Impaired Proximal Duodenal Mucosal Bicarbonate Secretion in Patients with Duodenal Ulcer

Abstract

The defensive factors that prevent the human duodenal mucosa from acidic and peptic damage have not been fully evaluated. To determine whether duodenal mucosal bicarbonate production was altered in patients with inactive duodenal ulcer, we measured basal and acid-stimulated bicarbonate output from the duodenal bulb and the distal duodenum in healthy subjects and patients with inactive duodenal ulcer. As compared with 16 normal subjects, the 12 patients had significantly less mean (+/- SE) basal proximal duodenal mucosal bicarbonate secretion (185 +/- 13 vs. 107 +/- 18 mumol per centimeter per hour; P less than 0.001). Moreover, in response to a physiologic amount of hydrochloric acid (2 mmol per five minutes) instilled directly into the duodenal bulb, peak proximal duodenal bicarbonate output in the patients was 41 percent of the normal response (263 +/- 65 vs. 642 +/- 77 mumol per centimeter per hour; P less than 0.01). There was little overlap between groups. In contrast, bicarbonate outputs in the distal duodenum were similar in the two groups. We conclude that most patients with duodenal ulcer disease have decreased proximal duodenal mucosal bicarbonate production at rest, in response to hydrochloric acid, and in relation to peak gastric acid secretion. Impaired proximal duodenal mucosal bicarbonate secretion may be an important factor in the development and natural history of duodenal ulcer.

Stimulation by nizatidine, a histamine H2-receptor antagonist, of duodenal HCO3-secretion in rats: relation to anti-cholinesterase activity

“…A number of studies demonstrated a close relationship between the mucosal ulcerogenic response and the duodenal HCO 3 -disorder [12,13,29] . Indeed, it is reported that patients with inactive duodenal ulcers have decreased production of HCO 3 -in the proximal duodenum during exposure to acid [30] , though the exact mechanism involved remains unknown. In the present study, perfusion of the proximal duodenum with 100mM HCl for 4h produced extensive hemorrhagic damage in rats in the presence of indomethacin.…”

Calcium-sensing receptor stimulates Cl−- and SCFA-dependent but inhibits cAMP-dependent HCO3− secretion in colon

“…Regulated HCO 3 Ϫ secretion is also required for mucosal defense against luminal acid (via neutralization) in the upper gastrointestinal (GI) tract and bacteria (via stimulation of mucus secretion and maintenance of intestinal barrier function) in the lower GI tract, the defect of which has been shown to be a risk factor for peptic ulcer diseases (2,20,28) and intestinal inflammation (24,51,52). The role of CaSR in basal and acid-induced HCO 3 Ϫ secretion is unknown although a recent study with gut-specific CaSR knockout mice suggests that this receptor is crucial for mucosal defense and immunity (15).…”

Isoflurane-induced acidosis depresses basal and PGE2-stimulated duodenal bicarbonate secretion in mice

“…Duodenal mucosal bicarbonate secretion (DMBS) is considered the main mechanism in duodenal protection against acid discharged from the stomach, and this secretion is impaired in patients with acute and chronic duodenal ulcer disease (14). Acid in the duodenal lumen is the main physiological stimulus of bicarbonate secretion, and the HCl-induced rise in secretion is in part mediated by endogenous prostaglandins and neural reflexes (25).…”