Peptic Ulcer Disease (PUD): H. Pylori, Nsaids

(Lancet 2002;360:933-41. N Engl J Med 2002;347:1175-86. Am J Gastroenterol 1998;93:2037-46 & 2330-38)

DEFINITION:

Ulcer: Mucosal break of the stomach or duodenum that penetrates the muscularis mucosae
Erosion: a lesion that is superficial to the muscularis mucosae

EPIDEMIOLOGY:

Duodenal ulcer (DU): ˜300,000 cases per year
Gastric ulcer (GU): ˜75,000 cases per year
Lifetime prevalence ˜10% (Up to 60% of the world’s population is estimated to harbor H. Pylori but only 15% will develop an ulcer)

ETIOLOGIES:

H. Pylori infection: (90% of DU and 70% of GU); See epidemiology above regarding lifetime prevalence
- H. Pylori: GNB with urease activity (basis for diagnostic testing): hydrolyzes urea » ammonia (NH₃) & CO₂ (helps resist stomach acid)
- Transmission thought to be fecal-oral or oral-oral and most infections acquired in childhood
- Natural habitat is gastric mucosa of the antrum (gets protection from acid in the mucosa but it is not intracellular)
  - If found in duodenum, they are associated with metaplastic gastric epithelium
- MOA: Suppresses epithelial cell immune response & generates autoantibodies which cross-react with G & D cells causing death/atrophy; This allows G cells to release gastrin without inhibition and leads to increased gastric acid secretion and ulcer formation
NSAIDs (10% of DU and 15-30% of GU, 0.1-4% UGIB) including aspirin; Up to 40% of patients may not report using these drugs
- High-risk group requiring prevention (PPI, Misoprostol, H2As prevent GU only):
  - Age >60, Prior GI bleed, High dose NSAIDs (2× normal), Concurrent steroids, Concurrent anticoagulants
- MOA #1: Inhibition of GI cyclooxygenase-1 (COX1), the enzyme responsible for GI prostaglandin synthesis (mucosal protectant)
  - Prostaglandins: ↑ bicarbonate and mucus secretion, ↑ mucosal blood flow, ↓ gastric secretion of H+
- MOA #2: Most are weak acids; exposure to gastric acid = protonated and allow cross of lipid membrane entering epithelial cells
  - Once inside, it ionizes (releases H+) and gets trapped inside; also may decrease hydrophobicity of mucus gel layer
  - Result is rapid epithelial cell death, superficial hemorrhage and erosion
Gastrinoma and other hypersecretory states such as Zollinger-Ellison Syndrome (consider if multiple recurrent ulcers) See also Esophagus/Gastric- ZES (Chapter 1.23)
Malignancy (5-10% of gastric ulcers): adenocarcinoma or lymphoma
Other: Crohn’s, Eosinophilic gastritis, C1 esterase deficiency, Stress, Viral (CMV, HSV), Steroids (alone don’t ↑ risk, with NSAID use ↑↑↑ risk)
DDX of patients dyspepsia: GERD, PUD, NUD, biliary tract disease, pancreatitis, cancer; See also Esophagus/Gastric- Dyspepsia (Chapter 1.04)