Kernicterus

Definition

Liver function tests, or LFTs, include tests for bilirubin, a breakdown product of hemoglobin, and ammonia, a protein byproduct that is normally converted into urea by the liver before being excreted by the kidneys. LFTs also commonly include tests to measure levels of several enzymes, which are special proteins that help the body break down and use (metabolize) other substances. Enzymes that are often measured in LFTs include gamma-glutamyl transferase (GGT); alanine aminotransferase (ALT or SGPT); aspartate aminotransferase (AST or SGOT); and alkaline phosphatase (ALP). LFTs also may include prothrombin time (PT), a measure of how long it takes for the blood to clot.

Purpose

Liver function tests are used to aid in the differential diagnosis of liver disease and injury, and to help monitor response to treatment.

Precautions

Bilirubin: Drugs that may cause increased blood levels of total bilirubin include anabolic steroids, antibiotics, antimalarials, ascorbic acid, Diabinese, codeine, diuretics, epinephrine, oral contraceptives, and vitamin A.

Ammonia: Muscular exertion can increase ammonia levels, while cigarette smoking produces significant increases within one hour of inhalation. Drugs that may cause increased levels include alcohol, barbiturates, narcotics, and diuretics. Drugs that may decrease levels include broad-spectrum antibiotics, levodopa, lactobacillus, and potassium salts.

ALT: Drugs that may increase ALT levels include acetaminophen, ampicillin, codeine, dicumarol, indomethacin, methotrexate, oral contraceptives, tetracyclines, and verapamil. Previous intramuscular injections may cause elevated levels.

GGT: Drugs that may cause increased GGT levels include alcohol, phenytoin, and phenobarbital. Drugs that may cause decreased levels include oral contraceptives.

Description

The liver is one of the most important organs in the body. As the body's "chemical factory," it regulates the levels of most of the main blood chemicals and acts with the kidneys to clear the blood of drugs and toxic substances. The liver metabolizes these products, alters their chemical structure, makes them water soluble, and excretes them in bile.

Liver function tests are used to determine if the liver has been damaged or its function impaired. Elevations of certain liver tests in relation to others aids in that determination. For example, aminotransferases (which include ALT and AST) are notably elevated in liver damage caused by liver cell disease (hepatocellular disease). However, in intrahepatic obstructive disease--which may be caused by some drugs or biliary cirrhosis--the alkaline phosphatases are most abnormal.

Alanine aminotransferase

Alanine aminotransferase (ALT), formerly called serum glutamate pyruvate transaminase, or SGPT, is an enzyme necessary for energy production. It is present in a number of tissues, including the liver, heart, and skeletal muscles, but is found in the highest concentration in the liver. Because of this, it is used in conjunction with other liver enzymes to detect liver disease, especially hepatitis or cirrhosis without jaundice. Additionally, in conjunction with the aspartate aminotransferase test (AST), it helps to distinguish between heart damage and liver tissue damage.

Aspartate aminotransferase

Aspartate aminotransferase (AST), formerly called serum glutamic-oxaloacetic transaminase, or SGOT, is another enzyme necessary for energy production. It, too, may be elevated in liver and heart disease. In liver disease, the AST increase is usually less than the ALT increase. However, in liver disease caused by alcohol use, the AST increase may be two or three times greater than the ALT increase.

Alkaline phosphatase

Alkaline phosphatase (ALP) levels usually include two similar enzymes (isoenzymes) that mainly come from the liver and bone and from the placenta in pregnant women. In some cases, doctors may order a test to differentiate between the alkaline phosphatase that originates in the liver and the alkaline phosphatase originating in bone. If a person has elevated ALP, does not have bone disease and is not pregnant, he or she may have a problem with the biliary tract, the system that makes and stores bile. (Bile is made in the liver, then passes through ducts to the gall bladder, where it is stored.)

Gamma-glutamyl transferase

Gamma-glutamyl transferase (GGT), sometimes called gamma-glutamyl transpeptidase (GGPT), is an enzyme that is compared with ALP levels to distinguish between skeletal disease and liver disease. Because GGT is not increased in bone disorders, as is ALP, a normal GGT with an elevated ALP would indicate bone disease. Conversely, because the GGT is more specifically related to the liver, an elevated GGT with an elevated ALP would strengthen the diagnosis of liver or bile-duct disease. The GGT has also been used as an indicator of heavy and chronic alcohol use, but its value in these situations has been questioned recently. It is also commonly elevated in patients with infectious mononucleosis.

Bilirubin

Bilirubin, a breakdown product of hemoglobin, is the predominant pigment in a substance produced by the liver called bile. Excess bilirubin causes yellowing of body tissues (jaundice). There are two tests for bilirubin: direct-reacting (conjugated) and indirect-reacting (unconjugated). Differentiating between the two is important diagnostically, as elevated levels of indirect bilirubin are usually caused by liver cell dysfunction (e.g. hepatitis), while elevations of direct bilirubin typically result from obstruction either within the liver (intrahepatic) or a source outside the liver (e.g. gallstones or a tumor blocking the bile ducts). Bilirubin measurements are especially valuable in newborns, as extremely elevated levels of unconjugated bilirubin can accumulate in the brain, causing irreparable damage.

Ammonia

Analysis of blood ammonia aids in the diagnosis of severe liver diseases and helps to monitor the course of these diseases. Together with the AST and the ALT, ammonia levels are used to confirm a diagnosis of Reye's syndrome (a rare disorder usually seen in children and associated with aspirin intake), which is characterized by brain and liver damage following an upper respiratory tract infection, chickenpox, or influenza. Ammonia levels are also helpful in the diagnosis and treatment of hepatic encephalopathy, a serious brain condition caused by the accumulated toxins that result from liver disease and liver failure.

