Diagnostic approach to increased liver enzyme activities in dogs (Proceedings)

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Diagnostic approach to increased liver enzyme activities in dogs (Proceedings)

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Aug 01, 2010
12345Next Elevations of in one or more serum liver enzyme activities (LEA) are a common finding on serum biochemical analysis. Liver enzyme measurements do not reflect liver function but rather hepatocyte membrane integrity, cholestasis and enzyme induction1. Increased LEA is highly sensitive but not specific for liver disease; extrahepatic disorders and normal breed variation can also cause abnormally increased LEA2. Interpretation of abnormal LEA requires consideration of the pattern and magnitude of abnormal LEA, patient factors such as age, breed, medication history, clinical signs, results of routine laboratory testing and whether or not there is evidence to suggest the abnormal LEA may be secondary to a non-hepatic condition1,3. Considered together, these factors will determine whether or not a specific evaluation for hepatobiliary disease is warranted. Increased serum alkaline phosphatase (ALP) activity is the most common and least specific liver enzyme abnormality in the dog1. Multiple forms, or isoenzymes, of ALP exist. The three main ALP iosenzymes in canine serum are liver-ALP (L-ALP), glucocorticoid- ALP (G-ALP) and bone-ALP (B-ALP)1. L-ALP, G-ALP and B-ALP do not leak from damaged cells; rather their expression is induced by intra- or extrahepatic cholestasis, endogenous or exogenous corticosteroids and osteoblast activity, respectively1,4. In healthy, adult dogs, L-ALP accounts for the majority of ALP measured2. Because glucocorticoids can induce G-ALP and L-ALP expression and because G-ALP can be induced by chronic stress and inflammatory mediators associated with systemic illness (including liver disease), identification of the predominant isoenzyme is of little clinical utility1,2. The half-life of ALP in the dog is approximately 70 hours1. Increased serum ALP activity is expected under the following non-hepatobiliary conditions: (1) Breed related increases in ALP activity have been documented in Scottish Terriers (up to 5x higher than other breeds, increases with age), Siberian Huskies and Miniature Schnauzers with hypertriglyceridemia (<2-3 x normal); (2) Mild increase (<2x normal) due to induction of B-ALP may be observed in young, growing animals1,5 ; (3) Induction of B-ALP due to increased osteoblastic activity may also be observed in bone tumours (namely osteosarcoma), secondary renal hyperparathyroidism and osteomyelitis1,6,7 ; (4) Large increases (up to 100 times normal or greater) in serum ALP activity are expected in dogs administered exogenous glucocorticoids1. Topical and ocular steroid formulations may also induce ALP5 , although to a lesser degree; (5) Phenobarbital therapy (2-6 x normal)1 ; (6) Endogenous glucocorticoids (i.e. hyperadrenocorticism); (7) Diabetes mellitus (2-5 x normal mildly increased ALT activity); (8) Hypothyroidism; (9) Mammary neoplasia; and (10) sepsis1,2,7. Increased serum ALP activity is expected under the following hepatobiliary conditions: (1) Marked increases occur in intra- or extrahepatic cholestatic disorders (see below); (2) Marked increases occur in primary or metastatic hepatic neoplasia1,7 ; and (3) Extension of pancreatic inflammation to the liver parenchyma can result in mild to moderate increases in serum ALP and ALT activities. Alternatively, moderate to marked increases in serum ALP activity may result from common bile duct obstruction due to pancreatic inflammation and swelling. 12345Next