ltm hemato
TRANSCRIPT
8/17/2019 Ltm hemato
http://slidepdf.com/reader/full/ltm-hemato 1/42
HEMATOPOIESIS
8/17/2019 Ltm hemato
http://slidepdf.com/reader/full/ltm-hemato 2/42
HEMATOPOIESIS Prenatal, postnatal hematopoiesis
Medullary hematopoiesis,extramedullary hematopoiesis
Effective hematopoiesis, ineffective
hematopoiesis
8/17/2019 Ltm hemato
http://slidepdf.com/reader/full/ltm-hemato 3/42
MED!!A"# HEMATOPOIESIS
8/17/2019 Ltm hemato
http://slidepdf.com/reader/full/ltm-hemato 4/42
$etus % & ' months (yol) sac*' & +% months (liver, spleen* & +% months (-one marro.*
Infants /one marro. (practically all -ones*
Adults 0erte-rae, ri-s, sternum, s)ull, sacrum andpelvis proximal ends of femurHoff-rand A01 '%%+
SITES O$ 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-
8/17/2019 Ltm hemato
http://slidepdf.com/reader/full/ltm-hemato 5/42
Dia;rammatic representation of -one marro. pluripotentstem cells and the cell lines1
Hoff-rand A01 '%%+
8/17/2019 Ltm hemato
http://slidepdf.com/reader/full/ltm-hemato 6/42
!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
8/17/2019 Ltm hemato
http://slidepdf.com/reader/full/ltm-hemato 7/42
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 $>1 +::9 = Hoff-rand A01 '%%+
8/17/2019 Ltm hemato
http://slidepdf.com/reader/full/ltm-hemato 8/42
Act on stromal cells I!?+
T3$
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 '%%+
8/17/2019 Ltm hemato
http://slidepdf.com/reader/full/ltm-hemato 9/42
THE "O!E O$ 4"O<TH $A2TO"S I3 3O"MA! HAEMOPOIESIS
Hierarchical model of haemotopoiesis and lymphopoiesis includin;
important cyto)inesSchiffman $>1 +::91
8/17/2019 Ltm hemato
http://slidepdf.com/reader/full/ltm-hemato 10/42
/lood cells
3OME3C!AT"
Throm-ocyte
/asophil
3eutrophil
Promonocyte
Prome;a)aryocyte
Proru-ricyte
Mono-last
Me;a)aryo-last
"u-ri-last
Prolymphocyte
Proplasmocyte
!ympho-last
Plasmo-last
Me;a)aryocyte
"u-ricyte
Metame;a)aryocyte
Metaru-ricyte Erythrocyte
Monocyte
Se;mented
Eosinophil
3eutrophil/and
31 Metamyelocyte31 Myelocyte
/1 Myelocyte
E1 Myelocyte
PromyelocyteMyelo-last
!ymphocyte
Plasmocyte
Erythrocyte/asophilicDiffusely
2I"2!ATI34 /!OOD
HEMATOPOIETI2 TISSES
S t e m
c e l l
Di;;s Sturm /ell1 '%%6
8/17/2019 Ltm hemato
http://slidepdf.com/reader/full/ltm-hemato 11/42
MAT"ATIO3 SEE32E O$ "/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
Di;;s Sturm /ell1 '%%6
8/17/2019 Ltm hemato
http://slidepdf.com/reader/full/ltm-hemato 12/42
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
Di;;s Sturm /ell1 '%%6
8/17/2019 Ltm hemato
http://slidepdf.com/reader/full/ltm-hemato 13/42
3ET"OPH#! 3O3 SE4ME3TED A3D SE4ME3TED
Terminolo;y -ased on indentation of nuclei1
3onse;mented
Se;mented
Di;;s Sturm /ell1 '%%6
M#E!O2#TE METAM#E!O2#TE /A3D SE4ME3TED
8/17/2019 Ltm hemato
http://slidepdf.com/reader/full/ltm-hemato 14/42
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
Di;;s Sturm /ell1 '%%6
8/17/2019 Ltm hemato
http://slidepdf.com/reader/full/ltm-hemato 15/42
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
8/17/2019 Ltm hemato
http://slidepdf.com/reader/full/ltm-hemato 16/42
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
8/17/2019 Ltm hemato
http://slidepdf.com/reader/full/ltm-hemato 17/42
!#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
