Whole Blood Manganese Concentrations in Dogs with Congenital Portosystemic Shunts

Abstract

Background: Manganese (Mn) is an essential mineral that is a cofactor for many enzymes required in the synthesis of proteins, carbohydrates, and lipids. Because hepatic clearance is essential in Mn homeostasis, conditions in humans resulting in hepatic insufficiency including cirrhosis and both acquired and congenital portosystemic shunting have been reported to result in increased blood Mn concentrations and increased Mn content in the central nervous system. Because Mn toxicity causes neurologic disturbances, increased Mn concentrations have been implicated in the pathogenesis of hepatic encephalopathy.Hypotheses: Dogs with congenital portosystemic shunts (cPSS) have significantly higher whole blood Mn concentrations than do healthy dogs or those with nonhepatic illnesses.Animals: Eighteen dogs with cPSS, 26 dogs with nonhepatic illnesses, and 14 healthy dogs. Methods: Whole blood Mn was measured by graphite furnace atomic absorption spectrometry. The diagnosis of cPSS was made by ultrasonography or during celiotomy either by visual inspection of a shunting vessel or portovenography.Results: Dogs with a cPSS had significantly higher whole blood Mn concentrations than did healthy dogs and dogs with nonhepatic illnesses. Whole blood Mn concentrations were not significantly different between healthy dogs and dogs with nonhepatic illnesses.Conclusion and Clinical Importance: Dogs with a cPSS have significantly increased whole blood Mn concentrations. Additional studies are warranted to investigate the role of Mn in cPSS-associated hepatic encephalopathy.

Hyperammonemia and Systemic Inflammatory Response Syndrome Predicts Presence of Hepatic Encephalopathy in Dogs with Congenital Portosystemic Shunts

“…This hypothesis is supported by our recent findings that dogs with cPSS have increased whole blood concentrations of manganese and that dogs with a cPSS have higher serum concentrations of C-reactive protein compared to dogs with a cPSS which were asymptomatic, observations which are similar to studies in human HE [9,11,30,31]. We investigated this hypothesis by measuring a range of clinical, haematological and biochemical variables, including plasma ammonia and sodium concentrations and systemic inflammatory response syndrome (SIRS) scores, in 120 dogs with a cPSS both with and without clinical signs of HE.…”

“…Longitudinal and provocative testing would be required to further investigate whether ammonia and inflammation play a causative role in spontaneous HE in dogs with a cPSS. In addition, we did not evaluate all other factors which have been linked to HE in dogs such as manganese [30], gastrointestinal derived endogenous benzodiazepines [46], hypercortisolism [47] and altered tryptophan metabolism [48]. However, our work clearly demonstrates that both ammonia and inflammation predicts the presence of HE in dogs with a cPSS and provides further evidence that dogs with a cPSS are a good spontaneous model of human HE, notably type B HE [1,49].…”

Surgical attenuation of spontaneous congenital portosystemic shunts in dogs resolves hepatic encephalopathy but not hypermanganesemia

“…We have demonstrated that the pathophysiology of HE in dogs with liver disease is very similar to human HE, with ammonia and inflammation playing a key role in the development of neurological abnormalities in dogs with a cPSS (Tivers et al 2014;Shawcross et al 2004Shawcross et al , 2007Gow et al 2012). Crucially, we have also demonstrated that dogs with a cPSS frequently have an increase in Mn concentrations (Gow et al 2010). Consequently, dogs with a cPSS are a highly informative, spontaneous model of human HE in which the pathogenesis of neurological complications associated with liver disorders can be explored without the need for the inducing liver disease in otherwise healthy animals.…”

“…Bile acid measurement was performed on an ILab 650 using a colorimetric, 2 point kinetic fixed time enzymatic reaction by Dialab. Whole blood Mn results from 14 previously reported dogs were used to define a range for healthy dogs (250-1052 μmol/L) (Gow et al 2010).…”

Hepatic encephalopathy in dogs and cats

“…Dogs with CPSS have increased whole blood manganese concentrations compared to healthy dogs . Blood manganese levels have not been reported in cats with HE.…”