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Red blood cells
3D rendering of human red blood cells (c. 6–8 μmin diameter)
Details
FunctionOxygentransport
Identifiers
Acronym(s)RBC
MeSHD004912
THH2.00.04.1.01001
FMA62845
Anatomical terms of microanatomy

Red blood cells(RBCs), referred to aserythrocytes(fromAncient Greekerythros'red' andkytos'hollow vessel', with -cytetranslated as 'cell' in modern usage) in academia and medical publishing, also known asred cells,[1]erythroid cells,and rarelyhaematids,are the most common type ofblood celland thevertebrate's principal means of deliveringoxygen(O2) to the bodytissues—via blood flow through thecirculatory system.[2]Erythrocytes take up oxygen in thelungs,or in fish thegills,and release it into tissues while squeezing through the body'scapillaries.

Thecytoplasmof a red blood cell is rich inhemoglobin(Hb), aniron-containingbiomoleculethat can bind oxygen and is responsible for the red color of the cells and the blood. Each human red blood cell contains approximately 270 million hemoglobin molecules.[3]Thecell membraneis composed ofproteinsandlipids,and this structure provides properties essential for physiologicalcellfunction such asdeformabilityandstabilityof the blood cell while traversing the circulatory system and specifically thecapillarynetwork.

In humans, mature red blood cells are flexiblebiconcave disks.They lack acell nucleus(which is expelled duringdevelopment) andorganelles,to accommodate maximum space for hemoglobin; they can be viewed as sacks of hemoglobin, with aplasma membraneas the sack. Approximately 2.4 million new erythrocytes are produced per second in human adults.[4]The cells develop in thebone marrowand circulate for about 100–120 days in the body before their components are recycled bymacrophages.Each circulation takes about 60 seconds (one minute).[5]Approximately 84% of the cells in the human body are the 20–30 trillion red blood cells.[6][7][8][9]Nearly half of the blood's volume (40% to 45%) is red blood cells.

Packed red blood cellsare red blood cells that have been donated, processed, and stored in ablood bankforblood transfusion.

Structure

Vertebrates

There is an immense size variation in vertebrate red blood cells, as well as a correlation between cell and nucleus size. Mammalian red blood cells, which do not contain nuclei, are considerably smaller than those of most other vertebrates.[10]
Mature red blood cells of birds have a nucleus, however in the blood of adult females of penguinPygoscelis papuaenucleated red blood cells (B) have been observed, but with very low frequency.

The vast majority of vertebrates, includingmammalsand humans, have red blood cells. Red blood cells are cells present in blood to transport oxygen. The only known vertebrates without red blood cells are the crocodile icefish (familyChannichthyidae); they live in very oxygen-rich cold water and transport oxygen freely dissolved in their blood.[11]While they no longer use hemoglobin, remnants of hemoglobin genes can be found in theirgenome.[12]

Vertebrate red blood cells consist mainly ofhemoglobin,a complexmetalloproteincontaininghemegroups whose iron atoms temporarily bind to oxygen molecules (O2) in the lungs or gills and release them throughout the body. Oxygen can easilydiffusethrough the red blood cell'scell membrane.Hemoglobin in the red blood cells also carries some of the waste productcarbon dioxideback from the tissues; most waste carbon dioxide, however, is transported back to thepulmonary capillariesof thelungsasbicarbonate(HCO3−) dissolved in theblood plasma.Myoglobin,a compound related to hemoglobin, acts to store oxygen inmusclecells.[13]

The color of red blood cells is due to the heme group of hemoglobin. Theblood plasmaalone 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. However, blood can appear bluish when seen through the vessel wall and skin.[14]Pulse oximetrytakes advantage of the hemoglobin color change to directly measure thearterialbloodoxygen saturationusingcolorimetrictechniques. Hemoglobin also has a very high affinity forcarbon monoxide,forming carboxyhemoglobin which is a very bright red in color. Flushed, confused patients with a saturation reading of 100% on pulse oximetry are sometimes found to be suffering from carbon monoxide poisoning.[citation needed]

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 lessviscousblood, higher concentrations of oxygen, and better diffusion of oxygen from the blood to the tissues. The size of red blood cells varies widely among vertebrate species; red blood cell width is on average about 25% larger thancapillarydiameter, and it has been hypothesized that this improves the oxygen transfer from red blood cells to tissues.[15]

Mammals

Typical mammalian red blood cells: (a) seen from surface; (b) in profile, forming rouleaux; (c) rendered spherical by water; (d) rendered crenate (shrunken and spiky) by salt. (c) and (d) do not normally occur in the body. The last two shapes are due to water being transported into, and out of, the cells, byosmosis.

