jaundice

View more Health videos

For more information on jaundice, visit Britannica.com.

The yellow staining of the skin and mucous membranes associated with the accumulation of bile pigments, such as bilirubin, in the blood plasma. Bile pigments are the normal result of the metabolism of blood pigments, and are normally excreted from the blood into the bile by the liver. An increase in circulating bile pigments can, therefore, come about through increased breakdown of blood (hemolytic jaundice), through lack of patency of the bile ducts (obstructive jaundice), through inability or failure of the liver to clear the plasma (parenchymal jaundice), or through combinations of these. Jaundice occurs when the level of these circulating pigments becomes so high that they are visible in the skin and mucous membranes. See also Gallbladder; Liver.

Hemolytic jaundice results from certain morbid states that include various hemolytic anemias, hemolysis resulting from incompatible blood transfusion, severe thermal or electric injuries, or introduction of hemolytic agents into the blood-stream. Similar jaundice occurs in pulmonary infarction.

Chronic obstructive jaundice may be brought about through a variety of means. In the infant there may be a severe maldevelopment of the bile ducts, while in the adult obstructive jaundice is most commonly caused by impaction of a gallstone in the ducts, or benign and malignant tumors of the gallbladder, bile ducts, pancreas, or lymph nodes.

A wide variety of diseases exists in which part of the jaundice can be accounted for by actual damage to liver cells. This group comprises such conditions as inflammations of the liver, including viral hepatitis, Weil's disease, syphilis, parasitic infestations, and bacterial infections; toxic conditions, including poisoning and in a broader sense the toxemias associated with severe systemic diseases; tumorous conditions; and other miscellaneous conditions, the most common of which is congestive heart failure.

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, Roger Williams

See also bile; haemoglobin; liver.

verb

To cause to have a prejudiced view: bias, prejudice, prepossess, warp. See affect/ineffectiveness, straight/bent.

Definition

Jaundice is a yellowing of the skin and/or whites of the eyes caused by high levels of bilirubin—a dark yellow-green or orange-red pigment—in the blood.

Description

Jaundice, also called icterus or hyperbilirubinemia, is a very common condition in newborns. Newborn or neonatal jaundice, sometimes referred to as physiologic or physiological jaundice, affects more than half of all full-term newborns and 80 percent of premature newborns within the first few days of life. It commonly lasts for one to two weeks. Jaundice that is present at birth or that lasts more than a couple of weeks may be abnormal jaundice and a symptom of an underlying problem. Jaundice in older children or adults is a symptom of hepatitis (inflammation of the liver) or some other liver disorder.

Jaundice results from higher than normal levels of bilirubin in the blood. Bilirubin is a breakdown product of red blood cells. Red blood cells normally are removed and broken down in the spleen after about 120 days in circulation. Heme (component of hemoglobin in red blood cells that carries oxygen throughout the body) is broken down into bilirubin, which moves to the liver where it is processed and added to bile, a digestive fluid. The bile travels through the bile ducts to the intestine and is excreted in the stool.

Infants are born with excess red blood cells that are rapidly recycled by the spleen and liver, releasing bilirubin. This pigment gives a newborn's stools their yellow color. If more bilirubin is produced than can be processed by the liver, blood levels of bilirubin rise, and the excess is deposited in tissues causing the skin to appear yellow.

Demographics

Although jaundice affects the majority of newborns, it often is more severe in Asian or Native American children. It also is more common in infants who are not breastfeeding efficiently, resulting in low fluid intake.

In 2001 the U.S. Centers for Disease Control and Prevention (CDC) reported that cases of brain damage associated with hyperbilirubinemia (called neonatal encephalopathy, bilirubin-induced brain injury, or kernicterus) had been increasing since about 1990, perhaps due to shorter hospital stays following birth. One cause of hyperbilirubinemia in seemingly healthy full-term or near-term infants is biliary atresia, an obstruction or inflammation of the bile ducts. This condition occurs in about one in every 15,000 live births, and girls are slightly more at risk than boys.

Causes and Symptoms

Neonatal Jaundice

Prior to birth the mother's liver processes bilirubin for the fetus. At birth, particularly with preterm births, an infant's immature liver may not be able to process all of the bilirubin formed as red blood cells are removed from circulation. The excess bilirubin causes jaundice by the third or fourth day after birth. The jaundice usually appears first on the face and progresses downward to the chest, abdomen, legs, and feet. If newborn feeding is delayed for any reason, such as illness, a digestive tract problem, or low fluid intake due to inefficient breast-feeding; the infant produces fewer stools, resulting in critically high blood levels of bilirubin and severe jaundice.

