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    HEMATOPOIESIS

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    ritaoktasari
    This document summarizes hematopoiesis, the formation of blood cells. It describes where blood cells are formed, including in the bone marrow and lymphoid tissues. It outlines the development pathways of the major blood cell types - erythrocytes, granulocytes, lymphocytes, monocytes, megakaryocytes - from stem cells to mature cells. Key stages and characteristics of each cell type are defined. The kinetics and regulation of hematopoiesis are also summarized.

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    HEMATOPOIESIS

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    ritaoktasari
    770 views7 pages
    This document summarizes hematopoiesis, the formation of blood cells. It describes where blood cells are formed, including in the bone marrow and lymphoid tissues. It outlines the development pathways of the major blood cell types - erythrocytes, granulocytes, lymphocytes, monocytes, megakaryocytes - from stem cells to mature cells. Key stages and characteristics of each cell type are defined. The kinetics and regulation of hematopoiesis are also summarized.

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    This document summarizes hematopoiesis, the formation of blood cells. It describes where blood cells are formed, including in the bone marrow and lymphoid tissues. It outlines the development pathways of the major blood cell types - erythrocytes, granulocytes, lymphocytes, monocytes, megakaryocytes - from stem cells to mature cells. Key stages and characteristics of each cell type are defined. The kinetics and regulation of hematopoiesis are also summarized.

    Copyright:

    Attribution Non-Commercial (BY-NC)
    Download as DOC, PDF, TXT or read online from Scribd
    Download as doc, pdf, or txt
    770 views7 pages

    HEMATOPOIESIS

    Uploaded by

    ritaoktasari
    This document summarizes hematopoiesis, the formation of blood cells. It describes where blood cells are formed, including in the bone marrow and lymphoid tissues. It outlines the development pathways of the major blood cell types - erythrocytes, granulocytes, lymphocytes, monocytes, megakaryocytes - from stem cells to mature cells. Key stages and characteristics of each cell type are defined. The kinetics and regulation of hematopoiesis are also summarized.

    Copyright:

    Attribution Non-Commercial (BY-NC)
    Download as DOC, PDF, TXT or read online from Scribd
    Download as doc, pdf, or txt
    of 7

    HEMATOPOIESIS

    Formation of Blood Cells


    • Blood cells have a limited life cycle
    – Cells are a component of the peripheral blood only in part of the life cycle
    – Production and destruction occur constantly
    • Bone Marrow
    – RBCs, granulocytes, monocytes and platelets are formed here
    – Lymphocytes are formed in marrow and in lymphoid tissues
    Hematopoiesis in Embryonic and Fetal Life
    • Primitive hematopoiesis
    – Transient production of blood cells in the “blood islands” of the yolk sac in embryos
    (days 15-18)
    – RBCs are nucleated and expressing embryonic globin chains
    • Definitive hematopoiesis
    – Hematopoietic centers appear in the liver & lymphoid tissues (days 335-342)
    – RBCs are non-nucleated and expressing fetal or adult globins
    – Origin of hematopoietic stem cells is the AGM
    • (dorsal aorta, gonads and mesonephros)

    Hematopoiesis after Birth


    • Occurs in the red bone marrow and lymphoid tissues
    • Pleuripotential Stem Cell
    – Long term repopulating hematopoietic stem cell
    • LTR-HSC
    • In vivo transplantation into lethally irradiated adults, resulted in long-term multi-
    lineage repopulation within 4-6 months
    – Colony-forming Unit
    • Nodular colonies contain all of the hemopoietic cell lines
    • All of the cells are progeny of one pleuripotential CFU
    Colony Forming Units
    • Multipotent progenitors
    – CFU-S, spleen
    – In vivo transplantation into lethally irradiated adults resulted in macroscopic colonies
    in the spleen within 8-16 days
    • Committed single and multi-lineage progenitors
    – CFU-C, culture
    – In vitro culture in semi-solid medium in the presence of hematopoietic factors.
    • Morphologically indistinguishable from lymphocytes
    • Only one in several thousand nucleated bone marrow cells is a CFU
    • Less common in peripheral blood
    – Only one in a million nucleated cells is a CFU

    Erythropoiesis
    • 2.5 x 10 11 erythrocytes are generated everyday
    • Two types of unipotential progenitor cells:
    – Burst-forming units (BFU-E)
    • Erythropoietin is produced by the kidney when RBC count is low
    • With IL3 and granulocyte-monocyte CSF, it induces CFU-S to differentiate into
    BFU-E
    • These cells undergo a burst of mitotic activity forming CFU-Es.
    – CFU-E
    • Require low levels of erythropoietin to survive and to form the first recognizable
    erythrocyte precursor
    – proerythroblast

