber tract, the corpus callosum  (kah-lo’sum), connects the cerebral hemispheres  (Figure 7.15). Such fiber tracts are called commissures.  The corpus callosum arches above the structures of  the brain stem and allows the cerebral hemispheres to  communicate with one another. This is important  because, as already noted, some of the cortical func-  tional areas are in only one hemisphere. Association  fiber tracts connect areas within a hemisphere, and  projection fiber tracts connect the cerebrum with lower  CNS centers, such as the brain stem.    Figure 7.15 Frontal section (facing posteriorly) of the brain showing  commissural, association, and projection fibers running through the  cerebrum and the lower CNS. Notice the internal capsule that passes between    Basal Nuclei Although most of the gray matter is in  the cerebral cortex, there are several “islands” of gray  matter, called the basal nuclei, buried deep within  the white matter of the cerebral hemispheres (see  Figure 7.15). The basal nuclei help regulate volun-  tary motor activities by modifying instructions  (particularly in relation to starting or stopping  movement) sent to the skeletal muscles by the pri-  mary motor cortex. A tight band of projection fibers,  called the internal capsule, passes between the thala-   Homeostatic J  £ Imbalance 7.3  Individuals who have problems with their basal  nuclei are often unable to walk normally or carry out  other voluntary movements in a normal way.  Huntington's disease and Parkinson's disease are two  examples of such syndromes. (See “A Closer Look”  on pp. 268-269.    12. What are the three major regions of the cerebrum?  13. What is the composition of white matter of the  brain?  For answers, see Appendix A.    The diencephalon, or interbrain, sits atop the brain  stem and is enclosed by the cerebral hemispheres  (see Figure 7.12). The major structures of the dien-  cephalon are the thalamus, hypothalamus, and epithal-  amus (Figure 7.16, p. 262). The thalamus, which  encloses the shallow third ventricle of the brain, is a  relay station for sensory impulses passing upward to  the sensory cortex. As impulses surge through the  thalamus, we have a crude recognition of whether  the sensation we are about to have is pleasant or  unpleasant. It is the neurons of the sensory cortex  that actually localize and interpret the sensation.    Figure 7.16 Diencephalon and brain stem structures. (a) A midsagittal section  of the brain illustrating the diencephalon (purple) and brain stem (green).    The hypothalamus (literally, “under the thala-  mus”) makes up the floor of the diencephalon. It is  an important autonomic center because it plays a  role in regulating body temperature, water balance,  and metabolism. The hypothalamus is also the cen-  ter for many drives and emotions, and as such it is an  important part of the so-called limbic system, or  “emotional-visceral brain.” For example, thirst, appe-  tite, sex, pain, and pleasure centers are in the hypo-  thalamus. Additionally, the hypothalamus regulates  the pituitary gland (an endocrine organ) and pro-  duces two hormones of its own. The pituitary gland  hangs from the anterior floor of the hypothalamus by  a slender stalk. (We discuss its function in Chapter 9.)  The mammillary bodies, reflex centers involved in  olfaction (the sense of smell), bulge from the floor of  the hypothalamus posterior to the pituitary gland.   The epithalamus (ep"i-thal’ah-mus) forms the  roof of the third ventricle. Important parts of the epi-  thalamus are the pineal gland (part of the endo-  crine system) and the choroid (ko'roid) plexus of  the third ventricle. The choroid plexuses, which are  knots of capillaries within each of the four ventricles,    and along with the ependymal cells lining the ventri-  cles, form the cerebrospinal fluid.    The brain stem is about the size of a thumb in  diameter and approximately 3 inches (approxi-  mately 7.5 cm) long. Its structures are the midbrain,  pons, and medulla oblongata. In addition to providing  a pathway for ascending and descending tracts, the  brain stem has many small gray matter areas. These  nuclei produce the rigidly programmed autonomic  behaviors necessary for survival. In addition, some  are associated with the cranial nerves and control  vital activities such as breathing and blood pressure.  Identify the brain stem areas (see Figure 7.16) as you  read the descriptions that follow.    Midbrain A relatively small part of the brain stem,  the midbrain extends from the mammillary bodies  to the pons inferiorly. The cerebral aqueduct, a tiny  canal that travels through the midbrain, connects the  third ventricle of the diencephalon to the fourth ven-  tricle below. Anteriorly, the midbrain is composed    primarily of two bulging fiber tracts, the cerebral  peduncles (pe’dun klz) (literally, “little feet of the  cerebrum”), which convey ascending and descend-  ing impulses. Dorsally located are four rounded pro-  trusions called the corpora quadrigemina  (kor’por-ah kwah"dri-jem'i-nah) because they  reminded some anatomist of two pairs of twins  (gemini). These bulging nuclei are reflex centers  involved with vision and hearing.    Pons The pons (ponz) is the rounded structure  that protrudes just below the midbrain. Pons means  “bridge,” and this area of the brain stem is mostly  fiber tracts (bundles of nerve fibers in the CNS).  However, it does have important nuclei involved in  the control of breathing.    Medulla Oblongata The medulla oblongata  (mé-dul’ah ob” long-ga’tah) is the most inferior part  of the brain stem. It merges into the spinal cord  below without any obvious change in structure. Like  the pons, the medulla is an important fiber tract area.  Additionally, the medulla is the area where the  important pyramidal tracts (motor fibers) cross over  to the opposite side. The medulla also contains  many nuclei that regulate vital visceral activities. It  contains centers that control heart rate, blood pres-  sure, breathing, swallowing, and vomiting, among  others. The fourth ventricle lies posterior to the  pons and medulla and anterior to the cerebellum.    Reticular Formation Extending the entire length of  the brain stem is a diffuse mass of gray matter, the    Figure 7.16 (continued) (b) The reticular  formation extends the length of the brain  stem. Ascending arrows indicate sensory  input to the cerebrum. Descending arrows  indicate efferent output of reticular  neurons.    reticular formation (Figure 7.16b). The neurons of  the reticular formation are involved in motor control  of the visceral organs—for example, controlling  smooth muscle in the digestive tract. A special group  of reticular formation neurons, the reticular  activating system (RAS), plays a role in conscious-  ness and the awake/sleep cycle. The RAS also acts as  a filter for the flood of sensory inputs that streams  up the spinal cord and brain stem daily. Weak or  repetitive signals are filtered out, but unusual or  strong impulses do reach consciousness. Damage to  this area can result in prolonged unconsciousness  (coma).    The large, cauliflower-like cerebellum  (ser”e-  bel’um) projects dorsally from under the occipital  lobe of the cerebrum. Like the cerebrum, the cerebel-  lum has two hemispheres and a convoluted surface.  Like the cerebrum, the cerebellum also has an outer  cortex made up of gray matter and an inner region of  white matter.   The cerebellum provides the precise timing for  skeletal muscle activity and controls our balance.  Thanks to its activity, body movements are smooth  and coordinated. It plays its role less well when it is  sedated by alcohol. Fibers reach the cerebellum from  the equilibrium apparatus of the inner ear, the eye,  the proprioceptors of the skeletal muscles and ten-  dons, and many other areas. The cerebellum can be  compared to an automatic pilot, continuously com-  paring the brain's “intentions” with actual body per-  formance by monitoring body position and the    amount of tension in various body parts. When  needed, the cerebellum sends messages to initiate  the appropriate corrective measures.    Homeostatic J  —S Imbalance 7.4  If the cerebellum is damaged (for example, by a  blow to the head, a tumor, or a stroke), movements  become clumsy and disorganized—a condition  called ataxia (uh-tax’e-uh). Victims cannot keep  their balance and may appear drunk because of the  loss of muscle coordination. They are no longer able  to touch their finger to their nose with eyes closed—  a feat that healthy individuals accomplish easily.    14. Which brain region controls such vital activities as  breathing and blood pressure—cerebrum, brain  stem, or cerebellum?   16. In what major brain region are the thalamus,  hypothalamus, and pineal gland found?    v Discuss the formation and function of cerebrospi-  nal fluid and the blood-brain barrier.    Nervous tissue is soft and delicate, and even slight  pressure can injure the irreplaceable neurons. As we  saw in Chapter 5, nature tries to protect the brain  and spinal cord by enclosing them within bone (the  skull and vertebral column). Now, let's focus on  three additional protections for the CNS: the menin-  ges, cerebrospinal fluid, and blood-brain barrier.   The three connective tissue membranes covering  and protecting the CNS structures are meninges  (mé-nin’jéz) (Figure 7.17). The outermost layer, the  leathery dura mater (du’rah ma’ter), meaning  “tough or hard mother,” is a double-layered mem-  brane where it surrounds the brain. One of its layers  is attached to the inner surface of the skull, forming  the periosteum (periosteal layer). The other, called the    meningeal layer, forms the outermost covering of the  brain and continues as the dura mater of the spinal  cord. The dural layers are fused together except in  three areas where they separate to enclose dural  venous sinuses that collect venous blood, such as the  superior sagittal sinus.   In several places, the inner dural membrane  extends inward to form a fold that attaches the brain  to the cranial cavity. Two of these folds, the falx (falks)  cerebri and the tentorium cerebelli, separate the  two cerebral hemispheres and the cerebellum from  the cerebrum, respectively (shown in Figure 7.17).   The middle meningeal layer is the weblike  arachnoid (ah-rak’noid) mater (see Figure 7.17).  Arachnida means “spider,” and some think the arach-  noid membrane looks like a cobweb. Its threadlike  extensions span the subarachnoid space to attach  it to the innermost membrane, the pia (pi’ah) mater  (“gentle mother”). The delicate pia mater clings  tightly to the surface of the brain and spinal cord,  following every fold.   The subarachnoid space is filled with cerebrospi-  nal fluid. (Remember that the choroid plexuses pro-  duce CSF). Specialized projections of the arachnoid  membrane, arachnoid granulations, protrude  through the dura mater. The cerebrospinal fluid is  absorbed into the venous blood in the dural sinuses  through the arachnoid granulations. Next, we will  discuss the production and flow of cerebrospinal   Homeostatic J  £ Imbalance 7.5  Meningitis, an inflammation of the meninges, is a  serious threat to the brain because bacterial or viral  meningitis may spread into the nervous tissue of the  CNS. This condition of brain inflammation is called  encephalitis (en-sef-ah-li’tis). Meningitis is usually  diagnosed by taking a sample of cerebrospinal fluid  from the subarachnoid space surrounding the  spinal cord.    Cerebrospinal Fluid  Cerebrospinal (ser”e-bro-spi’nal) fluid (CSF) is a  watery “broth” with components similar to blood  plasma, from which it forms. However, it contains  less protein and more vitamin C, and its ion compo-  sition is different.    Figure 7.17 Meninges of the brain. (a) Three-dimensional frontal section  showing the meninges—the dura mater, arachnoid mater, and pia mater—that  surround and protect the brain. The relationship of the dura mater to the falx  cerebri and the superior sagittal (dural) venous sinus is also shown. (b) Posterior    view of the brain in place surrounded by the dura mater.    ventricles, or enlarged chambers—continually form  CSF from blood. The CSF in and around the brain  and spinal cord forms a watery cushion that protects  the fragile nervous tissue from blows and other   Inside the brain, CSF is continually moving (as  indicated by the numbered pathway in Figure 7.18c,  p. 266). It circulates from the two lateral ventricles  (in the cerebral hemispheres) into the third ventricle  (in the diencephalon) and then through the cerebral  aqueduct of the midbrain into the fourth ventricle    aperture Fourth ventricle aperus  Lateral  Central canal aperture  (a) Anterior view (b) Left lateral view  Superior sagittal    J (4) CSF is produced by the  choroid plexus of each ventricle.    (2)CSF flows through the ventricles  and into the subarachnoid space via  the median and lateral apertures.  Some CSF flows through the central  canal of the spinal cord.    (4) CSF is absorbed into the dural  venous sinuses via the arachnoid  granulations.    Figure 7.18 Ventricles and (c) Circulatory pathway of the (The relative position of the right  location of the cerebrospinal cerebrospinal fluid (indicated by lateral ventricle is indicated by the  fluid. (a, b) Three-dimensional views arrows) within the central nervous pale blue area deep to the corpus    dorsal to the pons and medulla oblongata. Some of  the fluid reaching the fourth ventricle simply contin-  ues down into the spinal cord, but most of it circu-  lates into the subarachnoid space through three  openings, the paired lateral apertures and the median  aperture (aper = open), in the walls of the fourth  ventricle. The CSF returns to the blood in the dural  venous sinuses through the arachnoid granulations.  In this way, CSF is continually replaced.   Ordinarily, CSF forms and drains at a constant  rate so that its normal pressure and volume  (150 ml—about half a cup) are maintained. Any  significant changes in CSF composition (or the  appearance of blood cells in it) could indicate men-  ingitis or certain other brain pathologies (such as  tumors or multiple sclerosis). A procedure called a  lumbar (spinal) puncture can obtain a sample of CSF  for testing. Because the withdrawal of fluid decreases  CSF fluid pressure, the patient must remain hori-  zontal (lying down) for 6 to 12 hours after the proce-  dure to prevent an agonizingly painful “spinal  headache.”    (hi-dro-sef'ah-lus), literally, “water on the brain.”  Hydrocephalus in a newborn baby causes the head  to enlarge as the brain increases in size. This is pos-  sible in an infant because the skull bones have not  yet fused. However, in an adult this condition is  likely to result in brain damage because the skull is  hard, and the accumulating fluid creates pressure  that crushes soft nervous tissue and could restrict  blood flow into the brain. Today hydrocephalus is  treated surgically by inserting a shunt (a plastic  tube) to drain the excess fluid into a vein in the neck  or abdomen.    No other body organ is so absolutely dependent on  a constant internal environment as is the brain.  Other body tissues can withstand the rather small  fluctuations in the concentrations of hormones,  ions, and nutrients that continually occur, particu-  larly after eating or exercising. If the brain were  exposed to such chemical changes, uncontrolled  neural activity might result—remember that certain  ions (sodium and potassium) are involved in initiat-  ing nerve impulses and that some amino acids serve  as neurotransmitters.   Consequently, neurons are kept separated  from bloodborne substances by the blood-brain  barrier, composed of the least permeable capillar-  ies in the whole body. These capillaries are almost  seamlessly bound together by tight junctions all  around. Of water-soluble substances, only water,  glucose, and essential amino acids pass easily  through the walls of these capillaries. Metabolic  wastes, such as urea, toxins, proteins, and most  drugs, are prevented from entering brain tissue.  Nonessential amino acids and potassium ions not  only are prevented from entering the brain, but also  are actively pumped from the brain into the blood  across capillary walls. Although the bulbous “feet”  of the astrocytes that cling to the capillaries may  contribute to the barrier, the relative impermeabil-  ity of the brain capillaries is most responsible for  providing this protection.   The blood-brain barrier is virtually useless  against fats, respiratory gases, and other fat-soluble  molecules that diffuse easily through all plasma  membranes. This explains why bloodborne alcohol,  nicotine, and anesthetics can affect the brain.   disease (AD) is a progressive  degenerative disease of the brain that  ultimately results in dementia (mental  deterioration), memory loss (particu-  larly for recent events), a short atten-  tion span and disorientation, and  eventual language loss.   AD is associated with a shortage  of acetylcholine (ACh) and structural  changes in the brain.   Microscopic examinations of brain  tissue reveal senile plaques (aggrega-  tions of beta-amyloid peptide) littering  the brain like shrapnel between the  neurons. It has been frustratingly diffi-  cult for researchers to uncover how  beta-amyloid peptide acts as a neuro-  toxin, particularly because it is also  present in healthy brain cells (but  there is less of it). It is known that this  tiny peptide does its damage by    f Learn more at Mastering A&P > Study Area > |  Additional Study Tools > A Closer Look    brain neurons. High calcium levels can  play a role in initiating apoptosis, or  programmed cell death.   Another line of research has impli-  cated a protein called tau, which  appears to bind microtubule “tracks”  together, much like railroad ties. In  the brains of AD victims, tau grabs  onto other tau molecules, forming  spaghetti-like neurofibrillary  tangles within neuron cell  bodies. These degenerative  changes develop over sev-  eral years, during which  time family members  watch the person they  love “disappear.” It is  hoped that the lines of  investigation, particularly  stem cell research, will  eventually merge  and point to a  treatment, but    at present drugs that ease symptoms  by inhibiting ACh breakdown are  most useful.   Parkinson's disease, an example  of a basal nuclei problem, typically  strikes people in their fifties and  sixties (actor Michael J. Fox is an  unlucky exception who developed it   around age 30). It results  from degeneration of  specific neurons in  the substantia  nigra of the mid-  brain, which nor-  mally supply  dopamine to the  basal nuclei. The  dopamine-deprived  basal nuclei, which    17. What name is given to the cerebrospinal fluid-  filled cavities within the brain?   18. What name is given to the barrier that protects the  brain from toxic chemicals?   19. Which meningeal layer provides the means  for draining cerebrospinal fluid back into the  blood—dura mater, arachnoid mater, or pia  mater?    ı# Compare the signs of a CVA with those of  Alzheimer’s disease; of a contusion with those  of a concussion.    Brain dysfunctions are unbelievably varied. We dis-  cuss some of them—the “terrible three”’—in “A  Closer Look,” and we will discuss developmental  problems in the final section of this chapter. Here,  we will focus on traumatic brain injuries and cere-  brovascular accidents. We describe techniques used  to diagnose many brain disorders in “A Closer Look”  later in the chapter (p. 287).   Globally, traumatic brain injury is a major cause of  disability and death. Consider, for example, what  happens if you crash into the rear end of another car.  If you're not wearing a seatbelt, your head will jerk  forward and then violently stop as it hits the wind-  shield. Brain trauma is caused not only by injury at  the site of the blow, but also by the effect of the rico-  cheting brain hitting the opposite end of the skull.    help regulate voluntary motor activ-  ity, become overactive, causing symp-  toms of the disease. Afflicted  individuals have a persistent tremor  at rest (exhibited by head nodding  and a “pill-rolling” movement of the  fingers), a forward-bent walking pos-  ture and shuffling gait, and a stiff  facial expression. In addition, they  have trouble initiating movement.   The cause of Parkinson's disease is  still unknown. The drug L-dopa, which  is converted to dopamine in the brain,  helps alleviate some of the symptoms.  However, L-dopa is not a cure, and  as more and more neurons die, it  becomes ineffective. It also has unde-  sirable side effects: severe nausea,  dizziness, and, in some, liver damage.  In 2015, the FDA approved two new  extended-release versions of L-dopa  drugs. Both medications allow for  more consistent dopamine levels and  better control of symptoms.   A variety of treatment options have  been explored, but the most promising  (transplant of embryonic substantia    nigra tissue into the brain) is mired in  legal and ethical issues surrounding  the use of fetal tissue.   Huntington’s disease is a genetic  disease that strikes during middle age  and leads to massive degeneration of  the basal nuclei and later of the cere-  bral cortex. Its initial symptoms are  wild, jerky, and almost continuous  flapping movements called chorea  (Greek for “dance”). Although the  movements appear to be voluntary,  they are not. Late in the disease,  marked mental deterioration occurs,  resulting in a lack of focus, fatigue,  and irritability. Huntington's disease is  progressive, and the prognosis varies  from 10 to 30 years from the onset of  symptoms.   The signs and symptoms of early  Huntington's disease are essentially  the opposite of Parkinson's disease  (overstimulation rather than inhi-  bition of the motor drive), and  Huntington’s is usually treated  with drugs that block, rather than  enhance, dopamine's effects. Late in    the disease, however, dopamine lev-  els fall below normal levels, as seen  in Parkinson's patients. As with  Parkinson’s, fetal tissue or stem cell  implants may help Huntington's  patients in the future.    e Alzheimer's disease is associated  with low acetylcholine levels  and abnormally high amounts  of beta-amyloid peptide.   e Parkinson's disease results from  abnormally low dopamine levels  in the basal nuclei, resulting in  overactive motor neurons that  cause tremors.    e Huntington's disease is a heredi-  tary disease leading to the degen-  eration of basal nuclei and the  cerebral cortex.    e Fetal cells and stem cells repre-  sent hope for a cure, though  use of these cells raises many  legal and ethical concerns.    A concussion occurs when brain injury is slight.  The victim may be dizzy, “see stars,” or lose con-  sciousness briefly, but typically little permanent  brain damage occurs. A brain contusion results  from marked tissue destruction. If the cerebral cortex  is injured, the individual may remain conscious, but  severe brain stem contusions always result in a coma  lasting from hours to a lifetime due to injury to the  reticular activating system.   After head blows, death may result from intra-  cranial hemorrhage (bleeding from ruptured ves-  sels) or cerebral edema (swelling of the brain due  to inflammatory response to injury). Individuals  who are initially alert and lucid following head  trauma and then begin to deteriorate neurologically  are most likely hemorrhaging or suffering the  delayed consequences of edema, both of which com-  press vital brain tissue and require immediate medi-  cal intervention.   Commonly called strokes, cerebrovascular  (ser”e-bro-vas' ku-lar) accidents (CVAs) are the sec-  ond leading cause of death and the third leading  cause of disability worldwide. CVAs occur when  blood circulation to a brain area is blocked, as by a  blood clot or a ruptured blood vessel, and vital brain  tissue dies. The severity of impairment resulting from  a CVA depends on the location of the stroke and how  much damage occurred as a result. Thus, CVAs can  cause little to no damage, severe damage, or even  death. For example, if the patient has left-sided paral-  ysis (a one-sided paralysis is called hemiplegia), the  right motor cortex of the frontal lobe is most likely  involved. Aphasias (ah-fa’ze-ahz) are a common re-  sult of damage to the left cerebral hemisphere, where  the language areas are located. There are many types  of aphasias, but the most common are motor aphasia,  which involves damage to Broca’s area and a loss of    ability to speak, and sensory aphasia, in which a per-  son loses the ability to understand written or spoken  language. Aphasias are maddening to victims  because, as a rule, their intellect is unimpaired.   Brain lesions can also cause marked changes in a  person's disposition (for example, a change from a  sunny to a foul personality). In such cases, a tumor  as well as a CVA might be suspected. Some patients  recover at least part of their lost faculties because  undamaged neurons spread into areas where neu-  rons have died and take over some lost functions.  Indeed, most of the recovery seen after brain injury is  due to this phenomenon.   Not all strokes are “completed.” Temporary  brain ischemia, or restricted blood flow, is called a  transient ischemic attack (TIA). TIAs last from 5  to 50 minutes and are characterized by symptoms  such as numbness, temporary paralysis, and im-  paired speech. Although these defects are not per-  manent, they do constitute “red flags” that warn of  impending, more serious CVAs.    20. A person has been hit on the head with a baseball  and soon becomes comatose. Has he suffered a  concussion or a contusion?    The cylindrical spinal cord is a glistening white con-  tinuation of the brain stem. The spinal cord provides  a two-way conduction pathway to and from the  brain, and it is a major reflex center (spinal reflexes  are completed at this level). Enclosed within the ver-  tebral column, the spinal cord extends from the fora-  men magnum of the skull to the first or second  lumbar vertebra, where it ends just below the ribs  (Figure 7.19).   Like the brain, the spinal cord is cushioned and  protected by meninges. Meningeal coverings do not  end at the second lumbar vertebra (L}) but instead  extend well beyond the end of the spinal cord in the  vertebral canal. Because there is no possibility of  damaging the cord beyond L3, the meningeal sac    inferior to that point provides a nearly ideal spot for  a lumbar puncture to remove CSF for testing.   In humans, 31 pairs of spinal nerves arise from  the cord and exit from the vertebral column to serve  the body area close by. The spinal cord is about the  size of a thumb for most of its length, but it is  enlarged in the cervical and lumbar regions where  the nerves serving the upper and lower limbs arise    and leave the cord. Because the vertebral column  grows faster than the spinal cord, the spinal cord  does not reach the end of the vertebral column, and  the spinal nerves leaving its inferior end must travel  through the vertebral canal for some distance before  exiting. This collection of spinal nerves at the inferior  end of the vertebral canal is called the cauda equina  (kaw’da e-kwi'nah) because it looks so much like a  horse’s tail (the literal translation of cauda equina).    The gray matter of the spinal cord looks like a butter-  fly or the letter H in cross section (Figure 7.20). The  two posterior projections are the dorsal horns, or  posterior horns; the two anterior projections are  the ventral horns, or anterior horns. The gray  matter surrounds the central canal of the cord,  which contains CSF.   Neurons with specific functions can be located  in the gray matter. The dorsal horns contain inter-  neurons. The cell bodies of the sensory neurons,  whose fibers enter the cord by the dorsal root, are  found in an enlarged area called the dorsal root  ganglion. If the dorsal root or its ganglion is    damaged, sensation from the body area served will  be lost. The ventral horns of the gray matter contain  cell bodies of motor neurons of the somatic (volun-  tary) nervous system, which send their axons out the  ventral root of the cord. The dorsal and ventral    roots fuse to form the spinal nerves.  Homeostatic B  K Imbalance 7.8  Damage to the ventral root results in flaccid paraly-  sis of the muscles served. In flaccid paralysis, as  described in Chapter 6, nerve impulses do not reach  the muscles affected; thus, no voluntary movement  of those muscles is possible. The muscles begin to  atrophy because they are no longer stimulated.    White matter of the spinal cord is composed of  myelinated fiber tracts—some running to higher  centers, some traveling from the brain to the cord,  and some conducting impulses from one side of the  spinal cord to the other (Figure 7.21, p. 272).    Because of the irregular shape of gray matter, the  white matter on each side of the cord is divided into  three regions—the dorsal column, lateral column,  and ventral column. Each of the columns contains  a number of fiber tracts made up of axons with the  same destination and function. Tracts conducting  sensory impulses to the brain are sensory, or afferent,  tracts. Those carrying impulses from the brain to  skeletal muscles are motor, or efferent, tracts. All tracts  in the dorsal columns are ascending tracts that carry  sensory input to the brain. The lateral and ventral    Homeostatic J  K Imbalance 7.9  If the spinal cord is transected (cut crosswise) or  crushed, spastic paralysis results. The affected mus-  cles stay healthy because they are still stimulated by  spinal reflex arcs, and movement of those muscles  does occur. However, movements are involuntary    and not controllable, as described in Chapter 6. This  can be as much of a problem as complete lack of  mobility. In addition, because the spinal cord carries  both sensory and motor impulses, a loss of feeling or  sensory input occurs in the body areas below the  point of cord destruction. Physicians often use a pin  to see whether a person can feel pain after spinal  cord injury—to find out whether regeneration is  occurring. Pain is a hopeful sign in such cases. If the  spinal cord injury occurs high in the cord, so that all  four limbs are affected, the individual is a quadriple-  gic (kwod"ri-ple’jik). If only the legs are paralyzed,  the individual is a paraplegic (par’a-ple’jik).    Did You Get It?  21. What is found in the gray matter of the  spinal cord?  22. Which spinal cord pathways are sensory  pathways—ascending or descending?  23. Why is the leash of nerve fibers at the end  of the spinal cord called the cauda equina?  For answers, see Appendix A.    The peripheral nervous system (PNS) consists of  nerves and scattered ganglia (groups of neuronal cell  bodies found outside the CNS). We have already  considered one type of ganglion—the dorsal root  ganglion of the spinal cord. We will cover others in  the discussion of the autonomic nervous system.  Here, we will concern ourselves only with nerves.    As noted earlier in this chapter, a nerve is a bundle  of neuron fibers found outside the CNS. Within a  nerve, neuron fibers, or processes, are wrapped in  protective connective tissue coverings. Each fiber is  surrounded by a delicate connective tissue sheath  called an endoneurium (en”do-nu're-um). Groups  of fibers are bound by a coarser connective tissue  wrapping, the perineurium (per’i-nu're-um), to  form fiber bundles, or fascicles. Finally, all the  fascicles are bound together by a tough fibrous    Figure 7.22 Structure of a nerve. Three-dimensional  view of a portion of a nerve, showing its connective  tissue wrappings.    should seem familiar: We discussed similar structures in  the muscle chapter (Figure 6.1, p. 201). Names of mus-  cle structures include the root word mys, whereas the  root word neuro tells you that the structure relates to a  nerve. For example, the endomysium covers one indi-  vidual muscle fiber, whereas the endoneurium covers  one individual neuron fiber.    Like neurons, nerves are classified according to  the direction in which they transmit impulses.  Nerves that carry impulses only toward the CNS are    called sensory (afferent) nerves, whereas those  that carry only motor fibers are motor (efferent)  nerves. Nerves carrying both sensory and motor  fibers are called mixed nerves; all spinal nerves are  mixed nerves.    ~ Identify the cranial nerves by number and by  name, and list the major functions of each.    The 12 pairs of cranial nerves primarily serve the  head and neck. Only one pair (the vagus nerves)  extends to the thoracic and abdominal cavities.   The cranial nerves are numbered in sequence,  and in most cases their names reveal the most impor-  tant structures they control. Table 7.2 describes cra-  nial nerves by name, number, course, and major  function. The last column of the table describes how  cranial nerves are tested, which is an important part  of any neurological examination. You do not need to  memorize these tests, but this information may help  you understand cranial nerve function. As you read  through the table, also look at Figure 7.23, p. 277,  which shows the location of the cranial nerves on the  brain’s ventral surface.   This study tool may help you remember the cra-  nial nerves in order. The first letter of each word in  the saying is the first letter of the cranial nerve to be  remembered: “Oh, oh, oh, to touch and feel very  good velvet at home.”    v Describe the origin and fiber composition of  (1) ventral and dorsal roots, (2) the spinal nerve  proper, and (3) ventral and dorsal rami.    v@ Name the four major nerve plexuses, give  the major nerves of each, and describe their  distribution.    The 31 pairs of human spinal nerves are formed by  the joining of the ventral and dorsal roots of the spi-  nal cord. Although each of the cranial nerves issuing  from the brain is named specifically, the spinal  nerves are named for the region of the cord from  which they arise. (Figure 7.24, p. 278, shows how the  nerves are named in this scheme.)   Almost immediately after being formed, each  spinal nerve divides into the dorsal ramus and    ventral ramus (plural rami [ra’mi]), making each  spinal nerve only about 2 inch long. The rami, like  the spinal nerves, contain both motor and sensory  fibers. Thus, damage to a spinal nerve or either of its  rami results both in loss of sensation and in flaccid  paralysis of the area of the body served. The smaller  dorsal rami serve the skin and muscles of the poste-  rior body trunk. The ventral rami of spinal nerves T;  through T,, form the intercostal nerves, which supply  the muscles between the ribs and the skin and mus-  cles of the anterior and lateral trunk. The ventral  rami of all other spinal nerves form complex net-  works of nerves called plexuses, which serve the  motor and sensory needs of the limbs. (The four  nerve plexuses are described in Table 7.3, p. 279;  three of the four plexuses are shown in Figure 7.25,  p. 280.)    24. Where is the epineurium located?  25. Which cranial nerve pair is the only one to  serve structures outside the head and neck?  26. What is a nerve plexus?  27. Ron has a horrible pain in his right buttock,  thigh, and leg. He is told he has sciatica. Which  spinal nerve is involved, and what plexus does it  belong to?  For answers, see Appendix A.    4# Identify the site of origin, and explain the function  of the sympathetic and parasympathetic divisions  of the autonomic nervous system.    The autonomic nervous system (ANS) is the  motor subdivision of the PNS that controls body  activities automatically. It is composed of a special-  ized group of neurons that regulate cardiac muscle  (the heart), smooth muscles (found in the walls of  the visceral organs and blood vessels), and glands.  Although all body systems contribute to homeosta-  sis, the relative stability of our internal environment  depends largely on the workings of the ANS. At every  moment, signals flood from the visceral organs into  the CNS, and the autonomic nervous system makes  adjustments as necessary to best support body activ-  ities. For example, blood flow may be shunted to  more “needy” areas, heart and breathing rate may be  sped up or slowed down, blood pressure may be    Fibers arise from  olfactory receptors in  the nasal mucosa and  synapse with the  olfactory bulbs (which,  in turn, send fibers    Fibers arise from the  retina of the eye and  form the optic nerve.  The two optic nerves  form the optic chiasma  by partial crossover   of fibers; the fibers  continue to the thalamus  as the optic tracts;  thalamic fibers connect  to visual cortex    Fibers emerge from the  pons and form three  divisions that run to the  face    Purely motor; supplies motor  fibers to four of the six  muscles (superior, inferior,  and medial rectus, and  inferior oblique) that direct  the eyeball; to the eyelid; and  to the internal eye muscles  controlling lens shape and  pupil size    Mixed nerve; conducts  sensory impulses from the  skin of the face and mucosa  of the nose, mouth, and  corneas; also contains motor  fibers that activate the  chewing muscles    Purely motor; supplies motor  fibers to the lateral rectus  muscle, which rolls the eye  laterally    Subject is asked to sniff and  identify aromatic substances,  such as oil of cloves or vanilla    Vision and visual field are  tested with an eye chart and  by testing the point at which  the subject first sees an  object (finger) moving   into the visual field; eye  interior is viewed with an  ophthalmoscope    Pupils are examined for size,  shape, and size equality;  pupillary reflex is tested with  a penlight (pupils should  constrict when illuminated);  eye convergence is tested, as  is the ability to follow moving  objects    Tested in common with  cranial nerve Ill for the  ability to follow moving  objects    Sensations of pain, touch,  and temperature are tested  with a safety pin and hot  and cold objects; corneal  reflex tested with a wisp   of cotton; motor branch  tested by asking the subject  to open mouth against  resistance and move jaw  from side to side    Tested in common with  cranial nerve Ill for the ability  to move each eye laterally    Fibers run from the  equilibrium and hearing  receptors of the inner  ear to the brain stem    Fibers emerge from the  medulla and descend  into the thorax and  abdominal cavity    Mixed nerve; activates the  muscles of facial expression  and the lacrimal and salivary  glands; carries sensory  impulses from the taste  buds of anterior tongue    Mixed nerve; vestibular  branch transmits impulses for  the sense of balance, and  cochlear branch transmits  impulses for the sense    Mixed nerve; supplies motor  fibers to the pharynx (throat)  that promote swallowing and  saliva production; carries  sensory impulses from taste  buds of the posterior tongue  and from chemical and  pressure receptors of the  carotid artery    Mixed nerve; fibers carry  sensory impulses from and  motor impulses to the  pharynx, larynx, and the  abdominal and thoracic  viscera; most motor fibers are  parasympathetic fibers that  promote digestive activity  and help regulate heart  activity    Anterior two-thirds of tongue  is tested for ability to taste  sweet, salty, sour, and bitter  substances; subject is asked  to close eyes, smile, whistle,  etc.; tearing of eyes is tested  with ammonia fumes    Hearing is checked by air and  bone conduction, using a  tuning fork   reflexes are checked; subject  is asked to speak and cough;  posterior tongue may be  tested for taste    Tested in common with  cranial nerve IX because they  both serve muscles of the  throat    Sternocleidomastoid and  trapezius muscles are  checked for strength by  asking the subject to rotate  head and shrug shoulders  against resistance    Subject is asked to stick out  tongue, and any position  abnormalities are noted    *Until recently, it was thought that the accessory nerves also received a contribution from cranial rootlets, but it has now been determined that in almost  all people, these cranial rootlets are instead part of the vagus nerves. This raises an interesting question: Should the accessory nerves still be considered  cranial nerves? Some anatomists say yes because they pass through the cranium. Other anatomists say no because they don’t arise from the brain.    Figure 7.23 Ventral view of the brain showing the distribution of cranial  nerves. Sensory nerves are shown in blue, motor nerves in red. Cranial nerve VIII  has some motor fibers; however, these are not shown because this nerve is  mostly sensory.    *Note that the cervical nerve C, emerges inferior to the C, vertebra, while the other  seven cervical nerves emerge superior to the vertebrae for which they are named.    Figure 7.24 Spinal nerves. (a) Relationship of spinal nerves to the vertebrae.  Areas of plexuses formed by the ventral rami are indicated. (b) Relative distribution  of the ventral and dorsal rami of a spinal nerve (cross section of the left trunk).    Sciatic (largest nerve in  body; splits to common  fibular and tibial nerves  just above knee)    Deltoid muscle and skin of  shoulder; muscles and skin  of superior thorax    Triceps and extensor  muscles of the forearm;  skin of posterior upper limb   of lateral two-thirds of  anterior hand and posterior  of fingers 2 and 3    Some flexor muscles of  anterior forearm; wrist and  many hand muscles; skin of  medial hand    Lower abdomen, anterior  and medial thigh muscles  (hip flexors and knee  extensors), and skin of  anteromedial leg and thigh    Adductor muscles of  medial thigh and small hip  muscles; skin of medial  thigh and hip and knee  joints   Lower trunk and posterior  surface of thigh (hip  extensors and knee flexors)    Anterior and lateral aspect  of leg and superior aspect  of foot    Decreased ability to flex and  abduct hand and flex and  abduct thumb and index  finger—therefore, inability  to pick up small objects    Inability to extend leg and  flex hip; loss of cutaneous  sensation    Inability to extend hip  (maximus) or abduct and  medially rotate thigh  (medius)    Figure 7.25 Distribution of the major peripheral nerves of the upper and lower limbs.    adjusted, and stomach secretions may be increased  or decreased. Most of this fine-tuning occurs without  our awareness or attention—few of us realize when  our pupils dilate or our arteries constrict—hence the  ANS is also called the involuntary nervous system, as  noted at the beginning of this chapter.    Our previous discussions of nerves in the efferent  (motor) division of the PNS have focused on the  somatic nervous system, the PNS subdivision that  controls our skeletal muscles. So, before plunging  into a description of autonomic nervous system anat-  omy, let's note some important differences between  the somatic and autonomic subdivisions of the PNS.   Besides differences in their effector organs and in  the neurotransmitters they release, the patterns of  their motor pathways differ. In the somatic division,  the cell bodies of the motor neurons are inside the  CNS, and their axons (in spinal nerves and their  rami) extend all the way to the skeletal muscles they  serve. The autonomic nervous system, however, has a  chain of two motor neurons. The first motor neuron    of each pair, the preganglionic neuron, is in the  brain or spinal cord. Its axon, the preganglionic  axon (literally, the “axon before the ganglion”),  leaves the CNS to form a synapse with the second  motor neuron in a ganglion outside the CNS. The  axon of this ganglionic neuron, the postganglionic  axon, then extends to the organ it serves. (Figure 7.26  summarizes these differences.)   The autonomic nervous system has two arms, the  sympathetic and the parasympathetic (Figure 7.27,  p. 282). Both serve the same organs but cause essen-  tially opposite effects, counterbalancing each other's  activities to keep body systems running smoothly.  The sympathetic division mobilizes the body dur-  ing extreme situations (such as fear, exercise, or  rage), whereas the parasympathetic division allows  us to “unwind” and conserve energy. We examine  these differences in more detail shortly, but first let's  consider the structural characteristics of the two arms  of the ANS.    The preganglionic neurons of the parasympathetic  division are located in brain nuclei of several cranial    Figure 7.27 Anatomy of the autonomic nervous system. Parasympathetic  fibers are shown in purple, sympathetic fibers in green. Solid lines represent  preganglionic fibers; dashed lines indicate postganglionic fibers. Note the direct  connection between the sympathetic nervous system and the adrenal gland.    nerves—III, VII, IX, and X (the vagus being the most  important of these) and in the S, through S; levels  of the spinal cord (see Figure 7.27). For this reason,  the parasympathetic division is also called the  craniosacral division. The neurons of the cranial  region send their axons out in cranial nerves to serve  the head and neck organs. There they synapse with  the ganglionic motor neuron in a terminal ganglion.  From the terminal ganglion, the postganglionic axon  extends a short distance to the organ it serves. In the  sacral region, the preganglionic axons leave the spi-  nal cord and form the pelvic splanchnic (splank’ nik)  nerves, also called the pelvic nerves, which travel to the  pelvic cavity. In the pelvic cavity, the preganglionic  axons synapse with the second motor neurons in ter-  minal ganglia on, or close to, the organs they serve.    because its preganglionic neurons are in the gray mat-  ter of the spinal cord from T, through L, (see  Figure 7.27). The preganglionic axons leave the cord  in the ventral root, enter the spinal nerve, and then  pass through a ramus communicans, or small com-  municating branch, to enter a sympathetic trunk  ganglion (Figure 7.28). The sympathetic trunk, or  sympathetic chain, lies alongside the vertebral col-  umn on each side. After it reaches the ganglion, the  axon may synapse with the second (ganglionic) neu-  ron in the sympathetic chain at the same level  (Figure 7.28a) or a different level (Figure 7.28b), and  the postganglionic axon then reenters the spinal  nerve to travel to the skin. Or, the preganglionic axon  may pass through the ganglion without synapsing  and form part of the splanchnic nerves (Fig-  ure 7.28c). The splanchnic nerves travel to the viscera  to synapse with the ganglionic neuron, found in a  collateral ganglion anterior to the vertebral column.  The major collateral ganglia—the celiac and the    To effector:  blood vessels,  arrector pili  muscles, and  sweat glands  of the skin    Figure 7.28 Sympathetic pathways. (a) Synapse in a sympathetic trunk ganglion  at the same level. (b) Synapse in a sympathetic trunk ganglion at a different level.  (c) Synapse in a collateral ganglion anterior to the vertebral column.    superior and inferior mesenteric ganglia—supply the  abdominal and pelvic organs. The postganglionic ax-  on then leaves the collateral ganglion and travels to  serve a nearby visceral organ.   Now that we have described the anatomical  details, we are ready to examine ANS functions in a  little more detail.    x“ Contrast the effect of the parasympathetic and  sympathetic divisions on the following organs:  heart, lungs, digestive system, blood vessels.    Body organs served by the autonomic nervous sys-  tem receive fibers from both divisions. Exceptions  are most blood vessels and most structures of the  skin, some glands, and the adrenal medulla, all of  which receive only sympathetic fibers (Table 7.4,    p. 284). When both divisions serve the same organ,  they cause antagonistic effects, mainly because their  postganglionic axons release different neurotrans-  mitters (see Figure 7.26). The parasympathetic fibers,  called cholinergic (ko"lin-er'jik) fibers, release acetyl-  choline. The sympathetic postganglionic fibers,  called adrenergic (ad"ren-er’jik) fibers, release norepi-  nephrine (nor’ep-i-nef'rin). The preganglionic axons  of both divisions release acetylcholine. To emphasize  the relative roles of the two arms of the ANS, we will  focus briefly on situations in which each division is  “in control.”    Sympathetic Division The sympathetic division is  often referred to as the “fight-or-flight” system. Its  activity is evident when we are excited or find our-  selves in emergency or threatening situations, such as  being frightened by a stranger late at night. A pound-  ing heart; rapid, deep breathing; cold, sweaty skin; a    Table 7.4 Effects of the Sympathetic and Parasympathetic Divisions  of the Autonomic Nervous System    Adrenal medulla  Arrector pili muscles  attached to hair follicles  Blood vessels    Increases smooth muscle mobility (peristalsis)  and amount of secretion by digestive system  glands; relaxes sphincters    Constricts blood vessels in viscera and  skin (dilates those in skeletal muscle and  heart); increases blood pressure    Decreases activity of digestive system and  constricts digestive system sphincters (for  example, anal sphincter)    prickly scalp; and dilated eye pupils are sure signs of  sympathetic nervous system activity. Under such con-  ditions, the sympathetic nervous system increases  heart rate, blood pressure, and blood glucose levels;  dilates the bronchioles of the lungs; and brings about  many other effects that help the individual cope with  the stressor. Other examples are dilation of blood  vessels in skeletal muscles (so that we can run faster  or fight better) and withdrawal of blood from the  digestive organs (so that the bulk of the blood can be  used to serve the heart, brain, and skeletal muscles).    The sympathetic nervous system is working at  full speed not only when you are emotionally upset  but also when you are physically stressed. For exam-  ple, if you have just had surgery or run a marathon,  your adrenal glands (activated by the sympathetic  nervous system) will be pumping out epinephrine  and norepinephrine (see Figure 7.26). The effects of  sympathetic nervous system activation continue for  several minutes until its hormones are destroyed by  the liver. Thus, although sympathetic nerve impulses  themselves may act only briefly, the hormonal effects    they provoke linger. The widespread and prolonged  effects of sympathetic activation help explain why  we need time to calm down after an extremely stress-  ful situation.   The sympathetic division generates a head of  steam that enables the body to cope rapidly and vig-  orously with situations that threaten homeostasis. Its  function is to provide the best conditions for  responding to some threat, whether the best response  is to run, to see better, or to think more clearly.    Homeostatic J  £ Imbalance 7.10  Some illnesses or diseases are at least aggravated, if  not caused, by excessive sympathetic nervous system  stimulation. Certain individuals, called type A peo-  ple, always work at breakneck speed and push them-  selves continually. These are people who are likely to  have heart disease, high blood pressure, and ulcers,  all of which may be worsened by prolonged sympa-  thetic nervous system activity or the rebound from it.    Parasympathetic Division The parasympathetic  division is most active when the body is at rest and  not threatened in any way. This division, sometimes  called the “rest-and-digest” system, is chiefly con-  cerned with promoting normal digestion, with elim-  ination of feces and urine, and with conserving body  energy, particularly by decreasing demands on the  cardiovascular system. Its activity is best illustrated  by a person who relaxes after a meal and reads the  newspaper. Blood pressure and heart and respiratory  rates are being regulated at low-normal levels, the  digestive tract is actively digesting food, and the skin  is warm (indicating that there is no need to divert  blood to skeletal muscles or vital organs). The eye  pupils are constricted to protect the retinas from  excessive damaging light, and the lenses of the eyes  are “set” for close vision. We might also consider the  parasympathetic division as the “housekeeping” sys-  tem of the body.   An easy way to remember the most important  roles of the two ANS divisions is to think of the para-  sympathetic division as the D (digestion, defecation,  and diuresis [urination]) division and the sympa-  thetic division as the E (exercise, excitement, emer-  gency, and embarrassment) division. Remember,  however, that although it is easiest to think of the  sympathetic and parasympathetic divisions as    working in an all-or-none fashion, this is rarely the  case. A dynamic balance exists between the two divi-  sions, and both are continuously making fine adjust-  ments. Also, although we have described the  parasympathetic division as the “at-rest” system,  most blood vessels are controlled only by the sympa-  thetic fibers regardless of whether the body is “on  alert” or relaxing.   The major effects of each division are summa-  rized in Table 7.4.    28. Which regions or organs of the body are served by  the autonomic nervous system? Which are served  by the somatic nervous system?   29. How does the motor pathway of the autonomic  nervous system differ from that of the somatic  nervous system?    Learning Objectives  1# List several factors that may have harmful effects  on brain development.    1# Briefly describe the cause, signs, and conse-  quences of the following congenital disorders:  spina bifida, anencephaly, and cerebral palsy.   v Explain the decline in brain size and weight that  occurs with age.    Because the nervous system forms during the first  month of embryonic development, maternal infec-  tion early in pregnancy can have extremely harmful  effects on the fetal nervous system. For example,  German measles (rubella) in the mother often causes  deafness and other types of CNS damage. Also, be-  cause nervous tissue has the highest metabolic rate in  the body, lack of oxygen for even a few minutes kills  neurons. Because smoking decreases the amount of  oxygen that can be carried in the blood, a smoking  mother may be sentencing her infant to possible  brain damage. Radiation and various drugs (alcohol,  opiates, cocaine, and others) can also be very damag-  ing if taken during early fetal development.    Homeostatic J  £ Imbalance 7.11  In difficult deliveries, temporary lack of oxygen may  lead to cerebral palsy (pawl’ze), but this is only  one of the suspected causes. Cerebral palsy is a neu-  romuscular disability in which the voluntary mus-  cles are poorly controlled and spastic because of  brain damage. About half of its victims have seizures,  are intellectually disabled, and/or have impaired  hearing or vision. Cerebral palsy is the largest single  cause of physical disabilities in children. A number  of other congenital malformations—triggered by  genetic or environmental factors—also plague the  CNS. Most serious are hydrocephalus (see p. 267),  anencephaly, and spina bifida. Anencephaly is a  birth defect in which the cerebrum fails to develop.  Children with anencephaly cannot see, hear, or pro-  cess sensory information; these babies typically die  soon after birth. Spina bifida (spi’nah bi’ fi-dah;  “forked spine”) results when the vertebrae form  incompletely (typically in the lumbosacral region).  There are several varieties of spina bifida. In the least  serious, a dimple, and perhaps a tuft of hair, appears  over the site of malformation, but no neurological  problems occur. In the most serious, meninges,  nerve roots, and even parts of the spinal cord  protrude from the spine, rendering the lower part of  the spinal cord functionless. The child is unable to  control the bowels or bladder, and the lower limbs  are paralyzed.    This adult patient with cerebral palsy presses a pad to  communicate through a speaker.    One of the last areas of the CNS to mature is the  hypothalamus, which contains centers for regulating  body temperature. For this reason, premature babies  usually have problems controlling their loss of body  heat and must be carefully monitored. The nervous  system grows and matures all through childhood,  largely as a result of myelination that goes on during  this period. A good indication of the degree of  myelination of particular neural pathways is the level  of neuromuscular control in that body area.  Neuromuscular coordination progresses in a supe-  rior to inferior direction and in a proximal to distal  direction, and myelination occurs in the same se-  quence (as described in Chapter 6).   The brain reaches its maximum weight in the  young adult. Over the next 60 years or so, neurons  are damaged and die; and brain weight and volume  steadily decline. However, a nearly unlimited num-  ber of neural pathways is always available and ready  to be developed, allowing us to continue to learn  throughout life.   As we grow older, the sympathetic nervous sys-  tem gradually becomes less and less efficient, partic-  ularly in its ability to constrict blood vessels. When  older people stand up quickly, they often become  lightheaded or faint. The reason is that the sympa-  thetic nervous system is not able to react quickly  enough to counteract the pull of gravity by activating  the vasoconstrictor fibers, and blood pools in the  feet. This condition, orthostatic hypotension, is a  type of low blood pressure resulting from changes in  body position as described. Orthostatic hypotension  can be prevented to some degree if the person  changes position slowly, giving the sympathetic ner-  vous system time to adjust.   The usual cause of nervous system deterioration  is circulatory system problems. For example,  arteriosclerosis (ar-ter”e-o-sklé-ro’sis; decreased  elasticity of the arteries) and high blood pressure  reduce the supply of oxygen to brain neurons. A  gradual decline of oxygen due to the aging process  can lead to senility, characterized by forgetfulness,  irritability, difficulty in concentrating and thinking  clearly, and confusion. A sudden loss of blood and  oxygen delivery to the brain results in a CVA (stroke),  as described earlier. However, many people continue  to enjoy intellectual lives and mentally demanding  tasks their entire lives. In fact, fewer than 5 percent of  people over age 65 demonstrate true senility.   Sadly, many cases of “reversible senility,” caused  by certain drugs, low blood pressure, constipation,   tendon with a reflex hammer,  your thigh muscles contract, result-  ing in the knee-jerk reflex response.  This response shows that the spinal  cord and upper brain centers are  functioning normally. When reflex  tests are abnormal, more sophisti-  cated neurological tests may be  ordered to try to localize and identify  the problem.   An “oldie-but-goodie” procedure  used to diagnose and localize many  different types of brain lesions (such  as epileptic lesions, tumors, and  abscesses) is electroencephalography  (e-lek”tro-en-sef-ah-lah’ grah-fe).  Normal brain function involves the  continuous transmission of electrical  impulses by neurons. A recording of  that electrical activity, called an elec-  troencephalogram (EEG), can be  made by placing electrodes at various  points on the scalp and face and  connecting these to a recording  device. The patterns of electrical  activity are called brain waves.  Because people differ genetically,  and because everything we have ever  experienced has left its imprint in our  brain, each of us has a brain wave  pattern that is as unique as our fin-  gerprints. The four most commonly  seen brain waves are illustrated and  described in the figure.   Brain waves that are too fast or  too slow suggest that the function of  the cerebral cortex has been compro-  mised. Sleep and coma result in  brain-wave patterns that are slower  than normal, whereas epileptic sei-  zures and some kinds of drug over-  dose cause abnormally fast brain   seen even during coma, the  absence of brain waves (a flat apne  EEG) is taken as evidence of way AM A  clinical death.   New imaging techniques beta  (described in Chapter 1, pp. 32-33)  have revolutionized the diagnosis abn AVM /\WA NAIA Ae  of brain lesions. Together, theta  computed tomography (CT)  and magnetic resonance  imaging (MRI) scans allow quick Bee ay ya  identification of most tumors, delta    intracranial lesions, multiple  sclerosis plaques, and areas of  dead brain tissue (infarcts).  Positron emission tomography  (PET) scans can localize lesions  that generate epileptic seizures.   Take, for example, a patient  arriving in the ER with a stroke.  A CT scan will help determine  whether the stroke is due to a clot  or a bleed. Cerebral angiography,  which involves injecting a dye to  make arteries in the brain stand out  on X-ray imaging, might be used to  visualize a clot or directly deliver a  drug to the clot through a catheter.  Less expensive and invasive than  angiography, ultrasound imaging  can be used to quickly examine the  carotid arteries and even measure °  blood flow through them.   A new imaging procedure,  DaTscan, can assist with diagnosing  neurodegenerative conditions C5  involving dopamine, such as  Parkinson’s disease. The power of this  technique is that it can image both  the amount and distribution of  dopamine in the brain. Although  DaTscan cannot diagnose Parkinson's    Electroencephalography and brain  waves. Typical EEGs. Aloha waves are  typical of the awake, relaxed state; beta  waves occur in the awake, alert state; theta  waves are common in children but not in  normal adults; and delta waves occur  during deep sleep.    disease directly, it helps doctors  distinguish Parkinson's from other  neurological conditions characterized  by abnormal dopamine levels.    e Neurological function tests  include testing reflexes and  checking brain waves by EEG.    DaTscan is a technique used to  visualize the amount and distri-  bution of dopamine in the  brain.    Imaging techniques such as CT,  MRI, PET, angiography, and  ultrasound can help identify  tumors, lesions, multiple sclero-  sis plaques, and infarcts (dead  tissue) in the brain.    e Sympathetic division of the ANS  activates the adrenal medulla;  hypothalamus helps regulate the  activity of the anterior pituitary gland  and produces two hormones    e Nerves innervate lymphoid  organs; the brain plays a role  in regulating immune function   e Lymphatic vessels carry away  leaked interstitial fluids from tissues  surrounding nervous system  structures; immune elements  protect all body organs from  pathogens (CNS has additional  mechanisms)   e Cardiovascular system delivers  blood containing oxygen and  nutrients to the nervous system;  carries away wastes    ra T, i  E i e ANS regulates sexual erection  and ejaculation in males;  erection of the clitoris in females  e Testosterone masculinizes the  brain and underlies sex drive  and aggressive behavior    e Sympathetic division of the ANS  regulates sweat glands and  blood vessels of skin (therefore  heat loss/retention)   e Kidneys help to dispose of metabolic  wastes and maintain proper  electrolyte composition and pH of  blood for neural functioning    poor nutrition, depression, dehydration, and hor-  mone imbalances, go undiagnosed. The best way to  maintain your mental abilities in old age may be to  seek regular medical checkups throughout life.   Although eventual shrinking of the brain is nor-  mal, some individuals (professional boxers and  chronic alcoholics, for example) hasten the process.  Whether a boxer wins the match or not, the likeli-  hood of brain damage and atrophy increases with  every blow. The expression “punch drunk” reflects  the symptoms of slurred speech, tremors, abnormal  gait, and dementia (mental illness) seen in many  retired boxers.    7.1a. Structural classifications include the central  nervous system (CNS): brain and spinal cord; and  peripheral nervous system (PNS): nerves and  ganglia    7.1b. Functional classifications include sensory  division (afferent division) and motor division  (efferent division)    e The motor division is further divided into the  somatic nervous system (controls skele-  tal muscle) or autonomic nervous system  (ANS) (controls smooth/cardiac muscle and  glands)    o In the CNS: Microglia are phagocytes;  oligodendrocytes myelinate neuron pro-  cesses; ependymal cells line fluid-filled  cavities; astrocytes brace neurons and filter  nutrients    Everyone recognizes that alcohol has a profound  effect on the mind as well as the body. CT scans of  chronic alcoholics reveal reduced brain size at a  fairly early age. Like boxers, chronic alcoholics tend  to exhibit signs of mental deterioration unrelated to  the aging process.    31. Why must premature babies be placed in incuba-  tors until their hypothalamus matures?  32. What is orthostatic hypotension? Why do many  older people suffer from this condition?  For answers, see Appendix A.    i) Listen to the story of this chapter in a brief summary at Mastering A&P >  pt Study Area > Author Narrated Audio Summaries    e Anatomy: Neurons have a cell body and  processes (fibers) of two types    ° Dendrites (one to many per cell)—carry  electrical impulses toward the cell body    o Axons (one per cell)—generate and conduct  impulses away from the cell body  = Often release neurotransmitter at the axon  terminals  = Most large fibers are myelinated; myelin  speeds nerve impulse transmission    o Clusters of neuron cell bodies in the CNS are  nuclei; clusters of neuron cell bodies in the  PNS are ganglia    o Bundles of nerve fibers in the CNS are tracts;  bundles of nerve fibers in the PNS are nerves    ° Sensory neurons (afferent neurons), motor  neurons (efferent neurons) and interneu-  rons (association neurons)  = Dendritic endings of sensory neurons are    ° Unipolar neurons, bipolar neurons, and  multipolar neurons  = Motor and interneurons are multipolar; most  sensory neurons are unipolar; exceptions are  sensory neurons in some special sense organs  (ear, eye, etc.), which are bipolar    e The membrane of a neuron at rest is polarized; its  outer face is more positive compared to its inner  face because high concentrations of Na” ions are  found outside the neuron whereas K* ions are  found in high concentrations inside the neuron    o This state is maintained by the leakage of K*  ions out of the cell (fewer positive ions inside)    e During a nerve impulse, plasma membrane  permeability of the neuron changes    ° Once begun, the action potential is all-or-  nothing, and it continues over the entire surface  of the axon    o Electrical conditions of the resting state are  restored by the diffusion of potassium ions  (K+) out of the cell—repolarization    o Jonic conditions of the resting state are restored  by the sodium-potassium pump    o Until repolarization is complete, the neuron is  unable to send another impulse    e A neuron communicates with its target  (other neurons or tissue cells) by releasing  neurotransmitters    o Neurotransmitters diffuse across the synaptic  cleft, attach to membrane receptors on the  postsynaptic cell, and stimulate specific ion  channels to open, causing activation or inhibi-  tion, depending on the neurotransmitter  released and the target cell    ° A reflex arc has at least five components: recep-  tor, sensory neurons, CNS integration center,  motor neurons, and effector  = Normal reflexes indicate normal nervous   e Cerebral hemispheres—the largest part of the  brain; composed of superficial gray matter and  deep white matter    o Function in logical reasoning, moral conduct,  emotional responses, sensory interpretation,  and the initiation of voluntary muscle activity    ° The basal nuclei (regions of gray matter deep  within the white matter) modify voluntary  motor activity  = Parkinson's disease and Huntington’s disease    ° Hypothalamus—most important regula-  tory center of the autonomic nervous system  (regulates water balance, metabolism, thirst,  temperature, etc.)    ° Epithalamus— includes the pineal gland (an  endocrine gland) and the choroid plexus of  the third ventricle    ° Medulla oblongata—most inferior part of the  brain stem; contains fiber tracts and autonomic  nuclei involved in the regulation of vital life activ-  ities (breathing, heart rate, blood pressure, etc.)    ° Reticular formation—extends length of brain  stem; involved in motor control of visceral organs  and consciousness and the sleep/wake cycle    e Skull bones and vertebrae protect the brain and  spinal cord    ° Dura mater (tough, outermost), arachnoid  mater (middle, weblike), and pia mater  (innermost, delicate)    ° Formed by the choroid plexuses, found in the  subarachnoid space, ventricles, and central  canal    o CSF is continually formed and drained  into dural venous sinuses via arachnoid  granulations    e Head trauma may result in concussions (revers-  ible damage) or contusions (irreversible damage)    o When the brain stem is affected, unconscious-  ness (temporary or permanent) occurs    ° Trauma-induced brain injuries may be aggra-  vated by intracranial hemorrhage or cerebral  edema, both of which compress brain tissue  and may interrupt blood flow to the brain    e Cerebrovascular accidents (CVAs), or strokes—  blockage of blood circulation to brain neurons,  resulting in death of brain tissue    o May cause visual impairment, paralysis, and  aphasias (problems with speech and/or lan-  guage); depends where CVA occurred and how  severe it was    ° Transient ischemic attack (TIA)—temporary  restriction of blood flow to the brain; no tissue  death occurs    o Huntington’s is a genetic disease leading to  degeneration of the basal nuclei and cerebral  cortex; both motor and mental deterioration  occur    o° Dorsal roots and ventral roots combine to  form spinal nerves    7.4a. A nerve is a bundle of neuron pro-  cesses wrapped in connective tissue coverings  (endoneurium, perineurium, and epineurium)    7.4b. Cranial nerves: 12 pairs of nerves that  extend from the brain to serve the head and neck  region    e An exception is the paired vagus nerves, which  extend into the thorax and abdomen    7.4c. Spinal nerves: 31 pairs of nerves are formed  by the union of the dorsal and ventral roots of the  spinal cord on each side    e Each spinal nerve is very short and splits into dor-  sal and ventral rami    ° Ventral rami (except T,-T;2) form plexuses  (cervical, brachial, lumbar, sacral) that serve the  limbs  = Ventral rami of T)-T,, form the intercostal   nerves (supply intercostal muscles, and ante-  rior and lateral trunk muscles and skin)    7.4d. Autonomic nervous system: part of the  PNS; composed of neurons that regulate the activity  of smooth and cardiac muscles and glands    e Differs from the somatic nervous system in that  there is a chain of two motor neurons from the  CNS to the effector    e Two subdivisions serve the same organs with dif-  ferent effects   = First motor neurons are in brain or sacral  region of the cord; second motor neurons are  in the terminal ganglia close to the organ  served   = Preganglionic neurons are in gray matter of  the cord; ganglionic sympathetic neurons are  in the sympathetic trunk or in collateral  ganglia    System (pp. 285-289)  e Maternal and environmental factors can impair  embryonic brain development  ° Oxygen deprivation destroys brain cells  ° Severe congenital brain diseases include  cerebral palsy, anencephaly, hydrocephalus,  and spina bifida    e Premature babies have trouble regulating body  temperature because the hypothalamus is one of  the last brain areas to mature    o Brain growth ends in young adulthood; neu-  rons die throughout life and are not replaced;  brain mass declines with age    o Disease (particularly cardiovascular disease) is  the major cause of declining mental function    1. Which of the following is an example of integration 5. Which structures are found in the midbrain?  by the nervous system? a. Corpora c. Cerebral  a. The feel of a cold breeze quadrigemina aqueduct  b. Shivering and goose bumps in response to cold b. Epithalamus d. Basal nuclei  c. Perceiving the sound of rain 6. Choose the proper term to respond to the statements  d. The decision to go back for an umbrella describing various brain areas.  a. cerebellum  2. What is not affected by the parasympathetic division o  of the autonomic nervous system? b. corpora quadrigemina  a. Adrenal medulla c. corpus callosum  b: Heart tate d. hypothalamus  c. Iris e. medulla  d. Sweat glands f. midbrain  . pons  3. Which is the innermost delicate meningeal layer? 8: P  h. thalamus  1. Region where there is a gross crossover of  fibers of descending pyramidal tracts  2. Control of temperature, autonomic nervous  system reflexes, hunger, and water balance  3. Houses the substantia nigra and cerebral  aqueduct  4. Relay stations for visual and auditory stimuli  input; found in midbrain  5. Houses vital centers for control of the heart,  respiration, and blood pressure  6. Brain area through which all the sensory  input is relayed to get to the cerebral cortex  7. Brain area most concerned with equilibrium,  body posture, and coordination of motor  activity.  4. Histological examination of a slice of neural tissue 7. The nerves that arise from the spinal lumbar plexus  reveals a bundle of nerve fibers held together by cells include the  arya bap a ier aa around a nn a sdate c öbtüratot  and form a myelin sheath. The specimen is likely to be  M p 7 b. femoral. d. gluteal.    The cranial nerve responsible for activating the  lacrimal glands is the    forearm, and fingers would be affected by damage to  which one of these nerves?   Which cells are responsible for the formation of  myelin in the CNS?    12. Which of the following is (are) found in a three-neu-    a. Sensory (efferent) neuron  b. Motor (efferent) neuron  c. Sensory receptor    Explain both the structural and functional classifica-  tions of the nervous system. In your explanation,  include the subdivisions of each.    neurons and supporting cells such as astrocytes and  Schwann cells. Which are “nervous” cells? Why? What  are the major functions of the other cell group?    Briefly explain how nerve impulses are initiated and  transmitted, and why conduction at synapses is  always one-way.    Speech is a complex human skill. Where are the two  brain areas involved in the production of speech  located? What is the specific function of each area?    How many pairs of cranial nerves are there? Which  are purely sensory? Which activates the chewing  muscles? Which helps regulate heart rate and activity  of the digestive tract?    What region of the body is served by the dorsal rami  of the spinal nerves? By the ventral rami?    Name the four major nerve plexuses formed by the  ventral rami and the body region served by each.    Mark complains about weakness of the muscles in his  face. He informs his doctor that he also experiences a  dry mouth and enjoys his meals less because his taste  sensation is hampered. Which cranial nerve of Mark  is affected?    pital by friends after falling from a roof. She did not  lose consciousness immediately, and she was initially  lucid. After a while, though, she became confused and  then unresponsive. What is a likely explanation of her  condition?    Mrs. Chen, a new mother, brings her infant to the  clinic because he has suffered repeated seizures. When    questioned, she states that her labor was unusually  long and difficult. What condition do you suspect?  Will the infant's condition worsen?    Maria had an automobile accident that caused injury  to her head. As a result, she could not understand  what was said to her, though she was able to pro-  nounce words herself. What was her probable condi-  tion? What caused it?    Why does exposure to toxins have more devastating  neural effects during early pregnancy than in late    The special senses  respond to stimuli involved  in vision, hearing, balance,    Without your  special senses, you  could not smell or taste your  favorite food, appreciate  colors, or hear your  favorite song.    eople are responsive creatures. Hold freshly  baked bread before us, and our mouths water.  Sudden thunder makes us jump. These stimuli  (the bread and thunder) and many others continually  greet us and are interpreted by our nervous system.  We are told that we have five senses that keep  us in touch with what is going on in the external  world: touch, taste, smell, sight, and hearing.  Actually, touch is a mixture of the general senses  that we considered in Chapter 7—the temperature,  pressure, and pain receptors of the skin and the  proprioceptors of muscles and joints. The other  four “traditional” senses—smell, taste, sight, and    A variety of receptors,  housed in special sense  organs such as the eye, ear,  . and nose, help detect stimuli    hearing—are called special senses. Receptors  for a fifth special sense, equilibrium, are housed in  the ear, along with the organ of hearing. In con-  trast to the small and widely distributed general  receptors, the special sense receptors are either  large, complex sensory organs (eyes and ears) or  localized clusters of receptors (taste buds and  olfactory epithelium).    (Figure 7.1, p. 243). Each of the special senses gathers  unique sensory information that, once integrated, will  influence motor output. For example, if you saw a ball  moving toward your head, this sensory input might  result in a motor output that would move your body out  of the path of the ball. Additionally, recall that each  type of sensory information is processed in a specialized  area of the cerebrum (Figure 7.13c, p. 259).    Of all the senses, vision has been studied most.  Nearly 70 percent of all sensory receptors in the  body are in the eyes. The optic tracts that carry infor-  mation from the eyes to the brain are massive bun-  dles, containing over a million nerve fibers. We rely  heavily on our sight and often have to “see it to  believe it” (Figure 8.1).    wz When provided with a model or diagram, identify  the accessory eye structures, and list the functions  of each.    The adult eye is a sphere that measures about 1 inch  (2.5 cm) in diameter. Only the anterior one-sixth of  the eye’s surface is normally seen. The rest of it is  enclosed and protected by a cushion of fat and the  walls of the bony orbit. The accessory structures of  the eye include the extrinsic eye muscles, eyelids,  conjunctiva, and lacrimal apparatus.   Anteriorly the eyes are protected by the eyelids,  which meet at the medial and lateral corners of the  eye, the medial commissure (canthus) and lateral  commissure (canthus), respectively (Figure 8.1).  The space between the eyelids in an open eye is  called the palpebral fissure. Projecting from the border  of each eyelid are the eyelashes. Modified sebaceous  glands associated with the eyelid edges are the tarsal  glands. These glands produce an oily secretion that  lubricates the eye (Figure 8.2a, p. 296). Ciliary  glands, which are modified sweat glands, lie be-  tween the eyelashes (cilium = eyelash), and their  ducts open at the eyelash follicles. On the medial  aspect of each eye is the lacrimal caruncle (see  Figure 8.1), a raised area containing sebaceous and  sweat glands that produce an oily, whitish secretion  that also lubricates the eye.   A delicate membrane, the conjunctiva (kon-  junk”ti'vah), lines the eyelids and covers part of  the outer surface of the eyeball (Figure 8.2a). It  ends at the edge of the transparent cornea by fus-  ing with the corneal epithelium. The conjunctiva  secretes mucus, which helps to lubricate the eye-  ball and keep it moist.   (a) Sagittal section of the accessory structures  associated with the anterior part of the eye. (b) Anterior  view of the lacrimal apparatus.    Homeostatic J  K Imbalance 8.1  Inflammation of the conjunctiva, called conjunctivitis,  results in reddened, irritated eyes. Pinkeye, its infec-  tious form caused by bacteria or viruses, is highly  contagious.    The lacrimal apparatus (Figure 8.2b) consists  of the lacrimal gland and a number of ducts that  drain lacrimal secretions into the nasal cavity. The  lacrimal glands are located above the lateral end of  each eye. They continually release a dilute salt solu-  tion (tears) onto the anterior surface of the eyeball  through several small ducts. The tears flush across  the eyeball into the lacrimal canaliculi medially,  then into the lacrimal sac, and finally into the  nasolacrimal duct, which empties into the inferior  meatus of the nasal cavity (see Figure 8.2b). Tears  contain mucus, antibodies, and lysozyme (li’so-  zim), an enzyme that destroys bacteria. Thus, they  cleanse and protect the eye surface as they moisten  and lubricate it. When lacrimal secretion increases  substantially, tears spill over the eyelids and fill the  nasal cavities, causing congestion and the “sniffles.”  This happens when the eyes are irritated by foreign  objects or chemicals and when we are emotionally  upset. In the case of irritation, the enhanced tearing  acts to wash away or dilute the irritating substance.  The importance of “emotional tears” is poorly under-  stood, but some suspect that crying is important in  reducing stress. Anyone who has had a good cry  would probably agree, but this has been difficult to   Homeostatic J  K Imbalance 8.2  Because the nasal cavity mucosa is continuous with  that of the lacrimal duct system, a cold or nasal  inflammation often causes the lacrimal mucosa to  become inflamed and swell. This impairs the drainage  of tears from the eye surface, causing “watery” eyes.    Six extrinsic eye muscles (external eye muscles)  are attached to the outer surface of each eye. These  muscles produce gross eye movements and make it  possible for the eyes to follow a moving object.  Figure 8.3 gives the names, locations, actions, and  cranial nerve serving each of the extrinsic muscles.    Figure 8.3 Extrinsic muscles of the eye. (a) Lateral view of the right eye.  (b) Superior view of the right eye. The four rectus muscles originate from   the common tendinous ring, a ringlike tendon at the back of the eye socket.  (c) Summary of cranial nerve supply and actions of the extrinsic eye muscles.    Did You Get It?  1. What is the role of the eyelids?    2. Which four accessory glands or structures help 1# Name the layers of the wall of the eye, and  lubricate the eye? indicate the major function of each.  3. What is the role of lysozyme in tears? Explain how the functions of rods and cones differ.    4. What is the visual role of the external eye muscles?    Define blind spot, cataract, and glaucoma.  For answers, see Appendix A. se p g    1# Trace the pathway of light through the eye to the  retina.    Which layer of the eye would be the first to be  affected by deficient tear production?    Figure 8.4 Internal anatomy of the eye (sagittal section).  (a) Diagrammatic view. (b) Photograph.    The eye itself, called the eyeball, is a hollow sphere  (Figure 8.4). Its wall is composed of three tunics, or  layers, and its interior is filled with fluids called humors  ‘s1e9} Áq that help to maintain its shape. The lens, the main  focusing apparatus of the eye, is supported upright  within the eye cavity, dividing it into two chambers.    Now that we have covered the general anatomy of  the eyeball, we are ready to get specific.    Fibrous Layer ‘The outermost layer, called the fibrous  layer, consists of the protective sclera (sklé’rah) and  the transparent cornea (kor'ne-ah). The sclera (thick  white connective tissue) is seen anteriorly as the “white  of the eye.” The central anterior portion of the fibrous  layer is crystal clear. This “window” is the cornea  through which light enters the eye. The cornea is well  supplied with nerve endings. Most are pain fibers, and  when the cornea is touched, blinking and increased  tear production occur. Even so, the cornea is the most  exposed part of the eye, and it is very vulnerable to  damage. Luckily, its ability to repair itself is extraordi-  nary. Furthermore, the cornea is the only tissue in the  body that is transplanted from one person to another  without the worry of rejection. Because the cornea  has no blood vessels, it is beyond the reach of the  immune system.    Vascular Layer The middle, or vascular layer, of  the eyeball, has three distinguishable regions. Most  posterior is the choroid (ko’roid), a blood-rich  nutritive tunic that contains a dark pigment. The  pigment prevents light from scattering inside the  eye. Moving anteriorly, the choroid is modified to  form two smooth muscle structures, the ciliary  (sil’e-er-e) body, which is attached to the lens by a  suspensory ligament called the ciliary zonule, and  the iris. The pigmented iris has a rounded open-  ing, the pupil, through which light passes.  Circularly and radially arranged smooth muscle  fibers form the iris, which acts like the diaphragm  of a camera. That is, it regulates the amount of light  entering the eye so that we can see as clearly as pos-  sible in the available light. In close vision and  bright light, the circular muscles contract, and the  pupil constricts, or gets smaller. In distant vision  and dim light, the radial fibers contract to enlarge  (dilate) the pupil, which allows more light to enter  the eye. Cranial nerve III (oculomotor) controls the  muscles of the iris.    Sensory Layer The innermost sensory layer of the  eye is the delicate two-layered retina (ret'i-nah),  which extends anteriorly only to the ciliary body.  The outer pigmented layer of the retina is com-  posed of pigmented cells that, like those of the cho-  roid, absorb light and prevent light from scattering    inside the eye. They also act as phagocytes to remove  dead or damaged receptor cells and store vitamin A  needed for vision.   The transparent inner neural layer of the retina  contains millions of receptor cells, the rods and  cones, which are called photoreceptors because  they respond to light (Figure 8.5, p. 300). Electrical  signals pass from the photoreceptors via a two-  neuron chain—bipolar cells and then ganglion  cells—before leaving the retina via the optic nerve  and being transmitted to, and interpreted by, the  optic cortex. The result is vision.   The photoreceptor cells are distributed over the  entire retina, except where the optic nerve leaves the  eyeball; this site is called the optic disc. Since there  are no photoreceptors at the optic disc, it results in a  blind spot in our vision. When light from an object  is focused on the optic disc, the object disappears  from our view and we cannot see it.   The rods and cones are not evenly distributed in  the retina. The rods are densest at the periphery, or  edge, of the retina and decrease in number as the  center of the retina is approached. The rods allow us  to see in gray tones in dim light, and they provide  our peripheral vision.    Homeostatic J  K Imbalance 8.3  Anything that interferes with rod function hinders  our ability to see at night. This condition, called  night blindness, dangerously impairs our ability to  drive safely at night. Its most common cause is pro-  longed vitamin A deficiency, which eventually causes  the neural retina to deteriorate. Vitamin A is one of  the building blocks of the pigments the photorecep-  tor cells need to respond to light (see “A Closer  Look” on p. 301). Vitamin A supplements will  restore function if taken before degenerative changes  in the neural retina occur.    Cones are discriminatory receptors that allow us  to see the details of our world in color under bright  light conditions. They are densest in the center of the  retina and decrease in number toward the retinal edge  (the opposite of rods). Lateral to each blind spot is the  fovea centralis (fo've-ah sen-tră'lis), a tiny pit that  contains only cones (see Figure 8.4). Consequently,  this is the area of greatest visual acuity, or point of  sharpest vision, and anything we wish to view criti-  cally is focused on the fovea centralis.    Figure 8.5 The three major types of neurons  composing the retina. (a) Notice that light must pass  through the thickness of the retina to excite the rods  and cones. Electrical signals flow in the opposite  direction: from the rods and cones to the bipolar cells  and finally to the ganglion cells. The ganglion cells  generate the nerve impulses that leave the eye via the  optic nerve. (b) Schematic view of the posterior part of  the eyeball illustrating how the axons of the ganglion  cells form the optic nerve. The site where the optic  nerve meets the retina is the optic disc.    Figure 8.6 Sensitivities of the three cone types to  different wavelengths of visible light.    There are three varieties of cones. Each type is  most sensitive to particular wavelengths of visible  light (Figure 8.6). One type responds most vigorously  to blue light, another to green light. The third cone  variety responds to a range including both green and  red wavelengths of light. However, this is the only  cone population to respond to red light at all, so  these are called the “red cones.” Impulses received at  the same time from more than one type of cone by  the visual cortex are interpreted as intermediate col-  ors, similar to what occurs when two colors of paint  are mixed. For example, simultaneous impulses from  blue and red color receptors are seen as purple or  violet tones. When all three cone types are stimu-  lated, we see white. If someone shines red light into  one of your eyes and green into the other, you will  see yellow, indicating that the “mixing” and interpre-  tation of colors occur in the brain, not in the retina.    Homeostatic J  —S~ Imbalance 8.4  Lack of all three cone types results in total color  blindness, whereas lack of one cone type leads to  partial color blindness. Most common is the lack of  red or green receptors, which leads to two varieties of  red-green color blindness. Red and green are seen as  the same color—either red or green, depending on  the cone type present. Many color-blind people are    _ =; Learn more at Mastering A&P > Study Area > f  Additional Study Tools > A Closer Look   tor cells of the retina reflect their  shapes. As shown to the left, rods are  slender, elongated neurons, whereas    the fatter cones taper to pointed tips.  In each type of photoreceptor, there is  a region called an outer segment,  attached to the cell body. The outer  segment corresponds to a  light-trapping dendrite, in  which the discs containing  the visual pigments are  stacked like a row of  pennies.   The behavior of the visual  pigments is dramatic. When  light strikes them, they lose  their color, or are “bleached”;  shortly afterward, they regen-  erate their pigment. Absorp-  tion of light and pigment  bleaching cause electrical  changes in the photoreceptor  cells that ultimately cause  nerve impulses to be transmit-  ted to the brain. Pigment  regeneration ensures that you   A good deal is known about the  structure and function of rhodopsin,  the purple pigment found in rods  (see figure below). It is formed from  the union of opsin and retinal.  When light strikes rhodopsin, retinal  straightens out and releases the pro-  tein. As these changes occur, the pur-  ple color of rhodopsin changes to the  yellow of retinal and finally becomes  colorless as retinal changes to vitamin  A. Thus the term “bleaching” accu-  rately describes the color changes that  occur when light hits the pigment.  Rhodopsin is regenerated as vitamin A  is again converted to retinal and  recombined with opsin in an ATP-  requiring process. The cone pigments,  although similar to rhodopsin, differ  in the specific kinds of proteins they    e Rhodopsin, the pigment in rods, is formed when opsin (a protein)  binds to retinal (a modified form of vitamin A).    e Rhodopsin is visually purple, but in the presence of light, gradually  the eye sees yellow (retinal) then clear (vitamin A) in a process  called pigment “bleaching”.    unaware of their condition because they have learned  to rely on other cues—such as differences in intensi-  ties of the same color—to distinguish green from  red, for example, on traffic signals. Because the genes  regulating color vision are on the X (female) sex  chromosome, color blindness is a sex-linked condi-  tion. It occurs almost exclusively in males.    Light entering the eye is focused on the retina by the  lens, a flexible biconvex crystal-like structure. Recall  the lens is held upright in the eye by the ciliary zon-  ule attached to the ciliary body (see Figure 8.4).    Homeostatic j  £ Imbalance 8.5  In youth, the lens is transparent and has the consis-  tency of firm jelly, but as we age it becomes increas-  ingly hard and cloudy. Cataracts, the loss of lens  transparency, cause vision to become hazy and dis-  torted and can eventually cause blindness. Other risk  factors for forming cataracts include diabetes melli-  tus, frequent exposure to intense sunlight, and heavy  smoking. Current treatment of cataracts is either spe-  cial cataract glasses or surgical removal of the lens  and replacement with a lens implant.    The cataract in this photo appears as a milky structure that  seems to fill the pupil.    The lens divides the eye into two segments, or  chambers. The anterior (aqueous) segment, anterior to  the lens, contains a clear watery fluid called aqueous  humor. The posterior (vitreous) segment, posterior to  the lens, is filled with a gel-like substance called  vitreous (vit're-us) humor, or the vitreous body  (see Figure 8.4). Vitreous humor helps prevent the    eyeball from collapsing inward by reinforcing it  internally, just as water keeps a water balloon  inflated. Aqueous humor is similar to blood plasma  and is continually secreted by a special area of the  choroid. Like the vitreous humor, it helps maintain  intraocular (in"trah-ok'u-lar) pressure, the pressure  inside the eye. It also provides nutrients for the avas-  cular lens and cornea. Aqueous humor is reabsorbed  into the venous blood through the scleral venous  sinus, or canal of Schlemm (shlém), which is  located at the junction of the sclera and cornea.    Homeostatic 3  —S Imbalance 8.6  If drainage of aqueous humor is blocked, fluid backs  up like a clogged sink. Pressure within the eye may  increase to dangerous levels and compress the deli-  cate retina and optic nerve. The resulting condition,  glaucoma (glaw-ko’mah; “vision going gray”), can  lead to blindness unless detected early. Glaucoma  is a common cause of blindness in the elderly.  Unfortunately, many forms of glaucoma progress  slowly and have almost no symptoms at first. Thus,  sight deteriorates slowly and painlessly until the  damage is done. Signs of advanced glaucoma include  seeing halos around lights, headaches, and blurred  vision. A simple instrument called a tonometer (to-  nom’e-ter) is used to measure the intraocular pres-  sure, which should be tested yearly in people over  40. Glaucoma is commonly treated with eyedrops  that increase the rate of aqueous humor drainage.  Laser or surgical enlargement of the drainage chan-  nel is another option.    The ophthalmoscope (of-thal’mo-skop) is an  instrument that illuminates the interior of the eye-  ball, allowing the retina, optic disc, and internal  blood vessels at the fundus, or posterior wall of the  eye, to be viewed and examined (Figure 8.7). Such an  examination can detect certain pathological condi-  tions, such as diabetes, arteriosclerosis, and degener-  ation of the optic nerve and retina.    5. What is the meaning of the term blind spot in  relation to the eye?   6. What function does the choroid of the vascular layer  have in common with the pigmented layer of the  retina?   7. How do the rods and cones differ from each other?    Figure 8.7 The posterior wall (fundus) of the  retina as seen with an ophthalmoscope. Notice  the optic disc, from which the blood vessels radiate.    8.2a Pathway of Light through the  Eye and Light Refraction  Learning Objectives  v@ Describe image formation on the retina.  4 Define the following terms: accommodation,  astigmatism, emmetropia, hyperopia, myopia,  and refraction.  When light passes from one substance to another  substance that has a different density, its speed  changes and its rays are bent, or refracted. Light rays  are bent in the eye as they encounter the cornea,  aqueous humor, lens, and vitreous humor.   The refractive, or bending, power of the cornea  and humors is constant. However, that of the lens  can be changed by changing its shape—that is, by  making it more or less convex, so that light can be  properly focused on the retina. The greater the lens  convexity, or bulge (which makes it thicker), the  more it bends the light. The flatter (thinner) the lens,  the less it bends the light.   The resting eye is “set” for distant vision. In gen-  eral, light from a distant source (over 20 feet away)  approaches the eye as parallel rays (Figure 8.8a), and  the lens does not need to change shape to focus prop-  erly on the retina. However, light from a close object  tends to scatter and diverge, or spread out, and the lens    As you look at this figure, are your lenses relatively  thick or relatively thin?    Figure 8.8 Relative convexity of the lens during  focusing for distant and close vision. (a) Light rays  from a distant object are nearly parallel as they reach  the eye and can be focused without requiring changes  in lens convexity. (b) Diverging light rays from close  objects require that the lens bulge more to focus the  image sharply on the retina.    must bulge more to make close vision possible  (Figure 8.8b). To achieve this, the ciliary body contracts  toward the lens, slackening the ciliary zonules and  allowing the lens to become more convex. This ability  of the eye to focus specifically for close objects (those  less than 20 feet away) is called accommodation. The  image formed on the retina as a result of the light-  bending activity of the lens is a real image—that is, it  is reversed from left to right, upside down (inverted),  and smaller than the object (Figure 8.9, p. 304).   The normal eye is able to accommodate prop-  erly. However, vision problems occur when a lens  is too strong (overconverging) or too weak    Figure 8.9 Real image (reversed left to right, and  upside down) formed on the retina. Notice that  the farther away the object, the smaller its image on  the retina.    Axons carrying impulses from the retina are bundled  together at the posterior aspect of the eyeball and  leave the back of the eye as the optic nerve. At the  optic chiasma (ki-as’ mah; chiasm = cross) the fibers  from the medial side of each eye cross over to the  opposite side of the brain. The fiber tracts that result  are the optic tracts. Each optic tract contains fibers  from the lateral side of the eye on the same side and  the medial side of the opposite eye. For example, the  right optic tract contains lateral fibers from the right  eye and medial fibers from the left eye. The optic  tract fibers synapse with neurons in the thalamus,  whose axons form the optic radiation, which runs  to the occipital lobe of the brain. There they synapse  with the cortical cells, and visual interpretation, or  seeing, occurs. (Figure 8.10 shows the visual pathway  from the eye to the brain).   Each side of the brain receives visual input from  both eyes—from the lateral field of the eye on its  own side and from the medial field of the other eye.  Also notice that each eye “sees” a slightly different  view but that their visual fields overlap quite a bit. As  a result of these two phenomena, humans have bin-  ocular vision. Binocular vision, literally “two-eyed  vision,” provides for depth perception, also called  “three-dimensional” vision, as our visual cortex fuses  the two slightly different images delivered by the two  eyes into one “picture.”    Figure 8.10 Visual fields of the eyes and visual  pathway to the brain (inferior view). Notice that   the visual fields overlap considerably (area of binocular  vision). Notice also the retinal sites at which a real image  would be focused when both eyes are fixed on a close,  pointlike object.    Homeostatic J  £ Imbalance 8.7  Hemianopia (hem”e-ah-no’pe-ah) is the loss of  the same side of the visual field of both eyes,  which results from damage to the visual cortex on  one side only (as occurs in some strokes). Thus,  the person would not be able to see things past  the middle of the visual field on either the right or  left side, depending on the site of the stroke. Such  individuals should be carefully attended and  warned of objects in the nonfunctional side of the  visual field. Their food and personal objects should  always be placed on their functional side, or they  might miss them.    light rays before they enter the eye, so  that they converge farther back, on  the retinal surface.   Farsightedness, or hyperopia  (hi”per-o’ pe-ah; “far vision”), occurs  when the parallel light rays from dis-  tant objects are focused behind the  retina; see part (c) of the figure.  People with hyperopia see distant  objects clearly because their ciliary  muscles contract continuously to  increase the light-bending power of  the lens, which moves the focal point  forward onto the retina. Therefore,  nearby objects appear blurry, and  hyperopic individuals are subject to    eyestrain as their endlessly contracting  ciliary muscles tire from overwork.  Correction of hyperopia requires con-  vex corrective lenses that converge the  light rays before they enter the eye.   Unequal curvatures in different  parts of the cornea (think football  shaped, rather than round) or lens  cause astigmatism (ah-stig’ mah-  tizm); see part (d) of the figure. In this  condition, blurry images occur  because points of light are focused  not as points on the retina but as lines  (astigma = not a point). Special cylin-  drically ground lenses or contacts are  used to correct astigmatism.    e Light rays must converge directly  on the retinal surface for objects  to be seen in focus.    e Nearsighted people see near  objects clearly but need correc-  tive lenses to see distant objects.    e Farsighted people see distant  objects clearly but need correc-  tive lenses to see nearby objects.    e Astigmatism is the presence of  uneven curvatures in the cornea  or lens, resulting in multiple  focal points on the retina and    Both the internal and external (extrinsic) eye mus-  cles are necessary for proper eye function. The auto-  nomic nervous system controls the internal muscles.  As mentioned earlier, these muscles include those of  the ciliary body, which alters lens curvature, and the  radial and circular muscles of the iris, which control  pupil size. The external muscles are the rectus and  oblique muscles attached to the eyeball exterior (see  Figure 8.3), which control eye movements and make  it possible to follow moving objects. They are also  responsible for convergence, which is the reflexive  movement of the eyes medially when we view close  objects. When convergence occurs, both eyes are  aimed toward the near object being viewed. The  extrinsic muscles are controlled by somatic fibers of  cranial nerves III, IV, and VI (see Figure 8.3).   When the eyes are suddenly exposed to bright  light, the pupils immediately constrict; this is the  photopupillary reflex. This protective reflex pre-  vents excessively bright light from damaging the del-  icate photoreceptors. The pupils also constrict  reflexively when we view close objects; this  accommodation pupillary reflex provides more  acute vision.   Reading requires almost continuous work by  both sets of muscles. The muscles of the ciliary body    bring about the lens bulge, and the circular (or con-  strictor) muscles of the iris produce the accommoda-  tion pupillary reflex. In addition, the extrinsic  muscles must converge the eyes as well as move them  to follow the printed lines. This is why long periods  of reading tire the eyes and often result in what is  commonly called eyestrain. When you read for an  extended time, look up from time to time and stare  into the distance. This temporarily relaxes all the eye  muscles and provides an excellent opportunity to  think about what you just read!    8. What are the refractory media of the eye?  9. What name is given to the ability of the eye to  focus on close objects?  10. What is the difference between the optic tract and  the optic nerve?  11. In what way does the photopupillary reflex protect  the eyes?  12. How is astigmatism different from myopia and  hyperopia?  For answers, see Appendix A    PART II: THE EAR: HEARING  AND BALANCE  At first glance, the machinery for hearing and bal-    fluid to stimulate hearing receptors, whereas gross  movements of the head disturb fluids surrounding  the balance organs. Receptors that respond to such  physical forces are called mechanoreceptors  (mek”ah-no-re-sep’terz).   Our hearing apparatus allows us to hear an  extraordinary range of sound, and our highly sensi-  tive equilibrium receptors keep our nervous system  continually up to date on the position and move-  ments of the head. Without this information, it  would be difficult if not impossible to maintain our  balance or to know which way is up. Although these  two sense organs are housed together in the ear, their  receptors respond to different stimuli and are acti-  vated independently of one another.    Identify the structures of the external, middle, and  internal ear, and list the functions of each.    Anatomically, the ear is divided into three major  areas: the external, or outer, ear; the middle ear; and  the internal, or inner, ear (Figure 8.11). The external    and middle ear structures are involved with hearing  only. The internal ear functions in both equilibrium  and hearing.    The external ear, or outer ear, is composed of the  auricle and the external acoustic meatus. The auricle  (aw’ri-kul), or pinna (pin’nah), is what most peo-  ple call the “ear”—the shell-shaped structure sur-  rounding the auditory canal opening. In many  animals, the auricle funnels (collects and directs)  sound waves into the auditory canal, but in humans  this function is largely lost.   The external acoustic meatus (or auditory  canal) is a short, narrow chamber (about 1 inch long  by 1⁄4 inch wide) carved into the temporal bone of  the skull. In its skin-lined walls are the ceruminous  (sé-roo’mi-nus) glands, which secrete waxy yellow  cerumen. This earwax provides a sticky trap for  foreign bodies and repels insects.   Sound waves entering the auditory canal eventu-  ally hit the tympanic (tim-pan‘ik; tympanum =  drum) membrane, or eardrum, and cause it to  vibrate. The canal ends at the eardrum, which sepa-  rates the external from the middle ear.    Figure 8.11 Anatomy of the ear. Note that the inner ear structures (vestibule, cochlea,  semicircular canals) represent a cast of the cavity formed by the bony labyrinth.    The middle ear cavity, or tympanic cavity, is a  small, air-filled, mucosa-lined cavity within the tem-  poral bone. It is flanked laterally by the eardrum and  medially by a bony wall with two openings, the oval  window and the inferior, membrane- covered round  window. The pharyngotympanic (think throat-  eardrum: pharynx-tympanic) tube, or auditory tube,  runs obliquely and slightly downward to link the  middle ear cavity with the throat, and the mucosae  lining the two regions are continuous. Normally, the  pharyngotympanic tube is flattened and closed, but  swallowing or yawning can open it briefly to equal-  ize the pressure in the middle ear cavity with the  external, or atmospheric, pressure. This is an impor-  tant function because the eardrum does not vibrate  freely unless the pressure on both sides is the same.  When the pressures are unequal, the eardrum bulges  inward or outward, causing hearing difficulty (voices  may sound far away) and sometimes earaches. The  ear-popping sensation of the pressures equalizing is  familiar to anyone who has flown in an airplane.    Inflammation of the middle ear, otitis media  (o-ti'tis me’de-ah), is a fairly common result of a  sore throat, especially in children, whose pharyngo-  tympanic tubes run more horizontally. In otitis  media, the eardrum bulges and often becomes  inflamed. When large amounts of fluid or pus accu-  mulate in the cavity, an emergency myringotomy  (lancing of the eardrum) may be required to relieve  the pressure. A tiny tube is implanted in the eardrum  that allows pus to drain into the external ear canal.  The tube usually falls out by itself within the year.    The more horizontal course of the pharyngotym-  panic tube in infants also explains why it is never a  good idea to “prop” a bottle or feed them when they  are lying flat (a condition that favors the entry of the  food into that tube).   The tympanic cavity is spanned by the three  smallest bones in the body, the ossicles (os'si-kulz),  which transmit and amplify the vibratory motion of  the eardrum to the fluids of the inner ear (see  Figure 8.11). These bones, named for their shape, are  the hammer, or malleus (ma’le-us); the anvil, or  incus (in’kus); and the stirrup, or stapes (sta’péz).    Like dominoes falling, when the eardrum moves, it  moves the hammer and transfers the vibration to the  anvil. The anvil, in turn, passes the vibration on to  the stirrup, which presses on the oval window of the  inner ear. The movement at the oval window sets the  fluids of the inner ear into motion, eventually excit-  ing the hearing receptors.   The internal ear is a maze of bony chambers called  the bony labyrinth, or osseous labyrinth (lab’i-  rinth; “maze”), located deep within the temporal  bone behind the eye socket. The three subdivisions  of the bony labyrinth are the spiraling, pea-sized  cochlea (kok’le-ah, “snail”), the vestibule (ves’ti-  bul), and the semicircular canals. The vestibule is  situated between the semicircular canals and the  cochlea. The views of the bony labyrinth typically  seen in textbooks, including this one, are somewhat  misleading because we are really talking about a cav-  ity. Figure 8.11 can be compared to a cast of the bony  labyrinth—that is, a labyrinth that was filled with  plaster of paris and then had the bony walls removed  after the plaster hardened. The shape of the plaster  then reveals the shape of the cavity that worms  through the temporal bone.   The bony labyrinth is filled with a plasmalike  fluid called perilymph (per’i-limf). Suspended in  the perilymph is a membranous labyrinth, a sys-  tem of membrane sacs that more or less follows the  shape of the bony labyrinth. The membranous laby-  rinth itself contains a thicker fluid called endolymph  (en'do-limf).    13. Which region(s) of the ear (external, middle, or  internal) serve hearing only?  14. Which structures of the ear transmit sound  vibrations from the eardrum to the oval window?  For answers, see Appendix A.   1# Explain the function of the spiral organ of Corti in  hearing.   1# Define sensorineural deafness and conductive  deafness, and list possible causes of each.   Explain how a person is able to localize the source  of a sound.    Temporal Perilymph in scala vestibuli  ; bone  Spiral Vestibular  organ of membrane    Figure 8.12 Anatomy of the  cochlea. (a) A cross-sectional view  of one turn of the cochlea, showing  the position of the spiral organ of  Corti in the cochlear duct. The    Within the cochlear duct, the endolymph-containing  membranous labyrinth of the cochlea is the spiral  organ of Corti (kor'te), which contains the hearing  receptors, or hair cells (Figure 8.12a). The chambers  (scalae) above and below the cochlear duct bordered  by bone contain perilymph. Sound waves that reach  the cochlea through vibrations of the eardrum, ossi-  cles, and oval window set the cochlear fluids into  motion (Figure 8.13, p. 310). As the sound waves are  transmitted by the ossicles from the eardrum to the  oval window, their force (amplitude) is increased by  the lever activity of the ossicles. In this way, nearly the  total force exerted on the much larger eardrum  reaches the tiny oval window, which in turn sets the  fluids of the inner ear into motion, and these pressure  waves set up vibrations in the basilar membrane.    cavities of the bony labyrinth contain  perilymph. The cochlear duct (mem-  branous labyrinth) contains endo-  lymph. (b) Detailed structure of the  spiral organ of Corti. The receptor    cells (hair cells) rest on the basilar  membrane, and the hairs of the hair  cells are embedded in the tectorial  membrane.    The receptor cells, positioned on the basilar mem-  brane in the spiral organ of Corti, are stimulated by  the vibrating movement of the basilar membrane  against the gel-like tectorial (tek-to're-al) membrane  that lies over them. The “hairs” of the receptor cells  are embedded in the stationary tectorial membrane  such that when the basilar membrane vibrates against  it, the “hairs” bend (see Figure 8.12b). The length of  the fibers spanning the basilar membrane “tunes”  specific regions to vibrate at specific frequencies. In  general, high-pitched sounds disturb the shorter,  stiffer fibers of the basilar membrane and stimulate  receptor cells close to the oval window, whereas low-  pitched sounds affect longer, more floppy fibers and  activate specific hair cells further along toward the  apex of the cochlea (Figure 8.14, p. 310).    Figure 8.13 Route of sound waves through the ear. To excite the hair cells in the  spiral organ of Corti in the inner ear, sound wave vibrations must pass through air,    Once stimulated, the hair cells transmit impulses  along the cochlear nerve (a division of cranial  nerve VIII—the vestibulocochlear nerve) to the audi-  tory cortex in the temporal lobe, where interpreta-  tion of the sound, or hearing, occurs. Because sound  usually reaches the two ears at different times, we    could say that we hear “in stereo.” Functionally, this  helps us to determine where sounds are coming  from in our environment.   When the same sounds, or tones, keep reaching  the ears, the auditory receptors tend to adapt, or stop  responding, to those sounds, and we are no longer  aware of them. This is why the drone of a continu-  ously running motor does not demand our attention  after the first few seconds. However, hearing is the  last sense to leave our awareness when we fall asleep  or receive anesthesia and is the first to return as we  awaken.    Figure 8.14 Activation of the cochlear hair cells.  (a) The cochlea is drawn as though it were uncoiled to  make the events of sound transmission easier to follow.  Sound waves of low frequency (black arrows), below  the level of hearing, travel entirely around the cochlear  duct without exciting hair cells in the spiral organ of  Corti. But sounds of higher frequency penetrate  through the cochlear duct (white arrows) to the scala  tympani. This causes different areas of the basilar  membrane to vibrate maximally in response to different  frequencies of sound, stimulating particular hair cells  and sensory neurons. The differential stimulation of hair  cells is perceived in the brain as sound of a certain pitch.  (b) The length and stiffness of the fibers spanning the  basilar membrane tune specific regions to vibrate at  specific frequencies. The higher notes—up to 20,000  Hertz (Hz)—are detected by shorter, stiffer hair cells  along the base of the basilar membrane. Lower notes—  as low as 20 Hz—are detected by longer, floppy fibers  near the apex.    15. From the air outside the body, through what  substances do sound waves travel to excite the  receptor cells of the cochlea?   16. Which nerve transmits impulses from the spiral  organ of Corti to the brain?   17. Do high-pitched sounds peak close to or far from  the oval window?    Learning Objectives  4# Distinguish between static and dynamic  equilibrium.  1# Describe how the equilibrium organs help  maintain balance.  The equilibrium sense is not easy to describe because  it does not “see,” “hear,” or “feel.” What it does is  respond (frequently without our awareness) to vari-  ous head movements. The equilibrium receptors of  the inner ear, collectively called the vestibular  apparatus, can be divided into two branches—one  branch is responsible for monitoring static equilib-  rium, and the other monitors dynamic equilibrium.   Within the membranous sacs of the vestibule are  receptors called maculae (mak’u-le; “spots”) that  are essential to our sense of static equilibrium  (Figure 8.15). The maculae report on changes in the  position of the head in space with respect to the pull  of gravity when the body is not moving (static = at  rest). Because they provide information on which  way is up or down, they help us keep our head erect.  The maculae are extremely important to divers swim-  ming in the dark depths (where most other orienting  cues are absent), enabling them to tell which way is  up (to the surface). Each macula is a patch of recep-  tor (hair) cells with their “hairs” embedded in the  otolithic membrane, a gelatinous mass studded  with otoliths (o’td-liths), tiny stones made of cal-  cium salts. As the head moves, the otoliths “roll” in  response to changes in the pull of gravity. This move-  ment creates a pull on the gel, which in turn bends  the hairs of the hair cells. Bending activates the hair  cells, which send impulses along the vestibular  nerve (a division of cranial nerve VIII) to the cere-  bellum of the brain, informing it of the position of  the head in space.    Figure 8.15 Structure and function of maculae  (static equilibrium receptors). (a) Diagrammatic view  of part of a macula.(b) When the head is tipped, the  otoliths in the gelatinous otolithic membrane move in  the direction of gravitational pull, stimulating the  maculae. This creates a pull on the hair cells, causing  them to bend and send a nerve impulse.    Figure 8.16 Structure and function of a crista ampullaris  (dynamic equilibrium receptor region). (a) Arranged in the three  spatial planes, the ducts forming the semicircular canals each have a  swelling called an ampulla at their base. (b) Each ampulla contains a Nerve  crista ampullaris, a receptor that is a cluster of hair cells that project ——_ > fibers  into a gelatinous cap called the cupula. (c) When head position Direction of body   changes during rotation or in an angular direction, inertia causes the movement   endolymph in the semicircular ducts to lag behind; and as the cupula (c)   moves, it drags across the endolymph, which bends the hair cells in   if the angular motion (or rotation) continues at a constant speed.    8.5b Dynamic Equilibrium in an arclike or angular direction, the endolymph in  the canal lags behind the movement (Figure 8.16c).  Then, as the cupula drags against the stationary  endolymph, the cupula bends with the body's  motion. (The action is much like that of a diver's fins  in water—when the diver kicks forward, the fin  bends backward.) This stimulates the hair cells, and  impulses are transmitted up the vestibular nerve to  the cerebellum. Bending the cupula in the opposite  direction reduces impulse generation. When you are  moving at a constant rate, the receptors gradually  stop sending impulses, and you no longer have the  sensation of motion until your speed or direction of  movement changes.   Although the receptors of the semicircular canals  and vestibule are responsible for dynamic and static  equilibrium, respectively, they usually act together.    The dynamic equilibrium receptors, found in the  semicircular canals, respond to angular or rotational  movements of the head rather than to straight-line  movements. When you twirl on the dance floor or  suffer through a spinning carnival ride, these recep-  tors are working overtime. The semicircular canals  (each about 1⁄2 inch, or 1.3 cm, around) are oriented  in the three planes of space. Thus, regardless of  which plane you move in, there will be receptors to  detect the movement.   Within the ampullae, slightly wider regions at the  base of each membranous semicircular canal  (Figure 8.16a), are multiple receptor regions, each  called a crista ampullaris (kris’tah am”pu-lar’is), or  simply crista, which consists of a tuft of hair cells  covered with a gelatinous cap called the cupula ; es ;  (ku’pu-lah) (Figure 8.16b). When your head moves Besides these equilibrium senses, sight and the    Learn more at Mastering A&P > Study Area >  Additional Study Tools > Focus on Careers    A: the population ages, a growing  number of people find themselves  needing in-home medical care as they  recover from injuries or surgical proce-  dures. Many of these patients rely on  physical therapy assistants like Leslie  Burgess.   A licensed physical therapy assistant  visits the patient and uses a treatment  plan written by a licensed physical ther-  apist. The treatment  plan may incorpo-  rate strength, move-  ment, and/or  balance training,  with the goal of  improving mobility,  reducing pain, and/  or helping the  patient function  with a disability.   Burgess’s job is  to help patients  carry out these  treatment plans, vis-  iting the patient  two or three times a  week, for 6 to 8  weeks or more,  depending on the  patient's progress.    proprioceptors of the muscles and tendons are also  important in providing the cerebellum with infor-    In some cases, she will use electrical  stimulation or ultrasound to stimulate  nerves or muscles. If the patient has a  new piece of equipment, such as a  cane or a walker, she helps him or her  learn to use it. She reviews any pre-  scribed medication to make sure the  patient is taking it and discusses safety  concerns with the patient and family,  such as rugs or cords the patient could  trip on. Finally,  she leaves  instructions with  the patient to  continue exercis-  ing on his or her  own.   Anatomy is an  important part of  physical therapy  work, Burgess  says. “Working  with various devi-  ations of move-  ment, you need  to know what  bones and mus-  cles are involved  so that you know  which bones and  muscles to   Physical therapy assistants work any-  where physical therapists are found—  including hospitals, nursing homes, and  clinics. They usually work directly with  patients and under the supervision of a  physical therapist.   Many states require that physical  therapy assistants complete an associ-  ate’s degree and pass a board exam, in  addition to completing continuing  education.    e An understanding of anatomy is  essential for physical therapy  assistants (PTAs) to effectively  direct patient exercise.    e PTAs work in hospitals, clinics,  and nursing homes and may visit  patients at home.    e Supervising patient exercises,  teaching proper use of equipment,  and monitoring patient progress  are central tasks for a PTA.    18. What sense do the vestibule and semicircular  canals serve?  19. Describe the different receptors for static and  dynamic equilibrium and their locations.  20. What are otoliths, and what is their role in equilibrium?  For answers, see Appendix A.    Homeostatic B  K Imbalance 8.9  Children with ear problems or hearing deficits often  pull on their ears or fail to respond when spoken to.  Under such conditions, tuning fork or audiometry  testing is done to try to diagnose the problem.  Deafness is defined as hearing loss of any degree—  from a slight loss to a total inability to hear sound.  Generally speaking, there are two kinds of deafness,    conduction and sensorineural. Conduction  deafness results when something interferes with the  conduction of sound vibrations to the fluids of the  inner ear. It can be permanent or temporary; some-  thing as simple as a buildup of earwax may be the  cause. Other causes of conduction deafness include  fusion of the ossicles (a problem called otosclerosis  [o”to-sklé-ro’sis]), a ruptured eardrum, and otitis  media (inflammation of the middle ear).   Sensorineural deafness occurs when there is  degeneration or damage to the receptor cells in the  spiral organ of Corti, to the cochlear nerve, or to  neurons of the auditory cortex. This often results  from extended listening to excessively loud sounds.  Thus, whereas conduction deafness results from  mechanical factors, sensorineural deafness is a prob-  lem with nervous system structures.   A person who has a hearing loss due to conduction  deafness will still be able to hear by bone conduction,  even though his or her ability to hear air-conducted  sounds (the normal conduction route) is decreased or  lost. In contrast, individuals with sensorineural deaf-  ness cannot hear better by either conduction route.  