In a liver biopsy showing centrilobular pallor and swelling of hepatocytes due to decreased ATP production, what is the most likely mechanism of cellular swelling?

• A. Decreased Na/K ATPase activity due to ATP deficit
• B. Increased protein synthesis
• C. Enhanced fatty acid oxidation
• D. Activation of lysosomal enzymes

Answer: (A)

Cell swelling in early reversible liver injury comes from a failure of energy-dependent ion pumps. When ATP is depleted, the Na+/K+ ATPase cannot maintain the ionic gradients, so Na+ accumulates inside hepatocytes. Water follows this osmotic signal, producing cytoplasmic swelling (hydropic change) and the pale centrilobular appearance. This is a classic response to hypoxic/ischemic stress where ATP production drops first in the centrilobular zones. Other mechanisms described would not produce this immediate osmotic swelling: increasing protein synthesis doesn’t cause acute cellular edema, enhanced fatty acid oxidation is a metabolic shift rather than a pump-driven swelling, and activation of lysosomal enzymes leads to degradation rather than the initial water-driven swelling seen with ATP depletion.