MYELOID TISSUE

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MYELOID TISSUE
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Myeloid Tissue

• Bone marrow is found in the medullary canals of
  long bones and in the cavities of cancellous
  bones.
• Two types of bone marrow have been described
  based on their appearance on gross examination
• Red, or hematogenous, bone marrow, whose color is
  produced by the presence of blood and
  blood-forming cells
• Yellow bone marrow, whose color is produced by
  the presence of a great number of adipose cells.

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Myeloid Tissue

• In newborns, all bone marrow is red and is
  therefore active in the production of blood
  cells.
• As the child grows, most of the bone marrow
  changes gradually into the yellow variety.
• Under certain conditions, such as severe bleeding
  or hypoxia, yellow bone marrow is replaced by red
  bone marrow.

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Red Bone Marrow

• Red bone marrow is composed of a stroma ,
  hematopoietic cords (or islands), and sinusoidal
  capillaries.
• The stroma is a three-dimensional meshwork of
  reticular cells and a delicate web of reticular
  fibers containing hematopoietic cells and
  macrophages.
• The stroma of bone marrow contains collagen types
  I and III, fibronectin, laminin, and
  proteoglycans.
• The sinusoids are formed by a discontinuous layer
  of endothelial cells.

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Red Bone Marrow

• The islands of hemopoietic cells are composed of
  blood cells in various stages of maturation as
  well as macrophages.
• The macrophages destroy the extruded nuclei of
  erythrocyte precursors, malformed cells, and
  excess cytoplasm.
• Macrophages also regulate hemopoietic cell
  differentiation and maturation, transmit iron to
  developing erythroblasts to be utilized in the
  synthesis of the heme portion of hemoglobin.
• Frequently, processes of macrophages penetrate
  the spaces between endothelial cells to enter the
  sinusoidal lumina.

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HEMATOPOIESIS
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• Mature blood cells have a relatively short life
  span, and the population must be replaced with
  the progeny of stem cells produced in the
  hematopoietic organs.
• In the earliest stages of embryogenesis, blood
  cells arise from the yolk sac mesoderm.
• Later, the liver and spleen serve as temporary
  hematopoietic tissues.
• After Birth, the bone marrow becomes an
  increasingly important hematopoietic tissue.

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• Erythrocytes, granular leukocytes, monocytes, and
  platelets are derived from stem cells located in
  bone marrow. The origin and maturation of these
  cells are termed, respectively, erythropoiesis,
  granulopoiesis, monocytopoiesis, and
  megakaryocytopoiesis.
• The bone marrow also produces cells that migrate
  to the lymphoid organs, producing the various
  types of lymphocytes.

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Stem Cells

• Stem cells are pluripotential cells capable of
  self-renewal.
• Some of their daughter cells form specific,
  irreversibly differentiated cell types.
• Other daughter cells remain stem cells.
• A constant number of pluripotential stem cells is
  maintained in a pool, and cells recruited for
  differentiation are replaced with daughter cells
  from the pool.

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Progenitor Cells

• They have reduced potentiality and are committed
  to a single cell linage.
• They proliferate and differentiate into precursor
  cells in the presence of appropriate growth
  factors.
• They are morphologically indistinguishable
  (similar) to the stem cells, and both appear
  similar to small lymphocytes.

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Precursor Cells

• precursor cells (blasts) have their own
  morphological characteristics, and when they
  differentiate for the first time, they indicate
  the mature cell types which they will become.
• Whereas progenitor cells can divide and produce
  both progenitor and precursor cells, precursor
  cells produce only mature blood cells.

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Hemopoietic Growth Factors

• Hemopoiesis is regulated by a number of cytokines
  and growth factors, such as interleukins,
  colony-stimulating factors (CSF, macrophage
  inhibiting protein-a, and steel factor.
• Hemopoiesis is regulated by numerous growth
  factors produced by various cell types. Each
  factor acts on specific stem cells, progenitor
  cells, and precursor cells, generally inducing
  rapid mitosis, differentiation, or both.
• Some of these growth factors also promote the
  functioning of mature blood cells. Most
  hemopoietic growth factors are glycoproteins.

