TSBA concentrations sensitively detect cholestatic disorders and conditions associated with portosystemic shunting. TSBA concentration 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 lower before a meal than 2 hr after a meal. However, ~15%–20% of dogs and 5% of cats have higher TSBA concentrations before a meal than after, likely reflecting physiologic variables influencing the enterohepatic circulation of bile acids (ie, the rate of gallbladder contraction, gastric emptying, and intestinal transit of bile acids to the ileum where they are actively resorbed). TSBA concentrations in dogs >25 μM/L or in cats >20 μM/L are abnormal either before or after a meal (fasting ranges should not be applied because of the variables influencing the TSBA enterohepatic circulation). Collecting a single sample for TSBA measurement (random fasting or a single postprandial sample) can miss detection of abnormal values. Because TSBA concentrations are a more sensitive indicator of cholestasis than total bilirubin, measuring TSBA concentration is redundant in animals with nonhemolytic jaundice. Use of TSBAs as a liver function test can indicate need for a liver biopsy. TSBA concentrations should be routinely measured in all young (6 mo), small, "terrier-like breeds" to detect dogs with microvascular dysplasia (MVD). Finding increased TSBA concentrations in apparently healthy, young, terrier-like breeds, including but not restricted to Yorkshire Terriers, Maltese, Shih Tzus, Miniature Schnauzers, Cairn Terriers, Norfolk Terriers, Havanese, Papillons, Tibetan Spaniels, and Pugs, allows detection of dogs in which TSBA concentration will be misleading if discovered in later life during evaluation of illness.
Measurement of blood ammonia 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. Ammonia intolerance (impaired clearance) occurs in any disorder associated with portosystemic shunting and in acute fulminant hepatic failure. Ammonia is not influenced by cholestasis or liver disorders that do not deviate the portosystemic circulation or extensively reduce hepatic parenchymal mass.
Although ammonia is regarded as a pivotal cause of HE, animals with overt HE may have normal blood ammonia concentrations owing to complicated pathologic mechanisms driving HE. 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. Thus, ammonia measurements cannot reliably diagnose HE.
Measurement of blood ammonia is complicated. Spurious hyperammonemia can reflect slow blood collection, tight tourniquet technique, conditions promoting ammonia liberation from muscle (seizures, crush injuries), sample contamination (human sweat, cigarette smoke, open urine vials), and spontaneous generation in samples not immediately cooled on collection or not 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, with the most common disorders involving 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 portosystemic shunting suspected, an ammonia tolerance test 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 administered rectally (instilled 30 cm deep) after a cleansing enema, with blood ammonia measured at baseline and then at 20, 30, 40, or 60 min later. Unfortunately, an ammonia tolerance test may induce iatrogenic HE in susceptible animals.
The presence of ammonium biurate crystalluria in an animal with high TSBAs is pathognomonic for hyperammonemia and portosystemic shunting. A minimum of three urine samples collected at separate daily intervals should be inspected to optimize surveillance for crystal discovery. In animals on restricted protein intake using diets specifically formulated for hepatic insufficiency, finding ammonium biurates may be difficult because of the high efficacy of such diets to control hyperammonemia.