• Physiological stimulants of gastric acid secretion:
  • Major physiologic stimulus: food intake -- three phases:
    1. cephalic phase
       • gastric acid secretion responds to anticipation of food, sight, smell, taste
    2. gastric phase
       • stimulation of mechanical and chemical gastric wall receptors by luminal contents.
    3. intestinal phase
       • gastrin release (small amount); release of other peptides that stimulate gastric acid secretion
  • Food constituents:
    • Coffee (both caffeine containing and caffeine free) stimulates gastric acid secretion by stimulating gastric release
    • Beer and wine: stimulation of gastric acid secretion

return to main menu

• Physiologic inhibition- gastric acid release:
  • Factors that inhibit gastric acid secretion include:
    • hyperglycemia
    • hypertonic fluids
    • duodenal fat
    • duodenal acid
    • intragastric pH = 3; partial inhibition
    • intragastric pH < or = 1.5; complete blockade of gastrin release
  • Somatostatin effects:
    • Antral mucosal endocrine cells (D cells) contain somatostatin and impinge on nearby gastrin cells and parietal cells.
    • Somatostatin reduces gastrin release thereby reducing gastric acid secretion by:
      1. inhibiting parietal cells secretion
      2. inhibiting histamine release by enterochromaffin-like cells

return to main menu

•  Role of pepsin in peptic ulcer disease:
  • Secreted gastric acid plus effects of pepsin promote tissue injury
  • Gastric acid promotes cleavage of pepsinogen (inactive) to proteolytically-active pepsins
  • Pepsinogen classification:
    • Direct correlation between pepsinogen I serum concentrations and maximal gastric acid secretion

return to main menu

 Pathogenic Factors

• Peptic ulcer disease: an imbalance between aggressive factors (gastric acid and pepsin) and protective factors (gastric mucus, bicarbonate, prostaglandins)
• Helicobacter pylori: a principal role in peptic ulcer pathogenesis
  • H. pylori:
    • causes active, chronic gastritis
    • Bacterial protein products appear damaging
    • Proteases and phospholipases produced by H. pylori degrade glycoprotein-lipid mucus layer complex
    • H. pylori: proinflammatory
  •  Management of H. pylori infection: clinical consequences
    • 15% relapse rate for duodenal ulcer following H. pylori eradication
    • 75% relapse rate for duodenal ulcer following treatment with H₂ receptor blockers only
• Other Pathogenic Factors:
  • possible genetic factor in duodenal ulcer (frequency of GU ulcers -- three times its common in first-degree relatives of DU patients then in the general population; may however, reflect higher rate of H. pylori infection)
  • Cigarette smoking --
    1. increased incidence of DU
    2. decreased therapeutic response
    3. increased mortality rate from DU