Upper & Lower GI Pathology – Vocabulary Review

Upper Gastro-Intestinal (GI) Key Symptoms

• \text{Dysphagia}=\text{difficulty swallowing} – points to esophageal pathology.
• \text{Odynophagia}=\text{pain with swallowing} – esophageal mucosal injury.
• Heartburn (retrosternal burning) – gastric content refluxes into esophagus / stomach disorders.
• Hematemesis – vomiting of fresh blood or “coffee‐ground” material once mixed with gastric acid.
• Melena – black, tarry stool from upper-GI bleeding; implies blood has been exposed to acid/enzymes.

Infectious Esophagitis

• Candida: adherent white/gray pseudomembranes; underlying mucosa bleeds when scraped; budding yeast + pseudohyphae on microscopy.
• Herpes simplex virus-1: multiple sharply circumscribed “punched-out” ulcers; Cowdry type A eosinophilic intranuclear inclusions.
• Setting: immunocompromised, diabetics, steroid users, broad-spectrum antibiotics.

Tracheo-Esophageal Fistula (TEF) & Esophageal Atresia

• Congenital mis-partitioning of foregut (failure of tracheoesophageal septum).
• Presentation at birth: drooling, choking, vomiting immediately after feeds; inability to pass nasogastric tube >10–15\,\text{cm}; coiled tube on X-ray.
• High risk aspiration → pneumonia.
• Associated with other VACTERL anomalies.
• Embryology: laryngotracheal diverticulum buds wk 4–5.

Mechanical / Structural Esophageal Disorders

Webs vs Rings

• Web = thin, eccentric mucosal shelf (mostly cervical esophagus).
• Ring = concentric, symmetric narrowing; Schatzki (B-type) ring occurs at gastroesophageal (GE) junction; often due to chronic reflux.
• Barium swallow: smooth, regular ridge above diaphragm → dysphagia to solids.

Plummer-Vinson Syndrome

• Triad: dysphagia + upper-third webs + iron-deficiency anemia.
• Mnemonic: plumbers DIE (Dysphagia, Iron‐deficiency, Esophageal webs).
• Middle-aged women (40–70 yrs).
• ↑ risk squamous cell carcinoma (SCC).

Zenker (Pharyngoesophageal) Diverticulum

• False diverticulum through Killian triangle (between thyropharyngeus & cricopharyngeus).
• Impaired cricopharyngeal relaxation → ↑ intraluminal pressure → mucosa/submucosa herniate.
• Elderly men (70–90 yrs).
• Clinical: regurgitation of undigested food, halitosis, cough, aspiration pneumonia, palpable neck mass; rare SCC transformation.

Achalasia

• Primary: idiopathic loss of myenteric (Auerbach) inhibitory ganglion cells → failure of LES relaxation.
• Secondary: Chagas disease (Trypanosoma cruzi), diabetes (autonomic neuropathy), infiltrative malignancy.
• Manometry: high resting LES pressure, incomplete relaxation, absent peristalsis.
• Barium swallow: "bird-beak" tapering with proximal dilation.
• Complication: \approx5\% lifetime risk esophageal SCC.

Hiatal Hernia

• Protrusion of stomach through diaphragmatic hiatus.
• Sliding (95 %) – GE junction moves; associated reflux, esophagitis, Barrett.
• Paraesophageal (rolling) – fundus herniates, higher risk strangulation.

Lacerations

• Mallory–Weiss tears: mucosal longitudinal lacerations at GE junction from severe retching (alcoholics); 5–10 % of upper-GI bleed.
• Boerhaave syndrome: transmural rupture → mediastinitis (surgical emergency).

Esophageal Varices

• Portal hypertension (usually alcoholic cirrhosis) → dilated submucosal veins distal esophagus/proximal stomach.
• Asymptomatic until rupture → painless, massive hematemesis; high mortality.

Reflux Esophagitis & Barrett Esophagus

• GERD triggers: sliding hiatal hernia, obesity, alcohol, smoking, caffeine.
• Symptoms: heartburn, regurgitation, nocturnal cough/asthma.
• Complications: ulcer, stricture, Barrett metaplasia.

