erythropioesis
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erythropioesis
- 3. Scheme 1. Definition 2. Theories of erythropoiesis 3. Sites of erythropoiesis 4. Stages of erythropoiesis 5. Reticulocyte 6. Mature Red Cell 7. Factors affecting Erythropoiesis 8. Erythropoietin.Vitamin B12.Iron
- 4. Hemopoiesis Hemo: Referring to blood cells Poiesis: “The development or production of” The word Hemopoiesis refers to the production & development of all the blood cells: Erythrocytes: Erythropoiesis Leucocytes: Leucopoiesis Thrombocytes: Thrombopoiesis.
- 5. It is the process of development, differentiation and maturation of RBCs from primitive stem cells DEFINITION
- 6. Site of Erythropoiesis During intrauterine life Mesoblastic stage (3rd week to 3 months) Hepatic stage (after 3 months) Myeloid stage (3rd trimester) Intravascular erythropoiesis Extravascular erythropoiesis Nucleated RBCs Yolk sac Liver & spleen Bone marrow
- 7. In children - All bones with red bone marrow - Liver & spleen In adults (after 20yrs) - Ends of long bones like femur, humerus - Skull - Vertbrae - Ribs - Sternum - pelvis
- 9. PHSC Pluripotent Hemopoietic stem cell BFU-E (Burst Forming Unit Erythrocyte) CFU-E (Colony Forming Unit Erythrocyte) PROERYTHROBLAST BASOPHILIC ERYTHROBLAST POLYCHROMATOPHILIC ERYTHROBLAST ORTHOCHROMATIC ERYTHROBLAST RETICULOCYTE ERYTHROCYTEERYTHROCYTE E R Y T H R O P O I E S I S GM CSF erythroIL-1,IL-6,IL-3 GM CSF erythro
- 10. PHSC Pluripotent Hemopoietic stem cell BFU-E (Burst Forming Unit Erythrocyte) CFU-E (Colony Forming Unit Erythrocyte) PROERYTHROBLAST EARLY NORMOBLAST INTERMEDIATE NORMOBLAST LATE NORMOBLAST RETICULOCYTE ERYTHROCYTEERYTHROCYTE E R Y T H R O P O I E S I S GM CSF erythroIL-1,IL-6,IL-3 GM CSF erythro
- 11. 1. STEM CELLS1. STEM CELLS These cells have extensive proliferative capacity and also the: Ability to give rise to new stem cells (Self Renewal) Ability to differentiate into any blood cells lines (Pluripotency) Hematopoietic stem cells (HSCs) are bone marrow cells that are capable of producing all types of blood cells. They differentiate into one or another type of committed stem cells (progenitor cells).
- 12. 2. Progenitor cells BFU-E & CFU-E BFU-E Give rise each to thousands of nucleated erythroid precursor cells. Undergo some changes to become the Colony Forming Units-Erythrocyte (CFU-E) Regulator: Burst Promoting Activity (BPA) Committed stem cells lose their capacity for self- renewal. They become irreversibly committed.
- 13. Burst forming unit BFU(E) Unipotent progenitor cell Less sensitive to erythropoietin Responds to other stimulus forms Colony forming unit CFU (e) Highly sensitive and dependent on erythropoietin
- 14. ERYTHROPOIESIS 15-20µm- basophilic cytoplasm, nucleus with nucleoli. 14-17µm-mitosis, basophilic cytoplasm, nucleoli disappears. 10-15µm- ’POLYCHROMASIA’ Hb appears, nucleus condenses. 7-10µm- PYKNOTIC Nucleus. Extrusion, Hb is maximum. 7.3µm- Reticulum of basophilic material in the cytoplasm. 7.2µm- Mature red cell with Hb.
- 16. 3. Proerythroblast •15-20 microns •Nucleus with multiple nucleoli •Basophilic cytoplasm with perinuclear halo •No hemoglobin •Mitosis present
- 17. 4. Basophilic/ early normoblast Slight reduction in size 14-17µm Large nucleus, nucleoli reduce in number Basophilic cytoplasm Active mitosis
- 18. 5. Polychromatophilic/ intermediate normoblast 10-15µm size ’POLYCHROMASIA’ nucleus condenses Chromatin lumps Hb starts appearing Reduced mitoses
- 19. 6. Orthochromatic normoblast • 7-10µm •Acidophilic erythroblast which is the last precursor with a nucleus. • Nucleus is compact & situated near the membrane pyknotic nucleus is extruded • Cytoplasm is like mature red cell, reflecting a high Hb content. •Mitosis absent
- 20. 7. Reticulocyte Reticular nuclear fragments Nucleus extruded Slightly larger than RBCs
- 21. Reticulocyte Young erythrocytes with granular or reticular filamentous structures. Makes up 0.5-2% of all erythrocytes Vital staining required to make this visible. Reticulocytosis seen following hemolysis or acute blood loss
- 22. The Reticulocyte Has no nucleus Has no organelles Is larger than the mature RBC Is not concave Has many polyribosomes In severe anemia, many of these are released into the blood prematurely Reticulocyte response. Normally 1% of circulating blood, are reticulocytes.
