Pathology: injury, inflammation, neoplasia, and hemodynamics
Pathology tests the mechanisms linking injury to gross and microscopic change. PLE items ask for the dominant process, the reversible versus irreversible threshold, and the complication that follows.
Core rules
- Cell injury: ATP depletion, mitochondrial permeability, calcium influx, reactive oxygen species, and membrane damage drive necrosis. Reversible injury shows swelling; irreversible injury shows membrane rupture and mitochondrial failure.
- Inflammation: acute inflammation features neutrophils; chronic inflammation features macrophages and lymphocytes. Granulomas occur in tuberculosis, sarcoidosis, and foreign-body reactions.
- Neoplasia: metaplasia is a change in cell type, not malignancy; dysplasia shows disordered growth; carcinoma in situ keeps the basement membrane intact; invasion defines malignancy. Tumor markers support monitoring but are not diagnostic alone.
- Hemodynamics: Virchow triad is stasis, endothelial injury, and hypercoagulability. Transudates have low protein; exudates have high protein and cells.
Worked example
A 60-year-old smoker presents with weight loss, cough, and hypercalcemia. Imaging shows a central lung mass, and biopsy shows squamous cell carcinoma with keratin pearls and intercellular bridges. The hypercalcemia is best explained by tumor production of PTHrP, a paraneoplastic effect, rather than by bone metastases alone. Reasoning: PTH is suppressed by hypercalcemia, while PTHrP drives calcium release and renal calcium retention; histology confirms squamous differentiation.
Traps
Do not call metaplasia malignant; it is an adaptive change that can precede dysplasia. Do not attribute every hypercalcemia in cancer to bone metastases. Do not confuse transudate and exudate criteria. Do not label a tumor benign solely because it is slow-growing.