Hematopoiesis 2023 PDF

HEMATOPOIESIS CLINICAL PATHOLOGY DEPARTMENT FACULTY OF MEDICINE UNIVERSITAS AIRLANGGA 2023 11/13/2023  HEMATOPOIESIS Hematopoiesis = production , development , differentiation and maturation of all blood cells 11/13/2023...

HEMATOPOIESIS CLINICAL PATHOLOGY DEPARTMENT FACULTY OF MEDICINE UNIVERSITAS AIRLANGGA 2023 11/13/2023  HEMATOPOIESIS Hematopoiesis = production , development , differentiation and maturation of all blood cells 11/13/2023 2  All blood cells are derived from a common precursor Pluripotent Stem Cells and after mitotic division , one of the daughter cells retain the property of Pluript.SC while the other is committed to produce mature blood cells This committed SC later differentiate into a blast cell in one of the cell lines (Differentiation phase) 11/13/2023 3  The development of blood cells from the blast cell stage progresses through further phases : - Proliferation - Maturation → Release into the circulation Plurip.Stem Cells are found within the bone marrow and are the origin of all blood cells 11/13/2023 4 - The pluripot. SC differentiate into 2 lines of multipotential SC : → Lymphoid multipt. SC Myeloid multipt. SC 11/13/2023 5  * Blood cells’s Ontogeny - Embryo consists of : Amniotic-sac and yolk-sac, with an embryonic- plate in between Later the amniotic sac develop into Placenta , the Yolk-sac became the umbilical cord and the embryonic plate grow as the embryo 11/13/2023 6 - yolk-sac’s primitive mesenchymal cells develop the blood cells (Mesoblastic period, 2 weeks – 2 months) by aggregate the primitive cells into clusters (blood-islands) : - Blood island’s core → yolk-sac’s primitive Stem-Cells → only produce embryonal RBC - Blood island’s outer cells → vascular system 11/13/2023 7  Mesoblastic period produces : Primitive embryonic erythroblasts embryonic Hbs : HbGower-I and II HbPortland 11/13/2023 8  Blood cells development process Bone Yolk Sac marrow Vertebra/Pelvis Sternum Liver Costa Splee Femur/long n bones 3 6 9 15 30 45 Gestationa Age (year) l age Labor 11/13/2023 9 11/13/2023 10  The first fetal hemopoietic centre is Liver ( from 2-7 months’ fetal life) producing red cells, and small numbers of white cells and megakaryocytes → since 24-weeks-old the liver activities went down , and fetal marrow start to become as hemopoietic centre. Fetal’s liver hemopoietic activities practically ended at birth. 11/13/2023 11  Spleen, Thymus and lymph nodes together with liver , acts as hemopoietic centre producing red cells and lymphocytes, but after 7 months old, they only produce lymphoid system cells. During adult life, if marrow tissue depressed , liver & spleen hemopoietic will be re-activated (extramedullary hemopoiesis) and become enlarged (hepatosplenomegaly) 11/13/2023 12  RBC’s morphological characteristics - Hepatic phase : no nucleus, macrocytic, Fetal-Hb (HbF, α2γ2) - At birth (medullary hemopoiesis) : mature RBC, normocytic, Adult-Hb (HbA, α2β2) After 15 years-old hemopoietic activities in long bones ceased and leave the activities only at flat-bones (sternum, scapule, coxae and skull- bones) 11/13/2023 13 11/13/2023 14 11/13/2023 15  Hemopoiesis’s Stages Stem Cells ↓ proliferation Daughter’s cells ↓ diferentiation Precursor-cells ↓ maturation Erythrocyte - Leucocyte - Platelet 11/13/2023 16 11/13/2023 17  Proliferation : Proliferation ~ generation’s cycle Generation Time = time between mitosis to the next mitosis : Mother’s cells (G1, active, diploid DNA , interphase) → DNA synthesis (S-phase) → tetrapoid DNA (G2-phase, Prophase) → Mitosis (M-phase, Metaphase-Anaphase- Telophase) → 2 daughter’s cells (G1-phase) 11/13/2023 18 11/13/2023 19  In neonates-infants/ Childn Adult children : all active parts of marrow act as hemopoietic centre → Marrow’ 1200-1 2000-350 no hemopoietic tissue’s s 600 ml 0 ml reserve volume Hemop 1200-1 1100 – oietic 600 ml 1750 ml tissue’s volume. 