Hearing aids, which use skull bones to conduct sound  vibrations to the inner ear, are generally very successful  in helping people with conduction deafness to hear.  They are not helpful for sensorineural deafness.   Equilibrium problems are usually obvious.  Nausea, dizziness, and problems in maintaining bal-  ance are common symptoms, particularly when  impulses from the vestibular apparatus “disagree”  with what we see (visual input). There also may be  strange (jerky or rolling) eye movements.   A serious pathology of the inner ear is Méniére’s  (mān"e-airz') syndrome. The exact cause of this  condition is not fully known, but suspected causes  are arteriosclerosis, degeneration of cranial nerve  VIII, and increased pressure of the inner ear fluids. In  Méniére’s syndrome, progressive deafness occurs.  Affected individuals become nauseated and often  have howling or ringing sounds in their ears and  vertigo (a sensation of spinning) that is so severe  that they cannot stand up without extreme discom-  fort. Anti-motion sickness drugs are often prescribed  to decrease the discomfort.    21. How do sensorineural deafness and conduction  deafness differ from each other?  For the answer, see Appendix A.    Learning Objectives  Describe the location, structure, and function of  the olfactory and taste receptors.  v Name the five basic taste sensations, and list  factors that modify the sense of taste.  The receptors for taste and olfaction are classified as  chemoreceptors (ke’mo-re-sep’terz) because they  respond to chemicals in solution. Five types of taste  receptors have been identified, but the olfactory  receptors (for smell) are believed to be sensitive to a  much wider range of chemicals. The receptors for  smell and taste complement each other and respond  to many of the same stimuli.    Even though our sense of smell is far less acute than  that of many other animals, the human nose is still  no slouch in picking up small differences in odors.  Some people capitalize on this ability by becoming  tea and coffee blenders, perfumers, or wine tasters.   The thousands of olfactory receptors, receptors  for the sense of smell, occupy a postage stamp-sized  area in the roof of each nasal cavity (Figure 8.17). Air  entering the nasal cavities must make a 90° turn  downward to enter the respiratory passageway below,  so sniffing, which causes more air to flow superiorly  across the olfactory receptors, intensifies the sense of  smell.   The olfactory receptor cells are neurons  equipped with olfactory hairs, long cilia that pro-  trude from the nasal epithelium and are continu-  ously bathed by a layer of mucus secreted by  underlying glands. When the olfactory receptors  located on the cilia are stimulated by chemicals dis-  solved in the mucus, they transmit impulses along  the olfactory filaments, which are bundled axons  of olfactory neurons that collectively make up the  olfactory nerve (cranial nerve I). The olfactory  nerve conducts the impulses to the olfactory cortex  of the brain. There the odor is interpreted, and an  “odor snapshot” is made. The olfactory pathways are  closely tied into the limbic system (emotional-  visceral part of the brain). Thus, olfactory impres-  sions are long-lasting and very much a part of our  memories and emotions. For example, the smell of  chocolate chip cookies may remind you of your    grandmother, and the smell of a special cologne may  make you think of your father. Our reactions to  odors are rarely neutral. We tend to either like or dis-  like certain odors, and we change, avoid, or add  odors according to our preferences.   The olfactory receptors are exquisitely sensi-  tive—just a few molecules can activate them. Like the  auditory receptors, the olfactory neurons tend to  adapt rather quickly when they are exposed to an  unchanging stimulus, in this case, an odor. This is  why a woman stops smelling her own perfume after  a while but will quickly pick up the scent of another   Homeostatic J  —S~ Imbalance 8.10  Although it is possible to have either taste or smell  deficits, most people seeking medical help for loss of    chemical senses have olfactory disorders, or  anosmias (da-noz’me-uz). Most anosmias result    from head injuries, the aftereffects of nasal cavity  inflammation (due to a cold, an allergy, or smok-  ing), or aging. Some brain disorders can destroy the  sense of smell or mimic it. For example, some epi-  leptics experience olfactory auras (olfactory hallu-  cinations) just before they go into seizures.    The word taste comes from the Latin word taxare,  which means “to touch, estimate, or judge.” When  we taste things, we are, in fact, testing or judging our  environment in an intimate way, and many of us  consider the sense of taste to be the most pleasurable  of our special senses.   The taste buds, or receptors for the sense of  taste, are widely scattered in the oral cavity. Of the  10,000 or so taste buds that we have, most are on the  tongue. A few are scattered on the soft palate, supe-  rior part of the pharynx, and inner surface of the  cheeks.   The dorsal tongue surface is covered with small  peglike projections, or papillae (pah-pil’e). The    Figure 8.18 Location and structure of taste buds. (a) Taste buds on the  tongue are associated with papillae, projections of the tongue mucosa. (b) A  sectioned vallate papilla shows the position of the taste buds in its lateral walls.    taste buds are found on the sides of the large round  vallate papillae, or circumvallate (ser”kum-val'at)  papillae, on the tops of the more numerous  fungiform (fun’ji-form) papillae and in the foli-  ate papillae on the sides of the tongue (Figure 8.18).  The specific receptor cells that respond to chemicals  dissolved in the saliva are epithelial cells called  gustatory cells. Their long microvilli—the  gustatory hairs—protrude through the taste pore;  and when they are stimulated, they depolarize, and  impulses are transmitted to the brain. Three cranial  nerves—VII, IX, and X—carry taste impulses from  the various taste buds to the gustatory cortex. The  facial nerve (VII) serves the anterior two-thirds of  the tongue. The other two cranial nerves—the  glossopharyngeal nerve and vagus nerve—serve  the other taste bud-containing areas. Because of  their location, taste bud cells are subjected to huge  amounts of friction and are routinely burned by hot  foods. Luckily, they are among the most dynamic  cells in the body and are replaced every 7 to 10 days    by basal cells (stem cells) found in the deeper  regions of the taste buds.   There are five basic taste sensations. The sweet  receptors respond to substances such as sugars, sac-  charine, alcohols, some amino acids, and some lead  salts (such as those found in lead paint). Sour recep-  tors respond to hydrogen ions (H*), or the acidity of  the solution; bitter receptors to alkaloids; and salty  receptors to metal ions in solution. Umami  (u-mah'me; “delicious”), a taste discovered by the  Japanese, is elicited by the amino acids glutamate  and aspartate. Umami, appears to be responsible for  the “beef taste” of steak and the flavor of monoso-  dium glutamate, a food additive.   Historically, the tip of the tongue was believed to  be most sensitive to sweet and salty substances, its  sides to sour, the back of the tongue to bitter, and the  pharynx to umami. Actually there are only slight dif-  ferences in the locations of the taste receptors in dif-  ferent regions of the tongue, but the bitter receptors  do seem to be clustered more at the rear of the    tongue. Most taste buds respond to two, three, four,  or even all five taste modalities.   Taste likes and dislikes have homeostatic value. A  liking for sugar and salt will satisfy the body’s need  for carbohydrates and minerals (as well as some  amino acids). Many sour, naturally acidic foods  (such as oranges, lemons, and tomatoes) are rich  sources of vitamin C, an essential vitamin. Umami  guides the intake of proteins, and because many nat-  ural poisons and spoiled foods are bitter, our dislike  for bitterness is protective.   Many factors affect taste, and what is commonly  referred to as our sense of taste depends heavily on  stimulation of our olfactory receptors by aromas.  Think of how bland food tastes when your nasal pas-  sages are congested by a cold. Without the sense of  smell, our morning coffee would simply taste bitter.  In addition, the temperature and texture of food can  enhance or spoil its taste for us. For example, some  people will not eat foods that have a pasty texture  (avocados) or that are gritty (pears), and almost  everyone considers a cold greasy hamburger unfit to  eat. “Hot” foods such as chili peppers actually excite  pain receptors in the mouth.    22. What general name is used to describe both taste  and smell receptors? Why?  23. Where, relative to specific structures, are most taste  buds located?  24. Why does it help to sniff substances that you want  to smell?  For answers, see Appendix A.    v Describe changes that occur with age in the  special sense organs.    The special sense organs, essentially part of the ner-  vous system, are formed very early in embryonic  development. For example, the eyes, which are liter-  ally outgrowths of the brain, are developing by the  fourth week. All of the special senses are functional,  to a greater or lesser degree, at birth.    Homeostatic J  —S~ Imbalance 8.11  Congenital eye problems are relatively uncommon,  but we can give some examples. Strabismus (strah-  biz'mus), which is commonly called “crossed eyes,”  results from unequal pulls by the external eye muscles  that prevent the baby from coordinating movement of  the two eyes. If exercises to strengthen the weaker mus-  cles are not successful, surgery is always used to correct  the condition because if it is allowed to persist, the  brain may stop recognizing signals from the deviating    This infant with strabismus is unable to focus both eyes  simultaneously on the same object.    Maternal infections that occur during early preg-  nancy, particularly rubella (German measles), may  lead to congenital blindness or cataracts. If the  mother has a type of sexually transmitted infection  called gonorrhea (gon”o-re'ah), the bacteria will  infect the baby’s eyes during delivery. In the resulting  conjunctivitis, specifically called ophthalmia  neonatorum (of-thal’me-ah ne”o-na-to’rum), the  baby’s eyelids become red, swollen, and produce  pus. All states have enacted laws requiring that all  newborn babies’ eyes be routinely treated with silver  nitrate or antibiotics shortly after birth.    Generally speaking, vision is the only special  sense that is not fully functional when the baby is  born, and many years of “learning” are needed  before the eyes are fully mature. The eyeballs con-  tinue to enlarge until the age of 8 or 9, but the lens  grows throughout life. At birth, the eyeballs are fore-  shortened, and all babies are hyperopic (farsighted).  As the eyes grow, this condition usually corrects  itself. The newborn infant sees only in gray tones,  makes uncoordinated eye movements, and often  “sees” using only one eye at a time. Because the    lacrimal glands are not fully developed until about 2  weeks after birth, the baby is tearless for this period,  even though he or she may cry lustily.   By 5 months, the infant is able to focus on arti-  cles within easy reach and to follow moving objects,  but visual acuity is still poor. For example, an object  that someone with mature vision can see clearly 200  feet away has to be a mere 20 feet away before an  infant can see it clearly. (Such vision is said to be  20/200.) By the time the child is 5 years old, color  vision is well developed, visual acuity has improved  to about 20/30, and depth perception is present,  providing a readiness to begin reading. By school  age, the earlier hyperopia has usually been replaced  by emmetropia (normal vision). This condition con-  tinues until about age 40, when presbyopia  (pres”be-o'pe-ah, “old vision”) begins to set in, the  result of decreasing lens elasticity. This condition  makes it difficult to focus for close vision; it is basi-  cally farsightedness. Your grandmother holding a  magazine at arm’s length to read it provides a famil-  iar example of this developmental change in vision.   As aging occurs, the lacrimal glands become less  active, and the eyes tend to become dry and more  vulnerable to bacterial infection and irritation. The  lens loses its crystal clarity and becomes discolored.  As a result, it begins to scatter light, causing a dis-  tressing glare when the person drives at night. The  dilator muscles of the iris become less efficient; thus,  the pupils are always somewhat constricted. These  last two conditions work together to decrease the  amount of light reaching the retina, and visual acu-  ity is dramatically lower by one’s seventies. In addi-  tion to these changes, older people are susceptible  to certain conditions that may result in blindness,  such as glaucoma, cataracts, arteriosclerosis, and   Homeostatic J  £ Imbalance 8.12  Congenital abnormalities of the ears are fairly com-  mon. Examples include partly or completely missing  pinnas and closed or absent external acoustic  meatuses. Maternal infections can have a devastating  effect on ear development, and maternal rubella dur-  ing the early weeks of pregnancy results in sensori-  neural deafness.   A newborn infant can hear after his or her first  cry, but early responses to sound are mostly reflex-  ive—for example, crying and clenching the eyelids in  response to a loud noise. By the age of 3 or 4 months,    the infant is able to localize sounds and will turn to  the voices of family members. The toddler listens  critically as he or she begins to imitate sounds, and  good language skills are closely tied to an ability to  hear well.   Except for ear inflammations (otitis) resulting  from bacterial infections or allergies, few problems  affect the ears during childhood and adult life. By the  sixties, however, gradual deterioration and atrophy  of the spiral organ of Corti begin and lead to a loss  in the ability to hear high tones and speech sounds.  This condition, presbycusis (pres”bi-kyu’sis), is a  type of sensorineural deafness. In some cases, the ear  ossicles fuse (otosclerosis), which compounds the  hearing problem by interfering with sound conduc-  tion to the inner ear. Although presbycusis was once  considered a disability of old age, it is becoming  much more common in younger people as our  world grows noisier day by day. The damage caused  by excessively loud sounds is progressive and cumu-  lative. Music played and heard at deafening levels  definitely contributes to the deterioration of hearing  receptors.   The chemical senses, taste and smell, are sharp at  birth, and infants relish some food that adults con-  sider bland or tasteless. Some researchers claim the  sense of smell is just as important as the sense of  touch in guiding a newborn baby to its mother’s  breast. However, very young children seem indiffer-  ent to odors and can play happily with their own  feces. As they get older, their emotional responses to  specific odors increase.   There appear to be few problems with the chem-  ical senses throughout childhood and young adult-  hood. Beginning in the midforties, our ability to  taste and smell diminishes, which reflects the grad-  ual decrease in the number of these receptor cells.  Almost half of people over the age of 80 cannot  smell at all, and their sense of taste is poor. This may  explain why older adults are inattentive to formerly  disagreeable odors and why they often prefer highly  seasoned foods or lose their appetite entirely.    25. Fifty-year-old Mrs. Bates is complaining that she can’t  read without holding the newspaper out at arm's  length. What is her condition, and what is its cause?   26. Which of the special senses is least mature at birth?    o Ciliary glands (modified sweat glands) and  the tarsal glands (which produce an oily secre-  tion) both help keep the eye lubricated; associ-  ated with the eyelid edges    Conjunctiva—mucous membrane that covers the  anterior eyeball and lines the eyelids, produces a  lubricating mucus    Lacrimal apparatus— includes a series of ducts  and the lacrimal glands that produce tears, a  saline solution that washes and lubricates the eye-  ball and contains protective features, including  antibodies and lysozyme    8.1b. Internal eyeball structures  e Three layers form the wall of the eyeball    ° Fibrous layer (outer layer)—includes sclera  (white of the eye) and the cornea  = The cornea is transparent and allows light to  enter   a Ciliary body—made of smooth muscle; at-  taches to lens via ciliary zonule (ligaments);  when the ciliary body contracts, the lens  bulges to accommodate close vision   = Iris—made of smooth muscle; pigmented area  that regulates the size of the pupil and, by do-  ing so, regulates how much light enters the eye    Sensory layer—the retina; has two layers  = Outer pigmented layer prevents scattering  of light  = Inner neural layer contains photoreceptor  cells (rods and cones), bipolar cells and  ganglion cells, which transmit impulses to  the optic nerve  e Optic disc—site where optic nerve attaches  to the retina; lacks photoreceptors, result-  ing in a blind spot    A N Listen to the story of this chapter in a brief summary at Mastering A&P >  I Study Area > Author Narrated Audio Summaries    e Lens—crystal-like structure that bends (refracts)  light rays so they focus on the retina; divides the  eye into two chambers and is held in place by cili-  ary zonule attached to the ciliary body  o If light is not focused on the lens, myopia,   hyperopia, or astigmatism result; all can be  corrected with appropriate lenses    Humors—the anterior chamber contains  aqueous humor; the posterior chamber con-  tains vitreous humor    Aqueous humor—similar to blood plasma; a  clear, watery fluid anterior to lens; made by the  choroid; provides nutrients to avascular cornea  and lens; reabsorbed into the scleral venous  sinus (canal of Schlemm)    e Light enters the cornea and passes through the  aqueous humor, pupil, lens, and vitreous humor  to the retina    ° The shape of the lens is adjusted (more convex)  during the process of accommodation; the cili-  ary body contracts, the ciliary zonule slackens,  and the lens bulges; allows focus on a close  object (less than 20 feet)    e Overlap of the visual fields and inputs from  both eyes to each optic cortex provide for depth  perception  ° Optic chiasma—the site where medial fibers  from each eye cross over to the opposite side of  the brain    ° Pathway of nerve impulses from the retina:  optic nerve, optic chiasma, optic tract, thala-  mus, optic radiation, visual cortex in occipital  lobe of brain    e Eye reflexes include the photopupillary  reflex, accommodation pupillary reflex, and  convergence    e The ear is divided into three major areas: external  (outer) ear, middle ear, internal (inner) ear    8.3a. External ear—includes the auricle (pinna),  external acoustic meatus, and tympanic membrane  (eardrum); involved with sound transmission only    e Ceruminous glands secrete waxy cerumen to  protect the ear canal    e Sound entering the external acoustic meatus  causes the eardrum to vibrate    e Auditory ossicles (malleus, incus, stapes) trans-  mit and amplify vibratory motion from the ear-  drum to the oval window    e Pharyngotympanic tube allows pressure to be  equalized on both sides of the eardrum   e Cochlea houses hearing receptors; vestibule  houses static equilibrium receptors; semi-  circular canals house dynamic equilibrium  receptors    e In the cochlear duct, the spiral organ of Corti  has hearing receptors called hair cells    o Hair cells are anchored to the basilar mem-  brane; hairs of the hair cells are embedded ina  tectorial membrane    o When sound causes vibrations at the tympanic  membrane, those waves are transmitted to the  oval window by the ossicles, which cause the  fluids in the cochlea to vibrate  = The basilar membrane vibrates, bending the   hairs of the hair cells attached to the station-  ary tectorial membrane, and sends an im-  pulse to the brain that is processed as hearing   = Otoliths (calcium salt “stones”) are embed-  ded on surface of otolithic membrane; move  in response to body movement with respect  to the pull of gravity   = Movement causes otoliths to pull on otolithic  membrane, bending hair cells    8.5b. Dynamic equilibrium—report on rotational  movements of the head  e Receptors in the ampullae of the semicircular  canals are called crista ampullaris  o Crista have tufts of hair cells with hairs embed-  ded in gel cap (cupula)  = Movement of body causes endolymph to  move in opposite direction, bending cupula  and bending hair cells    e Olfactory receptors (smell receptors)—located  in the superior aspect of each nasal cavity  ° Sniffing helps to bring more air (containing  odors) over the olfactory mucosa    system; odors stimulate the recall of memories  and arouse emotional responses    ° Taste buds occur on or around papillae, pri-  marily on the tongue  = Fungiform papillae, foliate papillae, and  vallate papillae occur in the mouth    bitter, and umami  = Taste and appreciation of foods are influ-  enced by smell, temperature, and texture    5 or 6 months of pregnancy may cause visual  abnormalities as well as sensorineural deafness    1. Gustatory cells are  a. bipolar neurons.  b. multipolar neurons.  c. unipolar neurons.    2. Alkaloids excite gustatory hairs mostly at the  a. tip of the tongue.  b. back of the tongue.  c. vallate papillae.  d. fungiform papillae.  3. Parts of the olfactory mucosa include the  a. mucus layer.  b. olfactory bulb.  c. olfactory hairs.    Vision requires the most learning; infants have  poor visual acuity (are farsighted) and lack color  vision and depth perception; eye continues to  grow and mature until age 8 or 9    clude presbyopia, glaucoma, cataracts, and  arteriosclerosis of the eye’s blood vessels   ° Sensorineural deafness (presbycusis) is a nor-  mal consequence of aging    Taste and smell—most acute at birth; decrease in  sensitivity after age 40; the number of olfactory  and gustatory receptors decreases    a. requires contraction of the medial rectus muscles  of both eyes.    8. Which of the following are paired incorrectly?  a. Tympanic cavity—ossicles  b. Round window—stapes  c. Tympanic membrane—hammer    9. Movement of which structure triggers bending of  hairs of the hair cells in the spiral organ of Corti?   11. Match the letter of the appropriate structure on the  figure to its description.    1. Attachment of the optic nerve at this site  results in a blind spot    5. Crystal-like structure that refracts (bends)  light so it focuses on the retina    10. Sounds entering the external acoustic meatus are enter the eye    eventually converted to nerve impulses via a chain of  events including    c. stimulation of hair cells in the spiral organ of  Corti.    Compare and contrast emmetropia, hyperopia, and  myopia. What type of lenses will help correct each of  these?    Name the extrinsic eye muscles that allow you to  direct your eyes.    Some people suffer from total color blindness, whereas  others only have to reckon with partial color blind-  ness. What is the difference between the two forms?    Name the structures of the outer, middle, and inner  ears, and give the general function of each structure  and each group of structures.    Which mechanism makes it possible for us to deter-  mine the source of a sound? What makes us unaware  of repeating sounds?    Normal balance depends on information transmitted  from a number of sensory receptor types. Name at  least three of these receptors.    For each of the following descriptions, indicate  whether it applies to a macula or a crista ampullaris:  inside a semicircular canal; contains otoliths;  responds to linear acceleration and deceleration; has  a cupula; responds to rotational acceleration and  deceleration; inside the vestibule.    Nine children attending the same day-care center  developed red, inflamed eyes and eyelids. What are  the most likely cause and name of this condition?    Sylvia Marcus, age 70, recently had surgery for oto-  sclerosis. The operation was a failure and did not  improve her condition. What was the purpose of the  surgery, and exactly what was it trying to  accomplish?    taste is illustrated by the fact that 4 of the 12 cranial  nerves are involved in their registration. Clarify the  professor's explanation.    As the second control  system of the body, the  endocrine system releases  chemicals called hormones that  regulate complex body  processes.    our body cells have dynamic adventures on  Yu microscopic level all the time. For instance,   when insulin molecules leave the blood and  bind tightly to protein receptors on nearby cells, the  response is dramatic: bloodborne glucose molecules  begin to enter the cells, and cellular activity acceler-  ates. Such is the power of the second great control  system of the body, the endocrine system. Along  with the nervous system, it coordinates and directs  the activity of the body’s cells.   The speed of control in these two regulating sys-  tems is very different. The nervous system is “built  for speed.” It uses nerve impulses to prod the mus-  cles and glands into immediate action so that rapid  adjustments can be made in response to changes    Hormones  released by endocrine  glands travel through the  blood and alter the activity    occurring both inside and outside the body. By con-  trast, the endocrine system acts more slowly by using  chemical messengers called hormones, which are  released into the blood to be transported throughout  the body.   Hormones have widespread effects and control  several major processes: reproduction; growth and  development; mobilizing body defenses against  stressors; maintaining electrolyte, water, and nutrient  balance of the blood; and regulating cellular metab-  olism and energy balance. As you can see, the endo-  crine system regulates processes that go on for  relatively long periods and, in some cases, continu-  ously. The scientific study of hormones and endo-  crine organs is called endocrinology.   Compared to other organs of the body, the organs of  the endocrine system are small and unimpressive.  The endocrine system also lacks the structural or  anatomical continuity typical of most organ systems.  Instead, bits and pieces of endocrine tissue are  tucked away in separate regions of the body (see  Figure 9.3, p. 328). However, functionally the endo-  crine organs are impressive, and when their role in  maintaining body homeostasis is considered, they  are true giants.    Hormones are chemical substances secreted by  endocrine cells into the extracellular fluids that reg-  ulate the metabolic activity of other cells in the body.  Although the body produces many different hor-  mones, nearly all of them can be classified chemi-  cally as either amino acid-based molecules  (including proteins, peptides, and amines) or  steroids. Steroid hormones (made from choles-  terol) include the sex hormones made by the gonads  (ovaries and testes) and the hormones produced by  the adrenal cortex. All other hormones are nonste-  roidal amino acid derivatives. If we also consider the  hormones that act locally, called prostaglandins  (pros”tah-glan’dinz), we must add a third chemical  class. (Prostaglandins are described later in the chap-  ter—see Table 9.2, p. 346). The prostaglandins are  made from highly active lipids released from nearly  all cell membranes.   Although hormones circulate to all the organs of the  body via blood, a given hormone affects only certain  tissue cells or organs, referred to as its target cells or  target organs.    that of an enzyme to its substrate. Recall that enzymes  interact very specifically with their substrates (Chapter 2,    pp. 72-73). Hormone interactions with target cell  receptors are also very specific and fit together like two  pieces of a puzzle.    For a target cell to respond to a hormone, specific  protein receptors to which that hormone can attach  must be present on the cell’s plasma membrane or in  its interior. Only when this binding occurs can the  hormone influence the workings of a cell.   The term hormone comes from a Greek word  meaning “to arouse.” In fact, the body’s hormones  do just that. They “arouse,” or bring about their  effects on, the body’s cells primarily by altering cellu-  lar activity—that is, by increasing or decreasing the  rate of a normal metabolic process rather than by  stimulating performance of a new one. The precise  change(s) that follow hormone binding depend on  the specific hormone and the target cell type.  Hormones can:    e Change plasma membrane permeability or  membrane potential (electrical state) by open-  ing or closing ion channels    e Activate or inactive enzymes  e Stimulate or inhibit cell division  e Promote or inhibit secretion of a product    e Turn on or turn off transcription of certain genes  (such as those encoding proteins or regulatory  molecules)    Despite the huge variety of hormones, there are  really only two mechanisms by which hormones  trigger changes in cells. Steroid hormones (and,  strangely, thyroid hormone) can use the mechanism  of direct gene activation (Figure 9.1a, p. 326). Because  they are lipid-soluble molecules, the steroid hor-  mones can diffuse through the plasma membranes  of their target cells @. Once inside, the steroid hor-  mone enters the nucleus @) and binds to a specific  hormone receptor @). In this specific example, the  hormone-receptor complex then binds to specific  sites on the cell's DNA @, activating certain genes to  transcribe messenger RNA (mRNA) ©). The mRNA is  translated in the cytoplasm ©, resulting in the syn-  thesis of new proteins. Alternatively, the steroid hor-  mone may bind to receptors in the cytoplasm, and  then the complex moves into the nucleus to activate  certain genes. Instead of turning genes on, some hor-  mones turn genes off in step 4.    What determines whether a hormone will influence  a given body cell?    through either (a) direct gene activation or (b) second-messenger systems. =  Amino acid—based hormones typically act through second-messenger systems.    Steroid hormones can influence cell activity either by  direct gene activation or by the indirect pathway of  activating a second messenger. Protein and peptide  hormones, however, are usually water-soluble and  are unable to enter target cells directly. Instead, they  bind to hormone receptors situated on the target  cell’s plasma membrane and use a second-messenger  system. In these cases (Figure 9.1b), the hormone  (first messenger) binds to the receptor protein on the  membrane , and the activated receptor sets off a  series of reactions (a cascade) that activates an  enzyme @). The enzyme, in turn, catalyzes reactions  that produce second-messenger molecules @) (in this  case, cyclic AMP, also known as cAMP, or cyclic ade-  nosine monophosphate) that oversee additional  intracellular changes that promote the typical    response of the target cell to the hormone @). Think  of a postal service employee (first messenger) deliver-  ing a letter to campus, and a college mailroom  employee (second messenger) carrying the letter  from the college mailbox (cell membrane) to your  dorm mailbox (DNA). As you might guess, the same  hormone may have a variety of possible second mes-  sengers (including cyclic guanosine monophosphate, or  cGMP, and calcium ions) and many possible target  cell responses, depending on the tissue type  stimulated.    1. Walking barefoot, you step on a piece of broken  glass and immediately pull your foot back. Why is it  important that the signal triggering this motion  come from the nervous system and not from the  endocrine system?    9.1c Stimuli for Control of Hormone  Release  Learning Objectives  Explain how various endocrine glands are  stimulated to release their hormonal products.  1# Define negative feedback, and describe its role in  regulating blood levels of the various hormones.  Now that we've discussed how hormones work, the  next question is, “What prompts the endocrine  glands to release or not release their hormones?”  Let's take a look.   Recall that negative feedback mechanisms are  the chief means of regulating blood levels of nearly  all hormones (see Chapter 1, p. 41). In such systems,  some internal or external stimulus triggers hormone  secretion; then, a rising level of the hormone inhib-  its further hormone release (even while promoting a  response in the target organ). As a result, blood lev-  els of many hormones vary within a very narrow  range. With hormones, “a little goes a long way”!    The stimuli that activate endocrine glands fall into  three major categories—hormonal, humoral, and  neural (Figure 9.2). These three mechanisms represent  the most common systems that control hormone  release, but they by no means explain all of them. Some  endocrine organs respond to many different stimuli.    The most common stimulus is a hormonal stimulus,  in which endocrine organs are prodded into action  by other hormones. For example, hormones of the  hypothalamus stimulate the anterior pituitary gland  to secrete its hormones, and many anterior pituitary  hormones stimulate other endocrine organs to  release their hormones into the blood (Figure 9.2a).  As the hormones produced by the final target glands  increase in the blood, they “feed back” to inhibit the  release of anterior pituitary hormones and thus their  own release. Hormone release promoted by this  mechanism tends to be rhythmic, with hormone  blood levels rising and falling again and again.    Figure 9.3 Location of the major endocrine organs  of the body. (The parathyroid glands, which appear to  be on the anterior surface of the thyroid gland in this    Changing blood levels of certain ions and nutrients  may also stimulate hormone release. Such stimuli  are referred to as humoral (hyoo-mor'al) stimuli to  distinguish them from hormonal stimuli, which are  also bloodborne chemicals. The term humoral refers  to the ancient use of the word humor to indicate the  various body fluids (blood, bile, and others). For  example, a decreasing blood calcium ion level in the  capillaries serving the parathyroid glands prompts  the release of parathyroid hormone (PTH). Because  PTH acts by several routes to reverse that decline, the  blood Ca** level soon rises, ending the stimulus for  PTH release (Figure 9.2b). Other hormones released  in response to humoral stimuli include calcitonin,  released by the thyroid gland, and insulin, produced  by the pancreas.    In isolated cases, nerve fibers stimulate hormone  release, and the endocrine cells are said to respond  to neural stimuli. The classic example is sympathetic  nervous system stimulation of the adrenal medulla  to release the catecholamines norepinephrine and  epinephrine during periods of stress (Figure 9.2c).    Did You Get It?  4. What are three ways in which endocrine glands are  stimulated to secrete their hormones?  For the answer, see Appendix A.    Learning Objectives  Describe the difference between endocrine and  exocrine glands.  v@ Onan appropriate diagram, identify the major  endocrine glands and tissues.  1# List hormones produced by the endocrine glands,  and discuss their general functions.  v@ Discuss ways in which hormones promote body  homeostasis by giving examples of hormonal actions.  1# Describe major pathological consequences  of hypersecretion and hyposecretion of the  hormones considered in this chapter.  The major endocrine organs of the body include the  pituitary, pineal, thyroid, parathyroid, thymus and adre-  nal glands, pancreas, and gonads (ovaries and testes)  (Figure 9.3). The hypothalamus, which is part of the  nervous system, is also recognized as a major endo-  crine organ because it produces several hormones.  Some hormone-producing glands (the anterior pitu-  itary, thyroid, parathyroids, and adrenals) have purely  endocrine functions, but others (pancreas and go-  nads) have both endocrine and exocrine functions  and are thus mixed glands. Both types of glands are  formed from epithelial tissue, but the endocrine glands  are ductless glands that produce hormones that they  release into the blood or lymph. (As you might  expect, the endocrine glands have a rich blood sup-  ply.) Conversely, the exocrine glands release their prod-  ucts at the body’s surface or into body cavities through  ducts (exocrine glands have an exit). We have already  discussed the formation of and differences and simi-  larities between these two types of glands (recall what  you learned in Chapter 3). Here we will focus on the    endocrine glands. A summary of the endocrine or-  gans and their hormones’ main actions and regula-  tory factors appears in Table 9.1, pp. 343-345.    Did You Get It?  5. What are two important differences between  endocrine and exocrine glands?  For the answer, see Appendix A.   The pituitary (pi-too'i-tar’e) gland is approxi-  mately the size of a pea. It hangs by a stalk from the  inferior surface of the hypothalamus of the brain,  where it is snugly surrounded by the sella turcica  (“Turk’s saddle”) of the sphenoid bone (look back at  Figure 5.10, p. 167). It has two functional lobes—the  anterior pituitary (glandular tissue) and the posterior  pituitary (nervous tissue).    Describe the functional relationship between the  hypothalamus and the pituitary gland.    Despite its relatively small size, the anterior pituitary  gland controls the activity of so many other endo-  crine glands that it has often been called the “master  endocrine gland.” Its removal or destruction has a  dramatic effect on the body. The adrenal and thyroid  glands and the gonads atrophy, and results of hypo-  secretion by those glands quickly become obvious.  However, the anterior pituitary is not as all-powerful  as it might appear, because the release of each of its  hormones is controlled by releasing hormones  and inhibiting hormones produced by the hypo-  thalamus. The hypothalamus liberates these regula-  tory hormones into the blood of the portal  circulation, which connects the blood supply of the  hypothalamus with that of the anterior pituitary. (In  a portal circulation, two capillary beds are connected  by one or more veins; in this case, the capillaries of  the hypothalamus are drained by veins that empty  into the capillaries of the anterior pituitary. )   The hypothalamus also makes two additional  hormones, oxytocin and antidiuretic hormone,  which are transported along the axons of the hypo-  thalamic neurosecretory cells to the posterior pitu-  itary for storage (Figure 9.4). They are later released    Figure 9.4 Hormones released by the posterior  pituitary and their target organs. Neurosecretory  cells in the hypothalamus synthesize oxytocin and  antidiuretic hormone (ADH) and transport them  down their axons to the posterior pituitary. There, the  hormones are stored until nerve impulses from the  hypothalamus trigger their release.    into the blood in response to nerve impulses from  the hypothalamus.    Posterior Pituitary and Hypothalamic Hormones  The posterior pituitary is not an endocrine gland in the  strict sense because it does not make the peptide hor-  mones it releases. Instead, it acts as a storage area for  hormones made by hypothalamic neurons.  Oxytocin (ok’se-to’sin) is released in significant  amounts only during childbirth and nursing. It stimu-  lates powerful contractions of the uterine muscle dur-  ing sexual relations, during labor, and during  breastfeeding. It also causes milk ejection (the let-down  reflex) in a nursing woman. Both natural and synthetic  oxytocic drugs are used to induce labor or to hasten    What effect would elevated levels of thyroid  hormone in the blood have on TSH secretion?    | hormone (FSH) hormone (TH)  and luteinizing  Mammary hormone (LH) |    Figure 9.5 Hormones of the anterior pituitary and their major target organs.  Releasing hormones secreted by hypothalamic neurons stimulate secretion of anterior  pituitary hormones. The releasing hormones are secreted into a capillary network  that connects via portal veins to a second capillary bed in the anterior lobe of the    labor that is progressing at a slow pace. Less often, oxy-  tocics are used to stop postpartum bleeding (by caus-  ing constriction of the ruptured blood vessels at the  placental site) and to stimulate the let-down reflex.  The second hormone released by the posterior  pituitary is antidiuretic (an"ti-di’u-ret’ik) hormone  (ADH). Diuresis is urine production. Thus, an antidi-  uretic is a chemical that inhibits or prevents urine  production. ADH causes the kidneys to reabsorb  more water from the forming urine; as a result, urine  volume decreases, and blood volume increases.  Water is a powerful inhibitor of ADH release. In  larger amounts, ADH also increases blood pressure  by causing constriction of the arterioles (small    arteries). For this reason, it is sometimes referred to  as vasopressin (vas’o-pres’in).   Drinking alcoholic beverages inhibits ADH  secretion and results in output of large amounts of  urine. The dry mouth and intense thirst experienced  “the morning after” reflect this dehydrating effect of  alcohol. Certain drugs, classed together as diuretics,  antagonize the effects of ADH, causing water to be  flushed from the body. These drugs are used to man-  age the edema (water retention in tissues) typical of  congestive heart failure.    Homeostatic  K Imbalance 9.1  Hyposecretion of ADH leads to a condition of exces-  sive urine output called diabetes insipidus (di’ah-  be'téz in-sip'i-dus). People with this problem are  continually thirsty and drink huge amounts of water.    6. Both the anterior pituitary and the posterior pituitary  release hormones, but the posterior pituitary is not  an endocrine gland. What is it?   7. Barry is excreting huge amounts of urine. He has an  endocrine system problem, but it is not diabetes  mellitus, which has a similar sign. What is his  possible problem?    Anterior Pituitary Hormones The anterior pituitary  produces several hormones that affect many body  organs (Figure 9.5). Two of the six anterior pituitary  hormones in the figure—growth hormone and  prolactin—exert their major effects on nonendocrine  targets. The remaining four—follicle-stimulating  hormone, luteinizing hormone, thyrotropic hor-  mone, and adrenocorticotropic hormone—are all  tropic hormones. Tropic (tro’pik = turn on) hor-  mones stimulate their target organs, which are also  endocrine glands, to secrete their hormones, which  in turn exert their effects on other body organs and  tissues. All anterior pituitary hormones (1) are pro-  teins (or peptides), (2) act through second-messenger  systems, and (3) are regulated by hormonal stimuli  and, in most cases, negative feedback.   Growth hormone (GH) is a general metabolic  hormone. However, its major effects are directed to  the growth of skeletal muscles and long bones of the  body, and thus it plays an important role in deter-  mining final body size. GH is a protein-sparing and  anabolic hormone that causes the building of amino  acids into proteins and stimulates most target cells  to grow in size and divide. At the same time, it causes  fats to be broken down and used for energy while it  spares glucose, helping to maintain blood sugar  homeostasis.    Homeostatic J  £ Imbalance 9.2  If untreated, both deficits and excesses of GH may  result in structural abnormalities. Hyposecretion of  GH during childhood leads to pituitary dwarfism.  Body proportions are fairly normal, but the person  as a whole is a living miniature (with a maximum  adult height of 4 feet). Hypersecretion during child-  hood results in gigantism. The individual becomes  extremely tall; height of 8 to 9 feet is common.  Again, body proportions are fairly normal.    Disorders of pituitary growth hormone. This individual exhibit-  ing gigantism (right) stands 8 feet, 1 inch tall. The pituitary  dwarf (left) is 2 feet, 5.4 inches tall.   If hypersecretion occurs after long-bone growth  has ended, acromegaly (ak"ro-meg'ah-le) results.  The facial bones, particularly the lower jaw and the  bony ridges underlying the eyebrows, enlarge tre-  mendously, as do the feet and hands. Thickening of  soft tissues leads to coarse or malformed facial fea-  tures. Most cases of hypersecretion by endocrine  organs (the pituitary and the other endocrine organs)  result from tumors of the affected gland. The tumor  cells act in much the same way as the normal glan-  dular cells do; that is, they produce the hormones  normally made by that gland. Pharmacological  doses of GH have been used to reverse some of the  effects of aging. Read about this in “A Closer Look”  (p. 332).    Prolactin (PRL) is a protein hormone structur-  ally similar to growth hormone. Its only known tar-  get in humans is the breast (pro = for; lact = milk).  After childbirth, it stimulates and maintains milk  production by the mother’s breasts. Its function in  men is not known.    Go" hormone (GH) is adminis-  tered legally to children who do  not produce it naturally to allow these    When GH is administered to adults  with a growth hormone deficiency,  body fat decreases, and bone density  and muscle mass increase. GH also  appears to increase the performance  and muscle mass of the heart,  decreases blood cholesterol, boosts  the immune system, and perhaps  improves a person's psychological out-  look. Such effects (particularly those  involving increased muscle mass and  decreased body fat) have led to abuse  of GH by bodybuilders and athletes.  Based on these effects, GH is a  banned performance-enhancing drug,  and its use remains restricted.    Learn more at Mastering A&P > Study Area > | _  Additional Study Tools > A Closer Look \    Administration of GH to older  patients reverses the typical declines in  lean-to-fat mass. However, clinical  studies reveal that the administered  GH does not increase strength or  exercise tolerance in older patients  and have found that high doses of GH  are associated with increased  mortality.   GH may help AIDS patients at risk  for dying from weight loss called  “wasting.” Injections of GH can actu-  ally reverse wasting during AIDS, lead-  ing to weight gain and gain of lean  muscle.   GH is not a wonder drug, even in  cases where it is clearly beneficial. GH  treatment is expensive and has unde-  sirable side effects. It can lead to fluid  retention and edema, joint and muscle    pain, high blood sugar, glucose intol-  erance, and gynecomastia (breast  enlargement in men). Hypertension,  heart enlargement, diabetes, and  colon cancer are other possible results  of high doses of GH, and edema and  headaches accompany even the low-  est doses.    © Growth hormone (GH) can  increase muscle mass and bone  density, even in elderly patients.    e GH has a variety of side effects,  including edema, pain, high  blood sugar, hypertension,  diabetes, and colon cancer.    The gonadotropic (go’nad-o-tro'pik) hormones  regulate the hormonal activity of the gonads (ovaries  and testes). In women, the gonadotropin follicle-  stimulating hormone (FSH) stimulates follicle  development in the ovaries. As the follicles mature,  they produce estrogen, and eggs are readied for ovula-  tion. In men, FSH stimulates sperm development by  the testes. Luteinizing (lu'te-in-i’zing) hormone  (LH) triggers ovulation of an egg from the ovary and  causes the ruptured follicle to produce progesterone  and some estrogen. In men, LH stimulates testoster-  one production by the interstitial cells of the testes.    Homeostatic J  £ Imbalance 9.3  Hyposecretion of FSH or LH leads to sterility, the  lack of ability to successfully reproduce, in both  males and females. In general, hypersecretion does  not appear to cause any problems. However, some  drugs used to promote fertility stimulate the release  of the gonadotropic hormones, and multiple births  (indicating multiple ovulations at the same time  rather than the usual single ovulation each month)  are relatively common after their use.    Thyrotropic hormone (TH), also called  thyroid-stimulating hormone (TSH), influences  the growth and activity of the thyroid gland.  Adrenocorticotropic (ad-re’no-kor’ti-ko-tro’ pik)  hormone (ACTH) regulates the endocrine activity  of the cortex portion of the adrenal gland.    8. What are tropic hormones?  For the answer, see Appendix A.    The pineal (pin’e-al) gland is a small, cone-shaped  gland that hangs from the roof of the third ventricle  of the brain (see Figure 9.3). The endocrine function  of this tiny gland is still somewhat of a mystery.  Although many chemical substances have been iden-  tified in the pineal gland, only the hormone  melatonin (mel”ah-to’nin) appears to be secreted in  substantial amounts. The level of melatonin rises and  falls during the course of the day and night. The peak  level occurs at night and makes us drowsy; the lowest  level occurs during daylight around noon. Melatonin    is believed to be a “sleep trigger” that plays an impor-  tant role in establishing the body’s sleep-wake cycle.  It is believed to coordinate the hormones of fertility  and to inhibit the reproductive system (especially the  ovaries of females) until the body matures.    The thyroid gland is located at the base of the  throat, just inferior to the Adam’s apple, where it is  easily palpated during a physical examination. It is a  fairly large gland consisting of two lobes joined by a  central mass, or isthmus (Figure 9.6a). The thyroid  gland makes two hormones, one called thyroid hor-  mone, the other called calcitonin (produced by the  parafollicular cells). Internally, the thyroid gland is  composed of hollow structures called follicles  (Figure 9.6b), which store a sticky colloidal material.  Thyroid hormone is derived from this colloid.  Thyroid hormone, often referred to as the body’s  major metabolic hormone, is actually two active  iodine-containing hormones, thyroxine (thi-rok’sin),  or T, and triiodothyronine (tri’i’o-do-thi’ro-nén),  or T}. Thyroxine is the major hormone secreted by the  thyroid follicles. Most triiodothyronine is formed at  the target tissues by conversion of thyroxine to    triiodothyronine. These two hormones are very much  alike. Each is constructed from two tyrosine amino  acids linked together, but thyroxine has four bound  iodine atoms, whereas triiodothyronine has three  (thus, T, and T3, respectively).   Thyroid hormone controls the rate at which glu-  cose is “burned,” or oxidized, and converted to body  heat and chemical energy (ATP). Because all body  cells depend on a continuous supply of ATP to  power their activities, every cell in the body is a tar-  get. Thyroid hormone is also important for normal  tissue growth and development, especially in the  reproductive and nervous systems.    Homeostatic J  —S Imbalance 9.4  Without iodine, functional thyroid hormones can-  not be made. The source of iodine is our diet, and  foods richest in iodine are seafoods. Years ago many  people who lived in the Midwest, in areas with  iodine-deficient soil that were far from the seashore  (and a supply of fresh seafood), developed goiters  (goy’terz). So, that region of the country came to be  known as the “goiter belt.” A goiter is an enlargement  of the thyroid gland that results when the diet is    deficient in iodine (see the figure). TSH stimulates  the release of thyroxine, but as the peptide part of the  molecule is made, the thyroid gland enlarges because  the protein is nonfunctional without iodine. This  inactive form of thyroxine fails to provide negative  feedback to inhibit TSH release, resulting in contin-  ued production of the peptide component, which  makes the goiter larger. Simple goiter is uncommon  in the United States today because most of our salt is  iodized, but it is still a problem in some other areas  of the world.    Hyposecretion of thyroxine may indicate prob-  lems other than iodine deficiency, such as lack of  stimulation by TSH. If it occurs in early childhood,  the result is cretinism (kre’tin-izm). Cretinism  results in dwarfism in which adult body proportions  remain childlike, with a proportionally longer torso  and shorter legs compared to normal adults.  Untreated individuals with cretinism are intellectu-  ally impaired. Their hair is scanty, and their skin is  dry. If the hyposecretion is discovered early, hor-  mone replacement will prevent mental impairment  and other signs and symptoms of the deficiency.  Hypothyroidism occurring in adults results in  myxedema (mik’sah-de’mah), which is character-  ized by both physical and mental sluggishness (how-  ever, mental impairment does not occur). Other  signs are puffiness of the face, fatigue, poor muscle  tone, low body temperature (the person is always  cold), obesity, and dry skin. Oral thyroxine is pre-  scribed to treat this condition.   Hyperthyroidism generally results from a tumor  of the thyroid gland. Extreme overproduction of  thyroxine results in a high basal metabolic rate,  intolerance of heat, rapid heartbeat, weight loss,    nervous and agitated behavior, and a general inabil-  ity to relax. Graves’ disease is one form of hyper-  thyroidism. In addition to the symptoms of  hyperthyroidism described earlier, the thyroid gland  enlarges, and the eyes may bulge, or protrude anteri-  orly. This condition, called exophthalmos (ek’sof-  thal’mus), is shown in the figure. Hyperthyroidism  may be treated surgically by removal of part of the  thyroid (and/or a tumor if present) or chemically  with thyroid-blocking drugs or radioactive iodine,  which destroys some of the thyroid cells.    The second important hormone product of the  thyroid gland, calcitonin, decreases the blood cal-  cium ion level by causing calcium to be deposited in  the bones. It acts antagonistically to parathyroid hor-  mone, the hormone produced by the parathyroid  glands. Whereas thyroxine is made and stored in fol-  licles before it is released to the blood, calcitonin is  made by the parafollicular cells found in the con-  nective tissue between the follicles (see Figure 9.6b).  It is released directly to the blood in response to an  increasing level of blood calcium ions. Few effects of  hypo- or hypersecretion of calcitonin are known,  and calcitonin production is meager or ceases  entirely in adults. This may help to explain (at least  in part) the progressive decalcification of bones that  accompanies aging.    9. Why is iodine important for proper thyroid gland  function?  10. What hormone is called the “sleep hormone,” and  which endocrine organ produces it?  For answers, see Appendix A.    Figure 9.7 Hormonal control of the level of  calcium ions in the blood. PTH and calcitonin  operate in negative feedback control systems that  influence each other.    What effect would removal of the parathyroid glands  have on the blood calcium ion level?   Sace a  Calcium homeostasis of blood: 9-11 mg/100 ml  BALANCE BALANCE    the blood calcium ion concentration drops below a  certain level, the parathyroids release PTH, which  stimulates bone destruction cells (osteoclasts) to  break down bone matrix and release calcium ions  into the blood. Thus, PTH is a hypercalcemic hor-  mone (that is, it acts to increase the blood level of  calcium ions), whereas calcitonin is a hypocalcemic  hormone. (The negative feedback interaction  between these two hormones as they control the  blood calcium ion level during youth is illustrated in  Figure 9.7.) Although the skeleton is the major PTH  "Hid 40 snjnuns target, PTH also stimulates the kidneys and intestine  Sunsə6ıp-əuoq əy} 0} pəsodxə əq 1Ə6uo] ou pınom to absorb more calcium ions (from urinary filtrate  səuoq əy} asnedaq doup pinom sjana] wne poog A  and foodstuffs, respectively).    The parathyroid glands are tiny masses of glandu-  lar tissue most often found on the posterior surface  of the thyroid gland (look back at Figure 9.3).  Typically, there are two parathyroid glands on each  thyroid lobe, that is, a total of four parathyroids; but  as many as eight have been reported, and some may  be in other regions of the neck or even in the thorax.  The parathyroids secrete parathyroid hormone  (PTH), which is the most important regulator of    Figure 9.8 Microscopic structure of the adrenal gland. Diagram of the three    regions of the adrenal cortex and part of the adrenal medulla.    If the blood calcium ion level falls too low, neurons  become extremely irritable and overactive. They deliver  impulses to the muscles so rapidly that the muscles go  into uncontrollable spasms (tetany), which may be  fatal. Before surgeons knew the importance of the tiny  parathyroid glands on the backside of the thyroid, they  would remove a hyperthyroid patient's thyroid gland  entirely. Many times this resulted in death. Once it was  revealed that the parathyroids are functionally very dif-  ferent from the thyroid gland, surgeons began to leave  at least some parathyroid-containing tissue (if at all pos-  sible) to take care of blood calcium ion homeostasis.   Severe hyperparathyroidism causes massive bone  destruction—an X-ray examination of the bones  shows large punched-out holes in the bony matrix.  The bones become very fragile, and spontaneous  fractures begin to occur.   12. What hormone increases the blood calcium ion level,  and which endocrine gland produces this hormone?    13. What hormone reduces the blood calcium ion level,  and which endocrine gland produces this hormone?  For answers, see Appendix A.   The thymus is located in the upper thorax, posterior  to the sternum. Large in infants and children, it  decreases in size throughout adulthood. By old age,  it is composed mostly of fibrous connective tissue  and fat. The thymus produces a hormone called  thymosin (thi’mo-sin) and others that appear to be  essential for normal development of a special group  of white blood cells (T lymphocytes) and the immune  response. (We describe the role of the thymus and its  hormones in immunity in Chapter 12.)    The two adrenal glands curve over the top of the  kidneys like triangular hats. Although each adrenal  gland looks like a single organ, it is structurally and  functionally two endocrine organs in one. Much like  the pituitary gland, it has parts made of glandular  (cortex) and neural tissue (medulla). The central  medulla region is enclosed by the adrenal cortex,  which contains three separate layers of cells that  each produce different hormones (Figure 9.8).    Increases absorption of Nat (and  water); increased K* excretion  Increases blood volume  and/or blood pressure    Figure 9.9 Major  mechanisms controlling  aldosterone release from  the adrenal cortex.    selectively reabsorb the minerals or allow them to be  flushed out of the body in urine. When the blood  level of aldosterone rises, the kidney tubule cells  reabsorb increasing amounts of sodium ions and  secrete more potassium ions into the urine. When   The mineralocorticoids, mainly aldosterone  (al”dos-ter’on), are produced by the outermost adre-  nal cortex cell layer. As their name suggests, the min-  eralocorticoids are important in regulating the  mineral (or salt) content of the blood, particularly  the concentrations of sodium and potassium ions.  These hormones target the kidney tubules that    sodium is reabsorbed, water follows. Thus, the min-  eralocorticoids help regulate both water and electro-  lyte balance in body fluids. The release of aldosterone  is stimulated by humoral factors, such as fewer  sodium ions or more potassium ions in the blood  (and, to a lesser degree, by ACTH, a hormonal stimu-  lus) (Figure 9.9). Renin, an enzyme produced by the    kidneys when blood pressure drops, also causes the  release of aldosterone by triggering a series of reac-  tions that form angiotensin II, a potent stimulator  of aldosterone release. A hormone released by the  heart, atrial natriuretic (na’tre-u-ret'ik) peptide  (ANP), prevents aldosterone release, its goal being to  reduce blood volume and blood pressure.   The middle cortical layer mainly produces gluco-  corticoids, which include cortisone and cortisol.  Glucocorticoids promote normal cell metabolism  and help the body to resist long-term stressors, primar-  ily by increasing the blood glucose level. When blood  levels of glucocorticoids are high, fats and even pro-  teins are broken down by body cells and converted to  glucose, which is released to the blood. For this rea-  son, glucocorticoids are said to be hyperglycemic  hormones. Glucocorticoids also seem to control the  more unpleasant effects of inflammation by decreas-  ing edema, and they reduce pain by inhibiting the  pain-causing prostaglandins (see Table 9.2, p. 346).  Because of their anti-inflammatory properties, gluco-  corticoids are often prescribed as drugs to suppress  inflammation for patients with rheumatoid arthritis.  Glucocorticoids are released from the adrenal cortex  in response to a rising blood level of ACTH.   In both men and women, the adrenal cortex pro-  duces both male and female sex hormones through-  out life in relatively small amounts. The bulk of the  sex hormones produced by the innermost cortex layer  are androgens (male sex hormones), but some  estrogens (female sex hormones) are also formed.    Homeostatic Jj  —S Imbalance 9.6  A generalized hyposecretion of all the adrenal cortex  hormones leads to Addison's disease, characterized  by a peculiar bronze tone of the skin, which can  resemble a suntan. Because the aldosterone level is  low, sodium and water are lost from the body, which  leads to problems with electrolyte and water bal-  ance. This, in turn, causes the muscles to become  weak, and shock is a possibility. Other signs and  symptoms of Addison’s disease result from deficient  levels of glucocorticoids, such as hypoglycemia, a  lessened ability to cope with stress (burnout), and  suppression of the immune system (and thereby  increased susceptibility to infection). A complete  lack of glucocorticoids is incompatible with life.  Hypersecretion problems may result from an  ACTH-releasing tumor of the pituitary or from    adrenal cortical tumors. The resulting condition  depends on the cortical area involved. Hyperactivity  of the outermost cortical area results in  hyperaldosteronism (hi’per-al’dos’-teron-izm).  Excessive water and sodium ions are retained, leading  to high blood pressure and edema. Potassium ions are  lost to such an extent that the activity of the heart and  nervous system may be disrupted. When the tumor is  in the middle cortical area or the patient has been  receiving pharmacological doses (amounts higher  than those released in the body) of glucocorticoids  to counteract inflammatory disease, Cushing's  syndrome occurs. Excessive glucocorticoids result in  a swollen “moon face” and the appearance of a “buf-  falo hump” of fat on the upper back. Other common  and undesirable effects include high blood pressure,  hyperglycemia (steroid diabetes), weakening of the  bones (as protein is withdrawn to be converted to glu-  cose), and severe depression of the immune system.   Hypersecretion of the sex hormones leads to  masculinization, regardless of sex. In adult males  these effects may be masked, but in females the  results are often dramatic. A beard develops, and a  masculine pattern of body hair distribution occurs,  among other effects.    14. How do thymosin and other thymus hormones  help to protect the body?   15. What hormone stimulates the kidneys to reabsorb  more sodium ions?   16. Which group of hormones produced by the  adrenal cortex have anti-inflammatory effects and  participate in the long-term stress response?    Catecholamines 1. Increased heart rate  (epinephrine and 2. Increased blood pressure  norepinephrine) 3. Liver converts glycogen to  glucose and releases glucose  to blood  4. Dilation of bronchioles  5. Changes in blood flow patterns,  leading to increased alertness  and decreased digestive and  kidney activity  6. Increased metabolic rate    1. Retention of sodium 1. Proteins and fats  and water by kidneys converted to glucose  2. Increased blood volume or broken down for  and blood pressure energy  2. Increased blood sugar  3. Suppression of  immune system    Figure 9.10 Roles of the hypothalamus, adrenal medulla, and adrenal  cortex in the stress response. (Note that ACTH is only a weak stimulator of    The adrenal medulla, like the posterior pituitary, is a  knot of nervous tissue. When the medulla is stimu-  lated by sympathetic nervous system neurons, its cells  release two similar hormones, epinephrine (ep"ï-  nef'rin), also called adrenaline, and norepinephrine  (noradrenaline), into the bloodstream. Collectively,  these hormones are called catecholamines (kat’é-  kol’ah-ménz). Because some sympathetic neurons  also release norepinephrine as a neurotransmitter, the  adrenal medulla is often thought of as a “misplaced  sympathetic nervous system ganglion.”   When you are (or feel) threatened physically or  emotionally, your sympathetic nervous system  brings about the “fight-or-flight” response to help  you cope with the stressful situation. One of the    organs it stimulates is the adrenal medulla, which lit-  erally pumps its hormones into the bloodstream to  enhance and prolong the effects of the neurotrans-  mitters of the sympathetic nervous system. The cate-  cholamines increase heart rate, blood pressure, and  the blood glucose level and dilate the small passage-  ways of the lungs. These events result in more oxygen  and glucose in the blood and a faster circulation of  blood to the body organs (most importantly, to the  brain, muscles, and heart). Thus, the body is better  able to deal with a short-term stressor, whether the  job at hand is to fight, begin the inflammatory pro-  cess, or alert you so you think more clearly  (Figure 9.10).   The catecholamines of the adrenal medulla pre-  pare the body to cope with short-term stressful    Figure 9.11 Pancreatic tissue. (a) Location of pancreas relative to the stomach  and small intestine. (b) Photomicrograph of pancreas with exocrine and endocrine  (islets) areas clearly visible (140). (c) Diagrammatic view of a pancreatic islet. Beta  cells (blue) produce insulin; alpha cells (orange) produce glucagon.    situations and cause the so-called alarm stage of the  stress response. Glucocorticoids, by contrast, are pro-  duced by the adrenal cortex and are important when  coping with prolonged or continuing stressors, such  as dealing with the death of a family member or hav-  ing a major operation. Glucocorticoids operate pri-  marily during the resistance stage of the stress  response. If they are successful in protecting the  body, the problem will eventually be resolved with-  out lasting damage. When the stress continues on  and on, the adrenal cortex may simply “burn out,”  which is usually fatal. (The roles of glucocorticoids  in the stress response are also shown in Figure 9.10.)    Homeostatic B  K Imbalance 9.7  Damage to or destruction of the adrenal medulla has  no major effects as long as the sympathetic nervous  system neurons continue to function normally.  However, hypersecretion of catecholamines leads to  symptoms such as rapid heartbeat, high blood pres-  sure, and a tendency to perspire and be very irritable.  Surgical removal of the catecholamine-secreting cells  corrects this condition.    The pancreas, located close to the stomach in the  abdominal cavity (see Figure 9.3), is a mixed gland.  The pancreatic islets, also called the islets of  Langerhans (lahng’er-hanz), are little masses of  endocrine (hormone-producing) tissue scattered  among the exocrine (enzyme-producing) tissue of the  pancreas. The exocrine, or acinar, part of the pancreas  acts as part of the digestive system (see Chapter 14).  Here we will consider only the pancreatic islets.   Although there are more than a million islets  separated by exocrine cells, each of these tiny clumps  of cells works like an organ within an organ as it bus-  ily manufactures its hormones. Two important hor-  mones produced by the islet cells are insulin and  glucagon (gloo’kah-gon).   Islet cells act as fuel sensors, secreting insulin and  glucagon appropriately during fed and fasting states.  A high level of glucose in the blood stimulates the  release of insulin from the beta (ba’tah) cells  (Figure 9.11) of the islets. Insulin acts on just about  all body cells, increasing their ability to import glu-  cose across their plasma membranes. Once inside the  cells, glucose is oxidized for energy or converted to  glycogen or fat for storage. Insulin also speeds up    these “use it” or “store it” activities. Because insulin  sweeps the glucose out of the blood, its effect is said  to be hypoglycemic. As the blood glucose level falls,  the stimulus for insulin release ends—another classic  case of negative feedback control. Many hormones  have hyperglycemic effects (glucagon, glucocorti-  coids, and epinephrine, to name a few), but insulin  is the only hormone that decreases the blood glucose  level. Insulin is absolutely necessary for the use of  glucose by body cells. Without it, essentially no glu-    cose can get into the cells to be used.  Homeostatic J  K Imbalance 9.8  Without insulin, the blood glucose level (which nor-  mally ranges from 80 to 120 mg/100 ml of blood)  rises to a dramatically high level (for example,  600 mg/100 ml of blood). In such instances, glucose  begins to spill into the urine because the kidney  tubule cells cannot reabsorb it fast enough. As glu-  cose flushes from the body, water follows, leading to  dehydration. The clinical name for this condition is  diabetes mellitus (mé-li’tus), which literally means  that something sweet (mel = honey) is passing  through, or siphoning (diabetes = Greek “siphon”),  from the body. Because cells do not have access to  glucose, fats and even proteins are broken down and  used to meet the energy requirements of the body. As  a result, body weight begins to decline. Loss of body  proteins leads to a decreased ability to fight infec-  tions, so diabetics must maintain good hygiene and  care for even small cuts and bruises. When large  amounts of fats (instead of sugars) are used for  energy, the blood becomes very acidic (acidosis  [as"i-do'sis]) as ketones (intermediate products of fat  breakdown) appear in the blood. This type of acido-  sis is referred to as ketosis. Unless corrected, coma  and death result. The three cardinal signs of diabetes  mellitus are (1) polyuria (pol”e-u’re-ah)—excessive  urination to flush out the glucose and ketones;  (2) polydipsia (pol’e-dip’se-ah)—excessive thirst  resulting from water loss; and (3) polyphagia  (pol"e-fa’je-ah)—hunger due to inability to use sug-  ars and the loss of fat and proteins from the body.  People with mild cases of diabetes mellitus (most  cases of type 2, or adult-onset, diabetes) produce insulin,  but for some reason their insulin receptors are unable  to respond to it, a situation called insulin resistance.  Type 2 diabetics are treated with special diets or oral    hypoglycemic medications that prod the sluggish  islets into action and increase the sensitivity of the tar-  get tissues to insulin and of beta cells to the stimulat-  ing effects of glucose. To regulate the blood glucose  level in the more severe type 1 (juvenile) diabetic, insu-  lin is infused continuously by an insulin pump worn  externally or by a regimen of carefully planned insu-  lin injections is administered throughout the day.    Glucagon acts as an antagonist of insulin; that is,  it helps to regulate the blood glucose level but in a  way opposite that of insulin (Figure 9.12, p. 342). Its  release by the alpha (al’fah) cells (see Figure 9.11c) of  the islets is stimulated by a low blood level of glucose.  Its action is basically hyperglycemic. Its primary target  organ is the liver, which it stimulates to break down  stored glycogen to glucose and to release the glucose  into the blood. No important disorders resulting from  hypo- or hypersecretion of glucagon are known.    17. Mrs. Bellamy’s husband has suffered a heart attack  and is hospitalized. Would you expect her blood  glucose level to be elevated, normal, or lower than  normal? Why?   18. Insulin and glucagon are both pancreatic hormones.  Which stimulates cellular uptake of glucose?    The female and male gonads (see Figure 9.3) produce  sex cells (an exocrine function). They also produce  sex hormones that are identical to those produced by  adrenal cortex cells. The major differences from the  adrenal sex hormone production are the source and  relative amounts of hormones produced.    The female gonads, or ovaries, are paired, slightly  larger than almond-sized organs located in the pel-  vic cavity. Besides producing female sex cells (ova, or  eggs), ovaries produce two groups of steroid hor-  mones, estrogens and progesterone.   Alone, the estrogens are responsible for the  development of sex characteristics in women (pri-  marily growth and maturation of the reproductive  organs) and the appearance of secondary sex charac-  teristics (for example, hair in the pubic and axillary    What happens to the liver’s ability to synthesize and  store glycogen when the glucagon blood level rises?    Liver breaks  down glycogen  stores and  releases glucose  to the blood.    regions) at puberty. Acting with progesterone, estro-  gens promote breast development and cyclic changes  in the uterine lining (the menstrual cycle, or  menstruation).    Uptake of glucose  from blood is  enhanced in most  body cells.    Figure 9.12 Regulation of the blood glucose level by a negative feedback    Progesterone (pro-jes'té-ron), as already noted,  acts with estrogen to bring about menstruation.  During pregnancy, it quiets the muscles of the uterus  so that an implanted embryo will not be aborted  and helps prepare breast tissue for lactation.   Ovaries are stimulated to release their estrogens  and progesterone in a cyclic way by the anterior pitu-  itary gonadotropic hormones. We give more detail    on this feedback cycle and on the structure, function,  and controls of the ovaries in Chapter 16, but keep  in mind that hyposecretion of the ovarian hormones  severely hampers a woman’s ability to conceive and  bear children.    The paired oval testes of the male are suspended in a  sac, the scrotum, outside the pelvic cavity. In addition  to male sex cells, or sperm, the testes also produce male  sex hormones, or androgens, of which testosterone  (tes-tos'té-ron) is the most important. At puberty, tes-  tosterone promotes the growth and maturation of the  reproductive system organs to prepare the young man  for reproduction. It also causes the male’s secondary  sex characteristics (growth of facial hair, development  of heavy bones and muscles, and lowering of the  voice) to appear and stimulates the male sex drive.    In adults, testosterone is necessary for continu-  ous production of sperm. In cases of hyposecretion,  the man becomes sterile; such cases are usually  treated by testosterone injections. Testosterone pro-  duction is specifically stimulated by LH (luteinizing  hormone). (Chapter 16, which deals with the repro-  ductive system, contains more information on the  structure and exocrine function of the testes. )   Table 9.1 (pp. 343-345) summarizes the major  endocrine glands and some of their hormones.    19. Which gonadal hormone causes a young girl's  reproductive organs to mature at puberty—  estrogen or progesterone?    Hormones released by the posterior pituitary; releasing and inhibiting  hormones that regulate the anterior pituitary (see below)    Table 9.1 Major Endocrine Glands and Some of Their Hormones (continued)    Chemical  Gland Hormone class* Major actions Regulated by  Thyroid-stimulating Protein Stimulates thyroid Thyroxine in blood;  hormone (TSH) gland hypothalamic  hormones  Adrenocorticotropic Protein Stimulates adrenal Glucocorticoids;  hormone (ACTH) cortex to secrete hypothalamic  glucocorticoids hormones  Pineal gland Melatonin Amine Involved in Light/dark cycles  g  biological rhythms  (daily and  seasonal)  Thyroid gland Thyroxine (Tą and Amine Stimulates TSH  triiodothyronine (T3) metabolism  Calcitonin Peptide Reduces blood Calcium ion level in  calcium ion level blood  Parathyroid glands R l Parathyroid Peptide Raises blood Calcium ion level in  { Y hormone (PTH) calcium ion level blood  Thymus Thymosin Peptide “Programs” Not known  T lymphocytes  Adrenal glands  e Adrenal medulla Epinephrine and Amines Raise blood Nervous system  norepinephrine glucose level; (sympathetic division)  increase rate  of metabolism;  constrict certain  blood vessels  e Adrenal cortex F Glucocorticoids Steroids Increase blood ACTH  r glucose level  Mineralocorticoids Steroids Promote Changes in blood  reabsorption of volume or blood  Na* and excretion pressure; K* or Na*  of K* (potassium) level in blood  in kidneys  Androgens and  estrogens (see entry  under gonads)  Pancreas Insulin Protein Reduces blood Glucose level in blood  g glucose level  Glucagon Protein Raises blood Glucose level in blood    Gland Hormone  Gonads  e Testes | Androgens  e Ovaries Q Estrogens  Progesterone    4 Indicate the endocrine role of the kidneys,  the stomach and intestine, the heart, and the  placenta.    Besides the major endocrine organs, pockets of  hormone-producing cells are found in fatty tissue  and in the walls of the small intestine, stomach, kid-  neys, and heart—organs whose chief functions have  little to do with hormone production. Because we  describe most of these hormones in later chapters,  we summarize only their chief characteristics in  Table 9.2 (p. 346).   The placenta (plah-sen'tah) is a remarkable  organ formed temporarily in the uterus of pregnant  women. In addition to its roles as the respiratory,  excretory, and nutrition-delivery systems for the  fetus, it also produces several protein and steroid  hormones that help to maintain the pregnancy and  pave the way for delivery of the baby.   During very early pregnancy, a hormone called  human chorionic (ko"re-on’ik) gonadotropin  (hCG) is produced by the developing embryo and  then by the fetal part of the placenta. Similar to LH  (luteinizing hormone), hCG stimulates the ovaries    to continue producing estrogen and progesterone so  that the lining of the uterus is not sloughed off in  menses. (The home pregnancy tests sold over the  counter test for the presence of hCG in the woman’s    job of producing estrogen and progesterone, and the  ovaries become inactive for the rest of the pregnancy.  The high estrogen and progesterone blood levels  maintain the lining of the uterus (thus, the preg-  nancy) and prepare the breasts for producing milk.  Human placental lactogen (hPL) works coopera-  tively with estrogen and progesterone in preparing  the breasts for lactation. Relaxin, another placental  hormone, causes the mother’s pelvic ligaments and  the pubic symphysis to relax and become more flex-  ible, which eases birth passage.    v~ Describe the effect of aging on the endocrine  system and body homeostasis.    The embryonic development of the endocrine glands  varies. The pituitary gland is derived from epithe-  lium of the oral cavity and a neural tissue projection    Table 9.2 Hormones Produced by Organs Other Than the Major Endocrine Organs    Have many targets but act locally at site  of release. Examples of effects include  the following: increase blood pressure   by acting as vasoconstrictors; cause  constriction of respiratory passageways;  stimulate muscle of the uterus, promoting  menstrual pain and labor; enhance blood  clotting; promote inflammation and pain;  increase output of digestive secretions by  stomach; cause fever.   Stomach: reduces secretions and motility.  Pancreas: stimulates release of  enzyme-rich juice.   small intestine): causes sphincter to relax,  allowing bile and pancreatic juice to enter  duodenum.    Intestine: stimulates active transport of  dietary calcium ions across intestinal cell  membranes.   Adrenal cortex: inhibits secretion of  aldosterone, thereby decreasing blood  volume and blood pressure.    e Many hormones (growth hormone,  thyroxine, sex hormones) influence  normal maturation and function of  the nervous system   e Respiratory system provides  oxygen; disposes of carbon  dioxide; converting enzyme in  lungs converts angiotensin | to  angiotensin II    e Several hormones influence blood  volume, blood pressure, and heart  contractility; erythropoietin  stimulates red blood cell production   e Blood is the main transport medium  of hormones; heart produces atrial  natriuretic peptide   e Hypothalamic, anterior pituitary,  and gonadal hormones direct  reproductive system development  and function; oxytocin and prolactin  are involved in birth and  breastfeeding    e Aldosterone and ADH influence renal  function; erythropoietin released by  kidneys promotes red blood cell  formation   e Skin produces a precursor of vitamin  D (cholecalciferol or provitamin D)    e PTH is important in regulating  calcium blood levels; growth  hormone, T4, T4, and sex hormones  are necessary for normal skeletal    e Growth hormone is essential for  normal muscular development;  other hormones (thyroxine and  catecholamines) influence muscle    of the hypothalamus. The pineal gland is entirely  neural tissue. Most strictly epithelial glands develop  as little saclike outpocketings of the mucosa of the  digestive tract. These are the thyroid, thymus, and  pancreas. Formation of the gonads and the adrenal  and parathyroid glands is much more complex and  is not considered here.   Barring outright malfunctions of the endocrine  glands, most endocrine organs seem to operate  smoothly until old age. In late middle age, the effi-  ciency of the ovaries begins to decline, causing  menopause (“the change of life”). During this  period, a woman’s reproductive organs begin to atro-  phy, and the ability to bear children ends. Problems  associated with estrogen deficiency begin to occur,  such as arteriosclerosis, osteoporosis, decreased skin  elasticity, and changes in the operation of the sympa-  thetic nervous system that result in “hot flashes.” In  addition, fatigue, nervousness, and mood changes  such as depression are common. No such dramatic  changes seem to happen in men. In fact, many men  remain fertile throughout their life span, indicating  that testosterone is still being produced in adequate  amounts.   The efficiency of the endocrine system as a whole  gradually declines in old age. Striking changes in  aging women are due to decreasing levels of female  hormones, and there is no question that growth   e Endocrine system—a major control system of  the body; composed of a series of ductless  glands that secrete their products directly into the  blood  o Works through the action of hormones to    e Hormones alter the metabolic activities of  their target cells or target organs by turning    hormone output by the anterior pituitary declines,  which partially explains muscle atrophy in old age.  Elderly persons are less able to resist stress and infec-  tion. This decreased resistance may result from over-  production or underproduction of the defensive  hormones, because both “derail” the stress defense  equilibrium and alter general body metabolism.  Additionally, exposure to pesticides, industrial chem-  icals, dioxin, and other soil and water pollutants  diminishes endocrine function, which may explain  the higher cancer rates among older adults in certain  areas of the country. Older people are often mildly  hypothyroid. All older people have some decline in  insulin production, and type 2 diabetes is most com-  mon in this age group.    20. Which two digestive system organs are important  sources of hormones associated with digestion?   21. What temporary organ produces the same  hormones as the ovaries?   22. Failure of which endocrine organ(s) leads to  menopause in women?   23. In the elderly, the decline in the level of which  hormone is associated with muscle atrophy? With  osteoporosis in women?    a) Listen to the story of this chapter in a brief summary at Mastering A&P >  vt Study Area > Author Narrated Audio Summaries   o Amino acid-based hormones (except thyroid  hormone) act through second messengers   e The ability of a target organ to respond to a hor-  mone requires the presence of receptors to the    hormone in or on its cells to which the hormone  binds    e The pituitary gland hangs from the hypothala-  mus of the brain by a stalk and is enclosed by  bone    ° Releasing hormones and inhibiting  hormones made by the hypothalamus regu-  late release of hormones made by the anterior  pituitary   ° The hypothalamus also makes two hormones  that are transported along the axons of the  hypothalamic neurosecretory cells to the pos-  terior pituitary for storage and later release    e The posterior pituitary is neural tissue that  stores and releases hypothalamic hormones on  command    ° Oxytocin: Stimulates powerful uterine con-  tractions and causes milk ejection in nursing  women    ° Antidiuretic hormone (ADH): Causes kidney  tubule cells to reabsorb and conserve body  water and increases blood pressure by constrict-  ing blood vessels (also called vasopressin)    = Hyposecretion of ADH leads to diabetes  insipidus  e The anterior pituitary is glandular tissue  ° Except for growth hormone and prolactin, hor-  mones of the anterior pituitary are all tropic  hormones, meaning they stimulate other  glands to secrete hormones    ° Growth hormone (GH): An anabolic and  protein-conserving hormone that promotes  total body growth; major effects are directed at  skeletal muscles and bones    = Untreated hyposecretion during childhood  results in pituitary dwarfism; hypersecre-  tion produces gigantism (in childhood) and  acromegaly (in adulthood)    ° Adrenocorticotropic hormone (ACTH):  Stimulates the adrenal cortex to release its hor-  mones, mainly glucocorticoids   ° Thyroid-stimulating hormone (TSH):  Stimulates the thyroid gland to release thyroid  hormone    ° Gonadotropic hormones include FSH and  LH; hyposecretion of either results in sterility    a Follicle-stimulating hormone (FSH):  Stimulates follicle development and estrogen  production by the female ovaries (at puber-  ty); promotes sperm production in the testes    = Luteinizing hormone (LH): Stimulates  ovulation (at puberty), causes the ruptured  ovarian follicle to produce progesterone;  stimulates testes to produce testosterone    9.2b. Pineal gland—located posterior to the third  ventricle of the brain, releases melatonin, which  affects sleep-wake cycles    e Thyroid hormone is produced by thyroid  follicles and has two forms: thyroxine (T,) and  triiodothyronine (T3;); both require iodine to be  active    ° Thyroxine is the body's major metabolic hor-  mone, and increases the rate at which cells oxi-  dize glucose; it is necessary for normal growth  and development    ° Lack of iodine leads to goiter caused by a  buildup of inactive thyroid hormone    o Hyposecretion of thyroxine results in cretinism  in children and myxedema in adults    o Hypersecretion results from Graves’ disease  (often characterized by exophthalmos) or  other forms of hyperthyroidism    e Calcitonin is released by parafollicular cells  surrounding the thyroid follicles in response to a  high blood calcium ion level; results in calcium  being deposited in bones    9.2d. Parathyroid glands—four small glands  located on the posterior aspect of the thyroid gland    e Parathyroid glands to release parathyroid hormone  (PTH) in response to low blood calcium ion levels  o Osteoclasts are stimulated to release calcium  from bone into the blood  e Hyposecretion of PTH results in tetany    9.2e. Thymus—located in the upper thorax;  secretes the hormone thymosin, which promotes  maturation of T lymphocytes for body defense    9.2f. Adrenal glands—paired glands perched  on the kidneys; each gland has two functional  endocrine portions, the cortex and the medulla    e Adrenal cortex produces steroid hormones, col-  lectively called corticosteroids, which include  the following:    o Mineralocorticoids—aldosterone regulates  sodium ion (Na*) reabsorption and potassium  ion (K*) secretion by the kidneys    = Release is stimulated primarily by low Na*  and/or high K* levels in blood    = Release also stimulated by the renin-  angiotensin II system, which increases  blood volume and pressure    = Antagonized by atrial natriuretic peptide  (ANP), which reduces blood volume and  blood pressure    o Glucocorticoids—enable the body to resist  long-term stress by increasing the blood glucose  level and depressing the inflammatory response    ° Sex hormones (mainly androgens and some  estrogens) are produced in small amounts  throughout life    o Generalized hypoactivity of the adrenal cortex  results in Addison’s disease    o Hypersecretion can result in hyperaldo-  steronism, Cushing’s syndrome, and/or  masculinization    e The adrenal medulla produces catecholamines  (epinephrine and norepinephrine) in response  to sympathetic nervous system stimulation  ° Hormones enhance and prolong the effects of  the “fight-or-flight” (sympathetic nervous sys-  tem) response to short-term stress   o Hypersecretion leads to symptoms typical of  sympathetic nervous system overactivity    9.2g. Pancreatic islets, also called islets of  Langerhans—endocrine cells of the pancreas,  located in the abdomen close to the stomach; the  pancreas is a mixed gland    ° Insulin is released by beta cells in response to  high blood glucose levels    = It increases the rate of glucose uptake and  metabolism by body cells    = Hyposecretion of insulin results in diabe-  tes mellitus, which severely disturbs body  metabolism; cardinal signs are polyuria,  polydipsia, and polyphagia   = Poorly controlled diabetes can lead to  ketosis, a type of acidosis    o Glucagon is released by alpha cells in  response to low blood glucose levels    = Stimulates the liver to release glucose, in-  creasing blood glucose levels    = Stimulate maturation of the female reproduc-  tive organs and secondary sex characteristics.    = Work with progesterone to cause the  menstrual cycle, or menstruation    ° Progesterone—released from the ovary in  response to a high blood level of LH.    e The testes of the male begin to produce testos-  terone at puberty in response to LH stimulation    o Testosterone promotes maturation of the male  reproductive organs, male secondary sex charac-  teristics, and production of sperm by the testes    e Hyposecretion of gonadal hormones results in  sterility in both females and males    e Several organs that are generally nonendocrine in  overall function, such as the stomach, small intestine,  kidneys, and heart, have cells that secrete hormones    e The placenta is a temporary organ formed in the  uterus of pregnant women    ° Primary endocrine role—produce estrogen and  progesterone (stimulated by human chorionic  gonadotropin), which maintain pregnancy  and ready the breasts for lactation (in conjunc-  tion with human placental lactogen)    e Decreasing function of female ovaries at meno-  pause leads to such symptoms as osteoporosis,  increased chance of arteriosclerosis, and possible  mood changes   tes mellitus, immune system depression, lower  metabolic rate, and increasing rates of cancer    Multiple Choice 7. Which of the following is (are) associated with the    . Which of the following hormones is (are) secreted by b   conte! is the second messenger that will signal a change in   . ANP, the hormone secreted by the heart, has exactly cell activity.    the opposite function to this hormone secreted by the  outermost zone of the adrenal cortex.    11. Explain what mechanism of hormone action is occur-  ring in this image. How does it work? Give an exam- 13.  ple of a hormone that uses this mechanism.    Briefly describe how a steroid hormone affects the  activity of the target cell.    Provide one example for each way endocrine glands  are stimulated to release their hormones.    Describe the body location of each of the following  endocrine organs: anterior pituitary, pineal gland,  thymus, pancreas, ovaries, testes. Then, for each  organ, name its hormones and their effect(s) on body  processes. Finally, for each hormone, list the impor-  tant results of its hypersecretion or hyposecretion.    What anatomical feature makes it possible for the  releasing hormones from the hypothalamus to influ-  ence the activity of the anterior pituitary?    What is the role of alpha and beta cells in the regula-  tion of blood glucose?    The adrenal cortex produces corticosteroids. What is  the difference between mineralocorticoids and gluco-  corticoids with regard to their production sites? What  major functions do they monitor?    19. The parents of 14-year-old Megan are concerned  about her height because she is only 4 feet tall and  they are both close to 6 feet tall. After tests by their  doctor, certain hormones are prescribed for the girl.  What is the probable diagnosis? What hormones are  prescribed, and why might the girl expect to reach  normal height?    20. Mr. Flores brings his wife to the clinic, concerned  about her nervousness, heart palpitations, and  excessive sweating. Tests show hyperglycemia and    hypertension. What hormones are probably being  hypersecreted? What is the cause? What physical fac-  tors allow you to rule out thyroid problems?    Melissa, age 40, comes to the clinic, troubled by swell-  ing in her face and unusual fat deposition on her back  and abdomen. She reports that she bruises easily.  Blood tests show an elevated glucose level. What is  your diagnosis, and which glands might be causing  the problem?    Blood transports  oxygen, nutrients, and other  substances throughout the body  and participates in processes such  as clotting and fighting  infections.    Transportation via  blood is the only way substances  can be moved to distant body  locations. In addition, clotting  proteins are found only in  blood—without them, a minor cut  could be life-threatening!   place to another within the body—nutrients,  hormones, wastes (headed for elimination from the  body), and body heat—through blood vessels. Long  before modern medicine, blood was viewed as mag-  ical because when it drained from the body, life  departed as well.   In this chapter, we consider the composition and  function of this life-sustaining fluid. In the cardio-  vascular system chapter (Chapter 11), we discuss the  means by which blood is propelled throughout  the body.    Blood is moved  through blood vessels by the  pumping action of the heart. This  fluid contains red blood cells to carry  oxygen, clotting proteins to stop  bleeding, and white blood cells  to fight infections.    1# Describe the composition and volume of whole  blood.  1# Describe the composition of plasma, and discuss  its importance in the body.  Blood is unique: It is the only fluid tissue in the body.  Although blood appears to be a thick, homogeneous  liquid, the microscope reveals that it has both solid  and liquid components.    Blood is a complex connective tissue in which living  blood cells, the formed elements, are suspended in  plasma (plaz’mah), a nonliving fluid matrix. The  collagen and elastin fibers typical of other connec-  tive tissues are absent from blood; instead, dissolved  proteins become visible as fibrin strands during  blood clotting.   If a sample of blood is separated, the plasma  rises to the top, and the formed elements, being  heavier, fall to the bottom (Figure 10.1). Most of the  reddish “pellet” at the bottom of the tube is erythro-  cytes (é-rith'ro-sits; erythro = red), or red blood cells,  the formed elements that function in oxygen trans-  port. There is a thin, whitish layer called the buffy  coat at the junction between the erythrocytes and  the plasma (just barely visible in Figure 10.1). This  layer contains the remaining formed elements, leuko-  cytes (lu'ko-sits; leuko = white), white blood cells that  act in various ways to protect the body; and platelets,  cell fragments that help stop bleeding. Erythrocytes  normally account for about 45 percent of the total  volume of a blood sample, a percentage known as  the hematocrit (“blood fraction”). White blood  cells and platelets contribute less than 1 percent, and  plasma makes up most of the remaining 55 percent  of whole blood.   Blood is a sticky, opaque fluid that is heavier than  water and about five times thicker, or more viscous,  largely because of its formed elements. Depending  on the amount of oxygen it is carrying, the color of  blood varies from scarlet (oxygen-rich) to a dull red  or purple (oxygen-poor). Blood has a characteristic  metallic, salty taste (something we often discover as  children). Blood is slightly alkaline, with a pH  between 7.35 and 7.45. Its temperature (38°C, or  100.4°F) is always slightly higher than body temper-  ature because of the friction produced as blood flows  through the vessels. Blood accounts for approxi-  mately 8 percent of body weight, and its volume in  healthy adults is 5 to 6 liters, or about 6 quarts.   Plasma, which is approximately 90 percent water, is  the liquid part of the blood. Over 100 different sub-  stances are dissolved in this straw-colored fluid.  Examples of dissolved substances include nutrients,  salts (electrolytes), respiratory gases, hormones,    plasma proteins, and various wastes and products of  cell metabolism. (Other substances found in plasma  are listed in Figure 10.1).   Plasma proteins are the most abundant solutes in  plasma. Except for antibodies and protein-based  hormones, the liver makes most plasma proteins.  The plasma proteins serve a variety of functions. For  instance, albumin (al-bu’min) acts as a carrier to  shuttle certain molecules through the circulation, is  an important blood buffer, and contributes to the  osmotic pressure of blood, which acts to keep water  in the bloodstream. Clotting proteins help stem  blood loss when a blood vessel is injured, and anti-  bodies help protect the body from pathogens.  Plasma proteins are not taken up by cells to be used  as food fuels or metabolic nutrients, as are other sol-  utes such as glucose, fatty acids, and oxygen.   The composition of plasma varies continuously  as cells exchange substances with the blood.  Assuming a healthy diet, however, the composition  of plasma is kept relatively constant by various  homeostatic mechanisms of the body. For example,  when blood proteins drop to undesirable levels, the  liver is stimulated to make more proteins, and when  the blood starts to become too acidic (acidosis) or too  basic (alkalosis), both the respiratory and urinary sys-  tems are called into action to restore it to its normal,  slightly alkaline pH range of 7.35 to 7.45. Various  body organs make dozens of adjustments day in and  day out to maintain the many plasma solutes at life-  sustaining levels. Besides transporting various sub-  stances around the body, plasma helps to distribute  body heat, a by-product of cellular metabolism,  evenly throughout the body.    1. Which body organ plays the main role in producing  plasma proteins?  2. What are the three major categories of formed  elements?  3. What determines whether blood is bright red  (scarlet) or dull red?  For answers, see Appendix A.    4# List the cell types making up the formed elements,  and describe the major functions of each type.   vz Define anemia, polycythemia, leukopenia, and  leukocytosis, and list possible causes for each  condition.    How would a decrease in the amount of plasma  proteins affect plasma volume?    Substances transported by blood Platelets  Nutrients (glucose, fatty acids, amino è @ eg REO Blood clotting  acids, vitamins) a a  Waste products of metabolism  (urea, uric acid)    Figure 10.2 Photomicrograph of a blood smear.  Most of the cells in this view are erythrocytes (red blood  cells). Two kinds of leukocytes (white blood cells) are  also present: lymphocytes and neutrophils. Also note  the platelets.    If you observe a stained smear of human blood  under a light microscope, you will see disc-shaped  red blood cells, a variety of gaudily stained spherical  white blood cells, and some scattered platelets that  look like debris (Figure 10.2). However, erythrocytes  vastly outnumber the other types of formed ele-  ments. (Look ahead to Table 10.2 on p. 359, which  provides a summary of the important characteristics  of the various formed elements. )    Erythrocytes, or red blood cells (RBCs), function  primarily to ferry oxygen to all cells of the body. They  are superb examples of the link between structure  and function. RBCs differ from other blood cells  because they are anucleate (a-nu'kle-at); that is, they  lack a nucleus. They also contain very few organelles.  In fact, mature RBCs circulating in the blood are lit-  erally “bags” of hemoglobin molecules. Hemoglobin  (he’mo-glo’bin) (Hb), an iron-bearing protein,  transports most of the oxygen that is carried in the  blood. (It also binds with a small amount of carbon  dioxide but not at the same binding site as oxygen.)    (look back at Figure 2.19b, p. 71). Globular, or functional,  proteins have at least tertiary structure, meaning that they  are folded into a very specific shape. In this case, the folded  structure of hemoglobin, which has quaternary structure,  allows it to perform the specific function of binding and  carrying oxygen. The structure of globular proteins is also  very vulnerable to pH changes and can be denatured  (unfolded) by a pH that is too high (basic) or low (acidic);  denatured hemoglobin is unable to bind oxygen.    Moreover, because erythrocytes lack mitochon-  dria and make ATP by anaerobic mechanisms, they  do not use up any of the oxygen they are transport-  ing, making them very efficient oxygen transporters  indeed.   Erythrocytes are small, flexible cells shaped like  biconcave discs—flattened discs with depressed cen-  ters on both sides (see the photo on p. 357). Because  of their thinner centers, erythrocytes look like minia-  ture doughnuts when viewed with a microscope.  Their small size and peculiar shape provide a large  surface area relative to their volume, making them  ideally suited for gas exchange.   RBCs outnumber white blood cells by about  1,000 to 1 and are the major factor contributing to  blood viscosity. Although the numbers of RBCs in  the circulation do vary, there are normally about  5 million cells per cubic millimeter of blood. (A  cubic millimeter [mm?] is a very tiny drop of blood,  almost too small to be seen.) When the number of  RBC/mm? increases, blood viscosity, or thickness,  increases. Similarly, as the number of RBCs decreases,  blood thins and flows more rapidly.   Although the numbers of RBCs are important, it  is the amount of hemoglobin in the bloodstream at  any time that really determines how well the erythro-  cytes are performing their role of oxygen transport.  The more hemoglobin molecules the RBCs contain,  the more oxygen they will be able to carry. A single  red blood cell contains about 250 million hemoglo-  bin molecules, each capable of binding 4 molecules  of oxygen, so each of these tiny cells can carry about  1 billion molecules of oxygen! However, much more  important clinically is the fact that normal blood  contains 12-18 grams (g) of hemoglobin per  100 milliliters (ml) of blood. The hemoglobin  content is slightly higher in men (13-18 g/ml) than  in women (12-16 g/ml).    Homeostatic |  K Imbalance 10.1  A decrease in the oxygen-carrying ability of the  blood, whatever the reason, is called anemia (ah-  ne’me-ah; “lacking blood”). Anemia may be the  result of (1) a lower-than-normal number of RBCs or  (2) abnormal or deficient hemoglobin content in the  RBCs. There are several types of anemia (classified  and described briefly in Table 10.1, p. 358), but one  of these, sickle cell anemia, deserves a little more  attention because people with this genetic disorder  are frequently seen in hospital emergency rooms.   In sickle cell anemia (SCA), the body does not  form normal hemoglobin (as in the RBC shown in  part (a) of the figure). Instead, abnormal hemoglo-  bin is formed that becomes spiky and sharp (see part  (b) of the figure) when either oxygen is unloaded or  the oxygen content in the blood decreases below  normal. This change in hemoglobin causes the RBCs  to become sickled (crescent-shaped), to rupture eas-  ily, and to dam up small blood vessels. These events  interfere with oxygen delivery (leaving victims gasp-  ing for air) and cause extreme pain. It is amazing  that this havoc results from a change in just one of  the amino acids in two of the four polypeptide  chains of the hemoglobin molecule!   Sickle cell anemia occurs chiefly in dark-skinned  people who live in the malaria belt of Africa and  among their descendants. Apparently, the same gene  that causes sickling makes red blood cells infected by  the malaria-causing parasite stick to the capillary  walls and then lose potassium, an essential nutri-  ent for survival of the parasite. Hence, the malaria-  causing parasite is prevented from multiplying within  the red blood cells, and individuals with the sickle cell  gene have a better chance of surviving where malaria  is prevalent. Only individuals carrying two copies of  the defective gene have sickle cell anemia. Those car-  rying just one sickling gene have sickle cell trait  (SCT); they generally do not display the symptoms  but can pass on the sickling gene to their offspring.   An excessive or abnormal increase in the number  of erythrocytes is polycythemia (pol’e-si-the’me-  ah). Polycythemia may result from bone marrow  cancer (polycythemia vera). It may also be a normal  physiologic (homeostatic) response to living at high  altitudes, where the air is thinner and less oxygen is  available (secondary polycythemia). Occasionally, ath-  letes participate in illegal “blood doping,” which is  the infusion of a person’s own RBCs back into their  bloodstream to artificially raise oxygen-carrying    (a) Normal erythrocyte has  normal hemoglobin amino acid  sequence in the beta chain.    123 4 5 6 7 146  (b) Sickled erythrocyte results  from a single amino acid  change in the beta chain of  hemoglobin.    Comparison of (a) a normal erythrocyte to (b) a sickled  erythrocyte (6,550x).    capacity. The major problem that results from exces-  sive numbers of RBCs is increased blood viscosity,  which causes blood to flow sluggishly in the body  and impairs circulation.    Although leukocytes, or white blood cells  (WBCs), are far less numerous than red blood cells,  they are crucial to body defense. On average, there  are 4,800 to 10,800 WBCs/mm? of blood, and they  account for less than 1 percent of total blood volume.  White blood cells contain nuclei and the usual  organelles, which makes them the only complete  cells in blood.   Leukocytes form a protective, movable army that  helps defend the body against damage by bacteria,  viruses, fungi, parasites, and tumor cells. As such, they  have some very special characteristics. Red blood cells    factor required for absorption of the vitamin;  intrinsic factor is formed by stomach mucosa cells)    Lack of iron in diet or slow/prolonged bleeding (such  as heavy menstrual flow or bleeding ulcer), which    depletes iron reserves needed to make hemoglobin;  RBCs are small and pale because they lack hemoglobin    which becomes sharp and sickle-shaped under  conditions of increased oxygen use by body; or low  oxygen levels in general occurs mainly in people of    are confined to the bloodstream. White blood cells,  by contrast, are able to slip into and out of the blood  vessels—a process called diapedesis (di"ah-pé-de'’ sis;  “leaping across”). The circulatory system is simply  their means of transportation to areas of the body  where their services are needed for inflammatory or  immune responses (as described in Chapter 12).   In addition, WBCs can locate areas of tissue  damage and infection in the body by responding to  certain chemicals that diffuse from the damaged  cells. This capability is called positive chemotaxis  (ke”mo-tax’is). Once they have “caught the scent,”  the WBCs move through the tissue spaces by  amoeboid (ah-me’boid) motion (they form flow-  ing cytoplasmic extensions that help move them  along). By following the diffusion gradient, they pin-  point areas of tissue damage and rally round in large  numbers to destroy microorganisms and dispose of  dead cells.   Whenever WBCs mobilize for action, the body  speeds up their production, and as many as twice the  normal number of WBCs may appear in the blood  within a few hours. A total WBC count above  11,000 cells/mm? is referred to as leukocytosis  (lu"ko-si-to’sis) (cytosis = an increase in cells).  Leukocytosis generally indicates that a bacterial or  viral infection is stewing in the body. The opposite  condition, leukopenia (lu”ko-pe’ne-ah), is an    abnormally low WBC count (penia = deficiency). It is  commonly caused by certain drugs, such as cortico-  steroids and anticancer agents.    Homeostatic J  —S Imbalance 10.2  Leukocytosis is a normal and desirable response to  infectious threats to the body. By contrast, the exces-  sive production of abnormal WBCs that occurs in  infectious mononucleosis and leukemia is distinctly  pathological. In leukemia (lu-ke’me-ah), literally  “white blood,” the bone marrow becomes cancerous,  and huge numbers of WBCs are turned out rapidly.  Although this might not appear to present a prob-  lem, the “newborn” WBCs are immature and incapa-  ble of carrying out their normal protective functions.  Consequently, the body becomes easy prey for  disease-causing bacteria and viruses. Additionally,  because other blood cell lines are crowded out, severe  anemia and bleeding problems result.    WECs are classified into two major groups—  granulocytes and agranulocytes—depending on  whether or not they contain visible granules (when  stained) in their cytoplasm. Specific characteristics  and microscopic views of the leukocytes are pre-  sented in Table 10.2.    Salmon-colored biconcave  disks; anucleate; literally, sacs  of hemoglobin; most organelles  have been ejected    Cytoplasm stains pale pink and  contains fine granules, which  are difficult to see; deep purple  nucleus consists of three to  seven lobes connected by thin  strands of nucleoplasm    Cytoplasm has a few large blue-  purple granules; U- or S-shaped    Cytoplasm pale blue and appears  as thin rim around nucleus;  spherical (or slightly indented)  dark purple-blue nucleus    Transport oxygen bound to hemoglobin  molecules; also transport small amount  of carbon dioxide    Kill parasitic worms by deluging them  with digestive enzymes; play a complex  role in allergy attacks    Release histamine (vasodilator chemical)  at sites of inflammation; contain  heparin, an anticoagulant    Part of immune system; B lymphocytes  produce antibodies; T lymphocytes are  involved in graft rejection and in fighting  tumors and viruses via direct cell attack    Granulocytes (gran’u-lo-sitz”) are granule-  containing WBCs, named for the granules visible in  their cytoplasm when stained with Wright's stain.  They have lobed nuclei, which typically consist of  several rounded nuclear areas connected by thin  strands of nuclear material. The granulocytes include  neutrophils (nu’tro-filz), eosinophils (e”o-sin'o-  filz), and basophils (ba’so-filz).   e Neutrophils are the most numerous WBCs.  They have a multilobed nucleus and very fine  granules that respond to both acidic and basic  stains. Consequently, the cytoplasm as a whole  stains pink. Neutrophils are avid phagocytes at  sites of acute infection. They are particularly par-  tial to bacteria and fungi, which they kill during  a respiratory burst that deluges the phagocytized  invaders with a potent brew of oxidizing sub-  stances (bleach, hydrogen peroxide, and others).    e Eosinophils have a blue-red nucleus that  resembles earmuffs and brick-red cytoplasmic  granules. Their number increases rapidly during  infections by parasitic worms (tapeworms, etc.)  ingested in food such as raw fish or entering  through the skin. When eosinophils encounter a  parasitic worm, they gather around and release  enzymes from their cytoplasmic granules onto  the parasite’s surface, digesting it away.    e Basophils, the rarest of the WBCs, have large  histamine-containing granules that stain dark  blue to purple. Histamine is a potent inflamma-  tory chemical that makes blood vessels leaky  and attracts other WBCs to the inflamed site.    The second group of WBCs, agranulocytes, lack  visible cytoplasmic granules when stained. Their  nuclei are closer to the norm—that is, they are spher-  ical, oval, or kidney-shaped. The agranulocytes  include lymphocytes (lim’fo-sitz) and monocytes  (mon'o-sitz). Do not confuse lymphocytes (one  type of WBC) with leukocytes (all WBCs). A good  memory tool is “All lymphocytes are leukocytes, but  not all leukocytes are lymphocytes.”    e Lymphocytes have a large, dark purple nucleus  that occupies most of the cell volume. Only  slightly larger than RBCs, lymphocytes tend to  take up residence in lymphatic tissues, such as  the tonsils, where they play an important role in  the immune response. They are the second most  numerous leukocytes in the blood.    e Monocytes are the largest of the WBCs. Ex-  cept for their more abundant cytoplasm and    distinctive U- or kidney-shaped nucleus, they  resemble large lymphocytes. When they migrate  into the tissues, they change into macrophages  with huge appetites (macro = large; phage = one  that eats; so, “big eaters”). Macrophages are  important in fighting chronic infections, such as  tuberculosis, and in activating lymphocytes.    Students are often asked to list the WBCs in order  of relative abundance in the blood—from most to  least. The following phrase may help you with this  task: Never let monkeys eat bananas (neutrophils,  lymphocytes, monocytes, eosinophils, basophils).    Platelets are not technically cells. They are fragments  of bizarre multinucleate cells called megakaryocytes  (meg’ah-kar’e-o-sitz), which pinch off thousands of  anucleate platelet “pieces” that quickly seal themselves  off from the surrounding fluids. The platelets appear  as darkly staining, irregularly shaped bodies scattered  among the other blood cells. The normal platelet  count in blood is about 300,000 cells per mm’.  Platelets are needed for the clotting process that stops  blood loss from broken blood vessels (see Table 10.2).  (We explain this process on p. 363.)   4. What is the role of hemoglobin in the red blood  cell?   5. Which white blood cells are most important in body  immunity?   6. If you had a severe infection, would you expect  your WBC count to be closest to 5,000, 10,000, or  15,000 per mm??   7. Lisa, age 5, is pale and fatigued. What disorder of  erythrocytes might she be suffering from?    Blood cell formation, or hematopoiesis (hem”ah-  to-po-e’sis), occurs in red bone marrow, or myeloid  tissue. In adults, this tissue is found chiefly in the  axial skeleton, pectoral and pelvic girdles, and prox-  imal epiphyses of the humerus and femur. Each type  of blood cell is produced in different numbers in  response to changing body needs and different    Figure 10.3 The development of blood cells. All  blood cells differentiate from hemocytoblast stem cells  in red bone marrow. The population of stem cells  renews itself by mitosis. Some daughter cells become  lymphoid stem cells, which develop into two classes of  lymphocytes that function in the immune response. All  other blood cells differentiate from myeloid stem cells.    stimuli. After they mature, they are discharged into  the blood vessels surrounding the area. On average,  the red marrow turns out an ounce of new blood  containing 100 billion new cells every day.   All the formed elements arise from a common  stem cell, the hemocytoblast (he”mo-si'to-blast;  “blood cell former”), which resides in red bone mar-  row. Their development differs, however, and once a  cell is committed to a specific blood pathway, it can-  not change. The hemocytoblast forms two types of  descendants—the lymphoid stem cell, which produces  lymphocytes, and the myeloid stem cell, which can  produce all other classes of formed elements  (Figure 10.3).    Because they are anucleate, RBCs are unable to syn-  thesize proteins, grow, or divide. As they age, RBCs  become rigid and begin to fall apart in 100 to 120  days. Their remains are eliminated by phagocytes in  the spleen, liver, and other body tissues. Some RBC  components are salvaged for reuse or recycled to  their building blocks. Iron is bound to protein as fer-  ritin, and the balance of the heme group is degraded  to bilirubin, which is then secreted into the intestine    by liver cells. There it becomes a brown pigment  called stercobilin that leaves the body in feces.  Globin is broken down to amino acids, which are  released into the circulation.   Lost blood cells are replaced more or less contin-  uously by the division of hemocytoblasts in the red  bone marrow. The developing RBCs divide many  times and then begin synthesizing huge amounts of  hemoglobin. When enough hemoglobin has been  accumulated, the nucleus and most organelles are  ejected, and the cell collapses inward. The result is  the young RBC, called a reticulocyte (ré-tik’u-lo-sit)  because it still contains some rough endoplasmic  reticulum (ER). The reticulocytes enter the blood-  stream to begin their task of transporting oxygen.  Within 2 days of release, they have ejected the  remaining ER and have become fully functioning  erythrocytes. The entire developmental process from  hemocytoblast to mature RBC takes 3 to 5 days.   The rate of erythrocyte production is controlled  by a hormone called erythropoietin (€-rith”ro-po-  e’tin). Normally a small amount of erythropoietin  circulates in the blood at all times, and red blood  cells are formed at a fairly constant rate. Although  the liver produces some, the kidneys play the major  role in producing this hormone. When the blood  level of oxygen begins to decline for any reason, the  kidneys (a convenient location to monitor blood)  step up their release of erythropoietin. Erythropoietin  targets the bone marrow, prodding it into “high  gear” to turn out more RBCs. (Follow this sequence  of events in Figure 10.4, p. 362.)    Chapter 1, p. 41). In this case, erythropoietin is released  in response to a low blood oxygen level, which stimu-  lates the bone marrow to produce more red blood cells.  With their numbers increased, the red cells carry more  oxygen, increasing the blood oxygen level and reducing  the initial stimulus.    As you might expect, an overabundance of eryth-  rocytes, or an excessive amount of oxygen in the  bloodstream, depresses erythropoietin release and  red blood cell production. However, RBC produc-  tion is controlled not by the relative number of RBCs  in the blood, but by the ability of the available RBCs  to transport enough oxygen to meet the body’s  demands.    Like erythrocyte production, the formation of leuko-  cytes and platelets is stimulated by hormones. These  colony stimulating factors (CSFs) and interleukins not  only prompt red bone marrow to turn out leuko-  cytes, but also enhance the ability of mature leuko-  cytes to protect the body. Apparently, they are  released in response to specific chemical signals in  the environment, such as inflammatory chemicals  and certain bacteria or their toxins. The hormone  thrombopoietin, produced by the liver, accelerates the  production of platelets from megakaryocytes, but lit-  tle is known about how that process is regulated.   When bone marrow problems or a disease con-  dition such as leukemia is suspected, a special needle  is used to withdraw a small sample of red marrow  from one of the flat bones (ilium or sternum) close  to the body surface. This procedure provides cells for  a microscopic examination called a bone marrow  biopsy.    8. What is the name of the stem cell that gives rise to  all formed elements?  9. What property of RBCs dooms them to a limited  life soan of about 120 days?  10. How is the production of platelets different from  that of all other formed elements?   Normally, blood flows smoothly past the intact lin-  ing (endothelium) of blood vessel walls. But if a  blood vessel wall breaks, a series of reactions starts  the process of hemostasis (hem = blood; stasis =  standing still), or stopping the bleeding. This  response, which is fast and localized, involves many  substances normally present in plasma, as well as  some that are released by platelets and injured tissue  cells.    Hemostasis involves three major phases, which occur  in rapid sequence: vascular spasms, platelet plug  formation, and coagulation, or blood clotting.  Blood loss at the site is prevented when fibrous tis-  sue grows into the clot and seals the hole in the  blood vessel.    @ Vascular spasms occur. The immediate  response to blood vessel injury is vasoconstric-  tion, which causes blood vessel spasms. The  spasms narrow the blood vessel, decreasing  blood loss until clotting can occur. (Other fac-  tors causing vessel spasms include direct injury  to the smooth muscle cells, stimulation of  local pain receptors, and release of serotonin  by anchored platelets. )    @ Platelet plug forms. Platelets are repelled by  an intact endothelium, but when the under-  lying collagen fibers of a broken vessel are  exposed, the platelets become “sticky” and  cling to the damaged site. Anchored platelets  release chemicals that enhance the vascular  spasms and attract more platelets to the site.  As more and more platelets pile up, a platelet  plug forms.    @ Coagulation events occur. At the same time,  the injured tissues are releasing tissue factor  (TF), which interacts with PF; (platelet factor  3), a phospholipid that coats the surfaces of  the platelets. This combination interacts with  other clotting factors and calcium ions (Ca**),  which are essential for many steps in the clot-  ting process, to form an activator that leads  to the formation of thrombin, an enzyme.  Thrombin then joins soluble fibrinogen (fi-  brin’o-jen) proteins into long, hairlike mol-  ecules of insoluble fibrin. Fibrin forms a  meshwork that traps RBCs and forms the  basis of the clot (Figure 10.6, p. 364). Within  the hour, the clot begins to retract, squeezing  serum (plasma minus the clotting proteins)  from the mass and pulling the ruptured edges  of the blood vessel closer together.    Normally, blood clots within 3 to 6 minutes. As  a rule, once the clotting cascade has started, the trig-  gering factors are rapidly inactivated to prevent    Platelets release  chemicals that make  nearby platelets sticky;  more platelets are  attracted to the area;  platelet plug forms.   e Clotting factors present  in plasma and released  by injured tissue cells  interact with Ca?* in a  complex cascade  resulting in the  production of fibrin.    e Fibrin forms a mesh that 10  traps red blood cells and  platelets, forming the clot.    widespread clotting. Eventually, the endothelium  regenerates, and the clot is broken down. Once these  events of the clotting cascade were understood, it  became clear that placing sterile gauze over a cut or  applying pressure to a wound would speed up the  clotting process. The gauze provides a rough surface  to which the platelets can adhere, and the pressure  fractures cells, increasing the release of tissue factor  locally.    Figure 10.6 Fibrin clot. Scanning electron micrograph  (artificially colored) of red blood cells trapped in a mesh  of fibrin threads.    Undesirable Clotting  Despite the body’s safeguards against abnormal clot-  ting, undesirable clots sometimes form in unbroken  blood vessels, particularly in the legs. A clot that  develops and persists in an unbroken blood vessel is  called a thrombus (throm’bus). If the thrombus is  large enough, it may prevent blood from flowing to  the cells beyond the blockage. For example, if the  blockage forms in the blood vessels serving the lungs  (pulmonary thrombosis, as shown in the figure), the  consequences may be death of lung tissue and fatal  hypoxia (inadequate oxygen delivery to body tissues).  If a thrombus breaks away from the vessel wall and  floats freely in the bloodstream, it becomes an  embolus (em’bo-lus; plural emboli). An embolus is  usually no problem unless or until it lodges in a  blood vessel too narrow for it to pass through. For  example, a cerebral embolus may cause a stroke, in  which brain tissue dies.   