No abstract

Background-Gram negative septic events are the commonest source of morbidity and mortality as a result of surgery in jaundiced patients. The large intestine provides the major source of Gram negative bacteria in mammals and is implicated in the pathogenesis of systemic endotoxaemia in obstructive jaundice. Bile salts have an important part in maintaining indigenous microecological homeostasis through their emulsifying properties. Aims-The aim was to investigate the effects of biliary obstruction and isolated external biliary diversion on gastrointestinal structure and caecal bacterial flora in relation to bacterial translocation. Method-Six groups of adult male Wistar rats were studied (no operation, sham operated, and bile duct ligated (BDL) for one and three weeks and a choledochovesical fistula (CDVF) for one week). At the end of the study period plasma was assayed for evidence of endotoxaemia and the animals were tested for bacterial translocation to the mesenteric lymph node complex (MLNC), liver, lungs, and spleen. Quantitative and qualitative bacteriological studies were performed on the caecal contents and segments of colon and terminal ileum were washed and prepared for histological assessment. Results-Bacterial translocation was significantly increased in the BDLl (68.8%) and BDL3 (60%) groups compared with the shaml (6.3%), sham3 (9. 1%), No operation (0O/o), and CDVF1 (16.7%) groups. Although translocation was more pronounced in the BDL1 group, this was almost exclusively to the MLNC compared with the more widespread translocation to other organs in the BDL3 group. The BDL3 group was the only group with significantly raised concentrations of endotoxin and anticore glycolipid. The caecal Gram negative aerobic counts were significantly increased in the BDLl and CDVF1 groups compared with all other groups. There was evidence of structural abnormalities in the terminal ileum of rats jaundiced for three weeks, but not in the other groups.Conclusions-Biliary obstruction for one and three weeks promotes bacterial translocation although the mechanisms may be different. Absence of intralumenal bile results in a significant but self limiting increase in the Gram negative aerobic population, which may account for translocation in the early stages of biliary obstruction. As the duration of biliary obstruction increases systemic endotoxaemia is a consistent feature which, combined with factors such as immunological depression and physical disruption of gut barrier function, may promote bacterial translocation perpetuating systemic sepsis.

Intestinal mucosal barrier function in obstructive jaundice was assessed in an animal model and in patients. The effect of internal biliary drainage in patients was also examined. Bile duct ligation for 1 week in the rat resulted in significant bacterial translocation (in seven of 12 animals following ligation versus none of the shamoperated controls, P < 0.01). Intestinal permeability, measured by the urinary recovery of orally administered polyethylene glycol, was also significantly increased (+66.2 per cent for ligation versus -11.6 per cent for sham, P < 0.01). A prospective study was performed on 33 patients with obstructive jaundice undergoing internal biliary drainage, and results were compared with those in six non-jaundiced patients undergoing laparotomy or endoscopic retrograde cholangiopancreatography and in 11 health volunteers. The lactulose: mannitol ratio was used as an intestinal permeability index. Mean(s.e.m.) intestinal permeability assessed before operation was significantly increased in jaundiced patients compared with control patients (0.050(0.010) versus 0.016(0.003), P < 0.005). The mean(s.e.m.) lactulose: mannitol ratio in the healthy volunteers was 0.020(0.003), which was similar to that in control patients. In the jaundiced group of patients the intestinal permeability index fell to within normal levels after 28 days of internal biliary drainage (0.050 before operation versus 0.021 at 28 days, P < 0.02). These data indicate that intestinal barrier function is impaired in obstructive jaundice and that this impairment is reversed by return of bile to the gastrointestinal tract.

Background-Endotoxaemia is implicated in the pathophysiology of obstructive jaundice. The EndoCab enzyme linked immunosorbent assay (ELISA) is a novel assay which measures endogenous antibody (IgG) to the inner core region of circulating endotoxins (ACGA). Aims-To investigate the significance of endotoxaemia in biliary obstruction using the EndoCab assay and assess the specificity of the humoral response to endotoxin compared with an exogenous antigenic challenge (tetanus toxoid, TT). Methods-Three groups of adult male Wistar rats were studied: no operation, sham operation, and bile duct ligation for 21 days (BDL). In the second study, rats rats received prior immunisation with TT. Results-In the preliminary experiment, plasma ACGA was significantly increased in the BDL group (306.6 (18.3)% versus 119.9 (6.7)% and 105.2 (4.6)% in the sham and no operation groups, respectively; p<0.001). Although the mean endotoxin concentration in the BDL group was greater than that in the control groups this was not significant. There was a strong positive correlation between ACGA and endotoxin concentrations (p=0.0021). In the second study mean ACGA after 21 days of BDL was significantly elevated (267.1 (31.2)% versus 101.6 (21.2)% at baseline, p<0.0001). ACGA was unaffected in the other two groups. TT antibody concentrations fell in all three groups; only in the BDL group was the fall significant (97.6 (5.3)% versus 78.8 (4.2)% at baseline, p<0.05). Conclusions-The specific rise in ACGA supports the hypothesis that endotoxin has an integral role in the pathophysiology of obstructive jaundice. The production of anticore glycolipid antibodies specifically reflects systemic endotoxaemia in this model. The EndoCab assay provides a novel, sensitive, and specific method for endotoxin detection. (Gut 1998;42:293-299)