Tuesday, 31 May 2011

Pre - epithelial defense : physicochemical barrier

The Mucus leyer

The mucus layer forms a continuous coat over the gastric epithelium. Bicarbonate is secreted from the epithelium into the mucus layer, where it neutralizes acid that is back-diffused from the lumen of the stomach and forms a pH gradient, with a higher pH at the epithelial cell surface. The mucus layer A continuous layer of mucus gel, secreted by the surface epithelial mucous cells and the mucous neck cells, covers the gastric mucosa. The mucus gel serves as a physical barrier and molecules with the size of pepsin cannot penetrate through diffusion. However, hydrogen ions are able to diffuse through the gel, although their diffusion is approximately four times slower than that through The mucus consists of 5% high molecular weight glycoproteins (106, Allen 1989), called mucins, and 95% water together with electrolytes and small amounts of lipids and proteins, including immunoglobulin.

The surface mucous cells secrete mucins of the MUC5AC type and the mucous neck cells secrete MUC6 mucins. Whether the different mucins exhibit different physical behaviors and physiological functions is still unknown. It has recently been found possible to separate the mucus layer covering and adherent to the corpus mucosa into two different layers, in addition to the loose mucus in the gastric lumen. The most luminal of the two layers, the loosely adherent mucus, can be removed by suction or by rubbing with a cotton tip, while the inner layer, the firmly adherent mucus, cannot be removed by this physical means. The physical properties and physiological importance of the different layers are unknown, as is their composition, and it is not known whether they differ in permeability to acid.

The thickness of the mucus layers depends on the secretion of mucins and the degree of erosion and proteolytic degradation of the layers. Mucus secretion is stimulated by agents such as prostaglandins and nitric oxide, whereas the mucus layer is degraded by pepsin.

Cross-sectional view of the gastric mucosal barrier, with emphasis on the collapse of the mucin-lipid network under the impact of aggressive factors elaborated endogenously (acid, pepsin) or by Helicobacter pylori (protease, lipase, phospholipase A2).

Bicarbonate secretion

The surface epithelial cells secrete bicarbonate into the mucus gel. The bicarbonate neutralizes back-diffused acid and creates a pH gradient in the mucus layer, with a neutral pH at the cell surface when the luminal pH is low. Bicarbonate can be produced from carbon dioxide and water in the gastric mucosal surface epithelial cells by the enzyme carbonic anhydrase. Furthermore, Teorell (1951) demonstrated that for each proton secreted from the parietal cell, one bicarbonate ion is released from the basolateral membrane of the parietal cell to the capillaries of the mucosa. The capillaries are arranged along the gastric glands and are directed toward the surface epithelium. Thus, during acid secretion, bicarbonate will be transported by the blood to the surface epithelium, where it will be available for transport across the surface epithelial cells into the mucus.

Vagal stimulation , prostaglandins, gastric distension, and acid in the gastric lumen all increase gastric bicarbonate secretion. Experiments in vitro have shown that gastric bicarbonate secretion is dependent on luminal chloride ions, indicating the presence of an apical Cl-/HCO3 - exchanger (Flemström 1980). However, the route by which bicarbonate traverses the surface epithelium during acid secretion has not yet been established.

pH gradient in the mucus gel

A millionfold proton concentration gradient can exist between the gastric lumen and the blood, and pH gradients have been found in the mucus layer covering the gastric mucosa by means of inserted pH-sensitive electrodes (Ross et al. 1981, Schade et al. 1994). The gradient succeeds in keeping the epithelial surface neutral (juxtamucosal pH, pHjm) while the lumen pH is 2 in both acid-secreting and non-secreting mucosae. Naturally, bicarbonate secretion is necessary for the creation of a pH gradient. Moreover, the mucus layer is crucial for the existence of a pH gradient, since it consists of an unstirred layer in which neutralization of back-diffused acid by secreted bicarbonate can occur.

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