In ischemic cell injury, which change represents the POINT OF IRREVERSIBILITY?
- A Cell swelling and loss of microvilli
- B Mitochondrial permeability transition pore (mPTP) opening causing flocculent densities and irreversible ATP depletion ✓
- C Dilation of ER with ribosomes detaching
- D Increased cytosolic calcium from ER stores
Correct answer: B. Mitochondrial permeability transition pore (mPTP) opening causing flocculent densities and irreversible ATP depletion
Explanation
The point of irreversibility in ischemic injury corresponds to massive calcium influx triggering mPTP opening, causing formation of amorphous (flocculent) densities within mitochondria, inner membrane disruption, and catastrophic loss of ATP generation. Earlier changes (cell swelling, ER dilation, Ca2+ rise from ER stores) are reversible if reperfusion occurs promptly. Once mPTP opens, the cell is committed to death regardless of oxygen restoration.
Reference: Robbins & Cotran Pathologic Basis of Disease, 10th ed.
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