14.2 Esophagus, Stomach & Intestinal Pathology
Key Takeaways
- GERD can lead to Barrett esophagus (intestinal metaplasia) and risk of esophageal adenocarcinoma (distal); squamous cell carcinoma associates with smoking/alcohol and is more proximal/mid-esophagus worldwide.
- Achalasia: loss of myenteric inhibitory neurons → absent peristalsis and failure of LES relaxation (bird-beak on barium); Chagas can mimic. Varices = portal hypertension portosystemic collaterals with life-threatening bleed risk.
- H. pylori causes antral-predominant or pangastritis, peptic ulcers, MALT lymphoma, and intestinal-type gastric adenocarcinoma risk; autoimmune gastritis targets parietal cells (body/fundus), causes achlorhydria, G-cell hyperplasia, and B12 deficiency.
- Celiac disease: HLA-DQ2/DQ8, gluten → villous atrophy, crypt hyperplasia, IEL increase, proximal malabsorption; Crohn is transmural, skip lesions, any GI site, fistulas/granulomas; UC is continuous mucosal colitis from rectum with toxic megacolon and PSC links.
- Know complications: ulcer bleed/perforation/obstruction/penetration; diverticulitis vs diverticulosis; ischemic colitis at watersheds (splenic flexure, rectosigmoid); Hirschsprung distal aganglionosis; ZE gastrinoma, carcinoid syndrome, VIPoma patterns.
14.2 Esophagus, Stomach & Intestinal Pathology
Quick Answer: Barrett (intestinal metaplasia) → distal adenocarcinoma; smoking/alcohol → squamous ca. Achalasia = inhibitory neuron loss at LES. H. pylori vs autoimmune gastritis differ by site and B12/ulcer patterns. Celiac needs HLA-DQ2/8 and villous atrophy. Crohn = skip/transmural; UC = continuous rectum-up. Add varices, ulcers, diverticula, watershed ischemia, Hirschsprung, and neuroendocrine hypersecretion syndromes.
Pathology items reward pattern recognition: location, depth of injury, metaplasia type, and complication. Walk the tube from esophagus to colon with high-yield disease mechanisms.
Esophagus: Reflux, Metaplasia, Cancer, Motility, Varices
GERD reflects LES incompetence, transient relaxations, hiatal hernia, delayed clearance, or increased abdominal pressure. Chronic acid/pepsin (and bile) injury causes erosive esophagitis, strictures, and Barrett esophagus—replacement of stratified squamous epithelium by columnar epithelium with intestinal metaplasia (goblet cells) in the distal esophagus. Barrett is the major precursor of esophageal adenocarcinoma, which arises in the distal esophagus/GE junction and is linked to GERD, obesity, and Barrett. Esophageal squamous cell carcinoma is more common globally in mid-esophagus, associated with smoking, alcohol, hot beverages, caustic injury, achalasia stasis, and certain regions/diets; it is not primarily a Barrett pathway.
Achalasia is degenerative loss of inhibitory (NO/VIP) neurons in the myenteric plexus of the distal esophagus/LES → incomplete LES relaxation, absent peristalsis, progressive dysphagia to solids and liquids, regurgitation, bird-beak barium taper, high LES residual pressure on manometry. Trypanosoma cruzi (Chagas) destroys myenteric neurons and can produce achalasia-like megaesophagus. Contrast mechanical obstruction (progressive solids then liquids, older patients, weight loss—think cancer) versus motility disorders (solids and liquids early).
Esophageal varices are portosystemic collaterals (left gastric → esophageal veins → azygos) in portal hypertension, most often from cirrhosis. Thin-walled submucosal veins can bleed massively; management concepts (octreotide reduces splanchnic flow; banding) are clinically adjacent but mechanism (portal pressure + collaterals) is the CBSE core.
Other esophageal high-yield: Mallory–Weiss longitudinal mucosal tear at GE junction after retching (bleed); Boerhaave transmural perforation (mediastinitis); eosinophilic esophagitis (atopy, rings, furrows, eosinophils); infectious esophagitis in immunocompromised (Candida plaques, HSV punched-out ulcers, CMV linear ulcers).
Stomach: Gastritis, Ulcers, Cancer
H. pylori is a gram-negative curved/spiral urease-positive organism that lives in the mucus layer. Urease generates ammonia to buffer acid. Patterns: antral-predominant gastritis → ↑ gastrin → acid → duodenal ulcers; pangastritis/body → multifocal atrophy → hypochlorhydria, intestinal metaplasia, and increased gastric adenocarcinoma and MALT lymphoma risk (MALT often regresses with eradication when early). Virulence factors (CagA, VacA) appear in mechanisms questions.
Autoimmune gastritis targets parietal cell antigens (H+/K+-ATPase) via CD4 T cells and autoantibodies; body/fundus atrophy spares antrum relatively; achlorhydria → loss of feedback → hypergastrinemia and ECL hyperplasia (carcinoid risk); loss of intrinsic factor → B12 deficiency/pernicious anemia; associated with other autoimmune diseases. Ulcers are less classic than in H. pylori high-acid states.
Peptic ulcer disease (duodenal more common than gastric historically) complicates as bleeding (gastroduodenal artery posterior duodenal ulcer), perforation (free air, peritonitis; anterior duodenal), gastric outlet obstruction, and penetration. Gastric ulcers warrant malignancy exclusion; duodenal ulcers are usually benign. Zollinger–Ellison (gastrinoma) causes multiple refractory ulcers, often distal/jejunal, with diarrhea.
