بسم الله الرحمن الرحيم

1. بسم الله الرحمن الرحيم

2. MYELOID TISSUE

3. 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.

4. 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.

5. 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.

6. 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.

7. HEMATOPOIESIS

8. 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.

9. 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.

10. 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.

11. 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.

12. 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.

13. 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.

14. 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-α (MIP-α), and erythropoietin, are believed to be responsible for the mobilization and differentiation of these cells into unipotential progenitor cells.

15. 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.

16. 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)

17. 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-monocyte 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

18. 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.

19. 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.

20. 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.

21. 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.

22. 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 .

23. 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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