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In this section, we will cover the following liver topics:

  • Physiology: Structure and function of the liver.
  • Routine laboratory testing in liver disease: Assessment of liver disease requires the interpretation of clinical pathology data reflecting the state of the liver. This data comes from results of chemistry testing, but also hemogram and urinalysis results (i.e. don’t look at chemistry results in isolation to interpret results of liver tests) – all of this data provides clues as to the underlying presence of liver disease allowing for its laboratory detection. Essentially from these test results, we try and identify 4 main patholophysiologic processes:
    • Hepatocellular injury: This is determined by measuring the activities of enzymes found in high concentrations of liver cells and are released with injury to hepatocytes or biliary cells- so-called “liver leakage enzymes. These are: alanine aminotransferase or ALT, asparate aminotransferase or AST, sorbital dehydrogenase or SDH, glutamate dehydrogenase or GLDH, lactate dehydrogenase or LDH). However, some of the enzymes are found in other cell types (e.g. AST and LDH are also found in muscle) so increases in such enzymes are not specific for liver injury, unlike those found mostly in hepatocytes (SDH, GLDH).
    • Cholestasis: Cholestasis is defined as decreased or ceased bile flow and results in an increase in the so-called “inducible enzymes, alkaline phosphatase (ALP) and γ-glutamyl transferase (GGT) and in bilirubin concentrations. The membrane associated enzymes, ALP and GGT are induced (or, in the case of GGT, released from the membrane) as a consequence of cholestasis. Bilirubin is the serum indicator of cholestasis, specifically conjugated bilirubin, which accumulates in blood during cholestasis and spills into urine, causing bilirubinuria (in dogs, that is in excess for that expected for the degree of urine concentration or urine specific gravity).
    • Hepatic dysfunction or insufficiency: Tests of liver function evaluate the ability of the liver to clear substances from blood, including ammonia (produced daily from amino acid metabolism and must be converted to urea) and bile acids, which undergo enterohepatic circulation and are efficiently removed from blood by a normally functioning liver. Liver synthetic ability (the liver is the main source of many proteins produced in the body) can also be evaluated indirectly through measurement serum levels of various proteins, e.g. albumin, transferrin, urea, coagulation factors and coagulation inhibitors (antithrombin, protein C), however other disease processes can influence these proteins. Hepatic failure occurs when there is substantial loss of liver tissue (>70-80%), resulting in inability of the liver to produce proteins, clear antigens or other substances from blood (ammonia, bile acids). Specific clearance studies can be performed to confirm decreased liver function (i.e. ability to clear an exogenous substance from blood, e.g. caffeine [Golden et al 1994]). Note, you can have laboratory evidence of dysfunction (e.g. low urea nitrogen) without the animal being in synthetic liver failure (e.g. low urea nitrogen is common because of decreased functional mass in dogs with portosystemic shunts).
    • Alterations in hepatic portal circulation: The portal vein brings substances absorbed from the gastrointestinal system to the liver (the first organ these substances encounter). The liver then extracts and conserves substances that are normally secreted into the intestine through bile, particularly bile acids. Abnormalities in the portal supply, i.e. portosystemic shunting, allows blood to bypass the liver and directly enter the systemic circulation. This results in decreased liver extraction (which can also be a consequence of decreased liver function as well as shunting of blood away from the liver) and increased concentrations of these substances in peripheral blood, allowing us to detect such abnormalities in blood flow. Shunting also causes atrophy of the liver, with decreased functional mass, which may manifest with abnormalities in some of the synthetic functions of the liver (notably, low antithrombin, protein C and urea nitrogen).
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