Most full-term babies with neonatal jaundice have no other symptoms. However, if bilirubin levels continue to rise, other symptoms may include:

• sleepiness
• lethargy
• slow or reluctant feeding

Risk factors for hyperbilirubinemia include:

• birth more than two weeks before the due date
• jaundice within the first 24 hours after birth
• significant bruising or bleeding under the scalp caused by labor and delivery
• high bilirubin levels prior to hospital discharge
• difficulty breastfeeding, resulting in low fluid intake
• a parent or sibling who had high bilirubin levels at birth

Abnormal Jaundice in Newborns

Jaundice at birth or within the first 24 hours after birth can be a sign of abnormal jaundice. Abnormal jaundice can be dangerous, particularly in preterm or unhealthy newborns. Depending on the cause and extent of the jaundice, it also may be harmful in full-term infants.

The most common cause of abnormal jaundice is an ABO blood type incompatibility between mother and child. If the mother has O-type blood and the infant has either A or B blood type, or if the mother has A-type blood and the child has B-type or vice versa, the mother's antibodies circulating in the baby's blood attack the child's foreign blood type, causing damage to and destruction of the baby's red blood cells. This process, called hemolysis, is accompanied by the release of excess amounts of bilirubin.

In the past Rhesus (Rh) blood factor incompatibility between the mother and child was a major cause of kernicterus. An Rh-negative mother who was exposed to her fetus's Rh-positive blood during a previous pregnancy or delivery or who has accidentally received an Rh-positive blood transfusion has antibodies against Rh-positive blood cells. These antibodies can circulate in her Rh-positive newborn, initiating hemolysis and causing severe abnormal jaundice.

Rare Causes of Severe Neonatal Jaundice

Jaundice can result from a congenital (present at birth) malformation of the liver, bile ducts, or gall bladder. Jaundice resulting from a congenital defect usually does not appear until the baby is at least ten days old. Biliary atresia—the underdevelopment, inflammation, or obstruction of the bile ducts that carry bile from the liver to the gall bladder and small intestine—causes bile to build up in the liver and forces the bilirubin into the blood. The cause of biliary atresia was as of 2004 unknown, and jaundice may not appear until the infant is two to six weeks old. Other symptoms of biliary atresia include:

• itching
• dark brown urine due to excess bilirubin excreted in the urine
• light-gray or chalky-colored stools from lack of bilirubin excreted by the intestines

Jaundice that develops or persists after the second week of life also can be due to the following:

• breast milk jaundice (prolonged jaundice resulting from breastfeeding) that occurs when a chemical in the mother's breast milk interferes with the infant liver's ability to process bilirubin
• liver malfunction or damaged liver cells
• an enzyme deficiency
• an abnormality of the red blood cells such as anemia
• blood hemorrhaging
• a blood infection (sepsis)
• a liver infection such as hepatitis virus
• toxoplasmosis, an infection caused by an animal parasite and transmitted to the fetus via an infected mother (House cats can be carriers of toxoplasmosis.)
• an infection anywhere in the body that impairs the efficiency of the liver, including neonatal herpes simplex or salmonella

Such infections may be congenital, having been passed from the mother to the fetus, or may occur after birth.

Other Causes of Jaundice

There are numerous other causes of neonatal and childhood jaundice, including the following:

• liver cell damage resulting from a variety of conditions such as a viral infection, an adverse drug reaction, or drugs or other chemicals that damage the liver (Jaundice can be a late symptom of hepatitis in an older baby or child.)
• hemolytic jaundice caused by hemolytic anemia, in which red blood cells are turned over faster than usual
• Hodgkin's disease in teenagers

Symptoms accompanying jaundice caused by liver cell damage may include:

• nausea
• vomiting
• abdominal pain
• swollen abdomen

When to Call the Doctor

A doctor should be consulted any time a child develops jaundice. Infants who are discharged from the hospital before bilirubin levels begin to rise, about three days after birth, should have their bilirubin level tested within a few days, particularly if they were preterm infants. Infants who become lethargic or reluctant to feed should be examined immediately, because symptoms can be signs of severe hyperbilirubinemia that can cause brain damage.

