Larynx Trachea Lymphatic drainage There are no lymphatic vessels in the alveoli. The lymphatic vessels fro m the alveolar duct and bronchioles follow the bronchial tree back to the hilum and then th e mediastinum. Lymph nodes may occur along their intrapulmonary course. Beneath the viscera l pleura a plexus of lymphatics are present, they drain into the peribronchial lymphatics, through vessels that run in septae through the acini and segments. It is distension of thes e horizontally placed septae which causes Kerley B lines. Left upper lobe Right upper lobe Horizontal fissure Oblique fissure Oblique fissure Middle lobe Left lower lobe Right lower lobe Fig. 1.1.1 Lobes and \201 ssures. AUTHOR \200\231S TIP Since there is communication between the pulmonary and bronchial circu lation in the parenchyma, the bronchial arteries may contribute to gas exchange in pulmonar y vascular disorders. Parenchyma Terminal bronchioles (0.5mm diameter) are the last airway before the alveolar li ned respiratory bronchioles start. There are 20,000 \200\22330,000 terminal bronchioles, ea ch ending in an acinus (primary bronchiole). Respiratory bronchioles within an acinus will branch several times until they reach the further divided alveolar ducts which lead to the alveo- lar sacs and their alveoli. The secondary lobule is the smallest section of lung whi ch can be seen on high resolution computed tomography (HRCT); it contains 5 or 6 acini, who se interlobular septum consists of pulmonary lymphatics, veins and a discrete layer of conn ective tissue (Fig. 1.1.2). CHAPTER 1.1 Pulmonary anatomy 3 Pulmonary veins Trachea Right main bronchus Left main bronchus 1 2 1 3 2 4 Carina 3 4 5 5 10 6 6 9 8 7 10 7 8 9 RIGHT LEFT 1 Apical (RUL) 1 Apical (LUL) 2 Posterior (RUL) 2 Posterior (LUL) 3 Anterior (RUL) 3 Anterior (LUL) 4 Superior Lingular 4 Lateral (RUL) 5 Inferior Lingular 5 Medial (RUL) 6 Lateral Basal 6 Lateral Basal 7 Posterior Basal 7 Posterior Basal 8 Anterior Basal 8 Anterior Basal 9 Medial Basal 9 Medial Basal 10 Apical Lower 10 Apical Lower Fig. 1.1.3 Diagram of the bronchial tree with typical segmental bronchi. Nomenclature is th at used most commonly in the UK. J ASH-MILES & M DARBY 4 1.2 Radiology of the healthy chest The plain chest X-ray (CXR) Technical factors PA (postero-anterior) Full inspiration (mid-d iaphragm crossed by 5th \200\2237th ante- rior ribs) necessary to assess heart size and med iastinal contours. Less = reduced lung volume, obesity or poor patient cooperation. More = asthma, emphysema/chronic obstructive airways disease (COAD) or \201 t healthy young adul t. Heart size <50% of max. internal chest diameter. \200 Aortic knuckle Left pulmonary artery Left hilar point Right hilar point Horizontal fissure Emphysema/COAD, \200\230normal \200\231 heart size may be signi \201 - cantly less, due t o over expansion of rib cage \200\223 changes from previous may be more useful. In elderly /osteoporosis, chest diameter may be relatively less, and so \200\230normal \200\231 heart size could be up to 2/3rds chest diameter. Rotation \200\223 spinous processes over mid t rachea; clavicles and ribs symmetrical. If not, can cause apparent lucency/ increased densi ty of one lung. \200\230Hidden lung \200\231 Beware the \200\230hidden \200\231 zones \200\223 nearly 50% of lung area may be partiall y obscured on PA view by mediastinum and dia- phragm (anterior and posterior costophrenic r ecesses). These areas are even less well seen on portable \201 lms. Aortic knuckle Sternum AP (antero-posterior) supine Magni \201 cation of mediastinum makes sizes inaccurate, but gives useful information on gross lung pathologies and position of lines, drains and tubes. Left main pulmonary artery Ribs Irregular lower border smooth upper border Lateral Allows visualization of \200\230hidden \200\231 areas and localizes to a lobe a le sion seen on PA view. Carina Normal appearances (Fig 1.2.1) Mediastinum Left heart border made up of 4 \200\230moguls \200\231 = aortic knuckle (indents trachea), pulmonary artery, left atrial appendage and le ft ventricle. Right heart border made up from ascending aorta and right atrium. Hilar point s formed by the crossing of upper and lower zone broncho-vascular bundles. Left lies 1 \200 \2231.5cm higher than right. Bronchus intermedius Right and left main bronchi Fig. 1.2.1 Normal PA CXR. Assessing the CXR Systematic approach Mediastinum, lungs, bones and soft tissues. Lung parenchyma Branching pattern of bronchovascular bundles which taper towards periphery. Arteries accompany airways, but latter not discernable except above each hilum when seen e nd-on as rings. Absence of discernable structures in outer 1/3 of lungs. Interstitium only visible when pathological. Fissures may undulate and frequently incomplete (NB cause of col lateral air drift between lobes). Horizontal \201 ssure joins right