1. 1 RED BLOOD CELL FORMATION Dr. B.L. Mtinangi. Department of Physiology HKMU November, 2015

2. RED BLOOD CELL FORMATION Rbc’s are circular, biconcave, disk-like, dumbbell shaped, non nucleated living cell. Mean Cell Volume (MCV) is the average volume of each red cell (82-92cub micron) Mean Cell Volume (MCV) is the average volume of each red cell (82-92cub micron) Mean Cell Haemoglobin (MCH) is the average Hb in each cell (27-32 picogram) Mean Cell Haemoglobin (MCH) is the average Hb in each cell (27-32 picogram) Mean Cell Haemoglobin Concentration (MCHC) this indicates the degree of saturation of Rbc with Hb (32 to 38%) Mean Cell Haemoglobin Concentration (MCHC) this indicates the degree of saturation of Rbc with Hb (32 to 38%)

3. 3 RBC’s CONT. During Anaemia MCHC is less, it is known as hypochromic anaemia and During Anaemia MCHC is less, it is known as hypochromic anaemia and If MCHC is normal it is normochromic anaemia If MCHC is normal it is normochromic anaemia Biconcave shape gives certain advantages: Maximum surface area for gas diffusion Maximum surface area for gas diffusion Diffusion distance is minimised Diffusion distance is minimised Rbc can mould their shape while passing through narrow capillaries Rbc can mould their shape while passing through narrow capillaries

4. 4 RBC’s FORMATION There is some daily loss of Rbc’s ie the average life span of Rbc’s is about 120 days There is some daily loss of Rbc’s ie the average life span of Rbc’s is about 120 days To keep the Rbc’s count normal or to balance this loss To keep the Rbc’s count normal or to balance this loss Sufficient number of Rbc’s must be produced daily Sufficient number of Rbc’s must be produced daily

5. 5 FORMATION OF Rbc Formation/generation (ERYTHROPOIESIS) starts in the third week of INTRAUTERINE life. Third week to third month erythropoiesis occurs in the mesoderm of the york sac Third week to third month erythropoiesis occurs in the mesoderm of the york sac Third month to fifth month it occurs in the liver and spleen (HEPATIC PHASE) Third month to fifth month it occurs in the liver and spleen (HEPATIC PHASE) Fifth month onwards it occurs in the red bone marrow Fifth month onwards it occurs in the red bone marrow

6. HAEMATOPOIESIS 6

7. 7 FORMATION OF Rbc CONT. Post natal (after birth) red blood cell formation (erythropoiesis) occur in the RED BONE MARROW Main sites for erythropoiesis: Ribs, vertebra, sternum, cranium Ribs, vertebra, sternum, cranium Pelvis. Shaft of the femur and tibia Pelvis. Shaft of the femur and tibia

8. 8 BLOOD FORMING TISSUES Myeloid tissues produces Rbc,Wbc and Platelets. Myeloid tissues produces Rbc,Wbc and Platelets. Lymphoid tissues include the lymph node, thymus and spleen. All produce Lymphocytes Lymphoid tissues include the lymph node, thymus and spleen. All produce Lymphocytes

9. RBC maturation

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11. 11 Rbc DEVELOPMENTAL STAGES Pluripotent stem cell ( Uncommitted stem cell) develop into Pluripotent stem cell ( Uncommitted stem cell) develop into Committed stem cell into Pronormoblast or Myeloblast or Megaloblst or Lymphoblast Committed stem cell into Pronormoblast or Myeloblast or Megaloblst or Lymphoblast Pronormoblast (Proerythroblast) develop into Early normoblast then to Intermidiate normoblast then to Late normoblast then into immature Rbc (Reticulocyte) then within 2 to 3 days develop into mature Rbc

12. 12 FORMATION OF Rbc CONT. One committed stem cell produces 16 mature Rbc1 One committed stem cell produces 16 mature Rbc1 10% to 15% of Rbc undergo premature destruction during development 10% to 15% of Rbc undergo premature destruction during development

