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  • 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
        • cortical/hypothalamic elements: vagal activation
        • vagal activation:
          1. direct stimulation of ECL and parietal cells (primary)
          2. promotion of gastrin release (secondary)
      2. gastric phase
        • stimulation of mechanical in chemical gastric wall receptors by luminal contents.
          1. mechanical distention: increased gastric acid secretion
          2. mechanical effect: inhibited by atropine (suggesting vagal mediation)
          3. food (mainly protein and catabolic protein products) stimulates gastric acid secretion by increasing gastrin release.
      3. intestinal phase
        • gastrin release (small amount); release of other peptides that stimulate gastric acid secretion
        • absorbed amino acids: direct effect on parietal cells
    • 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 -- possibly constituent amines and related chemicals (ethanol by itself: weak stimulant of gastric acid secretion)

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  • Physiologic inhibition- gastric acid release:
    • Factors that inhibit gastric acid secretion include:
      • hyperglycemia
        • unknown mechanism
      • hypertonic fluids
        • unknown mechanism
      • duodenal fat
        • possibly gastrointestinal-peptide-mediated (GIP)
      • duodenal acid
        • reduction of stomach gastric acid secretion may be due to stimulating release into the circulation of intestinal peptides (e.g. secretin) that inhibit gastric acid secretion
      • intragastric pH = 3; partial in addition
      • intragastric pH < or = 1.5; complete blockade of gastrin release (probably somatostatin-mediated)
    • 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

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  • 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
    • Pepsin proteolytically activity: pH dependence
      • maximal activity: pH = 2
      • reduced activity: pH > 4
      • no activity (irreversible inactivation) pH > or = 7
    • Pepsinogen classification:
      • pepsinogen I: mucous cells in the body and fundus of the stomach
      • pepsinogen II:mucous cells in the body and fundus and pyloric gland cells
      • Direct correlation between pepsinogen I serum concentrations and maximal gastric acid secretion
        • Most compounds that stimulate gastric acid secretion, also stimulate pepsinogens secretion
          • (Example: cholinergic effects; Exception: secretin -- gastric acid secretion inhibition but stimulates pepsinogens secretion

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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:
      • short, spiral-shaped, microaerophilic, gram-negative bacillus: causes active, chronic gastritis
      • Bacterial protein products appear damaging
      • Proteases and phospholipases produced by H. pylori degrade glycoprotein-lipid mucus layer complex
      • H. pylori: produces chemotactic factors for neutrophils, monocytes, and secretes platelet-activating factor (proinflammatory)
      • H. pylori: activates monocytes that express HLA-DR and interleukin 2 surface receptors and produced superoxides, interleukin 1, and tumor necrosis factor
    • 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
    • Increased incidence:
      • chronic renal failure
      • alcoholic cirrhosis
      • renal transplantation
      • hyperparathyroidism
      • systemic mastocytosis
      • chronic obstructive pulmonary disease (COPD)
Friedman, L. S. and Peterson, W.L. Peptic Ulcer and Related Disorders In Harrison's Principles of Internal Medicine 14th edition, (Isselbacher, K.J., and Braunwald, E., Wilson, J.D., Martin, J.B., Fauci, A.S. and Kasper, D.L., eds) McGraw-Hill, Inc (Health Professions Division), 1998, pp. 1597-1616.