Cell Injury: Necrosis vs Apoptosis
Concept Name
Cell Death Mechanisms
Genetic Loci
BCL2 (18q21.33) – anti‑apoptotic; BAX (19q13.3) – pro‑apoptotic. CASP3 (4q35.1) encodes executioner caspase‑3. TP53 (17p13.1) activates pro‑apoptotic genes after DNA damage.
Intracellular Cascade
Apoptosis: intrinsic pathway (cytochrome c release → Apaf‑1 → caspase‑9 activation) or extrinsic (FasL → caspase‑8). Executioner caspases (3,6,7) cleave cellular substrates. Necrosis: ATP depletion → failure of ion pumps → cellular swelling → membrane rupture → inflammation.
Required Cofactors
ATP is required for apoptosis (apoptosome formation). Ca²⁺ overload triggers mitochondrial permeability transition in necrosis.
Histology Stains
TUNEL assay labels fragmented DNA in apoptotic cells. Cleaved caspase‑3 immunohistochemistry identifies apoptotic cells. H&E shows necrosis (karyolysis, pyknosis, karyorrhexis).
EM Findings
Apoptotic cells show chromatin condensation, nuclear fragmentation, membrane blebbing, and formation of apoptotic bodies. Necrotic cells show organelle swelling, membrane rupture, and amorphous debris.
Knockout Phenotype
Knockout of BAX and BAK in mice causes severe defects in apoptosis, leading to lymphadenopathy and resistance to chemotherapy. Caspase‑3 knockout causes perinatal lethality with brain hyperplasia.
Specific Toxins
Staurosporine induces apoptosis via broad‑spectrum kinase inhibition. FCCP (carbonyl cyanide‑p‑trifluoromethoxyphenylhydrazone) is a mitochondrial uncoupler that can trigger necrosis. Acetaminophen overdose causes centrilobular necrosis via NAPQI formation.