Hemopoiesis.pptx

Hemopoiesis is the formation of blood cellular components. All cellular blood components are formed by hematopoietic stem cells.

1. Presentation Maria Shafiq Qureshi & Samavia aftab

2. Hemopoiesis (Hematopoiesis) Hematopoiesis is the formation of blood cellular components (RBCs,WBCs & Platelets). All cellular blood components are formed by hematopoietic stem cells. In a healthy adult person, approximately 10 11 - 10 12 new blood cells are produced daily in order to maintain steady state levels in the peripheral circulation.

3. Hematopoietic stem cells (HSCs) _Haematpoietic stem cells reside in the medulla (bone marrow) and have the unique ability to give rise to all of the different mature blood cell types and tissues. _HSCs are self-renewing cells: When they proliferate, at least some of the daughter cells remain as HSCs, so the pool of stem cells is not depleted. This phenomenon is called asymmetric division.

4. The other daughters of HSCs (myeloid and lymphoid progenitor cells) can follow any of the other differentiation pathways that lead to the production of one or more specific types of blood cell but cannot renew themselves. The pool of progenitors is heterogeneous and can be divided into two groups; _long-term self-renewing HSC _short-term self-renewing HSC

5. Erythropoiesis: Erythropoiesis is the process which produces red blood cells, which is the development from erythropoietic stem cell for mature red blood cell. It is stimulated by decreased O₂ in circulation, which is detected by the kidneys, which then secrete the hormone erythropoietin . Stages : Myeloid stem cell transformed into proerythroblast. In 15 days proerythroblasts develops into basophilic, erythroblasts , and then into reticulocytes. Reticulocytes enter blood stream ; in 2 days mature RBC.

6. As myeloid stem cell transforms: 1-Ribosomes synthesized 2-Hemoglobin synthesized; iron accumulates 3-Ejection of nucleus; formation of reticulocyte (Young RBC) Reticulocyte ribosomes degraded; Then become mature erythrocytes Reticulocyte count indicates rate of RBC formation Hormonal control of erythropoiesis: Hormone Erythropoietin (EPO); Direct stimulus for erythropoiesis High RBC or O2 levels depress production Released by kidneys (some from liver) in response to Hypoxia Dialysis patients have low RBC counts

7. Causes of hypoxia: Decreased RBC numbers due to hemorrhage or increased destruction Insufficient hemoglobin per RBC (e.g., iron deficiency) Reduced availability of 02 (e.g., high altitude) Effects of EPO Rapid maturation of committed marrow cells Increased circulating reticulocyte count in 1-2 days Some athletes abuse artificial EPO Dangerous consequences Testosterone enhances EPO production, resulting in higher RBC counts in males.

8. Leukopoiesis: Le ukopoiesis is a form of hematopoiesis in which white blood cells are formed in bone marrow located in bones in adults and hematopoietic organs in the fetus. Leukopoiesis is stimulated by interleukins and colony stimulating factors (CSFs). They act as chemical stimuli, and their type and amount determines the type of leukocyte formed. Stages: 1-Myeloblast 2-Promyelocyte 3-Neutrophilic myelocyte 4-Neutrophilic metamyelocyte 5-Band cell 6-Neutrophil  

9. The process of formation of platelets is called thrombopoiesis. Platelets are formed from the cytoplasm of a large cell in a bone marrow known as megakaryocyte. These are produced in the bone marrow by fragmentation of the cytoplasm of megakaryocytes , once of the largest cells in the body. Stages : Platelets are formed through various stages of development in the bone marrow: 1-Megakaryoblast 2-Promegakaryocyte 3-Megakaryocyte 4-Platelet Thrombopoiesis:

10. The precursor of the megakaryocyte _the megakaryoblast _arises by the differentiation from the haemopoietic stem cell Platelets formed by fragmentation from the tips of cytoplasmic extensions of megakaryocyte cytoplasm , each megakaryocyte giving rise to approximately tom 1000_5000 platelets. The time interval from differentiation of the human stem cell to the production of platelets averages 10 days’ Thrombopoietin is the major regulator of platelet production and is constitutively produced by Liver and Kidneys .

