Jaundice

Definition

Jaundice is a condition in which a person's skin and the whites of the eyes are discolored yellow due to an increased level of bile pigments in the blood resulting from liver disease. Jaundice is sometimes called icterus, from a Greek word for "the condition."

Description

In order to understand jaundice, it is useful to know about the role of the liver in producing bile. The most important function of the liver is the metabolic processing of chemical waste products like cholesterol , and excreting them into the intestines as bile. The liver is the premier chemical factory in the body—most incoming and outgoing chemicals pass through it. It is the first stop for all nutrients, toxins, and drugs absorbed by the digestive tract. The liver also collects chemicals from the blood for processing. Many of these outward bound chemicals are excreted into the bile. One particular substance, bilirubin, is yellow. Bilirubin is a product of the breakdown of hemoglobin, which is the protein inside red blood cells. If bilirubin cannot leave the body, it accumulates and discolors other tissues. The normal total level of bilirubin in blood serum is between 0.2 mg/dL and 1.2 mg/dL. When it rises to 3 mg/dL or higher, the person's skin and the whites of the eyes become noticeably yellow.

Bile is formed in the liver. It then passes into the network of hepatic bile ducts, which join to form a single tube. A branch of this tube carries bile to the gallbladder, where it is stored, concentrated, and released on a signal from the stomach. Food entering the stomach is the signal that stimulates the gallbladder to release the bile. The tube, which is called the common bile duct, continues to the intestines. Before the common bile duct reaches the intestines, it is joined by another duct from the pancreas. The bile and the pancreatic juice enter the intestine through a valve called the ampulla of Vater. After entering the intestine, the bile and pancreatic secretions together help in the process of digestion.

Causes & symptoms

There are many different causes for jaundice, but they can be divided into three categories based on where they start—before (pre-hepatic), in (hepatic), or after (post-hepatic) the liver. When bilirubin begins its life cycle, it cannot be dissolved in water. Thus, the liver changes it so that it is soluble in water. These two types of bilirubin are called unconjugated (insoluble) and conjugated (soluble). Blood tests can easily distinguish between these two types of bilirubin.

Hemoglobin and bilirubin formation

Bilirubin begins as hemoglobin in the blood-forming organs, primarily the bone marrow. If the production of red blood cells (RBCs) falls below normal, the extra hemoglobin finds its way into the bilirubin cycle and adds to the pool.

Once hemoglobin is in the red cells of the blood, it circulates for the life span of those cells. The hemoglobin that is released when the cells die is turned into bilirubin. If for any reason the RBCs die at a faster rate than usual, then bilirubin can accumulate in the blood and cause jaundice.

Hemolytic disorders

Many disorders speed up the death of red blood cells. The process of red blood cell destruction is called hemolysis, and the diseases that cause it are called hemolytic disorders. If red blood cells are destroyed faster than they can be produced, the patient develops anemia .

Hemolysis can occur in a number of diseases, disorders, conditions, and medical procedures:

• Malaria . The malaria parasite develops inside red blood cells. When it is mature it breaks the cell apart and swims off in the blood. This process happens to most of the parasites simultaneously, causing the intermittent symptoms of the disease. When enough cells burst at once, jaundice may result from the large amount of bilirubin formed from the hemoglobin in the dead cells. The pigment may reach the urine in sufficient quantities to cause "blackwater fever," an often lethal form of malaria.
• Side effects of certain drugs. Some common drugs can cause hemolysis as a rare but sudden side effect. These medications include some antibiotic and antituberculosis medicines; drugs that regulate the heartbeat; and levodopa, a drug used to treat Parkinson's disease.
• Certain drugs in combination with a hereditary enzyme deficiency known as glucose–6–phosphate dehydrogenase (G6PD). G6PD is a deficiency that affects more than 200 million people in the world. Some of the drugs listed above are more likely to cause hemolysis in people with G6PD. Other drugs cause hemolysis only in people with this disorder. Most important among these drugs are such antimalarial medications, as quinine, and vitamins C and K.
• Poisons. Snake and spider venom, certain bacterial toxins, copper , and some organic industrial chemicals directly attack the membranes of red blood cells.
• Artificial heart valves. The inflexible moving parts of heart valves damage RBCs as they flutter back and forth. This damage is one reason to recommend pig valves and valves made of other organic materials.
• Hereditary RBC disorders. There are a number of hereditary defects that affect the blood cells. There are many genetic mutations that affect the hemoglobin itself, the best known of which is sickle cell disease. Such hereditary disorders as spherocytosis weaken the outer membrane of the red cell. There are also inherited defects that involve the internal chemistry of RBCs.
• Enlargement of the spleen. The spleen is an organ that is located near the upper end of the stomach and filters the blood. It is supposed to filter out and destroy only wornout RBCs. If it has become enlarged, it filters out normal cells as well. Malaria, other infections , cancers and leukemias, some of the hereditary anemias mentioned above, obstruction of blood flow from the spleen—all these and many more diseases can enlarge the spleen to the point where it removes too many red blood cells.
• Diseases of the small blood vessels. Hemolysis that occurs in diseased small blood vessels is called microangiopathic hemolysis. It results from damage caused by rough surfaces on the inside of the capillaries. The RBCs squeeze through capillaries one at a time and can easily be damaged by scraping against the vessel walls.
• Immune reactions to RBCs. Several types of cancer and immune system diseases produce antibodies that react with RBCs and destroy them. In 75% of cases, this reaction occurs all by itself, with no underlying disease to account for it.
• Transfusions. If a patient is given an incompatible blood type, hemolysis results.
• Kidney failure and other serious diseases. Several diseases are characterized by defective blood coagulation that can destroy red blood cells.
• Erythroblastosis fetalis. Erythroblastosis fetalis is a disease of newborns marked by the presence of too many immature red blood cells (erythroblasts) in the baby's blood. When a baby's mother has a different blood type, antibodies from the mother may leak into the baby's circulation and destroy blood cells. This reaction can produce severe hemolysis and jaundice in the newborn. Rh factor incompatibility is the most common cause.
• High bilirubin levels in newborns. Even in the absence of blood type incompatibility, the newborn's bilirubin level may reach threatening levels.

Normal jaundice in newborns

Normal newborn jaundice is the result of two conditions occurring at the same time—a prehepatic and a hepatic source of excess bilirubin. First of all, the baby at birth immediately begins converting hemoglobin from a fetal type to an adult type. The fetal type of hemoglobin was able to extract oxygen from the lower levels of oxygen in the mother's blood. At birth the infant can extract oxygen directly from his or her own lungs and does not need the fetal hemoglobin any more. So fetal hemoglobin is removed from the system and replaced with adult hemoglobin. The resulting bilirubin loads the system and places demands on the liver to clear it. But the liver is not quite ready for the task, so there is a period of a week or so when the liver has to catch up. During that time the baby is jaundiced.

In 2002 new studies found that infants younger than eight weeks old with jaundice often had hidden (asymptomatic) urinary tract infections. Previous studies have shown that newborn jaundice may be an early sign of bacterial infections in infants. The study recommended that pediatricians routinely test young infants with jaundice for urinary tract infections.

Hepatic jaundice

Liver diseases of all kinds threaten the organ's ability to keep up with bilirubin processing. Starvation, circulating infections, certain medications, hepatitis , and cirrhosis can all cause hepatic jaundice, as can certain hereditary defects of liver chemistry, including Gilbert's syndrome and Crigler-Najjar syndrome.

