Red blood cell

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Red blood cell_table_infobox_0

Red blood cellRed blood cell_header_cell_0_0_0
DetailsRed blood cell_header_cell_0_1_0
FunctionRed blood cell_header_cell_0_2_0 Oxygen transportRed blood cell_cell_0_2_1
IdentifiersRed blood cell_header_cell_0_3_0
Acronym(s)Red blood cell_header_cell_0_4_0 RBCRed blood cell_cell_0_4_1
MeSHRed blood cell_header_cell_0_5_0 Red blood cell_cell_0_5_1
THRed blood cell_header_cell_0_6_0 Red blood cell_cell_0_6_1
FMARed blood cell_header_cell_0_7_0 Red blood cell_cell_0_7_1

Red blood cells (RBCs), also referred to as red cells, red blood corpuscles (in humans or other animals not having nucleus in red blood cells), haematids, erythroid cells or erythrocytes (from Greek erythros for "red" and kytos for "hollow vessel", with -cyte translated as "cell" in modern usage), are the most common type of blood cell and the vertebrate's principal means of delivering oxygen (O2) to the body tissues—via blood flow through the circulatory system. Red blood cell_sentence_0

RBCs take up oxygen in the lungs, or in fish the gills, and release it into tissues while squeezing through the body's capillaries. Red blood cell_sentence_1

The cytoplasm of erythrocytes is rich in hemoglobin, an iron-containing biomolecule that can bind oxygen and is responsible for the red color of the cells and the blood. Red blood cell_sentence_2

Each human red blood cell contains approximately 270 million of these hemoglobin molecules. Red blood cell_sentence_3

The cell membrane is composed of proteins and lipids, and this structure provides properties essential for physiological cell function such as deformability and stability while traversing the circulatory system and specifically the capillary network. Red blood cell_sentence_4

In humans, mature red blood cells are flexible and oval biconcave disks. Red blood cell_sentence_5

They lack a cell nucleus and most organelles, in order to accommodate maximum space for hemoglobin; they can be viewed as sacks of hemoglobin, with a plasma membrane as the sack. Red blood cell_sentence_6

Approximately 2.4 million new erythrocytes are produced per second in human adults. Red blood cell_sentence_7

The cells develop in the bone marrow and circulate for about 100–120 days in the body before their components are recycled by macrophages. Red blood cell_sentence_8

Each circulation takes about 60 seconds (one minute). Red blood cell_sentence_9

Approximately 84% of the cells in the human body are 20–30 trillion red blood cells. Red blood cell_sentence_10

Nearly half of the blood's volume (40% to 45%) is red blood cells. Red blood cell_sentence_11

Packed red blood cells (pRBC) are red blood cells that have been donated, processed, and stored in a blood bank for blood transfusion. Red blood cell_sentence_12

Structure Red blood cell_section_0

Vertebrates Red blood cell_section_1

Almost all vertebrates, including all mammals and humans, have red blood cells. Red blood cell_sentence_13

Red blood cells are cells present in blood in order to transport oxygen. Red blood cell_sentence_14

The only known vertebrates without red blood cells are the crocodile icefish (family Channichthyidae); they live in very oxygen-rich cold water and transport oxygen freely dissolved in their blood. Red blood cell_sentence_15

While they no longer use hemoglobin, remnants of hemoglobin genes can be found in their genome. Red blood cell_sentence_16

Vertebrate red blood cells consist mainly of hemoglobin, a complex metalloprotein containing heme groups whose iron atoms temporarily bind to oxygen molecules (O2) in the lungs or gills and release them throughout the body. Red blood cell_sentence_17

Oxygen can easily diffuse through the red blood cell's cell membrane. Red blood cell_sentence_18

Hemoglobin in the red blood cells also carries some of the waste product carbon dioxide back from the tissues; most waste carbon dioxide, however, is transported back to the pulmonary capillaries of the lungs as bicarbonate (HCO3) dissolved in the blood plasma. Red blood cell_sentence_19

Myoglobin, a compound related to hemoglobin, acts to store oxygen in muscle cells. Red blood cell_sentence_20

The color of red blood cells is due to the heme group of hemoglobin. Red blood cell_sentence_21

The blood plasma alone is straw-colored, but the red blood cells change color depending on the state of the hemoglobin: when combined with oxygen the resulting oxyhemoglobin is scarlet, and when oxygen has been released the resulting deoxyhemoglobin is of a dark red burgundy color. Red blood cell_sentence_22

However, blood can appear bluish when seen through the vessel wall and skin. Red blood cell_sentence_23

