2011 Blood and Heme

8/18/2019 2011 Blood and Heme

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HEMATOPOIETIC SYSTEM I: PERIPHERAL BLOODMargaret Uthman, MD

Reading: Gartner and Hiatt, pages 89-101; Klein and McKenzie, pp155-181Learning Objeti!e":

• Describe the composition o normal peripheral blood, incl!ding the relati"e #!antities o the blood

cells$

• %denti& normal peripheral blood cells$

• Describe the !nction and 'lie c&cle' o normal peripheral blood cells$

#e$ %&rd"( )r&throc&tes, retic!loc&tes, ne!trophils, eosinophils, basophils, monoc&tes, l&mphoc&tes and platelets

COMPOSITIO'*lood is a l!id connecti"e tiss!e constit!ting abo!t + o o!r total bod& eight .abo!t 5 liters in the h!man/$he primar& components are(

P(a"ma( he li#!id in hich peripheral blood cells are s!spended$ omposed o ater, electrol&tes s!ch as 2a3

and l, .0$9/, + plasma proteins .s!ch as alb!min, ibrinogen, glob!lins/, hormones, ats, amino acids,

"itamins carboh&drates, lipoproteins as ell as other s!bstances$ he normal plasma "ol!me is 40 ml6g o bod& eight$

)&rmed E(ement" *b(&&d e(("+:

• Er$thr&$te" *red b(&&d e((" &r rb+: occ!p& abo!t 40-45 o the total blood "ol!me or 70 ml6g

bod& eight$

• Le-&$te" *.hite b(&&d e((" &r .b+ and P(ate(et": together ma6e !p abo!t 1- o the total

blood "ol!me$

reshl& dran blood is a red l!id .speciic gra"it& o 1$05-1$0:4/$ %t orms a ell&-li6e mass i alloed toclot$ he clot is ormed b& the con"ersion o ibrinogen to ibrin hich orms a meshor6 that entraps theormed elements$ % the gel is centri!ged, cell ree ser!m can be obtained$ % an anticoag!lant is added, blood

can be sedimented into three distinct la&ers d!e to dierent densities o elements( rbc < bc < plasma$ heloermost la&er .45 o the blood "ol!me/ consists o er&throc&tes$ =bo"e this region is a gra&ish hite la&er .b!& coat/ hich represents the platelets, l&mphoc&tes and gran!loc&tes .abo!t 1- "ol!me/$ >lasma is thetop la&er$

MORPHOLO/Y A'D )U'CTIO' O) THE BLOOD CELLS


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ERYTHROCYTES *matre red b(&&d e(("+

• C$t&(&g$

he mat!re h!man er&throc&te meas!res abo!t +-8 µm in diameter and appears as an an!cleate,

acidophilic cell$ %n addition to the n!cle!s, the mat!re er&throc&te also loses its Golgi apparat!s,

centrioles, )? and most o its mitochondria$

• *!l6 o the c&toplasm .90-95 o dr& eight/ consists o the iron-carr&ing pigment hem&g(&bin$

e organelles present$

• Sha0e: = bi&na!e di"- to achie"e a ma@im!m s!race area to c&toplasmic "ol!me ratio$ he

s!race area o an er&throc&te is calc!lated to be 18 µm$ h!s, the a"erage person has 7840 m o

rbc membrane area or respirator& e@change$ he cell is enclosed in a t&pical l!id, bila&ered cellmembrane hich is le@ible and elastic eno!gh to allo the cell to mo"e thro!gh capillaries$ ellsre#!entl& ass!me a c!p shape in capillaries$ >eripheral membrane proteins, spectrin and actin, ser"ea c&tos6eletal !nction$

>eripheral blood( red blood cells.air dried, Aright stain/ Bcanning

electron micrograph o red bloodcells

• Li1e "0an: he mat!re er&throc&te has a lie span o appro@imatel& 10 da&s in the circ!lation$ =s

red blood cells age, the s!race area decreases relati"e to c&toplasmic "ol!me res!lting in a sphereorm hich is more rigid and is !ltimatel& trapped in splenic cords$

