Jaundice

Jaundice refers to the yellow discolouration of the sclera and skin that is due to hyperbilirubinaemia (this usually occurs at around bilirubin levels >50 µmol/L). 

In this article, we shall look at the aetiology, investigation and management of a patient with jaundice.

Fig. 1 - Yellow sclera, as seen in a jaundice patient

Fig. 1 – Yellow sclera, as seen in a jaundice patient


Pathophysiology and Aetiology

Jaundice results from high levels of bilirubin in the blood. Bilirubin is the normal breakdown product from the catabolism of haem – and thus is formed from the destruction of red blood cells.

Under normal circumstances, bilirubin undergoes conjugation within the liver, making it water-soluble. It is then excreted via the bile into the GI tract, the majority of which egested in the faeces as urobilinogen. Around 10% is reabsorbed into the bloodstream and excreted through the kidneys. Jaundice occurs when this pathway is disrupted.

Fig 1 - Bilirubin is produced as a byproduct of haem metabolism.

Fig 2 – Bilirubin is produced as a byproduct of haem metabolism.

Types of Jaundice

There are three main types of jaundice – pre-hepatic, hepatocellular, and post-hepatic.

Pre-Hepatic

In pre-hepatic jaundice, there is excessive red cell breakdown – which overwhelms the liver’s ability to conjugate bilirubin. This causes an unconjugated hyperbilirubinaemia.

Any bilirubin that manages to become conjugated will be excreted normally, yet it is the unconjugated bilirubin that remains in the blood stream to cause the jaundice.

Hepatocellular

In hepatocellular (or intrahepatic) jaundice, there is dysfunction of the liver itself. The liver loses the ability to conjugate bilirubin, but as it becomes cirrhotic, it also compresses the intra-hepatic portions of the biliary tree – thus also causing a degree of obstruction.

This leads to unconjugated and conjugated bilirubin in the blood, termed a ‘mixed’ picture.

Post-Hepatic

Post-hepatic jaundice refers to obstruction of the biliary tree, which prevents the drainage and excretion of bile. The bilirubin that is not excreted will have been conjugated by the liver, hence the result is a conjugated hyperbilirubinaemia.

Pre-Hepatic Hepatocellular Post-Hepatic
Haemolytic anaemia

Gilbert’s syndrome or Criggler-Najjar syndrome

 

 

Alcoholic liver disease

Viral hepatitis

Medication

Hereditary haemochromatosis

Wilson’s disease

Alpha-1-antitrypsin deficiency

Autoimmune hepatitis

Primary biliary cirrhosis

Primary sclerosing cholangitis

Hepatocellular carcinoma

Intra-luminal causes, such as gallstones

Mural causes, such as cholangiocarcinoma, strictures, or drug-induced cholestasis

Extra-mural causes, such as pancreatic cancer or abdominal masses (e.g. lymphomas)

 

 

 

 

Table 1 – Differential Diagnosis for Jaundice 

Bilirubinuria

A good estimation of which type of jaundice is present (prior to any further investigation) can be made from observing the colour of the urine.

Conjugated bilirubin can be excreted via the urine (as it is water soluble), whereas unconjugated cannot. Consequently, dark (‘coca-cola’) urine manifests in conjugated or mixed hyperbilirubinaemias, whereas normal urine is seen in unconjugated disease.


Investigations

In many cases, the likely underlying cause can be elicited from the history, with the investigations simply confirming suspicions. Hence, whilst a complete list of investigations is given below, these should be tailored to the clinical features of the patient.

Laboratory Tests

A urine dipstick should be performed, as can confirm the presence of bilirubin (also excluding dark urine haematuria).

Any patient presenting with jaundice should have the following bloods taken:

  • Liver function tests (LFTs), as summarised in Table 2.
  • Coagulation studies (INR can be used as a marker of liver synthesis function)
  • FBC (raised MCV and thrombocytopenia seen in liver disease) and U&Es
  • Specialist blood tests:
    • Viral hepatitis screen (Hep A, B, C +/- D +/- E)
Table 2 – LFT Blood Markers
Blood Marker Significance
Bilirubin Quantify degree of any suspected jaundice
Albumin Marker of liver synthesising function
AST and ALT Markers of hepatocellular injury*
Alkaline Phosphatase Raised in biliary obstruction (or bone injury)
Gamma-GT Not in routine LFTs. Specific for biliary obstruction, requested if raised Alk Phos and unsure of cause

Table 2 – LFT Blood Markers. *If AST:ALT ratio >2, likely alcoholic liver disease; if AST:ALT around 1, likely viral hepatitis

Liver Screen

A liver screen can be performed for patients where the initial investigations are negative or there is no clear reason for the liver disease.

Tests involved in a liver screen can include:

  • Iron studies (hereditary haemochromatosis)
  • Caeruloplasmin (Wilson’s disease)
  • Immunoglobulins (autoimmune hepatitis)
  • Alpha-1-antitrypsin (alpha-1-antitrypsin deficiency)
  • Alpha fetoprotein (AFP, hepatocellular carcinoma and cholangiocarcinoma)
  • Autoantibodies

Common autoantibodies include anti-mitochondrial antibody (AMA), anti-smooth-muscle antibody (Anti-SMA), and anti-nuclear antibody (ANA). They are used to identify a variety of autoimmune liver conditions, such as primary sclerosing cholangitis (PSC).

Imaging

The imaging used will depend on the presumed aetiology. Ultrasound is usually first line. MRCP can be opted for in some cases as it visualises the biliary tree and does not require contrast.

A biopsy can be performed when the diagnosis has not been made despite the above investigations.


Management

The definitive treatment of jaundice will be dependent on the underlying cause. Obstructive causes may require removal of a gallstone through ERCP or open surgery, cholecystectomy, or stenting of the common bile duct.

Symptomatic treatment is often needed for the itching caused by hyperbilirubinaemia. An obstructive cause may warrant cholestyramine (acting to increase biliary drainage), whilst other causes may respond to simple anti-histamines.

Identify and manage any complications of liver failure where possible. Treat coagulopathy promptly (Vitamin K or fresh frozen plasma (FFP)) and treat hypoglycaemia orally if possible, otherwise 5% dextrose is needed.

Where patients become confused in liver failure (‘hepatic encephalopathy’), laxatives (lactulose or senna) with neomycin may be used, reducing the number of ammonia-producing bacteria in the bowel. In patients who are refractory to this, antibiotics which only work on the bowel may be trialled: this is usually fidaxamicin but will vary based on your local guidelines.

Fig 4 - Images from a laparoscopic cholecystectomy.

Fig 3 – Images from a laparoscopic cholecystectomy.

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