Pulse oximetry takes advantage of the hemoglobin color change to directly measure the arterial blood oxygen saturation using colorimetric techniques. Red blood cell_sentence_24

Hemoglobin also has a very high affinity for carbon monoxide, forming carboxyhemoglobin which is a very bright red in color. Red blood cell_sentence_25

Flushed, confused patients with a saturation reading of 100% on pulse oximetry are sometimes found to be suffering from carbon monoxide poisoning. Red blood cell_sentence_26

Having oxygen-carrying proteins inside specialized cells (as opposed to oxygen carriers being dissolved in body fluid) was an important step in the evolution of vertebrates as it allows for less viscous blood, higher concentrations of oxygen, and better diffusion of oxygen from the blood to the tissues. Red blood cell_sentence_27

The size of red blood cells varies widely among vertebrate species; red blood cell width is on average about 25% larger than capillary diameter, and it has been hypothesized that this improves the oxygen transfer from red blood cells to tissues. Red blood cell_sentence_28

Mammals Red blood cell_section_2

The red blood cells of mammals are typically shaped as biconcave disks: flattened and depressed in the center, with a dumbbell-shaped cross section, and a torus-shaped rim on the edge of the disk. Red blood cell_sentence_29

This shape allows for a high surface-area-to-volume (SA/V) ratio to facilitate diffusion of gases. Red blood cell_sentence_30

However, there are some exceptions concerning shape in the artiodactyl order (even-toed ungulates including cattle, deer, and their relatives), which displays a wide variety of bizarre red blood cell morphologies: small and highly ovaloid cells in llamas and camels (family Camelidae), tiny spherical cells in mouse deer (family Tragulidae), and cells which assume fusiform, lanceolate, crescentic, and irregularly polygonal and other angular forms in red deer and wapiti (family Cervidae). Red blood cell_sentence_31

Members of this order have clearly evolved a mode of red blood cell development substantially different from the mammalian norm. Red blood cell_sentence_32

Overall, mammalian red blood cells are remarkably flexible and deformable so as to squeeze through tiny capillaries, as well as to maximize their apposing surface by assuming a cigar shape, where they efficiently release their oxygen load. Red blood cell_sentence_33

Red blood cells in mammals are unique amongst vertebrates as they do not have nuclei when mature. Red blood cell_sentence_34

They do have nuclei during early phases of erythropoiesis, but extrude them during development as they mature; this provides more space for hemoglobin. Red blood cell_sentence_35

The red blood cells without nuclei, called reticulocytes, subsequently lose all other cellular organelles such as their mitochondria, Golgi apparatus and endoplasmic reticulum. Red blood cell_sentence_36

The spleen acts as a reservoir of red blood cells, but this effect is somewhat limited in humans. Red blood cell_sentence_37

In some other mammals such as dogs and horses, the spleen sequesters large numbers of red blood cells, which are dumped into the blood during times of exertion stress, yielding a higher oxygen transport capacity. Red blood cell_sentence_38

Human Red blood cell_section_3

A typical human red blood cell has a disk diameter of approximately 6.2–8.2 µm and a thickness at the thickest point of 2–2.5 µm and a minimum thickness in the centre of 0.8–1 µm, being much smaller than most other human cells. Red blood cell_sentence_39

These cells have an average volume of about 90 fL with a surface area of about 136 μm, and can swell up to a sphere shape containing 150 fL, without membrane distension. Red blood cell_sentence_40

Adult humans have roughly 20–30 trillion red blood cells at any given time, constituting approximately 70% of all cells by number. Red blood cell_sentence_41

Women have about 4–5 million red blood cells per microliter (cubic millimeter) of blood and men about 5–6 million; people living at high altitudes with low oxygen tension will have more. Red blood cell_sentence_42

Red blood cells are thus much more common than the other blood particles: there are about 4,000–11,000 white blood cells and about 150,000–400,000 platelets per microliter. Red blood cell_sentence_43

Human red blood cells take on average 60 seconds to complete one cycle of circulation. Red blood cell_sentence_44

The blood's red color is due to the spectral properties of the hemic iron ions in hemoglobin. Red blood cell_sentence_45

Each hemoglobin molecule carries four heme groups; hemoglobin constitutes about a third of the total cell volume. Red blood cell_sentence_46

Hemoglobin is responsible for the transport of more than 98% of the oxygen in the body (the remaining oxygen is carried dissolved in the blood plasma). Red blood cell_sentence_47

The red blood cells of an average adult human male store collectively about 2.5 grams of iron, representing about 65% of the total iron contained in the body. Red blood cell_sentence_48

