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RedbloodcellWikipedia

Redbloodcell
FromWikipedia,thefreeencyclopedia

Redbloodcells(RBCs),alsocallederythrocytes,arethemostcommontypeofbloodcellandthevertebrateorganism'sprincipal
meansofdeliveringoxygen(O2)tothebodytissuesviabloodflowthroughthecirculatorysystem.[1]RBCstakeupoxygeninthe
lungsorgillsandreleaseitintotissueswhilesqueezingthroughthebody'scapillaries.
Thecytoplasmoferythrocytesisrichinhemoglobin,anironcontainingbiomoleculethatcanbindoxygenandisresponsibleforthe
redcolorofthecells.Thecellmembraneiscomposedofproteinsandlipids,andthisstructureprovidespropertiesessentialfor
physiologicalcellfunctionsuchasdeformabilityandstabilitywhiletraversingthecirculatorysystemandspecificallythecapillary
network.
Inhumans,matureredbloodcellsareflexibleandovalbiconcavedisks.Theylackacellnucleusandmostorganelles,inorderto
accommodatemaximumspaceforhemoglobintheycanbeviewedassacksofhemoglobin,withaplasmamembraneasthesack.
Approximately2.4millionnewerythrocytesareproducedpersecondinhumanadults.[2]Thecellsdevelopinthebonemarrowand
circulateforabout100120daysinthebodybeforetheircomponentsarerecycledbymacrophages.Eachcirculationtakesabout20
seconds.Approximatelyaquarterofthecellsinthehumanbodyareredbloodcells.[3][4]Nearlyhalfoftheblood'svolume(40%to
45%)isredbloodcells.

Scanningelectron
micrographofhuman
redbloodcells(ca.68
mindiameter)

RedbloodcellsarealsoknownasRBCs,redcells,[5]redbloodcorpuscles,haematids,erythroidcellsorerythrocytes(fromGreekerythrosfor"red"andkytos
for"hollowvessel",withcytetranslatedas"cell"inmodernusage).Packedredbloodcells(pRBC)areredbloodcellsthathavebeendonated,processed,and
storedinabloodbankforbloodtransfusion.

Contents
1 History
2 Vertebrateerythrocytes
2.1 Nucleus
2.2 Secondaryfunctions
3 Mammalianerythrocytes
4 Humanerythrocytes
4.1 Lifecycle
4.1.1 Erythropoiesis
4.1.2 Functionallifetime
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5
6
7
8
9

4.1.2 Functionallifetime
4.1.3 Senescence
4.2 Membranecomposition
4.2.1 Membranelipids
4.2.2 Membraneproteins
4.3 Surfaceelectrostaticpotential
Clinicalnotes
5.1 Separationandblooddoping
5.2 Artificiallygrownredbloodcells
Diseasesanddiagnostictools
Seealso
References
Externallinks

History
ThefirstpersontodescriberedbloodcellswastheyoungDutchbiologistJanSwammerdam,whohadusedanearlymicroscopein1658tostudythebloodofa
frog.[6]Unawareofthiswork,AntonvanLeeuwenhoekprovidedanothermicroscopicdescriptionin1674,thistimeprovidingamoreprecisedescriptionofred
bloodcells,evenapproximatingtheirsize,"25,000timessmallerthanafinegrainofsand".
In1901,KarlLandsteinerpublishedhisdiscoveryofthethreemainbloodgroupsA,B,andC(whichhelaterrenamedtoO).Landsteinerdescribedtheregular
patternsinwhichreactionsoccurredwhenserumwasmixedwithredbloodcells,thusidentifyingcompatibleandconflictingcombinationsbetweentheseblood
groups.AyearlaterAlfredvonDecastelloandAdrianoSturli,twocolleaguesofLandsteiner,identifiedafourthbloodgroupAB.
In1959,byuseofXraycrystallography,Dr.MaxPerutzwasabletounravelthestructureofhemoglobin,theredbloodcellproteinthatcarriesoxygen.[7]
TheoldestintactredbloodcellseverdiscoveredwerefoundintzitheIceman,anaturalmummyofamanwhodiedaround3255BCE.Thesecellswere
discoveredinMay2012.[8]