Barrett Esophagus (“salmon pink” mucosa on endoscopy)
• Intestinal‐type columnar epithelium replaces stratified squamous.
• Occurs in \approx10\% chronic GERD; M :F 4:1, Caucasians.
• Risk of high-grade dysplasia → adenocarcinoma ↑ 30–40\times.

Esophageal Carcinoma

• Two major histologies:
– Squamous cell carcinoma (middle ± upper thirds). Risk factors: smoking, alcohol, Plummer-Vinson, prior lye ingestion, achalasia, hot beverages, HPV, low socioeconomic status.
– Adenocarcinoma (distal \lower third) from Barrett metaplasia.
• Symptoms: progressive dysphagia (solids→liquids), odynophagia, weight loss, hoarseness (recurrent laryngeal nerve).
• Staging (AJCC 7th): depth T0-T4, nodes N0–N3 (1-2 LN, 3-6, ≥7), metastasis M0/M1.

Congenital Gastric Abnormalities

Pyloric Stenosis

• Hypertrophy of pyloric muscularis.
• 1/300–900 births; M > F (3:1); first-born males.
• Onset 2–6 weeks: projectile non-bilious vomiting, palpable “olive” mass, visible peristaltic wave L→R.

Duodenal Atresia

• 1/2500–5000 births; associated Down syndrome (25–40 %).
• Bilious vomiting, “double‐bubble” on X-ray (dilated stomach + duodenum).

Gastric Heterotopia

• Islands of gastric mucosa in esophagus or small intestine; usually asymptomatic → may ulcerate.

Gastritis & Acute Gastric Ulceration

Acute Gastritis / Stress Ulcers

• Etiologies: severe trauma, burns (Curling), CNS injury ↑ ICP (Cushing), NSAIDs, corticosteroids, alcohol, chemo, uremia, shock, mechanical ventilation.
• Multiple small (<1\,\text{cm}) circular erosions/ulcers anywhere in stomach; neutrophils in mucosa.
• Symptoms: epigastric pain, nausea, hematemesis, melena; may be silent.

Chronic Gastritis

1. Autoimmune (Type A): anti-parietal & anti-intrinsic-factor Abs → gland destruction, achlorhydria, B_{12} deficiency → pernicious anemia.
2. H. pylori (Type B): antrum-predominant; urease+, flagellated.
   – Pathology: chronic active inflammation, gland loss, intestinal metaplasia ↑ adenocarcinoma risk, lymphoid aggregates ↑ MALT lymphoma.

Peptic Ulcer Disease (PUD)

• Chronic solitary mucosal defects penetrating ≥ submucosa; 98\% in duodenum (1st part) or stomach (lesser curvature) at 4{:}1 ratio.
• Major causes: H. pylori (10–20 % infected develop PUD), NSAIDs (↓ PGE_2), Zollinger–Ellison (Z-E) syndrome (gastrinomas), smoking, cirrhosis, COPD.
• Duodenal ulcer pain: burning 1–3 h post-meal, relieved by food → weight gain.
• Gastric ulcer pain: worse with meals → weight loss.
• Morphology: punched-out round ulcer 2–4 cm, radiating rugal folds; base shows 4 zones – Necrosis (N) → Acute inflammation (I) → Granulation (G) → Fibrosis (S).
• Complications: bleeding (gastroduodenal artery), perforation (anterior wall duodenum), obstruction (pyloric stenosis), malignancy (rare for duodenal).

Small Intestine – Congenital & Mechanical Disorders

Meckel Diverticulum (true)

• Failure of vitelline duct involution. Rule of 2’s: 2\% population; 2'' long;

Mechanical Obstruction

• Hernias (most common worldwide) → incarceration/strangulation.
• Adhesions (most common US) post-surgery, infection, endometriosis, Crohn.
• Volvulus: twisting (sigmoid > cecum) → obstruction + ischemia.
• Intussusception: telescoping (ileocecal junction); children – idiopathic/viral lymphoid hyperplasia; adults – tumor lead point; "currant jelly" stool.