Microstructure Red blood cell_section_4

Nucleus Red blood cell_section_5

Red blood cells in mammals anucleate when mature, meaning that they lack a cell nucleus. Red blood cell_sentence_49

In comparison, the red blood cells of other vertebrates have nuclei; the only known exceptions are salamanders of the genus Batrachoseps and fish of the genus Maurolicus. Red blood cell_sentence_50

The elimination of the nucleus in vertebrate red blood cells has been offered as an explanation for the subsequent accumulation of non-coding DNA in the genome. Red blood cell_sentence_51

The argument runs as follows: Efficient gas transport requires red blood cells to pass through very narrow capillaries, and this constrains their size. Red blood cell_sentence_52

In the absence of nuclear elimination, the accumulation of repeat sequences is constrained by the volume occupied by the nucleus, which increases with genome size. Red blood cell_sentence_53

Nucleated red blood cells in mammals consist of two forms: normoblasts, which are normal erythropoietic precursors to mature red blood cells, and megaloblasts, which are abnormally large precursors that occur in megaloblastic anemias. Red blood cell_sentence_54

Membrane composition Red blood cell_section_6

Red blood cells are deformable, flexible, are able to adhere to other cells, and are able to interface with immune cells. Red blood cell_sentence_55

Their membrane plays many roles in this. Red blood cell_sentence_56

These functions are highly dependent on the membrane composition. Red blood cell_sentence_57

The red blood cell membrane is composed of 3 layers: the glycocalyx on the exterior, which is rich in carbohydrates; the lipid bilayer which contains many transmembrane proteins, besides its lipidic main constituents; and the membrane skeleton, a structural network of proteins located on the inner surface of the lipid bilayer. Red blood cell_sentence_58

Half of the membrane mass in human and most mammalian red blood cells are proteins. Red blood cell_sentence_59

The other half are lipids, namely phospholipids and cholesterol. Red blood cell_sentence_60

Membrane lipids Red blood cell_section_7

The red blood cell membrane comprises a typical lipid bilayer, similar to what can be found in virtually all human cells. Red blood cell_sentence_61

Simply put, this lipid bilayer is composed of cholesterol and phospholipids in equal proportions by weight. Red blood cell_sentence_62

The lipid composition is important as it defines many physical properties such as membrane permeability and fluidity. Red blood cell_sentence_63

Additionally, the activity of many membrane proteins is regulated by interactions with lipids in the bilayer. Red blood cell_sentence_64

Unlike cholesterol, which is evenly distributed between the inner and outer leaflets, the 5 major phospholipids are asymmetrically disposed, as shown below: Red blood cell_sentence_65

Outer monolayer Red blood cell_sentence_66

Red blood cell_unordered_list_0

Inner monolayer Red blood cell_sentence_67

Red blood cell_unordered_list_1

This asymmetric phospholipid distribution among the bilayer is the result of the function of several energy-dependent and energy-independent phospholipid transport proteins. Red blood cell_sentence_68

Proteins called “Flippases” move phospholipids from the outer to the inner monolayer, while others called “floppases” do the opposite operation, against a concentration gradient in an energy-dependent manner. Red blood cell_sentence_69

Additionally, there are also “scramblase” proteins that move phospholipids in both directions at the same time, down their concentration gradients in an energy-independent manner. Red blood cell_sentence_70

There is still considerable debate ongoing regarding the identity of these membrane maintenance proteins in the red cell membrane. Red blood cell_sentence_71

The maintenance of an asymmetric phospholipid distribution in the bilayer (such as an exclusive localization of PS and PIs in the inner monolayer) is critical for the cell integrity and function due to several reasons: Red blood cell_sentence_72

Red blood cell_unordered_list_2

  • Macrophages recognize and phagocytose red cells that expose PS at their outer surface. Thus the confinement of PS in the inner monolayer is essential if the cell is to survive its frequent encounters with macrophages of the reticuloendothelial system, especially in the spleen.Red blood cell_item_2_5
  • Premature destruction of thallassemic and sickle red cells has been linked to disruptions of lipid asymmetry leading to exposure of PS on the outer monolayer.Red blood cell_item_2_6
  • An exposure of PS can potentiate adhesion of red cells to vascular endothelial cells, effectively preventing normal transit through the microvasculature. Thus it is important that PS is maintained only in the inner leaflet of the bilayer to ensure normal blood flow in microcirculation.Red blood cell_item_2_7
  • Both PS and phosphatidylinositol 4,5-bisphosphate (PIP2) can regulate membrane mechanical function, due to their interactions with skeletal proteins such as spectrin and protein 4.1R. Recent studies have shown that binding of spectrin to PS promotes membrane mechanical stability. PIP2 enhances the binding of protein band 4.1R to glycophorin C but decreases its interaction with protein band 3, and thereby may modulate the linkage of the bilayer to the membrane skeleton.Red blood cell_item_2_8

