Erythropoiesis

FORMATION OF RBC'S

1. ERYTHROPOIESIS

2. E R Y T HR O P O I E S IS

3. CONTENTS Definition Sites of erythropoiesis Stages of erythropoiesis Factors affecting Erythropoiesis Erythropoietin HYPOXIA FOLIC ACID Vitamin B 12 CLINICAL ASPECTS SUMMARY

4. It is the process of development , differentiation and maturation of RBCs from primitive stem cells D E FI N I T I O N

5. SITES OF HAEMOPOIESIS. First 2 months of gestation – yolk sac. 3 rd month onwards – liver 7 spleen. 20 th week onwards – till birth - bone marrow. Monday, December 7, 2015

6. SITES OF HAEMOPOIESIS.  s    In Young Children – axial skeleton & bones of extremitie i.e. Red Bone marrow. With fatty replacement it becomes Yellow Bone Marrow. In Adults – axial skeleton & proximal extremities of long bones. In Pathological conditions – extra medullary haemopoiesis i.e liver & spleen resumes .

7. HAEMOPOIESIS

8. 1. 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).

9. 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.

10. 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

11. 3. Proerythroblast 15-20 microns Nucleus with multiple nucleoli Basophilic cytoplasm with perinuclear halo No hemoglobin Mitosis present

12. 4. Basophilic/ early normoblast Slight reduction in size 14-17µm Large nucleus, nucleoli reduce in number Basophilic cytoplasm Active mitosis

13. 5. Polychromatophilic/ intermediate normoblast  10-15µm size ’ POLYCHROMASIA ’ nucleus condenses Chromatin lumps Hb starts appearing Reduced mitoses

14. 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

15. 7. Reticulocyte Reticular nuclear fragments Nucleus extruded Slightly larger than RBCs

16. 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

17. CELLS/FEATURES SIZE CYTOPLASM NUCLEUS H A EMOGL O B IN MITOSIS P R O N O R M O B L A S T 15-20 μm BASOPHILIC LARGE WITH RETICULAR FORMATION ABSENT SEEN LARGE,NUCL EARLY 12- BASOPHILIC EOLI ABSENT SEEN 16μm DISAPPEARE D. INTERMEDIATE 10- 14μm PO L YC H R O M ATIC CONDENSED APPEARS PRESENT LATE 8-10μm A C I D O P HILI C SMALL P Y K N OTIC INCREASES ABSENT RETICULOCYTE 7- 7.5μm R ETI C ULU M LIKE ABSENT INCREASES ABSENT

18. 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)

19. 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 calcium, bile salts, cobalt & nickel.

20. 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

21. ERYTHROPOEITIN r heart Stimuli for production Hypoxia Products of RBC destruction High altitude Anemia Chronic lung o diseases Catecholamines Prostaglandins Androgens

22. EFFECT OF HYPOXIA

23. VIT B 12 Vit B12 – Cyanocobalamin or extrinsic factor. Daily need – 1-2 μg. Sources – Milk, Meat, Liver of Animals  Also synthesized by bacterial Flora.

24. LIFE SPAN OF MEGALOBLAST IS 40 DAYS

25. FOLIC ACID Folic acid – Pteroylglutamic acid. Daily requirement – 100 μg. Sources – leafy veg, pulses, yeasts, liver. From breakdown of Polyglutamate to Monoglutamates.

26. Clinica l Aspects Anemias: Reduced RBC count / reduced Hb concentration Polycythemia: Increased RBC count Polycythemia vera Secondary polycythemia- due to hypoxia

27. SUMMARY MATURE RBC

28. BIBLIOGRAPHY Guyton and Hall Textbook of Medical Physiology E-Book (Guyton Physiology) Essentials of Medical Physiology by k.sembulingum Google TEXTBOOK OF PHYSIOLOGY BY AK JAIN 5. Ganongs Review Of Medical Physiology 25th Edition

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