• )nti&n: o pro"ide an en"ironment or the iron-containing respirator& pigment, heme, hich is

comple@ed to to alpha and to beta globin chains comprising the hemoglobin molec!le$ he maj&r0h$"i&(&gi r&(e &1 hem&g(&bin i" &2$gen and CO 3 tran"0&rt$ he er&throc&te also containsenz&mes that participate in the gl&col&tic and he@ose monophosphate biochemical patha&s$ Cnder normal circ!mstances, red blood cells ne"er lea"e the circ!lator& s&stem$

*lood content in each t&pe o blood "essel$ he amo!nt o is highest in arteries and l!ngcapillaries; it decreases in tiss!e capillaries, here e@change ta6es place beteen blood and tiss!e$


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• )re4en$ *nmber+

Male E 4$+-:$1 @ 10: cellsmm7; emale E 4$-5$4 @ 10: cellsmm7$RETICULOCYTES

hese are (e"" matre er$thr&$te"$ ?ed blood cells released rom the bone marro into the peripheralcirc!lation are considered retic!loc&tes or abo!t 3 da$"$

• C$t&(&g$

ontain resid!al ribon!cleoprotein particles hich impart a bl!ish h!e to the cell on ?omanos6&.Aright/ staining .the increased amo!nt o ?2= gi"es the ?* more o a red-bl!e color, termed pol&chromasia/$ = s!pra"ital stain s!ch as meth&lene bl!e is needed to deiniti"el& identi& the ribosomalremnants in retic!loc&tes$

• )re4en$: Ma6e !p 1- o red cells; ater appro@imatel& l da& in peripheral blood the& are

indisting!ishable rom mat!re blood cells$

'EUTROPHILS *netr&0hi(i gran(&$te"+:

• C$t&(&g$: he mat!re ne!trophil meas!res appro@imatel& 1-15 µm diameter in a smear$ %t is

characterized b& a prominent n!cle!s segmented into -5 lobes oined b& e@tremel& ine n!clear strands$M&"t nmer&" &1 the .hite b(&&d e((" in an ad(t .l&mphoc&tes are more n!mero!s in &o!ng children/$Blightl& less mat!re ne!trophils .bands/ ha"e a non-segmented or band-shaped n!cle!s$ ?arel&, earlier

orms s!ch as metam&eloc&tes ma& be seen in the >*$• /ran(e": &toplasm contains to maor t&pes o gran!les(

o S0ei1i *"e&ndar$+ gran(e"

Most n!mero!s t&pe; small ith a pin6ish h!e .airl& Fne!tral staining/, so not easil& seen,collagenase, lactoerrin, bacteriocidal phagoc&tins and l&soz&me$

o A5r&0hi(i *0rimar$+ gran(e"

hese are less n!mero!s, larger, and stain reddish p!rple$ he& are most commonl& o!nd in the prom&eloc&te stage o gran!loc&te prec!rsors and are not speciic or ne!trophils$ >rom&eloc&tesare o!nd in the bone marro, b!t not normall& in the peripheral blood$ he& are primar&l&sosomes hich contain m&elopero@idase and acid h&drolases characteristic o l&sosomes$

• &toplasm also contains gl&cogen and n!mero!s ilaments and microt!b!les .!nction in mo"ement/$

• 2e!trophils hich ha"e !st been released rom the bone marro oten ha"e a band-shaped or

horseshoe-shaped n!cle!s and are 6non as bands$• %n emales the inacti"ated chromosome can appear as a n!clear appendage .*arr bod&/$

• )re4en$

he hite cells o peripheral blood are generall& 50-+5 ne!trophils; abo!t 7-5 are band orms$ Ha(16(i1e in b(&&d i" &n($ 768 hr", 96 da$ (i1e"0an; 2e!trophils mo"e rom the peripheral circ!lation into thetiss!es in response to inection or tiss!e damage .e$g$, a m&ocardial inarct/$

• )nti&n"

• 'etr&0hi(" are the 1ir"t (ine &1 de1en"e again"t mir&&rgani"m", e"0eia(($ bateria$ he& are

ati!e 0hag&$te"$ >articles are ta6en !p in a "ac!ole, the pH is loered b& a membrane proton p!mp, then the az!rophilic gran!les !se and empt&$ Killing and digestion occ!r$ =cti"ated o@&gen

species also orm and 6ill microorganisms$ I&soz&me destro&s cell all o gram-positi"e bacteria$

