Liver Function Tests: Pieces of a Complex Diagnostic Puzzle

By Carolyn Penharlow, RN, MSN, ARNP, BC and Catherine Spader, RN
January 31, 2005

His skin is the color of a pumpkin, and his sclera banana-peel yellow. The reek of stale alcohol emanates from every pore, and despite a grossly distended abdomen, he appears frail and malnourished.

Nurses do not need to see a battery of diagnostic tests to know that this man probably has advanced liver disease
secondary to chronic alcoholism.

However, the physical signs that suggest the earliest stages of liver disease are far subtler, even invisible. Often, the only indication is a change in some of the multitude of liver function tests (LFTs). But understanding LFTs can be daunting. Trying to decipher what they tell us can be like fitting together the pieces of a complex diagnostic puzzle.

Abnormal LFTs mean damage

The liver plays a vital role in the metabolism of carbohydrates, fats, and proteins. It stores vitamins and iron; filters out harmful toxins; and produces prothrombin, fibrinogen, and other substances needed for blood coagulation. The liver is also an excretory organ, essential for the synthesis of organic wastes into bile and the conversion of
fat-soluble wastes to water-soluble material for excretion by the kidneys.

Damage to the liver may interrupt any of these processes, resulting in myriad physical manifestations and abnormal serum test results. Consequently, LFTs are more accurately a measure of liver damage than liver function. A differential diagnosis of specific liver diseases and other disorders requires a comprehensive evaluation. This includes a thorough assessment of patient history, physical examination, serum studies, radiological testing, and in some cases, biopsy.

LFTs — markers and monitors

Frequently ordered LFTs include alanine aminotransferase (ALT), formerly known as serum glutamate pyruvate transaminase (SGPT), and aspartate aminotransferase (AST), formerly known as serum glutamic oxaloacetic transaminase (SGOT). ALT and AST are found in the liver and are intracellular enzymes necessary for amino acid production. They are released into the blood when there is serious damage or tissue cell death occurs.

AST is relatively nonspecific, because it is also found in other organs with high metabolic activity, including the heart, kidney, brain, pancreas, spleen, lungs, and skeletal muscle. Therefore, AST levels rise, not only in liver disease, but also in MI, heart failure, muscle injury, and other nonhepatic disorders. (See “Liver Function Tests” sidebar.)

Because ALT is found primarily in the liver, it is a better marker of liver damage than AST. The degree of ALT serum elevation does not correlate with the degree of liver damage, however. Instead, it is a good test for monitoring the course of diseases that affect the liver.

Bilirubin and jaundice

Bilirubin is formed by the breakdown of hemoglobin from old erythrocytes. These cells are combined, or conjugated, in the liver with glucuronic acid, excreted in the bile, then passed into the intestine.

Although not a particularly sensitive test of liver dysfunction, serum bilirubin levels are helpful in detecting and monitoring liver disease and hemolytic disorders. The etiology or cause of problems associated with abnormal bilirubin levels includes the excessive destruction of red blood cells, the inability of the liver to excrete normal amounts of bilirubin, and the ineffective breakdown of red blood cells in the spleen .

An increase in direct bilirubin (conjugated bilirubin) may indicate an inability of the liver cells to excrete bile or a mechanical obstruction preventing the flow of bile into the common bile duct. Direct bilirubin levels will not rise until the liver has lost at least half its excretory capacity.

Increases in direct bilirubin are noted in hepatitis, biliary obstruction, and cancer of the pancreas. (See “Liver Function Tests” sidebar.)

On the other hand, an increase in indirect bilirubin (unconjugated bilirubin) may suggest a defect in the uptake or conjugation of bilirubin or an increase in the pigment presented to the liver, as in pernicious or hemolytic anemias or cirrhosis. Indirect bilirubin is released into the blood when there is serious damage or tissue cell death occurs.

Finally, total serum bilirubin is a measure of the sum of direct bilirubin plus indirect bilirubin levels. A total bilirubin level greater than 2.5 – 3 mg/dL results in jaundice, evidenced by yellowing of the sclera, hard palate, and palms. Light-skinned patients may also exhibit yellow skin as bilirubin levels increase, as in the patient at the beginning of this article. Associated diseases include hepatitis and alcoholism (See “Liver Function Tests” sidebar.) Other signs include tea-colored urine and clay-colored stools.

