USMLE Pathology Syllabus

Pathology syllabus — full chapter and topic list

Expand any chapter to see its topics and sub-topics. This is the whole examinable outline for Pathology in USMLE, not a summary of it.

1. 1

   General Pathology

   3 topics

   • Cell injury and death
   • Inflammation
   • Tissue repair
2. 2

   Systemic Pathology

   3 topics

   • Cardiovascular pathology
   • Pulmonary pathology
   • Renal pathology
3. 3

   Neuropathology

   3 topics

   • Cerebrovascular diseases
   • Demyelinating diseases
   • Degenerative diseases

Pathology flashcards for USMLE

24 of 50 cards from the Pathology deck — real questions with worked answers.

1. What is the earliest ultrastructural sign of reversible cell injury, and what causes it?

   Cellular swelling (hydropic change) from failure of the ATP-dependent $\ce{Na+/K+}$ pump, causing $\ce{Na+}$ and water influx. Other reversible changes: mitochondrial swelling, ribosomal detachment from the ER, and membrane blebbing.

2. List the hallmarks that distinguish irreversible cell injury from reversible injury.

   Irreversible injury is marked by severe mitochondrial dysfunction (amorphous densities), profound membrane damage, and lysosomal rupture. Nuclear changes are definitive: pyknosis (condensation), karyorrhexis (fragmentation), and karyolysis (dissolution).

3. Compare necrosis and apoptosis across ATP requirement, membrane integrity, and inflammation.

   Necrosis: passive, no ATP required, membrane ruptures, contents leak causing inflammation, affects groups of cells. Apoptosis: active/programmed, ATP-dependent, membrane intact (apoptotic bodies), no inflammation, affects single cells.

4. Match each necrosis morphologic pattern to its classic setting: coagulative, liquefactive, caseous, fat, fibrinoid, gangrenous.

   Coagulative = ischemia in most solid organs (except brain). Liquefactive = brain infarct / abscess. Caseous = TB and fungal granulomas. Fat = acute pancreatitis / breast trauma. Fibrinoid = immune vascular damage (vasculitis, malignant HTN). Gangrenous = limb ischemia (dry = coagulative, wet = superimposed infection).

5. What are the two intrinsic (mitochondrial) apoptosis regulators and their opposing roles?

   Pro-apoptotic BAX and BAK oligomerize to permeabilize the outer mitochondrial membrane, releasing cytochrome c to activate caspase-9. Anti-apoptotic BCL-2 and BCL-xL inhibit this. BCL-2 overexpression (t(14;18)) blocks apoptosis in follicular lymphoma.

6. Which caspases are the initiator versus executioner caspases in apoptosis?

   Initiator caspases: caspase-8 (extrinsic/death-receptor pathway, Fas-FasL, TNF) and caspase-9 (intrinsic/mitochondrial pathway). Executioner caspases: caspase-3 and caspase-6, which cleave the cytoskeleton and activate endonucleases.

7. By what mechanism does free-radical injury damage cells, and which enzymes/molecules neutralize reactive oxygen species?

   ROS cause lipid peroxidation of membranes, protein cross-linking, and DNA fragmentation. Antioxidant defenses: superoxide dismutase ($\ce{O2^{.-} -> H2O2}$), catalase and glutathione peroxidase ($\ce{H2O2 -> H2O}$), plus vitamins A, C, E and glutathione.

8. Define dystrophic versus metastatic calcification.

   Dystrophic: calcium deposits in damaged/necrotic tissue despite normal serum calcium (e.g., atherosclerotic plaques, caseous foci). Metastatic: deposits in normal tissue due to hypercalcemia (e.g., hyperparathyroidism, malignancy, sarcoidosis).

9. Name the five cardinal signs of acute inflammation and their Latin terms.

   Rubor (redness), calor (heat), tumor (swelling), dolor (pain), and functio laesa (loss of function).

10. What are the sequential steps of leukocyte extravasation in acute inflammation?

    1) Margination and rolling (selectins: E-, P-selectin on endothelium, sialyl-Lewis X on leukocytes); 2) Firm adhesion (integrins LFA-1/Mac-1 binding ICAM-1); 3) Transmigration/diapedesis (PECAM-1/CD31); 4) Chemotaxis toward C5a, LTB4, IL-8, and bacterial products.

11. Which vasoactive mediators cause the vascular changes of acute inflammation (vasodilation and increased permeability)?

    Vasodilation: histamine, prostaglandins ($\ce{PGI2}$, $\ce{PGD2}$, $\ce{PGE2}$), and nitric oxide. Increased permeability: histamine, serotonin, bradykinin, leukotrienes ($\ce{C4}$, $\ce{D4}$, $\ce{E4}$), and C3a/C5a.

