Within minutes of complete ischemia, a hepatocyte shows swelling of the endoplasmic reticulum and loss of ribosomes from its surface. Which primary event explains these ultrastructural changes?

• A Mitochondrial permeability transition pore opening with cytochrome c release
• B ATP depletion causing failure of the sodium-potassium pump and influx of water ✓
• C Oxidative modification of membrane phospholipids by hydroxyl radicals
• D Activation of caspase-3 with cleavage of cytoskeletal proteins

Explanation

Ischemia deprives cells of oxygen and substrates, causing rapid ATP depletion. Without ATP, the sodium-potassium pump fails, sodium and water enter the cell, and the cell and its organelles including the ER swell. Energy failure also causes detachment of ribosomes from the rough ER with reduced protein synthesis. These are hallmarks of early reversible injury. Permeability transition pore opening, oxidative damage, and caspase activation mark irreversible injury or apoptosis, not the earliest reversible phase.

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

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.