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Hemopoietic Growth Factors

• Certain growth factors such as steel factor (also
  known as stem cell factor), granulocyte-macrophage
  colony-stimulating factor (GM-CSF) and two
  interleukins (IL-3 and IL-7) stimulate
  proliferation of pluripotential stem cells, thus
  maintaining their populations.
• Additional cytokines, such as granulocyte
  colony-stimulating factor (G-CSF), monocyte
  colony-stimulating factor (M-CSF), IL-2, IL-5,
  IL-6, IL-11, IL-12, macrophage inhibitory
  protein-a (MIP-a), and erythropoietin, are
  believed to be responsible for the mobilization
  and differentiation of these cells into
  unipotential progenitor cells.

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Hemopoietic Growth Factors

• It has been suggested that there are factors
  responsible for the release of mature (and almost
  mature) blood cells from the marrow.
• These proposed factors have not yet been
  characterized completely, but they include
  interleukins, CSF, and steel factor.

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Erythropoiesis

• Erythropoiesis, the formation of red blood cells,
  is under the control of several cytokines, namely
  steel factor, IL-3, IL-9, GM-CSF, and
  erythropoietin.
• The process of erythropoiesis, red blood cell
  formation, generates 2.5 1011 erythrocytes
  every day.
• In order to produce such a huge number of cells,
  two types of unipotential progenitor cells arise
  from the CFU-GEMM (colony-forming units-
  granulocyte, erythrocyte, monocyte,
  megakaryocyte) the burst-forming
  units-erythrocyte (BFU-E) and colony-forming
  units-erythrocyte (CFU-E)

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Erythropoiesis

• If the circulating red blood cell level is low,
  the kidney produces a high concentration of
  erythropoietin, which, in the presence of IL-3,
  IL-9, steel factor, and GM-CSF (granulocyte-monocy
  te colony stimulating factor), induces CFU-GEMM
  to differentiate into BFU-E. These cells undergo
  a "burst" of mitotic activity, forming a large
  number of CFU-E

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Erythropoiesis

• CFU-E require a low concentration of
  erythropoietin not only to survive but also to
  form the first recognizable erythrocyte
  precursor, the proerythroblast.
• The proerythroblasts and their progeny form
  spherical clusters around macrophages (nurse
  cells) which phagocytose extruded nuclei and
  excess or deformed erythrocytes.
• Nurse cells may also provide growth factors to
  assist erythropoiesis.

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Monocytopoiesis

• Monocytes share their bipotential cells with
  neutrophils.
• CFU-GM undergoes mitosis and gives rise to CFU-G
  and CFU-M (monoblasts).
• The progeny of CFU-M are promonocytes, large
  cells (16 to 18 µm in diameter) that have a
  kidney-shaped, acentrically located nucleus.
• The cytoplasm of promonocytes is bluish and
  houses numerous azurophilic granules.

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Monocytopoiesis

• Electron micrographs of promonocytes disclose a
  well-developed Golgi apparatus, abundant RER, and
  numerous mitochondria.
• The azurophilic granules are lysosomes, about 0.5
  µm in diameter.
• Every day, the average adult forms more than 1010
  monocytes, most of which enter the circulation.
• Within a day or two, the newly formed monocytes
  enter the connective tissue spaces of the body
  and differentiate into macrophages.

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Platelet Formation

• The formation of platelets is under the control
  of thrombopoietin, which induces the development
  and proliferation of giant cells known as
  megakaryoblasts.
• The unipotential platelet progenitor, CFU-Meg,
  gives rise to a very large cell, the
  megakaryoblast (25 to 40 µm in diameter), whose
  single nucleus has several lobes.
• These cells undergo endomitosis, whereby the cell
  does not divide instead, it becomes larger and
  the nucleus becomes polyploid, as much as 64 N.

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Platelet Formation

• The bluish cytoplasm accumulates azurophilic
  granules. These cells are stimulated to
  differentiate and proliferate by thrombopoietin.
• Megakaryoblasts differentiate into megakaryocytes
  , which are large cells (40 to 100 µm in
  diameter), each with a single lobulated nucleus.
• Electron micrographs of megakaryocytes display a
  well-developed Golgi apparatus, numerous
  mitochondria, abundant RER, and many lysosomes .

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Platelet Formation

• Megakaryocytes are located next to sinusoids,
  into which they protrude their cytoplasmic
  processes. These cytoplasmic processes fragment
  along complex, narrow invaginations of the
  plasmalemma, known as demarcation channels, into
  clusters of proplatelets.
• Shortly after the proplatelets are released, they
  disperse into individual platelets. Each
  megakaryocyte can form several thousand
  platelets.
• The remaining cytoplasm and nucleus of the
  megakaryocyte degenerate and are phagocytosed by
  macrophages.

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