Causes of Cell Injury
The causes of cell injury range from the external gross physical violence of an automobile accident to subtle internal
abnormalities, such as a genetic mutation causing lack of a vital enzyme that impairs normal metabolic function. Most
injurious stimuli can be grouped into the following broad categories.
Oxygen Deprivation.
Hypoxia is a deficiency of oxygen, which causes cell injury by reducing aerobic oxidative respiration. Hypoxia is an extremely
important and common cause of cell injury and cell death. Causes of hypoxia include reduced blood flow (celled ischemia),
inadequate oxygenation of the blood due to cardiorespiratory failure, and decreased oxygen-carrying capacity of the blood,
as in anemia or carbon monoxide poisoning (producing a stable carbon monoxyhemoglobin that blocks oxygen carriage) or
after severe blood loss. Depending on the severity of the hypoxic state, cells may adapt, undergo injury, or die. For example,
if an artery is narrowed, the tissue supplied by that vessel may initially shrink in size (atrophy), whereas more severe or
sudden hypoxia induces injury and cell death.
Physical Agents.
Physical agents capable of causing cell injury include mechanical trauma, extremes of temperature (burns and deep cold),
sudden changes in atmospheric pressure, radiation, and electric shock.
Chemical Agents and Drugs.
The list of chemicals that may produce cell injury defies compilation. Simple chemicals such as glucose or salt in hypertonic
concentrations may cause cell injury directly or by deranging electrolyte balance in cells. Even oxygen at high
concentrations is toxic. Trace amounts of poisons, such as arsenic, cyanide, or mercuric salts, may destroy sufficient
numbers of cells within minutes or hours to cause death. Other potentially injurious substances are our daily companions:
environmental and air pollutants, insecticides, and herbicides; industrial and occupational hazards, such as carbon
monoxide and asbestos; recreational drugs such as alcohol; and the ever-increasing variety of therapeutic drugs.
Infectious Agents.
These agents range from the submicroscopic viruses to the large tapeworms. In between are the rickettsiae, bacteria, fungi,
and higher forms of parasites. The ways by which these biologic agents cause injury are diverse.
Immunologic Reactions.
The immune system serves an essential function in defense against infectious pathogens, but immune reactions may also
cause cell injury. Injurious reactions to endogenous self-antigens are responsible for several autoimmune diseases. Immune
reactions to many external agents, such as microbes and environmental substances, are also important causes of cell and
tissue injury.
Genetic Derangements.
As described, genetic abnormalities may result in a defect as severe as the congenital malformations associated with Down
syndrome, caused by a chromosomal anomaly, or as subtle as the decreased life span of red blood cells caused by a single
amino acid substitution in hemoglobin in sickle cell anemia. Genetic defects may cause cell injury because of deficiency of
functional proteins, such as enzyme defects in inborn errors of metabolism, or accumulation of damaged DNA or misfolded
proteins, both of which trigger cell death when they are beyond repair. Variations in the genetic makeup can also influence
the susceptibility of cells to injury by chemicals and other environmental insults.
Nutritional Imbalances.
Nutritional imbalances continue to be major causes of cell injury. Protein-calorie deficiencies cause an appalling number of
deaths, chiefly among underprivileged populations. Deficiencies of specific vitamins are found throughout the world.
Nutritional problems can be self-imposed, as in anorexia nervosa (self-induced starvation). Ironically, nutritional excesses
have also become important causes of cell injury. Excess of cholesterol predisposes to atherosclerosis; obesity is associated
with increased incidence of several important diseases, such as diabetes and cancer. Atherosclerosis is virtually endemic in
the United States, and obesity is rampant. In addition to the problems of undernutrition and overnutrition, the composition
of the diet makes a significant contribution to a number of diseases.
Carlos S. - Causes of Cell Injury