Chemical Pathology – Liver Function Tests
The following are looked at when assessing liver function:
- Bilirubin
o Unconjugated
o Conjugated
- Urine Urobilinogen
- Liver Enzymes
o Transaminases
AST
ALT
o Lactate Dehydrogenase
o ALP
o GGT
- Plasma Proteins
o Albumin
o Clotting factors
o Immunoglobulins
o AFP
- Plasma Ammonia
,Bilirubin:
Two forms are measured:
1.) Conjugated Bilirubin (aka Direct-reacting)
2.) Unconjugated Bilirubin (aka Indirect-reacting)
Lets us review the movement of bilirubin in the body:
- Haem broken down by the RES cells in the spleen
- (Unconjugated) Bilirubin produced
- This is attached to albumin which can be transported in the plasma
- NOTE: unconjugated bilirubin is found in plasma
- This is then taken to the liver and leaves the blood plasma
- Once in the hepatocytes, it becomes conjugated bilirubin
- This is then excreted into the duodenum
- In the colon it is converted into urobilinogen
- NOTE: conjugated bilirubin is not normally found in the blood plasma
When measuring the blood plasma (or serum) for bilirubin, the following should be noted:
- The normal total bilirubin should be <17 µmol/l
- This bilirubin will all be unconjugated of course
When things go wrong…
1.) ↑ unconjugated bilirubin in blood plasma:
- This may be due increased bilirubin production
o this is the case in haemolytic disorders
o this is the case in ineffective erythropoiesis
o These are your pre-hepatic liver disorders
- This may be due to decreased uptake or conjugation of bilirubin by the liver.
o This would occur in generalized hepatocellular dysfunction (thus the liver can’t carry out
its function of conjugating the bilirubin)
o This would also occur in specific rare inherited syndromes
Gilbert’s Syndrome – mutation in the conjugation enzymes
Criggler Najjar Syndrome - mutation in the conjugation enzymes
, When measuring the urine for bilirubin, the following should be noted:
- Normal urine should contain no bilirubin
- This is because unconjugated bilirubin is bound to albumin and thus does not get filtered
through the glomerulus
When things go wrong…
- If conjugated bilirubin does not get excreted into the bile canaliculi, they get shunted into the
blood plasma (serum)
- This then causes conjugated bilirubin to be found in blood plasma (serum)
- This conjugated bilirubin can thus enter the kidneys and be excreted in the urine as well
2.) ↑ conjugated bilirubin in blood plasma and urine:
- This may be due to obstructive liver disease (thus conjugated bilirubin is shunted back into the
blood)
- This would also occur in specific rare inherited syndromes
Rotor’s Syndrome
Dubin-Johnson Syndrome
Note: there is an exception when checking the urine for conjugated bilirubin. In the case of prolonged
obstructive jaundice (i.e. causing conjugated hyperbilirubinemia), the conjugated bilirubin does
something weird – it binds to albumin! This is known as delta-bilirubin. This is thus not able to be
excreted via the urine. Thus in this case we would expect to find that there is hyperbilirubinemia but no
bilirubinuria.
The following are looked at when assessing liver function:
- Bilirubin
o Unconjugated
o Conjugated
- Urine Urobilinogen
- Liver Enzymes
o Transaminases
AST
ALT
o Lactate Dehydrogenase
o ALP
o GGT
- Plasma Proteins
o Albumin
o Clotting factors
o Immunoglobulins
o AFP
- Plasma Ammonia
,Bilirubin:
Two forms are measured:
1.) Conjugated Bilirubin (aka Direct-reacting)
2.) Unconjugated Bilirubin (aka Indirect-reacting)
Lets us review the movement of bilirubin in the body:
- Haem broken down by the RES cells in the spleen
- (Unconjugated) Bilirubin produced
- This is attached to albumin which can be transported in the plasma
- NOTE: unconjugated bilirubin is found in plasma
- This is then taken to the liver and leaves the blood plasma
- Once in the hepatocytes, it becomes conjugated bilirubin
- This is then excreted into the duodenum
- In the colon it is converted into urobilinogen
- NOTE: conjugated bilirubin is not normally found in the blood plasma
When measuring the blood plasma (or serum) for bilirubin, the following should be noted:
- The normal total bilirubin should be <17 µmol/l
- This bilirubin will all be unconjugated of course
When things go wrong…
1.) ↑ unconjugated bilirubin in blood plasma:
- This may be due increased bilirubin production
o this is the case in haemolytic disorders
o this is the case in ineffective erythropoiesis
o These are your pre-hepatic liver disorders
- This may be due to decreased uptake or conjugation of bilirubin by the liver.
o This would occur in generalized hepatocellular dysfunction (thus the liver can’t carry out
its function of conjugating the bilirubin)
o This would also occur in specific rare inherited syndromes
Gilbert’s Syndrome – mutation in the conjugation enzymes
Criggler Najjar Syndrome - mutation in the conjugation enzymes
, When measuring the urine for bilirubin, the following should be noted:
- Normal urine should contain no bilirubin
- This is because unconjugated bilirubin is bound to albumin and thus does not get filtered
through the glomerulus
When things go wrong…
- If conjugated bilirubin does not get excreted into the bile canaliculi, they get shunted into the
blood plasma (serum)
- This then causes conjugated bilirubin to be found in blood plasma (serum)
- This conjugated bilirubin can thus enter the kidneys and be excreted in the urine as well
2.) ↑ conjugated bilirubin in blood plasma and urine:
- This may be due to obstructive liver disease (thus conjugated bilirubin is shunted back into the
blood)
- This would also occur in specific rare inherited syndromes
Rotor’s Syndrome
Dubin-Johnson Syndrome
Note: there is an exception when checking the urine for conjugated bilirubin. In the case of prolonged
obstructive jaundice (i.e. causing conjugated hyperbilirubinemia), the conjugated bilirubin does
something weird – it binds to albumin! This is known as delta-bilirubin. This is thus not able to be
excreted via the urine. Thus in this case we would expect to find that there is hyperbilirubinemia but no
bilirubinuria.
