Bile salt composition and concentration as determinants of canine gastric mucosal injury

Qualitative as well as quantitative differences in bile salts could be the reason why some patients with bilious reflux into the stomach developed gastritis or gastric ulcers, whereas others do not. The authors examined the hypothesis that both the composition and concentration of a bile salt solution determine the degree of damage to the gastric mucosa. First, they studied the effects of two mixtures of bile salts containing high and low levels of deoxycholate within the range of that found in man. They tested these solutions on the fundic gastric mucosa in Heidenhain pouches of five mongrel dogs. Net acid back diffusion (NABD) was measured by a recirculating system incorporating at pH stat, and transmucosal potential difference (PD) was recorded in a standard manner. Mixtures of the taurine conjugates of the sodium salts of cholate (TC), chenodeoxycholate (TCDC), and deoxycholate (TDC) were studied at pH 2. Bile mixture A (low TDC) consisted of 10% TDC, 20% TCDC, and 70% TC; mixture B (high TDC) consisted of 35% TDC, 35% TCDC, and 30% TC. At 3 mM concentration, bile salt mixture B increased NABD from 54 ± 23 to 101 ± 11 μEq/10 min (P < 0.05), whereas mixture A increased NABD slightly from 66 ± 11 to 72 ± 15 μEq/10 min (NS). In the same experiments, PD was reduced 18 ± 2 mV by mixture B, but only 10 ± 2 mV by mixture A (P < 0.05). Thus the mixture high in TDC was more damaging than the mixture low in TDC at 3 mM concentrations. At 1 mM, neither mixture was damaging, and at 5 mM both were similarly damaging. In a second series of experiments each of the three bile salts was tested individually at 5 mM concentration, and TDC produced greater increases in NABD and decreases in PD than either TC or TCDC. These findings are consistent with the hypothesis that damage to the gastric mucosa depends on the concentration as well as the composition of the bile salt mixture present.