Jaundice

Question 1

Describe the liver

Answer 1

• The largest internal organ of the body, weighing 1.2-1.5kg
• Can be divided into right, left, caudate and quadrate lobes

Question 2

Descibe the blood supply to the liver

Answer 2

It has a duel blood supply - 25% via the hepatic artery and the other 75% from the portal venous system

Question 3

Role of the liver

Answer 3

• Carbohydrate metabolism
• Lipid metabolism
• Synthesis of albumin
• Synthesis of clotting factors
  
  • coagulation factors (II, VII, IX, X) are produced in the liver via vitamin K dependent metabolic pathways
• Immunological function
• Bilirubin metabolism and bile production
• Drug and toxin metabolism

Question 4

What are the two forms of bilirubin?

What is the difference between them?

Answer 4

Unconjugated and conjugated bilirubin

Unconjugated bilirubin is insoluble in water which means it can only travel in the bloodstream bound to albumin and it cannot be directly excreted from the body.

Conjugated bilirubin is water soluble which allows it to travel through the blood stream without requiring transport proteins like albumin, which means it be excreted out of the body.

Question 5

What are the three stages of bilirubin metabolism?

Answer 5

1. Creation of bilirubin
2. Bilirubin conjugation
3. Bilirubin excretion

Question 6

Describe the creation of bilirubin

1. Which cells create bilirubin? What is their role?
2. What is haemoglobin metabolised into?

Answer 6

1. Reticuloendothelial cells are macrophages which are responsible for the maintainance of blood, through the destruction of old and abnormal cells.
2. Haemaglobin is metabolised into haem and globin. Globin is further broken down into amino acids which are subsequently recycled.

Haem is broken down into iron and biliverdin, a process which is catalysed by haem oxygenase. The iron gets recycled, while biliverdin is reduced to create unconjugated bilirubin.

Question 7

Describe bilirubin conjugation

1. How is bilirubin transported to the liver?
2. What happens to the bilirubin in the liver?
3. What happens to the conjugated bilirubin?

Answer 7

1. In the bloodstream, unconjugated bilirubin binds to albumin to facilitate its transport to the liver.
2. Glucuronic acid is added to unconjugated bilirubin by the enzyme UDP-glucuronyl transferase, forming conjugated bilirubin
3. Conjugated bilirubin is excreted into the duodenum as bile

Question 8

Bilirubin excretion

Once in the colon, colonic bacteria deconjugate bilirubin and convert it into A. Around 80% of A is further oxidised by intestinal bacteria and converted to B and then excreted through faeces. It is B which gives faeces their colour.

Around 20% of A is reabsorbed into the bloodstream as part of the enterohepatic circulation. It is carried to the liver where some is recycled for bile production, while a small percentage reaches the kidneys. Here, it is oxidised further into C and then excreted into the urine.

Answer 8

A - Urobilinogen

B - Stercobilin

C - Urobilin

Question 9

How is the release of bile from the gallbladder stimulated?

Answer 9

Cholecystokinin, which is produced by the duodenum

Question 10

What is jaundice?

When is it clinically noticeable?

Answer 10

Jaundice refers to yellow discolouration of the skin and sclera as a result of bilirubin accumulation within the tissues.

It is usually only clinically noticeable at serum levels >40μmol/L.

Question 11

How can the causes of jaundice be divided?

Answer 11

The causes of jaundice can be divided into pre-hepatic, hepatic and cholestatic or obstructive jaundice.

Question 12

Pre-hepatic causes of jaundice

Answer 12

Haemolysis

• Haemolytic anaemia
• Thalassaemia
• Malaria
• Drugs - antimalarials

Congenital hyperbilirubinaemia

• Gilbert syndrome
• Crigler-Najjar syndrome

Question 13

Hepatic causes of jaundice

Answer 13

• Hereditary
  
  • Haemachromatosis
  • Wilson disease
  • Alpha-1-antitrypsin deficiency
• Viral hepatitis
  
  • Hepatitis A-E
  • CMV, EBV
• Autoimmune hepatitis
• Alcohol/drugs

Question 14

Drugs causes of hepatic jaundice

Answer 14

• Alcoholic hepatitis
• Paracetamol
• Statins
• Rifampicin, isoniazid
• Ketoconazole

Question 15

Cholestatic causes of jaundice

Answer 15

• Biliary disease
  
  • Gallstones
  • Pancreatic cancer
  • Cholangiocarcinoma
• Autoimmue
  
  • PBC
  • PSC
• Drugs
  
  • Flucloxacillin
  • CO-amoxiclav
  • Sulphonylureas
  • COCP

Question 16

Investigations for pre-hepatic jaundice

Answer 16

• Urine
  
  • No bilirubin
  • ↑urobilinogen
• LFTs
  
  • ↑unconjugated Bilirubin
  • ↑LDH (haemolysis)
• Other tests
  
  • Coombs test
  • Blood film

Question 17

Investigations for hepatic jaundice

Answer 17

• Urine
  
  • ↑bilirubin
  • ↑urobilinogen
• LFTs
  
  • ↑conjugated Br
  • Hepatic picture (↑↑AST/ALT)
  • ALT >1000 (likely viral, drug cause)
  • ↑GGT (alcohol)
  • ↑PT, ↓albumin
• Other tests
  
  • Liver screen – autoimmune profile, immunoglobulins, iron studies, viral screen, caeruloplasmin
  • Liver biopsy

Question 18

Investigations for cholestatic jaundice

Answer 18

• Urine
  
  • ↑bilirubin
  • No urobilinogen
• LFTs
  
  • ↑↑conjugated bilirubin
  • Cholestasis picture
  • ↑↑ALP, GGT
  • ↑ALT/AST
• Other tests
  
  • Autoimmune screen
  • Abdo USS
  • ERCP/MRCP