hematopoiesis

Dr. Damajanty Pangemanan, MKes

Sistem hematopoietik
1. 2.

3.

Sel stem (progenitor awal), menyokong hematopoiesis Colony forming unit (CFU), pelopor yang selanjutnya berkembang dan berdeferensiasi dalam memproduksi sel Faktor regulator yang mengatur agar sistem berlangsung teratur

Stem sel

Sel induk yang mempunyai kemampuan berdeferensiasi menjadi beberapa turunan, membelah diri dan memperbaharui populasi sel stem sendiri dibawah pengaruh faktor pertumbuhan hematopoietik

Hematopoiesis
Pembentukan dan perkembangan dari selsel darah Dimulai pada awal kehidupan embrio dan berlangsung sampai dewasa Secara garis besar perkembangan ini dibagi dalam 3 periode :

Hematopoiesis yolk sac Hematopoiesis hati Hematopoiesis medular

Hematopoiesis yolk sac

Sel darah dibuat dari jaringan mesenkim 2-3 minggu setelah fertilisasi Sel eritrosit dapat diidentifikasi dalam yolk sac pada masa gestasi 16 hari Sel induk hematopoiesis mulai berkelompok dalam hati janin pada masa gestasi 5-6 minggu

Hematopoiesis hati
Berasal dari sel stem pluripoten yang berpindah dari yolk sac Perubahan tempat hematopoiesis ini mempunyai hubungan dengan regulasi perkembangan oleh lingkungan mikro, produksi sitokin dan ekspresi pada reseptor Masa gestasi 9 minggu, hematopoiesis sudah terbentuk dalam hati

Hematopoiesis hati
Yang terutama adalah eritropoiesis Mencapai puncak pada masa gestasi 4-5 bulan kemudian mengalami regresi perlahan Pada pertengahan kehamilan, tampak pelopor hematopoietik terdapat di limpa, thimus, kelenjar limfe dan ginjal

Hematopoiesis medular
Periode terakhir pembentukan sistem hematopoiesis Dimulai sejak masa gestasi 4 bulan Ruang meduler terbentuk dalam tulang rawan dan tulang panjang dengan proses reabsorbsi

Hematopoiesis medular
Masa gestasi 32 minggu lahir semua rongga sum-sum tulang terisi dengan jaringan hematopoietik yang aktif dan sum-sum tulang berisi sel-sel darah Pada perkembangan selanjutnya fungsi pembuatan sel darah diambil oleh sum-sum tulang Sel mesenkim yang mempunyai kemampuan membentuk sel darah menjadi kurang, tapi tetap ada dalam sumsum tulang, hati limpa,kelenjar getah bening dan dinding usus dikenal sebagai RES

Hematopoiesis medular
Pada bayi dan anak hematopoiesis yang aktif terjadi pada sumsum tulang, termasuk bagian distal tulang panjang Orang dewasa normal, hematopoiesis terbatas pada vertebra (tulang belakang),costa, sternum, pelvis, skapula, skull ( dan jarang berlokasi pada humerus dan femur)

Hematopoiesis in a fetus

Hemopoiesis in the embryo takes place in the yolk sac, liver and spleen, and bone marrow

Hematopoiesis in a fetus
Sel darah pertama yang dibentuk adalah eritrosit Pada 2-8 minggu pertama sel eritrosit primitif ditemukan di yolk sac

Hematopoiesis in a fetus
Selama 2 bulan pertama hematopiesis extrameduler berkembang, dan yolk sac berpindah ke liver Granulocytes also appear in the liver during the 2nd month The spleen also contributes to hematopoiesis at this point.

Hematopoiesis in a fetus
During the 4th month medullary hematopoiesis develops when the bone marrow begins to contribute to hematopoiesis. During the 5th month bone marrow takes over as chief production site and continues throughout life.

Hematopoiesis after birth

At birth the liver and spleen have ceased production of blood cells and hematopoiesis is occurring in the red bone marrow of almost every bone (axial and appendicular skeletons).

Hematopoiesis after birth

As a child develops and matures (beginning at 4 years) the hematopoietic activity begins to move to the axial skeleton (flat bones, skull, ribs, sternum, clavicle, vertebrae, pelvic bones) and proximal ends of long bones (humerus and femur). This move is completed by age 18

Hematopoiesis after birth

Remaining marrow cavities are replaced with fat (yellow bone marrow). By age 40 the marrow in sternum, ribs, pelvis and vertebrae is composed of equal amounts of hematopoietic tissue and fat.

