Bilirubin Metabolism ✅

Question 1

How is bilirubin produced?

Answer 1

From the breakdown of RBCs in the reticuloendothelial system

Question 2

What does the breakdown of RBCs in the reticuloendothelial system produce?

Answer 2

Haemoglobin

Question 3

What is haemoglobin broken down into?

Answer 3

• Fe
• Globin
• Carbon monoxide
• Biliverdin

Question 4

What is biliverdin converted into?

Answer 4

Bilirubin (unconjugated)

Question 5

What happens to unconjugated bilirubin in the plasma?

Answer 5

It binds to albumin to form a bilirubin-albumin complex

Question 6

What happens to the bilirubin-albumin complex?

Answer 6

It is taken up into the liver

Question 7

What happens to the bilirubin once it has been taken up by the liver?

Answer 7

It is conjugated and excreted into bile

Question 8

What happens to conjugated bilirubin in the gut?

Answer 8

Is is hydrolysed

Question 9

What is produced when conjugated bilirubin is hydrolysed in the gut?

Answer 9

• Stercobilinogen

- Urobilinogen

Question 10

How is stercobilinogen removed from the body?

Answer 10

Excreted via faeces

Question 11

How is urobilinogen removed from the body?

Answer 11

It is excreted via the kidney

Question 12

What happens to bilirubin that is not hydrolysed in the gut?

Answer 12

It enters the enterohepatic circulation, and is taken up again into the liver

Question 13

What molecules is haem present in?

Answer 13

• Haemoglobin
• Myoglobin
• Cytochromes

Question 14

What % of bilirubin is derived from haemoglobin?

Answer 14

80%

Question 15

How many molecules of bilirubin are produced from 1 molecule of haem?

Answer 15

1

Question 16

What increases red cell breakdown in neonates?

Answer 16

The high concentration of haemoglobin at birth

Question 17

What is the normal haemoglobin at birth?

Answer 17

150-220g/L

Question 18

Why is there a high concentration of bilirubin at birth?

Answer 18

It is a response to the relative hypoxia environment of the foetus

Question 19

Why is there a breakdown of haemoglobin in early postnatal life?

Answer 19

Because of the increased oxygen concentration

Question 20

What is the neonatal production rate of bilirubin?

Answer 20

100-120µmol/kg/day

Question 21

What is the adult production rate of bilirubin?

Answer 21

50-70µmol/kg/day

Question 22

How is fetal haemoglobin different from adult?

Answer 22

It has a shorter half life

Question 23

What practice increases neonatal red cell mass?

Answer 23

Delayed cord clamping

Question 24

Where is the haem molecule broken down?

Answer 24

In reticuloendothelial cells

Question 25

What is the haem molecule broken down into?

Answer 25

Biliverdin

Question 26

What breaks haem down into biliverdin?

Answer 26

The enzyme haem oxygenase

Question 27

What enzyme converts biliverdin into bilirubin?

Answer 27

Biliverdin reductase enzyme

Question 28

What happens to iron released from the breakdown of haem?

Answer 28

It is used in haem synthesis again

Question 29

How much CO is produced from the breakdown of 1 mole of haem?

Answer 29

1 mole

Question 30

What % of endogenous CO is derived from haem?

Answer 30

80-90%

Question 31

What is the clinical relevance of haem breaking down into CO when considering jaundice?

Answer 31

The end-tidal CO can be used as a surrogate measurement for bilirubin production

Question 32

What kind of bilirubin does red cell breakdown produce?

Answer 32

Unconjugated

Question 33

What happens if the albumin binding capacity is exceeded?

Answer 33

Free bilirubin is released into the circulation

Question 34

What is the problem with free bilirubin being released into the circulation?

Answer 34

As it is lipid soluble, it can cross the blood-brain barrier and result in acute encephalopathy or kernicterus

Question 35

What happens to unconjugated bilirubin bound to albumin?

Answer 35

It is transported to the liver for conjugation

Question 36

What happens to bound bilirubin in the liver?

Answer 36

The albumin-bilirubin compound is dissociated, and the bilirubin is transported to hepatocytes

Question 37

Is the process of bilirubin being transported to hepatocytes active or passive?

Answer 37

Mostly passive process

Question 38

What is the process of transportation of bilirubin to hepatocytes dependant on?

Answer 38

Certain transporter proteins

Question 39

What happens to bilirubin within hepatocytes?

Answer 39

It is bound to cytosolic proteins known as glutathione S-transferases or ligandins within hepatocytes

Question 40

What enzyme is responsible for conjugation of bilirubin within hepatocytes?

Answer 40

Uridine disphosphate glucuronyltransferase (UGT)

Question 41

What is produced from the conjugation of bilirubin by UGT?

Answer 41

Mostly bilirubin diglucuronide, but also some bilirubin monoglucuronide

Question 42

Is excretion of conjugated bilirubin into the biliary system an active or passive process?

Answer 42

Active and energy-dependent

Question 43

What mediates the excretion of conjugated bilirubin into the biliary system?

Answer 43

Specific carrier proteins

Question 44

Can conjugated bilirubin cross the blood brain barrier?

Answer 44

No

Question 45

Why can’t conjugated bilirubin cross the blood brain barrier?

Answer 45

Because it is water soluble

Question 46

What happens to most of the conjugated bilirubin excreted in the bile?

Answer 46

It is hydrolysed back to unconjugated bilirubin

Question 47

What converts conjugated bilirubin back to unconjugated?

Answer 47

Beta-glucuronidase

Question 48

Where is beta-glucuronidase present?

Answer 48

In the intestinal mucosa

Question 49

What happens to conjugated bilirubin that is converted back to unconjugated in the gut?

Answer 49

It is absorbed in the terminal ileum and transported back to the liver via the portal circulation

Question 50

Why does the enterohepatic circulation play an important role in bilirubin metabolism?

Answer 50

It allows bile acids to be recycled

Question 51

What factors increase enterohepatic circulation?

Answer 51

- Prolonged gut transit time - Delayed passage of meconium - Poor enteral feeding - Prematurity - Antibiotic treatment

Question 52

What happens to conjugated bilirubin that is not recycled in the gut?

Answer 52

- Some is converted to stercobilinogen | - Small amount is converted to urobilinogen

Question 53

What converts conjugated bilirubin to stercobilinogen?

Answer 53

Colonic bacteria

Question 54

What happens to stercobilinogen?

Answer 54

It is further oxidised to stercobilin, which gives faeces its brown colour

Question 55

What happens to urobilinogen?

Answer 55

It is excreted into the urine following further oxidation to urobilin, which gives urine its colour