Cell Injury, Necrosis, Apoptosis, and Cellular Adaptations

Irreversible Cell Injury: Necrosis

  • Necrosis is defined as the morphological changes that follow cell death in a living tissue.
  • It results from denaturation of intracellular proteins and enzymatic degradation of lethally injured cells.
  • Necrotic cells lose membrane integrity, leading to leakage of cellular contents and inflammation.
  • Enzymes involved in digestion of necrotic cells come from lysosomes of dying cells and leukocytes.
  • Digestion and host response take hours to develop; early myocardial infarcts may not show histologic evidence of necrosis until 4-12 hours later.

Morphology of Necrosis

Cytological Changes
  • Increased eosinophilia in H&E stains due to loss of cytoplasmic RNA and denatured cytoplasmic proteins.
    • Loss of cytoplasmic RNA: RNA binds to hematoxylin (blue dye).
    • Denatured cytoplasmic proteins: Proteins bind to eosin (red dye).
  • Glassy homogeneous appearance due to loss of glycogen particles.
  • Vacuolated, moth-eaten cytoplasm due to enzymatic digestion of organelles.
  • Myelin figures: Large, whorled phospholipid masses derived from damaged cell membranes.
  • Calcification: Fatty acid residues from degraded phospholipids may calcify, generating calcium soaps.
Nuclear Changes
  • Changes occur due to nonspecific breakdown of DNA.
    • Karyolysis: Fading of chromatin basophilia due to enzymatic DNA degradation by endonucleases.
    • Pyknosis: Nuclear shrinkage and increased basophilia; chromatin condenses into a solid, shrunken mass.
    • Karyorrhexis: Fragmentation of the pyknotic nucleus. Over time, the nucleus disappears.

Characteristics of Necrosis

  • Denaturation of cellular proteins.
  • Leakage of cellular contents through damaged membranes.
  • Local inflammation.
  • Enzymatic digestion of lethally injured cells.

Causes of Necrosis

  • Loss of oxygen supply (ischemia).
  • Exposure to microbial toxins.
  • Burns.
  • Physical and chemical injury.
  • Active proteases leak out of cell and damage surrounding tissue.

Microscopic Features of Necrosis (Electron Microscopy)

  • Discontinuities in plasma and organelle membranes.
  • Marked dilation of mitochondria with large amorphous densities.
  • Intracytoplasmic myelin figures.
  • Amorphous debris and aggregates of denatured protein.

Types of Necrosis

Basic Types
  1. Coagulative necrosis
  2. Liquefactive necrosis
Special Types
  1. Caseous necrosis
  2. Fat necrosis
  3. Fibrinoid necrosis
  4. Gangrenous necrosis

1) Coagulative Necrosis

  • Architecture of dead tissues is preserved for at least some days.
  • Affected tissues exhibit a firm texture.
  • Injury denatures structural proteins and enzymes, blocking proteolysis of dead cells.
  • Phagocytosis of eosinophilic, anucleate cells may persist for days or weeks.
  • Examples:
    • Infarction of any organ except the brain.
    • Myocardial infarction (MI).
    • Gumma of tertiary syphilis.

2) Liquefactive Necrosis

  • Digestion of dead cells results in transformation of tissue into a liquid viscous mass.
  • Seen in focal bacterial or fungal infections within the CNS.
  • Microbes stimulate accumulation of leukocytes and liberation of enzymes.
  • Necrotic material is frequently creamy yellow due to dead leukocytes (pus).
  • Examples:
    • Suppurative inflammation/abscess.
    • Infarction of the brain.

3) Caseous Necrosis

  • Distinctive form of coagulative necrosis, most often in tuberculous infection foci.