1. Cell Injury Dr. Shoaib Raza

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

3. Causes of cell injury • 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

4. Causes of cell injury • Nutritional disorders • Deficiency: • Protein Caloric Malnutrition (Kwashiorkor) • Vitamin deficiencies • Beri beri, Scurvy, Anemia, etc. • Excess of nutrition: • Hyperlipidemia • Pick wick disorder • Obesity

5. Causes of cell injury • Biological agents: • Infection • Bacteria • Virus • Fungi • Protozoa • Helminths

6. Causes of cell injury • Physical agents: • Temperature: • Increased: Thermal injury, syncope • Decreased: Frost bite • Pressure: • Trauma • pH

7. Causes of cell injury • Chemical agents: • Corrosive agents • Toxins and poisons • Drugs • Increased or decreased concentration of usual cellular chemicals • Glucose • Oxygen derived free radicals

8. Causes of cell injury • Immunological causes: • Immune system provides defense against foreign antigens • Autoimmune disorders: • Immune response against self antigens • Immunodeficiency disorders: • AIDS, Di-George Syndrome, Hyper IgM Syndrome

9. Causes of cell injury • Genetic abnormalities: • Mutation • Sickle cell anemia, Thalassemia etc • Chromosomal disorders • Down Syndrome, Klienefelter Syndrome • Other genetic abnormalities

10. Causes of cell injury • Aging: • Telomerase activity

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

13. Hypoxia as a leading cause of cell injury • Deficiency of oxygen impairs oxidative phosphorylation, this in turn causes: • Deficient aerobic glycolysis • Anaerobic glycolysis • Accumulation of lactic acid • Reducing pH • Displacement of ribosomes from RER • Clumping of chromatin network • Inactivation of Na + - K+ pump

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

16. Reversible Cell Injury • 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

17. Any Question?