General Pathology - 1 & 2 - Cell Injury and Death

  1. Radiolysis of water generates hydroxyl radical
  2. Depending on the status of the cell, hydroxyl radical can
    • Cause DNA damage in PROLIFERATING CELLS -> Inability to replicate
    • Cause Lipid peroxidation of membrane phospholipids in NONPROLIFERATING CELLS -> Loss of membrane integrity
    • Both lead to CELL DEATH
  3. Polyenoic fatty acid is susceptible damage by hydroxyl radical and (initiation) and O2 (peroxidation), and self-propagation, resulting low molecular weight aldehydes.
  4. O2 therapy -> Excess O2
  5. PMNs, macrophages -> Inflammation
  6. PMNs, Xanthine oxidase -> Reperfusion injury after ischemia
  7. Mixed function oxidases, Redox reactions -> Chemical toxicity
  8. Radiotherapy -> Ionizing radiation
  9. Initiators, promoters -> Chemical carcinogenesis
  10. OXIDATIVE STRESS comes from:
    • (1) ROS (Reactive oxygen species)
    • (2) RNOS (Reactive nitrogen oxide species) - Peroxynitrite (ONOO-·), Nitroxyl (NO-)
  11. Actions of superoxide
    • O2 + e -> O2-• (superoxide)
    • O2-• + O2-• + 2H -> H2O2 + O2 (with enzyme SOD, superoxide dismutase, protect from too much superoxide)
    • 2H2O2 -> O2 + 2H2O (with enzyme catalase; foam forms when O2 is released)
  12. Cellular defense mechanisms against free radicals
    vit A, C, E
  13. Intracellular accumulations
    • Water- cellular edema or swelling, reversible
    • Lipids- steatosis or fatty change, reversible
    • Proteins- usually aggregates in the cytoplasm providing clues to disease, diagnostic
  14. Ischemia leads to
    • decreased oxidative phosphorylation in mitochondria and decreased ATP production
    • decreased ATPase Na+ pump and less efflux of Na+ -> swelling of ER and cells, blebs
    • decreased glycogen and pH, clumping of nuclear chromatin
    • decreased protein synthesis
  15. The principal biochemical mechanisms and sites of damage in cell injury
    • Mitochondria - less ATP w/ consequences; more ROS, damaging to lipids, DNA and proteins
    • Increased entry of Ca2+ -> increased permeability of mitochondria and activation of cellular enzymes
    • Membrane damage - cell contents leaking out; lysosome leakage, digesting cellular components
    • Protein misfolding and DNA damamge -> apoptosis
  16. The production of ROS (_______) is increased by many injurious stimuli, eg _____. These free radicals are removed by ________ and by ________. Excessive production or inadequate removal leads to accumulation of free radicals in cells, which may damage lipids (by _______), proteins, and DNA, resulting in cell injury.
    • superoxide, hydrogen peroxide, hydroxyl radical
    • radiation, toxin, reperfusion
    • spontaneous decay
    • specialized enzymatic systems
    • peroxidation
  17. Important consequences of hypoxia :
    • Lowered production of ATP
    • Interference with Na+/K+ pump
    • Recruitment of secondary metabolic paths - glycogen; lactic acid
    • Distortion of cellular organelles - mitochondria
    • Accumulation of fat, CHO etc.
    • Clumping of chromatin
  18. reversible cell injury and irreversible necrosis.
    • ischemic injury - surface blebs, increased eosinophilia of cytoplasm, and swelling
    • Necrosis - loss of nuclei, fragmentation of cells, and leakage of contents
  19. Mechanisms of fatty change in liver cells
    • Oxidation of fatty acids
    • Accumulation of triglycerides
    • Triglycerides are transferred out by lipid acceptor proteins
  20. ________ due to chronic passive congestion
    • Nutmeg liver
    • Nodularity present
    • Fat can burst & damage surrounding tissues and vascular tissue
  21. Diphtheritic myocarditis show fatty change
  22. Fatty change in endocardium giving a ________ appearance.
    • patchy “thrush breast”
    • accumulated fat droplets
  23. _____ bodies in _______ hepatitis
    • Mallory
    • alcoholic
    • - Accumulation of protein in the liver, Suggests alcohol
    • - Accumulation of cytoskeletal elements in the heart
  24. ________ droplets in renal tubules indicating ______ diseases
    • Protein re-absorption
    • glomerular
    • protein leaking out of glomerular and resorpted by tubules
  25. __________ nuclei in uncontrolled diabetes
    Glycogen distending cell
  26. Swollen __________, with deposits, in necrosis
    mitochondria
  27. Mechanisms of membrane damage in cell injury.
    • Decreased O2 and increased cytosolic Ca2+ are typically seen in ischemia but may accompany other forms of cell injury. Reactive oxygen species, which are often produced on reperfusion of ischemic tissues, also cause membrane damage
    • ROS -> lipid peroxidation
    • decreased O2 -> decreased ATP -> decreased phospholipid synthesis
    • increased Ca2+ -> phospholipase activation -> increased phospholipid degradation -> lipid breakdown products
    • increased Ca2+ -> protease activation -> cytoskeletal damage
    • lipid peroxidation, decreased phospholipid synthesis, lipid breakdown products -> phospholipid loss
    • phospholipid loss, cytoskeletal damage, lipid breakdown products -> membrane damage
  28. Cellular Responses to Stress and Toxic Insults - hypertrophy
    • Mechanical sensors arevthe major triggers for physiologic hypertrophy
    • Agonists and growth factors more important in pathologic states
    • All activate certain pathway -> transcription factors -> hypertrophy -> increased mechanical performance
  29. Altered physiologic stimuli; some nonlethal injurious stimuli ->
    Cellular adaptations
  30. Increased demand, increased stimulation (e.g., by growth factors, hormones) ->
    Hyperplasia, hypertrophy
  31. Decreased nutrients, decreased stimulation ->
    Atrophy
  32. Chronic irritation (physical or chemical) ->
    Metaplasia
  33. Nutritional deprivation ->
    Autophagy
  34. Cumulative sublethal injury over long life span ->
    Cellular aging
Author
akhan
ID
322847
Card Set
General Pathology - 1 & 2 - Cell Injury and Death
Description
Gen Path L1,2
Updated