Clinical and pathophysiologic studies of increased alkaline phosphatase isoenzymes in the liver and serum of dogs
Solter, Philip Frederick
This item is only available for download by members of the University of Illinois community. Students, faculty, and staff at the U of I may log in with your NetID and password to view the item. If you are trying to access an Illinois-restricted dissertation or thesis, you can request a copy through your library's Inter-Library Loan office or purchase a copy directly from ProQuest.
Permalink
https://hdl.handle.net/2142/20188
Description
Title
Clinical and pathophysiologic studies of increased alkaline phosphatase isoenzymes in the liver and serum of dogs
Author(s)
Solter, Philip Frederick
Issue Date
1994
Doctoral Committee Chair(s)
Hoffmann, Walter E.
Department of Study
Pathobiology
Discipline
Pathobiology
Degree Granting Institution
University of Illinois at Urbana-Champaign
Degree Name
Ph.D.
Degree Level
Dissertation
Keyword(s)
Biology, Veterinary Science
Language
eng
Abstract
The clinical and pathophysiologic conditions necessary for liver alkaline phosphatase isoenzymes to increase in canine blood were examined. It was first shown by a clinical study that increased serum activity of the corticosteroid-induced isoenzyme of alkaline phosphatase (CALP), which is unique to dogs, occurs in many different disease states. Further studies were performed to determine the possible underlying mechanisms responsible for this increase. Using gas chromatography/mass spectrometry it was shown that both CALP and liver alkaline phosphatase (LALP) purified from canine serum, contain myo-inositol residues in near equimolar amounts to the respective alkaline phosphatase monomer. This is consistent with release of alkaline phosphatase from hepatocyte membranes by endogenous glycosyl-phosphatidylinositol phospholipase D (GPI-PLD). Release of CALP and LALP into serum by GPI-PLD activity was supported by Western blot analyses using anti-cross reacting determinant antibodies and non-denaturing polyacrylamide gel electrophoresis.
Results of hepatic nuclear scintigraphy and transmission electron microscopy suggested that cholestasis is minimal in dogs with experimentally-induced glucocorticoid hepatopathy. Paired serum samples from 11 clinically diseased dogs showed that the ratio of CALP to LALP activity in bile was substantially different from the ratio in serum. Histochemical stains revealed alkaline phosphatase activity on the sinusoidal surfaces of hepatocytes in dogs with glucocorticoid hepatopathy. From these findings, it was concluded that serum alkaline phosphatase activity likely originates from the sinusoidal surfaces of hepatocytes rather than from bile regurgitation.
Further experiments performed using isolated canine hepatocytes and hepatocyte membrane fragments revealed that membrane-bound alkaline phosphatase isoenzymes are highly resistant to GPI-PLD activity unless first treated with detergents, such as bile acids. However, hepatic bile acid concentrations in dogs with experimentally-induced glucocorticoid hepatopathy were not increased over values in healthy controls, in spite of significant increases in serum alkaline phosphatase activity. By inducing acute gall bladder emptying with intravenous infusions of cholecystokinin octapeptide (CCK-OP), a significant increase in alkaline phosphatase activity could be induced in dogs with glucocorticoid hepatopathy. This suggested that the release of alkaline phosphatase from hepatic membranes by GPI-PLD may occur secondary to the enterohepatic circulation of bile acids through the liver. However, a direct effect of CCK-OP on alkaline phosphatase release could not be ruled out.
Use this login method if you
don't
have an
@illinois.edu
email address.
(Oops, I do have one)
IDEALS migrated to a new platform on June 23, 2022. If you created
your account prior to this date, you will have to reset your password
using the forgot-password link below.
