Bilirubin Metabolism ✅ Flashcards
How is bilirubin produced?
From the breakdown of RBCs in the reticuloendothelial system
What does the breakdown of RBCs in the reticuloendothelial system produce?
Haemoglobin
What is haemoglobin broken down into?
- Fe
- Globin
- Carbon monoxide
- Biliverdin
What is biliverdin converted into?
Bilirubin (unconjugated)
What happens to unconjugated bilirubin in the plasma?
It binds to albumin to form a bilirubin-albumin complex
What happens to the bilirubin-albumin complex?
It is taken up into the liver
What happens to the bilirubin once it has been taken up by the liver?
It is conjugated and excreted into bile
What happens to conjugated bilirubin in the gut?
Is is hydrolysed
What is produced when conjugated bilirubin is hydrolysed in the gut?
- Stercobilinogen
- Urobilinogen
How is stercobilinogen removed from the body?
Excreted via faeces
How is urobilinogen removed from the body?
It is excreted via the kidney
What happens to bilirubin that is not hydrolysed in the gut?
It enters the enterohepatic circulation, and is taken up again into the liver
What molecules is haem present in?
- Haemoglobin
- Myoglobin
- Cytochromes
What % of bilirubin is derived from haemoglobin?
80%
How many molecules of bilirubin are produced from 1 molecule of haem?
1
What increases red cell breakdown in neonates?
The high concentration of haemoglobin at birth
What is the normal haemoglobin at birth?
150-220g/L
Why is there a high concentration of bilirubin at birth?
It is a response to the relative hypoxia environment of the foetus
Why is there a breakdown of haemoglobin in early postnatal life?
Because of the increased oxygen concentration
What is the neonatal production rate of bilirubin?
100-120µmol/kg/day
What is the adult production rate of bilirubin?
50-70µmol/kg/day
How is fetal haemoglobin different from adult?
It has a shorter half life
What practice increases neonatal red cell mass?
Delayed cord clamping
Where is the haem molecule broken down?
In reticuloendothelial cells
What is the haem molecule broken down into?
Biliverdin
What breaks haem down into biliverdin?
The enzyme haem oxygenase
What enzyme converts biliverdin into bilirubin?
Biliverdin reductase enzyme
What happens to iron released from the breakdown of haem?
It is used in haem synthesis again
How much CO is produced from the breakdown of 1 mole of haem?
1 mole
What % of endogenous CO is derived from haem?
80-90%
What is the clinical relevance of haem breaking down into CO when considering jaundice?
The end-tidal CO can be used as a surrogate measurement for bilirubin production
What kind of bilirubin does red cell breakdown produce?
Unconjugated
What happens if the albumin binding capacity is exceeded?
Free bilirubin is released into the circulation
What is the problem with free bilirubin being released into the circulation?
As it is lipid soluble, it can cross the blood-brain barrier and result in acute encephalopathy or kernicterus
What happens to unconjugated bilirubin bound to albumin?
It is transported to the liver for conjugation
What happens to bound bilirubin in the liver?
The albumin-bilirubin compound is dissociated, and the bilirubin is transported to hepatocytes
Is the process of bilirubin being transported to hepatocytes active or passive?
Mostly passive process
What is the process of transportation of bilirubin to hepatocytes dependant on?
Certain transporter proteins
What happens to bilirubin within hepatocytes?
It is bound to cytosolic proteins known as glutathione S-transferases or ligandins within hepatocytes
What enzyme is responsible for conjugation of bilirubin within hepatocytes?
Uridine disphosphate glucuronyltransferase (UGT)
What is produced from the conjugation of bilirubin by UGT?
Mostly bilirubin diglucuronide, but also some bilirubin monoglucuronide
Is excretion of conjugated bilirubin into the biliary system an active or passive process?
Active and energy-dependent
What mediates the excretion of conjugated bilirubin into the biliary system?
Specific carrier proteins
Can conjugated bilirubin cross the blood brain barrier?
No
Why can’t conjugated bilirubin cross the blood brain barrier?
Because it is water soluble
What happens to most of the conjugated bilirubin excreted in the bile?
It is hydrolysed back to unconjugated bilirubin
What converts conjugated bilirubin back to unconjugated?
Beta-glucuronidase
Where is beta-glucuronidase present?
In the intestinal mucosa
What happens to conjugated bilirubin that is converted back to unconjugated in the gut?
It is absorbed in the terminal ileum and transported back to the liver via the portal circulation
Why does the enterohepatic circulation play an important role in bilirubin metabolism?
It allows bile acids to be recycled
What factors increase enterohepatic circulation?
- Prolonged gut transit time
- Delayed passage of meconium
- Poor enteral feeding
- Prematurity
- Antibiotic treatment
What happens to conjugated bilirubin that is not recycled in the gut?
- Some is converted to stercobilinogen
- Small amount is converted to urobilinogen
What converts conjugated bilirubin to stercobilinogen?
Colonic bacteria
What happens to stercobilinogen?
It is further oxidised to stercobilin, which gives faeces its brown colour
What happens to urobilinogen?
It is excreted into the urine following further oxidation to urobilin, which gives urine its colour
