hematopoiesis-2024.pdf

Hemopoiesis Dr. Silvia Boyajian  Hemopoiesis -- prenataly postnataly Mostly...

Hemopoiesis Dr. Silvia Boyajian  Hemopoiesis -- prenataly postnataly Mostly In Bl of yolk Sternum, ribs, pelvis, proximal sac Mesoderm phases 1. Mesoblastic in of and -othweek pregnancy femur, vertebrae in end of spleen 2. Hepatic: in liverand freester in Br 3. Myeloid: in 3rdtrimester > nature - / - cell stem erythrocy - cell r of CFU-E  pluripotenthematopoietic blood call star cells: the potential to produce all types - proliferate and produce two cell lineage - - myeloid Stem Cells Multipotent lymphoid cells Multipotent progenitor d ↓ d ↓ unipotent, commited stem cell ↓ CFU-M CFU-M CFU-G CFU-L CFU-E oblastmegakaryoblastmyteloblast cells ↓ I precursor lymphoblast enythurblast1 ↓ ↓ ↓ Neutrophils cells He ↓ Basophils Nature Lymphocy cosinophils dre B T  Hemopoiesis:the process which blood cells are formed -postnataly ~ prenataby - - - ofyolk sac :in mesoderm pregnancy of phase (2nd-6th) Marrow To Mesoblastic - - in bone liver and splen in Hepatic phase- - second trimester 20 in 30 Myeloid passe, in bone,irratimester. -rot. Mature call -> Mature - precursorcal - Stem cell - ↳ -  the cells thatcan stem cells; hematopoietic pluripotent produce all blood call types from singletypeis -lymphoid stem cells & stem -els -> eloid stem cells (Mattipotently -My (Untipotent) ↓ ↓ ↓ CFU-E ↓ CfU- M cres from-enitoredat ↓ CFU-L ↓ ↓ ↓ ↓ loblast vourblast precursor cells lymphoblast Erythroblastregular o - ↓ ↓ ↓ ↓ ↓ Neutrophils Monocyte -> Mature calls a lymphocyte RBCs platelets Eusinophils basophils B dNK  Hemopoiesis Prenatally Postnatally 1- Mesoblastic phase: in mesoderm of yolk sac (2nd -6th) weeks of pregnancy Occurs almost exclusively in bone Sixis is6 marrow: 2- Hepatic phase: within the liver and spleen also play a role Sternum, ribs, pelvis, proximal ends of 7 E in second trimester femur, vertebrae - 5 32- 3- Myeloid phase: in bone marrow begins in the 3rd trimester Pluripotent hemopoietic stem cells It is believed that ALL blood cells arise from a single type of stem cell in the bone marrow called a pluripotent stem cell This cell can produce all blood cell types Proliferate and form TWO major cell lineages: one for myeloid cells One for lymphoid cells granulocytes, monocytes, (lymphocytes) all develop in bone marrow erythrocytes, megakaryocytes Early in their development, lymphoid cells migrate from the bone marrow to thymus or to the lymph nodes, spleen, and other lymphoid structures where they proliferate and differentiate  Stem cells are capable of asymmetric division and self-renewal Stem cells can maintain the original population Precursor cells produce only mature blood cells self - renewal Stem cell 11552,1 E Erythroblast Every time the stem cell multiplies, it All erythroblasts multiply and will give two cells, one differentiate differentiate into mature RBCs into mature RBCs and the other cell (erythrocytes) and no erythroblasts are add to the original population left in the end  all of calls give us types Pluripotent ·potential to - Stem cells Myeloid stem cell Lymphoid stem cell (Multipotent) potential to multiple (Multipotent) · give us types of cells Progenitor cells (committed, unipotent stem cells) factor unit colony CFU-E CFU-M CFU-G CFU-M CFU-L akaryocyte - - crythrocyte Granulocyte Monocyte lymphocyte Megakaryoblast NK Lymphoblast B Lymphoblast T Lymphoblast Precursor cells Myeloblast Monoblast Erythroblast Mature cells Progenitor and precursor cells: the pluripotent stem cells give rise to daughter cells with restricted potentials called: Progenitor cells or colony-forming units  CFUs (since they give rise to colonies of ONLY ONE cell type when cultured or injected into spleen) Progenitor cells are 4 types: A- Erythroid lineage of CFU-erythrocytes (CFU-E) B- Thrombocytic lineage of CFU- megakaryocytes (CFU-Meg) C- Granulocyte-monocyte