How long does erythropoietin withstand heat? The importance of erythropoietin in the body and ways to regulate its level

Erythropoietin is a glycopeptide hormone produced by the adrenal glands and in small amounts by the liver. It is involved in regulating the formation of red blood cells synthesized in the bone marrow. The task of red blood cells, in turn, is to supply cells with oxygen. The effect of erythropoietin on a person’s hematopoietic capacity is of interest to scientists and sports trainers, as this makes it possible to increase the resources of the human body.

Erythropoietin or, as it is commonly referred to in medicine, EPO begins to be produced even with the slightest oxygen deficiency. The hormone is transported throughout the body by a complex iron-containing protein, hemoglobin.

Oxygen is used by the body for the most different functions. Without it, the synthesis of cholesterol, bile acid, and steroid hormones would be impossible. The constituent elements of amino acids and so on. In addition, oxygen breaks down into harmless elements, toxins, poisons, and unnecessary drugs.

With hypoxia and oxygen starvation, internal organs, the cardiovascular system, and most importantly, the brain are destroyed. That is, severe cases of hypoxia end in human death.

The hormone erythropoietin, entering the blood, converts reticulocytes into red blood cells, significantly increasing their number, accordingly increasing the oxygen they carry. As oxygen levels rise, pressure rises in the arteries and the blood becomes more viscous.

EPO is produced not only during hypoxia; glucocorticoid, synthesized by the adrenal gland, also becomes a stimulator of its release in a stressful situation. This feature of the body allows it to increase the strength and speed of muscle tissue in a few seconds, and the influx of acid ensures endurance.

Metabolism working in this way allowed humans to survive as a species, since there were plenty of natural enemies in the wild, primitive nature. When attacked by a predator, a person managed to escape or win a fight with a strong animal.

True, such a surge in the activity of blood cell synthesis leads to depletion of iron, copper, vitamins B9 and B12, therefore, after a stressful situation, it is necessary to restore the balance of these substances in the body. Ancient man replenished the supply of iron and copper by eating the defeated animal.

Reasons for deviation from the norm

In the human body, the levels of various hormones are extremely precisely balanced, the same applies to erythropoietin. The normal range for women is the hormone content range from 8 to 30 IU/l. In men, respectively, 5.6 to 28.9 IU/l. If there is a deviation from the norm to a greater or lesser extent, this may mean the presence of some pathologies.

1. At elevated level erythropoietin, the number of red blood cells should be high, but if it is low, then this indicates anemia, which suppresses the hematopoietic function of the bone marrow.
2. Erythropoietin levels may be reduced by exposure to environment, for example in high altitude conditions, poor in oxygen.
3. Oxygen depleted, despite high level Erythropoietin deficiency can occur as a result of smoke poisoning, such as from cigarettes.
4. Decreased erythropoietin levels may be caused by renal failure or the presence of a cyst or tumor in the adrenal glands. The kidneys also stop producing the necessary hormone in case of urolithiasis or the presence of multiple cysts in the parenchyma of the organ.
5. Tumors can also affect the bone marrow, so high levels of erythropoietin in this situation do not cause an influx of red blood cells.
6. Bone marrow is susceptible to a variety of pathologies from various forms anemia to leukemia and all of them are accompanied low level red blood cells, white blood cells or platelets.
7. If, with elevated levels of erythropoietin, oxygen in the blood still does not rise, this may be a disease of the lungs or cardiovascular system.
8. Damage to the brain by hemangioblastoma leads to disruption of the level of erythropoietin in the blood.
9. Acquired immunodeficiency syndrome.
10. After transplantation of any organ, especially bone marrow, there is a significant hormonal disbalance accompanied by a deficiency of red blood cells.
11. Blood donation leads to a deficiency of red blood cells, despite high levels of erythropoietin.

The presence of all the mentioned pathologies and diseases becomes the reason for long-term and labor-intensive therapy, during which not only the hormonal and oxygen balance in the body is brought into order, but the very reason for the occurrence of such a situation is eliminated.

