Jaundice

Question 1

What is it?

Answer 1

Increased circulating bilirubin

Caused by altered metabolism of bilirubin

Question 2

What is the 3 step pathway of bilirubin metabolism?

Answer 2

Pre-hepatic
Hepatic
Post-hepatic

Question 3

What happens in the pre-hepatic stage?

Answer 3

Breakdown of haemoglobin in spleen to form harm and globing
Haem converted to bilirubin
Release of bilirubin into circulation

Question 4

What happens in the hepatic stage?

Answer 4

Uptake of bilirubin by hepatocytes
Conjugation of bilirubin in hepatocytes
Excretion of conjugated bilirubin into biliary system

Question 5

What happens in the post-hepatic stage?

Answer 5

Transport of conjugated bilirubin in biliary system
Breakdown of bilirubin conjugate in intestine
Re-absorption of bilirubin (entero-hepatic circulation of bilirubin)

Question 6

When bilirubin is reabsorbed where does it go?

Answer 6

If it is not reabsorbed bilirubin is excreted in faeces

If reabsorbed, it is excreted in the urine or it goes back to the liver and is put into bile again

Question 7

How is jaundice classified?

Answer 7

Pre-hepatic
Hepatic
Post-hepatic

Question 8

What is the causes of pre-hepatic jaundice?

Answer 8

Increased release of haemoglobin from red cells (haemolysis)

This therefore causes an increased quantity of bilirubin

Question 9

What are the hepatic causes of jaundice?

Answer 9

Cholestasis

Intra-hepatic bile duct obstruction

Question 10

What are the 3 things that can go wrong in the hepatic stage?

Answer 10

Defective uptake of bilirubin
Defective conjugation
Defective excretion

Question 11

What is cholestasis?

Answer 11

Accumulation of bile within hepatocytes or bile canaliculi (go onto form intrahepatic bile ducts)

Question 12

What causes cholestasis?

Answer 12

Viral hepatitis
Alcoholic hepatitis
Liver failure
Drugs: therapeutic, recreational

Question 13

Drug-induced cholestasis may be predictable or unpredictable. What does this mean?

Answer 13

Predictable: dose related
Unpredictable: not dose related

Question 14

What causes an intrahepatic bile duct obstruction?

Answer 14

Primary biliary cholangitis
Primary sclerosing cholangitis
Tumours of the liver

Question 15

What are some tumours that can arise in the liver?

Answer 15

Hepatocellular carcinoma
Tumours of intra-hepatic bile ducts
Metastatic tumours

Question 16

What do both primary biliary cholangitis and primary sclerosing cholangitis progress to?

Answer 16

Cirrhosis

Question 17

What is hepatic cirrhosis?

Answer 17

End stage chronic liver disease: response of liver to chronic injury

Question 18

What are some causes of cirrhosis?

Answer 18

Alcohol
Hepatitis B, C
Immune mediated liver disease: auto-immune hepatitis, primary biliary cholangitis
Obesity: diabetes mellitus
Metabolic disorders: excess iron (primary haemochromatosis), excess copper (Wilson’s disease)

Question 19

What are some complications of cirrhosis?

Answer 19

Altered liver function: liver failure
Abnormal blood flow: portal hypertension
Increased risk of hepatocellular carcinoma

Question 20

What is hepatocellular carcinoma?

Answer 20

Malignant tumour of hepatocytes

Question 21

What is cholangiocarcinoma?

Answer 21

Malignant tumour of bile duct epithelium

Question 22

Are metastatic tumours common in the liver?

Answer 22

The liver is a common site of metastasis

Question 23

What are some causes of hepatocellular jaundice?

Answer 23

Hepatocellular liver damage: drugs
Hepatitis: viral, alcohol, non-alcoholic steatohepatitis
Cirrhosis

Question 24

What are some causes of post hepatic jaundice?

Answer 24

Structural disorder of the bile ducts
Cholelithiasis
Pancreatic cancer
Pancreatitis
Congenital atresia of bile duct
Bile duct obstruction: cholangiocarcinoma/stricture
Primary sclerosing cholangitis

Question 25

What is cholelithiasis?

Answer 25

Gallstones

Question 26

What are the risk factors for gallstones?

Answer 26

Obesity | Diabetes

Question 27

What are the diseases of the gallbladder that can cause post-hepatic jaundice?

Answer 27

Inflammation of the gallbladder: Acute cholecystitis Chronic cholecystitis

Question 28

What are the complications of acute cholecystitis?

Answer 28

Empyema Perforation of gallbladder: biliary peritonitis Progression to chronic inflammation

Question 29

What are the complications of chronic cholecystitis?

Answer 29

Chronic inflammation and fibrosis of gallbladder

Question 30

What are some causes of common bile duct obstruction?

Answer 30

Gallstones Bile duct tumours Benign stricture External compression: tumours

Question 31

What are the effects of common bile duct obstruction?

Answer 31

Jaundice No bile excreted into duodenum Infection of bile proximal to obstruction: ascending cholangitis Secondary biliary cirrhosis if obstruction prolonged

Question 32

What does jaundice look like?

Answer 32

Yellow discolouration of mucous membranes, sclera and skin | Scratch marks from itching (pruritus)

Question 33

What is the urine and stool colour in each of the 3 types of jaundice?

Answer 33

Prehepatic: normal urine and stools Hepatic: dark urine and slightly pale stools Post hepatic: darkest urine and pale stools

Question 34

What type of hyperbilirubinaemia is each of the 3 types of jaundice?

Answer 34

Prehepatic: unconjugated Hepatic: mixed (unconjugated and conjugated) Post hepatic: conjugated

Question 35

Why does hepatic and post hepatic cause dark urine?

Answer 35

Conjugated bilirubin can be excreted via the urine (as it is water soluble), whereas unconjugated cannot

Question 36

What are some clues on history of prehepatic, hepatic and posthepatic jaundice?

Answer 36

Prehepatic: history of anaemia (fatigue, dyspnoea, chest pain) Hepatic: risk factors for liver disease (IVDU, alcohol), decompensation (ascites, variceal bleed, encephalopathy) Post hepatic: abdominal pain

Question 37

What are some clues on examination of prehepatic, hepatic and posthepatic jaundice?

Answer 37

Prehepatic: pallor, splenomegaly Hepatic: signs of CLD Post hepatic: palpable gall bladder

Question 38

When is jaundice detectable?

Answer 38

Detectable when total plasma bilirubin levels exceed 34 umol/L (normal is up to 20)

Question 39

What is the differential diagnosis of jaundice?

Answer 39

Carotenemia: caused by lots of carrots/beta carotene

Question 40

What are the investigations into the cause of the jaundice?

Answer 40

``` Liver screen: hepatitis B + C serology, autoantibody profile and serum immunoglobulins Ultrasound abdomen: most important test, differentiates extrahepatic and intrahepatic obstruction CT MRI ERCP MRCP PTC EUS ```

Question 41

How is jaundice treated?

Answer 41

Treat the underlying cause