Week 1 - Clinical Pathology of the Liver

Functions of the liver

• Carbohydrate dynamics

• Lipid metabolism

• Protein metabolism

• Management of endogenous waste

• Iron transfer

• Bile production & storage

• Synthesis of coagulation factors

• Metabolism of xenobiotics

Parameters used to assess hepatic function

• Bilirubin

• Bile acids

• Albumin

• Cholesterol

• Urea

• Clotting factors

• Glucose

Parameters used to investigate liver damage

• Hepatocellular enzymes

• Biliary enzymes

Hepatocellular enzymes

• ALT (alanine aminotransferase)

• AST (aspartate aminotransferase)

• SDH (sorbitol dehydrogenase)

• GLDH (glutamate dehydrogenase)

Biliary enzymes

• ALP (alkaline phosphatase)

• GGT (gamma glutamyl transferase)

ALT (alanine aminotransferase)

• Leaks from cytosol of damaged hepatocytes

• Hepatocytes are very sensitive to degenerative change resulting in increased ALT

• Only used in small animals

• Magnitude of increase roughly parallels hepatic mass affected

AST (aspartate aminotransferase)

• Cytoplasm and mitochondrial isoenzymes exist

• Also found in skeletal and cardiac muscle and erythrocytes

• May be elevated in animals w/ non-hepatic disease (can incr w/ hemolysis, in vitro, muscle injury)

SDH (sorbitol dehydrogenase)

• Cytosol of hepatocytes

• Useful in horses and cattle

• Unstable once taken (in vitro) (few labs offer this test)

GLDH (glutamate dehydrogenase)

• Cytosol of hepatocytes

• Sensitive marker for hepatic injury

• Useful in horses and cattle

ALP (alkaline phosphatase)

• Found in hepatocytes and biliary epithelial cells

• Impairment of bile flow (cholestasis) markedly increased ALP activity

• Isoenzymes (intestinal, tissue nonspecific, corticosteroid induced form in dogs)

GGT (gamma glutamyl transferase)

• Membrane bound enzyme

• Found in hepatobiliary system and renal tubules

• Useful in cattle, horses, cats

• Elevated serum levels can indicate cholestasis

• GGT may rise in dogs receiving corticosteroids

• Renal disease - GGT found in urine

Increased ALP can indicate

• Cholestasis

• Drug induction (ex; corticosteroids)

• Bone remodeling

Species specific considerations for ALP

• Dog - steroid induced ALP (SIALP) unique to dogs

• Cat - has less capacity for hepatic production of ALP (inc is more significant)

• Large animals wide reference ranges

• Young rapidly growing animals ALP can be elevated due to bone growth (bone isoenzyme)

What is Bilirubin?

• Pigment produced by degradation of the heme portion of hemoglobin (breakdown of rbc)

• Most produced in mononuclear phagocytes

• Bilirubin must be conjugated in the liver (made water soluble) before excretion

Hyperbilirubinemia

Prehepatic (increased RBC destruction)

• hemolysis

• Incr bilirubin overwhelms the hepatic uptake and it is unable to make it water soluble and secrete it

Hepatic (prblm w/ liver)

• Anorexia/fasting in horses may dec uptake by hepatocytes

• Decreased liver functional mass

• Intrahepatic cholestasis (within the liver stopping bile flow)

Bile acids

• Synthesized in liver from cholesterol

• Conjugated and secreted into bile

• Solubilize lipid, aid fat digestion

• Most are resorbed from intestine and recycled Enterohepatic Circulation

Bile acid testing

• Dogs and cats - fasting and post feeding (2hrs) serum bile acids measured

• Feeding induced a bolus of bile acids to be released into intestine

• Horses - a single bile acid measurement used

Increased bile acids caused by

Portosystemic Shunts

• Portal blood bypasses the liver

• Hepatic atrophy resulting from shunt reduces hepatic functional mass

Liver Failure

• Loss of functional mass results in decreased bile acid recycling

Cholestasis

• Stoppage of bile flow

• Causes reflux of bile acids into blood