hilum. Obliques pass from few centimeters behind anterior chest wall to 6th thoracic vertebra. Mediastinum Aorto-pulmonary window is concave (if not, is there nodal disease?). Additional , \200\230double \200\231 contours to heart border signify abnormal pathology. Shift of Hi lar points indicates either traction due to col- lapse/ \201 brosis or pressure from space -occupying lesions. Left heart border obscuration indicates lingular disease. Right heart b order obscuration indicates middle lobe disease. Superior mediastinal borders may widen in elderly due to ectasia of vessels, or by obesity. Diaphragms Right up to 2cm higher than left. If not \200\230dome \200\231 shape, suggests hyperin \202 ation. Localized bulge \200\223 \200\230eventration \200\231 due to muscle de \201 ciency, usually antero-medial portion. CHAPTER 1.2 Radiology of the healthy chest 5 Beware \200 Lungs Overall picture \200\223 lung volumes, symmetry of density and size. Variations with in a lung. Refer to \200\230zones \200\231, not lobes unless obvious or have a lateral \201 lm. \200\230Hidden \200\231 areas \200\223 behind heart, lung apices (partially obscured by o verlying bones), through diaphragm in anterior and posterior costophrenic recesses. Bones \200\223 lower borders of posterior ribs often indistinct, upper borders smooth and clear m argins. Fractures, metastases. Soft tissues \200\223 beware extra thoracic soft tissue lin es mimicking pathology (e.g. pneumothorax). Mastectomy causes unilateral lucency of a lung. Lateral CXR (Fig. 1.2.2) Retrosternal and retrocardiac areas should be more \200\230black \200\231. Gradual transition from whiter to blacker lung over spine as pass cranio-caudally . R Computed tomography (CT) Techniques Helical = spiral = multidetector CT Constant acquisitio n of images as patient passes through scanner. Modern scanners can acquire 64 (or more) ima ges per rotation of X-ray tube. A volume of information is acquired which can be manipulate d to give reformations in sagittal, coronal or oblique planes. IV contrast allows improved visualization of vascular structures. Protocol varies depending on clinical question: \200 Horizontal fissure Retrosternal space Oblique fissures Retro- cardiac space PE scans need high volume at high \202 ow rates, to prefer- entially visualize pulmonary arteries. Staging scans may be in 2 phases; \201 rst to show mediasti- num and second del ayed to show liver in portal venous phase. Pleural disease is better shown at delayed phase to improve soft tissue enhancement. Right Diaphragm Left Posterior Costophrenic spaces Fig. 1.2.2 Normal lateral CXR. AUTHOR \200\231S TIP Clinical information vital to ensure correct protocol followed. Common normal variants Pectus excavatum. Steeply angled anterior ribs, horizontal posterior ribs. Compression of mediastinum cause straight left heart border and poor de \201 nition right heart border \200\223 mimicking middle lobe disease \200\223 con \201 rmed by lat eral. Azygos \201 ssure (Figs. 1.2.13 and 1.2.14). <1% of population. Azygos vein at medi al end, as joins with SVC. Other accessory \201 ssures occasionally visible. Right-sided aortic arch (Fig. 1.2.11). <1%. May be associated with congenital heart disease. Indents ri ght side of trachea. Rib anomalies. Cervical ribs <8%. Congenital fused ribs or forked ante rior ends (Fig 1.2.3). HRCT Conventionally, HRCT is performed as single axial sections at intervals throughout che st. Therefore there are gaps, making it inadequate for excluding nodules or masses. There i s better resolution of \201 ne detail. With latest genera- tion scanners detail of a \200\230volume \200\231 scan can be good enough to show \201 ne detail adequately and the advantages of not \200\230missing \200\231 some portions of lung outweigh marginal qualit y differences. Uses: \200 \200 Assessment of interstitial lung disease. Expiratory scans improve visualization of air-trap ping in suspected small airway disease. Prone scans show if apparent posterior abnormalitie s disappear when patient is turned, So-called \200\230dependent \200\231 changes (normal). Bifid anterior left 4th rib Normal appearances (Figs. 1.2.4, 1.2.8 \200\22310) Mediastinum Trachea \200\223 posterior wall de \201 cient in cartilage and bows inwards in expiration. Diameter 12 \200\22318mm i n females; 16 \200\22320mm in males. Aorta \200\223 ascending <35mm; descending <25mm. Mai n pulmonary artery <3cm diameter. Lymph nodes \200\223 in high superior mediastinum \200 \230normal \200\231 <5mm; in hila <3mm; pre-tracheal and aorto-pulmonary <10mm but subcarin al and upper right hilum can be 10 \200\22315mm and still be \200\230normal \200\231. Thym us \200\223 up to early 20s can still be present as band of soft tissue in anterior medias tinum, molding around Fig. 1.2.3 Normal variant \200\223 bi \201 d rib. J ASH-MILES & M DARBY 6 