A researcher exposes cultured hepatocytes to graded periods of hypoxia and finds a time point beyond which reoxygenation fails to restore viability regardless of intervention. Ultrastructural study at this critical juncture shows rupture of lysosomal and plasma membranes with large amorphous calcium-rich densities in mitochondria. Which event constitutes the point of no return in this cell?
- A Irreversible damage to plasma and lysosomal membranes with massive influx of calcium ✓
- B Swelling of the endoplasmic reticulum with formation of whorls
- C Loss of ribosomes from the rough endoplasmic reticulum
- D Dispersion and clumping of nuclear chromatin
Correct answer: A. Irreversible damage to plasma and lysosomal membranes with massive influx of calcium
Explanation
The defining biochemical feature of irreversible injury is loss of integrity of plasma and lysosomal membranes. Membrane damage permits massive influx of calcium, which activates phospholipases, proteases, ATPases, and endonucleases that complete cellular destruction. Ribosomal detachment, ER swelling, and chromatin clumping are features of reversible injury and can recover on reoxygenation. Mitochondrial amorphous densities appear early but are not alone equivalent to membrane rupture, which marks lethality.
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.