13.4 Diseases of the Organ Systems
Key Takeaways
- Myocardial rupture through coagulative necrosis peaks at 3–7 days when macrophages clear debris and granulation is still weak; arrhythmias dominate the first day, Dressler pericarditis comes weeks later.
- Crohn disease is transmural, discontinuous, granulomatous, and ileum-loving; ulcerative colitis is continuous mucosal colitis with crypt abscesses starting at the rectum.
- Squamous-cell lung carcinoma is central, cavitating, and PTHrP-hypercalcemic; small-cell carcinoma is central, neuroendocrine, and ACTH/ADH/Lambert-Eaton-associated; adenocarcinoma is the peripheral, nonsmoker-capable EGFR/ALK tumor.
- Nephritic syndrome is hematuria, RBC casts, and hypertension; nephrotic syndrome is >3.5 g/day proteinuria, hypoalbuminemia, edema, and hyperlipidemia. Adult PKD is AD PKD1 with berry aneurysms.
- CML is t(9;22) BCR-ABL; APL is t(15;17) PML-RARA with Auer rods and DIC; follicular lymphoma is t(14;18) BCL2; Reed-Sternberg cells of classical Hodgkin lymphoma are CD15/CD30-positive.
Why organ-system disease is a scored Pathology topic
Quick Answer: Time the MI complication. Separate Crohn from UC by wall depth and skip lesions. Match lung-cancer histology to location and paraneoplastic syndrome. Nephritic versus nephrotic is the renal fork. Thyroid carcinoma is a nuclear-feature and spread-route table. Leukemias and lymphomas are translocations and CD markers.
Cardiovascular
Atherosclerosis is an intimal disease of large and medium arteries. Endothelial injury lets oxidized LDL recruit monocytes that become foam cells (fatty streak). Smooth-muscle cells migrate, lay collagen, and build a fibrous cap over a necrotic lipid core. Complicated plaques rupture, thrombose, calcify, or weaken the media (aneurysm). Ranked sites: abdominal aorta, coronary, popliteal, internal carotid, circle of Willis. Risk factors: age, male sex, family history, hyperlipidemia, hypertension, smoking, diabetes.
Myocardial infarction is coagulative necrosis after coronary thrombosis on a ruptured plaque. The left anterior descending is the most common artery. Transmural infarcts are STEMI; subendocardium is the watershed of the coronary tree (NSTEMI or global hypoperfusion).
| Time | Histology | Complication |
|---|---|---|
| 0–4 h | None by light microscopy (contraction bands if reperfused) | Arrhythmia, cardiogenic shock, CHF |
| 4–12 h | Early hypereosinophilia, pyknosis | Arrhythmia |
| 1–3 days | Neutrophils | Arrhythmia; fibrinous pericarditis if transmural |
| 3–7 days | Macrophages remove debris; wall is weakest | Free-wall rupture (tamponade), papillary-muscle rupture (mitral regurgitation), septal rupture (VSD) |
| 1–2 weeks | Granulation tissue | Still mechanically fragile early in this window |
| Weeks–months | Scar | Ventricular aneurysm, mural thrombus, Dressler autoimmune pericarditis (weeks) |
Hypertension writes two arteriolar scripts: hyaline arteriolosclerosis (benign, diabetes too) and hyperplastic onion-skin plus fibrinoid (malignant). The left ventricle hypertrophies concentrically (pressure overload).
Rheumatic heart disease follows group A streptococcal pharyngitis (not a sterile skin infection as often) by molecular mimicry (M protein vs cardiac myosin). Aschoff bodies contain Anitschkow (caterpillar) cells. The chronic valve is mitral stenosis (fish-mouth) more than aortic. Infective endocarditis: acute S. aureus destroys previously normal valves; subacute Streptococcus viridans seeds damaged valves; IV drug use seeds tricuspid S. aureus. Janeway (painless), Osler (painful), Roth spots, and splinter hemorrhages are embolic/immune. Libman-Sacks vegetations of SLE are sterile and can sit on both valve surfaces.
Aneurysms: infrarenal AAA is atherosclerotic; berry is circle of Willis; syphilitic is ascending aorta (tree-bark intima, vaso vasorum endarteritis); Marfan cystic medial degeneration of the ascending aorta. Cardiomyopathies: dilated (alcohol, coxsackie, doxorubicin, peripartum, hemochromatosis, wet beriberi, pregnancy); hypertrophic (sarcomere mutations, myofiber disarray, sudden death in a young athlete, SAM of the mitral leaflet); restrictive (amyloid, sarcoid, Loeffler).
