The causes of cell injury span a range from gross physical trauma, such as after a motor vehicle accident, to a single gene defect that results in a nonfunctional enzyme in a specific metabolic disease. Most injurious stimuli can be grouped into the following categories.
Hypoxia and ischemia. Hypoxia, which refers to oxygen deficiency, and ischemia, which means reduced blood supply, are among the most common causes of cell injury. Both deprive tissues of oxygen, and ischemia, in addition, results in a deficiency of essential nutrients and a build up of toxic metabolites. The most common cause of hypoxia is ischemia resulting from an arterial obstruction, but oxygen deficiency also can result from inadequate oxygenation of the blood, as in a variety of diseases affecting the lung, or from reduction in the oxygen-carrying capacity of the blood, as with anemia of any cause, and carbon monoxide (CO) poisoning.
Toxins. Potentially toxic agents are encountered daily in the environment; these include air pollutants, insecticides, CO, asbestos, cigarette smoke, ethanol, and drugs. Many drugs in therapeutic doses can cause cell or tissue injury in a susceptible patient or in many individuals if used excessively or inappropriately (Chapter 7). Even innocuous substances, such as glucose, salt, water and oxygen, can be toxic.
Infectious agents. All types of disease-causing pathogens, including viruses, bacteria, fungi, and protozoans, injure cells. The mechanisms of cell injury caused by these diverse agents are discussed in Chapter 9.
Immunologic reactions. Although the immune system defends the body against pathogenic microbes, immune reactions also can result in cell and tissue injury. Examples are autoimmune reactions against one’s own tissues, allergic reactions against environmental substances, and excessive or chronic immune responses to microbes (Chapter 5). In all of these situations, immune responses elicit inflammatory reactions, which are often the cause of damage to cells and tissues.
Genetic abnormalities. Genetic aberrations can result in pathologic changes as conspicuous as the congenital malformations associated with Down syndrome or as subtle as the single amino acid substitution in hemoglobin giving rise to sickle cell anemia (Chapter 7). Genetic defects may cause cell injury as a consequence of deficiency of functional proteins, such as enzymes in inborn errors of metabolism, or accumulation of damaged DNA or misfolded proteins, both of which trigger cell death when they are beyond repair.
Nutritional imbalances. Protein–calorie insufficiency among impoverished populations remains a major cause of cell injury, and specific vitamin deficiencies are not uncommon even in developed countries with high standards of living (Chapter 8). Ironically, excessive dietary intake may result in obesity and also is an important underlying factor in many diseases, such as type 2 diabetes mellitus and atherosclerosis.
Physical agents. Trauma, extremes of temperature, radiation, electric shock, and sudden changes in atmospheric pressure all have wide-ranging effects on cells (Chapter 8).
http://ebooksmedicine.net
Aging. Cellular senescence results in a diminished ability of cells to respond to stress and, eventually, the death of cells and of the organism. The mechanisms underlying cellular aging are discussed at the end of this chapter.
With this introduction, we proceed to a discussion of the progression and morphologic manifestations of cell injury, and then to the biochemical mechanisms in injury caused by different noxious stimuli.
Although various injurious stimuli damage cells through diverse biochemical mechanisms, all tend to induce a stereotypic sequence of morphologic and structural alterations in most types of cells.
Reversible injury is the stage of cell injury at which the deranged function and morphology of the injured cells can return to normal if the damaging stimulus is removed