Lactate Dehydrogenase (LD) Isoenzymes, Serum

CPT CODE:

USEFUL FOR:

LD is useful in the investigation of a variety of diseases involving the heart, liver, muscle, kidney, lung, and blood; and differentiatingheart-synthesized LD from liver and other sources of LD.
Isoenzymes are used by many clinicians in the diagnosis of MI incombination with total CK and CK-MB.
Investigating unexplained causes of LD elevations
Detection of macro-LD

SPECIMEN REQUIRED:

Draw blood in a plain, red-top tube(s) or a serum gel tube(s).Spin down and send 2 mL of serum divided into 2 tubes eachcontaining 1 mL of serum. Send 1 tube refrigerated and the othertube ambient. If only 1 tube is sent, the specimen must be sentambient.Note:   Patient's age is required on request form forprocessing.

TRANSPORT TEMPERATURE:

Ambient\Refrig NO\Frozen NO-LD IsoenzymesRefrig\Frozen OK\Ambient OK-LD

CLINICAL INFORMATION:

Total LDLactate dehydrogenase (LD) activity is present in all cells of the body with highest concentrations in heart, liver, muscle, kidney, lung, and erythrocytes. Serum LD is elevated in a number of clinical conditions.
IsoenzymesLD is a tetrameric cytoplasmic enzyme. The most usual designationof 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 fromthe 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(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.
As with other proteins used as tissue function markers, the appearance of LD in the serum occurs only after prolonged hypoxia. LD(1) appears elevated in the serum about 24 to 48 hours after a myocardial infarction (MI). Its use as a late marker of MI can be replaced by #81740 "Troponin T, Serum".
The LD(5) form is pronounced in patients with either primary liverdisease or liver hypoxia secondary to decreased perfusion.
The enzyme is significantly elevated in Mls involving large amounts of cardiac tissue, and this results in the quantitative observation that the LD(1) becomes higher than LD(2). There is a "flip" in the usual ratio of LD(1)/LD(2) from <1 to >1 (or at least >0.9). In following patients with an MI after 3 days, it is often apparent that a consequenceof an MI  is reduced liver perfusion since LD(5) may begin to increase subsequent to the usual increase of LD(1) due to an MI.
LD(1) is generally not as useful as troponin or creatine kinase-MB (CK-MB) for detection of Ml, unless the MI occurred 24 hours or more prior to the assay. Similarly, LD(5) is usually not as reliable as the transaminases as a liver function test.
Macro-LD (LD combined with an immunoglobulin) can cause idiosyncratic elevation of total LD.

CLINICAL INTERPRETATION:

Marked elevations in LD activity can be observed in megaloblasticanemia, untreated pernicious anemia, Hodgkin's disease,abdominal and lung cancers, severe shock, and hypoxia.
Moderate-to-slight increases in LD levels are seen in MI, pulmonaryinfarction, pulmonary embolism, leukemia, hemolytic anemia,infectious mononucleosis, progressive muscular dystrophy (especiallyin the early and middle stages of the disease), liver disease, and renaldisease.
In liver disease, elevations of LD are not as great as the increasesin aspartate amino transferase (AST) and alanine aminotransferase(ALT).
Increased levels of the enzyme are found in about 1/3 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 suggestthe presence of a hidden pulmonary embolus.
Isoenzymes: -  Although LD(2) is found in myocardium, the diagnostic ratio is 1 of    LD(1) divided LD(2) changing from <0.9 to >0.9 following a severe MI.    This is referred to as an LD "flip".
  - Elevation of LD(5) (least mobile) usually denotes liver damage.
  - It is rarely helpful in defining skeletal muscle disease.
  - LD(1) elevation not due to myocardial damage may indicate hemolytic    disease or other forms of in vivo hemolysis.
Macro-LD can occur, which results in an elevation of LD for no clinicalreason. Macro-LD greatly affects the migration of LD isoenzymes sincethe combination with an immunoglobulin greatly retards the migration of the usual LD isoenzymes. If macro-LD is present, the electrophoretogramwill show atypically migrating isoenzymes with LD activity localized nearthe origin.

REFERENCE VALUES:

LD, TOTAL

      1-30 days:  135-750 U/L

      31 days - 365 days:  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

LD ISOENZYMES

      I (fast band):  17.5-28.3%

      II:  30.4-36.4%

      III:  19.2-24.8%

      IV:  9.6-15.6%

      V (slow band):  5.5-12.7%