Undesirable clotting may be caused by anything  that roughens the endothelium of a blood vessel and    encourages clinging of platelets, such as severe burns,  physical blows, or an accumulation of fatty material.  Slowly flowing blood, or blood pooling, is another  risk factor, especially in immobilized patients. In this  case, clotting factors are not washed away as usual  and accumulate so that clot formation becomes  possible. A number of anticoagulants, the most  important of which are aspirin, heparin, and warfa-  rin, are used clinically for thrombus-prone patients.   The most common causes of abnormal bleeding are  platelet deficiency (thrombocytopenia) and deficits of  some of the clotting factors, such as might result  from impaired liver function or certain genetic  conditions.   Thrombocytopenia results from an insufficient  number of circulating platelets. It can arise from any  condition that suppresses the bone marrow, such as  bone marrow cancer, radiation, or certain drugs. In this  disorder, even normal movements cause spontaneous  bleeding from small blood vessels. This is evidenced by  many small purplish blotches, called petechiae (pé-  te’ke-e), that resemble a rash on the skin.   When the liver is unable to synthesize its usual  supply of clotting factors, abnormal and often severe  bleeding episodes occur. If vitamin K (needed by the  liver cells to produce the clotting factors) is deficient,  the problem is easily corrected with vitamin K supple-  ments. However, when liver function is severely  impaired (as in hepatitis and cirrhosis), only whole  blood transfusions are helpful. Transfusions of concen-  trated platelets provide temporary relief from bleeding.   The term hemophilia (he’mo-fil’e-ah) applies  to several different hereditary bleeding disorders that  result from a lack of any of the factors needed for  clotting. The hemophilias have similar signs and    symptoms that begin early in life. Even minor tissue  trauma results in prolonged bleeding and can be life-  threatening. Repeated bleeding into joints causes  them to become disabled and painful.   When a bleeding episode occurs, hemophiliacs  are given a transfusion of fresh plasma or injections  of the purified clotting factor they lack. Because  hemophiliacs are absolutely dependent on one or  the other of these therapies, some have become the  victims of blood-transmitted viral diseases such as  hepatitis and HIV. These problems have been largely  resolved because of the availability of genetically  engineered clotting factors and hepatitis vaccines.    Did You Get It?  11. What factors enhance the risk of thrombus  formation in intact blood vessels?  For the answer, see Appendix A.    Learning Objectives  v@ Describe the ABO and Rh blood groups.  Explain the basis for a transfusion reaction.    As we have seen, blood is vital for transporting sub-  stances through the body. When blood is lost, the  blood vessels constrict, and the bone marrow steps  up blood cell formation in an attempt to maintain  circulation. However, the body can compensate for a  loss of blood volume only up to a certain limit.  Losses of 15 to 30 percent lead to pallor and weak-  ness. Loss of over 30 percent causes severe shock,  which can be fatal.   Whole blood transfusions are routinely given to  replace substantial blood loss and to treat severe  anemia or thrombocytopenia. The usual blood bank  procedure involves collecting blood from a donor  and mixing it with an anticoagulant to prevent clot-  ting. The treated blood can be stored (refrigerated at  4°C, or 39.2°F) until needed for about 35 days.    Although whole blood transfusions can save lives,  people have different blood groups, and transfusing  incompatible or mismatched blood can be fatal.  How so? The plasma membranes of RBCs, like those  of all other body cells, bear genetically determined    proteins (antigens), which identify each person as  unique. An antigen (an’ti-jen) is a substance that the  body recognizes as foreign; it stimulates the immune  system to mount a defense against it. Most antigens  are foreign proteins, such as those that are part of  viruses or bacteria that have managed to invade the  body. Although each of us tolerates our own cellular  (self) antigens, one person’s RBC proteins will be rec-  ognized as foreign if transfused into another person  with different RBC antigens. The “recognizers” are  antibodies present in plasma that attach to RBCs  bearing surface antigens different from those on the  patient's (recipient's) RBCs. Binding of the antibod-  ies causes the foreign RBCs to clump, a phenomenon  called agglutination* (ah-gloo’ti-na’shun), which  leads to the clogging of small blood vessels through-  out the body. During the next few hours, the foreign  RBCs are lysed (ruptured), and their hemoglobin is  released into the bloodstream.   Although the transfused blood is unable to  deliver the increased oxygen-carrying capacity hoped  for and some tissue areas may be deprived of blood,  the most devastating consequence of severe transfu-  sion reactions is that the freed hemoglobin molecules  may block the kidney tubules, causing kidney failure  and death. Transfusion reactions can also cause fever,  chills, nausea, and vomiting, but in the absence of  kidney shutdown these reactions are rarely fatal.  Treatment is aimed at preventing kidney damage by  infusing fluids to dilute and dissolve the hemoglobin  and diuretics to flush it out of the body in urine.   There are over 30 common RBC antigens in  humans, so each person’s blood cells can be classi-  fied into several different blood groups. However, it  is the antigens of the ABO and Rh blood groups that  cause the most vigorous transfusion reactions. We  describe these two blood groups here.   The ABO blood groups are based on which of  two antigens, type A or type B, a person inherits  (Table 10.3, p. 366). Absence of both antigens results  in type O blood, presence of both antigens leads to  type AB, and the presence of either A or B antigen  yields type A or B blood, respectively. In the ABO  blood group, antibodies form during infancy against  the ABO antigens not present on your own RBCs. As  shown in the table, a baby with neither the A nor the  B antigen (group O) forms both anti-A and anti-B    *The RBC antigens that promote this clumping are sometimes  called agglutinogens (ag”loo-tin’o-jenz), and the antibodies  that bind them together are called agglutinins (ah-gloo’ti-ninz).    Blood that  Blood RBC Plasma can be  group antigens Illustration antibodies received White Black Asian Latino  AB A, B A None A, B, AB, O 4 4 7 2  B “Universal  recipient”  B B Anti-A (a B,O 11 19 25 10  Anti-A—\A oO. (a)  B =  A A Anti-B $ À Anti-B (b) A,O 40 26 28 31  x A  O None Anti-A (a) O “Universal 45 51 40 57  H Y Anti-B (b) donor”    antibodies; those with type A antigens (group A)  form anti-B antibodies, and so on. To keep this idea  straight, remember that antibodies against a person’s  own blood type will not be produced.   The Rh blood groups are so named because  one of the eight Rh antigens (agglutinogen D) was  originally identified in Rhesus monkeys. Later the  same antigen was discovered in humans. Most  Americans are Rh* (“Rh positive”), meaning that  their RBCs carry Rh antigen. Unlike the antibodies of  the ABO system, anti-Rh antibodies are not automat-  ically formed by Rh” (“Rh negative”) individuals.  However, if an Rh” person receives Rh* blood, shortly  after the transfusion his or her immune system  becomes sensitized and begins producing anti-Rh*  antibodies against the foreign antigen.   Hemolysis (rupture of RBCs) does not occur in  an Rh’ person with the first transfusion of Rh* blood  because it takes time for the body to react and start  making antibodies. However, the second time and  every time thereafter, a typical transfusion reaction  occurs in which the patient's antibodies attack and  rupture the donor's Rh* RBCs.    An important Rh-related problem occurs in preg-  nant Rh” women who are carrying Rh* babies. The  first such pregnancy usually results in the delivery of  a healthy baby. But because the mother is sensitized  by Rh* antigens that have passed through the pla-  centa into her bloodstream, she will form anti-Rh*  antibodies unless treated with RhoGAM® in the 28th  week of pregnancy and again shortly after giving  birth. RhoGAM® is an immune serum that prevents  this sensitization and subsequent immune response.  If she is not treated and becomes pregnant again  with an Rh* baby, her antibodies will cross through  the placenta and destroy the baby’s RBCs, producing  a condition known as hemolytic disease of the newborn.  The baby is anemic and becomes hypoxic and cya-  notic (the skin takes on a blue cast). Brain damage  and even death may result unless fetal transfusions  are done before birth to provide more RBCs for oxy-  gen transport.    The importance of determining the blood group of  both the donor and the recipient before blood is    $ Learn more at Mastering A&P > Study Area >  Additional Study Tools > Focus on Careers   procedure done for a medical labo-  ratory, says Michael Coté, who super-  vises the phlebotomy staff at Palo Alto  Veterans Administration Hospital in  California. “To make accurate diagnosis  and effective treatment possible, it's  vital to draw a good blood sample,  place it in a sterile container, and pro-    “Anatomy is a key requirement in  phlebotomy training,” Coté says,  “because you have to learn where all  the arteries and veins are located in the  body. You need to know the right  place to insert that needle. Although  90 percent of the blood we draw  comes from the antecubital region  inside the elbow, we may also draw    Cancer patients often show increased  sensitivity to pain, so we have to be  very gentle and use the smallest needle  possible.”   Coté says that a good phlebotomist  must also possess effective interper-  sonal skills: “People are apprehensive  about being stuck with needles, so you  have to be patient and be able to put   “Drawing blood from peo-  ple who are dehydrated can  be difficult because their  blood pressure is lower and  venous return is impaired.  Patients with poor circulation  are also harder to work with.  The blood tends to stay in the  body trunk rather than flow-  ing freely into the extremities °  because they're cold, and it’s  difficult to get a good return  from veins in the arms.    e Drawing blood for testing is the  most important medical lab pro-  cedure in medicine.    e Knowledge of anatomy is essen-  tial for phlebotomists so they can  determine where to insert the  needle.    Good interpersonal skills will help  a phlebotomist put the patient at  ease.    transfused is glaringly obvious. The general proce-  dure for determining ABO blood type essentially  involves testing the blood by mixing it with two dif-    RBCs of a type A person are mixed with the anti-A 14,  serum but not when they are mixed with the anti-B   by anti-B serum but not by anti-A serum. In order to   the Rh factors is done in the same manner as ABO    Cary is bleeding profusely after being hit by a truck  as he was pedaling his bike home. At the hospital,  the nurse asks him whether he knows his blood  type. He tells her that he “has the same blood as  most other people.” What is his ABO blood type?  . What is the difference between an antigen and an  antibody?    Which blood types can be transfused into a person  with type B blood?    Anti-A  Type A (contains Me:  antigen A;  agglutinates with  anti-A serum)    Type AB (contains  antigens A and B;  agglutinates with  both sera)    Type O (contains  no antigens;  does not  agglutinate with  either serum)    Figure 10.7 Blood typing of ABO blood groups.  When serum containing anti-A or anti-B antibodies  is added to a blood sample diluted with saline,  agglutination will occur between the antibody and  the corresponding antigen (if present).    v Explain the basis of physiologic jaundice seen in  some newborn babies.    # Indicate blood disorders that increase in frequency  in the aged.    In the embryo, the entire circulatory system develops  early. Before birth, there are many sites of blood cell    formation—the fetal liver and spleen, among  others—but by the seventh month of development,  the fetus’s red marrow has become the chief site of  hematopoiesis, and it remains so throughout life.  Generally, embryonic blood cells are circulating in  the newly formed blood vessels by day 28 of devel-  opment. Fetal hemoglobin (HbF) differs from the  hemoglobin formed after birth. It has a greater affin-  ity for (can more easily bind) oxygen, a characteris-  tic that is highly desirable because fetal blood is less  oxygen rich than that of the mother. After birth, fetal  blood cells are gradually replaced by RBCs that con-  tain the more typical hemoglobin A (HbA). In situa-  tions in which fetal RBCs are destroyed so fast that  the immature liver cannot rid the body of hemoglo-  bin breakdown products fast enough, the infant  becomes jaundiced (jawn' dist). This type of jaundice  generally causes no major problems and is referred  to as physiologic jaundice, to distinguish it from  more serious disease conditions.   £ Imbalance 10.4  Various congenital diseases result from genetic fac-  tors (such as hemophilia and sickle cell anemia) and  from interactions with maternal blood factors (such  as hemolytic disease of the newborn). Dietary factors  can lead to abnormalities in blood cell formation  and hemoglobin production. Iron-deficiency ane-  mia is especially common in women because of  their monthly blood loss during menses. The young  and the old are particularly at risk for leukemia.   With increasing age, chronic types of leukemias,  anemias, and diseases involving undesirable clot for-  mation are more prevalent. However, these are  usually secondary to disorders of the heart, blood  vessels, or immune system. The elderly are particu-  larly at risk for pernicious anemia, caused by a lack  of vitamin B,,, because the stomach mucosa (which  produces the intrinsic factor required to absorb  vitamin B,,) atrophies with age.    16. How does fetal hemoglobin differ from that of the  adult?  17. What blood-related disorders are particularly  common in the elderly?  For answers, see Appendix A.    A N Listen to the story of this chapter in a brief summary at Mastering A&P >  I Study Area > Author Narrated Audio Summaries    e Buffy coat—the fraction containing white blood  cells (WBCs) and platelets; 1% of whole blood    e Hematocrit—fraction made up of red blood cells  (RBCs); 45 percent of whole blood    e Color is scarlet to dull red, depending on the  amount of oxygen carried    e Temperature is 101.4°F, slightly above body tem-  perature, as a result of friction    10.1c. Plasma is 90 percent water and contains  dissolved nutrients, gases, hormones, wastes,  proteins, and salts    e Plasma composition changes as body cells remove  or add substances to it, but homeostatic mecha-  nisms act to keep it relatively constant    10.1d. Formed elements, the living blood cells that  make up about 45 percent of whole blood, include  the following:    e Erythrocytes, or red blood cells (RBCs) —  biconcave discs, anucleate, transport oxygen  bound to hemoglobin   = Possible causes are bleeding, a decrease in the  number of functional RBCs, or a decrease in  the amount of hemoglobin per cell   = Sickle cell anemia (SCA)—genetic condi-  tion where cells sickle under low oxygen  conditions; sickled cells rupture easily or get  caught in small vessels. Persons with sickle  cell trait (SCT) generally do not have symp-  toms but can pass on the gene to offspring    Polycythemia is an excessive number of RBCs  that may result from bone marrow cancer or a  move to a location where less oxygen is avail-  able in the air (at high altitude, for example)    cells involved in protecting the body; move  toward damaged tissues in response to chemicals  released by damaged cells (positive chemotaxis)  by amoeboid motion and can leave the blood-  stream via diapedesis    o When bacteria, viruses, or other foreign sub-  stances invade the body, WBCs increase in  number (leukocytosis) to fight them in vari-  ous ways  = An abnormal increase in WBCs is seen in    Granulocytes include neutrophils, eosino-  phils, and basophils. The granules in basophils  contain histamine, an agent in the inflamma-  tory process    Other chemicals (colony-stimulating factors,  interleukins, thrombopoietin) stimulate WBC  and platelet production   ° A complex cascade involving tissue factor  (TF), PF3, thrombin, and fibrinogen produces  fibrin, the mesh that forms the clot by trap-  ping other cells and particles. Clot retraction  squeezes serum from the mass and pulls rup-  tured edges of the blood vessel together    o ABO antigens are accompanied by preformed  antibodies against nonself blood antigens (a    10.3 Blood Groups and Transfusions between type B blood and anti-B antibodies   10.4 Developmental Aspects of Blood (p. 368)  Fetal hemoglobin (HbF) has a higher affinity for  oxygen (binds more easily) than does HbA (adult  hemoglobin)    e Complementary antibodies are present in blood  for ABO groups, but not for Rh    cific for are mixed, agglutination (clumping)  occurs as the agglutinogens (red blood cell anti-  gens) and agglutinins (the antibodies that bind    Leukemias are most common in the very young  and very old    e ABO blood groups are most commonly checked  for in patient blood    1. Which would lead to increased erythropoiesis? 4. Polycythemia vera will result in    2. In a person with sickle cell anemia, sickling of RBCs 5. Which of the following are normally associated with    . A person with blood group A can receive blood from    . Which of the following can cause problems in a trans-   If an Rh” mother becomes pregnant, when can hemo-  lytic disease of the newborn not possibly occur in the  child?    Place the letters of these events in the order they occur  during hemostasis.    Name as many different categories of substances car-  ried in plasma as you can.    Name the formed elements that arise from myeloid  stem cells. Name those arising from lymphoid stem  cells.    Explain why an Rh” person does not have a transfu-  sion reaction on the first exposure to Rh* blood. Why  is there a transfusion reaction the second time he or  she receives the Rh* blood?    Why is phlebotomy often considered the most impor-  tant procedure for a medical laboratory?    22. A bone marrow biopsy of Mr. Lee, a man on long- notices that he is short of breath when he walks up    term drug therapy, shows an abnormally high per-  centage of nonhematopoietic connective tissue. What  condition does this indicate? If the symptoms are crit-  ical, what short-term and long-term treatments are  indicated? Which treatment is he more likely to be  given: infusion of whole blood or of packed red cells?    shortness of breath, and chills. Blood tests show ane-  mia, and a bleeding ulcer is diagnosed. What type of  anemia is this?    Swiss Alps studying astronomy. He arrived two days  ago and plans to stay the entire year. However, he    steps and that he tires easily with any physical activity.  His symptoms gradually disappear; after two months,  he feels fine. Upon returning to the United States, he  has a complete physical exam and is told that his  erythrocyte count is higher than normal. (a) Attempt  to explain this finding. (b) Will his RBC count remain  at this higher-than-normal level? Why or why not?    Shao-Mei and Elisha, who are good friends, decide to  donate blood. Shao-Mei discovers that her blood  group is AB Rh” and Elisha’s blood group is O Rh”.  Explain how Elisha could help Shao-Mei if she ever  needed a blood transfusion. Why cannot Shao-Mei  help Elisha in the same way?    The cardiovascular  system delivers oxygen and  nutrients to the body tissues  and carries away wastes  such as carbon dioxide  via blood.   Body organs fail to function properly,  and then, once oxygen becomes    en most people hear the term cardiovas-  cular system, they immediately think of the  heart. We have all felt our own heart    “pound” from time to time when we are nervous.  The crucial importance of the heart has been recog-  nized for ages. However, the cardiovascular system  is much more than just the heart, and from a scien-  tific and medical standpoint, it is important to  understand why this system is so vital to life.   Night and day, minute after minute, our trillions  of cells take up nutrients and excrete wastes. Although  the pace of these exchanges slows during sleep, they  must go on continuously: when they stop, we die.  Cells can make such exchanges only with the intersti-  tial fluid in their immediate vicinity. Thus, some    The heart pumps  blood throughout the body  in blood vessels. Blood flow  requires both the pumping action  of the heart and changes in  blood pressure.    means of changing and “refreshing” these fluids is  necessary to renew the nutrients and prevent pollu-  tion caused by the buildup of wastes. Like a bustling  factory, the body must have a transportation system  to carry its various “cargoes” back and forth. Instead  of roads, railway tracks, and subways, the body’s  delivery routes are its hollow blood vessels.   Most simply stated, the major function of the car-  diovascular system is transportation. Using blood as  the transport vehicle, the system carries oxygen,  nutrients, cell wastes, hormones, and many other  substances vital for body homeostasis to and from  the cells. The force to move the blood around the  body is provided by the beating heart and by blood  pressure.    Figure 11.1 Location of the heart within the thorax. (a) Relationship of    The cardiovascular system includes a muscular  pump equipped with one-way valves and a system of  large and small blood vessels within which the  blood travels. (We discussed blood in Chapter 10.)  Here we will consider the heart (the pump) and the  blood vessels (the “plumbing”).    v Describe the location of the heart in the body,  and identify its major anatomical areas on an  appropriate model or diagram.    The modest size and weight of the heart give few  hints of its incredible strength. Approximately the  size of a person’s fist, the hollow, cone-shaped heart  weighs less than a pound. Snugly enclosed within  the inferior mediastinum (me’de-as-ti‘num), the  medial section of the thoracic cavity, the heart is  flanked on each side by the lungs (Figure 11.1). Its  pointed apex is directed toward the left hip and rests    on the diaphragm, approximately at the level of the  fifth intercostal space. (This is exactly where one  would place a stethoscope to count the heart rate for  an apical pulse.) Its broad posterosuperior aspect, or  base, from which the great vessels of the body  emerge, points toward the right shoulder and lies  beneath the second rib.    The heart is enclosed by a sac called the pericardium  (per’i-kar’de-um) that is made up of three layers: an  outer fibrous layer and an inner serous membrane  pair. The loosely fitting superficial part of this sac is  referred to as the fibrous pericardium. This fibrous  layer helps protect the heart and anchors it to sur-  rounding structures, such as the diaphragm and ster-  num. Deep to the fibrous pericardium is the slippery,  two-layered serous pericardium. The parietal layer  of the serous pericardium, or parietal pericardium,  lines the interior of the fibrous pericardium. At the  superior aspect of the heart, this parietal layer  attaches to the large arteries leaving the heart and  then makes a U-turn and continues inferiorly over  the heart surface as the visceral layer. The visceral  layer of the serous pericardium, or visceral    Figure 11.1 (continued) (b) Relationship of the heart to the sternum and ribs.  (c) Cross-sectional view showing relative position of the heart in the thorax.    pericardium, also called the epicardium, is part of  the heart wall (Figure 11.2, p. 376). In other words,  the visceral pericardium is the innermost layer of the  pericardium and the outermost layer of the heart  wall. Lubricating serous fluid is produced by the  serous pericardial membranes and collects in the  pericardial cavity between these serous layers. This  fluid allows the heart to beat easily in a relatively  frictionless environment as the serous pericardial  layers slide smoothly across each other.    Imbalance 11.1  Inflammation of the pericardium, pericarditis  (per’i-kar-di'tis), often results in a decrease in the  already small amount of serous fluid. This causes the  pericardial layers to rub, bind, and stick to each  other, forming painful adhesions that interfere with  heart movements.    The heart walls are composed of three layers: the  outer epicardium (the visceral pericardium just  described), the myocardium, and the innermost endo-  cardium (see Figure 11.2). The myocardium (mi’o-  kar’de-um) consists of thick bundles of cardiac  muscle twisted and whorled into ringlike arrange-  ments (see Figure 6.2b, p. 202). It is the layer that  actually contracts. Myocardial cells are linked  together by intercalated discs, which contain both  desmosomes and gap junctions. The gap junctions at  the intercalated discs allow ions to flow from cell to  cell, carrying a wave of excitement across the heart.  The myocardium is reinforced internally by a    network of dense fibrous connective tissue called the  “skeleton of the heart.” The endocardium (en"do-  kar’de-um) is a thin, glistening sheet of endothelium  that lines the heart chambers. It is continuous with  the linings of the blood vessels leaving and entering  the heart. (Figure 11.3 on pp. 376-377 shows two  views of the heart—an external anterior view and a  frontal section. As the anatomical areas of the heart  are described in the next section, keep referring to  Figure 11.3 to locate each of the heart structures or  regions.)    The heart has four hollow cavities, or chambers—two  atria (a’tre-ah; singular atrium) and two ventricles  (ven’tri-kulz). Each of these chambers is lined with  endocardium, which helps blood flow smoothly  through the heart. The superior atria are primarily  receiving chambers. As a rule, they are not important in  the pumping activity of the heart. Instead, they assist  with filling the ventricles. Blood flows into the atria  under low pressure from the veins of the body and  then continues on to fill the ventricles. The inferior,  thick-walled ventricles are the discharging chambers, or  actual pumps of the heart. When they contract, blood  is propelled out of the heart and into circulation. The  right ventricle forms most of the heart's anterior sur-  face; the left ventricle forms its apex (Figure 11.3a).  The septum that divides the heart longitudinally is    Figure 11.2 Heart wall and coverings. Note that the visceral layer of the  pericardium and the epicardium of the heart wall are the same structure.    Right atrium ;  Circumflex artery  Right coronary artery  in coronary sulcus (right  atrioventricular groove)    Left coronary artery in  coronary sulcus (left  atrioventricular groove)  Anterior cardiac vein .  Left ventricle  Right ventricle  Great cardiac vein  Marginal artery  Anterior interventricular  artery (in anterior  interventricular sulcus)    Small cardiac vein  Inferior vena cava  : . Apex  (a) Anterior view of heart showing major vessels    referred to as the interatrial septum where it divides  the atria and the interventricular septum where it  divides the ventricles.   Although it is a single organ, the heart functions  as a double pump, with arteries carrying blood away  from and veins carrying blood toward the heart. The  right side works as the pulmonary circuit pump. It  receives oxygen-poor blood from the veins of the  body through the large superior vena cava and  inferior vena cava (plural venae cavae; ka've) and  pumps it out through the pulmonary trunk. The  pulmonary trunk splits into the right and left  pulmonary arteries, which carry blood to the lungs,  where oxygen is picked up and carbon dioxide is  unloaded. Oxygen-rich blood drains from the lungs  and is returned to the left side of the heart through  the four pulmonary veins. This circuit, from the  right ventricle (the pump) to the lungs and back to  the left atrium (receiving chamber), is called the  pulmonary circulation (Figure 11.4, p. 378). Its  only function is to carry blood to the lungs for gas  exchange (oxygen enters the blood, and carbon    dioxide leaves the blood) and then return it to  the heart.   Oxygen-rich blood returned to the left atrium  flows into the left ventricle and is pumped out into the  aorta (a-or'tah), from which the systemic arteries    gen is delivered to tissues, oxygen-poor blood circu-  lates from the tissues back to the right atrium via the  systemic veins, which finally empty their cargo into  either the superior or inferior vena cava. This second  circuit, from the left ventricle through the body tissues  and back to the right atrium, is called the systemic  circulation (see Figure 11.4). It supplies oxygen- and  nutrient-rich blood to all body organs. Because the left  ventricle pumps blood over the much longer systemic  pathway through the body, its walls are substantially  thicker than those of the right ventricle (Figure 11.5,  p. 378), and it is a much more powerful pump.    1. What is the location of the heart in the thorax?    Figure 11.4 The systemic and pulmonary circula-  tions. The left side of the heart is the systemic pump;  the right side is the pulmonary circuit pump. (Although  there are multiple pulmonary arteries and veins to and  from the lungs, respectively, for simplicity only one of  each is shown.)    2. Which heart chamber has the thickest walls? What is  the functional significance of this structural difference?  3. How does the function of the systemic circulation  differ from that of the pulmonary circulation?  For answers, see Appendix A.    Figure 11.5 Anatomical differences in right and  left ventricles. The left ventricle has a thicker wall, and  its cavity is basically circular. The right ventricle cavity is  crescent-shaped and wraps around the left ventricle.    The heart is equipped with four valves, which allow  blood to flow in only one direction through the  heart chambers—from the atria through the ventri-  cles and out the great arteries leaving the heart (see  Figure 11.3b). The atrioventricular (AV) valves  (a”tre-o-ven-trik’u-lar) are located between the atria  and ventricles on each side. These valves prevent  backflow into the atria when the ventricles contract.  The left AV valve—the bicuspid valve, also called  the mitral (mi’tral) valve—consists of two flaps, or  cusps, of endocardium. The right AV valve, the  tricuspid valve, has three cusps. Tiny white cords,  the chordae tendineae (kor’de ten-din’e)—literally,  “tendinous cords” (think of them as “heart  strings” )—anchor the cusps to the walls of the ventri-  cles. When the heart is relaxed and blood is passively  filling its chambers, the AV valve cusps hang limply  into the ventricles (Figure 11.6a).   As the ventricles contract, they press on the  blood in their chambers, and the pressure inside the  ventricles (intraventricular pressure) begins to rise.  This forces the AV valve cusps upward, closing the  valves. At this point the chordae tendineae tighten  and anchor the cusps in a closed position. If the    © Blood returning  to the atria puts  pressure against  AV valves; the AV  valves are forced  open.    © Chordae tendineae  tighten, preventing  valve cusps from  everting into atria.    © As ventricles relax  and intraventricular  pressure falls, blood %@  flows back from  arteries, filling the  cusps of semilunar  valves and forcing    Figure 11.6 Operation of the heart valves. (a) Atrioventricular (AV) valves.    cusps were unanchored, they would blow upward  into the atria like an umbrella being turned inside  out by a gusty wind. In this manner, the AV valves  prevent backflow into the atria when the ventricles  are contracting.   The second set of valves, the semilunar (sem”ï-  lu’nar) valves, guards the bases of the two large  arteries leaving the ventricular chambers. Thus, they  are known as the pulmonary semilunar valve and  aortic semilunar valve (see Figure 11.3b). Each  semilunar valve has three cusps that fit tightly  together when the valves are closed. When the ven-  tricles are contracting and forcing blood out of the  heart, the cusps are forced open and flattened against  the walls of the arteries by the tremendous force of  rushing blood (Figure 11.6b). Then, when the ventri-  cles relax, the blood begins to flow backward toward  the heart, and the cusps fill with blood like a para-  chute filling with air, closing the valves. This main-  tains one-way blood flow and prevents arterial blood  from reentering the heart.   Each set of valves operates at a different time.  The AV valves are open during heart relaxation and  closed when the ventricles are contracting. The semi-  lunar valves are closed during heart relaxation and  are forced open when the ventricles contract. The  valves force blood to continually move forward  through the heart by opening and closing in response  to pressure changes in the heart.    Homeostatic J  —S~ Imbalance 11.2  Heart valves are simple devices, and the heart—like  any mechanical pump—can function with “leaky”  valves as long as the damage is not too great.  However, severely deformed valves can seriously  hamper cardiac function. For example, an incompe-  tent valve forces the heart to pump and repump the  same blood because the valve does not close prop-  erly, so blood backflows. In valvular stenosis, the valve  cusps become stiff, often because of repeated bacte-  rial infection of the endocardium (endocarditis).  This forces the heart to contract more vigorously  than normal to create enough pressure to drive  blood through the narrowed valve. In each case, the  heart's workload increases, and ultimately the heart  weakens and may fail. Under such conditions, the  faulty valve is replaced with a synthetic valve (see  photo), a cryopreserved human valve, or a chemi-  cally treated valve taken from a pig heart.    Although the heart chambers are bathed with blood  almost continuously, the blood contained in the  heart does not nourish the myocardium. The func-  tional blood supply that oxygenates and nourishes the  myocardium is provided by the right and left coro-  nary arteries. The coronary arteries branch from the  base of the aorta and encircle the heart in the  coronary sulcus (atrioventricular groove) at the  junction of the atria and ventricles (see Figure 11.3a).  The coronary arteries and their major branches (the  anterior interventricular artery and circumflex  artery on the left, and the posterior interventricular  artery and marginal artery on the right) are com-  pressed (flow is inhibited, not stopped completely)  when the ventricles are contracting and fill when the  heart is relaxed. The myocardium is drained by sev-  eral cardiac veins, which empty into an enlarged  vessel on the posterior of the heart called the  coronary sinus. The coronary sinus, in turn, emp-  ties into the right atrium.    Homeostatic J  £ Imbalance 11.3  When the heart beats at a very rapid rate, the myocar-  dium may receive an inadequate blood supply  because the relaxation periods (when the blood is  able to flow to the heart tissue) are shortened.  Situations in which the myocardium is deprived of  oxygen often result in crushing chest pain called  angina pectoris (an-ji’nah pek’tor-is). This pain is a  warning that should never be ignored, because if  angina is prolonged, the oxygen-deprived heart cells  may die, forming an area called an infarct. The result-  ing myocardial infarction (in-fark’shun), or MI, is  commonly called a “heart attack” or a “coronary.”    4. Why are the heart valves important?  5. Why might a thrombus in a coronary artery cause  sudden death?   As the heart beats, or contracts, the blood makes  continuous round-trips—into and out of the heart,  through the rest of the body, and then back to the  heart—only to be sent out again. The amount of  work that a heart does is almost too incredible to  believe. In one day it pushes the body’s supply of 6  quarts or so of blood (6 liters [L]) through the blood  vessels over 1,000 times, meaning that it actually  pumps about 6,000 quarts of blood (1500 gallons)  in a single day!    vz Name the elements of the intrinsic conduction  system of the heart, and describe the pathway of  impulses through this system.    v Explain what information can be gained from an  electrocardiogram.  What makes the heart beat? Unlike skeletal muscle  cells, which must be stimulated by nerve impulses  before they will contract, cardiac muscle cells can    Figure 11.7 The intrinsic  conduction system of the  heart. The depolarization  wave initiated by the sinoatrial  (SA) node passes successively  through the atrial myocardium  to the atrioventricular (AV)  node, the AV bundle, the right  and left bundle branches, and  the Purkinje fibers in the  ventricular walls.    and do contract spontaneously and independently,  even if all nervous connections are severed. Moreover,  these spontaneous contractions occur in a regular  and continuous way. Although cardiac muscle can  beat independently, the muscle cells in different  areas of the heart have different rhythms. Atrial cells  beat about 60 times per minute, but ventricular cells  contract more slowly (20-40 times per minute).  Therefore, without some type of unifying control  system, the heart would be an uncoordinated and  inefficient pump.   Two systems act to regulate heart activity. One of  these involves the nerves of the autonomic nervous  system, which act like brakes and gas pedals to 11  decrease or increase the heart rate, depending on  which division is activated. We consider this topic  later (see p. 385). The second system is the intrinsic  conduction system, or nodal system, that is built  into the heart tissue (Figure 11.7) and sets its basic  rhythm like a drummer sets the beat for a rock band  playing a song. The intrinsic conduction system is  composed of a special tissue found nowhere else in  the body; it is much like a cross between muscle and  nervous tissue. This system causes heart muscle  depolarization in only one direction—from the atria  to the ventricles.   In addition, the intrinsic conduction system  enforces a contraction rate of approximately 75  beats per minute on the heart; thus, the heart beats  as a coordinated unit.    similar to the one-way generation of an action potential  as it travels down the axon of a neuron like a wave  (Chapter 7, pp. 251-253). The signals that stimulate  cardiac muscle contraction also travel one way through-  out the intrinsic conduction system.    One of the most important parts of the intrinsic  conduction system is a crescent-shaped node of tissue  called the sinoatrial (si’no-a’tre-al) (SA) node,  located in the right atrium. Other components include  the atrioventricular (AV) node at the junction of the  atria and ventricles, the atrioventricular (AV) bundle  (bundle of His) and the right and left bundle  branches located in the interventricular septum, and  finally the Purkinje (pur-kin’je) fibers, which spread  within the myocardium of the ventricle walls.   The SA node is a tiny cell mass with a mammoth  job. Because it has the fastest rate of depolarization  in the whole system, it starts each heartbeat and sets  the pace for the whole heart. Consequently, the SA  node is often called the pacemaker. From the SA  node, the impulse spreads through the atrial walls to  the AV node, and then the atria contract. At the AV  node, the impulse is delayed briefly to give the atria  time to finish contracting. It then passes rapidly  through the AV bundle, the bundle branches, and  the Purkinje fibers, resulting in a “wringing” contrac-  tion of the ventricles that begins at the heart apex  and moves toward the atria. This contraction effec-  tively ejects blood superiorly into the large arteries  leaving the heart. “A Closer Look” (on p. 384)  describes electrocardiography, the clinical procedure  for mapping the electrical activity of the heart.    Homeostatic J  —S~ Imbalance 11.4  Because the atria and ventricles are separated from  one another by “insulating” connective tissue, which  is part of the fibrous skeleton of the heart, depolar-  ization waves can reach the ventricles only by travel-  ing through the AV node. Thus, any damage to the  AV node can partially or totally block the ventricles  from the control of the SA node. When this occurs,  the ventricles begin to beat at their own rate, which  is much slower, some or all of the time. This condi-  tion is called heart block.  There are other conditions that can interfere  with the regular conduction of impulses across the    heart—for example, damage to the SA node results  in a slower heart rate. When this is a problem, artifi-  cial pacemakers are usually installed surgically.  Ischemia (is-ke’me-ah), or lack of an adequate  blood supply to the heart muscle, may lead to  fibrillation—a rapid, uncoordinated quivering of  the ventricles (it looks like a bag of wiggling worms).  Fibrillation prevents the heart from pumping any  blood and is a major cause of death from heart  attacks in adults. Many businesses train their employ-  ees in the use of AEDs (automatic external defibrilla-  tors), which has proven to be lifesaving in many    Tachycardia (tak”e-kar'de-ah) is a rapid heart  rate (over 100 beats per minute). Bradycardia  (brad”e-kar'de-ah) is a heart rate that is substantially  slower than normal (less than 60 beats per minute).  Neither condition is pathological, but prolonged  tachycardia may progress to fibrillation.    4 Define systole, diastole, stroke volume, cardiac  cycle, heart sounds, and heart murmur.    In a healthy heart, the atria contract simultaneously.  Then, as they start to relax, the ventricles begin to  contract. Systole (sis’to-le) and diastole (di-as’to-  le) mean heart contraction and relaxation, respectively.  Because most of the pumping work is done by the  ventricles, these terms refer to the contraction and  relaxation of the ventricles unless otherwise stated.   The term cardiac cycle refers to the events of one  complete heartbeat, during which both atria and ven-  tricles contract and then relax. The average heart beats  approximately 75 times per minute, so the length of  the cardiac cycle is normally about 0.8 seconds. We  will consider the cardiac cycle in terms of events  occurring during five periods (Figure 11.8).    © Atrial diastole (ventricular filling). Our  discussion begins with the heart completely  relaxed. Pressure in the heart is low, the AV  valves are open, and blood is flowing passively  through the atria into the ventricles. The semi-  lunar valves are closed.    © Atrial systole. The ventricles remain in diastole  as the atria contract, forcing blood into the ven-  tricles to complete ventricular filling.    Are the ventricular cardiac cells contracting isometrically or  isotonically during phase 3?    opened again.  Low pressure in  both atria and  ventricles allows  passive filling of  the ventricles.    to backflow,  causing AV  valves to close.  All valves are  closed.    be ejected from the ventricles. During this phase,  the atria are again relaxed and filling with blood.    intraventricular pressure closes the AV valves,  preventing backflow of blood into the atria. For  a moment, the ventricles are completely closed  chambers.    @ Ventricular systole (ejection phase). The  ventricles continue to contract, causing the  intraventricular pressure to surpass the pressure  in the major arteries leaving the heart. This  causes the semilunar valves to open and blood to    ©) Isovolumetric relaxation. As ventricular dias-  tole begins, the pressure in the ventricles falls  below that in the major arteries, and the semi-  lunar valves close to prevent backflow into the  ventricles. For another moment, the ventricles  are completely closed chambers and intraven-  tricular pressure continues to decrease. Mean-  while, the atria have been in diastole, filling  with blood. When ventricular pressure falls  below atrial pressure, the AV valves open, and  the cycle repeats.    When using a stethoscope, you can hear two dis-  tinct sounds during each cardiac cycle. These heart  sounds are often described by the two syllables “lub”   the heart, electrical currents  are generated that spread through-  out the body. These impulses can be  detected on the body surface and  recorded with an electrocardiograph.    Learn more at Mastering A&P > Study Area >  Additional Study Tools > A Closer Look    The recording that is made, the elec-  trocardiogram (ECG), traces the  flow of current through the heart.  Abnormalities in the shape of the  waves and changes in their timing  signal that something may be wrong    with the nodal system, or they may  indicate a myocardial infarct (MI), or  heart attack. An MI is an area of  heart tissue in which the cardiac cells  have died; it is generally a result of  ischemia (inadequate blood flow).    During fibrillation (quivering of the  heart), the normal pattern of the  ECG is totally lost, and the heart  ceases to pump blood.   e The QRS complex represents  ventricular depolarization and  hides atrial repolarization.    and “dup,” and the sequence is lub-dup, pause, lub-  dup, pause, and so on. The first heart sound (lub) is  caused by the closing of the AV valves. The second  heart sound (dup) occurs when the semilunar valves  close at the end of ventricular systole. The first heart  sound is longer and louder than the second heart  sound, which tends to be short and sharp.  Homeostatic J  K Imbalance 11.5  Abnormal or unusual heart sounds are called heart  murmurs. Blood flows silently as long as the flow is  smooth and uninterrupted. If it strikes obstructions,  its flow becomes turbulent and generates sounds    that can be heard with a stethoscope. Heart murmurs  are fairly common in young children (and some    elderly people) with perfectly healthy hearts,  probably because their heart walls are relatively thin  and vibrate with rushing blood. However, murmurs  in patients who do not fall into either of these groups  most often indicate valve problems. For example, if a  valve does not close tightly (is incompetent), a swish-  ing sound will be heard as the blood flows back  through the partially open valve after that valve has  (supposedly) closed. Distinct sounds also can be  heard when blood flows turbulently through stenosed  (narrowed) valves.    6. What is the function of the intrinsic conduction  system of the heart?    7. To which heart chambers do the terms systole  and diastole usually apply?  8. During isovolumetric contraction of the cardiac  cycle, which chambers are relaxing, and which  are contracting?  9. What causes the lub-dup sounds heard with a  stethoscope?  For answers, see Appendix A.    v Describe the effect of each of the following  on heart rate: stimulation by the vagus nerve,  exercise, epinephrine, and various ions.    Cardiac output (CO) is the amount of blood  pumped out by each side of the heart (actually each  ventricle) in 1 minute. It is the product of the heart  rate (HR) and the stroke volume (SV). Stroke vol-  ume is the volume of blood pumped out by a ventri-  cle with each heartbeat. In general, stroke volume  increases as the force of ventricular contraction  increases. If we use the normal resting values for  heart rate (75 beats per minute) and stroke volume  (70 ml per beat), the average adult cardiac output  can be easily calculated:    CO = HR (75 beats/min) X SV (70 ml/beat)  CO = 5250 ml/min = 5.25 L/min    The normal adult blood volume is about  6,000 ml, so nearly the entire blood supply passes  through the body once each minute. Cardiac output  varies with the demands of the body. It rises when  the stroke volume is increased, or the heart beats  faster, or both; it drops when either or both of these  factors decrease. Let's take a look at how stroke vol-  ume and heart rate are regulated.    Regulation of Stroke Volume A healthy heart  pumps out about 60 percent of the blood present in  its ventricles. As noted previously, this is approxi-  mately 70 ml (about 2 ounces) with each heartbeat.  Three factors influence stroke volume: preload, con-  tractility, and afterload.   According to the Frank-Starling law of the heart,  the critical factor controlling stroke volume is how  much the cardiac muscle cells are stretched by the  filling of the chambers just before they contract.  This is called the preload. The more the muscle  cells are stretched, the stronger the contraction, and  the higher the stroke volume. Two things influence    preload: the amount of venous return (blood return-  ing to the heart) and the length of time the ventri-  cles are relaxed and filling (determined by heart  rate). Anything that increases the volume or speed  of venous return also increases stroke volume and  force of contraction (Figure 11.9, p. 386). For exam-  ple, a slow heartbeat allows more time for the ven-  tricles to fill, while exercise speeds venous return  because it results in increased heart rate and force.  The enhanced squeezing action of active skeletal  muscles on the veins helps return blood to the  heart, and this so-called muscular pump also plays  a major role in increasing the venous return. In  contrast, low venous return, such as might result  from severe blood loss or an abnormally rapid  heart rate, decreases stroke volume.   Contractility is the ability of cardiac muscle to  generate tension. Contractility is influenced by fac-  tors other than stretch, including the amount of cal-  cium ions present, sympathetic nervous stimulation,  and hormones such as epinephrine and thyroxine.  As contractility increases, stroke volume increases.   Afterload is the amount of pressure the ventri-  cles must overcome to eject blood. Afterload is deter-  mined by the blood pressure in the pulmonary trunk  and aorta pressing back on the semilunar valves. In  order to pump blood, the ventricles must generate a  force greater than the afterload. If afterload increases,  it will be more difficult for the ventricles to pump  blood, and stroke volume will decrease.    Factors Modifying Basic Heart Rate In healthy  people, stroke volume tends to be relatively con-  stant. However, when blood volume drops suddenly  or when the heart has been seriously weakened,  stroke volume declines, and cardiac output is main-  tained by a faster heartbeat. Although heart contrac-  tion does not depend on the nervous system, its rate  can be changed temporarily by the autonomic  nerves. Indeed, the most important external influ-  ence on heart rate is the activity of the autonomic  nervous system. Several chemicals, hormones, and  ions also modify heart rate. Some of these factors are  discussed next (see also Figure 11.9).    1. Neural (ANS) controls. During times of physical  or emotional stress, the nerves of the sympathetic  division of the autonomic nervous system more  strongly stimulate the SA and AV nodes and the  cardiac muscle itself. As a result, the heart beats  more rapidly. This is a familiar phenomenon to    Figure 11.9 Influence of selected factors on cardiac output. Note that any  decrease in heart rate or stroke volume will result in a corresponding decrease in  cardiac output.    anyone who has ever been frightened or has had  to run to catch a bus. As fast as the heart pumps  under ordinary conditions, it really speeds up  when special demands are placed on it. Because  a faster blood flow increases the rate at which  fresh blood reaches body cells, more oxygen and  glucose are made available to them during peri-  ods of stress. When demand declines, the heart  adjusts accordingly. Parasympathetic nerves, pri-  marily vagus nerve fibers, slow and steady the  heart, giving it more time to rest during noncri-  sis times.    . Hormones and ions. Various hormones and  ions can have a dramatic effect on heart activity.  Both epinephrine, which mimics sympathetic  nerves and is released in response to sympathetic  nerve stimulation, and thyroxine, a thyroid hor-  mone, increase heart rate and contractility.    Electrolyte imbalances pose a real threat to the  heart. For example, recall that calcium ions are  required for muscle contraction. A reduced level  of ionic calcium in the blood depresses the  heartbeat, whereas an excessive level of blood  calcium ions causes such prolonged contractions  that the heart may stop entirely. Either excess or  lack of needed ions such as sodium and potas-  sium also modifies heart activity. A deficit of  potassium ions in the blood, for example, causes  the heart to beat feebly, and abnormal heart  rhythms appear.    including age, gender, exercise, and body tem-  perature, influence heart rate. Resting heart rate  is fastest in the fetus (140-160 beats per min-  ute) and then gradually decreases throughout  life. The average adult heart rate is faster in    females (72-80 beats per minute) than in males  (64-72 beats per minute). Heat increases heart  rate by boosting the metabolic rate of heart cells.  This explains the rapid, pounding heartbeat you  feel when you have a high fever and accounts   in part for the effect of exercise on heart rate  (remember, working muscles generate heat).  Cold has the opposite effect; it directly decreases  heart rate. As noted previously, exercise acts  through nervous system controls (sympathetic  division) to increase heart rate (and also,  through the action of the muscular pump, to  increase stroke volume).    Homeostatic J  K Imbalance 11.6  The pumping action of the healthy heart maintains a  balance between cardiac output and venous return.  But when the pumping efficiency of the heart is  reduced so that circulation is inadequate to meet tis-  sue needs, congestive heart failure (CHF) occurs.  Congestive heart failure is usually a progressive con-  dition that reflects weakening of the heart by coro-  nary atherosclerosis (clogging of the coronary vessels  with fatty buildup), hypertensive heart disease, or  multiple myocardial infarctions (repaired with non-  contracting scar tissue). In these patients, the heart  pumps weakly and is nearly “worn out.” The weak  contractions of a heart in CHF result in a lower  stroke volume. For those patients, the drug digitalis  is routinely prescribed. It enhances contractility and  increases stroke volume of the heart, resulting in  greater cardiac output.   Because the heart is a double pump, each side  can fail independently of the other. If the left heart  fails, pulmonary congestion occurs. The right side of  the heart continues to propel blood to the lungs, but  the left side is unable to eject the returning blood  into the systemic circulation. As blood “backs up” in  the lungs, they become swollen with blood, the pres-  sure within them increases, and fluid leaks into the  lung tissue, causing pulmonary edema. If untreated,  the person “drowns” in these fluids.   If the right side of the heart fails, peripheral con-  gestion occurs as blood backs up in the systemic cir-  culation. Edema is most noticeable in the distal parts  of the body: The feet, ankles, and fingers become  swollen and puffy. Failure of one side of the heart  puts a greater strain on the opposite side, and even-  tually the whole heart fails.    10. What does the term cardiac output mean?  11. What would you expect to happen to the heart  rate of an individual with a fever? Why?  12. What is the most important factor affecting stroke  volume?  For answers, see Appendix A.    vz Compare and contrast the structure and function  of arteries, veins, and capillaries.    Blood circulates inside the blood vessels, which form a  closed transport system called the vascular system.  The idea that blood circulates, or “makes rounds,”  through the body is only about 300 years old. The  ancient Greeks believed that blood moved through the  body like an ocean tide, first moving out from the heart  and then ebbing back to it in the same vessels to get rid  of its impurities in the lungs. It was not until the seven-  teenth century that William Harvey, an English physi-  cian, proved that blood did, in fact, move in circles.   Like a system of roads, the vascular system has its  freeways, secondary roads, and alleys. As the heart  beats, it propels blood into the large arteries leaving  the heart. As the large arteries branch, blood moves  into successively smaller and smaller arteries and then  into the arterioles (ar-ter’e-olz), which feed the  capillaries (kap’i-lar’ez) in the tissues. Clusters of cap-  illaries, called capillary beds, are drained by venules  (ven’ulz), which in turn empty into veins that merge  and finally empty into the great veins (venae cavae)  entering the heart. Thus arteries, which carry blood  away from the heart, and veins, which drain the tissues  and return the blood to the heart, are simply conduct-  ing vessels—the freeways and secondary roads. Only  the tiny hairlike capillaries, which extend and branch  through the tissues and connect the smallest arteries  (arterioles) to the smallest veins (venules), directly  serve the needs of the body cells. The capillaries are the  side streets or alleys that intimately intertwine among  the body cells and provide access to individual  “homes.” It is only through their walls that exchanges  between tissue cells and the blood can occur.   Notice that we routinely depict arteries in red  and veins in blue. By convention, red indicates  oxygen-rich blood, the normal status of blood in  most of the body’s arteries, and blue indicates   (a) Light photomicrograph of a muscular artery and the  corresponding vein in cross section (85 x). (b) The walls of  arteries and veins are composed of three tunics: the tunica  intima, tunica media, and tunica externa. Capillaries—    composed only of the tunica intima. Notice that the tunica  media is thick in arteries and relatively thin in veins.    relatively oxygen-depleted, carbon dioxide-rich  blood, the normal status of blood in most of the  veins. However, there are exceptions. For instance, we  have seen that oxygen-poor blood is carried in the  pulmonary trunk, an artery, while oxygen-rich blood  is transported back to the heart in pulmonary veins.  An easy way to remember this difference is the fol-  lowing: Arteries are red and veins are blue, but for the  lungs there's an exception of two.   Except for the microscopic capillaries (which have  only one layer), the walls of blood vessels have three  layers, or tunics (Figure 11.10). The tunica intima  (tu’ni-kah in-tim’ah), which lines the lumen, or inte-  rior, of the vessels, is a thin layer of endothelium    (squamous epithelial cells) resting on a basement  membrane. Its cells fit closely together and form a  slick surface that decreases friction as blood flows  through the vessel lumen.   The tunica media (me’de-ah) is the bulky mid-  dle layer, made up mostly of smooth muscle and  elastic fibers. Some of the larger arteries have elastic  laminae, sheets of elastic tissue, in addition to the  scattered elastic fibers. The smooth muscle, which is  controlled by the sympathetic nervous system, is  active in changing the diameter of the vessels. As the  vessels constrict or dilate, blood pressure increases or  decreases, respectively.   The tunica externa (eks’tern-ah) is the outer-  most tunic. This layer is composed largely of fibrous  connective tissue, and its function is to support and  protect the vessels.    The walls of arteries are usually much thicker than  those of veins. The arterial tunica media, in particular,  tends to be much heavier. This structural difference is  related to a difference in function of these two types of  vessels. Arteries, which carry blood away from the  heart, must be able to expand (stretch) as blood is  forced into them and then recoil passively as the  blood flows off into the circulation during diastole.  Their walls must be strong and stretchy enough to  take these continuous changes in pressure without  stretching out permanently (see Figure 11.19).   Veins, in contrast, carry blood back toward the  heart, and the pressure in them tends to be low all  the time. Thus veins have thinner walls. However,  because the blood pressure in veins is usually too  low to force the blood back to the heart, and because  blood returning to the heart often flows against  gravity (up the legs, for example), veins are modified  to ensure that the amount of blood returning to the  heart (venous return) equals the amount being  pumped out of the heart (cardiac output) at any  time. The lumens of veins tend to be much larger  than those of corresponding arteries, and they tend  to have a thinner tunica media but a thicker tunica  externa. The larger veins have walves that pre-  vent backflow of blood like those in the heart (see  Figure 11.10).    e To see the effect of venous valves, perform the  following simple experiment on yourself: Allow  one hand to hang by your side for a minute or  two, until the blood vessels on its dorsal aspect    become distended (swollen) with blood. Place  two fingertips side by side on top of and perpen-  dicular to one of the distended veins. Then, press-  ing firmly, move your proximal finger along the  vein toward your heart. Now release that finger. As  you can see, the vein remains collapsed in spite of  gravity because your proximal finger pushed the  blood past a valve. Now remove your distal finger,  and watch the vein fill rapidly with blood.    Skeletal muscle activity, known as the muscular  pump, also enhances venous return. As the muscles  surrounding the veins contract and relax, the blood  is squeezed, or “milked,” through the veins toward  the heart (Figure 11.11). Finally, the drop in pressure  that occurs in the thorax just before we inhale causes  the large veins near the heart to fill. Thus, the respira-  tory pump also helps return blood to the heart (see  Figure 11.9).    Figure 11.11 Operation of the muscular pump.  When skeletal muscles contract and press against  the flexible veins, the valves proximal to the area of  contraction are forced open, and blood is squeezed  toward the heart like toothpaste from a tube. The  valves distal to the point of contraction are closed by  the backflowing blood.    Assume the capillary bed depicted here is in the biceps brachii The transpareni walls of the capillaries are only  muscle of your arm. What condition would the capillary bed ONE cell layer thick—just the tunica intima. Because  be in, (a) or (b), if you were doing push-ups at the gym? of this exceptional thinness, substances are  exchanged easily between the blood and the tissue  cells. The tiny capillaries tend to form interweaving  capillary beds. The flow of blood from an arteriole to  a venule—that is, through a capillary bed—is called  microcirculation. In most body regions, a terminal  arteriole branches into 10 to 20 capillaries, the  exchange vessels, which drain into a postcapillary  venule (Figure 11.12). Blood flow in the capillary  Postcapillary bed is controlled by the level of constriction in the  ea venule terminal arteriole and other arterioles feeding into it.   Arteriole Capillaries Venule If the terminal arteriole is dilated, blood enters the  (a) Arterioles dilated—blood flows through capillaries. Capillary bed, and exchange occurs. If the terminal  arteriole is constricted, no blood flows through the  capillary bed.   Special capillary beds are found in the mesenter-  ies (serous membranes holding the intestines in  place). These capillary beds have precapillary  sphincters, which regulate blood flow in the capil-  lary bed, and a vascular shunt (Figure 11.12c). A  vascular shunt is a vessel that directly connects the  arteriole and venule at opposite ends of the bed.  When the precapillary sphincters are relaxed (open),  blood flows through the capillaries and takes part in  exchanges with cells. When the sphincters are con-  (b) Arterioles constricted—no blood flows through tracted (closed), blood flows through the shunt and    Varicose veins are common in people who stand  for long periods of time (for example, cashiers and  hairdressers) and in obese (or pregnant) individu-  als. The common factors are the pooling of blood  in the feet and legs and inefficient venous return  resulting from inactivity or pressure on the veins. In  any case, the overworked valves give way, and the  veins become twisted and dilated. A serious com-  plication of varicose veins is thrombophlebitis  (throm”bo-flé-bi’tis), inflammation of a vein that  results when a clot forms in a vessel with poor cir-  culation. Because all venous blood must pass  through the pulmonary circulation before traveling  through the body tissues again, a common conse-  quence of thrombophlebitis is clot detachment and  pulmonary embolism, which is a life-threatening  condition in which the embolism lodges in a vessel  in the lung.    Figure 11.12 Anatomy of a capillary bed. In part (c),  the vascular shunt bypasses the capillaries when  precapillary sphincters controlling blood entry into the  capillaries are constricted.    13. Assume you are viewing a blood vessel under  the microscope. It has a large, lopsided lumen,  relatively thick tunica externa, and a relatively thin  tunica media. Which kind of blood vessel is this?  14. Arteries lack valves, but veins have them. How is  this structural difference related to blood pressure?  15. How is the structure of capillaries related to their  function in the body?  For answers, see Appendix A.    4# Identify the body's major arteries and veins, and  name the body region supplied by each.    The aorta is the largest artery of the body, and it is a  truly splendid vessel. In adults, the aorta is about the  size of a garden hose (with an internal diameter about  equal to the diameter of your thumb) where it leaves  the left ventricle of the heart. It decreases only slightly  in diameter as it runs to its terminus. Different parts  of the aorta are named for either their location or their  shape. The aorta springs upward from the left ventri-  cle of the heart as the ascending aorta, arches to the  left as the aortic arch, and then plunges downward  through the thorax, following the spine (thoracic  aorta) finally to pass through the diaphragm into the  abdominopelvic cavity, where it becomes the  abdominal aorta (Figure 11.13, p. 392).   The major branches of the aorta and the organs  they serve are listed next in sequence from the heart.  (Figure 11.13 shows the course of the aorta and its  major branches.) As you locate the arteries on the fig-  ure, use what you already know to make your learning  easier. In many cases the name of the artery tells you  the body region or organs served (for example, renal  artery, brachial artery, and coronary artery) or the  bone followed (femoral artery and ulnar artery).   e The only branches of the ascending aorta are  the right (R.) coronary artery and left (L.)  coronary artery, which serve the heart.    Arterial Branches of the Aortic Arch  e The brachiocephalic (bra”ke-o-sé-fal’ik) trunk  (the first branch off the aortic arch) splits into    the R. common carotid (kah-ro’tid) artery,  which further branches into the R. internal and  R. external carotid arteries, and the R. subclavian  (sub-kla’ve-an) artery. (See same-named vessels  on the left side of the body for organs served.)    The L. common carotid artery is the second  branch off the aortic arch. It divides, forming the  L. internal carotid, which serves the brain, and  the L. external carotid, which serves the skin  and muscles of the head and neck.   L. subclavian artery, gives off an important  branch—the vertebral artery, which serves part  of the brain. In the axilla, the subclavian artery  becomes the axillary artery and then continues  into the arm as the brachial artery, which  supplies the arm. At the elbow, the brachial  artery splits to form the radial artery and  ulnar artery, which serve the forearm.    The intercostal arteries (10 pairs) supply the  muscles of the thorax wall. Other branches of  the thoracic aorta supply the lungs (bronchial  arteries), the esophagus (esophageal arteries), and  the diaphragm (phrenic arteries). (These arteries  are not illustrated in Figure 11.13.)    The celiac trunk is the first branch of the  abdominal aorta. It is a single vessel that has  three branches: the L. gastric artery, which sup-  plies the stomach; the splenic artery, which sup-  plies the spleen; and the common hepatic artery, 11  which supplies the liver.    The unpaired superior mesenteric (mes”en-  ter'ik) artery supplies most of the small intestine  and the first half of the large intestine, or colon.    The gonadal (R. and L.) arteries supply the  gonads. They are called the ovarian arteries in  females (serving the ovaries) and the testicular  arteries in males (serving the testes).    The lumbar arteries (not illustrated in Figure 11.13)  are several pairs of arteries serving the heavy  muscles of the abdomen and trunk walls.    The inferior mesenteric artery is a small,  unpaired artery supplying the second half of the  large intestine.    Figure 11.13 Major arteries of the systemic  circulation, anterior view. All arteries are bilateral  unless otherwise stated in the text, although both  may not be represented in this figure.    Arteries of the head and trunk  Internal carotid artery  External carotid artery  Common carotid arteries  Vertebral artery  Subclavian artery  Brachiocephalic trunk  Aortic arch  Ascending aorta  Coronary artery    e The common iliac (R. and L.) arteries are the  final branches of the abdominal aorta. Each  divides into an internal iliac artery, which sup-  plies the pelvic organs (bladder, rectum, and so  on), and an external iliac artery, which enters  the thigh, where it becomes the femoral artery.  The femoral artery and its branch, the deep  artery of the thigh, serve the thigh. At the knee,  the femoral artery becomes the popliteal  artery, which then splits into the anterior  tibial artery and posterior tibial artery, which  supply the leg and foot. The anterior tibial artery  terminates in the dorsalis pedis artery, which  via the arcuate artery supplies the dorsum of  the foot. (The dorsalis pedis is often palpated in  patients with circulatory problems of the legs to  determine whether the distal part of the leg has  adequate circulation. )    Although arteries are generally located in deep, well-  protected body areas, many veins are more superficial,  and some are easily seen and palpated on the body  surface. Most deep veins follow the course of the major  arteries, and with a few exceptions, the naming of  these veins is identical to that of their companion  arteries. Major systemic arteries branch off the aorta,  whereas the veins converge on the venae cavae, which  enter the right atrium of the heart. Veins draining the  head and arms empty into the superior vena cava,  and those draining the lower body empty into the  inferior vena cava. (These veins are described next  and shown in Figure 11.14 on p. 394. As before, locate  the veins on the figure as you read their descriptions. )    Veins Draining into the Superior Vena Cava Veins  draining into the superior vena cava are listed in a  distal-to-proximal direction; that is, in the same direc-  tion the blood flows into the superior vena cava.    e The radial vein and ulnar vein are deep veins  draining the forearm. They unite to form the  deep brachial vein, which drains the arm and  empties into the axillary vein in the axillary  region.   e The cephalic (se-fal'ik) vein provides for the  superficial drainage of the lateral aspect of the  arm and empties into the axillary vein.   e The basilic (bah-sil’'ik) vein is a superficial vein  that drains the medial aspect of the arm and  empties into the brachial vein proximally. The    basilic and cephalic veins are joined at the ante-  rior aspect of the elbow by the median cubital  vein. (The median cubital vein is often chosen  as the site for withdrawing blood for the purpose  of blood testing.)    e The subclavian vein receives venous blood  from the arm through the axillary vein and from  the skin and muscles of the head through the  external jugular vein.    e The vertebral vein drains the posterior part of  the head.    e The internal jugular vein drains the dural  sinuses of the brain.    e The brachiocephalic (R. and L.) veins are large  veins that receive venous drainage from the sub-  clavian, vertebral, and internal jugular veins on  their respective sides. The brachiocephalic veins  join to form the superior vena cava, which enters  the heart.   e The azygos (az'i-gos) vein is a single vein that  drains the thorax and enters the superior vena  cava just before it joins the heart. (This vein is  not illustrated in Figure 11.14.)    Veins Draining into the Inferior Vena Cava The  inferior vena cava, which is much longer than the  superior vena cava, returns blood to the heart from  all body regions inferior to the diaphragm. As before,  we will trace the venous drainage in a distal-to-  proximal direction.    e The anterior tibial vein and posterior tibial vein  and the fibular vein drain the leg (calf and foot).  (The fibular vein is not shown in Figure 11.14.)  The posterior tibial vein becomes the popliteal  vein at the knee and then the femoral vein  in the thigh. The femoral vein becomes the  external iliac vein as it enters the pelvis.    e The great saphenous (sah-fe’nus) veins are  the longest veins in the body. They receive the  superficial drainage of the leg. They begin at the  dorsal venous arch in the foot and travel up  the medial aspect of the leg to empty into the  femoral vein in the thigh.    e Each common iliac (R. and L.) vein is formed  by the union of the external iliac vein and the  internal iliac vein (which drains the pelvis) on  its own side. The common iliac veins join to  form the inferior vena cava, which then ascends  superiorly in the abdominal cavity.    Figure 11.14 Major veins of the systemic  circulation, anterior view. The vessels of the  pulmonary circulation are not illustrated, accounting  for the incomplete appearance of the circulation from  the heart. All veins are bilateral unless specifically  stated in the text.    External jugular vein  Vertebral vein  Internal jugular vein  Right and left   Renal vein Median cubital vein  Superior Ulnar vein  mesenteric vein Radial vein    e The R. gonadal vein drains the right ovary in  females and the right testicle in males. (The  L. gonadal vein empties into the left renal vein  superiorly.) (The gonadal veins are not illustrated  in Figure 11.14.)    e The hepatic portal vein is a single vein that  drains the digestive tract organs and carries this  blood through the liver before it enters the sys-  temic circulation. (We discuss the hepatic portal  circulation in the next section.)    16. In what part of the body are the femoral, popliteal,  and arcuate arteries found?  17. In what part of the body are the axillary, cephalic,  and basilic veins located?  For answers, see Appendix A.    Discuss the unique features of the arterial circula-  tion of the brain, and hepatic portal circulation.    Arterial Supply of the Brain and the Circle of Willis  Because a lack of blood for even a few minutes causes  the delicate brain cells to die, a continuous blood  supply to the brain is crucial. The brain is supplied by  two pairs of arteries, the internal carotid arteries and  the vertebral arteries (Figure 11.15, p. 396).   The internal carotid arteries, branches of the  common carotid arteries, run through the neck and  enter the skull through the temporal bone. Once  inside the cranium, each divides into the anterior  cerebral artery and middle cerebral artery, which  supply most of the cerebrum.   The paired vertebral arteries pass upward from  the subclavian arteries at the base of the neck. Within  the skull, the vertebral arteries join to form the single  basilar artery. This artery serves the brain stem and  cerebellum as it travels upward. At the base of the  cerebrum, the basilar artery divides to form the  posterior cerebral arteries, which supply the pos-  terior part of the cerebrum.   The anterior and posterior blood supplies of the  brain are united by small communicating arterial  branches. The result is a complete circle of connecting    blood vessels called the cerebral arterial circle or  the circle of Willis, which surrounds the base of the  brain. The cerebral arterial circle protects the brain by  providing more than one route for blood to reach  brain tissue in case of a clot or impaired blood flow  anywhere in the system.    Hepatic Portal Circulation ‘The veins of the hepatic  portal circulation drain the digestive organs,  spleen, and pancreas and deliver this blood to the  liver through the hepatic portal vein (Figure 11.16,  p. 397). When you have just eaten, the hepatic portal  blood contains large amounts of nutrients. Because  the liver is a key body organ involved in maintaining  the proper glucose, fat, and protein concentrations  in the blood, this system allows blood to “take a  detour” to ensure that the liver processes these sub-  stances before they enter the systemic circulation.  The liver also helps detoxify blood by removing and  processing toxins absorbed by the stomach and  intestines. As blood flows slowly through the liver,  some of the nutrients are removed to be stored or  processed in various ways for later release to the  blood. The liver is drained by the hepatic veins that  enter the inferior vena cava.    of the brain and the anterior pituitary gland (Chapter 9,  p. 329), the hepatic portal circulation is a unique and  unusual circulation. Normally, arteries feed capillary  beds, which in turn drain into veins. In the hepatic  portal circulation, veins feed the liver circulation  (Figure 11.16).    The major vessels composing the hepatic portal  circulation (Figure 11.17, p. 398) include the infe-  rior and superior mesenteric veins, the splenic  vein, and the left gastric vein. The inferior  mesenteric vein, draining the terminal part of the  large intestine, drains into the splenic vein, which  itself drains the spleen, pancreas, and the left side  of the stomach. The splenic vein and superior  mesenteric vein (which drains the small intestine  and the first part of the colon) join to form the  hepatic portal vein. The L. gastric vein, which  drains the right side of the stomach, drains directly  into the hepatic portal vein.    Figure 11.15 Arterial supply of the brain. (a) Major arteries of the brain.  The four arteries composing the circle of Willis are indicated by bullet points. (The  cerebellum is shown only on the left side of the brain.) (b) Colorized arteriograph    18. Which vessel—the hepatic portal vein, hepatic  vein, or hepatic artery—has the highest content of  nutrients after a meal?   19. In what two important ways is the pulmonary  circulation different from the systemic circulation?    A fairly good indication of the efficiency of a per-  son’s circulatory system can be obtained by taking  arterial pulse and blood pressure measurements.  These measurements, along with those of respiratory    Figure 11.16 The basic scheme  of the hepatic portal system.  Note the presence of two capillary  beds within the portal system.    rate and body temperature, are referred to collec-  tively as vital signs in clinical settings.    The alternating expansion and recoil of an artery that  occurs with each beat of the left ventricle creates a  pressure wave—a pulse—that travels through the  entire arterial system. Normally the pulse rate (pres-  sure surges per minute) equals the heart rate (beats  per minute). The pulse averages 70 to 76 beats per  minute in a healthy resting person. It is influenced  by activity, postural changes, and emotions.   You can feel a pulse in any artery lying close to the  body surface by compressing the artery against firm  tissue; this provides an easy way of counting heart  rate. Because it is so accessible, the point where the  radial artery surfaces at the wrist (the radial pulse) is  routinely used to take a pulse measurement, but there  are several other clinically important arterial pulse  points (Figure 11.18, p. 399). Because these same  points are compressed to stop blood flow into distal  tissues during significant blood loss or hemorrhage,  they are also called pressure points. For example, if  you seriously cut your hand, you can stop the bleed-  ing somewhat by compressing the brachial artery.    Nutrients and toxins picked up  from capillaries in the stomach and  intestine are transported to the liver cava.  for processing. From the liver    sinusoids, the blood continues into  the hepatic veins and inferior vena    two or three fingers of one hand over the artery  at the site indicated. Do not use your thumb,  because it has its own pulse. Compress the artery  firmly as you begin and then immediately ease  up on your pressure slightly. In each case, notice  the regularity and relative strength of the pulse.    Did You Get It?  20. Which artery is palpated at the wrist? At the groin?  At the side of the neck?  For the answer, see Appendix A.   ı# Define blood pressure, and list factors affecting  and/or determining blood pressure.   1# Define hypertension and atherosclerosis, and  describe possible health consequences of these  conditions.   Any system equipped with a pump that forces fluid  through a one-way network of closed tubes operates  under pressure. Blood pressure is the pressure the  blood exerts against the inner walls of the blood ves-  sels, and it is the force that keeps blood circulating  continuously even between heartbeats. Unless stated    otherwise, the term blood pressure in this discussion is  understood to mean the pressure within the large  systemic arteries near the heart.    Blood Pressure Gradient When the ventricles con-  tract, they force blood into large, thick-walled elastic  arteries close to the heart that expand as the blood is  pushed into them.    substances move from areas of high pressure to areas of  low pressure through a filter (Chapter 3, p. 98). Blood  flow is driven by these same differences in pressure, but  without a filter.    The high pressure in these elastic arteries forces  the blood to continuously move into areas where the    pressure is lower. The pressure is highest in the large  arteries closest to the heart and continues to drop  throughout the systemic pathway, reaching zero at  the right atrium (Figure 11.19). Recall that the blood  flows into the smaller arteries, then arterioles, capil-  laries, venules, veins, and finally back to the large  venae cavae entering the right atrium of the heart. It  flows continuously along a pressure gradient (from  high to low pressure) as it makes its circuit, day in  and day out. The valves in the large veins, the milk-  ing activity of the skeletal muscles, and pressure  changes in the thorax are so important because  together they ensure blood flows back to the heart to  be pumped out to the body again. The pressure dif-  ferences between arteries and veins become very  clear when these vessels are cut. If a vein is cut, the  blood flows evenly from the wound; a lacerated  artery produces rapid spurts of blood. A similar pres-  sure drop occurs as blood flows through the pulmo-  nary pathway.    Figure 11.18 Body sites where the pulse is most  easily palpated. (Most of the specific arteries indicated  are discussed on pp. 391-393.)    Figure 11.19 Blood pressure in the systemic circuit  of the cardiovascular system.    Continuous blood flow absolutely depends on  the stretchiness of the larger arteries and their ability  to recoil and keep exerting pressure on the blood as  it flows into the rest of the vascular system. Think of  a garden hose with relatively hard walls. When the    water is turned on, the water spurts out under high  pressure because the hose walls don’t expand.  However, when the water faucet is suddenly turned  off, the flow of water stops just as abruptly. The rea-  son is that the walls of the hose cannot recoil to keep  pressure on the water; therefore, the pressure drops,  and the flow of water stops. The importance of the  elasticity of the arteries is best appreciated when it is  lost, as happens in arteriosclerosis, sometimes  called “hardening of the arteries.” The early stage of  arteriosclerosis, known as atherosclerosis, is dis-  cussed in “A Closer Look” on p. 403.    Did You Get It?  21. How does blood pressure change throughout the  systemic circulatory pathway?  For the answer, see Appendix A.    Measuring Blood Pressure ‘The off-and-on flow of  blood into the arteries as the heart alternately con-  tracts and relaxes causes the blood pressure to rise  and fall during each beat. Thus, two arterial blood  pressures are usually measured: systolic (sis-to’lik)  pressure, the pressure in the arteries at the peak of  ventricular contraction, and diastolic (di’us-td'lik)  pressure, the pressure when the ventricles are relax-  ing. Blood pressures are reported in millimeters of  mercury (mm Hg), with the higher systolic pressure  written first— 120/80 (read “120 over 80") translates  to a systolic pressure of 120 mm Hg and a diastolic  pressure of 80 mm Hg. Most often, systemic arterial  blood pressure is measured indirectly by the  auscultatory (os-kul’tuh-tor-e) method. This pro-  cedure is used to measure blood pressure in the bra-  chial artery of the arm (Figure 11.20, p. 400).    Effects of Various Factors on Blood Pressure Art-  erial blood pressure (BP) is directly related to cardiac  output (CO; the amount of blood pumped out of  the left ventricle per minute) and peripheral resis-  tance (PR). This relationship is expressed by the  equation BP = CO X PR. We have already considered  regulation of cardiac output, so we will concentrate  on peripheral resistance here.   Peripheral resistance is the amount of friction,  or resistance to flow, the blood encounters as it flows  through the blood vessels. Many factors increase  peripheral resistance, but probably the most impor-  tant is the constriction, or narrowing, of blood    (a) The course of the (b) The blood pressure (c) The pressure in the (d) As the pressure is    arm. Assume a blood  pressure of 120/70 in  a young, healthy  person.    around the arm just  above the elbow and  inflated until the cuff  pressure exceeds the  systolic blood  pressure. At this point,  blood flow into the arm  is stopped, anda  brachial pulse cannot  be felt or heard.    cuff is gradually  reduced while the  examiner listens  (auscultates) for  sounds in the brachial  artery with a  stethoscope. The  pressure read as the  first soft tapping  sounds are heard (the  first point at which a  small amount of blood  is spurting through the  constricted artery) is  recorded as the  systolic pressure.    vessels, especially arterioles, as a result of either sym-  pathetic nervous system activity or atherosclerosis.  Increased blood volume or increased blood viscosity  (thickness) also raises peripheral resistance. Any fac-  tor that increases either cardiac output or peripheral  resistance causes an almost immediate rise in blood  pressure. Many factors can alter blood pressure—age,  weight, time of day, exercise, body position, emo-  tional state, and various drugs, to name a few. The  influence of a few of these factors is discussed next.    Neural factors: the autonomic nervous system.  The parasympathetic division of the autonomic  nervous system has little or no effect on blood  pressure, but the sympathetic division is important.  The major action of the sympathetic nerves on the    reduced still further,  the sounds become  louder and more  distinct; when the  artery is no longer  constricted and blood  flows freely, the  sounds can no longer  be heard. The  pressure at which the  sounds disappear is  recorded as the  diastolic pressure.    vascular system is to cause vasoconstriction  (vas"o-kon-strik’shun), or narrowing of the blood  vessels, which increases the blood pressure. The  sympathetic center in the medulla oblongata of the  brain is activated to cause vasoconstriction in many  different circumstances (Figure 11.21). For exam-  ple, when we stand up suddenly after lying down,  gravity causes blood to pool very briefly in the ves-  sels of the legs and feet, and blood pressure drops.  This activates pressoreceptors, also called baroreceptors  (baro = pressure), in the large arteries of the neck  and chest. They send off warning signals that result  in reflexive vasoconstriction, quickly increasing  blood pressure back to the homeostatic level.    When blood volume suddenly decreases, as  in hemorrhage, blood pressure drops, and the  heart begins to beat more rapidly as it tries to  compensate by circulating the remaining blood  more quickly. However, because blood loss  reduces venous return, the heart also beats  weakly and inefficiently. In such cases, the sym-  pathetic nervous system causes vasoconstriction  to increase the blood pressure so that (it is  hoped) venous return increases and circulation  can continue. This phenomenon also happens  during severe dehydration.   The final example concerns sympathetic  nervous system activity when we exercise vigor-  ously or are frightened and have to make a hasty  escape. Under these conditions, generalized  vasoconstriction occurs except in the skeletal  muscles. The vessels of the skeletal muscles    dilate to increase the blood flow to the working  muscles. (However, note that the sympathetic  nerves never cause vasoconstriction of blood  vessels of the heart or brain.)    Renal factors: the kidneys. The kidneys play  a major role in regulating arterial blood pressure  by altering blood volume. As blood pressure  (and/or blood volume) increases above normal,  the kidneys allow more water to leave the body  in the urine. Because the source of this water is  the bloodstream, blood volume decreases,  which in turn decreases blood pressure. How-  ever, when arterial blood pressure falls, the  kidneys retain body water, maintaining blood  volume and blood pressure (see Figure 11.21).  In order to increase blood volume and blood  pressure, fluids must be ingested or adminis-  tered intravenously.    In addition, when arterial blood pressure is  low, certain kidney cells release the enzyme renin  into the blood. Renin triggers a series of chemi-  cal reactions that result in the formation of  angiotensin II, a potent vasoconstrictor chemical.  Angiotensin also stimulates the adrenal cortex to  release aldosterone, a hormone that enhances  sodium ion reabsorption by the kidneys. As  sodium ions move into the blood, water follows.  Thus, blood volume and blood pressure both  rise in response to aldosterone.    e Temperature. In general, cold has a vasocon-  stricting effect. This is why your exposed skin  feels cold to the touch on a winter day and why  cold compresses are recommended to prevent  swelling of a bruised area. Heat has a vasodilating  effect. This explains why skin reddens during  exercise as body temperature increases and why  warm compresses are used to speed the circula-  tion into an inflamed area.    e Chemicals. The effects of chemical substances,  many of which are drugs, on blood pressure are  widespread and well known in many cases. We  will give just a few examples here. Epinephrine  increases both heart rate and blood pressure.    which is produced by the adrenal medulla and helps us  deal with short-term stress (Chapter 9, p. 339).    Nicotine increases blood pressure by causing  vasoconstriction. Both alcohol and histamine  cause vasodilation and decrease blood pressure.  The reason a person who has “one too many”  becomes flushed is that alcohol dilates the skin  vessels.    e Diet. Although medical opinions tend to  change and are at odds from time to time, it is  generally thought that a diet low in salt, satu-  rated fats, and cholesterol helps to prevent  hypertension, or high blood pressure.    Did You Get It?  22. What is the effect of hemorrhage on blood  pressure? Why?  For the answer, see Appendix A.    Variations in Blood Pressure In normal adults at  rest, systolic blood pressure varies between 110 and 140  mm Hg, and diastolic pressure between 70 and 80 mm  Hg—but blood pressure varies considerably from one  person to another and cycles over a 24-hour period,  peaking in the morning. What is normal for you may  not be normal for your grandfather or your neighbor.  Blood pressure varies with age, weight, race, mood,  physical activity, and posture. Nearly all these varia-  tions can be explained in terms of the factors affecting  blood pressure that we have already discussed.   Hypotension, or low blood pressure, is gener-  ally considered to be a systolic blood pressure below  100 mm Hg. In many cases, it simply reflects individ-  ual differences and is no cause for concern. In fact,  low blood pressure is an expected result of physical  conditioning and is often associated with long life  and an old age free of illness.    Homeostatic J  —S~ Imbalance 11.8  Elderly people may experience temporary low blood  pressure and dizziness when they rise suddenly from  a reclining or sitting position—a condition called  orthostatic hypotension. Because an aging sympa-  thetic nervous system reacts more slowly to postural  changes, blood pools briefly in the lower limbs,  reducing blood pressure and, consequently, blood  delivery to the brain. Making postural changes more  slowly to give the nervous system time to make the  necessary adjustments usually prevents this problem.  Chronic hypotension (not explained by physical  conditioning) may hint at poor nutrition and inade-  quate levels of blood proteins. Because blood viscosity  is low, blood pressure is also lower than normal. Acute  hypotension is one of the most important warnings of  circulatory shock, a condition in which the blood  vessels are inadequately filled and blood cannot circu-  late normally. The most common cause is blood loss.  A brief elevation in blood pressure is a normal  response to fever, physical exertion, and emotional  upset, such as anger or fear. Persistent hypertension  (high blood pressure), is pathological and is  defined as a condition of sustained elevated arterial  pressure of 140/90 or higher.    ease that warns of increased peripheral resistance.  Although it progresses without symptoms for the first   in which the blood vessels  become narrowed by buildup of fatty  and fibrous deposits on the  vessel walls. The clog-  ging process  begins on the  inside: the  walls of the  vessels (usu-  ally arteries)  thicken and  then protrude  into the vessel  lumen. Once  this happens, a  roaming blood  clot or arterial  spasm can close  the vessel  completely.    What triggers this scourge of blood  vessels that indirectly causes half of  the deaths in the Western world?  There are thought to be four stages.    1. Endothelium becomes injured.  The tunica intima can be damaged  by bloodborne chemicals such as  carbon monoxide, by bacteria  or viruses, or by physical factors  such as a blow or persistent  hypertension.    2. Lipids accumulate and become  oxidized. Once a break has  occurred, blood platelets cling to  the injured site and initiate clotting  to prevent blood loss. The injured  endothelium initiates localized  inflammation and summons white  blood cells to repair the damage  while allowing fats and cholesterol    Atherosclerotic plaques nearly close  a human artery. The bracket shows  the area open for blood flow.    to accumulate just deep to the  tunica intima. The inflammatory  response in the area causes these  lipids to become oxidized and to  damage nearby cells, resulting  in the recruitment of more  WEBCs. Some WBCs,  such as macrophages,  take in so much fat  that they lose all  function and  become “foam  cells.”    3. Smooth muscle  cells deposit fibers.  Smooth muscle cells  migrating from the  tunica media of the  blood vessel wall  deposit collagen and  elastin fibers in the  area and also take in fat, becoming  foam cells. Dead or dying foam  cells form lesions called athero-  sclerotic plaques or fibrous  plaques that cause thickening of  the tunica intima. When these small,  fatty mounds of muscle begin to  protrude into the vessel lumen, the  condition is called atherosclerosis  (see photo).    cells at the center of the plaque  begin to die, the elastic fibers dete-  riorate and are gradually replaced  by nonelastic scar tissue. The addi-  tion of calcium salts to the lesions  results in complicated plaques.  The inflammatory process makes  the plaques susceptible to rupture,  exploding off fragments that trigger  massive clots that can cause lethal  heart attacks. Collectively, these  events cause the arterial wall to    Learn more at Mastering A&P > Study Area > A  y Additional Study Tools > A Closer Look    fray and ulcerate, conditions that  encourage thrombus formation.  The increased rigidity of the vessels  leads to hypertension. Together,  these events increase the risk of  myocardial infarctions, strokes, and  aneurysms.    Lifestyle factors that can help patients  improve cardiovascular health include  regular exercise, a diet low in saturated  fat, not smoking, and reducing emo-  tional stress—for example, through  mindful meditation. Pharmacological  treatments include anti-inflammatory  medications, cholesterol-lowering  drugs, and clot-busting drugs. Balloon  angioplasty is a procedure whereby a  balloon is used to compress the  plaques against the vessel wall;  sometimes, it involves placement of a  metal stent to keep the vessel open.  In coronary bypass surgery, a vessel   is taken from the patient's leg and  grafted onto the affected coronary  vessel to reroute blood flow around  the blockage.    e In atherosclerosis, artery walls  thicken and develop scar tissue,  resulting in high blood pressure  (hypertension).    e Atherosclerotic plaques cause  thickening of artery walls and  can promote thrombus (clot)  formation.    e Patients with atherosclerosis  are at increased risk for heart  attack, stroke, and aneurysms.    10 to 20 years, it slowly and surely strains the heart and  damages the arteries. For this reason, hypertension is  often called the “silent killer.” Because the heart is  forced to pump against increased resistance, it must  work harder, and in time, the myocardium enlarges.  When finally strained beyond its capacity to respond,  the heart weakens and its walls become flabby.  Hypertension also ravages blood vessels, causing small  tears in the endothelium that accelerate the progress of  atherosclerosis (the early stage of arteriosclerosis).   Although hypertension and atherosclerosis are  often linked, it is difficult to blame hypertension on  any distinct anatomical pathology. In fact, about  90 percent of hypertensive people have primary  (essential) hypertension, which cannot be attrib-  uted to any specific organic cause. However, factors  such as diet, obesity, heredity, race, and stress appear  to be involved. For instance, more women than men  and more Blacks than Caucasians are hypertensive.  Hypertension runs in families. The child of a hyper-  tensive parent is twice as likely to develop high blood  pressure compared to a child of parents with normal  blood pressure. High blood pressure is common in  obese people because the total length of their blood  vessels is greater than that in thinner individuals. For  each pound of fat, miles of additional blood vessels  are required, making the heart work harder to pump  blood over longer distances.    Capillaries form an intricate network among the  body’s cells, and no substance has to diffuse very far  to enter or leave a cell. The substances to be exchanged  diffuse through the interstitial fluid between cells.   Substances tend to move to and from body cells  according to their concentration gradients. Thus,  oxygen and nutrients leave the blood and move  into cells, and carbon dioxide and other wastes exit  the cells and enter the blood. Basically, substances  entering or leaving the blood may take one of four  routes across the plasma membranes of the single  layer of endothelial cells forming the capillary wall  (Figure 11.22).    1. Direct diffusion through membrane. As with  all cells, substances can diffuse directly through  (across) their plasma membranes if the substances    Figure 11.22 Capillary transport mechanisms. The  four possible pathways or routes of transport across the  wall of an endothelial cell of a capillary. (The endothelial  cell is illustrated as if cut in cross section.)    are lipid-soluble (such as the respiratory gases  oxygen and carbon dioxide).    2. Diffusion through intercellular clefts. Gaps  between cells in the capillary wall, called  intercellular clefts, allow limited passage of  fluid and small solutes. Most of our capillaries  have intercellular clefts, except for brain capillar-  ies, which are secured together entirely by tight  junctions (the basis of the blood-brain barrier,  described in Chapter 7).    3. Diffusion through pores. Fenestrated  capillaries allow free passage of small solutes and  fluids. These unique capillaries are found where  absorption is a priority (intestinal capillaries or  capillaries serving endocrine glands) or where fil-  tration occurs (the kidney). A fenestra is an oval  pore, or opening (fenestra = window), and is usu-  ally covered by a delicate membrane (see Figure  11.22). Even so, a fenestra is much more perme-  able than other regions of the plasma membrane.    4. Transport via vesicles. Certain lipid-insoluble  substances may enter or leave the blood and/or  pass through the plasma membranes of endo-  thelial cells within vesicles, that is, by endocyto-  sis or exocytosis.    Only substances unable to pass by one of these  routes are prevented from leaving (or entering) the  capillaries. These include protein molecules (in  plasma or interstitial fluid) and blood cells.    In addition to the exchanges made via passive diffusion  through capillary endothelial cell plasma membranes,  clefts, or fenestrations, and via vesicles, there are active  forces operating at capillary beds. Because of their inter-  cellular clefts and fenestrations, some capillaries are  leaky, and bulk fluid flow (fluid moving all at once)  occurs across their plasma membranes. Hence, blood  pressure tends to force fluid (and solutes) out of the  capillaries, and osmotic pressure (the ability of a solu-  tion to pull water toward itself) tends to draw fluid into  them because blood has a higher solute concentration  (due to its plasma proteins) than does interstitial fluid.  Whether fluid moves out of or into a capillary depends  on the difference between the two pressures. As a rule,  blood pressure is higher than osmotic pressure at the  arterial end of the capillary bed and is lower than  osmotic pressure at the venous end. Consequently,  fluid moves out of the capillaries at the beginning of  the bed and is reclaimed at the opposite (venule) end  (Figure 11.23). However, not quite all of the fluid forced  out of the blood is reclaimed at the venule end.  Returning fluid left in tissues to the blood is the chore  of the lymphatic system (discussed in Chapter 12).    23. Would you expect fluid to be entering or leaving  the capillaries at the venous end of a capillary bed?  For the answer, see Appendix A.    Learning Objectives  Briefly describe the development of the  cardiovascular system.  vw Name the fetal vascular modifications, or “fetal  shunts,” and describe their function before birth.  vy Describe changes in the cardiovascular system  that occur with aging, and list several factors that  help maintain cardiovascular health.  The heart begins as a simple tube in the embryo. It is  beating and busily pumping blood by the fourth  week of pregnancy. During the next 3 weeks, the    Assume there is a bacterial infection in the interstitial  fluid. How would this affect bulk fluid flow across the  capillary walls in the area?    At the arterial end of a  capillary, blood  pressure is more than  osmotic pressure, and  fluid flows out of the  capillary and into the  interstitial fluid.    At the venule end of  the capillary, blood  pressure is less than  osmotic pressure, and  fluid flows from the  interstitial fluid into the  capillary.    Figure 11.23 Bulk fluid flow across capillary walls.  Fluid flow depends largely on the difference between  the blood pressure and the osmotic pressure at different  regions of the capillary bed.    heart continues to change and mature, finally  becoming a four-chambered structure capable of act-  ing as a double pump—all without missing a beat!   Because the lungs and digestive system are imma-  ture and not functioning in a fetus, all nutrient, excre-  tory, and gas exchanges occur through the placenta.  The umbilical cord contains three blood vessels: one  large umbilical vein and two smaller umbilical  arteries (Figure 11.24). The umbilical vein carries  blood rich in nutrients and oxygen to the fetus. The  umbilical arteries carry blood laden with carbon diox-  ide and metabolic waste products from the fetus to  the placenta. As blood flows superiorly toward the  heart of the fetus, most of it bypasses the immature  liver through the ductus venosus (duk’tus ve-no’sus)  and enters the inferior vena cava, which carries the  blood to the right atrium of the heart.   Because the nonfunctional fetal lungs are col-  lapsed, two shunts (diverting vessels) make sure that  they are almost entirely bypassed. Some of the blood  entering the right atrium is shunted directly into the  left atrium through the foramen ovale (fo-ra’men  o-val'e), a flaplike opening in the interatrial septum.  Blood that does manage to enter the right ventricle is  pumped out to the pulmonary trunk, where it meets  a second shunt, the ductus arteriosus (ar-ter’e-  o’sus), a short vessel that connects the pulmonary  trunk and the aorta. Because the collapsed lungs are  a high-pressure area, blood tends to enter the sys-  temic circulation through the ductus arteriosus. The  aorta carries blood to the tissues of the fetal body  and ultimately back to the placenta through the  umbilical arteries.   At birth, or shortly after, the foramen ovale  closes. Its remnant, the fossa ovalis, is visible in the  right atrium (see Figure 11.3b). The ductus arteriosus  collapses and is converted to the fibrous ligamentum  arteriosum (lig’ah-men’tum ar-ter’e-o’sum) (see  Figure 11.3a). As blood stops flowing through the  umbilical vessels, they collapse, and the circulatory  pattern converts to that of an adult.    Homeostatic J  £ Imbalance 11.10  Congenital heart defects account for about half of  infant deaths resulting from all congenital defects.  Environmental interferences, such as maternal infec-  tion and drugs ingested during the first 3 months of  pregnancy (when the embryonic heart is forming),  seem to be the major causes of such problems.  Congenital heart defects may include a ductus    arteriosus that does not close, septal openings, and  other structural abnormalities of the heart. Such  problems can usually be corrected surgically.    In the absence of congenital heart problems, the  heart usually functions smoothly throughout a long  lifetime for most people. Homeostatic mechanisms are  so effective that we rarely are aware of when the heart is  working harder. The heart will hypertrophy and its car-  diac output will increase substantially if we exercise reg-  ularly and aerobically (that is, vigorously enough to  force it to beat at a higher-than-normal rate for  extended periods of time). The heart becomes not only  a more powerful pump but also a more efficient one:  pulse rate and blood pressure decrease. An added ben-  efit of aerobic exercise is that it clears fatty deposits  from the blood vessel walls, helping to slow the prog-  ress of atherosclerosis. However, let's raise a caution flag  here: The once-a-month or once-a-year tennis player or  snow shoveler has not built up this type of heart endur-  ance and strength. When such an individual pushes his  or her heart too much, it may not be able to cope with  the sudden demand. This is why many “weekend ath-  letes” are myocardial infarction (heart attack) victims.   As we get older, more and more signs of cardiovas-  cular system disturbances start to appear. In some peo-  ple, the venous valves weaken, and purple, snakelike  varicose veins appear. Not everyone has varicose veins,  but we all have progressive atherosclerosis. There’s an  old saying, “You are only as old as your arteries,” refer-  ring to this degenerative process. The gradual loss in  elasticity of the blood vessels leads to hypertension  and hypertensive heart disease. The insidious filling of  the blood vessels with fatty, calcified deposits leads  most commonly to coronary artery disease. Also,  the roughening of the vessel walls encourages throm-  bus formation (see Chapter 10). About 1.13 billion  people in the world have hypertension. This figure is  expected to increase as nations become more prosper-  ous through economic development. In Europe, car-  diovascular disease accounts for 45 percent of all  deaths. Although the aging process itself contributes  to changes in the walls of the blood vessels that can  lead to strokes or myocardial infarctions, most  researchers feel that diet, not aging, is the single most  important contributing factor to cardiovascular dis-  eases. There is some agreement that the risk is lowered  if people eat less animal fat, cholesterol, and salt.  Other recommendations include avoiding stress, elim-  inating cigarette smoking, and taking part in a regular,  moderate exercise program.    e The cardiovascular system  delivers oxygen and nutrients;  carries away wastes; blood serves  as a transport vehicle for hormones    oxygen and nutrients to lymphoid  organs, which house immune cells;  transports lymphocytes and  antibodies; carries away wastes   e The lymphatic system picks up  leaked fluid and plasma proteins  and returns them to the  cardiovascular system; its  immune cells protect  cardiovascular organs from  specific pathogens    provides nutrients to the  blood including iron and B  vitamins essential for RBC  (and hemoglobin) formation    e The cardiovascular system delivers  oxygen and nutrients; carries away  wastes; blood pressure maintains  kidney function    e The cardiovascular system delivers  oxygen and nutrients; carries away  wastes   e ANS regulates cardiac rate and  force; sympathetic division  maintains blood pressure and  controls blood distribution  according to need    e The cardiovascular system delivers  oxygen and nutrients; carries away  wastes    e The cardiovascular system delivers  oxygen and nutrients; carries away  wastes   e The skin’s blood vessels provide an  important blood reservoir and a site  for heat loss from body    e The cardiovascular system delivers  oxygen and nutrients and carries  away wastes   e Bones are the site of hematopoiesis;  protect cardiovascular organs by  enclosure; provide a calcium depot    A N Listen to the story of this chapter in a brief summary at Mastering A&P >  I Study Area > Author Narrated Audio Summaries    11.1a. Anatomy: the heart is located in the  mediastinum of the thorax; is flanked laterally  by the lungs and enclosed in a multilayered  pericardium    e The pericardium has three layers; from superficial  to deep, they are as follows:    e The heart wall has three layers—epicardium  (also called visceral pericardium), myocardium  (cardiac muscle), and endocardium  (endothelium)    11.1b. Chambers and associated great vessels—  the heart has four hollow chambers: two atria  (receiving chambers) and two ventricles  (discharging chambers); the heart is divided  longitudinally by a septum, referred to as the  interatrial septum where it divides the atria  and the interventricular septum where it  divides the ventricles    e The heart functions as a double pump. The right  ventricle is the pulmonary pump (right ventricle  to lungs to left atrium); the left ventricle is the  systemic pump (left ventricle to body tissues to  right atrium)    e The right ventricle drains into the pulmonary  trunk, which splits into the right and left  pulmonary arteries; the left ventricle drains  into the aorta    e The superior vena cava and inferior vena cava  return blood from the body to the right atrium;  the pulmonary veins return blood from the  lungs to the left atrium    e The atrioventricular (AV) valves—bicuspid  valve (mitral valve) and tricuspid valve—  prevent backflow into the atria when the  ventricles are contracting    e The semilunar (SL) valves (pulmonary  semilunar valve and aortic semilunar valve)    e Valves open and close in response to pressure  changes in the heart    e The myocardium is nourished by coronary  arteries, which branch off the aorta; are  drained by the cardiac veins and the coronary  sinus   e Sinoatrial (SA) node is the pacemaker; sets a  heart rate of about 75 beats per minute    ° Other components of the nodal system:  atrioventricular (AV) node, atrioventricu-  lar (AV bundle), bundle branches,  Purkinje fibers    o Extrinsic factors affecting heart rate include  neural and hormonal stimuli    e The cardiac cycle is a series of events in one  complete heartbeat    ° Heart sounds result from the closing of the  valves (“lub-dup”)  = Faulty valves reduce the efficiency of the  heart as a pump and result in abnormal  heart sounds (heart murmurs)    e Cardiac output (CO)—the amount of blood  pumped out by each ventricle in 1 minute    o Cardiac output (CO) = heart rate (HR) x  stroke volume (SV)  = SV is the amount of blood ejected by a  ventricle with each beat    ° Preload—the amount of stretch of cardiac  muscle cells; related to venous return  = The greater the venous return, the stronger  the contraction and the higher the SV   = Influenced by amount of calcium ions  present, hormones such as thyroxine, and  sympathetic nervous stimulation   = The more calcium or thyroxine present,  the greater the nerve stimulation, the  stronger the contraction, and the higher  the SV    hormones and ions, and physical characteristics  such as age, gender, and body temperature   o When the precapillary sphincters are closed,  blood flows directly through the vascular shunt   ° Common in people who are obese or who  stand for long hours    11.2b. Gross anatomy of blood vessels  e All major arteries of the systemic circulation    diverge into arterioles, which feed capillary  beds. (For the names and locations of the  systemic arteries, see pp. 391-393.)    e All major veins of the systemic circulation merge  and converge on one of the venae cavae    o Veins superior to the diaphragm drain into the  superior vena cava    o Veins inferior to the diaphragm drain into the  inferior vena cava  m (See pp. 393-395 for the names and  locations of the systemic veins.)    ° The circle of Willis (cerebral arterial cir-  cle) provides alternate routes for blood flow  in case of a blockage in the brain’s arterial  supply   e The hepatic portal circulation is formed by  veins draining the digestive organs, which empty  into the hepatic portal vein    11.2c. Physiology of circulation—the pulse is the  alternating expansion and recoil of a blood vessel  wall (the pressure wave) that occurs as the heart  beats    o Provides the force that causes blood to  flow down its pressure gradient in the  blood vessels    o Pressure is high in the arteries, lower in the  capillaries, and lowest in the right atrium    ° Both systolic pressure and diastolic  pressure are recorded when blood pressure  is measured    e Arterial blood pressure is directly influenced by:  o Cardiac output, which is related to heart rate    o° Peripheral resistance—high resistance  reduces blood flow  = The most important factors increasing the  peripheral resistance are a decrease in the  diameter or stretchiness of the arteries and  arterioles and an increase in blood viscosity  = Many factors influence blood pressure,  including the activity of the sympathetic  nerves and kidneys, drugs, and diet  e Hypertension (high blood pressure) reflects  an increase in peripheral resistance, strains the  heart, and damages blood vessels    e Substances move to and from the blood and  tissue cells through capillary walls mainly by  diffusion    Can occur directly through the endothelial cell  plasma membranes, through intercellular  clefts, or through fenestrated capillaries or  by bulk transport    Fluid is forced from the bloodstream by  blood pressure and drawn back into the  blood by osmotic pressure    e The heart begins as a tubelike structure that is a  four-chambered heart beating and pumping  blood by the second month of embryonic  development   e The fetal circulation is a temporary circulation  seen only in the fetus and has three special vessels:  ° A single umbilical vein carries nutrients and   oxygen to the fetus from the placenta (toward  the fetal heart)    ° Two umbilical arteries carry carbon dioxide  and waste from the fetus to the placenta  (away from the fetal heart)    ° Shunts bypass the lungs (ductus arteriosus)  and liver (ductus venosus)    ° The lungs are also bypassed by the passage of  blood directly from the right atrium to left  atrium via the foramen ovale    e Arteriosclerosis involves gradual loss of elastic-  ity in the arteries and buildup of fatty plaques;  atherosclerosis, the first step in arteriosclerosis,  results when artery walls thicken and develop  scar tissue    ° A healthy diet low in fat, cholesterol, and  salt; stopping smoking; and regular aerobic  exercise may help to reverse the atherosclerotic  process and prolong life    3. Which of the following depolarizes next after the AV  node?   . Given a volume of 150 ml at the end of diastole, a    volume of 50 ml at the end of systole, and a heart rate  of 60 bpm, the cardiac output is    a. 600 ml/min.  b. 6 liters/min.  c. 1200 ml/min.  d. 3 liters/min.    . To count the heart rate for an apical pulse, you would    place your stethoscope approximately at the level of the  a. third intercostal space.    one vessel of the pair occurs on each side of the body)?  a. Internal carotid artery   A stroke that occludes a posterior cerebral artery will  most likely affect    Most of the small intestine is supplied by the  a. superior mesenteric artery.    In which of the heart chambers does the coronary  sinus empty?    a. Right ventricle  b. Right atrium  c. Left ventricle  d. Left atrium    Which of the following are associated with aging?  a. Increasing blood pressure    What effects do the kidneys have on blood pressure?  a. They decrease pressure by causing vasodilation.  b. They increase pressure by increasing blood volume.  c. They decrease pressure by decreasing blood volume.  d. They increase pressure by decreasing blood volume.    Using the figure, identify the most external part of the  pericardium.    Which of the following are features of capillaries?  a. They allow direct diffusion of nutrients.   How many cusps does the semilunar valve at the base  of the aorta have?    Draw a diagram of the heart showing the three layers  composing its wall and its four chambers. Label each.  Show where the AV and semilunar valves are, and  name them. Show and label all blood vessels entering  and leaving the heart chambers.    How is blood supply to the brain provided? Which  special network offers an additional guarantee for  continuous blood supply to all brain parts?    How does the heart's ability to contract differ from  that of other muscles of the body?    Which system is responsible for decreasing heart rate  after a crisis has passed?    What causes the development of varicose veins in the  lower limbs?    What is the function of the hepatic portal circulation?  In what way is a portal circulation a “strange”  circulation?    In a fetus, the liver and lungs are almost entirely  bypassed by blood. Why is this? Name the vessel that  bypasses the liver. Name two lung bypasses. Three ves-  sels travel in the umbilical cord; which of these carries  oxygen- and nutrient-rich blood?    Which part of the nervous system plays an important  role in regulating blood pressure? By which action  does it increase blood pressure?    Jake was admitted to the hospital to receive a pace-  maker. His heart rate had become so slow that it was  giving him discomfort. An electrocardiogram was indic-  ative of a problem with the heart’s electrical system.  What is the cause of Jake’s condition, and why could an  artificial pacemaker help? What is the difference  between the natural pacemaker and an artificial one?    Following a viral infection, George has been feeling a  sharp stabbing pain in the retrosternal region. The  pain gets worse when he breathes deeply and when he  lies down. A physical examination reveals that he has  pericarditis. Can you explain why pericarditis causes  this severe pain?    Mrs. Rees is brought to the emergency room after being  involved in an auto accident. She is hemorrhaging and  has a rapid pulse that can barely be felt, but her blood  pressure is still within normal limits. Describe the com-  pensatory mechanisms that are maintaining her blood  pressure in the face of blood loss.    Mr. Grimaldi was previously diagnosed as having a  posterior pituitary tumor that causes hypersecretion of  ADH. He comes to the clinic regularly to have his  blood pressure checked. Would you expect his blood  pressure to be chronically elevated or depressed? Why?    The lymphatic system  carries excess interstitial fluid  from tissues back to cardiovascular  circulation and provides locations  for immune cells to monitor    1# Explain how the lymphatic system is functionally  related to the cardiovascular system and the  immune defenses.    vz Name the two major types of structures compos-  ing the lymphatic system.  1# Describe the source of lymph, and explain its  formation and transport.  When we mentally tick off the names of the body's  organ systems, the lymphatic (lim-fat’ik) system is    Porous lymphatic  vessels take in fluids from the  extracellular space and carry them  through lymph nodes, where  immune cells scan the fluids for  foreign particles.    probably not the first that comes to mind. Yet with-  out this system, our cardiovascular system would  stop working, and our immune system would be  hopelessly impaired. The lymphatic system consists  of two parts: (1) a meandering network of lymphatic  vessels and (2) various lymphoid tissues and organs  scattered throughout the body. The lymphatic vessels  transport fluids that have escaped from the blood  back to the cardiovascular system. The lymphoid tis-  sues and organs house phagocytic cells and lympho-  cytes, which play essential roles in body defense and  resistance to disease.    As blood circulates through the body, nutrients,  wastes, and gases are exchanged between the blood  and the interstitial fluid.    The fluid that remains behind in the tissue J  spaces, as much as 3 L daily, becomes part of the 5 - Lymphatic  interstitial fluid. This excess tissue fluid, as well as "y collecting  any plasma proteins that escape from the blood, eN  must be carried back to the blood if the vascular sys-  tem is to have sufficient blood volume to continue  to operate properly. If it does not, fluid accumulates )  in the tissues, producing edema, or swelling. | Lymph  Excessive edema impairs the ability of cells to make f capillary l  exchanges with the interstitial fluid and ultimately ~D o.  the blood. The function of the lymphatic vessels is DO zy D mph)  to form an elaborate drainage system that picks up æ a> q a  this excess interstitial fluid, now called lymph D #8 ad,  (lymph = clear water), and returns it to the blood d @ a | ey,  (Figure 12.1).    