Attenuation of Congenital Portosystemic Shunt Reduces Inflammation in Dogs

Liver disease is a major cause of morbidity and mortality. One of the most significant complications in patients with liver disease is the development of neurological disturbances, termed hepatic encephalopathy. The pathogenesis of hepatic encephalopathy is incompletely understood, which has resulted in the development of a wide range of experimental models. Congenital portosystemic shunt is one of the most common congenital disorders diagnosed in client owned dogs. Our recent studies have demonstrated that the pathophysiology of canine hepatic encephalopathy is very similar to human hepatic encephalopathy, which provides strong support for the use of dogs with a congenital portosystemic shunt as a naturally occurring model of human hepatic encephalopathy. Specifically, we have demonstrated an important role for ammonia and inflammation in the development of hepatic encephalopathy in dogs with a congenital portosystemic shunt. Despite the apparent importance of inflammation in driving hepatic encephalopathy in dogs, it is unclear whether inflammation resolves following the successful treatment of liver disease. We hypothesized that haematological and biochemical evidence of inflammation, as gauged by neutrophil, lymphocyte and monocyte concentrations together with C-reactive protein concentrations, would decrease following successful treatment of congenital portosystemic shunts in dogs. One hundred and forty dogs with a congenital portosystemic shunt were enrolled into the study. We found that the proportion of dogs with a monocyte concentration above the reference range was significantly greater in dogs with hepatic encephalopathy at time of initial diagnosis. Importantly, neutrophil and monocyte concentrations significantly decreased following surgical congenital portosystemic shunt attenuation. We also found a significant decrease in C-reactive protein concentrations following surgical attenuation of congenital portosystemic shunts. Our study demonstrates that haematological and biochemical indices of inflammation reduce following successful treatment of the underlying liver disorder

Pathogenesis of ascites and hepatorenal syndrome.

Ascites is one of the most common complications of cirrhosis and has a one year mortality of up to 50%. For fluid to accumulate in any clinical situation the amount of sodium ingested must exceed that excreted by the kidneys and the virtual absence of sodium from the urine of ascitic patients was first documented by Farnsworth and Krakusin in 1948. Five years later Chart and Shipley showed such patients to have an excess of a sodium retaining hormone in their urine (later identified as aldosterone). Four decades after these discoveries the inter-relationship between renal function, hormonal changes and ascites formation remains controversial. At the other extreme of functional renal changes up to 85% ofpatients dying with cirrhosis have renal failure and, where there is no apparent cause other than the liver disease, is termed 'hepatorenal syndrome. In 1863 Flint noted that proteinuria was uncommon and kidney morphology often normal, but some patients showed a variety of renal parenchymal changes Hecker and Sherlock confirmed the absence of proteinuria and normal histology in many patients and reported very low urine sodium concentrations - findings of a prerenal type of uraemi