Erythropoiesis (Production of red blood cells)

2. Erythropoiesis (Production of red blood cells)

3. Erythropoiesis • Yolk sac in embryonic life • Spleen & liver and lymph nodes in middle trimester of pregnancy, early fetal life • Red Bone marrowof all the bones in late fetal life and early childhood until age of 5 years. • The marrow of the long bones, except for the proximal portions of humeri and tibiae, becomes fatty, produce no more RBCs after 20 yrs.

4. Beyond this age , red cells are produced in membranous bones such as sternum, vertebrae, ribs and ilia.

5. Erythrogenesis in bone marrow

6. Erythropoiesis • Erythrocytes are derived fromcommitted erythroid proginator → series of mitotic divisions and maturation phases. • Erythropoietin, (kidneys) → stimulates erythropoiesis → proliferation of thecommitted stem cells and differentiation of erythrocytes

7. Blood cells are derived from pleuripotential hematopoietic stem cell. • A small portion remain exactly like the original pleuripotential cells. • When these cells become committed to form a particular line of cells ,these are called committed stem cells. • A committed stem cell that produces erythrocytes is called a CFU-E.

8. PHSC & blood cells

9. Stages of Erythropoiesis • Pluripotential hemopoietic stem cell • Committed stem cell (CFU-E) • Proerythroblast • Basophilic erythroblast • Poly chromatophilic erythroblast • Orthochromatic erythroblast • Reticulocyte • Erythrocyte

10. Erythropoiesis

11. Erythropoiesis • Tissue  hypoxia (lack of oxygen) is the main stimulus for erythropoietin production. • Nucleated red cell precursors in the bone marrow are collectively called erythroblasts. • RBCs that have matured to the non-nucleated stage gain entry to the peripheral blood. • Once the cells have lost their nuclei they are called erythrocytes.

12. Erythropoiesis • Young  erythrocytes that  contain  residual  RNA  are  called reticulocytes. • Bone marrow erythroblast proliferation and maturation occurs in  anorderly and well defined sequence. • gradual decrease in  cell  size, • condensation and eventual expulsion of the nucleus • an increase in hemoglobin production.  

13. Erythropoiesis • Reticulocytes enter into the peripheral blood → maturation into erythrocytes within 24 hours. • 1% reticulocytes in the peripheral smear • More in new born babies. • Visualized by staining with methylene blue • Remnants of the ribosomes on the endoplasmic reticulum may be visualized

14. Erythropoiesis

15. Erythrocyte kinetics • The normal erythrocyte concentration varies with age, sex, and geographic location. • ↑ RBC count at birth which • Decreases until the age of 2-3 months -physiologic anemia due to low erythropoietin production. • ↑RBC count to adult levels at about 14 years of age. • Males have higher RBC counts because testosterone stimulates erythropoietin production. • High altitude →↓ partial pressure of O2 →↑ erythropoietin → ↑ RBC

16. Hypoxia and erythrogenesis

17. Requirements for normal erythropoiesis • Vitamin B12 is required (Synthesis of DNA, maturation) • Folic Acid is required (Synthesis of DNA, maturation) • Both are required for Thymidine triphosphate • Iron • Proper porphyrin synthesis • Proper globin chain synthesis • Cobalt • Copper • Zinc

18. Vit B12 and FA are req for the formation of thymidine triphosphate ,one of the essential building blocks of DNA. • Failure of nuclear maturation and cell division . • Proerythrocytes fail to proliferate rapidly and produce larger than normal RBCs called macrocytes, shape is oval, large, irregular and fragile. • Hb content is normal ,life span short.

19. MATURATION FAILURE DUE TO POOR ABSORPTION OF B12 • pernicious anemia, atrophic gastritis. • Parietal cells of gastric glands produce IF • IF+ B12 • IF binds to specific receptor sites on the brush border membrane of the mucosal cells in the ileum. • Lack of IF causes faulty absorption of B 12. • Sprue, vit B 12 and folic acid not absorbed.

20. Factors influencing erythropoiesis • Growth inducers (interleukin-3),growth and reprod of all types of comitted stem cells. • Differentiation inducers cause one type of comitted stem cell to differentiate. • Erythropoietin • Hypoxia →↑ Renal erythropoietic factor →↑ Erythropoietin →↑ Growth inducers & differentiation inducers →↑erythrogenesis. • Low Oxygen for a long time results in growth induction, differentiation and production of large no. of erythrocytes eg. cardiac failure, high altitude. • Testosterone, Cortisol.

21. Erythropoiesis • Normally 1-15% of the RBCs die during  maturation. • Erythroblasts normally spend 4-7 days proliferating and maturing in the bone marrow. • The stages of maturation from the most immature to the most mature are:

22. Proerythroblast

23. Basophilic Erythroblast

24. Polychromatophilic Erythroblast

25. Orthochromic Erythroblast

26. Reticulocyte

27. Mature erythrocyte

28. Erythropoiesis

29. Erythropoiesis • Normal lifespan 100-120 days • Old RBCs are removed by the spleen.

30. The RBC membrane • Semi-permeable lipid bilayer • Supported by a protein cytoskeleton (contains both integral and peripheral proteins). • Extensive damage cannot be repaired • The mature cells lack enzymes and cellular organelles necessary to synthesize new lipid or protein.

31. Cellular Energetics • RBCs generate energy almost exclusively from the anaerobic breakdown of glucose .

32. Polycythemia • An increase in RBC mass is called polycythemia and it may lead to an increase in blood viscosity. • Polycythemia • Relative polycythemia due to decreased plasma volume e.g. in dehydration. • Absolute polycythemia due to actual increase in RBC mass. • This may occur in disorders that prevent adequate tissue oxygenation

33. Polycythemia • Secondary polycythemia • Individuals living at high altitudes have increased RBC levels because of the decreased partial pressure of O2 at high altitudes which leads to decreased O2 saturation. • Polycythemia vera • Uncontrolled proliferation/production/cancer of RBC

34. Choose the best response, During the middle trimester of gestation, which is the main organ for production of RBCs a)Bone marrow b)Liver c)Lymph nodes

35. Each gram of pure hemoglobin combines with a)15 ml of oxygen 2)1.34 ml of oxygen 3)20 ml of oxygen 4)2.24 ml of oxygen

36. Among Plasma proteins 80% of osmotic pressure is exerted by • Albumin • Globulin • fibrinogen

37. After 20 years of age, red cells are produced in the • Marrow of long bones • Liver • Vertebrae, sternum and ribs

38. Thank-you Questions ??