Pathology and Pathophysiology
Cell injury and adaptation
Reversible injury shows swelling and fatty change; irreversible injury shows membrane rupture, mitochondrial failure and nuclear dissolution. Necrosis patterns must be recognised: coagulative (ischaemia, except brain), liquefactive (brain, abscess), caseous (tuberculosis), fat (pancreatitis) and fibrinoid (vasculitis). Apoptosis is energy-dependent, non-inflammatory and caspase-mediated.
Inflammation and repair
Acute inflammation is neutrophil-predominant with vasodilatation and increased permeability mediated by histamine, bradykinin, prostaglandins, leukotrienes, complement and cytokines. Chronic inflammation is macrophage and lymphocyte rich; granulomas occur with tuberculosis, sarcoidosis, Crohn's disease and foreign material. Healing by first intention gives a fine scar; second intention heals by granulation and contraction. Keloid extends beyond the original wound and recurs; hypertrophic scar stays within it and regresses.
Neoplasia
Dysplasia is disordered growth confined by the basement membrane; carcinoma in situ breaches neither basement membrane nor stroma. Invasion and metastasis define malignancy. Key tumour suppressors include p53, RB, APC and BRCA; oncogenes include RAS and MYC. Grading describes differentiation, staging describes anatomical spread - stage predicts prognosis far better. Tumour markers (CEA, CA 19-9, AFP, hCG) are for monitoring, not screening.
Worked example: a sigmoid colon tumour invading through the muscularis propria into subserosa with one positive node is T3 N1 M0, stage III - an indication for adjuvant chemotherapy, whereas a T1 N0 lesion is stage I and managed by surgery alone.
Trap: metaplasia is a reversible substitution of one mature epithelium for another and is not premalignant in itself; dysplasia is the true precursor lesion.