Ltm hemato

8/17/2019 Ltm hemato

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HEMATOPOIESIS



HEMATOPOIESIS Prenatal, postnatal hematopoiesis

Medullary hematopoiesis,extramedullary hematopoiesis

Effective hematopoiesis, ineffective

hematopoiesis



MED!!A"# HEMATOPOIESIS



$etus % & ' months (yol) sac*' & +% months (liver, spleen* & +% months (-one marro.*

Infants /one marro. (practically all -ones*

Adults 0erte-rae, ri-s, sternum, s)ull, sacrum andpelvis proximal ends of femurHoff-rand A01 '%%+

SITES O$ HAEMOPOIETI2 TISSE I3 $ETS A3D

TH"O4HOT !I$E1

/onemarro.

Spleen

!iver 0erte-ra

SternumTi-ia

$emur

#ol)Sac

+%%per cent

MO3THS A4E I3 #EA"S

/I"TH

P"E3ATA! POST3ATA!

+ ' 5 6 7 8 9 : + 6 +6

+%

'%

%

5%

6%

7%

8%

"i-



Dia;rammatic representation of -one marro. pluripotentstem cells and the cell lines1

Hoff-rand A01 '%%+



!inea;e of lymphoid and non lymphoid cells

HEMATOPOIETI2STEM 2E!!

!#MPHOIDSTEM 2E!!

3O3!#MPHOIDSTEM 2E!!

T !#MPHO2#TE

/ !#MPHO2#TE

P!ASMO2#TE

E"#TH"O2#TE

4"A3!O2#TE

MO3O2#TE

TH"OM/O2#TE

Di;;s Sturm /ell1 '%%6



HEMATOPOIETI2 4"O<TH $A2TO"S Hematopoietic ;ro.th factors are ;lycoprotein

hormones that re;ulated the proliferation =

differentiation of hemopoietic pro;enitor cells = thefunction of mature -lood cells

2ontrol every step in the process of the

development of ne. -lood cells

Inhi-itoryStimulatory

Proliferation =differentiation

Mi;ration into

the circulationSchiffman $>1 +::9 = Hoff-rand A01 '%%+



Act on stromal cells I!?+

T3$

Act on pluripotential stem cells Stem cell factor (S2$* $lt li;and ($lt?!*

Act on multipotential pro;enitor cells I!? 4M?2S$ I!?7

4?2S$ throm-opoietin

Act on committed pro;enitor cells 4?2S$@

M?2S$ I!?6 (eosinophil?2S$*

HAEMOPOIETI2 4"O<TH $A2TO"S

4? and 4M?2S$ ;ranulocyte

and ;ranulocyte?macropha;ecolony?stimulatin; factorB

I! interleu)inB

M?2S$ macropha;e colony?stimulatin; factorB

T3$ tumour necrosis factor1

@ These also actsyner;istically .ith earlyactin; factors on pluripotential

pro;enitor1Hoff-rand A01 '%%+



THE "O!E O$ 4"O<TH $A2TO"S I3 3O"MA! HAEMOPOIESIS

Hierarchical model of haemotopoiesis and lymphopoiesis includin;

important cyto)inesSchiffman $>1 +::91



/lood cells

3OME3C!AT"

Throm-ocyte

/asophil

3eutrophil

Promonocyte

Prome;a)aryocyte

Proru-ricyte

Mono-last

Me;a)aryo-last

"u-ri-last

Prolymphocyte

Proplasmocyte

!ympho-last

Plasmo-last

Me;a)aryocyte

"u-ricyte

Metame;a)aryocyte

Metaru-ricyte Erythrocyte

Monocyte

Se;mented

Eosinophil

3eutrophil/and

31 Metamyelocyte31 Myelocyte

/1 Myelocyte

E1 Myelocyte

PromyelocyteMyelo-last

!ymphocyte

Plasmocyte

Erythrocyte/asophilicDiffusely

2I"2!ATI34 /!OOD

HEMATOPOIETI2 TISSES

S t e m

c e l l




MAT"ATIO3 SEE32E O$ "/2 S#STEM

MAT"ATIO3 SEE32E

A1 2ell sie and cytoplasm

color/1 3uclear sie and color

21 3uclear chromatinstructure

D1 2omposite (top to -ottom ru-ri-last, proru-ricyte,ru-ricyte, metaru-ricyte,diffusely -asophilicerythrocyte, erythrocyte




