Lactate Dehydrogenase (LDH), Isoenzymes of LDH
Lactate Dehydrogenase (LDH)
Sample for Lactate Dehydrogenase (LDH)
- LDH can be done on serum or plasma.
- Can store the sample at room temperature.
- Perform the test immediately.
- The hemolyzed sample is not acceptable because RBC has LDH.
- LDH can be done on urine and CSF.
Precautions for Lactate Dehydrogenase (LDH)
- The serum is preferred to plasma.
- The plasma may not be used due to platelets with high LDH.
- Separate the serum as soon as possible, immediately after the clot formation.
- Do not refrigerate or freeze and perform the test immediately.
- 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) for Lactate Dehydrogenase (LDH)
- LDH is used to diagnose diseases or injuries to:
- Heart muscles.
- RBCs.
- Kidney.
- Skeletal muscles.
- Lung.
- Brain.
- Liver.
- It is a late marker of AMI.
- It is a good marker for activity in cryptogenic fibrosing alveolitis and extrinsic allergic alveolitis.
- It is a marker for hemolytic anemia.
- It is a Nonspecific tumor marker.
- Helpful in the diagnosis of exudative fluid in malignant tumors.
- LDH-2 is high in 35% of the cases.
Precautions for Lactate Dehydrogenase (LDH)
- Hemolysis raises the LDH level, as seen in myocardial infarction.
- There is a raised level of LDH1 and 2 in megaloblastic anemia.
- Avoid poor venipuncture.
- Separate the clot from the serum as soon as possible.
- Avoid heating the sample.
Pathophysiology of Lactate Dehydrogenase (LDH)
- LDH values refer to the total LDH enzyme in the serum.
- LDH is an enzyme present in all body cells and present only in the cytoplasm of cells.
- The highest concentration is found in the heart, liver, skeletal muscles, kidneys, and RBCs.
- A lesser amount is found in the lungs, smooth muscles, and brain.
- LDH sites of origin released into the blood after the injury are:
- Heart.
- Liver.
- Skeletal muscles.
- RBCs.
- Kidneys.
- Malignant tumors.
- Lungs.
- Lymphocytes.
- Its molecular weight is 134,000 dalton (128,000).
- Its isoenzyme’s molecular structure consists of 4 polypeptide chains with a molecular weight of 32,000 daltons each.
- Two different polypeptide chains, given the name H (heart) and M (muscle), will combine into five different arrangements and give rise to 5 different isoenzymes.
- It consists of four peptide chains of two types, M (or A) and H (or B).
- This M is for muscles, and H is for the heart.
- These are controlled by the loci on human chromosomes no 11 and 12, respectively.
- Five isoenzymes make the total LDH. These are separated by electrophoresis (A thin layer of agarose gel).
Distribution of the isoenzymes of LDH:
Type of isoenzyme | Structure | Distribution % | Distribution in various organs | Diseases Association |
LDH-1 | HHHH (H4) | 14% to 26% |
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LDH-2 | HHHM (H3M) | 29% to 39% |
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LDH-3 | HHMM (H2M2) | 20% to 26% |
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LDH-4 | HMMM (HM3) | 8% to 16% |
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LDH-5 | MMMM (M4) | 6% to 16% |
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LDH enzyme level in U/g in various tissue is high as compared to the serum, e.g.:
LDH in various tissues | LDH level U/g in various tissues |
Skeletal muscles | 147 |
Liver | 145 |
Heart | 124 |
Kidneys | 106 |
RBC (U/g Hb) | 36 |
Tissue level | 500 times more than the serum |
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- The tissue level of LDH is roughly 500 times more than the serum. So contamination with damaged tissue will give very high values.
Lactate hydrogenase enzyme role in a chemical reaction:
- LDH is an enzyme of the oxidoreductase class that catalyzes the interconversion of Lactic and Pyruvic acid.
- LDH enzyme catalyzes the oxidation of L-Lactate to Pyruvate, where NAD acts as an H+ acceptor.
- This reaction depends upon the following:
- pH.
- Temperature.
- Substrate.
- Buffers concentration.
- This reaction depends upon the following:
- LDH enzyme catalyzes the oxidation of L-Lactate to Pyruvate, where NAD acts as an H+ acceptor.
- When there is an injury to the cells, LDH spells into the bloodstream.
- LDH is the total measure of isoenzymes of LDH.
- LDH 1 indicates myocardial injury.
- LDH 2 indicates a pulmonary injury.
- LDH 3 indicates a pulmonary injury.
- Total LDH indicates multi-organ injuries like :
- Myocardial infarction.
- Congestive heart failure causes pulmonary and hepatic congestion.
- Advanced malignancies.
- Autoimmune diseases.
- Oxalate and Borate both inhibit the LDH enzyme activity.
- EDTA also inhibits this enzyme activity.
Table showing various isoenzymes in various tissues.
