What is jaundice?

Jaundice is a condition of excessive build up of a substance called bilirubin in the blood. Bilirubin is a product of break down of red blood cells and is normally processed by the liver and excreted from the body in bile. When the liver malfunctions, bilirubin is not excreted and it gets deposited near the skin surface giving a yellow tinge to the skin, mucous membranes, and eyes.

Jaundice occurs when excess amounts of bilirubin circulating in the blood stream causes a yellowish appearance of the skin and the whites of the eyes. With the exception of physiologic jaundice in the newborn (normal newborn jaundice in the first week of life), all other jaundice indicates overload or damage to the liver, or inability to move bilirubin from the liver through the biliary tract to the gut.

Newborn jaundice is common and unless associated with an abnormal condition will clear without treatment. Another condition called Gilbert`s syndrome is a hereditary condition in which mild jaundice develops during times of stress. This condition, once recognised, requires no further treatment or evaluation. There are also other more rare hereditary causes of elevated bilirubin levels. All other jaundice is the result of an underlying disease, condition, or toxicity.

A yellow-to-orange colour may be imparted to the skin by excessive intake of beta carotene, the orange pigment seen in carrots. People who consume large quantities of carrots or carrot juice or take beta carotene tablets may develop a distinctly yellow-orange cast to their skin. This condition is called hypercarotenemia or just carotenemia. Hypercarotenemia is easily distinguished from jaundice in that the whites of the eye (sclera) remain white, while people with true jaundice have a yellow sclera.

What are the causes?

In children
Newborn jaundice (physiologic jaundice)
Breast feeding jaundice
Viral hepatitis (hepatitis A, hepatitis B, hepatitis C, hepatitis D, and hepatitis E)
Haemolytic anaemia
Congenital disorders of bilirubin metabolism (Gilbert`s syndrome)
Autoimmune hepatitis

In adults
Obstruction of the bile ducts (by infection, tumour or gallstones)
Viral hepatitis (hepatitis A, hepatitis B, hepatitis C, hepatitis D, and hepatitis E)
Drug-induced cholestasis (bile pools in the gallbladder because of the effects of drugs)
Drug-induced hepatitis (hepatitis triggered by medications, including erythromycin, sulpha drugs, antidepressants, anti-Cancer drugs, rifampicin, steroids, chlorpropamide, tolbutamide, oral contraceptives, testosteronel)
Bile duct stricture
Alcoholic liver disease (alcoholic cirrhosis)
Pancreatic carcinoma (cancer of the pancreas)
Primary biliary cirrhosis
Ischaemic hepatocellular jaundice (jaundice caused by inadequate oxygen or inadequate blood flow to the liver)
Intrahepatic cholestasis of pregnancy (bile pools in the gallbladder because of the pressure in the abdomen with pregnancy)
Haemolytic anaemia
Congenital disorders of bilirubin metabolism
Chronic active hepatitis

What are the symptoms?

Yellow pigmentation of the skin
Inside of the mouth (mucous membranes) turn yellow
Eyes turn yellow
Dark urine
Pale stools
Abdominal pain, systemic symptoms (eg, anorexia, vomiting, fever)

How is it diagnosed?

The medical history is obtained and a physical examination performed.

Medical history questions may include
Is the skin colour yellow (jaundice)?
Is the inside of the mouth (mucous membranes) yellow?
Are the eyes yellow?
When did the jaundice start?
Has the jaundice occurred repeatedly (recurrent)?
What other symptoms are also present?

During a physical examination, the doctor studies one’s body to determine the presence or absence of physical problems.

A typical physical examination includes
inspection (looking at the body)
palpation (feeling the body with hands)
auscultation (listening to sounds)
percussion (producing sounds)

Diagnostic tests that may be performed include
serum bilirubin
hepatic (liver) enzymes (see liver function tests) and cholesterol
prothrombin time
complete blood count
ultrasound of the abdomen
liver biopsy
urine and faecal urobilinogen

What causes jaundice?

Bilirubin comes from red blood cells. When red blood cells get old, they are destroyed. Hemoglobin, the iron-containing chemical in red blood cells that carries oxygen, is released from the destroyed red blood cells after the iron it contains is removed. The chemical that remains in the blood after the iron is removed becomes bilirubin.

