cell injury

• Irreversible cell injury

  : permanent pathological changes (cell death) when stressors exceed capacity of cell to adapt
• Homeostasis:

  normal balance between physiological demands and limitations of cell structure and metabolic capacity. Stress

   cell change functional state  maintain steady state
• Stimuli of cell injury

  excessive physiological stress or pathological
• Causes

  1. Deprivation or (--)O2 supply (hypoxia): common cause that affect aerobic respiration
  2. infectious agents: bacteria ,virus ,parasites, fungi
  3. physical agents: heat ,cold, electric shock, irradiation
  4. Chemical agents: drugs, poisons, metals, alcohol, narcotics, pollution
  5. Mechanical agents: trauma
  6. Immunological: hypersensitivity, auto immune disease
  7. Nutritional imbalance: (--) proteins, vitamins or over nutrition
  8. Genetic disorders: (mutation) sub lethal damage + environmental changes  tumor
• .Deprivation or (--)O2 supply (hypoxia)

  1. ischemia (arterial occlusion)
  2. (--) O2 carrying capacity(anemia, CO poisoning)
  3. (--) oxygenation of blood (cardiorespiratory failure)
• ATP reduction


  (--) oxidative phosphorylation (--) aerobic respiration

   stoppage of Na-K pump

   (++) osmotic pressure and influx, accumulation of water

   swelling

   anaerobic respiration

   accumulation of lactic acid (--) PH

   (--) protein synthesis and ribosomal function

   Chromatin condensation and clumping

   (++) intracellular Ca++ (levels are kept in check by ATP dependent enzymes)
• accumulation of ROS

  oxidative stress

  ROS: intracellular toxic oxygen – free radicals contains single unpaired electrons at outer orbit

  highly reactive

  interact with adjacent molecule

  (superoxide O2 - OH – H2O2) ( produced by small amounts during mitochondrial respiration and energy production)

  When defense mechanisms are overcome

  damage of proteins, DNA

  damage of lipids (peroxidation of cell membrane) (oxidative stress)

  antioxidants (VIT E, superoxide dismutase, glutathione)

  effects: Reperfusion injury (restoration of blood in ischemic tissues), cell aging, chemical , radiation injury
• disruption membrane permeability

  ATP depletion

  affect Na –K Pump of plasma membrane Free radicle peroxidation of li[ids membrane (++) intracellular Ca++ from mitochondria, SER

  disruption of lysosomal membranes

  phospholipase: degrade membrane phospholipids

  protease: break cellular ptns

  ATPase: deplete ATP

  endonuclease: DNA injury
• Degree of injury depends on

  • duration of injury

  • nature of injury

  • type of affected cells
• targets of cell injury

  • cell membrane

  • mitochondria

  • ribosomes (protein synthesis)

  • DNA
• cloudy swelling

  (earliest): swelling due to “water accumulation &lipid deposition “at liver, myocardial, kidney cells (tubular cells)

  
• HYDROPIC DEGENERATION:

  (advanced): Vacuolar degeneration (ballooning)

  · Gross: increase weight with pale color

  " Microscopic: Excess water accumulation in the

  cells > vacuoles in pale cytoplasm
• FATTY CHANGE:

  " with hypoxic and toxic injury

  " lipid appears as empty vacuoles

  · in cells involved or dependent on fat metabolism (hepatocytes and myocardial cells)

  · at myocardium spotty at ischemia or diffuse at diphteria