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Erythropoietin is a glycoprotein which is produced by the kidneys in an individual’s life, and by the liver in fetuses. It stimulates the growth of stem cells of the red blood cell system, platelets and the granulocytic system. The factor that stimulates the release of erythropoietin is the reduction of oxygen partial pressure (hypoxia).
Erythropoietin (EPO) is a hormone mainly produced by specialized cells in the kidney called interstitial cells. Once produced, it acts on red blood cells to protect them from destruction.
Although the exact mechanisms that control erythropoietin production are poorly understood, it is well known that specialized cells in the kidney are capable of detecting and responding to low oxygen levels (hypoxemia) by increasing erythropoietin production. When there is enough oxygen in the blood circulation, the production of erythropoietin is reduced, but as the oxygen level drops, the production of erythropoietin increases. This is an adaptive mechanism as it facilitates the production of more red blood cells to transport more oxygen around the body, thus increasing the oxygen level in the tissues. For example, when traveling to high altitudes, air pressure drops, which can cause hypoxia, which stimulates an increase in erythropoietin production.
Its concentration is also influenced by the weight of the active renal parenchyma (in the case of renal failure, the concentration of erythropoietin is reduced). Erythropoietin is a peptide hormone, much needed by athletes because it responds to the tissue’s oxygen demand. Exercise in the mountains is a natural way to improve your body’s aerobic capacity. The body, protecting itself against hypoxia, stimulates the bone marrow to produce erythrocytes with the help of erythropoietin (thanks to this, athletes can increase their effort). The second way is the use of erythropoietin preparations by athletes, but it is a prohibited form of doping.
In states of low oxygen levels, people risk developing hypoxia – oxygen deprivation. Hypoxia can also occur when there is poor lung ventilation, such as chronic lung disease, emphysema, and cardiovascular disease. Erythropoietin production is reduced in certain conditions such as renal failure, chronic diseases such as HIV / AIDS and certain cancers, and in chronic inflammatory diseases such as rheumatoid arthritis.
See also: What do the kidneys do and what do kidney diseases manifest?
The mechanism of action of erythropoietin
Erythropoietin (EPO) has been shown to exert its effects by binding to the erythropoietin receptor (EpoR). EPO binds to the erythropoietin receptor on the progenitor surface of red blood cells and activates the JAK2 signaling cascade. This initiates the STAT5, PIK3 and Ras MAPK pathways. This causes the erythroid cell to differentiate, survive and proliferate. SOCS1, SOCS3, and CIS, which act as negative regulators of the cytokine signal, are also expressed.
High level of erythropoietin receptor expression is localized in erythroid progenitor cells. While there are reports that erythropoietin receptors are found in many other tissues, such as the heart, muscle, kidney, and peripheral / central nervous system tissue, these results are confused with the non-specificity of reagents such as anti-EpoR antibodies. In controlled experiments, a functional erythropoietin receptor is not detected in these tissues. In the bloodstream, red blood cells themselves do not express the erythropoietin receptor, so they cannot respond to erythropoietin. However, it has been reported that red blood cell longevity is indirectly related to plasma erythropoietin levels, a process termed neocytolysis. Furthermore, there is conclusive evidence that erythropoietin receptor expression is elevated in the event of brain injury.
See also: What is proliferation – can it lead to cancer development?
The most common indications for an erythropoietin test are:
1. Anemia (differentiation) and monitoring of anemia treatment. The test is also performed in the course of renal failure. If an anemic patient has elevated levels of erythropoietin, but there is no increased production of new red blood cells, then the possible cause of the anemia is impaired bone marrow function.
2. Polyglobulism.
3. Kidney diseases (cystic kidneys). The test allows you to assess the functioning of the kidneys and their ability to produce erythropoietin.
4. Suspicion of an erythropoietin secreting tumor.
5. Differentiation of polycythemia, or ailments in which there is an excessive production of red blood cells.
6. Monitoring athletes (Erythropoietin is a doping agent).
7. The test shows that the amount of erythropoietin produced by the body is appropriate for the severity of the anemia.
8. Patients with abnormal blood counts, especially: hematocrit, erythrocytes and hemoglobin.
Erythropoietin – research
Material for the study of erythropoietin: plasma.
Preparation for erythropoietin testing: on an empty stomach (at least 8 hours).
The course of the study: one-time collection of blood from a vein in the arm into a disposable test tube. Then the obtained material is sent for further laboratory analysis in order to determine erythropoietin in the blood.
Waiting time for the erythropoietin result: 1 Day.
Standard: 10-20 mU/ml.
Comments: Erythropoietin is used as a medicine in anemia caused by renal failure and in oncology. The patient does not need to prepare for the erythropoietin level test.
No equal reference ranges have been established for erythropoietin. The reason for this is that the values depend on many factors, e.g. age, gender and the method of determination. Thus, the numerical values will vary from lab to lab. Always consult your doctor about the result.
Elevated erythropoietin values may suggest:
- polycythemia,
- they appear in people who smoke cigarettes,
- haemolytic anemia (faster breakdown of red blood cells),
- aplastic anemia (loss of bone marrow function),
- iron deficiency anemia,
- alpine training,
- hypoxia due to heart disease.
Reduced levels of erythropoietin occur in the case of:
- chronic uremia,
- anemia caused by kidney problems.
In patients with anemia caused by deficiency vitamin B12, iron or folic acid – the disease will persist despite the increased production of erythropoietin. In such people, erythrocytes may have an abnormal shape, size and hemoglobin content.
Erythropoietin and recombinant erythropoietin
Recombinant erythropoietin is an artificial version of natural erythropoietin. It is made by cloning the erythropoietin gene.
People with anemia caused by chronic kidney disease or who have received radiation or chemotherapy, synthetic erythropoietin is used, which increases the production of red blood cells. Recombinant erythropoietin drugs are known as erythropoiesis stimulants (ESAs). These medicines are given by injection (injection) and they work by stimulating the production of more red blood cells. These cells are then released from the bone marrow into the bloodstream.
The cost of such a procedure is very high. Bone marrow stimulation takes several hours after drug administration. Treatment with synthetic erythropoietin can help patients avoid blood transfusions and improve their quality of life. Unfortunately, recombinant erythropoietin is used by many athletes as one of the forms of doping. They use it to improve the oxygen transport capacity of the blood by increasing the number of red blood cells. This is extremely dangerous as it causes excessive blood viscosity and high blood pressure. For this reason, the use of erythropoietin has been banned by most sports organizations, including IAAF (International Association of Athletics Federations). For athletes participating in the Olympics, it is essential to assess the concentration of erythropoietin in the blood.
Also check: Tablets, injections and … poppy seed cake. How do athletes “coke”?
Erythropoietin – treatment
Erythropoietin available for use as a therapeutic agent is produced by recombinant DNA technology in cell culture. These are erythropoiesis stimulants (ESA), which are drugs that stimulate the bone marrow to produce red blood cells. They are used to treat anemia due to end-stage kidney disease, chemotherapy, major surgery, or some HIV / AIDS treatments. In such situations, they reduce the need for blood transfusions. The individual measures are more or less equivalent. They are given by injection.
Common side effects may include joint pain, rash, vomiting and headache. Serious side effects can include heart attack, stroke, increased cancer incidence, or pure red cell aplasia (PRCA). It is unclear whether it is safe to use them during pregnancy. They act similarly to the naturally occurring erythropoietin.
They were first approved for medical use in the United States in 1989. They are on the World Health Organization’s list of essential medicines. Commercially available agents include epoetin alfa and darbepoetin alfa, as well as biosimilars. Use among athletes is prohibited by the World Anti-Doping Agency.