3. Irreversible cell damage. Cell death (oncosis, apoptosis, autophagy, pyroptosis). Necrosis.

Cell Death Types

1 Oncosis

Definition: Type of accidental (uncontrolled) cell death associated with cellular swelling.

Mechanism: Severe ATP depletion → failure of ion pumps → massive cell and organelle swelling → membrane rupture → lysis.

Morphology: Cell swelling, plasma membrane blebs, organelle swelling.

2 Necrosis

Definition: Unregulated cell death caused by severe damage, resulting in leakage of cellular contents → inflammation.

Morphology:

• Cytoplasmic changes: Increased eosinophilia, loss of glycogen, cytoplasmic vacuolization.
• Nuclear changes:
• Pyknosis: nuclear shrinkage, basophilia.
• Karyorrhexis: nuclear fragmentation.
• Karyolysis: nuclear fading, chromatin dissolution.

Types of necrosis (based on tissue patterns):

• Coagulative necrosis: Architecture preserved (e.g., myocardial infarct).
• Liquefactive necrosis: Tissue digestion (e.g., brain infarct, abscess).
• Caseous necrosis: Granular, cheese- like (e.g., TB).
• Fat necrosis: Enzymatic (pancreatitis) or traumatic.
• Gangrenous necrosis: Large areas, often extremities (dry, wet, gas).

3 Apoptosis

Definition: Programmed, energy- dependent cell death without inflammation.

Causes:

• Physiologic: Embryogenesis, hormone-dependent involution, elimination of self- reactive lymphocytes.
• Pathologic: DNA damage, misfolded proteins, viral infections.

Mechanisms:

• Intrinsic (mitochondrial) pathway: Bcl-2 family proteins → cytochrome c release → caspase cascade.
• Extrinsic (death receptor) pathway: Fas-FasL, TNF receptor → caspase activation.

Morphology:

• Cell shrinkage.
• Chromatin condensation (pyknosis).
• Formation of apoptotic bodies.
• Phagocytosis by neighboring cells or macrophages (no inflammation).

4 Autophagy

Definition: "Self-eating"; survival mechanism where cell digests its own components to generate energy during stress.

Mechanism: Formation of double-membrane autophagic vacuoles → fusion with lysosomes → degradation.

Roles:

• Nutrient deprivation adaptation.
• Elimination of damaged organelles.Can lead to cell death if excessive.

5 Pyroptosis

Definition: Inflammatory form of programmed cell death, mainly in cells infected by microbes.

Mechanism:

• Activation of inflammasomes → caspase-1 (or caspase-11 in humans) activation.
• Caspase- 1 cleaves IL- 1β and IL- 18 precursors → inflammation.
• Plasma membrane pore formation → cell swelling and lysis.

Features:

• Combines features of apoptosis (caspase dependence) and necrosis (membrane rupture, inflammation).

Pathogenesis of Irreversible Cell Damage

Severe mitochondrial dysfunction → no ATP regeneration.

Loss of membrane integrity → leakage of cellular enzymes and ions.

Massive Ca² influx→ activation of lytic enzymes.

Lysosomal membrane rupture → enzymatic digestion.

Severe DNA and protein damage → loss of repair capacity.

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