Diagnosis

Newborns are examined under good light for signs of jaundice. A simple blood test, with a few drops of blood taken from the infant's heel, measures bilirubin levels in the blood. The test may be repeated frequently in a jaundiced newborn to assure that bilirubin levels are dropping. An instrument called a bilirubinometer can be held against the baby's skin to assess the level of jaundice. The Minolta/Hill-Rom Air-Shields Transcutaneous Jaundice Meter accurately measures bilirubin levels by shining lights of different colors through the skin and measuring the reflection, eliminating the need for blood tests via heel pricks.

If there is reason to believe that the newborn is suffering from an abnormal jaundice, additional tests must be performed. These include:

• blood cell counts to detect anemia
• tests for blood clotting function
• tests for excess destruction of red blood cells
• blood tests to assess liver function
• a liver biopsy, in which liver cells are removed and examined under a microscope to look for liver disease
• urine and stool samples to check for signs of bacterial or viral infection

Breast milk jaundice due to a reaction with a breast milk component is suspected when the more common causes of jaundice have been ruled out.

Biliary atresia must be detected before two months of age to prevent further liver damage. Diagnoses of biliary atresia and other liver conditions are made by imaging techniques, including the following:

• ultrasound scanning, which uses sound waves to obtain images of the liver, gallbladder, and biliary tract (Abdominal ultrasound can distinguish between jaundice caused by biliary atresia and jaundice caused by liver malfunction.)
• magnetic resonance imaging (MRI) of the liver
• computed tomography (CT) or computed axial tomography (CAT) scans, which use a thin, rotating x-ray beam to obtain an image
• endoscopic retrograde cholangiopancreatography (ERCP), in which a radiopaque dye that is visible on x rays is inserted into the upper portion of the small intestine so that it flows back up the biliary tract
• liver scans using radioactive dyes

Treatment

Neonatal jaundice usually requires only observation. The infant may stay in the hospital for an extra day or return within the next few days for an examination. However, jaundice in a preterm baby may require intensive care. As the infant's liver matures and the excess blood cells are removed, the jaundice disappears. The child may be given additional fluids, possibly intravenously, to help remove the bilirubin. Frequent feedings lead to more frequent stools, which reduces the reabsorption of bilirubin from the intestines into the blood. Breast milk usually is considered superior to water or formula for relieving jaundice because breast milk produces stool with every feeding, thereby excreting bilirubin. Breastfeeding should not be discontinued because of neonatal jaundice.

If an infant's bilirubin levels are quite high or rising rapidly, phototherapy can prevent complications. The child is undressed and placed in a lighted incubator to stay warm. A high-intensity, cool, blue-fluorescent light is absorbed by the bilirubin and converts it into a harmless form than can be excreted in the bile and urine. An eye shield protects the baby's eyes. The infant is removed from the incubator for feeding. Other photo-therapy methods—such as a fiber optic bilirubin blanket—incorporate the light into a blanket so that the child can be breastfed during treatment or treated at home. Phototherapy is continued until bilirubin levels have returned to normal, usually within a few days.

Side effects of phototherapy may include:

• loose stools
• rash
• dehydration
• sleepiness
• disinterest in breastfeeding

If bilirubin approaches a dangerous level, an exchange blood transfusion is used to rapidly lower it. A catheter is placed into the umbilical vein at the cut surface of the umbilical cord, and the newborn's blood is replaced with an equal volume of new blood. Rh incompatibility also may be treated by exchange transfusion.

Antibiotics may be used to prevent or treat a suspected infection in jaundiced infants. Babies with very severe jaundice have their hearing tested and are monitored for several months.

Surgery for biliary atresia must be performed within the first few weeks of an infant's life to prevent fatal liver damage. About 40–50 percent of infants with biliary atresia are candidates for replacement bile ducts leading from the liver into the intestine. Called the Kasai procedure or hepatoportoenterostomy, the obstructed ducts are replaced with sections from the infant's intestines. Infants with a duct obstruction within the liver itself usually require a liver transplant by the age of two.

Prolonged breast-milk jaundice may require breast-feeding to be halted for a few days until bilirubin levels drop. The breasts should be pumped in the interim so that the mother does not stop producing milk and breast-feeding can be resumed.

Prognosis

Neonatal jaundice disappears after one to two weeks. It may last slightly longer in breastfed infants. The jaundice does not harm the infant in any way, and breastfeeding should not be discontinued.

Severe untreated jaundice leading to kernicterus may result in the following:

• mental retardation
• cerebral palsy
• deafness
• death

Untreated biliary atresia leads to biliary cirrhosis, a progressive, irreversible scarring of the liver, by about two months of age. About 50 percent of bile duct replacement surgeries are successful, and the jaundice usually disappears within several weeks. Despite this success, the liver damage often progresses on to cirrhosis.