Post-hepatic jaundice

Post-hepatic forms of jaundice include the jaundices caused by failure of soluble bilirubin to reach the intestines after it has left the liver. These disorders are called obstructive jaundices. The most common cause of obstructive jaundice is the presence of gallstones in the ducts of the biliary system. Other causes have to do with birth defects and infections that damage the bile ducts; drugs; infections; cancers; and physical injury. Some drugs—and pregnancy on rare occasions—simply cause the bile in the ducts to stop flowing.

Symptoms and complications associated with jaundice

Certain chemicals in bile may cause itching when too much of them end up in the skin. In newborns, insoluble bilirubin may get into the brain and do permanent damage. Long-standing jaundice may upset the balance of chemicals in the bile and cause stones to form. Apart from these potential complications and the discoloration of skin and eyes, jaundice by itself is inoffensive. Other symptoms are determined by the disease producing the jaundice.

Diagnosis

Physical examination

In many cases, the diagnosis of jaundice is suggested by the appearance of the patient's eyes and complexion. The doctor will ask the patient to lie flat on the examining table in order to feel (palpate) the liver and spleen for enlargement and to evaluate any abdominal pain . The location and severity of abdominal pain and the presence or absence of fever help the doctor to distinguish between hepatic and obstructive jaundice.

Laboratory tests

Disorders of blood formation can be diagnosed by more thorough examination of the blood or the bone marrow, where blood is made. Occasionally a bone marrow biopsy is required, but usually the blood itself will reveal the diagnosis. The spleen can be evaluated by an ultrasound examination or a nuclear scan if the physical examination has not yielded enough information.

Imaging studies

Disease in the biliary system can be identified by imaging techniques, of which there are many. X rays are taken a day after swallowing a contrast agent that is secreted into the bile. This study gives functional as well as anatomical information. There are several ways of injecting x-ray dye directly into the bile ducts. It can be done through a thin needle pushed straight into the liver, or through a scope passed through the stomach that can inject dye into the ampulla of Vater. CT and MRI scans are very useful for imaging certain conditions, such as cancers in and around the liver, or gallstones in the common bile duct.

Liver disease is usually assessed from blood studies alone, but again a biopsy may be necessary to clarify less obvious conditions. A liver biopsy is performed at the bedside. The doctor uses a thin needle to take a tiny core of tissue from the liver. The tissue sample is sent to the laboratory for examination under a microscope.

Assessment of jaundice in newborns

Newborns are more likely to have problems with jaundice if:

• They are premature.
• They are of Asian or Native American descent.
• They have been bruised during the birth process.
• They have lost too much weight during the first few days.
• They are born at a high altitude.
• The mother has diabetes.
• Labor had to be induced.

In 2003, research was continuing to find noninvasive methods to determine bilirubin levels in newborns so that physicians did not have to rely on visual examination alone to determine which infants should receive blood tests. Once these measurements of skin pigment can be shown effective and cost-effective in clinical practice, they may become more widely available. Another study used this measurement method incorporated into home health visits to monitor babies within 24 hours of discharge from the hospital following birth.

Treatment

Jaundice is often an early warning sign of serious liver damage. Alternative medicine treatments should not be used as a substitute for conventional medical treatment. Patients should contact their doctors for diagnosis and treatment immediately if experiencing signs and symptoms of jaundice. Alternative therapies may be helpful as complementary measures for patients who have an underlying disease that already has been diagnosed.

Nutritional therapy

Naturopaths or nutritionists may recommend the following dietary changes:

• Drinking fresh vegetable or fruit juices during the first several weeks after diagnosis and eating a diet consisting mostly of raw fruits and vegetables, seeds, and nuts during the next month. These fruits and vegetables are easy to digest and contain lots of antioxidants , vitamins and minerals. They help the body remove toxins from the blood, and decrease stress/strain on the liver for digestion/metabolism.
• Fasting intermittently.
• Eliminating alcohol from the diet for good, and avoiding foods that are processed and high in fat. These foods are bad for the liver.
• Drinking a cup of lemonade (without sugar) early in the morning to improve liver and bile function.
• Incorporating olive oil or lemon oil into the diet as a liver flushing regimen.
• Taking nutritional supplements, such as multivitamins or minerals, vitamin C, vitamin B complex , other antioxidant-containing supplements, supplements containing alpha lipoic acid, protein supplements, essential fatty acids (EFAs), and digestive enzymes with bile (for patients having pale stools).

Traditional Chinese medicine

Depending on a patient's specific condition, an expert Chinese herbalist may prescribe herbal remedies that can help improve liver function. Animal studies have shown the following Chinese herbs may have liver protective effects:

• Bupleurum chinense
• Phellodendron wilsonii
• Clementis chinensis

Herbal therapy

Patients should consult an experienced herbalist for specific herbal treatments that may include milk thistle or artichoke.

Homeopathy

For homeopathic therapy, patients should consult a homeopathic physician who will prescribe specific remedies based on knowledge of the underlying cause.

Juice therapy

Juice therapy helps the liver detoxify toxins to be eliminated from the body. Patients should mix one part of pure juice with one part of water before drinking. Daily consumption of the following juices may be helpful:

• carrot and beet juice with a touch of radish or dandelion root juice
• grapes, pear, and lemon
• carrot, celery, and parsley
• carrot, beet, and cucumber

Aromatherapy

Essential oils of rosemary , lemon, and geranium may help improve liver function and relax the body. They can be given as inhalants, a soothing bath, or soak.

Other therapies

Other alternative treatments that may be help improve liver function include fasting, Ayurveda, hydrotherapy , and acupuncture .

Allopathic treatment

Jaundice in newborns

Newborns are the only major category of patients in whom the jaundice itself requires attention. If there is reason to suspect increased hemolysis in the newborn, the bilirubin level must be measured repeatedly during the first few days of life. If the level of bilirubin shortly after birth threatens to go too high, treatment must begin immediately. Exchanging most of the baby's blood was the only way to reduce the amount of bilirubin until a few decades ago. Jaundiced babies are now fitted with eye protection and placed under bright fluorescent blue lights. The light chemically alters the bilirubin in the blood as it passes through the baby's skin so that it may be more easily eliminated in the urine. In 2003 researchers were testing a new drug called Stanate that showed promise in blocking bilirubin production. However, debate concerning the use of the drug for treatment of only those infants with jaundice or as a preventive measure was delaying its FDA approval and widespread use.

Hemolytic disorders

Hemolytic diseases are treated, if at all, with medications and blood transfusions, except in the case of an enlarged spleen. Surgical removal of the spleen (splenectomy) can sometimes cure hemolytic anemia. Drugs that cause hemolysis or arrest the flow of bile must be stopped immediately.

Hepatic jaundice

Most liver diseases have no specific cure, but the liver is so robust that it can heal from severe damage and regenerate itself from a small remnant of its original tissue.

Posthepatic jaundice

Obstructive jaundice frequently requires a surgical cure. If the original passageways cannot be restored, surgeons have several ways to create alternate routes. To create alternate passageways, a surgeon will sew an open piece of intestine over a bare patch of liver. Tiny bile ducts in that part of the liver will begin to discharge their bile into the intestine, and pressure from the obstructed ducts elsewhere will find release in that direction. As the flow increases, the ducts grow to accommodate it. Soon, all the bile is redirected through the open pathways.