Gastric adenocarcinoma types: intestinal-type (gland-forming, linked to H. pylori, diet, precursor metaplasia/dysplasia, more distal); diffuse-type (signet-ring cells, linitis plastica, E-cadherin/CDH1 germline risk, not strongly H. pylori-stepwise). Virchow node, Sister Mary Joseph nodule, Krukenberg ovary mets are classic spread vignettes. GIST (ICC origin, KIT) is a separate stromal tumor concept.
| Feature | H. pylori gastritis | Autoimmune gastritis |
|---|---|---|
| Primary site | Antrum ± body | Body/fundus |
| Acid | Often ↑ early (antral) or ↓ later atrophy | Achlorhydria |
| Gastrin | Variable; can ↑ | Markedly ↑ |
| Key sequela | Ulcer, MALT, intestinal-type adenoCA | B12 deficiency, ECL carcinoids |
| IF / parietal cells | Not primarily autoimmune IF loss | Destroyed |
Small Bowel Malabsorption Pathologies
Celiac disease (gluten-sensitive enteropathy): genetically susceptible hosts (HLA-DQ2 or DQ8) mount adaptive immune injury to gluten peptides deamidated by tissue transglutaminase. Histology of proximal small bowel: villous atrophy, crypt hyperplasia, increased intraepithelial lymphocytes. Clinical: steatorrhea, weight loss, iron/folate deficiency, dermatitis herpetiformis, ↑ risk T-cell lymphoma and small-bowel adenocarcinoma. Serologies (tTG-IgA) are clinical; mechanism/HLA/histology are CBSE gold.
Tropical sprue: malabsorption after travel/residence in tropics; responds to antibiotics + folate; more extensive small-bowel involvement than classic celiac distribution alone; think infectious/post-infectious enteropathy pattern rather than gluten HLA story.
Whipple disease: Tropheryma whipplei; middle-aged men; malabsorption, arthralgias, neurologic and cardiac involvement; foamy PAS-positive macrophages in lamina propria packing villi; treat with prolonged antibiotics conceptually.
Other malabsorption contrasts: lactase deficiency (osmotic diarrhea, normal villi), pancreatic insufficiency (fat + fat-soluble vitamins, low fecal elastase), bile salt deficiency (ileal disease), abeta-lipoproteinemia (no chylomicrons, acanthocytes).
IBD: Crohn vs Ulcerative Colitis
Crohn disease: any GI tract (terminal ileum classic), skip lesions, transmural inflammation → fistulas, abscesses, strictures, creeping fat, cobblestoning; noncaseating granulomas (helpful when present, not required); smoking worsens disease; extraintestinal (arthritis, uveitis, erythema nodosum, pyoderma, gallstones/oxalate stones with ileal disease, B12 deficiency).
Ulcerative colitis: continuous involvement from rectum proximally, mucosa/submucosa, crypt abscesses, pseudopolyps, no granulomas; toxic megacolon risk; strongly associated with primary sclerosing cholangitis; smoking may be protective (contrast Crohn); ↑ colorectal cancer risk with extent/duration; bloody diarrhea more classic than Crohn’s often nonbloody ileitis.
| Feature | Crohn | UC |
|---|---|---|
| Distribution | Mouth to anus, skips | Colon continuous from rectum |
| Depth | Transmural | Mucosal |
| Granulomas | Possible | No |
| Fistula/stricture | Common | Rare |
| Surgery | Not curative (recurs) | Colectomy can cure colonic disease |
| PSC link | Weaker | Strong |
Colon & Motility Entities; Neuroendocrine Hypersecretion
Appendicitis: luminal obstruction (fecalith, lymphoid hyperplasia) → bacterial overgrowth, ischemia, necrosis; peri-umbilical pain migrates to RLQ (McBurney); perforation risk.
Diverticulosis: false diverticula (mucosa/submucosa through muscularis) at vasa recta entry points, sigmoid classic in Western low-fiber patterns; usually asymptomatic or bleed (painless hematochezia). Diverticulitis: microperforation/inflammation of a diverticulum → LLQ pain, fever; complications abscess, fistula, obstruction, free perforation.
Ischemic colitis: non-occlusive low-flow or embolic/thrombotic compromise; watershed zones—splenic flexure (Griffiths) and rectosigmoid (Sudeck)—are vulnerable; pain out of proportion or bloody diarrhea after hypoperfusion episode; thumbprinting on imaging conceptually.
Hirschsprung disease: failure of neural crest migration → aganglionic distal segment (always involves rectum when present) lacks Meissner/Auerbach plexuses → tonic contraction, proximal dilation (megacolon); failure to pass meconium, bilious emesis; associated with Down syndrome and RET pathway defects.
Neuroendocrine concepts:
- Carcinoid tumors (well-differentiated NETs), often midgut; carcinoid syndrome (flushing, diarrhea, bronchospasm, right-sided valvular lesions) when vasoactive mediators bypass hepatic metabolism (liver mets or extra-portal primary). Serotonin → urinary 5-HIAA.
- VIPoma (WDHA): watery diarrhea, hypokalemia, achlorhydria; VIP-driven secretory diarrhea.
- Zollinger–Ellison (gastrinoma): gastrin-secreting NET (duodenum/pancreas), MEN1 association, acid hypersecretion, refractory ulcers, diarrhea.
Tie each lesion back to a failed physiologic step—barrier, acid control, immune tolerance to gluten, transmural immunity, or enteric innervation—to answer mechanism stems efficiently.
A 58-year-old with longstanding GERD has distal esophageal intestinal metaplasia with goblet cells. Which neoplastic pathway is this patient most at risk for?
Which feature best distinguishes Crohn disease from ulcerative colitis?
Autoimmune gastritis is most likely to produce which constellation?