Breast-milk jaundice, resulting from a reaction to a breast milk component, is not dangerous. The baby's liver soon adapts to the problem and the jaundice disappears.

Prevention

In 2004 the American Academy of Pediatrics issued revised guidelines for identifying and managing neonatal jaundice. They recommend:

• that all newborns be assessed for their risk of developing severe jaundice, including measuring bilirubin levels before hospital discharge
• a follow-up visit occur within three to five days after birth when bilirubin levels are likely to peak
• breastfeeding a newborn at least eight to 12 times per day, since effective breastfeeding significantly reduces the risk of hyperbilirubinemia
• that parents be provided with written and oral information about the risks of neonatal jaundice

In cases of known Rh incompatibility, the mother is given an injection of RhoGAM, an immune globulin preparation, at about 28 weeks of pregnancy and again immediately after the child's birth. This destroys any Rh-positive fetal blood cells in the mother's circulation before her immune system can produce antibodies against them.

Parental Concerns

Parents should examine their infant in natural daylight and under fluorescent lighting for signs of jaundice. Jaundice may be harder to see in infants with darker skin. However, when a child's nose and forehead are pressed gently, the skin is white in healthy babies of all races, but yellowish if jaundice is present. If the skin appears yellow, the test should be repeated on the chest or abdomen. Parents also should be aware of symptoms that may accompany jaundice, including fussiness, unusual sleepiness, or difficulty feeding.

Mothers who are having difficulty breastfeeding should seek help. Although breast milk is an effective treatment for jaundice, breastfed babies may receive fewer calories than formula-fed babies during the first days of life, causing bilirubin levels to rise.

Resources

Books

Maisels, M. Jeffrey, and Jon F. Watchko, eds. Neonatal Jaundice. Amsterdam: Harwood Academic, 2000.

Periodicals

Blackmon, Lillian R., et al. "Research on Prevention of Bilirubin-Induced Brain Injury and Kernicterus: National Institute of Child Health and Human Development Conference Executive Summary." Pediatrics 114, no. 1 (July 2004): 229.

Johnston, Carden. "Help for Newborn Jaundice." Baby Talk 69, no. 6 (August 2004): 18.

"Management of Hyperbilirubinemia in the Newborn Infant 35 or More Weeks of Gestation." Pediatrics 114 (2004): 297–316.

Obstetrics Hospitals Need to Improve Jaundice Monitoring, Commission Says. Science Letter (September 21, 2004): 936.

Payne, Doug. "Skin Meter Detects Jaundice." Medical Post (Toronto) 40, no. 32 (August 24, 2004): 35.

Organizations

American Academy of Pediatrics. 141 Northwest Point Boulevard, Elk Grove Village, IL 60007–1098. Web site: www.aap.org.

American Liver Foundation. 75 Maiden Lane, Suite 603, New York, NY 10038. Web site: www.liverfoundation.org.

Web Sites

"Questions and Answers: Jaundice and Your Newborn." American Academy of Pediatrics, June 25, 2004. Available online at www.aap.org/family/jaundicefaq.htm (accessed January 11, 2005).

"What is Biliary Atresia?" American Liver Foundation. Available online at www.liverfoundation.org/db/articles/1012 (accessed January 11, 2005).

[Article by: Margaret Alic, PhD]

A condition in which the skin, the whites of the eye, and other tissues take on a yellowish color because of an excess of bile coloring in the blood.

Yellowness of skin, sclerae, mucous membranes, and excretions due to hyperbilirubinemia and deposition of bile pigments. Called also icterus. It is usually first noticeable in the sclera.
The pigment causing jaundice is called bilirubin. It is derived from hemoglobin that is released when erythrocytes are hemolyzed and therefore is constantly being formed and introduced into the blood as worn-out or defective erythrocytes are destroyed by the body. Normally the liver cells absorb the bilirubin and secrete it along with other bile constituents. If the liver is diseased, or if the flow of bile is obstructed, or if destruction of erythrocytes is excessive, the bilirubin accumulates in the blood and eventually will produce jaundice. Determination of the level of bilirubin in the blood is of value in detecting elevated bilirubin levels at the earliest stages before jaundice appears, when liver disease or hemolytic anemia is suspected.

