Lactate Dehydrogenase Isoenzymes Test
The enzyme lactate dehydrogenase (also known as lactic dehydrogenase, or LDH) is found in the cells of almost all body tissues. The enzyme is especially concentrated in the heart, liver, red blood cells, kidneys, muscles, brain, and lungs. The total LDH can be further separated into five components or fractions labeled by number: LDH-1, LDH-2, LDH-3, LDH-4, and LDH-5. Each of these fractions, called isoenzymes, is used mainly by a different set of cells or tissues in the body. For this reason, the relative amounts of a particular isoenzyme of LDH in the blood can provide valuable diagnostic information.
Strenuous exercise may raise levels of total LDH, specifically the isoenzymes LDH-1, LDH-2, and LDH-5. Alcohol, anesthetics, aspirin, narcotics, procainamide, fluorides, and mithramycin may also raise levels of LDH. Ascorbic acid (vitamin C) can lower levels of LDH.
LDH is found in the cells of almost all body tissues. When certain conditions injure cells in tissues containing LDH, it is released into the bloodstream. Because LDH is so widely distributed throughout the body, analysis of total LDH will not help make a diagnosis of a particular disease. Because this enzyme is actually composed of five different isoenzymes, however, analysis of the different LDH isoenzyme levels in the blood can help in the diagnosis of some diseases.
The five LDH isoenzymes are: LDH-1, LDH-2, LDH-3, LDH-4, and LDH-5. In general, each isoenzyme is used mostly by the cells in a specific tissue. LDH-1 is found mainly in the heart. LDH-2 is primarily associated with the system in the body that defends against infection (reticuloendothelial system). LDH-3 is found in the lungs and other tissues, LDH-4 in the kidney, placenta, and pancreas, and LDH-5 in liver and striated (skeletal) muscle. Normally, levels of LDH-2 are higher than those of the other isoenzymes.
Certain diseases have classic patterns of elevated LDH isoenzyme levels. For example, an LDH-1 level higher than that of LDH-2 is indicative of a heart attack or injury; elevations of LDH-2 and LDH-3 indicate lung injury or disease; elevations of LDH-4 and LDH-5 indicate liver or muscle disease or both. A rise of all LDH isoenzymes at the same time is diagnostic of injury to multiple organs. For example, a heart attack with congestive heart failure may cause symptoms of lung and liver congestion. Advanced cancer and autoimmune diseases such as lupus can also cause this pattern.
One of the most important diagnostic uses for the LDH isoenzymes test is in the differential diagnosis of myocardial infarction or heart attack. The total LDH level rises within 24-48 hours after a heart attack, peaks in two to three days, and returns to normal in approximately five to ten days. This pattern is a useful tool for a delayed diagnosis of heart attack. The LDH-1 isoenzyme level, however, is more sensitive and specific than the total LDH. Normally, the level of LDH-2 is higher than the level of LDH-1. An LDH-1 level higher than that of LDH-2, a phenomenon known as "flipped LDH," is strongly indicative of a heart attack. The flipped LDH usually appears within 12-24 hours after a heart attack. In about 80% of cases, flipped LDH is present within 48 hours of the incident. A normal LDH-1/LDH-2 ratio is considered reliable evidence that a heart attack has not occurred.
It should be noted that two conditions might cause elevated LDH isoenzymes at the same time and that one may confuse the other. For example, a patient with pneumonia may also be having an acute heart attack. In this instance, the LDH-1 level would rise with the LDH-2 and LDH-3. Because of this complication, some laboratories measure only the LDH-1 and consider an elevated LDH level with LDH-1 higher than 40% to be diagnostic of heart damage. LDH isoenzymes test is not used much anymore for diagnosis of heart attack. Tests for the protein troponin, which is found in myocardial cells, have been found to be more accurate.
This test requires a blood sample. The patient need not fast (nothing to eat or drink) before the test unless requested to do so by the physician.
Risks for this test are minimal. The patient may experience slight bleeding from the blood-drawing site, fainting or feeling lightheaded after the vein is punctured (venipuncture), or an accumulation of blood under the puncture site (hematoma).
Reference values for normal levels of LDH isoenzymes vary from laboratory to laboratory but can generally be found within the following ranges:
- LDH-1: 17-27%
- LDH-2: 27-37%
- LDH-3: 18-25%
- LDH-4: 8-16%
- LDH-5: 6-16%
Increased levels of LDH-1 are seen in myocardial infarction, red blood cell diseases like hemolytic anemia, kidney disease including kidney transplantation rejection, and testicular tumors. Increased levels of LDH-2 are found in lung diseases such as pneumonia and congestive heart failure, as well as in lymphomas and other tumors. Elevations of LDH-3 are significant in lung disease and certain tumors. Elevations of LDH-4 are greatly increased in pancreatitis. High levels of LDH-5 are found in liver disease, intestinal problems, and skeletal muscle disease and injury, such as muscular dystrophy and recent muscular trauma.
Diffuse disease or injury (for example, collagen disease, shock, low blood pressure) and advanced solid-tumor cancers cause significant elevations of all LDH isoenzymes at the same time.
Cahill, Mathew. Handbook of Diagnostic Tests. Springhouse, PA: Springhouse Corporation, 1995.
Jacobs, David S., et al. Laboratory Test Handbook. 4th ed. New York: Lexi-Comp Inc., 1996.
Pagana, Kathleen Deska. Mosby's Manual of Diagnostic and Laboratory Tests. St. Louis: Mosby, Inc., 1998.
Janis O. Flores
Differential diagnosis—Comparing and contrasting the signs, symptoms, and laboratory findings of two or more diseases to determine which is causing the patient's condition.
Isoenzyme—One of a group of enzymes that bring about the same reaction but are vary in their physical properties.