Cell injury

• Cell Injury


  • When the cell is exposed to a stimulus
  • When the cell is exposed to anything harmful
• Cell is exposed to harmful stimulus


  It will lead to harm - it will cause a malfunction
• So this cell will be damaged
• All diseases are caused by an imbalance in cells
• Reversible


  When a cell is damaged it can return to its normal state
• Irreversible


  The cells cannot return to their normal state
• Both lead to cell death
• Cellular response to injury

  • Acute cell injury
  • Reversible injury
  • Cell death (irreversible injury)
  • Necrosis
  • Apoptosis
  • Cellular adaptations
• Cellular adaptations


  • Atrophy
  • Hypertrophy
  • Hyperplasia
  • Metaplasia
• Intracellular accumulations


  • Calcification
• Factors that determine fate of cells


  • Type of injury (chemical or physical)
  • Severity of injury (Mild or moderate or severe)
  • Duration of exposure (short or long)
  • Type of cells
  • State of cell
  • Adaptability of the cell
• Cell division capacity


  • High capacity (labile cell)
  • Low capacity (stable cell)
  • Nil capacity (permanent cell)
• Reversible cell injury


  The cellular changes will regress and disappear when the injurious agent is removed; the cell will return to normal both morphologically and functionally
• Irreversible cell injury


  The injury persists or is severe from the start. The cell reaches the point of no return and progression to cell death is inevitable
• Causes of cell injury

  • Hypoxia
  • Physical injury
  • Chemical agents & drugs
  • Microbial agents
  • Immunologic reactions
  • Genetic derangement
  • Nutritional imbalance
  • Aging
• Mechanism of cell injury (pathogenesis)

  1. Cell membrane destruction

  2. ATP production lost

  3. Protein synthesis

  4. Genetic apparatus
• Free radicals


  Chemical species with unpaired electron in the outer shell, highly reactive & autocatalytic
• Sources of free radicals

  • Endogenous (leukocytes, macrophages & endothelial cells)
  • Metabolites of drugs & chemicals
  • Absorption of radiant energy
• Types of free radicals

  • Superoxide
  • Nitroxide
  • Hydroxyl
  • Hydrogen peroxide
  • Carbon trichloride
• Examples of free radical induced injury

  • Inflammation
  • Reperfusion injury
  • Aging process
  • O2 toxicity
  • Radiation
  • Chemical & drug injury
• Targets of free radical injury in cells

  • Membrane damage through lipid peroxidation
  • Cross linking proteins forming disulfide bonds
  • DNA: Single strand break & induction of mutation
• Classes of chemical injury

  • Direct interaction with cellular component
  • Indirect by converted in cell into toxic metabolite
• Types of microbial injury

  • Direct induced injury
  • Indirect induced injury
• Reversible cell injury morphology (Light Microscope)

  • Cellular swelling
  • Hydropic vacuolation
  • Fatty change
  • Clumping of chromatin
• Irreversible cell injury morphology (Light Microscope)

  • Nuclear changes: Pyknosis, Karyorrhexis, Karyolysis
  • Intensely eosinophilic cytoplasm
• Necrosis


  Morphologic changes that follow cell death in the living tissue or organs due to action of degradative enzymes or protein denaturation on irreversibly injured cells
• Mechanism of necrosis


  • Denaturation of proteins
  • Enzymatic digestion by autolysis or heterolysis
• Necrosis is associated with inflammation, randomly occurs, involves a group of cells, and is always pathologic
• Causes of necrosis


  • Ischemia
  • Chemical injury
  • Infarction
  • Nutritional
• Types of necrosis


  • Coagulative necrosis
  • Liquefactive necrosis
  • Caseous necrosis
  • Fat necrosis
  • Fibrinoid necrosis
  • Gummatous necrosis
• Coagulative necrosis


  The commonest type of necrosis, results from denaturation of all proteins including enzyme as a result of ischemia & acidosis, preservation of tissue architecture & cellular outline for sometime with loss of internal details including nuclei
• Infarct


  Ischemic necrosis caused by occlusion of either the arterial supply or the venous drainage
• Classification of infarcts


  • Red (haemorrhagic) infarction
  • White (anemic) infarction
  • Septic infarction
  • Sterile infarction
• Red (haemorrhagic) infarct


  Occurs in venous occlusion, loose tissue that allow the blood to collect, tissues with dual circulation, previously congested tissues, reperfusion of previously ischemic tissue
• White (anemic) infarct


  Occurs in arterial occlusion in solid organs with end-arterial circulation, sharply delineated, light yellow due to denaturated cellular proteins
• Liquefactive necrosis


  Early softening & liquefaction of the necrotic tissue, proteolytsis over protein denaturation, seen in ischemic necrosis of CNS and abscess formation
• Caseous necrosis


  Soft & yellow white, appears as cheese-like, characteristic of Tuberculosis, coagulative necrosis modified by capsule lip-polysaccharide of TB bacilli
• Fat necrosis


  Necrosis of adipose tissue, characterized by the formation of small quantities of calcium soaps when fat is hydrolyzed, caused by release of pancreatic enzymes or trauma
• Fibrinoid necrosis


  Intense eosinophilic staining of involved (necrotic) tissue, like fibrin, seen in malignant hypertension, vasculitis, and connective tissue disease
• Gummatous necrosis


  Modified type of coagulative necrosis, seen in the tertiary syphilis