A pathologist observes cells with hyperchromatic shrunken nuclei, condensed cytoplasm, and cytoplasmic membrane-bound vesicles being phagocytosed by neighboring cells without inflammation. This pattern of cell death involves which molecular executor?
- A Caspase-3 cleaving ICAD to release CAD (caspase-activated DNase), generating internucleosomal DNA fragmentation ✓
- B MLKL phosphorylation causing plasma membrane disruption (necroptosis)
- C Gasdermin D cleavage and pore formation (pyroptosis)
- D Lysosomal cathepsin B activation causing organelle swelling
Explanation
The described morphology is classic apoptosis: cell shrinkage, nuclear condensation (pyknosis and karyorrhexis), cytoplasmic fragmentation into apoptotic bodies, and engulfment by adjacent cells without triggering inflammation. The executioner caspases (caspase-3, -6, -7) cleave ICAD (inhibitor of caspase-activated DNase), releasing CAD which enters the nucleus and cleaves DNA between nucleosomes generating the characteristic ~180 bp ladder. MLKL mediates necroptosis; gasdermin D cleavage is pyroptosis; lysosomal rupture causes necrosis.
Reference: Robbins & Cotran Pathologic Basis of Disease, 10th ed.
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