The presence of specialized structures named "lipid rafts" in the red blood cell membrane have been described by recent studies. Red blood cell_sentence_73

These are structures enriched in cholesterol and sphingolipids associated with specific membrane proteins, namely flotillins, stomatins (band 7), G-proteins, and β-adrenergic receptors. Red blood cell_sentence_74

Lipid rafts that have been implicated in cell signaling events in nonerythroid cells have been shown in erythroid cells to mediate β2-adregenic receptor signaling and increase cAMP levels, and thus regulating entry of malarial parasites into normal red cells. Red blood cell_sentence_75

Membrane proteins Red blood cell_section_8

The proteins of the membrane skeleton are responsible for the deformability, flexibility and durability of the red blood cell, enabling it to squeeze through capillaries less than half the diameter of the red blood cell (7–8 μm) and recovering the discoid shape as soon as these cells stop receiving compressive forces, in a similar fashion to an object made of rubber. Red blood cell_sentence_76

There are currently more than 50 known membrane proteins, which can exist in a few hundred up to a million copies per red blood cell. Red blood cell_sentence_77

Approximately 25 of these membrane proteins carry the various blood group antigens, such as the A, B and Rh antigens, among many others. Red blood cell_sentence_78

These membrane proteins can perform a wide diversity of functions, such as transporting ions and molecules across the red cell membrane, adhesion and interaction with other cells such as endothelial cells, as signaling receptors, as well as other currently unknown functions. Red blood cell_sentence_79

The blood types of humans are due to variations in surface glycoproteins of red blood cells. Red blood cell_sentence_80

Disorders of the proteins in these membranes are associated with many disorders, such as hereditary spherocytosis, hereditary elliptocytosis, hereditary stomatocytosis, and paroxysmal nocturnal hemoglobinuria. Red blood cell_sentence_81

The red blood cell membrane proteins organized according to their function: Red blood cell_sentence_82

Transport Red blood cell_sentence_83

Red blood cell_unordered_list_3

Cell adhesion Red blood cell_sentence_84

Red blood cell_unordered_list_4

Structural role – The following membrane proteins establish linkages with skeletal proteins and may play an important role in regulating cohesion between the lipid bilayer and membrane skeleton, likely enabling the red cell to maintain its favorable membrane surface area by preventing the membrane from collapsing (vesiculating). Red blood cell_sentence_85

Red blood cell_unordered_list_5

  • Ankyrin-based macromolecular complex – proteins linking the bilayer to the membrane skeleton through the interaction of their cytoplasmic domains with Ankyrin.Red blood cell_item_5_23
    • Band 3 – also assembles various glycolytic enzymes, the presumptive CO2 transporter, and carbonic anhydrase into a macromolecular complex termed a "metabolon," which may play a key role in regulating red cell metabolism and ion and gas transport function.Red blood cell_item_5_24
    • RhAG – also involved in transport, defines associated unusual blood group phenotype Rhmod.Red blood cell_item_5_25
  • Protein 4.1R-based macromolecular complex – proteins interacting with Protein 4.1R.Red blood cell_item_5_26
    • Protein 4.1R – weak expression of Gerbich antigens;Red blood cell_item_5_27
    • Glycophorin C and D – glycoprotein, defines Gerbich Blood Group;Red blood cell_item_5_28
    • XK – defines the Kell Blood Group and the Mcleod unusual phenotype (lack of Kx antigen and greatly reduced expression of Kell antigens);Red blood cell_item_5_29
    • RhD/RhCE – defines Rh Blood Group and the associated unusual blood group phenotype Rhnull;Red blood cell_item_5_30
    • Duffy protein – has been proposed to be associated with chemokine clearance;Red blood cell_item_5_31
    • Adducin – interaction with band 3;Red blood cell_item_5_32
    • Dematin- interaction with the Glut1 glucose transporter.Red blood cell_item_5_33

Surface electrostatic potential Red blood cell_section_9

The zeta potential is an electrochemical property of cell surfaces that is determined by the net electrical charge of molecules exposed at the surface of cell membranes of the cell. Red blood cell_sentence_86

The normal zeta potential of the red blood cell is −15.7 millivolts (mV). Red blood cell_sentence_87

