Paediatric jaundice - Bilirubin metabolism

Question 1

What is measured when you do LFTs

Answer 1

Bilirubin:

• total bilirubin
• split bilirubin - direct (conjugated) & indirect (unconjugated)

ALT / AST - alanine aminotransferase / aspartate aminotransferase

ALP - alkaline phosphotase

GGT - gamma glutamyl transferase

Question 2

What generally causes LFTs to be abnormal?

a) Bilirubin
b) ALT / AST
c) ALP & GGT

Answer 2

Bilirubin - goes wonky in a lot of things

ALT / AST - elevated with hepatocellular damage (hepatitis)

ALP & GGT - elevated with biliary damage/disease

Question 3

Despite the name - mr lecture man says LFTs are not good for actually measuring the function of the liver - and only really represent damage

What tests are useful to measure functions of the liver

Answer 3

Coagulation (clotting factor synthesis):

• PT / INR
• aPTT

Albumin (protein synthesis)

Bilirubin (clearance of bile)

Blood glucose (hypoglycaemia feature of L failure)

Ammonia (clearance of toxins)

Question 4

What are the signs of chronic liver disease in children?

Answer 4

Jaundice - main one

Abnormal blood tests (incidental finding)

Signs of chronic liver disease (esp growth failure)

Question 5

Aside from jaundice & abnormal bloods - what are the signs of chronic liver disease in children?

Answer 5

Growth failure

Rest are more-or-less the same as adults

Question 6

Define jaundice

What blood level of ____ would be expected in jaundice?

Answer 6

yellow discolouration of skin and tissues due to accumulation of bilirubin

Usually visible when total bilirubin >40-50 umol/l

Question 7

What are the main stages of bilirubin metabolism?

Will go more into depth in 2 ticks

Answer 7

Post-mature erythrocytes

• broken down to -

Unconjugated bilirubin

• transported to the liver and turned into -

Conjugated bilirubin

• excreted in bile into the small intestine and then excreted from the body -

Question 8

Describe how dead RBCs are broken down into unconjugated bilirubin?

Answer 8

1) Dead RBCs broken down by the Reticuloendothelial system (mainly in the spleen) to form Haem
2) Haem is broken down into Biliverdin
3) Biliverdin acted upon by biliverdin reductase (is in all tissues) to make Unconjugated bilirubin

Question 9

How is unconjugated bilirubin is turned into conjugated bilirubin?

Answer 9

1) Unconjugated bilirubin is bound to by albumin and transported in the blood to the liver
2) Once in the liver, the enzyme ‘UDP glucoronyl transferase’ conjugates bilirubin with glucoronic acid - making conjugated bilirubin

Question 10

What happens to conjugated bilirubin once it has been made in the liver?

Answer 10

1) Conjugated bilirubin is put in bile - (its one of the ingredients of bile) - and is thus excreted into the small intestine
2) In the small intestine - it is converted into Urobilinogen

3) Once Urobilinogen - it either:

a. remains in the intestines and is shat out as Stercobilinogen

or is

b. reabsorbed, passed through the kidneys before being excreted as urine (as urobilinogen)

or is

c. reabsorbed and goes back to the liver in the enterohepatic circulation

Question 11

At which stages in bilirubin metabolism is bilirubin:

a) soluble
b) insoluble

Answer 11

a) Soluble - conjugated bilirubin is water soluble
b) Unconjugated bilirubin is insoluble - hence why albumin is needed to transport it in the blood

Question 12

Having done all the bilirubin metabolism - what stages would you get:

a) Pre-hepatic jaundice
b) (Intra)hepatic jaundice
c) Post-hepatic jaundice

Will conjugated or unconjugated bilirubin be present in each?

Answer 12

a) Dysfunction of the breakdown of RBCs into Unconjugated bilirubin

*mostly unconjugated bilirubin*

b) Dysfunction in the conjugation of unconjugated bilirubin and excretion of conjugated bilirubin into the bile

*mix of unconjugated and conjugated bilirubin*

c) Basically just cholestasis - ie there is problems getting the bile out of the liver and into the small intestine

*mostly conjugated bilirubin*