Jaundice in a horse's oral mucosa. By permission from Knottenbelt DC, Pascoe RR, Diseases and Disorders of the Horse, Saunders, 2003

• acholuric j. — jaundice without bilirubinemia, associated with elevated unconjugated bilirubin that is not excreted by the kidney.
• cholestatic j. — that resulting from abnormality of bile flow in the liver.
• hematogenous j. — hemolytic jaundice.
• hemolytic j. — jaundice associated with hemolytic anemia in which most of the bilirubin is unconjugated. Called also retention jaundice, prehepatic jaundice.
• hemorrhagic j. — leptospirosis.
• hepatocellular j. — jaundice caused by injury to or disease of the liver cells.
• j. index — see icteric index.
• nonhemolytic j. — that due to an abnormality in bilirubin metabolism.
• obstructive j. — that due to blockage of the flow of bile, resulting in conjugated hyperbilirubinemia. Called also regurgitation jaundice.
• physiological j. — mild icterus neonatorum during the first few days after birth.
• regurgitation j. — obstructive jaundice (above).
• toxic j. — see hepatocellular jaundice (above).

A condition characterized by an abnormal accumulation of bilirubin (red bile pigment) in the blood and manifested by a yellowish discoloration of the skin, mucous membranes, and cornea. Seen in hemolytic anemias, biliary obstruction, hepatitis, cholangiolitis, and cirrhosis of the liver. Oral mucous membranes may be pigmented.

Jaundice. (Neville/Damm/Allen/Bouquot, 2002)

• Signs and Symptoms - jaundice: yellowing of skin and whites of eyes from excess bilirubin in blood, often due to obstructed ducts or liver disease

"Yellowing" redirects here. For the plant disease, see lethal yellowing. For paper degradation, see foxing.

"Icterus" and "icteric" redirect here. For the physiological event, see Ictal. For the songbird Icteria, see Yellow-breasted Chat.

Jaundice

Jaundice of the skin caused by hepatic failure.
ICD-10	R17
ICD-9	782.4
DiseasesDB	7038
MedlinePlus	003243
MeSH	D007565

Jaundice (also known as icterus;^[1] 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 fluid. Concentration of bilirubin in blood plasma does not normally exceed 1 mg/dL (>17µmol/L). A concentration higher than 1.8 mg/dL (>30µmol/L) leads to jaundice.^[2] The term jaundice comes from the French word jaune, meaning yellow.

Jaundice is often seen in liver disease such as hepatitis or liver cancer. It may also indicate leptospirosis or obstruction of the biliary tract, for example by gallstones or pancreatic cancer, or less commonly be congenital in origin.

Yellow discoloration of the skin, especially on the palms and the soles, but not of the sclera and mucous membranes (i.e. oral cavity) is due to carotenemia—a harmless condition^[3] important to differentiate from jaundice.

Contents 1 Signs and symptoms 2 Differential diagnosis 2.1 Pre-hepatic 2.2 Hepatocellular 2.3 Post-hepatic 2.4 Neonatal jaundice 3 Pathophysiology 3.1 Hepatic events 4 Diagnostic approach 5 Complications 6 References 7 External links 7.1 Infants

Signs and symptoms

A 4-year-old boy with icteric (jaundiced) sclera which later proved to be a manifestation of hemolytic anemia due to G6PD deficiency following fava bean consumption.

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.^[4] 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.^[1][5]

Differential diagnosis

Types of jaundice

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:

Category	Definition
Pre-hepatic/ hemolytic	The pathology is occurring prior to the liver.
Hepatic/ hepatocellular	The pathology is located within the liver.
Post-Hepatic/ cholestatic	The pathology is located after the conjugation of bilirubin in the liver.

Pre-hepatic

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 bilirubin 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, urobilinogen > 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

Hepatocellular (hepatic) jaundice can be caused by acute or chronic hepatitis, hepatotoxicity, cirrhosis, drug induced hepatitis 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 because there is impairment of excretion of conjugated bilirubin into the bile. The blood contains abnormally raised amount of conjugated bilirubin and bile salts which are excreted in the urine. Jaundice seen in the newborn, known as neonatal jaundice, is common in newborns ^[6] 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.
• Plasma protein show characteristic changes.
• Plasma albumin level is low but plasma globulins are raised due to an increased formation of antibodies.

