Gastroduodenal mucus and bicarbonate: the defensive zone.

The surface mucosa of the stomach and duodenum is frequently exposed to a potentially corrosive mixture of hydrochloric acid and pepsin and intraluminal pH is often between 1 and 2. Such acidity would be injurious to ordinary epithelia so that it is clear that mechanisms exist to protect the stomach and duodenum under normal circumstances. The notion that gastric mucus and non-parietal gastric alkali secretion may be able to provide such protection is not new, having been proposed by Heatley as long ago as 1959 [1], but only recently have experimental techniques allowed this hypothesis to be tested. Gastric mucus consists of a glycoprotein tetramer whose structure determines its physical properties of adherence, elasticity and flow [2]. The polymeric structure of high molecular weight causes individual molecules to overlap in surface mucus resulting in gel formation [3] and the resultant layer can substantially reduce the rate of flow of hydrogen ions across it [4]. The sulphide bonds which bind the subunits are broken down by luminal pepsin [5] resulting in glycoprotein monomer or soluble mucus without the ability to form a gel. The adherent mucus gel layer is therefore in an equilibrium with fresh secretion from goblet cells continually replenishing that eroded from the surface. The thickness of this dynamic layer has now been measured both in experimental animals [6] and in man [7] using fresh unfixed specimens since ethanol used to fix specimens causes degradation and shrinkage of the gel layer. It is clear from such observations that the layer is continuous in vivo but has a variable thickness of 5-200,um in man [7]. Mucus gel is therefore clearly a potentially protective layer, and the mechanism by which this may occur has become clearer since the discovery of bicarbonate secretion from both gastric and proximal duodenal mucosa [8]. For many years such secretion had been inferred from the electrolyte content of gastric juice [9] but only since the advent of powerful inhibitors of the quantitively much greater acid secretion has bicarbonate secretion been convincingly demonstrated. We now know that the surface epithelium of both stomach and duodenum of experimental animals and man secretes endogenous alkali by an active process [10]. In the stomach bicarbonate is secreted at a basal rate amounting to 5-10 per cent maximal acid output [11], whilst duodenal mucosa secretes alkali at twice the rate of basal gastric bicarbonate production [12]. The gastric fundus appears to transport bicarbonate by a purely metabolically dependant process but in both antrum and duodenum around 30 per cent alkalinization is due to passive transfer [13]. Cellular mechanisms of secretion also appear to differ between gastric and duodenal mucosa, being chiefly electroneutral C1/HCO3 exchange in the stomach but electrogenic HCO3 transport in the duodenum [10]. Control mechanisms of gastroduodenal