03.12 GI/GS – Jaundice

Written By Joan

Physiology / Pathophysiology

= Yellowing of the skin secondary to raised bilirubin

  • Bilirubin levels need to be >50 µmol/L to produce clinically significant jaundice (ref)

    • Doesn’t seem to matter which fraction of bilirubin is raised

Example image

Bilirubin

  • Unconjugated bilirubin (UCB) is produced as a result of heme metabolism

  • UCB is insoluble, and is transported to the liver attached to albumin

  • UCB is converted to soluble conjugated bilirubin (CB) in the liver

  • CB is released into bile, which is then excreted from the body via the gut or kidneys (see diagram)

  • Raised levels of UCB or CB will result in hyperbilirubinaemia

    • Lab results usually note total bilirubin which includes both fractions

    • Direct bilirubin is an estimate of conjugated bilirubin – this has to be specifically requested on forms

    • Indirect bilirubin refers to unconjugated bilirubin

Causes of jaundice

Causes of jaundice can be broken down into pre-hepatic, intra-hepatic, and extra-hepatic.

Pre-hepatic jaundice

  • Pre-hepatic jaundice is caused by disease processes occurring before the liver; pre-hepatic jaundice is therefore related to a rise in unconjugated bilirubin.

  • Raised unconjugated bilirubin can be due to increased red blood cell breakdown, i.e., haemolytic anaemias.

    • Examples of these include hereditary spherocytosis, sickle cell anaemia, G6PD.

  • Raised unconjugated bilirubin can be due to reduced rate of conjugation,

    • An example of this is Gilbert syndrome, where there is a genetic defect resulting in lower levels of a specific enzyme required for conjugation of bilirubin (Wikipedia). Gilbert syndrome is benign, and jaundice only happens intermittently when the body is under increased levels of stress.

    • A more severe example is Crigler-Najjar syndrome, an autosomal recessive disorder resulting in defects in a specific enzyme required for conjugation of bilirubin. Type I requires liver transplant as a cure, while Type II can be managed with phenobarbitals

Intra-hepatic jaundice

  • Intra-hepatic jaundice is caused by [1] damage to the hepatocytes where conjugation of bilirubin occurs (≈ hepatitis), or [2] obstruction within the liver (= cholestasis).

  • Examples of damage to hepatocyte / hepatitis include viral hepatitis, alcoholic hepatitis, autoimmune hepatitis – all of which can result in cirrhosis.

  • Disease processes causing cholestasis include primary biliary cholangitis and Dubin-Johnson syndrome.

  • Hepatotoxic drugs can cause drug-induced liver injury (DILI) – either damage to hepatocytes, cholestasis, or both [see more comprehensive list in article here].

    • Hepatocellular damage: paracetamol(!), valproate, isoniazid, rifampicin, pyrazinamide, amiodarone, nitrofurantoin, etc

    • Cholestasis: COCP, amoxicillin & co-amoxiclav, flucloxacillin, co-trimoxazole, clarithromycin, erythromycin, etc

Extra-hepatic jaundice

  • Extra-hepatic jaundice is caused by obstruction preventing bile from being transported from the liver to the intestines.

  • Examples include gallstones in the common bile duct, cholangitis, primary sclerosis cholangitis, cholangiocarcinoma, and disorders causing extrinsic compression of the common bile duct (i.e., Mirrizi syndrome) such as pancreatic cancer or pancreatitis.

Clerking for jaundice

PC: Jaundice

HPC:
When did they first notice jaundice?
First episode? Comes and goes?

Ask about associated smx:
Abdominal pain
Abdominal swelling
Nausea, vomiting
CIBH – constipation / diarrhoea
Colour of stools
Any one else in the family sick?

PMH:


DHx:
Recent change in medications?
** Check for interactions

Allergies:

FHx:


SHx:
Alcohol
Smoking
Illicit drug use – IVDU?
Recent travel? (possibility of hepatitis)
Living situation

Obs: NEWS

Investigations
Bloods: LFTs
ECG:
CXR:
Other imaging

O/E
Check for stigmata of liver disease (see GeekyMedics)

Plan

Further investigations
- Bloods – including full set of LFTs (incl ALT & GGT), viral hepatitis screen (± BBV if at risk), EBV & CMV serology,

References

Daniel S. Pratt, Chapter 73 - Liver Chemistry and Function Tests, Editor(s): Mark Feldman, Lawrence S. Friedman, Lawrence J. Brandt, Sleisenger and Fordtran's Gastrointestinal and Liver Disease (Ninth Edition), W.B. Saunders, 2010, Pages 1227-1237.e2, ISBN 9781416061892,(https://www.sciencedirect.com/science/article/pii/B9781416061892000731)

Kalyan Ram Bhamidimarri, Eugene Schiff, Drug-Induced Cholestasis, Clinics in Liver Disease, Volume 17, Issue 4, 2013, Pages 519-531, ISSN 1089-3261, ISBN 9780323261067, https://doi.org/10.1016/j.cld.2013.07.015.

Joan
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03.11 GI/GS