Page 565 - Small Animal Internal Medicine, 6th Edition

CHAPTER 34 Diagnostic Tests for the Hepatobiliary and Pancreatic System 537

ammonia and/or the presence of portosystemic shunting, with a PSS appear to have the lowest protein C activity.
which disrupts presentation of ammonia to the liver for In a study by Toulza et al. (2006), protein C activity was
VetBooks.ir detoxification. However, ammonia is very labile in the blood significantly lower in dogs with a congenital or acquired
PSS, compared with dogs without a PSS. Plasma protein C
sample and can be falsely elevated—for example, if the blood
sample is taken in an environment contaminated with urine.
These findings suggest that plasma protein C activity reflects
Sample handling has to be undertaken with caution, and activity improved or normalized after surgery for the shunt.
some benchtop analyzers are inaccurate, particularly in the the adequacy of hepatoportal perfusion in dogs and that
moderately elevated range. For these reasons, determination protein C activity may prove useful as a means to monitor
of SBA levels is often a preferred test. The exception to this improvement of hepatic-portal perfusion after the ligation of
would be an animal with suspected HE and concurrent cho- portosystemic vascular anomalies. Plasma protein C activ-
lestasis. As outlined in the preceding paragraphs, bile acid ity may also help differentiate dogs with intrahepatic portal
concentrations will be high in cholestasis because they are vein hypoplasia from those with portal systemic vascular
excreted in the bile, independent of any reduction in liver anomaly—plasma protein C activity, ≥70% versus <70%,
function or shunting. Measuring blood ammonia in these respectively.
cases will provide useful additional information about
potential shunting and HE.
In one study, the 12-hour fasting plasma ammonia con- NONSPECIFIC TESTS OF
centration had higher sensitivity and specificity than the LIVER FUNCTION
12-hour fasting bile acid concentration for detecting porto- Serum Albumin Concentration
systemic shunting in a general population of dogs and in The liver is almost the only source of albumin production in
dogs with liver disease. However, a bile acid stimulation test the body, so hypoalbuminemia can be a manifestation of
(fasting and 2-hour postprandial bile acid) has a much hepatic inability to synthesize this protein. Causes other than
higher sensitivity for detecting a PSS than a single fasting lack of hepatic synthesis (i.e., marked glomerular or GI loss,
bile acid, and a single postprandial bile acid concentration is or bleeding) must be considered before ascribing hypoalbu-
likely as sensitive as a fasting ammonia concentration, minemia to hepatic insufficiency. Renal protein loss can be
although the author did not test this. detected presumptively by routine urinalysis. Consistent
Although reference ranges vary among laboratories, identification of positive protein dipstick reactions, espe-
fasting plasma ammonia values for normal dogs are typically cially in dilute urine with inactive sediment, justifies further
100 mg/dL or less and 90 mg/dL or less for normal cats. At evaluation by at least the measurement of the random urine
least 6 hours of fasting should precede sample collection. protein-to-creatinine ratio (normal ratio, <0.2 in cats and
Samples must be collected into iced ammonia-free heparin- dogs). If proteinuria is ruled out, diseases that cause GI
ized tubes and spun immediately in a refrigerated centrifuge. protein loss should be considered; however, these GI diseases
Plasma must be removed within 30 minutes so that values usually result in an equivalent loss of globulins and thus
will not be spuriously elevated by hemolysis because red panhypoproteinemia. This is not invariably the case in
blood cells contain two to three times the ammonia concen- inflammatory GI disease, in which a concurrent increase in
tration of plasma. To obtain accurate values, feline plasma gamma globulin levels masks the gut loss. Conversely,
can be frozen at −20° C and assayed within 48 hours; canine although panhypoproteinemia is reportedly not typical of
plasma must be assayed within 30 minutes. hypoproteinemia of hepatic origin, globulin concentrations
If signs are compatible with HE at the time of sample can be low in liver disease, particularly portosystemic shunts
collection, a single fasting sample will suffice. If there are no (PSS), because all plasma globulins except gamma globulins
signs of HE and results of other tests are equivocal, a post- are made in the liver. Globulin concentrations frequently are
prandial challenge test may be performed (see Box 34.3). The normal to increased in dogs and cats with chronic inflam-
older ammonium chloride challenge tests (oral or rectal) are matory hepatic disease because they reflect the inflammatory
contraindicated because of the significant potential for either response. The plasma half-life of albumin in cats and dogs is
test to trigger a severe encephalopathic crisis in the patient. long (8-10 days), and there must be a loss of approximately
The postprandial ammonia test is safer, with a 91% sensitiv- 80% of functioning hepatocytes before hypoalbuminemia
ity for portosystemic shunting but only a 31% sensitivity for occurs, so the finding of hypoalbuminemia usually indicates
diffuse hepatocellular disease. severe chronic hepatic insufficiency.
The exception to this is the hypoalbuminemia associated
Plasma Protein C Activity with a negative acute phase response in acute or acute-on-
Plasma protein C activity has been evaluated as a marker of chronic inflammatory liver disease. The serum albumin con-
hepatobiliary disease in dogs. Protein C is an anticoagulant centration can decrease when there is an increase in hepatic
protein that is synthesized in the liver and circulates as a production of acute phase proteins in animals without
plasma zymogen. Low protein C activity has been associ- hepatic insufficiency. Serum protein electrophoresis can help
ated with thrombotic disorders in humans and animals. Low differentiate this condition from a true lack of hepatic func-
protein C activity has also been documented in dogs with tion. Sevelius and Andersson (1995) have shown that a low
acquired and congenital hepatobiliary disorders, and dogs albumin concentration associated with a low concentration