How Does Erythropoietin Regulate Red Blood Cell Production?
Erythropoietin, also known as erythropoietin, hematopoietin, or hemopoietin, is a glycoprotein cytokine that stimulates red blood cell formation (erythropoiesis) in the bone marrow in response to cellular hypoxia. EPO erythropoietin is secreted at low levels (around 10 mU/mL) in order to compensate for normal red blood cell turnover. Any anaemia, as well as hypoxemia due to chronic lung disease, are common causes of cellular hypoxia resulting in elevated EPO levels (up to 10 000 mU/mL).
Interstitial fibroblasts in the kidney contain erythropoietin in near proximity to the peritubular capillary and proximal convoluted tubule. It's also made in the liver's perisinusoidal cells. In the foetal and perinatal age, liver production predominates; in adulthood, renal production predominates. It is linked to thrombopoietin.
This article will study recombinant human erythropoietin, erythropoietin therapy and erythropoietin treatment in detail.
Functions of EPO Erythropoietin
EPO Erythropoietin is a hormone that is needed for the development of red blood cells. It is required for conclusive erythropoiesis to occur. The kidney can generate and secrete erythropoietin in hypoxic conditions to increase red blood cell development by targeting CFU-E, proerythroblast, and basophilic erythroblast subsets in differentiation. Erythropoietin's primary effect is to promote the survival of red blood cell progenitors and precursors (which are located in the bone marrow of humans) by shielding them from apoptosis, or cell death.
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Erythropoietin is the main erythropoietic factor that works with a variety of other growth factors (such as IL-3, IL-6, glucocorticoids, and SCF) to help multipotent progenitors evolve into erythroid lineages. The burst-forming unit-erythroid (BFU-E) cells begin to express erythropoietin receptors and are erythropoietin responsive. The colony-forming unit erythroid (CFU-E) stage expresses the highest level of erythropoietin receptor density and is entirely reliant on erythropoietin for differentiation. Proerythroblasts and basophilic erythroblasts, which are precursors to red cells, express the erythropoietin receptor and are thus impaired by it.
Beyond erythropoiesis stimulation, erythropoietin has been shown to have a variety of actions, including vasoconstriction-dependent hypertension, angiogenesis stimulation, and cell survival through activation of EPO receptors, resulting in anti-apoptotic effects on ischemic tissues. However, several studies have shown that this proposal has little impact. It's also incongruent with the cells' low levels of EPO receptors.
Epogen/Procrit (epoetin alfa) and Aranesp are erythropoietin that are available for use as therapeutic agents and are developed using recombinant DNA technology in cell culture. They are used to treat anaemia caused by chronic kidney disease, chemotherapy-induced anaemia in cancer patients, and inflammatory bowel disease.
Recombinant Human Erythropoietin
Recombinant Erythropoietin
Recombinant DNA technology was used to manufacture recombinant human erythropoietin in vitro (outside the body). The purified recombinant hormone could help people with chronic renal failure who suffer from anaemia due to a lack of erythropoietin. The first hematopoietic growth factor to be produced for medicinal purposes is erythropoietin. In addition to treating anaemia caused by chronic renal failure, it is also used to treat anaemia caused by zidovudine (AZT) therapy in HIV patients. It can also aid in the reversal of anaemia in cancer patients who are undergoing chemotherapy. After strokes, recombinant human erythropoietin has also been used to stimulate or accelerate the development of neurons.
Erythropoietin Test
The primary purpose of the erythropoietin (EPO) test is to determine the cause of anaemia. A full blood count (CBC) with irregular findings, such as a low red blood cell (RBC) count, low haemoglobin, and low hematocrit, is normally followed up with an EPO examination. These tests aid in the diagnosis of anaemia and provide clues to the possible cause of the condition. Erythropoietin monitoring is used to see whether a lack of EPO is causing or exacerbating anaemia.
Erythropoietin Treatment
An EPO test can be ordered if you have chronic kidney disease to see if your kidneys are still producing enough erythropoietin. Testing will help you figure out whether you need erythropoietin replacement therapy. Erythropoietin replacement therapy can help increase red cell production in the bone marrow if the erythropoietin level is poor.
Did You Know?
Some athletes use synthetic erythropoietin as a "blood doping" agent. By increasing the count of RBCs in their blood, users hope to improve their stamina and oxygen capability. This type of drug use is risky, as it can cause hypertension and blood viscosity to rise. Most sports bodies, including the International Association of Athletics Federations, have banned its use, and erythropoietin is now being screened as part of the Olympic anti-doping programme.
FAQs on Erythropoietin (EPO): Definition, Functions & Importance
1. What is erythropoietin and what is its primary function in the body?
Erythropoietin, often abbreviated as EPO, is a glycoprotein hormone that plays a crucial role in the production of red blood cells (RBCs). Its primary function is to stimulate the process of erythropoiesis, which is the development and maturation of new red blood cells from progenitor cells in the red bone marrow.
2. Which organs are responsible for producing erythropoietin?
The production of erythropoietin primarily occurs in the kidneys. Specifically, the peritubular interstitial cells of the kidney are responsible for producing about 90% of the body's EPO. A smaller amount is also produced by the liver.
3. How does the body regulate the production of erythropoietin?
The body regulates erythropoietin production through a sensitive feedback mechanism based on oxygen levels. When the tissues, particularly in the kidneys, detect low oxygen levels (a condition called hypoxia), they are stimulated to produce and release more EPO. This increase in EPO leads to more red blood cells, which enhances the blood's oxygen-carrying capacity and corrects the hypoxia.
4. What are the biological consequences of having insufficient erythropoietin?
A deficiency in erythropoietin directly impairs the bone marrow's ability to produce an adequate number of red blood cells. This leads to anaemia, a condition characterized by a low RBC count. The consequences of this anaemia include:
- Fatigue and weakness
- Shortness of breath
- Pale skin
- Reduced oxygen delivery to organs and tissues
5. Why do individuals with chronic kidney disease often develop anaemia?
Individuals with chronic kidney disease often develop anaemia because the damaged kidneys lose their ability to produce sufficient amounts of erythropoietin. Since the kidneys are the main source of EPO, this failure leads to decreased stimulation of the bone marrow, resulting in reduced red blood cell production and causing what is known as 'anaemia of chronic disease'.
6. What does an abnormally high level of erythropoietin indicate?
An abnormally high level of erythropoietin is typically the body's response to chronic hypoxia. This can be caused by factors like living at high altitudes, chronic lung disease, or smoking. In some cases, certain tumours (especially kidney tumours) can produce excess EPO. The high EPO level leads to an overproduction of red blood cells, a condition called polycythemia, which can thicken the blood and increase the risk of clotting.
7. How does the mechanism of action of erythropoietin differ from that of thrombopoietin?
Both erythropoietin (EPO) and thrombopoietin (TPO) are hormones that regulate blood cell formation (haematopoiesis), but they target different cell lines.
- Erythropoietin specifically binds to receptors on erythroid progenitor cells in the bone marrow to stimulate the production of red blood cells (erythrocytes).
- Thrombopoietin, primarily produced by the liver, binds to receptors on megakaryocytes in the bone marrow to stimulate the production of platelets (thrombocytes).
8. Why is synthetic erythropoietin sometimes used in medical treatments?
Synthetic erythropoietin, known as recombinant human erythropoietin (rhEPO), is used medically to treat anaemia resulting from specific conditions. Its primary use is for patients with chronic kidney failure who cannot produce enough natural EPO. It is also used to treat anaemia caused by chemotherapy in cancer patients or by certain drugs used to treat HIV.
