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[[Image:LH Developing Erythrocyte Histology.jpg|right|thumb|200px|'''Developing erythrocytes''' ©RVC 2008]]
==Introduction==
==Introduction==
[[Erythrocytes|Erythrocytes]] contain no nucleus and are thus only produced from stem cells. During the fetal stage production is in both the [[Liver - Anatomy & Physiology|liver]] and [[Spleen - Anatomy & Physiology|spleen]] however production is transferred to the [[Bone Marrow - Anatomy & Physiology|bone marrow]] ([[Bone Marrow - Anatomy & Physiology#Red marrow|red marrow]]) in the final stages of gestation. Initially erythropoiesis occurs in all bones, however after puberty production is limited to membranous bones (ribs, vertebrae, pelvic bones etc.) as in the long bones adipose tissue replaces red marrow.
[[Erythrocytes|Erythrocytes]] contain no nucleus and are thus only produced from stem cells. During the fetal stage production is in both the [[Liver - Anatomy & Physiology|liver]] and [[Spleen - Anatomy & Physiology|spleen]] however production is transferred to the [[Bone Marrow - Anatomy & Physiology|bone marrow]] ([[Bone Marrow - Anatomy & Physiology#Red marrow|red marrow]]) in the final stages of gestation. Initially erythropoiesis occurs in all bones, however after puberty production is limited to membranous bones (ribs, vertebrae, pelvic bones etc.) as the long bones contain adipose tissue in place of red marrow.
Erythrocyte stem cells contain no haemoglobin and it is only after a few cell divisions that pro-erythrocyte haemoglobin starts to enter the cells. When the haemoglobin levels are at the correct concentration the nucleus reduces in size and is removed from cell. Cells at this stage still have ribosomes and other organelles and stain differently to mature erythrocytes. They are called reticulocytes. Reticulocytes contain some RNA and continue to produce haemoglobin. After a few days these mature having reached a final haemoglobin concentration of 34%.
Erythrocyte stem cells contain no haemoglobin and it is only after several cell divisions that pro-erythrocyte haemoglobin starts to be generated within the cells. When the haemoglobin levels are at the correct concentration the nucleus reduces in size and is removed from cell. Cells at this stage still have ribosomes and other organelles and stain differently to mature erythrocytes; they are known as '''reticulocytes'''. After a few days these mature having reached a final haemoglobin concentration of 34%.
Reticulocytes and mature [[Erythrocytes|erythrocytes]] leave the [[Bone Marrow - Anatomy & Physiology|bone marrow]] by ‘squeezing’ through the capillary endothelial cells. Precursors to these stages cannot change shape and therefore remain confined to the bone marrow.
==Development==
==Development==
[[Erythrocytes|Erythrocyte]] development is divided into several stages and at each stage the cell will divide several times. As [[Bone Marrow - Anatomy & Physiology|bone marrow]] does not act as storage, all erythrocytes produced are immediately released into the circulation.
[[Erythrocytes|Erythrocyte]] development is divided into several stages and at each stage the cell will divide several times. As bone marrow does not act as storage, all erythrocytes produced are immediately released into the circulation.
===Stem cell ===
===Stem cell ===
Stem cells give rise to precursors which eventually mature to form the fully developed erythrocyte.
Initially, the multipotential myeloid stem cell ([[Haematopoiesis - Overview#Colony Forming Units|CFU-GEMM]]) differentiates into the erythroid CFU ([[Haematopoiesis - Overview#Colony Forming Units|CFU-E]]). This develops into the first erythrocyte precursor, the proerythroblast.
The development process is controlled and influenced by a number of different factors including erythropoietin, IL-3, IL-4 and granulocyte-macrophage colony stimulating factor (GM-CSF).
===Nomenclature===
===Nomenclature===
The naming of the stages of the erythrocyte precursors varies.
The naming of the stages of the erythrocyte precursors varies.
The main headings for this section refer to each stage in terms of a histological description. Proerythroblast, basophilic erythroblast, polychromatic erythroblast, orthochromatic erythroblast and polychromatophilic erythrocyte.
The main headings for this section refer to each stage in terms of a histological description, namely the proerythroblast, basophilic erythroblast, polychromatic erythroblast, orthochromatic erythroblast and polychromatophilic erythrocyte.
Another classification of the stages is based upon the [[Haematopoiesis - Overview#Colony Forming Units|CFU-E]] being referred to as ‘rubri’. This system gives all developing blood cell lineages similar names. For example the first stage for erythrocytes is referred to as a [rubri]blast and the first stage for lymphocytes is called a [lympho]blast. The stages for the erythrocyte are rubriblast, prorubriblast, rubricyte and metarubricye.