• 2e!trophils !ndergo chemota@is$ he& are attracted b& de"italized tiss!e, bacteria, oreign bodies,

and complement components$

• >hagoc&tosis can be non-speciic b!t ill be enhanced i the bod& has made speciic antibodies d!e to

pre"io!s e@pos!re$ B(&&d b&rne antib&d$ *Ig/+ bind" t& "r1ae antigen &r bateria, and then&m0(ement C


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>eripheral blood( ne!trophils

EOSI'OPHILS

• C$t&(&g$

he mat!re eosinophil is abo!t the same size as the ne!trophil; abo!t 1-15 µm in diameter in dr& smears$

he eosinophil generall& contains a bilobed n!cle!s; hoe"er, three to o!r lobes are noted occasionall&$he c&toplasm has characteristics similar to the ne!trophil ith the notable e@ception that the speciicgran!les are reractile and stain bright orange .eosinophilic/ ith the ?omanos6& stain$ hese gran!lesare somehat !ni#!e beca!se b& electron microscop& the& can be seen to contain a den"e 1i(ament&"&re &1 maj&r ba"i 0r&tein *MBP+$ hese str!ct!res are 6non as cr&stalloids$ he matri@ o thegran!les contains l&sosomal enz&mes, and in partic!lar has a high content o pero@idase, ar&ls!latase,acid phosphatase, ?2ase and cathepsin$

• )re4en$

he peripheral blood contains abo!t 1-7 eosinophils$ he n!mber o eosinophils is high in indi"id!alsith allergies or parasitic inections$ A("& ir(ate" ab&t 8 h&r";

• )nti&n"

he !nction o eosinophils is not entirel& clear, b!t the& are inrea"ed in "&me 0ara"iti in1eti&n", ina((ergi re"0&n"e" t& a !ariet$ &1 "tim(i in(ding 0&((en, "&me drg reati&n"$

• Chem&ta2i"

hese cells are 6non to phagoc&tose antigen-antibod& comple@es and inacti"ate mediators o inlammation s!ch as Ie!6otrienes$

• Maj&r ba"i 0r&tein 6 Kills parasitic orms$

>eripheral blood( eosinophil

BASOPHILS


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• C$t&(&g$

he mat!re basophil meas!res 9-10 µm in diameter in smears and has a n!cle!s containing -7 lobes

hich are oten diic!lt to see beca!se o the (arge, dar-6"taining "0ei1i gran(e"$

• he c&toplasm contains n!mero!s metachromatic gran!les o "ar&ing size that stain a deep p!rple

color ith the !s!al stains !sed or peripheral blood smears$ hese gran!les contain highconcentrations o heparin .an anticoag!lant/, a n!mber o "asodilating agents hich ca!se increased"asc!lar permeabilit& s!ch as histamine, slo reacting s!bstance o anaph&la@is .le!6otriene/,serotonin, and eosinophil chemotactic actor$

• )re4en$

he peripheral blood contains 0$5-l basophils, and th!s basophils are the least n!mero!s gran!loc&te andleast n!mero!s hite blood cell in the peripheral blood$ *asophils are similar to mast cells b!t notidentical$ .Mast cells are seen in the bone marro and other tiss!es, b!t not the normal peripheral blood$/

• )nti&n

=ltho!gh the basophil possesses phagoc&tic capabilities, it is mainl& the secretor& cell hich mediate" theh$0er"en"iti!it$ reati&n$ *asophils .and mast cells/ can bind %g) antibod&, and, hen s!bse#!entl&e@posed to the corresponding antigen, release "asoacti"e s!bstances leading to h&persensiti"it& reactions.&pe % h&persensiti"it&/$

>eripheral blood( basophil

• Smmar$

'etr&0hi(", e&"in&0hi(" and ba"&0hi(" are the three t&pes o blood cells reerred to as gran(&$te"$he& ha"e a segmented n!cle!s in the mat!re stage and gran!les in the c&toplasm$

MO'OCYTES

• C$t&(&g$

he mat!re monoc&te meas!res 1-15 µm in diameter in blood smears and represents a circ!lating cell

deri"ed rom bone marro promonoc&tes$ he& spend abo!t a ee6 in blood and migrate into tiss!ehere the& become tiss!e macrophages or histioc&tes$ he& are the largest cell in the peripheral blood$