Jaundice in a newborn infant, however, is usually nonpathologic and results when the neonate’s still-developing liver is not yet able to eliminate bilirubin from the blood.

Hepatic vs. skeletal

Alkaline phosphatase (AP) is an enzyme found in high concentrations in bone, liver, bile ducts, the intestines, and placenta. It is released into the blood from diseased or damaged tissue and used to evaluate pathology of the bone and liver. The source of an elevated AP may be determined by examining the five varieties of AP, or isoenzymes, isolated from bone, liver, placental, biliary, and intestinal cells. However, due to the cost and complexity of such testing, the isoenzymes are infrequently examined. A more cost-effective test is the gamma-glutamyl transferase (GGT).

Gamma-glutamyl transferase (GGT), also known as gamma-glutamyl transpeptidase (GGT), is an excretory enzyme located in high concentrations in the liver, bile ducts, and kidneys. Because GGT is not found in bone tissue, an elevated GGT would indicate the liver as the source of an elevated AP. Increasing or decreasing GGT levels can be used in evaluating progression or regression of liver cancer. GGT is also useful in evaluating alcohol-induced liver disease and progress during alcohol detoxification.

Other screenings and monitors of progress

Albumin is a protein produced by the liver. Its primary functions are to maintain oncotic pressure and transport small molecules, such as bilirubin, drugs, and hormones, in the blood. Because of a long half-life of 22 days, albumin levels are not useful in monitoring mild or acute liver disease. However, decreased albumin occurs with ascites, alcoholism, viral hepatitis, liver disease, malabsorption, malnutrition, and severe burns.

Prothrombin, a protein produced by the liver, is necessary for the clotting of blood. Serum prothrombin time (PT) is a measure of the clotting time of plasma. PT is useful for monitoring anticoagulation therapy and screening for homeostatic dysfunction as a result of liver disease, vitamin K deficiency, clotting factor deficiency (X, VII, V, II, I) or disseminated intravascular coagulation (DIC).

Ammonia (NH 3) is a natural byproduct of bacterial action on proteins in the intestines. NH 3 is transported to the liver via portal venous blood, where it is metabolized to urea and, finally, excreted by the kidneys. Blood ammonia levels are most useful in evaluating patients with stupor or coma of unknown origin, diagnosing Reye’s syndrome, evaluating patients receiving hyperalimentation therapy, and determining the progress of severe liver disease and response to therapy.

Lactic dehydrogenase (LDH) is an enzyme found in most tissues of the body but is particularly concentrated in the heart, liver, kidneys, and skeletal muscle cells. An elevated LDH level reflects tissue injury; however, to pinpoint the specific source of damage, the five LDH isoenzymes must be further analyzed. LDH levels rise in patients with burns, cancer, heart failure, stroke, and hepatitis. (See “Liver Function Tests” sidebar.)

Although LFTs make up only a portion of a complete clinical picture, understanding their complexities helps nurses fit a big piece into the diagnostic puzzle.

Carolyn Penharlow, RN, MSN, ARNP, BC, is a nurse practitioner in employee health at Georgetown University Hospital, Washington, D.C., and Catherine Spader, RN, works in an ED in Bailey, Colo.

References

1. Bakerman S. Bakerman’s ABC’s of Interpretive Laboratory Data. 4th edition. Myrtle Beach, SC: Interpretive Laboratory Data, Inc.; 2002.

2. Chernecky CC, Berger BJ. Laboratory Tests and Diagnostic Procedures. 3rd ed. Philadelphia: WB Saunders; 2003.

Bibliography

Alsace NH, Maradiegue AH. Gastrointestinal health. In: Adult Primary Care. Meredith PV, Horan NM, eds. Philadelphia: WB Saunders; 2000: 380 – 430.

Fishbach FT. Overview of chemistry studies. Laboratory and diagnostic tests, 7th ed; 2004. Available at www3.georgetown.edu/dml/services/ezproxy.html. Accessed January 21, 2005.

Liver Function Tests. Compiled by the National Library of Medicine and National Institutes of Health. Available at www.nlm.nih.gov/medlineplus. Accessed January 21, 2005.

Seidel H, Ball JW, Dains JE, Benedict GW, eds. Mosby’s Guide to Physical Examination. 5th ed. St. Louis, Mo: Mosby Year Book; 2003.