Liver Function Tests Flashcards
alanine aminotransferase (ALT) is found
hepatocyte cytoplasm, some in muscle
aspartate transaminase (AST) is found
in hepatocyte cytoplasm and mitochondria
lactate dehydrogenase is found
in the cytoplasm; high concentrations in muscle and liver
alkaline phosphatase (ALP) is found
on the canalicular surface of hepatocytes and bone during formation
gammaglutamyl transpeptidase (GGT) is found
canalicular surface of hepatocytes
Liver necrosis releases which enzymes?
- AST (+toxins), ALT, LD
- due to virus, toxins, anoxia, paracetamol
In biliary disease causing obstruction, what liver enzymes are released?
ALP & GGT (via lymphatics)
Which liver enzymes are released in response to drugs (including alcohol)?
- not in response to damage
- increased production of ALT and GGT in response to alcohol, anticonvulsants
Which enzyme is most liver specific?
ALT
ALT catalyzes
pyruvate <–> alanine
AST is involved in
- aspartate –> glutamate
- oxaloacetate and malate movement in/out of mitochondria
Release of AST suggests
damage to cytosol and mitochondria of any cell containing them (liver, muscle, blood)
Elevated ALT suggests
cytosolic damage, most likely in liver (less so in muscle, kidney)
AST is removed
by the kidney, 2x as fast as ALT (18hrs)
ALT is removed
by the liver, slower than AST (36hrs)
If AST > ALT
- acute injury affecting cytoplasm and mitochondria
- eg alcohol, toxins
If ALT > AST
- chronic or resolving injury
- AST has gone away but the ALT is accumulating
- eg hepatitis
ALT levels in Hep A
- mild = 250
- moderate = 1000
- severe = 5000
- ALT > 10 000 = death
Normal ALT is
<50 IU/L
ALT in acute Hep B infection is
~2000-5000
(core positive IgM, current infection)
ALT in chronic Hep B infection is
much lower than acute, ~50-250
(SA Ag positive, chronic infection)
ALT levels in chronic hepatitis infections
are typically lower than in acute
What types of drugs can cause hepatic damage?
- antibiotics
- statins
- ethanol
- paracetamol
- herbal tea/kombucha
AST and ALT > 10x normal suggest
acute or severe insult:
drugs, acute viral hepatitis, CMV (glandular fever), hypoxia, splenomegaly
ALT and AST > 5x normal suggests
infection, alcohol, fatty liver disease, medications
Elevated AST without elevation in ALT suggests
muscle and/or red cell damage eg statins causing muscle wasting
(ie mitochondrial damage in tissues other than liver)
Creatine kinase levels can be estimated by
AST x 20
normally <200
ALT elevated without an elevation in AST suggests
chronic or resolving disease eg Hep B, Hep C
What happens to ALT and AST levels as the liver approaches cirrhosis?
they decrease; there are fewer hepatocytes left to damage and release ALT and AST
Total protein is normally
60-80g/L
normal albumin is
35-55g/L
normal ALP is
<120 IU/L
normal bilirubin is
<26mmol/L
normal GGT is
<50 IU/L
normal AST is
<45 IU/L
Raised ALP is normal in
3rd trimester of pregnancy; produced by placenta
Increased GGT suggests
biliary disease
What is the function of GGT?
- transfers glutamyl groups to AA
- helps transport of AA across membranes
- important in production of glutathione
What is the function of ALP?
- adds phosphate groups to things in membranes in alkaline environments
In extra-hepatic biliary obstruction (cancer, stones), GGT and ALP
increase significantly, up to 20-30x normal levels
In intra-hepatic biliary obstruction, GGT and ALP
will be mildly elevated, bilirubin should be normal
can be due to tumours affecting small parts of liver or induction by drugs etc.
Intrahepatic biliary obstruction can be due to
damage to a small part of the tree (tumour, lesion, etc.(
or drugs inducing enzymes (alcohol, convulsants)
What is the commonest cause of liver enzyme elevation?
obesity
Which enzyme does BMI affect?
ALT; AST less-so because it can disappear, GGT affected more in the intermediate/pre-diabetic stage of obesity
What causes fatty liver in obesity?
- fructose
- from high fructose corn syrup
- from sucrose (fructose + glucose)
How does fructose cause fatty liver in obesity?
- only body tissue it can enter is liver
- liver can convert fructose into glucose but not likely to do so because dietary glucose is sufficient
- insulin response tells liver not to make glucose from fructose bc sugar is abundant in blood
- fructose instead gets broken down into 3C units that are turned into fat