The use of erythropoietin in therapy

Many diseases and conditions can be treated with hormonal therapy, including drugs with erythropoietin. Any treatment in this direction is prescribed by an endocrinologist, since even the slightest deviation in the dosage of the drug can lead to a dangerous excess or, conversely, an underestimation of the number of red blood cells.

Treatment is carried out using both subcutaneous and intravenous drugs. During treatment, the patient is regularly checked for blood composition, hemoglobin level and erythropoietin content in the blood.

It is important to understand that the course of treatment with erythropoietin involves a gradual reduction in the amount of the drug taken, so that the body itself restores the required amount of hormones. As a result correct application drugs, the functioning of the endocrine system is completely restored.

For your information, the normal hemoglobin level is from 110 to 120 g/l, and the ratio of red blood cells to other blood elements should be at 30 -35%.

Along with medications containing erythropoietin, the patient should take medications containing iron, folic acid and B vitamins, this restores the level of substances used by the hematopoietic system in the body.

Erythropoietin in sports

Erythropoietin has found widespread use in sports. Its synthetic analogues are used to give muscles the ability to long time do hard work. Drugs that thus affect the athlete’s body are called doping.

An athlete taking erythropoietin-based doping is capable of for a long time without feeling tired, run, ride a bike or row with oars. In other words, such doping has found application in those sports that require long, uniform effort. But it is not very suitable for heavyweight athletes.

The price to pay for being able to run or pedal for a long time is accelerated metabolism and the burning of all iron reserves, folic acid and other elements of the hematopoietic system.

Several fatalities were recorded, specifically among cyclists, after which drugs with erythropoietin were officially recognized as dangerous doping and their use was banned. All athletes found using erythropoietin were disqualified for the rest of their lives.

Doping with erythropoietin is very difficult to determine from an athlete's blood or urine test. Therefore, since 1990, anti-doping laboratories have been developing methods for detecting a prohibited drug in athletes' samples. Since the synthetic hormone, in its composition and action, is identical to the natural one, and its presence in the blood is explained by the stressful situation caused by the competition, it is extremely difficult to detect.

Therefore, it was decided not to measure the amount of the hormone in the athletes’ blood, but the level of oxygen and hemoglobin. Although this method of measurement is quite subjective, because some were calm before the start and rested the day before, while others trained for a long time and are very nervous.

Despite the controversial methods for determining doping in an athlete’s blood, the conclusion in connection with the use of a drug with erythropoietin can be made simple - its effect can be fatal.

But there is another opinion, born in the light of recent events related to sports competitions of world significance, namely the Olympics. The main thing for sports officials is not to identify an athlete who uses doping, but to remove athletes from competitions from countries with a policy that is incorrect from their point of view. And few people in such a situation are interested in what effect the drug creates on a person.

Erythropoietin – important element in organism. This hormone performs many important functions. So, it is involved in the production of red blood cells in the blood and in maintaining their work, this process is called erythropoiesis. The synthesis of the hormone in an adult occurs directly in the kidneys, in newborns in the liver. A healthy body produces an almost identical volume of red blood cells on a constant basis, so the slightest change in their concentration can be harmful to the patient. Erythropoietin what is it?

The hormone erythropoietin helps increase the production of red cells, and this is especially important in cases of large blood loss, hypoxia and stressful situations. At in good condition destruction of red blood cells may occur in the body; in the case of sufficient synthesis of erythropoietin, strong destruction will not occur, erythropoiesis will be active. The lifespan of blood cells increases to 120 days.

In addition, the hormone affects the release of additional required quantity from their depot. As a result of modern research, it has been found that this hormone also has a positive effect on platelet synthesis.

The hormone that is produced in the human body is called endogenous erythropoietin. The kidneys produce up to 90% of all erythropoietin. About 10% is synthesized in the liver tissue, but the fetus in the womb produces this hormone 100% by the liver.

The production of erythropoietin follows a certain pattern. According to the most simplified system, hormone synthesis occurs, first starting with oxygen starvation or hypoxia, then the kidney tissues begin to be irritated from lack of nutrition and the production of prostaglandins begins in the glomeruli, and finally erythropoietin is released into the blood.

