hematologi tamb

8/19/2019 Hematologi tamb

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HematopoiHematopoi

esisesisDepartment of Clinical Pathology

Blok 234

FK Unswagati Cirebon

1 !eptember 2"14


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TIK TIK

• De#nisi$ tempat ter%a&inya hematopoiesisDe#nisi$ tempat ter%a&inya hematopoiesis

• Komponen &an sel &arahKomponen &an sel &arah

• 'ahapan hematopoeisis 'ahapan hematopoeisis

• Faktor yang mempengar(hiFaktor yang mempengar(hi

hematopoiesishematopoiesis

• Peran sistem hematopoeitik &alamPeran sistem hematopoeitik &alam

pertahanan t(b(hpertahanan t(b(h

• )acam &an t(%(an pemeriksaan)acam &an t(%(an pemeriksaan

laboratori(m &arah r(tinlaboratori(m &arah r(tin


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ReferensiReferensi

1.1. Essential Hematology. AVEssential Hematology. AV

Hobrand, JE Pettit, PAH oss.Hobrand, JE Pettit, PAH oss.

!t" ed.!t" ed.

#.#. $enise Harmening.$enise Harmening.

Hematology and Hemostasis.Hematology and Hemostasis.


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$e%nisi Hematopoeisis

• Hematopoeisis

proses pembent(kan

sel*sel &arah


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Tempat ter&adinyaTempat ter&adinya

"ematopoiesis"ematopoiesis

A'E (ITE

Fet(s+ "*2months

,olk sac

2*months

-i.er$ spleen

/*0months

Bone marrow

nfants Bone marrow$ practically all bones

&(lts ertebrae$ ribs$ stern(m$ sacr(m

an& pel.is$ proimal en&s of fem(r• !el berkembang &an bergerak &ari s(ms(m t(langmelal(i sin(s*sin(s 5sirk(lasi mikro s(ms(m t(lang6sel*sel mat(r &i sirk(lasi (m(m•7ematopoiesis &im(lai &engan sel stem pl(ripoten


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Hematopoiesis

• Yolk sac phase - blood in 'islands' in yolk sac, no leukocytes• Hepatic phase - primitive nucleated RBCs, fetal hemoglobin• Bone marro phase - mature RBCs, leukocytes, !"# eeks• $dult phase - pelvis, vertebrae, skull, ribs, ends of long bones


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Komponen Darah Dan Sel-Sel Darah

%aringan konektif khusus

Komponennya

"& lasma

#& (el-sel

$& )ritrosit

B& *ekosit

i& $granulosit

ii& +ranulosit

& rombosit


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Sel-Sel Darah Dan Trombosit

)ritrosit . bagian /001 of blood cells by number

Hematokrit . packed red blood cell 2RBC3 volume 21 volume

darah3

*ifespan - 4eutrophils, only "#-"5 hours

latelets, !"6 days

RBCs, !5 months 2!"#6 days3

*ymphocytes, many years

Sel% dari volumedarah

per mikroliter (µl)

Eritrosit!56 - 761 283

!7 - 571 293

5, . 7,: ;uta 283

,0 - 7 ;uta 293

Lekosit !"1 ,7 . "6,7 < "6

Trombosit ="1 "76 - 576 < "6


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lasma

>ater !0"1

roteins !:1 $lbumin, globulins, fibrinogen?ons !"1 Bicarbonate 2#"-#7 m83

Calcium 2#-#&: m83

Chloride 205-""" m83

otassium 25&"-7&@ m83

(odium 2":-"5A m83

(mall 8olecules !"1 +lucose 2&5-7&@ m83

*actate 2"&6-"&A m83rea 2&5-@&: m83

*ipids ="1 Cholesterol 2&5-7 m83

9atty acids 2free3 26-6&0 m83

riglycerides 26&5-"7 g*3


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Erythro!ytes

• ransports D# 2bound to hemoglobin3

•

Converts CD# into HCD-

2transported in plasma3• Biconcave disk-shape, deformable, resilient, no organelles

• lasma membrane and spectrin cytoskeleton present

• roteins - mainly hemoglobin 2α#β#3 and glycolytic enEymes

• Fuality control - spleen removes old or damaged RBCs

T " H t i ti


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Ta"apan Hematopoietis)(tem * (el Progenitor


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Pl+ripotent)ial Hematopoieti-(tem ell

• 8i.e rise to the separatecell lineage

• 9act phenotype (nkown imm(nological testing+CD34:$ CD3;*

• ppearance <small=me&i(m si>elymphocyte

• Cell &i?erentiation occ(rsfrom the stem cell &ownthe erythroi&$ gran(locytic

an& other lineages .ia the committe& hematopoieticprogenitors cells restricte& in their&e.elopmental potential@


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• !C has the capability of self/rene0al cell(larity remains constant in anormal healthy stea&y state@


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• 1 ( -apable of prod+-ing1 ( -apable of prod+-ing 121233 mat+re blood -ells after #2 -ellmat+re blood -ells after #2 -ell

di4isions.di4isions.