Bilirubin transport across the hepatocyte may be impaired at any point between the uptake of unconjugated bilirubin into the cell and transport of conjugated bilirubin into biliary canaliculi. In addition, swelling of cells and oedema due to inflammation cause mechanical obstruction of intrahepatic biliary tree. Hence in hepatocellular jaundice, concentration of both unconjugated and conjugated bilirubin rises in the blood. In hepatocellular disease, there is usually interference in all major steps of bilirubin metabolism—uptake, conjugation and excretion. However, excretion is the rate-limiting step, and usually impaired to the greatest extent. As a result, conjugated hyperbilirubinaemia predominates.^[7]

Post-hepatic

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, cholangiocarcinoma, 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 it is 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.^[8]

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.

Table of diagnostic tests^[9]

Function test	Pre-hepatic Jaundice	Hepatic Jaundice	Post-hepatic Jaundice
Total bilirubin	Normal / Increased	Increased
Conjugated bilirubin	Normal	Increased	Increased
Unconjugated bilirubin	Normal / Increased	Increased	Normal
Urobilinogen	Normal / Increased	Increased	Decreased / Negative
Urine Color	Normal	Dark (urobilinogen + conjugated bilirubin)	Dark (conjugated bilirubin)
Stool Color	Normal	Normal/Pale	Pale
Alkaline phosphatase levels	Normal	Increased
Alanine transferase and Aspartate transferase levels		Increased
Conjugated Bilirubin in Urine	Not Present	Present

Neonatal jaundice

Main article: Neonatal jaundice

Neonatal jaundice 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. Typical causes for neonatal jaundice include normal physiologic jaundice, jaundice due to breast feeding, and hemolytic disorders that include hereditary spherocytosis, glucose-6-phosphate dehydrogenase deficiency, pyruvate kinase deficiency, ABO/Rh blood type autoantibodies, or infantile pyknocytosis. 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 cases where bilirubin rises higher, a brain-damaging condition known as kernicterus can occur, leading to significant lifelong disability; there are concerns that this condition has been rising in recent years due to inadequate detection and treatment of neonatal hyperbilirubinemia. A Bili light is often the tool used for early treatment, which often consists of exposing the baby to intensive phototherapy. However, in third world countries where procuring such treatment is prohibitably expensive, parents often subject their children to regular daily treatments of baking in the sunlight and sunbathing. Bilirubin count is lowered through bowel movements and urination so regular and proper feedings are especially important.^[10]

Pathophysiology

In order to understand how jaundice results, the pathological processes that cause jaundice to take their effect must be understood. Jaundice itself is not a disease, but rather a sign of one of many possible underlying pathological processes that occur 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, or when they are damaged, their membranes become fragile and prone to rupture. As each red blood cell traverses through the reticuloendothelial system, its cell membrane ruptures when its membrane is fragile enough to allow this. Cellular contents, including hemoglobin, are subsequently released into the blood. The hemoglobin is phagocytosed by macrophages, and split into its heme and globin portions. The globin portion, a protein, is degraded into amino acids and plays no role in jaundice. Two reactions then take place with the heme molecule. The first oxidation reaction is catalyzed by the microsomal enzyme heme oxygenase and results in biliverdin (green color pigment), iron and carbon monoxide. The next step is the reduction of biliverdin to a yellow color tetrapyrol pigment called bilirubin by cytosolic enzyme biliverdin reductase. This bilirubin is "unconjugated," "free" or "indirect" bilirubin. Approximately 4 mg of bilirubin per kg of blood is produced each day.^[11] The majority of this bilirubin comes from the breakdown of heme from expired red blood cells in the process just described. However approximately 20 percent comes from other heme sources, including ineffective erythropoiesis, and the breakdown of other heme-containing proteins, such as muscle myoglobin and cytochromes.^[11]

Hepatic events

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-glucuronyl 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 to stercobilin and passed out in the feces, 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 feces and urine, respectively.

Diagnostic approach

Biliary tract dilation due to obstruction as seen on CAT scan

Biliary tract dilation due to obstruction

Most patients presenting with jaundice will have various predictable patterns of liver panel abnormalities, though significant variation does exist. The typical liver panel will include blood levels of enzymes found primarily from the liver, such as the aminotransferases (ALT, AST), and alkaline phosphatase (ALP); bilirubin (which causes the jaundice); and protein levels, specifically, total protein and albumin. Other primary lab tests for liver function include GGT and prothrombin time (PT).

