Morphological changes of the small-intestinal mucosa of guinea pig and hamster following incubation in vitro and perfusion in vivo with unconjugated bile salts.

Incubation in vitro of the intestine of the hamster and guinea pig with 5 mM sodium cholate and with 2 mM sodium deoxycholate and sodium chenodeoxycholate resulted in significant morphological changes compared with control incubations. Generally, no major differences were observed between proximal and distal small intestine or between the species used. Only when guinea pig intestine was incubated with 5 mM cholate was less damage found proximally than distally. Perfusion in vivo of the intestine of the hamster and guinea pig with Krebs-Ringer phosphate results in separation of the epithelium from the lamina propria without excessive shedding of epithelial cells from villous tips. This change was also seen in specimens taken before perfusion and probably represents unavoidable trauma during handling of the intestine. In contrast to studies in vitro, regional differences are readily demonstrable with perfusion of bile salts in vivo. Dihydroxy bile salts produce more marked alterations of both proximal and distal small intestine than the trihydroxy bile salt, sodium cholate. Dihydroxy bile salts result in significantly greater alterations in proximal than in distal mucosa. When 5 mM cholate at pH 6.8 is perfused in the guinea pig, absorption occurs approximately 30 times more rapidly from distal than from proximal segments, while in proximal segments 2 mM chenodeoxycholate is absorbed approximately 15 times more rapidly than 5 mM cholate. A correlation is suggested between the morphological alteration produced in the region of the small intestine by a bile acid and the amount of bile salt passing through the cell. Furthermore, it is proposed that the ileal cells may be damaged to a lesser extent by bile acids normally found in that particular species.