11/13/2023 20  In adult : marrow’s tissues replaced by fat tissue (yellow-marrow) beginning from long bones → hemopoietic activity only in flat-bones (pelvis, sternum, vertebrae, skull) If ↑ blood cells production is needed → the activities of the former hemopoietic centre ( long bones, liver and spleen) are re-activated = extramedularry hemopoiesis 11/13/2023 21  Stem Cells Replication model : - Symmetrical Replication - Asymmetrical Replication * Asymmetrical Replication : once the Stem Cells activate → 2 daughter-cells → 1 daughter-cell differentiate & maturate → 1 other daughter cell relocate the Stem cell’s former position. 11/13/2023 22  Symmetrical Replication : - activated stem cell → differentiate & maturate → stimulates the other stem cell and proliferate to become 2 daughter cells ; 1 of them relocate the mother’s position and the other daughter cell continue to differentiate and maturate. - Principally, the amount of Stem cells is rather unchanged. 11/13/2023 23 11/13/2023 24  Erythropoiesis Erythropoiesis stimulated by Erythropoietin , hormone produced in the kidney. This hormone is produced in response to low tissue oxygen tension ; stimulates Stem Cells to transform into proerythroblasts. Hb synthesis starts and ↑ with successive cell divisions. 11/13/2023 25  Each Committed Erythroid SC (Pronormoblast) goes through 4 cell divisions / maturational divisions → 16 mature RBC. (‹ 10% die before reach the final mature stage = ineffective ; note: in Megaloblastic Anemias, the ineffective erythropoiesis is abnormally high, › 50%) Normal process of proliferation and maturation lasts from 3-5 days 11/13/2023 26  Stages of Erythrocyte Development 1. Pronormoblast (proerythroblast) 2. Basophilic normoblast (erythroblast) 3. Polychromatophilic normoblast 4. Orthochromic normoblast 5. Reticulocyte 6. Erythrocyte 11/13/2023 27 11/13/2023 28  Normally no further cell division takes place during the orthochromatic normoblast, although such capacity still retained and will occur in certain situations (e.g in Iron Deficiency Anemia) Erythropoietic rate is depend on the rate of O2 transport to the tissue and is regulated by Erythropoietin (EPO) which will stimulate the committed SC to differentiate into normoblast 11/13/2023 29 A. Pronormoblast ; B. Basophilic normoblast ; C. Polychromatophilic normoblast ; D. Ortochromic normoblast ; E. Polychromatophil ; F. Mature RBC 2 Pronormoblast, Metamyelocyte, Stab neutrophil, Segmented neutrophil, normoblast Basophilic normoblast Basophilic normoblast ; 4 polychromatophilic normoblast Basophilic normoblast ; Polychromatophilic normoblast ; orthochromic normoblast  Leucopoiesis Leucopoiesis is under the control of Colony- Stimulating Factors (CSFs) , i.e G-M (Granulocyte-Macrophage) CSF Lymphoblasts give rise to Lymphocytes , some lymph.precursors leave the marrow and mature in the Thymus gland (produce T-lymphocytes) and lymphocytes which mature in marrow are called B-lymphocytes 11/13/2023 37 Myelocytic & Monocytic lines Granulocytic and Monocytic lines are derived from same precursor – Myelomonoblast , but with different maturation process : - Granulocytic line ended as segmented neutrophil in systemic circulation , and monocytic line ended as macrophage in tissues. 11/13/2023 38 11/13/2023 39 11/13/2023 40 Myeloblast 2. Promyelocyte ; 3. Myelocyte ; 6. Segmented neutrophil ; 9. normoblast 3. Myelocyte ; 4. Metamyelocyte ; 5. Stab neutrophil ; 7. Segmented eosinophil ; 10. normoblast ; 11. Monocyte Sel Plasma Megakaryocyte  Hemopoietic Growth Factors : = glycoprotein hormon , regulates the hemopoietic progenitors proliferation & differentiation and the immature’s blood cells function , locally activated or circulate in plasma. GF sources : - T-lymphocytes, Monocytes, Endothelial cells , Fibroblasts (Stroma cells) ; except Erithropoetin that 90% produced in kidney 11/13/2023 68  The action of GF regulated via specific reseptor in