Page 683 - Clinical Small Animal Internal Medicine

60 Approach to the Patient with Liver Disease 651

analytes are also affected by a variety of other extrahe- due to the toxic effects of accumulated bile salts, and
VetBooks.ir patic causes, neither test offers utility as a specific markers of hepatic insufficiency unchanged due to their
lack of sensitivity. Abdominal ultrasound is the next step
marker for liver disease. They are, however, useful in
contributing to the overall clinical picture and may aid
useful method to distinguish between hepatic and post-
in the identification of relevant extrahepatic illnesses. in examining such a patient, and is typically the most
Hypercholesterolemia occurs with severe hepatic hepatic jaundice (see later). In some patients, the distinc-
insufficiency or in animals with congenital or acquired tion between hepatic and posthepatic disease is blurred
PSS, but can occur with a variety of conditions, including with their presentation involving components of each,
gastrointestinal disease and hypoadrenocorticism. for example cholangitis.
Hypercholesterolemia may occur with cholestasis, but
again is not specific for liver disease as it can occur Bile Acids
with endocrinopathies, protein‐losing nephropathies, Bile acids are steroid acids that are a normal constituent of
pancreatitis, and primary hyperlipidemias. A mild bile and function in fat digestion within the intestine. The
hypertriglyceridemia may occur with cholestasis. two primary bile acids, cholic and chenodeoxycholic, are
In addition, hypertriglyceridemia has been associated synthesized in the liver from cholesterol and are then con-
with a proportion of dogs with biliary mucoceles. jugated, mainly with taurine, before being excreted in bile
for release into the gut or storage in the gallbladder. These
Others conjugated bile acids are ionized at intestinal pH and
Bilirubin metabolism was discussed in an earlier section. function in fat digestion by aiding the formation of
From a diagnostic standpoint, it is helpful to consider the micelles. Intestinal bacteria metabolize some of the pri-
potential causes of hyperbilirubinemia by dividing the mary bile acids to the secondary bile acids, deoxycholic
causes into prehepatic, hepatic, and posthepatic. The for- and lithocholic acid, within the gut lumen. Once in the
mer can be quickly identified by significant anemia and ileum, primary and secondary bile acids bind to specific
enhanced erythrocyte breakdown and once excluded, the receptors, allowing their reabsorption and enterohepatic
presence of hyperbilirubinemia becomes far more specific circulation. This system sees a maximum of approximately
for liver disease than many of the other clinical pathology 5% fecal loss per day of bile acids, with the remainder
analytes. Despite this, bilirubin measurement still has returned to the liver in the portal circulation for removal
important limitations. As with other parameters, it is still and reexcretion. The daily losses are replaced by liver
a relatively insensitive measure of hepatic insufficiency, manufacture of new bile acids, maintaining a constant bile
becoming elevated only once significant hepatic reserve is acid pool in the normal animal. This low‐level replace-
exhausted, for example with end‐stage cirrhosis patients. ment is not affected by reduced liver function.
In addition, hyperbilirubinemia does not distinguish This enterohepatic circulation of bile acids forms the
between primary and secondary hepatopathies. Sepsis basis of the serum bile acid assay, a dynamic liver function
can cause significant cholestasis and hyperbilirubinemia, test. The rationale for this test is that reduced liver function
and many of the causes of posthepatic jaundice are extra- or impairment of the enterohepatic circulation, due to
hepatic, such as pancreatitis and pancreatic or duodenal either reduced biliary excretion or disruption of the portal
neoplasia. In cats, hyperbilirubinemia is a more sensitive circulation, results in elevation of the serum bile acid con-
indicator of hepatobiliary disease than it is in dogs, reflect- centration measured in peripheral blood. The indications
ing the increased proportion of liver diseases in the cat for its use are in the diagnosis of PSS and the assessment of
that involve biliary disease. liver function in cases where liver disease is suspected but
When approaching a patient with hyperbilirubinemia, hyperbilirubinemia is not present. The latter is a less sensi-
having excluded prehepatic jaundice, the next stage is to tive indicator of hepatic dysfunction; once hyperbiliru-
try to establish whether hepatic or posthepatic pathology binemia is present in a patient, the measurement of serum
is most likely. Evaluation of the remainder of the bio- bile acids offers no further information.
chemistry panel is important to establish if there are A fasted serum bile acid is obtained after a 12‐hour fast
other features suggestive of hepatic insufficiency, for and assesses enterohepatic circulation in the fasted state.
example hypoalbuminemia, and to examine the hepatic A postprandial sample taken two hours after feeding pro-
enzyme activities. Typically, with posthepatic jaundice vides an endogenous challenge. The rationale for the lat-
there is dramatic elevation of the cholestatic liver ter is that feeding stimulates gallbladder contraction with
enzymes, more so than the hepatocellular leakage release of stored bile and hence increased quantities of
enzymes, hypercholesterolemia and no evidence of bile acids for enterohepatic circulation, thus providing an
hepatic insufficiency. However, the picture is often not additional challenge for the assessment of liver function.
clear‐cut, with hepatocellular enzyme activities increas- It has been shown that a proportion of PSS cases have
ing in patients with posthepatic cholestasis over time results within the reference interval for fasting bile acids