Vertebrateerythrocytes
Erythrocytesconsistmainlyofhemoglobin,acomplexmetalloproteincontaininghemegroupswhoseironatomstemporarilybindtooxygenmolecules(O2)inthe
lungsorgillsandreleasethemthroughoutthebody.Oxygencaneasilydiffusethroughtheredbloodcell'scellmembrane.Hemoglobinintheerythrocytesalso
carriessomeofthewasteproductcarbondioxidebackfromthetissuesmostwastecarbondioxide,however,istransportedbacktothepulmonarycapillariesof
thelungsasbicarbonate(HCO3)dissolvedinthebloodplasma.Myoglobin,acompoundrelatedtohemoglobin,actstostoreoxygeninmusclecells.[10]
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Thecoloroferythrocytesisduetothehemegroupofhemoglobin.Thebloodplasmaaloneisstrawcolored,buttheredblood
cellschangecolordependingonthestateofthehemoglobin:whencombinedwithoxygentheresultingoxyhemoglobinis
scarlet,andwhenoxygenhasbeenreleasedtheresultingdeoxyhemoglobinisofadarkredburgundycolor.However,blood
canappearbluishwhenseenthroughthevesselwallandskin.[11]Pulseoximetrytakesadvantageofthehemoglobincolor
changetodirectlymeasurethearterialbloodoxygensaturationusingcolorimetrictechniques.Hemoglobinalsohasavery
highaffinityforcarbonmonoxide,formingcarboxyhemoglobinwhichisaverybrightredincolor.Flushed,confusedpatients
withasaturationreadingof100%onpulseoximetryaresometimesfoundtobesufferingfromcarbonmonoxidepoisoning.
Thesequestrationofoxygencarryingproteinsinsidespecializedcells(asopposedtooxygencarriersbeingdissolvedinbody
fluid)wasanimportantstepintheevolutionofvertebratesasitallowsforlessviscousblood,higherconcentrationsofoxygen,
andbetterdiffusionofoxygenfromthebloodtothetissues.Thesizeoferythrocytesvarieswidelyamongvertebratespecies
erythrocytewidthisonaverageabout25%largerthancapillarydiameter,andithasbeenhypothesizedthatthisimprovesthe
oxygentransferfromerythrocytestotissues.[12]
Theonlyknownvertebrateswithouterythrocytesarethecrocodileicefishes(familyChannichthyidae)theyliveinvery
oxygenrichcoldwaterandtransportoxygenfreelydissolvedintheirblood.[13]Whiletheydonotusehemoglobinanymore,
remnantsofhemoglobingenescanbefoundintheirgenome.[14]

Nucleus
Erythrocytesinmammalsareanucleatewhenmature,meaningthattheylackacellnucleus.Incomparison,theerythrocytesof
othervertebrateshavenucleitheonlyknownexceptionsaresalamandersoftheBatrachosepsgenusandfishofthe
Maurolicusgenuswithcloselyrelatedspecies.[15][16]
Theeliminationofthenucleusinvertebrateerythrocyteshasbeenofferedasanexplanationforthesubsequentaccumulation
ofnoncodingDNAinthegenome.[17]Theargumentrunsasfollows:Efficientgastransportrequireserythrocytestopass
throughverynarrowcapillaries,andthisconstrainstheirsize.Intheabsenceofnuclearelimination,theaccumulationofrepeat
sequencesisconstrainedbythevolumeoccupiedbythenucleus,whichincreaseswithgenomesize.

Thereisanimmensesizevariation
invertebrateerythrocytes,aswell
asacorrelationbetweencelland
nucleussize.Mammalian
erythrocytes,whichdonotcontain
nuclei,areconsiderablysmaller
thanthoseofmostother
vertebrates. [9]

Nucleatedredbloodcellsinmammalsconsistoftwoforms:normoblasts,whicharenormalerythropoieticprecurorstomatureerythrocytes,andmegaloblasts,
whichareabnormallylargeprecursorsthatoccurinmegaloblasticanemias.

