In acute myocardial infarction, irreversible cell injury occurs after approximately 20–40 minutes of severe ischemia. Which ultrastructural feature on electron microscopy is the EARLIEST marker of irreversible myocardial injury?

• A Contraction bands (hypercontracted sarcomeres)
• B Cytoplasmic glycogen depletion
• C Nuclear chromatin clumping (pyknosis)
• D Flocculent densities (amorphous densities) in mitochondrial matrix ✓

Explanation

Amorphous flocculent densities (large, dense amorphous granules) within mitochondria on electron microscopy are the earliest ultrastructural marker of irreversible (lethal) myocardial cell injury, appearing within minutes of irreversible ischemia. They represent precipitated mitochondrial proteins and phospholipids. Contraction bands appear at reperfusion due to calcium influx. Cytoplasmic glycogen depletion is an early reversible feature of ischemia. Nuclear pyknosis is a later, light microscopy-detectable change that becomes apparent only hours after infarction.

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

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