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The gastric mucosal barrier

The gastric mucosa is constantly exposed to damaging insults, such as low pH, mechanical irritation, and digestive enzymes. The gastric mucosa has several defense mechanisms against damage by these insults.

The first line of defense consists of the secretion of bicarbonate and mucus by the epithelial cells. For each H+ that is secreted by a parietal cell into the gastric pit, a hydroxyl group is generated, which combines with CO2 to form HCO3-. This HCO3- then reaches the luminal surface through the capillary blood flow from parietal cells, from where it diffuses into the overlaying mucus layer. Mucus se­creted by mucous neck cells lines the luminal surface of the epithelial cells and together with the HCO3- maintains an al­kaline environment, preventing diffusion of gastric acid and pepsin into the tissue.

The structure of the epithelial cells itself constitutes another important defense mechanism against auto-digestion by gas­tric acid. The apical surface of the epithelial cells contains a high proportion of hydrophobic phospholipids that repel gas­tric acid. Additionally, the epithelial cells contain a high con­centration of intracellular bicarbonate that neutralizes any acid that back-diffuses from the gastric lumen into the epithelial cells. Capillary blood flow in between the epithelial cells pro­vides further support in maintaining the local acid-base bal­ance. Additionally, the gastric mucosa has the ability to self­repair when the above-mentioned defense mechanisms fail and cell injury occurs. The high turnover rate of the epithelial cells leads to a rapid regeneration of injured cells. Also, dam­aged mucosal cells secrete mucus that forms a protective layer over the gastric mucosa. Epithelial cells from areas adjacent to the injured cells migrate towards the damaged area and cover the lesion by growing over the basement membrane.

This pro­liferation is due to an enhanced expression of epidermal growth factor (EGF), transforming growth factor-alpha (TGF- alpha), trefoil peptides (TFPs), and nitric oxide (NO). Prostag­landins, particularly prostaglandin E2 and prostacyclin, play a major role in maintaining the integrity of the gastric mucosal barrier. Prostaglandins stimulate mucus and bicarbonate secre­tion, increase gastric mucosal blood flow, and have an effect on the cell regeneration of epithelial cells.

Key Facts

■ Mechanical and enzymatic digestion of food is initiated in the stomach.

■ The gastric mucosa contains several glands that secrete various secretory products including hydrochloric acid, pepsin, mucus, gastrin, and intrinsic factor in dogs.

■ Gastric acid secretion occurs in response to stimulation of histamine, gastrin, and acetylcholine receptors.

■ The gastric mucosal barrier protects the stomach from damage by gastric acid and proteolytic enzymes.

References

1. GeYB, Ohmori J, Tsuyama S et al. Immunocytochemistry and in situ hybridization studies of pepsinogen C-producing cells in devel­oping rat fundic glands. Cell Tissue Res 1998; 293: 121-131.

2. Suchodolski JS, Steiner JM, Ruaux CG et al. Purification and partial characterization of canine pepsinogen A and B. Am J Vet Res 2002; 63:1585-1590.

3. Simpson KW, Alpers DH, De Wille J et al. Cellular localization and hormonal regulation of pancreatic intrinsic factor secretion in dogs. Am J Physiol Gastrointest Liver Physiol 1993; 265: G178-G188.

4. Steiner JM, Berridge BR, Wojcieszyn J et al. Cellular immunolo­calization of gastric and pancreatic lipase in various tissues obtained from dogs. Am J Vet Res 2002; 63: 722-727.

5. Jeusette IC, Lhoest ET, Istasse LP et al. Influence of obesity on plasma lipid and lipoprotein concentrations in dogs. Am J Vet Res 2005; 66: 81-86.

6. Leung WK,Yu J, Chan FK et al. Expression of trefoil peptides (TFF1, TFF2, and TFF3) in gastric carcinomas, intestinal metaplasia, and non-neoplastic gastric tissues. J Pathol 2002; 197: 582-588.

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Source: Steiner J.M. (ed.). Small Animal Gastroenterology. Schluetersche,2008. — 387 p.. 2008

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