Secondaryfunctions
Whenerythrocytesundergoshearstressinconstrictedvessels,theyreleaseATP,whichcausesthevesselwallstorelaxanddilatesoastopromotenormalblood
flow.[18]
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Whentheirhemoglobinmoleculesaredeoxygenated,erythrocytesreleaseSnitrosothiols,whichalsoacttodilateblood
vessels,[19]thusdirectingmorebloodtoareasofthebodydepletedofoxygen.
Erythrocytescanalsosynthesizenitricoxideenzymatically,usingLarginineassubstrate,asdoendothelialcells.[20]
Exposureoferythrocytestophysiologicallevelsofshearstressactivatesnitricoxidesynthaseandexportofnitricoxide,[21]
whichmaycontributetotheregulationofvasculartonus.
Erythrocytescanalsoproducehydrogensulfide,asignallinggasthatactstorelaxvesselwalls.Itisbelievedthatthe
cardioprotectiveeffectsofgarlicareduetoerythrocytesconvertingitssulfurcompoundsintohydrogensulfide.[22]
Erythrocytesalsoplayapartinthebody'simmuneresponse:whenlysedbypathogenssuchasbacteria,theirhemoglobin
releasesfreeradicals,whichbreakdownthepathogen'scellwallandmembrane,killingit.[23][24]

Mammalianerythrocytes
Mammalianerythrocytesareuniqueamongthevertebratesastheyarenonnucleatedcellsintheirmatureform.Thesecells
havenucleiduringearlyphasesoferythropoiesis,butextrudethemduringdevelopmentastheymatureinordertoprovide
morespaceforhemoglobin.Theenucleatederythrocytes,calledreticulocytes,goontoloseallothercellularorganelles
suchastheirmitochondria,Golgiapparatusandendoplasmicreticulum.

Matureerythrocytesofbirdshavea
nucleus,howeverinthebloodof
adultfemalesofpenguinPygoscelis
papuaenucleatedredbloodcells(B)
havebeenobserved,butwithvery
lowfrequency.

Asaresultofnotcontainingmitochondria,thesecellsusenoneoftheoxygentheytransportinsteadthey
producetheenergycarrierATPbytheglycolysisofglucoseandlacticacidfermentationontheresulting
pyruvate.
Becauseofthelackofnucleiandorganelles,matureredbloodcellsdonotcontainDNAandcannotsynthesize
anyRNA,andconsequentlycannotdivideandhavelimitedrepaircapabilities.[25]Theinabilitytocarryout
proteinsynthesismeansthatnoviruscanevolvetotargetmammalianredbloodcells.[26]However,infection
withparvoviruses(suchashumanparvovirusB19)canaffecterythroidprecursors,asrecognizedbythe
presenceofgiantpronormoblastswithviralparticlesandinclusionbodies,thustemporarilydepletingtheblood
ofreticulocytesandcausinganemia.[27]

Typicalmammalianerythrocytes:(a)seenfrom
surface(b)inprofile,formingrouleaux(c)
renderedsphericalbywater(d)renderedcrenateby
salt.(c)and(d)donotnormallyoccurinthebody.

Mammalianerythrocytesaretypicallyshapedasbiconcavedisks:flattenedanddepressedinthecenter,witha
dumbbellshapedcrosssection,andatorusshapedrimontheedgeofthedisk.Thisdistinctivebiconcave
shapeoptimisestheowpropertiesofbloodinthelargevessels,suchasmaximizationoflaminarflowand
minimizationofplateletscatter,whichsuppressestheiratherogenicactivityinthoselargevessels.[28]However,
therearesomeexceptionsconcerningshapeintheartiodactylorder(eventoedungulatesincludingcattle,deer,andtheirrelatives),whichdisplaysawidevariety
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ofbizarreerythrocytemorphologies:smallandhighlyovaloidcellsinllamasandcamels(familyCamelidae),tinysphericalcellsinmousedeer(family
Tragulidae),andcellswhichassumefusiform,lanceolate,crescentic,andirregularlypolygonalandotherangularformsinreddeerandwapiti(familyCervidae).
Membersofthisorderhaveclearlyevolvedamodeofredbloodcelldevelopmentsubstantiallydifferentfromthemammaliannorm.[9][29]Overall,mammalian
erythrocytesareremarkablyflexibleanddeformablesoastosqueezethroughtinycapillaries,aswellastomaximizetheirapposingsurfacebyassumingacigar
shape,wheretheyefficientlyreleasetheiroxygenload.[30]
Inlargebloodvessels,redbloodcellssometimesoccurasastack,flatsidenexttoflatside.Thisisknownasrouleauxformation,anditoccursmoreoftenifthe
levelsofcertainserumproteinsareelevated,asforinstanceduringinflammation.
Thespleenactsasareservoirofredbloodcells,butthiseffectissomewhatlimitedinhumans.Insomeothermammalssuchasdogsandhorses,thespleen
sequesterslargenumbersofredbloodcellswhicharedumpedintothebloodduringtimesofexertionstress,yieldingahigheroxygentransportcapacity.