Various organs | LDH isoenzymes | LD-1 | LD-2 | LD-3 | LD-4 | LD-5 |
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Liver | 4 and 5 | 0.2% | 0.8% | 1% | 4% | 94% |
Lung | 3 and 2 | 10% | 18% | 28% | 23% | 21% |
Kidneys | 4 (another ref: 1 and 2) | 28% | 34% | 21% | 11% | 6% |
Heart | 1 and 2 | 60% | 30% | 5% | 3% | 2% |
Skeletal Muscle | 4 and 5 | 3% | 4% | 8% | 9% | 76% |
Cerebrum | 28% | 32% | 19% | 16% | 5% | |
RBCs | 1 and 2 | 40% | 30% | 15% | 10% | 5% |
Spleen |
3 | 5% | 15% | 31% | 31% | 18% |
Skin | 0 | 0 | 4% | 17% | 79% | |
Lymphocytes |
3 | |||||
Pancreas | 4 (another ref: 3) | |||||
Placenta | 4 | |||||
RES | 2 | |||||
In normal person |
Major LD-2 followed by LD1>LD3>LD4>LD5 |
Normal Lactate Dehydrogenase (LDH) in blood
Source 1
- Neonates = 415 to 690 U/L
- Adult = 140 to 280 U/L
Source 2
- Adult = 100 to 190 U/L at 37 °C.
- Newborn = 160 to 450 U/L (30° C)
- Infants = 100 to 250 U/L.
- Child = 60 to 170 U/L
- Isoenzymes: Adult / elderly
- LDH 1 = 17 to 27 %.
- LDH 2 = 27 to 37 %.
- LDH 3 = 18 to 25 %.
- LDH 4 = 3 to 8 %
- LDH 5 = 0 to 5 %.
- The reference ranges are highly method-dependent.
Normal LDH in CSF
- It is ∼10% of the serum level
Raised Lactate dehydrogenase (LDH) values are seen in the following:
- Liver disease:
- Ten times raised in toxic hepatitis with jaundice.
- LDH-5 is raised in primary liver disease.
- LDH-5 is raised in the case of liver anoxia.
- LDH-5 is raised in primary liver disease.
- In early hepatitis, there is an increase in LD-5. It may become normal when ALT is still raised.
- There is a moderate increase in cirrhosis, obstructive jaundice, and acute viral hepatitis.
- A marked increase in the LDH-5 occurs in the prodromal stage and is greatest at the onset of jaundice. Total LDH may be increased in 50% of the cases.
- ALT/LD or AST/LD ratio within 24 hours of S/S >1.5 favors acute hepatitis compared to acetaminophen or ischemic injury.
- There is a marked increase in the metastatic infiltrate of the carcinoma.
- LD-4/LD-5 ratio <1.05 favor the diagnosis of liver cell carcinoma.
- Ten times raised in toxic hepatitis with jaundice.
- Lung diseases:
- In pulmonary infarction, there is an increase in LD-2, LD-3, and LD-4.
- In pulmonary embolism, there is an increase in LD-2, LD-3, and LD-4.
- Increased in sarcoidosis.
- Hematological disease:
- The case of pernicious anemia and folic acid deficiency shows an increase in LDH, mainly in LD-1, which is >LDH-2, and when the Hb is <8 g/dL.
- LDH is increased in all hemolytic anemias and can be ruled out if LD-1 and LD-2 are not raised in anemic patients.
- LDH is normal in aplastic anemia and iron deficiency anemia, even in the case of severe anemia.
- In sickle cell crises, there is an increase in LD-1 and LD-2.
- Mothers carrying erythroblastic babies show an increase in LD-5.
- Alcohol.
- Medication, e.g., Warfarin, Antiepileptics.
- Acute Myocardial Infarction:
- LDH rises within 24 to 48 hours.
- The peak level is between 2 to 3 days (48 to 72 hours).
- Return to normal is a slow process that may take 5 to 10 days.
- It was used for the late diagnosis of AMI.
- That is why the LDH level helps diagnose MI in the late stage, after 4 days of chest pain history.
- LDH >2000 IU suggests a poor prognosis.
- In congestive heart failure, there is an increase in LD-2, LD-3, and LD-4.
- LDH may be raised moderately in the following:
- Cardiac failure.
- Acute Myocarditis.
- Rheumatic fever.
- Liver congestion.
- Malignant diseases:
- LDH is increased in 50% of the solid carcinomas and the advanced stage.
- LDH levels are raised in lymphomas and liver cell necrosis.
- 70% of the cases with metastasis to the liver have increased LDH.
- It is raised in 20% to 60% of cases without metastasis to the liver.
- High levels are seen in the case of Hodgkin’s disease, abdominal cancer, and lung.
- Leukemias has a moderate increase.
- Raised levels of LDH in cancers show poor prognosis.
- Carcinoma prostate shows increased LD-5, and the ratio of LD-5:1 is >1.0.
- Malignant lymphoma shows increased LD-3 and LD-4. There may be an increase in LD-2 as well.
- Kidney diseases:
- It is raised in 1/3 of cases of kidney diseases.
- Mostly in tubular necrosis.
- And in pyelonephritis.