• he& contain a airl& large n!cle!s hich is o"oid, 6idne&- or horseshoe-shaped, oten located in an

eccentric position$ 2!cleoli are sometimes seen$

• he c&toplasm is pale and ma& contain ine az!rophilic gran!les .l&sosomes/, small amo!nts o ?)?,

ree ribosomes, pol&ribososomes, and a ell-de"eloped Golgi apparat!s .ma6ing l&sosomes/$

>inoc&totic .clear/ "ac!oles are re#!entl& seen in c&toplasm$• ell membrane has man& inger-li6e micro"illi$

• >eripheral blood has 7-8 monoc&tes$ Iie span 5-8 da&s$

>eripheral blood( monoc&tes


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• )nti&n

• Monoc&tes belong to the monoc!clear-phagoc&te s&stem$ hese cells lea"e the blood and enter the

tiss!e, dierentiating into macrophages or tiss!e histioc&tes$ The$ inge"t *0hag&$ti5e+ and rem&!e0arti(ate matter, ti""e debri", and in1eti&" agent"$ Histioc&tesmacrophages are present inman& tiss!es, b!t are partic!larl& n!mero!s in the bone marro, li"er and spleen$

• %nteract ith l&mphoc&tes and pla& essential role ith antigen interaction o imm!nocompetent cells$

LYMPHOCYTES

• C$t&(&g$

Mat!re l&mphoc&tes sho a spectr!m o sizes ranging rom small l&mphoc&tes .:-8 microns in diameter/to larger orms .10-1 microns in diameter or e"en higher/$

• he& contain a single, deepl&-stained, spherical n!cle!s hich can ha"e an slight indentation$ he

chromatin in the n!cle!s is condensed into coarse cl!mps$ he n!cle!s is s!rro!nded b& a thin rim o lightl& basophilic c&toplasm in the smaller t&pes$ he c&toplasm is more ab!ndant in the larger l&mphoc&tes$

• he c&toplasm ma& contain a e nonspeciic gran!les .l&sosomes/, a e mitochondria, man&

ribosomes, and a Golgi apparat!s$

• o maor s!bt&pes o !s!all& morphologicall& indisting!ishable l&mphoc&tes can be identiied .b&

liespan, !nction, s!race receptors, site o dierentiation/ J cells and * cells$ = third t&pe o l&mphoc&te is reerred to as nat!ral 6iller .2K/ cells$

>eripheral blood( l&mphoc&tes

• )nti&n

L$m0h&$te" are an im0&rtant 0art &1 the immne "$"tem;

• T6($m0h&$te"

>rocessed b& the th&m!s and participate in cell-mediated imm!nit& .s!ch as grat reection/$ Bome -cells .c&toto@ic/ can elaborate c&toto@ic agents$ he& can ma6e l&mpho6ines .incl!ding intereron,macrophage migration inhibitor actor, chemotactic actors or basophils/$ here are also memor& -cells that s!r"i"e or &ears or decades$

• B6($m0h&$te"

.*!rsa deri"ed/ - these cells pla& a central role in h!moral or antibod&-mediated imm!nit&$ Bomedi"ide and dierentiate into plasma cells in tiss!e$ Bome are memor& cells$ he& are imm!nologicall&characterized b& imm!noglob!lin on their cell membrane$

• P(a"ma e((" 6 Deri"e rom *-l&mphoc&tes$ he& ha"e an eccentricall& placed n!cle!s, contain

ab!ndant amo!nts o ?)? hose cisternae can be illed ith antibod&, and ha"e a ell-de"elopedGolgi$ P(a"ma e((" 0r&de antib&die" *immn&g(&b(in"+;

• '# e(("6 2K cells lac6 the s!race antigens o and * cells and do not re#!ire prior stim!lation

to attac6 "ir!s-inected cells or t!mor cells$


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• )re4en$

=bo!t 0-50 o peripheral blood hite blood cells are l&mphoc&tes$ these, abo!t 80 are -cells, 15 *-cells, 5 2K cells$ >lasma cells are not normall& seen in the peripheral blood b!t are present in the bone marro and other tiss!es$

• Smmar$he m&n&$te" and ($m0h&$te" are reerred to as m&n&n(ear .hite b(&&d e((" beca!se their n!clei are not segmented .as opposed to the gran!loc&tes hich contain segmented n!clei/$ he& donot contain prominent gran!les in their c&toplasm, in contrast to the gran!loc&tes disc!ssed earlier$