M#E!O2#TI2 (4"A3!O2#TI2* S#STEM

A1Myelo-last

/1Promyelocyte

(pro;ranulocyte*21/asophilic

myelocyte

D1/asophilic

metamyelocyteE1/asophilic -and

$1/asophilic

se;mented

413eutrophilic

myelocyte

H13eutrophilic

metamyelocyteI13eutrophilic -and

>13eutrophilic

se;ment

C1Eosinophilic

myelocyte

!1Eosinophilic

metamyelocyteM1Eosinophilic

-and

31Eosinophilic

se;mented




3ET"OPH#! 3O3 SE4ME3TED A3D SE4ME3TED

Terminolo;y -ased on indentation of nuclei1

3onse;mented

Se;mented


M#E!O2#TE METAM#E!O2#TE /A3D SE4ME3TED



A Erythrocytes

/ !ar;e lymphocyte .ith

purplish?red (aurophil*

;ranules and deeply indented

-y adFacent erythrocytes2 3eutrophilic se;mented

D Eosinophilic se;mented

E 3eutrophilic se;mented

$ Monocyte .ith ;ray -luecytoplasm, coarse linear

chromatin, -lunt pseudopods

4 Platelets (throm-ocytes*

H !ymphocyte

I 3eutrophilic -and

2ell types found on -lood smearsfrom normal individuals




MO3O2#TES

A1Monocyte .ith

G;round?;lassappearance evenly

distri-uted fine

;ranules, occasional

aurophilic ;ranules,

and vacuoles in

cytoplasm

/1Monocyte .ith opaue

cytoplasm and ;ranules

and .ith lo-ulation of

nucleus and linear

chromatin21Monocyte .ith

prominent ;ranules and

deeply indented

nucleus

D1Monocyte .ithout

nuclear indentations

E1Monocyte .ith ;ray?

-lue color, -and typeof nucleus, linear

chromatin, -lunt

pseudopods, and

;ranules

$1Monocyte .ith ;ray?

-lue color, irre;ular

shape, and

multilo-ulated nucleus

41Monocyte .ith

se;mented nucleus

H1Monocyte .ithmultiple -lunt

non;ranular

pseudopods, nuclear

indentations, and folds

I1Monocyte .ith

vacuoles and .ithnon;ranular ectoplasmDi;;s Sturm /ell1 '%%6



Maturation and differentiation of -lood cells

myelocyte

promyelocytemyeloblast IImyeloblast I

monoblastpromonocyte

basophilic erythroblastpolychromatic erythroblast

proerythroblast

orthochromatic erythroblast

enucleation Reticulocyte (supravital stain) erythrocyte

metamyelocyte

metamyelocyte

metamyelocyte

band form

band form

band form segmented basophil

segmented basophil

segmented basophil

tissue basophil

monocyte

macrophage

neutrophilic

eosinophilic

basophilic

#a.ata #1 '%%+

Myeloid

Monocytic

Erythroid



!#MPHO2#TES

A1 Small mature

lymphocyte

/1 !ymphocyte of

intermediate sie

21 !ymphocyte .ith

indented nucleus

D1 !ymphocyte ofintermediate sie

E1 !ymphocyte .ith

pointed cytoplasmic

proFections (frayed

cytoplasm*, typical

nucleus$1 Spindle?shaped

lymphocyte .ith

indented nucleus

41 !ar;e lymphocyte

.ith indented

nucleus and pointed

H1!ar;e lymphocyte

I1!ar;e lymphocyte .ith

purplish?red

(aurophilic* ;ranules

>1!ar;e lymphocyte .ith

irre;ular cytoplasmic

contourC1!ar;e lymphocyte .ith

purplish?red


and .ith indentations

caused -y pressure of

erythrocytes!1!ar;e lymphocyte .ith

purplish?red



DI$$E"E3TIATIO3 A3D 2E!! MA"CE"S O$ !#MPHO2#TES



DI$$E"E3TIATIO3 A3D 2E!! MA"CE"S O$ !#MPHO2#TES


TdtCD 34

CD 7

Prothymocyte

Tdt D3

C

µ

Tdt

Tdt

CD 34+

Thymus

Pro-T cell

CD7CD2CD5CD4CD8

CD7CD3CD2CD5

CD7CD3CD2CD5

CD4TCR

CD34+

Early thymocyte

CD8TCR

Mature T cell Mature T cell

Myeloid restricted

precursor

ymphoid restricted

precursor

Pro-! cell

CD "#

CD "$

%& ' DR

Pre-! cell

CD 34

CD "#

%& ' DR

CD "#

CD 2$

CD 22

()M

%& ' DR

Pre-! cell

%& ' DR

CD "#

CD 2$

CD 22

&*ti)e*

Mature ! cell

Pluripote*t stem cell


http://slidepdf.com/reader/full/ltm-hemato 19/42#a.ata #1 '%%+

platelet

NK cell

small lymphocyte (mature T cell)

small lymphocyte (mature B cell)

