General Pathology and Pathophysiology
Overview
This domain tests mechanisms of disease rather than pattern recognition: how cells respond to injury, how inflammation resolves or fails to resolve, and how a neoplasm escapes growth control. Board items in this domain typically ask you to link a morphological finding to a molecular mechanism, or to predict the consequence of a specific defect.
Core rules
- Reversible versus irreversible injury: ATP depletion and cell swelling are reversible; loss of membrane integrity, mitochondrial permeability transition pore opening and lysosomal rupture mark the point of no return.
- Necrosis patterns: coagulative (ischemia everywhere except brain), liquefactive (brain infarct, abscess), caseous (mycobacterial, fungal), fat necrosis (pancreas, breast), fibrinoid (vasculitis).
- Apoptosis: the intrinsic pathway is Bax/Bak-driven with cytochrome c release and caspase-9; the extrinsic pathway is Fas/FasL with caspase-8. Bcl-2 is anti-apoptotic; p53 is a tumor suppressor, the "guardian of the genome".
- Amyloid: Congo red with apple-green birefringence under polarized light; AA in chronic inflammation, AL in plasma cell dyscrasia.
- Calcification: dystrophic in damaged tissue with normal serum calcium; metastatic with hypercalcemia.
Worked example
A patient dies 72 hours after a left MCA occlusion. At autopsy the infarcted territory is softened and cystic rather than firm and pale. Reasoning: the brain has high lipid and lysosomal enzyme content and little keratin intermediate filament support, so the dominant pattern is liquefactive necrosis; an identical event in kidney or heart would give coagulative necrosis with preserved tissue architecture. This single distinction is asked repeatedly.
Traps
Calling apoptosis necrosis on H&E (apoptosis shows shrinkage, chromatin condensation, apoptotic bodies and no inflammation). Labeling p53 an oncogene. Forgetting that caseous necrosis is a variant of coagulative necrosis with amorphous granular debris.