Bilirubin and jaundice

Question 1

What is jaundice?

Answer 1

-When high levels of bilirubin collect in the ECF causing the skin and sclera to turn yellow
(jaune - french for yellow)

Question 2

What are the symptoms of jaundice?

Answer 2

• Eyes and skin have a yellow tinge
• itchiness
• fatigue
• abdominal pain
• weight loss
• vomiting
• fever
• pale tools
• dark urine

Question 3

What tests are used to diagnose jaundice

Answer 3

• Bilirubin levels
• Full blood count
• Hep a, b, c
• Imagin? MRI
• Liver biopsy

Question 4

What questions should be asked when history taking a patient with jaundice?

Answer 4

• Are stools pale? (hepatic or post-hepatic)
• Is urine dark? (hepatic or post-hepatic)
• Any abdo pain? (obstruction)
• How much alcohol? (impaired liver function due to alcohol)
• Use of needles (hep a, b, c,)
• Occupation
• Travel ?

Question 5

What is pre-hepatic jaundice?

• where
• why
• symptoms
• causes

Answer 5

Pre-hepatic Jaundice

• Where? spleen/blood/periphery
• Why? due to increased bilirubin production (due to hemolysis, an acceleration in the breakdown of erythrocytes), this causes increased levels of unconjugated bilirubin
• What symptoms?
• normal stools and urine
• splenomegaly
• normal LFTs
• increased urobilnogen
• Causes?
• Genetics, sickle cell anemia, spherocytosis, thalassemia, glucose 6-phosphate
• Kidneys, haemolytic urenic syndrome
• Defects in bilirubin metabolism, gilbert’s syndrome,
• Infections, eg malaria

Question 6

What is hepatic jaundice?

• where
• why
• symptoms
• causes

Answer 6

Hepatic jaundice

Where? Hepatocytes in liver

Why? Swelling, odema, fibrosis
This leads to a problem transporting bilirubin from blood to biliary canaliculi, can lead to problems with bilirubin conjugation (increased conjugated and unconjugated bilirubin)

What symptoms?

• increased UCB
• increased urobilin (dark urine)
• normal/pale stools decreased Urobilinogen
• splenomegaly
• deranged LFTS

-Hepatocellular causes
acute/chronic hepatitis
hepatotoxicity
cirrhosis
drug induced hepatisis
alcohol induced liver disease

Question 7

What is post-hepatic jaundice?

• where
• why
• symptoms
• causes

Answer 7

Post-hepatic jaundice
-Where? Biliary tract

-Why? Generally due to obstruction, this means that conjugated bilirubin cannot make it to the small intestine
this leads to increased build up of bilirubin

• What symptoms?
• increased CB
• increased urobulin (dark urine)
• no splenomegaly (spleen is healthy)
• normal LFTs

-Causes? 
gall stones
pancreatic cancer
liver flukes
pancreatitis
pancreatic pseudocysts
cholongiocarcinoma - cancer of bile duct

Question 8

Describe the bilirubin metabolism

Answer 8

1. Erythrocytes (RBCs) are formed from the reticulocytes from bone marrow via erythropoesis
2. Erythrocytes combine with haemoglobin in carry O2 in the blood stream (life span is about 120 days)
3. Macrophages in the spleen and bone marrow engulf and degrade old and damaged erthrocytes
4. Erythrocytes release the hemoglobin, this broken into
   a) heme - Fe2+ and unconjugated bilirubin (UCB)
   b) globin (made of amino acids that are then recycled)
5. UCB is toxic so it needs to be removed (it is yellow/orange in colour)
6. UCB is lipid soluble, this means that it needs albumin to be transported to the liver
7. The liver has 2 sources of UCB. Those from the spleen and bone marrow and also those that the liver has broken down via kuffer cells (macrophages of the liver)
8. In the liver UCB combines with glucuronic acid to form conjugated bilirubin (this is water soluble and can be excreted via bile into the intestine via the common bile duct
9. At the beginning of the ileum intestinal bacteria convert CB to urobilinogen by removing the glucuronic acid
10. urobilinogen is lipid soluble
11. 10% binds to albumin and is transported back into the liver. about 5% participates in the entero-hepatic system and resecreted into bile again/ other 5% is taken to kidneys where it is converted to urobilin (yellow) and excreted in the urine
12. remaining 90% is oxidized to form sterocobilin (brown) and is excreted in the faeces

Question 9

Is bilirubin water/lipid soluble?

Answer 9

• Bilirubin is water soluble
• UCB is lipid soluble - needs albumin
• Urobilinogen - lipid soluble (binds to albumin or is oxidised)

Question 10

What does intestinal bacteria in the ileum convert CB into?

Answer 10

CB is converted into urobilirubin by removing glucuronic acid

Question 11

What is urobilirubin oxidised into?

Answer 11

sterocobilin