The red blood cells ofmammalsare typically shaped as biconcave disks: flattened and depressed in the center, with a dumbbell-shaped cross section, and atorus-shaped rim on the edge of the disk. This shape allows for a high surface-area-to-volume (SA/V) ratio to facilitate diffusion of gases.[16]However, there are some exceptions concerning shape in theartiodactylorder (even-toedungulatesincluding cattle, deer, and their relatives), which displays a wide variety of bizarre red blood cell morphologies: small and highly ovaloid cells inllamasand camels (familyCamelidae), tiny spherical cells in mouse deer (familyTragulidae), and cells which assume fusiform, lanceolate, crescentic, and irregularly polygonal and other angular forms in red deer and wapiti (familyCervidae). Members of this order have clearly evolved a mode of red blood cell development substantially different from the mammalian norm.[10][17]Overall, mammalian red blood cells are remarkably flexible and deformable so as to squeeze through tinycapillaries,as well as to maximize their apposing surface by assuming a cigar shape, where they efficiently release their oxygen load.[18]

Red blood cells in mammals are unique amongst vertebrates as they do not have nuclei when mature. They do have nuclei during early phases oferythropoiesis,but extrude them during development as they mature; this provides more space for hemoglobin. The red blood cells without nuclei, calledreticulocytes,subsequently lose all other cellularorganellessuch as theirmitochondria,Golgi apparatusandendoplasmic reticulum.

Thespleenacts as a reservoir of red blood cells, but this effect is somewhat limited in humans. 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.

Scanning electron micrograph of blood cells. From left to right: human red blood cell,thrombocyte(platelet),leukocyte.

Human

Two drops of blood are shown with a bright red oxygenated drop on the left and a darker red deoxygenated drop on the right.
Animation of a typical human red blood cell cycle in the circulatory system. This animation occurs at a faster rate (~20 seconds of the average 60-second cycle) and shows the red blood cell deforming as it enters capillaries, as well as the bars changing color as the cell alternates in states of oxygenation along the circulatory system.

A typical human red blood cell has a disk diameter of approximately6.2–8.2 μm[19]and a maximum thickness of 2–2.5 μm and a minimum thickness in the centre of 0.8–1 μm, being much smaller than most otherhuman cells.These cells have an average volume of about90 fL[20]with a surface area of about 136 μm2,and can swell up to a sphere shape containing 150 fL, without membrane distension.

Adult humans have roughly 20–30 trillion red blood cells at any given time, constituting approximately 70% of all cells by number.[21]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 altitudeswith low oxygen tension will have more. Red blood cells are thus much more common than the other blood particles: there are about 4,000–11,000white blood cellsand about 150,000–400,000plateletsper microliter.

Human red blood cells take on average 60 seconds to complete one cycle of circulation.[5][9][22]

The blood's red color is due to the spectral properties of thehemicironionsinhemoglobin.Each hemoglobin molecule carries four heme groups; hemoglobin constitutes about a third of the total cell volume. Hemoglobin is responsible for the transport of more than 98% of the oxygen in the body (the remaining oxygen is carried dissolved in theblood plasma). 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.[23][24]

Microstructure

Nucleus

Red blood cells in mammals areanucleatewhen mature, meaning that they lack acell nucleus.In comparison, the red blood cells of other vertebrates have nuclei; the only known exceptions aresalamandersof the familyPlethodontidae,where five different clades has evolved various degrees of enucleated red blood cells (most evolved in some species of the genusBatrachoseps), and fish of the genusMaurolicus.[25][26][27]

The elimination of the nucleus in vertebrate red blood cells has been offered as an explanation for the subsequentaccumulation of non-coding DNA in the genome.[17]The argument runs as follows: Efficient gas transport requires red blood cells to pass through very narrow capillaries, and this constrains their size. 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.

Nucleated red blood cellsin 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 inmegaloblastic anemias.

