Lecture II

• Necrosis is a pathologic process that is the consequence of severe injury
• Necrosis is characterized by denaturation of cellular proteins, leakage of cellular contents through damaged membranes, local inflammation, and enzymatic digestion of the lethally injured cell
• Two phenomena consistently characterize irreversibility:

  • The inability to reverse mitochondrial dysfunction (lack of oxidative phosphorylation and ATP generation) even after resolution of the original injury
  • Profound disturbances in membrane function
• Coagulative necrosis:

  • Caused by tissue ischemia that occurs in most tissues except the brain
  • Decreased oxygen delivery leads to ↓ ATP
  • Anaerobic metabolism leads to ↑ lactic acid production, ↓ pH, denaturation of proteins, including proteolytic enzymes, and cell death
  • Impaired Na+/K+-ATPase leads to ↑ intracellular Na+, ↑ intracellular H2O, and cell swelling
  • Preserved, anuclear, eosinophilic cellular architecture
  • Organ damage caused by acidic solutions
• Gangrenous necrosis:

  • A subtype of coagulative necrosis most commonly seen in the limbs
  • Dry gangrene caused by ischemia
  • Wet gangrene caused by superinfection of dry gangrene
  • Dry gangrene shows coagulative necrosis
  • Wet gangrene shows coagulative and liquefactive necrosis
  • Examples: peripheral arterial disease, acute limb ischemia, intestinal ischemia, Clostridium perfringens causing gas gangrene, sepsis
• Liquefactive necrosis:

  • Characterized by liquefaction/softening of the affected tissue
  • Release of hydrolytic enzymes from neutrophilic lysosomes that digest the affected tissue
  • Tissue softening leads to fluid necrosis, cavitation, and pseudocyst formation
  • Early stage involves macrophages and cellular debris
  • Late stage shows cavitations or cystic spaces
  • Examples: bacterial infections, stroke, pancreatitis
  • Organ damage caused by alkaline solutions
• Caseous necrosis:

  • Characterized by granular debris resulting from macrophages walling off a pathogen
  • Granuloma consists of cellular debris surrounded by lymphocytes, epithelioid cells, and multinucleated giant cells
  • Examples: tuberculosis, systemic fungi infection like histoplasmosis, Nocardiosis
• Fat necrosis:

  • Adipose cells die off prematurely
  • Enzymatic fat necrosis: release of lipase and triglycerides from damaged cells leads to breakdown of triglycerides by lipase, binding of fatty acids to calcium, saponification, and chalky-white appearance
  • Nonenzymatic fat necrosis: traumatic injury
  • Outlines of adipocytes with no peripheral nuclei
  • Combination of fat saponification and calcium leads to dark blue appearance on H&E stain
  • Examples: enzymatic fat necrosis in acute pancreatitis, nonenzymatic fat necrosis in traumatic breast injury
• Fibrinoid necrosis:

  • Characterized by small blood vessel injury with accumulation of fibrin and other plasma proteins
  • Vessel wall damage caused by immune complex deposition leads to fragmentation of collagenous and elastic fibers, leakage of fibrin and other plasma proteins
  • Visible damage includes thick walls with fragments of embedded cellular debris, serum, and fibrin
  • Examples: rheumatoid arthritis, peptic ulcer disease, immune vasculitis like polyarteritis nodosa, preeclampsia, hypertensive emergency