Gastrointestinal
Esophagus: mid-esophageal squamous carcinoma (smoke, alcohol, lye); distal adenocarcinoma on Barrett intestinal metaplasia. Mallory-Weiss is a mucosal tear; varices are portal hypertension; Boerhaave is transmural rupture.
Stomach: H. pylori intestinal-type adenocarcinoma and MALT lymphoma; diffuse signet-ring carcinoma (loss of E-cadherin, linitis plastica) is not the intestinal-metaplasia pathway. Duodenal ulcers are more common than gastric, H. pylori or NSAID, anterior perforation, posterior bleeding from the gastroduodenal artery.
| Feature | Crohn disease | Ulcerative colitis |
|---|---|---|
| Extent | Mouth to anus, terminal ileum favorite | Colon, always rectum, continuous |
| Depth | Transmural | Mucosa and submucosa |
| Pattern | Skip lesions, cobblestone, creeping fat, fistulas, strictures | Pseudopolyps, lead-pipe colon |
| Histology | Noncaseating granulomas (when present), lymphoid aggregates | Crypt abscesses, no granulomas |
| Cancer / extras | Fistula, B12/bile-salt loss, oxalate stones | Toxic megacolon, PSC, higher textbook CRC risk |
Celiac disease: HLA-DQ2/DQ8, gliadin, villous atrophy, crypt hyperplasia, intraepithelial lymphocytes, IgA anti-tTG; dermatitis herpetiformis; T-cell lymphoma and adenocarcinoma risk if untreated.
Cirrhosis is bridging fibrosis plus regenerative nodules. Portal hypertension: ascites, esophageal varices, caput medusae, splenomegaly. HCC risk: HBV (can insert without full cirrhosis), HCV, alcohol, aflatoxin, hemochromatosis, α1-AT. Acute pancreatitis (alcohol or gallstone) autodigests: fat necrosis, hypocalcemia, ARDS, gray-blue flanks. Chronic pancreatitis: chain-of-lakes ducts, fat-soluble vitamin deficiency, diabetes. Pancreatic adenocarcinoma of the head: painless jaundice, CA19-9, Trousseau migratory thrombophlebitis, smoking.
Colon carcinoma: adenoma–carcinoma via APC then KRAS then p53. FAP (APC) carpets the colon; Lynch/HNPCC is mismatch repair (MSH2, MLH1), right-sided, endometrial. Left-sided tumors obstruct (napkin-ring); right-sided bleed occult iron-deficiency anemia.
Respiratory
Obstructive versus restrictive mechanics are physiology; the lesions are pathology.
Emphysema is enlarged airspaces from alveolar-wall destruction. Centriacinar (respiratory bronchiole, upper lobe) is smoking. Panacinar (lower lobe) is α1-antitrypsin deficiency (PAS-positive globules in liver, cirrhosis). Protease–antiprotease imbalance is the shared idea. Chronic bronchitis is a clinical diagnosis (productive cough 3 months in 2 consecutive years); the gland metric is Reid index >0.4. Asthma is reversible obstruction: type I hypersensitivity, mucus plugs, Curschmann spirals, Charcot-Leyden crystals (eosinophil lysophospholipase), smooth-muscle hypertrophy.
Restrictive interstitial: IPF/UIP honeycomb, subpleural lower lobes; sarcoidosis noncaseating granulomas, asteroid and Schaumann bodies, bilateral hilar nodes, high ACE, macrophage 1-α-hydroxylase → hypercalcemia. Pneumoconioses were catalogued in environmental disease.
Pneumonia: lobar (S. pneumoniae) four stages (congestion, red then gray hepatization, resolution); bronchopneumonia patchy (Staph, Klebsiella currant-jelly in alcoholics, Pseudomonas in CF). TB: Ghon focus plus hilar node = Ghon complex; Ranke = calcified healed complex; secondary disease is apical cavitary; miliary is hematogenous millet seeds.
| Lung carcinoma | Location | Paraneoplastic / hook |
|---|---|---|
| Squamous | Central, cavitates | PTHrP hypercalcemia; keratin pearls; smoking |
| Small cell | Central, neuroendocrine | ACTH, ADH (SIADH), Lambert-Eaton (presynaptic Ca2+ channel); inoperable; smoking |
| Adenocarcinoma | Peripheral | Most common; nonsmokers, women; EGFR, ALK, KRAS; hypertrophic osteoarthropathy |
| Large cell | Peripheral | Undifferentiated, poor prognosis |
| Bronchial carcinoid | Central polypoid | Excellent; can bleed or obstruct |
Pancoast (superior sulcus) tumors, often squamous or adeno, add Horner syndrome and brachial plexopathy—anatomy meeting pathology.
