Lactate Dehydrogenase (LD) Isoenzymes

The Lactate Dehydrogenase (LD) Isoenzymes assay, also known as LDH or lactic acid dehydrogenase isoenzymes, serves as a broad indicator of cell damage and clarifies the origin of an elevated total LDH by evaluating the isoenzyme distribution. LD1‑predominant patterns, particularly an LD1 > LD2 inversion, support myocardial injury, megaloblastic anemia, hemolytic anemia, and, less commonly, renal infarction. A rise in LD5 favors hepatic disease or skeletal muscle injury. An isomorphic pattern—elevated total LDH without a dominant fraction—can be associated with neoplasia, cardiorespiratory disease, hypothyroidism, infectious mononucleosis, inflammatory states, uremia, and tissue necrosis. In the evaluation of acute chest pain, LDH isoenzymes increase later than creatine kinase‑MB and cardiac troponin; a delayed LD1 > LD2 “flip” can support myocardial infarction when interpreted with clinical findings. The test also aids in assessing hemolysis, disorders of the liver and kidneys, muscle disease, and in monitoring some malignancies during therapy.

LDH is a zinc‑containing intracellular enzyme composed of five isoenzymes that vary by subunit composition and tissue distribution. LD1 is most prominent in myocardium and brain; LD1 together with LD2 occurs in high amounts in erythrocytes, platelets, and renal cortex. LD3 is enriched in lung, spleen, thyroid, pancreas, adrenal, and lymphocytes. LD4 overlaps with LD3 and is also found in granulocytes, placenta, and male germ cells. LD5 characterizes liver and skeletal muscle. In serum from healthy individuals, the usual ordering of fractional activity is LD2 > LD1 > LD3 > LD4 > LD5. Tissue injury increases total LDH and shifts the fractional pattern. An LD1:LD2 inversion (the “flip”) supports myocardial infarction, though a minority of patients may lack the inversion and show an isolated LD1 rise instead. LD5 prominence accompanies hepatic or skeletal muscle disease, especially when the LD5:LD4 ratio is increased. LDH isoenzymes achieve diagnostic utility later than CK‑MB and troponin and return to baseline over several days; cardiac troponin is the preferred biomarker for acute myocardial infarction.