adjacent structures. Later in life small nodular remnants can still be seen. NB Relatively \200\230bare \200\231 or featureless zone in peripheral 1cm of subpleural lu ng is normal. Thymus Right and left main bronchi Horizontal fissure Internal mammary vessels Ascending and descending aorta Oblique fissures S.V.C. Fig. 1.2.6 HRCT of normal lungs (a). Fig. 1.2.4 Normal superior mediastinum. Pericardial recesses (Fig. 1.2.5) contain small amounts of pericardial \202 uid which may measure up to 15mm and can mimic adenopathy. Seen in pretracheal and aortopulmonary areas, but usually identi \201 able due to their molding to adjacent structures rather than bein g round or oval. Uniform density of lung parenchyma Few interlobular septae normal Arteries accompany airways, veins separate Bronchvascular bundles taper towards periphery Fig. 1.2.7 HRCT of normal lungs (b). Pericardial recesses Fig. 1.2.5 Pericardial recesses (mimic adenopathy). Normal variants \200\223 left SVC in 0.5%; aberrant right subcla- vian artery in 0.5% (ori ginates from distal aortic arch, passing from left to right, behind esophagus). Left common carotid artery Brachiocephalic artery Left subclavian artery Lung parenchyma (Figs. 1.2.6 and 1.2.7) Can see \200 Broncho-vascular bundles seen to 8th generation (diam- eter of bronchus up to that of accom panying artery when seen end-on). Pulmonary veins. Interlobular septae only occasionally se en peripherally. Visceral pleura only seen when double layer in \201 ssures. \200 \200 Occasional intrapulmonary lymph nodes. Cannot see \200 \200 \200 Fig. 1.2.8 Arteries arising from aortic arch. Lymphatic vessels. Alveoli and acini. Capillary vessels. CHAPTER 1.2 Radiology of the healthy chest 7 SVC + streak artifact due to IV contrast Main pulmonary artery Left subclavian artery Esophagus Aberrant right subclavian artery Right & Left pulmonary arteries Fig. 1.2.12 Normal variant \200\223 aberrant right subclavian artery. Fig. 1.2.9 Mediastinal structures just below carina. Right ventricle Right atrium Left ventricle/ aortic root SVC Lower lobe pulmonary arteries Azygos vein in azygos fissure Inferior pulmonary veins Fig. 1.2.13 Normal variant \200\223 azygos lobe (CT). Fig. 1.2.10 Mediastinal structures at level of aortic root. Right-sided aortic arch Azygos fissure Azygos lobe Azygos vein Incidental lung tumor Fig. 1.2.14 Normal variant \200\223 azygos lobe (PA CXR). Fig. 1.2.11 Normal variant \200\223 right-sided aortic arch. J ASH-MILES & M DARBY 8 Perf Perf Right SVC Left SVC R Antr Vent L L LtPObl Vent R Trachea in expiration Trachea in expiration Trachea in expiration (posterior wall (posterio r wall (posterior wall indented) indented) indented) Fig. 1.2.15 Normal variant \200\223 left-sided SVC. CT artifacts R Antr L L LtPObl R Cardiac motion \200\223 blurring and double contours in middle lobe and lingular. Respirat ory motion \200\223 blurring and double contours through- out scan. \200\230Streaking \200\231 \200\223 next to SVC/brachiocephalic veins when con- tain high density IV contras t. Mixing defects \200\223 contrast in SVC may have apparent \201 lling defect due to un opaci \201 ed blood entering from below, e.g. azygos \202 ow, or from opposite arm. Asse ssing CT of the chest Systematic approach Have a system and use it every time e.g. heart, p ericardium and mediastinal vessels, lymph nodes, airways, lungs, pleura, bones and soft tis sues, outside the thorax. Perf Perf RtPObl L R R L Post Vent Vent Mediastinum Know the normal anatomy (see p. 4) and what should be where. Follow structures up and down the scan to see if they are vessels or masses. Check for lymphadenopathy; pre/p ara-tracheal and sub carinal region, anterior mediastinum, aortopulmonary window; axillary and supra-clavicular regions. Lungs If you \201 nd an abnormality, assess it for position , size, shape and outline, density and presence of calci \201 cation or fat. Look at lung, mediastinum and bones on appropriate \200\230window \200\231 settings. Multi-planar refor mats in coronal and saggital planes help localization. L RtPObl R Post L R Fig. 1.2.16 Normal ventilation/perfusion lung scan. Ultrasound Useful in assessing pleural collections and pleurally based masses. Good at diff erentiating \202 uid from solid. Can show septations within \202 uid. Guidance for drai nage and biopsy procedures. In normals, unreliable at showing all layers of the chest wall/ pleura but \200\230real-time \200\231 ultrasound demonstrates the normal movement of lung against pleura. Magnetic resonance imaging (MRI) Of most use as a complementary test to CT in assessing chest wall invasion by masses, especially for diaphragmatic and apical lesions . Good non-invasive tool for assessment of congenital cardiac disease and myocardial ischae mia. Other imaging modalities Ventilation/perfusion scans (Fig. 1.2.16) Perfusion performed by I V injection of radioactively labeled micro-particles which lodge in pulmonary capillar- ies . A more proximal obstruction (i.e. embolus) will cause a \200\230defect \200\231 in the p erfusion image. Ventilation images performed by inhalation of a radioactive gas (usually kr ypton) or radioactively labeled particles. A normal V/Q scan has 95 \200\22398% accuracy in excluding a recent pulmonary embolus. Best performed in patient with no pre-existing lung com- plaints and normal CXR. Further reading Hansell DM, Armstrong P, David A, et al. Imaging of Diseases of the Chest. Elsevier Health Services: UK 2004. 