Causes of cell injury and disease Oxygen deprivation( hypoxia, ischemia) Nutritional imbalances ● Physical agents Chemical agents and drugs ● Infectious agents Immunologic reactions ● Genetic derangements
HYPOXIA Ischemia( loss of blood supply ) Inadequate oxygenation cardiorespiratory failure ) Loss of oxygen-carrying capacity of the blood( anemia or Co poisoning )
HYPOXIC INJURY Loss of oxidative phosphorylation and AtP generation by mitochondria Decreased atP(with increase in AMP) stimulating fructokinase and phosphorylation, resulting in aerobic glycolysis. ° Depleted glycogen. Reduced intracellular pH: Lactic acid and inorganic phosphate Clumping of nuclear chromatin
Four biochemical themes Oxygen-derived free radicals. Loss of calcium homeostasis and increased intracellular calcium atP depletion. Defects in membrane permeability