(aurophilic* ;ranules
and .ith indentations
caused -y pressure of
erythrocytes!1!ar;e lymphocyte .ith
purplish?red
(aurophilic* ;ranules
Di;;s Sturm /ell1 '%%6
DI$$E"E3TIATIO3 A3D 2E!! MA"CE"S O$ !#MPHO2#TES
8/17/2019 Ltm hemato
http://slidepdf.com/reader/full/ltm-hemato 18/42
DI$$E"E3TIATIO3 A3D 2E!! MA"CE"S O$ !#MPHO2#TES
Di;;s Sturm /ell1 '%%6
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
8/17/2019 Ltm hemato
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
8/17/2019 Ltm hemato
http://slidepdf.com/reader/full/ltm-hemato 20/42
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*
Di;;s Sturm /ell1 '%%6
8/17/2019 Ltm hemato
http://slidepdf.com/reader/full/ltm-hemato 21/42
Plasmocytic systems
A1 Plasmo-last/1 Proplasmocyte
21 Plasmocyte
A
/
2
Di;;s Sturm /ell1 '%%6
8/17/2019 Ltm hemato
http://slidepdf.com/reader/full/ltm-hemato 22/42
$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
Di;;s Sturm /ell1 '%%6
$AT 2E!!S
8/17/2019 Ltm hemato
http://slidepdf.com/reader/full/ltm-hemato 23/42
MA2"OPHA4ES$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
8/17/2019 Ltm hemato
http://slidepdf.com/reader/full/ltm-hemato 24/42
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
Di;;s Sturm /ell1 '%%6
8/17/2019 Ltm hemato
http://slidepdf.com/reader/full/ltm-hemato 25/42
"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
8/17/2019 Ltm hemato
http://slidepdf.com/reader/full/ltm-hemato 26/42
/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
Di;;s Sturm /ell1 '%%6
8/17/2019 Ltm hemato
http://slidepdf.com/reader/full/ltm-hemato 27/42
/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!
Di;;s Sturm /ell1 '%%6
8/17/2019 Ltm hemato
http://slidepdf.com/reader/full/ltm-hemato 28/42
EJT"AMED!!A"# HEMATOPOIESIS
8/17/2019 Ltm hemato
http://slidepdf.com/reader/full/ltm-hemato 29/42
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
8/17/2019 Ltm hemato
http://slidepdf.com/reader/full/ltm-hemato 30/42
+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
8/17/2019 Ltm hemato
http://slidepdf.com/reader/full/ltm-hemato 31/42
'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
8/17/2019 Ltm hemato
http://slidepdf.com/reader/full/ltm-hemato 32/42
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
8/17/2019 Ltm hemato
http://slidepdf.com/reader/full/ltm-hemato 33/42
I3E$$E2TI0E HEMATOPOIESIS
I3E$$E2TI0E HEMATOPOIESIS 2HA"A2TE"IED /#
8/17/2019 Ltm hemato
http://slidepdf.com/reader/full/ltm-hemato 34/42
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*
8/17/2019 Ltm hemato
http://slidepdf.com/reader/full/ltm-hemato 35/42
THALASEMIA
8/17/2019 Ltm hemato
http://slidepdf.com/reader/full/ltm-hemato 36/42
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).
8/17/2019 Ltm hemato
http://slidepdf.com/reader/full/ltm-hemato 37/42
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 &&
8/17/2019 Ltm hemato
http://slidepdf.com/reader/full/ltm-hemato 38/42
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
8/17/2019 Ltm hemato
http://slidepdf.com/reader/full/ltm-hemato 39/42
PATOFISIOLOGI
8/17/2019 Ltm hemato
http://slidepdf.com/reader/full/ltm-hemato 40/42
8/17/2019 Ltm hemato
http://slidepdf.com/reader/full/ltm-hemato 41/42
8/17/2019 Ltm hemato
http://slidepdf.com/reader/full/ltm-hemato 42/42