target tissues/cells. GF normally detected in plasma , or only found in plasma in inflammation or another stimulation. exmpl : Antigen and Endotoxin → activate T-lymphocytes / Macrophages → release IL-1 and TNF → stimulate another cells to produce GM-CSF, G- CSF, M-CSF, IL-6 etc 11/13/2023 69 11/13/2023 70 Thrombopoiesis To be mediated by Thrombopoietin hormone Platelet is fragments of the mature megakaryocyte’s plasma Megakaryoblast does not divide during mitosis and the cell simply increases its chromosome numbers (endomitosis) which results in a giant megakaryocyte with abundant cytoplasma from which the platelets bud 11/13/2023 71  Marrow’s Hemopoiesis Model Myeloid cells line : - the most numerous cells with complete maturation’s stages - specific morphological changes. - proliferation/mitosis capability still exists until myelocytic stage. - segmented neutrophils released to peripheral circulation. 11/13/2023 72  Marrow’s myeloid cells pooling : - Mitotic-Pool (myeloid progenitor cells , myeloblasts, promyelocytes, myelocytes) - Postmitotic-Pool (metamyelocytes, stabs & segmented neutrophils) Marrow’s pooling time : 6-10 days 11/13/2023 73  Peripheral myeloid cells pooling : Marginal-Pool = neutrophils that located along the vascular internal wall. Circulating-Pool = the circulating neutrophils. the calculated neutrophil on CBC = = circulating-pooled neutrophils. 11/13/2023 74  It is possible for Neutrophils to move from circulating pool to marginal pool (v versa) → the Leucocyte count become ↑ or ↓ From Marginal-Pool to Circulating-Pool → leucocyte count : - exercise / athletes - certain medicamentous 11/13/2023 75 11/13/2023 76  Bone Marrow’s Aspiration Aspiration of marrow’s hemopoitics fluid to evaluate hemopoitics appearance. It’s not uncommon that Aspiration followed by marrow’s biopsy (done in Histo-Pathology Department) 11/13/2023 77  Marrow’s Aspiration Indication : I. Diagnostic reasons : 1. Fever of unknown origin 2. Cytopenia 3. Monoclonal Gammopathy (Multiple Myeloma ) 4. Refractory Anemia 11/13/2023 78  II. Approving Diagnosis : 1. Multiple Myeloma 2. Acute Leukemia 3. Megaloblastic Anemia 4. Hypersplenisme III. Disease’s spreading / metastasis IV. Treatment monitoring V. Pre radiation/cytostatic preparation 11/13/2023 79  The Spleen as an indicator organ of hemopoietic health An fist-shaped soft organ, located on the left abdomen unpalpated, received 5% of C.O p. minute A blood-filled organ consists of red pulp (for red cell filtration) , white pulp (for lymphocyte processing) and marginal zone as a storage of white cells and platelets 11/13/2023 80  The functions of the Spleen 1. The Reservoir/Storage function : spleen traps 1/3 circulating granulocyte mass and 1/3 circulating platelet mass 2. The Filtration function : spleen inspects and examines each red cell and platelet abnormaities and inclusions Old red cells are culled by splenic phagocytes and release Bilirubin, Fe and globin byproducts 11/13/2023 81  Inclusions within red cell (Heinz bodies, Howell- Jolly bodies,etc) will be “pitted” and pulled from the cell and left the cell undestroyed Ab-coated red cells have the Ab removed and left the red cells appear as spherocytes in the circulation 11/13/2023 82 - 3. Immunologic Function : - promotes phagocytic activity for encapsulated organisms (H.influenzae, Strep.pneumoniae, or N.meningitidis) by opsonizing antibodies that strip the capsule from bacterial surface , so the unencapsulated bacteria is more vulnerable to the phagocytic RES and less able to mount an infection to the host system 11/13/2023 83  References 1. Hematology, Clinical Principles and Applications, Rodak B.F., 3rd ed., W.B Saunders Co, Philadelphia, 2007 2. Hematology in Clinical Practice, a Guide to Diagnosis And Management, Hillman R.S, Ault K.A, Rinder H.M., 4th ed., McGraw-Hill Medical Publishing Division , N.York, 2005 11/13/2023 84  Thank U 11/13/2023 85