LDH - Kresser Institute Membership Site

Marker Name: LDH

REFERENCE RANGES FOR LDH:

Laboratory reference range: 121–224 IU/L

Functional reference range: 140–180 IU/L

DESCRIPTION:

Lactate dehydrogenase (LDH) reversibly produces NADH and pyruvate from lactate and NAD⁺. The enzyme plays a key role in glycolysis, gluconeogenesis, and anaerobic metabolism.¹ In addition, LDH is critical for the oxygenation of long-chain fatty acids in liver peroxisomes.² LDH is a cytosolic enzyme that is found in virtually every cell, though levels are highest in heart, liver, muscle, kidney, lung, and red blood cells.³ When cells are injured, the LDH-containing cytosol is spilled into the serum. Therefore, serum LDH levels are a marker for tissue or cellular damage.⁴

LDH is a tetramer of two major subunits, the H type and the M type.⁵ The H type is primarily found in heart muscle, while the M type is found in skeletal muscle and liver.¹ These subunits form five types of tetramers: H₄, H₃M₁, H₂M₂, H₁M₃, and M₄.¹ The H₄ tetramer preferentially oxidizes lactate to pyruvate and is allosterically inhibited by high levels of pyruvate.¹ The M₄ tetramer, on the other hand, preferentially catalyzes the opposite reaction, pyruvate to lactate, allowing LDH to operate in anaerobic conditions. Tetramers containing both H and M type subunits share properties of the pure tetramers, according to the ratio of subtypes present.¹

The subunit composition and tissue location of LDH determine its primary physiological role. During aerobic exercise when the oxygen levels within cells are relatively low, LDH liberates NAD⁺ so that the molecule can participate in glycolysis.¹ This reaction also produces lactic acid, which tends to accumulate in muscle during anaerobic metabolism. Conversely, LDH can use lactate to produce pyruvate and NADH for glycolysis or gluconeogenesis.¹ However, since skeletal muscle LDH preferentially converts pyruvate to lactate, lactate that accumulates in skeletal muscle under anaerobic conditions must be shuttled to other tissues to recycle it into pyruvate and NADH. The shuttling system is known as the Cori cycle.

An elevation in serum LDH is a nonspecific indicator of tissue damage. Nevertheless, serum LDH levels can be clinically useful in certain circumstances.⁴ Serum LDH levels may be used to monitor chronic hematologic disorders, such as hemolytic anemia or megaloblastic anemia.^4,6 Serum LDH can be used to monitor treatment progress in individuals with germ cell line tumors who initially experienced increased LDH levels prior to treatment.^4,7,8 LDH levels will rise and exceed normal limits approximately 10 hours after the onset of myocardial infarction, peak within one to two days, and remain elevated for up to eight days.^9,10

Some individuals may have lactate dehydrogenase deficiency caused by an autosomal recessive mutation in one of the genes that code for an LDH protein subunit.⁵ Individuals with a deficiency in the M type subunit will have muscle stiffness after strenuous exercise, poor exercise capacity, and the presence of myoglobin in the urine.¹¹ A deficiency in the H type subunit of LDH has no discernible clinical consequences.⁵ Deficiency in the M type or H type subunits may or may not be reflected in the serum LDH levels.⁵ Excessive vitamin C ingestion may cause a false decrease in LDH levels; however, this is a laboratory artifact rather than a true reduction in serum LDH.¹²

It is quite common for LDH to be measured with a comprehensive metabolic panel, complete blood count, or liver function tests.⁴ Serum LDH levels may be ordered in the diagnosis of myocardial infarction; however, current recommendations suggest using cardiac troponins since they are a more specific indicator of heart muscle damage and cardiac ischemia.^9,13 In rare instances, individual lactate dehydrogenase isoenzymes may be measured in the serum for specific purposes.¹⁴ These isoenzymes are formed from various H and M subunits of LDH.⁹ The usefulness of LDH isozyme testing is very limited and not widely available.

PATHOLOGICAL/CONVENTIONAL RANGE INDICATIONS:

High in:¹⁵

Cardiac
- Myocyte injury (e.g., ischemia, trauma)
- Infection (e.g., myocarditis, rheumatic fever)
- Heart failure
Pregnancy
- Preeclampsia
- Adnexal mass in pregnancy
- HELLP syndrome
Rhabdomyolysis
Endocrine
- Hypothyroidism
- Acromegaly
- Cushing’s syndrome
Gastrointestinal
- Intestinal obstruction
- Early acute hepatitis
- Ischemic hepatitis
- Acute pancreatitis
Hematologic
- Folate deficiency
- Iron deficiency
- Pernicious anemia
- Hemolytic anemia
- Inherited hematologic conditions (e.g., spherocytosis, sickle cell disease)
- Ineffective erythropoiesis
- Primary myelofibrosis
Infection
- Pneumocystis pneumonia (late)
- Tuberculosis
- Malaria
- Parasitic
- Legionnaire’s disease
- Histoplasmosis
- Toxoplasmosis
Central nervous system disorders
- Bacterial meningitis
- Cerebral hemorrhage
- Cerebral venous thrombosis
Malignancy
- Leukemias
- Lymphomas
- Solid tumors (e.g., germ cell tumors)
- Tumor lysis syndrome
Neuromuscular
- Myopathies (inherited, acquired, drug)
- Periodic paralyses
Pulmonary
- Pulmonary embolism, infarction
- Pulmonary alveolar proteinosis
Rheumatologic
- Dermatomyositis
- Rheumatoid arthritis
- Scleroderma
- Sjögren’s syndrome
- Systemic lupus erythematosus
- Polyarteritis nodosa
- Eosinophilic granulomatosis with polyangiitis (Churg-Strauss vasculitis)
- Granulomatosis with polyangiitis (Wegener’s)
- Behçet’s syndrome
- Sarcoidosis
- Vasculitis
Renal infarction
Carbon monoxide exposure
Idiosyncratic LDH elevation
Drugs
- Chemotherapy
- Neuroleptic agents (neuroleptic malignant syndrome)
- Withdrawal from L-dopa or dopamine agonist
- Serotonin syndrome
- Malignant hyperthermia in response to anesthesia
- Recreational drugs (e.g., cocaine, methysergide, alcohol)
- Glucocorticoids
- Statins
- Colchicine
- Antimalarials

Low in:⁵

LDH deficiency

FUNCTIONAL RANGE INDICATIONS:

High in:

Early stages of conditions listed above
Non-pathological

Low in:

Hypoglycemia (if serum glucose below conventional reference range)
Reactive hypoglycemia (consider if serum glucose normal or below functional reference range)

References: