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

IV. Laboratory Assessment of Hepatic Function
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chronic liver disease has been considered a factor contributing
to the development of ascites, but current evidence
suggests the role is not primary. The intravascular and total
body albumin pools may not be greatly diminished in cirrhosis,
although the concentrations of albumin in plasma
often are decreased ( Rothschild et al., 1973 ; Witte et al.,
1971a, 1971b ). For ascites to develop, total body sodium
and water must expand. Excessive sodium chloride intake
greatly enhances development of ascites ( Berman and Hull,
1952 ), and ascites is preceded by increased sodium retention
by the kidney. Aldosterone levels have been shown
to be significantly increased in dogs with ascites caused
by hepatic vein obstruction ( Howards et al., 1968 ; Orloff
et al., 1965 ).
When associated with liver disease, ascites indicates a
chronic process and characteristically presents with cirrhosis
. There are important species differences in the occurrence
of ascites in chronic liver disease. In dogs with advanced
hepatic cirrhosis, ascites is a relatively common sign.
Ascites is almost never observed in horses with cirrhosis
(Tennant et al., 1975 ), and conspicuous ascites is unusual in
cattle with cirrhosis ( Finn and Tennant, 1974 ; Whitlock and
Brown, 1969 ) but may be observed at necropsy ( Pearson,
1977 ). Ascites has been observed in cattle with thrombosis
of the caudal vena cava secondary to liver abscess (Braun
et al., 1995), and, in such cases, marked hepatomegaly was
characteristic ( Breeze et al., 1976 ; Selman et al., 1974 ) and
due apparently to obstruction of hepatic vein outflow. In
sheep, ascites has been observed in cirrhosis but is unusual
in cases of severe sclerosing cholangitis associated with fascioliasis
( Hjerpe et al., 1971 ).
It is important clinically to differentiate between ascites
caused by liver disease and ascites caused by other primary
diseases. Biochemical and cytological examination of
ascitic fluid may be useful but alone is seldom diagnostic.
The protein concentration of ascitic fluid associated with
clinical cirrhosis may be variable depending on the stage
of the disease ( Center, 1996 ). In early stages, the protein
content may be expected to exceed 2 to 2.5 g/dl because it
is a reflection of the high protein content of hepatic lymph
but later, when the serum albumin has decreased and when
sinusoidal fibrosis and capillarization have developed, the
protein content of ascitic fluid will be correspondingly
lower (1 to 1.5 g/dl). The ascitic fluid associated with
peritonitis is high, whereas in neoplastic diseases of the
abdomen, the protein concentration is generally below 1.5
to 2.0 g/dl. Pembleton-Corbett et al. (2000) examined the
serum albumin/peritoneal effusion albumin (SA/EA) gradient
in dogs with ascites. They found the gradient was significantly
higher in dogs with liver disease than in those
with ascites of other causes. In 25 dogs with abdominal
effusions associated with hepatic disease, 23 had serum
albumin-effusion albumin (SA/EA) gradients equal to or
greater than 1.1 and the median SA/EA gradient was 1.4
(range 0.7 to 3.1). In human patients, SA/EA gradients
of 1.1 or greater are considered to indicate the presence
of portal hypertension. The clinical observations of
Pembleton-Corbett (2000) suggested that portal hypertension
is a significant factor in the pathogenesis of ascites in
dogs with hepatobiliary disease.
Total nucleated cell counts in ascitic fluid from dogs
with cirrhosis are seldom greater than 1000 to 2000 per μl.
Bloody or turbid fluid typically results from inflammatory
or neoplastic processes (e.g., feline infectious peritonitis,
bacterial peritonitis, neoplasia), and nucleated cell counts
are elevated. “ Bile acites ” or bile peritonitis is recognized
most frequently in the dog and cat associated with abdominal
trauma. In this case, the concentration of bilirubin in
peritoneal fluid exceeds that of plasma.
IV . LABORATORY ASSESSMENT OF
HEPATIC FUNCTION
The pathogenesis of the hepatic diseases of domestic animal
species is remarkably complex, involving acute and chronic
forms of hepatitis, cirrhosis, bile duct obstruction, intrahepatic
forms of cholestasis, neoplasia, and disorders of
hepatic vasculature. The frequency of these diseases varies
with species, breed, age, and, in some cases, by environment
(diet, geographical location). The differential diagnosis of
hepatic disease involves the evaluation of clinical history,
physical examination, biochemical tests, hepatic imaging,
and histopathological examination of hepatic biopsies. The
following section describes the biochemical tests used to
assess hepatic disease.
There are several diagnostic categories with which the
clinician dealing with problems of liver disease must be
concerned. In clinical patients with a history and signs suggestive
of hepatic disease, laboratory tests are used for confirmation.
Laboratory tests are used to assess the severity of
liver injury, to establish prognosis, to define treatable complications
of hepatic insufficiency (e.g., ascites, encephalopathy),
and to monitor clinical progress. Finally, biochemical
tests of hepatic function may be performed on clinically
healthy patients that are known to be at high risk of developing
liver disease (e.g., exposure to infectious agents that
cause hepatitis, or a familial history of chronic liver disease
that requires screening for inherited diseases of the liver).
A . Hepatic Enzymes
The presence of liver disease often is recognized on the
basis of elevated serum activities of enzymes of hepatic
origin. Although they are sometimes referred to as “ liver
function tests, ” serum enzymes do not measure hepatic
function directly but indicate alteration in the integrity of
the cell membrane of the hepatocyte, necrosis of hepatocytes
or biliary epithelium, impeded bile formation or bile