A Pathobiochemical Investigation of Glucocorticoid Hepatopathy and Alkaline Phosphatase Isozymes in the Dog
Rippy, Marian Kathleen
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https://hdl.handle.net/2142/71355
Description
Title
A Pathobiochemical Investigation of Glucocorticoid Hepatopathy and Alkaline Phosphatase Isozymes in the Dog
Author(s)
Rippy, Marian Kathleen
Issue Date
1988
Doctoral Committee Chair(s)
Kuhlenschmidt, Mark S.
Department of Study
Veterinary Medical Science
Discipline
Veterinary Medical Science
Degree Granting Institution
University of Illinois at Urbana-Champaign
Degree Name
Ph.D.
Degree Level
Dissertation
Keyword(s)
Agriculture, Animal Pathology
Chemistry, Biochemistry
Abstract
Glucocorticoids administered to dogs produce hepatic histologic changes, characterized by hepatocellular swelling and vacuolization (glucocorticoid hepatopathy), and dramatic serum increases of liver alkaline phosphatase (LALP) and a novel isozyme, corticosteroid alkaline phosphatase (CALP). Using liver biopsy, morphometric techniques and quantitative biochemical and immunochemical analyses to investigate the role of CALP in glucocorticoid hepatopathy, I have determined the early kinetics of: (1) appearance and degree of in vivo hepatocellular swelling, (2) hepatic glycogen accumulation and (3) increases of LALP and CALP in both serum and liver.
Hepatocytes from glucocorticoid treated (GT) dogs were approximatley three-fold greater in cell area than normal hepatocytes. Electron microscopy demonstrated peripheral displacement of cellular organelles and cytoplasmic glycogen accumulation within affected hepatocytes.
During the fifteen day treatment period, increases in LALP and glycogen paralleled the marked hepatocellular swelling. CALP in the liver increased only slightly following initial exposure to glucocorticoids but increased linearly throughout the remainder of the treatment period. The accumulation of glycogen and LALP was correlated to hepatocellular swelling while CALP was not directly involved.
Although CALP is not correlated to hepatocellular swelling, its appearance in serum is diagnostic for canine glucocorticoid hepatopathy. To further investigate the elevations of serum CALP and to gain insight about the mechanism of its production, I examined and compared the mode of membrane attachment to CALP to that of other ALP isozymes elevated in glucocorticoid hepatopathy.
To determine if dog ALP isozymes are anchored to the membrane by a covalent linkage to phosphatidylinositol (PI), suspended hepatocytes and intestinal brush border membranes were incubated with PI-specific phospholipase C and the amount of ALP released determined.
LALP, CALP, and intestinal alkaline phosphatase (IALP) were all, either partially or entirely, attached to their respective membranes through covalent attachment to PI. The percentage of ALP isozymes linked in this manner, however, differs between tissues and between normal and GT-dogs. Glucocorticoids not only affect the mode of IALP attachment in the intestine but cause marked increases in total and specific activities of both soluble and membranous pools of IALP. Glucocorticoids not only exert their effects on the liver but also on the intestine.
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