LDH (Lactate Dehydrogenase) - Patient Explanation & Causes of Elevation

How to Explain LDH to a Patient (Plain Language)

"Think of LDH as an alarm enzyme that lives inside your cells. Every cell in your body - your heart, liver, muscles, kidneys, red blood cells - contains LDH. Normally, a small amount is present in your blood. But when cells are damaged or destroyed for any reason, they burst open and release LDH into the bloodstream. So when we see a high LDH on your blood test, it's your body's way of telling us that somewhere, cells are being damaged. LDH itself is not a disease - it's a signal that something is happening. We then need to figure out WHERE the damage is coming from."

Key points to communicate:

• LDH is a natural enzyme - everyone has it; some in the blood is normal
• A high LDH = cell damage somewhere in the body - it is not specific to one organ
• LDH levels rise quickly after injury, peak, then gradually fall as healing occurs (e.g., after a heart attack, LDH peaks at 2-3 days and normalises in 10-14 days)
• LDH alone cannot tell us the diagnosis - doctors use it alongside other tests to narrow down the cause
• Normal range in adults: approximately 122-222 U/L (may vary by lab)

What Is LDH (For Clinicians)?

L-Lactate + NAD⁺ ⇌ Pyruvate + NADH + H⁺

Causes of Elevated LDH

1. Hematological Causes (Often Very High - Up to 50x Normal)

• Megaloblastic anemia (B12/folate deficiency) - most dramatic rises (up to 50x URL) due to ineffective erythropoiesis releasing massive amounts of LDH-1 and LDH-2 in the bone marrow
• Hemolytic anemia - LDH-1 dominates; used alongside haptoglobin (which falls) to confirm intravascular hemolysis
• Pernicious anemia - marked elevation
• Sickle cell disease - chronic hemolysis raises LDH persistently

2. Cardiac Causes

• Myocardial infarction - LDH-1 and LDH-2 rise, with a characteristic "flip" pattern (LDH-1 > LDH-2) appearing 12-24 hours after infarction and lasting 10-14 days. Historically used before troponin became standard.
• Cardiac surgery / myocarditis

3. Malignancy (Important Prognostic Marker)

• Lymphomas (Hodgkin's and Non-Hodgkin's) - LDH used to predict survival and monitor disease activity
• Leukemia - elevated LDH correlates with disease activity
• Multiple myeloma - elevated LDH signals aggressive disease biology (incorporated into the Revised International Staging System)
• Germ cell tumors (seminoma, testicular teratoma, dysgerminoma) - notably elevated LDH-1 in ~60% of cases; used as a tumor marker
• Metastatic cancer - up to 70% of patients with liver metastases and 20-60% with non-hepatic metastases (lymph nodes) have raised LDH
• Melanoma, renal cell carcinoma, lung cancer, osteosarcoma, prostate cancer - elevated LDH predicts poorer outcomes

"A raised LDH in a cancer patient is often a sign of aggressive or widespread disease."

4. Liver Disease

• Hepatitis (viral, alcoholic, drug-induced)
• Cirrhosis
• Liver congestion or infarction
• LDH-4 and LDH-5 dominate - but elevation is typically less dramatic than with AST/ALT, limiting its standalone utility in liver disease

5. Pulmonary Causes

• Pulmonary embolism - LDH may be the only abnormal lab finding
• Pneumonia - especially severe infections
• Pulmonary infarction
• Pleural effusion - serum LDH (with pleural fluid LDH) used in Light's Criteria to distinguish exudates from transudates

6. Renal Disease

• Tubular necrosis (acute kidney injury)
• Pyelonephritis
• Raised in ~1/3 of kidney disease patients, but does not correlate well with proteinuria

7. Muscle Disease / Trauma

• Rhabdomyolysis (muscle breakdown from crush injury, intense exercise, drugs like statins)
• Muscular dystrophies (e.g., Duchenne) - especially early and middle stages
• Fractures, major trauma, surgery

8. Infections & Inflammatory Conditions

• Infectious mononucleosis (Epstein-Barr virus)
• HIV - used as a marker in monitoring
• Severe malaria
• Encephalitis, meningitis
• Sepsis / severe systemic infection

9. Neurological Causes

• Intracranial hemorrhage - marked elevation
• CNS lymphoma, leukemia, or metastatic carcinoma - >40 U/L above normal in CSF/serum is characteristic

10. Other / Miscellaneous

• Hypoxia / severe shock - any cause of widespread tissue ischemia
• Anorexia nervosa - skeletal muscle breakdown
• Macro-LDH - a rare benign condition (autoantibody-enzyme complex) causing persistent elevation up to 8x without actual disease; important to exclude to avoid unnecessary investigations

Causes of LOW LDH

• High-dose Vitamin C or Vitamin E intake (analytical interference)
• LDH gene deficiency - rare inherited disorder

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