Prevention

Erythroblastosis fetalis can be prevented by giving an Rh-negative mother a gamma globulin solution called RhoGAM whenever there is a possibility that she is developing antibodies to her baby's blood. G6PD hemolysis can be prevented by testing patients before giving them drugs that can cause it. Medication side effects can be minimized by early detection and immediate cessation of the drug. Malaria can often be prevented by taking certain precautions when traveling in tropical or subtropical countries. These precautions include staying in after dark; using such prophylactic drugs as mefloquine; and protecting sleeping quarters with mosquito nets treated with insecticides and mosquito repellents. In 2003, new studies showed promise for a possible vaccine against malaria. Early trials showed that vaccination combination might stimulate T-cell activity against malaria, the best type of protection that researchers can hope to find. However, further studies will have to be done.

New research in 2002 linked a popular antidepressant drug called paroxetine (Paxil) to several newborn complications, including jaundice. Although research is preliminary, pregnant women might want to discuss use of the drug with their physicians to prevent complications like jaundice in their newborn babies.

Resources

BOOKS

Balistreri, William F. "Manifestations of Liver Disease." In Nelson Textbook of Pediatrics, edited by Waldo E. Nelson, et al. Philadelphia: W. B. Saunders, 1996.

"Jaundice." Alternative Medicine: The Definitive Guide. Tiburon, CA: Future Medicine Publishing, Inc., 1999.

"Jaundice." In Sleisenger & Fordtran's Gastrointestinal and Liver Disease, edited by Mark Feldman, et al. Philadelphia: W. B. Saunders, 1998.

Kaplan, Lee M., and Kurt J. Isselbacher. "Jaundice." In Harrison's Principles of Internal Medicine, edited by Kurt Isselbacher et al. New York: McGraw–Hill, 1998.

"Liver Problems." The Hamlyn Encyclopedia of Complementary Health. London, Reed International Books Limited.

McQuaid, Kenneth R. "Alimentary Tract." In Current Medical Diagnosis and Treatment, edited by Lawrence M. Tierney, Jr., et al. Stamford, CT: Appleton & Lange, 1996.

Scharschmidt, Bruce F. "Bilirubin Metabolism, Hyperbilirubinemia, and Approach to the Jaundiced Patient." In Cecil Textbook of Medicine, edited by J. Claude Bennett and Fred Plum. Philadelphia: W. B. Saunders, 1996.

PERIODICALS

Chin, Hui–Fen, Chun–Ching Lin, Chui–Ching Yang, and Fay Yang. "The Pharmacological and Pathological Studies on Several Hepatic Protective Crude Drugs from Taiwan." American Journal of Chinese Medicine XVI no. 3–4 (1988): 127–137.

Garcia, Francisco J., and Alan L. Nager. "Jaundice as an Early Diagnostic Sign of Urinary Tract Infection in Infancy." Pediatrics (May 2002): 846.

Grimm, David. "Baby Pigment Peril." U.S. News &World Report (July 28, 2003): 39.

Lawrence, David. "Combination Malaria Vaccine Shows Early Promise in Human Trials." The Lancet (May 31, 2003): 1875.

Morantz, Carrie, and Brian Torrey. "AHRQ Report on Neonatal Jaundice." American Family Physician (June 1, 2003): 2417.

"Paxil Linked to Complications in Newborns." Psychopharmacology Update (June 2002): 6.

Richmond, Glenn, Melissa Brown, and Patricia Wagstaff. "Using a Home Care Model to Monitor Bilirubin Levels in Early Discharged Infants." Topics in Health Information Management (January&-March 2003): 39–43.

ORGANIZATION

American Liver Foundation. 1425 Pompton Avenue, Cedar Grove, New Jersey 07009. (800) 223–0179.

Teresa G. Odle

Jaundice

Definition

Jaundice is a condition in which a person's skin and the whites of the eyes are discolored yellow due to an increased level of bile pigments in the blood resulting from liver disease. Jaundice is sometimes called icterus, from a Greek word for the condition.

Description

In order to understand jaundice, it is useful to know about the role of the liver in producing bile. The most important function of the liver is the processing of chemical waste products like cholesterol and excreting them into the intestines as bile. The liver is the premier chemical factory in the body—most incoming and outgoing chemicals pass through it. It is the first stop for all nutrients, toxins, and drugs absorbed by the digestive tract. The liver also collects chemicals from the blood for processing. Many of these outward-bound chemicals are excreted into the bile. One particular substance, bilirubin, is yellow. Bilirubin is a product of the breakdown of hemoglobin, which is the protein inside red blood cells. If bilirubin cannot leave the body, it accumulates and discolors other tissues. The normal total level of bilirubin in blood serum is between 0.2 mg/dL and 1.2 mg/dL. When it rises to 3 mg/dL or higher, the person's skin and the whites of the eyes become noticeably yellow.

Bile is formed in the liver. It then passes into the network of hepatic bile ducts, which join to form a single tube. A branch of this tube carries bile to the gallbladder, where it is stored, concentrated, and released on a signal from the stomach. Food entering the stomach is the signal that stimulates the gallbladder to release the bile. The tube, which is called the common bile duct, continues to the intestines. Before the common bile duct reaches the intestines, it is joined by another duct from the pancreas. The bile and the pancreatic juice enter the intestine through a valve called the ampulla of Vater. After entering the intestine, the bile and pancreatic secretions together help in the process of digestion.

Causes and symptoms

There are many different causes for jaundice, but they can be divided into three categories based on where they start-before, in, or after the liver (prehepatic, hepatic and post-hepatic). When bilirubin begins its life cycle, it cannot be dissolved in water. The liver changes it so that it is soluble in water. These two types of bilirubin are called unconjugated (insoluble) and conjugated (soluble). Blood tests can easily distinguish between these two types of bilirubin.

Hemoglobin and bilirubin formation

Bilirubin begins as hemoglobin in the blood-forming organs, primarily the bone marrow. If the production of red blood cells (RBCs) falls below normal, the extra hemoglobin finds its way into the bilirubin cycle and adds to the pool.

Once hemoglobin is in the red cells of the blood, it circulates for the life span of those cells. The hemoglobin that is released when the cells die is turned into bilirubin. If for any reason the RBCs die at a faster rate than usual, bilirubin can accumulate in the blood and cause jaundice.

Hemolytic disorders

Many disorders speed up the death of red blood cells. The process of red blood cell destruction is called hemolysis, and the diseases that cause it are called hemolytic disorders. If red blood cells are destroyed faster than they can be produced, the patient develops anemia. Hemolysis can occur in a number of diseases, disorders, conditions, and medical procedures:

• Malaria. The malaria parasite develops inside red blood cells. When it is mature it breaks the cell apart and swims off in the blood. This process happens to most of the parasites simultaneously, causing the intermittent symptoms of the disease. When enough cells burst at once, jaundice may result from the large amount of bilirubin formed from the hemoglobin in the dead cells. The pigment may reach the urine in sufficient quantities to cause "blackwater fever," an often lethal form of malaria.
• Side effects of certain drugs. Some common drugs can cause hemolysis as a rare but sudden side effect. These medications include some antibiotic and anti-tuberculosis medicines; drugs that regulate the heart-beat; and levodopa, a drug used to treat Parkinson's disease.
• Certain drugs in combination with a hereditary enzyme deficiency known as glucose-6-phosphate dehydrogenase (G6PD). G6PD is a deficiency that affects more than 200 million people in the world. Some of the drugs listed above are more likely to cause hemolysis in people with G6PD. Other drugs cause hemolysis only in people with this disorder. Most important among these drugs are anti-malarial medications such as quinine, and vitamins C and K.
• Poisons. Snake and spider venom, certain bacterial toxins, copper, and some organic industrial chemicals directly attack the membranes of red blood cells.
• Artificial heart valves. The inflexible moving parts of heart valves damage RBCs as they flutter back and forth. This damage is one reason to recommend pig valves and valves made of other organic materials.
• Hereditary RBC disorders. There are a number of hereditary defects that affect the blood cells. There are many genetic mutations that affect the hemoglobin itself, the best-known of which is sickle cell disease. Such hereditary disorders as spherocytosis weaken the outer membrane of the red cell. There are also inherited defects that involve the internal chemistry of RBCs.
• Enlargement of the spleen. The spleen is an organ that is located near the upper end of the stomach and filters the blood. It is supposed to filter out and destroy only worn-out RBCs. If it has become enlarged, it filters out normal cells as well. Malaria, other infections, cancers and leukemias, some of the hereditary anemias mentioned above, obstruction of blood flow from the spleen—all these and many more diseases can enlarge the spleen to the point where it removes too many red blood cells.
• Diseases of the small blood vessels. Hemolysis that occurs in diseased small blood vessels is called micro-angiopathic hemolysis. It results from damage caused by rough surfaces on the inside of the capillaries. The RBCs squeeze through capillaries one at a time and can easily be damaged by scraping against the vessel walls.
• Immune reactions to RBCs. Several types of cancer and immune system diseases produce antibodies that react with RBCs and destroy them. In 75% of cases, this reaction occurs all by itself, with no underlying disease to account for it.
• Transfusions. If a patient is given an incompatible blood type, hemolysis results.
• Kidney failure and other serious diseases. Several diseases are characterized by defective blood coagulation that can destroy red blood cells.
• Erythroblastosis fetalis. Erythroblastosis fetalis is a disease of newborns marked by the presence of too many immature red blood cells (erythroblasts) in the baby's blood. When a baby's mother has a different blood type, antibodies from the mother may leak into the baby's circulation and destroy blood cells. This reaction can produce severe hemolysis and jaundice in the newborn. Rh factor incompatibility is the most common cause.
• High bilirubin levels in newborns. Even in the absence of blood type incompatibility, the newborn's bilirubin level may reach threatening levels.

Normal jaundice in newborns

Normal newborn jaundice is the result of two conditions occurring at the same time—a pre-hepatic and a hepatic source of excess bilirubin. First of all, the baby at birth immediately begins converting hemoglobin from a fetal type to an adult type. The fetal type of hemoglobin was able to extract oxygen from the lower levels of oxygen in the mother's blood. At birth the infant can extract oxygen directly from his or her own lungs and does not need the fetal hemoglobin any more. So fetal hemoglobin is removed from the system and replaced with adult hemoglobin. The resulting bilirubin loads the system and places demands on the liver to clear it. But the liver is not quite ready for the task, so there is a period of a week or so when the liver has to catch up. During that time the baby is jaundiced.

Hepatic jaundice

Liver diseases of all kinds threaten the organ's ability to keep up with bilirubin processing. Starvation, circulating infections, certain medications, hepatitis, and cirrhosis can all cause hepatic jaundice, as can certain hereditary defects of liver chemistry, including Gilbert's syndrome and Crigler-Najjar syndrome.

Post-hepatic jaundice

Post-hepatic forms of jaundice include the jaundices caused by failure of soluble bilirubin to reach the intestines after it has left the liver. These disorders are called obstructive jaundices. The most common cause of obstructive jaundice is the presence of gallstones in the ducts of the biliary system. Other causes have to do with birth defects and infections that damage the bile ducts; drugs; infections; cancers; and physical injury. Some drugs—and pregnancy on rare occasions—simply cause the bile in the ducts to stop flowing.

Symptoms and complications associated with jaundice

Certain chemicals in bile may cause itching when too much of them end up in the skin. In newborns, insoluble bilirubin may get into the brain and do permanent damage. Long-standing jaundice may upset the balance of chemicals in the bile and cause stones to form. Apart from these potential complications and the discoloration of skin and eyes, jaundice by itself is inoffensive. Other symptoms are determined by the disease producing the jaundice.

Diagnosis

Physical examination

In many cases the diagnosis of jaundice is suggested by the appearance of the patient's eyes and complexion. The doctor will ask the patient to lie flat on the examining table in order to feel (palpate) the liver and spleen for enlargement and to evaluate any abdominal pain. The location and severity of abdominal pain and the presence or absence of fever help the doctor to distinguish between hepatic and obstructive jaundice.

Laboratory tests

Disorders of blood formation can be diagnosed by more thorough examination of the blood or the bone marrow, where blood is made. Occasionally a bone marrow biopsy is required, but usually the blood itself will reveal the diagnosis. The spleen can be evaluated by an ultrasound examination or a nuclear scan if the physical examination has not yielded enough information.

Liver disease is usually assessed from blood studies alone, but again a biopsy may be necessary to clarify less obvious conditions. A liver biopsy is performed at the bedside. The doctor uses a thin needle to take a tiny core of tissue from the liver. The tissue sample is sent to the laboratory for examination under a microscope.

Assessment of jaundice in newborns

Newborns are more likely to have problems with jaundice if:

• They are premature.
• They are Asian or Native Americans.
• They have been bruised during the birth process.
• They have lost too much weight during the first few days.
• They are born at high altitude.
• The mother has diabetes.
• Labor had to be induced.

In 2003, research was continuing to find noninvasive methods to determine bilirubin levels in newborns so that physicians did not have to rely on visual examination alone to determine which infants should receive blood tests. Once these measurements of skin pigment can be shown effective and cost-effective in clinical practice, they may become more available. Another study used this measurement method incorporated into home health visits to monitor babies within 24 hours of discharge from the hospital following birth.

Imaging studies

Disease in the biliary system can be identified by imaging techniques, of which there are many. X rays are taken a day after swallowing a contrast agent that is secreted into the bile. This study gives functional as well as anatomical information. There are several ways of injecting contrast dye directly into the bile ducts. It can be done through a thin needle pushed straight into the liver or through a scope passed through the stomach that can inject dye into the Ampulla of Vater. CT and MRI scans are very useful for imaging certain conditions like cancers in and around the liver or gallstones in the common bile duct.

Treatment

Jaundice in newborns

Newborns are the only major category of patients in whom the jaundice itself requires attention. Because the insoluble bilirubin can get into the brain, the amount in the blood must not go over certain levels. If there is reason to suspect increased hemolysis in the newborn, the bilirubin level must be measured repeatedly during the first few days of life. If the level of bilirubin shortly after birth threatens to go too high, treatment must begin immediately. Exchanging most of the baby's blood was the only way to reduce the amount of bilirubin until a few decades ago. Then it was discovered that bright blue light rendered the bilirubin harmless. Now jaundiced babies are fitted with eye protection and placed under bright fluorescent lights. The light chemically alters the bilirubin in the blood as it passes through the baby's skin. In 2003, researchers were testing a new drug called Stanate that showed promise in blocking bilirubin production. However, debate concerning the use of the drug for treatment of only those infants with jaundice or as a preventive measure was delaying its FDA approval and widespread use.

Hemolytic disorders

Hemolytic diseases are treated, if at all, with medications and blood transfusions, except in the case of a large spleen. Surgical removal of the spleen (splenectomy ) can sometimes cure hemolytic anemia. Drugs that cause hemolysis or arrest the flow of bile must be stopped immediately.