Membrane composition

Red blood cells are deformable, flexible, are able to adhere to other cells, and are able to interface with immune cells. Theirmembraneplays many roles in this. These functions are highly dependent on the membrane composition. The red blood cell membrane is composed of 3 layers: theglycocalyxon the exterior, which is rich incarbohydrates;thelipid bilayerwhich contains manytransmembrane proteins,besides its lipidic main constituents; and the membrane skeleton, a structural network of proteins located on the inner surface of the lipid bilayer. Half of the membrane mass in human and most mammalian red blood cells are proteins. The other half are lipids, namelyphospholipidsandcholesterol.[28]

Membrane lipids

The most common red blood cell membrane lipids, schematically disposed as they are distributed on the bilayer. Relative abundances are not at scale.

The red blood cell membrane comprises a typicallipid bilayer,similar to what can be found in virtually all human cells. Simply put, this lipid bilayer is composed ofcholesterolandphospholipidsin equal proportions by weight. The lipid composition is important as it defines many physical properties such as membrane permeability and fluidity. Additionally, the activity of many membrane proteins is regulated by interactions with lipids in the bilayer.

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

Outer monolayer

Inner monolayer

This asymmetric phospholipid distribution among the bilayer is the result of the function of several energy-dependent and energy-independentphospholipidtransport proteins. 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. 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. There is still considerable debate ongoing regarding the identity of these membrane maintenance proteins in the red cell membrane.

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:

  • Macrophagesrecognize andphagocytosered 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 thereticuloendothelial system,especially in thespleen.
  • Premature destruction ofthallassemicand sickle red cells has been linked to disruptions of lipid asymmetry leading to exposure of PS on the outer monolayer.
  • 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.
  • Both PS andphosphatidylinositol 4,5-bisphosphate(PIP2) can regulate membrane mechanical function, due to their interactions with skeletal proteins such asspectrinandprotein 4.1R.Recent studies have shown that binding of spectrin to PS promotes membrane mechanical stability. PIP2 enhances the binding ofprotein band 4.1Rtoglycophorin Cbut decreases its interaction withprotein band 3,and thereby may modulate the linkage of the bilayer to the membrane skeleton.

The presence of specialized structures named "lipid rafts"in the red blood cell membrane have been described by recent studies. These are structures enriched incholesterolandsphingolipidsassociated with specific membrane proteins, namelyflotillins,STOMatins(band 7),G-proteins,andβ-adrenergic receptors.Lipid raftsthat have been implicated in cell signaling events in nonerythroid cells have been shown in erythroid cells to mediateβ2-adregenic receptorsignaling and increasecAMPlevels, and thus regulating entry ofmalarialparasites into normal red cells.[29][30]

Membrane proteins

Red blood cell membrane proteins separated bySDS-PAGEandsilverstained[31]

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.

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. Approximately 25 of these membrane proteins carry the various blood group antigens, such as the A, B and Rh antigens, among many others. 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. Theblood typesof humans are due to variations in surfaceglycoproteinsof red blood cells. Disorders of the proteins in these membranes are associated with many disorders, such ashereditary spherocytosis,hereditary elliptocytosis,hereditary stomatocytosis,andparoxysmal nocturnal hemoglobinuria.[28][29]

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

Red blood cell membrane major proteins

Transport

Cell adhesion

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).

  • Ankyrin-based macromolecular complex – proteins linking the bilayer to the membrane skeleton through the interaction of their cytoplasmic domains withAnkyrin.
    • Band 3– also assembles variousglycolyticenzymes, the presumptive CO2transporter, andcarbonic anhydraseinto a macromolecular complex termed a "metabolon,"which may play a key role in regulating red cell metabolism and ion and gas transportfunction.
    • RHAG– also involved in transport, defines associated unusual blood group phenotype Rhmod.
  • Protein 4.1R-based macromolecular complex – proteins interacting withProtein 4.1R.
    • Protein 4.1R– weak expression ofGerbichantigens;
    • Glycophorin Cand D – glycoprotein, definesGerbich Blood Group;
    • XK– defines the Kell Blood Group and the Mcleod unusual phenotype (lack of Kx antigen and greatly reduced expression of Kell antigens);
    • RhD/RhCE– defines Rh Blood Group and the associated unusual blood group phenotype Rhnull;
    • Duffy protein– has been proposed to be associated withchemokineclearance;[34]
    • Adducin– interaction with band 3;
    • Dematin- interaction with the Glut1 glucose transporter.