Malabsorption Syndromes

Celiac Disease (Gluten-Sensitive Enteropathy)

• Gliadin triggers modified by tissue transglutaminase (tTG) → presented via HLA-DQ2/DQ8; CD4^+ Th cells release IFN-γ; IL-15 activates CD8^+ NK-like epitheliotoxic cells (NKG2D).
• Biopsy duodenum: ↑ intraepithelial CD8^+, crypt hyperplasia, villous atrophy.
• Serology: IgA anti-tTG, anti-endomysium, anti-gliadin (use IgG if IgA-deficient).
• Dermatitis herpetiformis: IgA deposits at dermal papillae.
• Treatment: lifelong gluten-free diet.

Tropical Sprue

• Environmental enteropathy in residents/travelers Caribbean & SE Asia; similar histology to celiac but involves entire small bowel; malabsorption of folate & B_{12} → megaloblastic anemia; responds to antibiotics.

Whipple Disease

• Tropheryma whipplei: PAS^+ foamy macrophages compress lacteals → lymphatic obstruction → fat malabsorption (steatorrhea), weight loss, arthralgia, hyperpigmentation; Caucasian men, farmers.

Large Intestine Disorders

Hirschsprung Disease (Congenital Aganglionic Megacolon)

• Neural crest migration failure → absence of Meissner & Auerbach plexuses in rectum ± sigmoid; functional obstruction → failure to pass meconium, abdominal distension; diagnosis: rectal suction biopsy lacking ganglia; treat by resection.

Inflammatory Bowel Disease (IBD)

• Pathogenesis: abnormal intestinal microbiota response + epithelial barrier defects + dysregulated immunity (IL-23R, NOD2).

Diverticular Disease

• Diverticulosis: acquired mucosa/submucosa herniation through muscularis at vasa recta (sigmoid); related to low-fiber constipation ↑ intraluminal pressure.
• Complications: hematochezia, diverticulitis (LLQ pain, fever), fistula (e.g., colovesical), abscess, perforation, strictures.
• Diverticulitis CT: pericolic fat stranding; treat antibiotics ± surgery.

Pancreas

Acute Pancreatitis

• Premature activation of trypsin → autodigestion.
• Etiologies (I GET SMASHED): Idiopathic, Gallstones (obstruction), Ethanol, Trauma, Steroids, Mumps, Autoimmune, Scorpion sting, Hypercalcemia/Hypertriglyceridemia, ERCP, Drugs.
• Labs: ↑ serum amylase (early), ↑ lipase (specific), hypocalcemia (saponification).
• Complications: DIC, ARDS, shock, pseudocysts (no epithelium), fat necrosis, renal failure.

Chronic Pancreatitis

• Alcohol (90 %), genetic (CFTR, PRSS1), obstruction; irreversible fibrosis & atrophy.
• Features: epigastric pain radiating to back, pancreatic calcifications, steatorrhea, fat-soluble vitamin deficiency, secondary diabetes mellitus.
• Major long-term complication: pancreatic insufficiency + pseudocysts.

Cystic Neoplasms

• Serous cystadenoma: glycogen-rich cuboidal cells, clear fluid; benign.
• Mucinous cystic neoplasm: ovarian-type stroma; body/tail; may progress to invasive carcinoma; filled with thick mucin.
• Intraductal papillary mucinous neoplasm (IPMN) – mucin in main duct.
• Solid-pseudopapillary neoplasm – young women, β-catenin mutation.

Pancreatic Cancer – Ductal Adenocarcinoma

• Risk: smoking (strongest), chronic pancreatitis, diabetes, BRCA2, Peutz-Jeghers.
• 60 % head → painless obstructive jaundice (Courvoisier gallbladder); 15 % body; 5 % tail (often silent).
• Markers: CA 19-9, CEA.
• Trousseau sign: migratory thrombophlebitis (hypercoagulability).
• Very poor prognosis (<10\% 5-yr survival); Whipple (pancreaticoduodenectomy) if localized.

