Cell Injury, Stress, Nutrition and Infectious Disease Pathology
UNIT 1: Cell Injury and Adaptations
1. Key Factors That Cause Cell Injury and How Injury Occurs
Causes:
Hypoxia/ischemia (most common): loss of blood supply, anemia, carbon monoxide, respiratory failure.
Physical agents: trauma, extreme heat/cold, radiation, electric shock, pressure changes.
Chemical agents and drugs: alcohol, acetaminophen overdose, carbon tetrachloride, heavy metals, poisons.
Infectious agents: bacteria, viruses, fungi, parasites (direct damage or toxins).
Immunologic reactions: hypersensitivity, autoimmunity.
Genetic derangements: enzyme deficiencies, sickle cell disease.
Nutritional imbalances: deficiency or excess (e.g., obesity, atherosclerosis).
Aging
How injury occurs (common mechanisms):
ATP depletion: the Na+/K+ pump fails, so sodium and water enter and the cell swells. Anaerobic glycolysis raises lactic acid (low pH), and ribosomes detach, so protein synthesis falls.
Mitochondrial damage: opening of the permeability transition pore releases cytochrome c, which can trigger apoptosis.
Calcium influx: high intracellular Ca2+ activates phospholipases, proteases, endonucleases and ATPases, which break down membranes, proteins and DNA.
Free radicals (ROS): superoxide, hydrogen peroxide and hydroxyl radicals cause lipid peroxidation, protein damage and DNA damage. Defences include superoxide dismutase, catalase, glutathione peroxidase and vitamins A, C and E.
Membrane damage, protein misfolding and DNA damage.
Reversible vs. irreversible injury: Reversible injury shows cell swelling and fatty change. Irreversible injury shows nuclear changes (pyknosis, karyorrhexis, karyolysis), membrane rupture and leakage of enzymes (e.g., troponin and CK-MB in MI, AST/ALT in liver injury) into the blood.
2. The Natural Process of Cell Degeneration
Cellular aging (senescence): accumulation of DNA damage, telomere shortening, reduced repair capacity, oxidative damage and build-up of lipofuscin (the