The above diagram does not fully disclose the entire system of erythropoietin formation. In addition to the above principles of formation, the synthesis of this hormone is influenced by several substances:

1. Testosterone.
2. Cortisol.
3. Prolactin.
4. Thyroxine.
5. Adrenocorticotropic hormone.
6. Somatotropic hormone.

Estrogens have been proven to directly affect low erythropoietin levels. The level of this hormone can change under the influence of certain factors and diseases.

Reasons for deviations from the norms

The concentration can be increased by diseases of various organs and systems in the human body. It can be increased by various reasons: pathologies of the circulatory system, diseases of the kidneys, lungs, heart.

Hormone-producing kidney tumors often cause the hormone to be elevated. This phenomenon also occurs with pheochromocytoma and hemiangioblastoma. Erythropoietin is used as a doping in sports; a blood test will help find out; when deciphered, the erythropoietin level will be significantly increased.

A decrease in the hormone occurs as a result of certain pathological processes such as diseases of the kidneys or other organs, causing chronic or renal failure, polycythemia vera. Therefore, to exclude the development of pathology, it is necessary to take a biochemical blood test to determine the level of erythropoietin. Based on a blood test, as a rule, additional differential diagnosis of all body systems is required in order to find out which system is affected.

Kidney disease is the most common cause of decreased erythropoietin concentrations. A deviation from the norm occurs when diagnosing the following kidney pathologies: renal artery stenosis, polycystic kidney disease, kidney stones, a condition in which the blood supply to the kidneys is reduced.

In kidney disease, it is the deterioration of blood circulation that causes increased production of erythropoietin. Red blood cells and erythropoiesis in the blood are controlled by special receptors that are responsible for the perception of these components. With reduced blood circulation, the receptors do not perceive red blood cells in full concentration, and to replenish, a hormone is actively produced that will actively stimulate erythropoiesis.

Polycythemia vera is characterized by the fact that erythropoietin is produced in minimal quantities. All components of the blood with this pathology are produced at increased levels. In this case, erythropoietin does not control erythropoiesis, and they are increased even without an increase in this hormone.

Other diseases

Pathologies of the blood system often cause an increase in the volume of erythropoietin in the blood. The most common disease provocateurs are anemia, myelodysplastic syndrome at the first stage, leukemia, and red bone marrow aplasia.

Diseases of this type lead to varying degrees of reduction in red blood cells. Therefore, the body, as a defense, has to produce the hormone in an enhanced mode in order to restore red cells in the required quantity.

Various respiratory diseases can also cause changes in erythropoietin levels. Such diseases are: chronic obstructive pulmonary disease, chronic bronchitis, silicosis and pneumoconiosis.

Pathologies of the respiratory system reduce the volume of oxygen and the blood becomes less saturated with it; accordingly, cell nutrition becomes insufficient. This is hypoxia and causes increased production of the hormone, which will be elevated when tested in the blood.

Those heart diseases that are directly related to a decrease in oxygen in the blood also cause an increase in the concentration of erythropoietin. Heart defect or congestive heart failure is characterized by mixing of arterial and venous blood, resulting in oxygen deficiency. This pathology is most typical for people in old age.

In medicine

After visiting a general practitioner or hematologist, the patient may receive a referral for a blood test for erythropoietin. This examination is prescribed to a patient if he has signs of anemia. And also if, when conducting a blood test to determine the level of red blood cells, folic acid and vitamin B 12, a decrease in these indicators is revealed.

At the same time, it is important to exclude from the patient the fact that the level of red blood cells is lowered not due to large blood loss and he does not suffer from hemolysis, that is, massive destruction of red blood cells. However, there are established indicators that must be considered normal for men, these are indicators at the level of 5.6 to 28.9 IU/l, and for women - from 8 to 30 IU/l.

The female body loses a certain amount of blood every month during menstruation, so the norm is higher for women than for men. Even the loss of such a small volume of red blood cells, as during menstruation, is felt by the body, so it is necessary to make up for this decrease.

The development of modern medicine is at a stage when treatment of patients with impaired production of this hormone is much easier. In the past, treatment relied on red blood cell transfusions. At the moment, recombinant human erythropoietin is the main substitute. For this purpose, a special therapy technique is used.