plasma cellplasmocytoid

lymphocyte

mature B cell

mature T cell

megakaryocyte

Maturation and differentiation of non?lymphoid linea;e (me;a)aryocyte*

Maturation and differentiation of lymphoid linea;e

megakaryocyte

megakaryocyte

megakaryocytemegakaryocyte

T-lymphoblast

B-lymphoblast

NK cell

B-intermediate

lymphoblast

T-intermediate

lymphoblast

Natural killer lymphocyte

Lymphoid cell of T-lineage

Lymphoid cell of B-lineage



ME4ACA"#O2#TI2 S#STEM

A1Me;a)aryo-last .ithsin;le oval nucleus,

nucleoli, and -luish

foamy mar;inal

cytoplasmic

structures/1Prome;a)aryocyte

.ith t.o nuclei,

;ranular -lue

cytoplasm, and

mar;inal -u--lycytoplasmic

structures

21Me;a)aryocyte .ith

;ranular cytoplasm

and .ithout discretethrom-oc tes

D1Metame;a)aryocyte.ith multiple nuclei

and .ith

throm-ocytes

(platelets*

E1Metame;a)aryocytenucleus .ith attached

throm-ocytes

$1Throm-ocytes

(platelets*




Plasmocytic systems

A1 Plasmo-last/1 Proplasmocyte

21 Plasmocyte

A

/

2




$IJED TISSE 2E!!S

A1Pha;ocytic

histiocyte .ith

vacuoles andpha;ocytied

malarial pi;ment

/1Stem cell .ith

partial rupture of

nuclear mem-rane

21 Tissue

neutrophil

.ith coarsenuclear

chromatin

structure,

neutrophilic

;ranules, and

$IJED TISSE 2E!!S

A1Tissue -asophil (mast cell* /1Tissue eosinophil 21Tissue neutrophil


$AT 2E!!S



MA2"OPHA4ES$AT 2E!!S

A1Pha;ocytic histiocyte

.ith reticularcytoplasmic structure,

vacuoles, and

pha;ocytied particles

/1Pha;ocytic histiocyte

(ame-oid macropha;e*

.ith pha;ocytied

erythrocytes and dar)?stainin articles

21Pha;ocytic histiocyte,

fixed tissue type .ithpha;ocytied

hemosiderin in cytoplasm

D1Ame-oid pha;ocyte

(.anderin; tissue

macropha;e* .ith

pha;ocytied particles

and vacuoles inc to lasm

Top fat cell .ithsmall round nucleus,

linear chromatin and

;lo-ular -ody in

nucleus, ample

cytoplasm .ith lipoid

;lo-ules, .in)ledmem-rane, reticular

/ottom fat cellsho.in; cytoplasmic

lipoid -odies

separated -y

reticular structures1

Structures

surroundin; fat cellsare matureDi;;s Sturm /ell1 '%%6



OSTEO/!ASTS A3D OSTEO2!AST

A1Osteo-last .ith

prominent li;ht

one in cytoplasm

located a.ay from

nucleus/1Osteo-last .ith

oval eccentric

nucleus, distinct

linear chromatin

and nucleus, -lue-u--ly cytoplasm

.ith prominent

li;ht one, and

fi-rillar mar;inal

stuctures

21Osteoclast lar;e

multinucleated cell

.ith uneven num-er

of separated oval

nuclei, -lue;ranules, and

frayed cytoplasmic

mar;ins




"e;ulation of erythropoiesis1

/lood oxy;entension

Erythropoietin

"ed cellproduction

Tissue ()idney*oxy;en tension

"e;ulation of .hite -lood cellproduction1

Pha;ocyte productionlymphocyte

differentiationInflammatory

mediators

Micro-ial invasion

"e;ulation of plateletproduction1

0ascularinte;rity

Platelet production

KThrom-opoietinL

InFury

/leedin;and hypoxia

/a-ior /M, Stossel TP1 Hematolo;y a pathophysiolo;ical approach1 +:951p19?:1



/one marro. cells 3ormal adult values (*

Myelo-last

Promyelocyte31 Myelocyte

31 metamyelocyte

31 /and

31 Se;mented

Eosinophil

/asophil

% & +

+ & 6' & +%

6 & +6

+% & 5%

+% & %

% &

% & +

!ymphocyte

Plasmocyte

Monocyte

6 & +6

% & +

% & '

Proerythro-last (ru-ri-last*

/asophilic erythro-last (proru-ricyte*

Polychromatophilic erythro-last (ru-ricyte*

Orthochromatic erythro-last (metaru-ricyte*

% & +

+ & 5

+% & '%

6 ? +%M eloid er throid M E ratio ' & 5 +

/one marro. cells normal adult values

Myeloid

Erythroid




/lood cells Percent Per u!