Hepatic jaundice

Most liver diseases have no specific cure, but the liver is so robust that it can heal from severe damage and regenerate itself from a small remnant of its original tissue.

KEY TERMS

Ampulla of Vater— The widened portion of the duct through which the bile and pancreatic juices enter the intestine. Ampulla is a Latin word for a bottle with a narrow neck that opens into a wide body.

Anemia— A condition in which the blood does not contain enough hemoglobin.

Biliary system/Bile ducts— The gall bladder and the system of tubes that carries bile from the liver into the intestines.

Bilirubin— A reddish pigment excreted by the liver into the bile as a breakdown product of hemoglobin.

Crigler-Najjar syndrome— A moderate to severe form of hereditary jaundice.

Erythroblastosis fetalis— A disorder of newborn infants marked by a high level of immature red blood cells (erythroblasts) in the infant's blood.

Gilbert's syndrome— A mild hereditary form of jaundice.

Glucose-6-phosphate dehydrogenase (G6PD) deficiency— A hereditary disorder that can lead to episodes of hemolytic anemia in combination with certain medications.

Hemoglobin— The red chemical in blood cells that carries oxygen.

Hemolysis— The destruction or breakdown of red blood cells.

Hepatic— Refers to the liver.

Icterus— Another name for jaundice.

Microangiopathic— Pertaining to disorders of the small blood vessels.

Pancreas— The organ beneath the stomach that produces digestive juices, insulin, and other hormones.

Sickle cell disease— A hereditary defect in hemoglobin synthesis that changes the shape of red cells and makes them more fragile.

Splenectomy— Surgical removal of the spleen.

Post-hepatic jaundice

Obstructive jaundice frequently requires a surgical cure. If the original passageways cannot be restored, surgeons have several ways to create alternate routes. A popular technique is to sew an open piece of intestine over a bare patch of liver. Tiny bile ducts in that part of the liver will begin to discharge their bile into the intestine, and pressure from the obstructed ducts elsewhere will find release in that direction. As the flow increases, the ducts grow to accommodate it. Soon all the bile is redirected through the open pathways.

Prevention

Erythroblastosis fetalis can be prevented by giving an Rh negative mother a gamma globulin solution called RhoGAM whenever there is a possibility that she is developing antibodies to her baby's blood. G6PD hemolysis can be prevented by testing patients before giving them drugs that can cause it. Medication side effects can be minimized by early detection and immediate cessation of the drug. Malaria can often be prevented by certain precautions when traveling in tropical or subtropical countries. These precautions include staying in after dark; using prophylactic drugs such as mefloquine; and protecting sleeping quarters with mosquito nets treated with insecticides and mosquito repellents. In 2003, new studies showed promise for a possible vaccine against malaria. Early trials showed that vaccination combination might stimulate T-cell activity against malaria, the best type of protection that researchers can hope to find. However, further studies will have to be done.

Resources

PERIODICALS

Grimm, David. "Baby Pigment Peril." U.S. News & World Report July 28, 2003: 39.

Lawrence, David. "Combination Malaria Vaccine Shows Early Promise in Human Trials." The Lancet May 31, 2003: 1875.

Morantz, Carrie, and Brian Torrey. "AHRQ Report on Neonatal Jaundice." American Family Physician June 1, 2003: 2417.

Richmond, Glenn, Melissa Brown, and Patricia Wagstaff. "Using a Home Care Model to Monitor Bilirubin Levels in Early Discharged Infants." Topics in Health Information Management January-March 2003: 39-43.

ORGANIZATIONS

American Liver Foundation. 1425 Pompton Ave., Cedar Grove, NJ 07009. (800) 223-0179. 〈http://www.liverfoundation.org〉.

Jaundice

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:

KEY TERMS

Antibody —A special protein made by the body's immune system as a defense against foreign material (bacteria, viruses, etc.) that enters the body. It is uniquely designed to attack and neutralize the specific antigen that triggered the immune response.

Bile —A bitter yellow-green substance produced by the liver. Bile breaks down fats in the small intestine so that they can be used by the body. It is stored in the gallbladder and passes from the gall-bladder through the common bile duct to the top of the small intestine (duodenum) as needed to digest fat.

Bile ducts —Tubes that carry bile, a thick yellow-green fluid that is made by the liver, stored in the gallbladder, and helps the body digest fats.

Biliary atresia —An obstruction or inflammation of a bile duct that causes bilirubin to back up into the liver.

Bilirubin —A reddish yellow pigment formed from the breakdown of red blood cells, and metabolized by the liver. When levels are abnormally high, it causes the yellowish tint to eyes and skin known as jaundice. Levels of bilirubin in the blood increase in patients with liver disease, blockage of the bile ducts, and other conditions.

Hemolysis —The process of breaking down of red blood cells. As the cells are destroyed, hemoglobin, the component of red blood cells which carries the oxygen, is liberated.

Hyperbilirubinemia —A condition characterized by a high level of bilirubin in the blood. Bilirubin is a natural byproduct of the breakdown of red blood cells, however, a high level of bilirubin may indicate a problem with the liver.

Kernicterus —A potentially lethal disease of newborns caused by excessive accumulation of the bile pigment bilirubin in tissues of the central nervous system.

Phototherapy —Another name for light therapy in mainstream medical practice.

• 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).

Margaret Alic, PhD

Jaundice

Definition

Jaundice is a condition in which the patient has a yellow hue because of high blood levels of bilirubin, a breakdown product of hemoglobin that is potentially toxic. The yellow discoloration is most noticeable in the skin, the sclera (whites of the eyes), and the inner surface of the eyelids.

Description

Jaundice is a physical sign or finding, not a disease. Many different diseases or conditions may cause a person's bilirubin level to be elevated. Most important to the understanding of causes of this sign is a good explanation of normal liver function with regard to the production and excretion of bile. Bile is a fluid excreted by the liver that aids in digestion and absorption of fats.

The liver is a large, solid organ in the right upper quadrant of the abdomen. It is the premier "chemical processing plant" in the body; most incoming and outgoing chemicals pass through it. It is the first stop for all nutrients, toxins, and drugs absorbed by the digestive tract. The liver also collects waste products from the blood for disposal. Many of these outward-bound chemicals (including bilirubin) are excreted into the bile.

Bile is made up of water; chemicals that act as detergents; and substances such as glycogen, bilirubin, cholesterol, and other byproducts of hepatic metabolism. It is formed by cellular metabolism and passes into the network of hepatic bile ducts, which join to form the common duct. A branch of this tube carries bile to the gallbladder, where it is stored and concentrated. When fats enter the stomach, the gallbladder secretes bile into the common bile duct. Before the common bile duct reaches the duodenum, it is joined by another duct from the pancreas. The bile and the pancreatic juice are triggered to enter the intestine through a valve called the ampulla of Vater by the presence of partially digested fats in the duodenum. After entering the intestine, the bile and pancreatic secretions together help to complete the process of digestion.

The liver removes toxins from the bloodstream, including bilirubin. Bilirubin is a potentially toxic waste product from the breakdown of hemoglobin, the oxygen-carrying molecule of red blood cells (RBCs). When bilirubin is first released from old RBCs or other sources, it cannot be dissolved in water. The liver changes it so that it is soluble in water. These two forms are called unconjugated (insoluble) and conjugated (soluble) bilirubin. Because of the type of laboratory test performed on the different forms of this molecule, unconjugated bilirubin is also called indirect bilirubin, and conjugated bilirubin is called direct bilirubin. Bilirubin is a bright yellow pigment and gives bile its characteristic color. If bilirubin cannot be cleared from the body in a timely fashion, it leaks into body tissues and stains them yellow temporarily, resulting in jaundice. The normal level of bilirubin in blood serum is between 0.2 mg/dL and 1.2 mg/dL. When it rises to 3 mg/dL or higher, jaundice becomes evident. "Icteric" is an adjective (based on the Greek word for jaundice) used to describe a jaundiced patient.