Hematopoiesis after birth

Extramedullary hematopoiesis may occur under two conditions:

If the bone marrow is no longer functional When the bone marrow is not able to keep up with the demand for blood cells

When extramedullary hematopoiesis occurs, the liver and spleen will become enlarged.

The Blood Cells

red blood cells (RBCs) or erythrocytes white blood cells (WBCs) or leukocytes platelets or thrombocytes (actually cytoplasm fragments)

Blood cell development in adults

All blood cells develop from pluripotent stem cells that are found in the red bone marrow. Stem cells are able to proliferate as well as differentiate into the different types of blood cells. They are also able to renew themselves.

Blood cell development in adults

The pluripotent stem cell is the progenitor of two multipotential stem cell lines: the myeloid and the lymphoid lines. Myeloid stem cells are precursors of granulocytes, monocyte, RBCs and platelets; lymphoid stem cells are precursor of lymphocytes

Control
Many Growth Factors (also known as cytokines and interleukins and hormones) precisely regulate all stages of the process. For example. 1.CSF - colony stimulating factors function at various stages of development of blood cells. There are several CSFs, each stimulating the development of different types of cells

2. Interleukins - protein molecules that work with the CSFs to stimulate particular cell lines to proliferate and differentiate. 3. Erythropoietin (EPO) the hormone produced by kidney to stimulate RBC production (regulates erythropoiesis) 4. filgrastim: is produced by stromal cells and regulates granulopoiesis 5. thrombopoietin: is produced by the liver, and regulates platelet production

They have many different effects:

proliferation differentiation maturation functional activation prevention of apoptosis (programmed cell death)

Pools of hematopoietic activity

1. Bone marrow Stem cell pool - comprised of multipotential stem cells and unipotential committed colonyforming units (CFUs), all of which are morphologically unidentifiable. Proliferating pool - cells are capable of DNA synthesis and are undergoing mitosis. Storage pool - mature cells that are stored for later release into the peripheral blood and cells that are maturing. They are no longer capable of mitosis.

2. Peripheral blood
a. Circulating pool
functioning cells in circulation, in transit to tissues. The blood we draw for evaluation comes from this pool. The circulating pool is found more towards the center of the tubular blood vessel.

b. Marginating pool Primarily a term used for white blood cells. The cells are adhered to walls of blood vessels and are ready to move through into the tissues (diapedesis). There is constant movement between the circulating and marginating pools. At a given time the ratio of cells in the circulating pool to the cells in the marginating pool is 50:50. Neutrophils move freely between the two pools.

The two pools of circulation in peripheral blood

Hemopoiesis

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from pluripotent stem cells to mature, differentiated, cellular effectors of immunity and more

Hematopoiesis

Th- Helper Cell B Cell Macrophage Neutrophil (alternative path) Mast Cell Platelets

Tc Cytotoxic Cell Dendritic Cell Neutrophil Eosinophil Basophil Erythrocyte

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Dendritic cell pathway

Sel dendritik
Sel dengan bentuk tidak teratur Ditemukan pada jaringan , pada kulit disebut sel Langerhans epidermal Berperan sebagai presentasi antigen ke sel T dan aktivasi limfosit

This is the undifferentiated precursor to all of the blood cells, red and white, and other immune effector cells, and platelets.

Pluripotent Stem Cell

daughters of the Pluripotent Stem Cells, these are the progenitors of a host of specialized white blood cells (WBCs), red blood cells (RBCs) and the blood platelets which are crucial to blood clotting.

Myeloid Stem Cells

Granulocyte -Monocyte Progenitor cells

can differentiate into monocytes or neutrophils

Monocytes

act as antigen presenting cells (APCs), as Antibody-Dependent Cytotoxic Cells (ADCC) , and promote inflammation.

cell is phagocytic it inhabits the tissues looking for foreign intruders to devour.