The liver has many functions. One of the liver’s functions is to produce and secrete bile into the intestines to help digest dietary fat. Another is to remove toxic chemicals or waste products from the blood, and bilirubin is a waste product. The liver removes bilirubin from the blood. After the bilirubin has entered the liver cells, the cells conjugate (attaching other chemicals, primarily glucuronic acid) to the bilirubin, and then secrete the bilirubin/glucuronic acid complex into bile. The complex that is secreted in bile is called conjugated bilirubin. The conjugated bilirubin is eliminated in the feces. (Bilirubin is what gives feces its brown color.) Conjugated bilirubin is distinguished from the bilirubin that is released from the red blood cells and not yet removed from the blood which is termed unconjugated bilirubin.

Jaundice occurs when there is 1) too much bilirubin being produced for the liver to remove from the blood. (For example, patients with hemolytic anemia have an abnormally rapid rate of destruction of their red blood cells that releases large amounts of bilirubin into the blood), 2) a defect in the liver that prevents bilirubin from being removed from the blood, converted to bilirubin/glucuronic acid (conjugated) or secreted in bile, or 3) blockage of the bile ducts that decreases the flow of bile and bilirubin from the liver into the intestines. (For example, the bile ducts can be blocked by cancers, gallstones, or inflammation of the bile ducts). The decreased conjugation, secretion, or flow of bile that can result in jaundice is referred to as cholestasis: however, cholestasis does not always result in jaundice.

What problems does jaundice cause?

Jaundice or cholestasis, by themselves, causes few problems (except in the newborn, and jaundice in the newborn is different than most other types of jaundice, as discussed later.) Jaundice can turn the skin and sclerae yellow. In addition, stool can become light in color, even clay-colored because of the absence of bilirubin that normally gives stool its brown color. The urine may turn dark or brownish in color. This occurs when the bilirubin that is building up in the blood begins to be excreted from the body in the urine. Just as in feces, the bilirubin turns the urine brown.

Besides the cosmetic issues of looking yellow and having dark urine and light stools, the symptom that is associated most frequently associated with jaundice or cholestasis is itching, medically known as pruritus. The itching associated with jaundice and cholestasis can sometimes be so severe that it causes patients to scratch their skin “raw,” have trouble sleeping, and, rarely, even to commit suicide.

It is the disease causing the jaundice that causes most problems associated with jaundice. Specifically, if the jaundice is due to liver disease, the patient may have symptoms or signs of liver disease or cirrhosis. (Cirrhosis represents advanced liver disease.) The symptoms and signs of liver disease and cirrhosis include fatigue, swelling of the ankles, muscle wasting, ascites (fluid accumulation in the abdominal cavity), mental confusion or coma, and bleeding into the intestines.

If the jaundice is caused by blockage of the bile ducts, no bile enters the intestine. Bile is necessary for digesting fat in the intestine and releasing vitamins from within it so that the vitamins can be absorbed into the body. Therefore, blockage of the flow of bile can lead to deficiencies of certain vitamins. For example, there may be a deficiency of vitamin K that prevents proteins that are needed for normal clotting of blood to be made by the liver, and, as a result, uncontrolled bleeding may occur.

What diseases cause jaundice?

Increased production of bilirubin
There are several uncommon conditions that give rise to over-production of bilirubin. The bilirubin in the blood in these conditions usually is only mildly elevated, and the resultant jaundice usually is mild and difficult to detect. These conditions include: 1) rapid destruction of red blood cells (referred to as hemolysis), 2) a defect in the formation of red blood cells that leads to the over-production of hemoglobin in the bone marrow (called ineffective erythropoiesis), or 3) absorption of large amounts of hemoglobin when there has been much bleeding into tissues (e.g., from hematomas, collections of blood in the tissues).

Acute inflammation of the liver
Any condition in which the liver becomes inflamed can reduce the ability of the liver to conjugate (attach glucuronic acid to) and secrete bilirubin. Common examples include acute viral hepatitis, alcoholic hepatitis, and Tylenol-induced liver toxicity.