capillaries weave between the tissue cells and blood : . : ,  capillaries in the loose connective tissues of the Figure 12.1 Relationship of lymphatic vessels to    body (Figure 12.2a, p. 416) and absorb the leaked blood vessels. Beginning at the bottom of this figure,  fuid: Although- similar to blood capillaries- Tym- we see that lymph, which begins as tissue fluid derived  8 P aa from blood capillaries, enters the lymph capillaries  hatic capillaries are so remarkably permeable that p ' ; EHA ’  paa P yP . travels through the lymphatic vessels and lymph nodes,  they were once thought to be open at one end like a and enters the bloodstream via the great veins at the  straw. Not so—instead, the edges of the endothelial root of the neck.  cells forming their walls loosely overlap one  another, forming flaplike minivalves (Figure 12.2b)  that act as one-way swinging doors. The flaps,  anchored by fine collagen fibers to surrounding  structures, gape open when the fluid pressure is  higher in the interstitial space, allowing fluid to “concer LINK  enter the lymphatic capillary. However, when the This is very similar to the way that valves in veins work  pressure is higher inside the lymphatic vessels, the to ensure blood returns to the heart, despite being  endothelial cell flaps are forced together, preventing under low pressure (Chapter 11, p. 389).    Figure 12.2 Special structural features of lymphatic capillaries. (a) Structural  relationship between blood capillaries and lymph capillaries. Black arrows indicate  direction of fluid movement. (b) Lymph capillaries begin as blind-ended tubes. The  endothelial cells forming their walls overlap one another, forming flaplike minivalves.    Proteins, and even larger particles such as cell  debris, bacteria, and viruses, are normally prevented  from entering blood capillaries, but they enter the  lymphatic capillaries easily, particularly in inflamed  areas. But there is a problem here—bacteria, viruses,  and cancer cells that enter the lymphatics can then  use them to travel throughout the body. This dilemma  is partly resolved by the fact that white blood cells  (WBCs) can also travel in lymph and that lymph  takes “detours” through the lymph nodes, where it is  cleansed of debris and “examined” by cells of the  immune system, as we explain in more detail shortly.   Lymph is transported from the lymph capillaries  through successively larger lymphatic vessels,  referred to as lymphatic collecting vessels, until it  is finally returned to the venous circulation through  two large ducts in the thoracic region. The right  lymphatic duct drains lymph from the right arm  and the right side of the head and thorax. The large  thoracic duct receives lymph from the rest of the  body (Figure 12.3). Both ducts empty the lymph into  the subclavian vein on their own side of the body.   Like veins of the cardiovascular system, lymphatic  vessels are thin walled, and the larger ones have valves.  The lymphatic system is a low-pressure, pumpless sys-  tem. Lymph is transported by the same mechanisms  that aid return of venous blood—the milking action    of the skeletal muscles and pressure changes in the  thorax during breathing (that is, the muscular and  respiratory “pumps”). In addition, smooth muscle in  the walls of the larger lymphatics contracts rhythmi-  cally, helping to “pump” the lymph along.    1. What is the function of lymphatic vessels?  2. How do lymphatic capillaries and blood capillaries  differ structurally from each other?  For answers, see Appendix A.    v Describe the function(s) of lymph nodes, tonsils,  the thymus, Peyer's patches, and the spleen.    In addition to returning tissue fluid to circulation, the  lymphatic system plays a major role in immunity. Cells  in lymph nodes in particular help protect the body by  removing foreign material such as bacteria and tumor  cells from the lymphatic stream and by providing a  place where lymphocytes that function in the immune  response can be activated.    What would be the consequence of blockage of the  thoracic duct?    Figure 12.3 Distribution of lymphatic vessels and lymph nodes. Note that    until recently, scientists thought that the CNS had no lymphatics. However, we now  know the CNS is drained by lymphatics near the venous dural sinuses.    As lymph is transported toward the heart, it is fil-  tered through the thousands of lymph nodes that clus-  ter along the lymphatic vessels (see Figure 12.1).  Particularly large clusters are found in the inguinal,  axillary, and cervical regions of the body (see  Figure 12.3). Within the lymph nodes are  macrophages (mak’ro-faj-ez), which engulf and  destroy bacteria, viruses, and other foreign sub-  stances in the lymph before it is returned to the  blood. Collections of lymphocytes (a type of white  blood cell, covered in Chapter 10) are also strategi-  cally located in the lymph nodes and respond to    foreign substances in the lymphatic stream. Although  we are not usually aware of the protective nature of  the lymph nodes, most of us have had “swollen  glands” during an active infection. What are actually  swollen in these cases are not glands at all but rather  lymph nodes (the term swollen glands is a misno-  mer), which swell as a result of the trapping function  of the nodes.   Lymph nodes vary in shape and size, but most  are kidney-shaped, about 1 centimeter long, and  “buried” in the connective tissue that surrounds  them. Each node is surrounded by a fibrous capsule  from which connective tissue strands called trabecu-  lae (trah-bek’yu-le) extend inward to divide the node  into a number of compartments (Figure 12.4, p. 418).    What is the benefit of having fewer efferent than  afferent lymphatic vessels?    Figure 12.4 Structure of a lymph node. Longitudinal  section of a lymph node and associated lymphatics.  Notice that several afferent lymphatics enter the node,  whereas fewer efferent lymphatics exit at its hilum.    The internal framework is a network of soft reticular  connective tissue, like “cellular bleachers,” that pro-  vides a place for the continually changing popula-  tion of lymphocytes to “sit” as they monitor the  lymphatic stream. Lymphocytes arise from the red  bone marrow but then migrate to the lymph nodes  and other lymphoid organs, where they reproduce  further (see Chapter 10).   The outer part of the node, its cortex, contains  collections of lymphocytes called follicles, many of  which have dark-staining centers called germinal  centers. These centers enlarge when specific B lym-  phocytes (the B cells) are generating daughter cells  called plasma cells, which release antibodies. The rest  of the cortical cells are lymphocytes “in transit,” the  so-called T cells that circulate continuously between  the blood, lymph nodes, and lymphatic stream,    performing their surveillance role. The medullary  cords are inward extensions of cortical tissue that con-  tain both B and T cells. Phagocytic macrophages are  located in the central medulla of the lymph node.   Lymph enters the convex side of a lymph node  through afferent lymphatic vessels. It then flows  through a number of sinuses (spaces) that meander  through the lymph node and finally exits from the  node at its indented (concave) region, the hilum  (hi'lum), via efferent lymphatic vessels. Because  there are fewer efferent vessels draining the node  than afferent vessels feeding it, the flow of lymph  through the node is very slow, kind of like sand flow-  ing through an hourglass. This allows time for the  lymphocytes and macrophages to perform their pro-  tective functions.    Homeostatic J  —S~ Imbalanc 12.1  Lymph nodes help rid the body of infectious agents  and cancer cells, but sometimes they are over-  whelmed by the very agents they are trying to destroy.  For example, when large numbers of bacteria or  viruses are trapped in the nodes, the nodes become  inflamed, swollen, and tender to the touch. The  lymph nodes can also become secondary cancer  sites, particularly in cancers that use lymphatic ves-  sels to spread throughout the body. Swelling is tem-  porary in lymph nodes fighting infection. In contrast,  swelling persists or nodes enlarge over time if they  contain cancer cells.    Lymph nodes are just one of the many types of  lymphoid organs in the body. Others include the  spleen, thymus, tonsils, Peyer's patches, and the  appendix (Figure 12.5), as well as bits of lymphoid  tissue scattered in epithelial and connective tissues.  All these organs have a predominance of reticular  connective tissue and lymphocytes. Although all  lymphoid organs have roles in protecting the body,  only the lymph nodes filter lymph.   The spleen is a soft organ located in the left side  of the abdominal cavity, just beneath the diaphragm,  that curls around the anterolateral aspect of the stom-  ach. Instead of filtering lymph, the spleen filters and  cleanses blood of bacteria, viruses, and other debris.  As with the other lymphoid organs, the spleen    provides a site for lymphocyte proliferation and  immune surveillance, but its most important func-  tion is to destroy worn-out red blood cells and  return some of their breakdown products to the liver.  For example, iron is used again for making hemoglo-  bin, and the rest of the hemoglobin molecule is  secreted in bile.   Other functions of the spleen include storing  platelets and acting as a blood reservoir (like the liver).  During hemorrhage, both the spleen and liver contract  and empty their blood into circulation to help bring  the blood volume back to its normal level. In the fetus,  the spleen is an important hematopoietic (blood  cell-forming) site, but as a rule the adult spleen pro-  duces only lymphocytes.   The thymus, which functions at peak level only  during youth, is a lymphoid mass found in the  anterior mediastinum overlying the heart.    and others, that function in the programming of T lym-  phocytes so they can carry out their protective roles in  the body (Chapter 9, p. 336).    The tonsils are small masses of lymphoid tissue  deep to the mucosa surrounding the pharynx  (throat). Their job is to trap and remove bacteria or  other foreign pathogens entering the throat. They  carry out this function so efficiently that sometimes  they become congested with bacteria and become  red, swollen, and sore, a condition called tonsillitis.   Peyer’s patches, which resemble tonsils, are  found in the wall of the distal small intestine.  Lymphoid follicles are also located in the wall of  the appendix, a tubelike offshoot of the proximal  large intestine. The macrophages of Peyer's patches  and the appendix are in an ideal position to capture  and destroy harmful bacteria (always present in tre-  mendous numbers in the intestine), thereby pre-  venting them from penetrating the intestinal wall.  Peyer's patches, the appendix, and the tonsils are  part of the collection of small lymphoid tissues  referred to as mucosa-associated lymphoid tissue  (MALT). Collectively, MALT acts as a sentinel to  protect the upper respiratory and digestive tracts  from the constant attacks of foreign matter entering  those cavities.    Figure 12.5 Lymphoid organs. Locations of the  tonsils, spleen, thymus, Peyer's patches, and appendix.    3. In which three regions of the body are the lymph  nodes most densely located?   4. What anatomical characteristic ensures that lymph  flows through the lymph nodes slowly?   5. Which lymphoid organ gets rid of aged red blood  cells?    Every second of every day, an army of microbes swarms  on our skin and invades our inner passageways—yet  we remain healthy most of the time. Although only  some of these microbes have the potential to cause  disease, the body seems to have developed a single-  minded approach toward such foes—if you're not  with us, you're against us!   Two types of mechanisms defend the body against  these tiny but mighty enemies: innate and adaptive  defense mechanisms (Figure 12.6, p. 420). Together  they make up the immune system. Although certain  body organs (lymphoid organs and blood vessels) are  intimately involved with the immune response, the  immune system is a functional system rather than an    organ system in an anatomical sense. Its “structures”  are a variety of molecules and trillions of immune  cells that inhabit lymphoid tissues and organs and cir-  culate in body fluids. The most important of the  immune cells are lymphocytes, dendritic cells, and mac-  rophages. Macrophages actually play an important role  in both innate and adaptive mechanisms. The innate  defense system, also called the nonspecific defense  system, responds immediately to protect the body  from all foreign substances, whatever they are. We are  born with our innate defenses, which include intact  skin and mucous membranes, the inflammatory  response, and a number of proteins produced by  body cells. These innate mechanisms reduce the work-  load of the adaptive defense mechanisms by generally  preventing the entry and spread of microorganisms  throughout the body.   The adaptive defense system, or specific  defense system, fights invaders that get past the  innate defenses by mounting an attack against one  or more particular foreign substances.   When our immune system is operating effectively,  it protects us from most bacteria, viruses, transplanted  organs or grafts, and even our own cells that have  “turned against” us (cancer cells). The immune system  does this both directly, by cell attack, and indirectly,  by releasing mobilizing chemicals and protective anti-  body molecules. The resulting highly specific resis-  tance to disease is called immunity (immun = free).   Unlike the innate defenses, which are always pre-  pared to defend the body, the adaptive system must  first “meet,” or be sensitized by, an initial exposure to  a foreign substance (antigen) before it can protect the  body against the invader. Another important feature  of the adaptive response is that it “remembers” which    invaders it has fought. In other words, the adaptive  immune response has both specificity and memory.  Nonetheless, what the adaptive system lacks in speed  it makes up for in the precision of its counterattacks.  Although we consider them separately, keep in mind  that innate and adaptive defenses always work hand-  in-hand to protect the body.    7. How do the innate and adaptive defenses differ?  For the answer, see Appendix A.    Some innate resistance to disease is inherited. For  instance, there are certain diseases that humans never  get, such as some forms of tuberculosis that affect  birds. Most often, however, the term innate, or nonspe-  cific, body defense refers to the mechanical barriers  that cover body surfaces and to the cells and chemicals  that act on the initial battlefronts to protect the body  from invading pathogens (harmful microorganisms).  Table 12.1 provides a detailed summary of the innate  defenses.    The body’s first line of defense against the invasion of  disease-causing microorganisms includes the skin    Intact skin (epidermis) Forms mechanical barrier that prevents entry of pathogens and  other harmful substances into body.  e Acid mantle Skin secretions make epidermal surface acidic, which inhibits  bacterial growth; sebum also contains bacteria-killing chemicals.  e Keratin Provides resistance against acids, alkalis, and bacterial enzymes.  Intact mucous membranes Form mechanical barrier that prevents entry of pathogens.  e Mucus Traps microorganisms in respiratory and digestive tracts.  e Nasal hairs Filter and trap microorganisms and other airborne particles in nasal  passages.  e Cilia Propel debris-laden mucus away from lower respiratory passages.  e Gastric juice Contains concentrated hydrochloric acid and protein-digesting  enzymes that destroy pathogens in stomach.  e Acid mantle of vagina Inhibits growth of bacteria and fungi in female reproductive tract.  e Lacrimal secretion (tears); saliva Continuously lubricate and cleanse eyes (tears) and oral cavity    (saliva); contain lysozyme, an enzyme that destroys microorganisms.  Cellular and chemical defenses—second line of defense    Phagocytes Engulf and destroy pathogens that breach surface membrane  barriers; macrophages also contribute to immune response.    Natural killer cells Promote cell lysis by direct cell attack against virus-infected or  cancerous body cells; do not depend on specific antigen recognition.    Inflammatory response Prevents spread of injurious agents to adjacent tissues, disposes of  pathogens and dead tissue cells, and promotes tissue repair; releases  chemical mediators that attract phagocytes (and immune cells) to    the area.  Antimicrobial chemicals  e Complement Group of plasma proteins that lyses microorganisms, enhances  phagocytosis by opsonization, and intensifies inflammatory  response.  e Interferons Proteins released by virus-infected cells that protect uninfected tissue    e Fluids with acid pH Normally acid pH inhibits bacterial growth; urine cleanses the lower 12  urinary tract as it flushes from the body.    Fever Systemic response triggered by pyrogens; high body temperature  inhibits multiplication of bacteria and enhances body repair  processes.    and mucous membranes. As long as the skin is unbro-  ken, its keratinized epidermis is a strong physical  barrier to most microorganisms that swarm on the  skin. Intact mucous membranes provide similar  mechanical barriers within the body. Recall that  mucous membranes line all body cavities open to  the exterior. Besides serving as physical barriers,  these membranes produce a variety of protective  secretions:    e The acidic pH of skin secretions (called the  acid mantle) and usually of urine (pH of 4.5  to 6) inhibits bacterial growth, and sebum con-  tains chemicals that are toxic to bacteria. The  vaginal secretions of adult females are also  very acidic.   e Sticky mucus traps many microorganisms that  enter digestive and respiratory passageways.    e The stomach mucosa secretes gastric juice con-  taining hydrochloric acid and protein-digesting  enzymes that both kill pathogens.    e Saliva and lacrimal secretions (tears) contain  lysozyme, an enzyme that destroys bacteria.    Some mucosae also have structural modifica-  tions that fend off potential invaders. Mucus-coated  hairs inside the nasal cavity trap inhaled particles,  and the respiratory tract mucosa is ciliated. The cilia  sweep dust- and bacteria-laden mucus (think  “sticky trap”) superiorly toward the mouth, pre-  venting it from entering the lungs, where the warm,  moist environment provides ideal conditions for  bacterial growth.   Although the surface barriers are quite effective,  some microbes may get through. Also, the barriers are  broken from time to time by small nicks and cuts  resulting, for example, from shaving or a paper cut.  When this happens and microorganisms do invade  deeper tissues, the internal innate mechanisms come  into play.   For its second line of defense, the body uses an enor-  mous number of cells and chemicals. These defenses  rely on the destructive powers of cells called phago-  cytes and natural killer cells, on the inflammatory  response, and on a variety of chemical substances  that kill pathogens and help repair tissue. Fever is  another nonspecific protective response.    Natural killer (NK) cells roam the body in blood and  lymph. They are a unique group of aggressive lympho-  cytes that can lyse (burst) and kill cancer cells, virus-  infected body cells, and some other nonspecific  targets well before the adaptive arm of the immune  system is enlisted in the fight. Natural killer cells can  act spontaneously against any such target by recog-  nizing certain sugars on the “intruder’s” surface as well  as its lack of certain “self” cell surface molecules. NK  cells are not phagocytic. They attack the target cell’s  membrane and release lytic chemicals called perforin,  which pokes holes in the membrane, and granzymes  (enzymes), which degrade target cell contents. Shortly  thereafter, the target cell dies as its membrane and  nucleus disintegrate. NK cells also release powerful  inflammatory chemicals.    The inflammatory response is a nonspecific response  that is triggered whenever body tissues are injured  (Figure 12.7). For example, it occurs in response to  physical trauma, intense heat, irritating chemicals, and  infection by viruses and bacteria. The four most com-  mon indicators, or cardinal signs, of acute inflamma-  tion are redness, heat (inflamm = set on fire), pain,  and swelling (edema). It is easy to understand why  these signs and symptoms occur, once you under-  stand the events of the inflammatory response.   The inflammatory process begins with a chemi-  cal “alarm.” When cells are damaged, they release  inflammatory chemicals, including histamine and  kinins (ki’ninz), that (1) cause blood vessels in the  area to dilate, (2) make capillaries leaky, and  (3) attract phagocytes and white blood cells to the  area. (This third phenomenon is called positive  chemotaxis because the cells are moving toward  a high concentration of signaling molecules.)  Dilation of the blood vessels increases the blood  flow to the area, accounting for the redness and heat  observed. Increased permeability of the capillaries  allows fluid to leak from the blood into the tissue  spaces, causing local edema (swelling) that also    Figure 12.7 Flowchart of inflammatory events. The four cardinal signs (most  common indicators) of acute inflammation are shown in red boxes. Limitation of  joint movement (box outlined in red) occurs in some cases and is considered to be    activates pain receptors in the area as pressure in the  tissues builds. If the swollen, painful area is a joint,  its function (movement) may be impaired tempo-  rarily. This forces the injured part to rest, which aids  healing. Some authorities consider limitation of  joint movement to be the fifth cardinal sign of  inflammation.   The inflammatory response prevents the spread  of damaging agents to nearby tissues, disposes of cell    debris and pathogens, and sets the stage for repair.  Let's look at how it accomplishes these tasks by  mobilizing phagocytes (Figure 12.8, p. 424). Once  the inflammatory process has begun:    @ Neutrophils, responding to a gradient of diffus-  ing inflammatory chemicals, enter the blood    Inflammatory chemicals  diffusing from the inflamed  site act as chemotactic  agents    Neutrophils enter blood from  bone marrow and roll along  the vessel wall    @ At the point where the chemical signal is the  strongest, they flatten out and squeeze through  the space between cells in the capillary walls, a  process called diapedesis.    @) Still drawn by the gradient of inflammatory  chemicals (positive chemotaxis), the neutrophils  gather at the site of tissue injury, and within an  hour, they are busily devouring any foreign  material present by phagocytosis.    As the counterattack continues, monocytes fol-  low neutrophils into the inflamed area. Monocytes  are fairly poor phagocytes, but within 12 hours after  entering the tissues they become macrophages with  insatiable appetites. The macrophages continue to  wage the battle, replacing the short-lived neutrophils  at the site of damage. Macrophages are the central  actors in the final disposal of cell debris as the  inflammation subsides.   Besides phagocytosis, other protective events are  also occurring at the inflamed site. Clotting proteins,  leaked into the area from the blood, are activated and  begin to wall off the damaged area with fibrin to    prevent the spread of harmful agents to neighboring  tissues. The fibrin mesh (think of a small fish net)  also forms scaffolding for permanent repair. The  local heat increases the metabolic rate of the tissue  cells, speeding up their defensive actions and repair  processes.   If the damaged area contains pathogens that  have previously invaded the body, the third line of  defense also comes into play—the adaptive response  mediated by lymphocytes.    Homeostatic J  £ Imbalanc 12.2  In severely infected areas, the battle takes a consider-  able toll on both sides, and creamy, yellow pus may  form in the wound. Pus is a mixture of dead or  dying neutrophils and macrophages, broken-down  tissue cells, and living and dead pathogens. If the  inflammatory mechanism fails to fully clear the area  of debris, the sac of pus may become walled off,  forming an abscess. Surgical drainage of abscesses is  often necessary before healing can occur.    Pathogens that make it through the mechanical barri-  ers are confronted by phagocytes (fag’o-sitz"; phago  = eat) in nearly every body organ. A phagocyte, such  as a macrophage or neutrophil, engulfs a foreign parti-  cle by the process of phagocytosis (Figure 12.9). (Recall  what you learned in Chapter 3.) Flowing cytoplasmic  extensions bind to the particle and then pull it inside,  forming a phagocytic vesicle. The vesicle then fuses  with a lysosome, where enzymes digest its contents.    v@ Name several antimicrobial substances produced  by the body that act in innate body defense.    A variety of antimicrobial proteins enhance the  innate defenses either by attacking microorganisms  directly or by hindering their ability to reproduce. The    For the answer, see Appendix A. : ;  gi most important of these are complement and interferon.    Phagocytes Complement The term complement refers to a  Learning Objective group of at least 20 plasma proteins that circulate in  v Explain the importance of phagocytes. the blood in an inactive state, much like inactive    clotting proteins. However, when complement  becomes attached, or fixed, to foreign cells such as    ©) Lysosomal  enzymes digest  the pathogens or  debris, leaving a  residual body.    (a) A macrophage (purple) uses its cytoplasmic  extensions to ingest bacillus-shaped bacteria  (pink) by phagocytosis. Scanning electron    membrane in step-by-step sequence, forming a  membrane attack complex (a MAC attack).    Figure 12.10 Activation of complement, resulting in lysis of a target cell.    bacteria, fungi, or mismatched red blood cells, it is  activated and becomes a major factor in the fight  against foreign cells (Figure 12.10). This complement  fixation occurs when complement proteins bind to  certain sugars or proteins (such as antibodies) on the  foreign cell’s surface. One result of complement fix-  ation is @) the formation of membrane attack  complexes (MAC) that produce holes, or pores, in  the foreign cell’s surface. @ These pores allow water  to rush into the cell, @) causing it to burst, or lyse.  Activated complement also amplifies the inflamma-  tory response. Some of the molecules released dur-  ing the activation process are vasodilators, and some  are chemotaxis chemicals that attract neutrophils and  macrophages into the region. Still others cause the  cell membranes of the foreign cells to become sticky  so they are easier to phagocytize; this effect (that  is, easing phagocytosis) is called opsonization.  Complement is a nonspecific defensive mechanism  that “complements,” or enhances, the effectiveness  of both innate and adaptive defenses. Complement  proteins must be activated in a particular sequence  called a cascade, which insures that complement is  not accidentally activated.    coat—that lack the cellular machinery required to  generate ATP or make proteins. They do their “dirty  work” in the body by taking over target cells (differ-  ent cells for different viruses), then using cellular  machinery and nutrients to reproduce themselves.  Although the virus-infected cells can do little to save  themselves, they help defend cells that have not yet  been infected by secreting small proteins called  interferons (in-ter-feer’onz). The interferon mole-  cules diffuse to nearby cells and bind to their mem-  brane receptors. This binding stimulates the synthesis  of proteins that “interfere” with the ability of viruses  to multiply within these still-healthy cells, reducing  the spread of the virus. Interferons do not assist with  fighting bacterial or fungal infections.    Fever, or abnormally high body temperature, is a  systemic response to invading microorganisms. Body  temperature is regulated by the hypothalamus,  referred to as the body’s “thermostat.” Normally the  thermostat is set at approximately 37°C (98.6°F),  but it can be reset upward in response to pyrogens  (pyro = fire), chemicals secreted by white blood cells    and macrophages exposed to foreign cells or sub-  stances in the body.   Although high fevers are dangerous because  excess heat “scrambles” (destroys protein structure)  enzymes and other body proteins, rendering them  nonfunctional, mild or moderate fever seems to ben-  efit the body. Bacteria require large amounts of iron  and zinc to multiply, but during a fever the liver and  spleen gather up these nutrients, making them less  available. Fever also increases the metabolic rate of  tissue cells in general, speeding up repair processes.    Did You Get It?  9. How does complement cause lysis of a pathogenic  microorganism?  10. Which type of infectious microorganism causes the  body’s level of interferons to rise?  For answers, see Appendix A.    Most of us would find it wonderfully convenient if we  could walk into a single clothing store and buy custom  outfits for every occasion—that fit us “to aT.” We know  that such a service is nearly impossible to find—yet we  take for granted our built-in specific defense system,  which stalks and eliminates with nearly equal preci-  sion almost any type of pathogen that intrudes into  the body.   The immune response to a threat involves tre-  mendously increased internal nonspecific defenses  (inflammatory responses and others) and also pro-  vides protection that is carefully targeted against spe-  cific antigens. Furthermore, the initial exposure to  an antigen “primes” (sensitizes) the body to react  more vigorously to later meetings with the same  antigen.   Referred to as the body’s third line of defense (see  Figure 12.6), the adaptive, or specific, defense mech-  anism is a functional system that recognizes foreign  molecules called antigens and acts to inactivate or  destroy them. Normally it protects us from a wide  variety of pathogens, as well as from abnormal body  cells. When it fails, malfunctions, or is disabled,  some of the most devastating diseases—such as can-  cer, rheumatoid arthritis, and AIDS—may result.   Although immunology, the study of immunity,  had not been established yet, the ancient Greeks    knew that once someone had suffered a certain  infectious disease, that person was unlikely to have  the same disease again. The basis of this immunity  was revealed in the late 1800s, when it was shown  that animals surviving a serious bacterial infection  have “factors” in their blood that protect them from  future attacks by the same pathogen. (These factors  are now known to be unique proteins called  antibodies.) Furthermore, it was demonstrated that if  antibody-containing serum from the surviving ani-  mals (immune serum) were injected into animals  that had not been exposed to the pathogen, those  animals would also be protected. This was exciting  news. But then, in the mid-1900s, it was discovered  that injection of serum containing antibodies did  not always protect a recipient from diseases the  donor had survived. In such cases, however, injection  of the donor's lymphocytes did provide immunity.  These landmark experiments revealed three impor-  tant aspects of adaptive defense:    As the pieces began to fall into place, two  separate but overlapping arms of the adaptive  defense system were recognized. Humoral  (hu’mor-al) immunity, also called antibody-  mediated immunity, is provided by antibodies  (immune proteins) present in the body’s “humors,”  or fluids. When lymphocytes themselves defend the  body, the immunity is called cellular immunity or  cell-mediated immunity because the protective  factor is living cells. The cellular arm also has cellu-  lar targets—virus-infected cells, cancer cells, and  cells of foreign grafts. The lymphocytes act against  such targets either directly, by lysing the foreign  cells, or indirectly, by releasing chemicals that  enhance the inflammatory response or activate  other immune cells. However, before we describe  the humoral and cellular responses individually, we  will consider both the remarkable cells involved in  these immune responses and the antigens that  trigger their activity.    Define antigen and hapten, and name substances  that act as complete antigens.    An antigen (an’ti-jen; Ag) is any substance capable of  provoking an immune response. Foreign antigens are  large, complex molecules that are not normally pres-  ent in our bodies. Consequently, they are foreign  intruders, or nonself. An almost limitless variety of  substances can act as antigens, including virtually all  foreign proteins, nucleic acids, many large carbohy-  drates, and some lipids. Of these, proteins provoke the  strongest responses. Pollen grains and microorganisms  such as bacteria, fungi, and virus particles are antigenic  because their surfaces bear such foreign molecules.   Our own cells are richly studded with a variety of  protein and carbohydrate molecules. As our immune  system develops, it takes inventory of all these mole-  cules so that, thereafter, they are recognized as self.  Although these self-antigens do not trigger an  immune response in us, they are strongly antigenic to  other people. This helps explain why our bodies reject  cells of transplanted organs or foreign grafts unless  special measures (drugs and others) are taken to  cripple or stifle the immune response. In the unusual  situations where self-antigens do elicit an immune  response, autoimmune disease results.    blood types can donate blood to one another. Recall  our discussion of blood antigens (Chapter 10, p. 365).  Depending on your individual blood type, one or more  blood antigen types may be self to your body, and one  or more may be nonself. For example, if you are blood  type A, type A antigen is self, but type B antigen is non-  self. However, in a person with type AB blood, both A  and B antigens are self-antigens.    As a rule, small molecules are not antigenic, but  when they link up with our own proteins, the immune  system may recognize the combination as foreign and  mount an attack that is harmful rather than protective.  In such cases, the troublesome small molecule is called  a hapten (haptein = to fasten) or incomplete antigen.  Besides certain drugs, chemicals that act as haptens are  found in poison ivy, animal dander, and even in some  detergents, hair dyes, cosmetics, and other commonly  used household and industrial products.    Homeostatic J  K Imbalanc 12.3  Perhaps the most dramatic and familiar example of a  drug hapten’s provoking an immune response involves  the binding of penicillin to blood proteins, which  causes a penicillin reaction in some people. The combi-  nation of blood protein and penicillin is recognized as  foreign. In such cases, the immune system mounts  such a vicious attack that the person’s life is  endangered.    Did You Get It?  11. What is the difference between an antigen and a  self-antigen?  For the answer, see Appendix A.    vz Name the two arms of the adaptive defense  system, and relate each to a specific lymphocyte  type (B or T cell).    v@ Compare and contrast the development of B and  T cells.  1# State the roles of B cells and T cells.  v Explain the importance of antigen-presenting cells  in immunity.  The crucial cells of the adaptive system are lympho-  cytes and antigen-presenting cells (APCs). We already  discussed the unique lymphocytes called NK cells  as part of the innate defenses. Lymphocytes exist in  two other major “flavors.” The B lymphocytes, or  B cells, produce antibodies and oversee humoral  immunity, whereas the T lymphocytes, or T cells,  constitute the cell-mediated arm of the adaptive  defenses and do not make antibodies. T lymphocytes  can recognize and eliminate specific virus-infected or  tumor cells, and B lymphocytes can target specific  extracellular antigens. In contrast, APCs do not  respond to specific antigens but instead play an  essential role in activating the lymphocytes that do.   Like all blood cells, lymphocytes originate from  hemocytoblasts in red bone marrow. The immature  (called naive) lymphocytes released from the marrow  are essentially identical. Whether a given lymphocyte  matures into a B cell or a T cell depends on where in    the body it becomes immunocompetent, that is,  capable of responding to a specific antigen by bind-  ing to it with antigen-specific receptors that appear  on the lymphocyte’s surface. T cells arise from lym-  phocytes that migrate to the thymus (Figure 12.11).  There they undergo a maturation process lasting 2 to  3 days, directed by thymic hormones (thymosin and  others). Within the thymus, the immature lym-  phocytes divide rapidly and their numbers increase  enormously, but only those maturing T cells with the    E] Red bone marrow: site of lymphocyte origin  E] Primary lymphoid organs: sites of  development of immunocompetence as   I| Secondary lymphoid organs: sites of  antigen encounter and activation to  become effector and memory B or T cells J    ©) Lymphocytes destined to become T cells  migrate (in blood) to the thymus and develop  immunocompetence there. B cells develop  immunocompetence in red bone marrow.    © Immunocompetent but still naive  lymphocytes leave the thymus and bone  marrow. They “seed” the lymph nodes,  spleen, and other lymphoid tissues, where  they encounter their antigens and become  activated.    © Antigen-activated (mature)  immunocompetent lymphocytes (effector  cells and memory cells) circulate  continuously in the bloodstream and lymph  and throughout the lymphoid organs of the  body.    sharpest ability to identify foreign antigens survive.  Lymphocytes capable of binding strongly with self-  antigens (and of acting against body cells) are  vigorously weeded out and destroyed. Thus, the de-  velopment of self-tolerance for the body's own  cells is an essential part of a lymphocyte’s “educa-  tion.” This is true not only for T cells but also for  B cells. B cells develop immunocompetence in bone  marrow, but less is known about the factors that reg-  ulate B cell maturation.    Once a lymphocyte is immunocompetent, it will  be able to react to one and only one distinct antigen,  because all the antigen receptors on its external sur-  face are the same, meaning they are specific for the  same antigen. For example, the receptors of one lym-  phocyte can recognize only a part of the hepatitis A  virus, those of another lymphocyte can recognize  only pneumococcus bacteria, and so forth.   Although all the details of the maturation pro-  cess are still being worked out, we know that lym-  phocytes become immunocompetent before meeting  the antigens they may later attack. Thus, it is our  genes, not antigens, that determine what foreign sub-  stances our immune system will be able to recognize and  resist. Only some of the possible antigens our lym-  phocytes are programmed to resist will ever invade  our bodies. Consequently, only some members of  our army of immunocompetent cells will be mobi-  lized during our lifetime.   After they become immunocompetent, both  T cells and B cells migrate to the lymph nodes and  spleen (and loose connective tissues), where their  encounters with antigens will occur (Figure 12.11 @).  Then, when the lymphocytes bind with recognized  antigens, they complete their differentiation from  naive cells into fully mature T cells and B cells.  Mature lymphocytes, especially T cells, circulate  continuously through the body (Figure 12.11 ©).  This makes sense because circulating greatly  increases a lymphocyte’s chance of coming into con-  tact with antigens, as well as with huge numbers of  macrophages and other lymphocytes along the  route.    The major role of antigen-presenting cells (APCs) in  immunity is to engulf antigens and then present  fragments of them, like signal flags, on their own  surfaces, where they can be recognized by T cells. In  other words, they present antigens to the cells that will  actually deal with the antigens. The major types of  cells acting as APCs are dendritic cells, macrophages,  and B lymphocytes.   All of these cell types are in sites that make it easy  to encounter and process antigens. Dendritic cells are  present in connective tissues and in the epidermis  (where they are also called Langerhans cells). These  cells are therefore at the body’s frontiers, best situated  to act as mobile sentinels. Macrophages are widely  distributed throughout the lymphoid organs and    connective tissues, where they act as phagocytes in  the innate defense system. Macrophages tend to  remain fixed in the lymphoid organs (as if waiting  for antigens to come to them).   When they present antigens, dendritic cells and  macrophages activate T cells. Activated T cells, in  turn, release chemicals (see Table 12.3, pp. 442-443)  that prod macrophages to become activated macro-  phages, true “killers” that are insatiable phagocytes  and secrete bactericidal (bacteria-killing) chemicals.  As you will see, interactions between lymphocytes,  and between lymphocytes and APCs, play roles in  virtually all phases of the immune response.   In addition to T cell circulation and passive  delivery of antigens to lymphoid organs by lymphat-  ics, there is a third antigen capture and delivery  system—migration of dendritic cells to secondary  lymphoid organs. With their long, wispy extensions,  dendritic cells are very efficient antigen catchers.  Once they have engulfed antigens by phagocytosis,  they enter nearby lymphatics to get to the lymphoid  organ where they will present the antigens to T cells.  Indeed, dendritic cells are the most effective antigen  presenters known—it's their only job. Dendritic cells  are a key link between innate and adaptive immu-  nity. They initiate adaptive immune responses partic-  ularly tailored to the type of pathogen that they have  encountered.   To summarize, the adaptive immune system is a  two-fisted defensive system, with a humoral arm and a  cellular arm. It uses lymphocytes, APCs, and specific  molecules to identify and destroy all substances—  both living and nonliving—that are in the body but are  not recognized as self. The immune system’s ability to  respond to such threats depends on the ability of its  cells (1) to recognize foreign substances (antigens) in  the body by binding to them and (2) to communicate  with one another so that the system as a whole  mounts a response specific to those antigens.    12. What are the two types of lymphocytes involved in  adaptive immune responses, and how do their  functions in body protection differ?   14. What is the essential role of macrophages and  dendritic cells in adaptive immunity?    Figure 12.12 Clonal selection of a  B cell. The initial meeting with the  antigen stimulates the primary  response, in which the B cell divides  rapidly, forming many clones (clonal  selection), most of which become    antibody-producing plasma cells.  Cells that do not differentiate into  plasma cells become memory cells,  which are primed to respond to  subsequent exposures to the same  antigen. Should such a meeting    occur, the memory cells quickly  produce more memory cells and  larger numbers of effector plasma  cells with the same antigen specific-  ity. Responses generated by memory  cells are called secondary responses.   1# State the role of plasma cells.  An immunocompetent but as yet immature (naive)  B lymphocyte is stimulated to complete its develop-  ment (from naive to fully mature B cell) when antigens  bind to its surface receptors. This binding event sensi-  tizes, or activates, the lymphocyte to “switch on” and    undergo clonal selection. In this process, the lympho-  cyte begins to grow and then multiplies rapidly to  form an army of cells exactly like itself and bearing the  same antigen-specific receptors (Figure 12.12). The  resulting family of identical cells descended from the  same ancestor cell are called clones, and clone forma-  tion is the primary humoral response to that anti-  gen. (As described later, a special group of T cells called  helper T cells also influence B cell activation.)   Most of the B cell clone members, or descen-  dants, become plasma cells. After an initial lag    Figure 12.13 Primary and secondary humoral  responses to an antigen. In the primary response, the  level of antibodies in the blood gradually rises and then  rapidly declines. The secondary response is both more  rapid and more intense, and the antibody level remains  high for a much longer time.    period, these antibody-producing “factories” swing  into action, producing the same highly specific anti-  bodies at an unbelievable rate of about 2,000 anti-  body molecules per second. However, this flurry of  activity lasts only 4 or 5 days; then the plasma cells  begin to die. The level of antibody in the blood dur-  ing this primary response peaks about 10 days after  the response begins and then slowly declines  (Figure 12.13).   B cell clone members that do not become plasma  cells become long-lived memory cells capable of  responding to the same antigen if they “see” it again.  Memory cells are responsible for the immunological  memory mentioned earlier. These later immune  responses, called secondary humoral responses, are  produced much faster, are more prolonged, and are  more effective than the events of the primary response  because all the preparations for this attack have  already been made. Within hours after recognition of  the “old-enemy” antigen, a new army of plasma cells  is being generated, and antibodies flood into the  bloodstream. Within 2 to 3 days, the blood antibody  level peaks (at a much higher level than seen in the  primary response), and the level remains high for  weeks to months. We will describe how antibodies  work shortly.    15. Suzy had the flu last winter and got it again this  year. However, her doctor says this year's flu is a  new strain. Is Suzy’s body mounting a primary or a  secondary immune response?   y Explain the function(s) of antibodies, and describe  clinical uses of monoclonal antibodies.    When your B cells encounter antigens and produce  antibodies against them, you are exhibiting active  immunity (Figure 12.14). Active immunity is  (1) naturally acquired during bacterial and viral infec-  tions, during which we may develop the signs and  symptoms of the disease and suffer a little (or a lot),  and (2) artificially acquired when we receive vaccines.  It makes little difference whether the antigen invades  the body under its own power or is introduced on  purpose in the form of a vaccine. The response of the  immune system is pretty much the same. Indeed,  once it was recognized that secondary responses are  so much more vigorous, the race was on to develop  vaccines to “prime” the immune response by provid-  ing a first meeting with various antigens. Most vac-  cines contain pathogens that are dead or attenuated  (living, but less able or unable to cause disease).  We receive two benefits from vaccines: (1) they  spare us most of the signs and symptoms (and dis-  comfort) of the disease that would otherwise occur  during the primary response and (2) the weakened  antigens are still able to stimulate antibody produc-  tion and promote immunological memory. So-called  booster shots, which may intensify the immune  response at later meetings with the same antigen, are  also available. Vaccines have virtually wiped out  smallpox and are currently available against micro-  organisms that cause pneumonia, polio, tetanus,  diphtheria, whooping cough, measles, and many  other diseases. Worldwide, most children today  receive lifesaving vaccines. Between 2-3 million  deaths are estimated to be prevented through active  immunization programs every year. The more chil-  dren who are vaccinated, the better the herd  immunity, a phenomenon in which a population of  people are generally protected because most of a  given population is immune to a disease or    infection. Herd immunity prevents an outbreak of  the disease or infection and thus helps to protect  individuals who have not been immunized.   Passive immunity is quite different from active  immunity, both in the antibody source and in the  degree of protection it provides (see Figure 12.14).  Instead of being made by your plasma cells, the anti-  bodies are obtained from the serum of an immune  human or animal donor. As a result, your B cells are not  challenged by the antigen, immunological memory  does not occur, and the temporary protection pro-  vided by the “donated antibodies” ends when they  naturally degrade in the body.   Passive immunity is conferred naturally on a fetus  when the mother’s antibodies cross the placenta and  enter the fetal circulation, and after birth during  breastfeeding. For several months after birth, the baby  is protected from all the antigens to which the  mother has been exposed.   Passive immunity is artificially conferred when a  person receives immune serum or gamma globulin  (donated antibodies). Gamma globulin is commonly  administered after exposure to hepatitis. Other  immune sera are used to treat poisonous snakebites  (an antivenom), botulism, rabies, and tetanus (an anti-  toxin) because these diseases will kill a person before  active immunity can be established. The donated anti-  bodies provide immediate protection, but their effect  is short-lived (2 to 3 weeks). Meanwhile, however, the  body’s own defenses take over.   In addition to their use to provide passive immu-  nity, antibodies are prepared commercially for use in  research, in diagnostic testing, and in treating certain  cancers. Monoclonal antibodies used for such pur-  poses are descendants of a single cell and are pure  antibody preparations that exhibit specificity for  one, and only one, antigen. Besides their use in  delivering cancer-fighting drugs to cancerous tissue,  monoclonal antibodies are being used for early can-  cer diagnosis and to track cancers hidden deep  within the body. They are also used for diagnosing  pregnancy, hepatitis, and rabies.   4# List the five antibody classes, and describe their  specific roles in immunity.   acquired  Antibodies  passed from  mother to  fetus via  placenta; or  to infant in  her milk    Figure 12.14 Types of humoral immunity. There  are two overall types of humoral immunity, active and  passive. Darker green boxes signify naturally acquired  immunity, whereas lighter green boxes show artificially  acquired immunity.    Antibodies, also referred to as immunoglobulins  (im”mu-no-glob'u-linz; Igs), constitute the gamma  globulin part of blood proteins. Antibodies are solu-  ble proteins secreted by activated B cells or by their  plasma-cell offspring in response to an antigen, and  they are capable of binding specifically with that  antigen.   Antibodies are formed (by different B cells) in  response to a huge number of different antigens.  Despite their variety, they all have a similar basic  anatomy that allows them to be grouped into five Ig  classes, each slightly different in structure and  function.    Basic Antibody Structure Regardless of its class,  every antibody has a basic structure consisting of  four polypeptide chains linked together by disulfide  (sulfur-to-sulfur) bonds (Figure 12.15, p. 434). Two  of the four chains are identical; these are the heavy  chains. The other two chains, the light chains, are also  identical to each other but are only about half as    combined, the antibody molecule formed has two  identical halves, each consisting of a heavy and a  light chain, and the molecule as a whole is com-  monly described as being Y-shaped.   When scientists began investigating antibody  structure, they discovered something very peculiar.  Each of the four chains forming an antibody had a    Figure 12.15 Basic antibody structure. Simplified  diagram. The monomer of each type of antibody is  formed by four polypeptide chains (two light chains and  two heavy chains) that are joined by disulfide bonds.  Each chain has a variable (V) region (antigen-binding site  that differs in different antibodies) and a constant (C)  region (essentially identical in different antibodies of the  same class).    variable (V) region at one end and a constant (C)  region at the other end. Antibodies responding to  different antigens had different variable regions, but  their constant regions were the same or nearly so.  This made sense when it was discovered that the vari-  able regions of the heavy and light chains combine  their efforts to form an antigen-binding site (see  Figure 12.15) uniquely shaped to “fit” a specific  antigen. Hence, each antibody has two such antigen-  binding regions.   The constant regions that form the “stem” of an  antibody can be compared to the handle of a key. A  key handle has a common function for all keys: it  allows you to hold the key and place its tumbler-  moving portion into the lock. Similarly, the constant  regions of the antibody chains serve common func-  tions in all antibodies: they determine the type of  antibody formed (antibody class), as well as how the  antibody class will carry out its immune roles in  the body, and the cell types or chemicals with  which the antibody can bind.    Did You Get It?  16. What is the importance of the variable region of  antibodies?  For the answer, see Appendix A.    Antibody Classes There are five major immuno-  globulin classes—IgM, IgA, IgD, IgG, and IgE.  (Remember the name MADGE to recall the five Ig  types.) Antibodies IgD, IgG, and IgE have the same  basic Y-shaped structure described previously and  are referred to as monomers (Table 12.2). IgA antibod-  ies occur in both monomer and dimer (two linked  monomers) forms. (Only the dimer form is shown  in the table.) Because they are constructed of five  linked monomers, IgM antibodies are called pentam-  ers (penta = five).   The antibodies of each class have slightly differ-  ent biological roles and locations in the body. For  example, IgG is the most abundant antibody in  blood plasma and is the only type that can cross the  placental barrier. Hence, the passive immunity that a  mother transfers to her fetus is “with the compli-  ments” of her IgG antibodies. Only IgM and IgG can  fix complement. The IgA dimer, secretory IgA, is found  mainly in secretions that bathe body surfaces, such as  mucus and tears. It plays a major role in preventing  pathogens from gaining entry into the body. IgE anti-  bodies are the “troublemaker” antibodies involved in  allergies.    Did You Get It?  17. Which class of antibody is found in saliva and  tears?  For the answer, see Appendix A.    Antibody Function Antibodies inactivate antigens  in a number of ways—by complement fixation, neu-  tralization, agglutination, opsonization, and precip-  itation (Figure 12.16, p. 436). Of these, complement  fixation and neutralization are most important to  body protection.   Complement is the chief antibody ammunition  used against cellular antigens, such as bacteria or  mismatched red blood cells. As noted earlier, com-  plement is fixed (activated) during innate defenses  and when it binds to antibodies attached to cellular  targets (Look back at Figure 12.10, p. 427). Antibody  binding also “tags” antigen for phagocytosis, a pro-  cess called opsonization.   Neutralization occurs when antibodies bind to  specific sites (usually at or close to the site where a  cell would bind) on bacterial exotoxins (toxic proteins  secreted by bacteria) or on viruses that can cause cell  injury. In this way, they block the harmful effects of    When bound to B cell membrane,  serves as antigen receptor; first    the exotoxin or virus by preventing them from bind-  ing to body cells.   Because antibodies have more than one antigen-  binding site, they can bind to more than one anti-  gen at a time; consequently, antigen-antibody  complexes can be cross-linked into large lattices.  When the cross-linking involves cell-bound anti-  gens, the process causes clumping of the foreign  cells, a process called agglutination. This type of  antigen-antibody reaction occurs when mismatched  blood is transfused (the foreign red blood cells are  clumped) and is the basis of tests used for blood  typing. (Look back at Figure 10.7, p. 368.) When the  cross-linking process involves soluble antigenic mol-  ecules, the resulting antigen-antibody complexes are    so large that they become insoluble and settle out  of solution. This cross-linking reaction is more  precisely called precipitation. Such agglutinated  bacteria and immobilized (precipitated) antigen  molecules are much more easily captured and  engulfed by the body's phagocytes than are freely  moving antigens.    18. Regarding the action of antibodies, what is  neutralization?  19. Distinguish among precipitation, agglutination,  and opsonization.  For answers, see Appendix A.    Complement and agglutination aid phagocytosis, but  they assist it in different ways. What is this difference?    Figure 12.16 Mechanisms of antibody action. Note that opsonization, the  process by which antibodies “mark” antigens for phagocytes, is not pictured here.    @ Distinguish the roles of helper, regulatory, and  cytotoxic T cells.    The main difference between the two arms of the  adaptive response is that B cells secrete their anti-  body weapons,” whereas T cells fight their antigens    directly in “cell-to-cell combat.” Like B cells, immu-  nocompetent T cells are activated to form a clone by  binding with a “recognized” antigen (look ahead to  Figure 12.19, p. 439). However, unlike B cells, T cells  are not able to bind with free antigens. Instead, the  antigens must be “presented” by a macrophage (or  other antigen-presenting cell), and a double recogni-  tion must occur. The APC engulfs an antigen and pro-  cesses it internally. Parts of the processed antigen are  then displayed on the external surface of the present-  ing cell in combination with one of the APC’s own  proteins. In effect, the APC is saying, “This is your  target.” Note that there are different classes of effector  T cells, those that carry out direct activities. Two types  that are involved in the activation process are called    Figure 12.17 T cell activation and  interactions with other cells of  the immune response. Dendritic  cells are important antigen-presenting  cells (APCs). After they ingest an  antigen, they display parts of it on  their surface, where it can be    helper T cells and cytotoxic T cells (Figure 12.17). We  will discuss more about the functions of these cells as  we work through this process. It is important to note  that although we are discussing humoral (antibody-  mediated) immunity and cell-mediated immunity  separately, many pathogens stimulate both branches  at the same time. One such example is SARS-CoV-2,  the virus that causes COVID-19. See “A Closer Look”  on pp. 440-441.   A T cell must recognize “nonself,” the antigen  fragment presented by the APC, and “self,” by cou-  pling with a specific glycoprotein on the APC’s sur-  face at the same time. Antigen binding alone is not  enough to sensitize T cells. They must be “spoon-  fed” the antigens by APCs, and something like a  “double handshake” must occur. This process of  antigen presentation is now known to be essential  for the activation and clonal selection of T cells. The  two-part process prevents a T cell response from  being turned on when one is not needed, which  would inevitably result in tissue damage. Without  the “presenters,” the immune response is severely  impaired. Cytokine chemicals released by macro-  phages and dendritic cells also play important roles  in the immune response (Table 12.3, pp. 442-443).   Cytotoxic T cells specialize in killing virus-  infected, cancer, or foreign graft cells directly  (Figure 12.18, p. 438). One way a cytotoxic T cell    recognized by a helper T cell specific  for the same antigen. During the  binding process, the helper T cell  binds simultaneously to the antigen  and to the APC (self) receptor, which  leads to helper T cell activation and  cloning (not illustrated). If the APC is    a macrophage, it releases cytokines,  which enhance helper T cell activa-  tion. Activated helper T cells release  cytokines, which stimulate prolifera-  tion and activity of other helper   T cells and help activate B cells and  cytotoxic T cells.    accomplishes this is by @ binding tightly to a for-  eign cell and Ø releasing toxic chemicals called per-  forin and granzymes from its granules. The  glycoprotein perforin @) enters the foreign cell’s  plasma membrane (delivering the so-called lethal  hit). Shortly thereafter, pores appear in the target  cell's membrane, allowing @ the granzymes (pro-  tein-digesting enzymes) to enter and kill the foreign  cell. The cytotoxic T cell then ©) detaches and seeks  other foreign prey to attack.   Helper T cells are the T cells that act as the  “directors” or “managers” of the adaptive immune  response. Once activated, they circulate through the  body, recruiting other cells to fight the invaders. For  example, helper T cells interact directly with B cells  (that have already attached to antigens), prodding  the B cells into more rapid division (clone produc-  tion) and then, like the “boss” of an assembly line,  signaling for antibody formation to begin. The  helper T cells also release a variety of cytokines (see  Table 12.3) that act indirectly to rid the body of  antigens by (1) stimulating cytotoxic T cells and  B cells to grow and divide; (2) attracting other types  of protective white blood cells, such as neutrophils,  into the area; and (3) enhancing the ability of mac-  rophages to engulf and destroy microorganisms.  (Actually, macrophages are good phagocytes even in  the absence of cytokines, but in the presence of    ©) Cytotoxic T cell  releases perforin and  granzyme molecules from  its granules by exocytosis.    (8) Perforin molecules  insert into the target  cell membrane and  form pores similar to  those produced by  complement activation.    ) Granzymes enter  the target cell via the  pores and degrade  cellular contents.    Figure 12.18 A proposed mechanism by which cytotoxic T cells kill    cytokines they develop an even bigger appetite.) As  the released cytokines summon more and more  cells into the battle, the immune response gains  momentum, and the antigens are often over-  whelmed by the sheer numbers of immune ele-  ments acting against them.   Another T cell population, regulatory T cells  (formerly called suppressor T cells), release chemicals  that suppress the activity of both T and B cells.  Regulatory T cells are vital for winding down and  stopping the immune response after an antigen has  been successfully inactivated or destroyed. This helps  prevent uncontrolled or unnecessary immune sys-  tem activity, which often harms healthy tissues.   Most of the T cells enlisted to fight in a particular  immune response are dead within a few days.  However, a few members of each clone are long-  lived memory cells that remain behind to provide  the immunological memory for each antigen  encountered and enable the body to respond quickly  to subsequent invasions.    The major elements of the immune response are  summarized in Figure 12.19.    20. T cells must take part in what is sometimes called  the “double handshake” in order to be activated.  What does this mean?   22. What is the role of regulatory T cells in the  adaptive immune response?    For people suffering with end-stage heart or kidney  disease, organ transplants are a desirable treatment  option. However, organ transplants have had mixed  success because the immune system is ever vigilant,  and rejection is a real problem.    Gives rise to Stimulates Stimulates Stimulates Gives rise to  Active  cytotoxic   binding to antigens and making them easier cancer by binding to and lysing the infected    Figure 12.19 A summary of the adaptive immune responses. In this    flowchart, green arrows track the primary response, and blue arrows track the  secondary response.    I December 2019, an outbreak  (higher-than-expected number of  cases of an illness) of a new coronavirus  suspected of originating in bats occurred  in Wuhan, China. Patients presented  with pneumonia of unknown origin,  and the main symptoms were fever and  cough. The number of cases began to  rise quickly, leading to an epidemic  (ongoing outbreak of a disease), and it  became clear that people with underly-  ing conditions were at higher risk for  severe disease. In March 2020, the  World Health Organization  (WHO) characterized COVID-19  as a pandemic (widespread  epidemic). As this is being  written (November 2020), *  the world has seen over  54.11 million confirmed  cases and nearly 1.31 mil-  lion deaths, with the United  States and the United King-  dom reporting the highest  and second highest number of  confirmed cases per million,  respectively.   The virus that causes COVID-  19 (COronaVlrus Disease 2019) was  named SARS-CoV-2 for its genetic  similarity to SARS-CoV, the virus that  causes severe acute respiratory syn-  drome (SARS), first observed in 2003.   SARS-CoV-2 is spread by respiratory  droplets, which people generate during  common activities such as breathing,  singing, talking, coughing, and sneez-  ing. It also appears that the virus may  spread via airborne transmission when  aerosols are produced during breathing  and speaking. This is prompting con-  cern because aerosols, which are much  smaller and more numerous than drop-  lets, remain airborne for hours and can  spread more than 2 meters.    The WHO has suggested a number of  strategies to prevent further spread of  the virus: social distancing (staying at  least 2 meters apart), wearing a mask  over both the nose and mouth, and  good hand hygiene (washing hands fre-  quently, not touching the face, and dis-  infecting surfaces regularly). SARS-CoV-2  is reported to replicate, or copy itself,  three times faster than the 2003 SARS  virus, resulting in faster transmission,    even in the absence of symptoms. In  fact, early estimates suggest that patients  without any symptoms accounted for 40  to 79 percent of transmission.   Although masks, when worn cor-  rectly, have been proven to reduce  transmission, their use does not guar-  antee protection from infection. Masks  are recommended primarily because  they help the wearers keep their germs  to themselves; in other words, masks  are most effective in preventing an  asymptomatic person with COVID-19  from actively spreading the infection.  This is especially important to protect  individuals in high-risk categories who  are most vulnerable to the disease,    such as the elderly, especially men, and  people with cardiovascular disease, dia-  betes, chronic lung disease, and other  underlying conditions. Compared to  those without underlying conditions,  patients with these conditions are 6  times more likely to be hospitalized and  12 times more likely to succumb to ill-  ness. A meta-analysis of 18,728,893  patients from 50 studies suggests that  individuals of Asian and Black ethnici-  ties are at increased risk of COVID-19  infection compared to White individu-  als. The study also reports that individu-  als of Asian ethnicity could be at higher  risk of intensive therapy unit (ITU)  admission or mortality.   While early cases were identified  largely on the basis of obvious lung and  respiratory infection, reports suggest the  possible involvement of many other  body systems, organs, and tissues.  Infection begins when viral particles are  inhaled or introduced onto mucous  membranes by touch. The virus is first  “primed” by a transmembrane serine  protease enzyme, TMPRSS2, that acti-  vates viral spike glycoproteins (the  receptor proteins on the viral surface) by  cutting them. Then, the virus enters  host cells by binding to ACE2, a mem-  brane-bound enzyme involved in the  renin-angiotensin system of blood pres-  sure control. These ACE2 and TMPRSS2  proteins are found in the lungs, heart,  bladder, pancreas, gut, kidneys, nose,  eyes, and brain, mainly on epithelial  cells lining the outer organ surfaces.  Although all of these tissues have recep-  tors for SARS-CoV-2, it is not yet known  whether the virus actually infects each  of these locations; however, viral nucleic  acid has been detected in the brain,  urine (suggesting possible bladder or  kidney involvement), and intestinal cells.    Fever, fatigue, and dry cough are  common symptoms of COVID-19, but  patients also report several other prob-  lems such as loss of taste or smell, nasal  congestion, and conjunctivitis (red  eyes). Gut-related problems, sore  throat, headache, muscle or joint pain,  different types of skin rash, chills, and  dizziness are also known symptoms.  Severe COVID-19 disease causes some  patients to overproduce cytokines, a  type of immune signaling molecule. The  resulting increase in stimulation and  recruitment of immune cells can cause  tissue damage and a further influx of  fluids and cells. This “cytokine storm”  shocks the body and often leads to mul-  tiple organ failure and even death.  Therefore, COVID-19 presents a very  real concern since it can be transmitted  via droplets (and potentially aerosols) in  the absence of symptoms and can be  fatal for people with severe disease.   Research on this emerging infec-  tious agent was (and continues to be)  conducted at a staggering pace, with  scientists and public health officials  working together in a global commu-  nity. The solution to end this pan-  demic seems to be widespread  vaccination. A variety of groups are  making aggressive efforts to produce  a vaccine. To help these groups, an  international initiative, COVID-NMA is  working with the WHO. This initiative  involves a broad multidisciplinary con-  sortium that collects and presents data    by producing up-to-date  mapping of trial evidence  concerning treatments  and vaccines. As of  November 11, 2020, the  initiative has collated 89  randomized controlled  trials (RCTs) and 28 non-  randomized studies of  vaccines from the  International Clinical  Trials Registry Platform  (ICTRP). Among the   117 ongoing trials, 22 are in phase III,  wherein the vaccine is tested on hun-  dred to several thousands of patients.  Many vaccine projects have been suc-  cessful in preclinical, phase |, and  phase II clinical trials using recombi-  nant DNA, mRNA, live-attenuated  virus, S-protein subunits, virus-like  particles, and viral vectors.   In normal times, vaccine production  is a challenging process that takes up  to 10 years or more. Given the severity  of COVID-19, some regulations have  been relaxed, and some steps may be  completed simultaneously instead of  consecutively. Exhaustive testing is  necessary to verify dose and low toxic-  ity and to confirm that the vaccine pro-  duces an immune response in at least  50 percent of people who receive it;  for reference, an effective flu vaccine  protects about 40 to 60 percent of    e SARS-CoV-2 is spread by respiratory droplets and may also be spread by    e The best precautions against COVID-19 include wearing a mask over both  nose and mouth, washing hands regularly, disinfecting surfaces that are    Learn more at Mastering A&P > Study Area >  4 Additional Study Tools > A Closer Look    recipients. Safety is paramount during  vaccine development regardless of the  timeline, and an accelerated produc-  tion schedule means that long-term  problems are less likely to be observed  during drug trials. The U.S. Food and  Drug Administration's (FDA) standing  policy states that all approved vaccines  will continue to be monitored for long-  term adverse side effects.   So far, no specific drug, like remde-  sivir, hydroxychloroquine, lopinavir, or  interferon, has shown beneficial effects  on hospitalized COVID-19 patients.  Mortality, initiation of ventilation, and  duration of hospital stay were not posi-  tively affected by these drugs. Several  trials with immunomodulatory mole-  cules like sarilumab, tocilizumab, janus  kinase inhibitors, and hyperimmune  convalescent plasma have, until  November 2020, shown mixed out-  comes in initial clinical stages.   Even with efforts to develop vac-  cines and effective treatments, the  focus remains on containing the  spread of infection. Social distancing  and mask wearing are still being  observed and, in many cases, required.   We must keep in mind this virus  only emerged in late 2019, and there  is still much to learn about both the  pathogen and the disease. Current  information will likely change and, at  best, tell only part of the story.    e There is much we don’t yet know about SARS-CoV-2, including the long-  term health risks of COVID-19 and the status of immunity for patients   B cell Lymphocyte that resides in the lymph nodes, spleen, or other lymphoid tissues, where it is  induced to replicate by antigen-binding and helper T cell interactions; its progeny (clone  members) form plasma cells and memory cells.   Helper T cell A T cell that binds with a specific antigen presented by an APC; it stimulates the  production of other immune cells (cytotoxic T cells and B cells) to help fight the invader;  acts both directly and indirectly by releasing cytokines.   Cytotoxic T cell Activity enhanced by helper T cells; its specialty is killing cells with intracellular antigens    (like viruses or some bacteria), as well as body cells that have become cancerous; involved    Slows or stops the activity of B and T cells once the infection (or attack by foreign cells)    has been conquered. Thought to be important in preventing autoimmune diseases.    Descendant of an activated B cell or T cell; generated during both primary and    secondary immune responses; may exist in the body for years thereafter, enabling  it to respond quickly and efficiently to subsequent infections or meetings with the    Any of several cell types (macrophage, dendritic cell, B cell) that engulfs and digests    (APC) antigens that it encounters and presents parts of them on its plasma membrane for  recognition by T cells bearing receptors for the same antigen; this function, antigen  presentation, is essential for normal cell-mediated responses. Macrophages and dendritic  cells also release chemicals (cytokines) that activate many other immune cells.    There are four major types of transplants, or  grafts:  e Autografts are tissue grafts transplanted from  one site to another in the same person.    e Isografts are tissue grafts donated by a geneti-  cally identical person, the only example being an  identical twin.    e Allografts are tissue grafts taken from a person  other than an identical twin.    e Xenografts are tissue grafts harvested from a dif-  ferent animal species, such as a porcine (pig) heart  valve transplanted into a human.    Autografts and isografts are ideal donor organs  or tissues and are just about always successful given  an adequate blood supply and no infection.  Although pig heart valves have been transplanted  with success, xenografts of whole organs are virtually  never successful. The graft type most used is an  allograft taken from a recently deceased person.    Before an allograft is even attempted, the ABO  and other blood group antigens of both the donor  and recipient must be determined and must match.  Then, the cell membrane antigens of their tissue cells  are typed to determine how closely they match. At  least a 75 percent match is needed to attempt a graft;  as you might guess, good tissue matches between  unrelated people are hard to find.   After surgery, to prevent rejection, the patient  receives immunosuppressive therapy, including  one or more of the following: corticosteroids to sup-  press inflammation, antiproliferative drugs to pre-  vent division of immune cells, and immunosuppressor  drugs. Many of these drugs kill rapidly dividing cells  (such as activated lymphocytes), and all of them have  severe side effects. However, the major problem with  immunosuppressive therapy is that while the  immune system is suppressed, it cannot protect the  body against other foreign agents. Explosive infection  (bacterial, fungal, viral) is the most frequent cause of    Antibody (immunoglobulin) Protein produced by a B cell or its plasma-cell offspring and released into body fluids  (blood, lymph, saliva, mucus, etc.), where it attaches to antigens, causing neutralization,  opsonization, precipitation, or agglutination, which “marks” the antigens for destruction  by phagocytes or complement.   Cytokines Chemicals released by sensitized T cells, macrophages, and certain other cells:    e Migration inhibitory factor (MIF)—" inhibits” macrophage migration and keeps them  in the local area, and regulates the production of several other proinflammatory  cytokines.    e Interleukin 2—stimulates T cells and B cells to proliferate; activates NK cells.  e Helper factors—enhance antibody formation by plasma cells.    e Suppressor factors—suppress antibody formation or T cell-mediated immune  responses (interleukin-10 transforming growth factor and others).    e Chemotactic factors—attract leukocytes (neutrophils, eosinophils, and basophils)  into inflamed area.    e Gamma interferon—secreted by lymphocytes; helps make tissue cells resistant to viral  infection; activates macrophages and NK cells; enhances maturation of cytotoxic T cells.    Tumor necrosis factor (TNF) Like perforin, causes cell killing; attracts granulocytes; activates T cells and macrophages.    Complement Group of bloodborne proteins activated after binding to antibody-covered antigens; when  activated, complement causes lysis of the microorganism and enhances inflammatory response.    Antigen Substance capable of provoking an immune response; typically a large, complex molecule  not normally present in the body.    Cytotoxins Perforin, granzymes—cell toxins released by cytotoxic T cells and NK cells.   their transplant within 10 years of receiving it. In rare  cases, transplant patients have been able to “ditch the  drugs,” and finding a way to induce such tolerance is  the goal of many current research projects.    The most important disorders of the immune system  are allergies, autoimmune diseases, and immunode-  ficiencies.   At first, the immune response was thought to be  purely protective. However, it was not long before its  dangerous potentials were discovered. Allergies,  or hypersensitivities, are abnormally vigorous 42  immune responses in which the immune system    24. Sheila is receiving a kidney transplant. The donor is  her fraternal twin. What name is given to this type   12.5f Disorders of Immunity tion) is used to distinguish this type of antigen from  Learning Objective those producing normal immune responses. Most of  1# Describe allergies, autoimmune diseases, and the time, people do not die of allergies; they are just    There are several different types of allergies,  including reactions where cells are lysed, such as  during a transfusion reaction, and inflammation  due to antigen-antibody complexes, such as those  of glomerulonephritis. The most common type  is immediate hypersensitivity, or acute  hypersensitivity. After sensitization to a particular  allergen, this type of response is triggered when that  allergen is encountered again. This secondary  response starts with the release of a flood of hista-  mine when IgE antibodies bind to mast cells.  Histamine causes small blood vessels in the area to  become dilated and leaky and is largely to blame  for the best-recognized symptoms of allergy: a  runny nose, watery eyes, and itchy, reddened skin  (hives). When the allergen is inhaled, symptoms of  asthma appear because smooth muscle in the walls  of the bronchioles contracts, constricting the pas-  sages and restricting air flow. Over-the-counter  (OTC) anti-allergy drugs contain antihistamines that  counteract these effects. Most of these reactions  begin within seconds after contact with the allergen  and last about half an hour.   Fortunately, the bodywide, or systemic, acute  allergic response known as anaphylactic (an’ah-fi-  lak'tik) shock is fairly rare. Anaphylactic shock  occurs when the allergen directly enters the blood  and circulates rapidly through the body, as might  happen with certain bee stings, spider bites, or an  injection of a foreign substance (such as horse  serum, penicillin, or other drugs that act as haptens)  into susceptible individuals. Food allergies (peanut  or wheat allergies) may also trigger anaphylaxis and  can be fatal. The mechanism of anaphylactic shock is  essentially the same as that of local responses, but  when the entire body is involved, the outcome is life-  threatening. For example, it is difficult to breathe  when the smooth muscles of lung passages contract,  and the sudden vasodilation (and fluid loss) that  occurs may cause circulatory collapse and death  within minutes. Epinephrine, found in emergency  EpiPen® shots, is the drug of choice to reverse these  histamine-mediated effects.   Delayed hypersensitivities, mediated mainly  by a special subgroup of helper T cells, cytotoxic  T cells, and macrophages, take much longer to  appear (1 to 3 days) than any of the acute reactions  produced by antibodies. Instead of histamine,  the chemicals mediating these reactions are  cytokines released by the activated T cells. Hence,    © Histamine causes blood vessels to dilate and  become leaky, which promotes edema;  stimulates release of large amounts of mucus;  and causes smooth muscles to contract.    antihistamine drugs are not helpful against the  delayed types of allergies. Corticosteroid drugs are  used to provide relief.   The most familiar examples of delayed hypersen-  sitivity reactions are those classed as allergic contact  dermatitis, which follow skin contact with poison  ivy, some heavy metals (lead, mercury, and others),  and certain cosmetic and deodorant chemicals.  These agents act as haptens; after diffusing through  the skin and attaching to body proteins, they are per-  ceived as foreign by the immune system. The  Mantoux and tine tests, skin tests for detecting tuber-  culosis, depend on delayed hypersensitivity reac-  tions. When the tubercle antigens are injected just  under the skin, a small, hard lesion forms if the per-  son has been sensitized to the antigen.    Autoimmune Diseases  Occasionally, the immune system loses its ability to  distinguish friend from foe, that is, to tolerate self-  antigens while still recognizing and attacking foreign  antigens. When this happens, the body produces  antibodies (auto-antibodies) and sensitized T cells  that attack and damage its own tissues. This puzzling  phenomenon is called autoimmune disease be-  cause it is a person’s own immune system that pro-  duces the disorder.   Some 5 percent of adults in North America—  two-thirds of them women—are afflicted with auto-  immune disease. Most common are the following:    e Rheumatoid arthritis (RA), which systemati-  cally destroys joints (see pp. 190-191)    e Myasthenia gravis, which impairs communi-  cation between nerves and skeletal muscles  (see p. 236)    e Multiple sclerosis (MS), which destroys the  white matter (myelin sheaths) of the brain and  spinal cord (see p. 248)    e Graves’ disease, in which the thyroid gland  produces excessive amounts of thyroxine  (see p. 334) in response to autoantibodies  that mimic TSH    e Type 1 diabetes mellitus, which destroys pan-  creatic beta cells, resulting in deficient produc-  tion of insulin (see p. 341)    e Systemic lupus erythematosus (SLE), a  systemic disease that occurs mainly in young  women and particularly affects the kidneys,  heart, lungs, and skin    e Glomerulonephritis, a severe impairment of  kidney function due to acute inflammation (see  p. 555)   How does the normal state of self-tolerance  break down? It appears that one of the following  may trigger it:   e New self-antigens appear. Such “hidden” anti-  gens are found in sperm cells, the eye lens, and  certain proteins in the thyroid gland. In addi-  tion, “new” self-antigens may appear as a result  of gene mutations that change the structure of  self-proteins or as a result of alterations in self-  proteins by hapten attachment or by bacterial or  viral damage.    e Foreign antigens resemble self-antigens. For  instance, antibodies produced during an infec-  tion caused by streptococcus bacteria (such as  strep throat or scarlet fever) are known to cross-  react with heart antigens, causing damage to  both the heart muscle and its valves, as well as to  the joints and kidneys. This age-old disease is  called rheumatic fever.   The immunodeficiencies include both congenital  and acquired conditions in which the production or  function of immune cells or complement is abnor-  mal. The most devastating congenital condition is  severe combined immunodeficiency disease  (SCID), in which there is a marked deficit of both B  and T cells. Because T cells are absolutely required  for normal operation of both arms of the adaptive  response, afflicted children have essentially no pro-  tection against pathogens of any type. Minor infec-  tions easily shrugged off by most children are lethal  to those with SCID. Bone marrow transplants and  umbilical cord blood, which provide normal lym-  phocyte stem cells, have helped some SCID victims.  Without such treatment, the only hope for survival is  living behind protective barriers (in a plastic “bub-  ble”) that keep out all infectious agents.   Currently, the most important and most devas-  tating of the acquired immunodeficiencies is  acquired immune deficiency syndrome (AIDS).  AIDS cripples the immune system by interfering with  the activity of helper T cells (see “A Closer Look” on  pp. 446-447).   going on for nearly 40 years.  AIDS, or acquired immune deficiency  syndrome, is a state in which the body  is immunocompromised as a result  of advanced human immunodefi-  ciency virus (HIV) infection. Not every-  one who has HIV develops AIDS.  According to the Centers for Disease  Control and Prevention (CDC), HIV  infection has progressed to AIDS  when a patient has a low count of  helper T cells (also called CD, cells  because they have a receptor called  CD, on their surfaces) and/or has an  opportunistic infection. Examples of  opportunistic infections include a  fungal brain infection called crypto-  coccal meningitis, a rare fungal  pneumonia called pneumocystis pneu-  monia, a viral eye infection called  cytomegalovirus retinitis, or Kaposi's  sarcoma, a cancerlike blood vessel   HIV is transmitted by body fluids  (blood, breast milk, semen, vaginal  secretions) and is a known sexually  transmitted infection. The virus cannot  be transmitted by casual contact  because it dies when exposed to air.  Once in the body, HIV infects helper  T cells (CD, cells) and interferes with  the adaptive immune response (both  humoral and cell-mediated branches).   As of 2018, new HIV infections glob-  ally per year numbered 1.7 million, and  37.9 million people worldwide were  living with HIV. Between 2000 and  2018, new infections fell by 37 percent.  Of those infected, only 62 percent were  receiving treatment. Since the pan-  demic began, over 32 million people  have died. Sub-Saharan Africa has the  highest population of HIV-infected  individuals, with more than two-thirds    of world cases. When the HIV pan-  demic began, hemophiliacs and  homosexual males were at highest  risk of becoming infected. Though  clotting factors for hemophiliacs are  now genetically engineered and safe,  homosexual men remain at high risk,  as do IV drug users.   According to the CDC, in 2018  youth ages 13 to 24 made up 21 per-  cent of new HIV cases in the United  States; Young adults ages 25 to 34  made up 36 percent of new cases. As  of 2018, one in seven HIV-infected  people in the United States did not  know they were infected and were  not receiving treatment, increasing  the likelihood of passing on the infec-  tion. The CDC cites numerous chal-  lenges to halting the spread of HIV:  lack of adequate sex education, and  behavioral factors, such as failing to  undergo testing, engaging in unsafe  sex, and having multiple sexual  partners.   26. What causes the difficulty in breathing that occurs  with anaphylactic shock?   27. What is the principal problem common to all  immunodeficiency diseases?    For answers, see Appendix A. j f : j  Describe the effects of aging on immunity.    The lymphatic vessels, which bud from the veins of  the blood vascular system, and the main clusters of  lymph nodes are obvious by the fifth week of devel-  opment. Except for the thymus and the spleen, the  lymphoid organs are poorly developed before birth.  However, soon after birth, they become heavily pop-  ulated with lymphocytes as the immune system  begins to function.    At present, there is no HIV vaccine  available. People who test positive for  HIV are given ART (antiretroviral  therapies), also called combination  therapies, that include reverse tran-  scriptase (an HIV enzyme) inhibitors,    safer sex practices (using condoms,  knowing the sexual history of  their partners). Abstinence remains    e AIDS, or acquired immune deficiency syndrome, results when HIV infection  progresses to the point where the body becomes immunocompromised.    Learn more at Mastering A&P > Study Area >  Additional Study Tools > A Closer Look    protease inhibitors, and fusion inhibi- e HIV, or human immunodeficiency virus, infects helper T cells, resulting in  tors to block viral entry into T cells. deficiencies in both the humoral and cell-mediated adaptive immune  Controlling the virus can delay, and in responses.    AIDS. The earlier the patient begins  treatment, the greater the chance for  a good prognosis. People who  engage in high-risk behaviors should  opt for regular testing and adopt    Lymphatic system problems are relatively  uncommon, but when they do occur they are pain-  fully obvious. For example, when the lymphatic ves-  sels are blocked (as in elephantiasis, a tropical disease  in which the lymphatics become clogged with para-  sitic worms) or when lymphatics are removed (as in  radical breast surgery), severe edema may result.  However, lymphatic vessels removed surgically do  grow back in time.   Stem cells of the immune system originate in the  spleen and liver during the first month of embryonic  development. Later, the bone marrow becomes the  predominant source of stem cells (hemocytoblasts),  and it persists in this role into adult life. In late fetal  life and shortly after birth, the young lymphocytes  develop self-tolerance and immunocompetence in  their “programming organs” (thymus and bone mar-  row) and then populate the other lymphoid tissues.    lication, inhibit specific enzymes the virus needs, and block viral entry into  T cells (fusion inhibitors).  HIV is transmitted in body fluids and sexually, so the only sure method of  protection is abstinence.    Upon meeting “their” specific antigens, the T and B  cells complete their development to fully mature  immune cells.   Although the ability of our adaptive immune  system to recognize foreign substances is determined  by our genes, the nervous system may help to control  the activity of the immune response. Stress hor-  mones also may influence the immune response for  better or worse depending on circumstances. The  immune response is definitely impaired in individu-  als who are under severe stress. Our immune system  normally serves us well throughout our lifetime,  until old age. But during the later years, its efficiency  begins to wane. As a result, the body becomes less  able to fight infections and destroy cells that have  become cancerous. Additionally, we become more  susceptible to both autoimmune and immunodefi-  ciency diseases.    e Lymphatic vessels pick up leaked  plasma and proteins; spleen destroys  aged RBCs, stores iron, and removes  debris from blood; immune cells  protect cardiovascular organs from  specific pathogens   e Blood is the source of lymph;  lymphatics develop from veins; blood  provides the route for circulation of  immune elements    e The lymphatic vessels pick up leaked  plasma fluid, proteins, and immune cells from  both central and peripheral nervous system  structures; immune cells protect nervous  system structures from specific pathogens    e Lymphatic vessels pick up leaked fluids  and proteins; lymph distributes  hormones; immune cells protect  endocrine organs from pathogens    e Lymphatic vessels pick up leaked fluid  and proteins from urinary organs;  immune cells protect urinary organs  from specific pathogens   e Urinary system eliminates wastes and  maintains homeostatic water/  acid-base/electrolyte balance of the  blood for immune cell functioning;  urine flushes some pathogens out of   e Lymphatic vessels pick up leaked 4, F  fluid ad proteins from respiratory Sat i Reproductive System  organs; immune cells protect i i  respiratory organs from specific  pathogens; plasma cells in the  respiratory mucosa secrete  IgA to prevent pathogen  invasion of deeper tissues    e Lymphatic vessels pick up leaked  fluid and proteins from reproductive  organs; immune cells protect the  organs from specific pathogens    e Lymphatic vessels pick up leaked  plasma fluid and proteins from the  dermis; lymphocytes in lymph enhance  the skin’s protective role by defending  against specific pathogens   e The skin’s keratinized epithelium  provides a mechanical barrier to  pathogens; acid pH of skin secretions  inhibits growth of bacteria on skin    e Lymphatic vessels pick up leaked fluids  and proteins from digestive organs; lymph  transports some products of fat digestion to  the blood; lymphoid nodules in the wall of  the intestine prevent invasion of pathogens    a) Listen to the story of this chapter in a brief summary at Mastering A&P >  ts Study Area > Author Narrated Audio Summaries    PART I: THE LYMPHATIC SYSTEM (pp. 414-419) 12.4 Innate Body Defenses (pp. 420-427)    The lymphatic system consists of the lym-  phatic vessels, lymph nodes, and certain  other lymphoid organs in the body    Lymphatic vessels, also called lymphatics,  have minivalves to ensure one-way flow toward  the heart    The fluid (lymph) flows into the larger lymphat-  ics (lymphatic collecting vessels) and finally  into the blood vascular system through the right  lymphatic duct and the left thoracic duct  Lymph transport is aided by the muscular and  respiratory pumps and by contraction of smooth  muscle in the walls of the lymphatic vessels    Serve as multiplication sites for lymphocytes;  phagocytic cells within them remove bacteria,  viruses, and other debris before lymph is  returned to the blood   ° The cortex contains follicles of lymphocytes,  and the medulla is full of macrophages    Immune system—functional system composed  of the innate defense system (nonspecific  defense system) and the adaptive defense  system (specific defense system)    act nonspecifically to lyse virus-infected, malig-  nant cells and other nonspecific targets    e The inflammatory response prevents spread of  harmful agents  ° Disposes of pathogens and dead tissue cells;  promotes healing  ° Protective leukocytes enter area by  diapedesis, fibrin walls off the area, and  tissue repair occurs    Phagocytes (macrophages, neutrophils) engulf  and destroy pathogens; process is enhanced  when the pathogen surface is altered by attach-  ment of antibodies and/or complement    Complement (a group of plasma proteins)  becomes fixed on the membrane of a foreign cell  to cause lysis    Interferons—a group of proteins synthesized  by virus-infected cells to prevent viruses from  multiplying in other body cells    Fever enhances the fight against infectious  microorganisms by increasing metabolism  (which speeds up repair processes) and by caus-  ing the liver and spleen to store iron and zinc  (which bacteria need for multiplication)    e The third line of defense is antigen specific, is  systemic, and provides memory  ° Two branches include humoral immunity  (mediated by antibodies) and cellular  immunity (mediated by T lymphocytes)   e Antigens—large, complex molecules (or parts  of them) recognized as foreign by the body  (nonself)    response and bind with products of that  response (antibodies or sensitized lymphocytes)    molecules that are unable to cause an immune  response by themselves; when they bind to body  proteins, the complex is recognized as foreign    e Lymphocytes and antigen-presenting cells  (APCs) are involved in adaptive defense    T cells (T lymphocytes) develop immuno-  competence (are trained to be self-tolerant)  in the thymus and oversee cell-mediated  immunity   B cells (B lymphocytes) develop immuno-  competence in bone marrow and provide  humoral immunity    Immunocompetent lymphocytes seed lym-  phoid organs, where antigen challenge occurs,  and circulate through blood, lymph, and lym-  phoid organs    e Macrophages arise from monocytes produced in  bone marrow. They and other APCs phagocytize  pathogens and present parts of the antigens on  their surfaces for recognition by T cells    e Clonal selection of B cells occurs when anti-  gens bind to their receptors, causing them to  proliferate    Most clone members become plasma cells,  which secrete antibodies. This is called the  primary humoral response    Other clone members become memory cells  capable of mounting a rapid attack against  the same antigen in subsequent meetings  (secondary humoral responses). These  cells provide immunological memory    e Active immunity is produced by a person's  own body during an infection or via vaccine  and provides memory    Passive immunity is conferred when antibodies  produced by another person are injected into  the bloodstream or when the mother’s antibod-  ies cross the placenta; no immunological mem-  ory occurs   B cells or plasma cells in response to an antigen;  they are capable of binding specifically with that  antigen    chains (two heavy and two light) that form a  Y-shaped molecule   = Variable regions form antigen-binding  sites, one on each arm of the Y    Five classes of antibodies, also called immu-  noglobulins (Igs) exist: IgM, IgA, IgD, IgG,  and IgE. They differ structurally and  functionally.    Antibody functions include agglutination,  complement fixation, neutralization, opso-  nization, and precipitation   Monoclonal antibodies are pure preparations  of antibodies specific for a single antigen useful  in diagnosing various infectious disorders and  cancer and in treating certain cancers    an antigen and a self-protein displayed on the  surface of an APC (antigen presentation)    o Clonal selection occurs, and clone members  differentiate into effector T cells or memory  T cells    Cytotoxic T cells specialize in killing foreign  or infected cells directly    Helper T cells direct the adaptive immune  response and interact to turn on both B and  T cells    Regulatory T cells turn off immune response  once foreign material is inactivated or destroyed    e Hypersensitivity (allergy)—immune system  overreacts to an otherwise harmless antigen;  tissue destruction occurs    o Immediate hypersensitivity (acute hyper-  sensitivity )—due to binding of IgE antibod-  ies to mast cells; seen in hay fever, hives, and  anaphylactic shock   e Autoimmune disease occurs when the body's  self-tolerance breaks down and antibodies and/  or T cells attack the body’s own tissues   ° Results from the appearance of formerly hidden  self-antigens or changes in the structure of self-  antigens, and antibodies formed against foreign  antigens that resemble self-antigens (as in rheu-  matic fever)   o Other autoimmune diseases include  rheumatoid arthritis (RA), myasthenia  gravis, multiple sclerosis (MS), Graves’  disease, type 1 diabetes mellitus, systemic  lupus erythematosus (SLE), and  glomerulonephritis    o Most serious are severe combined immuno-  deficiency disease (SCID) and acquired  immune deficiency syndrome (AIDS); AIDS  is caused by HIV, which infects helper T cells.    PART III: DEVELOPMENTAL ASPECTS OF THE  LYMPHATIC SYSTEM AND BODY  DEFENSES (pp. 446-448)    e Lymphatic vessels form by budding off veins; the  thymus and spleen are the first lymphoid organs  to appear in the embryo  ° Other lymphoid organs remain relatively   e The ability of immunocompetent cells to recog-  nize foreign antigens is genetically determined  o Stress appears to interfere with normal   e Efficiency of the immune response wanes in old  age, and infections, cancer, immunodeficiencies,  and autoimmune diseases become more common    2. Which parts of the lymph node show increased activ-  ity when antibody production is high?    Which of the following antibody capabilities causes  a transfusion reaction with A or B erythrocyte    a. Type 1 diabetes  b. Multiple sclerosis  Helper T cells directly stimulate  a. B cells.    What is complement? Besides bacterial lysis, what are  some of the roles of complement?    Binding of antigens to receptors of immunocompe-  tent lymphocytes leads to clonal selection. Describe  the process of clonal selection. What nonlymphocyte  cell is a central actor in this process, and what is its  function?    Describe the specific roles of helper, cytotoxic, and  regulatory T cells in cell-mediated immunity. Which  is thought to be disabled in AIDS?    Name the five classes of immunoglobulins. Which is  most likely to be found attached to a B cell mem-  brane? Which is most abundant in plasma? Which is  important in allergic responses? Which is the first Ig  to be released during the primary response? Which  can cross the placental barrier?    Distinguish between immediate types of allergy and  delayed allergic reactions in terms of cause and  consequences.    Mr. James, an 80-year-old man, is grumbling about  having to receive a flu shot every year. Flu viruses have  a high mutation rate (undergo rapid genetic changes),  which results in the appearance of new proteins on    Mrs. Morrow, a 59-year-old woman, has undergone a  left radical mastectomy (removal of the left breast and  left axillary lymph nodes and vessels). Her left arm is  severely swollen and painful, and she is unable to    raise it more than shoulder height. (a) Explain her  signs and symptoms. (b) Can she expect relief from  these symptoms in time? How so?    Lymphocytes continuously circulate through the  body using blood and lymph as their transport vehi-  cles. What is the importance of this recirculation  behavior?    Capillary permeability increase and plasma proteins  leak into the interstitial fluid as part of the inflamma-  tory process. Why is this desirable?    The respiratory  system provides oxygen  to the body, disposes of carbon  dioxide, and helps regulate  blood pH.   Too much carbon dioxide in the  blood will cause the blood pH  to become acidic, which will   gen, they give off carbon dioxide, a waste product the  body must get rid of.   The cardiovascular and respiratory systems share  responsibility for supplying the body with oxygen and  disposing of carbon dioxide. The respiratory system  organs oversee the gas exchanges that occur between  the blood and the external environment. Using blood  as the transporting fluid, the cardiovascular system  organs transport respiratory gases between the lungs    Gas exchange  occurs in the air sacs of  the lungs, called alveoli,  and at capillary beds  around the body.    and the cells in the rest of the body. If either system  fails, cells begin to die from oxygen starvation and  accumulation of carbon dioxide.    v@ Name the organs forming the respiratory  passageway from the nasal cavity to the alveoli  of the lungs (or identify them on a diagram or  model), and describe the function of each.    Figure 13.1 The major respiratory organs shown in relation to surrounding structures.    The organs of the respiratory system include the  nose, pharynx, larynx, trachea, bronchi and their  smaller branches, and the lungs, which contain the  alveoli (al-ve'o-li), or terminal air sacs (Figure 13.1).  Because gas exchange with the blood happens only in  the alveoli, the other respiratory system structures  are really just conducting passageways that carry  air through the lungs. The passageways from the  nose to the larynx are called the upper respiratory tract,  and those from the trachea to the alveoli are the  lower respiratory tract. These conducting passageways  also purify, humidify, and warm incoming air. Thus,  the air finally reaching the lungs has fewer irritants  (such as dust or bacteria) than the air outside, and it  is warm and damp.    system. During breathing, air enters the nose by pass-  ing through the nostrils, or nares. The interior of  the nose consists of the nasal cavity, divided by a  midline nasal septum. The olfactory receptors for the  sense of smell are located in the mucosa in the slit-    like superior part of the nasal cavity, just beneath the  ethmoid bone.    including respiratory passages, is lined with mucous  membrane (mucosa), which is a “wet,” or moist, mem-  brane (Chapter 4, p. 129).    The rest of the mucosa lining the nasal cavity,  called the respiratory mucosa, rests on a rich network  of thin-walled veins that warms the air as it flows  past. In addition, the sticky mucus produced by this  mucosa’s glands moistens the air and traps incoming    bacteria and other foreign debris, and lysozyme  enzymes in the mucus destroy bacteria chemically.  The ciliated cells of the nasal mucosa create a gentle  current that moves the sheet of contaminated mucus  posteriorly toward the throat (pharynx), where it is  swallowed and digested by stomach juices. We are  usually unaware of this important ciliary action, but  when the external temperature is extremely cold,  these cilia become sluggish, allowing mucus to accu-  mulate in the nasal cavity and to dribble outward  through the nostrils. This helps explain why you  might have a “runny” nose on a crisp, wintry day.   The lateral walls of the nasal cavity are uneven,  owing to three mucosa-covered projections called  conchae (kong’ke). The conchae greatly increase the  surface area of the mucosa exposed to the air (as  shown in Figure 13.2). The conchae also increase the  air turbulence in the nasal cavity. As the air swirls  through the twists and turns, inhaled particles are  deflected onto the mucus-coated surfaces, where they  are trapped and prevented from reaching the lungs.   The nasal cavity is separated from the oral cavity  below by a partition, the palate (pal’et). Anteriorly,  where the palate is supported by bone, is the hard  palate; the unsupported posterior part is the soft  palate.    Homeostatic J  -£ Imbalance 13.1  The genetic defect cleft palate (failure of the bones  forming the palate to fuse medially) results in  breathing difficulty as well as problems with oral  cavity functions, such as breastfeeding and speaking.    The nasal cavity is surrounded by a ring of para-  nasal sinuses located in the frontal, sphenoid, eth-  moid, and maxillary bones. (See Figure 5.13, p. 170.)  The sinuses lighten the skull and act as resonance  chambers for speech. They also produce mucus,  which drains into the nasal cavities. The suctioning  effect created by nose blowing helps to drain the  sinuses. The nasolacrimal ducts, which drain tears  from the eyes, also empty into the nasal cavities.    Homeostatic J  £ Imbalance 13.2  Cold viruses and various allergens can cause rhinitis  (ri-ni’tis), inflammation of the nasal mucosa. The  excessive mucus produced results in nasal conges-  tion and postnasal drip. Because the nasal mucosa is    continuous throughout the respiratory tract and  extends tentacle-like into the nasolacrimal (tear)  ducts and paranasal sinuses, nasal cavity infections  often spread to those regions as well. Sinusitis, or  sinus inflammation, is difficult to treat and can  cause marked changes in voice quality. When the  passageways connecting the sinuses to the nasal cav-  ity are blocked with mucus or infectious matter, the  air in the sinus cavities is absorbed. The result is a  partial vacuum and a sinus headache localized over  the inflamed area.    The pharynx (far’inks) is a muscular passageway  about 13 cm (5 inches) long that vaguely resembles  a short length of red garden hose. Commonly called  the throat, the pharynx serves as a common passage-  way for food and air (see Figure 13.2). It is continu-  ous with the nasal cavity anteriorly via the posterior  nasal aperture.   The pharynx has three regions (Figure 13.2a). Air  enters the superior portion, the nasopharynx  (na”zo-far’inks), from the nasal cavity and then  descends through the oropharynx (o0’ro-far’ inks)  and laryngopharynx (lah-ring”go-far’'inks) to enter  the larynx below. Food enters the mouth, then trav-  els the same route as air through the oropharynx and  laryngopharynx. But instead of entering the larynx,  food is directed into the esophagus (é-sof'ah-gus)  posteriorly by a flap called the epiglottis (ep’i-glot’is).   The pharyngotympanic tubes, which drain the mid-  dle ears, open into the nasopharynx. The mucosae of  these two regions are continuous, so ear infections  such as otitis media (o-ti'tis me’de-ah) may follow a  sore throat or other types of pharyngeal infections.   Clusters of lymphatic tissue called tonsils are also  found in the pharynx. The single pharyngeal (far-  rin'je-al) tonsil, often called the adenoid, is located  high in the nasopharynx. The two palatine tonsils  are in the oropharynx at the end of the soft palate, as  is the lingual tonsil, which lies at the base of the  tongue. The tubal tonsils protect the openings of  the pharyngotympanic tubes in the nasopharynx.  The tonsils also play a role in protecting the body  from infection (see Chapter 12).    Homeostatic J  £ Imbalance 13.3  If the pharyngeal tonsil becomes inflamed and  swollen (as during a bacterial infection), it obstructs   e Pharyngeal tonsil  e Tubal tonsil (ridge  posterior to opening  of pharyngotympanic  tube)    Chapter 13: The Respiratory System 457  Figure 13.2 Basic anatomy of the upper  respiratory tract, sagittal section.  Frontal sinus  Nasal cavity  e Nasal conchae (superior,  middle, and inferior)  e Nasal meatuses (superior,  middle, and inferior)  e Nasal vestibule  e Nostril  Hard palate  Soft palate  Tongue  Hyoid bone  Larynx  e Epiglottis  e Thyroid cartilage  e Vocal fold  e Cricoid cartilage    the nasopharynx and forces the person to breathe  through the mouth. In mouth breathing, air is not  properly moistened, warmed, or filtered before  reaching the lungs. Many children routinely get  this condition, called tonsillitis. Years ago the  belief was that the tonsils, though protective, were  more trouble than they were worth, and they were    routinely removed. Now, with the widespread use  of antibiotics, this is no longer necessary.    The larynx (lar’inks), or voice box, routes air and food  into the proper channels and plays a role in speech.    Located inferior to the pharynx (Figure 13.2b), it is  formed by eight rigid hyaline cartilages and a spoon-  shaped flap of elastic cartilage, the epiglottis. The  largest of the hyaline cartilages is the shield-shaped  thyroid cartilage, which protrudes anteriorly and is  commonly called the Adam’s apple.   Sometimes referred to as the “guardian of the  airway,” the epiglottis protects the superior open-  ing of the larynx. During regular breathing, the  epiglottis allows the passage of air into the lower  respiratory passages. When we swallow food or  fluids, the situation changes dramatically; the  larynx is pulled upward, and the epiglottis tips,  forming a lid over the larynx’s opening. This  routes food into the esophagus posteriorly, lead-  ing to the stomach. If anything other than air  enters the larynx, a cough reflex is triggered to pre-  vent the substance from continuing into the lungs.  Because this protective reflex does not work when  we are unconscious, never try to give fluids to an  unconscious person when attempting to revive  him or her.    e Palpate your larynx by placing your hand  midway on the anterior surface of your neck.  Swallow. Can you feel the larynx rising as you  swallow?    Part of the mucous membrane of the larynx  forms a pair of folds, called the vocal folds, or true  vocal cords, which vibrate with expelled air. This  ability of the vocal folds to vibrate allows us to  speak. The slitlike passageway between the vocal  folds is called the glottis.    Air entering the trachea (tra’ke-ah), or windpipe,  from the larynx travels down its length (10-12 cm,  or about 4 inches) to the level of the fifth thoracic  vertebra, which is approximately midchest (see  Figure 13.1).   The trachea is fairly rigid because its walls are  reinforced with C-shaped rings of hyaline cartilage  (Figure 13.3a). These rings serve a double purpose.  The open parts of the rings abut the esophagus (the  openings face posteriorly) and allow it to expand  anteriorly when we swallow a large piece of food.  The solid portions support the trachea walls and  keep it patent, or open, in spite of the pressure  changes that occur during breathing. The trachealis  muscle lies next to the esophagus and completes the  wall of the trachea posteriorly.    Homeostatic J  £ Imbalance 13.4  Because the trachea is the only way air can enter the  lungs, tracheal obstruction is life-threatening. Many  people have suffocated after choking on a piece of  food that suddenly closed off the trachea (or the  glottis of the larynx). The Heimlich maneuver, a  procedure in which the air in a person’s own lungs is  used to “pop out,” or expel, an obstructing piece of  food, has saved many people from becoming victims  of choking. The Heimlich maneuver is simple to  learn and easy to do. However, it is best learned by  demonstration because cracked ribs are a distinct  possibility when it is done incorrectly. In some cases  of obstructed breathing, an emergency tracheostomy  (tra’‘ke-ost’o-me; surgical opening of the trachea) is  done to provide an alternative route for air to reach  the lungs. Individuals with tracheostomy tubes in  place form huge amounts of mucus the first few days  because of irritation to the trachea. Thus, they must  be suctioned frequently during this time to prevent  the mucus from pooling in their lungs.    The trachea is lined with a ciliated mucosa  (Figure 13.3b). The cilia beat continuously in a superior  direction. They are surrounded by goblet cells that pro-  duce mucus. The cilia propel this mucus, loaded with  dust particles and other debris, away from the lungs to    the throat, where it can be swallowed or spat out.  Homeostatic J    Smokers with respiratory congestion should avoid  medications that inhibit the cough reflex.    1. Why is nose breathing preferable to mouth breathing?  2. What is the specific protective function of cilia in the    The right and left main (primary) bronchi  (brong’ki) are formed by the division of the trachea.  Each main bronchus runs obliquely before it plunges  into the medial depression (hilum) of the lung on its    In what direction is the power stroke of these cilia directed—superiorly  toward the mouth or inferiorly toward the lungs?    Figure 13.3 Anatomy of the trachea and esophagus. (a) A cross-sectional view of  the structural relationship between the trachea and esophagus. (b) Cilia in the trachea.  The cilia are the yellow, grasslike projections surrounded by the mucus-secreting goblet    own side (see Figure 13.1). The right main bronchus  is wider, shorter, and straighter than the left.  Consequently, it is the more common site for an  inhaled foreign object to become lodged. By the  time incoming air reaches the bronchi, it is warm,  cleansed of most impurities, and humid. The smaller  subdivisions of the main bronchi within the lungs  are direct routes to the air sacs.    Learning Objectives  v@ Describe the structure and function of the  lungs and the pleural coverings.  v Describe the structure of the respiratory  membrane.  The lungs are fairly large organs. They occupy the  entire thoracic cavity except for the most central area,  the mediastinum (me’de-as-ti‘num), which houses  the heart, the great blood vessels, bronchi, the    esophagus, and other organs (Figure 13.4, p. 460).  The narrow superior portion of each lung, the apex,  is just deep to the clavicle. The broad lung area rest-  ing on the diaphragm is the base. Each lung is  divided into lobes by fissures; the left lung has two  lobes, and the right lung has three.   The surface of each lung is covered with its own  visceral serosa, called the pulmonary pleura or  visceral pleura (ploor’ah), and the walls of the tho-  racic cavity are lined by the parietal pleura. The  pleural membranes produce pleural fluid, slippery  serous fluid, which allows the lungs to glide easily  over the thorax wall during breathing and causes the  two pleural layers to cling together. The pleurae can  slide easily from side to side across one another, but  they strongly resist being pulled apart. Consequently,  the lungs are held tightly to the thorax wall, and the  pleural space is more of a potential space than  an actual one. As we describe shortly, this tight  adherence of the pleural membranes is absolutely  essential for normal breathing. (Figure 13.4a  shows the position of the pleurae on the lungs  and the thorax wall.)   Part (a) includes a close-up illustration of the  pleurae. In (b), the size of the pleural (and  pericardial) cavity is exaggerated for clarity.    Homeostatic B  £ Imbalance 13.6  Pleurisy (ploo’ri-se), inflammation of the pleurae,  can be caused by insufficient secretion of pleural  fluid. The pleural surfaces become dry and rough,  resulting in friction and stabbing pain with each  breath. Conversely, the pleurae may produce  excessive amounts of fluid, which exerts pressure  on the lungs. This type of pleurisy hinders breath-  ing movements, but it is much less painful than  the dry rubbing type.    After entering the lungs, the main bronchi subdivide  into smaller and smaller branches (secondary and ter-  tiary bronchi, and so on), finally ending in the smallest    of the conducting passageways, the bronchioles  (brong’ke-dlz). Because of this branching and re-  branching of the respiratory passageways within the  lungs, the network formed is often referred to as the  bronchial, or respiratory, tree. All but the smallest  branches have reinforcing cartilage in their walls.    The terminal bronchioles lead into respiratory zone struc-  tures, even smaller conduits that eventually terminate  in alveoli (al-ve’o-li; alveol = small cavity), or air  sacs. The respiratory zone, which includes the respi-  ratory bronchioles, alveolar ducts, alveolar sacs, and alve-  oli, is the only site of gas exchange (Figure 13.5). All  other respiratory passages are conducting zone  structures that serve as conduits to and from the    Figure 13.6 Functional anatomy  of the respiratory membrane  (air-blood barrier). As shown in   the left illustration, the respiratory  membrane is composed of squamous  epithelial cells of the alveoli, the    respiratory zone. There are millions of the clustered  alveoli, which resemble bunches of grapes, and they  make up the bulk of the lungs. Consequently, the  lungs are mostly air spaces. The balance of the lung  tissue, its stroma, is mainly elastic connective tissue  that allows the lungs to stretch and recoil (spring  back) as we breathe. Thus, in spite of their relatively  large size, the lungs weigh only about 21⁄2 pounds,  and they are soft and spongy.   The walls of the alveoli are composed largely of  a single, thin layer of simple squamous epithelial  cells. The thinness of their walls is hard to imagine,  but a sheet of tissue paper is much thicker. Alveolar  pores connect neighboring air sacs and provide alter-  native routes for air to reach alveoli whose feeder  bronchioles have been clogged by mucus or other-  wise blocked. The external surfaces of the alveoli are  covered with a “cobweb” of pulmonary capillaries.  Together, the alveolar and capillary walls, their fused  basement membranes, and occasional elastic fibers  construct the respiratory membrane (air-blood  barrier) (Figure 13.6). The respiratory membrane    capillary endothelium, and the scant  basement membranes between.  Surfactant-secreting cells in the  alveoli are also shown. Small pores  connect neighboring alveoli. As  shown in the right illustration,    oxygen diffuses from the alveolar  air across this membrane into the  pulmonary capillary blood; carbon  dioxide diffuses from the pulmonary  blood into the alveolus.    has gas (air) flowing past on one side and blood  flowing past on the other. Gas exchange occurs by  simple diffusion through the respiratory mem-  brane—oxygen passes from the alveolar air into the  capillary blood, and carbon dioxide leaves the blood  to enter the alveoli (Figure 13.6). The total gas  exchange surface provided by the alveolar walls of a  healthy man is estimated to be 50 to 70 square  meters, or approximately 40 times greater than the  surface area of his skin!   The final line of defense for the respiratory sys-  tem is in the alveoli. Remarkably efficient alveolar  macrophages, sometimes called “dust cells,” wan-  der in and out of the alveoli picking up bacteria, car-  bon particles, and other debris. Also scattered amid  the epithelial cells that form most of the alveolar  walls are cuboidal surfactant-secreting cells, which  look very different from the squamous epithelial  cells. These cells produce a lipid (fat) molecule  called surfactant, which coats the gas-exposed alveo-  lar surfaces and is very important in lung function  (as described on p. 475).    3. Name the order of the following parts of the human  respiratory system from the site where air enters  the nostrils to the site where air reaches the end  passages of the lungs—bronchi, larynx, nasal cavity,  alveoli, trachea, pharynx, bronchioles.   4. Which main bronchus is the most likely site for an  inhaled object to become lodged? Why?   5. The lungs are mostly passageways and elastic tissue.  What is the role of the passageways? Of the elastic  tissue?   6. Name the four structures that make up the respira-  tory zone.    v@ Define cellular respiration, external respiration,  internal respiration, pulmonary ventilation,  expiration, and inspiration.    v Explain how the respiratory muscles cause volume  changes that lead to air flow into and out of the  lungs (breathing).   The major function of the respiratory system is to  supply the body with oxygen and to dispose of car-  bon dioxide. To do this, at least four distinct events,  collectively called respiration, must occur:    1. Pulmonary ventilation. Air must move into  and out of the lungs so that the gases in the alve-  oli of the lungs are continuously refreshed. This  process of pulmonary ventilation is commonly  called breathing.    2. External respiration. Gas exchange (oxygen  loading and carbon dioxide unloading) between  the pulmonary blood and alveoli must take  place. Remember that in external respiration,  gas exchanges are being made between the  blood and the body exterior.    3. Respiratory gas transport. Oxygen and car-  bon dioxide must be transported to and from  the lungs and tissue cells of the body via the  bloodstream.    4. Internal respiration. At systemic capillaries,  gas exchange occurs between the blood and cells  inside the body. This time, oxygen is unloaded  from blood and CO, is loaded.    Although only the first two processes are the spe-  cial responsibility of the respiratory system, all four  processes are necessary for gas exchange to occur.  Note that cellular respiration, the use of oxygen to    produce ATP and carbon dioxide, is the cornerstone  of all energy-producing chemical reactions and  occurs in nearly all cells (see Chapter 14).    Breathing, or pulmonary ventilation, is a mechanical  process that depends on volume changes occurring  in the thoracic cavity. Keep this rule in mind about  the mechanics of breathing: Volume changes lead to  pressure changes, which lead to the flow of gases to equal-  ize the pressure.   A gas, like a liquid, always conforms to the shape  of its container. However, unlike a liquid, a gas fills  its container. Consider a container with a large vol-  ume of gas. The gas molecules will be far apart, and  the pressure (created by the gas molecules colliding  with one another and the container walls) will be  low. Assuming the same amount of gas were in a  smaller container, the gas molecules would be closer  together, and the pressure would be higher than it  was in the larger container.    in the body, such as filtration (passive transport;  Chapter 3, pp. 96-98) and blood flow (Chapter 11). In  these processes, substances move from high to low  pressure and achieve a specific function, such as mem-  brane transport or circulation.    Let's see how volume changes relate to the two  phases of breathing—inspiration, when air is flow-  ing into the lungs, and expiration, when air is leav-  ing the lungs.    