Billirubin Metabolism

Question 1

What is billirubin and what type of billirubin is toxic?

Answer 1

By product of the breakdown of the haem portion of haemoglobin - in the spleen
Unconjugated fat soluble billirubin is toxic and has to be removed through metabolism in the liver and excretion through the gut/kidneys

Question 2

What does unconjugated mean? and where can this build up?

Answer 2

Means not attached to anything
It is fat soluble so can be excreted directly via the kidneys
This can build up in the fatty tissues and affect the brain and central nervous system.
Causes neural necrosis (cell death)

Question 3

What is the yellow staining of affected areas called?

Answer 3

Kernictercus

Question 4

What are the stages of billirubin production and metabolism

Answer 4

Production
Transport
Conjugation
Excretion

Question 5

Transport in a normal healthy neonate?

Answer 5

Billirubin is bound to albumin and transported in the plasma (circulation) to the liver.
albumin bound billirubin does not leave the circulation easily, size matters!

Question 6

Where does transport happen?

Answer 6

From the spleen to the liver?

Question 7

What is conjugation and where does this happen?

Answer 7

Occurs in the liver
Detaches from albumin
Carrier proteins Y and Z transport billirubin to smooth endoplasmic reticulum.
Billirubin then attaches to two glucoronic acid molecules
(Requires oxygen, glucose and the enzyme glucoronyl transferase)

Question 8

What do you end up with after conjugation?

Answer 8

Bilirubin di- glucoronide

Question 9

What is conjugated billirubin?

Answer 9

Water soluble
Safer for excretion via the gut/kidneys
Is however unstable

Question 10

what happens in excretion 1?

Answer 10

Bilirubin di- glucuronide
Excreted via bile in the bile duct
(goes Into the small intestine)

Question 11

What happens during excretion 2?

Answer 11

Catabolised in the small intestine by the normal gut flora
Turns into urobilinogen
It is then oxidised to form urobilin (orange colour)
Makes faeces brown

Question 12

But what can happen in the small intestine?

Answer 12

Beta glucoronidase can cause a breakup and cause bilirubin di glucoronide to become unconjugated (as it is unstable)

Question 13

What happens if the unconjugated billirubin re enters the circulation?

Answer 13

The cycle has to start again
Transport
Conjugation
Excretion

Question 14

What is jaundice?

Answer 14

The presence of bilirubin

Question 15

What are the different types of jaundice?

Answer 15

Early rising jaundice - rhesus incompatibility, ABO incompatibility, G6PD deficiency, sepsis.
Late rising - biliary atresia, neonatal hepatitis
Prolonged - urinary tract infection, hypothyroidism, breast milk jaundice, galactosaemia, obstructive jaundice.
Physiological - no pathology, urinary infection, minor blood group incompatibility.

Question 16

What is a rare genetic cause of jaundice?

Answer 16

glucose 6 phosphate dehydrogenase (G6PD)

Question 17

What happens during physiological jaundice?

Answer 17

reduced levels of glucoronyl transferase in the first 24 hours (needed for conjugation to take place)
Delayed feeding
Reduced bowel motility

Question 18

Why are preterm neonates more prone to jaundice?

Answer 18

Due to decreased albumin binding capacity

Question 19

What is breastfeeding linked to?

Answer 19

Both early and late onset jaundice

Question 20

Treatment for pathological jaundice?

Answer 20

Light therapy
blue light - changes the structure of bilirubin, so that it’s water soluble and can be excreted via the kidneys.
Maintain fluids.

Question 21

Causes of jaundice during production?

Answer 21

Rhesus incompatibility - undetected
G6PD
Sepsis
Polycythaemia - excess of RBC

Question 22

What are the causes of jaundice in transport?

Answer 22

Low/decreased albumin levels
Hypothermia
Hypoxia
Certain drugs (aspirin and ampicillin)

Question 23

What are the causes of Jaundice during conjugation?

Answer 23

Reduced capacity of the liver for conjugation due to:
Torch infection (toxoplasmosis, rubella, cytomegalovirus, herpes, Zika virus)
Dehydration
Metabolic disorders

Question 24

What causes jaundice during excretion?

Answer 24

Hepatic obstruction (blockage, biliary atresia)
idiopathic neonatal hepatitis (cause unknown)
pale grey stools

Question 25

Can unconjugated bilirubin be good?

Answer 25

A power antioxidant
protects against cellular damage
Another benefit of breastfeeding - preventing cellular damage of the baby.

Question 26

Babies at risk of jaundice?

Answer 26

pre term babies under 38wks
Exclusively breastfed babies
A previous sibling has required phototherapy for jaundice
Forceps/ traumatic delivery - bruising
Delayed cord clamping
neonatal liver condition

Question 27

How would you empower the parents?

Answer 27

Reassure them that this is a normal process
Encourage frequent feeds
Wake for feeds if they are sleepy
Educate on signs/symptoms they should look for - lethargy, sleepiness, reluctant/ poor feeding, pale stools, dark urine, reduced urine, yellow skin/ sclera.

Question 28

What is physiological jaundice

Answer 28

A mild transient form of jaundice, natural physiological process, that doesn’t require treatment, resolves on its own through regular feeding and excretion.

Question 29

What is pathological jaundice?

Answer 29

A form of jaundice requiring treatment, caused by an underlying health condition.

Question 30

How would you explain jaundice to parents?

Answer 30

Babies have extra RBC In utero
Breakdown of RBC required in the liver
Waste products from this process can build up
if they build up in the brain - Kernicterus
The body needs to get rid of these waste products
Therefore regular feeding and wet and dirty nappies will help the baby get rid of this waste.