Erythropoiesis
Encyclopedia
Red blood cell
Red blood cells are the most common type of blood cell and the vertebrate organism's principal means of delivering oxygen to the body tissues via the blood flow through the circulatory system...
s (erythrocytes) are produced. It is stimulated by decreased O2 in circulation, which is detected by the kidney
Kidney
The kidneys, organs with several functions, serve essential regulatory roles in most animals, including vertebrates and some invertebrates. They are essential in the urinary system and also serve homeostatic functions such as the regulation of electrolytes, maintenance of acid–base balance, and...
s, which then secrete the hormone erythropoietin
Erythropoietin
Erythropoietin, or its alternatives erythropoetin or erthropoyetin or EPO, is a glycoprotein hormone that controls erythropoiesis, or red blood cell production...
. This hormone stimulates proliferation and differentiation of red cell precursors, which activates increased erythropoiesis in the hemopoietic tissues, ultimately producing red blood cells. In postnatal
Postnatal
Postnatal is the period beginning immediately after the birth of a child and extending for about six weeks. Another term would be postpartum period, as it refers to the mother...
bird
Bird
Birds are feathered, winged, bipedal, endothermic , egg-laying, vertebrate animals. Around 10,000 living species and 188 families makes them the most speciose class of tetrapod vertebrates. They inhabit ecosystems across the globe, from the Arctic to the Antarctic. Extant birds range in size from...
s and mammal
Mammal
Mammals are members of a class of air-breathing vertebrate animals characterised by the possession of endothermy, hair, three middle ear bones, and mammary glands functional in mothers with young...
s (including humans), this usually occurs within the red bone marrow. In the early fetus, erythropoiesis takes place in the mesodermal cells of the yolk sac
Yolk sac
The yolk sac is a membranous sac attached to an embryo, providing early nourishment in the form of yolk in bony fishes, sharks, reptiles, birds, and primitive mammals...
. By the third or fourth month, erythropoiesis moves to the spleen and liver. After seven months, erythropoiesis occurs in the bone marrow. Decreased level of physical activity can cause an increase in erythropoiesis. However, in humans with certain diseases and in some animals, erythropoiesis also occurs outside the bone marrow, within the spleen
Spleen
The spleen is an organ found in virtually all vertebrate animals with important roles in regard to red blood cells and the immune system. In humans, it is located in the left upper quadrant of the abdomen. It removes old red blood cells and holds a reserve of blood in case of hemorrhagic shock...
or liver
Liver
The liver is a vital organ present in vertebrates and some other animals. It has a wide range of functions, including detoxification, protein synthesis, and production of biochemicals necessary for digestion...
. This is termed extramedullary erythropoiesis.
The bone marrow of essentially all the bones produces RBCs until a person is around five years old. The tibia
Tibia
The tibia , shinbone, or shankbone is the larger and stronger of the two bones in the leg below the knee in vertebrates , and connects the knee with the ankle bones....
and femur
Femur
The femur , or thigh bone, is the most proximal bone of the leg in tetrapod vertebrates capable of walking or jumping, such as most land mammals, birds, many reptiles such as lizards, and amphibians such as frogs. In vertebrates with four legs such as dogs and horses, the femur is found only in...
cease to be important sites of hematopoiesis by about age 25; the vertebrae, sternum, pelvis
Pelvis
In human anatomy, the pelvis is the lower part of the trunk, between the abdomen and the lower limbs .The pelvis includes several structures:...
and rib
Rib
In vertebrate anatomy, ribs are the long curved bones which form the rib cage. In most vertebrates, ribs surround the chest, enabling the lungs to expand and thus facilitate breathing by expanding the chest cavity. They serve to protect the lungs, heart, and other internal organs of the thorax...
s, and cranial bones continue to produce red blood cells throughout life.
Erythrocyte differentiation
In the process of red blood cell maturation, a cell undergoes a series of differentiationCellular differentiation
In developmental biology, cellular differentiation is the process by which a less specialized cell becomes a more specialized cell type. Differentiation occurs numerous times during the development of a multicellular organism as the organism changes from a simple zygote to a complex system of...
s. The following stages 1–7 of development all occur within the bone marrow
Bone marrow
Bone marrow is the flexible tissue found in the interior of bones. In humans, bone marrow in large bones produces new blood cells. On average, bone marrow constitutes 4% of the total body mass of humans; in adults weighing 65 kg , bone marrow accounts for approximately 2.6 kg...
:
- hemocytoblast a pluripotent hematopoietic stem cellStem cellThis article is about the cell type. For the medical therapy, see Stem Cell TreatmentsStem cells are biological cells found in all multicellular organisms, that can divide and differentiate into diverse specialized cell types and can self-renew to produce more stem cells...
- Common myeloid progenitor multipotent stem cell
- unipotent stem cell
- pronormoblast also commonly called proerythroblast or rubriblast.
- basophilic normoblast/early normoblast also commonly called erythroblast
- polychromatophilic normoblast/intermediate normoblast
- orthochromatic normoblast/late normoblast - Nucleus is Expelled before becoming a reticulocyte
- reticulocyteReticulocyteReticulocytes are immature red blood cells, typically composing about 1% of the red cells in the human body.Reticulocytes develop and mature in the red bone marrow and then circulate for about a day in the blood stream before developing into mature red blood cells. Like mature red blood cells,...
The cell is released from the bone marrow after stage 7, and so of circulating red blood cells there are ~1% reticulocytes. After 1–2 days these ultimately become "erythrocytes" or mature red blood cells.