When the inspiratory muscles, the diaphragm and  external intercostals, contract, the size (volume) of  the thoracic cavity increases. As the dome-shaped dia-  phragm contracts inferiorly, the superior-inferior  dimension (height) of the thoracic cavity increases  (Figure 13.7a, p. 464). Contraction of the external  intercostals lifts the rib cage and thrusts the sternum  forward, which increases the anteroposterior and lat-  eral dimensions of the thorax. The lungs adhere  tightly to the thorax walls (because of the surface ten-  sion of the fluid between the pleural membranes), so  they are stretched to the new, larger size of the thorax.  As intrapulmonary volume (the volume within the  lungs) increases, the gases within the lungs spread  out to fill the larger space. The resulting decrease in  gas pressure in the lungs produces a partial vacuum    the lungs  Figure 13.7 Rib cage and elevated, and diaphragm is depressed.  diaphragm positions during Lungs are stretched to the larger  breathing. Black arrows represent thoracic volume, causing the  the direction of diaphragm intrapulmonary pressure to fall and  movement. (a) At the end of a air to flow into the lungs. (b) At the  normal inspiration: Chest is end of a normal expiration: The    expanded laterally, rib cage is chest is depressed, and the lateral   Lungs recoil to a smaller volume,  intrapulmonary pressure rises, and air  flows out of the lungs.    Figure 13.8 Changes in (a) intrapulmonary pressure  and (b) air flow during inspiration and expiration.    (pressure in the lungs is less than atmospheric pres-  sure outside the body), which causes air to flow into  the lungs (down the pressure gradient). Air continues  to move into the lungs until the intrapulmonary pres-  sure equals atmospheric pressure (Figure 13.8a). This  series of events is called inspiration (inhalation).    substance moves from an area of high pressure to an  area of low pressure. In the lungs, after muscle action  has caused the cavity volume to change, air pressure  has changed (as a result of volume changes), and air will  flow down the pressure gradient from high to low until  the pressures are equal.   Expiration (exhalation) in healthy people is largely a  passive process that depends more on the natural elas-  ticity of the lungs than on muscle contraction. As the    inspiratory muscles relax and resume their initial rest-  ing length, the rib cage descends, the diaphragm  relaxes superiorly, and the lungs recoil (Figure 13.7b).  Thus, both the thoracic and intrapulmonary volumes  decrease. As the intrapulmonary volume decreases, the  gases inside the lungs are forced more closely together,  and the intrapulmonary pressure rises to a point  higher than atmospheric pressure (see Figure 13.8a).  This causes the gases to passively flow out to equalize  the pressure with the outside.   However, if the respiratory passageways are nar-  rowed by spasms of the bronchioles (as in asthma) or  clogged with mucus or fluid (as in chronic bronchitis  or pneumonia), expiration becomes an active process.  In such cases of forced expiration, the internal inter-  costal muscles are activated to help depress the rib  cage, and the abdominal muscles contract and help  to force air from the lungs by squeezing the abdom-  inal organs upward against the diaphragm.   Normally the pressure within the pleural space,  the intrapleural pressure, is always negative (mean-  ing it is lower than the pressure inside the lungs).  This is the major factor preventing lung collapse. If  for any reason the intrapleural pressure becomes  equal to the atmospheric pressure, the lungs imme-  diately recoil and collapse.    lapse, the lung is useless for ventilation. This phe-  nomenon occurs when air enters the pleural space    A colored chest X-ray film showing a pneumothorax, or  collapsed lung. The patient's right lung (on left side of X-ray  film, bright blue) has collapsed because air has built up  (purple) between the lung and chest wall.    Figure 13.9 Graph of the various respiratory volumes in a healthy young    through a chest wound, but it may also result from a  rupture of the visceral pleura, which allows air to  enter the pleural space from the respiratory tract. Air  in the intrapleural space, which is referred to as  pneumothorax (nu"mo-tho’raks), pushes in on the  lung, disrupting the fluid bond between the pleurae.   Pneumothorax is reversed by drawing air out of  the intrapleural space with a chest tube, which allows  the lung to reinflate and resume its normal function.    7. What is the most basic function of respiration?  8. What causes air to flow out of the lungs during  expiration?  For answers, see Appendix A.    v# Define the following respiratory volumes: tidal  volume, vital capacity, expiratory reserve volume,  inspiratory reserve volume, and residual air.   explain how they modify or differ from normal  respiratory air movements.   ml of air (about a pint) into and out of the lungs    As a rule, a person is capable of inhaling much  more air than is taken in during a tidal breath. The  amount of air that can be taken in forcibly above  the tidal volume is the inspiratory reserve volume  (IRV), which is around 3,100 ml.   Similarly, after a normal expiration, more air  can be exhaled. The amount of air that can be  forcibly exhaled beyond tidal expiration, the  expiratory reserve volume (ERV), is approxi-  mately 1,200 ml.   Even after the most strenuous expiration, about  1,200 ml of air still remains in the lungs and can-  not voluntarily be expelled. This is the residual  volume. Residual volume air is important because  it allows gas exchange to go on continuously even  between breaths and helps to keep the alveoli open  (inflated).   The total amount of exchangeable air (around  4,800 ml in healthy young men and 3,100 ml in  healthy young women) is the vital capacity (VC).  The vital capacity is the sum of the tidal volume plus  the inspiratory and expiratory reserve volumes.  Respiratory volumes of a male are summarized in  Figure 13.9.   Note that some of the air that enters the respira-  tory tract remains in the conducting zone passage-  ways and never reaches the alveoli to participate in  gas exchange. This is called the dead space volume  and during a normal tidal breath is about 150 ml.  The functional volume—air that actually reaches the  respiratory zone and contributes to gas exchange—is  about 350 ml.    Taking a deep breath, closing glottis, and forcing air superiorly from lungs against glottis. Then, glottis    opens suddenly, and a blast of air rushes upward. Coughs act to clear the lower respiratory passageways.    Similar to a cough, except that expelled air is directed through nasal cavities instead of through oral cavity.    The uvula (u’vu-lah), a dangling tag of tissue hanging from the soft palate, becomes depressed and closes  oral cavity off from pharynx, routing air through nasal cavities. Sneezes clear upper respiratory passages.    Inspiration followed by release of air in a number of short expirations. Primarily an emotionally induced    Essentially same as crying in terms of the air movements produced. Also an emotionally induced response.    Sudden inspirations resulting from spasms of diaphragm; initiated by irritation of diaphragm or phrenic    nerves, which serve diaphragm. The sound occurs when inspired air hits vocal folds of closed glottis.    Respiratory capacities are measured with a spi-  rometer (spi-rom’é-ter). As a person breathes, the vol-  umes of air exhaled can be read on an indicator,  which shows the changes in air volume inside the  apparatus. Spirometer testing is useful for evaluating  losses in respiratory function and in following the  course of some respiratory diseases. In pneumonia,  for example, inspiration is obstructed, and the IRV  and VC decrease. In emphysema, where expiration is  hampered, the ERV is much lower than normal, and  the residual volume is higher.    Many situations other than breathing move air into  or out of the lungs and may modify the normal  respiratory rhythm. Coughs and sneezes clear the air  passages of debris or collected mucus. Laughing and  crying reflect our emotions. For the most part, these  nonrespiratory air movements are a result of  reflex activity, but some may be produced volun-  tarily. (Examples of nonrespiratory movements are  given in Table 13.1.)    As air flows into and out of the respiratory tree, it  produces two recognizable sounds that can be  picked up with a stethoscope. Bronchial sounds are  produced by air rushing through the large respira-  tory passageways (trachea and bronchi). Vesicular  (vé-sik’u-lar) breathing sounds occur as air fills the  alveoli. The vesicular sounds are soft murmurs that  resemble a muffled breeze.    Very deep inspiration, taken with jaws wide open; ventilates all alveoli (some alveoli may remain collapsed    Homeostatic J  —S Imbalance 13.8  Diseased respiratory tissue, mucus, or pus can pro-  duce abnormal sounds such as crackle (a bubbling  sound), wheezing (a whistling sound), and rales,  which are abnormal bronchial sounds produced by  the presence of mucus or exudate in the lung pas-  sages or by thickening of the bronchial walls.   9. Which is the largest respiratory volume—ERY, IRV,  TV, or VC? Which is the smallest?   10. Dead space volume accounts for about 150 ml of  tidal volume. How much of a tidal breath actually  reaches the alveoli?   11. Jimmy broke a left rib when he fell from his bike.  The rib punctured the chest wall. What happened  to his left lung? Why?    v~ Describe the process of gas exchanges in the  lungs and tissues.  1# Describe how oxygen and carbon dioxide are  transported in the blood.  As we explore gas exchange in more detail, recall the  routes that blood follows in the pulmonary and sys-  temic circuits(see Chapter 11). Blood returning from    Figure 13.10 Gas exchanges in external and  internal respiration. Note that these exchanges occur  in the body according to the laws of diffusion.    the body delivers CO, to the lungs as it picks up O39. In  the systemic circuit, blood delivers O, to body tissues  and picks up CO). As explained earlier, external respira-  tion is the actual exchange of gases between the alveoli  and the blood (pulmonary gas exchange), and internal  respiration is the gas exchange process that occurs  between the blood and the tissue cells (systemic capil-  lary gas exchange). Keep in mind that all gas exchanges  obey the laws of diffusion; that is, movement occurs  toward the area of lower concentration of the diffusing  substance. The relative amounts of O, and CO, in the  alveolar tissues, and in the arterial and venous blood,  are illustrated in Figure 13.10.    During external respiration, dark red blood (reduced  oxygen) flowing through the pulmonary circuit is  transformed into the scarlet (high in oxygen) river  that is returned to the heart for distribution to the  systemic circuit. Although this color change is due to  oxygen pickup by hemoglobin in the lungs, carbon  dioxide is being unloaded from the blood equally  fast. Because body cells continually remove oxygen  from blood, there is always more oxygen in the    alveoli than in the blood. Thus, oxygen tends to dif-  fuse from the air of the alveoli through the respira-  tory membrane into the more oxygen-poor blood of  the pulmonary capillaries.   In contrast, as tissue cells remove oxygen from  the blood in the systemic circulation, they release  carbon dioxide into the blood. Because the concen-  tration of carbon dioxide is much higher in the pul-  monary capillaries than it is in the alveolar air, it will  diffuse from the blood into the alveoli and be  flushed out of the lungs during expiration. Relatively  speaking, blood draining from the lungs into the  pulmonary veins is rich in oxygen and poor in car-  bon dioxide.    Oxygen is transported in the blood in two ways.  Most attaches to hemoglobin molecules inside the  red blood cells (RBCs) to form oxyhemoglobin  (ok"se-he”’mo-glo’bin)—HbO, (Figure 13.11a). A  very small amount of oxygen is carried dissolved in  the plasma.   Carbon dioxide is 20 times more soluble in  plasma compared to oxygen. As a result, most car-  bon dioxide is transported in plasma as bicarbonate  ion (HCO; ), which plays a very important role in  buffering blood pH. Carbon dioxide is enzymati-  cally converted to bicarbonate ion within red blood  cells; then the newly formed bicarbonate ions diffuse  into the plasma.    and 7.45 (Chapter 10, p. 332). Buffers, such as bicarbon-  ate ion, minimize changes in pH in order to maintain  homeostasis.    A smaller amount of the transported CO,  (between 20 and 30 percent) is carried inside the  RBCs bound to hemoglobin. Carbon dioxide binds  to hemoglobin at a different site from oxygen, so it  does not interfere with oxygen transport.   Before carbon dioxide can diffuse out of the  blood into the alveoli, it must first be released from  its bicarbonate ion form. For this to occur, bicarbon-  ate ions (HCO; ) must enter the red blood cells,  where they combine with hydrogen ions (H*) to form  carbonic acid (H,CO3). Carbonic acid quickly splits  to form water and carbon dioxide, and carbon diox-  ide then diffuses from the blood into the alveoli.    Oxygen is loaded into the blood,  and carbon dioxide is unloaded.    Interstitial fluid Pulmonary capillary  Figure 13.11 The loading and  unloading of oxygen (O,) and  carbon dioxide (CO,) in the  body. Note that although the  conversion of CO, to bicarbonate  ion and the reverse reaction are    Impaired oxygen transport: Whatever the cause, inade-  quate oxygen delivery to body tissues is called hypoxia  (hi-pok’se-ah). This condition is easy to recognize in  light-skinned people because their skin and mucosae  take on a bluish cast (become cyanotic; si’ah-not’ ik).  In dark-skinned individuals, this color change can be  observed only in the mucosae and nailbeds. Hypoxia  may be the result of anemia, pulmonary disease, or  impaired or blocked blood circulation.   Carbon monoxide poisoning represents a  unique type of hypoxia. Carbon monoxide (CO) is  an odorless, colorless gas that competes vigorously  with oxygen for the same binding sites on hemoglo-  bin. Moreover, because hemoglobin binds to CO  more readily than to oxygen, carbon monoxide is a    shown occurring in the plasma in  (b), most such conversions occur  within the red blood cells before  bicarbonate ion diffuses into the  plasma for transport. Additionally,  though not illustrated, some CO,    Oxygen is unloaded and carbon  dioxide is loaded into the blood.    CO, +H,0 > H,CO, > H*+ HCO,~  Water Carbonic Bicar-  acid bonate    is carried within red blood cells  bound to hemoglobin, and very  small amounts of O, and CO,  are carried dissolved in blood  plasma.   Carbon monoxide poisoning is the leading cause  of death from fire. It is particularly dangerous  because it kills its victims softly and quietly. It does  not produce the characteristic signs of hypoxia—  cyanosis and respiratory distress. Instead, the victim  becomes confused and has a throbbing headache. In  rare cases, the skin becomes cherry red (the color of  the hemoglobin-CO complex), which is often inter-  preted as a healthy “blush.” People with CO poison-  ing are given 100 percent oxygen until the carbon  monoxide has been cleared from the body.    Internal respiration, the exchange of gases between  the blood and the tissue cells, is the opposite of    what occurs in the lungs. In this process, oxygen  leaves and carbon dioxide enters the blood (see  Figure 13.11b). In the blood, carbon dioxide com-  bines with water to form carbonic acid (H,COs),  which quickly releases bicarbonate ions. As previ-  ously mentioned, most of the conversion of carbon  dioxide to bicarbonate ions occurs inside the RBCs,  where a special enzyme (carbonic anhydrase) speeds  up this reaction. Then the bicarbonate ions diffuse  out into plasma, where they are transported. At the  same time, oxygen is released from hemoglobin,  and the oxygen diffuses quickly out of the blood to  enter the cells. As a result of these exchanges, venous  blood in the systemic circulation is much poorer in  oxygen and richer in carbon dioxide than blood  leaving the lungs.    12. Which type of cellular transport moves respiratory  gases between the blood and the body's cells?  13. What is the major form in which CO, is transported  in the blood?  14. What is cyanosis?  For answers, see Appendix A.    13.2d Control of Respiration  Learning Objectives  vz Name the brain areas involved in control of  respiration.  vz Name several physical factors that influence  respiratory rate.    v Explain the relative importance of oxygen and  carbon dioxide in modifying breathing rate and  depth.    v Explain why it is not possible to stop breathing  voluntarily.  v# Define apnea, hyperventilation, and  hypoventilation.  Although our tidelike breathing seems so beautifully  simple, its control is fairly complex. We will cover  only the most basic aspects of the respiratory  controls.    The activity of the respiratory muscles, the dia-  phragm and external intercostals, is regulated by  nerve impulses transmitted from the brain by the  phrenic nerves and intercostal nerves. Neural  centers that control respiratory rhythm and depth  are located mainly in the medulla oblongata and pons    (Figure 13.12). Much remains to be discovered about  neural regulation of breathing. A brief summary of  what we know follows.    e The medulla oblongata contains two respiratory  centers. The first, the ventral respiratory group  (VRG), contains both inspiratory and expiratory  neurons that alternately send impulses to con-  trol the rhythm of breathing. The inspiratory  neurons stimulate the diaphragm and external  intercostal muscles via the phrenic and intercos-  tal nerves, respectively, during quiet breathing.  Impulses from the expiratory neurons stop the  stimulation of the diaphragm and external inter-  costal muscles, allowing passive exhalation to  occur. Impulses from the VRG maintain a normal  quiet breathing rate of 12 to 15 respirations/  minute, a rate called eupnea (Up-ne’ah).    e The other medullary center, the dorsal respiratory  group (DRG), integrates sensory information from  chemoreceptors and peripheral stretch receptors.  The DRG communicates this information to the  VRG to help modify breathing rhythms.    e The pons respiratory centers, which also com-  municate with the VRG, help to smooth the  transitions (modify timing) between inhalation  and exhalation during activities such as singing,  sleeping or exercising.   The bronchioles and alveoli have stretch recep-  tors that respond to extreme overinflation (which  might damage the lungs) by initiating protective  reflexes. In the case of overinflation, the vagus nerves  send impulses from the stretch receptors to the  medulla oblongata; soon thereafter, inspiration ends  and expiration occurs. This is one example of DRG  integration during respiratory control.   During exercise, we breathe more vigorously and  deeply because the brain centers send more impulses  to the respiratory muscles. This respiratory pattern is  called hyperpnea (hy-perp’ne-ah). After strenuous  exercise, expiration becomes active, and the abdom-  inal muscles and any other muscles capable of  depressing the ribs are used to aid expiration.    Homeostatic J  £ Imbalance 13.10  If the medullary centers are completely suppressed  (as with an overdose of sleeping pills, morphine, or  alcohol), respiration stops completely, and without  intervention death occurs.    Figure 13.12 Neural control of respiration. This figure shows sensory inputs  to the breathing control centers, which send signals through effector nerves to    Physical Factors Although the medulla oblonga-  ta's respiratory centers set the basic rhythm of breath-  ing, physical factors such as talking, coughing, and  exercising can modify both the rate and depth of  breathing. We have already examined some of these  factors in our discussion of nonrespiratory air move-  ments. Increased body temperature also causes an  increase in the rate of breathing.    Volition (Conscious Control) We all have consci-  ously controlled our breathing pattern at one time or  another. During singing and swallowing, breath  control is extremely important, and many of us have  held our breath for short periods to swim underwa-  ter. However, voluntary control of breathing is limited,  and the respiratory centers will simply ignore    messages from the cortex (our wishes) when the oxy-  gen supply in the blood is getting low or blood pH  is falling. All you need do to prove this is to try to  talk normally or to hold your breath after running  at breakneck speed for a few minutes. It simply can-  not be done. Many toddlers try to manipulate  their parents by holding their breath “to death.”  Even though this threat causes many parents to be-  come anxious, they need not worry because the  involuntary controls take over and normal respiration  begins again.    Emotional Factors Emotional factors also modify  the rate and depth of breathing. Have you ever  watched a horror movie with bated (held) breath or  been so scared by what you saw that you were nearly  panting? Have you ever touched something cold and  clammy and gasped? All of these result from reflexes    Chemical Factors Although many factors can modify  respiratory rate and depth, the most important factors  are chemical—the levels of carbon dioxide and oxygen  in the blood (see Figure 13.12). An increased level of car-  bon dioxide and a decreased blood pH are the most  important stimuli leading to an increase in the rate and  depth of breathing. An increase in the carbon dioxide  level can cause a decreased blood pH because high CO,  results in more carbonic acid, which lowers blood pH.  However, a low blood pH could also result from meta-  bolic activities independent of breathing. Changes in the  carbon dioxide concentration or H* ion concentration  (which affects pH) in brain tissue seem to act directly on  the centers in the medulla oblongata by influencing the  pH of local tissues in the brain stem (see Figure 13.12).  Conversely, changes in oxygen concentration in  the blood are detected by peripheral chemoreceptor  regions in the aorta (aortic body in the aortic arch) and  in the fork of the common carotid artery (the carotid  body). These, in turn, send impulses to the medulla  oblongata when the blood oxygen level is dropping.  When oxygen levels are low, these same chemorecep-  tors are also able to detect high carbon dioxide levels.  Although every cell in the body must have oxygen to  live, it is the body’s need to rid itself of carbon dioxide  that is the most important stimulus for breathing. A  decrease in the oxygen level becomes an important  stimulus only when the level is dangerously low.    In people who retain carbon dioxide, such as peo-  ple with emphysema, chronic bronchitis, or other  chronic lung diseases, the brain no longer recognizes  an increased level of carbon dioxide as important. In  such cases, a dropping oxygen level becomes the  respiratory stimulus. This interesting fact explains  why such patients are always given a low level of oxy-  gen; it helps to maintain the prevailing stimulus for  breathing (a low oxygen level).    The respiratory system in healthy individuals has  homeostatic mechanisms. As carbon dioxide or other  sources of acids begin to accumulate in the blood and  tissues, and pH starts to drop, you begin to breathe  more deeply and more rapidly. Hyperventilation  is an increase in the rate and depth of breathing that  exceeds the body’s need to remove carbon dioxide.    In other words, during hyperventilation, we exhale  more CO, than we should, resulting in elevated  blood pH (there is less carbonic acid).   By contrast, when blood starts to become slightly  alkaline, or basic, breathing slows and becomes shal-  low. Slower breathing allows carbon dioxide to accu-  mulate in the blood and brings the blood pH back  into the normal range.   Indeed, control of breathing during rest is aimed  primarily at regulating the hydrogen ion concentration  in the brain. Hypoventilation (extremely slow or shallow  breathing) or hyperventilation can dramatically change  the amount of carbonic acid in the blood. Carbonic  acid increases dramatically during hypoventilation and  decreases substantially during hyperventilation. In both  situations, the buffering ability of the blood is likely to  be overwhelmed; the result is acidosis or alkalosis.    Homeostatic J  £ Imbalance 13.12  Hyperventilation, often brought on by anxiety  attacks, frequently leads to brief periods of apnea  (ap’ne-ah), cessation of breathing, until the carbon  dioxide builds up in the blood again. If breathing  stops for an extended time, cyanosis may occur as a  result of insufficient oxygen in the blood. In addi-  tion, the hyperventilating person may get dizzy and  faint because the resulting alkalosis causes cerebral  blood vessels to constrict. Such attacks can be pre-  vented by having the hyperventilating person breathe  into a paper bag. Because exhaled air contains more  carbon dioxide than atmospheric air, it upsets the  normal diffusion gradient that causes carbon diox-  ide to be unloaded from the blood and leave the  body. As a result, the carbon dioxide (and thus car-  bonic acid) level begins to rise in the blood, ending  alkalosis and returning blood pH to normal.    15. Which brain area is most important for setting the  basic respiratory rate and rhythm?  16. What chemical factor in blood normally provides  the most powerful stimulus to breathe?  For answers, see Appendix A.    1# Describe symptoms and probable causes of COPD  and lung cancer.    Homeostatic J  K Imbalance 13.13  The respiratory system is particularly vulnerable to  infections because it is open to airborne pathogens. We  have already considered some of these inflammatory  conditions, such as rhinitis and tonsillitis. Now we will  turn our attention to the most disabling respiratory dis-  orders, the group of diseases collectively referred to as  chronic obstructive pulmonary disease (COPD) and lung  cancer. These disorders are “living proof” of cigarette  smoking’s devastating effects on the body. Long known  to promote cardiovascular disease, cigarettes are per-  haps even more effective at destroying the lungs.    Chronic Obstructive Pulmonary Disease (COPD)  The chronic obstructive pulmonary diseases  (COPD), exemplified by chronic bronchitis and  emphysema (em"fi-se’mah), are a major cause of  death and disability in the world. These diseases have  certain features in common: (1) Patients almost  always have a history of smoking; (2) dyspnea  (disp’ne-ah), difficult or labored breathing, occurs  and becomes progressively worse; (3) coughing and  frequent pulmonary infections are common; and  (4) most COPD victims are hypoxic, retain carbon  dioxide and have respiratory acidosis, and ultimately  develop respiratory failure (see the figure).   In chronic bronchitis, the mucosa of the lower  respiratory passages becomes severely inflamed and  produces excessive mucus. The pooled mucus  impairs ventilation and gas exchange and dramati-  cally increases the risk of lung infections, including  pneumonias. Chronic bronchitis patients are some-  times called “blue bloaters” because hypoxia and  carbon dioxide retention occur early in the disease  and cyanosis is common.   In emphysema, the walls of some alveoli are  destroyed, causing the remaining alveoli to be  enlarged. In addition, chronic inflammation pro-  motes fibrosis (scarring) of the lungs. As the lungs  become less elastic, the airways collapse during expi-  ration and obstruct outflow of air. As a result, these  patients use an incredible amount of energy to  exhale, and they are always exhausted. Because air is  retained in the lungs, oxygen exchange is surpris-  ingly efficient, and cyanosis does not usually appear  until late in the disease. Consequently, emphysema  sufferers are sometimes referred to as “pink puffers.”  However, overinflation of the lungs leads to a perma-  nently expanded barrel chest.   Lung cancer is the leading cause of cancer death for  both men and women in North America, causing  more deaths than breast, prostate, and colorectal  cancer combined. This is tragic, because lung cancer  is largely preventable—nearly 90 percent of lung  cancers result from smoking. Lung cancer is aggres-  sive and metastasizes rapidly and widely, so most  cases are not diagnosed until they are well advanced.  The cure rate for lung cancer is notoriously low;  most victims die within 1 year of diagnosis. The  5-year survival rate of people with lung cancer diag-  nosed before metastasis is 56 percent; after metasta-  sis is 5 percent.   Ordinarily, nasal hairs, sticky mucus, and the  action of cilia do a fine job of protecting the lungs  from irritants, but smoking overwhelms these  cleansing devices, and they eventually stop function-  ing. Continuous irritation prompts the production  of more mucus, but smoking slows the movements  of cilia that clear this mucus (and may eventually  kill them) and depresses lung macrophages. One  result is a pooling of mucus in the lower respiratory  tract and an increased frequency of pulmonary  infections, including pneumonia and COPD.  However, it is the irritating effects of the “cocktail”  of toxic chemicals in tobacco smoke that ultimately  lead to lung cancer.    proposed to explain an increase in  allergies that occurred too rapidly to  be due to genetic factors. Most    recently, this rise in allergies has been  attributed to a decrease in natural  exposure to foreign antigens, largely  due to improved sanitation, more  effective medicines, clean food and  water, and a shift from rural to urban  living. Together, these improvements    uy, $ Learn more at Mastering A&P > Study Area > | __  Additional Study Tools > A Closer Look N   Imagine two children: one child is  never exposed to pets or dirt, is  washed multiple times per day, and  eats only clean foods prepared by a  parent; the other child plays in the  mud, shares ice cream with his dog,  and eats berries off the bush when  he wants a snack. Which child do  you suppose is healthier? To answer  that, recall that in Chapter 12, we  learned that B and T lymphocytes are  “trained” to recognize the differences  between self-antigens and nonself  antigens. However, part of their train-  ing involves being exposed to foreign  substances (nonself antigens). If the  body doesn’t have many interactions  with foreign substances, the immune  system is not as well developed as it  could have been had these exposures  occurred.   For the child who was not exposed  to pets or dirt, those antigens were  not there to train regulatory T cells,  meaning when this child is exposed to  these foreign antigens later in life,  allergy, asthma, or even autoimmune  disease could result. This explains the  rise in cases of asthma in the United    States across age, sex, and race since  the 1980s. And it is well documented  that developing nations have far fewer  cases of allergy and autoimmune dis-  eases. Maybe there is such a thing as  being too clean, and scientists are  now working on how to mimic these  exposure signals to train immune sys-  tems to recognize foreign substances  without stimulating allergy, asthma,  or autoimmune disease.    e Allergies, asthma, and autoim-  mune diseases are more com-  mon in developed countries.    e Regulatory T cells must be  exposed to antigens during  development in order to  become tolerant (not react) to  them upon later exposures.    e According to the hygiene  hypothesis, advances in sani-  tation and health care have  resulted in less antigen exposure  during regulatory T cell “training,”  opening the door for allergy  and autoimmune disease later  in life.    are (1) adenocarcinoma (40 percent of cases),  which originates as solitary nodules in peripheral  lung areas and develops from bronchial glands and  alveolar cells; (2) squamous cell carcinoma (25-  30 percent), which arises in the epithelium of the  larger bronchi and tends to form masses that hol-  low out and bleed; and (3) small cell carcinoma  (about 20 percent), which contains lymphocyte-like  cells that originate in the main bronchi and grow  aggressively in small grapelike clusters within the  mediastinum, a site from which metastasis is espe-  cially rapid.    complete removal of the diseased lung lobes in an  attempt to halt metastasis. However, removal is an  option only if metastasis has not already occurred. In  most cases, radiation therapy and chemotherapy are  the only options, but most lung cancers are resistant  to these treatments.   Fortunately, there are several new therapies on the  horizon. These include (1) antibodies that target spe-  cific molecules required by the tumor or that deliver  toxic agents directly to the tumor, (2) cancer vaccines  to stimulate the immune system, and (3) various  forms of gene therapy to replace the defective genes    that make tumor cells divide continuously. As clinical  trials progress, we will learn about the effectiveness of  these approaches. However, prevention is worth a  pound of cure. Quitting smoking is a valuable goal.    17. Alvin, a smoker, sees his doctor because he has a  persistent cough and is short of breath after very  little exertion. He has a barrel chest and explains  that it is difficult for him to exhale. What diagnosis  will the doctor make?    v@ Describe normal changes that occur in respiratory  system functioning from infancy to old age.    In the fetus, the lungs are filled with fluid, and all  respiratory exchanges are made by the placenta. At  birth, the fluid-filled pathway is drained, and the  respiratory passageways fill with air. The alveoli inflate  and begin to function in gas exchange, but the lungs  are not fully inflated for 2 weeks. The success of this  change—that is, from nonfunctional to functional  respiration—depends on the presence of surfactant  (sur-fak’tant), a fatty molecule made by the cuboidal  alveolar cells (see Figure 13.6). Surfactant lowers the  surface tension of the film of water lining each alveo-  lar sac so that the alveoli do not collapse between  each breath. Surfactant is not usually present in large  enough amounts to accomplish this function until    late in pregnancy (between 28 and 30 weeks).  Homeostatic J  K Imbalance 13.14  Infants who are born prematurely (before week 28)  or in whom surfactant production is inadequate (as  in many infants born to diabetic mothers) have  infant respiratory distress syndrome (IRDS).  These infants have dyspnea within a few hours after  birth and use tremendous amounts of energy just to  reinflate their alveoli, which collapse after each  breath. Although IRDS still accounts for over 20,000  newborn deaths a year, many babies with IRDS sur-  vive now because of the use of equipment that sup-  plies a positive pressure continuously and keeps the  alveoli open until the maturing lungs produce  enough surfactant.    Important birth defects of the respiratory system  include cleft palate and cystic fibrosis. Cystic fibrosis  (CF), the most common lethal genetic disease in the  United States, strikes in 1 out of every 3,500 to 4,000  births. CF causes oversecretion of a thick mucus that  clogs the respiratory passages and puts the child at  risk for fatal respiratory infections. It affects other  secretory processes as well. Most important, it impairs  food digestion by clogging ducts that deliver pancre-  atic enzymes and bile to the small intestine. Also,  sweat glands produce an extremely salty perspiration.  At the heart of CF is a faulty gene that codes for the  CFTR protein. CFTR works as a chloride ion (CI)  channel to control the flow of Cl” into and out of  cells. In people with the mutated gene, CFTR gets  “stuck” in the endoplasmic reticulum and is unable  to reach the plasma membrane to perform its normal  role. Consequently, less Cl” is secreted from the cells  and less water follows, resulting in the thick mucus  typical of CF. The goal of CF research is to restore nor-  mal salt and water movement. Conventional therapy  for CF includes mucus-dissolving drugs, bronchodila-  tors, “clapping” the chest to loosen the thick mucus,  exercise, and antibiotics to prevent infection. A sur-  prisingly simple approach is to inhale hypertonic  saline droplets, which thins the mucus and makes  coughing it out easier.    The respiratory rate is highest in newborn  infants, about 40 to 80 respirations per minute. It  continues to drop through life: in the infant it is  around 30 per minute, at 5 years it is around 25 per  minute, and in adults it is 12 to 18 per minute.  However, the rate often increases again in old age.  The lungs mature throughout childhood, and more  alveoli are formed until young adulthood. But in  people who begin smoking during the early teens,  the lungs never completely mature, and those addi-   Homeostatic 3  K Imbalance 13.15  In sudden infant death syndrome (SIDS), also  called crib death, apparently healthy infants stop  breathing and die in their sleep. Now believed to be a  problem with multifactorial origin, SIDS deaths saw a  significant reduction since the prone sleeping position  was discouraged for infants. Death rates from SIDS fell  by over 80 percent in England and Wales since the  start of the “Back to Sleep” campaign in 1991.    e Respiratory system provides  oxygen needed for normal neural  activity; disposes of carbon  dioxide   stretch receptors in lungs and  chemoreceptors in large arteries  provide feedback    e Respiratory system provides  oxygen; disposes of carbon  dioxide; tonsils in pharynx  house immune cells   for respiratory gas transport;  immune system protects  respiratory organs from  pathogens and cancer    e Respiratory system provides  oxygen; disposes of carbon  dioxide; carbon dioxide present  in blood as HCO,” and H,CO,  contributes to blood buffering   e Kidneys dispose of metabolic wastes  (other than carbon dioxide) of  respiratory system organs    e Respiratory system provides oxygen  needed for muscle activity; disposes  of carbon dioxide    Except for sneezes or coughs (responses to irri-  tants) and the occasional common cold that blocks  the upper respiratory passageways with mucus, the  respiratory system works so efficiently and smoothly  that we are mostly not even aware of it. Most prob-  lems that occur are a result of external factors—for  example, obstruction of the trachea by a piece of  food or aspiration of food particles or vomitus  (which leads to aspiration pneumonia). Some unfor-  tunate individuals are plagued by asthma, caused by  chronically inflamed, hypersensitive bronchial pas-  sages that respond to many irritants (such as dust  mite and cockroach droppings, dog dander, and  fungi) with dyspnea, coughing, and wheezing. “A  Closer Look” (see p. 474) discusses how hygiene  may be related to recent increases in cases of asthma.   Worldwide, tuberculosis and pneumonia still  figure in the top ten causes of death, killing 1.5 mil-  lion people in 2018. Antibiotics have significantly  decreased their lethal threat, but they remain danger-  ous diseases. Newly diagnosed, and frequently drug-  resistant, tuberculosis cases in AIDS patients are  increasing by leaps and bounds the world over, but  at present the most damaging and disabling respira-  tory diseases are still those described previously,  COPD and lung cancer.    e Respiratory system—body system responsible  for gas exchange; major structures include the  nose, pharynx, larynx, trachea, and lungs    13.1a. Nose—air enters the nasal cavity through  the nostrils (mares), which are divided by the  nasal septum    Lateral walls of the nasal cavity have projections  (conchae) that increase air turbulence and are  lined with mucosa that warms, filters, and  moistens incoming air    Paranasal sinuses surround the nasal cavity  and act as resonance chambers for speech; also  lighten the skull    e The nose is separated from the mouth by the  palate; cleft palate is a genetic defect resulting  in breathing difficulty and problems with speak-  ing and breastfeeding    As we age, the chest wall becomes more rigid and  the lungs begin to lose their elasticity, resulting in a  slowly decreasing ability to ventilate the lungs. Vital  capacity decreases by about one-third by the age of  70. In addition, the blood oxygen level decreases, and  sensitivity to the stimulating effects of carbon diox-  ide decreases, particularly in a reclining or supine  position. The risk of sleep apnea increases as we age.  It can occur when throat muscles relax, blocking the  airway, or when signals to the respiratory muscles are  improperly delivered or not delivered at all.   Additionally, many of the respiratory system's  protective mechanisms also become less efficient  with age. Ciliary activity of the mucosa decreases,  and the phagocytes in the lungs become sluggish.  The net result is that the elderly population is more  at risk for respiratory tract infections, particularly  pneumonia and influenza.    18. What happens to the alveoli if surfactant is not  produced in a newborn baby? What name is given  to this condition?    (ies Listen to the story of this chapter in a brief summary at Mastering A&P >  vt Study Area > Author Narrated Audio Summaries    13.1b. Pharynx—the throat, a muscular com-  mon passageway for food and air; connected  to the nasal cavity via the posterior nasal  aperture  e Three regions of the pharynx: nasopharynx,  oropharynx, laryngopharynx  ° The nasopharynx carries air only; the oro-  pharynx and laryngopharynx are common  passages for food and air  e Tonsils are clusters of lymphatic tissue that sur-  round the pharynx  ° Single pharyngeal tonsil (adenoid) high in  the nasopharynx  ° Paired palatine tonsils at the end of the soft  palate in the oropharynx    e Formed by eight rigid cartilages, including the  thyroid cartilage (Adam's apple) and a spoon-  shaped epiglottis, which covers the tracheal  opening as food is swallowed    e Contains vocal folds (true vocal cords)  responsible for speech; between the vocal folds  is an opening called the glottis    13.1d. Trachea—the windpipe connecting the  larynx and bronchi; is lined with ciliated mucosa  and contains rings of hyaline cartilage to keep  the trachea open   the mediastinum; composed mainly of elastic  connective tissue; the apex is the narrow superior  end near the clavicle, and the base is the broad  area resting on the diaphragm    e Each lung is covered with a serous membrane  layer called visceral pleura, also known as the  pulmonary pleura; the parietal pleura lines  the thoracic cavity    o Pleurisy is inflammation of the pleurae,  resulting either in dry membranes and  increased friction or in increased fluid  production that causes pressure on the lungs    e The bronchial tree represents the increasingly  small passageways branching from the trachea:  bronchi, secondary bronchi, and tertiary bron-  chi. Most of the bronchial tree is composed of  conducting zone structures, which simply  carry air toward alveoli; the smallest conducting  passages are bronchioles.    e The respiratory zone includes terminal bron-  chioles, respiratory bronchioles, alveolar ducts,  alveolar sacs, and alveoli, the air sacs where gas  exchange with blood occurs    o Alveoli contain several cell types: simple  squamous epithelial cells, simple cuboidal  surfactant-secreting cells, and alveolar  macrophages  = Alveolar macrophages patrol and protect    ° The respiratory membrane (air-blood bar-  rier) includes the alveolar and capillary walls  fused to their basement membranes; oxygen  and carbon dioxide diffuse across this mem-  brane during exchange    e Respiration includes four events to accomplish  delivery of oxygen and disposal of carbon dioxide    ° Pulmonary ventilation is the movement of  air into and out of the lungs, providing a con-  stant supply of oxygen; commonly called  breathing    ° External respiration is gas exchange between  the blood and exterior of the body (the air in  alveoli)    o Respiratory gas transport is transport of  gases around the body via blood   o Respiration is not the same as cellular respira-  tion, which is the use of oxygen to produce ATP    e Air is moved into the lungs during inspiration  and leaves the lungs during expiration  ° Lung inflation during inspiration is aided by  surfactant, which coats the inside of alveoli to  prevent collapse    o When these muscles contract, the thoracic cav-  ity gets larger, raising the intrapulmonary  volume, and pressure decreases, allowing air  to flow into the lungs (down the pressure  gradient)    ° When inspiratory muscles relax and the elastic  lungs recoil, the thoracic cavity gets smaller as  intrapulmonary volume is decreased and pres-  sure increases; this allows air to flow out of  the lungs.    e Intrapleural pressure is always negative except  in cases of pneumothorax, which occurs when  injury allows air into the intrapleural space; this  can lead to atelectasis (collapsed lung)    e Tidal volume (TV) is the amount of air moved  during normal quiet breathing; forcible inhala-  tion beyond tidal volume is the inspiratory  reserve volume (IRV). After normal exhalation,  the amount forcibly exhaled is the expiratory  reserve volume (ERV)   e The air remaining in the lung after expiration  (residual volume) helps keep the lungs in-  flated, which eases the next breath    e The total amount of exchangeable air is the vital  capacity (VC), and the dead space volume is  the amount of air that never reaches the alveoli    e Most nonrespiratory air movements are the  result of reflexes; examples include coughing  and sneezing    e Respiratory sounds can be heard as air moves  into and out of the lungs    o Bronchial sounds are heard when air rushes  through large passages    e During external respiration, oxygen diffuses  from the alveoli into pulmonary blood as car-  bon dioxide diffuses from pulmonary blood  into alveoli    e Oxygen is transported in blood as oxyhemo-  globin inside RBCs, and a small amount is  dissolved in plasma    e Carbon dioxide is much more soluble than oxy-  gen, and thus much of it is carried in plasma as  bicarbonate ion (HCO; ), which is essential  for buffering blood pH. The conversion of car-  bon dioxide to bicarbonate ion occurs inside  RBCs. Some carbon dioxide also travels bound  to hemoglobin, but at a different binding site  from oxygen   e Hypoxia is inadequate oxygen supply, which  can cause patients to become cyanotic, or  slightly blue    e Carbon monoxide poisoning is a specific type  of hypoxia caused when carbon monoxide  (CO), which binds more easily to hemoglobin,  competes for the same binding site as oxygen    e During internal respiration, carbon dioxide dif-  fuses from the tissues into capillary blood as  oxygen diffuses from capillary blood into tissues    e Impulses are sent to the diaphragm and external  intercostal muscles by the phrenic nerves and  intercostal nerves, respectively    ° The medulla oblongata contains the ventral  respiratory group (VRG) and the dorsal respi-  ratory group (DRG)  = VRG—contains inspiratory and expiratory    ° The pons respiratory centers also communi-  cate with the VRG to smooth transitions and  modify timing during activities such as sing-  ing or exercising   o Hyperpnea is vigorous, deep breathing, such  as breathing during exercise    and depth include physical factors (such as talk-  ing, exercise, or fever), volition, emotional fac-  tors, and chemical factors (such as carbon  dioxide levels)    ° Hyperventilation—an increase in breathing  rate and depth that results in exhaling more  carbon dioxide that necessary, leading to ele-  vated blood pH    ° Apnea—cessation of breathing, often brought  on by hyperventilation; allows carbon dioxide  levels to increase to normal levels; if apnea  goes on too long, cyanosis can occur    (COPD)—severe respiratory disease, such as  chronic bronchitis or emphysema, that usually  involves a history of smoking, dyspnea (dif-  ficulty breathing), coughing and frequent in-  fections, and one or more of the following:  hypoxia, carbon dioxide retention, respiratory  acidosis, and respiratory failure    o Patients with chronic bronchitis have severe  inflammation of lower respiratory passages,  overproduction of mucus, impaired ventilation  and gas exchange, and frequent lung infections    ° Patients with emphysema have enlarged alve-  oli, chronic inflammation, and reduced elas-  ticity due to fibrosis; airways collapse during  expiration, obstructing exhalation. Forced  exhalation is exhausting, and patients exhibit  a barrel chest due to trapped air in overin-  flated lungs    Small cell carcinoma—begins with  lymphocyte-like cells from the main bronchi  that grow aggressively in the mediastinum  and metastasize rapidly    Treatments of lung cancer include surgical  removal, radiation, and chemotherapy; new  treatments may include antibody-mediated  toxin delivered to target cancer cells, gene  therapy, and cancer vaccines    Cystic fibrosis (CF) is a lethal genetic disease  that interferes with normal chloride ion and  water movements, resulting in oversecretion of  thick mucus that clogs passages and increases  infection risk. Passages delivering pancreatic  enzymes can also be blocked, and extremely  salty sweat is produced    Normal respiratory rates are highest in infants  and continue to decrease as people age. In  adults, normal rates are 12 to 18 respirations  per minute    Sudden infant death syndrome (SIDS) occurs  when infants spontaneously stop breathing and  die in their sleep; the cause is still unknown but  is thought to involve a problem with neural con-    tion from fluid filled to air filled at birth; surfac-  tant is a fatty molecule that lines the alveoli and  lowers the surface tension of the film of water to  keep alveoli inflated between breaths    can occur in premature births when insufficient  surfactant is present; alveoli collapse between  breaths, and it exhausts the infant to reinflate  them with every breath; positive pressure ma-  chines are used to help keep alveoli inflated  until enough surfactant is produced    Alveolus, bronchiole, bronchus, larynx, trachea,  pharynx, nasal cavity  Alveolus, trachea, bronchus, bronchiole, larynx,  pharynx, nasal cavity    2. The structures that open into the nasal cavity include the    rigid, and lungs lose elasticity; vital capacity  decreases, and blood oxygen levels decrease    The risk of sleep apnea increases as we age; can  be caused by either obstruction (relaxation of  throat muscles) or a failure of signals sent to  respiratory muscles    3. Which of the following is (are) located in the larynx?    a. high surface tension of alveolar fluid.  b. adhesion of the pleural membranes.  c. high pressure in the pleural cavities.  d. high elasticity of lung tissue.    7. Which of the following is (are) not present in the   a. Increased level of CO,  b. Decreased level of CO,  c. Decreased blood pH  d. Increased blood pH    Why is it important that the trachea be reinforced  with cartilaginous rings? What is the advantage of the  fact that the rings are incomplete posteriorly?    What distinguishes the mucosa in the slitlike superior  part of the nasal cavity from that in the rest of the  nasal cavity?    What is it about the structure of the alveoli that makes  them an ideal site for gas exchange?    The contraction of the diaphragm and the external  intercostal muscles begins inspiration. What happens,  in terms of volume and pressure changes in the lungs,  when these muscles contract?    What determines in which direction carbon dioxide  and oxygen will diffuse in the lungs? In the tissues?    Name two respiratory centers in the medulla oblon-  gata. What are the functions of the respiratory centers  present in the medulla and the pons?    Define hyperventilation. If you hyperventilate, do you  retain or expel more carbon dioxide? What effect does  hyperventilation have on blood pH? On breathing  rate?    Mr. Alvarez bumped a bee’s nest while making repairs  on his roof. Not surprisingly, he was promptly stung  several times. Because he knew he was allergic to bee  stings, he rushed to the hospital. While waiting, he  went into a state of shock and had extreme difficulty  breathing. Examination showed his larynx to be  edematous, and a tracheostomy was performed. Why  is edema of the larynx likely to obstruct the airway?  What is a tracheostomy, and what purpose does it  serve?    After an unfortunate fall from his bicycle, Jim became  unconscious. To revive him, a friend poured water in  Jim’s mouth. Was that a good idea? Explain.    Nineteen-year-old Tyler stumbled into the drugstore  gasping for breath. Blood was oozing from a small  hole in his chest wall. When the paramedics arrived  they said that Tyler had been shot and suffered a  pneumothorax and atelectasis. What do both of these  terms mean, and how do you explain his respiratory  distress? How will it be treated?    The digestive system  breaks down the food you  eat into nutrients needed for  metabolic processes, such as  making ATP, and rids the body  of materials that cannot be  used, such as fiber.    The digestive system  is essential for providing the  body with the energy and  building blocks it requires to  maintain life.   stream, and then defecates (excretes) to rid the body  of the indigestible wastes.    Chewing breaks  down food into small pieces easy  for enzymes to access; enzymes then  chemically digest food into nutrients  that are actively transported into  blood and delivered to cells  around the body.    vz Name the organs of the alimentary canal and  accessory digestive organs, and identify each on  an appropriate diagram or model.    Figure 14.1 The human digestive system: Alimentary canal and accessory  organs. The organs of the alimentary canal have boldfaced labels, whereas  accessory organs do not. The liver and gallbladder are reflected superiorly and to    1# \dentify the overall function of the digestive  system as digestion and absorption of foodstuffs,  and describe the general activities of each  digestive system organ.  We can separate the organs of the digestive system  into two main groups: those forming the alimentary  (al”é-men’'tar-e; aliment = nourish) canal and the  accessory digestive organs (Figure 14.1). The alimentary  canal performs the whole menu of digestive functions    (ingests, digests, absorbs, and defecates) as it propels  the foodstuffs along its length. The accessory organs  (teeth, tongue, and several large digestive glands)  assist digestion in various ways, as described shortly.    The alimentary canal, also called the gastrointestinal  (GI) tract or gut, is a continuous, coiled, hollow    What is the protective value of having several sets of tonsils at  the oral entrance to the pharynx?   Tongue p (b)  | Laryngopharynx Figure 14.2 Anatomy of  the mouth (oral cavity).  (a) Sagittal view of the  oral cavity and pharynx.  (b) Anterior view of the  (a) oral cavity.    Food enters the digestive tract through the mouth, or  oral cavity, a mucous membrane-lined cavity (Fig-  ure 14.2). The lips, or labia, protect its anterior opening;  the cheeks form its lateral walls; the hard palate forms  its anterior roof; and the soft palate forms its posterior  roof. The uvula (u’vu-lah) is a fleshy fingerlike projec-  tion of the soft palate, which dangles from the posterior    muscular tube that winds through the ventral body  cavity from mouth to anus. Its organs are the mouth,  pharynx, esophagus, stomach, small intestine, and large  intestine. The large intestine leads to the terminal open-  ing, or anus. In a cadaver, the alimentary canal is  approximately 9 m (about 30 feet) long, but in a living  person, it is considerably shorter because of its mus-  cle tone. Food material within this tube is techni-    cally outside the body, because it has contact only  with cells lining the tract and the tube is open to the  external environment at both ends. This relationship  becomes clearer if you think of your alimentary canal  as an elongated doughnut. Then it’s easy to see that if  you stick your finger through a doughnut hole, your  finger is not really in the doughnut. Each organ of the  alimentary canal is described next (find the organs in  Figure 14.1).    edge of the soft palate. The space between the lips and  cheeks externally and the teeth and gums internally is  the vestibule. The area contained by the teeth is the  oral cavity proper. The muscular tongue occupies the  floor of the mouth. The tongue has several bony attach-  ments—two of these are to the hyoid bone and the  styloid processes of the skull. The lingual frenulum  (ling’gwal fren’u-lum), a fold of mucous membrane,  secures the tongue to the floor of the mouth and limits    torted speech. This congenital condition can be cor-  rected surgically by cutting the frenulum.    At the posterior end of the oral cavity are paired  masses of lymphatic tissue, the palatine tonsils. The  lingual tonsil covers the base of the tongue just  beyond. The tonsils, along with other lymphatic tis-  sues, are part of the body’s defense system (look back  at Figure 13.2, p. 457). When the tonsils become  inflamed and enlarge, they partially block the  entrance into the throat (pharynx), making swallow-  ing difficult and painful, as described in Homeostatic  Imbalance 13.3, p. 456.   As food enters the mouth, it is mixed with  saliva and masticated (chewed). The cheeks and  closed lips hold the food between the teeth during  chewing. The nimble tongue continuously mixes  food with saliva and initiates swallowing. Thus, the  breakdown of food begins before it has even left the  mouth.    receptors, are found on the tongue surface (see  Chapter 8, p. 315). So, besides its food-manipulating  function, the tongue allows us to enjoy and appreciate  the food we eat.    From the mouth, food passes posteriorly into the  oropharynx and laryngopharynx, both of which are  common passageways for food, fluids, and air. The  pharynx is subdivided into the nasopharynx, part of  the respiratory passageway; the oropharynx, poste-  rior to the oral cavity; and the laryngopharynx,  which is continuous with the esophagus inferiorly  (see Chapter 13).   The walls of the pharynx contain two skeletal  muscle layers. The cells of the outer layer run longi-  tudinally; those of the inner layer (the constrictor  muscles) run around the wall in a circular fashion.  Alternating contractions of these two muscle layers  propel food through the pharynx inferiorly into the  esophagus. Later we describe this propelling mecha-  nism, called peristalsis (per’i-stal’sis).   The esophagus (é-sof'ah-gus), or gullet, runs from  the pharynx through the diaphragm to the stomach.  About 25 cm (10 inches) long, it is essentially a pas-  sageway that conducts food (by peristalsis) to the  stomach.    The walls of the alimentary canal organs from the  esophagus to the large intestine are made up of the  same four tissue layers, or tunics (Figure 14.3, p. 486):    1. The mucosa is the innermost layer, a moist  mucous membrane that lines the hollow cav-  ity, or lumen, of the organ. It consists primar-  ily of surface epithelium plus a small amount of  connective tissue (lamina propria) and a scanty  smooth muscle layer. Beyond the esophagus,  which has a friction-resisting stratified squa-  mous epithelium, the epithelium is mostly  simple columnar.    2. The submucosa is found just beneath the  mucosa. It is soft connective tissue containing  blood vessels, nerve endings, mucosa-associated  lymphoid tissue (MALT), and lymphatic vessels.    3. The muscularis externa is a muscle layer typi-  cally made up of an inner circular layer and an  outer longitudinal layer of smooth muscle cells.    4. The serosa is the outermost layer of the wall. As  half of a serous membrane pair, the visceral  peritoneum (per’i-to-ne’um) consists of a sin-  gle layer of flat, serous fluid—producing cells.  The visceral peritoneum is continuous with the  slippery parietal peritoneum, which lines the  abdominopelvic cavity by way of a membrane  extension, the mesentery (mes’en-ter’e). A mes-  entery is formed when two layers of peritoneum  are fused together. Routes for nerves, blood ves-  sels, and lymphatic vessels are found between  the layers. Mesenteries anchor digestive organs  in place and store fat. (These relationships are  illustrated in Figure 14.5 on p. 488.)    Homeostatic J  Æ Imbalance 14.2  When the peritoneum is infected, a condition called  peritonitis (per’i-to-ni'tis), the peritoneal mem-  branes tend to stick together around the infection  site. This helps to seal off and localize many intraper-  itoneal infections (at least initially), providing time    The alimentary canal wall contains two impor-  tant intrinsic nerve plexuses—the submucosal nerve  plexus and the myenteric (mi-en’ter-ik; “intestinal  muscle”) nerve plexus. These networks of nerve  fibers are actually part of the autonomic nervous    system. They help regulate the mobility and secre-  tory activity of GI tract organs.    The C-shaped stomach (Figure 14.4) is on the left  side of the abdominal cavity, nearly hidden by the  liver and diaphragm. Different regions of the stom-  ach have been named. The cardial region, or cardia  (named for its position near the heart), sur-  rounds the cardioesophageal (kar"de-o-č-sof"ah-  je'al) sphincter, through which food enters the  stomach from the esophagus. The fundus is the  expanded part of the stomach lateral to the cardial  region. The body is the midportion of the stomach; in  the body, the convex lateral surface is the greater  curvature, and its concave medial surface is the  lesser curvature. As it narrows inferiorly, the body  becomes the pyloric antrum and then the funnel-  shaped pylorus (pi-lor'us), the terminal part of the  stomach. The pylorus is continuous with the small  intestine through the pyloric sphincter, or pyloric  valve.    Intrinsic nerve plexuses  e Myenteric nerve plexus  e Submucosal nerve plexus    blood flow in veins and through the heart (see Chapter 11,  pp. 378-380). The valves of the digestive system  (formed by sphincter muscles) control the flow of food  and digestive juices through the GI tract.    The stomach varies from 15 to 25 cm (6 to 10  inches) in length, but its diameter and volume  depend on how much food it contains. When it is  full, it can hold about 4 liters (1 gallon) of food.  When it is empty, it collapses inward on itself, and its  mucosa is thrown into large folds called rugae  (roo'ge; ruga = wrinkle, fold).   The lesser omentum (o-men’tum), a double  layer of peritoneum, extends from the liver to the  lesser curvature of the stomach. The greater    What modification of the stomach muscularis  externa allows it to mechanically digest food?    Figure 14.4 Anatomy of the stomach. Gross internal anatomy (frontal section). (a) Diagram.  (b) Photo. (c) Enlarged view of gastric pits and glands (longitudinal section). (d) Pepsinogen  produced by the chief cells is activated (converted to pepsin) by HCI secreted by the parietal cells.    omentum, another extension of the peritoneum,  drapes downward and covers the abdominal organs  like a lacy apron before attaching to the posterior  body wall (Figure 14.5). The greater omentum is  riddled with fat, which helps to insulate, cushion,  and protect the abdominal organs. It also has large  collections of lymphoid follicles containing macro-  phages and defensive cells of the immune system.  The stomach acts as a temporary “storage tank”  for food as well as a site for food breakdown. Besides    Figure 14.5 Peritoneal attachments of the abdominal  organs. (a) Anterior view; the greater omentum is shown  in its normal position, covering the abdominal viscera.   (b) Sagittal view of the abdominopelvic cavity of a female.  (c) Conceptualized cross-sectional view of peritoneum and  mesentery. Note that the peritoneal cavity is smaller than  represented.    the usual longitudinal and circular muscle layers, its  wall contains a third, obliquely arranged layer in the  muscularis externa (see Figure 14.4a). This arrange-  ment allows the stomach not only to move food  along the tract, but also to churn, mix, and pummel  the food, physically breaking it down into smaller  fragments. In addition, chemical breakdown of pro-  teins begins in the stomach.   The mucosa of the stomach is a simple columnar  epithelium composed entirely of mucous cells. They    produce a protective layer of bicarbonate-rich alkaline  mucus that clings to the stomach mucosa and pro-  tects the stomach wall from being damaged by acid or  digestive enzymes. This otherwise smooth lining is  dotted with millions of deep gastric pits, which lead  into gastric glands (Figure 14.4c) that secrete the  components of gastric juice. For example, some  stomach cells produce intrinsic factor, a substance  needed for absorption of vitamin B,, in the small  intestine. The chief cells produce inactive protein-  digesting enzymes, mostly pepsinogens. The  parietal cells produce corrosive hydrochloric acid  (HCl), which makes the stomach contents acidic and  activates the enzymes, as in the conversion of pepsin-  ogen to pepsin (shown in Figure 14.4d). The mucous  neck cells produce a thin acidic mucus with an  unknown function that is quite different from that  secreted by the mucous cells of the mucosa. Still other  cells, the enteroendocrine cells (entero = gut), pro-  duce local hormones, such as gastrin, that are impor-  tant in regulating the digestive activities of the  stomach (see Table 14.1).    Most digestive activity occurs in the pyloric  region of the stomach. After food has been processed  in the stomach, it is thick like heavy cream and is  called chyme (kim). The chyme enters the small  intestine through the pyloric sphincter.    1. What is the sequential order (mouth to anus) of  the digestive organs making up the alimentary  canal?   2. In which organ of the alimentary canal does protein  digestion begin?   3. The stomach epithelium secretes several substances,  including alkaline mucus and intrinsic factor. What is  the function of each of these two secretions?    v Explain how villi aid digestive processes in the  small intestine.    Hormone Source Stimulus for secretion  Gastrin Stomach Food in stomach,  particularly partially  digested proteins; ACh  released by nerve fibers  Intestinal gastrin Duodenum Food in stomach  Histamine Stomach Food in stomach   e Relaxes sphincter of duodenal papilla to allow bile  and pancreatic juice to enter the duodenum    The small intestine is the body’s major digestive  organ. Within its twisted passageways, usable nutri-  ents are finally prepared for their journey into the  cells of the body. The small intestine is a muscular  tube extending from the pyloric sphincter to the  large intestine (see Figure 14.1, p. 483). It is the lon-  gest section of the alimentary tube, with an average  length of 2 to 4 m (7 to 13 feet) in a living person.  Except for the initial part of the small intestine,  which mostly lies in a retroperitoneal position (pos-  terior to the parietal peritoneum), the small intestine  hangs in sausagelike coils in the abdominal cavity,  suspended from the posterior abdominal wall by the  fan-shaped mesentery (Figure 14.5b, p. 488). The  large intestine encircles and frames it in the abdom-  inal cavity.   The small intestine has three subdivisions: the  duodenum (doo”uh-de’num; “twelve finger widths  long”), the jejunum (jé-joo’num; “empty”), and the  ileum (il'’e-um; “twisted intestine”), which contrib-  ute 5 percent, nearly 40 percent, and almost 60 per-  cent of the length of the small intestine, respectively  (see Figure 14.1). The ileum joins the large intestine   Chemical digestion of foods begins in earnest in  the small intestine. The small intestine is able to  process only a small amount of food at one time.  The pyloric sphincter (literally, “gatekeeper”) controls  the movement of chyme into the small intestine  from the stomach and prevents the small intestine  from being overwhelmed. In the C-shaped duode-  num, some enzymes are produced by the intestinal  cells. More important are enzymes that are pro-  duced by the pancreas and then delivered to the  duodenum through the pancreatic ducts, where  they complete the chemical breakdown of foods in  the small intestine. Bile (formed by the liver) also  enters the duodenum through the bile duct in the  same area (Figure 14.6). The main pancreatic and  bile ducts join at the duodenum to form the flask-  like hepatopancreatic ampulla (hé-pa”to-pan-kre-a’ tik  am-pu’lah), literally, the “liver-pancreatic enlarge-  ment.” From there, the bile and pancreatic juice  travel through the duodenal papilla and enter the  duodenum together.    Figure 14.6 The duodenum of the small intestine and related organs.    What is the functional value of the microvilli in the absorptive cells of  the small intestine?    Figure 14.7 Structural modifications of the small intestine. (a) Several  circular folds (plicae circulares), seen on the inner surface of the small intestine.  (b) Enlargement of a villus extension of the circular fold. (c) Enlargement of an  absorptive cell to show microvilli (brush border).    Nearly all nutrient absorption occurs in the small  intestine. The small intestine is well suited for its    nutrients are absorbed through the mucosal cells into  both the capillaries and the lacteal (indicated in    function. Its wall has three structures that increase the  absorptive surface area tremendously—villi, micro-  villi, and circular folds (Figure 14.7). Villi are  fingerlike projections of the mucosa that give it a vel-  vety appearance and feel, much like the soft nap of a  towel. Within each villus is a rich capillary bed and a  modified lymphatic capillary called a lacteal. The    Figure 14.13 on p. 499). Microvilli (mi’kro-vil'i) are  tiny projections of the plasma membrane of the  mucosa cells that give the cell surface a fuzzy appear-  ance, sometimes referred to as the brush border.  The plasma membranes bear enzymes (brush border  enzymes) that complete the digestion of proteins and  carbohydrates in the small intestine. Circular folds,    also called plicae circulares (pli’se ser-ku-la’res),  are deep folds of both mucosa and submucosa layers.  Unlike the rugae of the stomach, the circular folds do  not disappear when food fills the small intestine.  Instead, they form an internal “corkscrew slide” to  increase surface area and force chyme to travel slowly  through the small intestine so nutrients can be  absorbed efficiently. All these structural modifica-  tions (villi, microvilli, circular folds), which increase  the surface area, decrease in number toward the end  of the small intestine. In contrast, local collections of  lymphatic tissue (called Peyer’s patches) found in  the submucosa increase in number toward the end of  the small intestine. This reflects the fact that the  remaining (undigested) food residue in the intestine  contains huge numbers of bacteria, which must be  prevented from entering the bloodstream if at all  possible.    4. Which muscular sphincter regulates the flow of  chyme into the small intestine?  5. What are villi, and why are they important?  For answers, see Appendix A.    The large intestine is much larger in diameter than  the small intestine (thus its name) but shorter in  length. About 1.5 m (5 feet) long, it extends from  the ileocecal valve to the anus (Figure 14.8). Its  major functions are to dry out the indigestible food  residue by absorbing water and to eliminate these  residues from the body as feces (fe’séz). It frames the  small intestine on three sides and has these subdivi-  sions: cecum (se’kum), appendix, colon, rectum, and  anal canal.   The saclike cecum is the first part of the large  intestine. Hanging from the cecum is the wormlike  appendix, a potential trouble spot. Because it can  easily become obstructed, it is an ideal location for  bacteria to accumulate and multiply. Inflammation  of the appendix, appendicitis, is the usual result.   The colon is divided into several distinct regions.  The ascending colon travels up the right side of the  abdominal cavity and makes a turn, the right colic (or  hepatic) flexure, to travel across the abdominal cavity  as the transverse colon. It then turns again at the  left colic (or splenic) flexure and continues down the  left side as the descending colon to enter the pelvis,    where it becomes the S-shaped sigmoid (sig’ moyd)  colon. The sigmoid colon, rectum, and anal canal  lie in the pelvis.   The anal canal ends at the anus (a’nus), which  opens to the exterior. The anal canal has two valves:  the external anal sphincter, composed of skeletal  muscle, is voluntary, and the internal anal  sphincter, formed by smooth muscle, is involun-  tary. These sphincters, which act rather like purse  strings to open and close the anus, are ordinarily  closed except during defecation, when feces are elim-  inated from the body.   Because most nutrients have been absorbed  before the large intestine is reached, no villi are pres-  ent in the large intestine, but there are tremendous  numbers of goblet cells in its mucosa that produce alka-  line (bicarbonate-rich) mucus. The mucus lubricates  the passage of feces to the end of the digestive tract.   In the large intestine, the longitudinal layer of  the muscularis externa is reduced to three bands of  muscle called teniae coli (ten'ne-e ko'li; “ribbons  of the colon”). Because these muscle bands usually  display some degree of tone (are partially contracted),  they cause the wall to pucker into small pocketlike  sacs called haustra (haws’trah).    Did You Get It?  6. What are the two main functions of the large  intestine?  For the answer, see Appendix A.    14.1b Accessory Digestive Organs  Learning Objectives  4# List the accessory digestive organs, and describe  the general function of each.  vz Name the deciduous and permanent teeth, and  describe the basic anatomy of a tooth.  1# Describe the composition and functions of saliva.    vz Name the main digestive products of the pancreas  and of the liver.    The role teeth play in processing food needs little  introduction. We masticate, or chew, by opening  and closing our jaws and moving them from side to  side while continuously using our tongue and cheek  muscles to keep the food between our teeth. In the  process, the teeth tear and grind the food, breaking it  down into smaller fragments.    Figure 14.8 The large intestine. A section of the cecum is removed to show the  ileocecal valve. Boldfaced terms are segments of the large intestine.    Ordinarily, by the age of 21, two sets of teeth  have been formed (Figure 14.9, p. 494). The first set  are deciduous (de-sid’u-us) teeth, also called baby  teeth or milk teeth. The deciduous teeth begin to  erupt around 6 months; the first teeth to appear are  the lower central incisors. A baby has a full set (20  teeth) by the age of 2 years.   As the second set of teeth, the deeper permanent  teeth, enlarge and develop, the roots of the milk  teeth are reabsorbed, and between the ages of 6 and  12 years they loosen and fall out. All of the perma-  nent teeth but the third molars have erupted by the  end of adolescence. The third molars, also called wis-  dom teeth, emerge between the ages of 17 and 25.  Although there are 32 permanent teeth in a full set,  the wisdom teeth often fail to erupt; sometimes they  are completely absent.    Homeostatic Gg  —S Imbalance 14.3  When teeth remain embedded in the jawbone, they  are said to be impacted. Impacted teeth can exert  pressure and cause a good deal of pain, so they usu-    ally must be removed surgically. Wisdom teeth are  the most commonly impacted.    We classify the teeth according to shape and Ie  function as incisors, canines, premolars, and molars  (see Figure 14.9). The chisel-shaped incisors are  adapted for cutting; the fanglike canines (eyeteeth)  are for tearing or piercing. The premolars (bicus-  pids) and molars have broad crowns with rounded  cusps (tips) and are best suited for crushing and  grinding.    Figure 14.9 Deciduous and permanent teeth.  Approximate time of tooth eruption is shown in  parentheses. The same number and arrangement of  teeth exist in both upper and lower jaws, so only the  lower jaw is shown in each case. The shapes of  individual teeth are shown on the right.    A tooth consists of two major regions, the crown  and the root (Figure 14.10). The enamel-covered  crown is the exposed part of the tooth above the  gingiva (jin’-jivah), or gum. The crown is covered  with enamel, a ceramic-like substance as thick as a  dime, that directly bears the force of chewing. It is  the hardest substance in the body and is fairly brittle  because it is heavily mineralized with calcium salts.   The portion of the tooth embedded in the jaw-  bone is the root; the root and crown are connected  by a region called the neck. The outer surface of the  root is covered by a substance called cement, which  attaches the tooth to the periodontal (per’e-o-don’ tal)  ligament. This ligament holds the tooth in place  in the bony jaw. Dentin, a bonelike material,    underlies the enamel and forms the bulk of the tooth.  It surrounds a central pulp cavity, which contains a  number of structures (connective tissue, blood ves-  sels, and nerve fibers) collectively called pulp. Pulp  supplies nutrients to the tooth tissues and provides  for tooth sensations. Where the pulp cavity extends  into the root, it becomes the root canal, which pro-  vides a route for blood vessels, nerves, and other pulp  structures to enter the pulp cavity of the tooth.    7. What is the general function of each of the four  types of teeth?  For the answer, see Appendix A.    Three pairs of salivary glands empty their secretions  into the mouth. The large parotid (pah-rot’id)  glands lie anterior to the ears. Mumps, a common  childhood disease, is an inflammation of the parotid  glands. If you look at the location of the parotid  glands (see Figure 14.1), you can readily understand  why people with mumps complain that it hurts to  open their mouth or chew.   The submandibular glands and the small  sublingual (sub-ling’gwal) glands empty their  secretions into the floor of the mouth through tiny  ducts. The product of the salivary glands, saliva, is a  mixture of mucus and serous fluids. The mucus  moistens and helps to bind food together into a  mass called a bolus (bo'lus), which makes chewing  and swallowing easier. The clear serous portion con-  tains an enzyme, salivary amylase (am’i-las), in a  bicarbonate-rich (alkaline) juice that begins the pro-  cess of starch digestion in the mouth. Saliva also  contains substances such as lysozyme and antibodies  (IgA) that inhibit bacteria; therefore, it has a protec-  tive function as well. Last but not least, saliva dis-  solves food chemicals so they can be tasted.    The pancreas is a soft, pink, triangular gland that  extends across the abdomen from the spleen to the  duodenum (look back at Figure 14.6). Most of the  pancreas lies posterior to the parietal peritoneum;  hence its location is referred to as retroperitoneal.   Only the pancreas produces enzymes (described  later) that break down all categories of digestible  foods. The pancreatic enzymes are secreted into the  duodenum in an alkaline fluid that neutralizes the  acidic chyme coming in from the stomach. The pan-  creas also has an endocrine function; it produces the  hormones insulin and glucagon (as explained in  Chapter 9).    The liver is the largest gland in the body. Located  under the diaphragm, more to the right side of the  body, it overlies and almost completely covers the  stomach (look back at Figure 14.5a). The liver has  four lobes and is suspended from the diaphragm  and abdominal wall by a delicate mesentery cord,  the falciform (fal’si-form) ligament.   The liver has many critical metabolic and regula-  tory roles; however, its digestive function is to produce  bile. Bile leaves the liver through the common    hepatic duct and enters the duodenum through the  bile duct (look back at Figure 14.6).   Bile is a yellow-to-green, watery solution con-  taining bile salts, bile pigments (chiefly bilirubin, a  breakdown product of hemoglobin), cholesterol,  phospholipids, and a variety of electrolytes. Of these  components, only the bile salts (derived from cho-  lesterol) and phospholipids help the digestive pro-  cess. Bile does not contain enzymes, but its bile salts  emulsify fats by physically breaking large fat globules  into smaller ones, thus providing more surface area  for the fat-digesting enzymes to work on.   The gallbladder is a small, thin-walled green sac  that snuggles in a shallow fossa in the inferior sur-  face of the liver (look back at Figure 14.6). When  food digestion is not occurring, bile backs up the  cystic duct and enters the gallbladder to be stored.  While in the gallbladder, bile is concentrated by the  removal of water. Later, when fatty food enters the  duodenum, a hormonal stimulus prompts the gall-  bladder to contract and spurt out stored bile, making  it available to the duodenum.    Homeostatic J  Æ Imbalance 14.4  If bile is stored in the gallbladder for too long or too  much water is removed, the cholesterol it contains  may crystallize, forming gallstones. Gallstones can  become stuck in one of the ducts leading from the  gallbladder to the duodenum, causing agonizing  pain when the gallbladder contracts (an event called  a gallbladder attack).   Blockage of the common hepatic or bile ducts  (for example, by wedged gallstones) prevents bile  from entering the small intestine, and it begins to  accumulate and eventually backs up into the liver.  This exerts pressure on the liver cells, and bile salts  and bile pigments begin to enter the bloodstream.  As the bile pigments circulate through the body, the  tissues become yellow, or jaundiced. Blockage of the  ducts is just one cause of jaundice. More often it  results from actual liver problems such as hepatitis,  an inflammation of the liver, or cirrhosis (sir-  ro’sis), a chronic inflammatory condition in which  the liver is severely damaged and becomes hard and  fibrous. Hepatitis is most often due to viral infection  resulting from drinking contaminated water or trans-  mitted in blood via transfusion or contaminated  needles. Cirrhosis is almost guaranteed when    someone drinks alcoholic beverages in excess for  many years, and it is a common consequence of  severe hepatitis.    8. Mary has a dry mouth—very little saliva is being  secreted. Digestion of which type of food will be  affected (decreased) by this situation?   9. What is the digestive role of bile? What organ  produces bile?   10. Which organ is the only one that produces  enzymes capable of digesting all groups of food?  For answers, see Appendix A.   1# List and describe the six main activities of the  digestive system.   v Describe how foodstuffs in the digestive tract are  mixed and moved along the tract.   vz Name the end products of protein, fat, and  carbohydrate digestion.    The major functions of the digestive tract are usually  summarized in two words—digestion and absorption.  However, many of its specific activities (such as  smooth muscle activity) and certain regulatory events  are not really covered by either term. To describe  digestive system processes a little more accurately, we  need to consider a few more functional terms. The  essential activities of the GI tract include the follow-  ing six processes (summarized in Figure 14.11).    1. Ingestion. Food must be placed into the mouth  before it can be acted on. This is an active, vol-  untary process called ingestion.    2. Propulsion. To be processed by more than one  digestive organ, foods must be propelled from   3 3 e Swallowing  (small intestine) (oropharynx)  ET e Peristalsis  Digestion ¢ (esophagus,  stomach,    Figure 14.11 Schematic summary of gastrointesti-  nal tract activities. Gastrointestinal tract activities  include ingestion, mechanical breakdown, chemical  (enzymatic) breakdown or digestion, propulsion,  absorption, and defecation. Sites of chemical digestion  are also sites that produce enzymes or that receive  enzymes or other secretions made by accessory organs.  The entire GI tract mucosa secretes mucus, which  protects and lubricates.    one organ to the next. Swallowing is one ex-  ample of food movement that depends largely  on the propulsive process called peristalsis.  Peristalsis is involuntary and involves alternat-  ing waves of contraction and relaxation of the  longitudinal muscles in the organ wall (Fig-   ure 14.12a). The net effect is to squeeze the food  along the tract.    3. Food breakdown: Mechanical breakdown.  Mechanical breakdown physically fragments  food into smaller particles, increasing surface  area and preparing food for further degradation  by enzymes. Chewing and mixing of food in the  mouth by the teeth and tongue, and churning of  food in the stomach are examples of processes  contributing to mechanical food breakdown. In  addition, segmentation (Figure 14.12b) in the  small intestine moves food back and forth across  the internal wall of the organ, mixing it with the  digestive juices. Although segmentation may  also help to propel foodstuffs through the small  intestine, it is more an example of mechanical  digestion than of propulsion.    4. Food breakdown: Digestion. The sequence of  steps in which large food molecules are chemi-  cally broken down to their building blocks by  enzymes (protein molecules that act as catalysts)  is called digestion.    sis reactions because a water molecule is added to each  bond to be broken (see Chapter 2, p. 60). Water is also  necessary as a dissolving medium and a softening agent  for food digestion.    Because each of the major food groups has very  different building blocks, let's take a little time to  review these organic molecules (which we first intro-  duced in Chapter 2). The building blocks, or units,  of carbohydrate foods are monosaccharides (mon"o-  sak'ah-ridz), or simple sugars. We need to remember  only three of these that are common in our diet—  glucose, fructose, and galactose. Glucose is by far the  most important, and when we talk about blood  sugar level, we are referring to glucose. Fructose is the  most abundant sugar in fruits, and galactose is found  in milk.   The only carbohydrates that our digestive system  digests, or breaks down to simple sugars, are sucrose  (table sugar), lactose (milk sugar), maltose (malt  sugar), and starch. Sucrose, maltose, and lactose are  referred to as disaccharides, or double sugars, because  each consists of two simple sugars linked together.  Starch is a polysaccharide (literally, “many sugars”)  formed by linking hundreds of glucose units.    Although we eat foods containing other polysaccha-  rides, such as cellulose, we do not have enzymes capa-  ble of breaking them down. The indigestible  polysaccharides do not provide us with any nutri-  ents, but they help move the foodstuffs along the  gastrointestinal tract by providing bulk, or fiber, in  our diet.   (b)  Figure 14.12 Peristaltic and segmental movements  of the digestive tract. (a) In peristalsis, adjacent or  neighboring segments of the intestine (or other alimen-  tary canal organs) alternately contract and relax, thereby  moving food distally along the tract. (b) In segmentation,  single segments of the intestine alternately contract and  relax. Because active segments are separated by inactive  ones, the food is moved forward and then backward.    Thus the food is mixed rather than simply propelled  along the tract.    Proteins are digested to their building blocks,  which are amino (ah-me’no) acids. The intermediate  product of protein digestion is polypeptides.   When lipids (fats) are digested, they yield two  different types of building blocks—fatty acids and  an alcohol called glycerol (glis’er-ol). Incomplete  digestion may preserve monoglycerides and fatty  acids. The digestion, or chemical breakdown, of car-  bohydrates, proteins, and fats is summarized in  Figure 14.13, and we describe it in more detail  shortly.   As we have already learned, nucleic acids (DNA,  RNA) are in all cells and are therefore also in the  food we eat. The pancreas produces nucleases to  digest nucleic acids into nucleotides, their building  blocks. Next, nucleosidases and phosphatases in  the brush border of the small intestine further  break down nucleotides into their components,  which are nitrogen bases, 5-carbon sugars, and  phosphate ions.    5. Absorption. Absorption is the transport of  digestive end products from the lumen of the  GI tract to the blood or lymph. For absorption  to occur, the digested foods must first enter the  mucosal cells by active or passive transport pro-  cesses. The small intestine is the major absorp-  tive site.    6. Defecation. Defecation is the elimination of  indigestible residues and gut bacteria from the  GI tract via the anus in the form of feces.    Some of these processes are the job of a single  organ. For example, only the mouth ingests, and  only the large intestine defecates. But most digestive  system activities occur bit by bit as food is moved  along the tract. Thus, in one sense, the digestive tract  can be viewed as a “disassembly line” in which food  is carried from one stage of its processing to the next  and its nutrients are made available to the cells in  the body along the way.   Throughout this book we have stressed the  body's drive to maintain a constant internal envi-  ronment, particularly in terms of homeostasis of the  blood, which comes into contact with all body cells.  The digestive system, however, creates an optimal  environment for itself to function in the lumen  (cavity) of the alimentary canal, an area that is actu-  ally outside the body. Conditions in that lumen are  controlled so that digestive processes occur  efficiently.    Digestive activity is mostly controlled by reflexes  via the parasympathetic division of the autonomic  nervous system. (This division is the “rest-and-  digest” arm. See Chapter 7.) The sensors (mechano-  receptors, chemoreceptors) involved in these reflexes  are located in the walls of the alimentary canal  organs and respond to a number of stimuli, the most  important being stretch of the organ by food in its  lumen, pH of the contents, and presence of certain  breakdown products of digestion. When these recep-  tors are activated, they trigger reflexes that activate or  inhibit (1) the glands that secrete digestive juices  into the lumen or hormones into the blood, and  (2) the smooth muscles of the muscularis that mix  and propel the food along the tract.   Now that we have summarized some points  that apply to the function of the digestive organs  as a group, we are ready to look at their special  capabilities.    11. What is the proper order of the following  stages of food processing—defecation, absorption,  digestion, ingestion?  12. How do mechanical breakdown and digestion  differ from each other?  For answers, see Appendix A.    14.2b Activities Occurring in the  Mouth, Pharynx, and Esophagus  Food Ingestion and Breakdown    Once food has been placed in the mouth, both  mechanical and digestive (chemical) processing  begins. First the food is physically broken down into  smaller particles as it is chewed. Then, as the food is  mixed with saliva, salivary amylase begins the diges-  tion of starch, chemically breaking it down into  maltose (see Figure 14.13). The next time you eat a  piece of bread, chew it for a few minutes before swal-  lowing it. You will notice that it begins to taste sweet  as the sugars are released.   Saliva is normally secreted continuously to keep  the mouth moist, but when food enters the mouth,  much larger amounts of saliva pour out. However,  the simple pressure of anything put in the mouth  and chewed, such as rubber bands or sugarless gum,  will also stimulate the release of saliva. Some emo-  tional stimuli can also cause salivation. For example,  the mere thought of a hot fudge sundae will make    Figure 14.13 Flowchart of digestion and absorption of foodstuffs.  Nucleic acids are not shown.    many a mouth water. All these reflexes, though initi-  ated by different stimuli, are brought about by para-  sympathetic fibers in cranial nerves VII and IX.   Essentially no food absorption occurs in the  mouth. (However, some drugs, such as nitroglycer-  ine, are absorbed easily through the oral mucosa.)  The pharynx and esophagus have no digestive func-  tion; they simply provide passageways to carry food  to the next processing site, the stomach.    For food to be sent on its way from the mouth, it must  first be swallowed. Deglutition (de”gloo-tish’un), or  swallowing, is a complex process that involves the  coordinated activity of several structures (tongue, soft  palate, pharynx, and esophagus). It has two major  phases, the buccal and the pharyngeal-esophageal.  The first phase, the voluntary buccal phase, occurs in  the mouth. Once the food has been chewed and well  mixed with saliva, the bolus (food mass) is forced  into the pharynx by the tongue. As food enters the  pharynx, it passes out of our control and into the  realm of reflex activity.   The second phase, the involuntary pharyngeal-  esophageal phase, transports food through the  pharynx and esophagus. The parasympathetic divi-  sion of the autonomic nervous system (primarily the  vagus nerve) controls this phase and promotes the  mobility of the digestive organs from this point on.  All routes that the food might take, except the desired  route further into the digestive tract, are blocked off.  The tongue blocks off the mouth, and the soft palate  closes off the nasal passages. The larynx rises so that  its opening (into the respiratory passageways) is cov-  ered by the flaplike epiglottis. Food is moved  through the pharynx and then into the esophagus  inferiorly by wavelike peristaltic contractions of their  muscular walls—first the longitudinal muscles con-  tract, and then the circular muscles contract. (The  events of the swallowing process are illustrated in  Figure 14.14.)   If we try to talk or laugh while swallowing, we  confuse our bodies with mixed messages, and as a  result food may enter the respiratory passages. This  triggers still another protective reflex—coughing—  during which air rushes upward from the lungs in an  attempt to expel the food.   Once food reaches the distal end of the esopha-  gus, it presses against the cardioesophageal sphinc-  ter, causing it to open, and the food enters the  stomach. The movement of food through the    pharynx and esophagus is so automatic that a person  can swallow and food will reach the stomach even if  he is standing on his head. Gravity plays no part in  the transport of food once it has left the mouth,  which explains why astronauts in the zero gravity of  outer space can still swallow and get nourishment.    Secretion of gastric juice is regulated by both neu-  ral and hormonal factors. The sight, smell, and taste  of food stimulate parasympathetic nervous system  reflexes, which increase the secretion of gastric juice  by the gastric (stomach) glands. In addition, the  presence of food and a rising pH in the stomach  stimulate the stomach cells to release the hormone  gastrin. Gastrin prods the gastric glands to produce  still more of the protein-digesting enzymes (such as  pepsinogen), mucus, and hydrochloric acid. Under  normal conditions, 2 to 3 liters of gastric juice are  produced every day.   Hydrochloric acid makes the stomach contents  very acidic. This can be dangerous because both  hydrochloric acid and the protein-digesting enzymes  have the ability to digest the stomach itself, causing  ulcers (see “A Closer Look” on p. 506). However, as long  as enough mucus is made, the stomach is protected.    Homeostatic J  £ Imbalance 14.5  Occasionally, the cardioesophageal sphincter fails to  close tightly and gastric juice backs up into the  esophagus, which has little mucus protection. This  results in a characteristic pain known as heartburn,  which, if uncorrected, leads to inflammation of the  esophagus (esophagitis [č-sof'ah-ji'tis]) and per-  haps even to ulceration of the esophagus. A common  cause is a hiatal hernia, a structural abnormality in  which the superior part of the stomach protrudes  slightly above the diaphragm. Because the dia-  phragm no longer reinforces the relatively weak car-  dioesophageal sphincter, gastric juice flows into the  unprotected esophagus. Conservative treatment  involves restricting food intake after the evening  meal, taking antacids, and sleeping with the head  elevated.    The extremely acidic environment that hydro-  chloric acid provides is necessary, because it activates  pepsinogen to pepsin, the active protein-digesting    Figure 14.14 Swallowing.  With the upper esophageal sphincter  contracted (closed), the tongue pushes the food bolus posteriorly and  against the soft palate. @ The soft palate rises to close off the nasal  passages as the bolus enters the pharynx. The larynx rises so that the  epiglottis covers the trachea as peristalsis carries the food through the  pharynx and into the esophagus. The upper esophageal sphincter relaxes to  allow food entry. @) The upper esophageal sphincter contracts again as the  larynx and epiglottis return to their former positions and peristalsis moves  the food bolus inferiorly to the stomach. @) The cardioesophageal sphincter    enzyme. Rennin, the second protein-digesting  enzyme produced by the stomach, works primarily  on milk protein and converts it to a substance that  looks like sour milk. Many parents mistakenly think  that the curdy substance infants spit up after feeding  is milk that has soured in their stomach. Rennin,  produced in large amounts in infants, is the same  enzyme used to make milk curdle into cheese. It is  not believed to be produced in adults.   Other than the beginning of protein digestion,  little chemical digestion occurs in the stomach.  Except for aspirin and alcohol (which seem some-  how to have a “special pass”), virtually no absorp-  tion occurs through the stomach walls.   As food enters and fills the stomach, its wall  begins to stretch (at the same time the gastric juices    are being secreted, as just described). Then the three  muscle layers of the stomach wall become active.  They compress and pummel the food, breaking it  apart physically, all the while continuously mixing  the food with the enzyme-containing gastric juice so  that the thick fluid chyme is formed. The process  looks something like the preparation of a cake mix,  in which the floury mixture is repeatedly folded on 44  itself and mixed with the liquid until it reaches a uni-  form texture.    Once the food has been well mixed, a rippling peri-  stalsis begins in the upper half of the stomach  (Figure 14.15, p. 502 @)). The contractions increase  in force as the food approaches the pyloric valve,    (4) Propulsion: Peristaltic waves —> (2)Grinding: The most >  vigorous peristalsis and    (3)Retropulsion: The peristaltic  wave closes the pyloric valve,  forcing most of the contents of the  pylorus backward into the stomach.    the stomach acts as a pump  that delivers small amounts of  chyme into the duodenum.    grinding the food into chyme. The pylorus of the  stomach, which holds about 30 ml of chyme, acts  like a meter that allows only liquids and very small  particles to pass through the pyloric sphincter.  Because the pyloric sphincter barely opens, each  contraction of the stomach muscle squirts 3 ml or  less of chyme into the small intestine (Figure 14.15,  @). The contraction also closes the valve, so the rest  of the chyme (about 27 ml) is propelled backward  into the stomach for more mixing, a process called  retropulsion (Figure 14.15, @).   When the duodenum is filled with chyme and its  wall is stretched, a nervous reflex, the enterogastric  (en"ter-o-gas’ trik) reflex, occurs. This reflex “puts the  brakes on” gastric activity. It slows the emptying of  the stomach by inhibiting the vagus nerve and tight-  ening the pyloric sphincter, thus allowing time for  intestinal processing to catch up. Generally, it takes  about 4 hours for the stomach to empty completely  after the person eats a well-balanced meal and  6 hours or more if the meal has a high fat content.    Homeostatic J  —S~ Imbalance 14.6  Local irritation of the stomach, such as occurs with  bacterial food poisoning, may activate the emetic  (é-met’ik) center in the brain (medulla oblongata).  The emetic center, in turn, causes vomiting, or emesis.    Vomiting is essentially a reverse peristalsis occurring in  the stomach (and perhaps the small intestine), accom-  panied by contraction of the abdominal muscles and  the diaphragm, which increases the pressure on the  abdominal organs. The emetic center may also be acti-  vated through other pathways; disturbance of the equi-  librium apparatus of the inner ear during a boat ride  on rough water is one example.   14. How does segmentation differ from peristalsis in  terms of moving substances along the GI tract?   16. Why is it necessary for the stomach contents to be  so acidic?    Chyme reaching the small intestine is only partially  digested. Carbohydrate and protein digestion has  begun, but virtually no fats or nucleic acids have  been digested up to this point. (Lingual lipase from    the mouth and gastric lipase from the stomach play  only minor roles in lipid digestion.) Here the process  of chemical digestion is accelerated as the food now  takes a rather wild 3- to 6-hour journey through the  looping coils and twists of the small intestine. By the  time the food reaches the end of the small intestine,  digestion will be complete, and nearly all food  absorption will have occurred.   As mentioned earlier, the microvilli of small intes-  tine cells bear several important enzymes, the so-called  brush border enzymes, that break down double sug-  ars into simple sugars and complete protein digestion  (see Figure 14.13). Intestinal juice itself is relatively  enzyme poor, and protective mucus is probably the  most important intestinal gland secretion. However,  foods entering the small intestine are literally deluged  with enzyme-rich pancreatic juice delivered via a  duct from the pancreas, as well as bile from the liver.   Pancreatic juice contains enzymes that digest all  major nutrient groups. Along with brush border  enzymes, pancreatic enzymes (1) complete the diges-  tion of starch (pancreatic amylase); (2) carry out  about half of protein digestion (via the action of  trypsin, chymotrypsin, carboxypeptidase, and others);  (3) are almost totally responsible for fat digestion,  because the pancreas is the most important source of  lipases; and (4) digest nucleic acids (nucleases).   In addition to enzymes, pancreatic juice contains  a rich supply of bicarbonate ions, which makes it  very basic (about pH 8). When pancreatic juice  reaches the small intestine, it neutralizes the acidic  chyme coming in from the stomach and provides the  proper environment for activation and activity of    intestinal and pancreatic digestive enzymes.  Homeostatic J  —S~ Imbalance 14.7  Pancreatitis (pan"kre-ah-ti'tis) is a rare but  extremely serious inflammation of the pancreas that  results from activation of pancreatic enzymes in the  pancreatic duct. Because pancreatic enzymes break  down all categories of biological molecules, they  cause digestion of the pancreatic tissue and duct.  This painful condition can lead to nutritional defi-  ciencies because pancreatic enzymes are essential for  digestion in the small intestine.    The release of pancreatic juice into the duode-  num is stimulated by both the vagus nerve and local  hormones. When chyme enters the small intestine, it    stimulates the mucosa cells to produce several hor-  mones (Table 14.1, p. 489). Two of these hormones,  secretin (se-kre’tin) and cholecystokinin (ko’le-  sis’to-kin’in) (CCK), influence the release of pancre-  atic juice and bile.   The hormones enter the blood and circulate to  their target organs, the pancreas, liver, and gallblad-  der. Both hormones work together to stimulate the  pancreas to release its enzyme- and bicarbonate-rich  product (Figure 14.16, p. 504). In addition, secretin  causes the liver to increase its output of bile, and  cholecystokinin causes the gallbladder to contract  and release stored bile into the bile duct so that bile  and pancreatic juice enter the small intestine  together. As mentioned before, bile is not an enzyme.  Instead, it acts like a detergent to emulsify, or  mechanically separate, large fat globules into thou-  sands of tiny ones, providing a much greater surface  area for the pancreatic lipases to work on. Bile is also  necessary for absorption of fats—and the fat-soluble  vitamins (K, D, E, and A) that are absorbed along    with them—from the intestinal tract.  Homeostatic J  £ Imbalance 14.8  If either bile or pancreatic juice is absent, essentially  no fat digestion or absorption goes on, and fatty,  bulky stools are the result. In such cases, blood-  clotting problems also occur because the liver  needs fat-soluble vitamin K to make prothrombin,  an important clotting factor.    Absorption of water and of the end products of  digestion occurs all along the length of the small  intestine. Most substances are absorbed through the  intestinal cell plasma membranes by the process of  active transport. Then they enter the capillary beds in  the villi to be transported in the blood to the liver  via the hepatic portal vein. The exception seems to  be lipids, which are absorbed passively by the pro-  cess of diffusion. Lipid breakdown products enter  both the capillary beds and the lacteals in the villi  and are carried to the liver by both blood and lym-  phatic fluids.   At the end of the ileum, all that remains is some  water, indigestible food materials (plant fibers such  as cellulose), and large amounts of bacteria. This  debris enters the large intestine through the ileocecal  valve. (The complete process of food digestion and  absorption is summarized in Figure 14.13 on p. 499.)    (I) Chyme entering  duodenum causes  duodenal enteroendocrine  cells to release  cholecystokinin (CCK)  and secretin. CCK and  secretin enter the  bloodstream.   enzyme-rich pancreatic  juice; secretin causes  secretion of bicarbonate-  rich pancreatic juice.    (4) CCK stimulates  the gallbladder to  release stored bile.  Stimulation by  vagal nerve fibers  causes weak  contractions of the  gallbladder.    (5) CCK causes the  hepatopancreatic  sphincter to relax,  allowing bile and  pancreatic juice to  enter the  duodenum.    Figure 14.16 Regulation of pancreatic juice and bile secretion  and release. Hormonal controls exerted by secretin and cholecystokinin @)—@), are  the main regulatory factors. Neural control ©) is mediated by the vagus nerves.    As mentioned previously, peristalsis is the major  means of propelling chyme through the digestive  tract. It involves waves of contraction that move  along the length of the intestine, followed by waves  of relaxation. The net effect is that the food is moved  through the small intestine in much the same way  that toothpaste is squeezed from a tube. Rhythmic  segmental movements produce local constrictions of  the intestine (see Figure 14.12b) that mix the chyme  with the digestive juices and help to propel food  through the intestine.   What is finally delivered to the large intestine con-  tains few nutrients, but that residue still has 12 to 24  hours more to spend there. The colon itself produces  no digestive enzymes. However, the “resident” bacte-  ria, called normal flora or microbiota, that live in its    lumen metabolize some of the remaining nutrients,  releasing gases (methane and hydrogen sulfide) that  contribute to flatulence and the odor of feces. About  500 ml of gas (flatus) is produced each day, much  more when certain carbohydrate-rich foods (such as  beans) are eaten.   Bacteria residing in the large intestine also make  some vitamins (vitamin K and some B vitamins).  Absorption by the large intestine is limited to the  absorption of these vitamins, some ions, and most of  the remaining water. Feces, the more or less solid  product delivered to the rectum, contains undigested  food residues, mucus, millions of bacteria, and just  enough water to allow its smooth passage.    When presented with food residue, the colon begins  contractions, but they are sluggish or short-lived. The  movements most seen in the colon are haustral  contractions, slow segmenting movements lasting  about 1 minute that occur every 30 minutes or so. As  a haustrum fills with food residue, the distension    stimulates its muscle to contract, which propels the  luminal contents into the next haustrum. These  movements also mix the residue, which aids in water  absorption.   Mass movements are long, slow-moving but  powerful contractile waves that move over large areas  of the colon three or four times daily and force the  contents toward the rectum. Typically, they occur  during or just after eating, when food begins to fill  the stomach and small intestine. Bulk, or fiber, in the  diet increases the strength of colon contractions and  softens the stool, allowing the colon to perform its   Homeostatic J  £ Imbalance 14.9  When the diet lacks bulk, the colon narrows and its  circular muscles contract more powerfully, increas-  ing the pressure on its walls. This encourages forma-  tion of diverticula (di’ver-tik’u-lah), in which the  mucosa protrudes through the colon walls, a condi-  tion called diverticulosis. Diverticulitis, a condi-  tion in which the diverticula become inflamed, can  be life-threatening if ruptures occur.    The rectum is generally empty, but when feces  are forced into it by mass movements and its wall is  stretched, the defecation reflex is initiated. The def-  ecation reflex is a spinal (sacral region) reflex that  causes the walls of the sigmoid colon and the rectum  to contract and the internal anal sphincter to relax.  As the feces are forced through the anal canal, mes-  sages reach the brain giving us time to decide  whether the external (voluntary) anal sphincter  should open or remain constricted to stop passage of  feces. If it is not convenient, defecation (bowel  movement) can be delayed temporarily. Within a  few seconds, the reflex contractions end, and the rec-  tal walls relax. With the next mass movement, the    time to absorb the water (as in irritation of the colon  by bacteria). Because fluids and ions are lost from the    body, prolonged diarrhea may result in dehydration  and electrolyte imbalance, which can be fatal if severe.   If food residue remains in the large intestine for  extended periods, too much water is reabsorbed, and  the stool becomes hard and difficult to pass. This  condition, called constipation, may result from lack  of fiber in the diet, poor bowel habits (“failing to  heed the call”), narcotic pain medications such as  hydrocodone, and laxative abuse. Stool softeners can  help increase water content of material in the colon  to ease passage during defecation.    17. What are the building blocks (and digestion  products) of proteins?  18. What is the role of CCK in digestion?  19. What are brush border enzymes?  For answers, see Appendix A.    The human body contains tens of trillions of cells—  and even more microbes. Research conducted as part  of the Human Microbiome Project suggests the  microbial residents, or microbiota, of the human  body could outnumber our cells by as many as 10 to  1. The microbiota, also called normal flora, includes  all bacteria, viruses, parasites, and fungi that live on  or in the human body, and this population can vary  widely from person to person. In recent years, mas-  sive research projects have been ongoing to define  what organisms make up the microbiota in healthy  individuals compared to those with disease; the data  confirms these microbial profiles do differ. Further  studies aim to make sense of the microbiome,  which is the intersection of the human body, the  microbiota and all of their genes, and our environ-  ment along with how these factors influence human  health. It is estimated that the microbiota contains as  many as 10,000 different species. They make vita-  mins our bodies need, routinely outcompete poten-  tial pathogens, and can influence our moods and  diets. Furthermore, they influence important aspects  of life, such as immune system development, energy  usage, and allergy and autoimmunity.   There is mounting evidence that cross talk  between resident microbes and the immune system  is responsible for healthy immune decisions (that is,    Although a stress-  ful lifestyle does  seem to aggravate  existing ulcers, recent  studies indicate that  most such ulcers are  caused by a strain of  acid-resistant bacte-  ria (Helicobacter  pylori) that burrow  through the mucus  coat of the stomach,  leaving unprotected  areas. This corkscrew-  shaped bacterium is  found in the stomachs  of 50 percent of  healthy people and  70 to 90 percent of  people with ulcers    ibuprofen, and aspirin, all of which  aggravate ulcers. Antacid drugs are sug-  gested to neutralize the stomach acids.  In ulcers colonized by H. pylori, a simple  2-week regimen of antibiotics perma- |  nently cures nearly all such patients. For  active ulcers, a histamine blocker (a  medication that suppresses acid produc-  tion in the stomach) can be combined  with the antibiotic therapy to speed  recovery.   Recent animal trials using a newly  developed vaccine against H. pylori  have been successful. Preventive vacci-  nation, coupled with antibiotic cures,  may eradicate peptic ulcers within the  next 25 years.    pe: ulcers are  typically round,  sharply defined cra-  ters 1 to 4 cm in  diameter in the  mucosa of any part of  the GI tract exposed  to secretions of the  stomach (see photo a).  Most occur in the  pyloric part of the  stomach (gastric  ulcers) or the first part  of the duodenum  (duodenal ulcers).  Peptic ulcers may  appear at any age,  but they develop most  frequently between  ages 50 and 70.  Duodenal ulcers are about three   _ tric pain that seems to bore through to  your back. Other symptoms include  loss of appetite, bloating, nausea, and    Peptic ulcers can produce serious  complications, including bleeding,  anemia, scarring, obstruction of the  pyloric opening, and perforation,  which is leakage of stomach or duo-  denal contents into the peritoneal    times more common than those  in the pylorus of the stomach.    vomiting. Not all people with ulcers  experience these symptoms, however,  and some exhibit no symptoms at all.    good protection without allergies). This occurs when  microbes are able to influence how genes are  expressed in cells of the gut mucosa. Several clinical  trials are currently underway to develop replacement  therapies that would provide patients with a healthy  microbiota, including microbes that convey protec-  tion from food allergies. One of the biggest chal-  lenges is how to get the new microbiota established  in a gut that already has a microbial population.   An understanding of how our microbiota influ-  ences our health and daily lives is just beginning to  be known. All signs point to the importance of the  microbiota; it can protect our health or play a role in  disease, depending on the microbes present. Maybe    e Most ulcers are caused by the  acid-resistant bacterium  Helicobacter pylori.    Clostridioides difficile (formerly Clostridium difficile),  known as C. diff, is a bacterium that grows in the  absence of oxygen (anaerobic), produces toxins and  survival structures called endospores, and is most  often observed in patients who have damaged their  microbiota by taking antibiotics. While antibiotic  treatments definitely save lives in many cases, the    Centers for Disease Control and Prevention (CDC)  estimates that 30 to 50 percent of antibiotics pre-  scribed in hospitals are unnecessary or incorrect.  Once the damage is done, however, normal flora no  longer outnumber C. diff, which colonizes the gut  and can cause diarrhea, colitis (inflammation of the  colon), and even bowel perforation and sepsis. This  bacterium is extremely difficult to get rid of. Each  time these bacteria begin to die, they produce endo-  spores, which are survival structures that even the  strongest antibiotics cannot harm.   Meanwhile, remaining microbiota are exposed  to stronger antibiotics, causing more damage and  making it even easier for C. diff to gain a stronghold.  C. diff is extremely contagious and spreads easily  through contact with an infected person or contam-  inated surfaces. Washing hands, isolating ill patients,  and using a separate bathroom if possible are all rec-  ommendations for preventing the spread of C. diff.  Despite these precautions, about one in six patients  gets C. diff again within 8 weeks.   The recurring nature of C. diff and the fact that  more than 80 percent of deaths due to C. diff occur  in patients 65 or older have prompted the explora-  tion of new strategies to treat the infection. The most  promising treatment option in the face of increasing  drug resistance is a fecal microbiota transplant (FMT).  While this may sound shocking, transplanting  microbiota from a healthy donor to patients with  recurring C. diff infections cures over 90 percent of  cases! After careful screening, donor feces is intro-  duced into the colon in an enema or into the duode-  num via a tube inserted through the nose. The rate of  FMT success is further evidence that the health and  diversity of our microbiota play an important role in  the health and well-being of the human body.    20. Why are microbiota important to consider in  regard to the health of the human body?  For the answer, see Appendix A.    Although it seems at times that people can be divided  into two camps—those who live to eat and those  who eat to live—we all recognize the vital impor-  tance of food for life. The common saying “You are  what you eat” is true in that part of the food we eat is  converted to our living flesh. In other words, a cer-  tain fraction of nutrients is used to build cellular  molecules and structures and to replace worn-out  parts. However, most foods are used as metabolic  fuels. That is, they are oxidized and transformed into  adenosine triphosphate (ATP), the chemical energy  form body cells need to drive their many activities.  The energy value of foods is measured in units called  kilocalories (kcal), or Calories (with a capital C),  the units conscientiously counted by dieters.   We have just considered how foods are digested  and absorbed. But what happens to these foods once  they enter the blood? Why do we need bread, meat,  and fresh vegetables? Why does everything we eat  seem to turn to fat? We will try to answer these ques-  tions in this section.    A nutrient is a substance in food that the body uses  to promote normal growth, maintenance, and repair.  The nutrients divide neatly into six categories. The  major nutrients—carbohydrates, lipids, and pro-  teins—make up the bulk of what we eat. Minor  nutrients—vitamins and  minerals—although  equally crucial for health, are required in very small  amounts. Water, which accounts for about 60 per-  cent of the volume of the food we eat, is also consid-  ered to be a major nutrient. However, because we  described its importance as a solvent and in many  other aspects of body functioning in the chapter on  basic chemistry (see Chapter 2), we will consider  only the other five groups of nutrients here.   Most foods offer a combination of nutrients. For  example, a bowl of cream of mushroom soup con-  tains all of the major nutrients plus some vitamins  and minerals. A diet consisting of foods selected  from each of the five food groups (Table 14.2,  p. 508)—grains, fruits, vegetables, meats and meat  alternatives, and milk products—normally guarantees  adequate amounts of all of the needed nutrients.   MyPlate is a food guide from 2011 that uses a round  dinner plate to illustrate dietary recommendations.  Issued by the United States Department of Agriculture    Breads, rolls, bagels;  cereals, dry and cooked;  pasta; rice, other grains;  tortillas, pancakes, waffles;  crackers; popcorn    Meat, fish, poultry; eggs;  seeds; nuts, nut butters;  soybeans, tofu; other  legumes (peas and beans)    (USDA), it shows food categories in healthy propor-  tions in sections of a place setting (Figure 14.17), in  contrast to the segments of a pyramid shown in its  1992 predecessor, the Healthy Eating Pyramid.  Occupying half the plate are fruits and vegetables  (more vegetable than fruit). The other half shows  grains and proteins (more grain than protein). A  glass represents dairy, the fifth food group. Links pro-  vide details on healthy choices in each food group.  You can personalize your MyPlate diet by age, sex,  and activity level by going to the MyPlate website  (www.choosemyplate.gov).   Nutrition advice is constantly in flux and often  mired in the self-interest of food companies.  Nonetheless, basic dietary principles have not    changed in years and are not in dispute: Eat less over-  all; eat plenty of fruits, vegetables, and whole grains;  avoid junk food; and exercise regularly.    Except for milk sugar (lactose) and small amounts  of glycogen in meats, all the carbohydrates—sugars  and starches—we ingest are derived from plants.  Sugars come mainly from fruits, sugar cane, and  milk. The polysaccharide starch is found in grains,  legumes, and root vegetables. The polysaccharide  cellulose, which is plentiful in most vegetables, is    not digested by humans, but it provides fiber that  increases the bulk of the stool and aids defecation.   Although we also ingest cholesterol and phospholip-  ids, most dietary lipids are triglycerides (neutral  fats). We eat saturated fats in animal products such  as meat and dairy foods and in a few plant products,  such as coconut. Unsaturated fats are present in    seeds, nuts, and most vegetable oils. Major sources of  cholesterol are egg yolk, meats, and milk products.    Animal products contain the highest-quality proteins,  molecules that are amino acid polymers. Eggs, milk,  fish, and most meat proteins are complete proteins that  meet all of the body’s amino acid requirements for tis-  sue maintenance and growth.   Legumes (beans and peas), nuts, and cereals are  also protein rich, but their proteins are nutritionally  incomplete because they are low in one or more of  the essential amino acids. The essential amino acids  are the eight amino acids (listed in Figure 14.18) that  our bodies cannot make. Hence we must obtain these  amino acids from our diet. As you can see, strict vege-  tarians must carefully plan their diets to obtain all the  essential amino acids and prevent protein malnutri-  tion. Cereal grains and legumes when eaten together  provide all the needed amino acids, and some variety  of this combination is found in the diets of all cul-  tures (for example, rice and beans). Soy and quinoa  ([keen’-wah], a seed but classified as a whole grain)  are also sources of complete plant-based proteins.    Figure 14.18 The eight essential amino acids.  Vegetarian diets must be carefully constructed to  provide all essential amino acids. A meal of corn and  beans fills the bill: Corn provides the essential amino  acids not in beans, and vice versa. Note that arginine  and histidine are essential in infants but not adults.    Vitamins are organic nutrients of various forms that  the body requires in small amounts. Most vitamins  function as coenzymes (or parts of coenzymes); that  is, they act with an enzyme to accomplish a particu-  lar type of catalysis.   Although vitamins are found in all major food  groups, no one food contains all the required vita-  mins. Thus, a balanced diet is the best way to ensure  a full vitamin complement, particularly because cer-  tain vitamins (A, C, and E) appear to have anticancer  effects. Diets rich in broccoli, cabbage, and brussels  sprouts (all good sources of vitamins A and C)  appear to reduce cancer risk. However, whether vita-  mins can work wonders is a controversial issue.    The body also requires adequate supplies of seven  minerals (which are inorganic substances)—  calcium, phosphorus, potassium, sulfur, sodium,  chloride, and magnesium—as well as trace amounts  of about a dozen others.   