Histologic, histochemical and atomic absorption studies on liver tissue from 71 West Highland white terriers are reported. Twenty-seven dogs had histologically normal liver and copper concentration comparable to mongrel control dogs. Forty-four dogs had hepatic copper concentrations up to 22 times the mean copper concentration found in clinically normal mongrel dogs. Hepatitis, hepatic necrosis and cirrhosis were associated with the increased copper concentration in some dogs. Matings between dogs with high liver copper concentration produced pups with high liver concentration. The copper storage defect is inherited.

Histomorphologic, histochemical, and atomic absorption analysis studies were performed on liver tissue from 623 clinically normal purebred and mixed-breed dogs to assess the range of hepatic copper concentrations, the histologic distribution of copper, and the histomorphologic changes associated with the various copper concentrations that were found. Atomic absorption analysis revealed a continuous numerical spectrum ranging from less than 100 parts per million on a dry weight basis (ppm dw) to more than 2,000. No decisive numerical criterion was found that could be used to separate normal from abnormal copper concentrations because of this continuous array. The threshold for histochemical demonstration of copper-containing granules using rhodanine or rubeanic acid staining was 400 ppm dw. At this concentration the copper-containing granules were located in the centrilobular hepatocytes (zone 3 of Rappaport). Copper-containing granules were found in the midzonal and periportal hepatocytes (zones 2 and 1 of Rappaport) in livers with 1,000 ppm dw and higher copper concentrations. The majority of the 623 livers were normal histomorphologically. Multifocal hepatitis characterized by mixed inflammatory cell accumulation and centrilobular distribution was found to be associated with copper concentrations in the range of 2,000 ppm dw or higher. An appropriate upper limit for normal hepatic copper concentration in the dog was not determined based on the present study.

Abstract. Liver tissue from 17 West Highland White Temers (WHWTs) with cirrhosis, subacute bridging necrosis, hepatitis, or massive necrosis were examined for the presence, composition, and distribution of inflammatory foci. Copper analysis was performed on the specimens. The foci of inflammation and necrosis composed a significant part of the lesion in 15 of the samples. The foci were of two types. One, characteristic of idiopathic chronic active hepatitis, consisted of one or two apoptotic hepatocytes attended by lymphocytes and plasma cells. These foci were found primarily in the vicinity of the portal tracts, not associated with centrolobular copper-laden hepatocytes. The other type of focus was characteristic of copper toxicosis. These foci were larger and composed of debris-filled macrophages, lymphocytes, plasma cells, and scattered neutrophils, and on occasion apoptotic hepatocytes were found at the periphery. These foci were always found around the central vein among the copper-laden hepatocytes. Such foci were found only in dogs with copper concentration >2,000 parts/million on a dry weight basis. These morphologic studies show that clinical liver disease in WHWTs is caused by more than one etiologic agent. Among 17 WHWTs with clinical liver disease, two had copper toxicosis, five had idiopathic chronic active hepatitis, and 10 had hepatic disease of undetermined type.