Genitourinary
Nephritic syndrome: hematuria, RBC casts, oliguria, hypertension, mild proteinuria. Nephrotic syndrome: >3.5 g/day protein, hypoalbuminemia, edema, hyperlipidemia, lipiduria, thrombosis (lost antithrombin), infection (lost immunoglobulin).
| Pattern | Mechanism / IF | Notes |
|---|---|---|
| Post-strep GN | Subepithelial humps, granular IgG/C3, low C3 | Nephritic, children, after pharyngitis or skin |
| RPGN (crescents) | Linear anti-GBM (Goodpasture), granular immune-complex, or pauci-immune ANCA | Rapid renal failure |
| Minimal-change | Foot-process effacement, IF-negative | Kids, nephrotic, steroids, NSAIDs/Hodgkin in adults |
| FSGS | Segmental sclerosis | HIV, heroin, APOL1; nephrotic |
| Membranous | Spike-and-dome, PLA2R | Nephrotic adult; HBV, solid cancers, NSAIDs, SLE |
| Diabetic | GBM thickening, mesangial expansion, Kimmelstiel-Wilson nodules | Both afferent and efferent hyaline arteriolosclerosis |
Adult polycystic kidney disease is AD PKD1 (chromosome 16): huge kidneys, berry aneurysms, hepatic cysts, MVP. Infantile PKD is AR, collecting-duct cysts, congenital hepatic fibrosis. RCC is clear-cell, VHL / chromosome 3p, hematuria-flank-mass, EPO/PTHrP/ACTH, invades renal vein and IVC. Wilms tumor is a childhood blastema tumor (WT1, 11p13; WAGR). Urothelial carcinoma of bladder: smoking, aniline dyes, cyclophosphamide, phenacetin; Schistosoma haematobium drives squamous bladder cancer. Prostate adenocarcinoma arises in the posterior peripheral zone (Gleason grade), osteoblastic vertebral mets, PSA; BPH is periurethral transitional zone (urinary obstruction, not cancer).
Cervix: HPV 16/18 E6 degrades p53, E7 inactivates RB, transformation-zone squamous (or adeno) carcinoma. Endometrium: type I endometrioid (unopposed estrogen, PTEN); type II serous (elderly, p53, aggressive). Ovary: epithelial serous carcinoma is the common malignant type (CA-125, peritoneal seeding, BRCA).
Endocrine
Pituitary: lactotroph adenoma is most common (dopamine normally inhibits prolactin); macroadenomas compress the optic chiasm (bitemporal hemianopsia). Sheehan is ischemic necrosis after postpartum hemorrhage.
| Thyroid carcinoma | Nuclei / spread | Genetics / setting |
|---|---|---|
| Papillary | Orphan Annie empty nuclei, grooves, inclusions, psammoma | Lymphatic; radiation; RET/PTC, BRAF; best prognosis |
| Follicular | Capsule/vascular invasion needed | Hematogenous (bone, lung); RAS, PAX8-PPAR-γ |
| Medullary | Amyloid from calcitonin, C cells | RET, MEN2A/2B |
| Anaplastic | Undifferentiated | Elderly, rock-hard, lethal |
Graves: TSH-receptor stimulating antibody, diffuse uptake, pretibial myxedema, ophthalmopathy. Hashimoto: Hurthle cells, germinal centers, hypothyroidism, later B-cell lymphoma risk.
Adrenal: Cushing can be pituitary ACTH, adrenal adenoma/carcinoma, ectopic ACTH (small-cell lung), or exogenous steroid (bilateral cortical atrophy). Conn (aldosterone adenoma): hypertension and hypokalemia. Addison: autoimmune or TB; Waterhouse-Friderichsen is meningococcal adrenal hemorrhage. Pheochromocytoma is chromaffin, episodic HTN, metanephrines; rule of 10s is outdated but MEN2, VHL, and NF1 still matter.
