Overview of Copper Poisoning

Acute copper poisoning causes severe gastroenteritis characterized by abdominal pain, diarrhea, anorexia, dehydration, and shock. Hemolysis and hemoglobinuria may develop after 3 days if the animal survives the GI disturbances. The sudden onset of clinical signs in chronic copper poisoning is associated with the hemolytic crisis. The time of onset is influenced by the concentration of copper in the diet. Signs in affected animals include depression, lethargy, weakness, recumbency, rumen stasis, anorexia, thirst, dyspnea, pale mucous membranes, hemoglobinuria, and jaundice. Several days or weeks before the hemolytic crisis, liver enzymes, including ALT and AST, are usually increased. During the hemolytic crisis, methemoglobinemia, hemoglobinemia, and decreases in PCV and blood glutathione are usually seen. In camelid species such as alpacas or llamas, no hemolytic crisis is seen, although extensive liver necrosis remains a consistent manifestation. Morbid animals often die within 1–2 days. Herd morbidity is often <5%, although usually >75% of affected animals die. Losses may continue for several months after the dietary problem has been rectified. Severe hepatic insufficiency is responsible for early deaths. Animals that survive the acute episode may die of subsequent renal failure. Photosensitization may occur in association with chronic copper poisoning, reflecting the hepatotoxicity common to both syndromes. Cirrhosis of the liver is also associated with the syndrome in dogs.

Evidence of blue-green ingesta and increased fecal (8,000–10,000 ppm) and kidney (>15 ppm, wet wt) copper levels are considered significant in acute copper poisoning. In chronic poisoning, blood and liver copper concentrations are increased during the hemolytic period. Blood concentrations often rise to 5–20 mcg/mL, as compared with normal levels of ~1 mcg/mL. Liver concentrations >150 ppm (wet wt) are significant in sheep. The concentration of copper in the tissue must be determined to eliminate other causes of hemolytic disease. Molybdenum tissue concentrations should be evaluated to determine whether the syndrome is due to primary or secondary chronic copper poisoning.

Often, treatment is not successful. The prognosis is poor in all species. GI sedatives and symptomatic treatment for shock may be useful in acute toxicity. Penicillamine (50 mg/kg/day, PO, for 6 days) or calcium versenate may be useful if administered in the early stages of disease to enhance copper excretion. Vitamin C (500 mg/day/sheep, SC) has been shown to reduce oxidative damage to RBCs during the hemolytic crisis. Ammonium tetrathiomolybdate (1.7 mg/kg, IV, every other day for 6 days) is effective for the treatment and prevention of copper poisoning. This treatment, which reduces copper absorption and enhances copper elimination, should be used conservatively. A withdrawal period of ~10 days is required for this medication. Daily oral administration of ammonium molybdate (100 mg) and sodium thiosulfate (1 g) for 3 wk reduces losses in affected lambs. Dietary supplementation with zinc acetate (250 ppm) may be useful to reduce the absorption of copper. Plant eradication or reducing access to plants that cause phytogenous or hepatogenous copper poisoning is desirable. Primary chronic or phytogenous poisoning may be prevented by top-dressing pastures with 1 oz of molybdenum per acre (70 g/hectare) in the form of molybdenized superphosphate or by molybdenum supplementation or restriction of copper intake. High-risk flocks of sheep may be supplemented with sodium thiosulfate in the diet to prevent or control chronic copper poisoning. In dogs, genetic testing is available to identify carriers of the autosomal recessive gene associated with abnormal copper accumulation, although the mode of inheritance is not known for all susceptible breeds. Periodic liver biopsies, tissue copper determination, and liver enzyme assessment may also be useful to evaluate disease status. In addition to previously described treatments, zinc supplementation and prednisone or prednisolone administration enhance copper excretion and limit development of liver disease.