4. RBC, Structure and Function

7/25/2019 4. RBC, Structure and Function

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RBC Structure and

Function


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RBC Structure and Function


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Production of RBCs: (1) Fetal Life Liver, Spleen, Bone

Marrow (BM) (2) Child/Adult BM. (Cild!lots of te

s"eleton is involved, #dult!$ostl% tea&ial s"eleton is involved).

(3) Extreme hematologic StressLiver and Spleen can revert to $a"in'RBC (&tra$edullar% *e$atopoiesis).&: "id wit severe ane$ia due totalasse$ia wit epatospleno$e'al%.


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BM nviron$ent: cellular proliferation and$aturation. # +ne reticular $eswor" supportscellular ele$ents as vascular sinuses coursetrou' te $arrow cavit% allowin' for te inow ofplas$a nutrients -ut retainin' developin' cellsuntil te% are $ature.

RBCs $ature around a central $acropa'e.

RBC evelop$ent: Ste$ cell / $ultipotent ste$ cell/ BF0! / CF0! / er%tro-last / / RBC

RBC Lifespan: Fro$ earliest reco'ni1a-le erythroblastto a mature RBCit ta"es 3-4 das, reticulocyte(nucleus as -een e&truded, -ut so$e R2# is leftover)for a-out 1 da, and $ature RBC lives 12!das"


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*e$o'lo-in s%ntesis: 3ree co$ponents ofe$o'lo-in: (4) 'lo-in, (5) protoporp%rin, (6) iron(protoporp%rin and iron co$-ine to for$ #eme).

7ron enters te developin' RBC and ulti$atel%

enters te $itocondria to support e$e s%ntesis. 7n te $itocondria te +rst step of e$es%ntesis ta"es place as 'l%cine and succin%l Co#co$-ine to for$ delta a$inolevulinic acid.

S%ntesis sifts into te c%toplas$ -ut ulti$atel%returns to te $itocondria for +nal steps in te

for$ation of protoporp%rin 78 and, eventuall%e$e, as protoporp%rin and iron co$-ine. Sidero-lastic ane$ia 9 Con'enital a-sence of

en1%$es alon' te pat of proto!porp%rins%ntesis $a% lead to severe i$pair$ent of e$es%ntesis


7/17

lo-in cain s%ntesis: various *'-;s:

*'- # 9 5 alpa cains and 5 -eta

cains*'- #59 5 alpa cains and 5 delta

cains

*'- F 9 5 alpa cains and 5'a$$a cains


8/17

Can'es of *'- trou'out life: Birt $ost *'-present is of te fetal variet%

=!> $onts appro&i$atel% ?@A of *'- is *'- #,

5A is *'- #!5 and 4A is *'- F Clinical correlate: -eta cain *'- disorders suc as

sic"le cell disease do not clinicall% $anifest until $ $, widt 9 5 $ $,volu$e 9 ? fe$toliters


9/17

3ree Constituents of RBCs: RBC$e$-rane D internal $eta-olic apparatus(ie a -it of c%toplas$) D e$o'lo-in

RBC $e$-rane: *as lipid -ila%er

$e$-rane wit proteins in it. 0nderneatit is a c%tos"eleton of proteins allowin'ru--er% elasticit% wit $ain protein -ein'S$ectri%. A%&ri%ancors c%tos"eletonto $e$-rane. 2aE #3Pase cannel is

a-undant on $e$-rane (#3P fro$pentose pospate sunt tats w%=P de+cient people ave pro-le$s).Me$-rane anti'en structure tere areover 6 RBC $e$-rane #'s. 3e% are

Pol%saccarides. (#, B, R, uG%, etc).


10/17

Em'de%-eerhof ath*a -glcolsis from glucose to

lactate+ %et 2 A,s $roduced a%dused to su$$ort mem'ra%e io%$um$s" he% de.cie%cies of theE- $ath exist+ 0C surial is

reduced+ leadi%g to hemolsis


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ethemoglo'i% eductase ath*a!prevents iron of *'- fro$ -ein' o&idi1ed,$a"es 2#* wic is reducin' power. *'- iron

$ust -e in reduced state (FeD5

) in order totransport H5. 3e environ$ent is constantl%'eneratin' o&idant stress and terefore atendenc% to o&idi1e iron to Fe6D. 3e$ete$o'lo-in reductase patwa% counteracts

tis -% reducin' iron to te D5 state. Patientswit $ete$o'lo-in reductase de+cienc% avea su-stantial Iuantit% of $ete$o'lo-in (*'-wit iron in te o&idated state) associated witreduced H5carr%in' capacit%.


