Learning Objective

By the end of this lesson, the learner will be able to distinguish reversible vs. irreversible cell injury, describe the biochemical and structural changes involved, and correlate these changes with disease processes.

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Cell Injury

Cells exposed to stress beyond their adaptive capacity undergo cell injury. Injury may be reversible or progress to irreversible damage, ultimately resulting in cell death.

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Reversible Cell Injury

Occurs early and is potentially reversible if the stress stimulus is removed.

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Key Features & Mechanisms

• ↓ ATP production
  → ↓ function of Ca²⁺ and Na⁺/K⁺-ATPase pumps
  → intracellular Na⁺ and water accumulate
  → cellular swelling (earliest morphologic sign)

Affected organelles include:
✔ cytosol
✔ mitochondria
✔ endoplasmic reticulum
✔ Golgi apparatus

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• Ribosomal detachment from the ER
  → ↓ protein synthesis
• Plasma membrane alterations
  → membrane blebs
• Nuclear changes
  → chromatin clumping
• Formation of myelin figures
  (aggregation of damaged/peroxidized membrane lipids)
• Functional loss precedes structural change
  Example:
  Myocardial cells lose contractility within 1–2 minutes of ischemia, even before injury becomes irreversible.

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Irreversible Cell Injury

Occurs when cellular damage cannot be reversed, leading to cell death (necrosis or apoptosis).

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Plasma Membrane Damage

• Loss of membrane integrity → leakage of intracellular enzymes
  Example: troponin leaks into the bloodstream
• Persistent Ca²⁺ influx
  → activates phospholipases, proteases, endonucleases → breakdown of essential structures

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Mitochondrial Dysfunction

• Loss of oxidative phosphorylation
• Failure of the electron transport chain
• ↓ ATP
• Swelling with the formation of amorphous mitochondrial densities

This step is considered a point of no return.

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Lysosomal Rupture

• Release of hydrolytic enzymes
• Autolysis of cell contents

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Progressive Nuclear Changes

These occur sequentially:

• Pyknosis – nuclear condensation
• Karyorrhexis – fragmentation due to endonuclease cleavage
• Karyolysis – complete dissolution of nuclear material

These nuclear changes signify irreversible injury and cell death.

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Summary Breakdown