[28][29]

Surface electrostatic potential

Thezeta potentialis 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. The normal zeta potential of the red blood cell is −15.7 millivolts(mV).[35]Much of this potential appears to be contributed by the exposedsialic acidresidues in the membrane: their removal results in zeta potential of −6.06 mV.

Function

Role in CO2transport

Recall thatrespiration,as illustrated schematically here with a unit of carbohydrate, produces about as many molecules of carbon dioxide, CO2,as it consumes of oxygen, O2.[36]

Thus, the function of the circulatory system is as much about the transport of carbon dioxide as about the transport of oxygen. As stated elsewhere in this article, most of the carbon dioxide in the blood is in the form of bicarbonate ion. The bicarbonate provides acritical pH buffer.[37]Thus, unlike hemoglobin for O2transport, there is a physiological advantage to not having a specific CO2transporter molecule.

Red blood cells, nevertheless, play a key role in the CO2transport process, for two reasons. First, because, besides hemoglobin, they contain a large number of copies of the enzymecarbonic anhydraseon the inside of their cell membrane.[38]Carbonic anhydrase, as its name suggests, acts as a catalyst of the exchange betweencarbonic acidand carbon dioxide (which is theanhydrideof carbonic acid). Because it is a catalyst, it can affect many CO2molecules, so it performs its essential role without needing as many copies as are needed for O2transport by hemoglobin. In the presence of this catalyst carbon dioxide and carbonic acid reach anequilibriumvery rapidly, while the red cells are still moving through the capillary. Thus it is the RBC that ensures that most of the CO2is transported as bicarbonate.[39][40] At physiological pH the equilibrium strongly favors carbonic acid, which is mostly dissociated into bicarbonate ion.[41]

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

The second major contribution of RBC to carbon dioxide transport is that carbon dioxide directly reacts with globin protein components of hemoglobin to formcarbaminohemoglobincompounds. As oxygen is released in the tissues, more CO2binds to hemoglobin, and as oxygen binds in the lung, it displaces the hemoglobin bound CO2,this is called theHaldane effect.Despite the fact that only a small amount of the CO2in blood is bound to hemoglobin in venous blood, a greater proportion of the change in CO2content between venous and arterial blood comes from the change in this bound CO2.[42]That is, there is always an abundance of bicarbonate in blood, both venous and arterial, because of its aforementioned role as a pH buffer.

In summary, carbon dioxide produced by cellular respiration diffuses very rapidly to areas of lower concentration, specifically into nearby capillaries.[43][44] When it diffuses into a RBC, CO2is rapidly converted by the carbonic anhydrase found on the inside of the RBC membrane into bicarbonate ion. The bicarbonate ions in turn leave the RBC in exchange forchloride ionsfrom the plasma, facilitated by theband 3 anion transport proteincolocated in the RBC membrane. The bicarbonate ion does not diffuse back out of the capillary, but is carried to the lung. In the lung the lowerpartial pressureof carbon dioxide in the alveoli causes carbon dioxide to diffuse rapidly from the capillary into the alveoli. The carbonic anhydrase in the red cells keeps the bicarbonate ion in equilibrium with carbon dioxide. So as carbon dioxide leaves the capillary, and CO2is displaced by O2on hemoglobin, sufficient bicarbonate ion converts rapidly to carbon dioxide to maintain the equilibrium.[38][45][46][47]

Secondary functions

When red blood cells undergoshear stressin constricted vessels, they releaseATP,which causes the vessel walls to relax and dilate so as to promote normal blood flow.[48]

When their hemoglobin molecules are deoxygenated, red blood cells releaseS-Nitrosothiols,which also act to dilate blood vessels,[49]thus directing more blood to areas of the body depleted of oxygen.

Red blood cells can also synthesizenitric oxideenzymatically, usingL-arginineas substrate, as doendothelial cells.[50]Exposure of red blood cells to physiological levels of shear stress activatesnitric oxide synthaseand export of nitric oxide,[51]which may contribute to the regulation of vascular tonus.

Red blood cells can also producehydrogen sulfide,a signalling gas that acts to relax vessel walls. It is believed that the cardioprotective effects of garlic are due to red blood cells converting its sulfur compounds into hydrogen sulfide.[52]

Red blood cells also play a part in the body'simmune response:whenlysedby pathogens such as bacteria, their hemoglobin releasesfree radicals,which break down the pathogen's cell wall and membrane, killing it.[53][54]

Cellular processes

As a result of not containingmitochondria,red blood cells use none of the oxygen they transport; instead they produce the energy carrierATPby theglycolysisofglucoseandlactic acid fermentationon the resultingpyruvate.[55][56]Furthermore, thepentose phosphate pathwayplays an important role in red blood cells; seeglucose-6-phosphate dehydrogenase deficiencyfor more information.

