During reperfusion injury after ischemia, the rapid restoration of pH from acidic conditions triggers massive cell death. Which molecular event specifically occurs at the moment of pH normalization?

• A Acute caspase-8 activation via FADD-DISC complex formation
• B pH-driven activation of lysosomal cathepsins causing lysosomal membrane permeabilization
• C Immediate activation of xanthine oxidase generating superoxide radicals
• D Sudden activation of MPTP (mitochondrial permeability transition pore) allowing cytochrome c release ✓

Explanation

During ischemia, the acidic intracellular pH actually partially protects cells by inhibiting the mitochondrial permeability transition pore (MPTP); when pH normalizes during reperfusion, this protection is lost and MPTP opens, collapsing ΔΨm and releasing cytochrome c, triggering apoptosis/necrosis. Xanthine oxidase-generated ROS also contributes to reperfusion injury, but the MPTP is the key lethal switch triggered by pH normalization. This is the mechanistic basis for acidic cardioplegia solutions used in cardiac surgery to delay MPTP opening during reperfusion.

Reference: Robbins & Cotran Pathologic Basis of Disease, 10th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.