Diabetes mellitus: type 1 is autoimmune insulitis (HLA-DR3/DR4), DKA; type 2 is insulin resistance plus amylin amyloid in islets, HHS. Complications run through nonenzymatic glycosylation (HbA1c, basement membranes) and aldose-reductase sorbitol (lens, Schwann, retina). Kimmelstiel-Wilson is the renal nodule.
MEN1 (menin): 3 Ps—pituitary, parathyroid, pancreas (gastrinoma/insulinoma). MEN2A (RET): medullary thyroid, pheo, parathyroid. MEN2B (RET): medullary thyroid, pheo, mucosal neuromas, marfanoid habitus, not hyperparathyroidism. Hyperparathyroidism itself: stones, bones (osteitis fibrosa cystica), groans, psychiatric overtones, high Ca and PTH, low phosphate.
Blood and lymphatics
Anemia first by MCV, then by mechanism.
| Microcytic | Lab / smear |
|---|---|
| Iron deficiency | Low ferritin, high TIBC, high RDW; blood loss until proven otherwise |
| Anemia of chronic disease | High ferritin, low TIBC, hepcidin |
| Thalassemia | High RBC count, target cells, normal/high ferritin |
| Sideroblastic | Ringed sideroblasts; lead or B6 or MDS |
B12 versus folate: both megaloblastic with hypersegmented neutrophils. B12 adds subacute combined degeneration and ↑ methylmalonic acid. Folate is diet/pregnancy/MTX, no SCD, MMA normal. Sickle cell: β-globin Glu6Val, deoxygenated polymers, Howell-Jolly bodies after autosplenectomy, Salmonella osteomyelitis, parvovirus aplastic crisis, acute chest. G6PD: X-linked, Heinz bodies, bite cells after oxidant stress. Hereditary spherocytosis: ankyrin/spectrin, splenomegaly, aplastic crisis.
| Neoplasm | Genetics / marker | Hook |
|---|---|---|
| APL (AML M3) | t(15;17) PML-RARA, Auer rods | DIC; ATRA differentiates |
| CML | t(9;22) BCR-ABL | Low LAP versus leukemoid; imatinib target |
| CLL | CD5+ CD23+ B cells | Smudge cells, older adult, autoimmune hemolysis |
| ALL | TdT+ lymphoblasts | Children; T-ALL mediastinal mass |
| Follicular lymphoma | t(14;18) IgH-BCL2 | Indolent; may transform to DLBCL |
| Burkitt | t(8;14) MYC | Starry-sky; endemic jaw/EBV vs sporadic abdomen |
| Classical Hodgkin | Reed-Sternberg CD15+ CD30+ CD20− | Nodular sclerosis: young woman, lacunar cells, good prognosis |
| Myeloma | Plasma-cell clone | CRAB, rouleaux, Bence Jones, punched-out skull, AL amyloid |
DIC consumes factors and platelets: ↑ PT, ↑ PTT, ↑ D-dimer, ↓ fibrinogen, schistocytes (sepsis, obstetric disaster, APL, snake). TTP is ADAMTS13 failure (huge vWF multimers): MAHA, thrombocytopenia, neurologic signs. HUS is Shiga toxin (EHEC) in children, more renal. ITP is anti-GpIIb/IIIa, kids post-viral (acute) or adult women (chronic).
Those six official organ groups—cardiovascular, GI, respiratory, genitourinary, endocrine, blood and lymphatics—are the entire 13.4 map. If a stem gives a translocation, a crystal, a paraneoplastic hormone, or a 3-to-7-day post-MI collapse, you are in this section. Cellular injury language still comes from /study-guides/nbce-part1/pathology-mechanisms/fundamentals-pathology; the organ is just where the mechanism landed.
A 58-year-old man is stable in hospital on day 5 after an anterior STEMI, then suddenly loses consciousness with pulseless electrical activity. Pericardial blood is found at autopsy and the anterior wall has a through-and-through tear. Why did rupture occur at this interval?
A central, smoking-associated lung mass is composed of small neuroendocrine cells. The patient has hyponatremia from inappropriate ADH and proximal-muscle weakness that improves with use, consistent with Lambert-Eaton syndrome. Which carcinoma is this?
A 34-year-old woman has a thyroid nodule. Histology shows branching papillae, nuclei with pale empty chromatin and grooves, and laminated calcifications. Lymph nodes in the central neck contain the same tumor. Which carcinoma and spread route are illustrated?