CLINICOPATHOLOGIC AND MORPHOLOGIC ALTERATIONS IN NATURALLY-OCCURRING HEPATIC DISEASE AND EXPERIMENTALLY-INDUCED GLUCOCORTICOID HEPATOPATHY IN THE DOG
Abstract
The present study compared the usefulness of serum alkaline phosphatase (ALP), alanine amino transferase (ALT), gamma glutamyl transpeptidase (GGT) and leucine aminopeptidase (LAP) activities, sulfobromophthalein (BSP) retention, and the prothrombin time (PT) and activated partial thromboplastin time (APTT) of serial plasma dilutions for detection of experimentally-induced and naturally-occurring hepatic disease in dogs. In addition, the study characterized the sequential morphologic alterations which occurred in dogs with experimentally-induced glucocorticoid hepatopathy. Glucocorticoid hepatopathy was induced in 2 Beagle dogs with daily intramuscular injections of 4.4 mg prednisone/kg for 14 consecutive days. Serum enzymic activities were monitored and percutaneous hepatic biopsy samples were taken for morphologic examination throughout the 15 day study. Treated dogs showed clinical signs of Cushing's disease. Clinicopathologic studies of treated dogs showed progressive increase of serum ALP, ALT and GGT activities. Serum LAP activity, BSP retention and the coagulation test values remained within the reference intervals throughout the study. Hepatic biopsies and necropsies of treated dogs showed grossly swollen, pale and friable livers with hepatocytic cytoplasmic vacuolation and glycogen accumulation. Extrahepatic lesions included gastric ulceration, catarrhal enteritis, splenic and lymph node atrophy and lymphocytolysis, and vacuolation of adrenal cortical cells of the zona fasciculata. Multiple tissues were collected at necropsy (day 15) from treated and placebo-treated dogs for determination of GGT activity. Tissue GGT activity of placebo-treated dogs was highest in the kidney with less, but marked, activity in the pancreas and much less activity in other tissues. Tissue GGT activity of treated dogs was highest in the pancreas, decreased in kidney, and mildly increased in all other tissues examined. A chronic study of experimentally induced glucocorticoid hepatopathy was done. Clinicopathologic test values for all dogs were similar to those in the acute study. However, serum ALP activity peaked at day 19, serum ALT activity peaked at day 12 and serum GGT activity peaked at day 29. These 3 serum enzymic activities slowly decreased but did not return to baseline (day 0) values throughout the 56 day study. Sequential histopathologic examination of hepatic biopsy samples from treated dogs showed hepatocellular vacuolation and glycogen accumulation persisted throughout the 56 day study. Ultrastructural examination of liver from treated dogs showed principle alterations of abundant glycogen accumulation and decreased numbers of mitochondria within hepatocytes. A separate experiment of this study showed the PT and APTT of serial plasma dilutions to be sensitive indicators of naturally-occurring hepatic disease in dogs. The coagulation tests were equal to serum activities of ALP, ALT and GGT activities and superior to serum LAP activity and BSP retention for detection of hepatic disease. The sensitivity of coagulation tests was enhanced by using serial dilutions of citrated, platelet-poor plasma. Specificity of the coagulation tests for hepatic disease (vs. extrahepatic disease) was good but did not distinguish between different types of hepatic disease. The present study showed dogs are sensitive to hepatic alterations induced by glucocorticoids and that hepatocytic vacuolation and glycogen accumulation are the principle morphologic alterations of glucocorticoid hepatopathy. Induction of increased cellular enzyme synthesis appears to be the cause of increased serum and tissue enzymic activities. Finally, this study showed the PT and APTT of serial plasma dilutions to be sensitive indicators of naturally-occurring hepatic disease in the dog.
Degree
Ph.D.
Subject Area
Pathology
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