Outcome : The student will understand : -The process of hematopoiesis

1. Course title: Hematology (1)Course code: MLHE-201 Supervisor: Prof. Dr Magda SultanDate : 31 / 10/2013 Outcome : The student will understand : -The process of hematopoiesis -The development of mature blood cells

2. Hematopoiesis Hematopoiesis is the process by which immature precursor cells develop into mature blood cells. A single type of stem cell gives rise to all the mature blood cells in the body. This stem cell is called the pluripotent stem cell.

3. SITES OF HEMATOPOIESIS Age Site of hematopoiesis Embryo ------------------------ yolk sac then liver 3rd to 7th month------------ spleen 4th and 5th months-------- marrow cavity - esp. granulocytes and platelets 7th month ------------------- marrow cavity - erythrocytes Birth---------------------------- mostly bone marrow; spleen and liver when needed Birth to maturity number of active sites in bone marrow decreases but retain ability for hematopoiesis. Adult--------------------------- bone marrow of skull, ribs, sternum, vertebral pelvis, proximal ends of femurs

4. STRUCTURE AND FUNCTION OF BONE MARROW Bone marrow has a vascular compartment and an extravascular compartment. Hematopoiesis takes place in the extravascular compartment. The daily output of mature blood cells in bone marrow is : 2.5 billion erythrocytes, 2.5 billion platelets, 50-100 billion granulocytes. The numbers of lymphocytes and monocytes is also very large.

5. In addition to hematopoiesis , bone marrow is the site of other activities . These include : -The removal of aged and defective erythrocytes -The differentiation of B lymphocytes -It is also the site of numerous plasma cells.

6. THE PROCESS OF HEMATOPOIESIS Pluripotent stem cells multiply to produce more pluripotent stem cells, thus ensuring the steady and lasting supply of stem cells. Some of the pluripotent stem cells differentiate into precursor cells that are at least partially committed to become one type of mature blood cell.

8. Pluripotent stem cells multiply slowly into one of five possible unipotential stem cells, which then multiply rapidly into the precursor of the specific mature blood cell for which they are destined.

10. Although the pluripotent stem cells and the unipotential stem cells cannot be distinguished from one another histologically, the precursor cells can be distinguished with a trained and practiced eye

11. Basically an immature, precursor cell goes from a cell that is making lots of protein to a cell that is making much less protein.

12. Thus, a cell that is making a lot of protein will have a nucleus containing dispersed or active chromatin. When this cell is making less protein, the chromatin is condensed or clumped.

13. ERYTHROPOIESIS As the cells are maturing in the erythrocytic series, the cells are usually getting smaller, the nucleus is becoming smaller and more condensed and is eventually lost, and the cytoplasm is becoming pinker rather than blue. The cells in the developing erythrocyte series are as follows: • Unipotent stem cell: cannot be distinguished from other unipotent stem cells by histology

14. • Proerythroblast: nucleus still rather large, taking up most of the cell; nucleus not condensed; cytoplasm still very blue or basophilic • Basophilic erythroblast (early) : very difficult to distinguish from the proerythroblast • Polychromatophilic erythroblast (intermediate) : nucleus is more condensed than that of the proerythroblast; cytoplasm less blue, more grayish . Orthochromatophilic erythroblast (late) : nucleus more condensed, smaller than that of previous cells and looks pyknotic by comparison; cytoplasm beginning to take on a more pinkish cast

15. • Reticulocyte: no nucleus; cytoplasm still stains somewhat bluish due to presence of remnants of polyribosomes • Erythrocyte: mature erythrocyte has no nucleus (in mammals); cytoplasm stains very pink due to lack of ribosomes and presence of high amounts of protein, i.e hemoglobin

16. Myelopoiesies • Unipotent stem cell: cannot be distinguished from other unipotent stem cells by histology • Myeloblast: large cell with blue-staining cytoplasm; large nucleus; and with nucleolus . • Promyelocyte: still a rather large cell with azurophilic granules • Myelocyte: overall cell still rather large; nucleus still round without indentation; granules staining appropriately for the series, i.e., pink for eosinophilic, blue for basophilic, neutral for neutrophilic

17. Metamyelocyte: cell is about the size of a mature granulocyte; nucleus with slight indentation; granules present that stain appropriately for the series, i.e., pink for eosinophilic, blue for basophilic, neutral for neutrophilic • Band cell: cell is about the size of a mature granulocyte; nucleus with definite indentation - looks like a horseshoe; prominent granules that stain appropriately for the series • Mature (segmented) granulocyte: cell is mature and looks like normal, mature granulocytes in the blood with lobed nucleus and prominent granules that stain appropriatly for the series .

18. Immune System This system consists of cells and tissues that have as their main function the protection of the body from the invasion by microorganisms and disease-. Components of this system are: • Lymphocytes T cells B cells • Plasma cells • Bone marrow • Thymus • Lymph Node • Spleen The bone marrow and thymus are considered as primary immune/lymphoid components because they contain the stem cells that will develop into T cells, B cells and natural killer cells of the functioning immune and lymphatic systems.

19. Megakaryopoiesis • Platelets, also called thrombocytes, play an important role in hemostasis • Platelets appear as round, oval or biconcave disks and have a diameter of about 1.5 to 3.5 μm. • Platelets are formed in the bone marrow from megakaryocytes (30-100 μm diameter), very large cells with a polyploid, multilobed nucleus and granular cytoplasm . Platelets are released from fragmenting megakaryocytes.

22. Training Questions : - Mention the cells of developing erythrocyte series . - What are the components of the immune system ? Reference Books : - Essential Hematology - Dacie .