Much of this potential appears to be contributed by the exposed sialic acid residues in the membrane: their removal results in zeta potential of −6.06 mV. Red blood cell_sentence_88

Function Red blood cell_section_10

Role in CO2 transport Red blood cell_section_11

Recall that respiration, as illustrated schematically here with a unit of carbohydrate, produces about as many molecules of carbon dioxide, CO2, and it consumes of oxygen, O2. Red blood cell_sentence_89

Thus, the function of the circulatory system is as much about the transport of carbon dioxide as about the transport of oxygen. Red blood cell_sentence_90

As stated elsewhere in this article, most of the carbon dioxide in the blood is in the form of bicarbonate ion. Red blood cell_sentence_91

The bicarbonate provides a critical pH buffer. Red blood cell_sentence_92

Thus, unlike hemoglobin for O2 transport, there is a physiological advantage to not having a specific CO2 transporter molecule. Red blood cell_sentence_93

Red Blood cells, nevertheless, play a key role in the CO2 transport process, for two reasons. Red blood cell_sentence_94

First, because, besides hemoglobin, they contain a large number of copies of the enzyme carbonic anhydrase on the inside of their cell membrane. Red blood cell_sentence_95

Carbonic anhydrase, as its name suggests, acts as a catalyst of the exchange between carbonic acid and carbon dioxide (which is the anhydride of carbonic acid). Red blood cell_sentence_96

Because it is a catalyst, it can affect many CO2 molecules, so it performs its essential role without needing as many copies as are needed for O2 transport by hemoglobin. Red blood cell_sentence_97

In the presence of this catalyst carbon dioxide and carbonic acid reach an equilibrium very rapidly, while the red cells are still moving through the capillary. Red blood cell_sentence_98

Thus it is the RBC that ensures that most of the CO2 is transported as bicarbonate. Red blood cell_sentence_99

At physiological pH the equilibrium strongly favors carbonic acid, which is mostly dissociated into bicarbonate ion. Red blood cell_sentence_100

The H+ ions released by this rapid reaction within RBC, while still in the capillary, act to reduce the oxygen binding affinity of hemoglobin, the Bohr effect. Red blood cell_sentence_101

The second major contribution of RBC to carbon dioxide transport is that carbon dioxide directly reacts with globin protein components of hemoglobin to form carbaminohemoglobin compounds. Red blood cell_sentence_102

As oxygen is released in the tissues, more CO2 binds to hemoglobin, and as oxygen binds in the lung, it displaces the hemoglobin bound CO2, this is called the Haldane effect. Red blood cell_sentence_103

Despite the fact that only a small amount of the CO2 in blood is bound to hemoglobin in venous blood, a greater proportion of the change in CO2 content between venous and arterial blood comes from the change in this bound CO2. Red blood cell_sentence_104

That is, there is always an abundance of bicarbonate in blood, both venous and arterial, because of its aforementioned role as a pH buffer. Red blood cell_sentence_105

In summary, carbon dioxide produced by cellular respiration diffuses very rapidly to areas of lower concentration, specifically into nearby capillaries. Red blood cell_sentence_106

When it diffuses into a RBC, CO2 is rapidly converted by the carbonic anhydrase found on the inside of the RBC membrane into bicarbonate ion. Red blood cell_sentence_107

The bicarbonate ions in turn leave the RBC in exchange for chloride ions from the plasma, facilitated by the band 3 anion transport protein colocated in the RBC membrane. Red blood cell_sentence_108

The bicarbonate ion does not diffuse back out of the capillary, but is carried to the lung. Red blood cell_sentence_109

In the lung the lower partial pressure of carbon dioxide in the alveoli causes carbon dioxide to diffuse rapidly from the capillary into the alveoli. Red blood cell_sentence_110

The carbonic anhydrase in the red cells keeps the bicarbonate ion in equilibrium with carbon dioxide. Red blood cell_sentence_111

So as carbon dioxide leaves the capillary, and CO2 is displaced by O2 on hemoglobin, sufficient bicarbonate ion converts rapidly to carbon dioxide to maintain the equilibrium. Red blood cell_sentence_112

Secondary functions Red blood cell_section_12

When red blood cells undergo shear stress in constricted vessels, they release ATP, which causes the vessel walls to relax and dilate so as to promote normal blood flow. Red blood cell_sentence_113

When their hemoglobin molecules are deoxygenated, red blood cells release S-nitrosothiols, which also act to dilate blood vessels, thus directing more blood to areas of the body depleted of oxygen. Red blood cell_sentence_114