- 23. 8. Mature erythrocyte • Reddish, circular, biconcave cells • 7-8 µ • No visible internal structure • High Hb content • Bright at centre due to biconcave shape 7.2 µm
- 25. Duration of erythropoiesis HSC to RBC- 21 days Differentiation phase: from pronormoblast to reticulocyte phase- 5 days Maturation phase: from reticulocyte to RBC- 2 days
- 26. Changes during erythropoiesis Decrease in size Loss of mitotic activity (later part of intermediate.normo) Hemoglobinization (intermediate normoblast) Change of cell shape (from globular to biconcave) Disappearance of nucleus, mitochondria, RNA, etc Change of staining (basophilic – eosinophilic)
- 27. Reticulocyte response Increase in reticulocyte count after treatment of anemia indicates bone marrow activity
- 28. 1. Definition 2. Theories of erythropoiesis 3. Sites of erythropoiesis 4. Stages of erythropoiesis 5. Reticulocyte 6. Mature Red Cell
- 30. Regulation of erythropoiesis General factors - Hypoxia erythropoietin - Growth inducers - Vitamins Maturation factors - Vitamin B 12 - Folic acid Factors necessary for hemoglobin production - Vitamin C Helps in iron absorption (Fe+++ Fe++) - Proteins Amino Acids for globin synthesis - Iron & copper Heme synthesis - calcium, bile salts, cobalt & nickel.
- 31. General factors Hypoxia erythropoietin
- 32. ERYTHROPOIETIN Glycoprotein MW-34000 (165 AA residues) Formation 85% formed in endothelial cells of the peritubular capillaries of the renal tubules. 15% formed in liver, hepatic cells & Kupffer cells. Breakdown In liver. Half life is 5hours
- 34. Regulation of erythropoietin secretion O2 sensor (heme protein) in kidney & liver Deoxy & oxy form of O2 sensor HYPOXIA INDUCIBLE FACTOR-1 (HIF-1) Erythropoietin gene Erythropoietin mRNA Erythropoietin
- 35. ERYTHROPOEITIN Stimuli for production Hypoxia Products of RBC destruction High altitude Anemia Chronic lung or heart diseases Catecholamines Prostaglandins Androgens Inhibition Blood transfusion
- 36. Functions of Erythropoietin Erythropoietin increases RBC production in 3 ways: Promotes pronormoblast production Shortens the transition time through the normoblast stage Promotes the early release of reticulocytes.
- 37. Renal failure
- 38. Growth inducers/ Differentiation inducers Interleukin 1, 3, 6 (IL-3 is a growth inducer for all cell lines ) CSF- E (colony stimulating factor – erythro)
- 39. Maturation factors Vitamin B 12 Folic acid Dietary factors - IRON
- 40. Vit B-12 Source : only animal tissues Absorption from ileum Functions • Promotes maturation of RBCs (plays an important role in folic acid synthesis of nucleic acid-DNA)
- 41. Sources of vitamin B12Sources of vitamin B12 41
- 43. Absorption of Vitamin B12 and the role of Intrinsic factorAbsorption of Vitamin B12 and the role of Intrinsic factor 43Namrata Chhabra
- 44. Folic acid Green leafy vegetables , yeast, liver Function : maturation of RBC
- 45. LIFE SPAN OF MEGALOBLAST IS 40 DAYS
- 46. 46
- 48. Iron
- 50. Other Factors Regulating erythropoiesis NUTRITIONALNUTRITIONAL FACTORFACTOR ProteinsProteins VITAMINSVITAMINS B12 & folic acid – forB12 & folic acid – for synthesis of DNAsynthesis of DNA Riboflavin – Normal BMRiboflavin – Normal BM divisiondivision Pyridoxine – HemePyridoxine – Heme synthesissynthesis Vitamin C – absorption ofVitamin C – absorption of Fe from gutFe from gut MINERALSMINERALS Iron – for HbIron – for Hb Cu, Zn, Co– HbCu, Zn, Co– Hb synthesissynthesis HORMONESHORMONES TestosteroneTestosterone Thyroxine, AdrenalThyroxine, Adrenal hormoneshormones Pituitary hormones –Pituitary hormones – stimulatestimulate ErythropoietinErythropoietin NEURAL Stimulation of Hypothalamus ↑ RBC production
Editor's Notes
- The axial skeleton Normally, 75% of the cells in the marrow belong to the white blood cell-producing myeloid series and only 25% are maturing red cells, even though there are over 500 times as many red cells in the circulation as there are white cells. This difference in the marrow reflects the fact that the average life span of white cells is short, whereas that of red cells is long.
- Hematopoietic stem cells (HSCs) are bone marrow cells that are capable of producing all types of blood cells. They differentiate into one or another type of committed stem cells (progenitor cells). These in turn form the various differentiated types of blood cells. There are separate pools of progenitor cells for megakaryocytes, lymphocytes, erythrocytes, eosinophils, and basophils; neutrophils and monocytes arise from a common precursor.
- Committed stem cells lose their capacity for self-renewal. They become irreversibly committed. These cells are termed as “Progenitor cells” They are regulated by certain hormones or substances so that they can: Proliferate Undergo Maturation.
- Smaller than Proerythroblast Nuclear chromatin shows sharp contrast between light & dark areas Cytoplasm is basophilic reflecting protein & RNA contents
- Polychromasia means having many colors Nucleus mature & condensed Cytoplasm has a gray hue derived from Hb (Hemoglobin)
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