Lactate Dehydrogenase (LDH)
Lactate dehydrogenase (LDH) is an enzyme that catalyzes the interconversion of lactate and pyruvate with NAD+/NADH coenzyme system, serving as an important biomarker for tissue damage and cellular death across multiple organ systems. 1
Biochemical Properties and Distribution
LDH is widely distributed throughout the body with varying concentrations in different tissues:
- High concentrations: Heart, liver, skeletal muscle, kidney, and erythrocytes
- Lower concentrations: Lung, smooth muscle, and brain 2
The enzyme exists as five different isoenzymes formed from combinations of two subunits (H and M), each with distinct tissue distribution:
| Isoenzyme | Tissue Distribution |
|---|---|
| LDH1 (H4) | Heart, erythrocytes |
| LDH5 (M4) | Liver, skeletal muscle |
| Other isoenzymes | Variable distribution in different tissues [1] |
Clinical Applications
LDH serves several important diagnostic functions:
1. Tumor Marker
- Used in the diagnosis, prognosis, and monitoring of various cancers
- The National Comprehensive Cancer Network recommends LDH as a tumor marker in germ cell tumors 3, 1
- Elevated LDH is associated with poor prognosis in advanced melanoma and other solid tumors 1
2. Pleural Fluid Analysis
- Helps differentiate exudative from transudative pleural effusions
- Threshold of >67% of the upper limit of normal serum LDH indicates exudate 1
3. Tissue Damage Assessment
- Elevated levels indicate cellular damage and death
- Used as a marker of cytotoxicity in various clinical settings 1
Interpretation of Elevated LDH
When LDH is elevated, it may indicate:
- Malignancy: Particularly metastatic cancer and hematologic malignancies 4
- Infection: Significantly associated with infectious processes 4
- Tissue damage: Including cardiac, hepatic, muscular, and renal diseases 1
Very high isolated LDH (≥800 IU/ml) warrants thorough investigation as it is associated with:
- Longer hospital stays
- Higher rates of in-hospital complications
- Increased mortality 4
Clinical Significance in Specific Conditions
- Cancer: LDH is elevated in many cancers due to increased aerobic glycolysis (Warburg effect) 5
- Cardiac disease: Used as a biomarker for myocardial infarction and cardiac damage 1
- COVID-19: Elevated LDH is a risk factor for mortality in severe COVID-19 patients 6
- Inflammatory diseases: Both LDH and lactate serve as potential markers for monitoring treatment response 6
Important Considerations
- An elevated total LDH value alone is nonspecific; isoenzyme fractionation provides more clinical significance 2
- LDH patterns should be interpreted in the context of the complete clinical picture, including other laboratory tests 1
- LDH activity and isoenzyme patterns show significant variations between species, which is particularly important in veterinary medicine 2
Pitfalls to Avoid
- Do not interpret elevated LDH in isolation; always consider it within the clinical context
- Remember that LDH elevation is nonspecific and requires additional diagnostic workup
- Avoid using LDH patterns from one species to interpret findings in another species 2
- Be aware that hemolysis during blood collection can falsely elevate LDH levels