What Do Lactate Dehydrogenase Isoenzymes Levels Mean?

Lactate dehydrogenase, or LDH, is an enzyme that helps your body’s cells produce energy by converting sugar. It is found in nearly all tissues throughout the body, with the highest amounts in the muscles, liver, kidneys, and red blood cells. Because it is so widespread, its presence in the blood is normal.

The Five Lactate Dehydrogenase Isoenzymes

The term isoenzyme refers to different forms of the same enzyme. These variations catalyze the same chemical reaction but have minor differences in their physical structure. LDH has five distinct forms, each concentrated in specific body tissues and composed of different combinations of two protein subunits, known as M (for muscle) and H (for heart).

LD-1 is most heavily concentrated in the heart muscle and red blood cells. LD-2 is also found in the heart and red blood cells, though in slightly lower amounts than LD-1. It is also present in white blood cells.

LD-3 is found primarily in the lungs. It is also located in smaller quantities in other tissues, including the pancreas and spleen. Damage to any of these areas can release this specific isoenzyme into the bloodstream.

LD-4 concentrations are highest in the kidneys, pancreas, and the placenta during pregnancy. LD-5 is located almost exclusively in the liver and skeletal muscles. The distinct tissue distributions of these five isoenzymes allow for a more targeted investigation when cellular damage is suspected.

The Purpose of LDH Isoenzyme Testing

A standard blood test can measure the total amount of lactate dehydrogenase in the bloodstream. When tissues containing LDH are damaged by injury or disease, they release the enzyme into circulation, causing the total level to rise. However, a high total LDH level is a non-specific finding. It signals that tissue injury has occurred somewhere in the body but does not reveal the location of the damage.

LDH isoenzyme testing separates the blood sample into the five different isoenzyme fractions and measures the level of each one individually. By examining the specific pattern of elevation among the five types, physicians can gain a much clearer picture of which organ or tissue is the likely source of the problem.

For example, if a patient presents with symptoms that could be attributed to the heart, lungs, or liver, analyzing the isoenzyme profile can point toward the affected organ. This allows for more targeted follow-up testing to confirm a diagnosis.

Interpreting Test Results

The pattern of elevated LDH isoenzymes in a blood test provides clues about specific medical conditions. The relative amounts of each of the five forms are compared to established normal ranges to identify significant increases.

A primary indicator of heart damage, such as a myocardial infarction, is a rise in LD-1 and LD-2 levels. Clinicians look for the “LD flipped pattern,” where the level of LD-1 becomes higher than the level of LD-2. Normally, LD-2 levels in the blood are slightly higher than LD-1. When this ratio inverts, it strongly suggests that heart muscle cells have been injured.

Elevations in other isoenzymes point to different areas of the body. A marked increase in LD-5, and to a lesser extent LD-4, is associated with liver or skeletal muscle issues. Conditions such as hepatitis, cirrhosis, or significant muscle trauma would cause LD-5 to spill into the bloodstream. Muscular dystrophy can also lead to chronically high LD-5 levels.

Damage to the lungs or other tissues is often associated with a rise in LD-3. A pulmonary embolism, which is a blood clot in the lungs, can cause lung tissue to die and release LD-3. Pancreatitis or other issues with the spleen may also lead to an increase in this specific isoenzyme. In some cases, multiple isoenzymes may be elevated simultaneously, suggesting a more systemic issue or widespread trauma affecting several organs.

Factors Influencing Test Results

The most common source of interference in an LDH isoenzyme test is hemolysis, which is the rupture of red blood cells. If the blood sample is handled incorrectly during or after the draw, these cells can break down, releasing their contents into the serum sample.

Since red blood cells are rich in LD-1 and LD-2, hemolysis can artificially raise the levels of these two isoenzymes. This can create a false “flipped pattern,” incorrectly suggesting a patient has had a heart attack when they have not. Laboratory staff must take care to avoid rough handling or temperature extremes to ensure the sample’s integrity.

Certain medical conditions unrelated to acute organ damage can also cause elevated LDH levels. For instance, some cancers, particularly lymphomas and leukemia, can lead to increased LD-2 and LD-3 levels. The rapid turnover and destruction of cancerous white blood cells release these isoenzymes.

Intense physical activity can cause a temporary and harmless spike in LDH levels, primarily LD-5. Strenuous exercise leads to microscopic tears and breakdown in skeletal muscle fibers, which then release their contents into the blood. This physiological response is normal and resolves on its own without any medical intervention.