lineage of CFU- granulocyte- monocytes (CFU-GM) D- Lymphoid lineage of CFU- lymphocytes of all types (CFU-L) All four progenitor/ CFUs produce  precursor cells or blasts Where morphologic characteristics begin to differentiate suggesting the mature cell types they will become Stem cells and Progenitor cells cannot be morphologically distinguished and resemble large lymphocyte Rate of cell division : slow in stem cells rapid in progenitor and precursor cells Progenitor cells: can divide and produce both progenitor cells and precursor cells Precursor cells: produce only mature blood cells ~ - Siss - Erythropoiesis (red cell formation) CEU-I Nature From stem cell to erythrocyte takes about 1 week - - Rate is controlled by the hormone erythropoietin secreted by the kidney and by the availability of iron, folic acid, and vitamin B12 and protein precursors &3 a 512, 5,;:cytoplasm in - cytoplasm),changes -2, of the cell cytoplasma nee ~ blue cytoplasm: nucleus,8, !, - cnuclear maturation -  - basophilic cytoplasm Proerythroblast: - 135412,-,9,982* 2Mm 585 * - the first recognizable erythrocyte precursor - sib;s-· nucleus: large jo g is numerous organelles but NO hemoglobin E S, reticulocyte ; (1853:,'8ss:12 0s) Hb X - j.ES. nuclei 15-20 µm in diameter (17 µm) ribosomes is (1- nucleoliE, s:,:S HB 12s nucleus Si hemoglobins's - - SY HB 11s basophilic cytoplasm basophilic cytoplasm - me Large pale neucleus with prominent nucleoli Basophilic erythroblast (early normoblast): 12-16 µm in diameter u(15µm) number ofribozomes Deeply basophilic cytoplasm because have very we large Nucleus: smaller and darker 5158;s,"elil = nucleoi s'85- - No nucleoli 7:5818 06:) - Hb -3- Hemoglobin synthesis begins and is completed by the end of reticulocyte stage &? Nucleus 11 - Cell division ceases deeply basophilic cytoplasm Marks the beginning of progressive loss of cytoplasmic organelles - -35,j) cell division 31 55- 5X1 ; >955 Polychromatophilic erythroblast (intermediate normoblast): 11;" · - violet;g;s?; Jsdicg=-.(gasms- 10-12 µm in diameter / Cytoplasm varies from blue-grey to state-grey (violet) basic cribosomess acidic (b) HB 19s Takes basic(ribosomes) and acidic stains (Hb) &1991 - Nucleus small with denser more compact chromatin structure  E - - · Orthochromatophilic erythroblast (late normoblast): changes in cytoplasm - Late normoblast nucleus - The cell become smaller (11 µm) is acidophilic cytoplasm Acidophilic erythroblast is! · - The cells have acquired almost their contents of hemoglobin and the cytoplasm cytoplasm is acidophilic - become eosinophilic (pink) ⑤ , ncus; -Sss Nucleus: smaller, darker and eccentric to be expelled outside 5.) I nucleus. - Nucleus extruded during this stage & nucleus (1 186- - Reticulocytes: Slightly larger than mature erythrocytes (9 µm) Acidophilic cytoplasm contains remnants of ribonuclear protein stainable gis;s. · (brilliant cresyl blue) as a network cytoplasm is acidophilic No nucleus - No nucleus - blood (!;= May appear in circulating blood (not more than 1%) - 1.1 - Their number may increase after hemorrhage and in certain anaemias Erythrocyte 7.577-8) Granulopoiesis (granulocyte formation) Takes about two weeks Erythropoiesis takes one week - of -> two types granules primary + secondary 5 - lobulated s Lobulation 2, I mono lobulated nucleus -> ↓ multi - -  g'dissi -" Myeloblast: Most immature recognizable cell in myeloid series -> no granules Light blue cytoplasm with NO granules Nucleus: five chromatin network 2-3 pale nucleoli are evident Promyelocyte: Basophilic (blue) cytoplasm with small dark azurophilic granules still mononuclear Nucleus: reddish-blue, coarse chromatin, nucleolus: present - The largest (20 µm) escD"* x5ese,56 eosinophilic is a lot Myelocyte: the cell can't divid [ses -S morphological 5.2 The cell become smaller changes The nucleus become smaller and darker Three types 3 start