Approach to Jaundice and Liver Function
Summary:
(Strictly speaking) Liver Function is measured by 3 main modalities (among all others):
1.) Albumin
2.) INR
3.) Ammonia
Approach to Jaundice:
Jaundice
Pre-hepatic Intra-hepatic Post-hepatic
•Haemolytic Disorders •Inherited Defects in Bilirubin •Gallstones
•Sickle Cell Anemia (abnormal Metabolism
Hb) •Gilbert’s Syndrome •Malignancy
•Hereditary Spherocytosis (RBC •Criggler Najjar Syndromes (2 types – •Pancreas
Membrane defect) type 1 and type 2) •CholangioCA
•G6PD Deficiency (RBC •Dubin Johnson and Rotor’s Syndromes •Duodenal/Ampullary
enzyme defect)
•Mechanical RBC damage (prosthetic •Acute Viral Hepatitis •Other
heart valves, chronic running) •Hepatitis B & C •Ascaris
•Blood group incompatibility (foetal-
maternal, transfusion) •Trauma/iatrogenic
•Toxic hepatitis •Lymph nodes
•Other causes = bacterial toxins, malaria,
•May be due to drugs or alcohol
autoimmune anemias
•Chronic Hepatitis/ Chronic Liver Disease
•Ineffective Erythropoiesis - leading
to a megaloblastic anemia •Most common causes = viral (Hep B and
C), toxic, autoimmune
•Alcoholic Liver Disease
•Non-alcoholic Steatohepatitis
•Intrahepatic Cholestasis
•Caused by drugs, preganancy
•Cirrhosis
•Final common pathway of many chronic
liver diseases → leads to hepatic failure
,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
Summary:
(Strictly speaking) Liver Function is measured by 3 main modalities (among all others):
1.) Albumin
2.) INR
3.) Ammonia
Approach to Jaundice:
Jaundice
Pre-hepatic Intra-hepatic Post-hepatic
•Haemolytic Disorders •Inherited Defects in Bilirubin •Gallstones
•Sickle Cell Anemia (abnormal Metabolism
Hb) •Gilbert’s Syndrome •Malignancy
•Hereditary Spherocytosis (RBC •Criggler Najjar Syndromes (2 types – •Pancreas
Membrane defect) type 1 and type 2) •CholangioCA
•G6PD Deficiency (RBC •Dubin Johnson and Rotor’s Syndromes •Duodenal/Ampullary
enzyme defect)
•Mechanical RBC damage (prosthetic •Acute Viral Hepatitis •Other
heart valves, chronic running) •Hepatitis B & C •Ascaris
•Blood group incompatibility (foetal-
maternal, transfusion) •Trauma/iatrogenic
•Toxic hepatitis •Lymph nodes
•Other causes = bacterial toxins, malaria,
•May be due to drugs or alcohol
autoimmune anemias
•Chronic Hepatitis/ Chronic Liver Disease
•Ineffective Erythropoiesis - leading
to a megaloblastic anemia •Most common causes = viral (Hep B and
C), toxic, autoimmune
•Alcoholic Liver Disease
•Non-alcoholic Steatohepatitis
•Intrahepatic Cholestasis
•Caused by drugs, preganancy
•Cirrhosis
•Final common pathway of many chronic
liver diseases → leads to hepatic failure
,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
