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 " 52Percent Activity Distribution of LD Isoenzymes in TissueView LargeTABLE 16 " 52Percent Activity Distribution of LD Isoenzymes in Tissue Organ LD Activity LD-1 LD-2 LD-3 LD-4 LD-5 Heart 60 30 " 5 " 3 " 2 Liver 0.2 0.8 " 1 " 4 94 Kidney 28 34 21 11 " 6 Cerebrum 28 32 19 16 " 5 Skeletal muscle " 3 " 4 " 8 " 9 76 Lung 10 18 28 23 21 Spleen " 5 15 31 31 18 RBCs 40 30 15 10 " 5 Skin " 0 " 0 " 4 17 79
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 " 53LD Isoenzyme Patterns in Various Disease ConditionsView LargeTABLE 16 " 53LD Isoenzyme Patterns in Various Disease Conditions Condition LD Isoenzyme(s) Increased AMI LD-1 more so than LD-2 Acute renal cortical infarction LD-1 more so than LD-2 PA LD-1 Sickle cell crisis LD-1 and LD-2 Electrical and thermal burn, trauma LD-5 Mother carrying erythroblastotic child LD-4 and v5 AMI with acute congestion of the liver LD-1 and LD-5 Early hepatitis LD-5 (may become normal, even when ALT is still rising) Malignant lymphoma LD-3 and LD-4 (LD-2 may also increase) (reflects effect of chemotherapy) Active chronic granulocytic leukemia LD-3 increased in >90% of cases but normal during remission Carcinoma of the prostate 5; 5:1 ratio >1 Dermatomyositis 5 SLE 3 and 4 Collagen disorders 2, 3, and 4 Pulmonary embolus and infarction 2, 3, and 4 Pulmonary embolus with acute cor pulmonale causing acute congestion of liver 3 and 5 Congestive heart failure 2, 3, and 4 Viral infections 2, 3, and 4 Various neoplasms 2, 3, and 4 Strenuous physical activity 4 and 5 Leptomeningeal carcinomatosis 5
- 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.