Clinical Pathology of the Liver Flashcards
-Know enzymes used to assess liver DISEASE -Be able to describe their use in different species, and their limitations -Know the parameters used to assess liver FUNCTION -Know and understand the variety of signs which may accompany liver dysfunction.
FUNCTIONS OF THE LIVER
- Carbohydrate dynamics
- Lipid metabolism
- Protein metabolism
- Management of endogenous waste
- Iron transfer
- Bile production and storage
- Synthesis of coagulation factors for blood clotting
- Metabolism of xenobiotics, including many veterinary drugs.
BIOCHEMICAL ASSESSMENT OF LIVER DAMAGE AND FUNCTION
Serum chemistry can measure liver DAMAGE- HEPATIC ENZYMES, and/or liver FUNCTION- Substances produced by the liver and substances excreted by the liver.
The liver is very ‘hardy’- it can often still function if damaged, and has a huge capacity to regenerate.
Many parameters measured to assess liver function/damage may not be specific for hepatic diseases (eg. hyperbilirubinaemia)- consider underlying diseases/problems.
HEPATOCELLULAR ENZYMES
Used to assess liver function. -ALANINE AMINOTRANSFERASE (ALT) -ASPARTATE AMINOTRANSFERASE (AST) -SORBITOL DEHYDROGENASE (SDH) -GLUTAMATE DEHYDROGENASE (GLDH) These enzymes are made in hepatocytes. Measuring them gives an indication of hepatocyte damage.
Hepatocellular enzymes are released from damaged hepatocytes.
REVERSIBLE damage- membrane blebbing, enzymes released to sinusoidal blood or lymph.
IRREVERSIBLE damage- blebbing, membrane damage can result in cell breakdown, or necrosis.
Liver damage results in INCREASED hepatocellular enzyme levels.
ALANINE AMINOTRANSFERASE (ALT)
Leaks out of cytosol of damaged hepatocytes.
Mostly liver specific (ie. increased ALT= liver damage)
Hepatocytes are very sensitive to degenerative change, leading to increased ALT.
ONLY USED IN SMALL ANIMALS- large animals have very low ALT levels in their hepatocytes.
Magnitude of increase roughly parallels hepatic mass affected.
There is no differentiation between sublethal injury and necrosis- enzyme is released either way.
Poor correlation between serum levels and hepatic dysfunction.
ASPARTATE AMINOTRANSFERASE (AST)
Cytosoloc and mitochondrial isoenzymes.
Also found in skeletal muscle, cardiac muscle and erythrocytes- not as specific to the liver as ALT- may be elevated in nonhepatic disease eg. haemolysis, muscle injury.
SORBITOL DEHYDROGENASE (SD)
Found in cytosol of hepatocytes
USEFUL IN HORSES AND CATTLE (can’t use ALT)
Few labs offer this test, as the enzyme is unstable in vitro.
GLUTAMATE DEHYDROGENASE (GLDH)
Found in cytosol of hepatocytes
USEFUL IN HORSES AND CATTLE
Sensitive marker for hepatic injury.
INDUCED ENZYMES
Used to assess liver function.
aka. Biliary enzymes- from the biliary tree.
- ALKALINE PHOSPHATASE (ALP)
- GAMMA GLUTAMYL TRANSFERASE (GGT)
ALKALINE PHOSPHATASE (ALP)
Found in hepatocytes and in biliary epithelial cells.
Impaired bile flow (cholestasis) increases ALP markedly (in some species; dog)
Isoenzymes are seen- hepatic, intestinal, bone, placental, corticosteroid induced (DOG ONLY).
Most labs just measure total ALP, which mostly comprises hepatic, bone and corticosteroid induced (in dogs) isoenzymes.
AKLALINE PHOSPATASE INDUCTION
Seen in the sick animal (normally, very little ALP is seen in the blood because very little is being produced by hepatocytes)
Also seen with certain drugs and metabolites.
Transcription of ALP is induced
More enzyme is seen on the membranes, including vessel endothelium (ie. in blood)
INCREASED ALKALINE PHOSPHATASE
Increased ALP can indicate:
-Cholestasis
-Drug induction eg. corticosteroids, phenobarbitone
-Bone remodelling- most relevant in young, growing animals- slightly raised levels are normal.
-CAT- hepatic ALP production is much less, and there is a much shorter half life.
No evidence of corticosteroid induced isoenzyme in cats.
RAISED ALP IS MUCH MORE SIGNIFICANT IN CATS
SPECIES SPECIFIC CONSIDERATIONS
- Steroid induced ALP (SIALP) is unique to dogs.
- Cats have less capacity for hepatic ALP production and it has a shorter half life
- Increased ALP is therefore more significant in the cat
- Feline hyperthyroidism increases ALP- hepatic and bone isoenzymes
- Large animals have wide reference ranges- species variation
- Young, rapidly growing animals normally show slightly elevated levels.
GAMMA GLUTAMYL TRANSFERASE (GGT)
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
GGT can be found in urine in renal disease (as it is produced in the renal tubules, increased production in disease)
PARAMETERS USED TO ASSESS HEPATIC FUNCTION
Substances produced by the liver eg. bile acids
Substances excreted by the liver eg. bilirubin
BILIRUBIN
A pigment produced by degradation of the haem portion of haemoglobin
Mostly produced in mononuclear phagocytes
Must be bound to albumin, transported to the liver and conjugated to make it water soluble, before it can be excreted in bile to the GI tract.
