hematopoeisis
DESCRIPTION
HEMATOPOEISIS. Dr. Bastiana Bermawi , SpPK. Hematopoiesis. Hematopoiesis ( hemopoiesis ) Pembentukan sel darah (Production of Blood cell) Where??. Tempat Hematopoeisis. - PowerPoint PPT PresentationTRANSCRIPT
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HEMATOPOEISIS
Dr. Bastiana Bermawi, SpPK
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Hematopoiesis Hematopoiesis (hemopoiesis)
Pembentukan sel darah
(Production of Blood cell)
Where??
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Tempat Hematopoeisis
Neonatus (semua sumsum merah tulang) : tulang pipih . tulang tengkorak, clavicula , sternum, tulang rusuk, vertebra dan tulang pelvis
Dewasa vertebra, tulang rusuk, sternum, tulang kepala, tulang pelvis, proksimal dan distal femur
50% sutul terisi lemak dan dapat diubah jadi tempat hematopoisis pada keadaan tertentu dapat terjadi hematopoisis ekstramedular ( hati , limpa ).
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White blood cells
Platelets
Red blood cells
Artery
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ERITROSIT
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neutrophil
neutrophilRBC
eosinophil
monocyte
lymphocyte
lymphocytebasophil
monocyte
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PLATELET/ TROMBOSIT
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DEFINISIHematopoeisis:
Proses pembentukan darah yang teregulasi dan berkesinambungan, meliputi cell renewal, proliferasi, diferensiasi dan maturasi
Cell renewal: kemampuan sel memperbarui diri sendiri
shg tidak akan habis meski terus membelah
Proliferasi: kemampuan membelah /memperbanyak diri
Difrensiasi: kemampuan berkembang menjadi sel dgn
fungsi tertentu
Maturasi: kemampuan mematangkan diri
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Pada orang dewasa, hematopoisis fisiologis hanya terjadi di sumsum tulang (sutul)
Hematopoeisis patologis terjadi di luar sutul, disebut hematopoeisis ekstramedularis
Selama perkembangan janin, proses ini terjadi di beberapa tempat, terdiri dari 3 fase, yaitu:
- fase mesoblastik (yolk sac);
- fase hepatik;
- fase medularis (mieloid)
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Hematopoisis:
1. Yolk sac: 0-3 bulan intra uterine
2. Hati dan Lien: ~3- 6 bulan intra uterine
3. sumsum tulang: ~ 4 bln intrauterine - dws
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PROSES HEMATOPOEISIS
Proses hematopoeisis memerlukan:
1. Sel induk hematopoisis (hematopoeitic-
stem cell)
2. Lingkungan mikro (microenvironment)
3. Bahan pembentuk darah
4. Mekanisme regulasi
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1. Sel induk hematopoesis (Hematopoetic stemsel)
Sel induk hematopoetik (SIH):
Sel yg akan berkembang mjd sel darah, yaitu: eritrosit, lekosit, trombosit dan sel lain dlm sutul, spt fibroblas
SIH paling primitif: Pluripoten/totipoten stem-cell, mempunyai sifat:
* self renewal
* proliferatif
* differensiatif
* maturatif
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Pluripotential stem cells rangsangan
Kemampuan: memperbaharui diri
proliferasi diferensiasi maturasi
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Lanjutan….Sel induk hematopoesis (SIH)
berdasarkan sifat diffrensiatif, SIH terbagi atas:
- pluripotent/totipoten stemcell: mampu
berdiffrensiasi jd seluruh jenis sel
- Commited stemcell: komitmen berdifrensiasi
menjadi satu cell line (cth : SIH mieloid, SIH
Limfoid)
- Oligopotent stemcell: hanya mampu berdifrensiasi
jd beberapa jenis sel, cth: CFU-GM (Colony-
forming unit- Granulocyte/monocyte hy menjadi
sel granulosit dan sel monosit.
- Unipotent stemcell:hanya mampu berdifrensiasi jd
satu jenis sel saja, cth: CFU-E eritrosit
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Pluripotent stemcells tingkat proliferasinya rendah
Unipotent stemcells tingkat proliferasinya tinggi
Jumlah Pluripotent hematopoietic stem cells di sumsum tulang dan di peredaran darah sedikit.
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2. Lingkungan mikro Sutul:- Fungsi: - - menyediakan nutrisi & bhn hemopoisis
- komunikasi antar sel: Adhesi molekul
- Menghasilkan zat yg mengatur hematopoeisis: sitokin,
hemopoetik growth factor.
- Meliputi:
a. mikrosirkulasi dlm sutul
b.sel stroma: sel endothel, makrofag, sel lemak,
fibroblast, sel retikulum.
c.matriks ekstraseluler: haemonektin, kolagen,
fibronektin,glikosaminoglikan.
