scholarly journals Conclusive evidence of endotoxaemia in biliary obstruction

Gut ◽  
1998 ◽  
Vol 42 (2) ◽  
pp. 293-299 ◽  
Author(s):  
W D B Clements ◽  
P Erwin ◽  
M D McCaigue ◽  
I Halliday ◽  
G R Barclay ◽  
...  

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.

2008 ◽  
Vol 23 (suppl 1) ◽  
pp. 2-7 ◽  
Author(s):  
Miguel Angel Dias ◽  
Reginaldo Ceneviva ◽  
Jorge Elias Jr. ◽  
Sergio Zucoloto ◽  
Caroline Floreoto Baldo ◽  
...  

PURPOSE: To evaluate liver alterations caused by biliary obstruction and drainage. METHODS: Thirty-nine male Wistar rats were randomly distributed in 4 groups: BO (n=18) bile duct ligation for 20 days, with a periodic evaluation of liver histological alterations, Doppler echography portal flow and measurements of NO and malondialdehyde (MDA); BO/DB (n=13) bile duct occlusion for 20 days followed by biliary drainage by choledochoduodenal anastomosis, 5 days follow-up, same BO group parameters evaluations; group CED (n=4) sham operation and portal flow evaluation trough 20 days; CHB (n=4) sham operation, with hepatic biopsy on 25th day and followed-up trough 25 days, by the same parameters of group BO, with exception of portal flow. Direct bilirubin (DB) and alkaline phosphatase (AP) were evaluated in the group BO, BO/DB and CHB. RESULTS: The bile duct ligation led to an increase of DB and AP, development of liver histological alterations, reduction of portal flow and increase of plasmatic NO and of MDA levels. The bile duct clearing resulted in a reduction of DB, AP, NO, MDA histological alterations and increase of portal flow. CONCLUSION: The biliary occlusion resulted in cholestasis and portal flow reduction, besides the increase of plasmatic NO and of hepatic MDA levels, and histological liver alterations, with a tendency of normalization after the bile duct clearing.


HPB Surgery ◽  
1993 ◽  
Vol 7 (2) ◽  
pp. 99-110 ◽  
Author(s):  
Jin Wen Ding ◽  
Roland Andersson ◽  
Vasile Soltesz ◽  
Roger Willén ◽  
Steffen Loft ◽  
...  

Patients with obstructive jaundice are prone to septic complications after biliary tract operations. Restoring bile flow to the intestine may help to decrease the complication rate. The present study is aimed at evaluating the effect of biliary decompression on bacterial translocation in jaundiced rats.Sixty-six male Sprague-Dawley rats were randomly allocated to six groups subjected to common bile duct ligation (CBDL) and transection (groups 2–6) or sham operation (group 1). In groups and 2 the incidence of enteric bacterial translocation was determined 2 weeks after sham operation or CBDL. In groups 3–6, biliary decompression was achieved by performing a choledochoduodenostomy after 2 weeks of biliary decompression. Bacterial translocation was then studied 1,2,3 and 5 weeks following biliary decompression.The rate of bacterial translocation to mesenteric lymph nodes in obstructive jaundice was significantly higher as compared with controls, and decreased with time to nil three weeks following biliary decompression. The incidence of bacterial translocation was closely correlated (r = 0.844; p = 0.034) with serum alkaline phosphatase activity and seemed to fit with the morphological changes noted in the small intestine. The decrease in bacterial translocation, however, lags behind the recovery of liver function as measured by routine liver function tests and antipyrine clearance.Obstructive jaundice thus promotes bacterial translocation in the rat. Biliary decompression gradually decreases the rate of bacterial translocation.