PLATELETS

• Strtre 6 2on-n!cleated lat, bicon"e@, ro!nd or o"oid dis6s .-5 µm diameter/; deri!ed 1r&m b&ne

marr&. mega-ar$&$te";

• ontain pale-bl!e peripheral h&alomere ith a s&stem o in"aginating channels .open canalic!lar

s&stem/ connecting ith the platelet membrane, a s&stem o electron-dense t!b!les, a marginal b!ndleo 10-15 circ!merential microt!b!les to maintain the dis6 shape, and actin and m&osin$ Ahen

platelets become acti"ated, the microt!b!lar s&stem Fs#!eezes the gran!les to the center o the platelet, the contents are released, and the coag!lation s&stem is triggered .see belo/$

• ontain thic6er central p!rple gran!lomere containing se"eral 6inds o gran!les$ =lpha gran!les are

az!rophilic and contain ibrinogen, platelet-deri"ed groth actor, etc$ Dense gran!les containcalci!m, p&rophosphate, =D> and =>$ he& also store serotonin$ Bmall "esicles .lambda gran!les/contain l&sosomal enz&mes$

>eripheral blood( platelets .and ?*s/ ransmission electron micrograph o a platelet

• )nti&n"

>latelets are in"ol"ed in hem&"ta"i" .stopping bleeding/$ >latelets aggregate on damaged endotheli!mand e@posed collagen, release contents o alpha and dense gran!les, 0r&m&te the &ag(ati&n a"adein"ol"ing plasma actors t& 1&rm a b(&&d (&t$ he ormation o the platelet pl!g is reerred to asFprimar& hemostasis$ he clotting process is good to limit hemorrhage b!t can be lie threatening on


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the all o a coronar& arter& .coronar& thrombosis/ or hen brea6ing ree rom "eins o e@tremitiesand going to l!ngs to ca!se p!lmonar& embolism$ A de1iien$ &1 0(ate(et" i" a((edthr&mb&$t&0enia$ hromboc&topenia ma& res!lt rom a n!mber o ca!ses, s!ch as imm!nedestr!ction b& antibodies directed against platelets, bone marro iniltration b& metastatic cancer, or primar& malignanc& o the bone marro$ Thr&mb&$t&0enia ma$ re"(t in bri"ing &r b(eeding$

• )re4en$*lood contains 150,000-750$000mm7$ Iie span is +-10 da&s

'&rma( Peri0hera( B(&&d Ce(("

Er$thr&$te" Le-&$te" *%hite B(&&d Ce(("+ P(ate(et"

/ran(&$te": M&n&n(ear e((": 2e!trophils I&mphoc&tes Monoc&tes)osinophils >lasma cells

*asophils

1$*asophil $>latelets 7$Monoc&te 4$)r&throc&tes 5$Monoc&te :$I&mphoc&te +$)osinophil

8$2e!trophil 9$I&mphoc&te

Pr&dt" and )nti&n" &1 the B(&&d Ce(("

Ce(( T$0e Main Pr&dt" &r C&m0&nent" Main )nti&n"

)r&throc&te Hemoglobin and transport

Ie!6oc&tes

2e!trophil Bpeciic gran!les and modiiedl&sosomes .az!rophilic gran!les/

>hagoc&tosis o bacteria

)osinophil Bpeciic gran!les, Deense against parasitic


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pharmacologicall& acti"es!bstances

helminths; mod!lation oinlammator& processes

*asophil Bpeciic gran!les containinghistamine and heparin

?elease o histamine and otherinlammation mediators

Monoc&te Gran!les ith l&sosomal enz&mes Generation o monoc!lear- phagoc&te s&stem cells in tiss!es;

phagoc&tosis and digestion o protozoa- and "ir!s-inected andsenescent cells

* l&mphoc&te .>lasma cell/

%mm!noglob!lins Generation o antibod&-prod!cingterminal cells .plasma cells/

l&mphoc&te B!bstances that 6ill cells,s!bstances that control theacti"it& o other le!6oc&tes.interle!6ins/

Killing o "ir!s-inected cells

2at!ral 6iller cell =ttac6s "ir!s-inected cells andcancer cells itho!t pre"io!sstim!lation

Killing o some t!mor and "ir!s-inected cells

>latelet *lood-clotting s!bstances lotting o blood HEMATOPOIETIC SYSTEM II: BO'E MARRO%