11. Hemoglobin structure and function Hemoglobin: Hemoglobin is  a protein in your red blood cells  that carries oxygen to your body's organs and tissues and transports carbon dioxide from your organs and tissues back to your lungs. If a hemoglobin test reveals that your hemoglobin level is lower than normal, it means you have a low red blood cell count (anemia). Structure of Hemoglobin: It consists of protein (globin) united with pigment heme. Heme: Iron containing porphyrin (iron-protoporphyrin IX) Porphyrin is tetreoyrole; _4 pyrrole rings joined by 4 methane bridges : -Methyl at 1,3,5,8 side chain -Vinyl at 2,4 -Propionic acid at 6,7 Fe2+ is called the  ferrous ion , attached to N(nitrogen) of pyrrole rings.

12. Globin: It consists of 4 polypeptide chain –two alpha and two beta chains. Alpha chains _141 amino acids Beta chain_146 amino acids Each polypeptide chain attach with one heme group. 1 hemoglobin have 4 iron attached with 4 molecules of oxygen. Functions of hemoglobin: Imparts red color to the blood. Helps to carry out the oxygen and other gases assisting the respiratory system. It buffers the blood pH and maintains it to the tolerate limits.

13. How is hemoglobin formed? Formation of hemoglobin begins in the proerythroblast stage . It continues till the reticulocyte stage of RBCs, when reticulocyte reach the bone marrow and pass into the blood stream , it forms some amount of hemoglobin until they become mature erythrocytes.

14. How is hemoglobin destroyed? Globin, the protein part of hemoglobin is broken down into amino acids which can be sent back to the bone marrow to be used in the production of new erythrocytes . Heme group is converted into bilirubin used to make bile in liver ,iron ions transferred to ferritin protein for storage into liver and then heme portion is converted into biliverdin for transport in blood , iron ions bind to blood protein transferrin for transport,

15. Iron : Iron is one of the most essential trace element. Total body iron content is 3 to 5 g.75% present in blood the rest is in liver , bone marrow and muscles. Heme is the most predominant iron containing substance . It is a constituent of proteins /Enzymes, hemoprotein(Hb),myoglobin and cytochromes. Sources of iron : Metabolism of iron : Absorption; Iron is called one way substance because it is absorbed and excreted from small intestine. Iron is absorbed in three forms;( 1 -Ferrous iron ) ( 2 - Ferric iron ) ( 3 - Heme iron) Iron is absorbed mainly in the ferrous form.

16. Ferric ion are reduced with ascorbic acid and glutathione of food to more soluble ferrous Fe2+ from cells which are more readily absorbed than Fe3+. After taken up by the intestinal mucosa iron is either stored in the form of Ferritin in the mucosal cells or transported across the mucosal cells to the plasma in the form of Transferrin. Transport of iron : Mucosal Cells The iron entering the mucosal cells by absorption is oxidized to Ferric form by the enzyme Ferroxidase. Major sources of iron is in the plasma is from degraded erythrocytes. Fe3+ combines with Apoferritin to form Ferritin, which is the temporary storage of form of iron . From the mucosal cells iron may enter the blood stream. In Plasma Iron enter plasma in the ferrous state. It is oxidized to ferric form by a copper containing protein Ceruloplasmins ,Ferroxidase activity. Ferric iron binds with a specific iron binding protein ‘’transferrin’’ . Transport form of iron is Transferrin. It is a glycoprotein synthesized in a liver. Total iron binding capacity of transferrin is 250-450 microgram/dl;.

17. Storage of iron: Iron is stored in liver, spleen and bone marrow in the form of Ferritin. In the mucosal cells, ferritin is the temporary storage form of the iron . Ferritin contains about 23% iron . Ferritin level in blood is an index of body iron storage. Hemosiderin; It is another storage protein which can hold about 35% of iron by weight. it accumulates when iron levels are increased.

18. Excretion; The normal iron excretion is about 1mg per day . The major excretory pathway is through intestine. Iron is not excreted in urine but in the nephrotic syndrome. Loss of transferrin may let to increased loss of iron in urine.

19. JAZAKALLAH KHAIR