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Cell Injury and Necrosis
Types, Causes, and Morphology
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Cell injury happens when a cell is exposed to stress that exceeds its ability to adapt. Early injury may be reversible, but severe or persistent damage can push the cell toward death. Necrosis is a form of cell death that usually follows major membrane damage, enzyme leakage, and inflammation in surrounding tissue. Understanding these patterns helps students connect pathology slides with real clinical disease.
The main causes of cell injury include hypoxia, ischemia, toxins, infection, immune reactions, and physical agents such as heat or trauma. A common mechanism is ATP depletion, which disrupts ion pumps, causes cell swelling, and impairs protein synthesis. If damage worsens, calcium enters the cell, mitochondria fail, membranes break down, and lysosomal enzymes digest cellular contents. Different tissues then show characteristic necrosis patterns such as coagulative, liquefactive, caseous, fat, fibrinoid, or gangrenous necrosis.
Key Facts
- Reversible injury often shows cellular swelling, fatty change, membrane blebs, and ribosome detachment.
- ATP depletion leads to Na+/K+ pump failure, causing Na+ and H2O influx and cell swelling.
- Anaerobic glycolysis increases when O2 falls, so glycogen decreases and lactic acid increases.
- Increased intracellular Ca2+ activates phospholipases, proteases, endonucleases, and ATPases.
- Necrosis is associated with membrane rupture, enzyme leakage, and inflammation in adjacent tissue.
- Nuclear changes in necrosis progress as pyknosis -> karyorrhexis -> karyolysis.
Vocabulary
- Reversible cell injury
- A stage of cell damage in which the cell can still recover if the harmful stimulus is removed.
- Necrosis
- Unregulated cell death caused by severe injury, marked by membrane breakdown and inflammation.
- Ischemia
- Reduced blood supply to tissue that limits oxygen and nutrient delivery and impairs waste removal.
- Pyknosis
- Irreversible nuclear shrinkage with increased basophilia due to chromatin condensation.
- Coagulative necrosis
- A pattern of necrosis in which tissue architecture is preserved for a time, commonly seen after infarction in solid organs.
Common Mistakes to Avoid
- Confusing ischemia with hypoxia, because ischemia reduces both oxygen and nutrient delivery and also prevents waste removal, so it is usually more damaging than hypoxia alone.
- Assuming all cell swelling means necrosis, because swelling is often an early reversible change before irreversible membrane damage occurs.
- Mixing up apoptosis and necrosis, because apoptosis is a regulated process with minimal inflammation while necrosis usually causes cell rupture and inflammation.
- Forgetting tissue-specific necrosis patterns, because brain infarcts typically cause liquefactive necrosis while most solid organ infarcts cause coagulative necrosis.
Practice Questions
- 1 A myocardial cell loses 70% of its ATP during severe ischemia. Name two membrane transport consequences and two visible reversible changes expected in the cell.
- 2 A patient has a cerebral infarct. Identify the most likely type of necrosis and explain which gross or microscopic feature would help distinguish it from coagulative necrosis.
- 3 Why does membrane damage mark the transition from reversible injury to necrosis, and how does this lead to inflammation in surrounding tissue?