Reading: Bheedlo hapter 8, p :+; Klein and McKenzie pp155-181Learning Objeti!e":

1$ Iist the t&pes o hematopoietic tiss!es$$ Describe the de"elopment o hematopoiesis thro!gho!t the lie o the indi"id!al$7$ Describe the de"elopmental stages o er&throid and m&eloid cells$4$ %denti& the other t&pes o cells in the bone marro, i$e$ mega6ar&oc&tes, l&mphoc&tes, plasma cells,

macrophages, adipoc&tes$5$ Describe the actors hich control hematopoiesis, e$g$ groth actors s!ch as er&thropoietin, GM-

B$#e$ %&rd": blood cell reneal, hematopoiesis, bone marro, er&thropoiesis, gran!lopoiesis,

mega6ar&opoiesis, groth actors$

Intr&dti&n*one marro is a richl& "asc!larized connecti"e tiss!e hich specializes in prod!ction o all the ormedelements o blood$ *one marro is the most rapidl& replicating tiss!e in the bod&$

BLOOD CELL RE'E%AL

• The 0r&b(em

he dierent blood cells ha"e inite and oten brie lie spans and m!st be reneed to maintain appropriatecirc!lating le"els$ he process o reneal is 6non as hematopoiesis .hemopoiesis/$

• In1(ene" &n hemat&0&ie"i"

%nection, hemorrhage, t!mors and other actors ma& ind!ce increases or decreases in the le"el o

hematopoiesis in one or more o the blood cell lines$• Be"eral groth actors and other prod!cts aect the prolieration and dierentiation o hematopoietic

cells$ Dierent actors are in"ol"ed in er&thropoiesis, gran!lopoiesis, etc$ .Bee table belo/

HEMATOPOIETIC TISSUESiss!es hich acti"el& or potentiall& prod!ce blood cells are hematopoietic tiss!es$

• T$0e" &1 hemat&0&ieti ti""e"

• M$e(&id ti""e"


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*lood orming tiss!es identiied as the 'red marro' o bones$ he amo!nt and location o redmarro is dierent in the et!s and the ad!lt$ .Bee belo/

• L$m0h&id ti""e"

Bome l&mphoc&tes o peripheral blood arise rom prolieration ithin l&mphoid tiss!es$I&mphoid tiss!es are elements o the larger l&mphatic s&stem .l&mph nodes, tonsils, >e&ers patches, etc$/ hese ill be addressed in another Histolog& lect!re$ .>lease note, the l&mphoc&te

'stem cell' is located in bone marro$/

HEMATOPOIESIS I' UTERO:

• Embr$& and 1et" *intraterine de!e(&0ment+

Hematopoiesis in the de"eloping organism is a d&namic process hich in"ol"es a "ariet& o tiss!esites$ he dierent tiss!es ser"e as maor blood cell prod!cers at dierent gestational ages$!rthermore, gestational hematopoiesis occ!rs in three maor a"es or phases and a e minor onesas ell$ he three phases are mesoblastic, hepatic and m&eloid$

G)B=%2=I =G) >H=B) I=%2 ee6s - months Mesoblastic Aall o &ol6 sac: ee6s - birth Hepatic Ii"er 1 month - birth M&eloid *one Marro

TABLE 9


11/15

=ll blood cell t&pes arise rom common or 0(ri0&tentia( stem cells$ Bome o the da!ghter cells ill become speciic, irre"ersibl& dierentiated cell t&pes, and other da!ghter cells remain stem cells$ hesecells prolierate and orm one cell lineage that ill become l&mphoc&tes .l&mphoid cells/ and another lineage that ill orm the m&eloid cells that de"elop in bone marro .gran!loc&tes, monoc&tes,er&throc&tes, and mega6ar&oc&tes/$ )arl& in their de"elopment, l&mphoid cells migrate rom the bonemarro to the th&m!s, l&mph nodes, spleen, and other l&mphoid tiss!es$ I&mphoid tiss!e ill be co"ered

in more detail in other lect!res$

Di11erentiati&n &1 0(ri0&tentia( "tem e((" dring hemat&0&ie"i"