Preparation

Preparation requirements for all these tests vary from laboratory to laboratory, so it is generally considered best that the patient be in a fasting state (nothing to eat or drink) after midnight the day before the test(s).

Aftercare

Because many patients with liver disease have prolonged clotting times, it is important to monitor the puncture site for bleeding after blood is drawn (venipuncture).

Risks

Risks for this test are minimal, but may include slight bleeding from the blood-drawing site, fainting or feeling lightheaded after venipuncture, or hematoma (blood accumulating under the puncture site).

Normal results

Reference ranges vary from laboratory to laboratory and also depend upon the method used. However, normal values can generally be found within the following ranges, unless specified differently.

• ALT: 5-35 IU/L (values for the elderly may be slightly higher, and values also may be higher in men and in African-Americans)
• AST: 0-35 IU/L
• ALP: 30-120 IU/L
• GGT: Normal values for this test vary widely, depending on the laboratory performing the test, and the age and sex of the patient. For example, females less than 45 years old have lower values than both males and females over 45 years of age. Values in the newborn can be as much as five times higher than in adults.
• Bilirubin: (Adult, elderly, and child) Total bilirubin: 0.1-1.0 mg/dL; indirect bilirubin: 0.2-0.8 mg/dL; direct bilirubin: 0.1-0.3 mg/dL. (Newborn) Total bilirubin: 1-12 mg/dL. Note: critical values for adult: greater than 1.2 mg/dL. Critical values for newborn (requiring immediate treatment): greater than 15 mg/dL.
• Ammonia: Normal values for this test vary widely, depending upon the laboratory performing the test, the age of the patient, and the type of specimen. For example, values are somewhat higher in arterial than in venous blood.
• PT: 9-12 seconds.

Abnormal results

ALT: Values are significantly increased in cases of hepatitis, and moderately increased in cirrhosis, liver tumor, obstructive jaundice, and severe burns. Values are mildly increased in pancreatitis, heart attack, infectious mononucleosis, and shock. Most useful when compared with ALP levels.

GGT: Increased levels are diagnostic of hepatitis, cirrhosis, liver tumor or metastasis, as well as injury from drugs toxic to the liver. Although the causes are unclear, GGT levels may increase with alcohol ingestion, heart attack, pancreatitis, infectious mononucleosis, and Reye's syndrome.

• AST: High levels may indicate liver cell damage, hepatitis, heart attack, heart failure, or gall stones.
• ALP: Elevated levels occur in diseases that impair bile formation (cholestasis). ALP may also be elevated in many other liver disorders, as well as some lung cancers (bronchogenic carcinoma) and Hodgkin's lymphoma. However, elevated ALP levels may also occur in otherwise healthy people, especially among older people.

Bilirubin: Increased indirect or total bilirubin levels can indicate various serious anemias, including hemolytic disease of the newborn and transfusion reaction. Increased direct bilirubin levels can be diagnostic of bile duct obstruction, gallstones, cirrhosis, or hepatitis. It is important to note that if total bilirubin levels in the newborn reach or exceed critical levels, exchange transfusion is necessary to avoid kernicterus, a condition that causes brain damage.

Ammonia: Increased levels are seen in primary liver cell disease, Reye's syndrome, severe heart failure, hemolytic disease of the newborn, and hepatic encephalopathy.

PT: Elevated in acute liver injury, vitamin K deficiencies, and disorders with impair the absorption of vitamin K, including cholestasis.

Key Terms

Cirrhosis

A serious disease of the liver caused by chronic damage to its cells and the eventual formation of scar tissue (fibrosis). The most common symptoms are mild jaundice, fluid collection in the tissues, mental confusion, and vomiting of blood. If left untreated, cirrhosis lead to liver failure and death.

Hemolytic disease of the newborn

Also known as erythroblastosis neonatorum, this is a condition in which a newborn's red blood cells are destroyed by antibodies that have crossed the placenta from the mother's blood. (Hemolytic disease begins in the fetus, in whom the disease is called erythroblastosis fetalis). Severe anemia caused by hemolytic disease is treated in the same way as other anemias, but when jaundice appears due to increased bilirubin, the jaundice is treated by exposing the infant to bright lights. In severe cases, exchange transfusion is required or brain damage may result.

Hepatitis

An inflammation of the liver, with accompanying liver cell damage or cell death, caused most frequently by viral infection, but also by certain drugs, chemicals, or poisons. May be either acute (of limited duration) or chronic (continuing). Symptoms include jaundice, nausea, vomiting, loss of appetite, tenderness in the right upper abdomen, aching muscles, and joint pain. In severe cases, liver failure may result.

Hepatic encephalopathy

Also called liver encephalopathy or hepatic coma, this is a disorder in which brain function deteriorates because toxic substances, which would normally be removed by the liver, accumulate in the bloodstream due to liver damage or disease. Early symptoms include subtle changes in logical thinking, personality and behavior. As the disorder progresses, signs of drowsiness and confusion increase until eventually the patient loses consciousness and lapses into coma.

Reye's syndrome

A rare disorder characterized by brain and liver damage following an upper respiratory tract infection, chickenpox, or influenza, almost entirely confined to children under age 15, and often related to aspirin ingestion for a viral infection. Symptoms include uncontrollable vomiting, often with lethargy, memory loss, disorientation, or delirium. Swelling of the brain may cause seizures, coma, and in severe cases, death.

Gale Encyclopedia of Medicine. Gale Research, 1999.