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

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Chapter | 13 Hepatic Function
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FIGURE 13-2 Comparative changes in serum alkaline phosphatase
activity associated with bile duct obstruction in sheep, cats, horses, and
dogs. Symbols: ● , ovine (5); , feline (6); Δ , equine (3); , canine (2).
Courtesy of Dr. D. Levy.
Increases in serum AP have been described in a variety
of canine cholestatic liver diseases ( Abdelkader and
Hauge, 1986 ; Center et al., 1985b ; Hoe and Jabara, 1967 ;
Solter and Hoffmann, 1995, 1999 ). Modest increases in
serum AP occur with hepatic necrosis ( Noonan and Meyer,
1979 ). Following the experimental production of hepatic
necrosis in dogs, the serum activities of arginase, ALT, and
AP increase within 1 day, a time point at which GGT is not
elevated. Following bile duct obstruction, the serum activity
of both AP and GGT increases remarkably along with
moderate elevations in ALT and AST, but arginase activity
does not increase. This has suggested that arginase (for
necrosis) and GGT (for cholestasis) may have the highest
specificity in evaluating the type of hepatobiliary disease in
the dog ( Noonan and Meyer, 1979 ). Although serum GGT
activity may be less affected during hepatocellular necrosis
than AP, GGT activity may not be as highly elevated as AP
in bile duct obstruction ( Guelfi et al., 1982 ).
7 . γ -Glutamyltranspeptidase
2 2 2
GGT is a membrane-bound enzyme that catalyzes the transfer
of γ -glutamyl groups from γ -glutamylpeptides such as
glutathione to other amino acids or peptides. Glutathione
and glutathione conjugates are the most abundant physiological
substrates (Hanigan, 1998) . GGT is found primarily
in cells with high rates of secretion or absorption, and
significant GGT activity is present in the liver, kidney,
pancreas, and intestine. GGT is considered a serum marker
primarily for diseases of the hepatobiliary system associated
with cholestasis ( Table 13-5 ; Braun et al., 1983 )
TABLE 13-5 Serum γ-Glutamyltransferase (GGT)
Activity of Normal Animals
Species U/liter Reference
Dog 11 10 Guelfi et al . (1982)
0–11 Abdelkader and Hauge (1986)
0–10 Shull and Hornbuckle (1979)
5 Bunch et al . (1985)
2–4 Bunch et al . (1982)
3 1 Meyer and Noonan (1981)
Cat 0.4 0.3 Center et al . (1986)
0.3 0.2 Meyer (1983)
Horse 4.5–32.5 Yamaoka et al . (1978)
13 6 Rico et al . (1977a)
6–24 Braun et al. (1982)
Cow 19 6 Rico et al . (1977b)
6–17 Keller (1978)
1 5 Unglaub et al . (1973)
Calf 15 4 Braun et al . (1978a)
Sheep 33 7 Braun et al . (1978b)
17–69 Towers and Stratton (1978)
23 5 Malherbe et al . (1977)
Goat 27 3 Moursi et al . (1979)
Pig 35 21 Rico et al . (1977c)
Piglet (8 weeks) 16 8 Enigk et al . (1976)
and is in general used for the diagnosis of liver diseases
of animals ( Table 13-6 ). GGT activity is relatively high
in the livers of cows, horses, sheep, and goats, but GGT
activity is considerably lower in the livers of dogs and cats.
Although activity is present in many tissues and is high
in the kidney, remarkable elevations in serum GGT activity
are observed primarily in diseases of the liver. Urinary
excretion of GGT, however, has been measured to assess
renal injury ( Ford, 1974 ; Shaw, 1976 ).
In experimental bile duct obstruction, serum GGT
activity is increased significantly in the dog ( Noonan and
Meyer, 1979 ; Shull and Hornbuckle, 1979 ), sheep ( Ford,
1974 ), and cattle . The sensitivity of GGT has been reported
to be similar to that of AP as an indicator of cholestasis
in the cat ( Spano et al., 1983 ; Zawie and Garvey, 1984 ).
Within a given species, there often is a direct relationship
between the activities of serum GGT and serum AP in
cholestatic liver injury. In primary hepatocellular disease,
elevations in GGT characteristically are not increased as
remarkably as AP ( Meyer, 1983 ).
Acute exposure to oxidative stress increases GGT transcription,
indicating that expression is an adaptive response
protecting the cell from oxidative injury. Although
increased enzyme synthesis contributes to elevated serum
GGT activity in hepatocellular injury, elevations in cholestatic
disorders are believed to be, in part, related to