study of the possible effects of acute common bile duct ligation on some hepatorenal functions, some cytokines, free radicals and gastric secretion [an experimental study]

Obstructive Jaundice is a clinical manifestation of a disease of biliary system. Jaundiced patients have an increased risk of morbidity and mortality compared with those without jaundice. Renal impairment is extremely common in the presence of obstructive jaundice with 60-75% of patients develop a drop in post operative glomerular filtration rate with the development of postoperative renal failure. Several important features appear to be important in the development of reticuloendothelial dysfunction and allows endotoxin to spill over into the systemic circulation causing impairment of immune function leading to systemic complications. In addition to the oxidative stress caused by the oxygen free radicals, the pro-inflammatory cytokines play a role in obstructive jaundice as well as in the pathogenesis of renal impairment in jaundiced patients. Gastric secretion is impaired with obstructive jaundice and the resulting uremia. The aim of the present study is to investigate the effect of common bile duct ligation on some hepatic and renal functions experimentally in dog, [Part I], some cytokines, nitric oxide and free radicals [Part II] and gastric secretion [Part III]. The study group consisted of 8 dogs of average weight 14.5kg. Biochemical analysis of total serum bilirubin [TSB], alkaline phosphatase [ALP]aspartate aminotransferase [AST], alanine aminotransferase [ALT], albumin, creatinine, urea, sodium [Na[+]] and potassium [k[+]], [part I] tumour necrosis factor alpha [TNF-alpha], interlukine one beta [IL-1 beta], nitric oxide [NO], and malondialdhyde [MDA], [part II], were estimated before common bile duct ligation [CBDL] and on the 2[nd], 5[th] and 8[th]day from ligation. Basal gastric secretion was collected simultaneously and measured for volume with determination of the free and total acidity and pepsin activity [part III] In part I of this study the results showed that CBDL resulted in highly significant increase in TSB, AST, ALT and ALP, on the 5[th] and 8[th] day from ligation [P<0.001]. Only ALP showed a significant increase on the 2[nd] day of ligation [P<0.05], while the other parameters showed insignificant increases [P>0.05]. Blood urea, serum creatinine, Na[+] and k[+] levels and the total proteins in urine were insignificantly increased in the sample taken on the 2[nd] day from ligation [P>0.05] whereas all these parameters showed significant increases in the samples taken on the 5[th] and 8[th] day from ligation [P<0.05]. In part II of this study the results showed highly significant increases of NO and MDA from the first sample on the 2[nd] day from ligation [P<0.001] and still high throughout the study. As regards TNF-alpha and IL-1-beta both showed insignificant changes on the 2[nd] day from ligation while they showed significant increases of both levels on the 5[th] and 8[th] day from ligation [P<0.05]. In part III of this study the results showed a highly significant reduction of the volume of gastric secretion and a highly significant increase in the concentration of both free and total acidity as well as pepsin activity [P<0.001] on the 5[th] and 8[th] day from ligation.During the first 48 hours of ligation significant increases of the volume of gastric secretion, concentration of both free and total acidities and in pepsin activity [P<0.05]. In conclusion at the end of part I of this study we concluded that during the first 48 hours of acute common bile duct obstruction, the hepatic and renal functions show no impairment which worsen later on.So early surgical interference in obstructive jaundice should take place as early as possible before the liver and kidney functions start to be impaired. At the end of part II of this study we concluded that pro-inflammatory cytokines and free radicals have to be considered in dealing with obstructive Jaundiced patients with enhancement of the role of antioxidants and anti-inflammatory agents as a part of the management. At the end of part III of this study we concluded that gastric hypersecretion occurs early in acute obstructive jaundice while gastric hyposecretion occurs in prolonged period of obstruction. This is of benefit during the management of obstructive Jaundiced patients according to the period of obstruction as each condition has its own medication to prevent gastric troubles. Correlation of the parameters measured in these three parts of this study is of great value to evaluate the condition of the patient according to the period of obstruction and giving him an appropriate dealing either medically or surgically