This type of substitute is produced from animal tissues containing the genetic code of human EPO. There are several types of this hormone, which do not differ in their effect on the patient - erythropoietin alpha and beta. This type of hormone is absolutely identical to those that are formed naturally in the tissues of the liver and kidneys, so no rejection reactions occur, so in some cases alpha can be replaced with beta, but only with the agreement of a doctor. The composition of the drugs includes the components epoetin alfa, beta.

It is strictly prohibited to use this hormone in sports, no matter what type is used, alpha or beta. Cases of death after taking recombinant erythropoietin are known for certain. The use of any method that will artificially produce additional erythropoietin is strictly prohibited for athletes and threatens with disqualification.

Medications

What is erythropoietin in medicine? Several drugs that contain recombinant erythropoietin are used in medicine. Medications are produced in ampoules, as it is administered subcutaneously or intravenously. The following synonyms of erythropoietin, which are INNs, are most often used in treatment:

1. Epoetin.
2. Erythrostim.
3. Recormon.
4. Vero-epoetin.

All drugs contain the same recombinant erythropoietin alpha, beta and the indications for use do not differ, however, they have different names, but the instructions for use practically do not change in any case.

Main indications for use:

1. Chronic renal failure.
2. Renal neoplasms of benign origin.
3. Rehabilitation after chemotherapy used to treat malignant lesions.
4. Anemia.
5. Postoperative recovery period.
6. For premature babies weighing less than 1.5 kg.

This medicine cannot be used for all groups of patients. Thus, the following features are contraindicated: uncontrolled arterial hypertension, unstable angina, decreased iron concentration in the blood, individual intolerance to some components of the drug.

It is also necessary to take into account possible risks when using such drugs by pregnant women. If the reception is advisable and does not entail negative influence on the fetus, then such treatment is possible, but it should only be carried out under the supervision of specialists in a hospital setting.

For some patients, taking the drugs goes away without a trace, however, cases of side effects have been reported. The most common manifestations are: headache, dizziness, nausea and vomiting, joint pain, asthenic condition, diarrhea, cramps, swelling and redness after the injection, fever. The specialist will warn you about possible manifestations, however, if side effects are present when visiting a doctor, you must notify them about this.

B.03.X.A Other hematopoiesis stimulants

Symptoms: hypertension, erythrocytosis, hyperhemoglobinemia, sharp increase

hematocrit values.

Treatment: symptomatic. In case of hypertension, it is necessary to avoid excessive hydration. In the presence of erythrocytosis and hyperhydration, measures to remove excess fluid are necessary.

If hemoglobin and hematocrit levels are high, phlebotomy is indicated.

Erythropoietin is a renal hormone that controls and regulates the process of red blood cell formation (erythropoiesis) in the red bone marrow. 90% of erythropoietin is synthesized in the capillary cells of the renal glomeruli and 10% is produced by liver cells. The release of erythropoietin into the blood is subject to a circadian rhythm; its level in the blood is higher in the morning than in the afternoon or evening. The production of this hormone increases under conditions of hypoxia (lack of oxygen). In pregnant women, the level of erythropoietin in the blood is increased. Some hormones regulate the synthesis of erythropoietin.

Hormones that enhance erythropoietin production:

• Somatotropic hormone(GH, growth hormone) is a pituitary hormone (the pituitary gland is the main endocrine gland, located at the base of the brain, regulates the action of the hormonal system).

• Adrenocorticotropic hormone(ACTH) – pituitary hormone
• Prolactin– pituitary hormone
• Thyroxine (T4) – thyroid hormone
• Cortisol– hormone of the adrenal cortex (the adrenal glands are a pair of small endocrine glands located above the kidneys)
• Testosterone– male sex hormone

Hormones that cause a decrease in erythropoietin production

• Estrogens– female sex hormones

Erythropoietin stimulates the formation and maturation of not only red blood cells (erythropoiesis), but also platelets (blood cells that participate in blood clotting). Determining the level of erythropoietin in the blood is important for differential diagnosis between primary (true) and secondary polycythemia.