9 Chapter 2 Respiratory physiology Chapter contents 2.1 Basic physiology 10 2.2 Lung function tests: a guide to interpretation 18 2.3 Exercise testing 24 2.4 Interpretation of arterial blood gasses and acid/base balan ce 28 2.5 Respiratory muscle function 32 A KENDRICK 10 2.1 Basic physiology The primary function of the lungs is gas exchange. This requires the movement of O2 into th e blood to support aerobic respiration in the mitochondria and the removal of the metabolic by-product CO2 from the blood. To achieve this, an integrated system of external respirati on (lungs), circulatory system linking the pulmonary and peripheral circulations and cellul ar respiration (internal respiration) must function harmoniously. This integration allows t he system to (1) maintain the acid \200\223base balance and (2) respond to applied stresses , such as exercise. Any part of the system that becomes compromised may affect gas exchange , the degree of which can be assessed at rest or during exercise. The external respiratory system consists of: \200 \200 \200 Functional residual capacity (FRC) \200\223 volume of air at the start of a tidal breath. Also known as end-expiratory lung volume (EELV). Residual volume (RV) \200\223 volume of a ir left after a full exhalation. Vital capacity (VC) \200\223 volume of air that can be ex haled from TLC to RV, or vise versa, either forcibly (FVC) or relaxed (VC). What determines FRC? \200 The chest wall and lungs are elastic structures coupled together by the pleural \202 uid. If air enters the pleural space, the lungs and chest sepa- rate with the chest wall expand ing outwards and the lungs collapse inwards. At FRC, the chest wall and lungs are not at th eir ideal equilibrium volumes. The chest wall is being held at a lower volume and the lungs are being stretched open at a higher volume. At some point, the outward pull of the chest wall and the inward collapse of the lungs are of equal magnitude, but of opposite direction , and hence a balance point occurs (Fig. 2.1.2). This is the FRC. the ventilatory pump; the gas exchanger; the respiratory controller. The ventilatory pump consists of the structures that form the bellows of the respiratory sy stem, and enables gas exchange between the alveoli and the pulmonary capilla- ries. The res piratory controller receives information from inputs throughout the body and alters the rat e and depth of breathing appropriately. The ventilatory pump This moves, by bulk \202 ow, air from the atmosphere to the alveoli and back out. The pump must: \200 generate suf \201 cient pressure within the thorax to move gas down the airways to the alv eoli; distribute the inhaled air throughout the lungs; overcome obstacles to gas movement, i.e. narrowed airways, as observed in COPD; achieve this with minimal energy expenditure; r espond to increased demands, e.g. exercise. \200 \200 Statics: the main static lung volumes (Fig. 2.1.1) are: Total lung capacity (TLC) \200\223 the maximal volume of the lungs after a full inhalation. Fig. 2.1.2 Pressure \200\223volume (P \200\223V) relationships of the lungs and chest wall. What determines TLC and RV? \200 At TLC the P \200\223V relationship of the lungs shows a pla- teau, whereas the chest wall does not. Hence it is the elas ticity of the lungs that determines TLC. At TLC, the inspira tory muscles are shortened and are less effective at generating tension. At RV, the P \200 \223V relationship of the chest wall shows a plateau, whereas the lungs do not. Hence it is the chest wall that determines the RV. At this volume, the dia- phragm and the external in tercostal muscles are long and are more effective at generating tension. For gas exchange to occur, air is bought to the alveoli (inhalation) and returned to atmosp here (exhalation). \200 Inhalation is an active process requiring inspiratory muscles, the diaphragm being the prim ary muscle. As the diaphragm contracts, it shortens, moves down- wards and moves the rib ca ge outwards. This change in chest wall shape results in the pleural pressure (Ppl) and alve olar pressure (Palv) becoming more negative so air \202 ows into the lungs. Fig. 2.1.1 Static lung volumes: VT \200\223 tidal volume, TLC \200\223 total lung capacit y, VC \200\223 vital capacity, FRC - functional residual capacity, RV \200\223 residual v olume. CHAPTER 2.1 Basic physiology 11 The magnitude of the pressure required is dependent on the compliance of the chest wall and the lungs: Exhalation at rest is a passive process. \200 When the inspiratory muscles stop contracting at the end of inhalation, the normal elastic properties of the lungs lead to a \202 ow of air out of the lungs. Compliance (C) = ZVolume ZPressure (Eq.1) In emphysema, the lungs are compliant ( \202 oppy) so a small ZP results in a large ZV. In \201 brosis the lungs are stiff, so a small ZP results in a small ZV. The compliance of the lungs (CL) changes with lung vol- ume (Fig 2.1.2). At FRC, the P \200\223V curve is steep and the lungs are compliant (measured \200 \223 2.0 l.kPa \210\2221). At TLC, the curve is \202 atter, the lungs are stiffer and les s compli- ant (measured \200\223 0.56 l.kPa \210\2221). l During exercise, exhalation is a combination of the passive recoil of the lungs and active contraction of the expiratory muscles of the abdominal wall and internal intercostals. Normal breathing Changes in the volume of the lungs requires pressure to be generated: \200 To breathe in, a pressure must be generated within the thorax to move air into the alveoli. The process of ventilation is summarized in Fig 2.1.3. \200 At FRC the system is balanced, there is no air \202 ow, Palv is zero and Ppl is negative. Fig. 2.1.3 Changes in various pressures during normal inhalation and exhalation. A KENDRICK 12 On inhalation, respiratory muscles contract, and Ppl becomes more negative. These changes i n Ppl are trans- mitted to the alveoli, resulting in Palv becoming negative with respect to atmospheric pressure (PAtm), so air moves down the airways into the alveoli. When the syst em \200\230switches off \200\231 inhalation, the system relaxes resulting in a Palv > PAtm , so air moves out of the lungs. In peripheral airways (r = 0.5mm) Re is <1000 indicating laminar air \202 ow. Gas velocity is low. Changing the radius of an airway or the gas composition affects Re. Breathing 20% O2, 80% helium reduces Re to <1000 in the trachea, indicating laminar air \202 ow and resu lting in a higher peak expiratory \202 ow (PEF). Airway radius The radius of the airways is important. \200 In terms of force vectors, when inhaling from FRC: \200 Poiseuille \200\231s law states that: l The respiratory muscle vector increases in magnitude as force is exerted to move the chest wall. The chest wall vector becomes smaller in magnitude as the chest wall approaches its e quilibrium position. The lung force vector increases in magnitude as the lung moves further from its equilibrium position. On reaching the maximum VT for that breath, the system rela xes back to FRC. V = ZP \200r4 8 l (Eq.6) where l is the tube length. l Airways resistance (Raw) = ZP V (Eq.7) Combining Eq.6 and Eq.7: l Raw \210\235 1/r4 Hence if r decreases by 50%, Raw increases 16-fold. Most of the resistan ce to air \202 ow occurs in the 5th \200\2237th airway generations (large airways). As air moves from the periphery of the lungs to the cen- tral airways, velocity increases. Small airways in the periphery are tethered open by the elastic recoil of the lung tissue. Smooth muscle of medium-sized airways is controlled by the autonomic system. Bronchial smooth mus cle tone is a major determinant of the cross-sectional area and hence the Raw of the medium sized airways. (Eq.8) Surfactant As the alveolus is the site of gas exchange function, it is essential that the a lveoli remain open. If we assume an alveolus is a sphere, we can apply: l (Eq.2) Laplace \200\231s law \210\222 P = 2T r where P is pressure inside a sphere, T is the tension in the sphere wall and r is the radius of a sphere: As r decreases, P must incr ease inside the alveolus to prevent it from collapsing. Alveoli increase and decrease in ra dius during the breathing cycle, but do not do this uniformly. In an unstable state, small alveoli will have a greater PAlv than large alveoli, and as pressure moves from high to low pressure small alveoli will empty into large alveoli. This does not happen in reality! Flow \200\223volume relationships The system can generate \202 ows of >10l.s \210\2221. A t TLC high \202 ows occur because: \200 \200 the elastic recoil of the lung tissue is maximal; the density of surfactant is least at TLC , so the surface forces are greatest; expiratory muscles are at their greatest length, and the chest wall at its farthest above relaxation volume; pleural pressure is at its most pos itive; airway radius is at its greatest so Raw is low. To ensure stable alveoli, Type II pneumocytes in the alveoli produce a detergent like subst ance called surfactant, which lines the alveolar surface. \200 \200 On inhalation, surfactant dT, so the lungs expand more easily. On exhalation surfactant