Page 562 - Small Animal Internal Medicine, 6th Edition

534 PART IV Hepatobiliary and Exocrine Pancreatic Disorders

disease. However, generalized hypoxia, regeneration, and Pharmacologic levels of corticosteroids administered orally,
metabolic activity will also cause moderate to marked eleva- by injection, or topically reliably provoke a unique AP isoen-
VetBooks.ir tions, which may be higher than those with primary chronic zyme that is separable from the others by electrophoretic and
immunoassay techniques. However, measurement of AP iso-
liver disease. The author has seen very marked hepatocellular
liver enzyme level elevations in a dog with a liver lobe
treated with phenobarbital or in dogs with hyperadreno-
trapped in a diaphragmatic hernia, with no underlying enzymes has been shown to be of limited usefulness in dogs
primary liver disease. The degree of elevation of liver enzyme corticism. In the latter, it has a high sensitivity but very low
activities cannot therefore be used as a prognostic indicator. specificity, so finding a low steroid-induced isoenzyme rules
ALT, and to a lesser extent AST, activities are also often out hypercortisolism, but a high concentration of steroid-
increased by glucocorticoids in dogs, although to a lesser induced isoenzyme may be found in many diseases other
extent than alkaline phosphatase. than hypercortisolism. Serum GGT activity rises similarly
The activities of serum enzymes that reflect new synthesis in response to corticosteroid influence but less spectacu-
and release of enzymes from the biliary tract in response to larly. Serum AP and GGT activities tend to rise in parallel
certain stimuli include the enzymes alkaline phosphatase in cholestatic hepatopathies of cats and dogs, although they
(AP) and γ-glutamyltransferase (GGT). Bile retention (i.e., are much less dramatic in cats. Simultaneous measurement
cholestasis) is one of the strongest stimuli for accelerated of serum AP and GGT levels may aid in differentiating seem-
production of these enzymes. Unlike ALT and AST, AP and ingly benign drug-induced effects from nonicteric choles-
GGT are in low concentration in the cytoplasm of hepato- tatic hepatic disease in dogs. Assessing serum AP and GGT
cytes and biliary epithelium, and are membrane-associated, activities together may also offer clues to the type of hepatic
so the fact that they simply leak out of damaged cells does disorder in cats. Both enzymes are in low concentration in
not account for increased serum activity. Measurable AP feline liver tissue compared with that in the canine liver
activity is also detectable in nonhepatobiliary tissues of cats and have short half-lives, so relatively smaller increases in
and dogs, including osteoblasts, intestinal mucosa, renal serum activity, especially of GGT, are important signs of the
cortex, and placenta, but serum activity in healthy adult cats presence of hepatic disease in cats. In cats, a pattern of high
and dogs arises only from the liver, with some contribution serum AP activity with less strikingly abnormal GGT activ-
by the bone isoenzyme in young, rapidly growing dogs and ity is most consistent with hepatic lipidosis (see Chapter 35),
in kittens younger than 15 weeks. The renal form is generally although extrahepatic bile duct obstruction (EBDO) must
measurable in the urine; the gut form has a very short half- also be considered.
life and is not usually measurable, although the steroid-
induced isoenzyme of AP in dogs is believed to be an altered
gut isoenzyme with a prolonged half-life. Cats do not have a DIAGNOSTIC TESTS TO ASSESS
steroid-induced isoenzyme of AP. The half-life of feline AP HEPATOBILIARY SYSTEM FUNCTION
is shorter than that of canine AP, so serum activity is rela- Serum Bilirubin Concentration
tively lower in cats than in dogs with a similar degree of Because of the large reserve capacity of the mononuclear-
cholestasis and, conversely, even mild elevations of AP levels phagocytic system and liver to process bilirubin (e.g., 70%
in cats are clinically significant. Markedly high serum AP hepatectomy will not cause jaundice), hyperbilirubinemia
activity of bone origin (mean total serum AP values > five- usually occurs only from greatly increased production or
fold higher than those in nonaffected individuals, with only decreased excretion of bile pigment. However, in severe
the bone isoenzyme detected) was identified in certain chronic liver disease in dogs, hepatocyte senescence may
healthy juvenile members (7 months old) of a family of Sibe- also play a role because senescent cells are no longer able
rian Huskies. This change is believed to be benign and famil- to process bilirubin (Kortum et al., 2018). Specific inborn
ial, and should be considered when results of serum AP errors of bilirubin uptake, conjugation, and excretion have
activity are interpreted in this breed. A young growing dog not been documented in cats or dogs. The increased produc-
of any breed can have a mild increase in serum AP. Increased tion of bilirubin from red blood cell destruction arises from
serum AP activity has also been described in adult Scottish intravascular or extravascular hemolysis and rarely from
Terriers. This is believed to be associated with a vacuolar resorption of a large hematoma; hyperbilirubinemia also
hepatopathy and adrenal dysfunction. More details are given occurs in association with rhabdomyolysis or after diffuse
in Chapter 36. subcutaneus bleeding in Greyhounds and other dog breeds.
Certain drugs, the most common of which are anticon- Under these circumstances, in dogs, serum bilirubin con-
vulsants (specifically phenytoin, phenobarbital, and primi- centrations are usually lower than 10 mg/dL; values rarely
done) and corticosteroids, can elicit striking increases (up to exceed 10 mg/dL unless there is a concurrent flaw in bili-
100-fold) in serum AP activity (and to a lesser extent GGT rubin excretion. This has been observed clinically in studies
and ALT activity) in dogs but not in cats. There usually is of dogs with immune-mediated hemolytic anemia in which
no other clinicopathologic or microscopic evidence of cho- high liver enzyme activities are observed, even before treat-
lestasis in these cases (i.e., hyperbilirubinemia). Anticon- ment with corticosteroids, and moderately delayed biliru-
vulsant drugs stimulate the production of AP identical to bin excretion has been documented. It has been proposed
the normal liver isoenzyme; GGT activity does not change. that cholestasis results from liver injury associated with