Red blood cells can also synthesize nitric oxide enzymatically, using L-arginine as substrate, as do endothelial cells. Red blood cell_sentence_115

Exposure of red blood cells to physiological levels of shear stress activates nitric oxide synthase and export of nitric oxide, which may contribute to the regulation of vascular tonus. Red blood cell_sentence_116

Red blood cells can also produce hydrogen sulfide, a signalling gas that acts to relax vessel walls. Red blood cell_sentence_117

It is believed that the cardioprotective effects of garlic are due to red blood cells converting its sulfur compounds into hydrogen sulfide. Red blood cell_sentence_118

Red blood cells also play a part in the body's immune response: when lysed by pathogens such as bacteria, their hemoglobin releases free radicals, which break down the pathogen's cell wall and membrane, killing it. Red blood cell_sentence_119

Cellular processes Red blood cell_section_13

As a result of not containing mitochondria, red blood cells use none of the oxygen they transport; instead they produce the energy carrier ATP by the glycolysis of glucose and lactic acid fermentation on the resulting pyruvate. Red blood cell_sentence_120

Furthermore, the pentose phosphate pathway plays an important role in red blood cells; see glucose-6-phosphate dehydrogenase deficiency for more information. Red blood cell_sentence_121

As red blood cells contain no nucleus, protein biosynthesis is currently assumed to be absent in these cells. Red blood cell_sentence_122

Because of the lack of nuclei and organelles, mature red blood cells do not contain DNA and cannot synthesize any RNA, and consequently cannot divide and have limited repair capabilities. Red blood cell_sentence_123

The inability to carry out protein synthesis means that no virus can evolve to target mammalian red blood cells. Red blood cell_sentence_124

However, infection with parvoviruses (such as human parvovirus B19) can affect erythroid precursors while they still have DNA, as recognized by the presence of giant pronormoblasts with viral particles and inclusion bodies, thus temporarily depleting the blood of reticulocytes and causing anemia. Red blood cell_sentence_125

Life cycle Red blood cell_section_14

Human red blood cells are produced through a process named erythropoiesis, developing from committed stem cells to mature red blood cells in about 7 days. Red blood cell_sentence_126

When matured, in a healthy individual these cells live in blood circulation for about 100 to 120 days (and 80 to 90 days in a full term infant). Red blood cell_sentence_127

At the end of their lifespan, they are removed from circulation. Red blood cell_sentence_128

In many chronic diseases, the lifespan of the red blood cells is reduced. Red blood cell_sentence_129

Creation Red blood cell_section_15

Erythropoiesis is the process by which new red blood cells are produced; it lasts about 7 days. Red blood cell_sentence_130

Through this process red blood cells are continuously produced in the red bone marrow of large bones. Red blood cell_sentence_131

(In the embryo, the liver is the main site of red blood cell production.) Red blood cell_sentence_132

The production can be stimulated by the hormone erythropoietin (EPO), synthesised by the kidney. Red blood cell_sentence_133

Just before and after leaving the bone marrow, the developing cells are known as reticulocytes; these constitute about 1% of circulating red blood cells. Red blood cell_sentence_134

Functional lifetime Red blood cell_section_16

The functional lifetime of a red blood cell is about 100–120 days, during which time the red blood cells are continually moved by the blood flow push (in arteries), pull (in veins) and a combination of the two as they squeeze through microvessels such as capillaries. Red blood cell_sentence_135

They are also recycled in the bone marrow. Red blood cell_sentence_136

Senescence Red blood cell_section_17

The aging red blood cell undergoes changes in its plasma membrane, making it susceptible to selective recognition by macrophages and subsequent phagocytosis in the mononuclear phagocyte system (spleen, liver and lymph nodes), thus removing old and defective cells and continually purging the blood. Red blood cell_sentence_137

This process is termed eryptosis, red blood cell programmed death. Red blood cell_sentence_138

This process normally occurs at the same rate of production by erythropoiesis, balancing the total circulating red blood cell count. Red blood cell_sentence_139

Eryptosis is increased in a wide variety of diseases including sepsis, haemolytic uremic syndrome, malaria, sickle cell anemia, beta-thalassemia, glucose-6-phosphate dehydrogenase deficiency, phosphate depletion, iron deficiency and Wilson's disease. Red blood cell_sentence_140

Eryptosis can be elicited by osmotic shock, oxidative stress, and energy depletion, as well as by a wide variety of endogenous mediators and xenobiotics. Red blood cell_sentence_141

Excessive eryptosis is observed in red blood cells lacking the cGMP-dependent protein kinase type I or the AMP-activated protein kinase AMPK. Red blood cell_sentence_142