2003 ◽  
Vol 10 (4) ◽  
pp. 664-669 ◽  
Author(s):  
D. Rohan Jeyarajah ◽  
Mariusz L. Kielar ◽  
Nicole Frantz ◽  
Guy Lindberg ◽  
Christopher Y. Lu

ABSTRACT Cholangitis requires bile duct obstruction and infection. Patients with cholangitis are often more affected than those with infections that reach the liver through the portal vein. We will attempt to study the influences of (i) route of entry and (ii) presence of bile duct obstruction on hepatic infection. C57BL/6 mice received injections of Escherichia coli or lipopolysaccharide into the obstructed bile duct or portal vein and were monitored for survival. Livers were assayed for bacteria, and cytokine mRNA was measured. In order to examine the effect of biliary obstruction on hepatic infection, animals were subjected to bile duct ligation 1 day prior to portal vein injection and were monitored for survival. The 50% lethal dose (LD50) for E. coli injected into the bile duct was 50 CFU/animal; the LD50 for E. coli injected into the portal vein was 5 × 107 CFU/animal. Initial hepatic delivery of bacteria was equivalent 1 h after injection into the bile duct or portal vein. However, by 24 h, a significantly greater amount of bacteria was recovered from the livers of the bile duct-injected group. Interleukin 10 (IL-10) and IL-1RA mRNA was expressed at greater levels in the bile duct-injected group. Prior bile duct ligation followed by portal vein injection resulted in a higher incidence of death than when sham operation was performed prior to portal vein injection. Our data suggest that the increased mortality from cholangitis, compared with that from other hepatic infections, is related to the different route of delivery of pathogen and the maladaptive response (possibly involving IL-10 and IL-1RA) to biliary obstruction itself.


2011 ◽  
Vol 26 (suppl 2) ◽  
pp. 31-37
Author(s):  
Edmilson Rodrigo Daneze ◽  
Guilherme Azevedo Terra ◽  
Júverson Alves Terra Júnior ◽  
Aline Gomes de Campos ◽  
Alex Augusto da Silva ◽  
...  

PURPOSE: To induce a total extra-hepatic obstructive jaundice in swines, by ligation of the common bile duct by laparoscopic surgery. METHODS: Eight swines of the Landrace race, 36-day-old, originated from the same matrix, distributed in two groups. Group A: was used titanium metal clip to the common bile duct ligation in three animals; group B: were ligated with 2-0 cotton thread in five animals. RESULTS: The ligation of the biliary ducts was performed successfully in all animals, with easy identification of the common bile duct by laparoscopy. There weren't difficulties in the procedures, mainly due to the increased surgical field provided by the excellent quality of light and image of the appliance. The clinical signs of jaundice were evident in the animals in seven days. In group A, two animals showed bile duct perforation near the clip, probably due to ischemic necrosis, progressing to peritonitis and death. In group B, five animals showed obstructive jaundice without any amendment. CONCLUSION: Under the conditions of this study, we therefore recommend the use of unabsorbed wires to experimental biliary obstruction, in order to avoid complications, such as ischemia and necrosis, followed by perforation of the wall of the bile ducts.


2014 ◽  
Vol 306 (3) ◽  
pp. G244-G252 ◽  
Author(s):  
Shingo Oya ◽  
Yukihiro Yokoyama ◽  
Toshio Kokuryo ◽  
Masanori Uno ◽  
Kohei Yamauchi ◽  
...  

The objective of this study was to elucidate the role of Toll-like receptor 4 (TLR4) in liver injury induced by biliary obstruction and subsequent intraportal lipopolysaccharide (LPS) infusion in rats. Biliary obstruction often leads to the development of bacterial translocation. Rats were subjected to either a sham operation (Sham group) or bile duct ligation for 7 days (BDL group). Seven days after each operation, LPS (0.5 μg) was injected through the ileocecal vein. In other experiments, rats that had undergone BDL were pretreated, before LPS challenge, with internal biliary drainage (Drainage group); intravenous TAK-242, a TLR4 inhibitor (TAK group); or intravenous GdCl3, a Kupffer cell deactivator (GdCl3group). The expression of the TLR4 protein and the number of Kupffer cells in the liver were significantly increased in the BDL group compared with the Sham group. These changes were normalized after biliary drainage. The expression of TLR4 colocalized with Kupffer cells, which was confirmed by double immunostaining. Serum levels of liver enzymes and proinflammatory cytokines after intraportal LPS injection were significantly higher in the BDL group than in the Sham group. However, pretreatment with TAK-242 or GdCl3strongly attenuated these changes to levels similar to those seen with biliary drainage. These results imply that blocking TLR4 signaling effectively attenuates liver damage to the same level as that observed with biliary drainage in rats with BDL and subsequent intraportal LPS infusion. TAK-242 treatment may be used for patients who are susceptible to liver damage by biliary obstruction and endotoxemia.


