Definition: Jaundice, also known as icterus, is a yellowish discoloration 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). [1] This hyperbilirubinemia subsequently causes increased levels of bilirubin in the extracellular fluids, resulting in the clinical presentation. 

Typically, the concentration of bilirubin in the plasma must exceed 1.5 mg/dL ( >35 nmol/l), three times the usual value of approximately 0.5 mg/dL, for the discoloration to be easily visible. [1]

Pathological Causes

In order to understand how jaundice results, the pathological processes that cause jaundice to take their effect must be understood. Jaundice is a sign related to problems with many possible underlying pathological processes. Usually jaundice occurs when there is a disruption in the physiological pathway of the metabolism of bilirubin. [2]

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. After the cell membrane 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 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 per kg of bilirubin is produced each day. [2] 

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. [2]

Diseases and Other Causes Associated with Jaundice

Many healthy babies have some jaundice during the first week of life (neonatal jaundice) that usually goes away. However, jaundice can happen at any age and may be a sign of a problem. Jaundice can happen for many reasons, [3] such as:

Chronic liver diseases Chronic inflammation of the liver can lead to scarring and cirrhosis. This can ultimately result in jaundice. Common examples include chronic hepatitis B and C or alcoholic liver disease with cirrhosis.[4]

Acute inflammation of the liver Any condition in which the liver becomes inflamed suddenly can reduce the ability of the liver to conjugate (attach glucuronic acid to) and secrete bilirubin. Common examples include viral hepatitis, alcoholic hepatitis, and Tylenol-induced liver toxicity. [4]

Inflammation of the bile ducts Diseases causing inflammation of the bile ducts, (ex: primary biliary cirrhosis or sclerosing cholangitis) can stop the flow of bile and elimination of bilirubin and lead to jaundice.[4]

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

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. [4] The most common example would be metastatic cancer, usually from cancers within the abdomen that have spread into the liver. Uncommon causes include a few diseases in which substances accumulate within the liver cells. Examples include: iron (hemochromatosis), alpha-one antitrypsin (alpha-one antitrypsin deficiency), and copper (Wilson’s disease).[4]


Many drugs can cause jaundice and/or cholestasis, leading to jaundice. Some drugs can cause liver inflammation (hepatitis) and others cause inflammation of the bile ducts, resulting in cholestasis and/or jaundice. Drugs also may interfere directly with the chemical processes within the cells of the liver and bile ducts that are responsible for the formation and secretion of bile to the intestine. [4] The best example of a drug that causes this latter type of cholestasis and jaundice is estrogen. Treatment for jaundice caused by drugs is discontinuation of the drug. Almost always the bilirubin levels will return to normal within a few weeks, though in a few cases it may take several months. [4]

Genetic disorders 

 The only common genetic disorder that may cause jaundice is Gilbert’s syndrome which affects approximately 7% of the population. Gilbert’s syndrome is caused by a mild reduction in the activity of the enzyme responsible for conjugating the glucuronic acid to bilirubin. The increase in bilirubin in the blood usually is mild and infrequently reaches levels that cause jaundice. Gilbert’s syndrome is a benign condition that does not cause health problems. [4]

There are several rare genetic disorders present from birth that give rise to jaundice. Dubin-Johnson and Rotor’s syndromes and Crigler-Najjar are examples. [4]

Developmental abnormalities of bile ducts 

There are rare instances in which the bile ducts do not develop normally and the flow of bile is interrupted. These diseases usually are present from birth though some of them may first be recognized in childhood or even adulthood. Cysts of the bile duct (choledochal cysts) or Caroli’s disease are associated with this.[4]

Neonatal jaundice  This 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. [4]


Blood tests 

Measurement of bilirubin can be helpful in determining the causes of jaundice. There are many different lab tests available. 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 like alkaline phosphatase (Alk Phos), suggest diseases or obstruction of the bile ducts.

Imaging  Imaging techniques such at CT Scans, ultrasounds, and MRI scans can all be used to evaluate the liver and bile ducts. CT scans are good for evaluation of possible cancer, while ultrasounds are better for identifying gallstones. MRI scans can be modified to visualize the bile ducts better than CT scans, but are often more expensive and involved.


Treatment of jaundice usually requires a diagnosis of the specific cause of the jaundice and treatment directed at the specific cause, e.g., removal of a gallstone blocking the bile duct.


  1. Guyton, Arthur, and John Hall, John. Textbook of Medical Physiology, Saunders, September 2005
  2. Pashankar, D; Schreiber, RA (July 2001). “Jaundice in older children and adolescents”. Pediatrics in Review 22 (7): 219–226.
  3. http://www.nlm.nih.gov/medlineplus/jaundice.html