Causes and symptoms

There are many different causes of jaundice, but they can be divided into three categories: before, during, or after the liver has performed its task of making bilirubin soluble. These categories can also be called prehepatic, hepatic, and posthepatic causes of jaundice.

Prehepatic causes of jaundice

There are many different prehepatic causes of jaundice. When old RBCs die, hemoglobin is released into the bloodstream. When the rate of formation of new RBCs and the rate of loss of old RBCs are well balanced, the normal liver can keep pace with disposal of used hemoglobin. If the body is having difficulty making RBCs (due to mineral or vitamin deficiencies), hemoglobin may leak into circulation and overwhelm the liver. Conversely, if RBCs are destroyed rapidly, the liver may also be overwhelmed. Disorders that cause RBCs to disintegrate prematurely are called hemolytic disorders.

One cause of hemolysis (or prematurely destroyed RBCs) starts at the neonatal point in babies born of Rh-negative mothers. Other causes include a long list of drugs, among them rifampin, methyldopa, certain antibiotics, quinine, and levodopa. Trauma can also destroy RBCs. Some common causes of trauma include surgery for mechanical heart valves, implants, and roughened surfaces of blood vessels such as those occurring in microangiopathic hemolytic anemia. The parasite that causes malaria develops inside red blood cells and ruptures the RBCs when it is mature. A number of hereditary defects affect red blood cells, including glucose-6-phosphate dehydrogenase (G6PD) deficiency (in which RBCs disintegrate under certain stresses, particularly when exposed to certain drugs), sickle-cell disease (in which the structure of hemoglobin is abnormal), and spherocytosis (in which a protein in the outer membrane of the RBC causes weakness in the membrane).

An enlarged spleen can also cause hemolysis. The spleen is the reservoir organ, located near the upper end of the stomach, that filters the blood. It is supposed to filter out and destroy only worn-out RBCs. If it becomes enlarged, it filters out normal cells as well. A wide variety of conditions, including many causes of hemolysis listed above, can enlarge the spleen to the point where it removes too many red blood cells. Also, in several types of cancer (such as chronic leukemia) and immune-system diseases, antibodies are produced that react with RBCs and destroy them. In addition, if a patient is given an incompatible blood type, it sets off an immune reaction, and hemolysis results.

In all causes of prehepatic jaundice, the predominant bilirubin is insoluble—that is, unconjugated. Hemolysis alone will rarely cause the total bilirubin level to rise above 7 mg/dL.

Hepatic causes of jaundice

Liver diseases of all kinds, whether temporary or life-long, threaten the organ's ability to keep up with bilirubin processing. Some of the more common causes of jaundice include infectious hepatitis (types A, B, C, D, and E, and various other viruses ), alcoholic hepatitis, and cirrhosis (scarring of the liver, due to various diseases, to the degree that it can no longer function). Starvation, circulating infections, and certain medications (acetaminophen overdose, isoniazid, and others) can cause inefficiency in bilirubin disposal. Certain hereditary defects also affect how the liver processes bilirubin (such as Gilbert's syndrome and Crigler-Najjar syndrome), causing elevated levels of unconjugated bilirubin. Also, there are several inherited conditions in which the liver cannot excrete bilirubin after it is made soluble (such as Dubin-Johnson syndrome and Rotor syndrome), resulting in direct (or conjugated) bilirubin being the predominant form of the molecule. Unlike hemolytic causes of jaundice, which always involve unconjugated bilirubin, the hepatic sources of jaundice often represent mixed results.

Posthepatic causes of jaundice

Posthepatic forms of jaundice include those caused when soluble bilirubin does not reach the intestines after it has left the liver, resulting in elevated direct bilirubin levels. These disorders are called obstructive jaundices. The most common cause of obstructive jaundice is the presence of gallstones in the ducts of the biliary system. Other causes include diseases where the bile ducts have been destroyed, such as the autoimmune disease primary biliary sclerosis, lesions (whether benign or malignant), and trauma. Some drugs (such as anabolic and contraceptive steroids), and occasionally pressures caused by a normal pregnancy, cause the bile in the ducts to stop flowing. This process is called cholestasis.

Neonatal jaundice

Several conditions can cause jaundice in a newborn baby. Erythroblastosis fetalis is a disease of newborns marked by the presence of too many immature red blood cells (erythroblasts) in the baby's blood. When a baby and mother have different Rh factors (positive-RH baby and negative-Rh mother), antibodies from the mother may leak into the baby's circulation through the placental exchange and destroy blood cells. This reaction may produce severe hemolysis and jaundice in the newborn. Rh-factor incompatibility is the most common cause. These births are usually induced a week or two early to keep third-trimester hemolysis to a minimum.

Even in the absence of Rh-factor incompatibility, the newborn's bilirubin level may reach threatening levels. Normal newborn jaundice is the result of two conditions occurring at the same time: a prehepatic and a hepatic source of excess bilirubin. During development, the fetal-type hemoglobin is important to extract oxygen from the mother's blood. At birth, the infant extracts oxygen directly from the lungs and no longer needs the fetal hemoglobin. So, fetal hemoglobin is removed from the system and replaced with mature hemoglobin. The resulting hemoglobin overload overwhelms the immature system, and bilirubin levels may rise until the third day of life, and then decline by day five to day 10. During that time, the baby is jaundiced.

These forms of jaundice in the newborn may result in high levels of unconjugated bilirubin. If conjugated bilirubin is found, it is usually due to serious causes, such as obstruction of the biliary system or overwhelming infection.

Symptoms

Certain chemicals in bile may cause itching in jaundiced patients. Fatigue is a very common symptom in people with liver disease. In more severe illness, nausea may occur. Poor appetite and weight loss can be a problem for some patients, usually those with acute infection or advanced scarring of the liver (cirrhosis). Depending on the cause of jaundice, patients may or may not have pain over the liver (upper right quadrant). Liver pain is common if there are gallstones, and may also occur in acute hepatitis. Patients whose bile does not drain into the small intestine adequately will have clay-colored stools. The conjugated form of bilirubin may be excreted by the kidneys and result in dark urine. Long-standing jaundice may upset the balance of chemicals in the bile and cause stones to form in the gallbladder or in the ducts.

In newborns, the concern about jaundice is that insoluble or unconjugated bilirubin may get into the brain and do permanent damage to the central nervous system. This serious condition is called kernicterus. It becomes a concern as bilirubin levels approach 20 mg/dL. Newborns are more likely to have problems with jaundice if they are premature, Asian or Native American, or bruised significantly during the birth process. Jaundice is also more common if a newborn was born after an induced labor, has lost too much weight during the first few days of life, was born at high altitude, or was born to a diabetic mother.

Diagnosis

In most cases, the sign of jaundice is identified based on the appearance of the patient's sclera and complexion. The liver and spleen are palpated to check for enlargement and to evaluate any abdominal pain. The location and severity of abdominal pain and the presence of masses in the abdomen, together with the presence of fever, help to distinguish among the causes for jaundice. The differential diagnosis of the cause of jaundice is primarily based on blood-test results.

