Clinical Biochemistry of Domestic Animals (Sixth Edition) - UMK ...

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Chapter | 4 Lipids and Ketones
Barrie, 1993 ). The main lipid that is increased is cholesterol,
but triacylglycerol may be increased too, and most of
the increased lipid is in LDL and HDL, but some animals
have increased VLDL or chylomicron levels as well ( Rogers,
1977 ; Whitney, 1992 ). The mechanism by which hypothyroidism
causes hyperlipidemia in dogs is unknown; however,
a similar phenomenon occurs in humans, and in that species,
it appears that hypothyroidism decreases lipoprotein lipase
and hepatic lipase activities ( Valdemarsson et al ., 1983 ). The
prolonged hypercholesterolemia associated with chronic
hypothyroidism in dogs may lead to atherosclerosis ( Liu
et al ., 1986 ; Patterson et al ., 1985 ), although other factors
may be involved as well.
Dogs with naturally occurring pancreatitis frequently
have hyperlipidemia ( Hardy, 1992 ; Whitney et al ., 1987 ).
Because the pancreatitis in some of these animals causes
diabetes, the hyperlipidemia in those individuals may be
due to diabetes. Plasma lipid levels of dogs with pancreatitis
induced by injecting bile into or ligating the pancreatic
duct are comparable to control dogs (Bass, 1976; Whitney
et al ., 1987 ; Zieve, 1968 ). In some cases, hyperlipidemia
may play a role in the pathogenesis of pancreatitis rather
than being a result of pancreatitis. This proposition is supported
by the fact that humans with some forms of hyperlipidemia
have increased risk of pancreatitis ( Cameron
et al ., 1974 ; Greenberger, 1973 ). One proposed mechanism
is that increased lipids, especially chylomicrons, entering
the pancreatic capillaries will be hydrolyzed by pancreatic
lipase, and the resultant LCFA may injure endothelial or
acinar cells ( Havel, 1969 ). Once the initial damage occurs,
there is a positive feedback in which more lipase enters
the circulation and hydrolyses more triacylglycerol leading
to more LCFA release and more damage. In support
of this theory, when dog pancreata were perfused with a
medium containing high levels of triacylglycerol or LCFA,
they became edematous and hemorrhagic and released
large amounts of amylase compared to pancreata perfused
without these additions ( Saharia et al ., 1977 ). In a related
proposed mechanism, large amounts of chylomicrons or
VLDL may impede the microcirculation of the pancreas,
leading to partial stasis, which allows blood lipids and their
hydrolysis products more contact with pancreatic cells
( Hardy, 1992 ).
Dogs with uncontrolled diabetes frequently have hyperlipidemia
( Medaille et al ., 1988 ; Rogers, 1977 ; Whitney,
1992 ). In naturally occurring cases, plasma triacylglycerol
levels are increased with concomitant increases in VLDL
levels and often hyperchylomicronemia is present as well
( DeBowes, 1987 ; Ford, 1995 ; Rogers, 1977 ; Rogers et al .,
1975b ). The increase in VLDL is due in part to increased
mobilization of LCFA from adipose. The liver removes
LCFA from plasma and reissues some of them to the
plasma as triacylglycerol in VLDL. In addition, synthesis of
lipoprotein lipase by peripheral tissues is partially dependent
on insulin, so less of this enzyme is available to remove triacylglycerol
from the circulation ( Brown and Goldstein, 1994 ).
Hyperlipidemia with increases in plasma triacylglycerol
and cholesterol levels have been noted in dogs with cholestasis
( Bauer et al ., 1989 ; Meyer and Chiapella, 1985 ).
The increase in cholesterol can be explained in part by the
inability of the liver to remove and catabolize cholesterol.
However, there is evidence of production of an abnormal
LDL, called lipoprotein-X, which is rich in cholesterol
( Bauer et al ., 1989 ; Blomhoff et al ., 1978 ; Danielsson
et al ., 1977 ; Meyer and Chiapella, 1985 ).
Dogs with hyperadrenocorticism (Cushing’s disease)
often have hyperlipidemia with increased total plasma cholesterol
levels ( Barrie et al ., 1993 ; Feldman, 1995 ; Ling
et al ., 1979 ; Medaille et al ., 1988 ; Scott, 1979 ). Most of the
increased plasma cholesterol is associated with LDL, and
although the mechanism of the hyperlipidemia is unclear,
it may be related to a decrease in activity of hepatic LDL
receptors ( Barrie et al ., 1993 ).
Dogs with nephrotic syndrome often have hyperlipidemia
( Ford, 1995 ; Lewis and Center, 1984 ; McCullagh,
1978 ; Medaille et al ., 1988 ). Hypercholesterolemia is
present most commonly, but hypertriacylglycerolemia
may be present as well, especially in more severe cases
( McCullagh, 1978 ). In humans with nephrotic syndrome,
the hyperlipidemia appears to be related to the loss of
albumin or regulatory factors in the urine, and infusion of
albumin or dextran into afflicted patients lowers lipid levels
( Glassock et al ., 1991 ). Albumin or regulatory factors
may inhibit VLDL production by the liver, and without
this inhibition, more VLDL will be released to the plasma
increasing VLDL and LDL levels ( Glassock et al ., 1991 ).
Idiopathic hyperlipidemia, which is probably inherited,
occurs in some miniature schnauzers ( Ford, 1993 ;
Richardson, 1989 ; Rogers et al ., 1975a ). Animals present
with abdominal pain, diarrhea, and vomiting, and sometimes
with seizures and pancreatitis. Affected animals
have hypertriacylglycerolemia, hypercholesterolemia, and
increased chylomicron levels and often have increased levels
of other lipoproteins as well. The animals often have
elevated liver enzymes as well (Xenoulis et al ., 2008). It
has been proposed that these animals may have low levels
of lipoprotein lipase or perhaps deficient apolipoprotein
C-II, the activator of lipoprotein lipase. However, some
dogs have shown clearing of the plasma following heparin
injection, so the mechanism remains unknown. The primary
treatment is to place the animal on a low-fat diet. A
similar syndrome has been reported in mixed-breed dogs
( Baum et al ., 1969 ; Rogers et al ., 1975a ) and in Brittany
spaniels ( Hubert et al ., 1987 ). Hypercholesterolemia, which
is probably inherited, has been reported in rough collie
dogs ( Jeusette et al ., 2004 ) and Shetland sheepdogs ( Sato
et al ., 2000 ). Corneal lipidosis, which responded to
dietary manipulation, was observed in the former, and