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Reversible versus irreversible cell injury

Reversible injury is damage a cell can recover from; irreversible injury is beyond the point of no return, as with pyknosis (a shrunken nucleus).

Remember

Swelling with the membrane still intact, blebs (small bulges in the cell membrane) and mild clumping of chromatin are changes of reversible injury, whereas even further swelling, lysosome rupture, membrane defects and pyknosis (a shrunken nucleus) show that the cell has passed the point of no return.

Cell injury can be reversible or irreversible. A light microscope makes reversible injury and cell death very hard to tell apart, whereas an electron microscope (which shows the fine internal structure of the cell) separates them much more easily. Reversible injury is damage that a cell can recover from if the cause is removed.

Take a cell that is short of oxygen. Its ATP (the cell's energy currency) falls, so the pumps that depend on ATP stop working, sodium and water enter, and the cell and its organelles swell. Other reversible changes are blebs (small bulges in the cell membrane), clumped chromatin (the cell's DNA with its packaging proteins) and ribosomes (the protein-making particles) drifting off the rough endoplasmic reticulum (the network of membranes they sit on).

Injury becomes irreversible when swelling goes even further, lysosomes (small sacs of digestive enzymes) rupture, the membranes develop defects and the endoplasmic reticulum breaks down. A ruptured lysosome exposes the cell to its own digestive enzymes.

The three recognisable nuclear changes that follow show that the cell has passed the point of no return. In pyknosis the chromatin condenses and the nucleus shrinks, so it looks small and dark. In karyorrhexis the nucleus breaks into fragments, and in karyolysis it dissolves away.

Key facts

Light microscope
reversible injury and cell death are very hard to tell apart.
Reversible changes
these include a swollen cell and swollen organelles, blebs in the membrane, clumped chromatin and ribosomes drifting off the rough endoplasmic reticulum.
Irreversible changes
lysosomes rupture, membranes show defects, the endoplasmic reticulum breaks down and swelling goes even further.
Pyknosis
the chromatin condenses and the nucleus shrinks, so it looks small and dark.
Karyorrhexis
the nucleus breaks into fragments.
Karyolysis
the nucleus dissolves away as enzymes digest its DNA.

Exam traps

  • Fragmentation of the nucleus is called karyorrhexis and marks irreversible injury: reversible injury may clump chromatin but does not fragment the nucleus.
  • Blebs on their own do not show that the membrane has failed: blebs are small bulges listed among the reversible changes, whereas membrane defects and rupture do show failure.
  • Clumped chromatin is not pyknosis: early clumping is listed among the reversible changes, but in pyknosis the chromatin is irreversibly condensed and the whole nucleus shrinks.

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Last updated 6 November 2026. For medical education only, not clinical advice.