Fats and sugars have practically no minerals, and  cereals and grains are poor sources. The most  mineral-rich foods are vegetables, legumes, milk,  and some meats.   The section on metabolism discusses the main  uses of the major nutrients in the body. (Appendix D  details some important roles of vitamins and miner-  als in the body.)   21. What is the major source of carbohydrates in our  diet?   22. Why is it important to include cellulose in a healthy  diet even though we cannot digest it?   24. What is the most significant role that vitamins play  in the body?   Metabolism (mé-tab'o-lizm; metabol = change) is a  broad term referring to all chemical reactions that  are necessary to maintain life. It involves catabolism  (kah-tab’o-lizm), the breakdown of substances to  simpler substances, and anabolism (ah-nab’o-  lizm), the building of larger molecules or structures  from smaller ones. During catabolism, bond energy  of foods is released and captured to make adenosine  triphosphate (ATP), the energy-rich molecule used  to energize all cellular activities, including catabolic  reactions.   Not all foodstuffs are treated in the same way by  body cells. For example, carbohydrates, particularly  glucose, are usually broken down to make ATP. Fats  are used to build cell membranes, make myelin  sheaths around neurons, and insulate the body with  a fatty cushion. They are also used as the body’s  main fuel for making ATP when there are inadequate  carbohydrates in the diet. Proteins are the major  structural materials used for building cell structures.    Just as a campfire burns wood (its fuel) to produce  heat, the cells of the body use carbohydrates as their  preferred fuel to produce cellular energy (ATP).  Glucose, also known as blood sugar, is the major  breakdown product of carbohydrate digestion.  Glucose is also the major fuel used for making ATP  in most body cells. The liver is an exception; it rou-  tinely uses fats as well, thus saving glucose for other  body cells. Essentially, glucose is “squeezed” in a  series of rearrangements and chemical reactions, and  some of the chemical energy released during this  process is captured and used to bind phosphate to  ADP molecules to make ATP.   The carbon atoms released from glucose leave  the cells as carbon dioxide, and the hydrogen atoms  removed (which contain energy-rich electrons) are  eventually combined with oxygen to form water.  (The overall reaction is summed up simply in  Figure 14.19.) These oxygen-using events are  referred to collectively as cellular respiration. The  three main metabolic pathways involved in cellular  respiration are glycolysis, the citric acid cycle, and the  electron transport chain (shown schematically in  Figure 14.20).   Oxidation via the removal of hydrogen atoms  (which are temporarily passed to vitamin-containing  coenzymes) is a major role of glycolysis and the  citric acid cycle. Glycolysis, which takes place in  the cytosol, also energizes each glucose molecule so  that it can be split into two pyruvic acid molecules  and yield a small amount of ATP in the process  (Figure 14.20). The citric acid cycle occurs in the  mitochondria and produces virtually all the carbon  dioxide that results during cell respiration. Like gly-  colysis, it yields a small amount of ATP by transfer-  ring high-energy phosphate groups directly from  phosphorylated substances to ADP, a process called  substrate-level phosphorylation. Free oxygen is not  involved.    phosphorylation  @) During glycolysis, each  glucose molecule is broken  down into two molecules of  pyruvic acid as hydrogen  atoms containing high-energy  electrons are removed.    (2) Pyruvic acid enters the  mitochondrion, where citric  acid cycle enzymes remove  more hydrogen atoms and  decompose it to COs. During  glycolysis and the citric acid  cycle, small amounts of ATP    © Energy-rich electrons (from liberated  hydrogen ions) picked up by coenzymes are  transferred to the electron transport chain, built  into the cristae membrane. The electron  transport chain carries out oxidative  phosphorylation, which accounts for most of  the ATP generated by cellular respiration, and  finally unites the removed hydrogen with  oxygen to form water.    Figure 14.20 The formation of ATP in the cytosol and the mitochondria during  cellular respiration. The maximum net energy yield per glucose molecule is 32 ATP.    The electron transport chain is the “big pay-  off” step for ATP production. The hydrogen atoms  removed during the first two metabolic phases are  loaded with energy. These hydrogens are delivered  by the coenzymes (NADH, FADH,) to the protein  carriers of the electron transport chain, which are  embedded in the mitochondrial cristae membranes  (Figure 14.21, p. 512). There the hydrogen atoms are  split into hydrogen ions (H*) and electrons (e~). The  electrons “fall down an energy hill,” going from each  carrier to a carrier of lower energy. Like moving water  powering a hydroelectric dam, the movement of  electrons “downhill” through the carriers of the elec-  tron transport chain powers proton pumps that form  a hydrogen ion gradient. Then as these ions travel  down their concentration gradient and through an  ATP synthase enzyme, a phosphate is added to ADP  to form ATP. Ultimately, free oxygen is reduced (the  electrons and hydrogen ions are united with    molecular oxygen), forming water and a large  amount of ATP. This more complicated process of  ATP formation is called oxidative phosphorylation. The  beauty of this system is that, unlike the explosive  reaction that usually happens when fuels are burned  (as when O, is combined with hydrogen), relatively  small amounts of energy are lost as heat and light.  Because glucose is the major fuel for making  ATP, homeostasis of the blood glucose level is criti-  cally important. If there is an excessively high level of  glucose in the blood (hyperglycemia [hi’per-gli-  se’me-ah]), some of the excess is stored in body cells  (particularly liver and muscle cells) as glycogen. If  the blood glucose level is still too high, excesses are  converted to fat. There is no question that eating  large amounts of empty-calorie foods such as candy  and other sugary sweets causes a rapid deposit of fat  in the body's adipose tissues. When the blood glu-  cose level is too low (hypoglycemia), the liver    Figure 14.21 Energy release in the electron transport chain In cellular respiration,  cascading electrons release energy in small steps and finally reduce O, and form water.  The energy released is in quantities easily used to form ATP. (NADH and FADH, are  coenzymes that deliver electrons to the electron transport chain.)    breaks down stored glycogen and releases glucose to  the blood for cellular use. (These various fates of car-  bohydrates are shown in Figure 14.22a, p. 514.)    25. What name is given to the process in which  glucose is combined with oxygen to yield CO3,  H20, and ATP?   26. What are the major end products of the citric acid  cycle?   27. What are the major products of the electron  transport chain?    As we will describe shortly, the liver handles most  lipid, or fat, metabolism that goes on in the body.  The liver cells use some fats to make ATP for their  own use; use some to synthesize lipoproteins,    thromboplastin (a clotting protein), and cholesterol;  and then release the rest to the blood in the form of  relatively small fat-breakdown products. Body cells  remove the fat products and cholesterol from the  blood and build them into their membranes or ste-  roid hormones as needed. Fats are also used to form  myelin sheaths (see Chapter 7) and fatty cushions  around body organs. In addition, stored fats are the  body's most concentrated source of energy.  (Catabolism of 1 gram of fat yields twice as much  energy as the breakdown of 1 gram of carbohydrate  or protein.)   For fat products to be used for ATP synthesis,  they must first be broken down to acetic acid (Figure  14.22b). Within the mitochondria, the acetic acid  (like the pyruvic acid product of carbohydrates) is  then completely oxidized, and carbon dioxide, water,  and ATP are formed.   When there is not enough glucose to fuel the  needs of the cells for energy, larger amounts of fats    are used to produce ATP. Under such conditions, fat  oxidation is fast but incomplete, and some of the  intermediate products, such as acetoacetic acid (two  acetic acids linked together) and acetone, begin to  accumulate in the blood. These cause the blood to  become acidic (a condition called acidosis or  ketoacidosis), and the breath takes on a fruity odor  as acetone diffuses from the lungs. Ketoacidosis is a  common consequence of “no-carbohydrate” diets,  uncontrolled diabetes mellitus, and starvation in  which the body is forced to rely almost totally on  fats to fuel its energy needs. Although fats are an  important energy source, cholesterol is never used as  a cellular fuel. Its importance lies in the functional  molecules and in the structures it helps to form.  Excess fats are stored in fat deposits such as the  hips, abdomen, breasts, and subcutaneous tissues.  Although the fat in subcutaneous tissue is important  as insulation for the deeper body organs, excessive  amounts restrict movement and place greater  demands on the circulatory system. (The metabo-  lism and uses of fats are shown in Figure 14.22b.)    Proteins make up the bulk of cellular structures.  Ingested proteins are broken down to amino acids.  Once the liver has finished processing the blood  draining the digestive tract and has taken its “fill” of  amino acids, the remaining amino acids circulate to  the body cells. The cells remove amino acids from  the blood and use them to build proteins, both for  their own use (enzymes, membranes, mitotic spin-  dle proteins, muscle proteins) and for export  (mucus, hormones, and others). Cells take few  chances with their amino acid supply. They use ATP  to actively transport amino acids into their interior  even though in many cases they may contain more of  those amino acids than are in the blood flowing past  them. Even though this may appear to be “cellular  greed,” there is an important reason for this active  uptake of amino acids. Cells cannot build their pro-  teins unless all the needed amino acids, which num-  ber around 20, are present. As mentioned earlier,  because cells cannot make the essential amino acids,  they are available to the cells only through the diet.  This helps explain the avid accumulation of amino  acids, which ensures that all amino acids needed will  be available for present and (at least some) future  protein-building needs of the cells (Figure 14.22c).  Amino acids are used to make ATP only when pro-  teins are overabundant and/or when carbohydrates    and fats are not available. When it is necessary to oxi-  dize amino acids for energy (Figure 14.22d), their  amine groups are removed as ammonia, and the rest of  the molecule enters the citric acid cycle pathway in the  mitochondria. The ammonia that is released during  this process is toxic to body cells, especially nerve cells.  We will discuss how the liver comes to the rescue in  this situation shortly.    Did You Get It?  28. Other than for ATP production, list two uses of fats  in the body.  For the answer, see Appendix A.    The liver is one of the most versatile and complex  organs in the body. Without it, we would die within  24 hours. Its role in digestion (manufacturing bile)  is important to the digestive process to be sure, but  it is only one of the many functions of liver cells.  The liver cells detoxify drugs and alcohol, degrade  hormones, and make many substances vital to the  body as a whole (cholesterol, blood proteins such as  albumin and clotting proteins, and lipoproteins).  They play a central role in metabolism as they pro-  cess nearly every class of nutrient. Because of the liv-  er's key roles, nature has provided us with a surplus  of liver tissue. We have much more than we need,  and even if part of it is damaged or removed, it is  one of the few body organs that can regenerate rap-  idly and easily.   A unique circulation, the hepatic portal circula-  tion, brings nutrient-rich blood draining from the  digestive viscera directly to the liver (see Chapter 11).  The liver is the body’s major metabolic organ,  and this detour that nutrients take through the  liver ensures that the liver’s needs will be met first.  As blood circulates slowly through the liver, liver  cells remove amino acids, fatty acids, and glucose  from the blood. These nutrients are stored for later  use or processed in various ways. At the same time,  the liver’s phagocytic cells (hepatic macrophages)  remove and destroy bacteria that have managed to  get through the walls of the digestive tract and into  the blood.    (b) Fats: composed of 1 glycerol  molecule and 3 fatty acids;  triglycerides    (d) ATP formation (fueling the metabolic  furnace): all categories of food can be  oxidized to provide energy molecules (ATP)    ATP formation if glucose and  fats are not available or if  essential amino acids are  lacking    Figure 14.22 Metabolism by body cells. (a) Carbohydrate metabolism.  (b) Fat metabolism. (c) Protein metabolism. (d) ATP formation.    The liver is vitally important in helping to maintain  the blood glucose level within the normal range  (around 100 mg glucose/100 ml of blood). After a  carbohydrate-rich meal, thousands of glucose mole-  cules are removed from the blood and combined to  form the large polysaccharide molecules called  glycogen (gli’ko-jen), which are then stored in the  liver. This process is glycogenesis (gli’ko-jen’é-sis),  literally, “glycogen formation” (genesis = beginning).   Later, as body cells continue to remove glucose  from the blood to meet their needs, the blood glu-  cose level begins to drop. At this time, liver cells  break down the stored glycogen by a process called  glycogenolysis (gli’ko-jen-ol'i-sis), which means  “glycogen splitting.” The liver cells then release glu-  cose bit by bit to the blood to maintain blood  glucose homeostasis.   If necessary, the liver can also make glucose from  noncarbohydrate substances, such as fats and pro-  teins. This process is gluconeogenesis (glu"ko-ne"o-  jen’é-sis), which means “formation of new sugar”  (Figure 14.23, p. 516). Hormones, such as thyroxine,  insulin, and glucagon are vitally important in con-  trolling the blood sugar level and in the handling of  glucose in all body cells (see Chapter 9).   Some of the fats and fatty acids picked up by the  liver cells are oxidized for energy (to make ATP) for  use by the liver cells themselves. The rest are broken  down to simpler substances such as acetic acid and  acetoacetic acid and then are released into the blood  or stored as fat reserves in the liver. The liver also  makes cholesterol and secretes cholesterol’s break-  down products in bile.   All blood proteins made by the liver are built  from the amino acids its cells pick up from the  blood. The completed proteins are then released back  into the blood to travel throughout the circulation.  Albumin, the most abundant protein in blood, holds  fluid in the bloodstream. When insufficient albumin  is present in blood, fluid leaves the bloodstream and  accumulates in the tissue spaces, causing edema. (In  Chapter 10, we discussed the role of the protective  clotting proteins made by the liver.) Liver cells also syn-  thesize nonessential amino acids and, as mentioned  earlier, detoxify ammonia. In this process, ammonia  is combined with carbon dioxide to form urea  (u-re’ah). Urea, which is not harmful to the body  cells, is then flushed from the body in urine.   Nutrients not needed by the liver cells, as well as  the products of liver metabolism, are released into    the blood and drain from the liver in the hepatic vein.  These materials then enter the systemic circulation,  where they become available to other body cells.    Although it’s a very important lipid in the diet, as we  mentioned, cholesterol is not used as an energy  fuel. Instead, it serves as the structural basis of ste-  roid hormones and vitamin D and is a major build-  ing block of plasma membranes. Because we hear so  much about “cutting down our cholesterol intake”  in the media, it may be surprising to learn that only  about 15 percent of blood cholesterol comes from  the diet. The other 85 percent or so is made by the  liver. Cholesterol is lost from the body when it is  broken down and secreted in bile salts, which even-  tually leave the body in feces.   Fatty acids, fats, and cholesterol are insoluble in  water, so they cannot circulate freely in the blood-  stream. Instead they are transported bound to the  small lipid-protein complexes called lipoproteins.  Although the entire story is complex, the important  thing to know is that the low-density lipoproteins,  or LDLs, transport cholesterol and other lipids to  body cells, where they are used in various ways. If  large amounts of LDLs are circulating, the chance that  fatty substances will be deposited on the arterial walls,  initiating atherosclerosis, is high. Because of this pos-  sibility, the LDLs are unkindly tagged as “bad lipopro-  teins.” By contrast, the lipoproteins that transport  cholesterol from the tissue cells (or arteries) to the liver  for disposal in bile are high-density lipoproteins, or  HDLs. A high HDL level is considered “good” because  the cholesterol is destined to be broken down and  eliminated from the body. Obviously both LDLs and  HDLs are “good and necessary”; it is just their relative  ratio in the blood that determines whether or not  potentially lethal cholesterol deposits are likely to be  laid down on the artery walls. In general, aerobic exer-  cise, a diet low in saturated fats and cholesterol, and  abstaining from smoking and drinking coffee all  appear to favor a desirable HDL/LDL ratio.    29. What is gluconeogenesis?  30. What happens to the ammonia released when  amino acids are “burned” for energy?  31. If you had your choice, would you prefer to have high  blood levels of HDLs or LDLs? Explain your answer.  For answers, see Appendix A.    Figure 14.23 Metabolic events  occurring in the liver as the blood  glucose level rises and falls. When  the blood glucose level is rising, the  liver removes glucose from the    1# Explain the importance of energy balance in  the body, and indicate consequences of energy  imbalance.    When any fuel is burned, it consumes oxygen and  liberates heat. The “burning” of food fuels by body  cells is no exception. Energy cannot be created or  destroyed—it can only be converted from one form  to another (see Chapter 2). If we apply this principle  to cellular metabolism, it means that a dynamic    blood and stores it as glycogen  (glycogenesis). When the blood  glucose level falls, the liver breaks  down stored glycogen (glycogenolysis)  and makes new glucose from amino    acids and fats (gluconeogenesis). The  glucose is then released to the blood  to restore homeostasis of blood  sugar.    balance exists between the body’s energy intake and  its energy output:    Energy intake = total energy output  (heat + work + energy storage)    Energy intake is the energy liberated during food  oxidation—that is, during the reactions of glycolysis,  the citric acid cycle, and the electron transport chain.  Energy output includes the energy we immediately  lose as heat (about 60 percent of the total), plus  energy used to do work (driven by ATP), plus energy  that is stored in the form of fat or glycogen. Energy    storage is important only during periods of growth  and during net fat deposit.    When energy intake and energy output are balanced,  body weight remains stable. When they are not, we  either gain or lose weight. Because body weight in  most people is surprisingly stable, mechanisms that  control food intake or heat production or both must  exist. Unhappily for many people, the body’s weight-  controlling systems appear to be designed more to  protect us against weight loss than weight gain.   But how is food intake controlled? That is a dif-  ficult question, and one that is still not fully  answered. For example, what type of receptor could  sense the body’s total calorie content and alert one  to start eating or to put down that fork? Despite  heroic research efforts, no such single receptor type  has been found.   We have known for some time that the hypothal-  amus releases several peptides that influence feeding  behavior. Current theories of how feeding behavior  and hunger are regulated focus most importantly on  neural signals from the digestive tract, bloodborne  signals related to body energy stores, hormones, and  signals from normal microbiota. To a smaller degree,  body temperature and psychological factors also  seem to play a role. All these factors appear to oper-  ate through feedback signals to the feeding centers of  the brain. Brain receptors include thermoreceptors,  chemoreceptors (for glucose, insulin, and others),  and receptors that respond to leptin and other poly-  peptides. Sensors in peripheral locations have also  been suggested, with the liver and gut itself (alimen-  tary canal) the prime candidates.    List several factors that influence metabolic rate,  and indicate each one’s effect.    When nutrients are broken down to produce cellular  energy (AIP), they yield different amounts of energy.  As mentioned earlier, the energy value of food  is measured in a unit called the kilocalorie (kcal).  In general, carbohydrates and proteins each yield  4 kcal/gram, and fats yield 9 kcal/gram when they  are broken down for energy production. Most meals,  and even many individual foods, are mixtures of car-  bohydrates, fats, and proteins. To determine the  caloric value of a meal, we must know how many    grams of each type of foodstuff it contains. For most  of us, this is a difficult chore indeed, but approxima-  tions can easily be made with the help of a simple  app such as MyFitnessPal.    Basal Metabolic Rate The amount of energy used  by the body is also measured in kilocalories. The basal  metabolic rate (BMR) is the amount of heat pro-  duced by the body per unit of time when it is under  basal conditions—that is, at rest. It reflects the energy  supply a person’s body needs just to perform essential  life activities such as breathing, maintaining the heart-  beat, and kidney function. An average 70-kg (154-  pound) adult has a BMR of about 60 to 72 kcal/hour.   Many factors influence BMR, including surface area  and gender. For example, small, thin males tend to have  a higher BMR than large, obese females (Table 14.3,  p. 518). Age is also important; children and adoles-  cents require large amounts of energy for growth and  have relatively high BMRs. In old age, the BMR decreases  dramatically as the muscles begin to atrophy.   The amount of thyroxine produced by the thy-  roid gland is probably the most important factor in  determining a person’s BMR; hence, thyroxine has  been dubbed the “metabolic hormone.” The more  thyroxine produced, the higher the oxygen consump-  tion and ATP use, and the higher the metabolic rate.  In the past, most BMR tests were done to determine  whether sufficient thyroxine was being made. Today,  thyroid activity is more easily assessed by blood tests.    Homeostatic J  —S~ Imbalance 14.12  Hyperthyroidism causes a host of effects due to the  excessive metabolic rate it produces. The body  catabolizes stored fats and tissue proteins, and  despite increased hunger and food intake, the person  often loses weight. Bones weaken, and body mus-  cles, including the heart, atrophy. In contrast,  hypothyroidism results in slowed metabolism, obe-  sity, and diminished thought processes.    must oxidize more glucose to provide energy for the  additional activities. Digesting food and even mod-  est physical activity increase the body’s caloric  requirements dramatically. These additional fuel  requirements are above and beyond the energy  required to maintain the body in the basal state.  Total metabolic rate (TMR) refers to the total  amount of kilocalories the body must consume to    Small surface area in relation to body volume, as in large,    fuel all ongoing activities. Muscular work is the  major body activity that increases the TMR. Even  slight increases in skeletal muscle activity cause  remarkable leaps in metabolic rate. When a well-  trained athlete exercises vigorously for several min-  utes, the TMR may increase to 15 to 20 times  normal, and it remains elevated for several hours  afterward.   When the total number of kilocalories con-  sumed is equal to the TMR, homeostasis is main-  tained, and our weight remains constant. However, if  we eat more than we need to sustain our activities,  excess kilocalories appear in the form of fat deposits.  Conversely, if we are extremely active and do not  properly feed the “metabolic furnace,” we begin to  break down fat reserves and even tissue proteins to  satisfy our TMR. This principle is used in every good  weight-loss diet. (The total kilocalories needed are  calculated on the basis of body size and age. Then,  20 percent or more of the requirements are cut from  the daily diet.) If the dieting person exercises regu-  larly, weight drops off even more quickly because the  TMR increases above the person’s former rate.    32. Which of the following would you expect to yield  a relatively high BMR: old age, large surface area  relative to body volume, female sex, deficient  thyroxine production?    Large surface area in relation to body volume, as in thin,    Body Temperature Regulation  Learning Objective  1# Describe how body temperature is regulated.    Although we have been emphasizing that foods are  “burned” to produce ATP, remember that ATP is not  the only product of cell catabolism. Most of the  energy released during food oxidation escapes as  heat. Less than 40 percent of available food energy is  actually captured to form ATP. The heat released  warms the tissues and, more important, the blood,  which circulates to all body tissues, keeping them at  homeostatic temperatures. This allows metabolism  to occur efficiently.   Body temperature reflects the balance between  heat production and heat loss. The body’s thermo-  stat is in the hypothalamus of the brain. Through  autonomic nervous system pathways, the hypothal-  amus continuously regulates body temperature  around a set point of 37°C, fluctuating within the  range of 35.6° to 37.8°C (96° to 100°F). The hypo-  thalamus does this by initiating heat-promoting  mechanisms or heat loss mechanisms (Figure 14.24).    Heat-Promoting Mechanisms When the environ-  mental temperature is low, the body must produce  more heat to maintain normal body temperature.  And if, for whatever reason, the temperature of circu-  lating blood falls, body heat must be conserved and  more heat generated to restore normal body (blood)    Skin blood vessels dilate:  Capillaries become flushed  with warm blood; heat  radiates from skin surface    Blood warmer is vaporized by body heat, temperature  than hypothalamic helping to cool the body declines, and  set point hypothalamus  heat loss center  “shuts off”  Stimulus:  Increased body Me,  temperature wal ANer  os e + HOMEOSTASIS = NORMAL BODY  not weather) TEMPERATURE (35.6°C-37.8°C)  z = Stimulus:  Decreased body  I < temperature  MBAL ~~ (e.g., due to cold  ANCE environmental  temperatures)  Skin blood vessels constrict:    temperature. Short-term means of accomplishing  this are vasoconstriction of blood vessels of the  skin and shivering.   When the skin vasculature constricts, the blood  temporarily bypasses the skin and is rerouted to the  deeper, more vital body organs. When this happens,  the temperature of the exposed skin drops to that of  the external environment.    Homeostatic J  £ Imbalance 14.13  Restriction of blood delivery to the skin is no prob-  lem for brief periods of time. But if it is extended, the  skin cells, chilled by internal ice crystals and deprived  of oxygen and nutrients, begin to die. This condi-  tion, called frostbite, can cause the loss of extremi-  ties such as fingers and toes.    When the core body temperature (the tempera-  ture of the deep organs) drops to the point beyond  which simple constriction of skin capillaries can  handle the situation, shivering begins. Shivering,  involuntary shuddering contractions of the volun-  tary muscles, is very effective in increasing the body  temperature because skeletal muscle activity pro-  duces large amounts of heat.    Homeostatic J  —S Imbalance 14.14  Extremely low body temperature resulting from pro-  longed exposure to cold is hypothermia. In hypo-  thermia, the individual's vital signs (respiratory rate,  blood pressure, heart rate) decrease. The person  becomes drowsy and oddly comfortable, even  though previously he or she felt extremely cold.  Uncorrected, the situation progresses to coma and  finally death as metabolic processes grind to a stop.    Heat Loss Mechanisms Just as the body must be  protected from becoming too cold, it must also be  protected from excessively high temperatures. Most  heat loss occurs through the skin via radiation or  evaporation. When body temperature increases  above the normal range, the blood vessels serving  the skin dilate, and capillary beds in the skin become  flushed with warm blood. As a result, heat radiates  from the skin surface. However, if the external envi-  ronment is as hot as or hotter than the body, heat  cannot be lost by radiation. In such cases, the only  means of getting rid of excess heat is by the evapora-  tion of perspiration off the skin surface. This is an  efficient means of liberating body heat as long as the  air is dry. If it is humid, evaporation occurs at a much  slower rate. Our heat-liberating mechanisms don’t  work well, and we feel miserable and irritable.    Homeostatic J  £ Imbalance 14.15  When normal heat loss processes become ineffective,  the resulting hyperthermia, or elevated body tem-  perature, depresses the activity of the hypothalamus.  As a result, a vicious positive feedback cycle occurs:  The soaring body temperature increases the meta-  bolic rate, which in turn increases heat production.  The skin becomes hot and dry; and, as the tempera-  ture continues to spiral upward, permanent brain  damage becomes a distinct possibility. This condi-  tion, called heat stroke, can be fatal unless rapid    corrective measures are taken immediately (immer-  sion in cool water and administration of fluids).   Heat exhaustion is the term used to describe  the heat-associated collapse of an individual during  or following vigorous physical activity. Heat exhaus-  tion results from excessive loss of body fluids (dehy-  dration) and is evidenced by low blood pressure, a  rapid heartbeat, and cool, clammy skin. In contrast  to heat stroke, heat loss mechanisms still operate in  heat exhaustion.    Fever is controlled hyperthermia. Most often, it  results from infection somewhere in the body, but it  may be caused by other conditions (cancer, allergic  reactions, and CNS injuries). Macrophages, white  blood cells, and injured tissue cells release chemical  substances called pyrogens (pi’ro-jenz) that act  directly on the hypothalamus, causing its thermostat  to be set to a higher temperature (pyro = fire). After  thermostat resetting, heat-promoting mechanisms  are initiated. Vasoconstriction causes the skin to  become cool, and shivering begins to generate heat.  This situation, called “the chills,” is a sure sign that  body temperature is rising. Body temperature is  allowed to rise until it reaches the new setting. Then,  it is maintained at the “fever setting” until natural  body defense processes or antibiotics reverse the dis-  ease process. At that point, the thermostat is reset  again to the lower normal level, causing heat loss  mechanisms to swing into action—the individual  begins to sweat, and the skin becomes flushed and  warm. Physicians have long recognized that these  signs signal a turn for the better, saying that the  patient's fever has “broken” once body temperature  begins falling.   Fever, by increasing the metabolic rate, helps  speed the various healing processes and also  appears to inhibit bacterial growth (see Chapter 12).  The danger of fever is that if the body thermostat is  set too high, body proteins may be denatured  (unfolded), and permanent brain damage may  occur.    33. What are two means of either maintaining or  increasing body temperature?  34. How does vasodilation of skin blood vessels affect  body temperature on a hot day?  For answers, see Appendix A.    vz Name important congenital disorders of the  digestive system and significant inborn errors of  metabolism.   The very young embryo is flat and pancake-shaped.  However, it soon folds to form a cylindrical body,  and its internal cavity becomes the cavity of the ali-  mentary canal. By the fifth week of development,  the alimentary canal is a continuous tubelike struc-  ture extending from the mouth to the anus. Shortly  after, the digestive glands (salivary glands, liver,  and pancreas) bud out from the mucosa of the ali-  mentary tube. These glands retain their connec-  tions (ducts) and can easily empty their secretions  into the alimentary canal to promote its digestive  functions.    tal defects that interfere with feeding. The most com-  mon is the cleft palate/cleft lip defect.    Of the two, cleft palate is more serious because  the child is unable to suck properly. Another relatively  common congenital defect is tracheoesophageal  fistula (tra”ke-o-é-sof’ah-je-al fis'tu-lah), an abnor-  mal connection between the esophagus and the tra-  chea. In addition, the esophagus often (but not  always) ends in a blind sac and does not connect to  the stomach. The baby chokes, drools, and becomes  cyanotic during feedings because food is entering the  respiratory passageways. All three defects can be cor-  rected surgically.   There are many types of genetic problems that  interfere with metabolism, but perhaps the two most  common are cystic fibrosis and phenylketonuria  (fen il-ke'to-nu’re-ah). Cystic fibrosis (CF) primar-  ily affects the lungs (see Chapter 13), but it also sig-  nificantly impairs the activity of the pancreas. In CF,  huge amounts of mucus are produced, which block  the passages of involved organs. Blockage of the pan-  creatic duct prevents pancreatic fluid from reaching  the small intestine. As a result, fats and fat-soluble  vitamins are not digested or absorbed, and bulky, fat-  laden stools result. This condition is usually handled  by administering pancreatic enzymes with meals.   Phenylketonuria (PKU) involves an inability  of tissue cells to use phenylalanine (fen’il-al’ah-  nin), an amino acid present in all protein foods. In  such cases, brain damage and intellectual dysfunc-  tion occur unless a special diet low in phenylalanine  is prescribed.    The developing infant receives all its nutrients  through the placenta, and at least at this period of  life, obtaining and processing nutrients is no prob-  lem (assuming the mother is adequately nourished).  Obtaining nutrition is the most important activity of  the newborn baby, and several reflexes present at this  time help in this activity. For example, the rooting  reflex helps the infant find the nipple (mother’s or  bottle), and the sucking reflex helps him or her to  hold on to the nipple and swallow. The stomach of a  newborn infant is very small, so feeding must be fre-  quent (every 3 to 4 hours). Peristalsis is rather ineffi-  cient at this time, and vomiting is not at all unusual.   Teething begins around age 6 months and con-  tinues until about the age of 2 years. During this  interval, the infant progresses to more and more  solid foods and usually is eating an adult diet by tod-  dlerhood. Appetite decreases in the elementary  school-aged child and then increases again during  the rapid growth of adolescence. (Parents of adoles-  cents can expect higher grocery bills!)   is that it is a condition of exces-  sive fat storage. A body fat content  that is 18 to 22 percent of body  weight (males and females, respec-  tively) is considered normal for adults.  Anything over that is defined as obesity.  However, dense bones and well-  developed muscles may make a  person technically overweight.   Body fat content can be estimated  using the body mass index (BMI) scale,  an index of a person's weight relative  to height. To estimate BMI, multiply  weight in pounds (lb) by 703 and then  divide by your height in inches squared:   A BMI of 25 or more is defined as  overweight, and a BMI of 30 or above is  defined as obese. Although BMI calcu-  lations are simple and inexpensive, they  are not diagnostic. In other words, BMI  does not measure body composition  directly, so a high BMI does not neces-  sarily represent a health crisis. There are  other methods to measure body com-  position, including the following:    e Air displacement plethysmogra-  phy technology, known widely  as the Bod Pod, is a way of  measuring body composition    All through childhood and into adulthood, the  digestive system usually operates with relatively few  problems unless there are abnormal interferences,  such as contaminated food or extremely spicy or irri-  tating foods (which may cause inflammation of the  gastrointestinal tract, or gastroenteritis [gas”tro-  en-ter-i’tis]). Inflammation of the appendix,  appendicitis, is particularly common in teenagers  for some unknown reason.   Between middle age and early old age, the meta-  bolic rate decreases by 5 to 8 percent in every 10-year    using air displacement to deter-  mine body volume and thus  body density (density is the mass,  or weight, divided by volume).   e There also exists a similar tech-  nology that uses a water-filled  rather than air-filled chamber.    Both of these are more accurate  than BMI, but they are also more  expensive and less readily available to  the general population.    Learn more at Mastering A&P > Study Area >  Additional Study Tools > A Closer Look    However it’s defined, obesity is  poorly understood. Despite its adverse  effects on health (a higher incidence of  arteriosclerosis, hypertension, coronary  artery disease, and diabetes mellitus),  obesity has reached epidemic propor-  tions globally; 13 percent of adults in  the world are obese, while one in five  children and adolescents is over-  weight. The prevalence of overweight  and obesity among children and ado-  lescents aged 5 to 19 has increased  drastically from 4 percent in 1975 to  over 18 percent in 2016. Overeating,  consuming fried and processed foods,  and sedentary activities, such as video  gaming or watching television, have  replaced healthy eating and exercise.    e Body mass index (BMI) can  estimate body fat but is not  diagnostic.    e Globally, 13 percent of adults  are obese and 39 percent are  overweight.    e Obesity is associated with a  higher incidence of arterioscle-  rosis, hypertension, and diabe-  tes mellitus.    period. This is the time of life when the weight seems to  creep up, and obesity often becomes a fact of life. To  maintain desired weight, we must be aware of this grad-  ual change and be prepared to reduce caloric intake.  Two distinctly middle-age digestive problems are ulcers  (see “A Closer Look” on p. 506) and gallbladder problems  (inflammation of the gallbladder or gallstones). For  some unknown reason, irritable bowel syndrome (IBS),  characterized by alternating bouts of diarrhea and con-  stipation, is becoming much more prevalent in adults,  but its cause has been difficult to pin down.    e Liver removes hormones from  blood, ending their activity; digestive  system provides nutrients needed for  energy fuel, growth, and repair; pancreas  has hormone-producing cells   e Neural controls of digestive function;  in general, parasympathetic fibers  accelerate and sympathetic fibers  inhibit digestive activity; reflex and  voluntary controls of defecation    e Digestive system provides nutrients for  energy metabolism, growth, and repair   e Respiratory system provides oxygen  and carries away carbon dioxide  produced by digestive system organs    e Digestive system provides nutrients  for normal functioning; HCI of  stomach provides nonspecific  protection against bacteria   e Lacteals drain fatty lymph from  digestive tract organs and convey  it to blood; Peyer's patches and  lymphoid tissue in mesentery  house macrophages and  immune cells that protect  digestive tract organs  against infection    e Digestive system provides nutrients to  heart and blood vessels; absorbs iron  needed for hemoglobin synthesis;  absorbs water necessary for normal  blood volume   nutrients absorbed by alimentary canal  to all tissues of the body; distributes  hormones of the digestive tract    e Digestive system provides nutrients  for energy fuel, growth, and repair  and extra nutrition needed to  support fetal growth    e Digestive system provides nutrients  for energy fuel, growth, and repair   e Kidneys transform vitamin D to its  active form, which is needed for  calcium absorption; excrete some  bilirubin produced by the liver    e Digestive system provides nutrients for  energy fuel, growth, and repair;  supplies fats that provide insulation in  subcutaneous tissues   e The skin synthesizes vitamin D needed  for calcium absorption from the  intestine; protects by enclosure    e Digestive system provides nutrients  for energy fuel, growth, and repair; energy fuel, growth, and repair;  liver removes laciic acid, resulting absorbs calcium needed for bone salts  from muscle activity, from the blood e Skeletal system protects some digestive    During old age, activity of the GI tract declines.  Fewer digestive juices are produced, and peristalsis  slows. Taste and smell become less acute, and peri-  odontal disease often develops. Many elderly indi-  viduals live alone or on a reduced income. These  factors, along with increasing physical disability,  tend to make eating less appealing, and nutrition is  inadequate in many of our elderly citizens.  Diverticulosis, the bulging of the mucosa outward  into the colon wall, and cancer of the gastrointesti-  nal tract are fairly common problems. Cancers of the  stomach and colon rarely show early signs and often  progress to an inoperable stage because they spread  to distant parts of the body before the individual  seeks medical attention. However, when detected  early, both diseases are treatable. A diet high in plant  fiber and low in fat may help to decrease the inci-  dence of colon cancer. Additionally, because most    PART I: ANATOMY AND PHYSIOLOGY OF THE  DIGESTIVE SYSTEM (pp. 482-507)    14.1 Anatomy of the Digestive System  (pp. 482-496)  e Digestive system is divided into two groups: organs  of the alimentary canal and accessory organs    e Alimentary canal—the hollow muscular tube  from mouth to anus; also called gastrointesti-  nal (GI) tract    o Includes mouth, pharynx, esophagus, stom-  ach, small intestine, large intestine, and anus    e Mouth, also called oral cavity—site where food  enters and is held between teeth and tongue by  lips (labia) and cheeks  ° Hard palate and soft palate form the roof  anteriorly and posteriorly, respectively   ° Lingual frenulum holds the tongue to the  floor of the mouth   ° Palatine tonsils and the lingual tonsil pro-  tect the entrance to the pharynx   e Pharynx—divided into oropharynx (posterior  to oral cavity) and laryngopharynx (continu-  ous with esophagus)   o Contains two muscle layers: the outer layer is  longitudinal, the inner layer circular    colorectal cancers derive from initially benign muco-  sal tumors called polyps, and because the incidence  of polyp formation increases with age, colonoscopy  screenings should begin at the age of 50 and be  repeated as the physician recommends, generally  every 10 years. However, very sensitive fecal occult  blood tests, which look for blood in the stool,  should be completed annually.   36. What dietary changes must be made to prevent  brain damage in children with PKU?   37. What occurs when your total caloric intake exceeds  your TMR?    LA Listen to the story of this chapter in a brief summary at Mastering A&P >  ot Study Area > Author Narrated Audio Summaries    Mucosa—innermost layer of moist mucous  membrane lining the lumen of the GI tract    Submucosa—deep to mucosa; made of con-  nective tissue containing blood vessels, nerves,  mucosa-associated lymphoid tissue (MALT),  and lymphatic vessels    Muscularis externa—smooth muscle layer with  inner circular layer and outer longitudinal layer    Serosa—outermost layer, also called visceral  peritoneum; is continuous with parietal  peritoneum lining the cavity; mesentery is  the name of the structure formed by a double  layer of peritoneum    Intrinsic nerve plexuses of the alimentary  canal (submucosal nerve plexus and myen-  teric nerve plexus) help regulate mobility  and secretory activity of GI tract organs  Stomach—located on the left side of the  abdominal cavity; regions include cardia, fun-  dus, body, and pylorus   ° The curves of the body are the greater curva-  ture (convex lateral surface) and lesser cur-  vature (concave medial surface)    ° Food leaves the stomach via the pyloric valve  (pyloric sphincter)    o When the stomach is empty, the mucosa has  folds called rugae    ° The stomach is anchored to the liver at the  lesser curvature via the lesser omentum  (a specific mesentery) and is covered anteri-  orly by the greater omentum (another mes-  entery) that drapes to cover abdominal organs  before connecting to the posterior abdominal  wall   of vitamin B43  = Chief cells—make pepsinogen (inactive  form of protein-digesting enzyme pepsin)  = Parietal cells—produce hydrochloric acid  = Mucous neck cells—produce thin acidic  mucus  = Enteroendocrine cells—make local hor-  mones such as gastrin to regulate activities  in the stomach    Small intestine— major digestive organ of the  body; has three sections: duodenum, jejunum,  and ileum; joins the large intestine at the ileo-  cecal valve    o Pancreatic enzymes that digest all major  nutrient groups enter the duodenum at the  pancreatic duct    o Surface area is very high because of the  presence of villi (fingerlike projections of  mucosa), microvilli (tiny projections of  mucosa on villi; also called brush border),  and circular folds, also called plicae circula-  res (deep folds of mucosa and submucosa)  = Each villus has a lacteal, a modified    ° The small intestine is protected by Peyer’s  patches, local collections of lymphatic tissues,  which increase in number toward the end of  the small intestine   = Ascending colon—travels superiorly up  right side of abdominal cavity; turns at right  colic flexure   = Transverse colon—travels laterally across the  abdominal cavity; turns at left colic flexure   = Once in the pelvis, S-shaped sigmoid co-  lon leads into the rectum and anal canal;  the anus leads out of the body    e The anal canal has two valves: external  anal sphincter (voluntary) and internal  anal sphincter (involuntary)   = Longitudinal muscles in the wall of the  large intestine consist of only three bands,  called teniae coli; normal tone causes small  sacs called haustra to form    o Two sets of teeth include deciduous teeth  (baby teeth or milk teeth) and permanent  teeth  = A full set of teeth includes 32 teeth, includ-  ing wisdom teeth   = Teeth are classified by shape and function:  incisors cut, canines tear or pierce, premo-  lars and molars grind and crush    ° Tooth anatomy:  = Crown—exposed part of the tooth cov-  ered with enamel; underneath enamel is  dentin, a bonelike material that forms the  bulk of the tooth    e Inside the dentin is the pulp cavity  containing pulp (connective tissue, blood  vessels, nerves)    e The root canal carries blood vessels and  nerves to pulp cavity  = Gingiva (gum)  = Root—part of tooth embedded in the man-  dible; outer surface is covered by cement    e Cement attaches the tooth to the  periodontal ligament, which holds the  tooth in the mandible    = All produce saliva—a mixture of mucus,  serous fluid, salivary amylase (which be-  gins carbohydrate digestion), lysozyme, and  antibodies (IgA)    e Liver and gallbladder—the liver is the largest  gland in the body; has four lobes; is suspended  from the diaphragm via the falciform ligament,  which is a cord of mesentery    ° Produces bile, which leaves the liver via the  common hepatic duct  = Bile contains a number of different sub-  stances, but only bile salts and phospholip-  ids help to emulsify fats    ° The gallbladder stores bile when it backs up  the cystic duct upon being denied entry to  the duodenum; while there, water is removed  from bile, and if too much is removed,  gallstones can occur  = If bile leaks into the blood, tissues can be-   come jaundiced, or yellow; jaundice can also  occur as a result of hepatitis (liver inflam-  mation) or cirrhosis (chronic inflammation  that causes severe liver damage and fibrosis)    e Digestion and absorption are the main func-  tions of the digestive tract; six main processes  make this possible    ° Propulsion—movement of foods through the  GI tract; accomplished by the process of peri-  stalsis, which is wavelike movement of longi-  tudinal muscles to propel food forward    o Mechanical breakdown—the physical grind-  ing of foods into smaller pieces as they are  mixed with digestive juices; the main effect is  to increase surface area; also involves the pro-  cess of segmentation, which involves alter-  nating contraction and relaxation of circular  muscles along the GI tract; segmentation  mixes food continually, particularly in the  small intestine   = Carbohydrate monomers are monosac-  charides, such as glucose, fructose, and  galactose    o Absorption—the transporting of digested  products into the blood or lymph; this often  involves active transport methods; most  absorption occurs in the small intestine   e Food is mechanically broken down as it is  chewed while the tongue mixes it with saliva; no  food absorption occurs in the mouth; carbohy-  drate digestion begins with salivary amylase    e The pharynx and esophagus have no digestive  function; they are routes to move food from the  mouth to the stomach    e Deglutition, also called swallowing, is a com-  plex coordinated effort involving the tongue,  soft palate, pharynx, and esophagus; it has two  phases:    ° Buccal phase—voluntary; occurs in the  mouth when the tongue forces the food bolus  toward the pharynx    ° Pharyngeal-esophageal phase—involun-  tary; transports food through the pharynx and  esophagus; controlled by the vagus nerves    o Gastrin release is stimulated by presence of  food and rising pH (decreasing acidity); gas-  trin in turn stimulates pepsinogen, mucus,  and hydrochloric acid production  = If the cardioesophageal sphincter fails to   close tightly, acidic gastric juice can back  up, resulting in heartburn; this can lead to  esophagitis if untreated   ° Pepsinogen is activated to pepsin in the pres-  ence of hydrochloric acid; rennin digests milk  proteins (curdles milk) in infants    contracting; once chyme is produced, it is  passed through the pyloric sphincter in very  small amounts; this turns on enterogastric  reflex, which slows gastric activity    e Chyme continues chemical digestion in the small  intestine through action of the brush border  enzymes (embedded in the walls of microvilli)  and pancreatic juice (which contains enzymes  to digest all four major molecule groups)    o Fat digestion has barely begun despite the  presence of both lingual and gastric lipases,  which play only minor roles; most lipid diges-  tion will require pancreatic enzymes  = Pancreatitis is inflammation of the   pancreas and can be very serious since the  pancreas produces many digestive enzymes;  during this inflammatory response, the en-  zymes become activated and begin digesting  the body's own tissues    e The vagus nerve and local hormones stimulate  the release of pancreatic juice into the duode-  num; chyme entry stimulates the release of:    ° Secretin—stimulates the liver to produce  more bile and stimulates the pancreas to  release bicarbonate-rich pancreatic juice    ° Cholecystokinin (CCK)—signals the gall-  bladder to contract, releasing bile from stor-  age, and stimulates the pancreas to release  enzyme-rich pancreatic juice  = Bile is not an enzyme; it emulsifies fats   (increases surface area by breaking fats  into tiny droplets) and is necessary for fat-  soluble vitamin absorption    e Absorption occurs by a mixture of diffusion and  active transport via blood, through the hepatic  portal vein, or via lymphatics    e Materials remaining in the small intestine as it  nears the ileocecal valve enter the large intestine  and include water, fiber (indigestibles), and  many bacteria    e The colon produces no digestive enzymes and  absorbs mainly water, ions, and vitamins; the  semisolid product (feces) is delivered to the rec-  tum for elimination from the body    e Resident microflora (bacteria) metabolize some  remaining foodstuffs and release gases; some  also produce vitamin K and some B vitamins    e Haustral contractions are the most common  movements in the colon; they are slow segment-  ing movements    e Mass movements are long, slow, powerful  wavelike contractions that move over large areas  of the colon several times per day, forcing con-  tents toward the rectum    o Fiber increases the bulk of feces, which results  in stronger colon contractions and more effi-  cient elimination of waste    e Diverticula are areas where the mucosa pro-  trudes through the colon wall; this condition,  often caused by insufficient fiber consumption,  is called diverticulosis, and when diverticula  become inflamed, it is called diverticulitis    e When contents reach and stretch the walls of the  rectum, the defecation reflex is initiated    o Watery stools are diarrhea, whereas hard  stools result in constipation    e The microbiota, or normal flora, includes all  microbes (bacteria, fungi, viruses, parasites) that  live on or inside the human body and outnum-  bers human cells 10 to 1; the health and diver-  sity of the microbiota influence immunity, how  our bodies use energy, food cravings, mood, and  allergy and autoimmune disease    e Studies continue to investigate the many roles  played by the microbiome, which is how the  microbiota, the human body, and the environ-  ment interact to influence health and disease    e When the microbiota are damaged by antibiot-  ics, C. difficile can colonize the gut and cause  diarrhea, colitis, perforation of the bowel, and  sepsis; many strains of C. diff are resistant to  antibiotics, and they all produce endospores,  which make the infection difficult to treat    ° The most promising treatment, with a cure  rate of over 90 percent, is a fecal microbiota  transplant (FMT)    e Most food is used as metabolic fuel; the energy  value of food is measured in kilocalories  (kcal), also called Calories    e A nutrient is a substance used by the body to  promote normal growth, maintenance, or repair    o Water is also an important nutrient (previ-  ously covered in Chapter 2)    e MyPlate is a food guide issued by the USDA  showing food categories and healthy portion  sizes    e Dietary advice principles remain the same: eat  less, exercise, eat a balanced diet, avoid junk  food    e Most carbohydrates (sugars and starches) come  from plants; exceptions include milk sugar and  small amounts of glycogen in meats    e Lipids in the diet are usually triglycerides, or  neutral fats; saturated fats come from animal  products, and unsaturated fats come from plants    e Proteins come from eggs, meats, fish, meat  products, and combinations of grains and vege-  tables (such as legumes) that provide all eight  essential amino acids    e Vitamins are organic nutrients found in foods;  not all vitamins are found in the same food, so  the body needs a balanced diet    e Minerals are inorganic nutrients required by the  body and include calcium, phosphorus, potas-  sium, sulfur, sodium, chloride, and magnesium;  mainly found in vegetables, legumes, dairy  products, and meat products    e Metabolism is a term that includes all chemical  reactions in the body    e Glucose, or blood sugar, is the major fuel for  making ATP in most body cells (except the liver,  where fats are used)    o Glucose is “squeezed” in a series of reactions  to release energy that will be used to make  ATP; any carbon released leaves as carbon  dioxide; hydrogens released will eventually  help form water when combined with oxygen    ° The reactions that use oxygen to ultimately  generate ATP are referred to as cellular  respiration and involve:  = Glycolysis—the process of breaking glucose  down to pyruvate (two molecules per glu-  cose molecule); a small amount of ATP is  also produced   = The citric acid cycle—processes pyruvate,  transferring hydrogens and their electrons to  electron carriers, which will proceed to the  electron transport chain; a small amount  of ATP is made by the process of substrate-  level phosphorylation; carbon is released as  carbon dioxide   = The electron transport chain—transfers  the electrons (split from the hydrogen  ions) carried from the citric acid cycle  down a gradient of carrier proteins to har-  ness energy to make many ATP; the hydro-  gen ions and electrons unite with oxygen  to form water    energy in the body; they are used to make or  repair cell membranes, myelin sheaths, and fatty  cushions around some organs    ° When glucose is lacking and fats are used for  ATP synthesis, by-products such as acetone  can build up in the blood and lower the pH,  a condition called acidosis or ketoacidosis    structural proteins; they are used to make ATP  only when in excess or when sugars and fats are  not available, such as during starvation    drugs and alcohol, degrades hormones, and pro-  duces essential products such as clotting pro-  teins and albumin; liver cells make nonessential  amino acids and detoxify ammonia by combin-  ing it with carbon dioxide into urea, which is  filtered out in urine    liver first via the hepatic portal circulation; liver  cells take what they need and remove harmful  bacteria before nutrients enter general  circulation    meostasis by storing glycogen, produced from  many glucose molecules during glycogenesis;  by releasing glucose from glycogen through the    process of glycogenolysis; or by making  additional glucose as needed through  gluconeogenesis    e Cholesterol is never used to make ATP; it is  used to make cell membranes, vitamin D, and  steroid hormones  ° Low-density lipoproteins (LDLs) carry   cholesterol to body cells  ° High-density lipoproteins (HDLs) carry  cholesterol to the liver from body cells    e Energy intake is the energy released during  food oxidation and equals total energy output  (work, heat, and energy storage)    e When energy intake and output are equal,  weight is stable    ° Feeding behavior is believed to be regulated  by a complex mixture of neural signals from  the GI tract, hormones, blood signals regard-  ing body energy stores, signals from gut  microbiota, and psychological factors    e Basal metabolic rate (BMR) is the amount of  energy the body uses at rest to carry out essential  life activities    ° BMR is influenced by age, gender, and body  surface area, but the primary influencer is the  level of thyroxine, the major metabolic hor-  mone produced by the thyroid gland  = Hyperthyroidism causes excessive metabo-   lism, causing the body to weaken because  it produces too much energy; hypothy-  roidism causes very slow metabolism and  weight gain    60 percent of food energy released is given off as  heat; 40 percent is available to make ATP or  build body molecules; the hypothalamus regu-  lates the body’s temperature    ° If body temperature falls below normal,  vasoconstriction diverts blood to core struc-  tures, and shivering helps generate heat by  muscle action  = Low body temperature for an extended   period of time can lead to ice crystal forma-  tion in the extremities, a condition called  frostbite    = Low body temperature resulting from  prolonged exposure to cold is hypother-  mia; all vital signs decrease; can lead to  death    o Heat is lost from the body via radiation and  evaporation; when normal heat loss pro-  cesses cannot keep up, hyperthermia slows  activity of the hypothalamus, leading to a pos-  itive feedback cycle of increasing body temper-  ature and increasing metabolic activity, which  increases body temperature further  = The point at which heat loss mechanisms  have stopped working is heat stroke   = Heat exhaustion is heat-associated collapse  during or after physical activity and results  from dehydration, but heat loss mecha-  nisms are still functional    Fever is controlled hyperthermia and can aid  body defenses and speed healing processes  because it increases metabolism    PART III: DEVELOPMENTAL ASPECTS OF THE  DIGESTIVE SYSTEM AND METABOLISM  (pp. 521-524)    By the fifth week of development, the cavity of  the alimentary canal has formed    The most common genetic defect of the diges-  tive system that interferes with feeding is cleft  palate/cleft lip defect    Another common defect is tracheoesophageal  fistula, an abnormal connection between the  trachea and esophagus    Genetic issues that interfere with metabolism  include phenylketonuria (PKU), in which  cells are unable to use the amino acid phenylal-  anine, and cystic fibrosis (CF), which involves  excessive mucus production that impairs pan-  creas activity and blocks the pancreatic duct,  preventing enzyme delivery to the duodenum    The rooting and sucking reflexes help the in-  fant eat; teething begins around 6 months of  age; appetite increases dramatically during  adolescence    Gastroenteritis, inflammation of the GI tract,  may be due to contaminated or spicy foods;  appendicitis, inflammation of the appendix, is  usually due to obstruction   Metabolic rate decreases after middle age; gall-  bladder problems and irritable bowel syndrome  may occur at this time of life    e Activity of the GI tract declines in old age: fewer e Cancers of the stomach and colon rarely show  digestive juices are produced, smell and taste early signs, but a colonoscopy can detect  decline, periodontal disease develops polyps, which often develop into cancers    Multiple Choice  More than one choice may apply.  1. Which of the following digestive organs are accessory  organs?  a. Esophagus  b. Stomach  c. Pancreas    2. Ducts that are part of the digestive system include the  a. bile duct.  b. pancreatic duct.  c. thoracic duct.  d. ejaculatory duct.  e. cystic duct.   3. The GI tube tissue layer responsible for the actions of  segmentation and peristalsis is the    b. mucosa.  c. muscularis externa. 5. Where in the stomach do the strongest peristaltic    4. Match the letter of the digestive organ shown in the  figure with its function.    6. Which of these organs lie in the left hypochondriac  region of the abdomen?    a. Spleen  b. Stomach  c. Cecum  d. Duodenum  7. Which of the following is (are) true about cholecys-  tokinin?  a. Produced in the duodenum  b. Increases bile output by the liver  c. Stimulates the gallbladder to expel stored bile  d. Stimulates insulin release  8. The pH of chyme entering the duodenum is adjusted by  a. bile.  b. intestinal juice.  c. enzyme secretions from the pancreas.  d. bicarbonate-rich secretions from the pancreas.  9. A 3-year-old girl is rewarded with a hug because she is    now completely toilet trained. Which muscle is one  that she has learned to control?   a. External anal sphincter  10. Hormones that act to decrease the blood glucose level   a. Use of amino acids as a major source of energy   b. Lipogenesis (and fat deposit)  c. Breakdown of fat reserves  d.    Increased uptake of glucose by skeletal muscles  and other body tissues    12. The material that forms the bulk of a tooth is    14. Name the layers of the alimentary tube wall from the  lumen outward.    15. What is the greater omentum? The lesser omentum?  16. Bile emulsifies fat. Define emulsify.  17. How do the enterogastric and defecation reflexes differ?    18. A cream cheese and jelly sandwich contains proteins,  carbohydrates, and fats. Describe what happens to the  sandwich when you eat it relative to events occurring  in ingestion, digestion, ab-sorption, and defecation.    19. Which structures greatly increase the absorptive sur-  face of the small intestine?    21. What is the harmful result when excessive amounts of  fats are burned to produce ATP? Name two conditions  that might lead to this result.    A young woman is put through an extensive battery of  tests to determine the cause of her stomach pains. She  is diagnosed with gastric ulcers. An antihistamine  drug is prescribed, and she is sent home. What is the  mechanism of her medication? What life-threatening  problems can result from a poorly managed ulcer?  Why did the clinic doctor warn the woman not to take  aspirin?    Ryan, a 6-year-old child who is allergic to milk, has  extremely bowed legs. What condition do you sus-  pect, and what is the connection to not drinking  milk?    John’s skin is tinted yellow and so are the whites of  his eyes. What can be the cause of his jaundice? John  admits to a history of excess drinking.    Charlie has been vomiting ever since he ate last  night's fast food for breakfast. What could be a possi-  ble cause of his emesis?    Kayla has been on antibiotics for an extended period.  A visit to her physician reveals that she has a vitamin  K deficiency. What is the cause-and-effect relationship  here?    The urinary system  filters nitrogenous wastes  from the blood and helps    The kidneys are directly  involved in maintaining proper  blood pressure, which is essential for  delivering oxygen and nutrients to  tissues and for proper filtration of  blood by the kidneys  themselves.   of homeostatic organs. Like sanitation workers  who keep a city’s water supply drinkable and dispose  of its waste, the kidneys are usually unappreciated until  there is a malfunction and “internal garbage” piles up.  Every day, the kidneys filter gallons of fluid from the  bloodstream. They then process this filtrate, allowing  wastes and excess ions to leave the body in urine while  returning needed substances to the blood in just the  right proportions. Although the lungs and the skin also  play roles in excretion, the kidneys bear the major  responsibility for eliminating nitrogenous (nitrogen-  containing) wastes, toxins, and drugs from the body.    The kidneys filter  blood in nephrons and  secrete or reabsorb electrolytes  under the direction of  hormones.    Disposing of wastes and excess ions is only part  of the kidneys’ work. As they perform these excretory  functions, the kidneys also regulate blood volume  and maintain the proper balance between water and  salts, and between acids and bases.   e The hormone erythropoietin, released by the kid-  neys, stimulates red blood cell production in  bone marrow (see Chapter 10).    e Kidney cells convert vitamin D produced in the  skin to its active form.    Figure 15.1 Organs of the urinary system. (a) Anterior  view of urinary organs of a female.(b) Posterior in situ  view of a male showing the relationship of the kidneys  to the 12th rib pair.    The kidneys alone perform the functions just  described and manufacture urine in the process. The  other organs of the urinary system—the paired ureters  and the single urinary bladder and urethra  (Figure 15.1a)—provide temporary storage for urine or  serve as transportation channels to carry it from the  kidneys to the outside of the body.    15.1a Location and Structure  Learning Objectives  1# Describe the location of the kidneys in the body.    1# \dentify the following regions of a kidney (longitu-  dinal section): hilum, cortex, medulla, medullary  pyramids, calyces, pelvis, and renal columns.   Although many people believe the kidneys are  located in the lower back, this is not the case. These  small, dark red organs with a kidney-bean shape lie  against the dorsal body wall in a retroperitoneal posi-  tion (behind the parietal peritoneum) in the superior  lumbar region (Figure 15.1b). The kidneys extend  from the T,, to the L, vertebra; thus they receive  some protection from the lower part of the rib cage.  Because it is crowded by the liver, the right kidney is  slightly lower than the left.    An adult kidney is about 12 cm (5 inches) long, 6 cm  (2.5 inches) wide, and 3 cm (1 inch) thick, or about  the size of a large bar of soap. It is convex laterally  and has a medial indentation called the renal hilum.  Several structures, including the ureters, the renal  blood vessels, and nerves, enter or exit the kidney  at the hilum (Figure 15.2, p. 536). Sitting atop each  kidney is an adrenal gland, which is part of the endo-  crine system and is a separate organ.   The kidney has three protective layers. Deep to  superficial, they are as follows:    e A transparent fibrous capsule encloses each kid-  ney and gives it a glistening appearance.    e A fatty mass, the perirenal fat capsule, surrounds  each kidney and cushions it against blows.    e The renal fascia, the most superficial layer made of  dense fibrous connective tissue, anchors the kid-  ney and adrenal gland to surrounding structures.    The fat surrounding the kidneys is important in  holding them in their normal body position. If the  amount of fatty tissue dwindles (as with rapid weight  loss), the kidneys may drop to a lower position, a  condition called ptosis (to’sis; “a fall”). Ptosis creates  problems if the ureters, which drain urine from the  kidneys, become kinked. When this happens, urine  that can no longer pass through the ureters backs up  and exerts pressure on the kidney tissue. This condi-  tion, called hydronephrosis (hi"dro-né-fro’sis), can  severely damage the kidney.    When a kidney is cut lengthwise, three distinct  regions become apparent (see Figure 15.2). The  outer region, which is light in color, is the renal  cortex (cortex = bark). Deep to the cortex is a darker  reddish brown area, the renal medulla. The  medulla has triangular regions with a striped  appearance, the renal pyramids, or medullary  (med’u-lar’e), pyramids. The broad base of each  pyramid faces toward the cortex; its tip, the apex,  points toward the inner region of the kidney. The  pyramids are separated by extensions of cortexlike  tissue, called renal columns.   Lateral to the hilum is a flat, funnel-shaped tube,  the renal pelvis. The pelvis is continuous with the  ureter leaving the hilum (see Figure 15.2b).  Extensions of the pelvis, calyces (kal’i-séz; singular  calyx), form cup-shaped “drains” that enclose the    tips of the pyramids. The calyces collect urine, which  continuously drains from the tips of the pyramids  into the renal pelvis. Urine then flows from the pel-  vis into the ureter, which transports it to the bladder  for temporary storage until it leaves the body.    The kidneys continuously cleanse the blood and  adjust its composition, so it is not surprising that they  have a rich blood supply (see Figure 15.2b and c).  Approximately one-quarter of the total blood supply  of the body passes through the kidneys each minute.  The artery supplying each kidney is the renal artery.  As the renal artery approaches the hilum, it divides  into segmental arteries, each of which gives off  several branches called interlobar arteries, which  travel through the renal columns to reach the cortex.  At the cortex-medulla junction, interlobar arteries  give off the arcuate (ar’ku-at) arteries, which arch  over the medullary pyramids. Small cortical radiate  arteries then branch off the arcuate arteries to sup-  ply the renal cortex. Venous blood draining from  the kidney flows through veins that trace the path-  way of the arterial supply but in a reverse direction—  cortical radiate veins to arcuate veins to interlobar  veins to the renal vein, which emerges from the  kidney hilum and empties into the inferior vena cava.  (There are no segmental veins. )    1. The kidneys are retroperitoneal. What does that mean?  2. Mary lost lots of weight, and suddenly she was  having problems with her urine flow. What would  you guess happened, and what caused the problem?  3. From the most superficial aspect of a kidney to its  ureter, name its three major regions.  For answers, see Appendix A.    w@ Recognize that the nephron is the structural and  functional unit of the kidney, and describe its  anatomy.    Nephrons (nef’ronz) are the structural and func-  tional units of the kidneys and are responsible for  forming urine. Each kidney contains over a million  of these tiny filters. In addition, there are thousands  of collecting ducts, each of which collects fluid from  several nephrons and conveys it to the renal pelvis.  Figure 15.3 p. 537, shows the anatomy and relative    Major calyx Segmental  arteries  Renal vein  Renal artery  Kma calyx Renal pelvis  Major calyx  Renal 3 \ \ Ureter  pyramid    Figure 15.2 Internal anatomy of the kidney. (a) Photograph of a coronally sectioned  kidney. (b) Diagram of coronal kidney section illustrating major blood vessels. (c) Summary  of the pathway of renal blood vessels.    Figure 15.3 Structure of the nephron. (a) Wedge-  shaped section of kidney tissue indicating the position  of nephrons in the kidney. (b) Detailed anatomy of a  nephron and its associated blood supply. Part of the  distal convoluted tubule and afferent arteriole have  been sectioned to reveal the location of the juxtaglo-  merular apparatus. (c) Diagrammatic view of the  relationship of the visceral layer of the glomerular  capsule to the glomerular capillaries. (d) Scanning  electron micrograph of podocytes clinging to the  glomerular capillaries.   Each nephron consists of two main structures:  a renal corpuscle and a renal tubule. Each renal  corpuscle consists of a glomerulus (glo-mer’u-lus),  which is a knot of capillaries (glom = little ball),  and a cup-shaped hollow structure that completely  surrounds the glomerulus like a well-worn base-  ball glove encloses a ball. This portion of the renal  corpuscle is called the glomerular capsule or  Bowman’s capsule. The inner (visceral) layer of  the capsule is made up of highly modified  octopus-like cells called podocytes (pod’o-sitz;  Figure 15.3c and d). Podocytes have long branch-  ing extensions called foot processes that intertwine  with one another and cling to the glomerulus.  Openings called filtration slits between these pro-  cesses allow the podocytes to form a porous, or  “leaky,” membrane around the glomerulus ideal  for filtration.   The renal tubule, which makes up the rest of  the nephron, is about 3 cm (approximately 1.25  inches) long. As it extends from the glomerular cap-  sule, it coils and twists before forming a hairpin  loop and then again becomes coiled and twisted  before entering a collecting duct. These different  regions of the tubule have specific names (see Figure  15.3a and b); in order from the glomerular capsule,  they are the proximal convoluted tubule (PCT);  the nephron loop, or loop of Henle (hen'le); and the  distal convoluted tubule (DCT). The surfaces of  the tubule cells exposed to the filtrate in the proxi-  mal convoluted tubules are covered with dense  microvilli, which increase their surface area tremen-  dously. Microvilli also occur on the tubule cells in  other parts of the tubule, but in much reduced  numbers.   Most nephrons are called cortical nephrons  because they are located almost entirely within the  cortex. In a few cases, the nephrons are called  juxtamedullary nephrons because they are situ-  ated close to the cortex-medulla junction, and  their nephron loops dip deep into the medulla  (see Figure 15.3a). The collecting ducts, each of  which receives urine from many nephrons, run  downward through the medullary pyramids, giv-  ing the pyramids a striped appearance. They  deliver the final urine product into the calyces and  renal pelvis.    Each and every nephron is associated with two  capillary beds—the glomerulus (mentioned earlier)  and the peritubular (per’ i-tu’bu-lar) capillary bed (see  Figure 15.3b). The glomerulus is fed by the afferent  arteriole, which arises from a cortical radiate artery.  The efferent arteriole receives the blood as it leaves  the glomerulus. The glomerulus, specialized for fil-  tration, differs from any other capillary bed in the  entire body because it is both fed and drained by  arterioles. Also, the afferent arteriole has a larger  diameter than the efferent, resulting in a much  higher blood pressure in the glomerular capillaries  compared to other capillary beds. This high pressure  forces fluid and small solutes out of the blood into  the glomerular capsule. Most of this filtrate (99 per-  cent) is eventually reclaimed by the renal tubule cells  and returned to the blood in the peritubular capil-  lary beds.   The second capillary bed, the peritubular capil-  laries, arises from the efferent arteriole that drains the  glomerulus. Unlike the high-pressure glomerulus,  these capillaries are low-pressure, porous vessels  adapted for absorption instead of filtration. They cling  closely to the whole length of the renal tubule, where  they are in an ideal position to receive solutes and  water from the tubule cells as these substances are  reabsorbed from the filtrate percolating through the  tubule. The peritubular capillaries drain into the  cortical radiate veins, arcuate veins, and ultimately  into the interlobar veins leaving the cortex.    v Describe the process of urine formation, identify-  ing the areas of the nephron that are responsible  for filtration, reabsorption, and secretion.    v Describe the function of the kidneys in excretion  of nitrogen-containing wastes.    Urine formation is a result of three processes—  glomerular filtration, tubular reabsorption, and tubular  secretion (Figure 15.4).    As just described, the glomerulus acts as a filter.  Glomerular filtration is a nonselective, passive pro-  cess in which fluid passes from the blood into the  glomerular capsule part of the renal tubule.    pressure gradient (Chapter 3, p. 98). The capillaries of  the glomerulus are under higher pressure compared to  the glomerular capsule; as a result, fluids move down  the pressure gradient, from the blood into the glomer-  ular capsule.    Once in the capsule, the fluid is called filtrate; it  is essentially blood plasma without blood proteins.  Both proteins and blood cells are normally too large  to pass through the filtration membrane, and when  either of these appears in the urine, there is usually a  problem with the glomerular filters. As long as the  systemic blood pressure is normal, filtrate will be  formed. If arterial blood pressure drops too low, glo-  merular pressure becomes inadequate to force sub-  stances out of the blood into the tubules, and filtrate  formation stops.    An abnormally low urinary output is called oliguria  (ol’i-gu're-ah) if it is between 100 and 400 ml/day,  and anuria (ah-nu’re-ah) if it is less than 100 ml/  day. Low urinary output usually indicates that glo-  merular blood pressure is too low to cause filtration,  but anuria may also result from transfusion reactions  and acute inflammation or from crushing injuries to  the kidneys.    Besides wastes and excess ions that must be removed  from the blood, the filtrate contains many useful  substances (including water, glucose, amino acids,  and ions), which must be reclaimed from the filtrate  and returned to the blood. Tubular reabsorption  begins as soon as the filtrate enters the proximal con-  voluted tubule (Figure 15.5, p. 540). The tubule cells  are “transporters,” taking up needed substances from  the filtrate and then passing them out their posterior  aspect into the extracellular space, from which they    How would liver disease, in which the liver is unable  to make many of the blood proteins, affect process 1?  (Reviewing Chapter 10 might help.)    @ => Glomerular filtration: Water and solutes  smaller than proteins are forced through the  capillary walls and pores of the glomerular  capsule into the renal tubule.    © => Tubular reabsorption: Water, glucose,  amino acids, and needed ions are  transported out of the filtrate into the tubule  cells and then enter the capillary blood.    © => Tubular secretion: H+, K+, creatinine, and  drugs are removed from the peritubular blood  and secreted by the tubule cells into the  filtrate.    millions of nephrons acting in parallel. Three processes  in the kidneys adjust the composition of plasma.    Figure 15.5 Sites of filtration, reabsorption, and secretion in a nephron.    are absorbed into peritubular capillary blood. Some  reabsorption is done passively (for example, water  passes by osmosis), but reabsorption of most sub-  stances depends on active transport processes, which  use membrane carriers, require ATP, and are very  selective. There is an abundance of carriers for sub-  stances that need to be retained, and few or no car-  riers for substances of no use to the body. Needed  substances (for example, glucose and amino acids)  are usually entirely removed from the filtrate. Most  reabsorption occurs in the proximal convoluted  tubules, but the distal convoluted tubule and the  collecting duct are also active.    Tubular secretion is essentially tubular reabsorp-  tion in reverse. Some substances, such as hydrogen  and potassium ions (H* and K*) and creatinine,  also move from the blood of the peritubular    capillaries through the tubule cells or from the  tubule cells themselves into the filtrate to be elimi-  nated in urine. This process seems to be important  for getting rid of substances not already in the fil-  trate, such as certain drugs or excess potassium ions,  or as an additional means for controlling blood pH  (see Figure 15.5).    “concert LINK  Recall that pH is a measure of free hydrogen ion (H+)    concentration (see Chapter 2, p. 62). When the body  has a high level of free hydrogen ions, which can lower  pH, the kidneys help by eliminating excess hydrogen  ions from the body via the urine.    Nitrogenous waste products are poorly reab-  sorbed, if at all. Tubule cells have few membrane    carriers to reabsorb these substances because we  do not need them. They tend to remain in the fil-  trate and are found in high concentrations in urine  excreted from the body. Various ions are reabsorbed  or allowed to go out in the urine, according to  what is needed at a particular time to maintain the  proper pH and electrolyte (solute) composition of  the blood. Common nitrogenous wastes include  the following:    e Urea (u-re’ah), formed by the liver as an end  product of protein breakdown when amino  acids are used to produce energy    e Creatinine (kre-at’i-nin), associated with cre-  atine (kre’ah-ten) metabolism in muscle tissue   4. What is the structural and functional unit of the  kidney?   5. What are two functions of the renal tubule and one  function of the peritubular capillaries?   6. How does a decrease in blood pressure affect  glomerular pressure?    In 24 hours, the marvelously complex kidneys fil-  ter some 150 to 180 liters of blood plasma through  their glomeruli into the tubules, which process the  filtrate by taking substances out of it (reabsorption)  and adding substances to it (secretion). In the same  24 hours, only about 1.0 to 1.8 liters of urine are  produced. Therefore, urine and filtrate are quite dif-  ferent. Filtrate contains everything that blood plasma  does (except proteins), but by the time it reaches the  collecting ducts, the filtrate has lost most of its water  and just about all of its nutrients and necessary ions.  What remains, urine, contains nitrogenous wastes  and unneeded or excess substances. Assuming we  are healthy, our kidneys can keep our blood compo-  sition fairly constant despite wide variations in diet  and cell activity.   Freshly voided urine is generally clear and pale  to deep yellow. The normal yellow color is due to  urochrome (u'ro-krom), a pigment that results from    the body's destruction of hemoglobin. The more  solutes are in the urine, the deeper yellow its color.  Dilute urine is a pale, straw color. At times, urine  may be a color other than yellow. This might be a  result of eating certain foods (beets, for example)  or the presence of bile or blood in the urine.   When formed, urine is sterile, and its odor is  slightly aromatic. If it is allowed to stand, it takes on  an ammonia odor caused by the action of bacteria  on the urine solutes. Some drugs, vegetables (such as  asparagus), and various diseases (such as diabetes  mellitus) alter the usual odor of urine.   Urine pH is usually slightly acidic (around 6),  but changes in body metabolism and certain foods  may cause it to be much more acidic or basic. For  example, a diet with large amounts of protein  (eggs and cheese) and whole-wheat products  causes urine to become quite acidic. Conversely, a  vegetarian diet makes urine quite alkaline as the  kidneys excrete excess bases. Bacterial infection of  the urinary tract also may cause the urine to be  alkaline.   Because urine is water plus solutes, urine is  denser (weighs more) than distilled water. Specific  gravity compares how much heavier urine is than dis-  tilled water. Whereas the specific gravity of pure water  is 1.0, the specific gravity of urine usually ranges  from 1.001 to 1.035 (dilute to concentrated urine,  respectively). Urine is generally dilute (has a low spe-  cific gravity) when a person drinks excessive fluids,  uses diuretics (drugs that increase urine output), or  has chronic renal failure, a condition in which the  kidney loses its ability to concentrate urine (see “A  Closer Look” on p. 545). Conditions that produce  concentrated urine with a high specific gravity include  inadequate fluid intake, fever, and kidney inflamma-  tion called pyelonephritis (pi"é-lo-né-fri’ tis).   Solutes normally found in urine include sodium  ions (Na*) and potassium ions (K*), urea, uric acid,  creatinine, ammonia, bicarbonate ions, and various  other ions, depending on blood composition. With  certain diseases, urine composition can change dra-  matically, and the presence of abnormal substances  in urine is often helpful in diagnosing the problem.  This is why a routine urinalysis should always be  part of a physical examination.   Substances not normally found in urine are glu-  cose, blood proteins, red blood cells, hemoglobin,  white blood cells (pus), and bile. Table 15.1, p. 542  lists conditions that may involve abnormal urinary  constituents and volumes.    Did You Get It?  7. Is the specific gravity of urine higher or lower than  that of water? Why?  For the answer, see Appendix A.   v Describe the general structure and function of the  ureters, urinary bladder, and urethra.   x“ Compare the course and length of the male  urethra to that of the female.    vy Describe the difference in control of the external  and internal urethral sphincters.    The ureters (yer’é-terz) are two slender tubes each  25 to 30 cm (10 to 12 inches) long and 6 mm  (‘4 inch) in diameter. Each ureter runs behind the  peritoneum from the renal hilum to the posterior  aspect of the bladder, which it enters at a slight angle  (Figure 15.6). The superior end of each ureter is con-  tinuous with the renal pelvis, and its mucosal lining  is continuous with the mucosa lining the renal pel-  vis and the bladder inferiorly.   The ureters carry urine from the kidneys to the  bladder. Although it might appear that gravity could    Bleeding in the urinary tract (due to trauma,  kidney stones, infection)    help drain urine to the bladder, it would not trans-  port urine while a person is lying down. Urine  reaches the bladder even when you're standing on  your head because the ureters do play an active role  in urine transport. Smooth muscle layers in their  walls contract to propel urine by peristalsis. Once  urine has entered the bladder, it is prevented from  flowing back into the ureters by small valvelike folds  of bladder mucosa that cover the ureter openings.    Homeostatic J  £ Imbalance 15.3  When urine becomes extremely concentrated, sol-  utes such as uric acid salts form crystals that precipi-  tate in the renal pelvis. These crystals are called renal  calculi (kal’ku-li; calculus = little stone) or kidney  stones (see photo).   Excruciating pain that radiates to the flank (lat-  eral, posterior lower back) occurs when the ureter  walls close in on the sharp calculi as they are being  eased through the ureter by peristalsis or when the  calculi become wedged in a ureter. Frequent bacte-  rial infections of the urinary tract, urinary retention,  and alkaline urine all favor calculi formation.  Surgery is one treatment option, but a noninvasive  procedure (lithotripsy) that uses ultrasound waves to  shatter the calculi is also available. The pulverized  remnants of the calculi are then painlessly elimi-  nated in urine.    The urinary bladder is a smooth, collapsible, mus-  cular sac that stores urine temporarily. It is located  retroperitoneally in the pelvis just posterior to the  pubic symphysis. A scan of the interior of the blad-  der reveals three openings—the two ureter openings  (ureteral orifices), and the single opening of the ure-  thra (u-re'thrah) (the internal urethral orifice), which  drains the bladder (see Figure 15.6). The smooth  triangular region of the bladder base outlined by  these three openings is called the trigone (tri’gon).  The trigone is important clinically because infections  tend to persist in this region. In males, the prostate  (part of the male reproductive system) surrounds the  neck of the bladder where it empties into the urethra.   The bladder wall contains three layers of smooth  muscle, collectively called the detrusor muscle, and its  mucosa is a special type of epithelium, transitional  epithelium (see Chapter 3, p. 113). Both of these struc-  tural features make the bladder uniquely suited for its  function of urine storage. When the bladder is empty,  it is collapsed, 5 to 7.5 cm (2 to 3 inches) long at  most, and its walls are thick and thrown into folds.  A urogram of a 35-year-old man after an injection of 80 ml As urine accumulates, the bladder expands and rises  of iodized contrast medium. The contrast medium (in yellow) superiorly in the abdominal cavity (Figure 15.7,    Figure 15.6 Basic structure of the female urinary bladder and urethra.    Figure 15.7 Position and shape of a distended and  an empty urinary bladder in an adult male.    epithelial layer thins, increasing its volume and  allowing the bladder to store more urine without  substantially increasing its internal pressure. A mod-  erately full bladder is about 12.5 cm (5 inches) long  and holds about 500 ml (1 pint) of urine, but it is  capable of holding more than twice that amount.  When the bladder is really distended, or stretched by  urine, it becomes firm and pear-shaped and may be  felt just above the pubic symphysis. Urine is formed  continuously by the kidneys, but it is stored in the  bladder until its release is convenient.    The urethra is a thin-walled tube that carries urine  by peristalsis from the bladder to the outside of the  body. At the bladder-urethra junction, a thickening  of the smooth muscle forms the internal urethral  sphincter (see Figure 15.6), an involuntary sphinc-  ter (think “internal is involuntary”) that keeps the  urethra closed when urine is not being passed. A sec-  ond sphincter, the external urethral sphincter,  is formed by skeletal muscle as the urethra passes  through the pelvic floor. This sphincter is voluntarily  controlled.   The length and relative function of the urethra  differ in the two sexes. In men, the urethra is  approximately 20 cm (8 inches) long and has three  named regions (look ahead to Figure 16.2a, p. 564):  the prostatic, membranous, and spongy (or penile) ure-  thrae. The urethra opens at the tip of the penis after  traveling down its length. The urethra of the male  has a double function. It carries both urine and  sperm (in semen) from the body, but never at the    same time. Thus, in males, the urethra is part of  both the urinary and reproductive systems.   In women, the urethra is about 3 to 4 cm (1%  inches) long, and its external orifice, or opening, lies  anterior to the vaginal opening (look ahead to Figure  16.8a, p. 573). Its only function is to conduct urine  from the bladder to the body exterior.    The female urinary orifice is close to the anal open-  ing, so improper toileting habits (wiping from back  to front rather than from front to back) can carry fecal  bacteria into the urethra. And because the mucosa of  the urethra is continuous with that of the rest of the  urinary tract organs, inflammation of the urethra, or  urethritis (u’re-thri’tis), can easily ascend the tract  to cause bladder inflammation (cystitis) or even kid-  ney inflammation (pyelonephritis, or pyelitis).  Symptoms of urinary tract infection (UTI) include  dysuria (painful urination), urinary urgency and fre-  quency, fever, and sometimes cloudy or blood-tinged  urine. When the kidneys are involved, back pain and  a severe headache are common.   Micturition (mik’tu-rish’un), or voiding, is the act  of emptying the bladder. As noted, two sphincters, or  valves—the internal urethral sphincter (more supe-  riorly located) and the external urethral sphincter  (more inferiorly located)—control the flow of urine  from the bladder (see Figure 15.6). Ordinarily, the  bladder continues to collect urine until about 200 ml  have accumulated. At this point, stretching of the  bladder wall activates stretch receptors. Impulses  transmitted to the sacral region of the spinal cord  and then back to the bladder via the pelvic splanch-  nic nerves cause the bladder to go into reflex contrac-  tions. As the contractions become stronger, stored  urine is forced past the internal urethral sphincter  (the smooth muscle, involuntary sphincter) into the  upper part of the urethra. The person will then feel  the urge to void. Because the lower external sphinc-  ter is skeletal muscle and is controlled voluntarily, we  can choose to keep it closed and postpone bladder  emptying temporarily. However, if it is convenient,  the external sphincter can be relaxed so that urine is  flushed from the body. When a person chooses not  to void, the reflex contractions of the bladder stop    Learn more at Mastering A&P > Study Area >  $% Additional Study Tools > A Closer Look   Americans, or about 15 percent  of American adults over age 18, have  some degree of kidney dysfunction.  Ninety percent of adults with chronic  kidney disease—that is, kidneys that  cannot effectively clean the blood—are  unaware of their status. The main risk    factors for chronic kidney disease  (CKD) are diabetes and hypertension  (high blood pressure); CKD is more  common in people over 65 years of  age, is more common in women, and  is 3.5 times more common in African  Americans than in Caucasians. Patients  who advance to end-stage kidney dis-  ease (kidney failure) need dialysis or a  kidney transplant to survive. More than  half of these patients have diabetes or  hypertension. Other warning signs may  include frequent urination, painful uri-  nation, or swollen hands or feet. Uri-  nalysis can detect proteinuria, a  sensitive and early marker of kidney  damage, and a simple blood test can  determine the creatinine level, which   High blood pressure impairs kidney  function by damaging renal blood ves-  sels and reducing circulation to the  organs, even as hypertension-battered  kidneys push blood pressure upward.  In renal failure, filtrate formation  decreases significantly  or stops completely.  Because toxic wastes  accumulate quickly in  the blood, hemodialysis  uses an “artificial kid-  ney” apparatus called a  dialyzer (see photo) to  cleanse the blood. The  patient's blood is passed  through tubing that is  semipermeable (only  select substances can  diffuse through it), and  the tubing is immersed in a solution  called dialysate. The dialysate is a  lower-pressure fluid that allows sub-  stances to be exchanged with the  blood via diffusion: nitrogenous wastes  and potassium ions diffuse out of the  blood, and electrolytes such as sodium  ions and bicarbonate ions diffuse into  the blood. As the concentration of  wastes in the dialysate increases, the  dialysate is replaced so that wastes can  continue to diffuse out of the blood.   Dialysis is typically done three times  per week and takes from 3 to 5 hours  on average, though depending on  patient size and kidney function, it  could take up to 8 hours. The year  2020 saw a drastic increase in the    number of patients needing dialysis  as a result of COVID-19 infection.  Although it is not yet understood  how COVID-19 leads to renal failure,  early data suggest 14 to 40 percent  of COVID-19 patients develop kidney  failure and require dialysis as a life-  saving measure. Risks of hemodialy-  sis include infection, thrombosis,   and hemorrhage due to the blood  thinners required to prevent clotting  in the hemodialysis machine. When  renal damage is irreversible, as in  chronic renal failure, continued dialy-  sis and a kidney transplant are the  only options for treatment. If a trans-  plant is done, except in cases where  the donor is an identical twin, recipi-  ents must take immunosuppressive  drugs to prevent rejection of the  donated organ.    e The most important risk factors  for chronic kidney disease are  diabetes and hypertension.    e Chronic kidney disease is more  common in people over 65  years of age, in women, and in  African Americans.    e Tests for proteinuria and creati-  nine are simple to perform and  can help identify kidney disease  early.   e Dialysis can remove toxins  from blood in patients whose  kidneys no longer function  sufficiently.    within a minute or so, and urine collection contin-  ues. After 200 to 300 ml more have been collected,  the micturition reflex occurs again. Eventually, mictu-  rition occurs whether the person wills it or not.    Homeostatic J  K Imbalance 15.5  Incontinence (in-kon'ti-nens) occurs when a per-  son is unable to voluntarily control the external  sphincter. Incontinence is normal in children 2 years  old or younger because they have not yet gained con-  trol over their voluntary sphincter. It may also occur  in older children who sleep so soundly that they are  not awakened by the stimulus. However, after the  toddler years, incontinence is usually a result of emo-  tional problems, pressure (as in pregnancy), or ner-  vous system problems (stroke or spinal cord injury).  Urinary retention is essentially the opposite of  incontinence. In this condition, the bladder is  unable to expel its contained urine. There are various  causes for urinary retention. It often occurs after sur-  gery in which general anesthesia has been given,  because it takes a little time for the smooth muscles  to regain their activity. Another cause of urinary  retention, occurring primarily in older men, is  enlargement, or hyperplasia, of the prostate, which  surrounds the neck of the bladder. As the prostate  gland enlarges, it narrows the urethra, making void-  ing very difficult. When urinary retention is pro-  longed, a slender flexible drainage tube called a  catheter (kath’i-ter) must be inserted through the  urethra to drain the urine and prevent bladder  trauma from excessive stretching.    8. A kidney stone blocking a ureter would interfere  with the flow of urine to which organ?  9. Why is the presence of transitional epithelium in  the urinary bladder important?  10. Structurally and functionally, how does the male  urethra differ from the female urethra?  11. What is a synonym for micturition?  For answers, see Appendix A.    15.3 Fluid, Electrolyte, and  Acid-Base Balance  The composition of the blood depends on three    major factors: diet, cellular metabolism, and urine  output. In general, the kidneys play four major roles,   e Maintaining electrolyte balance of the blood  e Ensuring proper blood pH    Excretion of nitrogenous wastes has already been  considered; the other roles of the kidneys are dis-  cussed next.   v# Explain the role of antidiuretic hormone (ADH) in  the regulation of water balance by the kidney.   v Explain the role of aldosterone in sodium ion and  potassium ion balance of the blood.    If you are a healthy young adult, water probably  accounts for half or more of your body weight—  50 percent in women and about 60 percent in men.  These differences reflect the fact that women have rel-  atively less muscle and a larger amount of body fat (of  all body tissues, fat contains the least water). Babies,  with little fat and low bone mass, are about 75 percent  water. This accounts for their “dewy” skin, like that of  a freshly picked peach. After infancy, total body water  content declines through life, finally accounting for  only about 45 percent of body mass in old age. Water  is the universal body solvent within which all solutes  (including the very important electrolytes) are dis-  solved. (We described the importance of water to the  functioning of the body and its cells in Chapter 2.)   Water occupies three main locations within the  body, referred to as fluid compartments (Figure 15.8).  About two-thirds of body fluid, the so-called  intracellular fluid (ICF), is contained within the living  cells. The remainder, called extracellular fluid (ECF),  includes all body fluids located outside the cells. ECF  includes blood plasma, interstitial fluid (IF) between  cells, lymph, and transcellular fluid (in chambers lined  with epithelium), which includes cerebrospinal and  serous fluids, the humors of the eye, and others.   the body. Approximate values are noted for a 70-kg  (154-pound) man. For simplicity, this figure shows only  interstitial fluid and plasma in the ECF.    the external and internal environments (Figure 15.9).  Exchanges occur almost continuously in the lungs,  gastrointestinal tract, and kidneys. Although these  exchanges alter plasma composition and volume,  adjustments in the other two fluid compartments  follow quickly so that balance is restored.    Water certainly accounts for nearly the entire vol-  ume of body fluids, which are all similar, regard-  less of type. But there is more to fluid balance than  just water. Recall from Chapter 2 that electrolytes  are charged particles (ions) that conduct an electri-  cal current in an aqueous solution. The types and  amounts of solutes in body fluids, especially electro-  lytes such as sodium, potassium, and calcium ions,  are also vitally important to overall body homeosta-  sis. Water and electrolyte balance, though we con-  sider them separately here, are tightly linked as the  kidneys continuously process the blood.    If the body is to remain properly hydrated, it can-  not lose more water than it takes in. Most water    Figure 15.9 The continu-  ous mixing of body fluids.  Nutrients and wastes are  exchanged between the intra-  cellular fluid and the plasma  through the interstitial fluid.  Blood plasma transports  nutrients and wastes between  the cells and the external  environment of the body.    How would the values shown here be affected by  (1) drinking a six-pack of beer and (2) ingesting  only water?    Figure 15.10 Water intake and output. Major  sources of body water and routes of water loss from  the body are shown. When intake and output are in  balance, the body is adequately hydrated.    intake comes from fluids and foods we ingest in our  diet (Figure 15.10). However, a small amount (about  10 percent) is produced during cellular metabolism  (explained in Chapter 14).   The thirst mechanism is the driving force for  water intake. An increase in plasma solute content of  only 2 to 3 percent excites highly sensitive cells in  the hypothalamus called osmoreceptors (0z’mo-  re-sep’torz), which in turn activate the hypothalamic  thirst center (Figure 15.11). The mouth also becomes  dry because the salivary glands obtain the water they  require from the blood. When less fluid leaves the  bloodstream, less saliva is produced, reinforcing the  thirst response. The same response results from a  decline in blood volume (or pressure), although this  is a less potent stimulus.    Figure 15.11 The thirst mechanism for regulating  water intake. The major stimulus is increased osmolarity  (concentration of solutes) of blood plasma. (A decrease  in plasma volume and blood pressure, not shown, is a  less important stimulus that acts primarily to control  blood pressure. Look ahead to Figure 15.12, p. 550.)    Water leaves the body by several routes. Some  water vaporizes out of the lungs (insensible water  loss), some is lost in perspiration, and some leaves  the body in the stool (see Figure 15.10). The job of  the kidneys is like that of a juggler. If large amounts    of water are lost in other ways, the kidneys compen-  sate by producing less urine to conserve body water.  However, when water intake is excessive, the kidneys  excrete generous amounts of water in urine to reduce  fluid volume.   In addition to regulating fluid volume, the kid-  neys ensure that proper concentrations of the various  electrolytes are present in both intracellular and  extracellular fluids. Most electrolytes enter the body  in foods and “hard” (mineral-rich) water. Although  very small amounts are lost in perspiration and in  feces, the major factor regulating the electrolyte com-  position of body fluids is the kidneys.   Reabsorption of water and electrolytes by the  kidneys is regulated primarily by hormones. When  blood volume drops for any reason (for example, as  a result of hemorrhage or excessive water loss  through sweating or diarrhea), arterial blood pres-  sure drops, which in turn decreases the amount of  filtrate formed by the kidneys. In addition, the hypo-  thalamic osmoreceptors react to the change in blood  composition (that is, less water and more solutes)  by becoming more active. The result is that nerve  impulses are sent to the posterior pituitary  (Figure 15.12, p. 550), which then releases  antidiuretic hormone (ADH). (The term antidi-  uretic is derived from diuresis |[di"u-re’sis], which  means “flow of urine from the kidney,” and anti,  which means “against.”) As you might guess, this  hormone prevents excessive water loss in the urine.    organ systems (see Figure 1.3, p. 30), and notice that the  interdependent events regulating sodium ion and water  balance (see Figure 15.12, p. 550) involve four body sys-  tems: urinary, nervous, endocrine, and cardiovascular.    ADH travels in the blood to its main target, the  kidney’s collecting ducts, where it causes the duct  cells to reabsorb more water. As more water is  returned to the bloodstream, blood volume and  blood pressure increase to normal levels, and only a  small amount of concentrated urine is formed.  ADH is released more or less continuously unless  the solute concentration of the blood drops too low.  When this happens, the osmoreceptors become  “quiet,” and excess water is allowed to leave the  body in the urine.   When ADH is not released (perhaps because of injury  or destruction of the hypothalamus or posterior  pituitary gland), huge amounts of very dilute urine  (up to 25 liters/day) flush from the body day after  day. This condition, diabetes insipidus (in-sip'ï-  dus), can lead to severe dehydration and electrolyte  imbalances. Affected individuals are always thirsty  and have to drink fluids almost continuously to  maintain normal fluid balance.    Very small changes in the electrolyte concentrations  in the various fluid compartments cause water to  move from one compartment to another. This move-  ment not only alters blood volume and blood pres-  sure, but also can severely impair the activity of  irritable cells, such as nerve and muscle cells. For  example, when the level of potassium ions in the  ECF is low, muscle cells may not be able to repolar-  ize properly, which can lead to muscle cramps.  Besides ADH, aldosterone (al’dos’ter-on) is a  second hormone that helps to regulate blood com-  position and blood volume by acting on the kidney.  Aldosterone is the major factor regulating sodium  ion content of the ECF and in the process helps reg-  ulate the concentration of other ions (potassium  [K*], chloride [C17], and magnesium [Mg%]) as well.  Sodium ions are the electrolytes most responsi-  ble for osmotic water flow. When too few sodium  ions are in the blood, water will leave the blood and  enter tissues, causing edema. If serious, this situation  can cause the circulatory system to shut down.  Regardless of whether aldosterone is present or not,  about 80 percent of the sodium ions in the filtrate  are reabsorbed in the proximal convoluted tubules  of the kidneys. When the aldosterone concentration  is high, most of the remaining sodium ions are  actively reabsorbed in the distal convoluted tubules  and the collecting ducts. Generally speaking, for  each sodium ion reabsorbed, a chloride ion follows,  and a potassium ion is secreted into the filtrate.  Thus, as the sodium ion content of the blood  increases, the potassium ion concentration decreases,  bringing these two ions back to their normal balance  in the blood. Still another effect of aldosterone is to  increase water reabsorption by the tubule cells; as    Figure 15.12 Flowchart of mechanisms regulating sodium ion and water balance  to help maintain blood pressure homeostasis. Blood solute levels, fluid volume, and  blood pressure are all interrelated. *Look back to Figure 15.11, and note the intersection  of blood pressure homeostasis and the thirst mechanism regulating water intake at the  hypothalamic osmoreceptors. This helps increase fluid volume and therefore blood  volume, which directly influences blood pressure.    sodium ions are reclaimed, water follows it passively  back into the blood. Here is a little rule to keep in  mind: Water follows salt.   Recall that aldosterone is produced by the adre-  nal cortex. Although a rising potassium ion level or  a falling sodium ion level in the ECF directly stimu-  lates the adrenal cells to release aldosterone, the  most important trigger for aldosterone release is the  renin-angiotensin mechanism (see Figure 15.12)  mediated by the juxtaglomerular (JG) apparatus of the  renal tubules. The juxtaglomerular apparatus (look  back at Figure 15.3b) consists of a complex of mod-  ified smooth muscle cells (JG cells) in the afferent  arteriole plus some modified epithelial cells forming  part of the distal convoluted tubule. The naming of  this cell cluster reflects its location close to (juxta)  the glomerulus. When the cells of the JG apparatus  are stimulated by low blood pressure in the afferent  arteriole or changes in solute content of the filtrate,  they respond by releasing the enzyme renin (re’nin)  into the blood. (Notice the different spelling and  pronunciation of this enzyme from rennin (rěn'in), an  enzyme secreted by stomach glands. See Chapter 14.)  Renin initiates the series of reactions that produce  angiotensin II. Angiotensin II in turn acts directly on  the blood vessels to cause vasoconstriction (leading  to an increase in peripheral resistance) and on the  adrenal cortical cells to promote aldosterone release.  As a result, blood volume and blood pressure  increase (see Figure 15.12). The renin-angiotensin  mechanism is extremely important for regulating  blood pressure.   When pressure drops, baroreceptors in large  blood vessels are also excited. These baroreceptors  alert sympathetic nervous system centers of the  brain to cause vasoconstriction (via release of epi-  nephrine and norepinephrine) (see Figure 15.12).  However, this neural mechanism’s major focus is  blood pressure regulation, not water or electrolyte   Homeostatic J  —S~ Imbalance 15.7  People with Addison's disease (hypoaldosteron-  ism) have polyuria (excrete large volumes of urine)  and so lose tremendous amounts of salt and water to  urine. As long as adequate amounts of salt and fluids  are ingested, people with this condition can avoid  problems, but they are constantly teetering on the  brink of dehydration.    12. What are the four main functions of the kidneys?  13. What is the chief mechanism prompting water  intake?  14. What is the role of aldosterone in water balance?  15. Where are osmoreceptors located, and to what  stimulus do they respond?  For answers, see Appendix A.    v@ Compare and contrast the relative speed of buf-  fers, the respiratory system, and the kidneys in  maintaining the acid-base balance of the blood.    For the cells of the body to function properly, blood  pH must be maintained between 7.35 and 7.45,  a very narrow range. Whenever the pH of arterial  blood rises above 7.45, a person is said to have  alkalosis (al’kah-lo’sis). A drop in arterial pH to  below 7.35 results in acidosis (as’i-do’sis). Because  a pH of 7.0 is neutral, any pH between 7.0 and 7.35  is not acidic, chemically speaking; however, it repre-  sents a lower-than-optimal pH for the functioning  of most body cells. Therefore, any arterial pH in this  range is called physiological acidosis.   Although small amounts of acidic substances  enter the body in ingested foods, most hydrogen ions  originate as by-products of cellular metabolism,  which continuously adds substances to the blood  that tend to disturb its acid-base balance. Many dif-  ferent acids are produced (for example, phosphoric  acid, lactic acid, and many types of fatty acids). In  addition, carbon dioxide, which is released during  energy production, forms carbonic acid. Ammonia  and other basic substances are also released to the  blood as cells go about their usual “business.”  Although the chemical buffers in the blood can tem-  porarily “tie up” excess acids and bases, and the lungs  have the chief responsibility for eliminating carbon  dioxide from the body, the kidneys assume most of  the load for maintaining acid-base balance of the  blood. Before describing how the kidneys function in  acid-base balance, let's look at how blood buffers  and the respiratory system help regulate pH.    Chemical buffers are systems of one or two mol-  ecules that act to prevent dramatic changes in the  hydrogen ion concentration when acids or bases    are added. They do this by binding to hydrogen  ions whenever the pH drops and by releasing hydro-  gen ions when the pH rises (See Concept Link on  p. 540.). The chemical buffers act within a fraction of  a second, so they are the first line of defense in resist-  ing pH changes.   To better understand how a chemical buffer sys-  tem works, let's review strong and weak acids and  bases (covered in Chapter 2). Acids are proton (H*)  donors, and the acidity of a solution reflects only the  free hydrogen ions, not those still bound to anions.  Strong acids such as hydrochloric acid (HCl) dissoci-  ate completely and liberate all their hydrogen ions  (H*) in water (Figure 15.13a). Consequently they can  cause large changes in pH. By contrast, weak acids  such as carbonic acid (H;CO3) release only some of  their H* (partial dissociation) and so have a lesser  effect on pH (Figure 15.13b). However, weak acids  are very effective at preventing pH changes because  they are forced to dissociate and release more H*  when the pH rises over the desirable pH range. This  feature allows them to play a very important role in  the chemical buffer systems.   Also recall that bases are proton, or hydrogen  ion, acceptors. Strong bases such as hydroxides disso-  ciate easily in water and quickly tie up H*, but weak  bases such as bicarbonate ion (HCO3 _) and ammonia    Figure 15.13 Dissociation of strong and weak acids  in water. Undissociated molecules are shown in colored  ovals.    (NH3) are slower to accept H*. However, as pH drops,  the weak bases become “stronger” and begin to tie up  more H*. Thus, like weak acids, they are valuable  members of the chemical buffer systems.   The three major chemical buffer systems of the  body are the bicarbonate, phosphate, and protein buffer  systems, each of which helps to maintain the pH in  one or more of the fluid compartments. They all  work together, and anything that causes a shift in  hydrogen ion concentration in one compartment  also causes changes in the others. Thus, any abnor-  mal pH level is resisted by the entire buffering sys-  tem. Because all three systems operate in a similar  way, we will examine just one, the bicarbonate buf-  fer system, which is important in preventing changes  in blood pH.   The bicarbonate buffer system is a mixture of  carbonic acid (H,CO3) and its salt, sodium bicarbonate  (NaHCO3). Carbonic acid is a weak acid, so it does  not dissociate much in neutral or acidic solutions.  Thus, when a strong acid such as hydrochloric acid is  added, most of the carbonic acid remains intact.  However, the bicarbonate ions (HCO3,) of the salt act  as bases to tie up the hydrogen ions released by the  stronger acid, forming more carbonic acid:    Because the strong acid is (effectively) changed to a  weak one, it lowers the pH of the solution only very  slightly.   Similarly, if a strong base such as sodium hydrox-  ide (NaOH) is added to a solution containing the  bicarbonate buffer system, NaHCO; will not dissoci-  ate further under such alkaline conditions. However,  carbonic acid (H,CO3) will be forced to dissociate  further by the presence of the strong base—releasing  more H* to bind with the OH released by NaOH.   NaOH + H,CO3— > NaHCO; + H,O  strong weak weak water  base acid base  The net result is replacement of a strong base by a weak  one, so that the pH of the solution rises very little.    The respiratory system eliminates carbon diox-  ide from the blood while it “loads” oxygen into  the blood. When carbon dioxide (CO) enters the  blood from the tissue cells, most of it enters the red  blood cells, where it is converted to bicarbonate ion    (HCO; ) for transport in the plasma, as shown by  the equation    CO, + HO — H,cO, — H* + HCO,”  carbon water carbonic hydrogen bicarbonate  dioxide acid ion ion  The double arrows reveal that this reaction goes both  ways. However, an increase in carbon dioxide pushes  the reaction to the right, producing more carbonic  acid (refer back to Figure 13.11, p. 469). Likewise, an  increase in hydrogen ions pushes the reaction to the  left, producing more carbonic acid.   In healthy people, carbon dioxide is expelled  from the lungs at the same rate as it is formed in the  tissues. Thus the H* released when CO, is loaded  into the blood is not allowed to accumulate, because  it is tied up in HO when CO, is unloaded in the  lungs. So, under normal conditions, the H* pro-  duced by CO, transport has essentially no effect on  blood pH.   However, when CO, accumulates in the blood  (for example, during restricted breathing) or more  H* is released to the blood by metabolic processes,  the chemoreceptors in the respiratory control centers  of the brain (or in peripheral blood vessels) are acti-  vated. As a result, breathing rate and depth increase,  and the excess H* is “blown off” as more CO; is  removed from the blood.   In contrast, when blood pH begins to rise  (alkalosis), the respiratory center is depressed.  Consequently, the respiratory rate and depth fall,  allowing CO, (and hence, H*) to accumulate in  the blood. Again blood pH is restored to the nor-  mal range. Generally, these respiratory system cor-  rections of blood pH (via regulation of CO,  content of the blood) are accomplished within a  minute or so.    Chemical buffers can tie up excess acids or bases  temporarily, but they cannot eliminate them from  the body. And although the lungs can decrease car-  bonic acid levels by eliminating carbon dioxide,  only the kidneys can rid the body of other acids gen-  erated during metabolism. Additionally, only the  kidneys have the power to regulate blood levels of  alkaline substances. Thus, although the kidneys act  slowly and require hours or days to change blood  pH, they are the most potent of the pH-regulating  mechanisms.    The most important means by which the kidneys  maintain acid-base balance of the blood are by  excreting bicarbonate ions and reabsorbing or gener-  ating new bicarbonate ions. Look back again at the  equation showing how the carbonic acid-bicarbonate  buffer system operates. Notice that losing a bicar-  bonate ion (HCO, _) from the body has the same  effect as gaining a hydrogen ion (H*) because it  pushes the equation to the right (that is, it leaves a  free H*). By the same token, reabsorbing or generat-  ing new HCO, is the same as losing H~ because it  tends to combine with an H* and pushes the equa-  tion to the left.   Renal mechanisms undertake these adjust-  ments: As blood pH rises, bicarbonate ions are  excreted and hydrogen ions are retained by the  tubule cells. Conversely, when blood pH falls,  bicarbonate is reabsorbed and generated, and  hydrogen ions are secreted. Urine pH varies from  4.5 to 8.0, which reflects the ability of the renal  tubules to excrete basic or acidic ions to maintain  blood pH homeostasis.    16. Why is blood pH between 7.0 and 7.35 considered  acidic even though basic chemistry defines any pH  above 7.0 as basic?   17. To minimize the pH shift that occurs when a strong  acid is added to water, would it be better to add a  strong base or a weak base? Why?   It is hot, and he neglected to bring a canteen of  water. Assume he is there all day. How would you  expect this situation to affect the solute concentra-  tion of his blood?   19. What are the two main ways the kidneys maintain  the acid-base balance of the blood?    Learning Objectives  v Describe three common congenital problems of  the urinary system.  v Describe the effect of aging on urinary system  functioning.  When you trace the embryonic development of the  kidneys, it almost seems as though they can’t “make  up their mind” about whether to come or go. The    Learn more at Mastering A&P > Study Area >  Additional Study Tools > Focus on Careers    Bae practical nurses work in hos-  pitals, doctor's offices, and nursing  homes, and some offer private inhome  care. LPNs provide basic patient care,  such as bathing, feeding, administering  medications, and recording vital signs.  They work closely with registered  nurses (RNs) to ensure patients are  comfortable. LPNs routinely interact  with patients, family members, RNs,  and doctors, so excellent communica-  tion skills are necessary. Good organi-  zational skills are also a must in this  fast-paced career.    Linda Davila, an LPN, specializes in  caring for the terminally ill. “Most of  our patients have cancer,” she says.  “Others have life-threatening kidney,  lung, or cardiac conditions. Most hos-  pice patients have been diagnosed as  having 6 months or less to live, and  they have chosen to forgo aggressive  medical treatments. My job is to help  them stay as comfortable and pain free  as possible for the remaining days of  their lives.”   Davila’s clinical skills and anatomy/  physiology training enable her to mon-  itor a patient’s con-  dition closely and  alert team mem-  bers to any  changes. LPN appli-  cants must hold a  high school  diploma or GED  and pass an  entrance examina-  tion if required. A  one-year program  is typical and    includes anatomy and physiology, as  well as mathematics and other general  educational requirements. After grad-  uating from an accredited LPN pro-  gram, the LPN must also pass a state  licensing examination, and continuing  education credits are necessary to  maintain licensure. LPNs also have  opportunities for career advancement  by continuing their education to be-  come registered nurses.    e LPNs provide basic patient care,  administer medications, and  record vital signs.    e Necessary knowledge and skills for  an LPN include an understanding  of anatomy and physiology and  mathematics and good communi-  cation and organizational skills.    e After graduating from an accred-  ited program, an LPN must also  successfully complete a state  licensing exam.    first tubule system forms and then begins to degener-  ate as a second, lower, set appears. The second set, in  turn, degenerates as a third set makes its appearance.  This third set develops into the functional kidneys,  which are excreting urine by the third month of fetal  life. However, the fetal kidneys do not work nearly as  hard as they will after birth, because exchanges with  the mother’s blood through the placenta allow her  system to clear many of the undesirable substances  from the fetal blood.    