Cell injury
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This document outlines the various causes and mechanisms of cell injury. It discusses how oxygen deprivation, physical and chemical agents, infections, immune reactions, and nutritional imbalances can all lead to cell injury through mechanisms like ATP depletion, mitochondrial damage, calcium dysregulation, and oxidative stress. These mechanisms disrupt critical cellular processes and structures like membranes, ultimately leading cells to die through necrosis or apoptosis.
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Cell injury
- 1. Overview + Stress Normal Adapted cell - Stress Cell ess Injury + Str es s Reversibly - Str injured cell Apoptosis Irreversibly Dead cell Injured cell Necrosis
- 4. Causes of Cell Injury • Oxygen Deprivation • Physical Agents • Chemical Agents and Drugs • Infectious Agents • Immunologic Reactions • Genetic Derangements • Nutritional Imbalances
- 5. Oxygen Deprivation • Hypoxia – deficiency of oxygen • Ischemia – loss of blood supply (arterial flow or reduced venous drainage)
- 6. Physical Agents • Mechanical trauma • Extremes of temperature – burns, deep cold • Radiation • Electric shock
- 7. 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
- 8. Infectious Agents • Parasites • Fungi • Bacteria • Rickettsiae • Viruses
- 9. Immunologic Reactions • Anaphylactic reaction to foreign protein or drug • Reactions to endogenous self-antigens – autoimmune diseases
- 10. Genetics Derangements • Congenital malformation – Down syndrome • Decreased life of red blood cell – Thalassemia, Sickle cell anemia • Inborn errors of metabolism
- 11. Nutritional Imbalances • Protein-calorie deficiencies • Vitamin deficiencies • Anorexia nervosa • Excesses of lipids – Obesity, Atherosclerosis • Metabolic diseases – Diabetes
- 12. 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
- 13. 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
- 14. Depletion of ATP Na+ K+ Ca2+
- 15. Mitochondrial Damage Causes Hypoxia, Toxins Cytosolic Ca2+ Oxidative stress Lipid breakdown product
- 16. Mitochondrial Damage • Mitochondrial permeability transition of inner membrane (formation of high-conductance channel) channel Mitochondrial Oxidative Phosphorylation ATP production • Leakage of Cytochrome c into cytosol
- 19. Accumulation of Oxygen-Derived Free Radicals (Oxidative Stress) • The Oxidation-Reduction reaction (normal metabolic processes) -superoxide anion (O2-) -hydrogen peroxide (H2O2) -hydroxyl ion (OH )
- 20. Accumulation of Oxygen-Derived Free Radicals (Oxidative Stress) • Absorption of radiant energy (ultraviolet light: UV, X-ray) Ionizing radiation H20 OH H
- 21. Accumulation of Oxygen-Derived Free Radicals (Oxidative Stress) • Transition Metals – iron, copper “Fenton reaction” H202 Fe2+ Fe3+ OH OH-
- 22. 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
- 23. 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
- 24. 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
- 26. Defects in Membrane Permeability Mechanism of Membrane damage in Cell Injury • Mitochondrial Dysfunction -Decreased phospholipid synthesis -Phospholipase activation • Loss of Membrane phospholipid
- 27. Defects in Membrane Permeability Mechanism of Membrane damage in Cell Injury • Cytoskeletal Abnormality Cytosolic Ca+ protease • Reactive Oxygen species • Lipid breakdown products (detergen effect on membrane)
- 28. Cellular and biochemical sites of damage in cell injury
Notas del editor
- Normal cell has relative narrow range of functions and structure Limited changes in metabolism = homeostasis (increased Glc and TG metabolism in active contracting muscle) Stress = demands in excess of normal homeostatic changes leads to adaptations If stress exceeds adaptive response of cell - injury In addition, a variety of agents can directly injure cells (ie CN, , Hg, pH, temp, etc)