Prolonged ischemia most directly leads to which tissue change?

• A. Hyperplasia
• B. Hypertrophy
• C. Necrosis
• D. Fibrosis

Answer: (C)

Prolonged ischemia deprives cells of oxygen and nutrients, causing energy failure from ATP depletion. This disrupts ion pumps, leads to calcium overload, and damages membranes. When injury becomes irreversible, the cell undergoes necrosis—uncontrolled cell swelling, membrane rupture, and release of intracellular contents that trigger inflammation. This is the direct tissue change seen with sustained ischemia. Hypertrophy and hyperplasia are adaptive increases in cell size or number in response to workload or hormonal signals, not the immediate consequence of ischemia, and fibrosis is scar formation that can follow necrosis as part of healing, not the initial change from ischemia itself.