Inhibitors of eryptosis include erythropoietin, nitric oxide, catecholamines and high concentrations of urea. Red blood cell_sentence_143

Much of the resulting breakdown products are recirculated in the body. Red blood cell_sentence_144

The heme constituent of hemoglobin are broken down into iron (Fe) and biliverdin. Red blood cell_sentence_145

The biliverdin is reduced to bilirubin, which is released into the plasma and recirculated to the liver bound to albumin. Red blood cell_sentence_146

The iron is released into the plasma to be recirculated by a carrier protein called transferrin. Red blood cell_sentence_147

Almost all red blood cells are removed in this manner from the circulation before they are old enough to hemolyze. Red blood cell_sentence_148

Hemolyzed hemoglobin is bound to a protein in plasma called haptoglobin, which is not excreted by the kidney. Red blood cell_sentence_149

Clinical significance Red blood cell_section_18

Disease Red blood cell_section_19

Blood diseases involving the red blood cells include: Red blood cell_sentence_150

Red blood cell_unordered_list_6

  • Anemias (or anaemias) are diseases characterized by low oxygen transport capacity of the blood, because of low red cell count or some abnormality of the red blood cells or the hemoglobin.Red blood cell_item_6_34

Red blood cell_description_list_7

  • Red blood cell_item_7_35
    • Iron deficiency anemia is the most common anemia; it occurs when the dietary intake or absorption of iron is insufficient, and hemoglobin, which contains iron, cannot be formedRed blood cell_item_7_36

Red blood cell_description_list_8

  • Red blood cell_item_8_37
    • Sickle-cell disease is a genetic disease that results in abnormal hemoglobin molecules. When these release their oxygen load in the tissues, they become insoluble, leading to mis-shaped red blood cells. These sickle shaped red cells are less deformable and viscoelastic, meaning that they have become rigid and can cause blood vessel blockage, pain, strokes, and other tissue damage.Red blood cell_item_8_38

Red blood cell_description_list_9

  • Red blood cell_item_9_39
    • Thalassemia is a genetic disease that results in the production of an abnormal ratio of hemoglobin subunits.Red blood cell_item_9_40

Red blood cell_description_list_10

  • Red blood cell_item_10_41
    • Hereditary spherocytosis syndromes are a group of inherited disorders characterized by defects in the red blood cell's cell membrane, causing the cells to be small, sphere-shaped, and fragile instead of donut-shaped and flexible. These abnormal red blood cells are destroyed by the spleen. Several other hereditary disorders of the red blood cell membrane are known.Red blood cell_item_10_42

Red blood cell_description_list_11

Red blood cell_description_list_12

  • Red blood cell_item_12_45

Red blood cell_description_list_13

  • Red blood cell_item_13_47
    • Pure red cell aplasia is caused by the inability of the bone marrow to produce only red blood cells.Red blood cell_item_13_48

Red blood cell_unordered_list_14

  • Hemolysis is the general term for excessive breakdown of red blood cells. It can have several causes and can result in hemolytic anemia.Red blood cell_item_14_49

Red blood cell_description_list_15

  • Red blood cell_item_15_50
    • The malaria parasite spends part of its life-cycle in red blood cells, feeds on their hemoglobin and then breaks them apart, causing fever. Both sickle-cell disease and thalassemia are more common in malaria areas, because these mutations convey some protection against the parasite.Red blood cell_item_15_51

Red blood cell_unordered_list_16

  • Polycythemias (or erythrocytoses) are diseases characterized by a surplus of red blood cells. The increased viscosity of the blood can cause a number of symptoms.Red blood cell_item_16_52

Red blood cell_description_list_17

  • Red blood cell_item_17_53
    • In polycythemia vera the increased number of red blood cells results from an abnormality in the bone marrow.Red blood cell_item_17_54

Red blood cell_unordered_list_18

Transfusion Red blood cell_section_20

Main article: Blood transfusion Red blood cell_sentence_151

Red blood cells may be given as part of a blood transfusion. Red blood cell_sentence_152

Blood may be donated from another person, or stored by the recipient at an earlier date. Red blood cell_sentence_153

Donated blood usually requires screening to ensure that donors do not contain risk factors for the presence of blood-borne diseases, or will not suffer themselves by giving blood. Red blood cell_sentence_154

Blood is usually collected and tested for common or serious blood-borne diseases including Hepatitis B, Hepatitis C and HIV. Red blood cell_sentence_155

The blood type (A, B, AB, or O) or the blood product is identified and matched with the recipient's blood to minimise the likelihood of acute hemolytic transfusion reaction, a type of transfusion reaction. Red blood cell_sentence_156

