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Sample

  1. LDH can be done on serum or plasma.
  2. Can store the sample at room temperature.
  3. Perform the test immediately.
  4. The hemolyzed sample is not acceptable because RBC has LDH.
  5. LDH can be done on urine and CSF.

Precautions

  1. The serum is preferred to plasma.
  2. The plasma may not be used due to the presence of platelets which has a high quantity of LDH.
  3. Separate the serum as soon as possible, immediately after the clot formation.
  4. Do not refrigerate or freeze and perform the test immediately.
  5. The hemolyzed serum has 150 times more LDH due to the RBCs, particularly LDH-1 and LDH-2 than the clear serum.

Purpose of the test (Indication)

  1. LDH used to diagnose the diseases or injury to:
    1. Heart muscles.
    2. RBCs.
    3. Kidney.
    4. Skeletal muscles.
    5. Lung.
    6. Brain.
    7. Liver. 
  2. Nonspecific tumor marker.
  3. Helpful in the diagnosis of exudative fluid near the malignant tumors.
    1. LDH-2 is high in 35% of the cases.

Precautions

  1. Hemolysis raises the LDH level like myocardial infarction.
  2. There is raised the level of LDH 1 and 2 in megaloblastic anemia.

Pathophysiology

  1. LDH is an enzyme present in all the body cells and presents only in the cytoplasm of cells.
    1. LDH is present in the heart, liver, RBCs, kidney, skeletal muscles, lung and brain.
    2. Its molecular weight is 134,000.
    3. It consists of four peptides chains of two types, M (or A) and H (orB).
      1. This M is for muscles and H is for the heart.
        1. LDH-1 = HHHH (H4).
        2. LDH-2 = HHHM (H3M).
        3. LDH-3 = HHMM (H2M2).
        4. LDH-4 = HMMM (HM3).
        5. LDH-5 = MMMM (M4)
    4. These are controlled by the loci on human chromosomes no 11 and 12 respectively.
    5. Five isoenzymes make the total LDH. These are separated by electrophoresis (Thin layer agarose gel)  and  These are:
      1. LDH 1 is present in the cardiac muscle, RBCs, and kidney cortex.
      2. LDH 2 is present in the cardiac muscle and RBCs.
      3. LDH 3 is present mainly in the lung and other tissues.
      4. LDH 4 is present in the kidneys, pancreas, and placenta.
      5. LDH 5 is present in the skeletal muscles and liver.
  2. LDH enzyme level in U/g in various tissue is high as compared to the serum e.g:
    1. Skeletal muscles = 147
    2. liver = 145
    3. Heart = 124
    4. Kidney = 106
    5. RBC (U/g Hb) = 36
    6. Tissue level of LDH is roughly 500 times more than the serum. So contamination with damaged tissue will give very high values.
  3. LDH is an enzyme of the oxidoreductase class that catalyzes the reduction of pyruvate to L-lactate.
    1. LDH enzyme catalyzes the oxidation of L-Lactate to Pyruvate where NAD acts as H+ acceptor.
      1. This reaction depends upon the:
        1. pH.
        2. Temperature.
        3. Substrate.
        4. Buffers concentration.

  1. When there is an injury to the cells LDH spells into the bloodstream.
  2. LDH is the total measure of isoenzymes of LDH.
    1. LDH 1 indicates myocardial injury.
    2. LDH 2 indicate pulmonary injury.
    3. LDH 3 indicate pulmonary injury.
  3. Total LDH indicates multi-organ injury like :
    1. Myocardial infarction.
    2. Congestive heart failure causing pulmonary and hepatic congestion.
    3. Advanced malignancies.
    4. autoimmune diseases.
  4. Oxalate and Borate both inhibit the LDH enzyme activity.
    1. EDTA also inhibits this enzyme activity.

Table showing various isoenzymes in various tissues.

