General Pathology

Faced with a sustained stimulus, a cell will "change its size, its number, or its form" in order to survive. At first glance the questions seem to test a lookup table matching atrophy, hypertrophy, hyperplasia, and metaplasia to examples; the real key is to think through what the stimulus is, whether the cell is capable of dividing, and whether it ends up changing its dimensions or its identity. Once you grasp this logic, the table grows in your mind by itself.

Hypertrophy is the exact opposite: when a cell's capacity to divide is limited (cardiac muscle, skeletal muscle) yet it is loaded with extra work for a long time, it cannot "make more of itself" and can only "bulk itself up" — this is hypertrophy, driven by increased protein synthesis. Cells that can divide, when stimulated by growth factors or hormones, undergo "hyperplasia" — an increase in number, as in endometrial hyperplasia or prostatic enlargement (BPH is in fact hyperplasia, not true hypertrophy). Put simply: cells that cannot divide enlarge themselves (hypertrophy); cells that can divide make more of themselves (hyperplasia).

Metaplasia has one criterion that is easily switched under your nose: the two cell types must be different. In recurrent bladder infection, urothelium sloughs and urothelium grows back; that is regeneration and hyperplasia, not metaplasia — replacement by the same cell type does not count. Examiners love this as a trap: the stem reads like metaplasia while the cell types are quietly tampered with. One sentence breaks it: "switching to a different epithelium" is metaplasia; "restoring the same one" is merely regeneration.

In questions on intracellular accumulations, the cardinal sin is "see foam, recite cholesterol." What you must remember is why the material is stored here: when hepatocytes are overloaded with fatty acids (alcohol, obesity, hypoxia), triglyceride (TG) is packaged into the cytoplasm as large vacuoles — this is steatosis; when macrophages in the arterial intima engulf oxidized LDL, their cytoplasm fills with cholesterol crystals and looks foamy — these are foam cells, the hallmark of atheromatous plaque and xanthoma; the yellow-brown lipofuscin in long-lived organs (heart, liver, adrenal) is a pigment accumulated over years of cellular metabolism, a badge of aging and wear-and-tear; and hemosiderin is the golden-brown pigment left after red cells are phagocytosed and metabolized following hemorrhage, positive on Prussian blue stain, seen after bleeding and in hemochromatosis.

The contrast between apoptosis and necrosis is another line of easy marks. Apoptosis is programmed suicide (programmed cell death): active, energy-consuming, a single cell quietly dismantling itself, membrane intact, no inflammation, ending as apoptotic bodies that are engulfed; necrosis is being struck dead by accident: passive, the cell swells and bursts, enzymes leak, inflammation floods in. The two initiating pathways of apoptosis are also tested, and behind them lies a complete enzymatic cascade: the intrinsic pathway runs through the mitochondrion — Bcl-2 is inhibited, cytochrome c is released, caspase-9 is activated; the extrinsic pathway runs through death receptors — Fas/TNFR binding activates caspase-8. Both converge on caspase-3, which carries out the final cleavage and yields DNA laddering (fragments in multiples of 180 bp) — utterly unlike necrosis, where DNA is chopped into random sizes; this is the discriminating detail in high-resolution questions. Collect the three major patterns of necrosis while you are here: coagulative (ischemia of heart and kidney), liquefactive (brain, suppuration), caseous (TB).

A tissue's capacity to regenerate is decided by the proliferative class of its cells. Labile cells — epidermis, intestinal mucosa, bone marrow — divide continuously and are replaced quickly after injury. Stable cells — hepatocytes, renal tubular cells, fibroblasts — are quiescent at rest yet can divide when needed; among them the hepatocyte is ranked as having the strongest regenerative capacity, which is why the liver refills rapidly after partial hepatectomy and why living-donor liver transplantation is feasible at all. Permanent cells — neurons and cardiac muscle — have almost no capacity to divide, and after injury their function can only be patched with scar; this explains why a myocardial infarction leaves fibrous scar rather than new myocardium, and why nerve injury so often fails to recover completely. Skeletal muscle requires a distinction: mature myofibers do not divide, but satellite cells can activate, proliferate and participate in regeneration. Skeletal muscle tissue is therefore not wholly incapable of repair.