2. Regulation of Erythropoiesis Dr Ghulam Mustafa

3. Regulation of Erythropoiesis Importance Factors affecting Erythropoiesis  Tissue Oxygenation Anemia, High Altitudes, Cardiac failure, Resp Problem ERYTHROPOITEN  Vitamins  Metals  Proteins  Hormones  Other factors/Conditions

4. Normal RBC Count Importance: Must Not fall To supply oxygen from lungs to tissues Must Not rise Blood viscosity may increase May impede blood flow

5. Factors affecting Erythropoiesis 1. Tissue Oxygenation 2. Vitamins 3. Metals 4. Proteins 5. Hormones

6. 1. Tissue Oxygenation – Most Important Regulator of Erythropoiesis ANY CONDITION Decrease Tissue Oxygenation Increase Erythropoiesis Anemia Immediately Increase RBCs production Bone marrow destruction: Hyperplasia of remaining cells Increase production of RBCs

7. High altitudes:  Partial pressure of oxygen in air less  Decrease in oxygen transport to tissues  Tissue hypoxia  Result? Cardiac Failure  Inefficient pumping by heart  Decreased blood flow to peripheral vessels  Tissue hypoxia  Result?

8. Lung diseases:  Failure of oxygen absorption in Lungs  Blood carries less Oxygen  Tissue hypoxia  Result? All conditions have one common problem HYPOXIA ERYTHROPOIETIN

9. Erythropoietin Glycoprotein Mol weight 34000 Sites of production  Kidneys  Liver  Brain, Uterus If Erythropoiten production reduced  Effect of Hypoxia?

10. Stimulants of Erythropoiten production: RENAL MECHANISM  Anemic blood to kidney  Less oxygen supplied  Renal tubular cells - High O 2 consuming  Stimulates production of Erythropoiten NON RENAL MECHANISM  Hypoxia in other parts – Non renal sensor  Nor epinephrine, epinephrine, prostaglandins In Renal failure?

11. Formation of Erythropoiten Erythrogenin – Renal Erythropoitic factor Erythropoitinogen  Alpha globulin  Substrate for Erythropoiten Stimulants of Erythrogenin  Hypoxia  cAMP  NAD  Hemosylates

13. Role of EP in Erythropoiesis Formed in response to Hypoxia within minutes RBC production in 5 days Erythropoiten  Stimulates Proerythroblasts formation  Causes cells to pass through various stages of Erythropoiesis rapidly

14. Recombinant Erythropoiten Anemia – Renal Failure Blood doping  Erythropoiten - Athletes  Running – Increase Oxygen demand  Breathlessness  ERYTHROPOITEN – Increase RBC’s  Less dyspnea DNA Recombinant Technique

16. 2.Vitamins Vit B 12 & Folic acid Essential for formation of thymidine triphosphate Essential building block of DNA Diminished DNA Failure of nuclear maturation Inadequate Erythropoiesis

17. Vitamin C  Potentiate the effect of Folic acid  Also helpful in Iron Absorption Reducing Ferric to ferrous form Pyridoxine:  Coenzyme for condensation of Glycine and succinyl-CoA Riboflavin and Pantothenic acid  Heme formation  Cell growth and division

18. 2.Minerals Iron Copper  Ceruloplasmin  Necessary for Iron transfer from storage sites Bone marrow, Liver and Spleen Cobalt  Forms a part of Vitamin B 12 Nickel and Manganese

19. 3.Proteins Adequate protein diet essential Formation of Globin Protein deficiency  Kwashiorkor  Prisoners  Protein losing Enteropathies  Renal disease- Proteinuria

20. 4.Hormones Testosterone Growth hormone Thyroid hormone Cortisol Adrenocorticotrophic hormone ACTH

21. 5.Other Conditions Stimulating Erythropoiesis Exercise Excitement Menstruation Pregnancy Menopause More RBC Count in fetal life  HbF – Binds more oxygen

23. Regulation of Erythropoiesis Importance Factors affecting Erythropoiesis 1Tissue Oxygenation Anemia, High Altitudes, Cardiac failure, Resp Problem ERYTHROPOITEN Site of production Stimulants for production Mechanism of production Role in Erythropoiesis

24. 2Vitamins  Vit B 12 and Folic acid  Pyridoxine  Vitamin C  Riboflavin and Pantothenic acid 3Metals  Iron, Cu, Co, Ni, Mn 4Proteins 5Hormones  GH, TH, CORTISOL, TESTOSTERONE, ACTH 5Other conditions affecting…..

25. If you complain about your transport system, What about them?