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3. Bahan Pembentuk darah
Bahan Pembentuk darah:
* as folat, vit B12
* Fe
* Co, Mg, Cu, Zn
* As amino
* vitamin: vitamin B komplek, Vitamin C
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4. Mekanisme regulasi
Mekanisme Regulasi:
- Untuk mengatur arah & kuantitas pertumbuhan & pelepasan sel darah matur
dari sutul darah tepi.
- sistim ‘feed back mechanism’
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Zat yg berpengaruh dlm mekanisme Regulasi
1. Faktor pertumbuhan Hemopoisis:
- GM-CSF
- G-CSF
- M-CSF, dll.
2. Sitokin: - IL-3, IL-4, IL-6, IL-11 dll.
- Ada yg merangsang & menekan
pertumbuhan sel induk.
3. Hormon hemopoitik spesifik: Erytropoetin
4. Hormon non spesifik (dlm jumlah kecil)
- androgen
- estrogen
- Hormon tiroid.
- glukokortikoid
- growth hormon
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Hematopoitic growth factors and some of their characteristics
Factor Cell stimulated
Production sources
M-CSF Monocytes Endothelial cells, monocytes, fibroblasts
GM-CSF All granulocytes, megakaryocytes,erythrocytes, stem cell, leukemic blast
Tcells, endothelial cells, fibroblast
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G-CSF Granulocytes, megakaryocytes, erythrocytes, stem cell, leukemic blast
Endotelial cells, placenta, monocytes
IL-3 Granulocytes, erythroid cells, multipotential progenitors, leukemic blasts
T cells
1L-4 B,T cells T cells
Factor Cell stimulated
Production sources
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IL-5 B cells, CFU-EO T cells
IL-6 B,T cells, CFU-GM GFU-GEMM, BFU-E, Macrophages, neural cells, hepatocytes
Fibroblasts, leucocytes, endo- thelial cells
IL-7 B cells leucocytes
IL-8 T cells, neutrophils
leucocytes
Factor Cell stimulated
Production sources
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IL-9 BFU-E, CFU-GEMM
Lymphocytes
IL-11 B,T cells, CFU-GEMM, macrophages
macrophages
Erythropoitin CFU-E, BFU-E Kidney , liver
Factor Cell stimulated
Production sources
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Sel progenitor mempunyai reseptor untuk faktor humoral tertentu yang sesuai Invitro
BFU-E-, CFU-E + Eritropoitin Eritropoisis
CFU-MEG. + MEG-CSF Megakariosit
CFU-GM + GM-CSF Netrofil, monosit
CFU-EO + EO.CSF Eosinofil.
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Gangguan hematopoeisis
1. Gangguan pada sel induk hematopoeisis (SIH): keganasan, disfungsi/ defisiensi SIH (an.aplastik)
2. Gangguan Organ tempat hematopoisis:
semua kerusakan sutul (fibrosis, infeksi metastase)
3. Gangguan pada bahan yang diperlukan:
(faktor nutrisi, gangguan Hormon, bahan bahan beracun).
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Eritropoesis
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Eritropoeisis Eritropoeisis:
Pembentukan/produksi eritrosit (red blood cell production)
Hematopoetic stem-cell berdifrensiasi menjadi proerythroblast
Proerythroblasts early erythroblasts Fase Perkembangan selanjutnya:
1. Ribosome synthesis
2. Hemoglobin accumulation
3. Ejection of the nucleus and formation of reticulocytes
Retikulosit eritrosit matur
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Figure 17.5
Stem cell
HemocytoblastProerythro-blast
Earlyerythroblast
Lateerythroblast Normoblast
Phase 1Ribosomesynthesis
Phase 2Hemoglobinaccumulation
Phase 3Ejection ofnucleus
Reticulo-cyte
Erythro-cyte
Committedcell
Developmental pathway
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Eritropoisis
Membutuhkan:Nutrisi :
Mineral ( Fe, mangan, cobalt ) Vitamin ( B12, C, B6, B1,asam folat, dll)
Asam amino
Faktor perangsang :Eritropoitin, tiroksin, androgen
Keutuhan jaringan sumsum tulang (microenvironment )
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Tiroksin: meningkatkan kebutuhan jaringan terhadap oksigen
Androgen :
merangsang eritropoitin
meningkatkan sensitivitas stem cell terhadap eritropoitin.
mempengaruhi langsung eritropoisis
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Proerythroblast
No hemoglobin
Nucleus 12 um
Contain nucleoli
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Basophil erythroblast
Early normoblast
Nucleoli disappear
Show mitosis
Cytoplasm deep blue
Increase in RNA
Hemoglobin starts
appearing – Little Hb
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Polychromatophil erythroblast
Late normoblast
Nucleus smaller
Coarse Chromatin
Hemoglobin increase
Eosinophil Stain
RNA – Basophil stain
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Orthochromatic Erythroblast
Normoblast
Nucleus smaller
Pyknosis
Nuclear lysis and
Nuclear
extrusion
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Reticulocyte
Reticulum
Remnant of ER
Synthesize Hb
Few Mitochondria
Young RBCs (34% Hb)
1 % of Red Cells
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GRANULOPOESIS
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Contoh GRANULOPOESIS
Mieloblas segmen netrofil
Promielosit mielosit N metamielosit N stab N
GRANULOPOEISIS (Line: neutrofil)
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Fungsi utama netrofil:
Pertahanan tubuh migrasi ke tempat infeksi.
