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

IV. Laboratory Assessment of Hepatic Function
391
simple, specific, or direct method for determining the origin
of increased serum AST activity, but additional laboratory
tests may be useful. When AST is increased because
of skeletal muscle disease including trauma (e.g., intramuscular
injections) or degenerative disease, it may be useful
to measure serum creatine kinase (CK). In muscle disease,
AST and CK both are expected to be elevated. In acute
muscle injury, elevation in the CK activity of serum may
occur before AST is maximally elevated, and CK activity
characteristically decreases before AST activity fully
declines. When coincidental myopathy and liver disease
occur in dogs and cats, measurement of serum ALT may
be useful, but severe primary muscle disease is sometimes
associated with increased serum ALT activity.
Transaminase activity is known to increase following
vigorous exercise in dogs ( Valentine et al., 1990 ), but the
origin of the enzyme is not clear ( Bolter and Critz, 1974 ;
Loegering and Critz, 1971 ). A 1.4- to 2-fold increase in
plasma AST in dogs associated with increases in CK and
lactic dehydrogenase has been observed after short-term
exercise and similar increases in plasma AST and lactic
dehydrogenase activity were detected following electrophysiological
stimulation of hind limb muscles (Heffron
et al., 1976).
The results of measurement of the half-life of transaminases
following intravenous injection of hepatic homogenates
have varied widely. In one study, three dogs injected
with a 20% liver homogenate and sampled over 3 days, the
average T ½ for AST was 263 min and for ALT was 149 min
(Zinkl et al., 1971) . In another study, seven dogs received
the supernatant of a liver homogenate intravenously, and a
much longer time period was required for clearance with
the T ½ for ALT determined to be 59 9 h and for AST
22 1.6 h ( Dossin et al., 2005 ). The plasma T ½ of AST in
the cat has been estimated to be 77 min (Nilkumhang and
Thornton , 1979) . Sustained elevations in transaminase in
acute liver disease may be the result of delayed clearance.
Catabolism of plasma transaminases, in part, is the result of
endocytosis by hepatocytes, and enzyme clearance may be
delayed because of the underlying hepatic disease (acquired
portosystemic shunting, nodular regeneration, hepatic
fibrosis; Horuichi et al., 1985 ; Kamimoto et al., 1985 ) .
The major value of serum AST and ALT measurements
is in detecting hepatocellular injury and monitoring clinical
progress ( Table 13-1 ). Because both enzymes are increased
in a variety of hepatic diseases, they are of limited value
for differential diagnosis. Although elevations of the aminotransferases
are generally considered indicative of hepatocellular
injury, in severe forms of liver disease, both
hepatocellular and cholestatic forms of hepatic injury often
coexist. The highest aminotransferase levels are associated
with acute hepatitic injury, but more modest increases in
aminotransferase activity are seen in chronic liver disease
including chronic hepatocellular disease, cirrhosis, parasitic
hepatopathy, and primary or metastatic neoplasia.
TABLE 13-1 Serum Alanine Aminotransferase (ALT)
Activity of Normal Animals
Species U/liter Reference
Dog 15–50 Crawford et al . (1985)
2.5–25 Van Vleet and Alberts (1968)
0–69 Abdelkader and Hauge (1986)
20–45 Bunch et al. (1985)
5–80 Johnson et al. (1982)
3–61 Mia and Koger (1979)
Cat 0–36 Center et al . (1983a)
10–80 Peterson et al . (1983)
16 9 Meyer (1983)
30 (1–59) Mia and Koger (1979)
Minipig 35 12 Kroker and Romer (1984)
Pig 71 (37–106) Mia and Koger (1979)
2 . Sorbitol Dehydrogenase
Because of the relatively low ALT activity in the livers
of large domestic species ( Cornelius, 1963 ; Keller et al.,
1985 ), other liver-specific enzymes have been validated for
clinical use. One of these, SDH, is a zinc metalloenzyme
that is responsible for the conversion of sorbitol to fructose
using NAD as a cofactor. SDH is one of the enzymes in
the polyol pathway believed to have a central role in the
pathogenesis of some of the complications of diabetes mellitus
( Hoshi et al., 1996 ; Lee et al., 1995 ). SDH is found in
abundance primarily in the liver and kidney, and the serum
activity of SDH ( Table 13-2 ) has been shown to be useful
in assessment of hepatocellular injury in most domestic
species including the dog ( Noonan, 1981 ; Valentine
et al., 1990 ; Zinkl et al., 1971 ), horses ( Asquith et al.,
1980 ; Bortell et al., 1983 ; Johnson et al., 2006 ; Noonan,
1981 ), and ruminants ( Kalaitzakis et al., 2007 ). Clinically,
SDH is used as a liver-specific enzyme primarily for the
large domestic species. In dogs and cats, it appears to have
no advantage over ALT (Center, 2006) . SDH activity is not
stable in serum and activity declines rapidly. Therefore, it
is necessary to perform the assay for SDH as soon after the
sample is taken as possible, optimally within 8 to 12 h.
3 . Arginase
Arginase is responsible for the terminal step of the urea
cycle in which arginine is converted to urea and ornithine.
In mammals, two isoforms of arginase exist, arginase type I
and type II, which are encoded by different genes and differ
in tissue distribution, intracellular location, and in molecular
and immunochemical characteristics (Grody et al., 1989 ;
Jenkinson et al., 1996) . Arginase type I is a cytosolic
enzyme (Ikemoto et al., 1990) that is expressed primarily in
the liver where it has a key role in urea synthesis. Arginase