2002 ◽  
Vol 282 (4) ◽  
pp. G656-G662 ◽  
Author(s):  
Yuji Tanaka ◽  
Yoshinao Kobayashi ◽  
Esteban C. Gabazza ◽  
Kunihiro Higuchi ◽  
Toshinori Kamisako ◽  
...  

Regulation of bilirubin glucuronide transporters during hyperbilirubinemia in hepatic and extrahepatic tissues is not completely clear. In the present study, we evaluated the regulation of the bilirubin glucuronide transporters, multidrug resistance-associated proteins (MRP)2 and 3, in rats with obstructive jaundice. Bile duct ligation (BDL) or sham operation was performed in Wistar rats. Liver and kidneys were removed 1, 3, and 5 days after BDL ( n = 4, in each group). Serum and urine were collected to measure bilirubin levels just before animal killing. MRP2 And MRP3 mRNA expressions were determined by real-time RT-PCR. Protein expression of MRP2 and MRP3 was determined by Western blotting. Renal MRP2 function was evaluated by para-aminohippurate (PAH) clearance. The effect of conjugated bilirubin, unconjugated bilirubin, human bile, and sulfate-conjugated bile acid on MRP2 gene expression was also evaluated in renal and hepatocyte cell lines. Serum bilirubin and urinary bilirubin excretion increased significantly after BDL. In the liver, the mRNA expression of MRP2 decreased 59, 86, and 82%, and its protein expression decreased 25, 74, and 93% compared with sham-operated animals after 24, 72, and 120 h of BDL, respectively. In contrast, the liver expression of MRP3 mRNA increased 138, 2,137, and 3,295%, and its protein expression increased 560, 634, and 612% compared with sham-operated animals after 24, 72, and 120 h of BDL, respectively. On the other hand, in the kidneys, the mRNA expression of MRP2 increased 162, 73, and 21%, and its protein expression increased 387, 558, and 472% compared with sham-operated animals after 24, 72, and 120 h of BDL, respectively. PAH clearance was significantly increased after BDL. The mRNA expression of MRP2 increased in renal proximal tubular epithelial cells after treatment with conjugated bilirubin, sulfate-conjugated bile acid or human bile. Upregulation of MRP2 in the kidneys and MRP3 in the liver may be a compensatory mechanism to improve bilirubin clearance during obstructive jaundice.


1988 ◽  
Vol 60 (01) ◽  
pp. 025-029 ◽  
Author(s):  
M Colucci ◽  
D F Altomare ◽  
G Chetta ◽  
R Triggiani ◽  
L G Cavallo ◽  
...  

SummaryMicrovascular thrombosis is considered an important pathogenetic factor in renal failure associated with obstructive jaundice but the mechanisms leading to fibrin deposition are still unknown. The plasma levels of plasminogen activator inhibitor (PAI) in 29 patients with obstructive jaundice were found significantly increased as compared to 20 nonjaundiced patients. Fibrin autography of plasma supplemented with tissue plasminogen activator (t-PA) revealed that in icteric samples most of the added activator migrated with an apparent Mr of 100 kDa, corresponding to t-PA-PAI complex, whereas in control samples virtually all t-PA migrated as free enzyme. PAI activity detected in icteric samples is similar to the endothelial type PAI since it is neutralized by a monoclonal antibody against PAI-1.Venous stasis in jaundiced patients was neither associated with an increase in blood fibrinolytic activity nor with a decrease in PAI activity. Immunologic assay showed that t-PA release was impaired in 3 out of 4 patients. In controls, venous occlusion induced an increase in both fibrinolytic activity and t-PA antigen and a reduction in PAI activity. Bile duct recanalization in jaundiced patients subjected to surgery was accompanied by a decrease in plasma PAI activity which paralleled the decrease in serum bilirubin levels. In nonjaundiced patients, surgical treatment did not cause significant changes in either parameter. Rabbits made icteric by bile duct ligation showed an early and progressive increase in plasma PAI activity indicating that obstructive jaundice itself causes the elevation of circulating PAI. It is concluded that obstructive jaundice is associated with a severe impairment of fibrinolysis which might contribute to microvascular thrombosis and renal failure.