RED MARRO%

• Hi"t&(&g$

?ed marro is composed o a netor6 o "asc!lar sin!ses .specialized blood "essels/ sit!ated thro!gho!ta sponge-li6e netor6 o hematopoietic cells$ Bin!ses are interposed beteen arteries and "eins andcontain, essentiall&, peripheral blood$ ?ed Marro is organized into sacs .al"eoli/ ithin hichhematopoietic cells de"elop in nests or oci$ ?etic!lar cells and retic!lar ibers orm a s!pporti"e


12/15

rameor6 or the de"eloping blood cells and sin!ses$

• L&ati&n

%n red marro, cells o the ?* line de"elop near the sin!s all$ )ach ?* nest has an associatedmacrophage hich contains iron$ ells o the gran!loc&te series .eosinophilic, ne!trophilic, and basophilic/ de"elop aa& rom the sin!s$ Mega6ar&oc&tes .cells prod!cing platelets/ also de"elop ne@t tosin!ses$

*one Marro .HL) stained histologic section/

DE=ELOPME'TAL STA/ES O) BLOOD CELLS

• Er$thr&0&ie"i" *RBC"+

>rocess o ormation and dierentiation o ?*s$ .Bee diagram belo and on page 9+/

• Pr&er$thr&b(a"t 6 di"ides$• Ba"&0hi(i er$thr&b(a"t > di"ides

• P&($hr&mat&0hi(i er$thr&b(a"t 6 di"ides$

• Orth&hr&mi er$thr&b(a"t 6 no di"ision$

• Reti(&$te 6 no di"ision$

• Er$thr&$te 6 no di"ision$

• C&ntr&( &1 er$thr&0&ie"i"

De"elopment rom a basophilic normoblast to a mat!re er&throc&te in"ol"es 1:-7 cell di"isionsand ta6es appro@imatel& one ee6$ ?* ormation is !nder the control o a 6idne&-prod!cedhormone 6non as er$thr&0&ietin$ Dietar& iron, itamin *1 and olic acid are re#!ired or thenormal prod!ction o ?*s$

/RA'ULOPOIESIS>rocess o ormation and dierentiation o gran!loc&tes$

• he olloing are stages in gran!lopoiesis

1) M$e(&b(a"t 6 Di"ides$

2) Pr&m$e(&$te 6 Di"ides$

3) 'etr&0hi(i, e&"in&0hi(i, &r ba"&0hi(i m$e(&$te 6 Di"ides$

4) 'etr&0hi(i, e&"in&0hi(i, &r ba"&0hi(i metam$e(&$te 6 2o di"ision$

5) 'etr&0hi(i, e&"in&0hi(i, &r ba"&0hi(i band 6 2o di"ision$

6) Segmented netr&0hi(, e&"in&0hi(, &r ba"&0hi( - 2o di"ision$

/ran(&0&ie"i" Er$thr&0&ie"i"


13/15

• C&ntr&( &1 gran(&0&ie"i"

Gran!lopoiesis is stim!lated b& B .&(&n$ "tim(ating 1at&r"/, s!bstances released b& themacrophagemonoc&te comm!nit&, s!ch as G-B or GM-B$ ne stim!l!s or B release is

increased cell migration into tiss!es, s!ch as o!ld occ!r in a bacterial inection$

• #ineti" &1 'etr&0hi( Pr&dti&n

he total time ta6en or a m&eloblast to emerge as a mat!re ne!trophil in the circ!lation is abo!t 11 da&s$Cnder normal circ!mstances, i"e mitotic di"isions occ!r in the m&eloblast, prom&eloc&te and ne!trophilicm&eloc&te stages o de"elopment$ 2e!trophils pass thro!gh se"eral !nctionall& and anatomicall& deinedcompartments(

9+ he med!llar& ormation compartment can be s!bdi"ided into a mitotic compartment and amat!ration compartment$ his compartment is in the bone marro$

3+ he med!llar& storage compartment acts as a b!er s&stem, capable o releasing large n!mbers o mat!re ne!trophils !pon demand$ his compartment is in the bone marro$


14/15

THROMBOPOIESIS 6 >rocess o ormation o platelets$

• Mega-ar$&b(a"t 6 Iarge cell ith a big n!cle!s .4n/ sit!ated close to sin!ses$

• Pr&mega-ar$&$te > Iarger than a mega6ar&oblast, this cell contains a "ol!mino!s pol&ploid

n!cle!s .8n/$ De"elops platelet demarcation channels$

• Mega-ar$&$te - = giant cell ith a large pol&ploid n!cle!s .7n-:4n/$ >latelet demarcation

channels "er& distinct$ = massi"e protr!sion o the cell penetrates a sin!s and ragments into platelets$