Some bone and heart disorders can lead to an increase in ALP and the aminotransferases, so the first step in differentiating these from liver problems is to compare the levels of GGT, which will only be elevated in liver-specific conditions. The second step is distinguishing from biliary (cholestatic) or liver (hepatic) causes of jaundice and altered lab results. The former typically indicates a surgical response, while the latter typically leans toward a medical response. ALP and GGT levels will typically rise with one pattern while AST and ALT rise in a separate pattern. If the ALP (10–45 IU/L) and GGT (18–85) levels rise proportionately about as high as the AST (12–38 IU/L) and ALT (10–45 IU/L) levels, this indicates a cholestatic problem. On the other hand, if the AST and ALT rise is significantly higher than the ALP and GGT rise, this indicates an hepatic problem. Finally, distinguishing between hepatic causes of jaundice, comparing levels of AST and ALT can prove useful. AST levels will typically be higher than ALT. This remains the case in most hepatic disorders except for hepatitis (viral or hepatotoxic). Alcoholic liver damage may see fairly normal ALT levels, with AST 10x higher than ALT. On the other hand, if ALT is higher than AST, this is indicative of hepatitis. Levels of ALT and AST are not well correlated to the extent of liver damage, although rapid drops in these levels from very high levels can indicate severe necrosis. Low levels of albumin tend to indicate a chronic condition, while it is normal in hepatitis and cholestasis.

Lab results for liver panels are frequently compared by the magnitude of their differences, not the pure number, as well as by their ratios. The AST:ALT ratio can be a good indicator of whether the disorder is alcoholic liver damage (10), some other form of liver damage (above 1), or hepatitis (less than 1). Bilirubin levels greater than 10x normal could indicate neoplastic or intrahepatic cholestasis. Levels lower than this tend to indicate hepatocellular causes. AST levels greater than 15x tends to indicate acute hepatocellular damage. Less than this tend to indicate obstructive causes. ALP levels greater than 5x normal tend to indicate obstruction, while levels greater than 10x normal can indicate drug (toxic) induced cholestatic hepatitis or Cytomegalovirus. Both of these conditions can also have ALT and AST greater than 20× normal. GGT levels greater than 10x normal typically indicate cholestasis. Levels 5–10× tend to indicate viral hepatitis. Levels less than 5× normal tend to indicate drug toxicity. Acute hepatitis will typically have ALT and AST levels rising 20–30× normal (above 1000), and may remain significantly elevated for several weeks. Acetaminophen toxicity can result in ALT and AST levels greater than 50x normal.

Complications

Complications of jaundice include sepsis especially cholangitis, biliary cirrhosis, pancreatitis, coagulopathy, renal and liver failure. Other complications are related to the underlying disease and the procedures employed in the diagnosis and management of individual diseases. Cholangitis especially the suppurative type (Charcot’s triad or Raynaud’s pentad) is usually secondary to choledocholithiasis. It may also complicate procedures like ERCP. Treatment should include correction of coagulopathy, fluid/electrolyte anomaly, antibiotics and biliary drainage with ERCP where available or trans-hepatic drainage or surgery.

References

1. ^ ^{a b} http://www.medterms.com/script/main/art.asp?articlekey=3890
2. ^ Silbernagl S, Despopoulos A (2009). Color atlas of physiology (6 ed.). Thieme. p. 252. ISBN 978-3-13-545006-3. 
3. ^ Carotenemia, Author: Robert A Schwartz, MD, MPH; Chief Editor: Dirk M Elston, MD, http://emedicine.medscape.com/article/1104368-overview#showall
4. ^ Findarticles.com, accessed Nov. 22, 2008
5. ^ http://dictionary.reference.com/browse/icterus
6. ^ Collier J, Longore M, Turmezei T, Mafi AR (2010). "Neonatal jaundice". Oxford Handbook of Clinical Specialties. Oxford University Press. ISBN 978-0-19-922888-1. 
7. ^ Medicine: Prep Manual for Undergraduates, 3/e By Mathew K.G. pages 296-297
8. ^ Beckingham, IJ; Ryder, SD (2001). "Investigation of liver and biliary disease". BMJ (Clinical research ed.) 322 (7277): 33–6. PMC 1119305. PMID 11141153. //www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1119305. 
9. ^ Goljan, Edward F., Rapid Review Pathology 2nd edition. Pg. 368–369. 2007.
10. ^ O'Keefe, Lori (2001-05-05). "Increased vigilance needed to prevent kernicterus in newborns". American Academy of Pediatrics 18 (5): 231. http://aapnews.aappublications.org/cgi/content/full/18/5/231. Retrieved 2007-06-27. 
11. ^ ^{a b} Pashankar, D; Schreiber, RA (July 2001). "Jaundice in older children and adolescents". Pediatrics in Review 22 (7): 219–226. doi:10.1542/pir.22-7-219. PMID 11435623. 