2001 ◽  
Vol 16 (2) ◽  
pp. 75-81 ◽  
Author(s):  
Gracinda De Lourdes Jorge ◽  
Luiz Sergio Leonardi ◽  
Ilka de Fatima Santana Ferreira Boin ◽  
Orlando de Castro e Silva Jr ◽  
Cecilia Amelia Fazzio Escanhoela

The aim of this study was to describe a method for the induction of experimental secondary biliary fibrosis (SBF). Forty-seven Wistar rats were submitted to hepatic duct obstruction (OB group) for thirty days without ligature, section or cannulization causing interruption of biliary flow. This technique was carried out by simple traction of the bile duct passing it through the xiphoid appendix. Nine rats were submitted to a sham operation for bile duct stricture and seven rats comprised the control group. Blood samples were collected for the measurement of total bilirubin (TB), alkaline phosphatase (AP), alanine aminotransferase (ALT) and aspartate aminotransferase (AST). Liver fragments were removed for morphological study. Thirty days after surgery TB, AP, ALT and AST levels were significantly increased in the hepatic duct ligation group compared to the sham operated group and the presence of SBF in the OB group was confirmed by morphological study of the liver. There was technical failure in 31.92% cases. The survival was 100% at fifteen days and 82.97% at the end of the experiment. We concluded that this simple surgical technique may be used to study the consequence of bile duct obstruction which could be a reversible process depending on the obstruction time. This technique can be carried out from cholestasis to fibrosis.


2021 ◽  
Vol 5 (02) ◽  
pp. 127-130
Author(s):  
Kazuki Matsushita ◽  
Ken Kageyama ◽  
Natsuhiko Kameda ◽  
Yurina Koizumi ◽  
Akira Yamamoto

AbstractHepatocellular carcinoma (HCC) with bile duct invasion is considered rare. A case in which a fragment of intraductal tumor dropped into the common bile duct after transarterial chemoembolization (TACE) and caused abdominal pain, and obstructive jaundice secondary to biliary obstruction is presented. This case was successfully managed by emergent endoscopic sphincterotomy. Physicians should recognize one of the complications due to TACE for HCC with intraductal tumor invasion.


2012 ◽  
Vol 19 (04) ◽  
pp. 436-441
Author(s):  
ASMA AFZAL KIANI ◽  
RANA HASSAN JAVAID ◽  
ABDUL GHAFFAR ◽  
Shamrez Khan

Objective: To evaluate the validity of ultrasonography in patients who have obstructive jaundice. Design: Descriptive study.Place and duration of study: The study was carried out from September 2006 to May 2008 in department of Radiology Combined MilitaryHospital Quetta. Patients and Methods: A total of 30 patients; 14 male and 16 female underwent operation for obstructive jaundice. All of themhad preoperative ultrasonography. The site and nature of biliary obstruction were noted and the accuracy was determined with per-operativefindings / histological diagnosis as gold standard. Results: The cause of obstructive jaundice identified by ultrasonography with reasonablesensitivity of 90% and specificity of 90% for choledocholithiasis and sensitivity of 55.5% and specificity of 95.2% for pancreatic head tumours.Conclusions: Ultrasonography should be the first and best initial imaging procedure in patients who have obstructive jaundice and showsreasonable sensitivity and specificity to identify causes of obstruction in obstructive jaundice.


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