Endocrine (Islet-Cell) Tumors

• Insulinoma: β-cell; Whipple triad – hypoglycemia, neuroglycopenic symptoms, relief with glucose; majority benign; stains insulin (+).
• Gastrinoma (Z-E): multiple refractory ulcers, diarrhea; often malignant; measure fasting gastrin; associated with MEN 1.
• VIPoma (WDHA syndrome): watery diarrhea, hypokalemia, achlorhydria.

Peritoneum & Peritonitis

• Sterile causes: bile leak, pancreatic enzymes, endometriosis hemorrhage, foreign body.
• Bacterial: appendiceal or diverticular perforation, bowel ischemia, trauma, salpingitis; spontaneous bacterial peritonitis (cirrhosis + ascites) – E. coli.
• Presentation: acute abdomen, rebound tenderness, guarding, paralytic ileus, leukocytosis.
• Paracentesis indications: new/worsening ascites, suspected infection; labs – neutrophils >250/\mu L diagnostic for SBP.

Liver: Cirrhosis, Failure, Portal Hypertension

Cirrhosis

• End-stage fibrosis with regenerative nodules (micro

Liver Failure (loss >80–90\% function)

• Acute: fulminant viral (HAV, HBV), acetaminophen, halothane, isoniazid, Amanita phalloides, autoimmune hepatitis.
• Chronic: cirrhosis of any etiology.
• Clinical: jaundice, hypoalbuminemia (edema), coagulopathy (↑ PT), hyperammonemia → encephalopathy (asterixis), hyperestrogenism (spider angiomas, palmar erythema, gynecomastia, testicular atrophy), fetor hepaticus.

Portal Hypertension

• Causes: prehepatic (portal vein thrombosis), intrahepatic (cirrhosis), posthepatic (Budd–Chiari, right heart failure).
• Complications: ascites, splenomegaly, portosystemic shunts (varices, caput medusae, hemorrhoids), hepatorenal syndrome, hepatopulmonary syndrome, portopulmonary hypertension.

Ascites

• Serum–ascites albumin gradient (SAAG) ≥1.1\,\text{g/dL} indicates portal hypertension.
• Paracentesis therapeutic and diagnostic.

Jaundice & Cholestasis

• Clinical jaundice at bilirubin >2\,\text{mg/dL}.
• Pre-hepatic (hemolysis) – ↑ unconjugated (indirect) bilirubin.
• Hepatic (hepatocellular injury) – mixed pattern.
• Post-hepatic (obstruction) – predominantly conjugated (direct) bilirubin back-leaks via tight-junction disruption.

Laboratory Panels

• AST (mitochondrial) & ALT (cytosolic, liver-specific) – hepatocellular damage.
– ALT > AST → viral hepatitis.
– AST > ALT >2{:}1 → alcoholic hepatitis.
• Alkaline phosphatase (ALP) – canalicular membrane; ↑ in cholestasis or bone turnover.
• γ-Glutamyl transpeptidase (GGT) parallels ALP for cholestasis and is inducible by alcohol/CYP 450 drugs; normal GGT + high ALP → non-hepatic source (bone).
• Synthetic function: albumin (low in chronic failure), PT/INR (↑ earliest sign), BUN (↓ in liver failure), ammonia (↑ encephalopathy).
• Immune markers: anti-mitochondrial Ab (primary biliary cholangitis), p-ANCA (PSC/UC), anti-smooth muscle & ANA (autoimmune hepatitis).
• Tumor marker \alpha-fetoprotein ↑ in hepatocellular carcinoma.

Quick Clinical Vignette Correlations

• Hereditary spherocytosis + jaundice → unconjugated hyperbilirubinemia (labs: % CB

Summary / Integration

This compendium ties congenital malformations (TEF, pyloric stenosis), structural disorders (achalasia, diverticulosis), inflammatory entities (IBD, pancreatitis), neoplasia (esophageal SCC vs adenocarcinoma, pancreatic ductal adenocarcinoma), metabolic & immune liver disease, and laboratory diagnostics into an integrated framework for GI pathology. Reinforce each entity with classical presentation, mechanism, morphology, complications, and unique buzzwords (e.g., "bird-beak," "string sign," "lead-pipe," "Courvoisier gallbladder").