Laboratory testing reveals the total bilirubin and its components. The capability to evaluate total bilirubin levels and the fractionation into direct (conjugated) and indirect (unconjugated) components is available in most laboratories. The jaundice may be determined to be of indirect (prehepatic sources, Gilbert's syndrome, or Crigler-Najjar syndrome) or direct (primarily obstructive posthepatic sources, and some hepatic diseases) origin. Liver enzymes, such as aspartate aminotransferase (AST) and alanine aminotransferase (ALT), should be evaluated; elevations would be signs of inflammation or destruction of liver cells. If the AST is at least twice the level of the ALT, this finding strongly supports the suggestion of alcohol abuse as a source of liver disease. If alkaline phosphatase is elevated, this suggests an obstructive (posthepatic) component in the cause of jaundice. Albumin levels and prothrombin times will be abnormal (elevated) if the liver is severely damaged. Microscopic analysis of blood smears for signs of hemolysis is performed.

Each time a newborn is tested for jaundice, it generally requires a needle prick in the baby's heel. In 2004, a new device was created to screen newborns for jaundice and lessen the need for painful heel pricks. The device shines a light through the baby's skin and measures the reflection instead of drawing blood. It can help tell how yellow a baby's skin is, indicating possible jaundice. The new device doesn't eliminate the need for blood tests. If jaundice is suspected, the physician may follow up with a heel prick and newborns known to have jaundice must have bilirubin levels monitored as treatment proceeds.

Liver disease is usually assessed from blood studies and physical-examination findings, but a biopsy may be necessary to clarify less obvious disease. A liver biopsy may be performed at the bedside. A thin, cannulated needle is inserted to draw a core of tissue from the liver. The tissue sample is sent for pathologic examination.

Diseases of the biliary system may be identified by imaging techniques, especially with the use of contrast dye. The most common and cost-effective method for beginning to assess the liver and bile ducts is ultrasound. Dilated bile ducts are very suggestive of obstruction, and abnormal amounts of fat or scar tissue may be noticed. Much more detailed information about the structure of the liver and biliary tree is gained with computed tomography (CT) or magnetic resonance imaging (MRI). Very detailed investigation of the bile ducts is achieved with endoscopic retrograde cholangiopancreatography (ERCP), in which a fiber-optic scope is put down the gastrointestinal tract via the mouth, all the way to the ampulla of Vater. Dye is injected to map the bile ducts and identify obstruction. A tiny brush-tipped device at the end of the scope light is used to scrape tissue from the duct lining for analysis. Treatment can also be achieved at the same time, as stones can be removed or stents placed to aid in passage of a stone or maintaining bile flow in spite of a tumor.

Treatment

Newborns are the one group of patients in whom the jaundice itself requires attention. Because the insoluble bilirubin can get into the brain, the amount in the blood must not go over certain levels. If there is reason to suspect increased hemolysis in the newborn, the bilirubin level must be measured repeatedly during the first few days of life. If the level of bilirubin shortly after birth threatens to go too high, treatment must begin immediately. Exchanging most of the baby's blood (an exchange transfusion) was the only way to reduce the amount of bilirubin until the late 1960s. Then it was discovered that bright blue light renders the bilirubin harmless. Now jaundiced babies are fitted with eye protection and placed under special lights, wearing only a diaper so that more skin surface can be exposed. The phototherapy alters the bilirubin in the blood as it passes through and close to the baby's skin. Under certain conditions, exchange transfusions are still done to rapidly gain control over bilirubin levels.

In 2004, a new drug was being developed to treat neonatal jaundice. Called stannsoporfin (Stanate), it is an enzme inhibitor that blocks conversion of heme into bilirubin for a few days, allowing sufficient time in most cases for the baby's liver to mature and begin excreting bilirubin on its own.

Most adult patients are treated based on the underlying cause of the jaundice. Surgical removal of the spleen (splenectomy) may arrest hemolytic anemia. Drugs that cause hemolysis or arrest the flow of bile are discontinued or replaced with alternate therapy. The abuse of alcohol or street drugs must stop if the liver is to begin to heal and the jaundice given a chance to subside. Obstructive jaundice frequently requires surgical repair. The gallbladder may need to be removed, or small stones removed from lower in the biliary tract. If there is neoplasm of the liver or biliary tree, partial or total removal is necessary. If the original biliary passageways cannot be restored, new ones are created in surgery.

Prognosis

Prognosis is based on the underlying cause of jaundice. The liver is a very resilient organ, and many patients do well after supportive therapy or surgical intervention for acute causes of jaundice. High bilirubin levels themselves are not dangerous to patients other than neonates, so all symptoms of high bilirubin levels are reversible if the underlying condition is treatable.

Health care team roles

Good supportive care of the jaundiced patient, regardless of the underlying disorder, is important. If alcohol abuse has been an acute or long-standing problem, nursing staff can contribute much in educating the patient about the importance of avoiding alcohol.

Prevention

Many of the numerous causes of jaundice cannot be anticipated or avoided. Alcohol abuse in patients should be identified and support provided to aid in recovery. Erythroblastosis fetalis can be prevented by giving an Rh-negative mother a gamma globulin solution called RhoGAM as a routine part of prenatal care. This will decrease the chances her antibody titer will rise against her baby's blood. Liver problems due to medications can be minimized with appropriate screening blood tests and cessation of the drug if necessary. One cause of liver failure not mentioned previously is anorexia nervosa, in which patients intentionally starve themselves, disabling the body's immune-defense system and overwhelming the liver's ability to detoxify the blood. Patients with this condition need specific psychiatric therapy in addition to adequate nutritional supplementation therapy to prevent liver failure. If it occurs, transplantation may be the only recourse. Malaria may be prevented by taking certain precautions when traveling in tropical or subtropical countries and climates.

KEY TERMS

Ampulla of Vater— A valve at the distal end of the widened portion of the common bile duct, through which the bile and pancreatic juices enter the duodenum.

Anemia— A condition in which the blood does not contain enough hemoglobin. There are many causes of anemia, including hemolysis, bleeding, and problems producing red blood cells (RBCs).

Biliary system/bile ducts— The gallbladder and the system of tubes that carries bile from the liver into the intestines.

Bilirubin— A breakdown product of hemoglobin that is potentially toxic. The liver collects bilirubin from the bloodstream, alters it, and secretes it into bile.

Hemoglobin— The red pigment in red blood cells that carries oxygen.

Hemolysis— The premature destruction of red blood cells.

Hepatic jaundice— A cause of jaundice; jaundice that occurs while the liver is performing its task of making bilirubin soluble.

Icteric— An adjective, based on the Greek word for jaundice, used to describe a jaundiced patient.

Liver— A large, solid organ in the right upper quadrant of the abdomen that is the body's premier "chemical processing plant" of drugs, nutrients, and toxins.

Neonatal jaundice— Jaundice in a newborn baby, resulting from various conditions.

Pancreas— The organ adjacent to the stomach that produces digestive juices, insulin, and other hormones.

Posthepatic jaundice— A cause of jaundice; jaundice that occurs after the liver has performed its task of making bilirubin soluble.

Prehepatic jaundice— A cause of jaundice; jaundice that occurs before the liver has performed its task of making bilirubin soluble.

Rh incompatibility— When a baby and mother have different Rh factors; a common cause of jaundice in newborns.

Splenectomy— Surgical removal of the spleen, sometimes necessary to control certain types of hemolytic anemia.

