Jaundice

Question 1

What is jaundice?

Answer 1

Hyperbilirubinemia

Question 2

Where is bilirubin produced and metabolised?

Answer 2

Bilirubin is produced from breakdown of RBCs and is usually removed from the circulation in the urine and faeces. In each case, it gives the urine and faeces colour.

Question 3

Normal metabolism:

Answer 3

• PRE-HEPATIC
• Macrophages phagocytose free Hb and split into heme and globin
• Heme is turned into biliverdin by heme oxygenase
• Biliverdin is reduced to bilirubin by biliverdin reductase
• This bilirubin is unconjugated and fat-soluble
• It is carried to the liver by albumin
• HEPATIC
• Once unconjugated bilirubin arrives in the liver, UDP-glucuronyl transferase (UGT) conjugates bilirubin and glucuronic acid into bilirubin diglucuronide (conjugated bilirubin). This is water-soluble and excreted in the gallbladder
• POSTHEPATIC
• Bilirubin is converted into urobilinogen by symbiotic intestinal bacteria
• Most is converted into stercobilinogen and further oxidised to stercobilin which is excreted in the faeces
• A small portion of urobilinogen is reabsorbed back into the blood and undergoes hepatobiliary recirculation.
• A smaller potion is filtered into the kidneys where it is converted into urobilin (colours urine yellow)

Question 4

Aetiology

Answer 4

• Pre-hepatic: EXCESSIVE PRODUCTION OF BILIRUBIN Increased rate of erythrocyte haemolysis, leading to raised bilirubin production, higher risk of pigmented gallstones and therefore darker faeces and urine
• Hepatic: PATHOLOGY OF LIVER
• Post-hepatic (also called obstructive): LACK OF BILE FLOW INTO GUT
• Note: there is debate over whether movement of conjugated bile into canaliculi is a hepatic, or post-hepatic form of jaundice. They may be used interchangeably.
• Causes of increased production of bilirubin:

o Intravascular haemolysis: congenital and acquired

o Extravascular haemolysis: congenital and acquired

• Causes of decreased conjugation:

o Reduced hepatocyte uptake: drugs, portosystemic shunts

o Congenital enzymatic problems: Gilbert’s syndrome, Crigler-Najjar syndrome

• Causes of decreased excretion of bilirubin:

o INVITE MD

o Infection: viral hepatitis, hepatocellular carcinoma, pancreatic cancer, cholangiocarcinoma

o Vascular: Budd-Chiari syndrome (thrombosis in hepatic vein)

o Inflammation: PBC, PSC, autoimmune hepatitis, pancreatitis

o Trauma: gallstones, stricture (after ECRP or cholecystectomy)

o Endocrine: cholestasis of pregnancy

o Metabolic: Wilson’s disease, haemochromatosis

o Drugs: some induce paralysis of biliary system such as co-amoxiclav, OCP and nitrofurantoin, while others affect the ability of hepatocytes to excrete bilirubin such as alcohol and paracetamol overdose

Question 5

Classification

Answer 5

Jaundice can also be categorised into CHOLESTATIC (caused by problem of bilirubin flow out of CBD from obstruction e.g., gallstone or paralysis e.g., ileus which can be drug-induced), UNCOJUGATED (jaundice from accumulation of unconjugated bilirubin from increased RBC breakdown or decreased capacity to conjugate bilirubin – this includes ALL pre-hepatic causes), and CONJUGATED (accumulation of conjugated bilirubin and therefore includes ALL post-hepatic causes)

Question 6

Gilbert’s syndrome?

Answer 6

BLOODS: High CB and very high UCB Gilbert’s syndrome (hepatic, unconjugated jaundice) Inherited disorder leading to less effective UGT enzyme As such, in times of infection, stress or starvation where there is increased haemolysis, there is temporary overload and jaundice.

Question 7

Crigler-Najjar Syndrome?

Answer 7

BLOODS: High CB and very high UCB Crigler-Najjar Syndrome have no UGT so get kernicterus (unconjugated hyperbilirubinemia leading to toxic deposition in the grey matter of the CNS and irreversible brain damage).

Question 8

Dubin-Johnson syndrome?

Answer 8

Dubin-Johnson syndrome (hepatic/post-hepatic, conjugated jaundice) MRP2 transporter protein deficient leading to ineffective transport of conjugated bilirubin into bile canaliculus. As such, it can only be removed in the kidneys leading to dark urine.

Question 9

Obstructive jaundice?

Answer 9

BLOODS: Obstructive jaundice – very high CB and high UCB Physical obstruction such as gallstones (painful jaundice) or pancreatic-/cholangio-carcinoma (painless jaundice) results in raised conjugated bilirubin and bile salts. In complete obstruction, this leads to no further bilirubin conjugation due to congestion. In obstructive cases, there is leakage of bile salt acids and cholesterol through the interstitium and into the blood causing pruritis, dyslipidaemia and xanthomas. Conjugated bilirubin gives urine an abnormally dark brown colour with associated pale stool (stercobilin absent from faeces)