Pathophysiology

Under typical physiological conditions, the cells of the gastric mucosa secrete a gastric juice (an acidic fluid composed of HCl, pepsinogen, intrinsic factor, and mucus), which may damage the native cells of the GI tract. Protective mechanisms (e.g., secretion of mucus and HCO3- to form a protective barrier) prevent the gastric juices from digesting and eroding the gastric epithelial cells. Ulcer formation occurs when either the protective mechanisms are disrupted and/or excessive acids or pepsin are secreted.

• Parietal cells

  • Secrete hydrochloric acid (HCl) and intrinsic factor

  • Stimulated by acetylcholine, histamine, and gastrin

  • Inhibited by prostaglandins and somatostatin

• Mucosal cells

  • Secrete protective mucus

  • Stimulated by acetylcholine, prostaglandins (which inhibit HCl secretion), and secretin

• Chief cells

  • Secrete pepsinogen

  • Stimulated by acetylcholine, gastrin, secretin, and vasoactive intestinal polypeptide (VIP)

• H. pylori

  • Gastric ulcers

    • H. pylori secretes urease → conversion of urea to NH3 → alkalinization of acidic environment → survival of bacteria in gastric lumen

    • Bacterial colonization and attachment to epithelial cells → release of cytotoxins (e.g., cagA toxin) → disruption of the mucosal barrier and damage to underlying cells

  • Duodenal ulcers

    • H. pylori inhibits somatostatin secretion → ↑ gastrin secretion → ↑ H+ secretion → excess H+ delivery to the duodenum

    • Direct spread of H. pylori to the duodenum → inhibition of duodenal HCO3- secretion→ acidification and insufficient neutralization of duodenal contents

• NSAIDs

  • Inhibit COX-1 and COX-2 → decrease in prostaglandin production → erosion of the gastric mucosa

  • Decrease mucosal blood flow

  • Inhibit mucosal cell proliferation

• Acid hypersecretion: acid hypersecretion (e.g., Zollinger-Ellison syndrome) and increased gastrin production → ↑ H+ secretion and parietal cell mass → delivery of excessive acid to the duodenum