These stages correspond to specific appearances of the cell when stained with Wright's stain
Wright's stain
Wright's stain is a histologic stain that facilitates the differentiation of blood cell types. It is used primarily to stain peripheral blood smears and bone marrow aspirates which are examined under a light microscope...
and examined by light microscopy, but correspond to other biochemical changes.
In the process of maturation a basophilic pronormoblast is converted from a cell with a large nucleus
Cell nucleus
In cell biology, the nucleus is a membrane-enclosed organelle found in eukaryotic cells. It contains most of the cell's genetic material, organized as multiple long linear DNA molecules in complex with a large variety of proteins, such as histones, to form chromosomes. The genes within these...
and a volume of 900 fL to an enucleated disc with a volume of 95 fL. By the reticulocyte stage, the cell has extruded its nucleus, but is still capable of producing hemoglobin.
Essentially important for the maturation of RBC'S are two vitamins B12
Vitamin B12
Vitamin B12, vitamin B12 or vitamin B-12, also called cobalamin, is a water-soluble vitamin with a key role in the normal functioning of the brain and nervous system, and for the formation of blood. It is one of the eight B vitamins...
and folic acid
Folic acid
Folic acid and folate , as well as pteroyl-L-glutamic acid, pteroyl-L-glutamate, and pteroylmonoglutamic acid are forms of the water-soluble vitamin B9...
. Lack of any one of these causes maturation failure in the process of erythropoiesis, which manifests clinically as reticulocytopenia
Reticulocytopenia
Reticulocytopenia, or "aplastic crisis", is the medical term for an abnormal decrease of reticulocytes in the body. Reticulocytopenia can originate from congenital hemolytic anemia, especially when exacerbated by Parvovirus B19 infection...
, an abnormally low amount of reticulocytes.
Characteristics seen in erythrocytes during erythropoiesis
The following characteristics can be seen changing in the erythrocytes when they are maturing:- They show a reduction in the cell size;
- The cytoplasmic matrix increases in amount;
- Staining reaction of the cytoplasm changes from blue to pinkish red (this is because of the decrease in the amount of RNARNARibonucleic acid , or RNA, is one of the three major macromolecules that are essential for all known forms of life....
and DNADNADeoxyribonucleic acid is a nucleic acid that contains the genetic instructions used in the development and functioning of all known living organisms . The DNA segments that carry this genetic information are called genes, but other DNA sequences have structural purposes, or are involved in...
); - Initially the nucleus was large in size and contained open chromatin. But with the maturation of RBC's the size of the nucleus decreases and finally disappears with the condensation of the chromatin material.
Regulation of erythropoiesis
A feedback loop involving erythropoietinErythropoietin
Erythropoietin, or its alternatives erythropoetin or erthropoyetin or EPO, is a glycoprotein hormone that controls erythropoiesis, or red blood cell production...
helps regulate the process of erythropoiesis so that, in non-disease states, the production of red blood cells is equal to the destruction of red blood cells and the red blood cell number is sufficient to sustain adequate tissue oxygen levels but not so high as to cause sludging, thrombosis
Thrombosis
Thrombosis is the formation of a blood clot inside a blood vessel, obstructing the flow of blood through the circulatory system. When a blood vessel is injured, the body uses platelets and fibrin to form a blood clot to prevent blood loss...
, or stroke
Stroke
A stroke, previously known medically as a cerebrovascular accident , is the rapidly developing loss of brain function due to disturbance in the blood supply to the brain. This can be due to ischemia caused by blockage , or a hemorrhage...
. Erythropoietin is produced in the kidney and liver in response to low oxygen levels. In addition, erythropoietin is bound by circulating red blood cells; low circulating numbers lead to a relatively high level of unbound erythropoietin, which stimulates production in the bone marrow.
Recent studies have also shown that the peptide hormone hepcidin
Hepcidin
Hepcidin is a peptide hormone produced by the liver. It was discovered in 2000, and appears to be the master regulator of iron homeostasis in humans and other mammals. In humans, HAMP is the gene that encodes for hepcidin.-Structure:...
may play a role in the regulation of hemoglobin production, and thus affect erythropoiesis. The liver produces hepcidin. Hepcidin controls iron absorption in the gastrointestinal tract and iron release from reticuloendothelial tissue. Iron must be released from macrophages in the bone marrow to be incorporated into the heme group of hemoglobin
Hemoglobin
Hemoglobin is the iron-containing oxygen-transport metalloprotein in the red blood cells of all vertebrates, with the exception of the fish family Channichthyidae, as well as the tissues of some invertebrates...
in erythrocytes.
There are colony forming units that the cells follow during their formation. These cells are referred to as the committed cells including the granulocyte monocyte colony forming units
Also, loss of function of the erythropoietin receptor or JAK2 in mice cells causes failure in erythropoiesis, so production of red blood cells in embryos and growth is disrupted.
Also, if there is no feedback inhibition, such as SOCS (Suppressors of Cytokine Signaling) proteins in the system, that would cause giantism in mice.
See also
- AnemiaAnemiaAnemia is a decrease in number of red blood cells or less than the normal quantity of hemoglobin in the blood. However, it can include decreased oxygen-binding ability of each hemoglobin molecule due to deformity or lack in numerical development as in some other types of hemoglobin...
: a condition with an abnormally low level of functional haemoglobin - PolycythemiaPolycythemiaPolycythemia is a disease state in which the proportion of blood volume that is occupied by red blood cells increases...
: a condition with an abnormally high level of red blood cells