Jaundice, (also known as icterus, attributive adjective: icteric) is a yellowish pigmentation of the skin, the conjunctival membranes over the sclerae (whites of the eyes), and other mucous membranes caused by hyperbilirubinemia (increased levels of bilirubin in the blood). This hyperbilirubinemia subsequently causes increased levels of bilirubin in the extracellular fluids. Typically, the concentration of bilirubin in the plasma must exceed 1.5 mg/dL ( > 35 micromoles/L), three times the usual value of approximately 0.5 mg/dL, for the coloration to be easily visible. Jaundice comes from the French word jaune, meaning yellow.
The conjunctiva of the eye are one of the first tissues to change color as bilirubin levels rise in jaundice. This is sometimes referred to as scleral icterus. However, the sclera themselves are not “icteric” (stained with bile pigment) but rather the conjunctival membranes that overlie them. The yellowing of the “white of the eye” is thus more properly termed conjunctival icterus. The term “icterus” itself is sometimes incorrectly used to refer to jaundice that is noted in the sclera of the eyes, however its more common and more correct meaning is entirely synonymous with jaundice.
It was once believed persons suffering from the medical condition jaundice saw everything as yellow. By extension, the jaundiced eye came to mean a prejudiced view, usually rather negative or critical. Alexander Pope, in “An Essay on Criticism” (1711), wrote: “All seems Infected that th’ Infected spy, As all looks yellow to the Jaundic’d Eye.” Similarly in the mid-19th century the English poet Alfred Lord Tennyson wrote in the poem Locksley Hall: “So I triumphe’d ere my passion sweeping thro’ me left me dry, left me with the palsied heart, and left me with a jaundiced eye.”
When a pathological process interferes with the normal functioning of the metabolism and excretion of bilirubin just described, jaundice may be the result. Jaundice is classified into three categories, depending on which part of the physiological mechanism the pathology affects. The three categories are:
|Pre-hepatic||The pathology is occurring prior to the liver.|
|Hepatic||The pathology is located within the liver.|
|Post-Hepatic||The pathology is located after the conjugation of bilirubin in the liver.|
Pre-hepatic jaundice is caused by anything which causes an increased rate of hemolysis (breakdown of red blood cells). In tropical countries, malaria can cause jaundice in this manner. Certain genetic diseases, such as sickle cell anemia, spherocytosis, thalassemia and glucose 6-phosphate dehydrogenase deficiency can lead to increased red cell lysis and therefore hemolytic jaundice. Commonly, diseases of the kidney, such as hemolytic uremic syndrome, can also lead to coloration. Defects in bilirubin metabolism also present as jaundice, as in Gilbert’s syndrome (a genetic disorder of bilirubin metabolism which can result in mild jaundice, which is found in about 5% of the population)and Crigler-Najjar syndrome.
In jaundice secondary to hemolysis, the increased production of bilirubin, leads to the increased production of urine-urobilinogen. Bilirubin is not usually found in the urine because unconjugated bilirubinn is not water-soluble, so, the combination of increased urine-urobilinogen with no bilirubin(since, unconjugated)in urine is suggestive of hemolytic jaundice.
Laboratory findings include:
- Urine: no bilirubin present, urobilirubin > 2 units (i.e., hemolytic anemia causes increased heme metabolism; exception: infants where gut flora has not developed).
- Serum: increased unconjugated bilirubin.
- Kernicterus is associated with increased unconjugated bilirubin.
Hepatocellular (hepatic) jaundice can be caused by acute hepatitis, hepatotoxicity, and alcoholic liver disease. Cell necrosis reduces the liver’s ability to metabolize and excrete bilirubin leading to a buildup of unconjugated bilirubin in the blood. Other causes include primary biliary cirrhosis leading to an increase in plasma conjugated bilirubin. Jaundice seen in the newborn, known as neonatal jaundice, is common, occurring in almost every newborn as hepatic machinery for the conjugation and excretion of bilirubin does not fully mature until approximately two weeks of age. Rat fever (leptospirosis) can also cause hepatic jaundice. In hepatic jaundice, there is invariably cholestasis.
Laboratory findings depend on the cause of jaundice.
- Urine: Conjugated bilirubin present, urobilirubin > 2 units but variable (except in children). Kernicterus is a condition not associated with increased conjugated bilirubin.
Post-hepatic jaundice, also called obstructive jaundice, is caused by an interruption to the drainage of bile in the biliary system. The most common causes are gallstones in the common bile duct, and pancreatic cancer in the head of the pancreas. Also, a group of parasites known as “liver flukes” can live in the common bile duct, causing obstructive jaundice. Other causes include strictures of the common bile duct, biliary atresia, ductal carcinoma, pancreatitis and pancreatic pseudocysts. A rare cause of obstructive jaundice is Mirizzi’s syndrome.
In complete obstruction of the bile duct, no urobilinogen is found in the urine,since bilirubin has no access to the intestine and its in the intestine that bilirubin gets converted to urobilinogen to be later released into the general circulation. In this case, presence of bilirubin(conjugated) in the urine without urine-urobilinogen suggests obstructive jaundice, either intra-hepatic or post-hepatic.
The presence of pale stools and dark urine suggests an obstructive or post-hepatic cause as normal feces get their color from bile pigments. However, although pale stools and dark urine are a feature of biliary obstruction, they can occur in many intra-hepatic illnesses and are therefore not a reliable clinical feature to distinguish obstruction from hepatic causes of jaundice.
Patients also can present with elevated serum cholesterol, and often complain of severe itching or “pruritus” because of the deposition of bile salts.
No single test can differentiate between various classifications of jaundice. A combination of liver function tests is essential to arrive at a diagnosis.
|Function test||Pre-hepatic Jaundice||Hepatic Jaundice||Post-hepatic Jaundice|
|Total bilirubin||Normal / Increased||Increased|
|Unconjugated bilirubin||Normal / Increased||Increased||Normal|
|Urobilinogen||Normal / Increased||Increased||Decreased / Negative|
|Urine Color||Dark(urobilinogen)||Dark (urobilinogen + conjugated bilirubin)||Dark (conjugated bilirubin)|
|Alkaline phosphatase levels||Normal||Increased|
|Alanine transferase and Aspartate transferase levels||Increased|
|Conjugated Bilirubin in Urine||Not Present||Present|
(more at: http://en.wikipedia.org/wiki/Jaundice)