Lactate Dehydrogenase (LD) Isoenzymes, Serum
Clinical Information Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test
Total Lactate Dehydrogenase (LD):
LD activity is present in all cells of the body with highest concentrations in heart, liver, muscle, kidney, lung, and erythrocytes. As with other proteins used as tissue-function markers, the appearance of LD in the serum occurs only after prolonged hypoxia and is elevated in a number of clinical conditions including cardiorespiratory diseases, malignancy, hemolysis, and disorders of the liver, kidneys, lung, and muscle.
LD is a tetrameric cytoplasmic enzyme, composed of H and M subunits. The most usual designation of the isoenzyme is LD-I (H4), LD-II (H3M), LD-III (H2M2), LD-IV (HM3), and LD-V (M4). Tissue specificity is derived from the fact that there is tissue-specific synthesis of subunits in well-defined ratios. Most notably, heart muscle cells preferentially synthesize H subunits, while liver cells synthesize M subunits nearly exclusively. Skeletal muscle also synthesizes largely M subunits so that LD-V is both a liver and skeletal muscle form of LD. The LD-I and LD-V forms are most often used to indicate heart or liver pathology, respectively.
LD-I appears elevated in the serum about 24 to 48 hours after a myocardial infarction (MI), but is generally not as useful as troponin or creatine kinase-MB (CK-MB) for detection of MI, unless the MI occurred at least 24 hours prior to testing. Normally, LD-II is greater than LD-I; however, when a MI has occurred, there is a "flip" in the usual ratio of LD-I/LD-II from <1 to >1 (or at least >0.9). Use of the ratio for evaluation of patients with possible cardiovascular injury has largely been replaced by TPNT / Troponin T, Serum.
The LD-V form is pronounced in patients with either primary liver disease or liver hypoxia secondary to decreased perfusion, such as occurs following an MI. However, LD-V is usually not as reliable as the transaminases (eg, aspartate aminotransferase, alanine aminotransferase) for evaluating liver function. LD-V also may be elevated in muscular damage and diseases of the skin.
Although it does not appear to cause or be associated with any symptoms or particular diseases, the presence of macro-LD (LD combined with an immunoglobulin) can cause an idiosyncratic elevation of total LD.
Investigating a variety of diseases involving the heart, liver, muscle, kidney, lung, and blood
Differentiating heart-synthesized lactate dehydrogenase (LD) from liver and other sources
As an aid in the diagnosis of myocardial infarction when used in combination with total creatine kinase (CK) and CK-MB
Investigating unexplained causes of LD elevations
Detection of macro-LD
Marked elevations in lactate dehydrogenase (LD) activity can be observed in megaloblastic anemia, untreated pernicious anemia, Hodgkin disease, abdominal and lung cancers, severe shock, and hypoxia.
Moderate-to-slight increases in LD levels are seen in myocardial infarction (MI), pulmonary infarction, pulmonary embolism, leukemia, hemolytic anemia, infectious mononucleosis, progressive muscular dystrophy (especially in the early and middle stages of the disease), liver disease, and renal disease.
In liver disease, elevations of LD are not as great as the increases in aspartate amino transferase and alanine aminotransferase.
Increased levels of the enzyme are found in about one-third of patients with renal disease, especially those with tubular necrosis or pyelonephritis. However, these elevations do not correlate well with proteinuria or other parameters of renal disease.
On occasion, a raised LD level may be the only evidence to suggest the presence of a hidden pulmonary embolus.
LD-II is found in myocardium. Following a severe MI, the diagnostic ratio of LD-I divided by LD-II will change from <0.9 to >0.9. This is referred to as an LD "flip".
LD-I elevation not due to myocardial damage may indicate hemolytic disease or other forms of in vivo hemolysis.
Elevation of LD-V (least mobile isoenzyme) usually denotes liver damage. It is rarely helpful in defining skeletal muscle disease.
Macro-LD can occur, which results in an elevation of LD for no clinical reason. Macro-LD greatly affects the migration of LD isoenzymes since the addition of an immunoglobulin molecule greatly retards the migration of the usual LD isoenzymes. If macro-LD is present, the electrophoretogram will show atypically migrating isoenzymes with LD activity localized near the origin.
Cautions Discusses conditions that may cause diagnostic confusion, including improper specimen collection and handling, inappropriate test selection, and interfering substances
A hemolyzed specimen is not acceptable as red blood cells contain much more lactate dehydrogenase (LD) than serum. Causes of hemolysis can include transportation via pneumatic tube, vigorous mixing, or traumatic venipuncture. Tubes should be void of air bubbles to prevent minor hemolysis. LD activity is one of the most sensitive indicators of in vitro hemolysis. Hemolysis causes anomalous elevation of LD-I such that any ex vivo hemolysis must be strictly avoided.
Freezing or prolonged storage at 4 degrees C (>12 hours) causes LD-V to be lost.
Elevations of intermediate forms, LD-II through LD-IV, are rarely used to define a tissue of origin and such reports are largely anecdotal.
While increases in serum LD also are seen following an myocardial infarction, the test has been replaced by the determination of troponin (TPNT / Troponin T, Serum).
Reference Values Describes reference intervals and additional information for interpretation of test results. May include intervals based on age and sex when appropriate. Intervals are Mayo-derived, unless otherwise designated. If an interpretive report is provided, the reference value field will state this.
1-30 days: 135-750 U/L
31 days-11 months: 180-435 U/L
1-3 years: 160-370 U/L
4-6 years: 145-345 U/L
7-9 years: 143-290 U/L
10-12 years: 120-293 U/L
13-15 years: 110-283 U/L
16-17 years: 105-233 U/L
> or =18 years: 122-222 U/L
I (fast band): 17.5-28.3%
V (slow band): 5.5-12.7%
Clinical References Provides recommendations for further in-depth reading of a clinical nature
Tietz Textbook of Clinical Chemistry and Molecular Diagnostics. Edited by CA Burtis, ER Ashwood. Philadelphia, WB Saunders Company, 2006