Jaundice

What is it?

Jaundice is a yellowing of the skin, whites of the eyes and body fluids. It is caused by an increase in the amount of bilirubin in the blood. Bilirubin is a yellow pigment that is produced from the breakdown of haem, mostly from haemoglobin in red blood cells (RBCs). Bilirubin is transported by the blood to the liver, where an enzyme links it to a sugar, a process called conjugation. The conjugated bilirubin is excreted from the liver as bile, eventually reaching the small intestine. Jaundice may arise from an increase the breakdown of red blood cells, from liver disease or from a problem with the excretion of bile.

Examples of common conditions that may cause jaundice

Haemolytic anaemia: may be caused by an abnormal haemoglobin variant in the red blood cells, malaria, an autoimmune process, haemolytic disease of the newborn or any other condition that lead to a significant increase in the destruction of red blood cells and to an increase in the production of bilirubin. The jaundice is mild and due to unconjugated bilirubin.
Physiological (normal) jaundice: mild jaundice is seen in more than 50% of newborns due to the immaturity of the baby's liver enzyme which is needed to conjugate bilirubin. It usually appears at 2 to 4 days and disappears by 7 to 10 days. If the jaundice appears early, persists or is severe the infant will be investigated for other causes and is likely to need treatment.
Gilbert’s syndrome: about 3% of the UK population have this condition. It is associated with decreased bilirubin conjugation in the liver due to an inherited decrease in enzyme activity and therefore reduced excretion in the bile. Those affected may have temporary mild jaundice during times of illness or stress caused by increases in their blood unconjugated bilirubin levels.
Acute hepatitis: liver inflammation due to a variety of causes including hepatitis A, B, C, D, and E viral infections, alcohol abuse, and some medicines and toxins. More than half of the bilirubin in the blood is conjugated and bilirubin appears in the urine.
Obstruction of the bile ducts inside or outside the liver may be due to liver damage and scarring in the late stages of cirrhosis, cancer in the liver or biliary atresia, a congenital condition with abnormal development of the bile ducts. Gallstones can block bile ducts and pancreatic cancer can sometimes lead to a blockage of the main bile duct. Back-up of bile behind an obstruction leads to the appearance of conjugated bilirubin in the blood and urine. If the obstruction is severe, the stools become pale.

Examples of more rare conditions that may cause jaundice

Wilson’s Disease: an inherited disorder of copper metabolism which results in excessive deposits of copper in the liver, causing cirrhosis and jaundice, as well as in the brain and cornea of the eye.
Alpha 1 Antitrypsin Deficiency: an inherited condition in which defective alpha 1 antitrypsin accumulates in the liver cell causing liver damage and jaundice. The severe form of alpha 1 antitrypsin deficiency is the most common genetic cause of liver disease in babies and children
Crigler-Najjar syndrome: an inherited condition that may lead to high bilirubin concentrations; a gene mutation leads to a deficiency in the enzyme necessary for bilirubin conjugation.
Dubin-Johnson syndrome: an inherited disorder that impairs the secretion of bilirubin from liver cells after it has been conjugated; patients may have intermittent jaundice.
Rotor’s syndrome: an inherited cause of mild intermittent jaundice; similar to Dubin-Johnson without the retention of bilirubin in the liver cells.
Pseudojaundice: the skin of a person may turn yellowish when they eat large quantities of carrots, pumpkin or melon due to the presence of beta-carotene; a temporary and benign condition not related to bilirubin or bile

About Jaundice

Tests
The goal of testing is to determine the cause of the jaundice and to evaluate the severity of the underlying disease. Initial testing is usually focused on the liver. Specific additional tests, such as viral hepatitis testing or testing to evaluate increased RBC destruction, may be requested with or following the initial tests based on the patient’s clinical findings and the doctor’s suspicions of the cause of the jaundice.

Laboratory Tests

Tests may include:

Liver function tests, which usually include total bilirubin, ALT (alanine aminotransferase), ALP (alkaline phosphatase), total protein and albumin

Conjugated and unconjugated bilirubin

AST (aspartate aminotransferase)

GGT (gamma-glutamyl transferase)

Copper (serum and/or urine)

Caeruloplasmin

Alpha 1 antitrypsin level (pheno/genotype if indicated)

Hepatitis A

Hepatitis B

Hepatitis C

FBC (Full blood count)

Reticulocyte count (if FBC is abnormal)

PT (prothrombin time)

Less commonly requested tests include G6PD (glucose-5-phosphate dehydrogenase), haemoglobin variants, ASMA (anti-smooth muscle antibodies) and ANA (anti-nuclear antibodies).

Non-Laboratory Tests

Imaging tests and liver biopsies may be used to help evaluate the status and structure of the liver, gallbladder, and bile ducts. Tests may include:

Abdominal ultrasound

Computed tomography (CT)

Cholangiography (an imaging of the bile ducts)

ERCP(endoscopic retrograde cholangiopancreatography, imaging of the pancreatic and bile ducts)

Liver biopsy
Treatments

Jaundice in newborns must be treated if it becomes severe, usually by exposure of the skin to blue light, because high unconjugated bilirubin levels can cause permanent brain damage. In all other cases it is not the jaundice that needs to be treated but the underlying condition. Should the condition resolve, then the jaundice will resolve as well. If an obstruction is present surgery may be necessary.