Humanerythrocytes
Atypicalhumanerythrocytehasadiskdiameterofapproximately6.28.2m[31]andathicknessatthethickestpointof2
2.5mandaminimumthicknessinthecentreof0.81m,beingmuchsmallerthanmostotherhumancells.Thesecellshave
anaveragevolumeofabout90fL[32]withasurfaceofabout136m2,andcanswelluptoasphereshapecontaining150fL,
withoutmembranedistension.
Adulthumanshaveroughly20301012(2030trillion)redbloodcellsatanygiventime,comprisingapproximately70%of
thetotalhumanbodycellnumber.[33]Womenhaveabout4to5millionerythrocytespermicroliter(cubicmillimeter)ofblood
andmenabout5to6millionpeoplelivingathighaltitudeswithlowoxygentensionwillhavemore).Redbloodcellsarethus
muchmorecommonthantheotherbloodparticles:thereareabout4,00011,000whitebloodcellsandabout150,000
400,000plateletsineachmicroliterofhumanblood.

Scanningelectronmicrographof
bloodcells.Fromlefttoright:
humanerythrocyte,thrombocyte
(platelet),leukocyte.

Humanredbloodcellstakeonaverage20secondstocompleteonecycleofcirculation.[3][4][34]
Asredbloodcellscontainnonucleus,proteinbiosynthesisiscurrentlyassumedtobeabsentinthesecells.
Theblood'sredcolorisduetothespectralpropertiesofthehemicironionsinhemoglobin.Eachhumanredbloodcell
containsapproximately270millionofthesehemoglobinbiomolecules,eachcarryingfourhemegroupshemoglobin
comprisesaboutathirdofthetotalcellvolume.Thisproteinisresponsibleforthetransportofmorethan98%oftheoxygen
(theremainingoxygeniscarrieddissolvedinthebloodplasma).Theredbloodcellsofanaverageadulthumanmalestore
collectivelyabout2.5gramsofiron,representingabout65%ofthetotalironcontainedinthebody.[35][36](SeeHumaniron
metabolism.)
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Twodropsofbloodareshown
withabrightredoxygenateddrop
ontheleftandadeoxygenated
dropontheright.

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Lifecycle
Humanerythrocytesareproducedthroughaprocessnamederythropoiesis,developingfromcommittedstemcellstomature
erythrocytesinabout7days.Whenmatured,inahealthyindividualthesecellsliveinbloodcirculationforabout100to120
days(and80to90daysinafullterminfant).[37]Attheendoftheirlifespan,theybecomesenescent,andareremovedfrom
circulation.Inmanychronicdiseases,thelifespanoftheerythrocytesismarkedlyreduced(e.g.patientsrequiring
haemodialysis).
Erythropoiesis
Erythropoiesisisthedevelopmentprocessbywhichnewerythrocytesareproduceditlastsabout7days.Throughthisprocess
erythrocytesarecontinuouslyproducedintheredbonemarrowoflargebones,atarateofabout2millionpersecondina
healthyadult.(Intheembryo,theliveristhemainsiteofredbloodcellproduction.)Theproductioncanbestimulatedbythe
hormoneerythropoietin(EPO),synthesisedbythekidney.Justbeforeandafterleavingthebonemarrow,thedevelopingcells
areknownasreticulocytesthesecompriseabout1%ofcirculatingredbloodcells.
Functionallifetime

Ananimationofatypicalhuman
redbloodcellcycleinthe
circulatorysystem.Thisanimation
occursatrealtime(20secondsof
cycle)andshowstheredblood
celldeformasitenterscapillaries,
aswellaschangingcolorasit
alternatesinstatesofoxygenation
alongthecirculatorysystem.