- In the case of renal infarction, the picture is like myocardial infarction.
- LD-1/LD-2 ratio >1 may occur in acute renal infarction, hemolysis, pregnancy, muscle disorders, and cancers.
- It is raised in 1/3 of cases of kidney diseases.
- Muscular dystrophy:
- There is a moderate increase in progressive muscular dystrophy, particularly in the disease’s early and mid stages.
- LDH-5 is mainly increased in the anoxic injury of the striated muscle.
- After damage or loss of the large mass of the muscle, the LDH level declines.
- There is an increase in total LDH in electrical and thermal burns and trauma of the muscles.
- Cerebrospinal fluid:
- Normally it is low than the serum.
- LDH-4 and LDH-5 are not found in the CSF.
- In bacterial meningitis, WBCs raise the level of LDH-4 and LDH-5.
- In the case of viral meningitis, the lymphocytes increase the level of LDH-1 and LDH-3.
- Cerebrovascular accidents:
- LDH increases in most cases, and peak levels are 1 to 3 days.
- It does not relate to xanthochromia, RBCs, WBCs, protein, sugar, or chloride.
- The subarachnoid and subdural hemorrhage causes an increase in all subclasses of LDH; especially, there is an increase in LD 3, 4, and 5.
- CNS neoplasia:
- There is an increased LD5 >9% and decreased LD-1: LD-5 ratio <2.5 in the absence of infection or hemorrhage, suggesting neoplasia in the meninges.
- LD-5 >10% suggests high-grade neoplasm.
- LD-3 and LD-4 increase; occasionally, LD-5 is seen in the leukemic and lymphomatous infiltration.
- Meningitis:
- There is a mild increase in viral meningitis.
- There is an increase in LD-1 and LD-2 in viral meningitis.
- There is a marked increase in bacterial meningitis.
- There is an increase in the LD-4 and LD-5 in bacterial meningitis.
- TB meningitis shows an increase in LD-1, LD-2, and LD-3, especially LD-3.
- HIV infection does not make much difference.
- There is a mild increase in viral meningitis.
- Urine:
- Total LDH raised level in the urine indicates urologic injury.
- Three to five times raised level is seen in:
- Chronic glomerulonephritis.
- Systemic lupus erythematosus.
- Diabetic nephropathy.
- Urinary bladder and kidney tumors.
- LDH levels may be done in the pleural, cardiac, or peritoneal fluids to differentiate exudate or transudate.
- LDH isoenzymes increased in various diseases :
- LDH-1 increased in renal infarction.
- It is raised in the testes’ germ cell tumor-like seminoma and teratoma.
- And dysgerminoma of the ovary.
- It is raised in the testes’ germ cell tumor-like seminoma and teratoma.
- LDH-3 increased in pulmonary infarction.
- LDH-3 and LD-4 increased in lymphoproliferative disorders.
- LDH-4 may be the main isoenzyme in acute lymphoblastic leukemia.
- Normal LDH-1: LDH-2 ratio = <0.80, while in the myocardial infarction is >0.80.
- LDH-1 > LDH-2 in hemolytic anemias and pernicious anemia.
- LDH-1 increased in renal infarction.
- Miscellaneous conditions are:
- Parasitic infestation.
- Various infections.
- Viral infections show an increase in LD-2, LD-3, and LD-4.
- Subacute thyroiditis and hypothyroidism.
- Acute pancreatitis.
- Collagen vascular diseases.
- SLE (LD-3 and LD-4).
- Drugs.
- Intestinal obstruction.
- Sarcoidosis.
- Bacterial meningitis, cerebral hemorrhage, or thrombosis.
- Dermatomyositis (LD-5).
Decreased level of LDH may be seen in:
- It may be seen in irradiation.
LDH is distributed in multiple organs, so the total LDH is not a specific disease or injury marker.
Serum LDH Isoenzymes in various diseases:
Diseases | LDH Isoenzymes raised |
Acute Myocardial infarction | I and II (LD-1>LD-2) |
Congestive heart failure | LD2, LD3, LD4 |
Acute renal cortical infarction | LD 1 > LD2 |
Pulmonary embolus without hemorrhage | III (LD-3) |
Pulmonary embolism with hemorrhage | I, II, III (LD-1, LD-2, LD-3) |
Sickle cell crises | I, II (LD-1 and LD-2) |
Pernicious anemia | I (LD-1) |
Acute MI with congestion of the liver | I, V (LD-1 and LD-5) |
Early hepatitis | V (LD-5) |
Malignant Lymphomas | III, IV (LD-3 and LD-4 |
Dermatomyositis | V (LD-5) |
Lupus erythematosus | III, IV (LD-3, and LD-4) |
Prostatic carcinoma | V (LD-5), 5:1 ratio >1 |
Viral infection | LD2, LD3, LD4 |
Strenuous exercise | LD4 and LD5 |
Question 1: What is the significance of LDH in active chronic granulocytic leukemia.
Question 2: Which isoenzyme is increased in pernicious anemia.
Laboratory technician