Question 16

Describe the formation of gastric acid (50% marks) and the regulation of gastric acid secretion (50% marks).

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College Answer

The is question was divided into two sections offering equal marks. The first section required a description of the generation and transport of both H+ and Cl- into the stomach lumen by the parietal cell. The contributions of basolateral and luminal ion channels, the role of carbonic anhydrase and accurate description of the net flux was expected for full marks. The second section required comments on the roles of neural and endocrine regulation. Increased acid secretion via acetylcholine (via muscarinic M3), histamine (via H2) and gastrin were expected as was reduced secretion via secretin and somatostatin. Better responses were able to combine and integrate these into cephalic, gastric, and intestinal phases. The nature and function of other gastric secretions and the role of pharmacologic agents was not asked for and therefore not awarded any marks.


  • Parietal cell structure:
    • Apical secretory canaliculi which increase the surface area
    • Numerous vesicles containing proton pump proteins
    • With stimulation, these vesicles fuse with the apical canaliculi to rapidly increase the secretory capacity of these cells
  • Basal membrane ion transport in parietal cells
    • CO2 and water are able to diffuse into parietal cells passively
    • Carbonic anhydrase converts the CO2 and H2O into HCO3- and H+
    • HCO3-  is then exchanged for chloride at the basal membrane
  • Apical membrane ion transport in parietal cells
    • H+ is  exported by an ATP-powered H+/K+"proton pump"
    • The potassium used in this exchange is returned to the gut lumen 
    • Chloride is exported through apical chloride channels
  • Net effect of parietal cell activity
    • In the gut lumen:
      • Chloride concentration increases from 120 mmol/L up to 180 mmol/L
      • pH decreases to 1.5
    • In the portal circulation:
      • Carbonic anhydrase activity consumes CO2
      • Thus, portal venous CO2 is lower than PaCO2
      • This is a negative respiratory quotient
      • This increases the pH of portal venous blood during the cephalic and gastric phases of digestion, a phenomenon known as the "alkaline tide"
  • Influences that stimulate acid secretion by the parietal cells during the cephalic and gastric phases of digestion:
    • Acetylcholine (M3 receptors) during the cephalic phase
    • Gastrin (gastrin and CCK-B receptors) during the cephalic and gastric phase
    • Histamine (H2 receptors) during the cephalic and gastric phase
  • Inhibitory influences mainly take effect during the intestinal phase, and include:
    • Somatostatin
    • Vasoactive intestinal polypeptide (VIP)
    • Secretin
    • Cholecystokinin


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