Lactate Dehydrogenase, or LDH, is an enzyme present in the cytoplasm of nearly every cell in the body, where its function is to facilitate energy production. The presence of LDH in the bloodstream is a general marker of cell death or tissue injury because the enzyme is released into circulation when cells are damaged or destroyed. A standard total LDH blood test measures the overall concentration of the enzyme but cannot pinpoint the exact location of the injury due to the enzyme’s widespread distribution. This is where the LDH isoenzyme panel provides significantly more specific information, allowing healthcare providers to identify the likely source of tissue damage.
The Role of Lactate Dehydrogenase in the Body
Lactate dehydrogenase functions as a core component of the body’s anaerobic metabolic pathway, helping cells convert glucose into usable energy. The enzyme catalyzes the reversible reaction between lactate and pyruvate, a process that is particularly important when oxygen is limited, such as during intense exercise. This conversion is necessary to regenerate the coenzyme NAD+, which keeps the energy production cycle running.
Because LDH is contained within the cell’s cytoplasm, it is released into the bloodstream whenever a cell membrane is compromised. The enzyme is found in high concentrations in tissues like the liver, skeletal muscle, kidneys, lungs, and red blood cells. When a total LDH test shows an elevated level, it confirms that tissue damage has occurred, but it does not specify which organ is affected. The enzyme may remain elevated in the blood for up to seven days following an acute injury.
Understanding the LDH Isoenzyme Panel
The specificity of the LDH panel comes from the fact that the enzyme exists in five distinct forms, known as isoenzymes, which differ slightly in their structure and tissue preference. These five forms, labeled LDH-1 through LDH-5, are tetramers composed of two different subunits, designated as Heart (H) and Muscle (M). The concentration of H and M subunits varies depending on the metabolic needs of the tissue, leading to different isoenzyme ratios in different organs.
LDH-1 is formed exclusively from four H subunits, making it the predominant form in the heart muscle and red blood cells. LDH-2 is also concentrated in the heart and red blood cells, but it is typically the most abundant isoenzyme found in normal, healthy serum. The LDH-3 isoenzyme, which consists of two H and two M subunits, is found in the lungs, lymph tissue, and pancreas.
Conversely, LDH-5 is composed entirely of four M subunits, found primarily in the liver and skeletal muscle. LDH-4 is similar to LDH-5, being prevalent in the kidneys and often co-elevated with LDH-5 in liver and muscle injuries. Measuring the relative proportion of these five isoenzymes provides a biochemical fingerprint that helps trace the source of the enzyme back to the damaged organ.
Interpreting Abnormal LDH Levels
An elevated total LDH level serves as a general warning sign of significant cellular injury, but the isoenzyme panel is what provides the diagnostic direction. The pattern of the isoenzyme elevation is compared against the normal distribution to determine the probable site of damage. For instance, a marked elevation of LDH-5, possibly exceeding LDH-4, strongly suggests injury to the liver or skeletal muscles, which is common in conditions like hepatitis or muscular dystrophy.
In cases of a recent heart attack, a specific pattern emerges where the LDH-1 level becomes higher than the LDH-2 level, historically called a “flipped” ratio. While heart injury is now primarily diagnosed using the more specific troponin test, the elevated LDH-1 fraction still points toward damage to the heart or red blood cell destruction, such as hemolytic anemia, because red blood cells contain high amounts of LDH-1.
An increase in the LDH-3 fraction is often associated with damage to the lungs, frequently seen in a pulmonary embolism. Many types of cancer can also cause a generalized increase in LDH, often involving multiple isoenzymes (LDH-3, LDH-4, and LDH-5) due to rapid cell turnover or tumor spread. LDH levels are often used to assess the severity of certain cancers and monitor a patient’s response to treatment. Low LDH levels are extremely rare and are usually not considered a health concern.
Test Preparation and Procedure
The LDH isoenzyme panel requires a simple blood sample, typically collected from a vein in the arm. No special fasting is required before the test. However, certain activities and substances can interfere with the accuracy of the results, leading to a false elevation of the enzyme.
Patients should avoid strenuous physical activity for up to 24 hours before the blood draw, as this can temporarily raise LDH levels. Several medications can also influence the results, including aspirin, certain anesthetics, and narcotics, which may cause an increase in measured LDH. High doses of Vitamin C can potentially lower LDH levels. Hemolysis, the mechanical breakdown of red blood cells during collection, is a common issue that artificially inflates results by releasing high concentrations of LDH-1 into the sample.