Chronic liver diseases
Chronic inflammation of the liver can lead to scarring and cirrhosis, and can ultimately result in jaundice. Common examples include chronic hepatitis B and C, alcoholic liver disease with cirrhosis, and autoimmune hepatitis.

Infiltrative diseases of the liver
Infiltrative diseases of the liver refer to diseases in which the liver is filled with cells or substances that don’t belong there. The most common example would be metastatic cancer to the liver, usually from cancers within the abdomen. Uncommon causes include a few diseases in which substances accumulate within the liver cells, for example, iron (hemochromatosis), alpha-one antitrypsin (alpha-one antitrypsin deficiency), and copper (Wilson’s disease).

Inflammation of the bile ducts
Diseases causing inflammation of the bile ducts, for example, primary biliary cirrhosis or sclerosing cholangitis and some drugs, can stop the flow of bile and elimination of bilirubin and lead to jaundice.

Blockage of the bile ducts
The most common causes of blockage of the bile ducts are gallstones and pancreatic cancer. Less common causes include cancers of the liver and bile ducts.

What is neonatal jaundice (jaundice in newborn infants)?

Neonatal jaundice is jaundice that begins within the first few days after birth. (Jaundice that is present at the time of birth suggests a more serious cause of the jaundice.) In fact, bilirubin levels in the blood become elevated in almost all infants during the first few days following birth, and jaundice occurs in more than half. For all but a few infants, the elevation and jaundice represents a normal physiological phenomenon and does not cause problems.

The cause of normal, physiological jaundice is well understood. During life in the uterus, the red blood cells of the fetus contain a type of hemoglobin that is different than the hemoglobin that is present after birth. When an infant is born, the infant’s body begins to rapidly destroy the red blood cells containing the fetal-type hemoglobin and replaces them with red blood cells containing the adult-type hemoglobin. This floods the liver with bilirubin derived from the fetal hemoglobin from the destroyed red blood cells. The liver in a newborn infant is not mature, and its ability to process and eliminate bilirubin is limited. As a result of both the influx of large amounts of bilirubin and the immaturity of the liver, bilirubin accumulates in the blood. Within two or three weeks, the destruction of red blood cells ends, the liver matures, and the bilirubin levels return to normal.

There is another uncommon syndrome associated with neonatal jaundice, referred to as breast-milk or breast feeding jaundice. In this syndrome, jaundice appears to be caused by or at least accentuated by breast feeding. Although the cause of this type of jaundice is unknown, it has been hypothesized that there is something in breast milk that reduces the ability of the liver to process and eliminate bilirubin. With breast-milk jaundice, the bilirubin levels rise and reach peak levels in approximately two weeks, remain elevated for a week or so, and then decline to normal over several weeks or months. This timing of the elevation in bilirubin and jaundice is different than normal physiological jaundice described previously and allows the two causes of jaundice to be differentiated. The real importance of the more prolonged jaundice associate with breast-milk jaundice is that it raises the possibility that there is a more serious cause for the jaundice that needs to be sought, for example, biliary atresia (destruction of the bile ducts). Breast-milk jaundice alone usually does not cause problems for the infant.

Physiologic jaundice and breast-milk jaundice usually do not cause problems for the infant; however, there is a concern that high or prolonged elevations in levels of unconjugated bilirubin (the type of bilirubin that is not attached to glucuronic acid and the main type of bilirubin that is present in physiologic and breast-milk jaundice) will cause neurologic damage to the infant. Therefore, when unconjugated bilirubin levels are high or prolonged, treatment usually is started to lower the levels of bilirubin. Treatment may be started earlier in infants who are born prematurely since their livers take longer to mature, and the risk of higher and more prolonged elevations of bilirubin is greater. Treatment involves phototherapy with artificial or natural sunlight and, if phototherapy is not successful, exchange transfusion in which the infant’s blood is exchanged for normal blood from blood donors.

The benign nature of physiologic and breast-milk allergy need to be distinguished from hemolytic disease of the newborn, a much more serious, even life-threatening cause of jaundice in newborns that is due to blood group incompatibilities between mother and fetus, for example Rh incompatibility. The incompatibility results in an attack by the mother’s antibodies on the babies red blood cells leading to hemolysis. Fortunately, because of modern management of pregnancy, this cause of jaundice is rare.

