Changes in gastrointestinal morphology associated with obstructive jaundice

Abstract

Bacterial translocation has been consistently demonstrated in experimental models of obstructive jaundice. An important factor which promotes this phenomenon is physical injury of the intestinal mucosa. Some previous studies have presented suggestive evidence of this, following bile duct ligation. The aims of this study were to analyse objectively intestinal mucosal morphometric characteristics, to examine for evidence of bacterial translocation, and to assess enterocytes for ultrastructural abnormalities. Adult female Wistar rats were assigned to one of three groups: control (n=8), bile duct ligation (BDL; n=11), or sham operation (n=10). One week later, portal blood, mesenteric lymph nodes, liver, and spleen were harvested and cultured aerobically and anaerobically for evidence of bacterial translocation. Segments of jejunum, ileum, caecum, and large bowel were examined histologically, using light microscopy and morphometrically, using an image analysis system. Electron microscopy was performed on regions of the gastrointestinal tract where significant morphometric alterations had been identified. Significant bacterial translocation was identified following BDL (63. 6% BDL vs. 0% sham vs. 0% control, p<0.01, Fisher's exact test). There was a significant reduction in total mucosal thickness (standard error) [650 microm (23) BDL vs. 731 microm (27) sham vs. 744 microm (95) control] and villous height [451 microm (20) BDL vs. 515 microm (18) sham vs. 559 microm (79) control] in jaundiced animals, compared with sham-operated and control animals (p<0.02, Mann-Whitney U-test). Electron microscopy revealed oedematous change associated with mild inflammation, disruption of desmosomes, and the formation of lateral spaces between enterocytes. In addition, enterocytes showed vacuolation of their cytoplasm and mitochondrial swelling. Increased numbers of bacteria appeared to be attached to the mucosa. These data provide evidence of physical disruption of intestinal mucosa in jaundiced animals, most marked in the distal ileum. Significant bacterial translocation occurs following bile duct ligation and this supports the hypothesis of gut barrier dysfunction with obstructive jaundice.