Lactate Dehydrogenase (\(\text{LDH}\)) is an enzyme found in nearly all cells of the body. It is often included in routine blood panels, and elevated levels suggest that cells somewhere in the body are damaged or dying. Because this enzyme is so widely distributed, a high total \(\text{LDH}\) result is considered non-specific, meaning it signals injury but does not identify the precise location or cause. Understanding what \(\text{LDH}\) is and the degree of elevation helps clarify the potential severity of the underlying medical issue.
Understanding Lactate Dehydrogenase
Lactate Dehydrogenase is a protein that plays a specific role in cellular metabolism, particularly in the process of energy production when oxygen is scarce. The enzyme catalyzes the reversible conversion of pyruvate to lactate, a reaction that is necessary for regenerating the coenzyme \(\text{NAD}^+\). This regeneration allows the cell to continue producing energy through glycolysis, even during periods of anaerobic conditions, such as intense exercise or oxygen deprivation.
\(\text{LDH}\) resides inside the cell’s cytoplasm. When a cell is injured or undergoes lysis (cell death), its contents spill out into the surrounding fluids and eventually enter the circulation. The amount of \(\text{LDH}\) detected in a blood sample therefore directly correlates with the volume of cell damage that has occurred.
Since \(\text{LDH}\) is present in high concentrations in tissues like the heart, liver, skeletal muscle, kidneys, and red blood cells, damage to any of these organs can cause its level to rise. This ubiquitous presence is why the total \(\text{LDH}\) test is considered a non-specific indicator of injury, rather than a diagnostic tool pointing to a single organ.
Defining Normal and Concerning Levels
The typical reference range for total \(\text{LDH}\) in adults falls between \(140\text{ and }280\text{ units per liter}\) (\(\text{U/L}\)). This range can vary depending on the specific laboratory and testing method used. Normal ranges for infants and children are significantly higher, sometimes reaching up to \(750\text{ U/L}\) in newborns, due to their different metabolic rates and cell turnover.
An \(\text{LDH}\) level that is only mildly elevated, slightly above the upper limit of normal, may result from minor issues such as recent strenuous exercise or rough handling of the blood sample during collection. Moderate elevations often suggest a localized, acute injury, such as a muscle strain, a bone fracture, or early-stage infection. These moderate increases require further investigation but are not immediately alarming.
Significantly concerning levels are those that are two to five times the upper limit of normal, suggesting widespread or severe tissue destruction. Extremely high \(\text{LDH}\) values are often seen in severe medical crises, including extensive cancers, massive hemolysis, or multiple organ failure. The degree of \(\text{LDH}\) elevation is commonly used as an indicator of the severity and scope of the underlying disease process.
Common Medical Conditions That Elevate LDH
Hematological disorders, particularly those involving rapid destruction of red blood cells (RBCs), are a common source of elevation. Hemolytic anemia and megaloblastic anemia cause \(\text{RBCs}\) to break down prematurely, releasing their high concentration of \(\text{LDH}\) into the blood.
Damage to major organs also contributes to elevated \(\text{LDH}\) levels. Acute liver diseases, such as severe hepatitis or cirrhosis, lead to the necrosis of liver cells, which are rich in \(\text{LDH}\). Similarly, conditions causing muscle cell breakdown, such as trauma, muscular dystrophy, or rhabdomyolysis, flood the bloodstream with the enzyme.
Acute events that cause tissue ischemia, or lack of blood flow, are another primary cause of \(\text{LDH}\) elevation. These include a heart attack (myocardial infarction), where heart muscle tissue dies, or a pulmonary embolism, which causes death of lung tissue. In these cases, the cell death is rapid, leading to a quick rise in circulating \(\text{LDH}\).
In oncology, \(\text{LDH}\) acts as a general tumor marker for several types of cancer, including lymphoma, leukemia, and metastatic solid tumors. High \(\text{LDH}\) levels in cancer patients often correlate with a greater tumor burden or more aggressive disease activity, making it a prognostic tool for monitoring treatment effectiveness and predicting outcomes. Severe infections, such as sepsis, also cause high \(\text{LDH}\) by triggering systemic cell damage across multiple organs.
The Role of LDH Isoenzymes in Diagnosis
While total \(\text{LDH}\) is a non-specific marker of cell injury, the enzyme is composed of five distinct subtypes, called isoenzymes (\(\text{LDH-1}\) through \(\text{LDH-5}\)). When a total \(\text{LDH}\) test returns a concerningly high result, doctors may order an isoenzyme test to determine the specific source of the enzyme release. This refinement helps transition the diagnosis from a general indicator of damage to a more specific localized injury.
For instance, \(\text{LDH-1}\) is found primarily in the heart and red blood cells, while \(\text{LDH-5}\) is concentrated in the liver and skeletal muscle. A disproportionate elevation of \(\text{LDH-5}\) strongly suggests a problem with the liver, such as hepatitis, or with the muscles, such as rhabdomyolysis. Conversely, if \(\text{LDH-1}\) is higher than \(\text{LDH-2}\)—a pattern sometimes called “flipped \(\text{LDH}\)“—it often points toward a heart injury or severe red blood cell destruction.
The \(\text{LDH-3}\) isoenzyme is mainly associated with the lungs and lymph tissue, and its elevation can suggest conditions like pulmonary embolism or certain cancers. Isoenzyme testing is not a standalone diagnostic tool and is used in conjunction with other specific tests, such as troponin for heart damage or transaminases for liver injury, to confirm the precise nature of the tissue damage.