Dendritic Cell like the macrophage, this

Macrophage pathway

Monosit/macrofag
Merupakan sel darah terbesar Mengandung granul dan nucleus bentuk lobular Mempunyai aktivitas baktericidal Monosit bermigrasi dari sirkulasi kejaringan seperti sel Kupfer di hepar Berperan penting pada imunitas spesifik dan non spesifik

This is the undifferentiated precursor to all of the blood cells, red and white, and other immune effector cells, and platelets.

Pluripotent Stem Cell

daughters of the Pluripotent Stem Cells, these are the progenitors of a host of specialized white blood cells (WBCs), red blood cells (RBCs) and the blood platelets which are crucial to blood clotting.

Myeloid Stem Cells

Granulocyte -Monocyte Progenitor cells

can differentiate into monocytes or neutrophils

Monocytes

act as antigen presenting cells (APCs), as Antibody-Dependent Cytotoxic Cells (ADCC) , and promote inflammation.

presenting cell (APC), in inflammation, and in ADCC (antibody-dependent cell-mediated cytotoxicity

Macrophagefunctions as antigen

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leukosit
Sel darah putih Konsentrasi : 4800 10.800/mm kubik darah Berfungsi sebagai alat pertahanan tubuh terhadap bakteri, virus, parasit, racun dan sel tumor Tdd :

Granulosit (neutrofil, basofil dan eusinofil) Agranulosit (limfosit dan monosit)

Granulopoiesis

Granulocytes include 3 types of cells:

neutrophils or polymorphs eosinophils basophils

Granulopoiesis

Granulocytes and a fourth cell type - the monocyte are made in the bone marrow from a common precursor cell, the mixed myeloid progenitor cell or CFUGEMM.

This process takes between 6-10 days in the marrow. Once released from the marrow, into the marrow sinusoids, and from there into the peripheral blood, these cells circulate for only 6-10 hours. They then take up residence in tissue where they live for 4-5 days before they die.

Neutrofil
Jumlahnya paling banyak dari jenis leukosit (50-70%) Fungsi : fagositik, terutama terhadap bakteri

Neutrophil Pathway

This is the undifferentiated precursor to all of the blood cells, red and white, and other immune effector cells, and platelets.

Pluripotent Stem Cell

daughters of the Pluripotent Stem Cells, these are the progenitors of a host of specialized white blood cells (WBCs), red blood cells (RBCs) and the blood platelets which are crucial to blood clotting.

Myeloid Stem Cells

Granulocyte -Monocyte Progenitor cells

can differentiate into monocytes or neutrophils

Monocytes

act as antigen presenting cells (APCs), as Antibody-Dependent Cytotoxic Cells (ADCC) , and promote inflammation.

activity, inflammation response, and antibodydependent, cell-mediated cytotoxicity (ADCC)

Neutrophilsfunction in antimicrobial

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Alternative Neutrophil pathway

This is the undifferentiated precursor to all of the blood cells, red and white, and other immune effector cells, and platelets.

Pluripotent Stem Cell

daughters of the Pluripotent Stem Cells, these are the progenitors of a host of specialized white blood cells (WBCs), red blood cells (RBCs) and the blood platelets which are crucial to blood clotting.

Myeloid Stem Cells

Granulocyte -Monocyte Progenitor cells

can differentiate into monocytes or neutrophils

activity, inflammation response, and antibodydependent, cell-mediated cytotoxicity (ADCC)

Neutrophilsfunction in antimicrobial

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Eosinophil Pathway

Eosinofil
Merupakan 2-5% dari leukosit Fungsi sebagai fagosit yang lemah Berperan juga pada imunitas parasit dan reaksi alergi

This is the undifferentiated precursor to all of the blood cells, red and white, and other immune effector cells, and platelets.

Pluripotent Stem Cell

daughters of the Pluripotent Stem Cells, these are the progenitors of a host of specialized white blood cells (WBCs), red blood cells (RBCs) and the blood platelets which are crucial to blood clotting.

Myeloid Stem Cells

Eosinophil Progenitorwill produce

eosinophils

Eosinophilthese cells are active in the

immune response to asthma, allergies, and parasites.

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Mast Cell Pathway

This is the undifferentiated precursor to all of the blood cells, red and white, and other immune effector cells, and platelets.

Pluripotent Stem Cell

daughters of the Pluripotent Stem Cells, these are the progenitors of a host of specialized white blood cells (WBCs), red blood cells (RBCs) and the blood platelets which are crucial to blood clotting.

