Hemolytic Crisis in a Dog with Copper-Associated Chronic Hepatitis
Background: Copper is an essential micronutrient for the body to function properly. However, although it is a vital element, an excess of copper in the body is extremely toxic. Copper toxicity has been reported mainly in sheep. In dogs, clinicopathological signs of toxicity are characterized by chronic liver failure. This means that the hemolytic crisis so common in sheep is a condition rarely associated with toxicity in dogs, so there are very few descriptions of this condition in the veterinary literature. The purpose of this report is to describe a case of hemolytic crisis in a dog with copper-associated chronic hepatitis.
Case: A medium-sized 6-year-old bitch was brought to the Veterinary Hospital of the Federal University of Santa Maria, with clinical presentation of apathy, anorexia and red urine. A physical examination revealed mildly jaundiced mucosa and dark brown urine. A urinalysis indicated the presence of protein, bilirubin and occult blood. The blood count revealed hypochromic macrocytic anemia, leukocytosis due to left shift neutrophilia and thrombocytopenia. Serum biochemistry showed elevated levels of alanine aminotransferase and alkaline phosphatase. The animal was given a blood transfusion due to the severity of her anemia, but her clinical condition worsened and she died, whereupon her body was sent for necropsy. This necropsy revealed conspicuous signs of jaundice, splenomegaly and altered liver and kidney color. The liver was brownish, with its natural surface firm and slightly irregular. The kidneys were diffusely blackened. The urine was dark brown. Fragments of different organs were collected, fixed in 10% buffered formalin solution, routinely processed for histopathology and stained with hematoxylin and eosin. A histological dissection of the liver showed the hepatic lobes dissected by fibrosis, forming islands of hepatocytes and numerous lymphocytes and plasmocytes. Brown granular pigment was observed in periportal hepatocytes. Perls Prussian blue and rubeanic acid staining techniques were performed to characterize this pigment. Most of the pigment reacted strongly to rubeanic acid and but not to Perls’ Prussian blue, thus characterizing it as copper. Random hepatic necrosis was visible. The kidneys contained hemoglobin and necrotic epithelial cells obstructing the renal tubules. Based on the clinical and anatomopathological aspects, a diagnosis of hemolytic crisis due to copper-associated chronic hepatitis was established.
Discussion: The most accepted mechanism to explain the occurrence of hemolysis is that copper long stored in hepatocytes is massively released into the bloodstream due to some stressful condition. When too much copper circulates in the bloodstream it inhibits enzymes that act on the energy metabolism of red blood cells, thereby lowering the synthesis of energy and nucleotides needed for glutathione activity, and causing hemoglobin to transform into methemoglobin. In the case reported here, copper toxicosis presumably originated from the animal’s diet since, according to the literature, the periportal distribution of copper revealed during histology suggests that the event resulted from excessive copper intake or was secondary to previous cholestatic liver injury. This paper describes a case of hemolytic crisis in a dog with copper-associated chronic hepatitis and, emphasizes the importance of including copper toxicity as a differential diagnosis for dogs presenting hemolytic crisis, in order to assist veterinarians in managing their patients.
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