Expansion
Membrane damage and mitochondrial failure mark irreversibility
Expansion
Reversible changes
- Cellular swelling (hydropic change), from failure of the sodium-potassium ATPase
- Fatty change, especially in liver
- Blebbing of the plasma membrane, ribosome detachment from the endoplasmic reticulum
- Mitochondrial swelling
- Switch to anaerobic glycolysis, with falling pH and glycogen depletion
Irreversible changes
- Severe membrane damage, with enzyme leakage (hence rising troponin, ALT and creatine kinase in blood)
- Massive calcium influx, activating phospholipases, proteases and endonucleases
- Mitochondrial amorphous densities
- Nuclear change: pyknosis (shrinkage), karyorrhexis (fragmentation), karyolysis (dissolution)
The mechanistic common pathway is ATP depletion, whether from hypoxia, toxins or free radicals, followed by loss of ionic gradients and then of membrane integrity.
Reperfusion injury is the paradox: restoring blood flow generates a burst of free radicals, admits calcium and recruits neutrophils, so some cells that were still viable are killed by the rescue itself.