jaundice

jaundice The occurrence of jaundice — the yellow discolouration of skin, the sclerae of the eyes and other heavily perfused tissues — is well recorded in ancient writings, including those from Assyria, where epidemic jaundice was first described. In these ancient times, however, jaundice was considered a disease in itself, rather than a sign of an underlying disorder. It was Baillie, a Scottish physician in the early 1800s, who first linked the occurrence of jaundice to cirrhosis of the liver. Shortly afterwards, Bright (the Guy's Hospital physician most famous for his description of kidney disease) distinguished four hepatic causes of jaundice: ‘hepatic congestion’, ‘biliary obstruction’, ‘chronic changes in the liver’ and ‘acute, diffuse inflammation of the substance of the liver’, which would either resolve or progress to chronic disease.

Accumulation of the pigment bilirubin in the bloodstream, leading to jaundice, may result from either overproduction of bilirubin or impaired hepatic metabolism of this substrate. About 80% of the bilirubin normally circulating is derived from the continual turnover of red blood cells, which become senescent when they reach their normal lifespan of approximately 120 days. Destruction of these cells releases haem from their haemoglobin, which is quickly metabolized in the liver to biliverdin and, in turn, to bilirubin. The remaining 20% of circulating bilirubin is derived either from the destruction of maturing blood cells in the bone marrow or from the metabolism of various haem-containing enzymes. The liver plays an essential role in the metabolism of bilirubin and the excretion of its metabolites into the bile. Jaundice usually becomes clinically evident only when the level of bilirubin in the serum increases to at least twice the normal upper limit.

In practical terms, therefore, jaundice is the consequence either of abnormal haemolysis, when excessive destruction of red blood cells releases increased quantities of bilirubin, overwhelming the liver's metabolic reserve; or of liver cell or bile duct disorders, in which the hepatic uptake, metabolism, or biliary excretion of bilirubin is impaired. Common examples of these latter disorders include disturbance of liver cell function by acute hepatitis and obstruction of the bile ducts by impacted gallstones. Mild elevation of the bilirubin level in the blood, especially evident during fasting or any general illness, and usually to less than twice the upper limit of normal, is most often due to ‘ Gilbert's syndrome’ — described by this French physician in 1900 and later explained as a benign genetic variant in which the activity of a liver enzyme called ‘glucuronyl transferase’, is reduced. Normally this enzyme converts bilirubin to a water soluble conjugate prior to excretion in the bile. Gilbert's syndrome is present in at least 1% of the normal population and is not associated with either liver disease or haemolysis.

Stephen M. Riordan, and Roger Williams

See also bile; haemoglobin; liver.