Jaundice, also known as icterus (attributive adjective: "icteric"), is yellowish discoloration of the skin, sclerae (whites of the eyes) and 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, three times the usual value of approximately 0.5mg/dL, for the coloration to be easily visible. Jaundice comes from the French word jaune, meaning yellow.
In order to understand how jaundice results, it is important to understand where the pathological processes that cause jaundice take their effect. It is also important to further recognize that jaundice itself is not a disease, but rather a symptom of an underlying pathological process that occurs at some point along the normal physiological pathway of the metabolism of bilirubin.
When red blood cells
have completed their life span of approximately 120 days, their membranes become fragile and prone to rupture. As the cell traverses through the reticuloendothelial system
, their cell membranes rupture and the contents of the red blood cell is released into the blood. The component of the red blood cell that is involved in jaundice is hemoglobin
. The hemoglobin released into the blood is phagocytosed by macrophages
, and split into its heme
portions. The globin portion, being protein
, is degraded into amino acids
and plays no further role in jaundice. Two reactions then take place to the heme molecule. The first reaction is the oxidation
of heme to form biliverdin
.This reaction is catalyzed by microsomal enzyme heme oxygenase and it results in biliverdin (green color pigment), iron and carbon monoxide. Next step is reduction of biliverdin to yellow color tetrapyrol pigment bilirubin by cytosolic enzyme biliverdin reductase. This bilirubin is known as "unconjugated", "free" or "indirect" bilirubin. Approximately 4 mg per kg of bilirubin is produced each day. The majority of this bilirubin comes from the breakdown of heme from expired red blood cells in the process just described. However approximately 20 per cent comes from other heme sources, including ineffective erythropoiesis, breakdown of other heme-containing proteins, such as muscle myoglobin
The unconjugated bilirubin then travels to the liver
through the bloodstream. Because this bilirubin is not soluble, however, it is transported through the blood bound to serum albumin
. Once it arrives at the liver, it is conjugated with glucuronic acid
(to form bilirubin diglucuronide, or just "conjugated bilirubin") to become more water soluble. The reaction is catalyzed by the enzyme UDP-glucuronide transferase.
This conjugated bilirubin is excreted from the liver into the biliary and cystic ducts as part of bile
. Intestinal bacteria convert the bilirubin into urobilinogen
. From here the urobilinogen can take two pathways. It can either be further converted into stercobilinogen
, which is then oxidized
and passed out in the faeces
, or it can be reabsorbed by the intestinal cells, transported in the blood to the kidneys
, and passed out in the urine
as the oxidised product urobilin
. Stercobilin and urobilin are the products responsible for the coloration of faeces and urine, respectively.
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 the liver
- Hepatic: The pathology is located within the liver
- Post-Hepatic: The pathology is located after the conjugation of bilirubin in the liver
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
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. Jaundice usually comes with high fevers.
Laboratory findings include:
- Urine: no bilirubin present, urobilirubin > 2 units (except in infants where gut flora has not developed).
- Serum: increased unconjugated bilirubin.
jaundice causes include acute hepatitis
and alcoholic liver disease
, whereby cell necrosis reduces the liver's ability to metabolise and excrete bilirubin
leading to a buildup in the blood. Less common causes include primary biliary cirrhosis
, Gilbert's syndrome
(a genetic disorder of bilirubin metabolism which can result in mild jaundice, which is found in about 5% of the population), Crigler-Najjar syndrome
, metastatic carcinoma
and Niemann Pick Type C
disease. 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.
Laboratory Findings include:
- Urine: Conjugated bilirubin present, Urobilirubin > 2 units but variable (Except in children)
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
" live in the common bile duct, causing obstructive jaundice. Other causes include strictures of the common bile duct, biliary atresia
, ductal carcinoma
and pancreatic pseudocysts
. A rare cause of obstructive jaundice is Mirizzi's syndrome
The presence of pale stools and dark urine suggests an obstructive or post-hepatic cause as normal feces get their color from bile pigments.
Patients also can present with elevated serum cholesterol, and often complain of severe itching or "pruritus".
No one test can differentiate between various classifications of jaundice. A combinations of liver function tests is essential to arrive at a diagnosis.
|| Pre-hepatic Jaundice
|| Hepatic Jaundice
|| Post-hepatic Jaundice |
| Total bilirubin
|| Normal / Increased
|| Increased |
| Conjugated bilirubin
|| Normal / Decreased
|| Increased |
| Unconjugated bilirubin
|| Normal / Increased
|| Normal |
|| Normal / Increased
|| Decreased / Negative |
| Urine Colour
|| Dark |
| Stool colour
|| Pale |
| Alkaline phosphate levels
|| increased |
| Alanine transferase n Aspartate transferase levels
|| normal |
is usually harmless: this condition is often seen in infants
around the second day after birth, lasting until day 8 in normal births, or to around day 14 in premature births
. Serum bilirubin
normally drops to a low level without any intervention required: the jaundice is presumably a consequence of metabolic and physiological adjustments after birth. In extreme cases, a brain-damaging condition known as kernicterus
can occur; there are concerns that this condition has been rising in recent years due to inadequate detection and treatment of neonatal hyperbilirubinemia. Neonatal jaundice is a risk factor for hearing loss.
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 the infected spy, As all looks yellow to the jaundiced eye." Similarly in the mid 19th century the English poet Lord Alfred 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."