Another classification of the stages is based upon the [[Haematopoiesis - Overview#Colony Forming Units|CFU-E]] being referred to as ‘rubri’. This system gives all developing blood cell lineages similar names. For example the first stage for erythrocytes is referred to as a [rubri]blast and the first stage for lymphocytes is called a [lympho]blast. The stages for the erythrocyte are rubriblast, prorubriblast, rubricyte and metarubricye.
Finally the stages can also be named according to the development of the normoblast stage. This gives the stages pronormoblast, early normoblast, intermediate normoblast, late normoblast, polychromatic cell.
Finally the stages can also be named according to the development of the normoblast stage. This gives the stages pronormoblast, early normoblast, intermediate normoblast, late normoblast, polychromatic cell.
===Stages===
===Stages of Development===
[[Image:Erythropoiesis pathway.jpg|right|thumb|100px|'''Erythropoiesis pathway''']]
[[Image:Erythropoiesis pathway.jpg|right|thumb|175px|'''Erythropoiesis pathway''']]
====Proerythroblast====
====Proerythroblast====
The first [[Erythrocytes|erythrocyte]] precursor produced directly from the [[Haematopoiesis - Overview#Colony Forming Units|CFU-GEMM]] under the influence of erythropoietin. It has a large nucleus with free ribosomes in the cytoplasm giving the cytoplasm a basophilic appearance.
The first [[Erythrocytes|erythrocyte]] precursor produced directly from the [[Haematopoiesis - Overview#Colony Forming Units|CFU-GEMM]] under the influence of erythropoietin. It has a large nucleus with free ribosomes in the cytoplasm giving the cytoplasm a basophilic appearance.
==Nutritional factors==
==Nutritional factors==
Normal [[Erythrocytes|erythrocyte]] production requires protein, copper, iron, folic acid and vitamins B6 and B12. Deficiencies lead to inadequate production of haemoglobin.
Normal erythrocyte production requires protein, copper, iron, folic acid and vitamins B6 and B12. Deficiencies lead to inadequate production of haemoglobin.
===Iron===
===Iron===
Iron is found within each haem component of haemoglobin and binds oxygen.
Iron is found within each haem component of haemoglobin and binds oxygen.
===Folic acid and vitamin B12===
===Folic acid and vitamin B12===
These elements are required for DNA synthesis and are important for the formation of new erythrocytes. Deficiencies leads to the formation of '''macrocytes''', which are enlarged erythrocytes with a higher than normal mean corpuscular volume (MCV).
==Regulation==
==Regulation==
Production of [[Erythrocytes|erythrocytes]] is regulated by '''erythropoietin''' (EPO) which is produced in the yolk sac, [[Liver - Anatomy & Physiology|liver]] and kidney from embryonic life until early neonatal life. In the adult it is produced in the kidneys. Erythropoietin is a glycoprotein hormone and acts under a negative feedback. Levels are normally kept low with sufficient amounts to maintain production of enough new erythrocytes. However, as the blood oxygen concentration decreases, the release of erythropoietin increases.
Production of [[Erythrocytes|erythrocytes]] is regulated by '''erythropoietin''' (EPO) which is produced in the yolk sac, [[Liver - Anatomy & Physiology|liver]] and kidney from embryonic life until early neonatal life. In the adult it is produced only in the kidneys. Erythropoietin is a glycoprotein hormone and is controled by a negative feedback mechanism. Normal levels are low with sufficient amounts to maintain a basal level of new erythrocyte production. If blood oxygen concentration falls, the release of erythropoietin rises.
EPO is transported from kidneys to [[Bone Marrow - Anatomy & Physiology|bone marrow]] where it acts upon receptors on the CFU-E’s and causes differentiation into erythrocyte precursors. It also increases the rate of division and maturation of the developing erythrocyte precursors by increasing gene transcription. Thus it is not the number of [[Erythrocytes|erythrocytes]] but the oxygen concentration that regulates its release. EPO release can be affected by any form of renal pathology.
EPO is transported from kidneys to [[Bone Marrow - Anatomy & Physiology|bone marrow]] where it acts upon receptors on the CFU-E’s and causes differentiation into erythrocyte precursors. It also increases the rate of division and maturation of developing erythrocyte precursors by increasing the rate of gene transcription. Thus it is not the number of [[Erythrocytes|erythrocytes]] but the oxygen concentration that controls erythrocyte numbers. EPO release can be affected by any form of renal pathology. Inflammatory induced release of interleukins reduces the secretion of erythropoietin.
The mechanism of oxygen concentration detection is via HIF-1 (hypoxia inducible factor 1) which is a transcription activator that is oxygen sensitive.
[[Category:Haematopoiesis]]
[[Category:Haematopoiesis]]