Laboratory assay overview
Lactate dehydrogenase (LD) is an enzyme that is found in almost all of the body's cells, but only a small amount of it is usually detectable in the blood. LD is released from the cells into the bloodstream when cells are damaged or destroyed. Because of this, the LD test can be used as a general marker of injury to cells. Although there is some overlap, each of the five LD isoenzymes tends to be concentrated in specific body tissues. In general, the isoenzyme locations are as follows: • LD1: Heart, red blood cells, kidney • LD2: Heart, red blood cells, kidney (lesser amounts than LD1) • LD3: Lungs and other tissues • LD4: White blood cells, lymph nodes, muscle, liver (lesser amounts than LD5) • LD5: Liver, skeletal muscle Changes of LD isoenzymes periodically measured following onset of chest pain, studying the relationships of the anodic fractions, provide important information for the differential diagnosis of acute infarct of myocardium. The differential diagnosis of certain other diseases is enhanced as well with the use of LD isoenzymes. Useful in the differential diagnosis of acute myocardial infarction, megaloblastic anemia (folate deficiency, pernicious anemia), hemolytic anemia, and very occasionally renal infarct. These entities are characterized by LD1 increases, often with LD1:LD2 inversion. The isomorphic pattern (total LD significantly high with no increase in percentage, of any fraction) is seen with neoplasia, cardiorespiratory diseases, hypothyroidism, infectious mononucleosis, and other inflammatory states, uremia, and necrosis. LD5 increases are seen with striated muscle lesions (eg, trauma) and with liver diseases (eg, hepatic congestion, congestive heart failure, hepatitis, cirrhosis, alcoholism). LD5 increase is probably more significant when the LD5:LD4 ratio is increased. Although a modicum of controversy exists regarding the most suitable criteria for LD isoenzymes for the diagnosis of acute myocardial infarction, almost all laboratories recognize abnormality when LD1 equals or is greater than LD2. Alternatives to LD1 greater than LD2 have been proposed. Using an electrophoretic method (Helena), Rotenberg et al suggested the criterion of LD1 >90 units/L.1 A 1988 study examines application of LD1:LD4 and other ratios and finds that the LD1:LD4 ratio optimizes earlier and is the most powerful diagnostic ratio for acute myocardial infarction.2 A few percent of normal individuals may have LD1:LD2 ratios as high as 0.81. A ratio of 0.82−0.99 is suspicious of myocardial injury. A ratio >1.0 is diagnostic of myocardial injury, if other clinical criteria are met. In unstable angina, an increase of the LD1:LD2 ratio is described with normal total LD;3 however, progressively increasing LD1:LD2 ratio without complete inversion may have diagnostic significance for acute myocardial infarct.4 Persistent LD1:LD2 flip following acute myocardial infarct may represent a marker for reinfarction.5 Especially when acute myocardial infarction is complicated by shock, the isomorphic pattern may be found.6 LD1:LD2 inversion commonly appears subsequent to the isomorphic pattern in instances of acute myocardial infarction.7 The appearance of an LD “flip” (when LD1 is greater than LD2) is extremely helpful in diagnosis of MI. The presence of a LD “flip” a day following or with the detection of CK-MB is essentially diagnostic of MI, if baseline cardiac enzymes/isoenzymes are normal and if rises and falls are as anticipated for the diagnosis of acute MI. While CK-MB peaks 12 to 24 hours after onset of infarction, LD isoenzymes usually become diagnostic at about 36 to 55 hours after onset and return to normal between 3 and 14 days after onset.
View complete laboratory reference notes
• Total: See table.
• LD1: 17% to 32%
• LD2: 25% to 40%
• LD3: 17% to 27%
• LD4: 5% to 13%
• LD5: 4% to 20%
Age
Male (IU/L)*
Female (IU/L)*
*LabCorp internal studies.
0 to 7 d
123−237
123−237
8 to 30 d
126−331
130−275
1 to 11 m
143−381
128−376
1 to 3 y
195−361
192−352
4 to 6 y
180−313
180−311
7 to 9 y
166−291
166−290
10 to 12 y
155−280
135−260
13 to 15 y
126−244
118−215
16 to 17 y
118−222
114−209
>17 y
121−224
119−226
LD Isoenzyme Interpretation
Abbrev*
Total LDH
LD1
LD2
LD3
LD4
LD5
*See following interpretation of abbreviations.
H = high (increased).
− = within reference (normal) interval or decreased.
N = within reference (normal) interval.
Case 1
H
H
H
−
−
−
Case 2
H
H
H
−
−
−
Case 3
H
H>
H
−
−
−
Case 4
H
H>
H
−
−
H
Case 5
H
H
H
−
−
H
Case 6
H
−
−
−
H
H
Case 7
H
−
H
H
H
−
Case 8
H
H
H
H
H
H
Case 9
H
−
−
−
−
−
Case 10
N
−
−
−
−
−
Case 11
H
−
−
−
−
H
Case 12
Other patterns not shown above
Interpretations:
• Case 1: Patient specimen was visibly hemolyzed, which may have produced the elevations of LD1 and LD2 on the LD isoenzyme pattern.
• Case 2: The LD isoenzyme pattern demonstrates elevations of LD1 and LD2. These increases would be compatible with diagnostic considerations involving myocardial infarction, megaloblastic anemia, acute renal infarction, in vivo hemolytic process (eg, hemolytic anemia), or in the later stages of muscular dystrophy.
• Case 3: The LD isoenzyme pattern demonstrates LD1 greater than LD2. In the appropriate clinical setting, this pattern is most compatible with postmyocardial infarction occurring at least 8 to 12 hours prior to venipuncture.
• Case 4: The LD isoenzyme pattern demonstrates LD1 greater than LD2 and an increase of LD5. This pattern would be most compatible with passive hepatic congestion following an acute myocardial infarction or right-sided congestive heart failure associated with myocardial infarction.
• Case 5: The LD isoenzyme pattern demonstrates elevations of LD1 and LD2 and an increase of LD5. This pattern would be compatible with diagnostic considerations involving passive hepatic congestion or right-sided congestive heart failure which may have followed acute myocardial damage.
• Case 6: The LD isoenzyme pattern demonstrates elevations of LD4 and LD5. These increases would be compatible with hepatic (cirrhosis, viral hepatitis, toxic hepatitis) or skeletal muscle injury. This pattern may also be associated with congestive heart failure.
• Case 7: The LD isoenzyme pattern demonstrates elevations of LD2, LD3, and LD4. Increases of these isoenzymes fractions are nonspecific but have been associated with septic shock, pulmonary emboli, and some neoplastic processes.
• Case 8: The LD isoenzyme pattern demonstrates elevations of all isoenzymes without dominating fractions. This pattern is nonspecific but has been associated with septic shock, pulmonary emboli, and some neoplastic processes.
• Case 9: The LD isoenzyme pattern appears normal despite elevation of the total LD. The LD total is significantly elevated, and there is no increase in the relative percentage of any fraction. The LD isoenzyme pattern is an "isomorphic pattern." This pattern may be seen with neoplasia, cardiorespiratory diseases, hypothyroidism, infectious mononucleosis, and other inflammatory states, uremia, and necrosis.
• Case 10: The LD isoenzyme pattern appears normal with a normal total LD.
• Case 11: The LD isoenzyme pattern demonstrates an elevated LD5 fraction which may be associated with hepatic anoxia due to congestive heart failure or the early stages of muscular dystrophy.
• Case 12: The LD isoenzyme pattern is nonspecific. Recommend correlation with the clinical condition of the patient.