Thefunctionallifetimeofanerythrocyteisabout100120days,duringwhichtimetheerythrocytesarecontinuallymovedby
thebloodflowpush(inarteries),pull(inveins)andacombinationofthetwoastheysqueezethroughmicrovesselssuchascapillaries.
Senescence
Theagingerythrocyteundergoeschangesinitsplasmamembrane,makingitsusceptibletoselectiverecognitionbymacrophagesandsubsequentphagocytosisin
themononuclearphagocytesystem(spleen,liverandlymphnodes),thusremovingoldanddefectivecellsandcontinuallypurgingtheblood.Thisprocessis
termederyptosis,erythrocyteprogrammedcelldeath.[38]Thisprocessnormallyoccursatthesamerateofproductionbyerythropoiesis,balancingthetotal
circulatingredbloodcellcount.Eryptosisisincreasedinawidevarietyofdiseasesincludingsepsis,haemolyticuremicsyndrome,malaria,sicklecellanemia,
betathalassemia,glucose6phosphatedehydrogenasedeficiency,phosphatedepletion,irondeficiencyandWilson'sdisease.Eryptosiscanbeelicitedbyosmotic
shock,oxidativestress,energydepletionaswellasawidevarietyofendogenousmediatorsandxenobiotics.Excessiveeryptosisisobservedinerythrocytes
lackingthecGMPdependentproteinkinasetypeIortheAMPactivatedproteinkinaseAMPK.Inhibitorsoferyptosisincludeerythropoietin,nitricoxide,
catecholaminesandhighconcentrationsofurea.
Muchoftheresultingbreakdownproductsarerecirculatedinthebody.ThehemeconstituentofhemoglobinarebrokendownintoFe3+andbiliverdin.The
biliverdinisreducedtobilirubin,whichisreleasedintotheplasmaandrecirculatedtotheliverboundtoalbumin.Theironisreleasedintotheplasmatobe
recirculatedbyacarrierproteincalledtransferrin.Almostallerythrocytesareremovedinthismannerfromthecirculationbeforetheyareoldenoughtohemolyze.
Hemolyzedhemoglobinisboundtoaproteininplasmacalledhaptoglobin,whichisnotexcretedbythekidney.[39]
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Membranecomposition
Themembraneoftheredbloodcellplaysmanyrolesthataidinregulatingtheirsurfacedeformability,flexibility,adhesiontoothercellsandimmunerecognition.
Thesefunctionsarehighlydependentonitscomposition,whichdefinesitsproperties.Theredbloodcellmembraneiscomposedof3layers:theglycocalyxonthe
exterior,whichisrichincarbohydratesthelipidbilayerwhichcontainsmanytransmembraneproteins,besidesitslipidicmainconstituentsandthemembrane
skeleton,astructuralnetworkofproteinslocatedontheinnersurfaceofthelipidbilayer.Halfofthemembranemassinhumanandmostmammalianerythrocytes
areproteins.Theotherhalfarelipids,namelyphospholipidsandcholesterol.[40]
Membranelipids
Theerythrocytecellmembranecomprisesatypicallipidbilayer,similartowhatcanbefoundinvirtuallyallhuman
cells.Simplyput,thislipidbilayeriscomposedofcholesterolandphospholipidsinequalproportionsbyweight.The
lipidcompositionisimportantasitdefinesmanyphysicalpropertiessuchasmembranepermeabilityandfluidity.
Additionally,theactivityofmanymembraneproteinsisregulatedbyinteractionswithlipidsinthebilayer.
Unlikecholesterol,whichisevenlydistributedbetweentheinnerandouterleaflets,the5majorphospholipidsare
asymmetricallydisposed,asshownbelow:
Outermonolayer
Phosphatidylcholine(PC)
Sphingomyelin(SM).
Innermonolayer
Phosphatidylethanolamine(PE)
Phosphoinositol(PI)(smallamounts).
Phosphatidylserine(PS)
Thisasymmetricphospholipiddistributionamongthebilayeristheresultofthefunctionofseveralenergydependent
andenergyindependentphospholipidtransportproteins.ProteinscalledFlippasesmovephospholipidsfromthe
outertotheinnermonolayer,whileotherscalledfloppasesdotheoppositeoperation,againstaconcentration
gradientinanenergydependentmanner.Additionally,therearealsoscramblaseproteinsthatmovephospholipidsin
bothdirectionsatthesametime,downtheirconcentrationgradientsinanenergyindependentmanner.Thereisstill
considerabledebateongoingregardingtheidentityofthesemembranemaintenanceproteinsintheredcellmembrane.

