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    HEMOPOIESIS &

    ERYTHROPOIESIS

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    HEMOPOIESIS: INTRO

    Hemo: Referring to blood cells

    Poiesis: The development or production of

    The word Hemopoiesis refers to the production &

    development of all the blood cells: Erythrocytes: Erythropoiesis

    Leucocytes: Leucopoiesis

    Thrombocytes: Thrombopoiesis.

    Begins in the 20thweek of life in the fetal liver &spleen, continues in the bone marrow till youngadulthood & beyond!

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    Appendicular

    skeleton:

    Bones of the

    Upper & Lower

    limbs

    In Adults active

    hemopoietic marrow is

    found only in:

    The axial skeleton

    The proximal ends of theappendicular skeleton.

    SITES OF HEMOPOIESIS

    Active Hemopoietic

    marrow is found, in

    children throughout

    the:

    Axial skeleton:

    Cranium

    Ribs.

    Sternum

    Vertebrae

    Pelvis

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    STEM CELL THEORY

    The dazzling array of all the blood cells are

    produced by the bone marrow.

    They all come from a single class of primitive

    mother cells called as: PLURIPOTENT STEM CELLS.

    These cells give rise to blood cells of:

    Myeloid series: Cells arising mainly from the bonemarrow.

    Lymphoidseries: cells arising from lymphoid

    tissues.

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    CLONAL HEMOPOIESIS

    PLURIPOTENT STEM CELL

    STEM CELL

    MULTIPLICATION COMMITTMENT

    COMMITTED

    STEM CELL

    COMMITTED

    STEM CELL

    MULTIPLICATION

    PROGENITOR

    CELL

    CFU: COLONY

    FORMING UNIT

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    CLONAL HEMOPOIESIS: (Contd)

    COLONY FORMING UNIT(CFU)

    INTERMEDIATE

    BLAST CELLS

    MATURE BLOOD CELLS

    END CELLS: FINITE LIFE SPAN

    MORPHOLOGICALLYRECOGNIZABLE

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    STEM CELLS

    These cells have extensive proliferative

    capacity and also the:

    Ability to give rise to new stem cells (Self

    Renewal) Ability to differentiate into any blood cells lines

    (Pluripotency)

    They grow and develop in the bone marrow.

    The bone marrow & spleen form a supportingsystem, called the

    hemopoietic microenvironment

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    Pluripotent Stem cells: Has a diameter of 1823 .

    Giving rise to: both Myeloid and Lymphoid seriesof cells

    Capable of extensive self-renewal. Myeloid Stem cells: Generate myeloid cells:

    Erythrocytes

    Granulocytes: PMNs, Eosinophils & Basophils.

    Thrombocytes. Lymphoid Stem cells: Giving rise only to:

    Lymphocytes: T type mainly.

    STEM CELLS: Types

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    PROGENITOR CELLS

    Committed stem cells lose their capacity for

    self-renewal.

    They become irreversibly committed.

    These cells are termed as Progenitor cells

    They are regulated by certain hormones or

    substances so that they can:

    Proliferate Undergo Maturation.

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    CELL LINE REGULATORS

    CELL LINE REGULATOR

    ERYTHROID: BFU-E:

    CFU : E

    BURST PROMOTING ACTIVITY

    ERYTHROPOIETIN

    GRANULOCYTE-MONOCYTE:CFU-GM

    COLONY STIMULATINGFACTOR(CSF)

    MEGAKARYOCYTES: CFU-M MEGAKARYOCYTICSTIMULATING ACTIVITY

    MEGAKARYOCYTES THROMBOPOIETIN

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    BLOOD CELLS: DEVELOPMENT

    PROGENITORCELLS

    LYMPHOIDCELLS

    PRONORMOBLAST

    MEGAKARYOBLAST MYELOBLAST MONOBLAST

    LYMPHOCYTES ERYTHROCYTES THROMBOCYTES GRANULOCYTES MONOCYTES

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    ERYTHROPOIESIS:

    SITES/PHASES

    INTRAUTERINELIFE: INTRAVASCULAR PHASE:Upto 3rdmonth of

    Intra Uterine Life.Endothelial cells = = = RBCs

    HEPATIC PHASE: 3rdto 5th month IULLiver SpleennRBCs from Mesenchymal cells.

    MYELOID PHASE: From 5thmonth of IULonwards.

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    POST NATAL LIFE:

    CHILDREN:

    Predominantly Red Bone Marrow of skeleton:

    Axial &

    Appendicular.

    ADULTS:

    Red Bone Marrow of Axial Skeleton.

    ERYTHROPOIESIS: SITES/PHASES

    contd.

