Pathology, epidemiology, and biostatistics
**Pathology basics:** • **Reversible cell injury** — cellular swelling, ribosomal detachment, lipid accumulation. • **Irreversible** — membrane damage, Ca²⁺ influx, mitochondrial permeability transition, nuclear changes (pyknosis → karyorrhexis → karyolysis). • Necrosis types: coagulative (ischemic except brain), liquefactive (brain, abscess), caseous (TB, fungi), fat (pancreatitis), fibrinoid (vessel walls, immune-mediated), gangrenous (limb). • Apoptosis — caspase-mediated; intrinsic (mitochondrial, Bcl-2 family) vs. extrinsic (Fas/TNF death receptor).
**Inflammation:** acute (neutrophil, TNF/IL-1/IL-6/IL-8, CRP) vs. chronic (macrophage/lymphocyte/plasma; granulomatous diseases — TB, sarcoid, Crohn, leprosy).
**Epidemiology test performance:** • **Sensitivity** = TP/(TP+FN) — rules OUT disease (SnNOUT). • **Specificity** = TN/(TN+FP) — rules IN (SpPIN). • **PPV** = TP/(TP+FP); **NPV** = TN/(TN+FN). PPV/NPV depend on prevalence. • **LR+** = sens/(1−spec); **LR−** = (1−sens)/spec.
**Study designs:** • **Case-control** (retrospective, rare disease) — OR. • **Cohort** (prospective) — RR, incidence. • **Cross-sectional** — prevalence, no causality. • **RCT** — gold standard causality; blinding reduces bias. • **Meta-analysis** — pools RCTs; I² heterogeneity.
**Biostatistics:** • Type I error (α, false positive) vs. Type II (β, false negative). Power = 1−β (typically ≥0.8). • p <0.05 conventional; confidence intervals more informative. If 95% CI for RR/OR crosses 1.0 → NSD. • NNT = 1 / ARR; NNH = 1 / ARI. • Biases: selection, measurement (recall, observer), confounding (control via matching/RCT/regression), effect modification, length-time, lead-time.
**Public health reporting:** CDC NNDSS — nationally notifiable conditions reported via state health departments; MMWR publishes weekly summaries.