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Difficulty: EasyCellular Injury and Adaptation

A 55-year-old man experiences a myocardial infarction, resulting in abrupt cessation of blood flow to a portion of the left ventricle. This ischemic event triggers a predictable sequence of subcellular changes leading to reversible cellular injury. Arrange the following pathophysiological events of ischemic cellular injury in the correct chronological order, from earliest to latest.

  1. 1Decreased mitochondrial oxidative phosphorylation
  2. 2Depletion of intracellular ATP stores
  3. 3Failure of the plasma membrane Na+/K+ ATPase pump
  4. 4Intracellular accumulation of sodium and water
  5. 5Cellular and endoplasmic reticulum swelling

Answer

The correct sequence begins with decreased mitochondrial oxidative phosphorylation, followed by depletion of intracellular ATP stores, failure of the plasma membrane Na+/K+ ATPase pump, intracellular accumulation of sodium and water, and finally cellular and endoplasmic reticulum swelling.
Ischemic injury begins with hypoxia, which directly halts mitochondrial oxidative phosphorylation. This immediately depletes cellular ATP. Without ATP, energy-dependent processes such as the Na+/K+ ATPase pump fail. The loss of this pump causes sodium to accumulate intracellularly, which draws in water osmotically, ultimately leading to cellular and organelle swelling (hydropic change).

Step-by-Step Solution

1
Identify the primary insult of ischemia at the cellular level.
Decreased oxygen halts mitochondrial oxidative phosphorylation.
Oxygen is required as the final electron acceptor in the electron transport chain.
2
Determine the immediate biochemical consequence of halting oxidative phosphorylation.
Depletion of intracellular ATP stores.
The cell loses its primary source of energy production, and anaerobic glycolysis cannot fully compensate.
3
Identify the effect of ATP depletion on membrane transport.
Failure of the plasma membrane Na+/K+ ATPase pump.
This pump relies heavily on ATP to transport ions against their concentration gradients.
4
Assess the ionic shifts caused by pump failure.
Intracellular accumulation of sodium and water.
Sodium normally extruded by the pump remains inside the cell, pulling water with it via osmosis.
5
Determine the morphological result of this fluid influx.
Cellular and endoplasmic reticulum swelling.
The excess water physically expands the cell and its organelles, representing the classic hallmark of reversible cell injury.

Key Concept

Sequence of biochemical events in reversible ischemic cellular injury
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Topics

Cellular Injury and Adaptation

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