1. Blood Physiology Professor A.M.A Abdel Gader MD, PhD, FRCP (Lond., Edin), FRSH (London) Professor of Physiology, College of Medicine & The Blood Bank, King Khalid University Hospital King Saud University Riyadh

2. BLOOD

3. Lecture # 1 & 2 Topic: Red Blood Cells (RBCs) Composition & functions of the Blood Morphological Features of RBCs. Production of RBCs Regulation of production of RBCs Nutritional substances need for RBC production Haemoglobin (Iron metabolism)

4. Sites of blood formation Adults………….. Bone Marrow ( Flat bones) Children …………. Bone Marrow (Flat & long bones) Before Birth: …. Bone Marrow Liver & spleen,lymph nodes Fetus 1 st 4 months …Yalk Sac

5. Production of RBC- cont.

6. Monophyletic theory of cell formation Red blood cells

7. Genesis of RBC

8. Hematopoiesis (17.9)

9. Erythropoiesis, (Formation/genesis of RBC) Growth factors (inducers): Control growth and maturation of stem cells: –Interleukin-3 –Erythropoeitin –Granulocyte stimulating factor (GSF)

10. Production of Erythrocytes: Erythropoiesis Figure 17.5

11. Erythropoiesis, (Formation/genesis of RBC) –Stages of RBC development Pluripotential haemopoietic STEM CELL Committed Stem cell Proerthroblast early, intermediate and late normoblast Reticulocytes Erythrocytes

12. Maturation Sequence

14. Stages of differentiation of RBC

15. Features of the maturation process of RBC 1.Reduction in size 2.Disappearance of the nucleus 3.Acquisition of haemoglobin

16. Lecture # 1 & 2 Topic: Red Blood Cells (RBCs) Composition & functions of the Blood Morphological Features of RBCs. Production of RBCs Regulation of production of RBCs Nutritional substances need for RBC production Haemoglobin (Iron metabolism)

17. Control of Erythropoiesis

18. Erythropoiesis is stimulated by erythropoietin hormone Stimulated by: Hypoxia (low oxygen) –Anaemia –Hemorrhage –High altitude –Lung disease –Heart failure

19. Role of the kidneys in RBC formation

20. Tissue oxygenation and RBC formation

21. Control of erythropoiesis Cont. Erythropoietin glycoprotein 90% from kidneys 10% liver Stimulates the growth of: early RBC-committed stem cells Can be measured in plasma & urine High level of erythropoietin –anemia –High altitude –Heart failure

22. Maturation Times

23. Control of erythropoiesis cont. Other hormones –Androgens, Thyroid, cortisol & growth hormones are essential for red cell formation –Deficiencies of any one of these hormones results in anaemia

24. Control of erythropoiesis

25. Erythropoitein- Mechanism of production of Hypoxia, (blood loss)   Blood O2 levels  Tissue (kidney) hypoxia   Production of erythropoietin   plasma erythropoietin  Stimulation of erythrocytes production   Erythrocyte production

26. Lecture # 1 & 2 Topic: Red Blood Cells (RBCs) Composition & functions of the Blood Morphological Features of RBCs. Production of RBCs Regulation of production of RBCs Nutritional substances need for RBC production Haemoglobin (Iron metabolism)

27. Nutritional requirements for RBC formation 1.Amino acid –HemoGlobin 2.Iron –HemoGlobin –Deficiency  small cells (microcytic anaemia )

28. Nutritional requirements for RBC formation cont. 3. Vitamins Vit B12 and Folic acid –Synthesis of nucleoprotein DNA –Deficiency  macrocytes megaloblastic (large) anemia Vit C –Iron absorption

29. Production of Erythrocytes: Erythropoiesis Figure 17.5

30. Vitamin B12 & Folic acid Important for cell division and maturation Deficiency of Vit. B12 > Red cells are abnormally large (macrocytes) Deficiency leads: –Macrocytic (megaloblastic) anaemia Dietary source: meat, milk, liver, fat, green vegetables

31. Vitamin B12 Absorption of VB12 needs intrinsic factor secreted by parietal cells of stomach VB12 + intrinsic factor is absorbed in the terminal ileum Deficiency arise from –Inadequate intake –Deficient intrinsic factors Pernicious anaemia

32. Nutritional requirements for RBC formation cont. –Essential elements Copper, Cobalt, zinc, manganese, nickel Cobalt  Erythropoietin

33. ANAEMIAS –Definiation Decrease number of RBC Decrease Hb –Symptoms: Tired, Fatigue, short of breath, (pallor, tachycardia)

35. Causes of anaemia 1. Blood Loss –acute  accident –Chronic  ulcer, worm 2. Decrease RBC production –Nutritional causes Iron  microcytic anaemia VB12 & Folic acid  megaloblastic anaemia –Bone marrow destruction by cancer, radiation, drugs  Aplastic anaemia. 3. Haemolytic  excessive destruction –Abnormal Hb (sickle cells) –Incompatible blood transfusion

36. The most common cause for a hypochromic microcytic anemia is iron deficiency. The most common nutritional deficiency is lack of dietary iron. Thus, iron deficiency anemia is common. Persons most at risk are children and women in reproductive years (from menstrual blood loss and from pregnancy).

37. The most common cause for a hypochromic microcytic anemia is iron deficiency. The most common nutritional deficiency is lack of dietary iron. Thus, iron deficiency anemia is common. Persons most at risk are children and women in reproductive years (from menstrual blood loss and from pregnancy)

38. Macrocytic anemia The RBC are almost as large as the lymphocyte. Note the hypersegmented neurotrophil. There are fewer RBCs.

39. The RBC's here are smaller than normal and have an increased zone of central pallor. This is indicative of a hypochromic (less hemoglobin in each RBC) microcytic (smaller size of each RBC) anemia. There is also increased anisocytosis (variation in size) and poikilocytosis (variation in shape).

40. Macrocytic anemia Note the hypersegmented neurotrophil and also that the RBC are almost as large as the lymphocyte. Finally, note that there are fewer RBCs.

41. Polycythemia –Increased number of RBC –Types: True or absolute –Primary (polycythemia rubra vera): uncontrolled RBC production –Secondary to hypoxia: high altitude, chronic respiratory or cardiac disease Relative –Haemoconcentration: »loss of body fluid in vomiting, diarrhea, sweating