Lactate Dehydrogenase

LD occurs in the cytoplasm of all cells; there are five isoenzymes. The highest concentrations are found in the heart, liver, skeletal muscle, kidney, and the RBCs, with lesser amounts in the lung, smooth muscle, and brain. LD catalyzes the interconversion of lactate and pyruvate.

Normal range: 110 " “240 IU/L.

Use

To monitor tumor activity involving anemias and lung cancer

Liver and renal disease

After AMI (the use of LDH for MI detection has been replaced by cardiac troponins.)

Marker for hemolysis, in vivo (e.g., hemolytic anemias) or in vitro (artifactual)

Interpretation

Increased In

Cardiac diseases

AMI. Increases in 10 " “12 hours, peaks in 48 " “72 hours (approximately three times normal). Prolonged elevation over 10 " “14 days was formerly used for late diagnosis of AMI; now replaced by C-troponins. An LD reading >2,000 IU suggests a poorer prognosis. An LD-1/LD-2 ratio >1 ( "flipped " ¯ LD) may also occur in acute renal infarction, hemolysis, some muscle disorders, pregnancy, and some neoplasms.

CHF: LD isoenzymes are normal, or LD-5 may be increased due to liver congestion.

Insertion of intracardiac prosthetic valves consistently causes chronic hemolysis, with increase of total LD, LD-1, and LD-2. This is also often present before surgery in patients with severe hemodynamic abnormalities of cardiac valves.

Cardiovascular surgery: LD is increased ≤2 times normal without cardiopulmonary bypass and returns to normal in 3 " “4 days; with extracorporeal circulation, it may increase ≤4 " “6 times normal; this increase is more marked when the transfused blood is older.

Increases have been described in acute myocarditis and RF.

Liver diseases

Cirrhosis, obstructive jaundice, and acute viral hepatitis show moderate increases.

Hepatitis " ”most marked increase is of LD-5, which occurs during prodromal stage and is greatest at time of onset of jaundice; total LD is also increased in 50% of the cases. LD increase is isomorphic in infectious mononucleosis. An ALT-to-LD or AST-to-LD ratio within 24 hours of admission ≥1.5 favors acute hepatitis over acetaminophen or ischemic injury.

Acute and subacute hepatic necrosis: LD-5 is also increased with other causes of liver damage (e.g., chlorpromazine hepatitis, carbon tetrachloride poisoning, exacerbation of cirrhosis, or biliary obstruction) even when total LD is normal.

Metastatic carcinoma to the liver may show marked increases. It has been reported that an LD-4 " “to " “LD-5 ratio <1.05 favors diagnosis of hepatocellular carcinoma, compared to a ratio >1.05, which favors liver metastases in >90% of cases.

If liver disease is suspected but total LD is very high and isoenzyme pattern is isomorphic, rule out cancer.

Liver disease, per se, does not produce marked increase of total LD or LD-5.

Various inborn metabolic disorders affecting the liver (e.g., hemochromatosis, Dubin-Johnson syndrome, hepatolenticular degeneration, Gaucher disease, McArdle disease).

Hematologic diseases

Untreated PA and folic acid deficiency show some of the greatest increases, chiefly in LD-1, which is >LD-2 ( "flipped " ¯), especially with Hb <8 g/dL.

Increased in all hemolytic anemias, which can probably be ruled out if LD-1 and LD-2 are not increased in an anemic patient; normal in aplastic anemia and iron deficiency anemia, even when the anemia is very severe.

Diseases of the lung

Pulmonary embolus and infarction " ”pattern of moderately increased LD with increased LD-3 and normal AST 24 " “48 hours after onset of chest pain

Sarcoidosis

Malignant tumors

Increased in approximately 50% of patients with various solid carcinomas, especially in advanced stages.

In patients with cancer, a higher LD level generally indicates a poorer prognosis. Whenever the total LD is increased and the isoenzyme pattern is nonspecific or cannot be explained by obvious clinical findings (e.g., MI, hemolytic anemia), cancer should always be ruled out. LD is moderately increased in approximately 60% of patients with lymphomas and lymphocytic leukemias and approximately 90% of patients with acute leukemia; degree of increase is not correlated with WBC counts; levels are relatively low in lymphatic types of leukemia. LD is increased in 95% of patients with chronic myelogenous leukemia, especially LD-3.

Diseases of muscle

Marked increase of LD-5, likely due to anoxic injury of striated muscle

Electrical and thermal burns and trauma; marked increase of total LD (about the same as in MI) and LD-5

Renal diseases

Renal cortical infarction may mimic pattern of AMI. Rule out renal infarction if LD-1 (>LD-2) is increased in the absence of MI or anemia or if increased LD is out of proportion to AST and ALP levels.

May be slightly increased (LD-4 and LD-5) in nephrotic syndrome. LD-1 and LD-2 may be increased in nephritis.

Miscellaneous conditions

These conditions may be related to hemolysis, involvement of the liver, striated muscle, or heart

Various infectious and parasitic diseases

Hypothyroidism, subacute thyroiditis

Collagen vascular diseases

Acute pancreatitis

Intestinal obstruction

Sarcoidosis

Various CNS conditions (e.g., bacterial meningitis, cerebral hemorrhage, or thrombosis)

Drugs

Decreased In

Irradiation

Genetic deficiency of subunits

Limitations

RBCs contain much more LD than serum. A hemolyzed specimen is not acceptable.

LD activity is one of the most sensitive indicators of in vitro hemolysis. Causes can include transportation via pneumatic tube, vigorous mixing, or traumatic venipuncture.