#HCLProduction

#Biology

#HumanDigestiveSystem

Production

• HCl is produced by parietal cells in the stomach and plays a crucial role in digestion by breaking down food and activating digestive enzymes.

• The tight regulation of parietal cells ensures the proper secretion of HCl.

• Acid secretion by gastric parietal cells occurs in a stepwise process.

• Step 1: Water and carbon dioxide react to form carbonic acid through the catalytic action of carbonic anhydrase. When formed at cytoplasmic pH, the carbonic acid is unstable and dissociates into H+ and bicarbonate ion.

• Step 2: H+ ions are actively secreted into the lumen in exchange for K+ ions, which enter the cell. The H+–K+ transporter is an ATPase, which hydrolyzes ATP to provide energy for the “up-hill” transport of H+. The H+–K+ ATPase is also called the proton pump.

• Step 3: Bicarbonate ions diffuse out of the parietal cell and into the blood in exchange for Cl− ions by a

  Cl

  −

  HCO

  3

  −

  exchanger located at the basolateral membranes. This makes the blood alkaline during active acid secretion. The increase of bicarbonate ions in the blood after a meal is called the “alkaline tide.” It occurs coincident with increased acid secretion during digestion of a meal.

• Step 4: Cl− ions are secreted into the lumen via Cl− channels. Water passes through the mucosa into the gastric lumen by osmosis as the luminal concentration of ions increases.

  
  

• Gastric parietal cells express three kinds of receptors, each of which stimulate acid secretion when activated. The receptors are: (1) muscarinic m3 receptors for ACh; (2) CCKB receptors for gastrin; (3) H2 receptors for histamine.

• Stimulation of any one of these three receptor types causes more H+/K+ ATPase and Cl− channels to be inserted into the apical membrane, and thereby elevates gastric acid secretion.

• Stimulation of these three receptors together results in a response greater than the sum of activation of each receptor alone (i.e., there is a synergistic effect when more than one of the receptor types become activated).

  
  

• A meal in the stomach stimulates G-type enteroendocrine cells in the gastric mucosa to secrete gastrin, which in turn stimulates the secretion of HCl.

• Accumulation of HCl and lowering of the pH in the gastric lumen stimulate D-type enteroendocrine cells in the gastric mucosa to secrete somatostatin, which in turn feeds back in negative fashion to suppress the release of gastrin.