Resources

BOOKS

Braunwald, E., et al. Harrison's Principles of Internal Medicine, 15th ed. McGraw-Hill, 2001: 255-259, 1715-1720.

Fischbach, F. A Manual of Laboratory and Diagnostic Tests. Lippincott, 2000:385-389.

Tierney, L. M., S. J. McPhee, and M. A. Papadakis. Current Medical Diagnosis and Treatment 2001. Lange Medical Books/McGraw-Hill, 2000:662-667.

PERIODICALS

Furuta, S., et al. "Anorexia Nervosa with Severe Liver Dysfunction and Subsequent Critical Complications." Internal Medicine 38, no. 7 (July 1999): 575-579.

Himal, H. S. "Common Bile Duct Stones: The Role of Preoperative, Intraoperative, and Postoperative ERCP." Seminars in Laparoscopic Surgery 7, no. 4 (December 2000): 237-245.

Madlon-Kay, D. J. "Health Nurse Clinical Assessment of Neonatal Jaundice: Comparison of Three Methods." Archives of Pediatric and Adolescent Medicine 155, no. 5 (May 2001): 583-586.

Narang, A., P. Kumar, and R. Kumar. "Neonatal Jaundice in Very Low Birth Weight Babies." Indian Journal of Pedatrics 68, no. 4 (April 2001): 307-309.

Rippey, Lauren. "An Ouch-free Jaundice Test." Baby Talk (Nov. 1, 2004): 25.

"U.S. Patent and Trademark Office Publishes Patent for Neonatal Jaundice." Drug Week (Dec. 31, 2004): 558.

Jaundice

Liver and bile

Bilirubin

Jaundice

Causes

Identification

Jaundice is a condition in which a person’s skin and the whites of the eyes are discolored a shade of yellow due to an increased level of bile pigments in the blood resulting from liver disease. It is sometimes called icterus, from a Greek word for the condition. Jaundice is not a disease buta symptom of an underlying disease or condition. It is caused by too much bilirubin in the blood stream, and is characterized by yellowness of skin, sclera (white of eyes), mucous membranes, and of body fluids such urine and blood plasma. The resulting yellow color (jaune means yellow in French) is also described by the Latin term icterus.

Liver and bile

In order to understand jaundice, it is useful to know about the role of the liver in producing bile. The most important function of the liver is the processing of chemical waste products like cholesterol and excreting them into the intestines as bile. The liver is the premier chemical factory in the body—most incoming and outgoing chemicals pass through it. It is the first stop for all nutrients, toxins, and drugs absorbed by the digestive tract. The liver also collects chemicals from the blood for processing. Many of these outward-bound chemicals are excreted into the bile. One particular substance, bilirubin, is yellow. Bilirubin is a product of the breakdown of hemoglobin, which is the protein inside red blood cells. If bilirubin cannot leave the body, it accumulates and discolors other tissues. The normal total level of bilirubin in blood serum is between 0.2 milligrams per deciliter (mg/dL) and 1.2 mg/dL. When it rises to 3 mg/dL or higher, the person’s skin and the whites of the eyes become noticeably yellow.

Bile is formed in the liver. It then passes into the network of hepatic bile ducts, which join to form a single tube. A branch of this tube carries bile to the gallbladder, where it is stored, concentrated, and released on a signal from the stomach. Food entering the stomach is the signal that stimulates the gallbladder to release the bile. The tube, which is now called the common bile duct, continues to the intestines. Before the common bile duct reaches the intestines, it is joined by another duct from the pancreas. The bile and the pancreatic juice enter the intestine through a valve called the ampulla of Vater. After entering the intestine, the bile and pancreatic secretions together help in the process of digestion.

Bilirubin

Most bilirubin, which is a reddish pigment, is a byproduct of red blood cells. When a red blood cell, which has a lifespan of about 120 days, is no longer functional. It is recycled by organs such as the spleen and liver. Hemoglobin, the red pigment in a red blood cell, is broken down, or catabolized, into several substances that are either used to make new blood cells, proteins, or other pigments. After the bilirubin is liberated from the red blood cell, it is bound to albumin and transported via blood plasma to the liver, where it is conjugated or joined to glucuronic acid, and excreted into the bile ducts. Bilirubin is also the prominent pigment of bile, a digestive substance secreted by the liver into the gallbladder and small intestine (jejunum), and it is also responsible for the brown color of feces.

Jaundice

There are several ways in which a person can have too much bilirubin, or become jaundiced. Hemolytic jaundice occurs when the liver is overloaded with bilirubin. In conditions and diseases causing hemolysis (the separation of hemoglobin from the red blood cells), including hemolytic anemias, incompatible blood transfusion, and extreme heat or cold, the liver is unable to remove enough bilirubin from the blood stream. Liver cells which are damaged by hepatocellular disease (hepatitis, cirrhosis), toxins, tumors, or inflammatory conditions, are unable to conjugate bilirubin, thus preventing normal excretion. Neonatal jaundice, especially in premature infants, is fairly common. This type of jaundice is caused by the fact that the liver is immature and lacks specific enzymes to conjugate bilirubin, and a large amount of bilirubin is consequently excreted into the blood stream instead of being incorporated into bile.

Causes

There are many different causes for jaundice, but they can be divided into three main categories based on where they start—before, in, or after the liver (prehepatic, hepatic, and post-hepatic). When bilirubin

begins its life cycle, it cannot be dissolved in water. The liver changes bilirubin so that it becomes soluble in water. These two types of bilirubin are called uncon-jugated (insoluble) and conjugated (soluble). Blood tests can easily distinguish between these two types of bilirubin. The most common cause of jaundice is obstruction of bile flow through the biliary system. For example, a gallstone, a liver tumor, or a pancreatic tumor can block a biliary duct. The treatment of jaundice depends on the cause.

Identification

Disease in the biliary system can be identified by imaging techniques, of which there are many types. X rays are taken a day after swallowing a contrast agent that is secreted into the bile. This study gives functional as well as anatomical information. There are several ways of injecting x-ray dye directly into the bile ducts. It can be done through a thin needle pushed straight into the liver or through a scope passed through the stomach that can inject dye into the Ampulla of Vater. CT (computed tomography) and MRI (magnetic resonance imaging) scans are very useful for imaging certain conditions like cancers in and around the liver or gall stones in the common bile duct.

Newborns are the only major category of patients in whom the jaundice itself requires attention. Because the insoluble bilirubin can get into the brain, the amount in the blood must not go over certain levels. If there is reason to suspect increased hemolysis in the newborn, the bilirubin level must be measured repeatedly during the first few days of life. If the level of bilirubin shortly after birth threatens to go too high, treatment must begin immediately. Exchanging most of the baby’s blood was the only way to reduce the amount of bilirubin until the middle part of the twentieth century. At that time, it was discovered that bright blue light renders the bilirubin harmless. (Actually, in 1956, Sister Ward, a nurse at Rochford General Hospital in England, accidentally discovered the use of blue light for this purpose.) Now jaundiced babies are fitted with eye protection and placed under bright fluorescent lights. The light chemically alters the bilirubin in the blood as it passes through the baby’s skin.

Hemolytic diseases are treated, if at all, with medications and blood transfusions, except in the case of a large spleen. Surgical removal of the spleen (splenectomy) can sometimes cure hemolytic anemia. Drugs that cause hemolysis or arrest the flow of bile must be stopped immediately.

Most liver diseases have no specific cure, but the liver is so robust that it can heal from severe damage and regenerate itself from a small remnant of its original tissue.