Overview of gastroduodenal mucosal protection

The ability of the gastric mucosa to resist autodigestion has been recognized for over 200 years. Since these early observations, several components of gastroduodenal defense against injury from damaging luminal contents have been identified. The first line of defense is the thick layer of mucus gel into which bicarbonate is secreted by the underlying epithelial cells. The "mucus-bicarbonate" barrier sustains a pH gradient between the lumen and cell surface such that epithelial cells are maintained at pH 7 to 8, despite the presence of intraluminal acid. The epithelial cells form a second line of defense; since the pH gradient may be overwhelmed by physiologic concentrations of intraluminal acid, this mechanism may be important in maintaining mucosal integrity. The physical properties of the apical cell membrane and intercellular junctions and the presence of surface-active phospholipids on the membrane may be responsible for preventing hydrogen ions (H+) from diffusing into the mucosa by providing a physical barrier to their movement. Furthermore, epithelial cells are capable of rapid turnover and migration and may breach a defect in the epithelium within hours. The aftermath of mucosal damage may generate a further defense mechanism: a thick layer of mucus containing sloughed epithelial cells together with passive movement of bicarbonate-rich fluid from the damaged mucosa. This may prevent exposure of undamaged cell nests to acid and thus aid re-epithelialization. Finally, mucosal blood flow plays a vital role in maintaining epithelial integrity. Studies have shown that increasing or decreasing mucosal blood flow will, respectively, reduce or enhance susceptibility to damage. Although the precise physiologic control mechanisms for mucosal protection have not been defined, there is evidence that local endogenous prostaglandin metabolism may play an important role [4]. The release of neurotransmitters and hormones may also contribute to or modulate the defense mechanisms.