LDH - Lactic dehydrogenase

LDH - Lactic dehydrogenase

What is lactic dehydrogenase (LDH)?

There lactic dehydrogenase or lactate dehydrogenase (LDH) it is an enzyme involved in the metabolism of glucose, a carbohydrate essential for the functioning of our body.
It is localized in different tissues, but mainly at the level of:

  • skeletal muscles
  • in the liver
  • cardiac
  • renal
  • pulmonary
  • pancreatic

Therefore it turns out to be a important marker of organ damage.
After cell damage, this enzyme is released into the bloodstream and / or at the level of biological fluids, resulting in a significant increase.
The dosage of LDH values it can be evaluated through blood sampling and / or through the sampling of the biological liquid of interest.

At the level of our cells we can distinguish membrane enzymes (eg. γ-GT or GGT or gamma-glutamyltranspeptidase), which can increase in circulation as a result of "simple" changes in the cell membrane, and cytoplasmic enzymes (eg LDH), which are poured into circulation as a result of insults of greater entity.

The reaction catalyzed by lactate dehydrogenase determines, in a bidirectional way, the production of lactate and restoring NAD+ (starting from NADH), which is involved in the oxidation process of glyceraldehyde 3-phosphate or 3-phosphoglycerine aldehyde, an intermediate glycolysis and of gluconeogenesis.
These metabolic processes, glycolysis before and gluconeogenesis after, take place mainly to compensate for the reduction in blood sugar (hypoglycemia), a condition typical of the fasting phases.

According to Cycle of choirs, that is a metabolic cycle that unites the muscle and the liver, in a condition of anaerobiosis (a situation that can be established for example during excessive muscular effort) lactate is produced. The lactate it is transported in an extracellular environment and subsequently introduced into the blood stream, through which it reaches the liver. In the liver, starting with lactate, thanks to lactic dehydrogenase, we get the pyruvate, from whose conversion, in the process of gluconeogenesis, is obtained glucose (essential for the sustenance of our organs, especially for the brain which is an exclusively glucose-dependent organ), in what is called lactic fermentation.

There lactate dehydrogenase it is a tetramer, therefore it is made up of 4 monomers, whose 2 variants are encoded by two different genes.
These 2 variants are divided into:

  • H (heart): or the variant most expressed in the heart.
  • M (muscle): that is the variant most expressed in skeletal muscle.

According to the monomeric composition we distinguish 5 isoforms or isoenzymes:

  • LDH1: typical of myocardium and gods Red blood cells (or erythrocytes). Also localized, albeit to a lesser extent, at level renal and in skeletal muscle.
  • LDH2: prevalent in myocardium and in erythrocytes; it is also found in the kidney, lung and skeletal muscle
  • LDH3: mainly located in lungsit is also found in skeletal muscles, the pancreas and the placenta.
  • LDH4: located in the kidney at the level of the medulla, skeletal muscle, lungs and placenta.
  • LDH5: typical of muscle he was born in liver; it is also found in the pancreas and renal medulla.
LDH or lactate dehydrogenase

Chemical formula of the action of lactate dehydrogenase or LDH.

Normal LDH values

What are the reference values for lactic dehydrogenase? The normal range of lactate dehydrogenase varies according to age:

  • Normal values (adults): 122 - 222 U / l
  • Normal values (children): 140 - 390 U / I
  • Normal values (newborns): 135 - 750 U / I

Percentage of isoenzymatic variants:

LDH1: 17 - 28 %
LDH2: 30 - 36 %
LDH3: 19 - 25 %
LDH4: 9 - 15 %
LDH5: 5.5 - 12 %

Indications

When is the LDH dosage recommended?
The dosage of lactic dehydrogenase level blood is carried out in the presence of suspicion of:

  • tissue damage
  • diagnosis is monitoring (follow - up) of some pathologies (eg anemia, as a result of haemolysis or the destruction of erythrocytes in circulation, we will have an increase in LDH).
  • infection
  • follow up some treatments (e.g. chemotherapy)
  • As tumor marker, in the staging of some cancers (e.g. haematological cancers: lymphomas and leukemia, ovarian cancers, testicular cancers, melanoma, etc.)

The LDH assay is also performed on other biological liquids:

  • Pleural fluid
  • Ascitic fluid
  • Cephalorachidian liquor (distinction between viral or bacterial meningitis).

High LDH

What does it mean to have increased LDH on blood tests? The measurement of lactic dehydrogenase in other biological samples allows us to distinguish an infectious condition from a non-infectious one. Furthermore, the relationship between the serum LDH and the LDH present in the biological liquid allows us to distinguish a exudate (inflammatory fluid) from a oozed (non-inflammatory liquid).
Unlike exudate, the presence of non-inflammatory fluid (oozed) is indicative of an alteration in the pressures that regulate capillary exchanges, also resulting from changes in the protein component of the blood, which regulates oncotic pressure (regulation mediated above all by albumin).

Causes of high LDH

What are the main pathological conditions associated with high LDH values? An increase in LDH can be a consequence of tissue alterations affecting various organs. It is certainly indicative of cell damage. It is a highly sensitive marker, therefore a high lactic dehydrogenase can be observed already during the onset of cellular insult, reaching the maximum concentration during the acute phase of damage, and then reducing.

Furthermore, following chronic inflammatory diseases, the persistence of a slight increase in LDH can be observed, an indication of the state of inflammation.