• - Primary polycythemia, true - a malignant disease of the hematopoietic system, leukemia, with an increase in the content of hemoglobin and red blood cells in the blood, cherry red coloration of the face and other signs
• - Secondary polycythemia is not associated with disorders of the hematopoietic organ. The number of red blood cells in the blood can be increased due to loss of water due to heavy diarrhea, oxygen deficiency in the mountains, as well as heart defects and pulmonary emphysema.

In primary polycythemia, the level of erythropoietin is reduced, in secondary polycythemia it is increased.

A decrease in erythropoietin levels can be detected:

• - in patients with anemia developed as a result of oncological and hematological diseases (hematological diseases are a large group of diseases associated with impaired function or structure of blood cells)
• - in patients with anemia due to chronic inflammatory diseases
• - in patients after extensive surgical interventions
• - in patients with rheumatoid arthritis
• - in patients with chronic renal failure

Due to a lack of the hormone erythropoietin, patients develop severe normochromic anemia (with a low number of red blood cells in the blood, but a normal hemoglobin content in the red blood cells). Due to the low number of red blood cells, the level of hemoglobin in the blood decreases to 50-80 g/l, while the norm in women is 110-152 g/l and men 120-172 g/l. Such patients are indicated for treatment with recombinant human erythropoietin preparations. The effectiveness of such treatment decreases with iron deficiency in the body.

An increase in erythropoietin levels can be detected:

• - in patients with various types of anemia (iron deficiency, folate deficiency, B12 deficiency, aplastic)
• - in patients with chronic obstructive pulmonary diseases (obstructive - associated with narrowing of the lumens of the cavities)
• - in patients with tumors that secrete erythropoietin, such as kidney tumors, pheochromocytoma(benign adrenal tumor), cerebellar hemangioblastoma (tumor originating from blood vessels).
• - in patients with polycystic kidney disease (a disorder of the development of renal tissue, leading to the appearance of cysts in it; combined with pathology of the urinary system).

Erythropoietin (EPO) is a glycoprotein hormone that controls the rate of erythropoiesis in the human body. The substance presented is synthesized mainly in the kidneys, a small amount (about 10 percent) is formed in the liver. The hormone erythropoietin activates the division and differentiation of erythroid precursors. The level of endogenous hormone in the blood plasma of healthy people varies over a wide range and is inversely related to the concentration of hemoglobin and the degree of tissue oxygenation. The work on isolating and producing this hormone for medical purposes is very useful.

Structure and significance of the hormone

The hormone molecule consists of amino acids. With a deficiency of endogenous erythropoietin, a sharp decrease in the level of hemoglobin and red blood cells in the blood is observed, and the so-called erythropoietin deficiency anemia develops. Until recently, drug correction of such anemia remained impossible due to the lack of appropriate pharmaceuticals. Nowadays, when there is a deficiency of the above hormone in the human body, doctors prescribe recombinant erythropoietin. The drug is obtained from animal cells into which the gene code for human EPO is introduced. Recombinant human erythropoietin is identical in amino acid and carbohydrate composition to the natural hormone, increases the number of red blood cells, reticulocytes, and activates hemoglobin biosynthesis in cells. The biological activity of the resulting substance is no different from the endogenous hormone. Recombinant erythropoietin does not exhibit cytotoxic effects and does not affect leukopoiesis. Scientists suggest that EPO interacts with specific erythropoietin-sensitive receptors that are localized on the cell surface.

Method for purifying recombinant human erythropoietin

Recombinant human EPO is one of the most common proteins produced by many biological and pharmaceutical companies around the world for drug therapy. The presented compound is synthesized by Chinese hamster ovary (CHO) cells using the recombinant DNA method. One polypeptide chain of recombinant EPO contains 165 amino acids, the calculated molecular weight of which is 24,000 Da, and the observed molecular weight of the glycosylated protein is 30,400 Da. Separation of erythropoietin from impurities is carried out using ion exchange and Human recombinant EPO has a purity of 98%.