As red blood cells contain no nucleus,protein biosynthesisis currently assumed to be absent in these cells.

Because of the lack of nuclei and organelles, mature red blood cells do not containDNAand cannot synthesize anyRNA(although it does contain RNAs),[57][58]and consequently cannot divide and have limited repair capabilities.[59]The inability to carry outprotein synthesismeans that no virus can evolve to target mammalian red blood cells.[60]However, infection withparvoviruses(such as humanparvovirus B19) can affect erythroid precursors while they still have DNA, as recognized by the presence of giantpronormoblastswith viral particles andinclusion bodies,thus temporarily depleting the blood of reticulocytes and causinganemia.[61]

Life cycle

Human red blood cells are produced through a process namederythropoiesis,developing from committedstem cellsto mature red blood cells in about 7 days. 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 terminfant).[62]At the end of their lifespan, they are removed from circulation. In many chronic diseases, the lifespan of the red blood cells is reduced.

Creation

Erythropoiesisis the process by which new red blood cells are produced; it lasts about 7 days. Through this process red blood cells are continuously produced in the redbone marrowof large bones. (In theembryo,theliveris the main site of red blood cell production.) The production can be stimulated by thehormoneerythropoietin(EPO), synthesised by the kidney. Just before and after leaving the bone marrow, the developing cells are known asreticulocytes;these constitute about 1% of circulating red blood cells.

Functional lifetime

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 (inarteries), pull (inveins) and a combination of the two as they squeeze through microvessels such as capillaries. They are also recycled in the bone marrow.[63]

Senescence

The aging red blood cell undergoes changes in itsplasma membrane,making it susceptible to selective recognition bymacrophagesand subsequentphagocytosisin themononuclear phagocyte system(spleen,liverandlymph nodes), thus removing old and defective cells and continually purging the blood. This process is termederyptosis,red blood cell programmed death.[64]This process normally occurs at the same rate of production by erythropoiesis, balancing the total circulating red blood cell count. Eryptosis is increased in a wide variety of diseases includingsepsis,haemolytic uremic syndrome,malaria,sickle cell anemia,beta-thalassemia,glucose-6-phosphate dehydrogenase deficiency,phosphate depletion, iron deficiency andWilson's disease.Eryptosis can be elicited by osmotic shock, oxidative stress, and energy depletion, as well as by a wide variety of endogenous mediators andxenobiotics.Excessive eryptosis is observed in red blood cells lacking the cGMP-dependent protein kinase type I or the AMP-activated protein kinase AMPK.Inhibitorsof eryptosis includeerythropoietin,nitric oxide,catecholaminesand high concentrations ofurea.

Much of the resulting breakdown products are recirculated in the body. The heme constituent of hemoglobin are broken down into iron (Fe3+) andbiliverdin.The biliverdin is reduced tobilirubin,which is released into the plasma and recirculated to the liver bound toalbumin.The iron is released into the plasma to be recirculated by a carrier protein calledtransferrin.Almost all red blood cells are removed in this manner from the circulation before they are old enough tohemolyze.Hemolyzed hemoglobin is bound to a protein in plasma calledhaptoglobin,which is not excreted by the kidney.[65]

Clinical significance

Disease

Affected bySickle-cell disease,red blood cells alter shape and threaten to damage internal organs.

Blood diseasesinvolving the red blood cells include:

  • 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.
  • Iron deficiency anemiais the most common anemia; it occurs when the dietary intake or absorption of iron is insufficient, and hemoglobin, which contains iron, cannot be formed.
  • Sickle-cell diseaseis 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 andviscoelastic,meaning that they have become rigid and can cause blood vessel blockage, pain, strokes, and other tissue damage.
  • Thalassemiais a genetic disease that results in the production of an abnormal ratio of hemoglobin subunits.
  • Hereditary spherocytosissyndromes are a group of inherited disorders characterized by defects in the red blood cell'scell 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 thespleen.Several other hereditary disorders of the red blood cell membrane are known.[66]
Effect ofosmotic pressureon blood cells
Micrographs of the effects of osmotic pressure
  • Hemolysisis the general term for excessive breakdown of red blood cells. It can have several causes and can result inhemolytic anemia.
  • Themalariaparasite spends part of its life-cycle in red blood cells, feeds on their hemoglobin and then breaks them apart, causing fever. Bothsickle-cell diseaseandthalassemiaare more common in malaria areas, because these mutations convey some protection against the parasite.
  • 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.
  • Inpolycythemia verathe increased number of red blood cells results from an abnormality in the bone marrow.

