Copper toxicosis with hemoglobinuric nephrosis in three adult sheep

Abstract

Acute and, particularly, chronic copper exposures, along with defects in hepatic copper metabolism, altered excretion of copper, and/or nutritional imbalances between copper and other trace elements, can lead to hepatic accumulation of copper and primary copper toxicosis. There is interspecies variation in susceptibility to copper toxicosis, with sheep being the species most likely to develop this condition. The current report is rather unusual in that it describes instances of naturally occurring copper toxicosis with hemolysis and hemoglobinuric nephrosis in 3 adult sheep. In 2 of these sheep, a possible source of excessive dietary copper was investigated but not definitively identified. In the third goat, the etiologic factors associated with the copper toxicosis were not determined. It appears that mature sheep are susceptible to the hemolytic stage of chronic copper toxicosis, which was not observed in a recent, large-scale copper intoxication involving lactating dairy sheep (3, 5, 6, 12). Copper analyses on both kidney samples were necessary to confirm the diagnosis of copper toxicosis in all 3 sheep. All feedstuffs associated with instances of copper toxicosis should be analyzed for iron, molybdenum, sulphur, and zinc as well as copper to determine what nutritional factors are contributing to the pathogenesis of this disease. Consideration also should be given to the ingestion of hepatotoxic plants and other toxic exposures, which could predispose an animal to secondary chronic copper toxicosis (4, 7, 8, 11). It is thought that sheep are predisposed to chronic copper toxicosis because of their reduced biliary and urinary excretion of copper, the distribution of zinc- and copper-binding proteins in the liver, and the relatively small difference between the copper concentrations reported to be adequate for sheep rations (5–10 mg/kg, 7–11 mg/kg, or 10–20 mg/kg on a dry matter basis, depending on the reference) and those dietary copper concentrations considered to be potentially toxic (>15, 20, or 30 mg/kg on a dry matter basis). In contrast, cattle, horses, swine, and poultry tend to be more resistant to copper accumulation and chronic copper toxicosis, with maximum tolerable dry matter concentrations of dietary copper being approximately 50 mg/kg for cattle and horses, 250 mg/kg for swine, and 300–500 mg/kg for poultry. In a previous study, ponies were even reported to tolerate dietary copper concentrations approaching 800 mg/kg for 6 months. However, histopathologic examinations of the kidney were not apparently performed, and it is extremely important to recognize that copper bioavailability and dietary concentrations of molybdenum also play important roles in the pathogenesis of chronic copper toxicosis (9, 10, 13)