dT, preventing alveolar collapse and minimizing any effects on gas exchange. Surfactant minimi zes fluid transudation from the pulmonary capillaries, i.e. it helps keeps the alveoli dry. As lung volume decreases from TLC to RV, airflow decreases because: \200 \200 \200 \200 \200 driving pressure decreases as lung volume decreases; elastic recoil of the lung and chest w all decreases; expiratory muscles are shorter, producing less tension airway radius decreas es, so Raw increases (Eq.6); the pressure across the airways is normally positive. In force d exhalation, this pressure becomes negative and small airways collapse; when pressure in t he airways equals Ppl, the pressure across the airways = 0 and the equal pressure point (EP P) is attained so airway compression may follow; when the EPP is reached, \202 ow limitat ion exists; the EPP is determined principally by the elastic recoil of the lungs. Low elast ic recoil (emphysema) shifts the EPP towards the periphery of the lungs; after PEF, most of the expiratory portion of the \202 ow- volume curve is effort independent and \202 ow limitation has been attained; \202 ow rates after 75% VC has been exhaled (MEF25%FVC) may be used as a guide to small airways function; inspiratory F \200\223V curves are effort de pendent. Dynamics The respiratory system is a dynamic organ. The movement of air into and out of the airways and lungs are affected by: Air \202 ow This is either laminar or turbulent. \200 Laminar \202 ow, occurs in the peripheral airways, where \202 ow (V) is proportional to driving pressure (ZP): ZP \210\235 V \200 l (Eq.3) Turbulent \202 ow conditions occurs in the larger airways: ZP \210\235 V2 l (Eq.4) Where laminar and turbulent air \202 ow occurs depends on the structural \200\223fu nctional relationship at that location, and may be determined by the Reynolds number (Re): Re=(2ru \201) (Eq.5) r \200\223 radius, \201 \200\223 gas density, u \200\223 gas v elocitys \200\223 gas viscosity. A value <2000 indicates laminar air \202 ow. \200 l In the trachea (r = 15mm) breathing air, Re is >2000, hence turbulent air \202 ow. Gas vel ocity is high. CHAPTER 2.1 Basic physiology 13 If VCO2 i and VA i in sync, i.e. exercise \200\223 hyperpnoea. If fb is >20/min, without i VE, then VT d (Eq.10) \200\223 BUT VD/VT i, so PaCO2 i (Eq11) \200\223 tachypnoea. \200 Work of breathing (W) To move the lungs and chest wall requires energy. \200 Total W is t he sum of elastic and resistive work. \200 Resistive work decreases with increasing lung volume and widening of the airways (ir, dR \200\223 Eq.8). Elastic work increases at low a nd high lung volumes. W is normally at a minima close to FRC. Changes in W occur when the b alance of elastic and resistive work are altered as in emphysema (iFRC to dR to dW) or \201 brosis (dFRC to dElastic to dW, BUT a dFRC leads to iR). At rest, W requires 1 \200 \2232% of O2 uptake (VO2), which increases during exercise. Breathing frequency (fb) at res t is 10 \200\22315/min, which is ef \201 cient. With increased elastic resistance fb incre ases, whilst in increased air \202 ow resistance, fb decreases. Distribution of ventilation At FRC in the upright position the lung apex, compared to the l ung base: \200 \200 \200 \200 \200 \200 have larger alveoli which are less compliant; have a more negative Ppl (-0.8 kPa vs -3 kPa) ; requires greater ZP to expand each alveolus; has less volume distributed i.e. ZV of the b asal alveoli is greater. Distribution of perfusion The pulmonary circulation is a high-compliance, low-resist- ance system, enabling it to adjust to changes in \202 ow with little change in resistance. \200 \200 Gravity distributes blood \202 ow (Q) to the lung bases. Some capillaries receive little or no blood \202 ow, particu- larly at the lung apex \200\223 hence VD,alv. With iQ or i pulmonary vascular resistance, capillaries may be recruited and participate in gas exchange . Pulmonary capillaries have very compliant walls, so if PAlv > pulmonary capillary pressur e (Pc), the capillary will narrow or collapse. What determines \202 ow is the relationshi p of Pa, PAlv and pulmonary venous pressure (Pv). The gas exchanger For gas exchange to occur 3 simple rules must be met: \200 \200 \200 The alveoli are ventilated. The alveoli are perfused. Ventilation and perfusion are matched . Ventilation May be described in terms of total ventilation and alveolar ventilation. Total ventilation (VE, l.min \210\2221) is \200 measured at the mouth; \200 the sum of alveol ar (VA) and dead space ventilation (VD), hence: The lung may be divided into three zones (Table 2.1.1) Table 2.1.1 The three zones of the lung. Zone Pressures Flow l VE = VA + VD (Eq.9) PAlv > Pa > Pv Little \202 ow Apical Central Pa > PAlv > Pv iFlow from upper to lower part of zone Basal The product of fb and tidal volume (VT), hence: l VE = fb x VT (Eq.10) Pa> Pv > PAlv Unimpeded \202 ow Note VT must be >VD for gas exchange to occur. Dead space ventilation is composed of the: \200 \200 A 70kg person therefore has a VD 8 180ml/breath and a VD/VT ratio = 180/500 = 0.36. If fb = 15/min and VT = 500ml, then VE = 7500ml. If VD = 180ml/breath, total VD = 270 0ml.min \210\2221, and VA = 4800ml.min \210\2221. If VD = 300ml/breath, VA = 3000ml.min \210\2221 Questions 1 Is a VA = 4800ml.min \210\2221 able to maintain arterial PO2 and PCO2 at the required levels? 