13. 13 NORMAL VALUES Total normal Rbc count: Total normal Rbc count: men 4.5 to 6.4 mill/cumm men 4.5 to 6.4 mill/cumm women 3.9 to 5.6 mill/cumm women 3.9 to 5.6 mill/cumm Normal Haemoglobin (Hb) concentration: Normal Haemoglobin (Hb) concentration: men 13 to 17g/dl men 13 to 17g/dl women 11 to 16g/dl women 11 to 16g/dl

14. 14 FACTORS INFLUENCING ERYTHROPOIESIS 1. Erythropoietin. Is a hormone produced in JuxtaGlomerular Apparatus(JGA) in the macula densa (kidney) Is a hormone produced in JuxtaGlomerular Apparatus(JGA) in the macula densa (kidney) Is a glycoprotein with MW 36000 Is a glycoprotein with MW 36000 Stimulate proliferation and differentiation of erythroblast Stimulate proliferation and differentiation of erythroblast Stimulate Hb synthesis Stimulate Hb synthesis Promote Rbc maturation Promote Rbc maturation

15. 15 2. VITAMINS VITAMIN B12 Is essential for erythropoiesis ie it stimulates erythropoiesis Is essential for erythropoiesis ie it stimulates erythropoiesis Present only in meat, fish and diary products Present only in meat, fish and diary products Absent in vegetables Absent in vegetables In the GIT it combines with the intrinsic factor which protect & transport it to the terminal ileum In the GIT it combines with the intrinsic factor which protect & transport it to the terminal ileum Absorbed in the terminal ILEUM Absorbed in the terminal ILEUM Required for DNA and RNA SYNTHESIS Required for DNA and RNA SYNTHESIS

16. 16 3. FOLIC ACID Folic acid is another vitamin that is essential Stimulates erythropoiesis Stimulates erythropoiesis Required for DNA and RNA synthesis Required for DNA and RNA synthesis Present in vegetables and fruits Present in vegetables and fruits

17. 17 4.IRON IRON: Found in the meat and vegetable Found in the meat and vegetable Required for Haemoglobin synthesis Required for Haemoglobin synthesis Daily intake is about 10 to 20 mg Daily intake is about 10 to 20 mg 5% to 10% of iron daily intake is absorbed ie (0.5 to 2mg/day) 5% to 10% of iron daily intake is absorbed ie (0.5 to 2mg/day) 2/3 of Iron is found in the Rbc 2/3 of Iron is found in the Rbc It circulate in the blood as Transferrin It circulate in the blood as Transferrin Stored in the bone as Ferritin and Haemosiderin Stored in the bone as Ferritin and Haemosiderin

18. Red Blood Cell Turnover

19. A summary of: Bilirubin formation, circulation and elimination

20. Senescent (old) Red blood cell destruction Hb is degraded to Haem & Globin Globin is reutilised as Amino Acid Haem an Iron component is degraded to a porphyrin ring Porphyrin ring is converted to choleglobin

21. CONT Choleglobin in the presence of an enzyme haem oxygenase is converted to BILIVERDIN Biliverdin in the presence of an enzyme biliverdin reductase is converted to BILIRUBIN Bilirubin is released into plasma

22. CONT In the plasma Bilirubin is bound to ALBUMIN and transported to the liver In the liver bilirubin is conjugated with GLUCURONIC ACID to conjugated bilirubin (bilirubin glucuronide)

23. CONT. Conjugated bilirubin is transported to the intestine through the bile duct In the intestine bilirubin is further conjugated by the bacteria to STERCOBILINOGEN Stercobilinogen is oxidized to stercobilin after exposure to air in the feces

24. CONT The reminder 5% is absorbed (enterohepatic circulation) and transported to the kidney as UROBILINOGEN Urobilinogen is oxidized to UROBILIN after exposure to air in the urine

25. ANAEMIA Anaemia is defined as the reduction of:  Haemoglobin  Total red cell count  Haematocrit (Packed cell volume – PCV) According to age and sex 25

26. CAUSES OF ANAEMIA Causes could be due to:  Nutritional deficiences, eg iron, folic acid, vitamin B12 ect ects  Excessive destruction of Rbc eg due to malaria, sickle cell disease etc etc  External/ internal bleeding  Infestations eg hookworm  Bone marrow failure 26

27. Thank you