How is the cause of jaundice diagnosed?

Many tests are available for determining the cause of jaundice, but the history and physical examination are important as well.

The history can suggest possible reasons for the jaundice. For example, heavy use of alcohol suggests alcoholic liver disease, whereas use of illegal, injectable drugs suggests viral hepatitis. Recent initiation of a new drug suggests drug-induced jaundice. Episodes of abdominal pain associated with jaundice suggests blockage of the bile ducts usually by gallstones.

Physical examination
The most important part of the physical examination in a patient who is jaundiced is examination of the abdomen. Masses (tumors) in the abdomen suggest cancer infiltrating the liver (metastatic cancer) as the cause of the jaundice. An enlarged, firm liver suggests cirrhosis. A rock-hard, nodular liver suggests cancer within the liver.

Blood tests
Measurement of bilirubin can be helpful in determining the causes of jaundice. Markedly greater elevations of unconjugated bilirubin relative to elevations of conjugated bilirubin in the blood suggest hemolysis (destruction of red blood cells). Marked elevations of liver tests (aspartate amino transferase or AST and alanine amino transferase or ALT) suggest inflammation of the liver (such as viral hepatitis). Elevations of other liver tests, e.g., alkaline phosphatase, suggest diseases or obstruction of the bile ducts.

Ultrasonography is a simple, safe, and readily-available test that uses sound waves to examine the organs within the abdomen. Ultrasound examination of the abdomen may disclose gallstones, tumors in the liver or the pancreas, and dilated bile ducts due to obstruction (by gallstones or tumor).

Computerized tomography (CT or CAT scans)
Computerized tomography or CT scans are scans that use x-rays to examine the soft tissues of the abdomen. They are particularly good for identifying tumors in the liver and the pancreas and dilated bile ducts, though they are not as good as ultrasonography for identifying gallstones.

Magnetic resonance imaging (MRI)
Magnetic Resonance Imaging scans are scans that utilize magnetization of the body to examine the soft tissues of the abdomen. Like CT scans, they are good for identifying tumors and studying bile ducts. MRI scans can be modified to visualize the bile ducts better than CT scans (a procedure referred to as MR cholangiography), and, therefore, are better than CT for identifying the cause and location of bile duct obstruction.

Endoscopic retrograde cholangiopancreatography (ERCP) and endoscopic ultrasound
Endoscopic retrograde cholangiopancreatography (ERCP) provides the best means for examining the bile duct. For ERCP an endoscope is swallowed by the patient after he or she has been sedated. The endoscope is a flexible, fiberoptic tube approximately four feet in length with a light and camera on its tip. The tip of the endoscope is passed down the esophagus, through the stomach, and into the duodenum where the main bile duct enters the intestine. A thin tube then is passed through the endoscope and into the bile duct, and the duct is filled with x-ray contrast solution. An x-ray is taken that clearly demonstrates the contrast-filled bile ducts. ERCP is particularly good at demonstrating the cause and location of obstruction within the bile ducts. A major advantage of ERCP is that diagnostic and therapeutic procedures can be done at the same time as the x-rays. For example, if gallstones are found in the bile ducts, they can be removed. Stents can be placed in the bile ducts to relieve the obstruction ca used by scarring or tumors. Biopsies of tumors can be obtained.

Ultrasonography can be combined with ERCP by using a specialized endoscope capable of doing ultrasound scanning. Endoscopic ultrasound is excellent for diagnosing small gallstones in the gallbladder and bile ducts that can be missed by other diagnostic methods such as ultrasound, CT, and MRI. It also is the best means of examining the pancreas for tumors and can facilitate biopsy through the endoscope of tumors within the pancreas.

Liver biopsy
Biopsy of the liver provides a small piece of tissue from the liver for examination under the microscope. The biopsy most commonly is done with a long needle after local injection of the skin of the abdomen overlying the liver with anesthetic. The needle passes through the skin and into the liver, cutting off a small piece of liver tissue. When the needle is withdrawn, the piece of liver comes with it. Liver biopsy is particularly good for diagnosing inflammation of the liver and bile ducts, cirrhosis, cancer, and fatty liver.