Recombinant erythropoietins and their analogues

To stimulate the processes of erythropoiesis, doctors use different drugs:

• "Aranesp";
• "Aeprin";
• "Epobiocrine";
• "Bioein";
• "Vepox";
• "Binocrit";
• "Epocrine";
• "Gemaks";
• "Epogen";
• "Eprex";
• "Epovitan";
• "Epomax";
• "Hypercrit";
• "Eralfon";
• "Erytrostim";
• "Recormon";
• "Epostim";
• "Eposino";
• Epoetin Beta.

Before replacing recombinant erythropoietin with analogs, you should consult with your doctor.

Indications for use

Medical practitioners quite often have to deal with erythropoietin deficiency anemia (EDA). This group includes the following pathologies:

• anemia in malignant neoplasms;
• early anemia of premature babies (up to 34 weeks of pregnancy) with body weight from 750 to 1500 g;
• nephrogenic anemia;
• anemia in chronic diseases (hepatitis C, rheumatoid arthritis, HIV infection, diseases of the digestive canal).

A distinctive feature of the above anemias is that they are not treated with iron supplements. Until recently, the only effective treatment method was blood transfusions. Due to the fact that this type of therapy has a huge number of side effects and a high risk of transmitting pathogens of a number of dangerous infectious diseases (HIV, hepatitis viruses, etc.) through the blood, this method is practically not used in modern medicine. Recombinant human erythropoietin helps improve the quality of life of patients diagnosed with erythropoietin deficiency anemia. The biosynthesis and introduction into practice of recombinant human EPO has opened a new era in the treatment of erythropoietin-dependent anemia.

Contraindications

• thromboembolism;
• hypersensitivity to the drug;
• inability to carry out effective anticoagulant therapy;
• previous cerebral stroke or myocardial infarction;
• unstable angina;
• uncontrolled arterial hypertension;
• the period of bearing a child and breastfeeding;
• refractory arterial hypertension.

Dosage regimen

The dosage, regimen and duration of treatment are established on a strictly individual basis, depending on the severity of anemia, the general condition of the patient and the nature of the pathology. The drugs are intended for parenteral use. Initial doses range from 50 to 150 IU/kg. The dose must be adjusted depending on the age of the patient. Recombinant erythropoietin is usually administered 3 times a week. With an overdose of the drug, increased side effects are observed. The result becomes more or less noticeable after 2-3 weeks of use.

Side effect

Are you prescribed recombinant human erythropoietin? Instructions for use do not exclude the development of side effects. This:

• myalgia;
• dizziness;
• hyperthermia;
• drowsiness;
• vomit;
• headache;
• diarrhea;
• arthralgia;
• hypertension;
• chest pain;
• thrombocytosis;
• tachycardia;
• hypertensive crisis;
• convulsions;
• hepatosis;
• increased activity levels of AST, ALT in the blood;
• erythrocyte lineage aplasia;
• eczema;
• angioedema;
• skin rash and itching;
• asthenia;
• urticaria, hyperemia and burning at the injection site;
• hyperkalemia;
• decreased concentration of ferritin protein in blood plasma;
• hyperphosphatemia.

Erythropoiesis stimulants in sports

Recently, the drug Epovitan (recombinant human erythropoietin) is often used. The presented product is often used in sports (athletics, bodybuilding, swimming, biathlon). This drug activates the biosynthesis of red blood cells, which, in turn, leads to an increase in the oxygen content per unit volume of blood and, accordingly, to an increase in the oxygen capacity of the blood and the delivery of O 2 to organs and tissues. This mechanism of action increases the athlete’s aerobic endurance. A similar effect is observed when an athlete trains in mid-altitude conditions, when a lack of O 2 in the air provokes the development of hypoxia, which, in turn, activates the biosynthesis of endogenous erythropoietin. EPO preparations are used in combination with insulin, somatotropin (GH, growth hormone) and stanazolol.

Excessive, uncontrolled use of the drug "Erythropoietin" in sports can provoke the formation of blood clots, which is usually fatal. It is quite difficult to detect recombinant EPO, since the structure of the synthetic compound is identical to its physiological counterpart, therefore this biocompound is still used illegally in professional sports as a doping.