2 What effect does increasing VD have on arterial PO2 and PCO2? CO 2 elimination CO2 is eliminated by the ventilatory pump, so any compro- mise to this, will affect the PaCO2. l Pulmonary artery walls contain smooth muscle, and the tone of this muscle plays an importan t role on determining the radius of the vessel, and hence its resistance (Eq.8). Pulmonary vessels constrict: \200 anatomical dead space (2.2ml = 1kg body weight); alveolar dead space \200\223 20 to 50ml. when exposed to low levels of O2 \200\223 hypoxic vasocon- striction \200\223 which re \202 ects reduced alveolar ventilation due to air \202 ow obstruction or alveoli \201 ll ed with \202 uid, thereby affecting gas exchange; iR and resulting in redistribution of b lood to areas that are well ventilated. Pulmonary vessels dilate: \200 when exposed to nitric oxide (NO) produced by nitric oxide synthase. NO acts locally. Its p roduction is increased by mechanical or by biochemical stimulation. As \202 ow increases, NO production increases to dilate the vessel and hence diminish resistance; when prostacyc lins are produced in the lungs as they act as vasodilators. (Eq.11) where k is a constant and VCO2 is the CO2 produced by cellular respiration. VA \210\235 VCO2, 6 i or d in VCO2 must be matched by appropriate changes in VA to maintain Pa CO2. If VA does not increase with increases in VCO2, the PaCO2 will increase \200\223 hypo ventilation. If VA is greater than that required to match for VCO2, then PaCO2 will be redu ced \200\223 hyperventilation. VA = k.VCO2 PaCO2 For gas exchange to occur, ventilation must match per- fusion. At the lung apices, ventilat ion exceeds perfusion (V/Q <1), whilst at the lung base, perfusion exceeds venti- lation (V /Q >1). Hence V/Q matching is not perfect. CO2 transportation CO2 is carried by blood: \200 Bound to hemoglobin. \200 Dissolved in the plasma. \200 Dissolved CO2 in equilibr ium with carbonic acid: CO2 + H2O \207\224 H2CO3 \207\224 H+ + HCO3 l \210\222 (Eq.12) A KENDRICK 14 \200 A d[Hb] i.e. anemia dO2 content, so the amount of O2 delivered to the tissues is lower. It does not change the PaO2 and hence there is no change in SaO2. The alveolar gas equation es timates PAO2 in an ideal alveolus and is a guide to alveolar gas exchange: The PaCO2 of normal blood is 4.8 \200\2235.9 kPa. CO2 is in high concentration in the tissu es relative to the blood, so diffuses from the tissues into the blood. The relationship of CO2 content and PaCO2 is linear over the normal physiological range. This relationship allo ws hyperventilation of normal alveoli to compensate for hypoventilation of diseased lung un its. The Haldane Effect describes the shift to the right of the CO2 \200\223Hb curve in the presence of O2. CO2 is displaced from Hb and enters the blood as dissolved gas. l (Eq.14) PIO2 \200\223 PO2 in inspired air; R is VO2 VCO2 and is assumed to be 0.8. PAO2 = PIO2 \200\223 (PaCO2 R) From Eq.14 a number of inferences can be made: \200 For a given PIO2 and R, there is only one PaCO2 for each value of PAO2. A mild reduction in PAO2 can be normalized by iVA, so d PaCO2. Hypoventilation results in an iPACO2 and 6dPAO2 . Maximum PaO2 breathing room air is determined by how low the PaCO2 and hence PACO2 can be reduced to. Normally PaO2 does not exceed 16 kPa. In respiratory failure, PaCO2 may increa se to 12 kPa, if the PaO2 decreases to 4 kPa. Chronically hypoxic patients may manage on a PaO2 of 2.5 kPa. An elevated PaCO2 may occur because of: 1. d VE \200\223 refer to Eq.9 and Eq.10 for chang es in fb and VT; 2. d VA (Eq.11); 3. iVCO2 with no change in VE or VA; 4. V/Q mismatch. A d ecreased PaCO2 indicates an iVA (Eq.11) and the cause of this may be acute (whilst taking t he blood sample) or due to other causes, i.e. hyperventilation syndrome O2 transportation T he binding of O2 to hemoglobin is different to that of CO2. \200 \200 \200 For - PIO2 = 19.7kPa, PaCO2 = 5.33kPa and R = 0.8, the PAO2 = 13.0 kPa. If PaO2 is 13.2kPa, the alveolar \200\223arterial O2 difference (AaDO2) is 0.2kPa. This is within 2kPa and re \202 ects the V/Q mismatch that occurs in normal lungs. The PaO2 of normal blood is 11.3 \200\22313.3 kPa. The O2 \200\223Hb curve is sigmoid shape d and relates O2 saturation (SO2) to PaO2 (Fig. 2.1.4). Gas diffusion Having ventilated and perfused the alveoli, gas exchange of O2 and CO2 across the alveolar