The main causes of High LDH I'm: 

  • Hemolytic anemia
  • Megaloblastic anemia
  • Infections (meningitis, mononucleosis, etc.)
  • Septicemia or sepsis
  • Acute kidney damage
  • Acute and / or chronic liver damage
  • Acute muscle damage (trauma, strenuous exercise)
  • Chronic muscle damage (muscular dystrophy, use of drugs such as statins)
  • Pancreatitis
  • Bone fractures
  • Neoplasms (lymphomas, leukemias, ovarian tumors, etc.)
  • Myocardial infarction

In the presence of autoimmune diseases, a condition may arise anemia (reduced hemoglobin: cut off <12.5 g / 100 mL for men; <11.5 g / 100 mL for women) associated on the one hand with increased hemolysis, with consequent increase in LDH, on the other hand to the chronic inflammatory state (chronic inflammation) which results in a reduction of transferrin (iron transport protein) and an increase in ferritin (iron depot protein). All this is due to an increase in hepcidin, a positive acute phase protein (i.e. a protein that increases in conditions of inflammation) and that inhibits carrier, which is responsible for the mobilization of iron from the intracellular to the extracellular side.

There are also non-pathological conditions that can lead to an increase in LDH:

  • Exercise very intense
  • Laboratory artifacts: hemolysis of the blood sample, resulting from laboratory errors in the storage of the sample.

LDH has been a marker of acute myocardial infarction; now, however, this has been replaced by other notoriously more sensitive and specific markers (eg troponin T or high sensitivity troponin I, modified albumin).
However, the LDH dosage can still be recommended for the evaluation of previous heart attack since, having a longer half-life than the previously mentioned markers (troponin), its values remain elevated for a longer interval of time, thus allowing to associate a previous chest pain (reported by the patient at the time of the anamnesis), a myocardial infarction (also previous).

Taking the biological sample

If the withdrawal Sara blood, it will be done as a classic withdrawal of venous blood, fasted for at least 8 hours.

The collection of other biological samples instead it requires different, more invasive methods:

  • Thoracentesis: collection of pleural fluid carried out by inserting a needle in the patient's chest, and aspiration of the fluid
  • Paracentesis: withdrawal of fluid from the peritoneal cavity.
  • Rachicentesis (lumbar puncture): Cephalorachidian fluid sampling, carried out in the intervertebral space between the third and fourth lumbar vertebrae (L3 or L4).

The more the liquid is inflammatory in nature, the more likely it is that the LDH value is elevated. Therefore, the absolute value of the concentration of lactic dehydrogenase in liquids, especially in the pleural fluid, is one of the parameters that allows us to define it as inflammatory.

To evaluate the nature of a collection, inflammatory or not, it is therefore appropriate to evaluate:

LDH in a non-inflammatory picture

  • LDH Index: Liquid LDH / serum LDH <0.8
  • Albumin gradient: serum albumin concentration - liquid albumin concentration> 1.2
  • Albumin index: serum albumin concentration / liquid albumin concentration> 2.5

LDH in framework inflammatory

  • LDH Index: Liquid LDH / serum LDH> 0.8
  • Albumin gradient: serum albumin concentration - liquid albumin concentration <1.2
  • Albumin index: serum albumin concentration / liquid albumin concentration <2.5

Light's criteria - Classification criteria for pleural fluid

  • Protein ratio (mainly albumin) pleural fluid / serum protein
    <0.5 = transudate; > 0.5 exudate
  • LDH ratio in pleural fluid / LDH in serum
    <0.6 = transudate; > 0.6 exudate
  • Pleural fluid LDH> 200 IU = exudate
  • Pleural fluid proteins> 3 g / dL = exudate

Classification criteria for ascitic fluid

  • Cell count> 250 µl = infected ascites
  • Albumin gradient <1.1 g / dL = infected ascites
  • Ascitic fluid protein ascites / serum protein> 0.5 = exudate
  • Ascitic fluid LDH / serum LDH> 0.6 = exudate

High LDH Symptoms 

Symptoms related to an increase in LDH depend on and are related to the pathological picture that led to the increase.
Some of the symptoms associated with elevated LDH are therefore:

  • Pallor
  • Chest pain
  • Tachycardia
  • Dyspnea
  • Splenomegaly
  • Muscle aches

The assessment of lactic dehydrogenase is often associated with the measurement of other typical parameters of organ damage:

  • Transaminases (AST and ALT)
  • γ-GT or GTT
  • Alkaline phosphatase
  • Complete blood count

The prescription of these tests serves to confirm and support the clinical suspicion of organ damage.
In addition to its use as a diagnostic marker, we remind you that it can be used in the monitoring of pathologies.

Low LDH

What does it mean to have a reduced LDH on blood tests? Although sometimes there may be conditions of blood reduction of lactic dehydrogenase values, generally these are not situations of great clinical interest and therefore should not cause great concern.

Causes of low LDH

An infrequent cause of reduced LDH is the ingestion of excessive amounts of Vitamin C (ascorbic acid).

Low LDH Symptoms

Symptoms associated with this condition are:

  • Nausea
  • Headache
  • Diarrhea
  • He retched
  • Stomach ache
  • Gastric burning

An increase in vitamin C involves a greater risk of the onset of stones and an increase in the iron present in our body (with a consequent increase in ferritin).

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