to appear and gradually increase in Early:CSpecific (secondary) granules quantity and eventually occupy most of the cytoplasm the cell can't divide -18: P. Late: further condensation of nucleus  Metamyelocyte: -2,stotas"miniganingest Three types - Cannot divide Undergo metamorphosis Cytoplasm: paler in color Nucleus: kidney shaped, eccentric dense and dark chromatin absent nucleoli Band cell (Stab): Three types Cytoplasm: both azurophilic and specific granules are present Nucleus: horse-shoe shaped dark blue with a very coarse granules absent nucleoli Mature cells: Enters the blood stream  $5 & Neutrophil band cells Their percentage does not exceed 5% in peripheral blood The appearance of large numbers of immature neutrophils (band cells) in the blood is called a shift to the left and is clinically significant, usually indicating bacterial infection This means that the bone marrow has been signaled to release more neutrophils and increase production of neutrophils  Hematopoietic pluripotent stem cell Myeloid stem cell Colony forming unit-megakaryocyte X Megakaryoblast Promegakaryocyte Megakaryocyte  Hematopoietic pluripotent stem cell Myeloid stem cell Colony forming unit-monocyte X Monoblast Promonocyte Monocyte  Hematopoietic pluripotent stem cell Lymphoid stem cell X Lymphocyte colony forming cell Lymphoblast Bone marrow Recall: There are two types of bone marrow : red and yellow Red bone marrow: abundance of blood and hemopoietic cells Yellow bone marrow: filled with adipocytes In newborn: ALL bone marrow is RED and active in blood cell production as the child grows most of the marrow changes gradually to the yellow variety under certain conditions (severe bleeding, hypoxia)  yellow marrow reverts to red Reticular cells of bone marrow also called adventitial cells produce steel factor (stem cell factor) that promote hematopoiesis through a paracrine effect Functions of the red bone marrow: 1- production of blood cells 2- destruction of red cells (along with spleen and liver): removal of aged and defective erythrocytes from the circulation 3- plays a central role in the immune system 4- being the site of B lymphocyte differentiation 5- containing large numbers of antibodies-secreting plasma cells Red bone marrow: S Is a highly cellular structure that is located in the medullary cavities of the bone It consists of: NS 2) 1- stroma: meshwork reticular cells, reticular fibres containing hematopoietic cells and macrophages contains type I and III collagen 2- Sinusoidal capillaries:OExhibit wide diameters with wide gaps between endothelial cells ( and discontinuous basement membrane some regions of the endothelium are thin (little more than the inner and outer layers of plasma membrane, which are sites for migration of mature cells from stroma  sinusoid  blood 3- Hematopoeitic cells * (1570:inactive it, yellow). I Severe bleeding blood cells's1100. As the individual ages and becomes an adult, the red marrow is found primarily in the axial skeleton (flat bones of the skull, sternum and ribs, vertebrae, and pelvic bones). The remaining bones, primarily the long bones in the limbs of the body, gradually accumulate fat, and their marrow becomes yellow. Consequently, they lose the hemopoietic functions. Under certain conditions (severe bleeding or hypoxia), yellow marrow reverts to red red - fats is" - hematopoietic cells yellow -> Fat + hematopoietic cells capil aries ~ j  in number of blasts 11 - ;52:15.64665118141-97 Leukemia: - large of precursorcells) leukemia. types (different Malignant proliferation of white cell precursors in the bone marrow Vast number of white cells and their precursors, many of which spell over into the blood Classification according to the cell line involved (ie. Granulocytic, monocytic, lymphocytic), + degree of malignancy the cell Abnormal stages Cearly of developmentof blastcell + precursor ji Cell ! Normal