Yellow pigmentation of the skin, sclerae (referred to as icterus) and mucosae due to increased plasma bilirubin.
An Overview of Bilirubin Metabolism
At death, red blood cells rupture, releasing haemoglobin (Hb). The globin portion degrades into amino acids. Haem is acted on by enzymes to ultimately become bilirubin. This is unconjugated (not water-soluble) - it is transported to the liver bound to albumin.
In the liver the bilirubin is conjugated and secreted as part of bile. In the intestine bacteria act on the bilirubin to convert it to urobilinogen, which is either:
- Resorbed by the intestine and transported to the kidneys to be secreted as part of urine (giving it its yellow pigment)
- Converted further by gut flora to stercobilinogen, which is secreted in faeces (giving its dark pigment)
Causes of Jaundice
Causes of jaundice can be classified by the point in this metabolic pipeline at which they occur.
|Pre-hepatic||Before the liver. generally anything which causes increased haemolysis||malaria, sickle-cell anaemia, thalassemia|
|Hepatic||Hepatic cell necrosis reduces ability to conjugate and excrete bilirubin||Illness causing hepatitis or cirrhosis - viral hepatitis, alcoholic liver disease, Wilson's disease|
|Post-Hepatic||Obstruction of the biliary tree||gallstones, cancer in head of pancreas.|
Clinical Signs of Jaundice
The skin, sclera and mucosal membrane changes can be seen in all classifications of jaundice. However, changes to stool and urine are deliniated by the cause:
- Pre-hepatic jaundice causes no change to stool or urine - there's a greater amount of bilirubin in the body, but the metabolic pathway is intact
- Hepatic jaundice causes dark urine - bilirubin is slowly conjugated but the defective liver can't utilise it quickly enough in bile so it spills over into blood. Now that it is water-soluble it can enter the urinary system.
- Post-hepatic jaundice causes dark urine and pale stools - Bilirubin is conjugated, but the biliary tree is blocked, so none of the bile is reaching the gut and so is not pigmenting stool at all. Spills into blood and darkens urine
|ALP, AST and AST levels||Normal||Increased||Increased|
|Conjugated bilirubin in urine||Not present||Present||Present|
Jaundice in Children
Jaundice in first 24 hours of life is always pathological. Jaundice in the following 2-14 days is common and usually physiological and commonest in breast-fed babies. After 14 days jaundice should be treated with suspicion and a full jaundice screen performed. Since the immature neonatal liver cannot metabolise bilirubin it accumulates more quickly than in children and adults. Furthermore the blood-brain barrier is less effective leading to an accumulation of bilirubin to in the grey matter, known as Kernicterus. This can cause irreversible neurological damage.
The commonest causes of early jaundice are:
- Rhesus haemolytic disease (haemolytic disease of the newborn) - haemolysis due to maternal IgG to newborn's ABO
- Hereditary spherocytosis - an autosomal dominant genetic condition causes erythrocytes to be spherical rather than their usual bi-concave shape. These abnormally shaped cells are destroyed by the spleen.
- Glucose-6-phosphate dehydrogenase (G6PD) deficiency - an X linked recessive condition where deficiancy in the G6PD enzyme causes haemolysis due to oxidative free radical build-up.
- Infection - sepsis & TORCH infection