U01.04.002 Cell injury

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Learning Objectives

Identify the structural and functional differences between reversible and irreversible cell injury by examining metabolic failure and membrane integrity. Master the specific morphological markers of cellular swelling versus membrane rupture, and understand the biochemical progression of nuclear degradation (pyknosis, karyorrhexis, and karyolysis) as it relates to clinical diagnosis and cell death.

1. Reversible Cell Injury

Reversible injury occurs when cellular stress is manageable or the insult is removed early. The hallmark is cellular swelling (hydropic change), caused by the failure of energy-dependent ion pumps. This leads to an influx of Na^+ and water, affecting the cytosol and organelles like the mitochondria and endoplasmic reticulum.

Feature Mechanism / Manifestation Morphology
ATP Depletion โ†“ Na^+/K^+-ATPase activity โ†’ Na^+ stays in cell. Cellular swelling (Earliest sign).
Organelle Stress Ribosomal detachment from Rough ER. โ†“ Protein synthesis; Mitochondrial swelling.
Membrane/Nucleus Chromatin clumping and surface blebbing. Myelin figures (lipid aggregations).

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2. Irreversible Cell Injury (Cell Death)

The “point of no return” is defined by profound membrane damage. Once the plasma, mitochondrial, or lysosomal membranes rupture, the cell can no longer maintain a metabolic gradient or contain its own digestive enzymes, leading inevitably to necrosis.

Target Membrane Biochemical Result Clinical Significance
Plasma Membrane Leakage of enzymes and Ca^{2+} influx. Elevated Troponin or CK-MB in serum.
Mitochondrial Permanent loss of the Electron Transport Chain (ETC). Amorphous densities in the matrix.
Lysosomal Release of acid hydrolases into the cytoplasm. Autolysis (The cell digests itself).

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3. Nuclear Degradation Sequence

Nuclear changes provide the most definitive microscopic evidence of cell death. This process follows a specific sequence as the genetic material is fragmented and eventually dissolved.

Stage Description
1. Pyknosis Nuclear shrinkage and increased basophilia.
2. Karyorrhexis Fragmentation of the nucleus (“nuclear dust”).
3. Karyolysis Dissolution and fading of the nucleus.

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High-Yield Mnemonics & Tips:

  • Point of No Return: Remember that membrane damage is the critical threshold. If the plasma membrane is broken, the cell is dead.
  • Nuclear PKK: Pyknosis (shrink), Karyorrhexis (fragment), Karyolysis (ghost).
  • Functional Loss: In a myocardial infarction, cells stop contracting within 1โ€“2 minutes (reversible phase), but death (irreversible phase) occurs after 20โ€“40 minutes.

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