The dividing line is mitochondrial permeability and membrane integrity — not swelling or blebbing.
Why this is true
Injury begins with ATP depletion: the Na⁺/K⁺-ATPase fails, sodium and water enter, and the cell swells. All of that is recoverable. The point of no return is opening of the mitochondrial permeability transition pore, which collapses the proton gradient so that even restored oxygen cannot regenerate ATP, and releases cytochrome c. Combined with plasma membrane defects and massive calcium influx activating phospholipases and proteases, the cell can no longer be rescued. This is also why restoring blood flow can *worsen* infarction — oxygen returning to damaged mitochondria generates free radicals rather than ATP.
Key points
- Reversible: cellular swelling, membrane blebs, ribosomal detachment, chromatin clumping, fatty change.
- Irreversible: mitochondrial vacuolisation with amorphous densities, lysosomal rupture, plasma membrane defects, nuclear pyknosis → karyorrhexis → karyolysis.
- Coagulative necrosis everywhere except brain (liquefactive), TB (caseous), pancreas and breast (fat necrosis), vessels (fibrinoid).
- Apoptosis is ATP-dependent, affects single cells, and does not incite inflammation — necrosis does both opposites.
- Intrinsic apoptosis: BAX/BAK release cytochrome c; extrinsic: Fas–FasL or TNF activating caspase-8. Both converge on caspase-3.
Necrosis patterns
| Pattern | Typical site | Mechanism |
|---|---|---|
| Coagulative | Heart, kidney, spleen | Ischaemia with protein denaturation |
| Liquefactive | Brain, abscess | Enzymatic digestion |
| Caseous | Tuberculosis, fungi | Granulomatous inflammation |
| Fat | Pancreas, breast | Lipase-mediated saponification |
| Fibrinoid | Vessel walls | Immune complex deposition |
Common traps
- Cellular swelling is reversible; mitochondrial vacuolisation is not. Both look like 'swelling' in a stem.
- Apoptotic bodies are cleared without inflammation — a stem mentioning a neutrophil infiltrate is describing necrosis.
Test yourself
Three days after successful thrombolysis a myocardial infarct is larger than the initial perfusion defect predicted.
High-yield
Reperfusion injury is oxygen-radical and calcium mediated, worsening the initial infarct.