31 /and

31 Se;mented

Eosinophil

/asophil

!ymphocyte

Monocyte

' & 7

6% & 8%

+ &

% & +

'% & 5%

+ & 7

+%% & 7%%

'16%% & 81%%%

6% & %%

N +%%

+1%%% & 51%%%

6% & 7%%

/lood cells normal adult values

Total leu)ocyte counts 61%%% & +%1%%% u!




EJT"AMED!!A"# HEMATOPOIESIS



EJT"AMED!!A"# HEMATOPOIESIS (EMH*

Is found in condition

+1 Excessive hematopoiesis

'1 /one marro. replacement

1 Dystrophic hematopoiesis

One or more hematopoietic cell lines may -e present

EMH occur in

+1 Myeloproliferative disorders (MPD*'1 Myelodysplastic syndrome (MDS*

1 Acute leu)emia



+1 EMH EJ2ESSI0E HEMATOPOIESIS

Excessive hematopoiesis .ith -lood formin; cells

fill and expand the /M cavity, and eventuallyextend -eyond the -one to involve adFacent areas,commonly paraverte-ral and epidural spaces

The liver, spleen and lymph nodes are also ofteninvolved

Excessive hematopoiesis caused -y

+1 2onstitutional disorders thalassemia, H-S

disease, hereditary spherocytosis'1 Acuired disorders in neonatal periode,

immune hemolytic anemia, severe folate = vit

/+' deficiency



'1 EMH /O3E MA""O< "EP!A2EME3T

"eplacement of /M -y non hematopoietic tissue forces the distri-utrion of hematopoiesis to othersites commonly the liver, spleen and lymph nodes

/M occupied -y histiocytes, ;ranuloma, fi-roustissue -one or mali;nant cell

P/ sho.s leu)oerythro-lastosis immature;ranulocytes, nucleated red -lood cell (3"/2*

/one marro. replacement caused -y

+1 2onstitutional disorders osteopetrosis,4oucher disease

'1 Acuired disorders histoplasmosis,tu-erculosis, myeloma, metastatic carcinoma,

osteosarcoma



1 EMH D#ST"OPHI2 HEMATOPOIESIS

Dystrophic hematopoiesis foci of disordered

;ro.th, inflammation repair, and ossification Dystrophic hematopoiesis caused -y

+1 Tumours may sho. area of EMH as dystrophic

element

'1 "esult of tumours production of erythropoietin

EMH reported in the tumours of hepatic tissue,soft tissue, ;onads uterus, central nervous

system, )idney and thyroid

Parhi D2, 2hai 22, Edelman AS, Parveen T, 0o T!T1 Patholo;y of -one marro. and -lood cells1+ st ed1Philadel hia !i incott <illiams = <il)insB '%%51 1'?1



I3E$$E2TI0E HEMATOPOIESIS

I3E$$E2TI0E HEMATOPOIESIS 2HA"A2TE"IED /#



I3E$$E2TI0E HEMATOPOIESIS 2HA"A2TE"IED /#

Shortened -lood cell survival

+1 sually macrocytic anemia

'1 "eticulocyte count may -e raised -ut is lo.relative to the de;ree of anemia

↑ indirect -iliru-in serum

4 ↑

activity !actate Dehydro;enase (!DH* Morpholo;ic a-normal -lood cell precursors in the /M

A1 Morpholo;y a-normality of erythropoiesis(dyserythropoiesis*

/1 Morpholo;y a-normality of ;ranulopoiesis(dys;ranulopoiesis*

21 Morpholo;y a-normality of throm-opoiesis

(dysthrom-opoiesis*



THALASEMIA



DEFINISI

Thalassemia adalah suatu kelainangenetic yang sangat beraneka ragam

yang ditandai oleh penurunan

sintesis rantai α atau β dari globin.Ditandai oleh penurunan kecepatansintesis atau absennya pembentukan

satu atau lebih rantai globinsehingga mengurangi sintesishemoglobin normal (kuantitatif).



ETIOLOGI THALASEMIA

Adanya mutasi ataupun delesi DNA pada gensehingga produksi rantai Alfa atau Beta darihemoglobin berkurang.

ada thalasemia Alfa ! D"#"$% rantai globin alfa

kromosom &' ada thalasemia Beta ! TA$% rantai globin

beta kromosom &&



KLASIFIKASI

$ecara klinis* thalasemia dikelompokkanmen+adi , yaitu! Thalasemia mayor* yang sangat bergantung

pada transfusi

Thalasemia minor atau carrier * tanpa gr+ala(asimptomatik)

Thalasemia intermedia

Berdasarkan rantai asam amino yangterkena* thalasemia digolongkan men+adi- +enis utama* yaitu! Thalasemia Alfa

Thalasemia Beta



PATOFISIOLOGI







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