Transfusion

Main article:Blood transfusion

Red blood cells may be given as part of ablood transfusion.Blood may bedonatedfrom another person, or stored by the recipient at an earlier date. Donated blood usually requiresscreeningto ensure that donors do not contain risk factors for the presence of blood-borne diseases, or will not suffer themselves by giving blood. Blood is usually collected and tested for common or seriousblood-borne diseasesincludingHepatitis B,Hepatitis Cand HIV. Theblood type(A, B, AB, or O) or the blood product is identified and matched with the recipient's blood to minimise the likelihood ofacute hemolytic transfusion reaction,a type oftransfusion reaction.This relates to the presence ofantigenson the cell's surface. After this process, the blood is stored, and within a short duration is used. Blood can be given as a whole product or the red blood cells separated aspacked red blood cells.

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

In 2008 it was reported that humanembryonic stem cellshad been successfully coaxed into becoming red blood cells in the lab. The difficult step was to induce the cells to eject their nucleus; this was achieved by growing the cells onstromal cellsfrom the bone marrow. It is hoped that these artificial red blood cells can eventually be used for blood transfusions.[67]

A human trial is conducted in 2022, using blood cultured from stem cells obtained from donor blood.[68]

Tests

Variations of red blood cell shape, overall termedpoikilocytosis

Severalblood testsinvolve red blood cells. These include aRBC count(the number of red blood cells per volume of blood), calculation of thehematocrit(percentage of blood volume occupied by red blood cells), and theerythrocyte sedimentation rate.Theblood typeneeds to be determined to prepare for ablood transfusionor anorgan transplantation.

Many diseases involving red blood cells are diagnosed with ablood film(or peripheral blood smear), where a thin layer of blood is smeared on a microscope slide. This may revealpoikilocytosis,which are variations in red blood cell shape. When red blood cells sometimes occur as a stack, flat side next to flat side. This is known asrouleauxformation,and it occurs more often if the levels of certain serum proteins are elevated, as for instance duringinflammation.

Separation and blood doping

Red blood cells can be obtained fromwhole bloodbycentrifugation,which separates the cells from theblood plasmain a process known asblood fractionation.Packed red blood cells,which are made in this way from whole blood with the plasma removed, are used intransfusion medicine.[69]Duringplasma donation,the red blood cells are pumped back into the body right away and only the plasma is collected.

Some athletes have tried to improve their performance byblood 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 cells can be conserved for 5 weeks at −79 °C or −110 °F, or over 10 years using cryoprotectants[70]) This practice is hard to detect but may endanger the humancardiovascular systemwhich is not equipped to deal with blood of the resulting higherviscosity.Another method of blood doping involves injection witherythropoietinto stimulate production of red blood cells. Both practices are banned by theWorld Anti-Doping Agency.

History

The first person to describe red blood cells was the young Dutch biologistJan Swammerdam,who had used an earlymicroscopein 1658 to study the blood of a frog.[71]Unaware of this work,Anton van Leeuwenhoekprovided 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".

In the 1740s,Vincenzo Menghiniin Bologna was able to demonstrate the presence of iron by passing magnets over the powder or ash remaining from heated red blood cells.

In 1901,Karl Landsteinerpublished his discovery of the three mainblood groups—A, B, and C (which he later renamed to O). Landsteiner described the regular patterns in which reactions occurred whenserumwas mixed with red blood cells, thus identifying compatible and conflicting combinations between these blood groups. A year later Alfred von Decastello and Adriano Sturli, two colleagues of Landsteiner, identified a fourth blood group—AB.

In 1959, by use ofX-ray crystallography,Max Perutzwas able to unravel thestructure of hemoglobin,the red blood cell protein that carries oxygen.[72]

The oldest intact red blood cells ever discovered were found inÖtzithe Iceman, a natural mummy of a man who died around 3255 BCE. These cells were discovered in May 2012.[73]

See also

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