• ( -apable of responding to( -apable of responding to

"ematopoieti- gro0t" fa-tors"ematopoieti- gro0t" fa-tors

0it" in-reased prod+-tion of one0it" in-reased prod+-tion of one

or ot"er -ell line 0"en t"e needor ot"er -ell line 0"en t"e needarises.arises.


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5a6tor 7ang empengar+"iHematopoeisis


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Bone )arrow !troma

• !(itable en.ironment for!C growth A &e.@

• Compose& of stromalcells : micro.asc(larnetwork@

(tromal-ells8• a&ipocytes• Fibroblast• etic(l(mcella

• 9n&othelial

E9tra-ell+larmole-+les8• Collagen

• 8lycoprotein5#bronectin$

thrombospon&in6• 8lycosaminoglycans

5hyal(ronic aci& A

chon&roitin &eri.ates6• 8rowth factors for

se-rete


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7emopoietic 8rowth Factors

• 8lycoprotein hormones reg(lateproliferation A &i?erentiation of 7PC Af(nction of mat(re bloo& cells@

• Biological e?ects of 78F me&iate&thro(gh speci#c receptors on targetcells@

• ct+ . -ocally at the site where they are

pro&(ce by -ell/-ell -onta-t@

. Circ(late in plasma


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H'5H'5

• )ay bin& to 9C matri form niches towhich !C A P7C a&here@

• )a%or so(rces 5ecept erythropoietin6+

. '*lymphocytes

. )onocytes 5A macrophages6

. !tromal cells

• 9rythropoietin 0" synthesi>e& inki&ney

• 'hrombopoietin largely ma&e in li.er


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-e(kopoiesis also stim(lates by en&otoin


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'eneral "ara-teristi-s of yeloid and:ymp"oid 'ro0t" 5a-tors

• 8lycoprotein that act at .ery low concentration• ct hierarchically• Us(ally pro&(ce& by many cell types

• Us(ally a?ect more than 1 cell lineage• Us(ally acti.e on stem=progenitor cells an& on

f(nctional en& cells• Us(ally show synergistic or a&&iti.e interactions with

other growth factors

• ften act on the neoplastic eE(i.alent of a normal cell• )(ltiple actions+ proliferations$ &i?erentiation$mat(ration$ f(nctional acti.ation$ pre.ention ofapoptosis@


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Hematopoieti-

'ro0t"5a-tor

(ite of a-tion H'5

!tromal cell -*1$ 'F

Pl(ripotential stem cell !tem cell factor 5!CF6$ Flt ligan&5Flt*-6

)(ltipotential progenitorcell

-*3$ 8)*C!F$ -*G$ 8*C!F$thrombopoietin

Committe& progenitor 8*C!FH$ )*C!F$ -*/ 5eosinophil*


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!tem Cell Plasticity

• 9mbryonic !C totipotent generate alltiss(es@

• 9.i&ence a&(lts !C 5in&i?erent organs6 pl(ripotent@

• Bone marrow+ . 7ematopoietic !C

. )esenchymal !C clinicalapplication th=mesenchymal &isease


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poptosis

• 7omeostasis+

cell pro&(ction I cell &estr(ction• eg(late& process of physiological cell &eath

triggere& to acti.ate intracell(lar proteins lea&

to cell &eath@• )orphologically+

. Cell shrinkage . Con&ensation of n(clear chromatin . Fragmentation of the n(cle(s

. Clea.age of intran(cleosomal D• mportant proses for maintaining tiss(e

homeostasis in hematopoiesis A lymphocytes&e.elopment


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Pathway of apoptosis


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8rowth Factoreceptors A !ignal

'rans&(ction

Control hematopoiesis bygrowth factors+• Factors acts on cellsepressing thecorrespon&ing receptors@

