Peptic ulcer disease (PUD) occurs most commonly in duodenal bulb (duodenal ulcer, DU) and stomach (gastric ulcer, GU). It may also occur in esophagus, pyloric channel, duodenal loop, jejunum, and Meckel's diverticulum. PUD results when “aggressive” factors (gastric acid, pepsin) overwhelm “defensive” factors involved in mucosal resistance (gastric mucus, bicarbonate, microcirculation, prostaglandins, mucosal “barrier”) and from effects of Helicobacter pylori.
H. pylori is a spiral urease-producing organism that colonizes gastric antral mucosa in up to 100% of persons with DU and 80% with GU. It is also found in normals (increasing prevalence with age) and in those of low socioeconomic status. H. pylori is invariably associated with histologic evidence of active chronic gastritis, which over years can lead to atrophic gastritis and gastric cancer. The other major cause of ulcers (those not due to H. pylori) is nonsteroidal anti-inflammatory drugs (NSAIDs). Fewer than 1% are due to gastrinoma (Zollinger-Ellison [Z-E] syndrome). Other risk factors and associations: hereditary (? increased parietal cell number), smoking, hypercalcemia, mastocytosis, blood group O (antigens may bind H. pylori). Unproven: stress, coffee, alcohol.
Mild gastric acid hypersecretion resulting from (1) increased release of gastrin, presumably due to (a) stimulation of antral G cells by cytokines released by inflammatory cells and (b) diminished production of somatostatin by D cells, both resulting from H. pylori infection; and (2) an exaggerated acid response to gastrin due to an increased parietal cell mass resulting from gastrin stimulation. These abnormalities reverse rapidly with eradication of H. pylori. However, a mildly elevated maximum gastric acid output in response to exogenous gastrin persists in some pts long after eradication of H. pylori, suggesting that gastric acid hypersecretion may be, in part, genetically determined. H. pylori may also result in elevated serum pepsinogen levels. Mucosal defense in duodenum is compromised by toxic effects of H. pylori infection on patches of gastric metaplasia that result from gastric acid hypersecretion or rapid gastric emptying. Other risk factors include glucocorticoids, NSAIDs, chronic renal failure, renal transplantation, cirrhosis, and chronic lung disease.
H. pylori is also principal cause. Gastric acid secretory rates are usually normal or reduced, possibly reflecting earlier age of infection by H. pylori than in DU pts. Gastritis due to reflux of duodenal contents (including bile) may play a role. Chronic salicylate or NSAID use may account for 15-30% of GUs and increase risk of associated bleeding, perforation.
Duodenal Ulcer
Burning epigastric pain 90 min to 3 h after meals, often nocturnal, relieved by food.
Gastric Ulcer
Burning epigastric pain made worse by or unrelated to food; anorexia, food aversion, weight loss (in 40%). Great individual variation. Similar symptoms may occur in persons without demonstrated peptic ulcers (“nonulcer dyspepsia”); less responsive to standard therapy.
Bleeding, obstruction, penetration causing acute pancreatitis, perforation, intractability.
Duodenal Ulcer
Upper endoscopy or upper gastrointestinal (GI) barium radiography.
Gastric Ulcer
Upper endoscopy preferable to exclude possibility that ulcer is malignant (brush cytology, ≥6 pinch biopsies of ulcer margin). Radiographic features suggesting malignancy: ulcer within a mass, folds that do not radiate from ulcer margin, a large ulcer (>2.5-3 cm).
Detection of antibodies in serum (inexpensive, preferred when endoscopy is not required); rapid urease test of antral biopsy (when endoscopy is required). Urea breath test generally used to confirm eradication of H. pylori, if necessary. The fecal antigen test is sensitive, specific, and inexpensive (Table 150-1 Tests for Detection of H).
| TREATMENT | ||
Peptic Ulcer DiseaseMEDICALObjectives: pain relief, healing, prevention of complications, prevention of recurrences. For GU, exclude malignancy (follow endoscopically to healing). Dietary restriction unnecessary with contemporary drugs; discontinue NSAIDs; smoking may prevent healing and should be stopped. Eradication of H. pylori markedly reduces rate of ulcer relapse and is indicated for all DUs and GUs associated with H. pylori (Table 150-2 Recommended First-Line Therapies for H). Acid suppression is generally included in regimen. Reinfection rates are <1%/year. Standard drugs (H2 receptor blockers, sucralfate, antacids) heal 80-90% of DUs and 60% of GUs in 6 weeks; healing is more rapid with omeprazole (20 mg/d). SURGERYUsed for complications (persistent or recurrent bleeding, obstruction, perforation) or, uncommonly, intractability (first screen for surreptitious NSAID use and gastrinoma). For DU, see Table 150-3 Surgical Treatment of Duodenal Ulcer. For GU, perform subtotal gastrectomy. COMPLICATIONS OF SURGERY(1) Obstructed afferent loop (Billroth II), (2) bile reflux gastritis, (3) dumping syndrome (rapid gastric emptying with abdominal distress + postprandial vasomotor symptoms), (4) postvagotomy diarrhea, (5) bezoar, (6) anemia (iron, B12, folate malabsorption), (7) malabsorption (poor mixing of gastric contents, pancreatic juices, bile; bacterial overgrowth), (8) osteomalacia and osteoporosis (vitamin D and Ca malabsorption), (9) gastric remnant carcinoma. |