Erythropoietin Production and Tests
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Published: Fri, 01 Jun 2018
EPO is produced mainly by peritubular fibroblasts of the renal cortex. It is synthesized by renal peritubular cells in adults, with a small amount being produced in the liver. Regulation is believed to rely on a feed-back mechanism measuring blood oxygenation. Constitutively synthesized transcription factors for EPO, known as hypoxia-inducible factors (HIFs), are hydroxylated and proteosomally digested in the presence of oxygen. It binds to the erythropoietin receptor (EpoR) on the red cell surface and activates a JAK2 cascade. This receptor is also found in a large number of tissues such as bone marrow cells and peripheral/central nerve cells, many of which activate intracellular biological pathways upon binding with Epo.
Primary role in red cell blood line
Erythropoietin has its primary effect on red blood cells by promoting red blood cell survival through protecting these cells from apoptosis. It also cooperates with various growth factors involved in the development of precursor red cells. Specifically, the colony forming unit-erythroid (CFU-E) is completely dependent on erythropoietin. The burst forming unit-erythroid (BFU-E) is also responsive to erythropoietin.
Under hypoxic conditions, the kidney will produce and secrete erythropoietin to increase the production of red blood cells by targeting CFU-E.
It has a range of actions including vasoconstriction-dependent hypertension, stimulating angiogenesis, and inducing proliferation of smooth muscle fibers.
Erythropoietin is available as a therapeutic agent produced by recombinant DNA technology in mammalian cell culture. It is used in treating anaemia resulting from chronic kidney disease and myelodysplasia, from the treatment of cancer (chemotherapy and radiation), and from other critical illnesses (heart failure).
Erythropoietin (EPO) is a hormone produced by the kidney that promotes the formation of red blood cells by the bone marrow.
The kidney cells that make erythropoietin are specialized so that they are sensitive to low oxygen levels in the blood that travels through the kidney. These cells make and release erythropoietin when the oxygen level is too low. The low oxygen level may indicate anemia, a diminished number of red blood cells, or hemoglobin molecules that carry oxygen through the body.
Chemically, what is erythropoietin (EPO)?
Erythropoietin is a protein with an attached sugar (a glycoprotein). It is one of a number of similar glycoproteins that serve as stimulants for the growth of specific types of blood cells in the bone marrow.
What exactly does erythropoietin (EPO) do?
Erythropoietin stimulates the bone marrow to produce more red blood cells. The resultant rise in red cells increases the oxygen-carrying capacity of the blood.
As the prime regulator of red cell production, erythropoietin’s major functions are to:
Promote the development of red blood cells.
Initiate the synthesis of hemoglobin, the molecule within red blood cells that transports oxygen.
Is the kidney the sole source of erythropoietin?
No. Erythropoietin is produced to a lesser extent by the liver. Only about 10% of the erythropoietin is produced in the liver. The erythropoietin gene has been found on human chromosome 7 (in band 7q21). Different DNA sequences flanking the erythropoietin gene act to control liver versus kidney production of erythropoietin.
Why is an erythropoietin test performed?
The erythropoietin hormone can be detected and measured in the blood. The level of erythropoietin in the blood can indicate bone marrow disorders, (such as polycythemia, or increased red blood cell production) kidney disease, or erythropoietin abuse. Testing erythropoietin blood levels is thus of value if:
Too little erythropoietin might be responsible for too few red blood cells (such as in evaluating anemia, especially anemia related to kidney disease).
Too much erythropoietin might be causing too many red blood cells (polycythemia).
Too much erythropoietin might be evidence for a kidney tumor.
Too much erythropoietin in an athlete may suggest erythropoietin abuse.
How is the erythropoietin test performed?
The patient is usually asked to fast for 8-10 hours (overnight) and sometimes to lie quietly and relax for 20 or 30 minutes before the test. The test requires a routine sample of blood, which is sent to the laboratory for analysis.
What are normal erythropoietin levels?
Normal levels of erythropoietin range from 4 up to 24 mU/ml (milliunits per milliliter).
What does an abnormal erythropoietin level indicate?
Lower than normal values of erythropoietin are seen, for example, in anemia due to chronic (longstanding) kidney failure.
Elevated erythropoietin levels can be seen, for example, in polycythemia rubra vera, a disorder characterized by an excess of red blood cells.
The correct interpretation of an abnormal erythropoietin level depends on the particular clinical situation.
Can a person without a medical disease or condition have a high erythropoietin level?
Yes. For example, erythropoietin has been misused as a performance-enhancing drug in athletes such as cyclists (in the Tour de France), long-distance runners, speed skaters, and Nordic (cross-country) skiers. When misused in such situations, erythropoietin is thought to be especially dangerous (perhaps because dehydration due to vigorous exercise can further increase the thickness (viscosity) of the blood, raising the risk for heart attacks and strokes. Erythropoietin has been banned by the Tour de France, the Olympics, and other sports organizations.
Is erythropoietin available as a prescribed medication?
Yes. Using recombinant DNA technology, erythropoietin has been synthetically produced for use as a treatment for persons with certain types of anemia. Erythropoietin can be used to correct anemia by stimulating red blood cell production in the bone marrow in these conditions. The medication is known as epoetin alfa (Epogen, Procrit). It can be given as an injection intravenously (into a vein) or subcutaneously (under the skin).
What are the clinical uses of erythropoietin?
Erythropoietin [epoetin alfa (Epogen, Procrit)] is used in many clinical settings. The most common use is in people with anemia (low blood count) related to kidney dysfunction. When the kidneys are not properly functioning, they produce less than normal amounts of erythropoietin, which can lead to low red blood cell production, or anemia. Therefore, by replacing the erythropoietin with an injection of synthetic erythropoietin, anemia related to kidney disease may be treated. Currently, Epogen or Procrit is a standard part of therapy in patients with kidney disease who require dialysis to both treat and prevent anemia.
Other uses of erythropoietin may include treatment of anemia related to the medication AZT (used to treat AIDS) and anemia associated with cancer.
Erythropoietin At A Glance
- Erythropoietin (EPO) is a hormone produced by the kidney.
- Erythropoietin promotes the formation of red blood cells by the bone marrow.
- The erythropoietin hormone level can be detected and measured in the blood (the EPO test).
- Measurement of the blood erythropoietin level can be used to detect certain conditions.
- Erythropoietin can be synthesized and used as a treatment of some forms of anemia.
- Erythropoietin has been misused as a performance-enhancing drug by some athletes.
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