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Lue'eri%g-a$a$ort ath*a! $odi+esaJnit% of -indin' of *'- and H5, $a"es 5,6!Pwic sifts saturation curve to te ri't. 3ispatwa% is an oG!sute of te !M patwa%

leadin' to 'eneration of 5!6 P. 5!6 P is ani$portant re'ulator of *'-!H5release (increased5!6 P 'ivin' rise to increased H5release). #nincreased rate of 'l%col%sis leads to an increasein intracellular 5!6 P concentration. Ken

venous -lood is increasin'l% deo&%'enated, terate of 'l%col%sis increases leadin' to increased5!6 P production and increased H5release tote tissues. 3is is an appropriate response toensure adeIuate H5deliver%.


13/17

#exose-o%o$hos$hate Shu%t(Pospo'lucoate Patwa%)-3is patwa%couples o&idative $eta-olis$ wit 2#P

and 'lutatione reductase to provide anti!o&idant su-strate wic ulti$atel%co$-ats te eGects of o&%'en stresses(environ$ental, $edications). 7f te suntis defective (as is te case in patients wit

=P de+cienc%) o&idative insults lead too&idation of 'lo-in cains and denaturationof *'- leadin' to precipitates (*ein1-odies) in te RBC, $e$-rane da$a'eand, ulti$atel%, cell deat.


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P9 PH5at wic *'- is A saturatedRi't sift (H5 released easil%) of te

curve is caused -%: H5aJnit%, p*, N5,6!P, N pCH5, N te$p

Left sift (H5 -ound ti'tl%) of te curveis caused -%: N H5aJnit%, N p*, 5,6!

P, pCH5, te$pidne%s are sensors (Ou&tatu-ular cells)

for H5deliver% / N PH


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Reticuloendotelial cells participate in te destruction ofsenescent RBC;s.

estruction of RBCs appens witin reticuloendotelialcells 2H3 in te circulation. lo-in and e$e 'etrec%cled, porp%rin is de'raded to -iliru-in wic isconu'ated -% te liver and e&creted in te 'ut. Rateli$itin' step is conu'ation. 7ndirect (unconu'ated)-iliru-in is result if tis doesnt appen.

2or$all% Q4A RBCs l%se wile in circulation / *'- 'ets

released into circulation and rapidl% disassociates intoalpa and -eta di$ers wic are -ound -% apto'lo-in.3e *'-Eapto'lo-in co$ple& is transported to te liver.7f apto'lo-in is depleted, free *'- circulates and is+ltered -% te "idne%. Free *'- is eiter rea-sor-ed -%renal tu-ular cells or e&creted as free *'- in te urine


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,he role of the 0C i% the tra%s$ort of 2from the lu%gs tothe tissues is ce%tral" A ariet of i%tegrated $hsiologiccom$o%e%ts co%tri'utes to actie 2su$$l to tissuesi%cludi%g $ulmo%ar fu%ctio%+ a%d hemod%amic factors(C""+ regio%al 'lood o*+ 'lood olume+ iscosit)"

egulatio% of the Erthro% 5% the 'asal ideal state+ 'loode%ters the tissue at a 2of 67 a%d exits at a 2of 4!",herefore+ 278 of 2tra%s$orted ' #g' is release" 2delier ma 'e altered ' (1) #g'-2a9%it a%d (2)i%crease i% the %um'er of 0C:s"

ulmo%ar fu%ctio%/hemod%amic factors ,he lu%gs a%d

heart ma%ifest a $hsiologic res$o%se i% the face ofdecreased 2carri%g ca$acit associated *ith a%emia"Alteratio%s i% regio%al 'lood o* as *ell as a mar&edi%crease i% cardiac out$ut ca% com$e%sate for 7!8 fall i%2carri%g ca$acit i% the a%emic $atie%t" As a result+$atie%ts *ith sig%i.ca%t a%emia fre;ue%tl haetachcardia a%d a% i%creased cardiac e

4. RBC, Structure and Function

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4. RBC, Structure and Function