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At the end of session student should be able to Enlist causes of cell injury Identify effect of injurious agents on cell

LO. At the end of session student should be able to Enlist causes of cell injury Identify effect of injurious agents on cell cytoplasm and nucleus. Causes of Cell Injury. Oxygen Deprivation. Hypoxia – deficiency of oxygen

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At the end of session student should be able to Enlist causes of cell injury Identify effect of injurious agents on cell

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  1. LO • At the end of session student should be able to • Enlist causes of cell injury • Identify effect of injurious agents on cell cytoplasm and nucleus

  2. Causes of Cell Injury Oxygen Deprivation • Hypoxia – deficiency of oxygen • Ischemia – loss of blood supply(arterial flow or reduced venous drainage)

  3. Causes of Cell Injury Physical Agents • Mechanical trauma • Extremes of temperature – burns, deep cold • Radiation • Electric shock

  4. Causes of Cell Injury Chemical Agents and Drugs • Hypertonic concentration of salt – deranging electrolyte homeostasis • Poisons–arsenic, cyanide, or mercuric salts • Insecticides and Herbicides • Air pollutant – carbon monoxide • Occupational hazard – asbestos • Alcohol and Narcotic drugs

  5. Causes of Cell Injury Infectious Agents • Parasites • Fungi • Bacteria • Rickettsiae • Viruses

  6. Causes of Cell Injury Immunologic Reactions • Anaphylactic reaction to foreign protein or drug • Reactions to endogenous self-antigens – autoimmune diseases

  7. Causes of Cell Injury Genetics Derangements • Congenital malformation – Down syndrome • Decreased life of red blood cell – Thalassemia, Sickle cell anemia • Inborn errors of metabolism

  8. Causes of Cell Injury Nutritional Imbalances • Protein-calorie deficiencies • Vitamin deficiencies • Anorexia nervosa • Excesses of lipids – Obesity, Atherosclerosis • Metabolic diseases– Diabetes

  9. Mechanisms of Cell Injury • Depletion of ATP • Mitochondrial Damage • Influx of Intracellular Calcium and Loss of Calcium Homeostasis • Accumulation of Oxygen-Derived free radical (Oxidative stress) • Defects in Membrane Permeability

  10. Mechanisms of Cell Injury Depletion of ATP Causes Hypoxia, Ischemia Chemical Injury Membrane transport ATP Na+K+ATPase(Na-pump), Ca2+Mg2+ATPases (Ca-pump) Protein synthesis, Lipogenesis etc

  11. Na+ K+ Ca2+ Mechanisms of Cell Injury Depletion of ATP

  12. Mechanisms of Cell Injury Mitochondrial Damage Causes Hypoxia, Toxins Cytosolic Ca2+ Oxidative stress Lipid breakdown product

  13. Mechanisms of Cell Injury Mitochondrial Damage • Mitochondrial permeability transition of inner membrane (formation of high-conductance channel) • Leakage of Cytochrome c into cytosol Mitochondrial Oxidative Phosphorylation ATP production

  14. Mechanisms of Cell Injury Mitochondrial Damage

  15. Mechanisms of Cell Injury Influx of Intracellular Calcium and Loss of Calcium Homeostasis

  16. Mechanisms of Cell Injury

  17. Mechanisms of Cell Injury Accumulation of Oxygen-Derived Free Radicals (Oxidative Stress) • The Oxidation-Reduction reaction (normal metabolic processes) -superoxide anion (O2-) -hydrogen peroxide (H2O2) -hydroxyl ion (OH )

  18. OH H Mechanisms of Cell Injury Accumulation of Oxygen-Derived Free Radicals (Oxidative Stress) • Absorption of radiant energy (ultraviolet light: UV, X-ray) Ionizing radiation H20

  19. OH Mechanisms of Cell Injury Accumulation of Oxygen-Derived Free Radicals (Oxidative Stress) • Transition Metals – iron, copper “Fenton reaction” OH- H202 Fe3+ Fe2+

  20. Mechanisms of Cell Injury Accumulation of Oxygen-Derived Free Radicals (Oxidative Stress) Effects of the free radicals on cell injury • Lipid peroxidation of Membranes - Plasma membrane - Organellar membrane Double bonds in unsaturated fatty acids membrane damage

  21. Mechanisms of Cell Injury Accumulation of Oxygen-Derived Free Radicals (Oxidative Stress) Effects of the free radicals • Oxidative modification of proteins -Oxidation of amino acid side chains Protein-protein cross-linkages -Oxidation of the protein backbone Protein fragmentation

  22. Mechanisms of Cell Injury Accumulation of Oxygen-Derived Free Radicals (Oxidative Stress) Effects of the free radicals • Lesions in DNA Reaction with Thymine DNA single-stranded break DNA fragmentation

  23. Superoxide dismutase (SOD)

  24. Mechanisms of Cell Injury Defects in Membrane Permeability • Mitochondrial Dysfunction -Decreased phospholipid synthesis -Phospholipase activation • Loss of Membrane phospholipid Mechanism of Membrane damage in Cell Injury

  25. Mechanisms of Cell Injury Defects in Membrane Permeability • Cytoskeletal Abnormality • Reactive Oxygen species • Lipid breakdown products (detergen effect on membrane) Mechanism of Membrane damage in Cell Injury protease Cytosolic Ca+

  26. Cellular and biochemical sites of damage in cell injury

  27. Thanks

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