Lactate Dehydrogenase Isoenzymes

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Subject: Lactate Dehydrogenase Isoenzymes

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Definition

  • LD is a tetrameric cytoplasmic enzyme. The most usual designation of the isoenzyme is LD-1 (H[4]), LD-2 (H[3]M), LD-3 (H[2]M[2]), LD-4 (HM[3]), and LD-5 (M[4]). The 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, whereas liver cells synthesize M subunits nearly exclusively. Skeletal muscle also synthesizes largely M subunits so that LD(5) is both a liver and skeletal muscle form of LD. The LD-1 and LD-5 forms are ones most often used to indicate heart or liver pathology, respectively. LD isoenzyme patterns cannot be interpreted without the knowledge of clinical history (see Table 16.52).

 
TABLE 16–52
Percent Activity Distribution of LD Isoenzymes in Tissue

Use

  • LD is useful in the investigation of a variety of diseases involving the heart, liver, muscle, kidney, lung, and blood; and differentiating heart-synthesized LD from liver and other sources of LD.

  • Isoenzymes are used by many clinicians in the diagnosis of MI in combination with total CK and CK-MB.

  • Investigating unexplained causes of LD elevations.

  • Detection of macro-LD.

Interpretation

See Table 16.53.
 
TABLE 16–53
LD Isoenzyme Patterns in Various Disease Conditions
 
  • Macroenzymes, high molecular weight complexes, occur with LD as well as with CK and other enzymes. LD isoenzymes may complex to IgA or IgG. Such LD macroenzymes are characterized by abnormal position of isoenzyme bands, broadening or abnormal motility of a band, and otherwise unexplained increase of total serum LD. Some of these patients have abnormal ANA results and IgG complexes. Some have abnormalities of light chains but not in amounts that are useful for diagnosis. Treatment with streptokinase was found to produce an LD-streptokinase complex, which was seen as a band at the origin in electrophoresis.

  • Increased total LD with normal distribution of isoenzymes may be seen in myocardial infarction, arteriosclerotic heart disease with chronic heart failure, and various combinations of acute and chronic diseases (this may represent a general stress reaction).

  • About 50% of patients with malignant tumors have altered LD patterns. This change often is nonspecific and of no diagnostic value. Solid tumors, especially those of germ cell origin, may increase LD-1.

  • In megaloblastic anemia, hemolysis, renal cortical infarction, and some patients with cancer, the isoenzyme pattern may mimic that of MI, but the time to peak value and the increase help to differentiate these conditions.

  • An isoenzyme band cathodal to LD-5 has been called LD-6. It is not an immunoglobulin complex. It has occurred in subjects with liver disease and is said to indicate a grave prognosis.

Limitations

  • A hemolyzed specimen is not acceptable as RBCs contain much more LD than serum. Causes 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-1 such that any ex vivo hemolysis must be strictly avoided.

  • Freezing or prolonged storage at 4°C (>12 hours) causes LD-5 to be lost.

  • Elevations of intermediate forms (LD-2–LD-4) of LD are rarely used to define a tissue of origin, and such reports are largely anecdotal.

  • Although increases in serum LD also are seen following an MI, the test has been replaced by the determination of troponins.

 
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