    Erythrocyte Development: Proerythroblast


    • First recognizable cell beginning the process of erythropoiesis
    • Derived from a CFU
    • Relatively large cell (12-15 um)
    • Large spherical nucleus
    – 1 or 2 nucleoli
    • Cytoplasm shows mild basophilia
    – Presence of free ribosomes

    Erythrocyte Development: Basophilic Erythroblast (N1)


    • Smaller than a proerythroblast
    • Nucleus
    – Becomes smaller
    – Progressively more heterochromatic
    • Deeply basophilic cytoplasm
    – Large number of free ribosomes that are making hemoglobin

    Erythrocyte Development: Polychromatophilic Erythroblast (N2)


    • Smaller cell (9-12 um)
    • Markedly condensed nucleus
    – Coarse checkerboard pattern
    • Lilac colored cytoplasm
    – Presence of increasing amounts of hemoglobin
    – May see distinct colored regions (pink or blue)
    • Last cell in series capable of mitosis

    Erythrocyte Development: Normoblast (N3)


    • Orthochromatophilic erythrocyte
    • Slightly larger than mature erythrocyte
    • Small, compact, intensely stained nucleus
    – pyknotic
    • Nucleus is extruded at this stage
    – Passes into blood sinus of marrow
    • Cytoplasm acquires acidophilia

    Erythrocyte Development: Reticulocyte


    • Polychromatophilic erythrocyte
    • Constitute 1-2% of RBCs
    • No nucleus!
    • Acidophilic cytoplasm with trace of grey
    • Special stains demarcates reticular network of polyribosomes
    – Still able to synthesize hemoglobin

    Kinetics of Erythropoiesis
    • Erythroblasts will undergo mitosis
    – Proerythroblasts
    – Basophilic erythroblasts
    – Polychromatophilic erythroblasts
    • Nearly all erythrocytes are released into circulation as soon as they are formed
    • Bone marrow is not a storage site for RBCs!
    • RBC formation and release are under the regulatin of erythropoietin
    – Glycoprotein secreted by kidney in response to decreased oxygen tension.

    Breakdown of RBCs
    • At 4 months (120 days), they become fragile and subject to breakage
    • Macrophage system phagocytoses the degrading RBCs
    • Iron is separated from the hemoglobin
    – Stored as ferritin in spleen
    – Reused in hemoglobin synthesis
    • Heme moiety binds to albumin
    – Transported to liver where it is partially degraded, conjugated and excreted via
    gallbladder as bilirubin

    Granulocyte Development: Myeloblast (M)


    • 14-16 um in diameter
    • Derived from CFU
    • Oval nucleus with finely dispersed chromatin
    • Thin rim of basophilic cytoplasm
    • Devoid of granules

    Granulocyte Development: Promyelocyte (P)


    • First recognizable cell in granulopoiesis
    • 17-26 um in diameter
    – Largest cell in series
    • Large oval nucleus
    – Muliple nucleoli
    • Azurophilic (primary) granules in cytoplasm
    – Produced only at this stage!

    Granulocyte Development: Myelocyte (M1)


    • Spherical nucleus
    – Becomes increasingly heterochromatic
    • Prominent Golgi apparatus
    – Negative image
    • Lots of azurophilic granules
    • Formation of specific granules
    – Emerge from Golgi (cis face) complex
    – Characteristic staining reactions for each line

    Granulocyte Development: Metamyelocyte (M2)


    • First stage that is clearly divided into separate lines
    • Few hundred granules present in the cytoplasm
    – Specific granules outnumber the azurophlic granules 4:1
    • Nucleus
    – Heterochromatic
    – Indentation deepens to form horse-shoe shape

    Granulocyte Development: Band Cell (M3)


    • Last immature stage in Neutrophilic series
    • Sometimes seen in circulation
    – Particularly during states of chronic infection
    • Nucleus is elongated and of uniform width
    • Nucleus constricts
    – 2-5 lobes are formed
    – PMNs

    Kinetics of Granulopoiesis
    • Mitotic stage
    – Stops by late myelocyte stage (lasts ~ 1 week)
    • Postmitotic stage
    – Metamyelocyte to mature granulocyte (~ 1 week)
    • Mature granulocytes circulate in peripheral blood for 8-12 hours
    • Leave to go into perivascular CT
    – Neutrophils live for ~ 1-2 days, then they are destroyed by macrophages
    – Unknown exactly how long eosinophils and basophils live in the CT

    Megakaryocyte Development: Megakaryoblast


    • Derived from Pleuripotential CFU
    • ~30um in diameter
    • Non-lobulated nucleus
    • No evidence of platelet formation is seen at this stage
    • Successive endomitoses occurs
    – Chromosomes replicate
    – No karyokinesis nor cytokinesis
    – Ploidy increases to 16-64n, chromosomes cease to replicate >>>> Megakaryocyte