External links

Look up jaundice in Wiktionary, the free dictionary.

Infants

• Children's Liver Disease Foundation
• National Niemann Pick Disease Foundation: jaundice at birth, enlarged spleen and/or enlarged liver
• Jaundice_in_newborn.jpg

v t e Symptoms and signs: digestive system and abdomen (R10–R19, 787,789) GI tract Upper GI tract Nausea/Vomiting · Heartburn · Dysphagia (Oropharyngeal, Esophageal) Halitosis Lower GI tract Gas: Flatulence · Abdominal distension · Bloating · Belching (Wet burp) · Tympanites Stool: Fecal incontinence (Encopresis) · Rectal tenesmus Blood: Fecal occult blood Diarrhea Football sign Psoas sign · Obturator sign · Rovsing's sign Accessory Hepatosplenomegaly/Hepatomegaly Jaundice Abdominopelvic Ascites Abdominal – general Abdominal pain (Acute abdomen, Colic, Baby colic) Splenomegaly Abdominal guarding · Abdominal mass · Rebound tenderness Shifting dullness · Bulging flanks · Puddle sign · Fluid wave test M: DIG anat(t, g, p)/phys/devp/enzy noco/cong/tumr, sysi/epon proc, drug(A2A/2B/3/4/5/6/7/14/16), blte

This entry is from Wikipedia, the leading user-contributed encyclopedia. It may not have been reviewed by professional editors (see full disclaimer)

Dansk (Danish)
n. - gulsot, misundelse, skinsyge
v. tr. - være misundelig

idioms:

• jaundiced eye    misunde

Nederlands (Dutch)
geelzucht, afgunst, iemand jaloers/wrokkig maken, geelzucht veroorzaken

Français (French)
n. - (Méd) jaunisse, (fig) jalousie, amertume
v. tr. - voir d'un mauvais ¯il

idioms:

• jaundiced eye    voir qch d'un mauvais ¯il

Deutsch (German)
n. - Gelbsucht
v. - verbittern, gelbsüchtig machen

idioms:

• jaundiced eye    Neid

Ελληνική (Greek)
n. - (παθολ.) ίκτερος (κν. χρυσή), (μτφ.) ζηλοτυπία, φθόνος
v. - προκαλώ πείσμα, κακεντρέχεια

idioms:

• jaundiced eye    φθονερό ή φιλόψογο μάτι

Italiano (Italian)
itterizia, rendere invidioso

idioms:

• jaundiced eye    invidia

Português (Portuguese)
n. - icterícia (f) (Med.)
v. - hostilizar, invejar, fazer mau juízo de

idioms:

• jaundiced eye    inveja (f), ciúme (m), hostilidade (f), preconceito (m)

Русский (Russian)
желтуха, желчность, предубежденность, зависть, ревность, вызывать разлитие желчи, вызывать зависть

idioms:

• jaundiced eye    завистливый взгляд, преубежденность

Español (Spanish)
n. - ictericia, envidia, celos, displicencia, desazón
v. tr. - dar ictericia a, amargar, predisponer, avinagrar el genio a, llenar de envidia, desazonar

idioms:

• jaundiced eye    envidioso, avinagrado, celoso, con cinismo

Svenska (Swedish)
n. - gulsot, avundsjuka, bitterhet, missunnsamhet
v. - behäfta med gulsot, göra svartsjuk

中文（简体）(Chinese (Simplified))
黄疸, 偏见, 黄疸病, 嫉妒, 使患黄疸, 使怀偏见

idioms:

• jaundiced eye    因嫉妒等而有偏见的

中文（繁體）(Chinese (Traditional))
n. - 黃疸, 偏見, 黃疸病, 嫉妒
v. tr. - 使患黃疸, 使懷偏見

idioms:

• jaundiced eye    因嫉妒等而有偏見的

한국어 (Korean)
n. - 황달, 편견
v. tr. - 비뚤어지게 하다, 황달에 걸리게 하다, 편견을 가지게 하다

日本語 (Japanese)
n. - 黄疸, ひがみ, 偏見

العربيه (Arabic)
‏(الاسم) يرقان, مرض الصفراء, صفار (فعل) اصاب باليرقان‏

עברית (Hebrew)
n. - ‮צהבת (מחלה)‬
v. tr. - ‮גרם לצהבת‬

If you are unable to view some languages clearly, click here.