In ischemia-reperfusion injury, which mechanism is primarily responsible for the paradoxical increase in cell death upon restoration of blood flow?
- A Persistent ATP depletion preventing membrane pump recovery
- B Direct toxicity of lactic acid accumulated during ischemia
- C Massive generation of reactive oxygen species and calcium overload upon reoxygenation ✓
- D Hypertonic reperfusion causing osmotic cell lysis
Correct answer: C. Massive generation of reactive oxygen species and calcium overload upon reoxygenation
Explanation
Reperfusion injury occurs because resumption of blood flow delivers oxygen to cells containing accumulated NADH and xanthine oxidase substrates, generating a burst of reactive oxygen species. Concurrently, intracellular calcium overload (due to impaired Na+/K+ ATPase and Na+/Ca2+ exchanger during ischemia) activates destructive enzymes. Together these cause mitochondrial permeability transition pore opening, amplifying cell death beyond that caused by ischemia alone.
Reference: Robbins & Cotran Pathologic Basis of Disease, 10th ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
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