This relates to the presence of antigens on the cell's surface. Red blood cell_sentence_157

After this process, the blood is stored, and within a short duration is used. Red blood cell_sentence_158

Blood can be given as a whole product or the red blood cells separated as packed red blood cells. Red blood cell_sentence_159

Blood is often transfused when there is known anaemia, active bleeding, or when there is an expectation of serious blood loss, such as prior to an operation. Red blood cell_sentence_160

Before blood is given, a small sample of the recipient's blood is tested with the transfusion in a process known as cross-matching. Red blood cell_sentence_161

In 2008 it was reported that human embryonic stem cells had been successfully coaxed into becoming red blood cells in the lab. Red blood cell_sentence_162

The difficult step was to induce the cells to eject their nucleus; this was achieved by growing the cells on stromal cells from the bone marrow. Red blood cell_sentence_163

It is hoped that these artificial red blood cells can eventually be used for blood transfusions. Red blood cell_sentence_164

Tests Red blood cell_section_21

Several blood tests involve red blood cells. Red blood cell_sentence_165

These include a RBC count (the number of red blood cells per volume of blood), calculation of the hematocrit (percentage of blood volume occupied by red blood cells), and the erythrocyte sedimentation rate. Red blood cell_sentence_166

The blood type needs to be determined to prepare for a blood transfusion or an organ transplantation. Red blood cell_sentence_167

Many diseases involving red blood cells are diagnosed with a blood film (or peripheral blood smear), where a thin layer of blood is smeared on a microscope slide. Red blood cell_sentence_168

This may reveal abnormalities of red blood cell shape and form. Red blood cell_sentence_169

When red blood cells sometimes occur as a stack, flat side next to flat side. Red blood cell_sentence_170

This is known as rouleaux formation, and it occurs more often if the levels of certain serum proteins are elevated, as for instance during inflammation. Red blood cell_sentence_171

Separation and blood doping Red blood cell_section_22

Red blood cells can be obtained from whole blood by centrifugation, which separates the cells from the blood plasma in a process known as blood fractionation. Red blood cell_sentence_172

Packed red blood cells, which are made in this way from whole blood with the plasma removed, are used in transfusion medicine. Red blood cell_sentence_173

During plasma donation, the red blood cells are pumped back into the body right away and only the plasma is collected. Red blood cell_sentence_174

Some athletes have tried to improve their performance by blood doping: first about 1 litre of their blood is extracted, then the red blood cells are isolated, frozen and stored, to be reinjected shortly before the competition. Red blood cell_sentence_175

(Red blood cells can be conserved for 5 weeks at −79 °C or −110 °F, or over 10 years using cryoprotectants) This practice is hard to detect but may endanger the human cardiovascular system which is not equipped to deal with blood of the resulting higher viscosity. Red blood cell_sentence_176

Another method of blood doping involves injection with erythropoietin in order to stimulate production of red blood cells. Red blood cell_sentence_177

Both practices are banned by the World Anti-Doping Agency. Red blood cell_sentence_178

History Red blood cell_section_23

The first person to describe red blood cells was the young Dutch biologist Jan Swammerdam, who had used an early microscope in 1658 to study the blood of a frog. Red blood cell_sentence_179

Unaware of this work, Anton van Leeuwenhoek provided another microscopic description in 1674, this time providing a more precise description of red blood cells, even approximating their size, "25,000 times smaller than a fine grain of sand". Red blood cell_sentence_180

In 1901, Karl Landsteiner published his discovery of the three main blood groups—A, B, and C (which he later renamed to O). Red blood cell_sentence_181

Landsteiner described the regular patterns in which reactions occurred when serum was mixed with red blood cells, thus identifying compatible and conflicting combinations between these blood groups. Red blood cell_sentence_182

A year later Alfred von Decastello and Adriano Sturli, two colleagues of Landsteiner, identified a fourth blood group—AB. Red blood cell_sentence_183

In 1959, by use of X-ray crystallography, Dr. Max Perutz was able to unravel the structure of hemoglobin, the red blood cell protein that carries oxygen. Red blood cell_sentence_184

The oldest intact red blood cells ever discovered were found in Ötzi the Iceman, a natural mummy of a man who died around 3255 BCE. Red blood cell_sentence_185

These cells were discovered in May 2012. Red blood cell_sentence_186

See also Red blood cell_section_24

Red blood cell_unordered_list_19

Credits to the contents of this page go to the authors of the corresponding Wikipedia page: blood cell.