Pengenalan & pengolahan antigen asingFagositosis
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Distribusi netrofil setelah masuk sirkulasi darah
Sutul Sirkulasi darah Jaringan
MGP
CGP T1/2 = 6,3 -7,6 jam MGP
CGP = Circulating granulocyte poolMGP = Marginated granulocyte poolTGP = Total blood granulocyte pool = CGP + MGP
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Perubahan pola distribusi Netrofil :Olah-ragaEpinefrin → me↑ CGP sampai 50% ,Hipoksia me↓ MGP, tapi TGP Stres tetap →
pseudonetrofilia
Endotoksin mobilisasi MGP ke CGP,Kortikosteroid mobilisasi dari sutul ke
CGP → TGP ↑
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Faktor yg mempengaruhi mobilisasi netrofil
dari sutul ke sirkulasi:
Bakteri / organisme Endotoksin → merusak dinding sinusoid . Besarnya pori-pori dinding sinusoid . Tingkat maturasi sel . Netrofil batang / segmen dapat
lewat pori2 dgn Ø 1 μm ; promielosit dapat lewat pori2 dgn Ø 8 μm .
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Nama monosit di jaringan
Di hati -------- sel KupferDi limpa -------- sel retikulumDi tulang -------- osteoclastDi jaringan ikat -------- histiositDi sutul -------- makrofagDi otak -------- neurogIia
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LIMFOPOESIS
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Limfopoisis Di organ primer (sutul, timus) tak perlu rangsangan Di organ sekunder (kelenjar getah bening, limpa,
perlu rangsangan antigen).
Limfosit T Limfosit B
Di sirkulasi darah 15-20% Umur lebih Resirkulasi + + Rangsangan antigen atipis blast
transform (sel plasma) Fungsi imunitas seluler humoral
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Rangkuman
Hematopoisis:
Pembentukan, perkembangan, dan proses pegkhususan/spesialisasi sel darah cara fungsional.
Fase hematopoesis: mesoblastik, hepatik dan medularis
Organ tempat hematopoesis: Hati, Limpa, lymphnodus, Timus dan Sumsum tulang
Sumsum tulang: tempat utama hematopoeisis mulai dari lahir sampai seumur hidup
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Rangkuman
Pada keadaan tertentu, produksi sel darah bisa terjadi luar sumsum tulang (sutul), disebut hematopoeisis ekstramedular
Lingkungan mikro pada sutul penting untuk proliferasi dan difrensiasi stemsel
Sel matur, karakteristik umum: penurunan ukuran sel dan inti sel, hilangnya nukleoli, kondensasi kromatin inti, pengurangan basofilia di sitoplasma.
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DARAH
merupakan komponen esensial makhluk hidup, yang berfungsi, a.l:
1. sebagai pembawa oksigen,
2. mekanisme pertahanan tubuh thd infeksi
3. mekanisme hemostasis terdiri dari 2 komponen utama, yakni:
1. Plasma: bgn cair darah: air, elektrolit, protein
2. Sel darah (blood corpuscles):
a. eritrosit (sel darah merah)
b. leukosit (sel darah putih)
c. trombosit sel /butir pembeku darah)
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• Membawa O2 (Deliver O2)
• Membuang produk sisa metabolisma tubuh
• Mengatur suhu, pH, dan volume cairan
• Melindungi dari kehilangan darah/sumbat
perdarahan-trombosit (Protection from blood
loss- platelets)
• Mencegah infeksi- antibodi dan leukosit
• Transpor hormon
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Erythrocyte7.5m in diameter · Anucleate- so can't reproduce; however, repro
in red bone marrow· Hematopoiesis- production of RBC· Function- transport respiratory gases· Hemoglobin- quaternary structure, 2 chains
and 2 chains· 1 RBC contains 280 million hemoglobin
molecules· Men- 5 million cells/mm3
· Women- 4.5 million cells/mm3
· Life span 100-120 days and then destroyed in spleen (RBC graveyard)
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RBC Formation before birth Mesoblastic stage
Nucleated RBCs - Yolk sac and Mesothelial
layers of the placenta – 3rd week Hepatic stage
• At 6 weeks - Liver form blood cells
Spleen + lymphoid tissues form blood
cells.
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RBC Formation before birth
Myeloid stage
• From the third month onwards - the
bone marrow gradually becomes the
principal source of the RBCs
• Last month – Bone marrow exclusively