Alteration of the renal regulatory hormonal pattern during experimental obstructive jaundice

Abstract

Objective: the alteration of hormones regulating sodium and water status is related to renal failure in obstructive jaundice (OJ).Experimental design: OJ was induced by common bile duct ligation. Samples were obtained from the control (SO) and OJ groups at 24 and 72 hours, and at 7 days. Different parameters related to biliary obstruction, liver and renal injury, and vasoactive mediators such as renin, aldosterone, endothelin-1 (ET-1) and prostaglandin E 2 (PGE 2 ) were studied.Results: bile duct ligation caused an increase in total bilirubin (p < 0.001) and alkaline phosphatase (AP) (p < 0.001). The SO and OJ groups had the same values for diuresis, renin, and creatinine clearance at 24 h. However, animals with OJ had a lower sodium concentration in urine than SO animals (p < 0.01), as well as an increase in aldosterone levels (p < 0.03). ANP levels were moderately increased during OJ but did not reach statistical significance when compared to the SO group. In contrast, OJ animals showed a rise in serum ET-1 concentration (p < 0.001) and increased PGE 2 in urine (p < 0.001).Conclusions: biliary obstruction induced an increase in ET-1 release and PGE 2 urine excretion. These hormones might play a role during the renal complications associated with renal disturbances that occur during OJ. INTRODUCTIONCholestasis is a clinical and biochemical syndrome caused by the impaired bile flow often associated with extrahepatic complications (1). Acute renal failure is a major complication of obstructive jaundice (OJ), with 8% incidence in several series (2). Biliary obstruction was first linked to renal failure in the early study carried out by Clairmont and von Haberer (1910) (3). Several hypotheses have sought to explain the pathogenesis of renal dysfunction in OJ. The depletion of the extracellular compartment (4), myocardial dysfunction, and altered hemodynamic status (5) have been linked to renal failure in biliary obstruction. In addition, severe oxidative stress has been implicated in the renal dysfunction associated to experimental OJ (6,7) as well as other liver diseases (8). Other lines of research have looked at the involvement of vasoactive mediators such as endothelin-1 (ET-1). ET-1 is a powerful paracrine vasoconstrictor that acts by means of specific type-A and type-B receptors. In biochemical terms, it is a 21-amino acid peptide derived from what is known as big ET-1 by the action of the endothelin-converter enzyme. It is synthesized mainly by endothelial cells and to a lesser degree by stellate cells in the liver and biliary epithelium (9,10). ET-1 changes have been related to different human diseases (11). ET-1 both acts on the mesangial cells and causes vasoconstriction in the renal microcirculation, which may contribute -along- Enferm Dig 2009; 101: 408-412.

Morphological Changes in the Endocrine and Exocrine Pancreas of Rats after Experimental Obstructive Jaundice

“…Our results confirmed the presence of CCK-AR immunoreactivity in the majority of β cells as previously reported [12,14,22], and that the immunoreactivity is weaker in the 4-week BDL group than in all the other groups. The results suggest that CCK stimulated the release of insulin from  cells and caused elevated serum insulin levels at 3 days after the BDL.…”

Risk factors for acute kidney injury after partial hepatectomy

“…The presence of biliary obstruction was an independent predictor of postoperative AKI according to the authors’ results, and the mechanism by which bilirubin may be toxic to the kidneys seems to be inflammatory as well as obstructive[35], and hemodynamic changes may also play a role in biliary cast nephropathy[36]. In addition to the aforementioned effects, patients who are candidates for surgery in the presence of biliary obstruction with congestive cholestasis in the liver[37,38] may undergo major hepatic resections, with consequent decrease in the volume of a functionally deficient liver parenchyma, predisposing for PHLF.…”

Do Biliary Salts Have Role on Acute Kidney Injury Development?

“…Hemodynamic changes could also have a role in AKI induced by biliary salts, as shown by Paddillo et al in another experimental study where obstructive jaundice has the ability to increase renin and aldosterone levels. As a result, renal blood flow in this situation is compromised [ 15 ]. That study strengthened the idea that the main mechanism of AKI is indeed functional but with a role of biliary salts underlying (behind) these alterations.…”