    Megakaryocyte
    • 50-70um in diameter
    • Multi-lobulated nucleus
    – Increased in size in proportion to ploidy of cell
    • Scattered azurophlic granules
    • Clusters of platelets at edge

    Lymphopoiesis
    • Lymphocytes constitute ~30% of all nucleated cells in the bone marrow
    • Progeny of T-cell lymphopoietic stem cells
    – Leave marrow and go to the thymus
    – Complete their differentiation there
    – Enter circulation as long-lived small lymphocytes
    • Progeny of B-cell lymphopoietic stem cells
    – Originate in several sites
    • Bone marrow, gut-associated lymph tissue (GALT) and the spleen
    • Precursors to small lymphocytes in the marrow are called “transitional cells”
    • Slightly larger than small lymphocytes
    • Thin rim of cytoplasm
    • Nucleus is filled with fine chromatin

    Monocyte Development
    • Derived from Pleuripotential CFU
    • Promonoctyes represent progenitor cells for this line
    – Half are rapidly dividing
    – Other half are reserve population of near stem cells
    • Stem cell to monocyte transformation takes ~55 hours
    • Monocytes remain in circulation only about 16 hours prior to emigrating into tissues
    – Differentiate into macrophages

    Bone Marrow
    • Consists of:
    – Blood Vessels
    – Specialized Units of blood vessels – sinuses
    – Sponge-like network of hemopoietic cells
    • Lie in cords between sinuses or between sinuses and bone

    Red Bone Marrow


    • Active bone marrow
    • Cords of hemopoietic cells
    – Developing blood cells
    – Megakaryocytes
    – Macrophages, mast cells & fat cells
    • Appears unorganized
    – Specific types develop in nests or clusters
    • Once mature, cells penetrate the endothelium to enter the circulation
    Yellow Bone Marrow
    • Non-active
    • Found in medullary cavities of bones in adult
    • Retains its hemopoietic potential
    – When necessary it can revert to red bone marrow to resume hemopoiesis

    Komplikasi
    Akibat anemia yang berat dan lama, sering terjadi gagal jantung. Transfusi darah yang
    berulang-ulang dan proses hemolisis menyebabkan kadar besi dalam darah tinggi,
    sehingga ditimbun dalam berbagai jaringan tubuh seperti hepar, limpa, ku.lit, jantung
    dan lainnya. Hal ini dapat mengakibatkan gangguan fungsi alat tersebut
    (hemokromatosis). Limpa yang besar mudah rupture akibat trauma yang ringan.
    Kadang-kadang thalasemia disertai oleh tanda hipersplenisme seperti leukopenia dan
    trombopenia.
    Kematian terutama disebabkan oleh infeksi dan gagal jantung.

    Prognosis
    Dubia ad malam

    Pencegahan dan edukasi


    Pencegahan primer
    Penyuluhan sebelum perkawinan (marriage counselling) untuk mencegah
    perkawinan diantara pasien Thalasemia agar tidak mendapatkan keturunan
    yang homozigot. Perkawinan antara 2 hetarozigot (carrier) menghasilkan
    keturunan: 25 % Thalasemia (homozigot), 50 % carrier (heterozigot) dan 25
    normal.

    Pencegahan sekunder
    Pencegahan kelahiran bagi homozigot dari pasangan suami istri dengan
    Thalasemia heterozigot salah satunya adalah dengan inseminasi buatan
    dengan sperma berasal dari donor yang bebas dan Thalasemia trait.
    Diagnosis prenatal melalui pemeriksaan DNA cairan amnion merupakan suatu
    kemajuan dan digunakan untuk mendiagnosis kasus homozigot intra-uterin
    sehingga dapat dipertimbangkan tindakan abortus provokotus (Soeparman
    dkk, 1996).

    Edukasi
    Sampaikan kepada pasien dan keluarga mengenai kondisinya sekarang.
    Beri saran agar sebelum melakukan pernikahan, cek pasangan untuk kemungkinan
    thalasemia.
    Hindari pemakaian obat pencetus hemolitik seperti fenasetin, klorpromazin
    (tranquilizer), penisilin, kina, dan sulfonamid.
    Makan-makanan bernutrisi khususnya asupan B12 dan folic acid.

    Kompetensi doker umum


    Tingkat Kemampuan
    3aMampu membuat diagnosis klinik berdasarkan pemeriksaan fisik dan
    pemeriksaanpemeriksaan tambahan yang diminta oleh dokter (misalnya :
    pemeriksaanlaboratorium sederhana atau X-ray). Dokter dapat memutuskan dan
    memberi terapi pendahuluan, serta merujuk ke spesialis yang relevan (bukan kasus
    gawat darurat.

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