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    PROERYTHROBLAST

    BASOPHILICERYTHROBLAST

    POLYCHROMATOPHILICERYTHROBLAST

    ORTHOCHROMATICERYTHROBLAST

    RETICULOCYTE

    MATURE ERYTHROCYTES

    ERYTHROPOIESIS

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    FACTORS REGULATING

    ERYTHROPOIESIS

    SINGLE MOST IMPORTANT REGULATOR:

    TISSUE OXYGENATION

    BURST PROMOTING ACTIVITY

    ERYTHROPOIETIN

    IRON

    VITAMINS:

    Vitamin B12

    Folic Acid

    MISCELLANEOUS

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    ERYTHROPOIETIN

    A hormone produced by the Kidney.A circulating GlycoproteinNowadays available as Synthetic EpoietinActs mainly on CFU E. Increases the number of:

    Nucleated precursors in the marrow. Reticulocytes Mature Erythrocytes in the

    blood.

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    VITAMINS

    B12: Cyanocobalamine Folic Acid: Is also called Extrinsic Factor of Castle. Needs the Intrinsic Factorfrom the Gastric juice

    for absorption from Small Intestine. Deficiency causes Pernicious (When IF is

    missing) or Megaloblastic Anemia. Stimulates Erythropoiesis Is found in meat diary products.

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    IRON

    Essential for the synthesis of Hemoglobin.Deficiency causes Microcytic, Hypochromic

    Anemia.TheMCV, Color Index MCHare low.

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    ERYTHROPOIESIS: SEQUENTIAL CHANGES

    I II III IV V

    VIPRONORMOBLAST

    EARLYNBLAST

    INTERNBLAST

    LATENBLAST

    RETICULOCYTE

    MATURERBC

    MITOCHONDRIA

    BASOPHILIA

    HEMOGLOBIN

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    ERYTHROID PROGENITOR CELLS

    BFU-E: Burst Forming Unit Erythrocyte: Give rise each to thousands of nucleated

    erythroid precursor cells, in vitro. Undergo some changes to become the Colony

    Forming Units-Erythrocyte (CFU-E) Regulator: Burst Promoting Activity (BPA)

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    CFU-E: Colony Forming Unit- Erythrocyte:Well differentiated erythroid progenitor cell. Present only in the Red Bone Marrow. Can form upto 64 nucleated erythroid precursorcells. Regulator: Erythropoietin.

    Both these Progenitor cells cannot bedistinguished except by in vitro culturemethods.

    ERYTHROID PROGENITOR CELLS

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    Normoblastic Precursors

    PROERYTHROBLAST: Large cell: 15 20 Microns in diameter. Cytoplasm is deep violet-blue staining Has no Hemoglobin. Large nucleus 12 Microns occupies 3/4thof the

    cell volume. Nucleus has fine stippled reticulum manynucleoli.

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    EARLY NORMOBLAST:

    Smaller in size.

    Shows active Mitosis.

    No nucleoli in the nucleus.

    Fine chromatin network with few

    condensation nodes found.

    Hemoglobin begins to form.

    Cytoplasm still Basophilic.

    Normoblastic Precursors

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    INTERMEDIATE NORMOBLAST:

    Has a diameter of 1014 Microns.

    Shows active Mitosis.

    Increased Hemoglobin content in the

    cytoplasm

    Cytoplasm is Polychromatophilic.

    Normoblastic Precursors

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    LATE NORMOBLAST:

    Diameter is 710 Microns.

    Nucleus shrinks with condensed

    chromatin.

    Appears like a Cartwheel

    Cytoplasm has a Eosinophilic appearance.

    Normoblastic Precursors

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    RETICULOCYTE:

    The penultimate stage cell.

    Has a fine network of reticulum like a

    heavy wreath or as clumps of dots This is the remnant of the basophilic

    cytoplasm, comprising RNA.

    In the Neonates, Count is 26/Cu.mm.

    Falls to

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    MATURE ERYTHROCYTE:

    Biconcave disc.

    No nucleus.

    About One-third filled with Hemoglobin.

    Normoblastic Precursors

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    Regulation of Erythropoiesis

    CFU

    E

    ProerythroblastsMature Erythrocytes

    Tissue OxygenationFactors decreasing:

    Hypovolemia Anemia

    Poor blood flow Pulmonary Disease

    ERYTHROPOIETINDecreases

    Stimulates

    An exampleof a

    Negativefeed backmechanism

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    HEMOPOIESIS: REVIEW I

    Hemopoiesis: Production of bloodcells.

    Site: Predominantly in the BoneMarrow.

    Both axial & appendicular skeletons. Erythropoiesis: Production of

    Erythrocytes. Leucopoiesis: Production of

    Leucocytes. Thrombopoiesis: Production of

    Thrombocytes.

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    HEMOPOIESIS: REVIEW II

    Cell lines:

    Pluripotent Stem Cell

    Progenitor Stem Cells: Committed

    Proerythroblasts

    Myeloblasts

    Monoblasts

    Lymphoid cellsMegakaryoblasts

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