Total Serum Bile Acids
TSBA concentrations can sensitively detect cholestatic disorders and conditions associated with portosystemic shunting. TSBA should be measured before and 2 hr after meal ingestion; fasting is not required. Insufficient hepatic mass or deviated portal circulation to the systemic circulation via extrahepatic portosystemic shunts (congenital or acquired) or microscopic shunts within the liver (congenital microvascular dysplasia) cause high TSBA concentrations, particularly in postprandial samples. TSBA concentrations are usually less before a meal than 2 hr after, but ~15–20% of dogs and 5% of cats have higher pre-meal than postprandial TSBA concentrations. TSBA concentrations in dogs >25 μM/L or in cats >20 μM/L should be considered abnormal either before or after a meal. However, random fasting samples and collection of only postprandial samples can miss detection of abnormal values. Because TSBA are a more sensitive indicator of cholestasis than total bilirubin, measuring TSBA is redundant in nonhemolytic jaundice. Use of TSBA as a liver function test can indicate when a liver biopsy is appropriate. TSBA may be increased in hepatic disorders secondary to other primary organ disorders, eg, inflammatory bowel disease, pancreatitis, and hyperadrenocorticism.
Measurement of blood ammonia concentrations can detect hepatic disorders associated with HE. Ammonia is derived predominantly from protein degradation, with most generated in the intestines from consumed food and enteric bacterial ureases that catabolize urea into ammonia and carbon dioxide. Portal transport of ammonia from the intestines to the liver results in a direct 85% detoxification to urea. Impaired clearance occurs in disorders associated with portosystemic shunting and in acute fulminant hepatic failure. Because ammonia is not affected by cholestasis, it is not affected by liver disorders that do not deviate the portosystemic circulation.
While ammonia is regarded as a pivotal cause of HE, animals with overt HE may have normal random blood ammonia concentrations owing to the complicated pathomechanisms underlying this syndrome. A single normal ammonia value cannot discount HE in an animal with suspected chronic liver disease, and serial ammonia measurements may not correlate with an evolving clinical scenario of HE. Therefore, ammonia measurement cannot be relied on to diagnose HE.
Measurement of blood ammonia concentrations is complex. Spurious increases in ammonia can reflect slow blood collection, tight tourniquet techniques, conditions promoting ammonia liberation from muscle (seizures, crush injuries), sample contamination, and spontaneous generation in samples not properly cooled on collection or promptly analyzed. Ammonia is highly volatile, and samples cannot be mailed for analyses. Blood samples should be collected into pre-cooled tubes and transported on melting ice to the laboratory for analysis within 20 min. Enzymatic-based methodologies are difficult to standardize. Nonhepatic causes of hyperammonemia also exist. The most common of these involves bacterial infection of the urinary tract with a urease-producing organism associated either with uroabdomen or obstructive uropathy.
If a random blood ammonia concentration is within normal limits, but hepatic insufficiency and shunting are suspected, an ammonia tolerance test (ATT) can be conducted. Ammonium chloride is given at 100 mg/kg in a 5% solution orally (can induce vomiting) or at 2 mL/kg of a 5% solution rectally 30 min after a cleansing enema, and blood ammonia measured 20, 30, 40, or 60 min later. An ATT should be done with caution because of the potential for iatrogenic HE in susceptible patients.
The presence of ammonium biurate crystals in urine in an animal with high TSBA is pathognomonic for hyperammonemia and portosystemic shunting. A minimum of 3 urine samples collected at separate daily intervals should be inspected to increase likelihood of crystal identification. In animals on restricted protein intake using diets specifically formulated for hepatic insufficiency, finding ammonium biurates may be difficult because of their high efficacy in controlling hyperammonemia.
Last full review/revision March 2012 by Sharon A. Center, DVM, DACVIM