There are many congenital abnormalities of the uri-  nary system. Two of the most common are polycys-  tic kidney and hypospadias.   Adult polycystic (pol"e-sis'tik)kidney disease  is a degenerative condition that appears to run in  families. One or both kidneys enlarge, sometimes to  the size of a football, and have many blisterlike sacs  (cysts) containing urine. These cysts interfere with    renal function by obstructing but initially not stop-  ping urine drainage. Currently, little can be done for  this condition except to prevent further kidney dam-  age by avoiding infection. Renal failure is the even-  tual outcome, but kidney transplants improve  chances for survival.   In the rarer, infantile form of the disease, the kid-  ney has blind pouches into which the filtrate flows,  totally blocking drainage. The disease progresses rap-  idly, resulting in death by 2 years of age.   Hypospadias (hi’po-spa’de-as) is a condition  found in male babies only. It occurs when the ure-  thral orifice is located on the ventral surface of the  penis. Corrective surgery is generally done when the  child is around 12 months old.    Because the bladder is very small and the kid-  neys are unable to concentrate urine for the first  2 months, a newborn baby voids from 5 to 40 times  per day, depending on fluid intake. By 2 months of  age, the infant is voiding approximately 400 ml/day,  and the amount steadily increases until adolescence,  when adult urine output (about 1500 ml/day) is  achieved.   Control of the voluntary urethral sphincter coin-  cides with nervous system development. By 15 months,  most toddlers are aware when they have voided. By  18 months they can hold urine in their bladder for  about 2 hours, which is the first sign that potty train-  ing can begin. The child usually achieves daytime  control well before nighttime control, which usually  is not complete until the child is 4 years old.   During childhood and through late middle age,  most urinary system problems are infectious or  inflammatory conditions. Many types of bacteria  may invade the urinary tract to cause urethritis, cys-  titis, or pyelonephritis. Escherichia coli (esh"er-ike-ah  ko'li) bacteria are normal residents of the digestive  tract and generally cause no problems there, but they  act as pathogens (disease-causing agents) in the ster-  ile environment of the urinary tract and account for  80 percent of urinary tract infections. Bacteria and  viruses responsible for sexually transmitted infections  (STIs), which are primarily reproductive tract infec-  tions, may also invade and cause inflammation in  the urinary tract, which leads to the clogging of some  of its ducts.    Homeostatic J  £ Imbalance 15.9  Childhood streptococcal (strep’to-kok’al) infec-  tions, such as strep throat and scarlet fever, may  cause inflammatory damage to the kidneys if the  original infections are not treated promptly and  properly. A common sequel to untreated childhood  strep infections is glomerulonephritis (glo-mer’u-  lo-né-fri’tis), in which the glomerular filters become  clogged with antigen-antibody complexes resulting  from the strep infection.    As we age, kidney size and function progressively  decline. By age 70, the rate of filtrate formation is  only about half that of the middle-aged adult. This is  believed to result from impaired renal circulation  due to atherosclerosis, which affects the entire circu-  latory system of the aging person. In addition to a  decrease in the number of functional nephrons, the  tubule cells become less efficient in their ability to  concentrate urine.   Another consequence of aging is bladder shrink-  age and loss of bladder tone, causing many elderly  individuals to experience urgency (a feeling that it is  necessary to void) and frequency (frequent voiding  of small amounts of urine). Nocturia (nok-tu’re-  ah), the need to get up during the night to urinate,  plagues almost two-thirds of this population. In  many, incontinence is the final outcome of the aging  process. Urinary retention is another common prob-  lem; most often it is a result of hypertrophy of the  prostate gland in males. Older adults can avoid some  of the problems of incontinence and retention by  maintaining a regular regimen of activity that keeps  the body as a whole in optimum condition and pro-  motes alertness to elimination signals.    20. What is hypospadias?  21. What is urgency as related to the urinary system?  What is frequency?  22. What is the difference between polycystic kidney  disease and glomerulonephritis?  For answers, see Appendix A.    e Kidneys dispose of  nitrogenous wastes; maintain  fluid, electrolyte, and acid-base  balance of blood; produce the  hormone erythropoietin; renal  regulation of Na* and water balance is  essential for blood pressure homeostasis   e ADH, aldosterone, ANP, and other  hormones help regulate renal  reabsorption of water and electrolytes    e Kidneys dispose of nitrogenous wastes;  maintain fluid, electrolyte, and acid-base  balance of blood; renal regulation of  Na+, K+, and Ca?* content in ECF is  essential for normal neural function   e Neural controls are involved in micturition;  sympathetic nervous system activity  triggers the renin-angiotensin mechanism    e Kidneys dispose of nitrogenous  wastes; maintain fluid, electrolyte,  and acid-base balance of blood   e Respiratory system provides oxygen  required by kidney; disposes  of carbon dioxide; cells in the lungs  convert angiotensin | to angiotensin II   e Kidneys dispose of nitrogenous  wastes; maintain fluid, electrolyte,  and acid-base balance of blood   e By returning leaked plasma fluid to  cardiovascular system, lymphatic  vessels help maintain normal systemic  blood pressure needed for kidney  function; immune cells protect  urinary organs from infection, cancer, |  and other foreign substances |    e Kidneys dispose of nitrogenous  wastes; maintain fluid, electrolyte,  and acid-base balance of blood;  renal regulation of Nat and water  balance is essential for blood  pressure homeostasis. Na+, K+,  and Ca?* regulation help maintain    also, metabolize vitamin D to the  active form needed for calcium  absorption   e Digestive organs provide nutrients  needed for kidney health; liver  synthesizes most urea, a nitrogenous  waste that must be excreted by  the kidneys   e Kidneys dispose of nitrogenous wastes;  maintain fluid, electrolyte, and acid-base  balance of blood    e Kidneys dispose of nitrogenous wastes;  maintain fluid, electrolyte, and acid-base  balance of blood   e Skin provides external protective barrier;  serves as site for vitamin D synthesis and  water loss (via perspiration)    e Kidneys dispose of nitrogenous  wastes; maintain fluid, electrolyte,  and acid-base balance of blood; renal  regulation of Na+, K+, and Ca?* content  in ECF is crucial for muscle activity   e Muscles of pelvic diaphragm and  external urethral sphincter function  in voluntary control of micturition; e Kidneys dispose of nitrogenous wastes;  muscle metabolism generates 13 maintain fluid, electrolyte, and acid-base  creatinine, a nitrogenous waste balance of blood  product that must be excreted by e Bones of rib cage provide some  the kidneys protection to kidneys    e The urinary system includes the kidneys, ure-  ters, urinary bladder, and urethra    e The kidneys are located along the dorsal wall in  a retroperitoneal position from vertebra T, to L;    e Each roughly the size of a large bar of soap, the  kidneys sit inferior to the adrenal glands and are  protected by a renal fascia, perirenal fat capsule,  and fibrous capsule (superficial to deep)    e When the kidney is viewed in a longitudinal sec-  tion, the outermost portion is the renal cortex;  inside that are the renal pyramids (also called  medullary pyramids) separated by renal  columns; draining the kidney are the calyces  and the renal pelvis    e Blood is supplied to the kidney by the follow-  ing vessels: renal artery, segmental arteries,  interlobar arteries, arcuate arteries, cortical  radiate arteries    e Blood is drained from the kidney by the fol-  lowing vessels: cortical radiate veins, arcuate  veins, interlobar veins, renal vein    e A nephron is the structural and functional unit  of the kidney; each acts as a blood filter    ° Cortical nephrons are located in the cortex;  juxtamedullary nephrons are located near  the junction between the cortex and medulla  of the kidney    o Nephrons have two parts: renal corpuscle  (the glomerulus) and glomerular capsule  (Bowman’s capsule) and the renal tubule  = Each renal tubule includes the proximal   convoluted tubule (PCT), nephron loop  (loop of Henle), distal convoluted tubule  (DCT), collecting duct   = The glomerulus is a special capillary bed  fed by the afferent arteriole and drained  by the efferent arteriole, which maintains  sufficient pressure for filtration to occur   = The peritubular capillaries are low-pressure  vessels closely associated with the renal  tubule that participate in reabsorption and  secretion    (À Listen to the story of this chapter in a brief summary at Mastering A&P >  E Study Area > Author Narrated Audio Summaries    Glomerular filtration—nonselective, passive fil-  tration of blood from higher-pressure glomerulus  into lower-pressure glomerular capsule; the fluid  that enters the glomerular capsule is called filtrate    ° If glomerular pressure is too low for adequate  filtration, oliguria (low urine output of 100  to 400 ml per day) or anuria (less than 100 ml  per day) may result  Tubular reabsorption—beginning in the proxi-  mal convoluted tubule, substances that the body  needs such as glucose, water, and amino acids are  reclaimed from filtrate; some items are claimed  by diffusion, but most require active transport    Tubular secretion—the active secretion of  items the body no longer needs into the renal  tubule for disposal; includes potassium ions,  hydrogen ions, creatinine, drugs, and others    Nitrogenous waste products—generally not  reabsorbed because the body does not need them;  include urea (from use of amino acids for energy),  uric acid (from digestion of nucleic acids) and  creatinine (from creatine metabolism in muscle)    Urine—fluid remaining after tubular reabsorp-  tion and tubular secretion; clear, yellow, sterile,  and slightely aromatic; pH can vary but is usu-  ally about pH 6; the specific gravity (density  compared to that of water) of urine is 1.035 or  less depending on the concentration of solutes  ° Urochrome (from breakdown of hemoglobin)  provides yellow color; pH varies with diet  from acidic to basic  o Healthy urine does not contain proteins, glu-  cose, blood cells (red or white), or bile    e The muscular tubes that carry urine from the  renal pelvis to the bladder are ureters  o Urine is propelled by peristalsis, not gravity  o When urine is extremely concentrated, renal  caliculi, or kidney stones, can occur, causing  pain when the ureter walls squeeze them or  when they get stuck in a ureter    e The urinary bladder is a temporary storage  tank for urine; the trigone is a triangular area  that includes the openings from both ureters  and the urethral opening    ° The bladder is lined with transitional epithelium  that stretches to accommodate more urine vol-  ume without increasing internal pressure; on  average, the bladder holds about 500 ml of urine    e The urethra is the passageway that carries urine  from the bladder outside the body via peristalsis    ° There are two sphincters: the internal ure-  thral sphincter is involuntary, and the exter-  nal urethral sphincter is voluntary    o The urethra differs in males and females; in  males, it is longer and carries both urine and  semen; in females, it is shorter and carries  only urine    ° The female urethral opening is close to the  anal opening, so improper hygiene can result  in urethritis (inflammation of the urethra)  or, if the infection ascends the urethra, cystitis  (bladder inflammation) or pyelonephritis  (kidney inflammation). Urinary tract infec-  tion (UTI) symptoms can include dysuria,  urgency and frequency of urination, blood in  urine, headache, and back pain    e Micturition, or voiding, is the act of emptying  the bladder    e The urge to void begins when the bladder holds  about 200 ml of urine    e Incontinence is loss of voluntary control of the  external urethral sphincter; urinary retention is  an inability of the bladder to expel stored urine    o Urinary retention can occur after general anes-  thesia; in men it can be due to hyperplasia,  or enlargement, of the prostate, which sur-  rounds the urethra    e The kidneys help maintain water, electrolyte,  and pH balance of the blood  15.3a. Maintaining water balance of blood    e Water is a major contributor to adult body weight  (50 percent in women; 60 percent in men)    e Water is found in three major compartments:  intracellular fluid (ICF), interstitial fluid (IF),    and plasma; interstitial fluid and plasma make  up the bulk of extracellular fluid (ECF)    e The thirst mechanism drives water intake;  it is stimulated when osmoreceptors in the  hypothalamus detect increased plasma solute  concentrations    o Signals are also sent to the posterior pituitary,  which releases antidiuretic hormone (ADH);  ADH then acts on the collecting ducts to stim-  ulate water reabsorption    o When ADH is not released, diabetes insipidus  results: large volumes of dilute urine are pro-  duced, resulting in severe dehydration and elec-  trolyte imbalance    e Water leaves via vaporization in lungs, via sweat,  via stool, and via urine    e Changes in electrolyte concentrations cause  water to move among compartments, which  influences blood volume and blood pressure  and the activity of irritable cells such as neurons  and muscle fibers    e Aldosterone acts on the kidney tubule to stim-  ulate sodium ion reabsorption and potassium  ion secretion; chloride ions are reabsorbed with  sodium ions. Water follows sodium ions    o Most important trigger for aldosterone release  is the renin-angiotensin mechanism    ° Renin—an enzyme secreted by cells of the  juxtaglomerular apparatus in response to low  blood pressure in the afferent arteriole or to  decreasing sodium concentration in the fil-  trate; this enzyme initiates reactions that pro-  duce angiotensin II  = Angiotensin II actions include the following:   vasoconstriction directly increases blood  pressure (by increasing peripheral resistance);  stimulates aldosterone release from adrenal  cortex; stimulates ADH release by posterior  pituitary; further stimulates the hypothalamic  thirst mechanism    ° Addison's disease—condition in which the  body produces too little aldosterone, resulting  in polyuria (production of large volumes of  urine) and, as a consequence, salt and water loss    e Blood pH must be 7.35 to 7.45; pH that is too  low is acidosis, too high is alkalosis. Because  the lowest normal pH of blood is 7.35, a pH  between 7.00 and 7.35, while not technically  acidic, is called physiological acidosis because  it is lower than normal    Blood buffers bind hydrogen ions (H*) or pro-  tons when pH is too low and release hydrogen  ions when pH is too high    ° Strong acids completely dissociate in water;  weak acids partially dissociate in water    o Bases are proton acceptors; weak bases will  accept protons more easily when pH is lower  than normal    There are three major buffer systems: bicarbon-  ate buffer system, phosphate buffer system, and  protein buffer system; all three operate similarly  to the bicarbonate buffer system  ° CO, + H2O < HCO; < H* + HCO37  o Carbon dioxide combines with water to form  carbonic acid; then dissociates partially (it is a  weak acid) to produce some hydrogen ions  and bicarbonate ions  = At capillaries, bicarbonate ions are formed as  carbon dioxide is loaded into the blood; H*  is released in the blood and influences pH  = In the lungs, carbon dioxide is released from  the blood (H* is no longer influencing pH)    Respiratory mechanisms regulate breathing  rate and depth; when carbon dioxide accumu-  lates in the blood, pH decreases (acidosis),  and rate and depth of breathing increase to  breathe off the excess CO,; when blood pH  increases (alkalosis), breathing rate and depth  decrease, allowing CO, to accumulate and  raise pH back to the normal range    ° Renal mechanisms: when in acidosis, body  secretes excess hydrogen ions and retains or  produces new bicarbonate ions; when in alka-  losis, body retains hydrogen ions and secretes  bicarbonate ions    Adult polycystic kidney disease—a degener-  ative condition in which kidneys enlarge and  have cysts (blisterlike sacs) of urine that  obstruct urine drainage    Hypospadias—occurs in male babies; the  urethral orifice is located on the ventral sur-  face (underside) of the penis; can be repaired  surgically   Babies urinate often because the kidneys cannot  concentrate urine and the bladder is small; as  the nervous system develops, control of the  external urethral sphincter improves    As we age, kidney function declines because of  general decline of the circulation. The bladder  shrinks and loses tone, leading to urgency and  frequency (the need to urinate often, but only  small amounts). Nocturia is the need to urinate  during the night; incontinence and urinary re-  tention also occur in old age    Multiple Choice  More than one choice may apply.  1. Match each letter from the figure with the correct   blood vessel name.  1. Arcuate vein  2. Segmental arteries  3. Renal artery  4. Cortical radiate artery  5. Interlobar vein   . Which of the following substances should not be pres-  ent in normal urine?  a. Red blood cells  b. Uric acid    . The antidiuretic hormone (ADH)  a. is released by the posterior pituitary.  b. causes the formation of very dilute urine.    c. Removal of excess potassium ions from the blood  d. Control of blood pH   . Low blood pressure detected by the cells in the green  box directly stimulates the release of    Name the organs of the urinary system, and describe  the general function of each organ.    Using the image provided, identify and label the cor-  tex, medulla, medullary pyramids, renal columns,  and pelvis.    Trace the pathway a uric acid molecule takes from a  glomerulus to the urethra. Name every gross or micro-  scopic structure it passes through on its journey.    What is the function of the collecting ducts? What do  they contain?   Where do the peritubular capillaries arise from, and  how do they differ from the glomerular capillaries?    Which part of the glomerulus is under the highest  pressure? What is the significance of this?    Through which parts of the nephron is NaCl trans-  ported out? Is this active transport or passive  transport?    In which condition presence of proteins can be  observed in urine? Is this condition pathological or  nonpathological? Explain.    Describe the role of the respiratory system in control-  ling acid-base balance.    Why is urinalysis a routine part of any good physical  examination?    How do the internal and external urethral sphincters  differ structurally and functionally?    Contrast the following homeostatic imbalances: oli-  guria, anuria, polyuria, and nocturia.    Describe the changes that occur in kidney and blad-  der function in old age.    Jessica has been experiencing a raging and insatiable  thirst for some months. The unfortunate consequence  of her increased water intake is a constant need to uri-  nate. She is finding it difficult to get enough sleep and  this is now interfering with her work. Explain her  symptoms.    What happens to the rate of RBC production in a  patient on dialysis with total renal failure? What  could be given to the patient to counteract such a  problem? (Hint: You might want to check Table 9.2  on p. 346 for help with this one.)    Alexander is 72 and is in good health. However, he is  recently having difficulties emptying his bladder.  What is the likely cause?    A trainee nurse at the urology department of a hospi-  tal notices that significantly more women than men  come in complaining about urinary bladder infec-  tion. She asks her tutor whether this is a coincidence  or if there is an explanation for this. Explain the  answer her tutor would offer her.    Raymond is hypertensive and was recently diagnosed  with impaired kidney function based on urinalysis  and a blood test for creatinine. What sorts of test  results would you expect, and how is hypertension  related to kidney function?    The reproductive  organs of men and  women produce gametes  and also contribute to the  development of secondary  sex characteristics.    The reproductive  systems of men and  women produce offspring to  ensure the survival of the  human species.   being of the individual. The reproductive  system, however, appears to “slumber” until puberty,  when reproductive organs become functional. The  gonads (go’nadz; “seeds”), or primary sex organs,  are the testes in men and the ovaries in women. The  gonads produce sex cells, or gametes (gam’éts), and  secrete sex hormones. The remaining reproductive sys-  tem structures are accessory reproductive organs.    Male testes produce  sperm, whereas female  ovaries produce eggs. When  an egg and a sperm join, an    Although male and female reproductive sys-  tems are quite different, their joint purpose is to pro-  duce offspring. The reproductive role of the man is  to manufacture male gametes called sperm and  deliver them to the woman’s reproductive tract. The  woman, in turn, produces female gametes, called  ova (singular ovum), or eggs. If the conditions are  suitable, a sperm and egg fuse to produce a fertilized  egg, called a zygote. Once fertilization has occurred,  the female uterus provides a protective environment  in which the embryo, later called the fetus, develops  until birth.   The sex hormones play vital roles both in the  development and function of the reproductive    organs, and in sexual behavior and drives. These hor-  mones also influence the growth and development  of many other organs and tissues of the body.    1# When provided with a model or diagram, identify  the organs of the male reproductive system, and  discuss the general function of each.   1# Discuss the composition of semen, and name the  glands that produce it.   1# Trace the pathway followed by a sperm from the  testis to the body exterior.    As already noted, the primary reproductive organs of  the male are the paired testes (tes'tēz), which have  both an exocrine function (sperm production) and  an endocrine function (testosterone production).  The accessory reproductive structures are ducts or  glands that aid in the delivery of sperm to the body  exterior or to the female reproductive tract.    Each golf ball-sized testis is approximately 4 cm  (1.5 inches) long and 2.5 cm (1 inch) wide and is  connected to the trunk via the spermatic cord, a  connective tissue sheath that encloses blood vessels,  nerves, and the ductus deferens. A fibrous connective  tissue capsule, the tunica albuginea (tu'ni-kah  al"bu-jin’e-ah; “white coat”) surrounds each testis.  Extensions of this capsule (septa) plunge into the tes-  tis and divide it into a large number of wedge-shaped  lobules (Figure 16.1). Each lobule contains one to  four tightly coiled seminiferous (sem’i-nif’er-us)  tubules, the actual “sperm-forming factories.”  Seminiferous tubules of each lobule empty sperm  into another set of tubules, the rete (re’te) testis,  located to one side of the testis. Sperm travel through  the rete testis to enter the first part of the duct sys-  tem, the epididymis (ep"i-did’i-mis), which hugs the  posterior surface of the testis.    is testosterone. Thus, the sperm-producing and  hormone-producing functions of the testes are car-  ried out by completely different cell populations.    The accessory organs forming the male duct sys-  tem, which transports sperm from the body, are the  epididymis, ductus deferens, and urethra (Figure 16.2,  p. 564).   The cup-shaped epididymis is a highly convoluted  tube about 6 m (20 feet) long that hugs the posterior  side of the testis (see Figure 16.1). The epididymis is  the first part of the male duct system and provides a  temporary storage site for the immature sperm. 16  While the sperm make their way along the tortuous  course of the epididymis (a trip that takes about  20 days), they complete maturation and develop the  ability to swim. When a man is sexually stimulated  and ejaculates (ejac = to shoot forth), the walls of  the epididymis contract to expel the sperm into the  next part of the duct system, the ductus deferens.    The ductus deferens (duk’tus def’er-enz; “carrying  away”), or vas deferens, runs upward from the epidid-  ymis via the spermatic cord through the inguinal  canal into the pelvic cavity and arches over the supe-  rior aspect of the urinary bladder. The ductus defer-  ens then loops medially over the ureter and descends  along the posterior bladder wall. The end of the duc-  tus deferens expands as the ampulla and then emp-  ties into the ejaculatory (e-jak’u-lah-to”re) duct,  which passes through the prostate to merge with the  urethra. The main function of the ductus deferens is  to propel live sperm from their storage sites—the    epididymis and distal part of the ductus deferens—  into the urethra. At the moment of ejaculation, the  thick layers of smooth muscle in its walls create per-  istaltic waves that rapidly squeeze the sperm  forward.   Part of the ductus deferens lies in the scrotum, a  skin sac that hangs outside the body cavity and holds  the testes (see Figure 16.2). Some men voluntarily  opt to take full responsibility for birth control by  having a vasectomy (vah-sek'to-me; “cutting the vas”).  In this relatively minor operation, the surgeon makes  a small incision into the scrotum and then cuts  through and ties off the ductus deferens. Sperm are  still produced, but they can no longer leave the body,  and eventually they deteriorate and are phagocy-  tized. A man is sterile after this procedure, but  because testosterone is still produced, he retains his  sex drive and secondary sex characteristics.    The urethra, which extends from the base of the uri-  nary bladder to the tip of the penis, is the terminal  part of the male duct system. It has three regions:  (1) the prostatic urethra, surrounded by the prostate  gland; (2) the membranous urethra, spanning the  distance from the prostatic urethra to the penis; and  (3) the spongy (penile) urethra, running within  the length of the penis and opening to the body exte-  rior via the external urethral orifice (see Figure 16.2).  The male urethra carries both urine and semen to the  body exterior; thus, it serves two masters, the urinary  and reproductive systems (recall Chapter 15).  However, urine and sperm never leave the body at  the same time. When ejaculation occurs and sperm  enter the prostatic urethra from the ejaculatory ducts,  the bladder sphincter (internal urethral sphincter)  constricts. This event not only prevents urine from    passing into the urethra, but also prevents semen  from entering the urinary bladder.    1. What are the two major functions of the testes?  2. What is the role of the seminiferous tubules?  3. Name the organs of the male duct system, in order,  from the scrotum to the body exterior.  For answers, see Appendix A.    16.1c Accessory Glands and Semen  The accessory glands include the paired seminal  (sem’i-nul) vesicles, the single prostate, and the paired  bulbourethral (bul-bo-u-re'thral) glands (see Figure  16.2). These glands produce the bulk of semen  (se’men), the sperm-containing fluid that is pro-  pelled out of the male’s reproductive tract during  ejaculation.    The seminal vesicles are located at the base of the  bladder. These large hollow glands, each 6 to 7 cm  (about the shape and size of the little finger), pro-  duce about 60 percent of seminal fluid, the fluid por-  tion of semen. Their thick, yellowish secretion is rich  in sugar (fructose), vitamin C, prostaglandins, and  other substances that nourish and activate the sperm  passing through the tract. The duct of each seminal  vesicle joins that of the ductus deferens on the same  side to form the ejaculatory duct (see Figure 16.2).  Thus, sperm and seminal fluid enter the urethra  together during ejaculation.    The prostate is a single doughnut-shaped gland  about the size of a peach pit (see Figure 16.2). It  encircles the prostatic urethra just inferior to the uri-  nary bladder. Prostate fluid is milky and plays a role  in activating sperm. During ejaculation, the fluid  enters the urethra through several small ducts.  Because the prostate is located immediately anterior  to the rectum, its size and texture can be palpated  (felt) by digital (finger) examination through the  anterior rectal wall.    x Homeostatic J  Imbalance 16.1  The prostate has a reputation as a common cause of    health problems. Hypertrophy of the prostate, an  increase in its size independent of the body’s    growth, affects nearly every older man and strangles  the urethra. This troublesome condition makes uri-  nation difficult and enhances the risk of cystitis  (bladder infections) and kidney damage. Traditional  treatment used to be surgery, but some less invasive  options are becoming more popular. These include  the following:    e Inserting a scope through the urethra and  removing all but the outer part of the prostate    Prostatitis, inflammation of the prostate, is the  single most common reason for a man to consult a  urologist, and prostate cancer is the third most  prevalent cancer in men. Most cases of prostate can-  cer are slow-growing, but it can also be a swift and  deadly killer.    The bulbourethral glands are tiny, pea-sized glands  inferior to the prostate gland. They produce a thick,  clear mucus that drains into the penile urethra. This  secretion is the first to pass down the urethra when a  man becomes sexually excited. It cleanses the urethra  of trace acidic urine prior to ejaculation, and it serves  as a lubricant during sexual intercourse.    Semen is a milky white, somewhat sticky mixture of  sperm and accessory gland secretions. The liquid  portion acts as a transport medium for nutrients and  chemicals that protect the sperm and aid their move-  ment. Mature sperm cells are streamlined cellular  “tadpoles” containing little cytoplasm or stored  nutrients. The fructose in the seminal vesicle secre-  tion provides essentially all of their energy fuel.  Sperm are very sluggish under acidic conditions  (below pH 6). The relative alkalinity of semen as a  whole (pH 7.2-7.6) helps neutralize the acidic envi-  ronment (pH 3.5-4) of the female’s vagina, protect-  ing the delicate sperm. Semen also contains  antibiotic chemicals that destroy certain bacteria, the  hormone relaxin, enzymes that enhance sperm  motility, and substances that inhibit an immune  response in the female reproductive tract.   Semen also dilutes sperm; without such dilu-  tion, sperm motility is severely impaired. The  amount of semen propelled out of the male duct sys-  tem during ejaculation is relatively small, only 2 to    5 ml (about a teaspoonful), but each milliliter con-  tains between 50 and 150 million sperm.    Homeostatic j  —S Imbalance 16.2  Male infertility, the inability to conceive a child, may  be due to obstructions of the duct system, hormonal  imbalances, environmental estrogens, pesticides,  excessive alcohol, or many other factors. One of the  first series of tests done when a couple has been unable  to conceive is semen analysis. Factors analyzed include  sperm count, motility and morphology (shape and  maturity), and the volume, pH, and fructose content  of semen. A sperm count lower than 20 million per  milliliter makes impregnation improbable.    The male external genitalia (jen’i-tal’e-ah) include  the scrotum and the penis (see Figure 16.2). The scrotum  (skro'tum; “pouch”) is a divided sac of skin with  sparse hairs that hangs outside the abdominal cavity,  between the legs at the root of the penis. This is a  rather exposed location for a man’s testes, which  contain his entire genetic heritage, but viable sperm  cannot be produced at normal body temperature.  The scrotum provides a temperature about 3°C  (5.4°F) lower than body temperature, which is nec-  essary for the production of healthy sperm. When  the external temperature is very cold, the scrotum  becomes heavily wrinkled as it pulls the testes closer  to the warmth of the body wall. Thus, changes in  scrotal surface area can maintain a temperature that  favors viable sperm production.   The penis (pe’nis; “tail”) functions to deliver  sperm into the female reproductive tract. The skin-  covered penis consists of a shaft, which ends in an  enlarged tip, the glans penis. The skin covering the  penis is loose, and it folds downward to form a  sleeve of skin, the prepuce (pre’pus), or foreskin,  around the proximal end of the glans penis.  Frequently in many countries, the foreskin is surgi-  cally removed shortly after birth, in a procedure  called circumcision.   Internally, the spongy urethra (see Figure 16.2)  is surrounded by three elongated areas of erectile  tissue, a spongy tissue that fills with blood during  sexual excitement. This causes the penis to enlarge  and become rigid. This event, called erection, helps  the penis serve as the male organ of copulation (sex-  ual intercourse) to deliver the semen into the female  reproductive tract.   4. What is the function of the erectile tissue of the  penis?   5. What is an important function of each of these two  components of semen—sperm and seminal fluid?   6. Adolph, a 68-year-old gentleman, has trouble  urinating and is given a rectal exam. What is his  most probable condition, and what is the purpose of  the rectal exam?   v Describe the structure of a sperm, and relate its  structure to its function.    v Describe the effect of FSH and LH on testis  functioning.    The chief role of the male in the reproductive process  is to produce sperm and the hormone testosterone.    Sperm production, or spermatogenesis (sper’mah-  to-jen’é-sis), begins during puberty and continues  throughout life. A man makes millions of sperm  daily. Only one sperm fertilizes an egg, so it seems  that nature has made sure that the human species  will not be endangered for lack of sperm.   Sperm are formed in the seminiferous tubules of  the testis, as noted earlier. The process is begun by  primitive stem cells called spermatogonia  (sper’mah-to-go’ne-ah), found in the periphery  (outer edge), of each tubule (Figure 16.3).  Spermatogonia go through rapid mitotic divisions to  build up the stem cell line. From birth until puberty,  all such divisions simply produce more stem cells.  During puberty, however, follicle-stimulating hormone  (FSH) is secreted in increasing amounts by the ante-  rior pituitary gland.    gets the testes and stimulates sperm production  (Chapter 9, p. 332).    From puberty on, each division of a spermatogo-  nium produces one stem cell, called a type A daughter  cell, and another cell, called a type B daughter cell. The    Figure 16.3 Spermatogenesis. Flowchart showing  the relative position of the spermatogonia in the wall  of the seminiferous tubule. Although the stem cells and  the primary spermatocytes have the same number of  chromosomes (46, designated as 2n) as other body  cells, the products of meiosis (spermatids and sperm)  have only half as many (23, designated as n).    type A cell remains at the tubule periphery to main-  tain the stem cell population. The type B cell gets  pushed toward the tubule lumen, where it becomes  a primary spermatocyte destined to undergo meio-  sis (mi-o'sis) and form four sperm.   Meiosis is a special type of nuclear division that  occurs only in the gonads (testes and ovaries). It dif-  fers from mitosis (described in Chapter 3) in two  major ways. Meiosis consists of two successive divi-  sions of the nucleus (called meiosis I and II), instead  of only one division. It results in four (instead of  two) daughter cells, or gametes.   In spermatogenesis, the gametes are called  spermatids (sper’mah-tidz). Spermatids have only  half as much genetic material as other body cells. In  humans, this is 23 chromosomes (or the haploid  number [n] of chromosomes) rather than the usual  46 (diploid, or 2n). Then, when the sperm and the  egg (which also has 23 chromosomes) unite, form-  ing the fertilized egg, or zygote, the normal 2n num-  ber of 46 chromosomes is reestablished and is  maintained in subsequent body cells by the process  of mitosis (Figure 16.4).   As meiosis occurs, the dividing cells (primary  and then secondary spermatocytes) are pushed  toward the lumen of the tubule. Thus, we can follow  the progress of meiosis from the tubule periphery to  the lumen. The spermatids, produced by meiosis, are  not functional sperm. They are nonmotile and have  too much excess baggage to function well in    reproduction. They must undergo further physical  changes, in which their excess cytoplasm is stripped  away and a tail is formed (see Figure 16.3). In this  last stage of sperm development, called  spermiogenesis (sper’me-o-gen’é-sis), all the excess  cytoplasm is sloughed off, and what remains is  reshaped into the three regions of the fully formed  sperm—the head, midpiece, and tail (Figure 16.5). The  mature sperm is a greatly streamlined cell equipped  with a high rate of metabolism and a means of pro-  pelling itself, enabling it to move long distances in a  short time to get to the egg. It is a prime example of  the relationship between structure and function.  (See Chapter 1.) Remember that sperm continue  their maturation as they travel through the epididy-  mis and develop the ability to swim, so although  they are physically mature, at this stage of develop-  ment they are not yet fully functional.   Sperm “pack” light. The sperm head is the  nucleus and contains compacted DNA, the genetic  material. Anterior to the nucleus is the helmetlike  acrosome (ak'ro-som), which is produced by the  Golgi apparatus and is similar to a large lysosome.  When a sperm comes into close contact with an egg  (or more precisely, an oocyte), the acrosomal mem-  brane breaks down and releases enzymes that help  the sperm penetrate the capsule of follicle cells that  surround the egg. Filaments, which form the long  tail, arise from centrioles in the midpiece.  Mitochondria wrapped tightly around these fila-  ments provide the ATP needed for the rolling, one-  sided movements of the tail that propel the sperm  along the female reproductive tract. This newly-  discovered and unique motion is accomplished as  the head of the sperm rotates while the tail beats to  only one side.   The entire process from the formation of a pri-  mary spermatocyte to release of immature sperm in  the tubule lumen takes 64 to 72 days. But sperm in  the lumen are still unable to “swim” and so are still  incapable of fertilizing an egg. They are moved by  peristalsis through the tubules of the testes into the  epididymis. There they undergo further maturation,  which results in increased motility and fertilizing  power.    Homeostatic J  K Imbalance 16.3  Environmental threats can alter the normal process  of sperm formation. For example, some common  antibiotics, such as penicillin and tetracycline, may  suppress sperm formation. Radiation, lead, certain  pesticides, marijuana, tobacco, and excessive alcohol    What is the importance of the mitochondria in the sperm  midpiece?    Figure 16.5 Structure of sperm. (a) Scanning electron micrograph of mature sperm  (1,525). (b) Diagrammatic view of a sperm.    can cause production of abnormal sperm (two- amounts of testosterone are produced to influence  headed, multiple-tailed, and so on). embryonic development of male structures. During  puberty, as the seminiferous tubules are being prod-  ded by FSH to produce sperm, the interstitial cells  are being stimulated by luteinizing hormone (LH),  which is also released by the anterior pituitary gland  (Figure 16.6, p. 570). From this time on, testosterone  is produced continuously (more or less) for the rest  of a man’s life. The rising blood level of testosterone  in the young man stimulates the adolescent growth  spurt, prompts his reproductive organs to develop to  their adult size, underlies the sex drive, and causes  the male secondary sex characteristics to appear.  Secondary sex characteristics are features induced  in nonreproductive organs by sex hormones. Male  secondary sex characteristics include the following:   As noted earlier, the interstitial cells produce testos-  terone (tes-tos’té-ron), the most important hor-  monal product of the testes. In a male embryo, small    e Increased hair growth all over the body, particu-  larly in the axillary and pubic regions and on the  face    What is the effect of negative feedback of testosterone on  anterior pituitary and hypothalamic cells?    Hypothalamus <- - - - - - - - 1 (4)The hypothalamus releases  gonadotropin-releasing  hormone (GnRH).    e Increased heaviness of the skeleton due to bone  growth in both size and density    Because testosterone is responsible for the  appearance of these typical masculine characteris-  tics, it is often referred to as the “masculinizing”  hormone.    Homeostatic J  —S Imbalance 16.4  If testosterone is not produced in a young man, his  secondary sex characteristics never appear, and his  other reproductive organs remain childlike. This  condition is called sexual infantilism. Castration of  the adult male (or the inability of his interstitial cells  to produce testosterone) results in a decrease in the  size and function of his reproductive organs, as well  as a decrease in his sex drive. Sterility also occurs  because testosterone is necessary for the final stages  of sperm production.   8. How does the final product of meiosis differ from  the final product of mitosis?   10. Which pituitary hormone prompts testosterone  production?  For answers, see Appendix A.   v# Identify the organs of the female reproductive  system, and discuss the general function of each.   v Describe the functions of the vesicular follicle and  corpus luteum of the ovary.    # Indicate the location of the following regions of  the female uterus: cervix, fundus, body.    The reproductive role of the female is much more  complex than that of the male. Not only must she  produce the female gametes (ova), but her body  must also nurture and protect a developing fetus  during 9 months of pregnancy. Ovaries (o'vah-réz)  are the primary female reproductive organs. Like the    testes, ovaries produce both an exocrine product  (eggs, or ova) and endocrine products (estrogens and  progesterone). The other organs of the female repro-  ductive system serve as accessory structures to trans-  port, nurture, or otherwise serve the needs of the  reproductive cells and/or the developing fetus.    The paired ovaries resemble almonds in their shape  but are nearly twice as large. An internal view of an  ovary reveals many tiny saclike structures called  ovarian follicles (Figure 16.7, p. 572). Each follicle  consists of an immature egg, called an oocyte (0’o-  sit; o0 = egg), surrounded by one or more layers of  very different cells called follicle cells. As a develop-  ing egg within a follicle begins to mature, the follicle  enlarges and develops a fluid-filled central region  called an antrum. At this stage, the follicle, called a  vesicular follicle or Graafian (graf'e-an) follicle, is  mature, and the developing egg is ready to be ejected  from the ovary, an event called ovulation. After ovu-  lation, the ruptured follicle is transformed into a  very different-looking structure called a corpus  luteum (kor’pus lu’te-um; “yellow body”), which  eventually degenerates. Ovulation generally occurs  every 28 days, but it can occur more or less fre-  quently in some women.   The ovaries flank the uterus laterally (Figure 16.8,  p. 573). These organs are secured to the lateral walls  of the pelvis by the suspensory ligaments and are  anchored to the uterus medially by the ovarian  ligaments. In between, they are enclosed and  held in place by a fold of peritoneum, the broad  ligament.    The uterine tubes, uterus, and vagina form the duct sys-  tem of the female reproductive tract (see Figure 16.8).    The uterine (u’ter-in) tubes, or fallopian (fal-  lo'pe-an) tubes, form the initial part of the duct sys-  tem. They receive the ovulated oocyte and provide a  site where fertilization can occur. Each of the uterine  tubes is about 10 cm (4 inches) long and extends  medially from an ovary to empty into the superior  region of the uterus. Like the ovaries, the uterine tubes  are enclosed and supported by the broad ligament.  Unlike in the male duct system, which is contin-  uous with the tubule system of the testes, there is    Figure 16.7 Sagittal section of a human ovary showing the developmental stages    little or no actual contact between the uterine tubes  and the ovaries. The distal end of each uterine tube  expands as the funnel-shaped infundibulum, which  has fingerlike projections called fimbriae (fim'bre-e)  that partially surround the ovary (see Figure 16.8b).  As an oocyte is expelled from an ovary during ovula-  tion, the waving fimbriae create fluid currents that  carry the oocyte into the uterine tube, where it begins  its journey toward the uterus. (Many potential eggs,  however, are lost in the peritoneal cavity.) The oocyte  is carried toward the uterus by a combination of  peristalsis and the rhythmic beating of cilia from the  endothelial lining of the uterine tube.   Because the journey to the uterus takes 3 to  4 days and the oocyte is viable for at most 24 hours  after ovulation, the usual site of fertilization is the  uterine tube. To reach the oocyte, the sperm must  swim upward through the vagina and uterus to reach  the uterine tubes. Because they must swim against  the downward current created by the cilia, it is rather  like swimming against the tide!    The fact that the uterine tubes are not continuous  distally with the ovaries places women at risk for  infections spreading from the reproductive tract into  the peritoneal cavity. Gonorrhea (gon”o-re’ah) and    other sexually transmitted bacteria sometimes infect  the peritoneal cavity in this way, causing a severe  inflammation called pelvic inflammatory disease  (PID). Unless treated promptly, PID can cause scar-  ring and closure of the narrow uterine tubes, which  is one of the major causes of female infertility.    The uterus (u’ter-us; “womb”), located in the pelvis  between the urinary bladder and rectum, is a hollow  organ that functions to receive, retain, and nourish a  fertilized egg and, eventually, to aid in childbirth. In  a woman who has never been pregnant, it is about  the size and shape of a pear. During pregnancy, the  uterus increases tremendously in size and during  the latter part of pregnancy can be felt well above the  umbilicus. The uterus is suspended in the pelvis by  the broad ligament and anchored anteriorly and  posteriorly by the round ligaments and uterosacral  ligaments, respectively (see Figure 16.8).   The major portion of the uterus is referred to as  the body. Its rounded region superior to the entrance  of the uterine tubes is the fundus, and its narrow  outlet, which protrudes inferiorly into the vagina, is  the cervix.   The thick wall of the uterus is composed of three  layers. The inner layer, or mucosa, is the endometrium    Figure 16.8 The human female reproductive organs. (a) Sagittal section. (The plurals  of labium minus and majus are labia minora and majora, respectively.) (b) Posterior view.  The posterior organ walls have been removed on the right side to reveal the shape of the  lumen of the uterine tube, uterus, and vagina.    (en-do-me’tre-um). If fertilization occurs, the fertilized  egg (actually the young embryo by the time it reaches  the uterus) burrows into the endometrium, in a pro-  cess called implantation, and resides there for the rest  of its development. When a woman is not pregnant,  the endometrial lining sloughs off periodically, usually  about every 28 days, in response to changes in the  levels of ovarian hormones in the blood. This process,  called menstruation or menses, is often referred to as a  woman getting her “period” (discussed on p. 578).    Cervical cancer is relatively common among  women between the ages of 30 and 50. Risk factors  include sexually transmitted diseases such as human  papillomavirus (HPV), frequent cervical inflamma-  tion, multiple pregnancies, and many sexual part-  ners. Although HPV infection is a major cause of  cervical cancer, other factors may also be involved. A  yearly Pap smear is the single most important diag-  nostic test for detecting this slow-growing cancer.  When results are inconclusive, a test for HPV can be  done from the same Pap sample or from a blood  sample.   Gardasil, a three-dose vaccine that provides pro-  tection from the most common types of HPV-  induced cervical cancer, is a relatively recent addition  to the official childhood immunization schedule. It  is recommended for all 11- and 12-year-old girls but  can also be given to boys and girls ages 13 to 26. In  unexposed girls, the vaccine specifically blocks two  cancer-causing kinds of HPV as well as two addi-  tional types that are not associated with cervical  cancer. Whether or not this vaccine will become a  requirement for school is currently decided on a  state-to-state basis.    The bulky middle layer of the uterus wall is the  myometrium (mi-o-me'tre-um), which is com-  posed of interlacing bundles of smooth muscle (see  Figure 16.8b). The myometrium plays an active role  during childbirth, when it contracts rhythmically to  force the baby out of the mother’s body. The outer-  most serous layer of the uterus wall is the  perimetrium (per-i-me’tre-um), or the visceral  peritoneum.    Vagina  The vagina (vah-ji'nah) is a thin-walled tube 8 to 10 cm  (3 to 4 inches) long. It lies between the bladder and    rectum and extends from the cervix to the body exte-  rior (see Figure 16.8). Often called the birth canal,  the vagina provides a passageway for the delivery of  an infant and for the menstrual flow to leave the  body. Because it receives the penis (and semen) dur-  ing sexual intercourse, it is the female organ of  copulation.   The distal end of the vagina is partially closed by  a thin fold of the mucosa called the hymen (hi’men).  The hymen is very vascular and tends to bleed when  it is ruptured during the first sexual intercourse.  However, its durability varies. In some women, it is  torn during sports activity, tampon insertion, or  pelvic examination. Occasionally, it is so tough that  it must be ruptured surgically if intercourse is to  occur.   The female reproductive structures that are located  external to the vagina are the external genitalia  (Figure 16.9). The external genitalia, also called the  vulva, include the mons pubis, labia, clitoris, urethral  and vaginal orifices, and greater vestibular glands.   The mons pubis (“mountain on the pubis”) is a  fatty, rounded area overlying the pubic symphysis.  After puberty, this area is covered with pubic hair.  Running posteriorly from the mons pubis are two    elongated hair-covered skin folds, the labia majora  (la'be-ah ma-jo’ra), which enclose two delicate,  hair-free folds, the labia minora. The labia majora  enclose a region called the vestibule, which con-  tains the external openings of the urethra, * followed  posteriorly by that of the vagina.   Just anterior to the vestibule is the clitoris  (kli’to-ris; “hill”), a small, protruding structure that  corresponds to the male penis. Like the penis, it is  hooded by a prepuce and is composed of sensitive  erectile tissue that becomes swollen with blood dur-  ing sexual excitement. The clitoris differs from the  penis in that it lacks a reproductive duct.   A pair of mucus-producing glands, the greater  vestibular glands, flank the vagina, one on each  side (see Figure 16.8a). Their secretion lubricates  the distal end of the vagina during intercourse. The  diamond-shaped region between the anterior end  of the labial folds, the anus posteriorly, and the  ischial tuberosities laterally is the perineum  (per’i-ne’um).   12. Which organ of the female duct system serves as  an “incubator” for fetal development? What is the  most common site of fertilization?   13. What name is given to an ovarian follicle that is  ready to ovulate?    Although sperm production in men continues  throughout life, the production of eggs in women is  quite different. The total supply of eggs that a female  can release is already determined by the time she is  born. In addition, a female’s reproductive ability  (that is, her ability to release eggs) begins during  puberty, heralded by the beginning of her menstrual  cycle, and usually ends in her fifties. The period in  which a woman’s reproductive capability ends is  called menopause (see p. 595).    *Unlike the male urethra, which carries both urine and  semen, the female urethra has no reproductive function—  it is strictly a passageway for urine.    v Describe the influence of FSH and LH on ovarian  function.    Meiosis, the special kind of cell division that occurs  in the testes to produce sperm, also occurs in the  ovaries. But in this case, ova (female gametes) are  produced, and the process is called oogenesis (0"o-  jen’é-sis; “the beginning of an egg”). This process is  shown in Figure 16.10, p. 576.   In the developing female fetus, oogonia (0”o-  go'ne-ah), the female stem cells, multiply rapidly to  increase their number, producing daughter cells called  primary oocytes. These primary oocytes then push  into the ovary connective tissue, where they become  surrounded by a single layer of cells to ultimately  form the primordial follicles, which grow to become  primary follicles. By birth, the oogonia no longer  exist, and a female’s lifetime supply of primary oocytes  (approximately 1 to 2 million of them) is already in  place in the ovarian follicles, awaiting the chance to  undergo meiosis to produce functional eggs. Because  the primary oocytes remain in this state of suspended  animation all through childhood, their wait is a long  one—usually from 10 to 14 years. During this time,  the number of primary oocytes decreases to about  400,000 as a result of programmed cell death.   At puberty, the anterior pituitary gland begins to  release FSH (follicle-stimulating hormone), which  stimulates a small number of primary follicles to  grow and mature each month, and ovulation begins  to occur each month. These cyclic changes that occur  monthly in the ovary constitute the ovarian cycle.  At puberty, perhaps 400,000 oocytes remain; and,  beginning at this time, a small number of oocytes are  activated each month. As the reproductive life of a  female is about 40 years (from the age of 11 to  approximately 51), and there is typically only one  ovulation event per month, fewer than 500 ova out  of the potential 400,000 are released during her life-  time. Again, nature has provided us with a generous  oversupply of sex cells.   As a follicle prodded by FSH grows larger, it  accumulates fluid in the central chamber called the  antrum (look back at Figure 16.7), and the primary  oocyte it contains replicates its chromosomes and  begins meiosis. The first meiotic division produces    Birth to menopause  Primordial follicles  grow and develop;  before puberty, all  degenerate    two cells that are very dissimilar in size (see Figure  16.10). The larger cell is a secondary oocyte, and  the other, very tiny, cell is a polar body. By the time  a follicle has ripened to the mature (vesicular follicle)  stage, it contains a secondary oocyte and protrudes  from the external surface of the ovary. Follicle devel-  opment to this stage takes about 14 days, and ovula-  tion (of a secondary oocyte) occurs at just about that  time in response to the burstlike release of a second  anterior pituitary hormone, luteinizing hormone  (LH) (Figure 16.11). The ovulated secondary oocyte   Some women experience a twinge of abdominal  pain in the lower abdomen when ovulation occurs.  The precise cause of this phenomenon, called mittel-  schmerz (mit'el-shmerts; German for “middle pain”),  is unknown, but may include intense stretching of  the ovarian wall leading up to ovulation and irrita-  tion of the peritoneum by the small amount of  blood or fluid released by the ruptured follicle.    Figure 16.11 Ovulation. A secondary oocyte is  released from a follicle at the surface of the ovary. The  orange mass below the ejected oocyte is part of the  ovary. The “halo” of follicle cells around the secondary  oocyte is the corona radiata.    Generally speaking, one of the developing folli-  cles outstrips the others each month to become the  dominant follicle. Just how this follicle is selected or  selects itself is not understood, but the follicle that is  at the proper stage of maturity when the LH level  surges is the one that ovulates its oocyte. The mature  follicles that are not ovulated soon become overripe  and deteriorate. In addition to playing a major role  in triggering ovulation, LH also causes the ruptured  follicle to transform into a very different hormone-  producing structure, the corpus luteum. (Both the  maturing follicles and the corpus luteum produce  hormones, as we will describe later.)   If the ovulated secondary oocyte is fertilized by a  sperm in one of the uterine tubes, the oocyte quickly  completes the second meiotic division that produces  the ovum and another polar body. Once the ovum is  formed, its 23 chromosomes are combined with  those of the sperm to form the zygote. However, if a  sperm does not penetrate the secondary oocyte, it  simply deteriorates without ever completing meiosis  to form a functional egg. Although meiosis in males  results in four functional sperm, meiosis in females  yields only one functional ovum and three tiny polar  bodies. The polar bodies, produced to reduce the  number of chromosomes in the developing oocyte,  have essentially no cytoplasm, so they die quickly.   Another major difference between male and  female gametes concerns the size and structure of  these cells. Sperm are tiny and equipped with tails    for locomotion. They have little nutrient-containing  cytoplasm; thus, the nutrients in seminal fluid are  vital to their survival. In contrast, the egg is a large,  nonmotile cell, well stocked with nutrient reserves  that nourish the developing embryo until it can take  up residence in the uterus. The egg also supplies the  zygote with all of the cellular organelles each grow-  ing cell will need.    14. Besides the one functional gamete (ovum), what  other cell types are produced during oogenesis,  and what happens to them?   15. Which anterior pituitary hormone promotes follicle  development in the ovary?   As the ovaries become active at puberty and oocyte  production resumes, they also begin to produce ovar-  ian hormones. The follicle cells of the growing and  mature follicles produce estrogens,* which cause  the appearance of secondary sex characteristics in the  young woman. Such changes include the following:    e Enlargement of the accessory organs of the  female reproductive system (uterine tubes,  uterus, vagina, external genitals)   e Increased deposits of fat beneath the skin in  general, and particularly in the hips and breasts   Estrogen also has metabolic effects. For example,  it helps maintain low total blood cholesterol levels    at Figure 16.7). As mentioned earlier, after ovulation  occurs, the ruptured follicle is converted to the corpus  luteum, which looks and acts completely different    *Although the ovaries produce several different estrogens,  the most important are estradiol, estrone, and estriol. Of these,  estradiol is the most abundant and is most responsible for  estrogenic effects.    from the growing and mature follicle. Once formed,  the corpus luteum produces progesterone (and some  estrogen) as long as LH is still present in the blood.  Generally speaking, the corpus luteum stops produc-  ing hormones by 10 to 14 days after ovulation.  Except for working with estrogens to establish the  menstrual cycle, progesterone does not contribute to  the appearance of the secondary sex characteristics.  Its other major effects are exerted during pregnancy,  when it helps to maintain the pregnancy and prepare  the breasts for milk production. However, the main  source of progesterone after the second month of  pregnancy is the placenta, not the ovaries.    Although the young embryo implants and develops  in the uterus, this organ is receptive to implantation  only for a very short period each month. Not surpris-  ingly, this brief interval coincides exactly with the  time when a fertilized egg would begin to implant,  approximately 7 days after ovulation. The uterine  cycle, or menstrual cycle, is a series of cyclic  changes that the endometrium (mucosa of the  uterus) goes through each month as it responds to  changing blood levels of ovarian hormones.   The cyclic production of estrogens and progester-  one by the ovaries is, in turn, regulated by the ante-  rior pituitary gonadotropic hormones, FSH and LH.  It is important to understand how these “hormonal  pieces” fit together. Generally speaking, both female  cycles (the ovarian and the uterine cycles) are about  28 days long. Ovulation typically occurs midway in  the cycles, on or about day 14. Figure 16.12 illus-  trates the events of the ovarian cycle and the uterine  cycle at the same time.    e Days 0-4: Menstrual phase. During this inter-  val, the superficial functional layer of the thick  endometrial lining of the uterus is sloughing off  (detaching) from the uterine wall. The detached  tissues and blood pass through the vagina as  menstrual flow (the “period”) for 3 to 5 days.  The average blood loss during this period is 50  to 150 ml (or about 4 to 2 cup). By day 4,  growing ovarian follicles are beginning to pro-  duce more estrogens.    e Days 5-14: Proliferative phase. Stimulated by  a rising level of estrogens produced by the grow-  ing follicles of the ovaries, the basal layer of the  endometrium regenerates the functional layer,  glands form in it, and the endometrial blood  supply increases. The endometrium once again  becomes velvety, thick, and well vascularized.  (Ovulation occurs in the ovary at the end of this  stage, in response to the sudden surge of LH in  the blood.)    e Days 15-28: Secretory phase. A rising level of  progesterone production by the corpus luteum  acts on the estrogen-primed endometrium  and increases its blood supply even more.  Progesterone also causes the endometrial glands  to grow and begin secreting nutrients into the  uterine cavity. These nutrients will sustain a  developing embryo (if one is present) until it  has implanted. If fertilization does occur, the  embryo produces a hormone very similar to  LH that causes the corpus luteum to continue  producing its hormones until the placenta can  take over.    If fertilization does not occur, the corpus luteum  begins to degenerate toward the end of this period as  the LH blood level declines. Lack of ovarian hor-  mones in the blood causes the blood vessels supply-  ing the functional layer of the endometrium to go  into spasms and kink. When deprived of oxygen and  nutrients, those endometrial cells begin to die,  which sets the stage for menses to begin again on  day 28.   Although this explanation assumes a classic  28-day cycle, the length of the menstrual cycle is  quite variable. It can be as short as 21 days or as long  as 40 days. Only one interval is fairly constant in all  females—the time from ovulation to the beginning  of menses is almost always 14 or 15 days.    The mammary glands are present in both sexes, but  they normally function only in women. Because the  biological role of the mammary glands is to produce  milk to nourish a newborn baby, they are actually  important only when reproduction has already been    (a) Fluctuation of gonadotropin levels:  Fluctuating levels of pituitary  gonadotropins (follicle-stimulating  hormone and luteinizing hormone) in the  blood regulate the events of the ovarian  cycle.    Degenerating (b) Ovarian cycle: Structural changes in  corpus luteum vesicular ovarian follicles and the  corpus luteum are correlated with  & i changes in the endometrium of the  uterus during the uterine cycle (d). Only  vesicular (Graafian) follicles require  gonadotropic hormones for further  development. Primary and secondary  follicles develop in waves independent  of gonadotropins.   phases: phase (Day 14) phase  g (c) Fluctuation of ovarian hormone  2 levels: Fluctuating levels of ovarian  g hormones (estrogens and progesterone)  ° cause the endometrial changes of the  £ uterine cycle. The high estrogen levels  2 are also responsible for the LH/FSH  g surge in (a).  5  o    (d) The three phases of the uterine  cycle:  e Menstrual: The functional layer of the    Both the menstrual and proliferative phases  Menstrual phase occur before ovulation, and together they   correspond to the follicular phase of the  ovarian cycle. The secretory phase   Figure 16.12 Hormonal interactions of the female cycles. corresponds in time to the luteal phase of   The illustrations show the correlation between relative levels of the ovarian cycle.    Figure 16.13 Female mammary glands. (a) Anterior view. (b) Sagittal section.    accomplished. Stimulation by female sex hormones,  especially estrogens, causes the female mammary  glands to increase in size at puberty.   The mammary glands are modified sweat glands  that are part of the skin. Each mammary gland is  contained within a rounded skin-covered breast  anterior to the pectoral muscles. Slightly inferior to  the center of each breast is a pigmented area, the  areola (ah-re’o-lah), which surrounds a central pro-  truding nipple (Figure 16.13).   Internally, each mammary gland consists of 15  to 25 lobes that radiate around the nipple. The lobes  are padded and separated from one another by con-  nective tissue and fat. This connective tissue forms  suspensory ligaments, which anchor the breast to  surrounding tissues, including muscle and the    dermis. Within each lobe are smaller chambers  called lobules, which contain clusters of alveolar  glands that produce milk when a woman is lactat-  ing (producing milk). Milk produced by the alveolar  glands exits each lobule by passing into lactiferous  (lak-tif’er-us) ducts, which open to the outside at  the nipple. Just deep to the areola, each duct has a  dilated region called a lactiferous sinus, where    milk accumulates during nursing.  Homeostatic 3  £ Imbalance 16.7  Worldwide, breast cancer is the most common can-  cer in women and the first cause of female cancer  death. About one in twenty women will be diag-  nosed with breast cancer in their lifetime, although  this number varies significantly by country. Fewer  than 1 percent of breast cancers occur in men.   Some 10 percent of breast cancers stem from  hereditary defects, and half of these can be traced to    dangerous mutations in a pair of genes (BRCA1 and  BRCA2). Fifty to 80 percent of women who carry the  altered gene develop breast cancer. Risk factors  increasing the global breast cancer burden include  alcohol use, obesity, low physical activity, and  smoking.   Breast cancer is often signaled by a change in  skin texture, puckering, or leakage from the nip-  ple. Early detection by breast self-examination and  mammography is unquestionably the best way  to increase a woman’s chances of surviving breast  cancer. Most breast lumps are discovered by women  themselves during routine monthly breast exams.  Currently the American Cancer Society recom-  mends scheduling mammography—xX-ray exami-  nation that detects breast cancers too small to be  felt (less than 1 cm)—yearly for women between 45  and 54 years old and every 2 years thereafter if the  results are normal (Figure 16.14).    17. Which ovarian hormone promotes the formation  of female secondary sex characteristics?   18. What happens during the proliferative stage of the  uterine cycle?   19. What are three important functions of progester-  one in women?   Distinguish between an embryo and a fetus.  # List the major functions of the placenta.    Because the birth of a baby is such a familiar event,  we tend to lose sight of the wonder of this accom-  plishment. In every instance it begins with a single  cell, the fertilized egg, and ends with an extremely  complex human being consisting of trillions of cells.  The development of an embryo is very complex, and  the details of this process can fill a book. Our inten-  tion here is simply to outline the important events of  pregnancy and embryonic development.   Let's begin by defining some terms. The term  pregnancy refers to events that occur from the time  of fertilization (conception) until birth. The preg-  nant woman's developing offspring is called the  conceptus (kon-sep’tus; “that which is conceived”).  Development occurs during the gestation period    from the last menstrual period (a date the woman is  likely to remember) until birth, approximately  280 days.   From fertilization through week 8, the embryonic  period, the conceptus is called an embryo, and from  week 9 through birth, the fetal period, the conceptus  is called a fetus (“the young in the womb”).    Figure 16.15 Diagrams showing the approximate size of a human conceptus  from fertilization to the early fetal stage. Measurements indicate the length from    Figure 16.15 shows the changing size and shape of  the conceptus as it progresses from fertilization to  the early fetal stage. At birth, the fetus becomes an  infant.   For fertilization to occur, a sperm must reach the  ovulated secondary oocyte. The oocyte is viable for  12 to 24 hours after ovulation, and sperm generally  retain their fertilizing power within the female repro-  ductive tract for up to 5 days after ejaculation.  Consequently, for fertilization to occur, sexual inter-  course must occur no more than 2 days before ovu-  lation and no later than 24 hours after. At this point,  the oocyte is approximately one-third of the way  down the uterine tube. Remember that sperm are  motile cells that can propel themselves by rolling,  one-sided movements of their tails. If sperm are  deposited in a female's vagina at the approximate  time of ovulation, they are attracted to the oocyte by  chemicals that act as “homing devices,” allowing  them to locate the oocyte.    toward or away from a stimulus (positive and negative  chemotaxis, respectively) (Chapter 12, p. 422).    It takes 1 to 2 hours for sperm to complete the  journey up the female duct system into the uterine  tubes, even though they are only about 12 cm  (5 inches) away. However, millions of sperm leak out  of the vagina, and of those remaining, millions more  are destroyed by the vagina’s acidic environment.  Only a few hundred to a few thousand sperm make  it to the ege’s vicinity.   When the swarming sperm reach the oocyte  (Figure 16.16), their cell surface hyaluronidase  enzymes break down the “cement” that holds the  follicle cells of the corona radiata together around  the oocyte. Once a path has been cleared through the  corona, thousands of sperm undergo the acrosomal  reaction, in which the acrosome membranes break  down, releasing enzymes that digest holes in the sur-  rounding oocyte membrane. Then, when the    membrane is adequately weakened and a single  sperm makes contact with one of the oocyte’s mem-  brane receptors for sperm, the head (nucleus) of the  sperm fuses with the oocyte membrane, and the  snakelike sperm contents enter the oocyte cyto-  plasm. This is one case that does not bear out the  adage “The early bird catches the worm,” because  sperm that are in the best position to be the fertiliz-  ing sperm are the ones that come along after hun-  dreds of sperm have undergone acrosomal reactions  to expose the oocyte membrane. Once a single sperm  has penetrated the oocyte, the oocyte nucleus com-  pletes the second meiotic division, forming the  ovum and a polar body.   In humans, of the millions of sperm ejaculated,  only one can penetrate an oocyte. The ovum sheds its  remaining membrane surface receptors for sperm,  preventing more sperm from gaining entry.  Fertilization occurs at the moment the genetic  material of a sperm combines with that of an ovum  to form a fertilized egg, or zygote (zi’got), with a  complete set of 46 chromosomes. The zygote repre-  sents the first cell of the new individual.   As the zygote journeys down the uterine tube (pro-  pelled by peristalsis and cilia), it begins to undergo  rapid mitotic cell divisions—forming first two cells,  then four, and so on. This early stage of embryonic  development is called cleavage (Figure 16.17, p. 584).    Because there is not much time for cell growth  between divisions, the daughter cells become smaller  and smaller. Cleavage provides a large number of  cells to serve as building blocks for constructing the  embryo. Consider for a moment how difficult it  would be to construct a building from one huge  block of granite. If you now consider how much eas-  ier your task would be if you could use hundreds of  brick-sized granite blocks, you will quickly grasp the  importance of cleavage.   By the time the developing embryo reaches the  uterus (about 3 days after ovulation, or on day 17 of  the woman’s cycle), it is a morula, a tiny ball of 16  cells that looks like a microscopic raspberry. The  uterine endometrium is still not fully prepared to  receive the embryo at this point, so the embryo floats  free in the uterine cavity, temporarily using the uter-  ine secretions for nutrition. While still unattached,  the embryo continues to develop until it has about  100 cells, and then it hollows out to form a ball-like  structure called a blastocyst (blas’to-sist). At the  same time, it secretes an LH-like hormone called  human chorionic gonadotropin (hCG), which  prods the corpus luteum of the ovary to continue  producing its hormones. (If this were not the case,  the functional layer of the endometrium would be  sloughing off shortly in menses.) Many home preg-  nancy tests detect hCG in urine.   The blastocyst has two important functional  areas: the trophoblast, which forms the large fluid-  filled sphere, and the inner cell mass, a small clus-  ter of cells on one side (see Figure 16.17e). By day 7  after ovulation, the blastocyst has attached to the  endometrium and has eroded away the lining in a  small area, embedding itself in the thick velvety  mucosa. All of this is occurring even while develop-  ment is continuing and the three primary germ lay-  ers are being formed from the inner cell mass  (Figure 16.18, p. 585). The primary germ layers are the  ectoderm (which will become the nervous system  and the epidermis of the skin), the endoderm  (which forms mucosae and associated glands), and  the mesoderm (which will become virtually every-  thing else). Implantation has usually been com-  pleted and the uterine mucosa has grown over the  burrowed-in embryo by day 14 after ovulation—the  day the woman would ordinarily be expecting to  start her period (menses).   After it is securely implanted, the trophoblast  part of the blastocyst develops elaborate projections,  called chorionic villi, which combine with the    Figure 16.17 From fertilization  and cleavage to implantation.  Cleavage is a rapid series of mitotic  divisions that begins with the zygote  and ends with the blastocyst. The  zygote begins to divide about    tissues of the mother’s uterus to form the placenta  (plah-sen’tah) (Figure 16.19). Once the placenta has  formed, the platelike embryonic body, now sur-  rounded by a fluid-filled sac called the amnion    24 hours after fertilization and  continues to divide rapidly (undergo  cleavage) as it travels down the  uterine tube. The embryo reaches  the uterus 3 to 4 days after ovula-  tion and floats freely for another    (e) Implanting  blastocyst  (consists of a sphere  of trophoblast cells  and an eccentric  cell cluster called  the inner cell mass)  7 days    (d) Early blastocyst  (morula hollows out  and fills with fluid)  4 days    2 to 3 days, nourished by secretions  of the endometrial glands. At the  late blastocyst stage, the embryo  implants into the endometrium;  this begins at about day 7 after  ovulation.    (am’ne-on), is attached to the placenta by a blood  vessel-containing stalk of tissue, the umbilical cord  (see Figure 16.19). (We discussed the special features  of the umbilical blood vessels and fetal circulation in  Chapter 11.)   Generally by the third week, the placenta is func-  tioning to deliver nutrients and oxygen to and  remove wastes from the embryonic blood. All  exchanges are made through the placental barrier. By  the end of the second month of pregnancy, the pla-  centa has also become an endocrine organ and is    Figure 16.18 Embryo of approximately 18 days. At this stage of development,    producing estrogens, progesterone, and other hor-  mones that help to maintain the pregnancy. At this  time, the corpus luteum of the ovary becomes inac-  tive and degenerates.    Figure 16.19 The 7-week embryo. A 7-week embryo,  encased in its amniotic sac, and the chorionic villi (to the  right), which cooperate with maternal uterine tissues to  form the placenta.    By the eighth week of embryonic development,  all the groundwork has been completed. All the  organ systems have been laid down, at least in rudi-  mentary form, and the embryo looks distinctly  human. Beginning in the ninth week of develop-  ment, we refer to the embryo as a fetus. From this  point on, the major activities are growth and organ  specialization, accompanied by changes in body  proportions. During the fetal period, the developing  fetus grows from a crown-to-rump length of about 3  cm (slightly more than 1 inch) and a weight of  approximately 1 g (0.03 ounce) to about 36 cm  (14 inches) and 2.7 to 4.1 kg (6 to 10 pounds) or  more. (Total body length at birth is about 55 cm, or  22 inches.) As you might expect with such tremen-  dous growth, the changes in fetal appearance are  quite dramatic (Figure 16.20, p. 587). The most  significant of these changes are summarized in  Table 16.1 on pp. 586-587. By approximately    270 days after fertilization, the fetus is said to be 16    21. How does cleavage differ from cell divisions  occurring after birth?  22. What are three roles of the placenta?  For answers, see Appendix A.    Limbs present; though initially webbed, fingers and toes are free  8 weeks by the end of this interval   All body systems present in at least rudimentary form  Approximate crown-to-rump length: 22 mm (0.9 inch); weight:  2 grams (0.07 ounce)    Approximate crown-to-rump length at end of interval: 90 mm (9 cm)    General sensory organs are present; eyes and ears assume  characteristic position and shape; blinking of eyes and sucking  motions of lips occur    Approximate crown-to-rump length at end of interval: 140 mm  (14 cm)    17-20 weeks Vernix caseosa (fatty secretions of sebaceous glands) covers body;  (fifth month) silklike hair (lanugo) covers skin    Approximate crown-to-rump length at end of interval: 190 mm  21-30 weeks Substantial increase in weight (may survive if born prematurely at  (sixth and 27-28 weeks, but hypothalamus still too immature to regulate   Skin is wrinkled and red; fingernails and toenails are present  Body is lean and well proportioned    4 List several agents that can interfere with normal  fetal development.    The period from conception to birth can be a diffi-  cult time for the mother. Pregnancy causes not only  obvious anatomical changes in the mother, but also  striking changes in her physiology.    Approximate crown-to-rump length at end of interval: 360 mm  (14 inches); weight: 3.2 kg (7 pounds)    The ability of the uterus to enlarge during pregnancy  is nothing less than remarkable. Starting as a fist-  sized organ, the uterus grows to occupy most of the  pelvic cavity by 16 weeks. As pregnancy continues,  the uterus pushes higher and higher into the abdom-  inal cavity ( , p. 588). As birth nears, the  uterus reaches the level of the xiphoid process and  occupies the bulk of the abdominal cavity. The  crowded abdominal organs press superiorly against  the diaphragm, which intrudes on the thoracic cavity.  As a result, the ribs flare, causing the thorax to widen.    Examples of fetal development. (a) Fetus in month 3, about  6 cm a (2. 5 inches) long. (b) Fetus late in month 5, about 19 cm (8 inches) long.    (a) Before conception  (Uterus is the size of a fist  and resides in the pelvis.)    (c) 7 months (d) 9 months  (Fundus is well above (Fundus reaches  the umbilicus.) the xiphoid    Figure 16.21 Relative size of the uterus before conception and during pregnancy.    The increasing bulkiness of the abdomen  changes the woman’s center of gravity, and many  women develop an accentuated lumbar curvature  (lordosis), often accompanied by backaches, during  the last few months of pregnancy. Placental produc-  tion of the hormone relaxin causes pelvic ligaments  and the pubic symphysis to relax, widen, and  become more flexible. This increases the width of the  birth canal to ease birth passage, but it may also  result in a waddling gait during pregnancy.   Good maternal nutrition is necessary through-  out pregnancy if the developing fetus is to have all  the building materials (proteins, calcium, iron, and  the like) to form its tissues and organs. The old  expression “A pregnant woman is eating for two” has  encouraged many women to eat twice the amount of  food actually needed during pregnancy, which, of  course, leads to excessive weight gain. Actually, a  pregnant woman needs only about 300 additional  calories daily to sustain proper fetal growth. The  emphasis should be on high-quality nutrition, not    through the placental barrier into the fetal blood;  therefore, a pregnant woman should be very aware    of what she is taking into her body. Substances that  may cause life-threatening birth defects (and even  fetal death) include alcohol, nicotine, and many  types of drugs (anticoagulants, antihypertensives,  sedatives, and some antibiotics). Maternal infec-  tions, particularly German measles (rubella), may  also cause severe fetal damage. Natural termination  of a pregnancy before a fetus can survive on its own  is called miscarriage. A medical termination of a  pregnancy is called abortion.    Gastrointestinal System Many women suffer nau-  sea, commonly called morning sickness, during the  first few months of pregnancy, until their system  adjusts to the elevated levels of progesterone and  estrogens. Heartburn is common because the esoph-  agus is displaced and the stomach is crowded by the  growing uterus, which favors reflux of stomach acid  into the esophagus. Another problem is constipation  due to decline in motility of the digestive tract dur-    Urinary System The kidneys have the additional  burden of disposing of fetal metabolic wastes, and  they produce more urine during pregnancy. Because  the uterus compresses the bladder, urination    becomes more frequent, more urgent, and some-  times uncontrollable. The last condition is called  stress incontinence.    Respiratory System The nasal mucosa responds to  estrogens by becoming swollen and congested; thus,  nasal stuffiness and occasional nosebleeds may  occur. Vital capacity and respiratory rate increase  during pregnancy, but residual volume declines, and  many women exhibit dyspnea (difficult breathing)  during the later stages of pregnancy.    Cardiovascular System Perhaps the most dramatic  physiological changes occur in the cardiovascular  system. Total body water rises, and blood volume  increases by 25 to 40 percent to accommodate the  additional needs of the fetus. The rise in blood  volume also acts as a safeguard against blood loss  during birth. Blood pressure and pulse typically rise  and increase cardiac output by 20 to 40 percent; this  helps propel the greater blood volume around the  body. Because the uterus presses on the pelvic blood  vessels, venous return from the lower limbs may be  impaired somewhat, resulting in varicose veins or  swollen ankles and feet.    v@ Describe how labor is initiated, and briefly discuss  the three stages of labor.    Childbirth, also called parturition (par’tur-ish’un;  “bringing forth young”), is the culmination of preg-  nancy. It usually occurs within 15 days of the calcu-  lated due date (which is 280 days from the last  menstrual period). The series of events that expel the  infant from the uterus is referred to as labor.    Several events work together to trigger labor. During  the last few weeks of pregnancy, estrogens reach their  highest levels in the mother’s blood. This has two  important consequences: it causes the myometrium  to form abundant oxytocin receptors (so that it  becomes more sensitive to the hormone oxytocin),  and it interferes with progesterone’s quieting influ-  ence on the uterine muscle. As a result, weak, irregu-  lar uterine contractions begin to occur. These  contractions, called Braxton Hicks contractions, have  caused many women to go to the hospital, only to be  told that they were in false labor and sent home.    As birth nears, two more chemical signals coop-  erate to convert these false labor pains into the real  thing. Certain cells of the fetus begin to produce oxy-  tocin, which in turn stimulates the placenta to  release prostaglandins. Both hormones stimulate  more frequent and powerful contractions of the  uterus. At this point, the increasing emotional and  physical stresses activate the mother’s hypothalamus,  which signals for oxytocin release by the posterior  pituitary. The combined effects of rising levels of  oxytocin and prostaglandins initiate the rhythmic,  expulsive contractions of true labor. Once the hypo-  thalamus is involved, a positive feedback mecha-  nism is propelled into action: stronger contractions  cause the release of more oxytocin, which causes  even more vigorous contractions, forcing the baby  ever deeper into the mother’s pelvis (Figure 16.22,  p. 590).    Chapter 1, p. 41). A stimulus triggers a receptor, the  information is sent to the brain for processing, and a  signal is sent to an effector with instructions for a  response. Most of the feedback in the body is negative  feedback, in which the response decreases the initial  stimulus. Labor, however, involves positive feedback:  The response (stronger contractions) actually increases  the initial stimulus (oxytocin release) until the child  is born.    Because both oxytocin and prostaglandins are  needed to initiate labor, anything that interferes with  production of either of these hormones will hinder  the onset of labor. For example, antiprostaglandin  drugs such as aspirin and ibuprofen can inhibit  labor at the early stages, and such drugs are used  occasionally to prevent premature births.    The process of labor is commonly divided into three  stages (Figure 16.23, p. 590).    Stage 1: Dilation Stage The dilation stage is the  time from the appearance of true contractions until  the cervix is fully dilated by the baby’s head (about  10 cm in diameter). As labor starts, regular but weak  uterine contractions begin in the upper part of the  uterus and move inferiorly toward the vagina.  Gradually, the contractions become more vigorous  and more rapid, and, as the infant's head is forced    (4) Hypothalamus sends efferent  impulses to posterior pituitary,  where oxytocin is stored    Figure 16.22 Oxytocin promotes labor contractions  during birth by a positive feedback mechanism.    against the cervix with each contraction, the cervix  begins to soften, becomes thinner (effaces), and  dilates. Eventually, the amnion ruptures, releasing  the amniotic fluid, an event commonly referred to  as the woman’s “water breaking.” The dilation stage  is the longest part of labor and usually lasts for 6 to  12 hours or more.    Stage 2: Expulsion Stage The expulsion stage is  the period from full dilation to delivery of the infant.  In this stage, the infant passes through the cervix and  vagina to the outside of the body. During this stage,  a mother experiencing natural childbirth (that is,  undergoing labor without local anesthesia) has an    increasing urge to push, or bear down, with the  abdominal muscles. Although this phase can take as  long as 2 hours, it is typically 50 minutes in a first  birth and around 20 minutes in subsequent births.   When the infant is in the usual head-first (vertex)  position, the skull (its largest diameter) acts as a  wedge to dilate the cervix. The head-first presenta-  tion also allows the baby to be suctioned free of  mucus and to breathe even before it has completely  exited from the birth canal. Once the head has been  delivered, the rest of the baby’s body is delivered  much more easily. After birth, the umbilical cord is  clamped and cut. In breech (buttocks-first) presenta-  tions and other nonvertex presentations, these  advantages are lost and delivery is often much more  difficult, sometimes requiring the use of forceps or a  vacuum extractor.    Homeostatic J  —S Imbalance 16.9  During an extremely prolonged or difficult stage 2, a  condition called dystocia (dis-to’se-ah) may occur.  In dystocia, oxygen delivery to the infant is inad-  equate, leading to fetal brain damage (resulting in  cerebral palsy or epilepsy) and decreased viability of  the infant. To prevent these outcomes, a cesarean  (se-zayr’e-an) section, also called a C-section, may  be performed. A C-section is delivery of the infant  through a surgical incision made through the abdom-  inal and uterine walls.    Stage 3: Placental Stage ‘The placental stage, or  the delivery of the placenta, is usually accomplished  within 15 minutes after birth of the infant. The  strong uterine contractions that continue after birth  compress uterine blood vessels, limit bleeding, and  cause the placenta to detach from the uterine wall.  The placenta and its attached fetal membranes, col-  lectively called the afterbirth, are then easily  removed by a slight tug on the umbilical cord. All  placental fragments must be removed to prevent  continued uterine bleeding after birth (postpartum  bleeding).    23. Explain how pregnancy affects a woman's respira-  tory and digestive processes.  24. What are the three stages of labor?  For answers, see Appendix A.    1# Describe the importance of the presence/absence  of testosterone during embryonic development of  the reproductive system organs.   1# List common reproductive system problems seen  in adult and aging men and women.    Although the genetic sex of an individual is deter-  mined at the time of fertilization (males have X and  Y sex chromosomes and females have two X sex  chromosomes), the gonads do not begin to form  until about the eighth week of embryonic develop-  ment. Prior to this time, the embryonic reproductive  structures of males and females are identical and are  said to be in the indifferent stage.   At the sixth week of development, a complex  dance between genes and hormones drives the  development of primary sexual organs. In male  embryos, a gene on the Y chromosome promotes tes-  ticle development; its absence favors ovary growth.  The testes produce testosterone, which stimulates the  growth of male genitalia, whereas the absence of tes-  tosterone results in the development of female  genitalia.   After the gonads have formed, development of  the accessory structures and external genitalia begins.  Whether male or female structures will form depends  entirely on whether testosterone is present or absent.  The usual case is that, once formed, the embryonic  testes produce testosterone, and the development of  the male duct system and external genitalia follows.  When testosterone is not produced, as is the case in  female embryos that form ovaries, the female ducts  and external genitalia result.    Homeostatic J  K Imbalance 16.10  Any interference with the normal pattern of sex hor-  mone production in the embryo results in abnor-  malities. For example, if the embryonic testes fail to  produce testosterone, a genetic male develops the  female accessory structures and external genitalia. If  a genetic female is exposed to testosterone (as might  happen if the mother has an androgen-producing  tumor of her adrenal gland), the embryo has ovaries  but develops male accessory ducts and glands, as  well as a penis and an empty scrotum. Individuals   traception, is dependability. As  shown by the red arrows in the  accompanying flowchart, the birth  control techniques and products cur-  rently available provide many options    uct in the United States is the birth  control pill, or simply, “the pill.” It  contains tiny amounts of estrogens  and progestins (progesterone-like    Learn more at Mastering A&P > Study Area >  Additional Study Tools > A Closer Look    hormones), except that for the last 7  days of the 28-day cycle the tablets  are hormone-free. The relatively con-  stant blood levels of ovarian hormones  make it appear that the woman is  pregnant. Ovarian follicles do not  mature, ovulation ceases, and men-  strual flow is much reduced. The inci-  dence of failure is less than 1 percent.  A different combination hormone  pill, the morning-after pill (WAP) or  emergency contraceptive pill (EQ), is    Flowchart of points at which the events that must occur to produce a baby  can be interrupted. Techniques or products that interfere with this process are  indicated by red arrows at the site of interference; they act to prevent the next step.    the therapy of choice for rape victims  and is now available over the counter.  Taken within 3 days of unprotected  intercourse, the concentrated estrogen-  progesterone combination pills “mess  up” the normal hormonal signals so  much that fertilization is prevented  altogether or a fertilized egg is pre-  vented from implanting.   Sterilization techniques, such as  tubal ligation and vasectomy (cutting  or cauterizing the uterine tubes or  ductus deferens, respectively), are  nearly foolproof.   Barrier methods, such as dia-  phragms and condoms are quite  effective, especially when used by  both partners. But many people avoid  them because they can reduce the  spontaneity of sexual encounters.   In the final analysis, however, the  only 100 percent effective means of  birth control is the age-old one—  abstinence.    e Dependability and proper, timely  use are the most important  aspects of birth control.    e The “pill” is the most common  contraceptive. It prevents ovula-  tion by providing prescribed  hormone levels over 28 days  and has a failure rate of less  than 1 percent when taken as  directed.    e Barrier methods, such as con-  doms, work but interfere with  spontaneity, so they are often  not used.    e Abstinence is the only 100 per-  cent effective method of birth  control.    with external genitalia that do not “match” their  gonads are called pseudohermaphrodites (su"do-  her-maf'ro-ditz) to distinguish them from true  hermaphrodites, rare individuals who possess both  ovarian and testicular tissues. In recent years, many  pseudohermaphrodites have sought sex change  operations to match their outer selves (external gen-  italia) with their inner selves (gonads).   Additionally, abnormal separation of chromo-  somes during meiosis can lead to congenital defects  of this system. For example, males who have an extra  female sex chromosome (XXY) have the normal  male accessory structures, but their testes atrophy,  causing them to be sterile. Other abnormalities occur  when a child has only one sex chromosome. An XO  female appears normal but lacks ovaries; YO males  die during development. Other, much less serious,  conditions affect males primarily; these include  phimosis (fi-mo’sis), which essentially is a narrow-  ing of the foreskin of the penis, and misplaced ure-  thral openings.   The male testes, formed in the abdominal cavity  at approximately the same location as the female  ovaries, descend to enter the scrotum about one  month before birth. Failure of the testes to make  their normal descent leads to a condition called  cryptorchidism (krip-tor’ki-dizm). Because this  condition results in sterility of a male (and also puts  him at risk for cancer of the testes), surgery is usually  performed during childhood to rectify this problem.    Because the reproductive system organs do not  function until puberty, there are few problems with  this system during childhood. Puberty is the period  of life, generally between the ages of 10 and 15 years,  when the reproductive organs grow to their adult size  and become functional under the influence of rising  levels of gonadal hormones (testosterone in men and  estrogens in women). After this time, reproductive  capability continues until old age in men and meno-  pause in women. Earlier we described the secondary  sex characteristics and major events of puberty, so we  will not repeat these details here. It is important to  remember, however, that puberty represents the ear-  liest period of reproductive system activity.   The events of puberty occur in the same sequence  in all individuals, but the age at which they occur var-  ies widely. In boys, the event that signals puberty’s  onset is enlargement of the testes and scrotum,  around the age of 13 years, followed by the appear-  ance of pubic, axillary, and facial hair. Growth of the    penis goes on over the next 2 years, and sexual matu-  ration is indicated by the presence of mature sperm in  the semen. In the meantime, the young man has  unexpected erections and occasional nocturnal emis-  sions (“wet dreams”) as his hormones surge and hor-  monal controls struggle to achieve a normal balance.   The first sign of puberty in girls is budding  breasts, often apparent by the age of 11 years. The  first menstrual period, called menarche (mé-  nar’ke), usually occurs about 2 years later.  Dependable ovulation and fertility are deferred until  the hormonal controls mature, an event that takes  nearly 2 more years.    Homeostatic J  —S Imbalance 16.11  In adults, the most common reproductive system  problems are infections. Vaginal infections are more  common in young and elderly women and in  women whose immune resistance is low. Common  infections include those caused by Escherichia coli  (spread from the digestive tract); sexually transmit-  ted microorganisms (such as gonorrhea, syphilis,  and genital warts); and yeasts (a type of fungus).  Untreated vaginal infections may spread throughout  the female reproductive tract, causing pelvic inflam-  matory disease and sterility. Problems involving  painful or abnormal menses may result from infec-  tion or hormone imbalance.   The most common inflammatory conditions in  men are urethritis, prostatitis, and epididymitis  (ep’i-did-i-mi’tis), all of which may follow sexual  contacts in which sexually transmitted microorgan-  isms are transmitted. Orchitis (or’ki’ tis), inflamma-  tion of the testes, is rather uncommon but is serious  because it can cause sterility. Orchitis most com-  monly follows sexually transmitted infection (STI)  or mumps in an adult man.   As noted earlier, neoplasms represent a major  threat to reproductive system organs. Tumors of the  breast and cervix are the most common reproductive  cancers in adult women, and prostate cancer (a com-  mon sequel to prostatic hypertrophy) is a wide-  spread problem in adult men.    Most women reach peak reproductive abilities in  their late twenties. After that, a natural decrease in  ovarian function occurs. As production of estrogens  declines, ovulation becomes irregular, and menstrual  periods become scanty and shorter in length.  Eventually, ovulation and menses cease entirely,    e Sex hormones masculinize or feminize  the brain and influence sex drive    e Gonadal hormones exert  feedback effects on  hypothalamic-pituitary axis;  placental hormones help to  maintain pregnancy    e Late stages of pregnancy impair  descent of the diaphragm, causing  difficult breathing   e Respiratory system provides oxygen;  disposes of carbon dioxide; vital  capacity and respiratory rate increase  during pregnancy    e Estrogens lower blood cholesterol  levels and promote cardiovascular  health in premenopausal women;  pregnancy increases workload of the  cardiovascular system   e Cardiovascular system transports  needed substances to organs of  reproductive system; local  vasodilation is involved in erection;  blood transports sex hormones    e Male sex hormones (androgens)  activate oil glands, which lubricate skin  and hair; gonadal hormones stimulate  characteristic fat distribution and  appearance of pubic and axillary hair;  estrogen increases skin hydration;  enhances facial skin pigmentation  during pregnancy    e Hypertrophy of the prostate  inhibits urination; compression of  bladder during pregnancy leads to  urinary frequency and urgency   balance of blood of mother and  fetus; semen exits the body  through the urethra of the male   muscle mass  e Abdominal muscles are active during  childbirth; muscles of the pelvic floor  support reproductive organs and aid  erection of penis/clitoris    e Androgens masculinize the skeleton  and increase bone density; estrogen  feminizes skeleton and maintains bone  mass in women   e The bony pelvis encloses some  reproductive organs; if narrow, the  bony pelvis may hinder vaginal delivery  of an infant    ending childbearing ability. This event, called  menopause, normally occurs between the ages of 46  and 54 years. A woman is said to have reached  menopause when she has gone a whole year without  menstruation.   Although production of estrogens continues for  a while after menopause, the ovaries eventually stop  functioning as endocrine organs. When deprived of  the stimulatory effects of estrogens, the reproductive  organs and breasts begin to atrophy. The vagina  becomes dry; intercourse may become painful (par-  ticularly if infrequent), and vaginal infections  become increasingly common. Other consequences  of the deficit of estrogens include irritability and  other mood changes (depression in some); intense  vasodilation of the skin’s blood vessels, which causes  uncomfortable sweat-drenching “hot flashes”; grad-  ual thinning of the skin and loss of bone mass; and  slowly rising blood cholesterol levels, which place  postmenopausal women at risk for cardiovascular  disorders. At one time, physicians prescribed low-  dose estrogen-progesterone preparations to help  women through this often difficult period and to  prevent the skeletal and cardiovascular complica-  tions. These seemed like great bonuses until  July 2002, when the Women’s Health Initiative (WHI)  abruptly ended a clinical trial of 16,000 postmeno-  pausal women, reporting that those taking a popular  estrogen—progesterone hormone combination expe-  rienced an increase of 51 percent in heart disease, 24  percent in invasive breast cancer, 31 percent in stroke,  and a doubling of the risk of dementia compared to  those taking placebos. The backlash of this informa-  tion has dampened enthusiasm for hormone  replacement therapy (HRT).    e The reproductive systems of men and women  become active at puberty; the gonads, or primary  sex organs, produce gametes and secrete hor-  mones; all other reproductive structures are con-  sidered accessory reproductive organs   e The purpose of the reproductive system is to pro-  duce offspring; men produce sperm; women pro-  duce ova, or eggs    In 2011, the American Association of Clinical  Endocrinologists published clinical guidelines  acknowledging that HRT (estrogen alone or a com-  bination of estrogen and progesterone) may be an  appropriate treatment for the relief of severe meno-  pausal symptoms. However, this recommendation  was accompanied by stringent guidelines to balance  the risks and rewards of such treatments for each  individual patient. Major risks of HRT include heart  disease, stroke, blood clots, and breast cancer. At  present, quality-of-life considerations take into  account patient age, symptom severity, and repro-  ductive health. HRT does seem to bestow a benefit  for many patients, provided they take the lowest  effective dose, continue to make healthy life choices  (no smoking), and begin HRT before age 60 or  within 10 years of reaching menopause.   There is no equivalent of menopause in males.  Although aging men exhibit a steady decline in tes-  tosterone secretion and a longer latent period after  orgasm, a condition called andropause, their repro-  ductive capability continues until death. Healthy  men well into their eighties and beyond are able to  father offspring.    25. Which sex chromosome combination yields a  boy—XX or XY? What hormone must be produced  by an XY fetus during development to stimulate  the formation of the male duct system?   26. What is cryptorchidism, and what results if it is not  rectified?   27. What are the major health threats to the adult  woman's reproductive system?    A A) Listen to the story of this chapter in a brief summary at Mastering A&P >  Ii Study Area > Author Narrated Audio Summaries    e The paired testes are the primary reproductive  organs of males; they attach to the trunk via the  spermatic cord, a bundle enclosing nerves,  blood vessels, and the ductus deferens    Each testis is divided into lobules that contain  several seminiferous tubules, where sperm are  produced; between them are interstitial cells  that produce testosterone    ° After production, sperm travel through the rete  testis to the epididymis    The duct system transports sperm from the body  and includes the epididymis, ductus deferens, and  urethra    After sperm are produced, they enter the epididy-  mis, where they mature further and develop the  ability to swim over about 20 days; a man  ejaculates sperm from the epididymis    The ductus deferens (formerly called the vas def-  erens) carries sperm from the epididymis to the  ampulla (enlarged end of the ductus deferens);  the ampulla empties into the ejaculatory duct,  which passes through the prostate to join the  urethra    ° Sperm are still produced in men who have a  vasectomy; the ductus deferens is cut, so sperm  cannot leave the body and are eventually  phagocytized    Paired seminal vesicles produce a thick, yellow  secretion rich in sugar, vitamin C, and prostaglan-  dins to nourish and activate sperm; makes up 60  percent of seminal fluid (the liquid portion of  semen)    ° Hypertrophy of the prostate can lead to cystitis  (bladder infection) and urinary retention    o Inflammation of the prostate is prostatitis;  prostate cancer is the third most common  cancer in men    Paired bulbourethral glands produce clear  mucus that leaves the body before sperm to  neutralize residual urine in the urethra    Semen is the mixture of accessory gland secretions  and sperm; the fluids feed, protect, and dilute  sperm as they leave the body and enter the female  reproductive tract    ° The scrotum—houses the testes outside the  body at a slightly lower temperature, ideal for  sperm production    ° The penis—delivers sperm to the female repro-  ductive tract; consists of a shaft, glans penis  (enlarged tip), prepuce (or foreskin), and  erectile tissues  = The foreskin is often removed shortly after    Spermatogenesis is sperm production; it be-  gins with stem cells called spermatogonia that  divide, each forming a stem cell and a primary  spermatocyte, which undergoes meiosis to form  spermatids  o Spermatids have 23 chromosomes  Spermiogenesis is the process by which a sper-  matid develops into a fully formed sperm; excess  cytoplasm is lost, and shape is streamlined  ° The acrosome covers the head of the sperm  and contains digestive enzymes to help pene-  trate the egg   o Testosterone is also responsible for the develop-  ment of secondary sex characteristics, such  as deepening voice, increased hair growth, and  increased muscle mass    The female reproductive role is much more com-  plex than that of the male    Ovaries are the primary reproductive organs  that produce ova, or eggs; they contain ovarian  follicles that each contain a developing oocyte  surrounded by follicle cells    A vesicular follicle (or Graafian follicle), is  mature and will leave the ovary during ovulation;  the ruptured follicle becomes a hormone-producing  corpus luteum    e Ovaries are held in place by suspensory  ligaments, ovarian ligaments, and the  broad ligament    e The uterine tubes, uterus, and vagina make up the  female duct system    e The uterus receives, retains, and nurtures the fer-  tilized egg and also participates in childbirth;  it is held in place by the broad ligament, round  ligaments, and uterosacral ligaments    ° The region of the uterus superior to the uterine  tubes is the fundus; the main portion is the  body; the narrow outlet protruding into the  vagina is the cervix    ° The wall of the uterus includes the perime-  trium, myometrium, and endometrium    e The vagina is the female copulatory organ  and the birth canal; it is partially closed by the  hymen, though a variety of activities can cause it  to rupture    e The external genitalia, or vulva, include repro-  ductive structures located exterior to the vagina:  mons pubis, labia majora, labia minora,  vestibule, clitoris, greater vestibular glands,  and the perineum    e Girls are born with the total supply of ova they  will have; fertility begins at puberty and ends at  menopause    e Oogenesis is the production of eggs; it begins  with stem cells (oogonia) that produce primary  oocytes   e At puberty, the ovarian cycle begins; each month  a few follicles begin to develop in response to  follicle-stimulating hormone (FSH); typically  one becomes dominant    o° After meiosis I, a secondary oocyte and polar  body are formed; polar bodies are small, con-  tain little cytoplasm, and are produced for the  purpose of reducing chromosome number    completed to form an ovum only if the secondary  oocyte is fertilized    puberty; estrogen is the main female sex hor-  mone and is produced by follicle cells    ° Estrogen drives the ovarian cycle and stimulates  secondary sex characteristics, such as breast  development, growth of axillary and pubic hair,  increased fat deposits, widening and lightening  of the pelvis, and menses; also has metabolic  effects    16.4c. Uterine (menstrual) cycle  e The uterine cycle (or menstrual cycle) includes    cyclic changes to the endometrium of the uterus  in response to changing ovarian hormone levels  in the blood    ° Proliferative phase—when the endometrium  begins to regenerate, glands form in it, and  blood supply increases    ization has occurred the corpus luteum degener-  ates, causing progesterone levels to decline;  endometrial lining is shed as blood vessels kink  in response to low ovarian hormone levels    function in milk production only in females; they  are modified sweat glands    Each breast has a pigmented area (areola) around  the nipple; when a woman is lactating, milk is  produced in alveolar glands, empties via lactif-  erous ducts and the lactiferous sinus, and exits  at the nipple    Breast cancer is the second most common  cancer worldwide, affecting about one in twenty  women; fewer than one 1 percent of breast  cancers occur in men; mammography can  detect breast cancers while they are still very  small and thereby can lead to early diagnosis    e Pregnancy—event from the time of fertilization to  birth; the developing offspring is the conceptus;  development occurs during the gestation period    e The conceptus is called different things depend-  ing on the time period    e The egg is viable for 12 to 24 hours after ovula-  tion; sperm can survive in the female reproductive  tract for about 5 days; they usually meet in a uter-  ine tube    e When sperm swarm the egg, the acrosomal  reaction occurs, and enzymes begin to digest a path  through the membrane of the egg; the first sperm to  reach the egg is usually not the one to fertilize it    ° Once one sperm has entered, the receptors for  sperm are shed from the ovum surface, prevent-  ing a second sperm from entering    o Fertilization occurs the moment the sperm  DNA and ovum DNA merge, forming a zygote    e Early, rapid mitotic divisions of the zygote are  called cleavage; this provides large cell numbers  for development to continue    e The blastocyst is a ball of about 100 cells with a  hollow center and begins secreting human chori-  onic gonadotropin (hCG), which prompts the  corpus luteum to continue producing progester-  one to maintain the pregnancy; the blastocyst has  two parts: the trophoblast and inner cell mass    ° The trophoblast forms a fluid-filled sphere  that will form the chorionic villi, which com-  bine with uterine tissue to form the placenta    ° The inner cell mass gives rise to the three pri-  mary germ layers: ectoderm, mesoderm, and  endoderm    e Once the placenta is formed, the fluid-filled  amnion surrounds the primary germ layers (what  will become the embryo), and the umbilical  cord forms to attach the amnion to the placenta    By the end of 8 weeks, the placenta is producing  estrogens, progesterone, and other hormones to  maintain pregnancy, and the corpus luteum  degenerates    e Anatomical changes during pregnancy include a  drastic increase in the size of the uterus, widening  of the thorax as the uterus pushes into the tho-  racic cavity, shifts in the center of gravity, lordosis  of the lumbar region, and relaxation of the pubic  symphysis due to effects of the hormone relaxin    e Physiological changes include heartburn; consti-  pation; increased urination and stress inconti-  nence; increased respiratory rate and dyspnea;  increased blood volume, blood pressure, and  heart rate; and swelling of the ankles and feet    e Childbirth is also called parturition; the events  leading to expulsion of the infant from the uterus  are labor    ° False labor—weak, irregular uterine contrac-  tions (Braxton Hicks contractions); occurs  when estrogens reach highest levels and the qui-  eting influence of progesterone on the uterus is  interrupted    o Oxytocin and prostaglandins from the placenta  are needed to initiate labor    ° Dilation stage—the time from the beginning  of true contractions until the cervix is fully  dilated    ° Expulsion stage—the time from full dilation  to delivery of the infant  = If the infant doesn’t get enough oxygen dur-  ing this stage, (a condition called dystocia),  a cesarean section (C-section) may be  performed to speed delivery via surgery    Reproductive System (pp. 591-595)  e Prior to gonad formation in the eighth week, the  embryo is in the indifferent stage  ° Pseudohermaphrodites— individuals whose  external genitalia do not match their gonads  ° Hermaphrodites— individuals who have both  ovaries and testes  e Phimosis—narrowing of the foreskin of the penis  e Cryptorchidism—failure of the testes to descend  from the abdominal cavity  e Puberty—the period of life when reproductive  organs grow to adult size and begin to make  gametes under the direction of sex hormones    ° In boys, includes growth of the scrotum and  penis, development of secondary sex character-  istics   ° In girls, includes menarche (first menstrual  period), breast development, and secondary sex  characteristics    Which of the following can be found in semen?  a. Sperm   b. They contain 46 chromosomes.  c. They contain 23 chromosomes.  d. They are motile.    e Men continue to produce sperm throughout life;  women lose reproductive capabilities at menopause   e Most common problems in adulthood are infec-  tions: in women, vaginal infections; in men,  urethritis, prostatitis, epididymitis, and  orchitis    a. about the same number of each is produced per  month.    b. they have the same degree of motility.  c. they are about the same size.   The outer layer of the blastocyst, which attaches to the  uterine wall, is the   b. inner cell mass.  The crown-to-rump length of an 8-week human  embryo is  a. 3mm.  b. 10 mm.    What are the primary sex organs, or gonads, of males?  What are their two major functions?    What is the function of seminal fluid? Name the three  types of glands that help produce it.    Why are the male gonads not found in the abdominal  cavity? Where are they found?    Testosterone causes the male secondary sex character-  istics to appear at puberty. Name three examples of  male secondary sex characteristics.    Name the three structures that anchor the ovaries to  their surroundings.    Why is the term urogenital system more applicable to  males than females?    Name the structures of the female duct system, and  describe the important functions of each.    What is mittelschmerz, and when is it most likely to  occur?    What is the most important diagnostic method to  detect cervical cancer?    List and describe the events of the menstrual cycle.  Why is the menstrual cycle so important?    Define fertilization. Where does fertilization usually  occur? Describe the process of implantation.    How is body functioning of a pregnant woman  altered by her pregnancy?    Why is it essential to remove all parts of the placenta after  birth?    33. A pregnant woman in substantial pain called her doc-  tor and explained that she was about to have her baby  “tight away.” The doctor asked how she had come to  that conclusion. She said that her water had broken  and that her husband could see the baby’s head.  (a) Was she right to believe that birth was imminent?  If so, what stage of labor was she in? (b) Do you think  she had time to make it to the hospital 60 miles away?  Why or why not?    34. Jane is 48 years old. She tells you that she has gone    without menstruation for about 6 months now. A  pregnancy test proved negative. What could be the  reason for Jane’s missed periods?    A sperm enters a polar body, and their nuclei fuse.  Why would it be unlikely for the resulting cell to  develop into a healthy embryo?    Answers to Did You Get It? Questions  and Multiple Choice Review Questions   1. Anatomy and physiology are related.  A given function can occur only if  the corresponding structure allows it.  2. False. They are all topics of physiology.  3. The stomach exhibits the organ level  of structural organization. Glucose is  at the chemical level. 4. These organs  are part of the respiratory system.  5. The urinary system rids the body of  waste and helps regulate blood pressure.  6. Survival also depends on the ability to  maintain one’s boundaries, to move, to  respond to stimuli, and to reproduce.  7. Oxygen is required for the chemical  reactions that release energy from food and  form ATP. Metabolism is the life function  in which oxygen directly participates.  8. The anatomical position is a standard  position that serves as a reference point in  descriptions of the body and its structures.  In this position, the body is standing erect,  feet are parallel, arms hang at the sides,  and palms face forward. It's important to  understand it because most descriptions  of the body using anatomical terminology  refer to body regions as if the body is in  the anatomical position regardless of its  actual position. 9. The axillary region is the  armpit. The acromial region is the point of  the shoulder. 10. Left posterior antebrachial  region. 11. To separate the thoracic and  abdominal cavities, you would make a  transverse section (cross section). 12. Of  these organs, the small intestine and uterus  are in the abdominopelvic cavity. 13. Joe  might have appendicitis. 14. No. We mean  that they vary within a narrow and regulated  range. 15. Thirst is part of a negative  feedback system. Thirst prods us to drink  fluids (the response), which in turn causes  the thirst sensation to decrease and end. Were  it a positive feedback mechanism, we would  become even more thirsty (the stimulus for  drinking would increase).   1. d; 2. c 3. superior, superficial,  proximal, lateral, medial, posterior; 4. 1-e,  2-c, 3-i, 4-f, 5-h, 6-a, 7-b, 8-d, 9-g; 5. c;  6. c; 7.b, c,d; 8. 1-b, 2-a, 3-a, 4-c    1. Matter is the substance of living and  nonliving objects. Energy is the mover  of the substance—the ability to do work.  2. Electrical and chemical energy are both  involved in transmitting messages in the  body. Chemical energy (ATP) fuels cellular  processes. 3. Potential energy and kinetic  energy, respectively. 4. Every time energy  changes from one form to another, some  heat is given off to the environment (is  lost) and is unusable. 5. Carbon, oxygen,  hydrogen, and nitrogen. 6. An atom is  the smallest particle of an element that  still retains the element's properties.  7. The atom’s atomic number (#p) is 4;  its atomic mass number (#n + p) is 9.  8. Radioisotope. 9. A molecule is  two or more atoms chemically bound  together. 10. A molecule of an element  is a chemical combination of two or more  atoms of the same kind. In a molecule of a  compound, the atoms differ. 11. In ionic  bonds, electrons are completely transferred  from one atom to another. In covalent  bonds, the interacting atoms share one  or more electron pairs. 12. Hydrogen  bonds. 13. It isa decomposition reaction.  14. A reversible reaction is shown by  double reaction arrows. 15. The high heat  capacity of water prevents rapid changes in  body temperature. 16. Acids are proton  donors. 17. A pH of 11 is basic. A pH of  5 is 1,000,000-fold more acidic than pH  11. 18. All chemical reactions in the  body take place in a watery environment.  19. They conduct an electrical current when  dissolved in water. 20. The structural units  of carbohydrates are monosaccharides.  Those of lipids are glycerol and fatty  acids. 21. Phospholipids and cholesterol  are in cellular membranes; phospholipids  are the more abundant. 22. Dehydration  synthesis. 23. A chain of amino acids.  24. Fibrous proteins. 25. The enzyme is  able to specifically bind with its substrate(s).  26. DNA contains the bases A, T, G, and  C, and the sugar deoxyribose. RNA contains  the bases A, G, C, and U, and its sugar is  ribose. 27. ATP is the immediately useful  form of energy for all body cells.    Review Questions  1.b¢64¢6¢2.b6¢4d4 3-4, b-a d e A G  5. b, œ 6. b; 7.a, e; 8. c; 9.a; 10. a, c;  11.a, d   1. A cell is the (living) unit of life. 2. What  its cells can do. 3. The phospholipids have  both polar (heads) and nonpolar (tails)  regions. Polar aligns with polar (water and  other polar molecules inside and outside  the cell). Nonpolar aligns with nonpolar  in the membrane interior. 4. They act as  receptors, determine blood type, and  play a role in cell-to-cell interactions.  5. Communication and binding together,  respectively. 6. Plasma membrane =  external barrier that regulates what enters  and leaves the cell. Cytoplasm = the area  where most cell activities occur. Nucleus  = control center of the cell. 7. The  generalized cell is a concept that describes  organelles and functions common to all  cells. 8. Nucleoli are the sites of synthesis  of ribosomes, which are important in  protein synthesis. 9. The cytosol is the  liquid portion of the cytoplasm. Cytoplasm  includes cytosol, organelles, and inclusions.  10. Lysosomes break down ingested  bacteria, worn-out organelles, and dead  cells. Peroxisomes detoxify a number of  harmful toxic substances and disarm free  radicals. 11. Mitochondria are the major  site of ATP synthesis. The Golgi apparatus  is the packaging site. 12. Microtubules  and microfilaments are involved in cell  mobility. 13. The basis of centrioles is  microtubules; that of microvilli is a core  of actin filaments. 14. Microvilli increase  the cell surface area for absorption.  15. Fibroblasts and erythrocytes.  16. Neurons gather information and  control body functions. 17. Kinetic  energy is the energy source for diffusion.  18. The concentration gradient determines  the direction that water and solutes  move by diffusion. Movement is from  high to low concentration of a given  substance. 19. A channel protein is an  opening formed by membrane proteins  for diffusion of certain small solutes. A    604 Appendix A: Answers to Did You Get It? Questions and Multiple Choice Review Questions    carrier protein undergoes shape changes  that allow diffusion of a specific substance  through the membrane. 20. “Down the  concentration gradient” means to move  from where there is a lot of something  (high concentration) to where there is  not a lot (low concentration). 