• Thr&mb&$te *0(ate(et+ 6he inal end prod!ct hich circ!lates in the peripheral blood$ ?esponsible

or primar& hemostasis .clot ormation/$

• C&ntr&( &1 thr&mb&0&ie"i" 6 = ser!m gl&coprotein, 6non as thr&mb&0&ietin, has been

demonstrated$ hromboc&topenia stim!lates mega6ar&oc&tes and platelet prod!ction$

OTHER RED MARRO% CELLS

• Mar&0hage" 6

hese cells are the tiss!e co!nterparts o monoc&tes o the peripheral blood$ %n the bone marro, the&!nction in phagoc&tosis and iron storage$ .Bometimes e reer to macrophages as histioc&tes/$

• Strtra( e(("

hese incl!de at cells .adipoc&tes/, retic!lar cells, and endothelial cells$

• L$m0h&$te"


15/15

= e l&mphoc&tes and plasma cells are !s!all& present in the bone marro$

• Ma"t e((" 6 = mast cell originates rom the bone marro and is normall& o!nd thro!gho!t the

connecti"e tiss!e o the bod&$ %t is a normal component o the imm!ne s&stem and as it releaseshistamine it is associated ith allergic reactions$ Mast cells also respond to tiss!e tra!ma$ Mastcell gran!les contain histamine, heparin, platelet-acti"ating actor , and other s!bstances$

@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@@

HEMATOLO/Y LAB BI%D) 44 J *ID BM)=? IN THIS LAB YOU NEED TO USE OIL. ONE DROP ON THE SLIDE ONLY AND SHIFT TO

THE 100X MAGNIFICATION LENS

Go rom one edge o the smear to the other and co!nt the dierent cell t&pes and see ho close &o!come to the normal range$

• 2ormal ad!lt range . peripheral hite cells/

• 2e!trophils 50-+5 .7-5 stab or band orm/

• I&mphoc&tes 0-50 .80 , 15 *, 5 2!ll/

• Monoc&tes 7-8

• )osinophils 1-7

• *asophils 0$5-1

he dierential co!nt is an e@cellent diagnostic tool or diagnosis, %n "iral inections there is predominance o l&mphoc&tes, in bacterial inections it is ne!trophils$ Disease progress can also beolloed s!ch as m&eloprolierati"e disorders, inectio!s monon!cleosis and s!ch$

BI%D) 45 J *2) M=??A =B>%?=)

• n this slide &o! ill be loo6ing or members o the gran!loc&tic and er&throid cell lines$ he

marro is obtained b& inserting a needle thro!gh cortical bone and ithdraing the aspirate,a proced!re that is oten "er& pain!l$

• Ioo6 or members o the er&thropoietic series rom basophilic normoblast thro!gh to

er&throc&te and or members o the gran!loc&te series rom prom&eloc&te to ne!trophil$%denti& a blast cell and a Mega6ar&oc&te
http://en.wikipedia.org/wiki/Bone_marrowhttp://en.wikipedia.org/wiki/Connective_tissuehttp://en.wikipedia.org/wiki/Immune_systemhttp://en.wikipedia.org/wiki/Histaminehttp://en.wikipedia.org/wiki/Allergyhttp://en.wikipedia.org/wiki/Physical_traumahttp://en.wikipedia.org/wiki/Granulehttp://en.wikipedia.org/wiki/Heparinhttp://en.wikipedia.org/wiki/Platelet-activating_factorhttp://en.wikipedia.org/wiki/Bone_marrowhttp://en.wikipedia.org/wiki/Connective_tissuehttp://en.wikipedia.org/wiki/Immune_systemhttp://en.wikipedia.org/wiki/Histaminehttp://en.wikipedia.org/wiki/Allergyhttp://en.wikipedia.org/wiki/Physical_traumahttp://en.wikipedia.org/wiki/Granulehttp://en.wikipedia.org/wiki/Heparinhttp://en.wikipedia.org/wiki/Platelet-activating_factor

2011 Blood and Heme

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Transcript of 2011 Blood and Heme