• Bin&ing of 8F to its receptoracti.ates

by JKs then phosphorylate!''s

which translocate to then(cle(s an&

acti.ate transcription ofspeci#c

genes


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&hesion )olec(les

• 8lycoprotein• )e&iate the attachment of marrow

prec(rsors$ le(kocytes an& platelet to.ario(s components of the etracell(lar

matri to+ . 9n&otheli(m . ther s(rfaces . 9ach other

• n le(kocyte receptors interact withligan&• 3 main families+ mm(noglob(lin$ selectins$

integrin

"#$ l b Sk l t


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"#$ lasma embrane Skeleton

Resilientand fle


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&ree'e-ra!ture E o "#$ embrane"& 9reeEe-fracture

9reeEe and fracture

)


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Leuko!ytes

ranulo!ytes4eutrophil 2)3

Band 4eutro& 2?3

)osinophil 2G3

Basophil 2%3

*+ranulo!ytes

8onocyte 293*ymphocyte 2H3

latelets 2+3


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Leuko!ytes

Si'e - larger than erythrocytes 2"6 - "A Im diameter3

*ll - contain non-specific aEurophilic 2primary3

granules that are eJuivalent to lysosomes

ranulo!ytes - contain specific 2secondary3 granules

that contain specific enEymes for each cell type*+ranulo!ytes - no specific granules present

+ranulocyte 4eutrophil !@61

)osinophil !51

Basophil ="1

$granulocyte *ymphocyte 2, B, 4K3 !#@1

8onocyte !01


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Leuko!ytes

Distribution - blood and C 2as transient or andering cells3&un!tion - immune protection, movement 2cell motility3

Diapedesis - movement out of blood into connective tissue

$hemota,is - movement directed by homing molecules


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eutrophil

• 8ost common leukocyte - 50-@:1 of leukocytes• $Europhilic granules - 4$GH o


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ha+osome and.or

E,tra!elluar spa!e

*DH

/,idase

$omple,

*DH

e-

&*D

Heme

Heme

/

-

0

/0 e-Supero,ide anion

*D1 1 H1

/

///-

pero,ynitriteanion

H0/0

H0/

1

/0

!atalase

/H-

hydro,yl

anion

&e01

&e21&enton ",n

H/$lhypo!hlorous a!id

$l-

/

/0$l

nitryl

!hloride

*TH/ES

ha+o!yti! $ell embrane

$ytoplasmi! spa!e

/0-

S/D

"ea!tive /,idants Kill atho+ens

hagocytic cells kill pathogens ith reactive o


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Eosinophil

• ?ntermediate abundance - #-71 of leukocytes• $Europhilic granules - lysosomal acid hydrolases•

(pecific granules 2eosinophilic3 - eosinophilic cationic protein,ma;or basic protein, eosinophilic pero


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#asophil

• *east common leukocyte - ="1 of leukocytes•

$Europhilic granules - lysosomal acid hydrolases• (pecific granules 2basophilic3 - histamine, heparin,

heparan sulfate, chemotactic factors for other granulocytes• 9unctions - similar to mast cells, upon stimulation it

releases preformed and nely synthesiEed secretory

products that initiate, maintain, and control inflammation


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ono!yte

• *argest cell in peripheral blood 2"A Im diameter3• $granulocyte - lysosomal acid hydrolases, myelopero


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Lympho!yte

• B lymphocyte - humoral immunity 2!#6-613• lymphocyte - cell-mediated immunity 2!@6-A613• 4atural killer 24K3 cell - cell-mediated immunity 2!7-"613

• $granulocyte - lysosomal acid hydrolases

latelets


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latelets

• Cell fragment - small 2!# Im3, irregular disk shape, no nucleus• (tructure - granules, mitochondria, glycogen, cytoskeleton• +ranules - alpha 2clotting factors3, dense core 2histamine3• 8egakaryocyte - produces platelets in bone marro sinus• 9unction - clot formation, bind to in;ured blood vessel all,

aggregate ith RBCs forms hemostatic plug 2stops bleeding3

HematopoiesisKiersEenbaum, 9ig& @-"@L


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Hematopoiesisg

(ee Ross 7th )d able "6&5

(C

Stem $ell #asi!s


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• (tem cell - asymmetric cell division yields cells ith different

fates 2one is stem cellL one is transient amplifying cell3• (elf-reneal - capacity of stem cell to regenerate itself • ransient amplifying cells - symmetric cell division yields

daughter cells ith same fate 2transient amplifying cells3

• Gifferentiated cells - cells e


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Hematopoieti! Stem $ells

luripotent hematopoieti! stem !ell (HS$)

ndifferentiated cell producing blood cells of all lineages,

capable of self-reneal

ultipotent HS$

ndifferentiated cell producing cells of multiple lineages,

limited self-reneal 2e&g&, myeloid (C, lymphoid (C3

$ommitted pro+enitor - undifferentiated cell capable of

producing cells of one lineage, colony forming units 2C9s3

2e&g&, erythroid C9, granulocyte-macrophage C93


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roerythroblast

Basophilic

erythroblast

olychromatophilic

erythroblast

Drthochromatic

erythroblast

2normoblast3

Reticulocyte

)rythrocyte

)arly ?ntermediate *ate

Sta+es in Erythropoiesis

Er thropoiesis


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Erythropoiesis

roerythroblast

2pronormoblast3

active rR4$ and ribosome synthesis 2nucleoli visible3

active gene e


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Leukopoiesis - yeloid Linea+e