Myeloid Stem Cells

Basophil Progenitor a product of the

specialization of Myeloid stem cells, this cell will produce either Mast Cells or Basophils

cells function in inflammation and allergic response. When mature, they become granulated and are found in tissues, not in peripheral blood.

Mast Celllike the related basophils these

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Basophil pathway

basofil
Jumlah yang ditemukan dalam darah sangat sedikit, sekitar <0,5% dari seluruh leukosit Mempunyai fungsi fagosit mirip sel mast Melepaskan bahan-bahan yang mempunyai aktivitas biologik, antara lain meningkatkan permeabilitas vaskular dan respons inflamasi

This is the undifferentiated precursor to all of the blood cells, red and white, and other immune effector cells, and platelets.

Pluripotent Stem Cell

daughters of the Pluripotent Stem Cells, these are the progenitors of a host of specialized white blood cells (WBCs), red blood cells (RBCs) and the blood platelets which are crucial to blood clotting.

Myeloid Stem Cells

Basophil Progenitor a product of the

specialization of Myeloid stem cells, this cell will produce either Mast Cells or Basophils

characterized by cytoplasmic granules which, when released, function in destruction of parasites and also in allergic reactions. The cell releases histamine and platelet activator and other chemical signals.

Basophilthis IgE responsive cell is

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Platelet pathway

Megakaryopoiesis

Platelets are produced from very large cells called megakaryocytes which develop in the bone marrow from megakaryoblasts which, like other cells in the marrow, are derived from a haemopoietic stem cell. The nucleus in a megakaryocyte reduplicates, but the cell does not divide so eventually a very large cell with multiple nuclear lobes is formed. This is referred to as "endomitosis".

Each megakaryocyte makes approximately 4000 platelets and this process takes about 10 days. The megakaryocyte straddles the marrow sinusoids and little bits of cytoplasm - the platelet - are extruded through the sinus wall and into the blood stream.

The normal lifespan of a platelet is 7-11 days

This is the undifferentiated precursor to all of the blood cells, red and white, and other immune effector cells, and platelets.

Pluripotent Stem Cell

daughters of the Pluripotent Stem Cells, these are the progenitors of a host of specialized white blood cells (WBCs), red blood cells (RBCs) and the blood platelets which are crucial to blood clotting.

Myeloid Stem Cells

Megakaryocytefragments into
subcellular pieces called platelets

Plateletsare blood elements without nuclei

that circulate and are involved in blood clotting and inflammation.

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Erythrocyte Pathway

Erythropoiesis
Erythropoiesis, or the production of red cells, is regulated by a hormone called erythropoietin. Approximately 1012 new red cells are made each day through successive doubling of a progenitor cell called a proerythroblast until 16 cells are formed. The cells become progressively smaller and contain increasing amounts of haemoglobin It circulates for 1-2 days and finally becomes a mature red cell

eritrosit

Sel darah merah Discus/lempeng biconkcaf Diameter 7,5 um Faktor penentu utama kekentalan darah Konsentrasi normal :
Wanita : 4,3-5,2 juta/mm kubik darah Pria : 5,1-5,8 juta/mm kubik darah

Masa hidup : 120 hari Fungsi : transportasi gas respirasi

hemoglobin
Bagian eritrosit yang berkaitan dengan gas respirasi Tdd : protein globin dengan empat rantai polipeptida dan empat pigmen merah heme yang mengandung besi tempat oksigen diangkut Mengandung 250 juta molekul oksigen Kadar normal :

Pria : 13,9-16 gr/dl Wanita : 12-15 gr/dl

This is the undifferentiated precursor to all of the blood cells, red and white, and other immune effector cells, and platelets.

Pluripotent Stem Cell

daughters of the Pluripotent Stem Cells, these are the progenitors of a host of specialized white blood cells (WBCs), red blood cells (RBCs) and the blood platelets which are crucial to blood clotting.

Myeloid Stem Cells

myeloid stem cell, this is destined to produce the most common blood cell, the erythrocyte.

Erythroid Progenitorderived from a

(RBCs)are enucleated cells that travel throughout the Circulatory System and carry Oxygen to all parts of the body via the abundant hemoglobin found within them.

Erythrocytesor red blood cells