Various organs LDH isoenzymes
Liver 5
Lung 3 and 2
Kidneys 4
Heart 1 and 2
Sk.Muscle 5
Pancreas 4
Placenta 4
RBCs 1
RES 2

Normal

Source 1

Source 2

  1. Adult = 100 to 190 U/L at 37 °C.
  2. Newborn = 160 to 450 U/L (30° C) 
  3. Infants = 100 to 250 U/L.
  4. Child = 60 to 170 U/L 
  5. Isoenzymes : Adult /  elderly
    1. LDH 1 = 17 to 27 %.
    2. LDH 2 = 27 to 37 %.
    3. LDH 3 = 18 to 25 %.
    4. LDH 4 = 3 to 8 %
    5. LDH 5 = 0 to 5 %.
      • The reference ranges are highly method dependent.

Raised LDH values are seen in:

  1. Liver disease:
    1. Ten times raised in toxic hepatitis with jaundice.
      1. LDH-5 is raised in the primary liver disease.
        1. LDH-5 is raised in case of liver anoxia.
  2. Lung diseases:
    1. Pulmonary infarction.
    2. In pulmonary embolism.
  3. hemolysis.
  4. Alcohol.
  5. Medication e.g. Warfarin, Antiepileptics.
  6. Myocardial Infarction
    1. LDH rises within 24 to 48 hours.
    2. Peak level is between 2 to 3 days.
    3. Return to normal is slow process may take 5 to 10 days.

  1. LDH may be raised moderately in the :
    1. Cardiac failure.
    2. Myocarditis.
    3. Liver congestion.
  2. That is why the LDH level is helpful for the diagnosis of MI in the late stage, after 4 days of the history of chest pain.
  3. Malignant diseases:
    1. LDH levels are raised in lymphomas and liver cell necrosis.
    2. 70% of the cases with metastasis to the liver has raised LDH.
    3. Without metastasis to liver, it is raised in 20 to 60% of the cases.
    4. High levels are seen in the case of Hodgkin's disease, abdominal cancer, and lung. 
    5. Leukemias has a moderate increase.
  4. Kidney diseases: 
    1. It is raised in 1/3 cases of kidney diseases.
      1. Mostly in tubular necrosis.
      2. And in pyelonephritis.
      3. In case of renal infarction, the picture is like myocardial infarction.
  5. Muscular dystrophy:
    1. There is a moderate increase in the progressive muscular dystrophy particularly in the early and mid-stages of the disease.
    2. LDH-5 is mainly increased.
    3. After damage or loss of the large mass of the muscle, LDH level declines.
  6. Cerebrospinal fluid:
    1. Normally it is low than the serum.
    2. LDH-4 and LDH-5 are not found in the CSF.
    3. In bacterial meningitis, WBCs raise the level of LDH-4 and LDH-5.
    4. In the case of viral meningitis, the lymphocytes increase the level of LDH-1 and LDH-3.
  7. Urine:
    1. Total LDH raised the level in the urine indicates urologic injury.
    2. Three to five times raised level is seen in:
      1. Chronic glomerulonephritis.
      2. Systemic lupus erythematosus.
      3. Diabetic nephropathy.
      4. Urinary bladder and kidney tumors.
  8. LDH level may be done in the pleural, cardiac or peritoneal fluids to differentiate exudate or transudate.
  9. LDH isoenzymes increased in various diseases :
    1. LDH-1 increased in renal infarction.
      1. It is raised in the germ cell tumor-like seminoma and teratoma of the testes.
        1. And dysgerminoma of the ovary.
    2. LDH-3 increased in pulmonary infarction.
    3. LDH-3 and LD-4 increased in lymphoproliferative disorders.
    4. LDH-4 may be the main isoenzyme in acute lymphoblastic leukemia.
    5. Normal LDH-1: LDH-2 ratio = <0.80 while in the myocardial infarction is >0.80.
    6. LDH-1 > LDH-2 in hemolytic anemias and pernicious anemia.

           As LDH is distributed in the multiple organs, so the total LDH is not a marker of specific disease or injury.

Serum LDH Isoenzymes in various diseases:

Diseases LDH Isoenzymes raised
Myocardial infarction I and II
Pulmonary embolus without hemorrhage III
Pulmonary embolism with hemorrhage I, II, III
Sickle cell crises I, II
Pernicious anemia I
Acute MI with congestion of the liver I, V
Early hepatitis V
Malignant Lymphomas III, 1V
Dermatomyositis V
Lupus erythematosus III 1V
Prostatic carcinoma V

Possible References Used

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