jaundice (redirected from toxic jaundice)

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.

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jaundice /jaun·dice/ (jawn´dis) icterus; yellowness of the skin, scleras, mucous membranes, and excretions due to hyperbilirubinemia and deposition of bile pigments.

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acholuric jaundice  jaundice without bilirubinemia, associated with elevated unconjugated bilirubin that is not excreted by the kidney.

acholuric familial jaundice  hereditary spherocytosis.

breast milk jaundice  elevated unconjugated bilirubin in some breast-fed infants due to the presence of 5-β-pregnane-3-α-20-β-diol in breast milk, which inhibits glucuronyl transferase conjugating activity, or to dehydration.

cholestatic jaundice  that resulting from abnormal bile flow in the liver.

hemolytic jaundice  that due to increased production of bilirubin from hemoglobin under conditions causing accelerated degradation of erythrocytes.

hepatocellular jaundice  that due to injury to or disease of liver cells.

hepatogenic jaundice , hepatogenous jaundice that due to disease or disorder of the liver.

leptospiral jaundice  Weil's syndrome.

mechanical jaundice  obstructive j.

neonatal jaundice , jaundice of the newborn icterus neonatorum.

nuclear jaundice  kernicterus.

obstructive jaundice  that due to blocking of bile flow.

physiologic jaundice  mild icterus neonatorum lasting the first few days of life.

retention jaundice  that due to inability of the liver to dispose of the bilirubin provided by the circulating blood.

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jaun·dice (jônds, jän-)

n.

Yellowish discoloration of the whites of the eyes, skin, and mucous membranes caused by deposition of bile salts in these tissues, occurring as a symptom of various diseases, such as hepatitis, that affect the processing of bile. Also called icterus.

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jaundice

[jôn′dis, jän′dis]

Etymology: Fr, jaune, yellow

a yellow discoloration of the skin, mucous membranes, and sclerae of the eyes caused by greater than normal amounts of bilirubin in the blood. Because persons with dark skin sometimes have yellow-tinged sclerae, the hard palate of the mouth is often the best place to assess for jaundice. Persons with jaundice may experience nausea, vomiting, and abdominal pain and may pass dark urine and clay-colored stools. Jaundice is a symptom of many disorders, including liver diseases, biliary obstruction, and the hemolytic anemias. Physiologic jaundice commonly develops in newborns and disappears after a few days. Rarer disorders causing jaundice are Crigler-Najjar syndrome and Gilbert's syndrome. Useful diagnostic procedures include a clinical evaluation of the signs and symptoms, tests of liver function, and techniques for direct or indirect visualization, such as x-ray film, computed tomographic scan, ultrasound, endoscopy or exploratory surgery, and biopsy. Also called icterus [ik′tərəs] . See also anicteric hepatitis, hyperbilirubinemia. jaundiced, adj.

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jaundice (jändis),

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

Jaundice.

jaundice, acholuric

(ak´lr´ik),
n a type without bile in the urine.

jaundice, congenital hemolytic

(knjen´itl hē´mlit´ik), (acholuric icterus, spherocytic anemia, hereditary spherocytosis) (sfer´ōsītō´sis),
n a familial hemolytic anemia transmitted as a Mendelian dominant trait. The intrinsic defects of the red blood cells include a spheroidal shape, which allows them to be trapped by the spleen, and increased mechanical fragility.

jaundice, epidemic,

n See disease, Weil's.

jaundice, hemolytic (prehepatic jaundice),

n excess bile pigments in the blood resulting from increased destruction of erythrocytes.

jaundice, hepatic,

n See jaundice, hepatocellular.

jaundice, hepatocellular (hepatic jaundice, infective jaundice, medical jaundice, toxic jaundice),

n a type resulting from disease of liver cells by infectious agents or toxins, decreasing the ability of the liver to handle the bile pigments that are continually produced by the destruction of red blood cells.

jaundice, homologous serum,

n See hepatitis, homologous serum.

jaundice, infective,

n See jaundice, hepatocellular.

jaundice, latent,

n increased bilirubin in the blood without clinical signs of jaundice.

jaundice, medical,

n See jaundice, hepatocellular.

jaundice, obstructive (posthepatic jaundice),

n extrahepatic and intrahepatic obstruction of the biliary tract, resulting in retrograde retention of bile pigments and jaundice.

jaundice, posthepatic,

n See jaundice, obstructive.

jaundice, prehepatic,

n See jaundice, hemolytic.

jaundice, regurgitating,

n jaundice resulting from reentry of conjugated bilirubin into the blood as a result of obstruction of the biliary tract or hepatocellular damage and failure to excrete conjugated bilirubin from liver cells.

jaundice, retention,

n an increase in bilirubin in the blood from hemolysis; failure of the liver cells to conjugate bilirubin or remove free bilirubin.

jaundice, surgical,

n extrahepatic obstruction of the biliary tract.

jaundice, syringe,

n See hepatitis, homologous serum.

jaundice, toxic,

n See jaundice, hepatocellular.

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jaundice

yellowness of skin, sclerae, mucous membranes, and excretions due to hyperbilirubinemia and deposition of bile pigments. Called also icterus. It is usually first noticeable in the sclera.

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

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

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acholuric jaundice

jaundice without bilirubinemia, associated with elevated unconjugated bilirubin that is not excreted by the kidney.

cholestatic jaundice

that resulting from abnormality of bile flow in the liver.

hematogenous jaundice

hemolytic jaundice.

hemolytic jaundice

jaundice associated with hemolytic anemia in which most of the bilirubin is unconjugated. Called also retention jaundice, prehepatic jaundice.

hemorrhagic jaundice

leptospirosis.

hepatocellular jaundice

jaundice caused by injury to or disease of the liver cells.

jaundice index

see icteric index.

nonhemolytic jaundice

that due to an abnormality in bilirubin metabolism.

obstructive jaundice

that due to blockage of the flow of bile, resulting in conjugated hyperbilirubinemia. Called also regurgitation jaundice.

physiological jaundice

mild icterus neonatorum during the first few days after birth.

regurgitation jaundice

obstructive jaundice (above).

toxic jaundice

see hepatocellular jaundice (above).

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jaundice

Icterus Hepatology A condition characterized by the deposition of excess–> 2 mg/dL, 34 µmol/L free or conjugated BR in peripheral circulation, and in skin, mucosa and sclerae; it is either physiologic–eg, due to hemolysis or pathologic–eg, seen in hepatitis or bile stasis. See Breast milk jaundice, Hyperbilirubinemia, Obstructive jaundice.

Jaundice types–unconjugated hyperbilirubinemia

Physiologic jaundice Jaundice develops ≥ 72 hrs after birth; total BR rises to greater than 15 mg/dL; direct BR is < 15% of total BR; jaundice resolves within 1–2 weeks Etiology Sluggish glucuronyl transferase activity, ↑ of BR 'load,' ↓ plasma clearance of BR Management Phototherapy, exchange transfusion

Pathological jaundice Jaundice develops in 72 hrs after birth; total BR peaks at ≤ 15 mg/dL; direct BR is > 15% of total BR; jaundice may require > 2 weeks to resolve Etiology HDN, hemolysis, extravascular loss of blood, ↑ enterohepatic circulation, breast feeding, defective BR metabolism, sepsis, metabolic disease Management Phototherapy, exchange transfusion