CELL INJURY Dr Shoaib Raza CELL INJURY v

CELL INJURY Dr. Shoaib Raza

CELL INJURY v When the adaptive capabilities of the cell are exceeded, the cell is said to be injured v Abnormal homeostasis • Change in the internal environment of the cell v Certain stimulus (triggering agent) is required to produce such change

CAUSES OF CELL INJURY v Hypoxia is the most frequent cause • Hypoxic hypoxia • High altitude • Ischemic hypoxia • Secondary to ischemia • Anemic hypoxia • Secondary to anemia • Histotoxic (Cytotoxic) hypoxia • Cyanide poisoning

CAUSES OF CELL INJURY v Nutritional disorders • Deficiency: • Protein Caloric Malnutrition (Kwashiorkor) • Vitamin deficiencies • Beri beri, Scurvy, Anemia, etc. • Excess of nutrition: • Hyperlipidemia • Pick wick disorder • Obesity

CAUSES OF CELL INJURY v Biological agents: • Infection • • • Bacteria Virus Fungi Protozoa Helminths

CAUSES OF CELL INJURY v Physical agents: • Temperature: • Increased: Thermal injury, syncope • Decreased: Frost bite • Pressure: • Trauma • p. H

CAUSES OF CELL INJURY v Chemical agents: • • Corrosive agents Toxins and poisons Drugs Increased or decreased concentration of usual cellular chemicals • Glucose • Oxygen derived free radicals

CAUSES OF CELL INJURY v Immunological causes: • Immune system provides defense against foreign antigens • Autoimmune disorders: • Immune response against self antigens • Immunodeficiency disorders: • AIDS, Di-George Syndrome, Hyper Ig. M Syndrome

CAUSES OF CELL INJURY v Genetic abnormalities: • Mutation • Sickle cell anemia, Thalassemia etc • Chromosomal disorders • Down Syndrome, Klienefelter Syndrome • Other genetic abnormalities

CAUSES OF CELL INJURY v Aging: • Telomerase activity

REVERSIBLE CELL INJURY v In early stages or mild forms of injury, the functional and morphological changes are reversible if the stimulus is removed v Hallmark features of hypoxic injury are: • • ↓ Oxidative phosphorylation ↓ ATP synthesis Cellular swelling Alterations in intracellular organelles

HYPOXIA AS A LEADING CAUSE OF CELL INJURY v Deficiency of oxygen impairs oxidative phosphorylation, this in turn causes: • Deficient aerobic glycolysis • Anaerobic glycolysis • Accumulation of lactic acid • Reducing p. H • Displacement of ribosomes from RER • Clumping of chromatin network • Inactivation of Na + - K+ pump

INACTIVATION OF NA + K + PUMP v Na+ K+ pump is ATPase dependent, thus ATP deficiency leads to inactivation of Na+ K+ pump v Inactivation leads to: • ↑ Na+ influx inside the cell • Intracellular water accumulation • Cell swelling • Swelling of cytoplasmic organelles • Mitochondrial swelling • Lysosomal swelling • ER swelling

REVERSIBLE CELL INJURY v Due to cellular swelling and impaired function of the cell membrane, certain enzymes (stored in particular cells) are released and their serum levels are raised • Lipase, amylase etc during pancreatic cell injury • CK-MB, LDH etc during myocardial injury • AST, ALT, CPK etc during hepatocellular damage

ANY QUESTION?