KiersEenbaum

9ig& @-#6L

(ee Ross 7th

)d able "6&5

Band (tage

yeloid Linea+e (eutrophili!)


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yeloid Linea+e (eutrophili!)

"& romyelocyte

5& Band 9orm

& 8etamyelocyte

#& 8yelocyte

KiersEenbaum, 9ig& @-#"

l id Li


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yeloid Linea+e

8yeloblast2do not identify

in lab3

active rR4$ and ribosome synthesis 2nucleoli visible3,active gene e


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Leukopoiesis -

Lymphoid Linea+e

• *ymphoid stem cell gives rise to

-lymphocyte and B-lymphocyte

lineages• -cell maturation - thymus

• B-cell maturation - bone marro

•

lasma cells - present in marro,lymphatic tissue, connective tissue

stem cell

(ee Ross 7th )d able "6&5


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Hematopoieti! ro3th &a!tors

Erythropoietin 2)D3 - ma;or regulator of erythropoiesis,

stimulates erythroid C9 cells and proerythroblasts

Thrombopoietin 2D3 - increases platelet production,

stimulates megakaryocyte C9 cells

ranulo!yte $S& 2+-C(93 - increases production of

neutrophils, stimulates granulocyte-macrophage C9 cells

ranulo!yte-ma!ropha+e $S& 2+8-C(93 - increases

macrophage production, stimulates granulocyte-macrophage C9 cells

4nterleukins - stimulate B- and -cell formation, function

together ith +-C(9 and +8-C(9

#one arro3


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• Bone marro cavity - marro proper and venous sinuses• Bone marro cells - stromal cells, adipocytes, endothelial

cells, macrophages, hematopoietic cells• Blood vessels - nutrient arteries supply marro cavity• (tem cells and early precursor cells do not leave marro

KiersEenbaum,9ig& @-"5

#one arro3


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#one arro3

*nemia


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*nemia

"edu!ed "#$ rodu!tion

9actor Geficiency?ron - reJuired for heme synthesis

itamin B"# - reJuired for G4$ synthesis

9olate - reJuired for G4$ synthesis

Gietary limitations - most common cause

Hematopoietic Cell Gamage

Grugs

Radiation

?nfections

o


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e+aloblasti! *nemia

Gefect in hematopoiesis

eripheral blood - macroovalocytes 2large oval RBCs3

Bone marro - megaloblasts

$nemia - autohemolysis of megaloblasts, short life span

of macroovalocytes

Causes - usually deficiency of folic acid or vitamin B-"#,

hich are reJuire for G4$ synthesis during cell division

Dther causes - leukemia, myelofibrosis, multiple

myeloma, hereditary disorders, chemotherapy drugs

2that affect G4$ synthesis, e&g&, methotre


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e+aloblasti! *nemia

eripheral blood - macroovalocytes and hypersegmented neutrophileripheral blood - macroovalocytes and hypersegmented neutrophil

e+aloblasti! *nemia


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8egaloblasts in8egaloblasts in

bone marrobone marro

4ormal erythroids4ormal erythroids

in bone marroin bone marro

e+aloblasti! *nemia

Leukemia


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Leukemia• roliferation of leukocytes from hemopoietic tissue

•

9our ma;or forms $cute 8yelogenous *eukemia 2$8*3

$cute *ymphocytic *eukemia 2$**3

Chronic 8yelogenous *eukemia 2C8*3

Chronic *ymphocytic *eukemia 2C**3

• 8yelogenous - proliferation of cells of myeloid lineage

• *ymphocytic - proliferation of cells of lymphoid lineage

• $cute - rapidly progressing, cells are immature and do not

carry out their normal functions

• Chronic - progresses sloly, more developed cells that

carry out normal functions

• Blood test - measure leukocyte alkaline phosphatase 2*$3


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Any;+estions


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T"an6 7o+ Very +-"T"an6 7o+ Very +-"

hematologi tamb

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