1. BLOOD AND BODY DEFENCE Dr. Amel Eassawi Dr. Abdelrahman Mustafa 1

2. HMIM 224 L 2: ERYTHROCYTES 1 2

3. OBJECTIVES The student should be able to:  Know the normal range of RBCs.  Recognize different functions of hemoglobin.  Know the sites of erythropoiesis in different stages during human life.  Discuss the stages of erythropoiesis.  Discuss the requirements for erythropoiesis.  Explain the clinical conditions related to erythropoiesis. 3

4. ERYTHROCYTES Normal RBC count - 5 million per cubic millimeter (mm 3 ) of blood. Male 5 – 5.5 / mm 3 Female 4.5 – 5 / mm 3 RBC contain hemoglobin which carries O 2. 4

5. ERYTHROCYTES 5

6. RBC are biconcave discs 7.5 - 8 micrometer (µm) in diameter and 2µm thick at outer edge and 1µm thick at the center. RBC membrane is flexible and can change as RBC pass through capillary with a narrow diameter of 5µm. 6

7. ERYTHROCYTES RBCs is mainly a plasma membrane having hemoglobin. RBCs has no nucleus and organelle. Enzymes in RBC: - Glycolytic enzyme, it generates energy ATP for active transport at membrane. - Carbonic anhydrase enzyme important in CO 2 transport. 7

8. ERYTHROCYTES In every person, 25 trillion – 30 trillion RBCs are moving through our blood vessels. Average life of RBC is 120 days. RBC are replaced at average rate of 2 millions to 3 millions/sec. 8

9. HEMOGLOBIN Hemoglobin is found only in RBC. Normal Hemoglobin – 15 gram / dl. Structure of Hemoglobin It has two parts 1. Globin: protein has 4 polypeptide chain 2 α chain [141 amino acid in each chain] 2 β chain [146 amino acid in each chain] 2. Heme: 4 iron containing groups, each is bound to one polypeptide chain. 9

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11. HEMOGLOBIN Each iron atom present in Heme [iron is in ferrous state] can combine reversibly with one molecule of O 2, therefore, each hemoglobin molecule can take four O 2 molecules in the lungs. 98.5% of O 2 is carried in the blood bound to hemoglobin. Hemoglobin is a pigment naturally colored because of iron content. 11

12. HEMOGLOBIN Hemoglobin appears reddish when combine with O 2, e.g. Arterial blood. Hemoglobin appears bluish when deoxygenated, e.g. venous blood. 12

13. HEMOGLOBIN Functions: Transports O 2. Transports CO 2. Buffer: combines with H + ion Combines with carbon monoxide (CO), therefore, can cause CO poisoning. The affinity of hemoglobin to CO is more than O 2. Nitric Oxide (NO) gas combines with hemoglobin and this NO is released at the tissues and causes vasodilation. 13

14. ERYTHROPOIESIS Formation and maturation of RBCs. In adult RBC are formed in bone marrow. Bone marrow normally generates new RBC to replace old ruptured cells. In the fetus – RBC formation takes place in yolk sac during first 3 months, then liver and spleen up to 7 th month of intrauterine life. Bone marrow starts from 4 th month till birth of baby. 14

15. ERYTHROPOIESIS In children, most bones produce RBC by red bone marrow then red bone marrow is replaced by fatty yellow bone marrow that does not produce RBC. In adults, red bone marrow remains in sternum, ribs, vertebrae, pelvis, upper end of long bones e.g. femur, humerus. If we need bone marrow sample for examination, we usually take from iliac crest or sternum. 15

16. MAJOR STEPS IN ERYTHROPOIESIS 16

17. ERYTHROPOIESIS As RBC matures, it involves: - Reduction in size. - Disappearance of nucleus. - Acquiring of hemoglobin. 17

18. ERYTHROPOIESIS Nutritional Requirements of Erythropoiesis: 1. Amino Acids – for synthesis of globin of hemoglobin. 2. Iron 3. Vitamins – Vitamin B 12 and folic acid for synthesis of nucleo protein. 4. Trace elements – e.g. copper, zinc, cobalt 5. Hormones – Cortisol, growth hormone. 18

19. ERYTHROPOIESIS Control of Erythropiesis: Controlled by Erythropoietin hormone. Erythropoietin is produced by the kidneys due to reduced O 2 delivery to kidney. Main stimulus for production of erythropoietin is hypoxia e.g. high altitude, anemia. Erythropoietin is secreted in the blood to stimulates erythropoiesis in the bone marrow. In case of hemorrhage [blood loss], the rate of Erythropoiesis will increase more than 6 times. 19

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21. ERYTHROPOIESIS When you donate blood, your circulating RBC supply is replaced. During blood donation about 450 ml of blood is donated. Donated Plasma is replaced in 2-3 days. RBCs are replaced in 36 days [range 20–59 days], therefore, repeat donation of blood is recommended after 3 months. 21

22. ERYTHROPOIESIS Reticulocytes: It is immature erythrocyte. Normal reticulocyte count 0.5 – 1.5% in blood. Increased reticulocyte count in blood indicates high rate of erythropoietic activity. 22

23. ERYTHROPOIESIS Synthetic Erythropoietin: Synthetic erythropoietin is given to kidney failure patients or those patients under going chemotherapy for cancer as chemotherapy affects bone marrow and developing RBC. 23

24. ERYTHROPOIESIS Erythrocytes Breakdown: Average life of RBC is 120 days then it is destroyed. When RBC breakdown, they release hemoglobin. Hemoglobin is taken by macrophages. Hemoglobin is broken into heme + globin. Globin is degraded into amino acids which are used. From Hemoglobin, iron is released and passes back to blood. Porphyrin portion of hemoglobin molecule is converted into bilirubin. Bilirubin is carried to liver [bound with albumin] and secreted in bile by liver. 24

25. REFERENCES  Human Physiology, Lauralee Sherwood, seventh edition.  Text book Physiology by Guyton &Hall,11 th edition.  Text book of Physiology by Linda S. Contanzo, third edition.  Physiology by Berne and Levy, sixth edition. 25