Themostcommonerythrocytecell
membranelipids,schematicallydisposedas
theyaredistributedonthebilayer.Relative
abundancesarenotatscale.

Themaintenanceofanasymmetricphospholipiddistributioninthebilayer(suchasanexclusivelocalizationofPSandPIsintheinnermonolayer)iscriticalfor
thecellintegrityandfunctionduetoseveralreasons:
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MacrophagesrecognizeandphagocytoseredcellsthatexposePSattheiroutersurface.ThustheconfinementofPSintheinnermonolayerisessentialifthe
cellistosurviveitsfrequentencounterswithmacrophagesofthereticuloendothelialsystem,especiallyinthespleen.
PrematuredestructionofthallassemicandsickleredcellshasbeenlinkedtodisruptionsoflipidasymmetryleadingtoexposureofPSontheouter
monolayer.
AnexposureofPScanpotentiateadhesionofredcellstovascularendothelialcells,effectivelypreventingnormaltransitthroughthemicrovasculature.Thus
itisimportantthatPSismaintainedonlyintheinnerleafletofthebilayertoensurenormalbloodflowinmicrocirculation.
BothPSandphosphatidylinositol4,5bisphosphate(PIP2)canregulatemembranemechanicalfunction,duetotheirinteractionswithskeletalproteinssuch
asspectrinandprotein4.1R.RecentstudieshaveshownthatbindingofspectrintoPSpromotesmembranemechanicalstability.PIP2enhancesthebinding
ofproteinband4.1RtoglycophorinCbutdecreasesitsinteractionwithproteinband3,andtherebymaymodulatethelinkageofthebilayertothe
membraneskeleton.
Thepresenceofspecializedstructuresnamed"lipidrafts"intheerythrocytemembranehavebeendescribedbyrecentstudies.Thesearestructuresenrichedin
cholesterolandsphingolipidsassociatedwithspecificmembraneproteins,namelyflotillins,stomatins(band7),Gproteins,andadrenergicreceptors.Lipidrafts
thathavebeenimplicatedincellsignalingeventsinnonerythroidcellshavebeenshowninerythroidcellstomediate2adregenicreceptorsignalingandincrease
cAMPlevels,andthusregulatingentryofmalarialparasitesintonormalredcells.[41][42]
Membraneproteins
Theproteinsofthemembraneskeletonareresponsibleforthedeformability,flexibilityanddurabilityoftheredbloodcell,
enablingittosqueezethroughcapillarieslessthanhalfthediameteroftheerythrocyte(78m)andrecoveringthediscoid
shapeassoonasthesecellsstopreceivingcompressiveforces,inasimilarfashiontoanobjectmadeofrubber.
Therearecurrentlymorethan50knownmembraneproteins,whichcanexistinafewhundreduptoamillioncopiesper
erythrocyte.Approximately25ofthesemembraneproteinscarrythevariousbloodgroupantigens,suchastheA,BandRh
antigens,amongmanyothers.Thesemembraneproteinscanperformawidediversityoffunctions,suchastransporting
ionsandmoleculesacrosstheredcellmembrane,adhesionandinteractionwithothercellssuchasendothelialcells,as
signalingreceptors,aswellasothercurrentlyunknownfunctions.Thebloodtypesofhumansareduetovariationsin
surfaceglycoproteinsoferythrocytes.Disordersoftheproteinsinthesemembranesareassociatedwithmanydisorders,
suchashereditaryspherocytosis,hereditaryelliptocytosis,hereditarystomatocytosis,andparoxysmalnocturnal
hemoglobinuria.[40][41]
Theredbloodcellmembraneproteinsorganizedaccordingtotheirfunction:
Transport
Band3Aniontransporter,alsoanimportantstructuralcomponentoftheerythrocytecellmembrane,makesupto
25%ofthecellmembranesurface,eachredcellcontainsapproximatelyonemillioncopies.DefinestheDiegoBlood
Group[44]
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Redbloodcellmembraneproteins
separatedbySDSPAGEand
silverstained [43]

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Aquaporin1watertransporter,definestheColtonBloodGroup
Glut1glucoseandLdehydroascorbicacidtransporter
Kiddantigenproteinureatransporter
RhAGgastransporter,probablyofcarbondioxide,definesRhBloodGroupandtheassociatedunusualblood
groupphenotypeRhnull
Na+/K+ATPase
Ca2+ATPase
Na+K+2Clcotransporter
Na+Clcotransporter
NaHexchanger
KClcotransporter
GardosChannel.