capillary membrane must take place. \200 Gas moves from a high pressure to a lower pressure, i.e. O2 moves from the alveoli to the c apillary blood. Gas uptake (V) depends on - pressure difference (P1 \200\223 P2), the prop erties of the gas (D), membrane surface area (A) and membrane thickness (t). Fick \200\231s law of diffusion states: l (Eq.15) D, A and t cannot be measured and are lumped together as TL \200\223 transfer fact or or DL \200\223 diffusing capacity (DL), so Eq.15 becomes. l V = [D x A x (P1 \200\223 P2)] t TL = V (P1 \200\223 P2) (Eq.16) TL is a number of resistances in parallel; Dm \200\223 diffusing membrane capacity , \230 - the reaction rate of CO with hemoglobin and Vc - pulmonary capillary blood vol- u me. These are combined as: l Fig. 2.1.4 Oxyhaemoglobin dissociation curve. V \200\223 mixed venous blood, a \200\223 a rterial blood. The effects of changes in temperature, PCO2, [H+] and 2-3 diphosphoglycerate (DPG) on the af \201 nity of Hb for O2 are shown. 1/TL = 1/Dm + 1/ \230Vc Disease states may reduce gas uptake and TL due to: The upper \202 at portion of the curve (PO2 > 8 kPa) allows for quite large changes in PO 2 with little change in SO2 \200\223 SO2 \211 90%. Within the steeper middle portion of t he curve, small changes in PO2 result in large changes in SO2. It is essen- tial to record the on-air SO2 if studying changes over- night in SO2 using pulse oximetry. Consciousness i s lost when PO2 8 3.5 kPa (SO2 8 50%). The amount of O2 carried is the O2 content and is th e sum of the O2 bound to Hb and of that dissolved in the plasma. l (Eq.17) 1. loss of surface area (dA or dDm - emphysema); 2. imembrane thickness (it or dDm - \201 brosis); 3. d \230 (anemia); 4. dVc (reduced cardiac output). \200 Blood \202 ow through the capillary at rest takes 8 0.75s and equilibrium between pulmona ry venous and alveo- lar gas takes 8 0.25s for PO2 and 8 0.30s for PCO2. At maximal exercis e, blood \202 ow through the capillary takes 8 0.25s, but generally there is little affec t on the equilibration of PO2 and PCO2. O2 and CO2 diffusion are perfusion-limited in norma l lungs, but may be diffusion-limited in diseased lungs. \200 O2 content = (1.39[Hb] x SO2) + (0.023PaO2) (Eq.13) For an [Hb] = 14.6 g.dl \210\2221, SO2 = 98% and PaO2 = 13.33 kPa, the O2 content = 20.18 ml.dl \210\2221. CHAPTER 2.1 Basic physiology 15 The respiratory controller The control of breathing is complex and not fully under- stood. Respiratory control involves both autonomic and volitional elements. In the medulla there are: \200 inspiratory neurons with a pacemaker function, \201 ring at a given rate, but may be modi \201 ed by other factors; neurons that \201 re during (a) inspiration, (b) exhalation o r (c) transition from inhalation to exhalation. Autonomic control The neural structures responsible for the autonomic con- trol are: \200 \200 Hence, the neurons responsible for the autonomic rhyth- mic breathing form the central patt ern generator (CPG), which controls the minute-to-minute breathing in the normal person. located in the medulla oblongata; the dorsal (DRG) and ventrolateral (VRG) respiratory grou ps, each with inspiratory and expiratory neurons. Volitional breathing The system permits: \200 \200 \200 The DRG: \200 breath-holding for periods of time; hyperventilation by ifb and iVT; alteration of the Ti a nd time of exhalation, by dfb and iVT under conscious controlled breathing conditions; chan ges in the breathing pattern in the presence of dis- comfort and anxiety. When experiencing pain or short- ness of breath, ifb and iVE are observed. processes information from the receptors in the lungs, chest wall and chemoreceptors; has a key role in the activation of the diaphragm and the VRG; shows increased neuron activity d uring inhalation; has an important role in (a) determining the rhythm of breathing and (b) regulating the changes in upper airway radius, by stimulating muscles to expand the upper a ir- way during inhalation. \200 Inputs to autonomic controller The brain receives information from a variety of sources (Fi g. 2.1.5): Mechanoreceptors: Activated by distortion of their local environment. Includes r eceptors in: \200 In the pons, the pontine respiratory group (PRG): \200 \200 contributes to switching from inhalation to exhalation; if damaged, there is iinhalation ti me (Ti), dfb and iVT. Upper Airways: sense and monitor \202 ow, probably by temperature change. Inhibit central controller. Nasal receptors Sneeze Diving reflex Epipharyngeal receptors Aspiration reflex Pharyngeal receptors Swallowing Laryngeal receptors Cough Apnoea Slowly adapting receptors Hering \200\223Breuer inflation reflex Hering \200\223Breuer defl ation reflex Bronchodilation Tachycardia Rapidly adapting receptors Cough Hering \200\223Breuer deflation reflex Hyperpnoea Bronchoc onstriction Mucus secretion