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PA1.1-3,PA2.1-2 | Introduction to Pathology & Mechanisms of Cell Injury — Summary & Reflection

REFLECT

Take 3–4 minutes to reflect before moving to the summary.

The opening case showed a patient whose myocardium continued to die after the artery was reopened. You can now explain the mechanism to a colleague in 3 sentences — what would you say?

Think of a patient scenario (real or hypothetical from your pharmacology/physiology reading) where understanding the type of cell (labile vs. stable vs. permanent) would change how you counsel a patient about recovery.

Which of the six biochemical mechanisms of cell injury do you find most conceptually difficult? What analogy or diagram would help you remember it?

KEY TAKEAWAYS

Module summary — Introduction to Pathology & Mechanisms of Cell Injury

Pathology's four aspects: Etiology → Pathogenesis → Morphologic changes → Clinical significance. Pathologists work in anatomic pathology (surgical, cytology, autopsy) and clinical pathology (haematology, biochemistry, microbiology).

History: Cellular pathology established by Virchow (1858); now extended to molecular/genomic diagnostics.

Proliferative capacity: Labile (always cycling) → full regeneration; Stable (G0, re-enter on demand) → regeneration if scaffold intact; Permanent (non-dividing) → replaced by scar. Regenerative medicine uses iPSCs to target permanent-cell loss.

Causes of cell injury: Hypoxia/ischaemia, physical, chemical, infectious, immunologic, genetic, nutritional.

Six biochemical mechanisms: ATP depletion → cellular swelling; mitochondrial damage → ↓ATP + apoptotic signal; ↑[Ca²⁺]i → phospholipases/proteases; ROS/oxidative stress → membrane + DNA damage; membrane damage → lysosomal enzyme release; protein misfolding → ER stress + p53.

Reversible injury: Cellular swelling (hydropic change) and fatty change — morphological changes that normalise on removal of the stimulus.

Irreversible injury: MPT mega-channel opening + severe membrane disruption + massive Ca²⁺ influx mark the point of no return → necrosis.

IR injury: Reperfusion itself causes extra injury via xanthine oxidase ROS burst + Ca²⁺ overload + neutrophil activation + MPT. Time-critical in myocardium (≥20 min) and brain (≥4 min).