Cellular Injury: Reversible Vs. Irreversible

Cellular injury occurs on a continuum from reversible (cell recovery if stressor removed) to irreversible (cell death). The point of irreversibility is marked by two critical events: mitochondrial membrane damage (loss of oxidative phosphorylation and ATP generation) and severe plasma membrane damage (loss of cellular integrity). Reversible injury mechanisms: ATP depletion reduces Na+/K+-ATPase pump activity → sodium and water influx → cellular swelling (hydropic change) — the earliest ultrastructural change. Endoplasmic reticulum swelling causes ribosomal detachment and decreased protein synthesis. Mitochondrial swelling occurs but function can be restored. Cytoplasmic blebs form on the plasma membrane. Irreversible injury hallmarks: massive calcium influx activates destructive enzymes (phospholipases destroy membranes, proteases destroy cytoskeleton, endonucleases fragment DNA, ATPases deplete remaining ATP). Mitochondrial permeability transition pore opens → cytochrome c release → apoptosis cascade. Lysosomal membrane rupture releases acid hydrolases causing autolysis. Two patterns of cell death: Necrosis (pathological death from external injury — coagulative, liquefactive, caseous, fat, fibrinoid, gangrenous types) causes inflammation; Apoptosis (programmed cell death — physiological or pathological) is orderly, energy-dependent, involves caspase activation, and does NOT cause inflammation. Ischemia-reperfusion injury paradoxically...