Redbloodcellmembranemajor
proteins

Celladhesion
ICAM4interactswithintegrins
BCAMaglycoproteinthatdefinestheLutheranbloodgroupandalsoknownasLuorlamininbindingprotein.
StructuralroleThefollowingmembraneproteinsestablishlinkageswithskeletalproteinsandmayplayanimportantroleinregulatingcohesionbetweenthe
lipidbilayerandmembraneskeleton,likelyenablingtheredcelltomaintainitsfavorablemembranesurfaceareabypreventingthemembranefromcollapsing
(vesiculating).
Ankyrinbasedmacromolecularcomplexproteinslinkingthebilayertothemembraneskeletonthroughtheinteractionoftheircytoplasmicdomainswith
Ankyrin.
Band3alsoassemblesvariousglycolyticenzymes,thepresumptiveCO2transporter,andcarbonicanhydraseintoamacromolecularcomplextermed
a"metabolon,"whichmayplayakeyroleinregulatingredcellmetabolismandionandgastransportfunction)
RhAGalsoinvolvedintransport,definesassociatedunusualbloodgroupphenotypeRhmod.
Protein4.1RbasedmacromolecularcomplexproteinsinteractingwithProtein4.1R.
Protein4.1RweakexpressionofGerbichantigens
GlycophorinCandDglycoprotein,definesGerbichBloodGroup
XKdefinestheKellBloodGroupandtheMcleodunusualphenotype(lackofKxantigenandgreatlyreducedexpressionofKellantigens)
RhD/RhCEdefinesRhBloodGroupandtheassociatedunusualbloodgroupphenotypeRhnull
Duffyproteinhasbeenproposedtobeassociatedwithchemokineclearance[45]
Adducininteractionwithband3
DematininteractionwiththeGlut1glucosetransporter.
[40][41]

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Surfaceelectrostaticpotential
Thezetapotentialisanelectrochemicalpropertyofcellsurfacesthatisdeterminedbythenetelectricalchargeofmoleculesexposedatthesurfaceofcell
membranesofthecell.Thenormalzetapotentialoftheerythrocyteis15.7millivolts(mV).[46]Muchofthispotentialappearstobecontributedbytheexposed
sialicacidresiduesinthemembrane:theirremovalresultsinzetapotentialof6.06mV.

Clinicalnotes
Separationandblooddoping
Redbloodcellscanbeobtainedfromwholebloodbycentrifugation,whichseparatesthecellsfromthebloodplasmainaprocessknownasbloodfractionation.
Packedredbloodcells,whicharemadeinthiswayfromwholebloodwiththeplasmaremoved,areusedintransfusionmedicine.[47]Duringplasmadonation,the
redbloodcellsarepumpedbackintothebodyrightawayandonlytheplasmaiscollected.
Someathleteshavetriedtoimprovetheirperformancebyblooddoping:firstabout1litreoftheirbloodisextracted,thentheredbloodcellsareisolated,frozen
andstored,tobereinjectedshortlybeforethecompetition.(Redbloodcellscanbeconservedfor5weeksat79Cor110F)Thispracticeishardtodetectbut
mayendangerthehumancardiovascularsystemwhichisnotequippedtodealwithbloodoftheresultinghigherviscosity.Anothermethodofblooddoping
involvesinjectionwitherythropoietininordertostimulateproductionofredbloodcells.BothpracticesarebannedbytheWorldAntiDopingAgency.

