• Parietal cell structure

• Acid formation:

- Na⁺-K⁺-ATPase

- H⁺-K⁺-ATPase

• Gastric mucosal barrier:

- mucus layer

- alkaline barrier

- feedback inhibition

 

In the body of the stomach, including the fundus, the glands contain parietal cells, which secrete hydrochloric acid. The acid is required to stimulate the secretion of pepsinogen and to convert it into its active form, pepsin. As the pH of the stomach is less than that of the parietal cells, pumping of H⁺ into the stomach is an active process. It is the H⁺-K⁺-ATPase in the apical membrane of the parietal cells that pumps H⁺ against a concentration gradient.

The parietal cells are polarized, with an apical membrane facing the lumen of the gastric glands and a basolateral membrane in contact with the interstitial fluid. Canaliculi extend from the apical surface into the cell. At rest, the cells also contain abundant tubulovesicular structures with H⁺-K⁺-ATPase molecules in their walls. When the parietal cells are stimulated, the tubulovesicular structures move to the apical membrane and fuse with it, thus inserting many more H⁺-K⁺-ATPase molecules into the membrane. This increases their surface area and forms numerous microvilli, which project into the membrane.

The H⁺ to be secreted comes from carbon dioxide in the blood which diffuses into the parietal cells from the basolateral membrane. Carbonic anhydrase present in the parietal cells catalyzes the formation of carbonic acid from carbon dioxide and water. The carbonic acid formed dissociates to give hydrogen ions and bicarbonate ions. Hydrogen ions is actively transported to the lumen by a H⁺-K⁺-ATPase located on the apical membrane of the parietal cell which exchanges H⁺ for K⁺. Bicarbonate ions flows down its electrochemical gradient across the basolateral membrane in a process mediated by a CI^—HCO₃^- -exchanger which transport chloride ions into the parietal cell. The chloride ions leaves the parietal cell at the apical membrane via an electrogenic anion channel. Water passes into the canaliculus by osmosis because of the secretion of ions into the canaliculi.

The gastric mucosal barrier protects the gastric lining cells from damage from intraluminal HCI. Its chief component is a thick viscous alkaline mucous layer over 1mm thick that is secreted by the mucous cells. Mucus is secreted by mucous neck cells located in the neck of gastric glands and by surface epithelial cells of the stomach. Mucus is stored in large granules in the apical cytoplasm of mucous neck cells and surface epithelial cells, and is released by exocytosis. The surface epithelial cells secrete a watery fluid that contains Na⁺ and CI^- concentrations similar to those of plasma, but with higher K⁺ and bicarbonate concentrations than that of plasma. Bicarbonate is trapped by the viscous mucus that coats the surface of the stomach; the high bicarbonate concentration makes the mucus layer alkaline. The mucus gel layer separates the bicarbonate-rich secretions of the surface epithelial cells from the acidic contents of the gastric lumen. Thus, the mucus allows the pH of the epithelial cells to be maintained at nearly neutral pH, despite a luminal pH of 2. Mucus also slows the diffusion of acid and pepsins to the epithelial surface cell.

The gastric mucosa is also protected from excessive acidity by an intrinsic feedback mechanism. If the pH of the stomach falls below 2, acid secretion stops. A low pH directly inhibits HCI and gastric secretion. Lowering the pH also releases somatostatin, which inhibits secretion of gastrin by the G cells and HCI by the parietal cells.