The role of mucus in the protection of the gastroduodenal mucosa.

There is good evidence that the adherent mucus plays an important role in the protection of gastroduodenal mucosa from the endogenous aggressors acid and pepsin. Adherent mucus provides a stable unstirred layer which supports surface neutralization of acid by mucosal bicarbonate output and acts as a permeability barrier to luminal pepsin. The adherent mucus layer is continuous. True thickness of the mucus layer and its continuity can only be observed on unfixed sections of mucosa, since histological fixatives and preparation for electron microscopy can cause dehydration and shrinkage of the mucus gel. The structure of adherent gastric mucus is deficient in patients with peptic ulcer disease because of decreased polymerization of the component glycoproteins. This impairment of the mucus barrier is associated with raised amounts of pepsin 1, which digests the mucus layer more aggressively than the major pepsin, pepsin 3, under conditions that pertain both in the stomach (pH 2) and duodenum (pH 4-5). Adherent mucus does not appear to offer much protection against exogenous damaging agents, e.g. alcohol and aspirin. These agents permeate the mucus barrier, damaging the underlying epithelium. The subsequent epithelial repair process is protected by a gelatinous coat over ten times thicker and distinct from the normal adherent mucus layer. Our recent studies show this gelatinous coat to be primarily a fibrin-based gel with mucus and necrotic cells.