Artificiallygrownredbloodcells
In2008itwasreportedthathumanembryonicstemcellshadbeensuccessfullycoaxedintobecomingerythrocytesinthelab.Thedifficultstepwastoinducethe
cellstoejecttheirnucleusthiswasachievedbygrowingthecellsonstromalcellsfromthebonemarrow.Itishopedthattheseartificialerythrocytescan
eventuallybeusedforbloodtransfusions.[48]

Diseasesanddiagnostictools
Blooddiseasesinvolvingtheredbloodcellsinclude:
Anemias(oranaemias)arediseasescharacterizedbylowoxygentransportcapacityoftheblood,becauseoflowredcellcountorsomeabnormalityofthe
redbloodcellsorthehemoglobin.
Irondeficiencyanemiaisthemostcommonanemiaitoccurswhenthedietaryintakeorabsorptionofironisinsufficient,andhemoglobin,which
containsiron,cannotbeformed

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Sicklecelldiseaseisageneticdiseasethatresultsinabnormalhemoglobinmolecules.Whenthesereleasetheiroxygen
loadinthetissues,theybecomeinsoluble,leadingtomisshapedredbloodcells.Thesesickleshapedredcellsareless
deformableandviscoelasticmeaningthattheyhavebecomerigidandcancausebloodvesselblockage,pain,strokes,and
othertissuedamage.
Thalassemiaisageneticdiseasethatresultsintheproductionofanabnormalratioofhemoglobinsubunits.
Hereditaryspherocytosissyndromesareagroupofinheriteddisorderscharacterizedbydefectsintheredbloodcell'scell
membrane,causingthecellstobesmall,sphereshaped,andfragileinsteadofdonutshapedandflexible.Theseabnormal
redbloodcellsaredestroyedbythespleen.Severalotherhereditarydisordersoftheredbloodcellmembraneare
known.[49]
Perniciousanemiaisanautoimmunediseasewhereinthebodylacksintrinsicfactor,requiredtoabsorbvitaminB12from
food.VitaminB12isneededfortheproductionofhemoglobin.
Aplasticanemiaiscausedbytheinabilityofthebonemarrowtoproducebloodcells.

AffectedbySicklecell
disease,redbloodcells
altershapeandthreaten
todamageinternal
organs.

Pureredcellaplasiaiscausedbytheinabilityofthebonemarrowtoproduceonlyredbloodcells.
Hemolysisisthegeneraltermforexcessivebreakdownofredbloodcells.Itcanhaveseveralcausesandcanresultin
hemolyticanemia.
Themalariaparasitespendspartofitslifecycleinredbloodcells,feedsontheirhemoglobinandthenbreaks
themapart,causingfever.Bothsicklecelldiseaseandthalassemiaaremorecommoninmalariaareas,because
thesemutationsconveysomeprotectionagainsttheparasite.
Polycythemias(orerythrocytoses)arediseasescharacterizedbyasurplusofredbloodcells.Theincreasedviscosity
ofthebloodcancauseanumberofsymptoms.

Effectofosmoticpressureonblood
cells

Inpolycythemiaveratheincreasednumberofredbloodcellsresultsfromanabnormalityinthebonemarrow.
Severalmicroangiopathicdiseases,includingdisseminatedintravascularcoagulationandthrombotic
microangiopathies,presentwithpathognomonic(diagnostic)redbloodcellfragmentscalledschistocytes.These
pathologiesgeneratefibrinstrandsthatseverredbloodcellsastheytrytomovepastathrombus.
Hemolytictransfusionreactionisthedestructionofdonatedredbloodcellsafteratransfusion,mediatedbyhost
antibodies,oftenasaresultofabloodtypemismatch.
Severalbloodtestsinvolveredbloodcells,includingtheRBCcount(thenumberofredbloodcellspervolumeofblood),
thehematocrit(percentageofbloodvolumeoccupiedbyredbloodcells),andtheerythrocytesedimentationrate.Many
diseasesinvolvingredbloodcellsarediagnosedwithabloodfilm(orperipheralbloodsmear),whereathinlayerofblood
https://en.wikipedia.org/wiki/Red_blood_cell

Micrographsoftheeffectsofosmotic
pressure

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issmearedonamicroscopeslide.Thebloodtypeneedstobedeterminedtoprepareforabloodtransfusionoranorgantransplantation.

Seealso
Altitudetraining
Bloodserum
Erythrocytedeformability
Erythrocytefragility
Hemoglobinbasedoxygencarriers
Packedredbloodcells
Redbloodcellindices

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Externallinks
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