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.

Discussion

  • 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

References

Gamble, James L., Monroe A. McIver, and With the Assistance of Pauline Marsh and Elizabeth Matteson. "The acid-base composition of gastric secretions." The Journal of experimental medicine 48.6 (1928): 837-847.

Strong, J. A., D. Cameron, and M. J. Riddell. "The electrolyte concentration of human gastric secretion." Quarterly Journal of Experimental Physiology and Cognate Medical Sciences: Translation and Integration 45.1 (1960): 1-11.

Kauffman Jr, G. L. "Gastric mucus and bicarbonate secretion in relation to mucosal protection." Journal of clinical gastroenterology 3.Suppl 2 (1981): 45-50.

Gargouri, Youssef, et al. "Importance of human gastric lipase for intestinal lipolysis: an in vitro study." Biochimica et Biophysica Acta (BBA)-Lipids and Lipid Metabolism 879.3 (1986): 419-423.

Jacobs, A., and P. M. Miles. "Role of gastric secretion in iron absorption." Gut 10.3 (1969): 226.

Schubert, Mitchell L. "Functional anatomy and physiology of gastric secretion." Current opinion in gastroenterology 31.6 (2015): 479-485.

Gribble, Fiona M., Frank Reimann, and Geoffrey P. Roberts. "Gastrointestinal hormones." Physiology of the gastrointestinal tract (2018): 31-70.

Ahmed, Monjur, and Sarah Ahmed. "Functional, diagnostic and therapeutic aspects of gastrointestinal hormones." Gastroenterology research 12.5 (2019): 233.

Martinsen, Tom C., Reidar Fossmark, and Helge L. Waldum. "The Phylogeny and biological function of gastric juice—microbiological consequences of removing gastric acid." International journal of molecular sciences 20.23 (2019): 6031.

Ong, Bill Y., Richard J. Palahniuk, and Maureen Cumming. "Gastric volume and pH in out-patients." Canadian Anaesthetists’ Society Journal 25.1 (1978): 36.