12. Distinguish the cyclooxygenase and lipoxygenase branches of arachidonic acid metabolism and where NSAIDs and steroids act.

    COX pathway produces prostaglandins and thromboxane; lipoxygenase pathway produces leukotrienes. NSAIDs inhibit COX. Corticosteroids inhibit phospholipase $\ce{A2}$ (blocking arachidonic acid release), suppressing both pathways. Zileuton inhibits lipoxygenase; montelukast blocks $\ce{LTD4}$ receptors.

13. What functions do the anaphylatoxins C3a and C5a, and the opsonin C3b, serve in the complement system?

    C3a and C5a are anaphylatoxins triggering mast-cell histamine release; C5a is also a potent neutrophil chemotactic factor. C3b is the major opsonin promoting phagocytosis. C5b-9 forms the membrane attack complex (MAC).

14. Which cytokines mediate the acute-phase response and induce fever?

    IL-1, IL-6, and TNF are the key endogenous pyrogens; they act on the hypothalamus (raising $\ce{PGE2}$) and drive hepatic acute-phase reactants (CRP, fibrinogen, hepcidin, serum amyloid A). IL-6 chiefly drives CRP synthesis.

15. What defines a granuloma histologically, and what cytokines drive its formation?

    A granuloma is a focal collection of activated epithelioid macrophages, often with multinucleated giant cells and a rim of lymphocytes. Th1 cells secrete IFN-$\gamma$ (activating macrophages) and TNF (maintaining the granuloma). Caseating granulomas suggest TB/fungi; non-caseating suggest sarcoidosis.

16. Contrast labile, stable, and permanent cell populations with examples relevant to tissue repair.

    Labile (continuously dividing): skin epithelium, gut mucosa, bone marrow. Stable (quiescent, $\ce{G0}$, can re-enter cycle): hepatocytes, renal tubular cells, fibroblasts. Permanent (non-dividing): neurons, cardiac myocytes, skeletal muscle — these heal by scar.

17. What is granulation tissue composed of, and which growth factors drive angiogenesis and fibrosis in wound healing?

    Granulation tissue = new capillaries, proliferating fibroblasts, and loose ECM. VEGF and FGF-2 drive angiogenesis; PDGF, TGF-$\beta$, and FGF drive fibroblast proliferation and collagen deposition. TGF-$\beta$ is the most important fibrogenic agent.

18. Compare healing by primary versus secondary intention.

    Primary intention: clean, apposed wound edges (surgical incision), minimal tissue loss, small scar, fast. Secondary intention: large tissue defect with wide gap, healing by abundant granulation tissue, more prominent wound contraction (via myofibroblasts) and larger scar.

19. Which collagen type predominates early versus late in scar maturation, and what enzymes remodel it?

    Type III collagen predominates in early granulation tissue/scar; it is gradually replaced by stronger type I collagen during maturation. Zinc-dependent matrix metalloproteinases (MMPs) degrade collagen for remodeling; TIMPs inhibit them. Wounds regain only ~70–80% of original tensile strength.

20. Distinguish a hypertrophic scar from a keloid.

    Hypertrophic scar: excess collagen confined within the original wound borders; may regress. Keloid: collagen (predominantly type III then I) extending beyond the wound margins, does not regress, has a genetic predisposition (more common in darker skin), and frequently recurs after excision.

21. What is the fatty-streak-to-plaque sequence in atherosclerosis, and what are the components of a mature plaque?

    Endothelial injury → LDL entry and oxidation → macrophage uptake forming foam cells → fatty streak → smooth-muscle migration/proliferation and ECM deposition. A mature atheroma has a fibrous cap (smooth muscle + collagen) over a necrotic lipid core with cholesterol clefts and foam cells.

22. List the major modifiable and non-modifiable risk factors for atherosclerosis.

    Non-modifiable: age, male sex, family history, genetics. Modifiable: hyperlipidemia (high LDL, low HDL), hypertension, diabetes mellitus, and smoking. Smoking and diabetes are especially strong. Homocysteinemia is an additional risk factor.

23. Give the timeline of gross and microscopic changes after a myocardial infarction from 0–24 h through weeks.

    0–24 h: wavy fibers, coagulative necrosis begins, contraction bands. 1–3 days: neutrophil infiltrate (risk of fibrinous pericarditis). 3–7 days: macrophages remove debris (weakest wall — free-wall/septal rupture risk). 1–3 weeks: granulation tissue, neovascularization. >1 month: dense collagenous scar.

24. Which cardiac biomarkers are used to diagnose MI and what is the timing of troponin?

    Cardiac troponins I and T are most sensitive/specific: rise at 2–4 h, peak ~24–48 h, stay elevated 7–10 days. CK-MB rises at 2–4 h, peaks ~24 h, normalizes in 48–72 h — useful for detecting reinfarction because it returns to baseline sooner.

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