1. Blood Physiology
Red Blood Cells

2. BLOOD

3. Topic: Red Blood Cells (RBCs)
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 1st 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. Maturation Sequence

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

13. Erythropoiesis Starts in red bone marrow with proerythroblast
Cell near the end of development ejects nucleus and becomes a reticulocyte
Develop into mature RBC within 1-2 days
Negative feedback balances production with destruction
Controlled condition is amount of oxygen delivery to tissues
Hypoxia stimulates release of erythropoietin

15. Stages of differentiation of RBC

16. Features of the maturation process of RBC
Reduction in size
Disappearance of the nucleus
Acquisition of haemoglobin

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

18. Erythropoietin(EPO) A glycoprotein
- a hematopoietic growth factor of red blood
cells (erythrocytes) in mammals
A cytokine for erythrocyte precursors (hematopoietin or hemopoietin)
- produced in the kidney and liver

19. Erythropoietin
Erythropoietin use should be targeted to patients aged under 70 years who are scheduled for major blood losing surgery and who have a presenting haemoglobin <130 g/l.
Erythropoietin can be used to prepare patients with objections to allogeneic transfusion for surgery that involves major blood loss.

20. Functional EPO
Haematocrit 紅血球容積
Erythrocyte precursor cells reside in the bone marrow, and are part of erythropoesis, the formation of circulating erythrocytes (i.e., red blood cells).
The erythroid progenitor cells develop in two phases: erythroid burst-forming units ( BFU-E) followed by erythroid colony-forming units ( CFU-E); BFU-E differentiate into CFU-E on stimulation by erythropoietin, and then further differentiate into erythroblasts when stimulated by other factors.
Also :
playing a significant role in the brain's response to neuronal injury
involvement in the process of wound healing

21. The effect of erythropoietin
The effect of erythropoietin in minimising allogeneic blood exposure compared to placebo has been studied in patients undergoing orthopaedic , cardiac or colon cancer surgery.
With the exception of one study, all showed a significant reduction in allogeneic transfusion

22. Hemoglobin Globin – 4 polypeptide chains Heme in each of 4 chains
Iron ion can combine reversibly with one oxygen molecule
Also transports 23% of total carbon dioxide
Combines with amino acids of globin
Nitric oxide (NO) binds to hemoglobin
Releases NO causing vasodilation to improve blood flow and oxygen delivery

23. Shapes of RBC and Hemoglobin
Copyright 2009, John Wiley & Sons, Inc.

24. Tissue oxygenation and RBC formation

25. 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

26. Maturation Times

27. 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

28. Control of erythropoiesis

29. 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

30. Topic: Red Blood Cells (RBCs)
Morphological Features of RBCs.
Production of RBCs
Regulation of production of RBCs
Nutritional substances need for RBC production
Haemoglobin
(Iron metabolism)

31. Nutritional deficiency anaemia clinical application
Angular
Cheilosis
Glossitis
Koilonychia
Marrow iron stores
Plummer-Vinson
syndrome

32. Nutritional requirements for RBC formation
Amino acid
HemoGlobin
Iron
Deficiency  small cells
(microcytic anaemia )

33. 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

34. Production of Erythrocytes: Erythropoiesis
Figure 17.5

35. Hemoglobin Globin – 4 polypeptide chains Heme in each of 4 chains
Iron ion can combine reversibly with one oxygen molecule
Also transports 23% of total carbon dioxide
Combines with amino acids of globin
Nitric oxide (NO) binds to hemoglobin
Releases NO causing vasodilation to improve blood flow and oxygen delivery .

36. Vitamin B12 & Folic acid Macrocytic (megaloblastic) anaemia
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

37. Vitamin B12 Pernicious anaemia
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

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

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

40. 40

41. Causes of anaemia 1. Blood Loss 2. Decrease RBC production
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

42. 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).

43. 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)

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

45. 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).

46. 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.

47. Polycythemia Increased number of RBC Relative 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