Sunday, 29 May 2011

Physiology of gastric secretion

Hydrochloric acid and pepsinogen are the two principal gastric secretory products capable of inducing mucosal injury. Acid secretion should be viewed as :
  1. Basal acid production occurs in a circadian pattern, with highest levels occurring during the night and lowest levels during the morning hours. Cholinergic input via the vagus nerve and histaminergic input from local gastric sources are the principal contributors to basal acid secretion.
  2. Stimulated conditions. Stimulated gastric acid secretion occurs primarily in three phases based on the site where the signal originates : cephalic, gastric, and intestinal.
  • Cephalic phase : Sight, smell, and taste of food are the components of it which stimulates gastric secretion via the vagus nerve.
  • Gastric phase is activated once food enters the stomach. This component of secretion is driven by nutrients that directly stimulate the G cell to release gastrin, which in turn activates the parietal cell via direct and indirect mechanisms.Distention of the stomach wall also leads to gastrin release and acid production.
  • Intestinal phase is initiated as food enters the intestine and is mediated by luminal distention and nutrient assimilation. A series of pathways that inhibit gastric acid production are also set into motion during these phases. The gastrointestinal hormone somatostatin is released from endocrine cells found in the gastric mucosa (D cells) in response to HCl which can inhibit acid production by both direct (parietal cell) and indirect mechanisms [decreased histamine release from enterochromaffin-like cells and gastrin release from G cells].

The acid-secreting parietal cell is located in the oxyntic gland, adjacent to other cellular elements (ECL cell, D cell) important in the gastric secretory process.

  • The parietal cell expresses Receptors for several stimulants of acid secretion, including histamine (H2), gastrin (cholecystokinin B/ gastrin receptor), and acetylcholine (muscarinic, M3).
  • Binding of histamine to the H2 receptor leads to activation of adenylate cyclase and an increase in cyclic AMP.
  • Activation of the gastrin and muscarinic receptors results in activation of the protein kinase C/phosphoinositide signaling pathway. Each of these signaling pathways in turn regulates a series of downstream kinase cascades, which control the acid-secreting pump, H+,K+-ATPase.
  • The enzyme H+,K+-ATPase is responsible for generating the large concentration of H+ This enzyme uses the chemical energy of ATP to transfer H+ ions from parietal cell cytoplasm to the secretory canaliculi in exchange for K+. Proton pumps are recycled back to the inactive state in cytoplasmic vesicles once parietal cell activation ceases.


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