Abstract

Measuring duodenal epithelial intracellular pH (pH_i), blood flow and mucus gel thickness (MGT), we studied duodenal defense mechanisms in vivo so as to more fully understand the protective mucosal response to luminal acid. Exposure of the mucosa to physiologic acid solutions promptly lowered pH_i, followed by recovery after acid was removed, indicating that acid at physiologic concentrations readily diffuses into, but does not damage duodenal epithelial cells. Cellular acid then exits the cell via an amiloride-inhibitable process, presumably sodium-proton exchange (NHE1). MGT and blood flow increase promptly during acid perfusion; both decrease after acid challenge and are inhibited by vanilloid receptor antagonists or by sensory afferent denervation. Bicarbonate secretion does not increase during acid perfusion but increases following acid challenge. Inhibition of cellular alkali uptake by anion transport inhibitors lowers pH_i, and increases mucosal injury, whereas inhibition of apical alkali secretion alkalinizes pH_i and diminishes injury. These observations support the following hypothesis: luminal acid diffuses into the epithelial cells, lowering pH_i. Acidic pH_i increases the activity of a basolateral NHE, acidifying the submucosal space and increasing cellular alkali loading. The acidic submucosal space activates capsaicin receptors on afferent nerves, increasing MGT and blood flow. With continued acid exposure, a new steady state with thickened mucus gel, increased blood flow, and a higher cellular buffering power protects the mucosa from acid injury. After acid challenge, mucus secretion, blood flow and pH_i return to normal, while bicarbonate secretion increases. Through these integrated mechanisms, the epithelial cells are protected from damage due to repeated pulses of concentrated gastric acid. (Keio J Med 51 (1): 29-35, March 2002)

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