21. When  the pump protein is phosphorylated,  it changes shape. When K* binds,  phosphate is released. 22. Phagocytosis  moves large particles into the cell.  23. Receptor-mediated endocytosis.  24. DNA is double-stranded. When  it is replicated, each strand serves as a  template to build a complementary strand.  Thus, if the template strand is ACT, the  complementary strand formed at that site  is TGA. 25. Cytokinesis is the division  of the cytoplasm. If cytokinesis does  not occur, the result is a binucleate cell.  26. mRNA carries the coded information  for building proteins from the DNA to the  ribosome where protein synthesis occurs.  tRNA delivers amino acids to the ribosome  and “checks” the location by recognizing  the mRNA codon with its anticodon.  27. Transcription and translation. Proteins  are synthesized during translation.  Transcription is the production of mRNA  using DNA asa template. 28. Cell shape and  cell arrangement (layers) are the two criteria  used to classify epithelium. 29. Exocrine  glands have ducts that carry their secretion  (typically a protein-containing secretion  other than hormones) to a free body surface.  Endocrine glands produce only hormones  and are ductless glands. 30. Can repair  itself; cells have specialized cell junctions.  31. The two hallmarks of epithelial  tissue include having one free surface  and being avascular. 32. The two unique  features of connective tissues include  variations in blood supply and the  production of a nonliving, extracellular  matrix that surrounds their living cells.  33. Collagen fibers provide strength.  34. Skeletal muscle. 35. It allows neurons  to control structures some distance away.  36. Nervous tissue is irritable, meaning it  is able to respond to stimuli. 37. Dense  fibrous connective tissue is the basis for  fibrosis, or scar formation. 38. Neoplasm  means “new growth.” It is an abnormal  growth that occurs when normal control of  cell division is lost; this was also described as  “mitosis gone wild.”    Review Questions  1.a; 2.a,d; 3.b; 4.¢ 5.c¢ 6.a,c¢ 7.b;  8.b; 9.a; 10.a; 11.b,e; 12. c¢    1. Serous membranes line ventral body  cavities closed to the exterior. Mucous  membranes line body cavities open  to the exterior (respiratory, digestive,  urinary, and reproductive organ cavities).  2. Parietal pleura, visceral pleura, (lung),  visceral pleura, parietal pleura, parietal  pericardium, visceral pericardium,  (heart). 3. Lining a fibrous capsule  surrounding a joint. 4. The skin is the  epithelial membrane that covers the body  surface. Cutaneous membrane is a synonym  for skin, as is integument, which means  “covering.” The integumentary system  is the skin and its derivatives (nails, hair,  glands). 5. Any three of the functions  listed in Table 4.1. 6. Keratinocytes  are the most abundant cell type in  the epidermis. 7. The stratum basale.  8. The stratum corneum. 9. Cells begin to  die as they leave the stratum granulosum.  10. The dermal papillae in the papillary  layer of the dermis are responsible for  fingerprints. 11. Just the epidermis.  12. Melanin, carotene, and hemoglobin all  contribute to skin color. 13. The sebaceous  glands, which produce oily secretions.  14. Both are dilute salt solutions containing  vitamins and wastes. Apocrine secretion also  contains proteins and fatty acids. 15. No,  the nail won't regrow, because the growth  region (nail matrix) is torn off. 16. Loss  of body fluids containing needed proteins  and electrolytes, resulting in circulatory  shock, and overwhelming infection.  17. First-degree burns are red and swollen;  only epidermis damaged. Second-degree  burns damage the epidermis and the  superficial part of the dermis; blisters  appear, but epithelial regeneration can  occur. Third-degree burns destroy the  entire skin thickness and can extend  into the subcutaneous tissue; the  burn is gray and painless; must graft.  Fourth-degree burns destroy all layers  of the skin; appear charred; extend into  deep tissues such as muscle or bone.  18. ABCDE rule. 19. UV radiation  exposure (sun or tanning bed).  20. Because stratum corneum cells are dead  and thus no longer are dividing. 21. Loss  of subcutaneous fat. 22. The sebaceous  glands of the baby.   1.c; 2.b,e; 3.a,b,c; 4.a,c,e; 5. a,c, d;  6. 1-b, 2-e, 3-d, 4-c, 5-a; 7. cœ 8. a, G;  9. 1-c, 2-h, 3-f, 4-a, 5-d, 6-e, 7-b, 8-g    1. Muscles use bones as levers to bring  about body movements. 2. Red bone  marrow provides a site for hematopoiesis,  and yellow bone marrow is a storage site  for fat. 3. Most long bones are found in the  limbs. 4. Shaft = diaphysis; bone ends =  epiphyses. 5. Compact bones appear solid  and very dense with few holes. Spongy  bone areas look like the cross-beams of  a house with lots of space between the  bone spicules. 6. They carry nutrients to  the bone cells. 7. Membranes or cartilage.  8. The hormonal stimulus (PTH) maintains  blood calcium homeostasis. 9. Bones  will become thinner and weaker because  osteoclasts are bone-destroying cells. 10. A  fracture is a break in a bone. Compression  and comminuted fractures are common in  the elderly. 11. Skull, vertebral column,  and bony thorax. 12. Eating or talking.  These are the temporomandibular  joints. 13. Maxillae. 14. Ethmoid  bone. 15. Frontal joins with the parietals  at the coronal suture. Parietals join one  another at the sagittal suture. 16. Cervical,  thoracic, lumbar, sacral, coccygeal.  17. All typical cervical vertebrae are small,  have holes in their transverse processes,  and have a split spinous process. Lumbar  vertebrae are large, blocklike vertebrae  with a blunt spinous process that projects  directly back. They have a large body  and no foramina in their transverse  processes. 18. A true rib is attached  directly to the sternum by its own costal  cartilage. A false rib attaches indirectly (by  the costal cartilage of a superior rib) or  not at all. 19. Vertebrae. 20. Flat bones.  21. The thoracic and sacral curvatures  are present. 22. At birth the newborn’s  spine is an arc (C-shaped), whereas an  adult's spine has two additional curvatures  and is S-shaped. 23. The axial skeleton  forms the body axis and protects the brain  and viscera. The appendicular skeleton  allows for mobility and manipulation  of the external environment. 24. The  clavicle attaches medially to the sternum.  25. The humerus forms the skeleton  of the arm. 26. Carpals are the short  bones found in the wrist. 27. Radius  and ulna. 28. Ilium, ischium, and pubis  form the hip bone. Each pelvic girdle is  formed by two coxal (hip) bones and the  sacrum. 29. The female pelvis is broader  and lighter, and it has a less acute pubic  angle, a wider inlet and outlet, and shorter    Appendix A: Answers to Did You Get It? Questions and Multiple Choice Review Questions    ischial spines. 30. Tibia and fibula form  the skeleton of the leg. 31. The talus  allows toe pointing. 32. The femur has  those markings. 33. Joints connect bones  together while allowing flexibility of the  body. 34. The difference is material  between the articulating bone ends,  which is connective tissue fibers in fibrous  joints and cartilage in cartilaginous joints.  35. It lines a synovial joint capsule to provide  a source of lubricating fluid in the joint.  36. The shoulder and hip joints are  ball-and-socket joints. The carpometacarpal  joint of the thumb is a saddle joint.  37. Compression fracture; osteoporosis.  38. Lower limbs and facial skeleton grow  most rapidly during childhood.   1. a, b; d; 2. a-5, b-1; c-4, d-3, e-2;  3. a, d; 4. a, c d; 5. a, b, c d, e; 6. a, G;  7. b, d; 8. b, d, e; 9. c; 10. b; 11. 1-a, b,  2-a, 3-a, 4-a, 5-b, 6-c, 7-c, 8-a, 9-c; 12. 1-f;  2-c, e; 3-b; 4-a, d    striations. Cardiac cells are branching,  typically uninucleate cells with less  obvious striations but obvious junctions.  Smooth muscle fibers are spindle-  shaped uninucleate cells, nonstriated.  2. Skeletal muscle. 3. Striped or  having bands = striated. 4. Skeletal  muscle movements can be very forceful  and rapid, whereas smooth muscle  movements tend to be slow and often  rhythmic. 5. The alignment of the bands  on the myofilaments is responsible for the  banding pattern in skeletal muscle cells.  6. The axon ending of a motor neuron and  the sarcolemma of the skeletal muscle fiber.  7. Sodium ions enter the cells during  action potential generation. 8. Calcium  stimulates the release of neurotransmitter  (ACh) at the axon terminal of the  motor neuron and causes the regulatory  proteins blocking the myosin-binding  sites on actin to move so cross bridges  can form and allow contraction.  9. Calcium ions trigger the sliding of the  myofilaments. 10. Pulling a bucket out  of a well. 11. Phosphorylation of ADP  by CP, stored ATP, and ATP generated  by glucose oxidation. 12. Stored ATP.  13. Isometric contraction. 14. Oxygen  deficit occurs when a person is not able  to take in oxygen fast enough to keep    the muscles supplied with all the oxygen  they need when working vigorously.  15. Resistance exercise leads to increased  muscle size. 16. Abduction. 17. Flexion  and extension. 18. They anchor or aid the  activity of the prime mover. 19. Tibialis  anterior—a muscle overlying the tibia  anteriorly. Erector spinae—muscles that  straighten the spine. Rectus abdominis—  muscle that runs straight up the abdomen.  Extensor carpi radialis longus—long  muscle on the posterior of the forearm  that extends the wrist and attaches at the  distal radius. 20. Circular. 21. Frontalis  raises the eyebrows. 22. Masseter  and temporalis are synergists in jaw  closure. 23. Erector spinae. 24. It’s like  plywood. The various abdominal muscles  run in different directions across the  abdomen, making the abdominal wall very  strong. 25. Latissimus dorsi. 26. Triceps  brachii. 27. Quadriceps on anterior thigh.  28. The medial gluteal site and  the deltoid muscle of the shoulder.  29. Soleus and gastrocnemius. They  plantar flex the foot. 30. Nerve fibers  must be myelinated. 31. Exercise defers  or reduces the natural loss in muscle mass  and strength that occurs in old age.   1. CNS = brain and spinal cord. PNS =  nerves that extend to and from the CNS.  2. Astrocytes are the most numerous  neuroglia. Oligodendrocytes produce  myelin. 3. Neuroglia can divide. Most  neurons cannot. A criterion of cancer  cells is their uncontrolled division.  4. A tract is a bundle of nerve fibers in the  CNS. A nerve is a bundle of nerve fibers  in the PNS. 5. A ganglion is a cluster of  nerve cell bodies in PNS; a nucleus is a  cluster of nerve cell bodies in the CNS.  6. Dendrites conduct impulses toward  the nerve cell body; the axon terminal  releases neurotransmitters. 7. The fiber  that conducts at 40 m/sec. 8. A graded  potential is a local current that dies out  with distance. An action potential is a  current that is continuously regenerated  along the length of the axon and does not  die out. 9. The synapse is the location  where an impulse passes from one  neuron to another or to a target cell. The  synaptic cleft is the gap at the synapse that    neurotransmitter must cross to transmit  the signal. Chemically via the release of  a neurotransmitter and binding of the  neurotransmitter to the postsynaptic  membrane. 10. Dendrites. 11. A reflex  is a rapid, predictable, and involuntary  response to a stimulus. 12. Cerebral  cortex, white matter, and basal nuclei.  13. Mostly myelinated nerve fibers.  14. The brain stem controls vital  activities. 15. The cerebellum provides  precise timing for skeletal muscle  act-ivity and helps control our balance  and equilibrium. 16. Diencephalon.  17. Ventricles. 18. Blood-brain barrier.  19. Arachnoid mater. 20. Contusion.  21. Nerve cell bodies of interneurons and  motor neurons. 22. Sensory pathways are  ascending pathways. 23. Because the leash  of nerve fibers there looks like a horse's  tail, the literal translation of cauda equina.  24. Around each nerve fiber. 25. Vagus  nerves. 26. Nerve plexus = complex  network of nerves. 27. Sciatic nerve of the  sacral plexus. 28. Visceral organs (smooth  and cardiac muscles and glands) are served  by the ANS. Skeletal muscles are served  by the somatic nervous system. 29. The  ANS has a two-motor neuron pathway  from the CNS to the organ to be served.  The somatic nervous system has just one  motor neuron in the motor pathway.  30. Sympathetic division. 31. They are  unable to regulate their body temperature  until the hypothalamus matures. 32. It  is hypotension caused by a rapid change  in position, such as getting up quickly  from a reclining position. The sympathetic  nervous system, which regulates blood  pressure, is less efficient in old age.   1. d; 2. a, d; 3.c¢ 4. d; 5. a,c 6. 1-e,  2-d, 3-f, 4-b, 5-e, 6-h, 7-a; 7. b, c 8. d;  9.b; 10. a; 11.b; 12.b,c,d   1. The eyelids protect the eyes. 2. The tarsal  glands, ciliary glands, conjunctiva, and  lacrimal glands all contribute to lubricating  the eye, though their secretions differ.  3. Lysozyme is a component of tears that  helps to destroy bacteria and protect the eye  from infection. 4. They direct the eyeball  toward what you wish to view. 5. The  blind spot contains no photoreceptors; it  is the site where the optic nerve leaves the  eyeball. 6. Both contain pigment, which  prevents light scattering in the eye. 7. Rods    606 Appendix A: Answers to Did You Get It? Questions and Multiple Choice Review Questions    have a rodlike outer segment containing the  photopigment, whereas cones have a shorter  cone-shaped outer segment. Rods respond to  low light conditions and produce black-and-  white vision; cones need bright light and  provide color vision. 8. Refractory media  include the cornea, aqueous humor, the lens,  and vitreous humor. 9. Accommodation.  10. The optic nerves leave the eyeballs, and  the medial half of the fibers of each optic  nerve cross over to the opposite side, joining  there with the fibers from the outside half  of the opposite eye to form the optic tracts.  11. It causes pupillary constriction in very  bright light. Intense light stimulation can  injure the photoreceptors. 12. Astigmatism  results from unequal curvatures on the  lens surface, not from an eyeball that is  too long or too short to focus the image  on the retina. The unequal curvatures of  astigmatism result in points of light that  focus on the retina as lines, not points,  leading to blurry images. 13. External  and middle ears serve hearing only.  14. The ossicles (hammer, anvil, and stirrup).  15. Tympanic membrane to bones of  ossicles to fluids of the cochlear scalae.  16. Cochlear nerve (division of cranial  nerve VIII). 17. Close to the oval window.  18. Balance or equilibrium. 19. Dynamic  receptors located in the semicircular  canals (crista ampullaris) are embedded  in the gel-like cupula; static receptors  located in the vestibule (maculae) have  otoliths that move when the head moves,  causing hairs embedded in the otolithic  membrane to bend. 20. Otoliths are  tiny stones made of calcium salts that are  located in the maculae of the vestibule.  They respond to static equilibrium cues  relative to the position of the head in space.  21. Sensorineural deafness results from  damage to neural structures involved in  hearing (cochlear nerve, auditory region  of the brain), whereas conductive deafness  results from anything that prevents sound  vibrations from reaching the cochlea  (earwax, fusion of the ossicles, fluid in the  middle ear). 22. Chemoreceptors, because  they respond to chemicals in solution.  23. On the tongue. 24. Odor receptors  are located at the superior aspect of the  nasal cavity. Sniffing brings the air upward.  25. Presbyopia; caused by reduced  elasticity of the lens as a result of aging.  26. Vision. 27. Deafness of old age.    Review Questions  1. d; 2. b, œ 3. a, œ 4. d; 5. d; 6. a, G  7. a, b, c d; 8. b, d; 9. c; 10. a, b, G    11. 1. j, optic disc; 2. e, vitreous humor; 3.  a, ciliary body; 4. g, choroid; 5. d, lens; 6. i,  fovea centralis; 7. b, cornea; 8. f, sclera; 9.  h, retina; 10. c, iris    1. The endocrine system delivers its  commands slowly via hormones carried by  the blood. The nervous system uses rapid  electrical messages that are much faster,  allowing you to lift your foot off the glass  more quickly. 2. A hormone is a chemical  messenger used by the endocrine system.  The target organ of a hormone is the specific  cells or tissues that the hormone affects.  3. Because cAMP is not a first messenger, which  is a molecule that attaches to a receptor on  the cell's plasma membrane and triggers  the reactions leading to synthesis of the  second messenger in the cell. 4. Endocrine  organs are stimulated by hormones, by  chemicals other than hormones, and by the  nervous system. 5. Endocrine glands are  ductless, and they release their hormone  products directly into the intercellular fluid.  Exocrine glands release their nonhormonal  products to an epithelial surface via  a duct. 6. The posterior pituitary is  nervous tissue that acts as a storage and  releasing area for hormones sent to it by  the hypothalamus. 7. Diabetes insipidus,  in which copious amounts of urine are  voided as a result of hyposecretion of ADH.  8. Tropic hormones stimulate certain  endocrine organs to secrete their  hormones. 9. Functional thyroid  hormone has iodine as part of its structure.  10. Melatonin, produced by the pineal  gland. 11. The parathyroid glands  reside on the posterior thyroid gland.  12. PTH, produced by the parathyroid  glands, increases the blood calcium ion  level. 13. Calcitonin, produced by the  parafollicular cells of the thyroid gland,  reduces the blood calcium ion level.  14. Thymosin programs the T lymphocytes,  which essentially direct our immune  responses. 15. Aldosterone stimulates  the kidneys to reabsorb more sodium  ions. 16. Glucocorticoids such as cortisol.  17. Her blood glucose level would be  elevated because of her stress. When we  are stressed, both glucocorticoids (adrenal  cortical hormones) and epinephrine  and norepinephrine (adrenal medullary  hormones) are produced in increased  amounts. Both sets of hormones  promote a rise in the blood glucose level.  18. Insulin stimulates cellular uptake of    glucose. 19. Estrogen. 20. Stomach  and small intestine. 21. Placenta.  22. Ovaries. 23. Growth hormone decline  results in muscle atrophy; estrogen decline  leads to osteoporosis.    Review Questions  T: d; 2: b c 3. a, G 4c 5:4a; bd  6.a, b,c d; 7. c,d; 8. b; 9. b; 10.a, d    1. The liver is the major source of plasma  proteins. 2. Erythrocytes, leukocytes, and  platelets. 3. The color of blood varies  with the amount of oxygen it is carrying.  From most oxygen to least, the blood  goes from scarlet to dull red or purple.  4. Hemoglobin transports oxygen and a  small amount of carbon dioxide in the blood.  5. Lymphocytes are the main actors in body  immunity. 6. Infection in the body causes an  increase in WBC count, thus 15,000 /mm?.  7. Anemia. 8. The hemocytoblast gives  rise to all formed elements. 9. Lack of a  nucleus; therefore, they cannot carry out  transcription and translation to produce  proteins (enzymes and others). 10. The  stem cell (megakaryocyte) undergoes mitosis  many times, forming a large multinucleate  cell, which then fragments into platelets.  11. Inactivity, leading to blood pooling,  and anything that roughens or damages  the lining of a blood vessel (laceration,  atherosclerosis, or physical trauma).  12. The self-antigens (agglutinogens) the  RBCs bear. 13. A transfusion reaction, in  which the RBCs are lysed and hemoglobin  enters the bloodstream, potentially leading  to kidney shutdown. 14. O-positive.  15. An antigen is a substance foreign to the  body that activates and is attacked by the  immune system. An antibody is a protein  released by immune cells that binds with a  specific antigen and inactivates it in some  way. 16. Fetal HbF has a greater ability to  bind oxygen and binds it more strongly  than adult HbA. 17. Leukemia, pernicious  anemia, and clotting disorders are particularly  common in the elderly.   T-a b, d; 2: a b, c d; 3: d; 4- G  5. a, œ 6. c, d; 7. b, d; 8. cœ 9. b, c d;  10. a, d; 11. d; 12.a; 13.d,a,c,b    1. The heart is in the mediastinum between  the lungs. 2. The left ventricle has the    Appendix A: Answers to Did You Get It? Questions and Multiple Choice Review Questions    thickest walls. This reflects its function, which  is to pump blood through the whole body.  3. Pulmonary circulation strictly serves gas  exchange. Oxygen is loaded and carbon  dioxide is unloaded from the blood in the  lungs. Systemic circulation provides oxygen-  laden blood to all body organs. 4. Heart  valves keep blood flowing in one direction  through the heart. 5. The coronary arteries  supply the myocardium (cardiac muscle)  with oxygen. If that circulation fails, the  heart fails. 6. The intrinsic conduction  system of the heart coordinates the action  of the heart chambers and causes the heart  to beat faster than it would otherwise.  7. Ventricles 8. The atria are relaxing, and the  ventricles are contracting. 9. The operation  of the heart valves. 10. CO = amount of  blood pumped out by each side of the heart  in 1 minute. 11. Fever increases the heart  rate because the rate of metabolism of the  cardiac muscle increases. 12. The amount  of preload, also known as venous return.  13. It is a vein. 14. Blood pressure in veins  is much lower than that in arteries because  veins are farther along in the circulatory  pathway. Hence, veins need extra measures to  force blood back to the heart. 15. Capillary  walls consist only of the innermost intima  layer, which is very thin. The thinness of their  walls enables capillaries to carry out their  function as the exchange vessels between  the blood and tissue cells. 16. Lower limb.  17. Upper limb. 18. Hepatic portal  vein. 19. The pulmonary circulation is  much shorter and requires a less powerful  pump than the systemic circulation does.  Pulmonary arteries carry oxygen-depleted/  carbon dioxide-rich blood, whereas the  pulmonary veins carry oxygen-rich/carbon  dioxide-depleted blood. The opposite is  true of the arteries and veins of the systemic  circulation. 20. Radial artery at the wrist;  femoral at the groin; common carotid at the  side of the neck. 21. It decreases from heart  to venae cavae. 22. Hemorrhage reduces  blood pressure initially because blood  volume drops. 23. Fluid enters the capillary  bed at its venous end.    Review Questions  1. c 2: b; 3c 4: b; 5.¢66.ac¢ 7c  8. a, c 9. a, d; 10. b; 11. a; 12. b;  13. a, b, œ 14. b, cœ 15. a; 16. a, b, G  17. b; 18. c,d; 19. d    Did You Get It?  1. Lymphatic vessels pick up fluid and  proteins leaked from the blood into the    interstitial space. 2. Lymphatic capillaries  are blind-ended and not fed by arteries  as blood capillaries are. They also have  flaplike minivalves that make them  more permeable than blood capillaries.  3. Particularly large collections of lymph  nodes occur in the axillary, inguinal,  and cervical regions. 4. The number of  afferent lymphatic vessels entering the  node is greater than the number of efferent  vessels leaving the node at the hilum.  Therefore, lymph flow stagnates somewhat.  5. The spleen destroys worn-out RBCs.  6. The lymphoid tissue associated with the  mucosa—tonsils in the throat, and Peyer's  patches in the intestinal walls—which  acts to prevent pathogens from entering  the body through the mucosa. 7. Innate  defenses are nonspecific and always ready  to protect the body. They include intact  membranes (mucosa, skin), inflammatory  response, and several protective cell  types and chemicals. Adaptive defenses  must be programmed and specifically  target particular pathogens or antigens.  8. Redness, heat, swelling (edema), and pain.  9. It attaches to foreign cells, and when it  is activated, membrane attack complexes  (MACs) are inserted in the foreign cell's  membrane and produce lesions that allow  water entry and cause lysis. 10. Viruses  elicit interferon formation. 11. An  antigen is a foreign substance in the body.  A self-antigen is a body protein, typically  displayed in the plasma membrane,  that is foreign to anyone but oneself.  12. B lymphocytes and T lymphocytes. B  lymphocytes mount a humoral response  by producing antibodies. T lymphocytes  mount the cellular response by activating B  cells and cytotoxic T cells and stimulating  the inflammatory response. 13. In the  thymus. 14. They are antigen presenters  to the T cells. 15. Primary response—  this year’s new strain will be seen by the  body as a different virus. 16. This is the  region that binds to the antigen. 17.  IgA, a dimer. 18. Neutralization occurs  when antibodies attach to viruses or  bacterial toxins, thereby blocking the  virus or toxin from injuring the body.  19. Agglutination cross-links cell-bound  antigen; precipitation cross-links soluble  antigen, which then falls out of solution  like clotting proteins that have been  activated; opsonization is the “marking”  of antigen for phagocytosis, which also  makes it a bit sticky so it is easier for  phagocytes to “catch.” 20. T cells have to  bind to both an antigenic particle and to a    self-protein on the antigen-presenting cell.  21. The cytotoxic T cell inserts perforin  (toxic chemicals) into the foreign antigen’s  plasma membrane, which then develops  holes. Then granzymes, enzymes from the  T cell’s cytoplasmic granules, enter and  kill the foreign cell. 22. To slow or stop  the immune response once the “enemy”  has been conquered. 23. Helper T cells  “direct” both humoral and cell-mediated  adaptive responses; they interact with  both B cells and T cells to stimulate cell  division; release cytokines to recruit  other phagocytes, such as neutrophils;  and enhance macrophage activity.  24. Allograft. 25. An overzealous  immune response against an otherwise  harmless substance that causes injury  to the body. 26. In anaphylactic shock,  released histamine causes constriction  of the bronchioles, sudden vasodilation,  and fluid loss. 27. Abnormal production  or functioning of immune cells or  complement. 28. Self-proteins that were  not previously exposed to the immune  system appear in the circulation, or foreign  antigens that resemble self-antigens arouse  antibodies that attack the self-antigens.   1.d; 2.a; 3.c,d; 4.a,c¢ 5.a; 6.b,d; 7.c  8. c, d; 9. b; 10. b; 11.d; 12. a, b, c, d;  13.a, b    1. Because the respiratory mucosa rests  on thin-walled veins that warm the  incoming air, mucus produced by mucous  glands and goblet cells moistens the air  and traps dust and bacteria. The oral  mucosa performs none of these functions.  2. Ciliated cells of the mucosa move  the sheet of contaminated mucus away  from the lungs and toward the throat for  swallowing. 3. Nasal cavity, pharynx,  larynx, trachea, bronchi, bronchioles,  alveoli. 4. The right bronchus, because it’s  wider and straighter. 5. The passageways  conduct air. The elastic tissue allows  lungs to recoil passively when exhaling,  saving energy. 6. Respiratory bronchiole,  alveolar duct, alveolar sac, and individual  alveoli. 7. To exchange gases between  the external environment and the  blood—oxygen in, carbon dioxide out.  8. Increased air pressure in the lungs as  they recoil. 9. VC is largest; TV is smallest.  10. About 350 ml reaches the alveoli.  11. His left lung collapsed because the    608 Appendix A: Answers to Did You Get It? Questions and Multiple Choice Review Questions    pressure in the intrapleural space (normally  negative) became equal to atmospheric  pressure. 12. Diffusion. 13. As  bicarbonate ion. 14. Cyanosis is a bluish  cast to the skin (in light-skinned people),  mucous membranes, and nailbeds due  to inadequate oxygenation of the blood.  15. The medulla oblongata. 16. Increased  CO,, which results in a drop in blood  pH. 17. He has COPD, specifically,  emphysema. 18. The lung alveoli will  collapse after every breath; IRDS.    Review Questions  1. d; 2. a, d; 3. a, b, d; 4. b; 5. b, d;  6.a,c¢ 7.c,e; 8b   1. Mouth, pharynx, esophagus,  stomach, small intestine, large intestine,  anus. 2. Protein digestion begins  in the stomach. 3. Alkaline mucus  protects the stomach wall from being  digested. Intrinsic factor is needed for  intestinal absorption of vitamin By).  4. The pyloric sphincter. 5. Villi are  extensions of the mucosa of the small  intestine. They increase the surface area  of the small intestine tremendously for  nutrient absorption. 6. Water absorption  and absorption of some vitamins made  by resident bacteria. 7. The incisors cut,  the canines tear or pierce, the premolars  and molars crush and grind. 8. Starch.  Saliva contains salivary amylase.  9. Bile, produced and secreted by the  liver, acts as a detergent to mechanically  break up large fat masses into  smaller ones for enzymatic digestion.  10. The pancreas. 11. Ingestion,  digestion, absorption, and defecation.  12. Mechanical breakdown breaks  food down physically by squeezing  and pummeling it. Digestion uses  enzymes to break the chemical bonds  of the food molecules and release the  nutrients. 13. This is the voluntary  stage in which the chewed food is  pushed into the pharynx by the tongue.  14. The main goal of segmentation is  to mix the food thoroughly, though  some propulsion occurs. Peristalsis is a  propulsive activity. 15. Food went down  the air passageway (trachea) instead of the  digestive passage (esophagus). 16. Pepsin,  the main enzyme of the stomach, needs  acidic conditions to work. 17. Amino  acids. 18. CCK causes the pancreas to  secrete enzyme-rich fluid and stimulates the    gallbladder to contract and the duodenal  papilla to open. 19. Enzymes located  on the microvilli of intestinal absorptive  cells. 20. Microbiota differ among  healthy people and those with disease,  communicate with the immune system,  influence mood, and may contribute to  health or disease, depending on which  organisms are present. 21. Plants—fruits,  vegetables, and grains. 22. It provides  fiber, which is important for moving  feces along the colon and defecation.  23. Oils are unsaturated lipids. 24. Most  are coenzymes that work with enzymes  to bring about metabolic reactions.  25. Cellular (aerobic) respiration.  26. Carbon dioxide and reduced  coenzymes. 27. ATP and water. 28. Fats  are used in synthesis of myelin sheaths  and of cellular membranes, and as body  insulation. 29. Making glucose from  noncarbohydrate molecules, such as fats  and proteins. 30. The liver combines  ammonia with carbon dioxide to form  urea. Urea is then eliminated from the  body in urine. 31. HDLs, because they  are headed back to the liver for breakdown  and elimination from the body. 32. Large  surface area relative to body volume.  33. Vasoconstriction of blood vessels  serving the skin, and shivering.  34. It decreases body temperature.  35. Cystic fibrosis causes excessive  production of mucus, which clogs the  pancreatic ducts so that pancreatic enzymes  cannot reach the small intestine; as a result,  fat digestion is virtually stopped, resulting  in fatty stools and an inability to absorb  fat-soluble vitamins. 36. A diet low in  phenylalanine. 37. You gain weight (fat).   1. c, d; 2. a, b, e; 3. c 4. 1-e, 2-h, 3-c,  4-b, 5-d, 6-a, 7-f, 8-g; 5. d; 6.a,b; 7. a, c;  8.d; 9.d; 10.a; 11.b,d; 12.b; 13.a,d    1. Retroperitoneal = behind, or in back  of, the peritoneum. 2. Fat helps keep the  kidneys anchored against the body trunk  wall. When she lost weight, the amount  of fat decreased, and the kidneys fell to  a lower position (ptosis), causing the  ureter(s) to kink and inhibit urine flow.  3. Cortex, medulla, pelvis. 4. The  nephron. 5. The renal tubule carries  out tubular reabsorption and secretion.  The peritubular capillaries receive the  fluid, nutrients, and needed ions to    be returned to the general circulation.  6. It decreases glomerular pressure. 7. The  specific gravity of urine is higher because it  contains more solutes than water contains.  8. The bladder. 9. It allows the cavity  of the bladder to increase in volume to  store more urine when necessary. 10. It  is longer (8” vs. 1.5”), and it transports  both urine and semen. The female urethra  transports urine only. 11. Voiding or  urination. 12. Excreting nitrogenous  wastes and maintaining acid-base balance,  water balance, and electrolyte balance of  the blood. 13. Thirst. 14. Aldosterone  increases sodium ion reabsorption by  the kidney tubules, and water follows  (if able). 15. Osmoreceptors are in the  brain (hypothalamus), and they respond  to changing (increasing) solute content  (osmolarity) of the blood. 16. The  homeostatic pH of blood in the body  varies between 7.35 and 7.45. Any blood  pH below 7.35 is considered too acidic for  normal body function. 17. A weak base,  because a weak base will neutralize acidity  by tying up only enough hydrogen ions to  maintain a physiological pH, and there is  no chance of overshoot and making the pH  strongly basic. 18. It will increase, because  water will be lost in sweat (and urine).  19. Kidneys maintain acid-base balance by  excreting bicarbonate ions (HCO; ) and  reabsorbing or generating new HCO; .  20. A condition in a newborn baby boy,  in which the urethral opening is on the  ventral surface of the penis. 21. Urgency  is the urgent feeling that you have to  urinate. Frequency is the condition in  which you urinate small amounts of urine  frequently. 22. Polycystic kidney disease  is a degenerative condition in which cysts  (blisterlike sacs) of urine interfere with  normal kidney function and lead to kidney  failure; glomerulonephritis is clogging of  the glomerular filter with antigen-antibody  complexes.    Review Questions  1. 1-b, 2-d, 3-e, 4-a, 5-c; 2. b, œ 3. a, d;  4.a,c 5.a,b,c,d; 6.b; 7.¢ 8.c    1. The testes produce male gametes  (sperm) and secrete sex hormones, mainly  testosterone. 2. The seminiferous tubules  produce sperm. 3. Epididymis, ductus  deferens, ejaculatory duct, and urethra  (prostatic, membranous, and spongy  regions). 4. To make the penis firm by    Appendix A: Answers to Did You Get It? Questions and Multiple Choice Review Questions    allowing it to fill with blood, so that it  can serve as a penetrating device during  sexual activity. 5. Sperm are male gametes  that fertilize the female’s “eggs.” Seminal  fluid serves as a transport medium for  sperm and contains various substances that  nourish and protect the sperm or aid their  movement. 6. His prostate is probably  hypertrophied. The prostate is immediately  anterior to the rectum and can be examined  digitally through the anterior rectal wall.  7. FSH stimulates spermatogenesis. 8. The  final product of mitosis is two diploid  cells that are genetically identical to  each other and to the mother cell. The  final product of meiosis is four cells,  each with half the normal number of  chromosomes (haploid). Genetic variation  is introduced by meiosis. 9. Excess  cytoplasm is discarded, and what remains  is compacted into the head, midpiece, and  tail regions. Final maturation processes    in the epididymis result in increased  motility. 10. Luteinizing hormone  stimulates testosterone production.  11. Female gametes (eggs, or ova). 12. The  uterus serves as an incubator. The uterine  (fallopian) tubes are the most common  site of fertilization. 13. Vesicular, or  Graafian, follicle. 14. Polar bodies are also  produced. They deteriorate and die because  they lack sustaining cytoplasm. 15. FSH  promotes follicle development. 16. LH  stimulates ovulation. 17. Estrogen.  18. The functional layer of the endometrium  is rebuilt. 19. Progesterone (1) causes  the secretory phase of the menstrual  cycle, (2) helps prepare the breasts for  lactation, and (3) helps quiet the uterine  muscle to maintain pregnancy. 20. A  large percentage (80%) of women who  carry the altered gene(s) develop breast  cancer. 21. Cleavage involves successive  divisions not separated by growth of the    cells, so the cells get smaller with each  division. 22. The placenta produces  hormones of pregnancy, delivers nutrients  and oxygen to the fetus, and removes  wastes from the fetal blood. 23. During  pregnancy, many women have heartburn  because the uterus crowds the stomach.  Constipation is another problem  because mobility of the digestive tract  decreases. Nasal stuffiness and difficulty  breathing are common. 24. Dilation,  expulsion, and placental stages. 25. XY;  testosterone. 26. Cryptorchidism is failure  of the testes to descend into the scrotum;  if uncorrected, the result is infertility.  27. Vaginal infections (E. coli, STIs, and  fungal infections), which may lead to PID;  abnormal or painful menses.   1.a,b; 2.a; 3.b; 4.c¢ 5.a,c¢ 6.a, b, d;  7. d; 8. d; 9. c 10. b; 11. d; 12. c;  13.a; 14. 1-c, 2-b, 3-e, 4-a, 5-d    Representative Representative  (main group) (main group)  elements elements  IA VINA  1 2  H a He  1.0079 | IIA Periodic Table of the Elements IIA IVA VA VIA VIIA | 4o03  4 5 6 z 8 9 10  Be B Cc N O F Ne  9.012 a 10.811 | 12.011 | 14.007 | 15.999 | 18.998 | 20.180  72 Transition metals 13 14 15 16 17 18  Na | Mg VIIIB Al | Si P S CI | Ar  22.990 | 24.305 || IIB IVB VB VIB VIIB eee IB IIB |} 26.982 | 28.086 | 30.974 | 32.065 | 35.453 | 39.948  20 25 27 29  K | Ca | Sc | Ti V Cr | Mn | Fe | Co | Ni | Cu | Zn | Ga | Ge | As | Se | Br | Kr  39.098 | 40.078 | 44.956 | 47.867 | 50.942 | 51.996 | 54.938 | 55.845 | 58.933 | 58.69 | 63.546 | 65.38 | 69.723 | 72.64 | 74.922 | 78.96 | 79.904 | 83.8  37 38 39 40 a 42 43 44 45 46 47 48 49 50 51 52 53 54  Rb | Sr Y Zr Nb | Mo | Tc | Ru | Rh | Pd | Ag | Cd In Sn | Sb | Te l Xe  85.468 | 87.62 | 88.906 | 91.224 | 92.906 | 95.96 98 | 101.07 | 102.906 | 106.42 | 107.868 | 112.411 | 114.82 | 118.71 | 121.76 | 127.60 | 126.905 | 131.29  55 56 57 72 73 74 75 76 77 78 79 80 81 82 83 84 85 86  Cs | Ba | La Hf | Ta | W | Re | Os | Ir Pt | Au | Hg | TI | Pb | Bi | Po | At | Rn  137.327 | 138.906 178.49 | 180.948 | 183.84 | 186.207 | 190.23 | 192.22 | 195.08 | 196.967 | 200.59 | 204.383 | 207.2 | 208.980] 209 210 222  104 105 106 107 108 109 110 111 112 113 114 115 116 117 118  Rf | Db | Sg | Bh | Hs | Mt | Ds | Rg | Cn | Uut | Uug | Uup | Uuh | Uus | Uuo  267 268 271 272 270 276 281 280 285 284 289 288 293 292 294    58 59 60 el 62  Lanthanides | Ce | Pr | Nd | Pm | Sm  140.116 | 140.908 | 144.24 | 145 | 150.36   Actinides | Th Pa U Np Pu  232.038 | 231.036 | 238.029 | 237.048 | 244    63 64 65 66 67 68 69 70 71  Eu | Gd | Tb | Dy | Ho | Er | Tm | Yb | Lu  151.964 | 157.25 | 158.925 162.5 164.93 167.26 | 168.934 | 173.054 | 174.967  95 96 97 98 99 100 101 102 103  Am | Cm | Bk | Cf | Es | Fm | Md | No | Lr  243 247 247 251 252 257 258 259 262    The periodic table arranges elements according to atomic num-  ber and atomic weight into horizontal rows called periods and  18 vertical columns called groups or families. The elements in the  groups are classified as being in either A or B classes.   Elements of each group of the A series have similar chemical  and physical properties. This reflects the fact that members of a  particular group have the same number of valence shell elec-  trons, which is indicated by the number of the group. For exam-  ple, group IA elements have one valence shell electron, group HA  elements have two, and group VA elements have five. In contrast,  as you progress across a period from left to right, the properties  of the elements change in discrete steps, varying gradually from  the very metallic properties of groups IA and IIA elements to the  nonmetallic properties seen in group VIIA (chlorine and    *Atomic weights of the elements per IUPAC Commission on Isotopic  Abundances and Atomic Weights, 2007.    others), and finally to the inert elements (noble gases) in group  VIIIA. This change reflects the continual increase in the number  of valence shell electrons seen in elements (from left to right)  within a period.   Class B elements are referred to as transition elements.  All transition elements are metals, and in most cases they  have one or two valence shell electrons. (In these elements,  some electrons occupy more distant electron shells before  the deeper shells are filled.)   In this periodic table, the colors are used to convey  information about the phase (solid, liquid, or gas) in which  a pure element exists under standard conditions (25 degrees  centigrade and 1 atmosphere of pressure). If the element's  symbol is solid black, then the element exists as a solid. If its  symbol is red, then it exists as a gas. If its symbol is dark  blue, then it is a liquid. If the element’s symbol is green, the  element does not exist in nature and must be created by  some type of nuclear reaction.    Required for ability of eyes to  adjust to changes in light  Protects color vision   Assists cell differentiation  Required for sperm  production in men and  fertilization in women  Contributes to healthy bone  Contributes to healthy  immune system    As a powerful antioxidant,  protects cell membranes,  polyunsaturated fatty acids,  and vitamin A from oxidation  Protects white blood cells  Enhances immune function  Improves absorption of  vitamin A    Serves as a coenzyme during  production of specific proteins  that assist in blood coagula-  tion and bone metabolism    Preformed retinol:  Beef and chicken liver,  egg yolks, milk  Carotenoid precursors:  Spinach, carrots,  mango, apricots,  cantaloupe, pumpkin,  yams    Pork, fortified cereals,  enriched rice and  pasta, peas, tuna, |  egumes    Beef liver, shrimp, milk  and dairy foods,  fortified cereals,  enriched breads and  grains    Beef liver, most cuts  of meat/fish/poultry,  fortified cereals,  enriched breads and  grains, canned tomato  products    * Abbreviations: RDA, Recommended Dietary Allowance; UL, upper limit; Al, adequate intake.    Toxicity: Fatigue; bone and joint pain;  spontaneous abortion and birth  defects of fetuses in pregnant  women; nausea and diarrhea; liver  damage; blurred vision; hair loss;  skin disorders    614 Appendix D: Key Information about Vitamins and Many Essential Minerals    Required as enzyme cofactor  for amino acid metabolism  Required for DNA synthesis  Involved in metabolism of   Men and women aged  19 to 50: 1.3 mg/day  Men aged >50:   Men: 90 mg/day  Women: 75 mg/day  Smokers: 35 mg more  per day than RDA    Chickpeas (garbanzo  beans), most cuts of  meat/fish/poultry,  fortified cereals, white  potatoes    Fortified cereals,  enriched breads and  grains, spinach,  legumes (lentils,  chickpeas, pinto  beans), greens  (spinach, romaine  lettuce), liver    Shellfish, all cuts of  meat/fish/poultry, milk  and dairy foods,  fortified cereals    Table salt, pickles,  most canned soups,  snack foods, cured  luncheon meats,  canned tomato  products    Most fresh fruits and  vegetables: potatoes,  bananas, tomato  juice, orange juice,  melons    * Abbreviations: RDA, Recommended Dietary Allowance; UL, upper limit; Al, adequate intake.    Toxicity: Nerve damage, skin lesions  Deficiency: Anemia; seborrheic  dermatitis; depression, confusion,  and convulsions    Toxicity: Masks symptoms of vitamin  B42 deficiency, specifically signs of  nerve damage   Deficiency: Macrocytic anemia;  neural tube defects in a developing  fetus; elevated homocysteine levels   Deficiency: Pernicious anemia;  tingling and numbness of  extremities; nerve damage; memory  loss, disorientation, and dementia    Toxicity: Nausea and diarrhea,  nosebleeds, increased oxidative  damage, increased information of  kidney stones in people with kidney  disease    Toxicity: Water retention, high blood  pressure, loss of calcium in urine  Deficiency: Muscle cramps, dizziness,  fatigue, nausea, vomiting, mental  confusion    Component of certain B  vitamins and amino acids  Acid-base balance  Detoxification in liver    Women aged 19 to  30: 310 mg/day  Women aged >30:  320 mg/day   UL: 2.2 mg/day for  children aged 4 to 8;  10 mg/day for children  aged >8    Milk/cheese/yogurt,  soy milk and tofu,  legumes (lentils, black  beans), nuts (almonds,  peanuts and peanut  butter), poultry    Milk/yogurt/cheese  (best-absorbed form  of calcium), sardines,  collard greens and  spinach, calcium-  fortified juices    Greens (spinach, kale,  collard greens), whole  grains, seeds, nuts,  legumes (navy and  black beans)    * Abbreviations: RDA, Recommended Dietary Allowance; UL, upper limit; Al, adequate intake.   Deficiency: Low blood calcium,  muscle spasms or seizures, nausea,  weakness, increased risk of chronic  diseases such as heart disease,  hypertension, osteoporosis, and  type 2 diabetes    Toxicity: Brittle hair and nails, skin  rashes, nausea and vomiting,  weakness, liver disease   Deficiency: Specific forms of heart  disease and arthritis, impaired  immune function, muscle pain and  wasting, depression, hostility    Toxicity: Fluorosis of teeth and bones  Deficiency: Dental caries, low bone  density   Deficiency: Goiter, hypothyroidism,  cretinism in infant of mother who is  iodine deficient    616 Appendix D: Key Information about Vitamins and Many Essential Minerals    *Abbreviations: RDA, Recommended Dietary Allowance; UL, upper limit; Al, adequate intake.   Deficiency: Elevated blood glucose  and blood lipids, damage to brain  and nervous system    Toxicity: Impairment of  neuromuscular system  Deficiency: Impaired growth and  reproductive function, reduced  bone density   rapid heartbeat, organ damage, death  Deficiency: lron-deficiency microcytic  (small red blood cells), hypochromic  anemia    Toxicity: Nausea, vomiting, and  diarrhea; headaches, depressed  immune function, reduced absorption  of copper   Deficiency: Growth retardation,  delayed sexual maturation, eye and  skin lesions, hair loss, increased  incidence of illness and infection   Deficiency: Anemia, reduced levels of  white blood cells, osteoporosis in  infants and growing children    Pronunciations in the text and this glossary  use the following rules:    2. Unless otherwise noted, assume that vowels  at the ends of syllables are long and vow-  els followed by consonants are short. Ex-  ceptions to this rule are indicated by a bar  (C) over the vowel, which indicates a long  vowel, or a breve sign  over the vowel,  indicating that the vowel is short.    For example, the phonetic spelling of “thrombo-  phlebitis” is throm”bo-flé-bi'tis. The next-to-last  syllable (bi’) receives the greatest stress, and the  first syllable (throm”) gets the secondary stress.  The vowel in the second syllable comes at the  end of the syllable and is long. The vowel that  comes at the end of the third syllable is short  because it has a breve sign.    Accommodation (1) adaptation in response  to differences or changing needs; (2) adjustment  of the eye for seeing objects at close range.  Acetylcholine (ACh) a’se-til-ko'lén a chem-  ical transmitter substance released by certain  nerve endings.    Acid a substance that liberates hydrogen ions  when in an aqueous solution; proton donor;  compare with base.    Acid-base balance the maintenance of proper  pH in the body; involves buffers, the respiratory  system, and the kidneys.    Acidosis as" i-do'sis a condition in which the  blood has an excess hydrogen ion concentration  and a decreased pH; also called ketoacidosis.    Acquired immune deficiency syndrome  (AIDS) immunodeficiency caused by human  immunodeficiency virus (HIV) attacking T cells;  symptoms include severe weight loss, night  sweats, swollen lymph nodes, and opportunistic  infections.   Acrosome ak'ro-sõm an enzyme-containing  structure covering the nucleus of the sperm.  Actin ak'tin one of the principal contractile  proteins found in muscle; makes up the thin  filaments.   Action potential an electrical event occurring  when a stimulus of sufficient intensity is applied  to aneuron or muscle cell, allowing sodium ions  to move into the cell and reverse the polarity.  Active immunity immunity produced by an  encounter with an antigen; provides immuno-  logical memory.   Active site region on the surface of a globular  protein (such as an enzyme) where it interacts  with other molecules of complementary shape  and charge (such as substrate).   Active transport net movement of a substance  across a membrane against a concentration or  electrical gradient; requires release and use of cel-  lular energy.    Access a comprehensive glossary and flashcards, including audio pronunciation  for selected terms: Mastering A&P > Study Area > Additional Study Tools    Adaptive defense system branch of the  immune system that targets specific antigen;  involves B and T lymphocytes and antigen-  presenting cells; also called specific defense system.  Adenosine triphosphate (ATP) = ah-den"o-sén  tri-fos‘fat the compound that is the important  intracellular energy source; cellular energy.  Adipose tissue ad'ï-põs fat.   Adrenal glands ah-dre'nal glanz hormone-  producing glands located superior to the kidneys;  each consists of a medulla and a cortex.  Aerobic respiration respiration in which oxy-  gen is consumed and glucose is broken down  entirely; water, carbon dioxide, and large  amounts of ATP are the final products.   Afferent af er-ent carrying to or toward a center.  Afterload the force of blood pressing back on  the semilunar valves that the ventricles must  overcome in order to pump blood.  Agglutinins ah-gloo'ti-ninz antibodies in  blood plasma that cause clumping of corpuscles  or bacteria.   Agglutinogens ag" loo-tin'o-jenz (1) antigens  that stimulate the formation of a specific aggluti-  nin; (2) antigens found on red blood cells that  are responsible for determining the ABO blood  group classification.   Albumin al-bu'min a protein found in virtually  all animals; the most abundant plasma protein.  Aldosterone major mineralocorticoid hor-  mone; regulates sodium levels in the blood by  targeting kidney tubules.   Alkalosis al" kah-lo’sis a condition in which the  blood has a lower hydrogen ion concentration  than normal and an increased pH.   Allergy al'er-je overzealous immune response  to an otherwise harmless antigen, resulting in  tissue damage; also called hypersensitivity.  Alveolus al-ve'o-lus (1) a general term referring  to a small cavity or depression; (2) an air sac in  the lungs.   Amino acid ah-me'no an organic compound  containing nitrogen, carbon, hydrogen, and oxy-  gen; the building block of protein.  Amphiarthrosis am" fe-ar-thro'sis a slightly  movable joint.   Anabolism ah-nab'o-lizm the energy-requiring  building phase of metabolism in which simpler  substances are combined to form more complex  substances.   Anaerobic glycolysis an-a'er-ōb-ik a process in  which glucose is broken down in the absence of  oxygen, resulting in the formation of 2 ATP mol-  ecules and lactic acid.   Anatomical position reference point for  regional and directional terminology; standing,  feet parallel, palms facing forward.    Anemia ah-ne'me-ah reduced oxygen-carrying  capacity of the blood caused by a decreased num-  ber of erythrocytes or decreased percentage of  hemoglobin in the blood.    Antecubital anterior surface of the elbow.  Antibody an"ti-bod'e a specialized substance  produced by the body that can provide immunity  against a specific antigen.   Antigen (Ag) an'tī-jen any substance—includ-  ing toxins, foreign proteins, or bacteria—that,  when introduced to the body, is recognized as  foreign and activates the immune system.  Antigen-presenting cells (APCs) cells that dis-  play portions of foreign antigens to T cells; include  dendritic cells, macrophages, and B lymphocytes.  Antimicrobial proteins defensive proteins  that assist the innate defenses by attacking  microbes directly or by preventing their repro-  duction; see complement and interferon.   Aorta a-ortah the major systemic artery; arises  from the left ventricle of the heart.   Apocrine gland ap’o-krin the less numerous  type of sweat gland. Its secretions contain water,  salts, fatty acids, and proteins.   Appendicular skeleton ap’ en-dik'u-lar bones  of the limbs and limb girdles that are attached to  the axial skeleton.   Aqueous humor a'kwe-us hu'mer the watery  fluid in the anterior chambers of the eye.  Arachnoid granulation special projections of  the arachnoid mater that protrude through the  dura mater; site of cerebrospinal fluid absorption  into the dural venous sinuses.   Arachnoid mater middle layer of the menin-  ges; has weblike extensions attach to the inner  layer, the pia mater.   Arrector pili ah-rek'tor pi'li tiny, smooth mus-  cles attached to hair follicles; when activated,  they cause the hair to stand upright.   Arteriole ar-ter'e-ðl minute artery.  Arteriosclerosis ar-tér'e-o-skler-o'sis any of a  number of proliferative and degenerative changes  in the arteries leading to their decreased elasticity  and hardening; end stage of atherosclerosis.  Artery a vessel that carries blood away from the  heart.    Arthritis ar-thri'tis inflammation of the joints.  Articular cartilage hyaline cartilage covering  the epiphysis of a bone at a joint.   Asthma az'mah disease or allergic response  characterized by bronchial spasms and difficult  breathing.   Astigmatism = ah-stig’mah-tizm a visual defect  resulting from irregularity in the lens or cornea of  the eye causing the image to be out of focus.  Astrocyte as'tro-sīt type of CNS supporting  cell; assists in exchanges between blood capillar-  ies and neurons.   Atherosclerosis a" ther-o’skler-o'sis changes in  the walls of large arteries consisting of lipid  deposits on the artery walls; the early stage of  arteriosclerosis and increased rigidity.    Atlas the first cervical vertebra; articulates with  the occipital bone of the skull and the second  cervical vertebra (axis).   Atom at'um the smallest part of an element;  indivisible by ordinary chemical means.   Atomic mass number the sum of the number  of protons and neutrons in the nucleus of an  atom; also known as mass number.    Atomic symbol a one- or two-letter symbol  indicating a particular element.  Atrioventricular (AV) node =a’ tre-o-ven-trik'u-  lar a specialized mass of conducting cells located  at the atrioventricular junction in the heart.  Atrioventricular (AV) valves two valves set  between the atria and ventricles to prevent back-  flow; includes the mitral (bicuspid) on the left  and the tricuspid on the right.   Atrium a'tre-um a chamber of the heart re-  ceiving blood from the veins; superior heart  chamber.   Atrophy afťro-fe a reduction in size or wasting  away of an organ or cell resulting from disease or  lack of use.   Auricle the external part of the ear surrounding  the auditory canal; also called pinna.  Autonomic nervous system the division of  the nervous system that functions involuntarily;  innervates cardiac muscle, smooth muscle, and  glands; also called involuntary nervous system.   Axial skeleton ak'se-al the skull, vertebral col-  umn, ribs, and sternum.   Axis (1) the second cervical vertebra; has a  vertical projection called the dens around which  the atlas rotates; (2) the imaginary line about  which a joint or structure revolves.    Axon ak’son neuron process that carries  impulses away from the nerve cell body; efferent  process; the conducting portion of a nerve cell.    Axon terminal one of multiple ends of the  axon that branch from the motor neuron axon;  interacts with the sarcolemma of different muscle  cells to form neuromuscular junctions.    B cells lymphocytes that oversee humoral  immunity; their descendants differentiate into  antibody-producing plasma cells; also called B  lymphocytes.   Ball-and-socket joint multiaxial synovial  joint in which the rounded head of one bone fits  into a socket (depression) on the other.    Basal metabolic rate (BMR) met’ ah-bol'ik  the rate at which energy is expended (heat pro-  duced) by the body per unit time under con-  trolled (basal) conditions: 12 hours after a meal,  at rest.    Basal nuclei nu'kle-i gray matter areas deep  within the white matter of the cerebral hemi-  spheres; also called basal ganglia.    Base (1) a substance that accepts hydrogen  ions; proton acceptor; compare with acid; (2) the  broad, posterosuperior aspect of the heart where  large vessels enter or leave the heart; (3) the  broad inferior area of each lung resting on the  diaphragm.    Basement membrane a thin layer of extracel-  lular material to which epithelial cells are  attached in mucosa surfaces.   Basilar membrane the membrane in the  cochlear duct that vibrates to transmit sound waves  and also houses the receptor cells for hearing.  Basophils ba'so-filz white blood cells whose  granules stain deep blue with basic dye; have a  relatively pale nucleus and granular-appearing  cytoplasm.   Bicarbonate buffer system system com-  posed of bicarbonate ion (HCO;,) and its salt,  sodium bicarbonate (NaHCO3), that resists  changes in blood pH.   Bile a greenish yellow or brownish fluid pro-  duced in and secreted by the liver, stored in the  gallbladder, and released into the small intestine.  Blind spot gap in vision caused by a lack of  photoreceptors at the optic disc.   Blood liquid connective tissue composed of  plasma and cells responsible for transporting  substances such as nutrients and oxygen around  the body.   Blood pressure the pressure exerted by blood  against the inner walls of blood vessels.    Bone markings surface features of bones  where muscles, tendons, and ligaments attach,  and where blood vessels and nerves pass.   Bone remodeling the process of repairing or  maintaining bone by adding or removing bone  matrix in response to damage or mechanical  stress.   Bony thorax bøn'e tho'raks bones of the thorax,  including ribs, sternum, and thoracic vertebrae;  also called thoracic cage.   Brachial bra'ke-al pertaining to the arm.  Bradycardia brad"e-kar'de-ah slow heart rate,  usually defined as a rate under 60 beats per minute.  Brain stem the portion of the brain consisting  of the medulla, pons, and midbrain.   Broad ligament large ligament formed by a  fold of peritoneum that encloses the ovaries and  holds them in place, and suspends the uterus  from the pelvis.   Brush border enzymes enzymes embedded  in the plasma membranes of the brush border  cells that help complete digestion in the small  intestine.   Buffer a substance or substances that help to  stabilize the pH of a solution.   Bulbourethral glands tiny glands inferior to  the prostate that produce clear mucus that neu-  tralizes urine prior to ejaculation.   Burn tissue damage resulting in cell death  caused by electricity, chemicals, too much heat or  UV radiation. Burns vary in degree of severity. See  rule of nines.   Bursa ber'sah a small sac filled with fluid and  located at friction points, especially joints.   Calyx ka'liks a cuplike extension of the pelvis of  the kidney.   Cancer a malignant, invasive cellular neo-  plasm that has the capability of spreading  throughout the body or body parts.  Carbohydrate kar”bo-hi'drāt organic com-  pound composed of carbon, hydrogen, and oxy-  gen; includes starches, sugars, cellulose.   Cardiac cycle sequence of events encompass-  ing one complete contraction and relaxation of  the atria and ventricles of the heart.   Cardiac muscle specialized muscle of the  heart with striations and intercalated discs; invol-  untary muscle.   Cardiac output (CO) the blood volume (in  liters) ejected per minute by each ventricle.  Cardiac veins veins that drain the myocar-  dium and empty into the coronary sinus.  Cardiovascular system organ system that dis-  tributes blood to all parts of the body.   Carpal kar'pal (1) one of the eight bones of the  wrist; (2) pertaining to the wrist.   Cartilaginous joint = kar’ti-laj'i-nus bones  united by cartilage; no joint cavity is present.  Catabolism kah-tab'o-lizm the process in which  living cells break down substances into simpler  substances; destructive metabolism.   Cataract = kat'ah-rakt partial or complete loss of  transparency of the crystalline lens of the eye.  Catecholamines — kat’ é-kol'ah-ménz epineph-  rine and norepinephrine.   Cauda equina kaw'da e-kwi'nah the collection  of spinal nerves at the inferior end of the verte-  bral canal.   Cell the basic biological unit of living organ-  isms, enclosed by a limiting membrane; cells in  more complex organisms contain a nucleus and  a variety of organelles.   Cell body the part of a neuron containing the  nucleus; the metabolic center of a neuron.   Cell division the phase of a cell's life cycle  when it reproduces itself.   Cellular immunity | sel'u-lar i-mu'ni-te im-  munity conferred by lymphocytes called T cells;  also called cell-mediated immunity.  Central nervous system (CNS)  and the spinal cord.   Centriole _ sen'tre-dl a minute body found near  the nucleus of the cell composed of microtu-  bules; active in cell division.   Centromere sen'tro-mear button-like body  holding sister chromatids together; also, the site  of attachment to the mitotic spindle.   Cephalic seh-fa'lik pertaining to the head.  Cerebellum _ ser’e-bel'um part of the hindbrain;  involved in producing smoothly coordinated  skeletal muscle activity.    Cerebral white matter area of the cerebrum  deep to the cerebral cortex containing fiber tracts  carrying impulses to, from, or within the cortex.  Cerebrospinal fluid (CSF) the fluid pro-  duced by choroid plexuses; fills the ventricles and  surrounds the central nervous system.    Cerebrovascular accident (CVA) a condi-  tion in which brain tissue is deprived of a blood  supply, as in blockage of a cerebral blood vessel;  also called a stroke.    Cerebrum  sé-ré’brum the largest part of the  brain; consists of right and left cerebral hemi-  spheres.  Cerumen  Cervical _ ser’vi-kal term referring to the neck or  the necklike portion of an organ or structure.    Cervical cancer uncontrolled cellular growth  in the cervix that is almost always associated with  one or more strains of human papilloma virus  (HPV).   Cervix serviks the inferior necklike portion of  the uterus leading to the vagina.    Chemical reaction process in which mole-  cules are formed, changed, or broken down.   Chief cells cells of the gastric glands that  secrete inactive pepsinogen.   Cholesterol ko-les'ter-ol a steroid found in ani-  mal fats as well as in most body tissues; made by  the liver.   Chordae tendineae tendinous chords that  anchor the flaps of the closed AV valves to prevent  inversion and backflow of blood.   Chorionic villi embryonic tissue projections  that will combine with tissue of the uterine lining  to form the placenta.   Choroid ko'roid the pigmented nutritive layer  of the eye; part of the vascular layer.   Choroid plexus structure in each of the four  brain ventricles that produces cerebrospinal fluid  (CSF).   Chromatid kro'mah-tid one copy of the DNA  after replication but before cell division; still  paired with the other copy, together called sister  chromatids, by a centromere.    Chromatin kro'mah-tin the structures in the  nucleus that carry the hereditary factors (genes).  Chromosome kro'ma-sõm barlike body of  tightly coiled chromatin; visible during cell  division.   Chyme kīm the semifluid stomach contents  consisting of partially digested food and gastric  secretions.   Cilia sil’e-ah tiny, hairlike projections on cell  surfaces that move in a wavelike manner.  Ciliary body _ sil'e-er-e smooth muscle of the  vascular tunic of the eye that is connected to the  lens by the ciliary zonule.   Ciliary zonule suspensory ligament that attaches  the lens to the ciliary body in the anterior eye.    Citric acid cycle the aerobic pathway occur-  ring within the mitochondria, in which energy is  liberated during metabolism of carbohydrates,  fats, and amino acids and CO; is produced.  Clavicle — klav'i-kl collar bone; part of the pecto-  ral girdle that attaches medially to the manu-  brium and laterally to the scapula.   Cleavage klév'ij an early embryonic phase con-  sisting of rapid cell divisions without intervening  growth periods.   Cleavage furrow indentation formed by a  contractile ring of microfilaments; continues to  contract until cytokinesis is complete and two  daughter cells are formed. See cytokinesis.  Clitoris kli'to-ris a small, erectile structure in  the female, homologous to the penis in the male.  Clonal selection klo'nul the process during  which a B cell or T cell becomes sensitized  through binding contact with an antigen.    Coccyx kok'siks three to five fused bones form-  ing the inferior section of the spine; tailbone.  Cochlea kok’le-ah a cavity of the inner ear resem-  bling a snail shell; houses the hearing receptor.  Cochlear duct the location of the spiral organ  of Corti in the cochlea; contains endolymph.    Codon ko'don the three-base sequence on a  messenger RNA molecule that provides the  genetic information used in protein synthesis;  codes for a given amino acid.   Coenzymes nonprotein molecules, such as  vitamins, that are necessary for the function of  some enzymes.   Colitis  Colon the part of the large intestine between  the cecum and the rectum.  Common hepatic duct  bile from the liver.    Compact bone dense bone composed of  osteons that makes up the outer layer of flat,  short and irregular bones; major component of  long bones.   Complement a group of plasma proteins that  normally circulate in inactive forms; when acti-  vated by complement fixation, causes lysis of  foreign cells and enhances phagocytosis and  inflammation.   Compound substance composed of two or  more different elements, the atoms of which are  chemically united.   Concentration gradient a difference in  amount of a substance between two areas.    Conchae kong‘ke projections from the walls of  the nasal cavity that increase air turbulence and  the surface area of mucous membrane exposed to  the air to aid in warming and moistening.  Concussion brain injury with reversible  damage.   Conducting zone structures all respiratory  passages that carry air to the terminal bronchioles  and beyond.   Conduction deafness hearing loss due to  interference in transmitting sound waves to the  inner ear.   Condylar joint —kon'di-ler biaxial synovial joint  in which the convex surface of one bone fits into  the concave surface of another.    Cones one of the two types of photoreceptor  cells in the retina of the eye. Provides for color  vision.   Conjunctiva = kon" junk-ti'vah the thin, protec-  tive mucous membrane lining the eyelids and  covering the anterior surface of the eyeball.  Connective tissue a primary tissue; form and  function vary extensively. Functions include sup-  port, storage, and protection.   Control center component of homeostatic  control receiving sensory input and sending  motor output.    Coronal suture interlocking joint formed at  the intersection of the two parietal bones with  the frontal bone; also called the frontal suture.    Coronary arteries arteries that branch off the  aorta and supply the myocardium.    Coronary sinus enlarged vessel that receives  blood from the cardiac veins and empties into  the right atrium.   Corpus callosum korpus kah-lo'sum large fiber  tract of the cerebral white matter that connects  the cerebral hemispheres.    Corpus luteum korpus lu'te-um structure  formed by the ruptured follicle cells after ovula-  tion; secretes estrogen and progesterone.    Corticosteroids hormones secreted by the  adrenal cortex, including mineralocorticoids,  glucocorticoids, and sex hormones.  Covalent bond ko-va'lent a bond involving the  sharing of electrons between atoms.    Cranial nerves the 12 pairs of nerves that arise  from the brain.    Cranium part of the skull that encloses and  protects the brain.   Creatine phosphate (CP) kre’ah-tén fos'fat a  compound that transfers a phosphate group to  ADP to regenerate ATP in muscle fibers.   Crista ampullaris receptors in the ampullae  of the semicircular canals that detect dynamic  equilibrium.   Cross bridge the link formed when a myosin  head binds to the corresponding binding site on  actin during contraction.    mental defect in which one or both testes fail to  descend into the scrotum.    Cupula = ku'pu-lah a domelike structure; in the  cristae of the inner ear, a gel-like cap covering the  “hairs” of receptor cells.   Cushing’s syndrome koosh'ingz sin'drom a dis-  ease produced by excess secretion of glucocorti-  coids (such as cortisol); characterized by adipose  tissue accumulation, weight gain, and osteoporosis.   Cytokinesis _ si” to-ki-ne'sis division of cytoplasm  that occurs after the cell nucleus has divided.  Cytoplasm sīi'to-plazm” the substance of a cell  other than that of the nucleus.   Cytoskeleton literally, cell skeleton; inter-  nal framework of proteins that determine cell  shape. See microtubules, intermediate filaments, and  microfilaments.   Cytotoxic T cell effector T cell that directly  kills foreign cells; also called a killer T cell.    Dead space volume volume of air that never  reaches the alveoli and does not participate in gas  exchange.   Decomposition reaction a destructive chem-  ical reaction in which complex substances are  broken down into simpler ones.   Defecation reflex def”ih-ka'shun the elimina-  tion of the contents of the bowels (feces).  Deglutition de”gloo-tish'un the act of swallowing.  Dehydration synthesis process by which a  larger molecule is synthesized from smaller ones  by removal of a water molecule at each site of  bond formation.   Dendrites den'drītz the branching extensions  of neurons that carry electrical signals to the cell  body; the receptive portion of a nerve cell.  Deoxyribonucleic acid (DNA) de-ok"sï-ri”bo-  nu-kle'ik nucleic acid found in all living cells:  carries the organism's hereditary information.  Depolarization de-po”lar-i-za'shun the loss of a  state of polarity; the loss of a negative charge  inside the plasma membrane.   Dermis dermis the deep layer of the skin; com-  posed of dense, irregular connective tissue.  Desmosome dez'mo-sõm cell junction com-  posed of thickened plasma membranes joined by  filaments.   Diabetes mellitus di”ah-be'tēz mel'i-tus a disease  caused by deficient insulin release or inadequate  responsiveness to insulin, leading to inability of the  body cells to use carbohydrates at a normal rate.  Diapedesis di” ah-pé-de’sis the passage of blood  cells through intact vessel walls into the tissues.  Diaphragm di'ah-fram (1) any partition or  wall separating one area from another; (2) a  muscle that separates the thoracic cavity from the  abdominopelvic cavity.    Diastole di-as'to-le a period (between contrac-  tions) of relaxation of the heart during which it  fills with blood.    Diastolic pressure di’as-to'lik the arterial  blood pressure during ventricular relaxation  (diastole).   Diencephalon di" en-sef ah-lon that part of the  forebrain between the cerebral hemispheres and  the midbrain including the thalamus, the third  ventricle, and the hypothalamus; also called  interbrain.   Diffusion  di-fu'zhun the spreading of particles  in a gas or solution with a movement toward  uniform distribution of particles; also called sim-  ple diffusion.   Digestive system system that processes food  into absorbable units and eliminates indigestible  wastes.   Digital pertaining to the digits; fingers, toes.  Distal convoluted tubule (DCT) segment of  kidney tubule between the ascending nephron  loop and the collecting duct; site of some reab-  sorption and some secretion.   Diverticulum = di" ver-tik’u-lum a pouch or sac  in the walls of a hollow organ or structure.  Dorsal ramus branch of a spinal nerve that  serves the skin and muscles of the posterior trunk.  Dorsal root the root at which sensory neurons  enter the spinal cord.   Dorsal root ganglion the location of cell  bodies of sensory neurons which enter the spinal  cord via the dorsal root.   Ductus arteriosus a shunt in the fetal heart  that connects the aorta and pulmonary trunk in  order to bypass the immature lungs.   Ductus deferens duk'tus def ‘er-enz segment of  the male duct system that links the epididymis to  the ejaculatory duct.   Ductus venosus a shunt in the fetal heart that  bypasses the immature liver.   Dura mater du'rah ma'ter the outermost and  toughest of the three membranes (meninges)  covering the brain and spinal cord.   Dynamic equilibrium sense that reports on  angular or rotatory movements of the head in  space.    Eccrine gland ek'rin the more numerous type  of sweat gland found all over the body, but par-  ticularly abundant on the palms, soles of feet,  and the forehead. Its secretions contain water,  salts and metabolic wastes such as urea and uric  acid.   Edema č-de'mah an abnormal accumulation of  fluid in body parts or tissues; causes swelling.  Effector ef-fek'tor an organ, gland, or muscle  capable of being activated by nerve endings.  Efferent ef er-ent carrying away or away from.  Efferent arteriole arteriole leaving the  glomerulus and connecting it to the peritubular  capillaries.   Ejaculation = e-jak"u-la'shun the sudden ejec-  tion of semen from the penis.   Electrical energy energy form resulting from  the movement of charged particles.  Electrocardiogram (ECG) e-lek"tro-kar'de-o-  gram” a graphic record of the electrical activity of  the heart.    Electroencephalogram (EEG)  (e-lek" tro-en-  sefah-lo-gram) graphic record of the electrical  activity of the brain.   Electrolyte e-lek'tro-līt a substance that breaks  down into ions when in solution and is capable  of conducting an electric current.   Electron transport chain metabolic pathway  within the mitochondria in which energy har-  vested from high-energy hydrogen atoms is used  to make ATP. Final delivery of H to molecular  oxygen produces water.   Element = el'é-ment any of the building blocks of  matter; oxygen, hydrogen, carbon, for example.    Embolus a free-floating clot in an unbroken  vessel.  Embryo em'bre-o an organism in its early stages   Endocardium = en"do-kar'de-um the endothelial  membrane lining the interior of the heart.  Endocrine glands  en'do-krin ductless glands  that empty their hormonal products directly into  the blood.   Endocytosis en”do-si-to'sis means by which  fairly large extracellular molecules or particle  enter cells. See phagocytosis, pinocytosis, receptor-  mediated endocytosis.   Endolymph_ = en'do-limf thick fluid inside the  membranous labyrinth similar to perilymph.  Endometrium en-do-me'tre-um the mucous  membrane lining of the uterus.   Endomysium = en"do-mis‘e-um the thin connec-  tive tissue surrounding each muscle cell.  Endoneurium a delicate connective tissue  sheath surrounding each fiber in a nerve.  Endoplasmic reticulum (ER) en”do-plas'mik  ré-tik'u-lum a membranous network of tubular or  saclike channels in the cytoplasm of a cell.  Energy the ability to do work.  Enteroendocrine cells cells of the gastric glands  that secrete locally acting hormones, such as gastrin.  Enzyme en'zīm a substance formed by living  cells that acts as a catalyst in chemical reactions  in the body; see catalyst.   Eosinophils e”o-sin'o-filz granular white  blood cells whose granules readily take up a  stain called eosin.   Ependymal cell é-pen'di-mal type of CNS sup-  porting cell; lines the central cavities of the brain  and spinal cord and circulates cerebrospinal fluid  with their beating cilia.   Epicardium visceral layer of a serous mem-  brane that tightly hugs the external surface of the  heart and is actually part of the heart wall; also  called visceral pericardium.   Epididymis ep’ i-did'i-mis that portion of the  male duct system in which sperm mature. Emp-  ties into the ductus deferens (vas deferens).  Epiglottis ep”ř-gloť'is the elastic cartilage at the  back of the throat; covers the glottis during  swallowing.    Epimysium = ¢p"i-mis‘e-um the sheath of fibrous  connective tissue surrounding a muscle.  Epineurium a tough, fibrous sheath that binds  together the fascicles in a nerve.   Epiphyseal line calcified line in the epiphysis  of a long bone that contained hyaline cartilage  during the period of long bone growth, which  ends when calcification is complete.   Epiphyseal plate plate of hyaline cartilage in  the epiphysis of a long bone that allows for  growth in length.   Epiphysis  Epithalamus roof of the third ventricle; com-  posed of the pineal gland and the choroid plexus  of the third ventricle.   Epithelial membranes membranes com-  posed of epithelial tissue with an underlying  layer of connective tissue; covering and lining  membranes. See mucous membrane and serous  membrane.    Epithelium = ep" i-the'le-um one of the primary  tissues; covers the surface of the body and lines  the body cavities, ducts, and vessels.   Erection enlargement and increased rigidity of  the penis resulting when erectile tissue fills with  blood.  Erythrocytes  Erythropoietin hormone that stimulates  erythrocyte production; secreted by kidneys.  Esophagus muscular tube that carries food  from the pharynx to the stomach.   Estrogens es'tro-jenz hormones that stimulate  female secondary sex characteristics; female sex  hormones.    Eupnea 1ip-ne’ah easy, normal breathing.  Exchange reaction a chemical reaction in  which bonds are both made and broken; atoms  become combined with different atoms.  Excretion ek-skre'shun the elimination of waste  products from the body.   Exocrine glands ek'so-krin glands that have  ducts through which their secretions are carried  to a body surface (skin or mucosa).   Exocytosis ek”so-si-to'sis method for the move-  ment of substances from the cell interior to the  extracellular space as a secretory vesicle fuses with  the plasma membrane.   Extracellular fluid (ECF) fluid within the  body but outside the cells; see interstitial fluid.  Extracellular matrix nonliving material in  connective tissue consisting of ground substance  and fibers that separate the living cells.    Facilitated diffusion passive transport pro-  cess driven by a concentration gradient and  requiring a membrane protein to act as a carrier  or channel.    Fertilization fer'ti-lï-za'shun fusion of the  nuclear material of an egg and a sperm.   Fetus fe'tus the unborn young; in humans, the  period from the third month of development  until birth.   Fibrillation _fi-bri-la'shun irregular, uncoordi-  nated contraction of muscle cells, particularly of  the heart musculature.   Fibrin fibrin the fibrous insoluble protein  formed during the clotting of blood.  Fibrocartilage callus repair tissue formed  during bone remodeling; “splint” composed of  cartilage matrix, bony matrix, and collagen fibers.  Fibrous joint bones joined by fibrous tissue;  no joint cavity is present.   Fibrous pericardium loose-fitting sac sur-  rounding the heart that anchors the heart to sur-  rounding structures.   Fibrous protein a strandlike protein that  appears most often in body structures; very  important in binding structures together and for  providing strength in certain body tissues; also  called structural protein.   Fibular pertaining to the area of the fibula, the  lateral bone of the leg.   Filtration fil-tra'shun the passive process of  forcing water and solutes through a membrane  using a fluid pressure gradient.   Fimbriae fim'bre-e fingerlike projections that line  the distal end of each uterine tube that create fluid  currents to wave the oocyte inside after ovulation.  Fissure fiszher (1) a groove or cleft; (2) the  deepest depressions or inward folds on the brain.  Flaccid flă'sid soft; flabby; relaxed.   Flagella flah-jel'ah long, whiplike extensions of  the cell membrane of some bacteria and sperm;  serve to propel the cell.   Follicle _fol'li-kul (1) structure in an ovary con-  sisting of a developing egg surrounded by follicle  cells; (2) colloid-containing structure in the thy-  roid gland; (3) collection of lymphocytes in a  lymph node.   Follicle cells cells that surround and help  nourish a developing oocyte.    Fovea centralis fo've-ah sen-tra'lis pit contain-  ing only cones lateral to the blind spot of the eye.  Frequency (1) the number of sound waves per  unit time, measured in Hertz; (2) the need to  urinate often.   Frontal (coronal) section (plane) a longi-  tudinal plane that divides the body or an organ  into anterior and posterior portions.   Fused tetanus tet'ah-nus a completely smooth,  sustained muscle contraction resulting from rapid  stimulation with no time for relaxation between  stimulation events; also called complete tetanus.    Gallstones particles of hardened cholesterol  or calcium salts that are occasionally formed in  the gallbladder and bile ducts.   Ganglion gang'le-on a group of nerve cell bod-  ies located in the peripheral nervous system.  Gap junction a passageway between two  neighboring cells; formed by transmembrane  proteins called connexons.   Gastric glands glands within the gastric pits  of the stomach that secrete the components of  gastric juice and include chief, parietal, mucous  neck, and enteroendocrine cells.   Gastric juice fluid formed by secretions of the  gastric glands, characterized by extreme acidity  and pepsin, a protein-digesting enzyme.  Gastrin gas'trin a hormone that stimulates gas-  tric secretion, especially release of hydrochloric  acid.   Gastrointestinal (GI) tract continuous hol-  low muscular tube including all structures from  mouth to anus.   Gene jën biological units of heredity located in  chromatin; transmits hereditary information.  Gland an organ specialized to secrete or excrete  substances for further use in the body or for  elimination.   Glaucoma glaw-ko'mah an abnormal increase  of the pressure within the eye.   Globular protein a protein whose functional  structure is basically spherical. Also referred to as  functional protein; includes hemoglobin, enzymes,  and some hormones.   Glomerular capsule glo-mer'u-ler double-  walled cuplike end of a renal tubule; encloses a  glomerulus; also called Bowman's capsule.  Glomerular filtration the process of forcing  fluids and small particles out of the blood and  into the glomerular capsule and renal tubule.  Glomerulus glo-mer'u-lus a knot of coiled cap-  illaries in the kidney; forms filtrate.   Glottis gloťis the opening between the vocal  cords in the larynx.   Gluconeogenesis = glu"ko-ne"o-jen'é-sis the for-  mation of new glucose molecules from noncar-  bohydrate substances, such as fats and proteins.  Glucose = gloo’kés the principal sugar in the  blood; a monosaccharide.   Glucocorticoids hormones of the adrenal cor-  tex that regulate cell metabolism and mediate the  long-term stress response.   Gluteal gloo'te-al pertaining to the buttock.  Glycerol glis'er-ol a sugar alcohol; one of the  building blocks of fats.   Glycogen gli'ko-jen the main carbohydrate  stored in animal cells; a polysaccharide.  Glycogenesis gli" ko-jen’é-sis formation of gly-  cogen from glucose.   Glycolysis gli-kol'i-sis breakdown of glucose to  pyruvic acid; an anaerobic process.   Golgi apparatus gol'je ap"uh-rat'is membrane-  bound organelle responsible for modifying,  packaging, and shipping proteins produced by  rough ER to the appropriate destination.   Gout gouty arthritis; caused by uric acid  buildup in joints. See arthritis.   Graded potential a local change in mem-  brane potential that varies directly with the  strength of the stimulus; declines with distance.  Graded response a response that varies  directly with the strength of the stimulus.   Gray matter the gray area of the central ner-  vous system; contains unmyelinated nerve fibers  and nerve cell bodies.   Gum the tissue that surrounds the teeth like a  tight collar; also called gingiva (jin'ji-vah).  Gustatory hairs long microvilli of gustatory  cells; protrude through the taste pore in the  tongue epithelium and transmit signals to the  brain.   Gyrus jirus an outward fold of the surface of  the cerebral cortex.    Hair flexible epithelial structure composed of  keratinized cells; produced by hair follicle.   Hair follicle Structure with inner root sheath  of epithelial tissue that produces the hair; the  outer root sheath is dermal connective tissue that  provides the blood supply to epithelial cells.  Hard palate roof of mouth formed by the  fusion of the two maxillae bones.   Haustra pocketlike sacs caused by tone of the  teniae coli (longitudinal muscle bands) of the  colon.    Heartburn pain in the esophagus due to reflux  of gastric juice.   Helper T cell the type of T lymphocyte that  orchestrates cellular immunity by direct contact  with other immune cells and by releasing  chemicals called cytokines; also helps to medi-  ate the humoral response by interacting with  B cells.   Hemocytoblasts he” mo-si'to-blastz stem cells  that give rise to all the formed elements of the  blood.   Hemoglobin (Hb) he”mo-glo'bin the oxygen-  transporting pigment of erythrocytes.  Hemolysis he-mol'ï-sis the rupture of erythro-  cytes.  Hemostasis  Hepatic portal vein single vein that drains  the digestive tract organs and carries nutrient-  rich blood to the liver before it enters general  circulation.    Hiatal hernia protrusion of the superior part  of the stomach above the diaphragm, resulting in  entry of gastric juice into the esophagus.  High-density lipoproteins proteins that  carry cholesterol from the tissues to the liver for  destruction.   Hilum hilum a depressed area where vessels  enter and leave an organ.    Histamine _ his'tah-mén a substance that causes  vasodilation and increased vascular permeability.  Homeostasis ho”me-o-sta'sis a state of dynamic  body equilibrium or stable internal environment  of the body.   Homeostatic imbalance a disturbance or  change in homeostasis that effects function.  Hormones hor’médnz chemical messengers  secreted by endocrine glands; responsible for  specific regulatory effects on certain cells, tissues,  or organs.   Human chorionic gonadotropin (hCG) an  LH-like hormone produced by the developing  embryo that tells the corpus luteum to continue  producing hormones to prevent menses.  Humerus long bone of the upper arm; articu-  lates with the scapula to form the shoulder joint  and the radius and ulna to form the elbow joint.  Humoral immunity hu'mor-al immunity pro-  vided by antibodies released by sensitized B cells  and their plasma cell progeny. Also called  antibody-mediated immunity.   Hyaline cartilage cartilage connective tissue  containing collagen fibers; has glassy appearance;  found on ends of long bones and forms C-shaped  rings in trachea.   Hydrocephalus a condition in which cerebro-  spinal fluid accumulates and puts pressure on the  brain of an adult; in an infant, the skull may  expand because the skull bones are not yet fused.  Hydrogen bond weak bond in which a hydro-  gen atom forms a bridge between two electron-  hungry atoms. An important intramolecular  bond.   Hydrolysis hi-drol'i-sis the process in which  water is used to split a substance into smaller  particles.   Hydrophilic hi’ dro-fil'ik refers to molecules, or  portions of molecules, that interact with water  and charged particles.   Hydrophobic hi" dro-fo'bik refers to molecules,  or portions of molecules, that interact only with  nonpolar molecules.   Hyperpnea hy-perp'ne-ah pattern of breathing  faster and deeper during exercise.  Hypersensitivities allergies; overreaction of  the immune system to a perceived threat, result-  ing in tissue damage.   Hyperthyroidism overactivity of the thyroid,  resulting in higher-than-normal levels of thyroid  hormone, causing an increased metabolic rate.  Hypertonic hi" per-ton'ik excessive, above nor-  mal, tone or tension.   Hypertrophy hi-per'tro-fe an increase in the  size of a tissue or organ independent of the  body’s general growth.   Hyperventilation pattern of breathing in  which excess carbon dioxide is exhaled in an  effort to raise blood pH to its normal range.  Hypodermis adipose tissue beneath the skin.  See subcutaneous.    Hypospadias hi" po-spa'’de-as condition occur-  ring in male babies only where the urethral  opening is located on the ventral surface of the  penis.   Hypothalamus hi" po-thal'ah-mus the region of  the diencephalon forming the floor of the third  ventricle of the brain.   Hypoxia hi-pok'se-ah a condition in which  inadequate oxygen is available to tissues.    Ileum = il'e-um the terminal part of the small  intestine; between the jejunum and the cecum of  the large intestine.   Ilium _ il'e-um large flaring bone of the hip; the  most superior bone of the pelvis.   Immune response antigen-specific defenses  mounted by activated lymphocytes (T cells and B  cells).    Immune system the body system responsible  for protecting the body from pathogens and  foreign cells; involves both humoral and cell-  mediated defenses.   Immunodeficiency — im" mu-no-de-fish'en-se dis-  ease resulting from the deficient production or  function of immune cells or certain molecules  (complement, antibodies, and so on) required  for normal immunity.   Immunoglobulin (Ig) im” mu-no-glob'u-lin a  protein molecule, released by plasma cells, that  mediates humoral immunity; an antibody.  Inclusions in-klu'zhun chemical substances  stored in the cytoplasm of a cell.   Infarct in'farkt a region of dead, deteriorating  tissue resulting from a lack of blood supply.  Inferior vena cava large vein that carries  blood from veins inferior to the diaphragm back  to the right atrium.   Inflammatory response in-flam'ah-tor’e a  physiological response of the body to tissue  injury; includes dilation of blood vessels and  increased blood vessel permeability.   Inguinal in'gwï-nal pertaining to the groin region.  Innate defense system natural defenses that  protect against all foreign material, not specifi-  cally for any one antigen; also called nonspecific  defense system.   Insertion in-ser'shun the movable attachment  of a muscle as opposed to its origin.  Inspiration in" spi-ra'shun the drawing of air  into the lungs; inhalation.   Inspiratory reserve volume (IRV) amount  of air that can be forcibly inhaled in addition to  tidal volume.   Integration the process in which the nervous  system processes and interprets sensory input  and makes decisions about what should be done.  Integumentary system in-teg”u-men'tuh-re  the skin and its accessory organs (jin'ji-vah).    Intercalated discs in-ter'kah-la'ted specialized  connections for communication between car-  diac muscle cells containing gap junctions and  desmosomes.    Interferons antimicrobial proteins produced  by virus-infected cells to stimulate neighboring  cells to produce antiviral proteins that either  block binding or block replication of the virus.  Intermediate filaments one of three types of  rods in the cytoskeleton of a cell; resists pulling  forces on the cell.   Interneuron completes the pathway between  afferent and efferent neurons; also called an asso-  ciation neuron.    Interosseous membrane flexible fibrous con-  nective tissue attachment connects the radius and  ulna, and the tibia and fibula along their lengths.  Interphase the period in a cell’s life cycle  when it performs its usual metabolic activities  and prepares for cell division by copying the  DNA (genes).   Interstitial fluid (tissue fluid) in”ter-stish'al  the fluid between the cells; also called extracellu-  lar fluid.   Intervertebral discs in" ter-ver'té-bral the discs  of fibrocartilage between the vertebrae.    Intrapleural pressure pressure in the space  between the pleurae; always negative compared  to intrapulmonary pressure.   Intrinsic conduction system control system  built into the heart that sets the rate of contrac-  tion by stimulating the myocardium in an atrial  to ventricular direction; also called nodal system.  Intrinsic factor in-trin’sik a substance pro-  duced by the stomach that is required for vitamin  B,, absorption.   Ion řon an atom with a positive or negative  electric charge.   Ionic bond bond formed by the complete  transfer of electron(s) from one atom to another  (or others). The resulting charged atoms, or ions,  are oppositely charged and attract each other.  Iris iris the pigmented, involuntary muscle  that acts as the diaphragm of the eye; part of the  vascular tunic of the eye.    Isotope i'sï-tōp different atomic form of the  same element. Isotopes vary only in the number  of neutrons they contain.    Jaundice jawn'dis an accumulation of bile pig-  ments in the blood producing a yellow color of  the skin.   Jejunum = jé-joo’num the part of the small intes-  tine between the duodenum and the ileum.   Juxtamedullary nephrons nephrons that sit  close to the cortex-medulla junction, with neph-  ron loops that dip deep into the renal medulla.    Keratin = ker’ah-tin a tough, insoluble protein  found in tissues such as hair, nails, and epidermis  of the skin.   Ketoacidosis low blood pH due to the metab-  olism of fats to produce ATP in the absence of  sufficient glucose.   Kilocalories (kcal) unit used to measure the  energy value of food.   Kinins ki'ninz group of polypeptides that  dilate arterioles, increase vascular permeability,  and induce pain.   Kyphosis _ ki-fo'sis hump formed by the abnor-  mal curvature of the thoracic spine in a posterior  direction.   Lacteal lak'te-al special lymphatic capillaries of  the small intestine that take up lipids.   Lactic acid lak'tik the product of anaerobic  metabolism, especially in muscle.   Lacuna lah-ku'nah a little depression or space;  in bone or cartilage, lacunae are occupied by cells.  Lambdoid suture interlocking joint between  the occipital bone and the parietal bones.  Lamella concentric rings of bone matrix with  lacuna between them.   Lamina lam 'i-nah (1) a thin layer or flat plate;  (2) the portion of a vertebra between the trans-  verse process and the spinous process.   Larynx larinks the cartilaginous organ located  between the trachea and the pharynx; voice box.  Leukemia lu-ke'me-ah a cancerous condition in  which there is an excessive production of imma-  ture leukocytes.   Lingual tonsils pair of tonsils at the base of  the tongue.    Liver gland of the digestive tract that produces  bile and is the major metabolic gland of the body.  Long bone a bone that is longer than it is  wide. See humerus and femur.   Lordosis lor-do'sis the abnormal curvature of  the lumbar spine in an anterior direction.  Low-density lipoproteins proteins that carry  cholesterol to the tissues.   Lumbar lum'bar the portion of the back  between the thorax and the pelvis; the loin.  Lumen lu'men the space inside a tube, blood  vessel, or hollow organ.   Lungs organs of the respiratory system respon-  sible for air exchange with the outside and gas  exchange with the blood.    Luteinizing hormone (LH)  gonadotropic  hormone released by the anterior pituitary gland.  Lymph limf the watery fluid in the lymph ves-  sels collected from the tissue spaces.   Lymphatic system lim-fat'ik the lymphatic  vessels and the lymphoid tissues and organs,  including lymph nodes.   Lymphocytes lim'fo-sītz agranular white blood  cells formed in the bone marrow that mature in  the lymphoid tissue.   Lymphoid organs organs in the lymphatic  system, including lymph nodes, spleen, and ton-  sils; see lymphatic system.   Lysosomes li'so-sõmz organelles that originate  from the Golgi apparatus and contain strong  digestive enzymes.   Lysozyme li'so-zīm an enzyme found in sweat,  saliva, and tears that is capable of destroying cer-  tain kinds of bacteria.    Macrophage mak'ro-fāj” cell particularly abun-  dant in lymphatic and connective tissues; impor-  tant in the immune response as an antigen  presenter to T cells and B cells.   Main (primary) bronchi divisions of the tra-  chea that lead into the right and left lungs.  Major nutrients nutrients the body requires  in significant amounts; include carbohydrates,  proteins, and fats.   Malignant = mah-lig'nant life-threatening; per-  tains to neoplasms that spread and lead to death,  such as cancer.   Malleus mã'le-us lateral bone of the middle  ear; also called the hammer.   Manubrium = mah-nu'bre-um the most superior  of the three bones of the sternum.   Mass movements long, powerful, slow-moving  contractions of the large intestine that move  materials toward the rectum.   Maxillary bones mak-sil'uh-re paired facial  bones that fuse to form the upper jaw and articu-  late with all other facial bones except the man-  dible; also called maxillae.   Mechanical energy energy form directly  involved in putting matter into motion.  Mechanoreceptors mek” ah-no-re-sep'terz  receptors sensitive to mechanical pressures such  as touch, sound, or contractions.   Median (midsagittal) section specific sagit-  tal plane that lies exactly in the midline.  Mediastinum me”de-as-ti'num the region of  the thoracic cavity between the lungs that houses  the heart.   Medulla oblongata most inferior part of  brainstem involved in visceral control.  Medullary cavity central cavity in the diaphy-  sis of a long bone containing marrow.  Megakaryocytes large, multinucleate cells  that fragment to produce platelets.    Meiosis mi-o'sis the two successive cell divi-  sions in gamete formation producing nuclei with  half the full number of chromosomes (haploid).  Melanin = mel'ah-nin the dark pigment synthe-  sized by melanocytes; responsible for skin color.  Membranous urethra the part of the male ure-  thra that connects the prostatic urethra to the penis.    Memory cell member of T cell and B cell  clones that provides for immunological memory.   Menstrual cycle the periodic, cyclic discharge  of blood, secretions, tissue, and mucus from the  mature female uterus in the absence of pregnancy;  a series of cyclic changes of the endometrium in  response to changing ovarian hormone levels; also  called menstruation, uterine cycle.    Merkel cell cells associated with nerve endings  that serve as touch receptors.    Mesentery mes‘en-ter"e the double-layered  membrane of the peritoneum that supports most  organs in the abdominal cavity.   Messenger RNA (mRNA) long nucleotide  strands that reflect the exact nucleotide sequence  of the DNA gene; carry this information to the  ribosome for protein synthesis.    Metabolism — mé-tab'o-lizm the sum total of the  chemical reactions that occur in the body.    Metacarpal met’ ah-kar'pal one of the five  bones of the palm of the hand.    Metastasis mč-tas'tah-sis the spread of cancer  from one body part or organ into another not  directly connected to it.    Metatarsal — met" ah-tar'sal one of the five bones  between the tarsus and the phalanges of the foot.    Microbiome the intersection of the human  body, the microbiota and all their genes, and the  body's environment, along with how these fac-  tors influence human health.    Microbiota the microbial residents of the  body, including bacteria, fungi, viruses, and para-  sites. Also called normal flora.   Microfilaments = mi"kro-fil'ah-ments thin  strands of the contractile protein actin; one of  three types of rods in the cytoskeleton of a cell.  Microglia mi-krog'le-ah type of CNS supporting  cell; phagocytes that ingest debris such as bacteria  or dead cells.    Microtubules — mi" kro-too’bulz one of three types  of rods in the cytoskeleton of a cell; hollow tubes  made of spherical protein that determine the cell  shape and the distribution of cellular organelles.  Microvilli mi”kro-viľi the tiny projections on  the free surfaces of some epithelial cells; increase  surface area for absorption.   Midbrain part of the brain stem containing  reflex centers for vision and hearing, and fiber  tracts (cerebral peduncles) that convey both  ascending and descending impulses.   Minor nutrients vitamins and minerals;  nutrients the body needs in small amounts.    Miscarriage termination of a pregnancy before  the embryo or fetus is viable outside the uterus.  Mitochondria = mi” to-kon'dre-ah the rod-like  cytoplasmic organelles responsible for ATP  generation.   Mitosis mi-to'sis the division of the cell  nucleus; often followed by division of the cyto-  plasm of a cell.   Mixed nerves nerves containing the processes  of motor and sensory neurons; their impulses  travel to and from the central nervous system.    Molecule — mol'é-kyool particle consisting of two  or more atoms held together by chemical bonds.  Monoclonal antibodies mon"o-klon'ul pure  preparations of identical antibodies that exhibit  specificity for a single antigen.   Monocyte mon'o-sīt large single-nucleus white  blood cell; agranular leukocyte.  Monosaccharide —mon"o-sak'i-rid literally, one  sugar; the building block of carbohydrates; exam-  ples include glucose and fructose.   Motor division the part of the PNS that sends  motor signals from the CNS to muscles or glands;  also called efferent division.    Motor unit a motor neuron and all the muscle  cells it supplies.    Mucous membrane (mucosa) membrane  that forms the linings of body cavities open to the  exterior (digestive, respiratory, urinary, and repro-  ductive tracts).   Multiple sclerosis (MS) autoimmune disor-  der of the CNS where the myelin sheaths are  converted into hardened scleroses in the brain  and spinal cord; results in loss of control.    Multipolar neuron structural class of neuron  with more than two processes extending from the  cell body.   Muscle tissue one of four main tissue types;  specialized to contract (shorten) in order to pro-  duce a force that will cause movement.    Muscle tone sustained partial contraction of a  muscle in response to stretch receptor inputs;  keeps the muscle healthy and ready to react.  Muscle twitch a single rapid contraction of a  muscle followed by relaxation.   Muscular system organ system consisting of  skeletal muscles and their connective tissue  attachments.    Muscularis externa smooth muscle layer of  the gastrointestinal tract composed of an inner  circular layer and an outer longitudinal layer.  Myasthenia gravis = mi’as-the'ne-ah gră'vis an  autoimmune disease affecting muscles; character-  ized by weakness and fatigue due to a shortage of  acetylcholine receptors.    Myelin  Myocardial infarction mi”o-kar'de-al in-  fark'shun a condition characterized by dead tissue  areas in the myocardium caused by interruption  of blood supply to the area.   Myocardium = mi"o-kar'de-um the cardiac mus-  cle layer of the heart wall.    Myofilament = mi"o-fil'ah-ment filaments com-  posing the myofibrils. Of two types: actin and  myosin.   Myosin mi'o-sin one of the principal contrac-  tile proteins found in muscle; makes up the thick  filaments.    Nasal septum tissue at midline that separates  the nasal cavity into right and left sides.   Natural killer (NK) cells unique lympho-  cytes that are part of the nonspecific defenses; kill  cells that do not exhibit self markers.   Neck (1) portion of the body connecting the  head to the thorax that contains the trachea and  esophagus; (2) portion of a tooth connecting the  crown and root.   Negative feedback feedback that causes the  stimulus to decline or end.   Nephron loop portion of the renal tubule  between the proximal and distal convoluted  tubules; also called loop of Henle.    Nerve bundle of neuronal processes (axons)  outside the central nervous system.    Nerve impulse a self-propagating wave of  depolarization; also called an action potential.  Nervous system fast-acting control system  that employs nerve impulses to trigger muscle  contraction or gland secretion.    Nervous tissue one of four main tissue types;  specialized for irritability (respond to stimuli)  and conductivity.   Neuroglia nu-rōg'le-ah the nonneuronal tissue  of the central nervous system that performs sup-  portive and other functions; also called glial cells  or glia.   Neuromuscular junction nu”ro-mus'ku-lar  the region where a motor neuron comes into  close contact with a skeletal muscle cell.    Neurons nu'ronz cells of the nervous system  specialized to transmit messages throughout the  body.   Neurotransmitter chemical released by neu-  rons that may, upon binding to receptors of  neurons or effector cells, stimulate or inhibit  them.   Neutralization — nu" tral-i-za'shun (1) a chem-  ical reaction that occurs between an acid and a  base; (2) blockage of the harmful effects of bacte-  rial exotoxins or viruses by the binding of anti-  bodies to their functional sites.    Nose  system.  Nuclear envelope the double membrane bar-  rier of the nucleus; separates the nucleoplasm  from the cytoplasm.    Nucleoli nu-kle'o-li small spherical bodies in  the cell nucleus; function in ribosome synthesis.   Nucleus — nu’kle-us (1) a dense central body in  most cells containing the genetic material of the  cell; (2) cluster of neuronal cell bodies in the  brain or spinal cord.   Nutrient chemical substance used by the body  for normal growth, maintenance, and repair.    Obturator foramen ob'tu-ra"tor opening  formed by fusion of the rami of the ischium  posteriorly and the pubis anteriorly; allows blood  vessels and nerves to pass into the anterior thigh.  See foramen.    Occipital ok-sip'i-tal pertaining to area at the  back of the head.   Oligodendrocyte  ol'i-go-den'dro-sit type of  CNS supporting cell that has many cellular pro-  cesses, each of which makes up a myelin sheath.  Oocyte  Oogenesis 0”o-jen'č-sis the process of forma-  tion of the ova.   Opsonization _ the process of easing phagocyto-  sis, typically by an antibody or complement pro-  tein that binds antigen to mark it for destruction.  Optic chiasma op'tik ki-as'mah the partial  crossover of fibers of the optic nerves.   Optic disc site where the optic nerve meets the  retina; causes the blind spot.   Organ a part of the body formed of two or  more tissues that performs a specialized function.    Organ system a group of organs that work  together to perform a vital body function; e.g.,  nervous system.   Organic compound a compound containing  carbon; examples include proteins, carbohy-  drates, and fats.   Origin the muscle attachment that is not mov-  able or is less movable than the insertion.  Orthostatic hypotension temporary hypo-  tension due to abrupt movement from a sitting  or reclining position to an upright position.  Osmoreceptor 02" mo-re-sep'tor a structure sen-    Osmosis oz-mo'sis the diffusion of water (a  solvent) through a membrane from a dilute solu-  tion into a more concentrated one.   Ossicles os'sï-kulz the three bones of the mid-  dle ear: hammer (malleus), anvil (incus), and  stirrup (stapes); also called the auditory ossicles.  Ossification the process of bone formation.  Osteoarthritis (OA) most common form of  arthritis; caused by wear and tear at joints that  leads to articular cartilage breakdown. See arthritis.    Osteoclasts os'te-o-klasts” large cells that resorb  or break down bone matrix.    Osteocyte os'te-o-sīt” a mature bone cell.  Osteon os'te-on the structural and functional  unit of compact bone; Haversian system.  Osteoporosis os" te-o-po-ro'sis an increased  softening of the bone resulting from a gradual  decrease in rate of bone formation; a common  condition in older people.   Otolith o'to-lith one of the small calcified  masses in the maculae of the vestibular apparatus  in the inner ear.    Otosclerosis 0" to-sklé-ro'sis fusion of the ossi-  cles (bones) in the middle ear; results in conduc-  tion deafness.   Oval window the superior, membrane-covered  opening in the middle ear wall; sound is con-  veyed to the oval window by the stirrup (stapes).  Ovarian cycle o-va're-an the monthly cycle of  follicle development, ovulation, and corpus  luteum formation in an ovary.   Ovarian follicles saclike structures consisting  of follicle cells and a developing oocyte.  Ovarian ligaments bilateral ligaments that  anchor the ovaries to the uterus.   Ovary o'var-e the female sex organ in which  ova (eggs) are produced.   Ovulation ov”u-la'shun the release of an ovum  (or oocyte) from the ovary.    P wave wave on an ECG representing depolar-  ization of the atria.   Pancreas pan'kre-as gland posterior to the  stomach, between the spleen and the duode-  num; produces both endocrine and exocrine  secretions.   Pancreatic juice pan"kre-at'ik a secretion of  the pancreas containing enzymes for digestion of  all food categories.   Papilla pah-pil'ah small nipplelike projection.  Papillary layer superficial layer of dermis bor-  dering epidermis; contains dermal papillae, the  cause of fingerprints. See dermal papillae.  Paranasal sinuses air-filled spaces within the  maxillae on either side of the nasal cavity that are  lined with mucous membrane; help lighten the  skull.   Parasympathetic division par’ ah-sim'pah-  thet'ik a division of the autonomic nervous sys-  tem; also referred to as the craniosacral division.  Parathyroid glands par”ah-thi'roid small  endocrine glands located on the posterior aspect  of the thyroid gland.    Parathyroid hormone (PTH) hormone  released by the parathyroid glands that regulates  blood calcium level.   Parietal cells cells of the gastric glands that  produce hydrochloric acid (HCI).   Parietal pericardium outermost layer of the  serous pericardium that lines the interior surface  of the fibrous pericardium.   Parietal peritoneum lining of the abdomino-  pelvic cavity that is continuous with the serosa, or  visceral peritoneum of the gastrointestinal tract.    Parietal pleura ploor'ah serous membrane  layer covering the cavity in which the lung  resides.    ula and clavicle, that attach the upper limb to the  axial skeleton; also called the shoulder girdle.    Pedicle bony extension connecting the cen-  trum and transverse process of a vertebra.   Pelvic girdle incomplete bony basin formed  by the two coxal bones and the sacrum.   Pepsin an enzyme capable of digesting pro-  teins in an acid pH.   Perforating canal canal running at right  angles to the central canal in an osteon. Also  called Volkmann’s canal.    Perforating fibers connective tissue fibers  that secure the periosteum to the bone; also  called Sharpey’s fibers.   Perimysium per’ i-mis'e-um the connective tis-  sue enveloping bundles of muscle fibers.  Perineum per”i-ne'um that region of the body  extending from the anus to the scrotum in males  and from the anus to the vulva in females.    Perineurium coarse connective tissue wrap-  ping that binds groups of fibers in a nerve, form-  ing fascicles, or fiber bundles.   Periosteum per-e-os'te-um double-layered con-  nective tissue membrane that covers and nour-  ishes the bone.   Peripheral nervous system (PNS) _ pé-rif er-al  a system of nerves that connects the outlying  parts of the body with the central nervous system.    Peripheral resistance the resistance to blood  flow offered by the systemic blood vessels; a  measure of the amount of friction encountered  by blood.   Peristalsis per"i-stal'sis the waves of contrac-  tion seen in tubelike organs; propels substances  along the tract.    Peritoneum per’i-to-ne’um the serous mem-  brane lining the interior of the abdominal cavity  and covering the surfaces of the abdominal  organs.   Peritubular capillaries low-pressure capillar-  ies that arise from the efferent arteriole and sur-  round the renal tubule of each nephron to aid in  reabsorption.   Peroxisomes per-ok'sih-sõmz membranous sacs  in the cytoplasm containing powerful oxidase  enzymes that use molecular oxygen to detoxify  harmful or toxic substances, such as free radicals.  Petechiae pč-te'ke-e rashlike spots on the skin  that indicate widespread bleeding.   pH the symbol for hydrogen ion concentra-  tion; a measure of the relative acidity or alkalinity  of a solution.   Phagocyte fag'o-sīt cell capable of engulfing  and digesting particles or cells harmful to the  body using the process of phagocytosis.  Phagocytosis fag" o-si-to'sis the ingestion of  solid particles by cells.   Pharyngeal tonsil far-rin'je-al single tonsil,  also called adenoid, located in the nasopharynx.  Pharyngotympanic tube tube that connects  the middle ear and the pharynx; allows pressure  to be equalized on both sides of the eardrum;  also called the auditory tube and the eustachian  tube.   Pharynx farinks the muscular tube extending  from the posterior of the nasal cavities to the  esophagus.   Photopupillary reflex protective reflex that  constricts the pupil upon exposure to bright light  to prevent damage to photoreceptors.  Photoreceptors fo" to-re-sep'torz specialized  receptor cells that respond to light energy.  Physiology fiz’ e-ol'o-je the science of the func-  tioning of living organisms.   Pia mater innermost meningeal layer; clings  to the surface of the brain and spinal cord.  Pinocytosis pin”uh-si-to'sis the engulfing of  extracellular fluid by cells.   Pivot joint uniaxial synovial joint in which  the rounded end of one bone fits into a sleeve or  ring of bone or ligaments.   Placenta plah-sen'tah the temporary organ that  provides nutrients and oxygen to the developing  fetus, carries away wastes, and produces the hor-  mones of pregnancy.   Plane joint nonaxial synovial joint in which  the two bones have flat articular surfaces; a plane  joint allows only short gliding movements.  Plantar plan'tar pertaining to the sole of the  foot.   Plasma membrane membrane that encloses  cell contents; outer limiting membrane.  Platelet plat'let one of the irregular cell frag-  ments of blood; involved in clotting.    Pleura ploo'rah the serous membrane covering  the lung and lining the thoracic cavity.   Plexus network of nerves formed by joining  ventral rami of spinal nerves; contains both sen-  sory and motor fibers.   Plicae circulares pli'kuh” ser-ku-lar'éz cork-  screw-like folds within the small intestine that  increase the surface area and slow the progression  of food through the small intestine; also called  circular folds.   Polar body a minute cell produced during  meiosis in the ovary.   Polycythemia pol"e-si-the'me-ah presence of an  abnormally large number of erythrocytes in the  blood.   Pons (1) any bridgelike structure or part; (2)  the brain area connecting the medulla with the  midbrain, providing linkage between upper and  lower levels of the central nervous system.  Popliteal related to the posterior knee.    Positive feedback feedback that tends to  cause a variable to change in the same direction  as the initial change; enhances the stimulus.  Potential energy stored energy; energy at rest;  compare to kinetic energy.   Precipitation formation of insoluble com-  plexes that settle out of solution.   Preload the amount of stretch of cardiac mus-  cle; related to venous return.   Presbyopia pres"be-o'pe-ah a decrease in lens  elasticity, due to aging, that leads to farsightedness.  Pressure gradient difference in hydrostatic  (fluid) pressure that drives filtration.   Primary curvatures spinal curvatures in the  thoracic and sacral areas that are present at birth.  Primary (essential) hypertension high  blood pressure that cannot be directly linked to  any specific cause.   Primary humoral response the initial  response of the humoral arm of the immune  system to an antigen; involves clonal selection  and establishes immunological memory.  Primary motor area area of the cerebral cor-  tex responsible for voluntary movement; located  in the precentral gyrus.   Primary somatic sensory area area of the  cerebral cortex responsible for interpreting  impulses from cutaneous sense organs and pro-  prioceptors; located in the postcentral gyrus.  Progesterone ovarian hormone produced by  the corpus luteum and later the placenta; respon-  sible for maintaining the uterine lining during  pregnancy, inhibiting contraction of uterine  muscle, and helping to prepare the breasts for  lactation.   Proprioceptor pro" pre-o-sep'tor a receptor  located in a muscle or tendon; concerned with  locomotion, posture, and muscle tone.  Prostate accessory organ of the male repro-  ductive tract that produces a milky fluid that  contributes to semen by activating sperm.    Prostatic urethra the segment of the urethra  that passes through the prostate.   Proximal convoluted tubule (PCT) seg-  ment of the renal tubule between the glomerular  capsule and the descending nephron loop; site of  most reabsorption and some secretion.   Puberty pu'ber-te the period at which repro-  ductive organs become functional.   Pubic symphysis cartilaginous joint formed  at the anterior of the two hip bones where the  pubis bones articulate.   Pubis pu'bis most anterior bone of the hip; the  pubis from each hip bone meets to articulate at  the pubic symphysis joint anteriorly. See pubic  symphysis.   Pulmonary circulation system of blood ves-  sels that carry blood to and from the lungs for gas  exchange.   Pulmonary edema č-de'mah a leakage of fluid  into the air sacs and tissue of the lungs.  Pulmonary pleura ploor'ah serous membrane  layer covering the surface of each lung; also called  visceral pleura.   Pulmonary trunk large artery connecting the  right ventricle with the pulmonary arteries.   Pulp the part of the tooth that provides nutri-  ents and sensation; composed of blood vessels,  connective tissue, and nerves.   Pulse the rhythmic expansion and recoil of  arteries resulting from heart contraction; can be  felt from the outside of the body.   Pupil an opening in the center of the iris  through which light enters the eye.   Purkinje fibers pur-kin'je the modified cardiac  muscle fibers of the conduction system of the  heart that carry impulses to the myocardium.  Pus the fluid product of inflammation, com-  posed of white blood cells, the debris of dead  cells, and a thin fluid.    Pyelonephritis pi”č-lo-ně-fri'tis an inflamma-  tion of the kidney pelvis and surrounding kidney  tissues.   Pyloric valve valve formed by the pyloric  sphincter between the stomach and small intestine.  Pyramidal tracts major motor pathways con-  cerned with voluntary movement; connect pri-  mary motor area in the frontal lobes of each  cerebral hemisphere with the spinal cord; also  called corticospinal tracts.    QRS complex wave on an ECG representing  depolarization of the ventricles.    Radiant energy energy of the electromagnetic  spectrum, which includes heat, light, ultraviolet  waves, infrared waves, and other forms.  Radioactivity the process of spontaneous  decay seen in some of the heavier isotopes, dur-  ing which particles or energy is emitted from the  atomic nucleus; results in the atom becoming  more stable.    the capitulum of the humerus at the elbow and  the carpals distally.   Real image image formed on the retina that is  reversed left to right and inverted (upside down)  as a result of the refraction bending of light by  the lens.   Receptor re-sep'tor (1) a peripheral nerve end-  ing specialized for response to particular types of  stimuli; (2) molecule that binds specifically with  other molecules, e.g., hormones and neurotrans-  mitters.   Receptor-mediated endocytosis the type of  endocytosis in which engulfed particles attach to  receptors on the cell surface before endocytosis  occurs.    Rectum portion of the large intestine between  the sigmoid colon and the anal canal.   Red marrow bone marrow that is the site of  blood cell production; see hematopoiesis.    Reduction restoring broken bone ends (or a  dislocated bone) to its original position.   Reflex automatic reaction to a stimulus.  Refract bend; usually refers to light.  Regulatory T cell type of T lymphocyte that  slows or stops activity of B and T cells once the  antigenic threat is ended.   Renin re'nin an enzyme released by the kidneys  that is involved with raising blood pressure.  Renin-angiotensin mechanism system trig-  gered by low blood pressure or changes to filtrate    solute concentrations that results in angiotensin  II production and rising blood pressure.    Repolarization restoration of the membrane  potential to the initial resting (polarized) state.  Reproductive system organ system that func-  tions to produce offspring.    Resistance exercise refers to building muscle  mass and strength; also called isometric exercise.    Respiration the process of supplying the body  with oxygen and removing carbon dioxide;  includes both internal and external respiration.  Respiratory membrane (air-blood bar-  rier) membrane composed of the alveolar  wall, the capillary wall, and their basement mem-  branes; gases must cross this membrane for  proper exchange to occur.   Respiratory system organ system that carries  out gas exchange; includes the nose, pharynx,  larynx, trachea, bronchi, and lungs.  Respiratory zone part of the lung that leads  into the alveoli and is involved in gas exchange.  Responsiveness the ability to sense changes  (stimuli) in the environment and then to react to  them; see also irritability.   Rete testis re'te structures that carry sperm  from the seminiferous tubules to the epididymis.  Reticular layer deep layer of the dermis; con-  tains hair follicles, sweat glands, sebaceous  glands and is highly vascular.   Retina retï-nah light-sensitive layer (tunic) of  the eye; contains rods and cones.    Rheumatoid arthritis (RA) chronic inflam-  matory form of arthritis caused by an autoim-  mune disorder in which the immune system  mistakenly attacks the joints bilaterally. See  arthritis.   Ribonucleic acid (RNA) ri’bo-nu-kle'ik the  nucleic acid that contains ribose; acts in protein  synthesis.   Rickets disease in which the bones of children  fail to calcify properly, leading to bowing of the  leg bones.   Rods one of the two types of photosensitive  cells in the retina.    Round ligaments ligaments that anchor the  uterus to the pelvis anteriorly.   Round window inferior, membrane-covered  opening in the middle ear wall between the vesti-  bule and the cochlea.    Rule of nines method of computing the  extent of burns by dividing the body into 11  areas, each accounting for 9 percent of the total  body area plus an area around the genitals repre-  senting 1 percent of the body.    Sacral sa'krul referring to the lower portion of  the back, just superior to the buttocks at the base  of the spine.   Sacrum sa'krum bone made up of five fused  bones; forms the posterior of the pelvis.   Saddle joint biaxial synovial joint in which  both articulating bones have both convex and  concave surfaces.   Sagittal section (plane) saj'ř-tal a longitudi-  nal (vertical) plane that divides the body or any  of its parts into right and left portions.   Sagittal suture interlocking joint formed by  the intersection of the two parietal bones at the  midline of the skull.    Salivary amylase enzyme in saliva that begins  the digestion of starch.   Salivary glands three pairs of glands that pro-  duce a mixture of mucus and serous fluid con-  taining the enzyme salivary amylase, lysozyme,  and IgA antibodies.   Salt ionic compound that dissociates into  charged particles (other than hydrogen or  hydroxyl ions) when dissolved in water.  Sarcomere  sar’ko-mér the smallest contractile  unit of muscle; extends from one Z disc to the next.    Sarcoplasmic reticulum specialized smooth  endoplasmic reticulum found in muscle cells  that stores and releases calcium during muscle  contraction.   Satellite cell type of neuroglia in the PNS; pro-  tects and cushions peripheral nerve cell bodies.  Scapula skap'u-luh triangular bone of the pec-  toral girdle that articulates with the clavicle and  humerus.    Schwann cell type of neuroglia in the PNS;  many Schwann cells form the myelin sheath on a  single neuron.   Sclera skle'rah the firm white fibrous outer  layer of the eyeball; protects and maintains eye-  ball shape.   Scoliosis sko”le-o'sis the abnormal curvature of  the spine in a lateral direction.    Scrotum skro'tum a divided sac that suspends  the testes outside the body at the root of the penis.    Sebaceous glands seh-ba'shus glands that  empty their sebum secretion into hair follicles.    Second messenger intracellular molecule  generated by binding of a chemical to a mem-  brane receptor; mediates intracellular responses.  Secondary curvatures spinal curvatures in the  cervical and lumbar regions that develop after birth.    Secondary humoral response second and  subsequent responses of the humoral arm of the  immune system to a previously met antigen;  more rapid and more vigorous than the primary  response.   Secondary oocyte the developing oocyte after  the first meiotic division; the cell that gets  ovulated.    Secondary sex characteristics anatomical  features that develop under influence of sex hor-  mones that are not directly involved in the repro-  ductive process. Include male or female pattern of  muscle development, bone growth, body hair, etc.  Secretion se-kre'shun (1) the passage of mate-  rial formed by a cell to its exterior; (2) cell prod-  uct that is transported to the cell exterior.  Segmentation the mixing of foodstuffs by the  alternating contraction and relaxation of the cir-  cular muscle layer in the muscularis externa of  the gastrointestinal tract.    Selective permeability characteristic exhi-  bited by a barrier, such as a membrane, that  allows some substances through and excludes  others. 
essentials-of-human-anatomy-physiology-13th-edition Essentials of Human Anatomy & Physiology, 13th edition_djvu.txt