Basic Hematology Lectures PDF

Basic Hematology Lectures For Medical Laboratory Assistants (MLA) (undergraduate level) Blood cells formation...

Basic Hematology Lectures For Medical Laboratory Assistants (MLA) (undergraduate level) Blood cells formation And Hemoglobin synthesis =========================================================== MSC: Khaled Hussein M.Nassr -------------------------------------------------------------------------------------------------------------------------------- - – - - 1 Content Chapter N0 Title Page No Chapter 1 Composition of the Blood 2 Chapter 2 Hematopoietic Organs 10 Chapter 3 Hematopoiesis 16 Chapter 4 Erythropoiesis 27 Chapter 5 Leukopoiesis and Thrombopoiesis 32 Chapter 6 Red Cell membrane developing-Metabolic pathways 43 Chapter 7 Essential substances for RBC (Iron+Vitam.B12+Folic acid 47 Chapter 8 Hemoglobin synthesis , structure and function 54 Chapter 9 Blood composition and Anticoagulant materials 60 Chapter 10 The Peripheral Blood Cells 66 Chapter 11 FBC evaluation and methods 72 References 78 - 2 Chapter 1 Introduction -- Composition of the Blood Hematology is the study of blood formation and function.  Blood: is the fluid where the cells are free and suspended.  It can cross the tissues.  Has red color.  Has volume of 5-6 liters, this is 7-8% of the total body weight.  Has pH of 7.3-7.4 (alkaline).  Specific gravity is 1.055-1.056 Picture of Blood Blood is a constantly circulating fluid providing the body with 1. Nutrition 2. Oxygen 3. and waste removal.  Blood is mostly liquid, with numerous cells and proteins suspended in it, making blood "thicker" than pure water.  The average person has about 5 liters of blood. Composition of the Blood The blood composed of two parts 1-liquid part called plasma and constitute about 55% of whole blood 2-cellular part (formed elements) 45 % Plasma consists of 90% water, and 8-9%solids. Written By -Dr.Abdulrazzaq Othman Alagbare -M.Bhc.MSc.Lecturer of hematology 3 Plasma and blood cells A liquid called plasma makes up about half of the content of blood. Plasma contains proteins that help blood to 1. Clot 2. Transport substances through the blood, 3. And perform other functions. Blood plasma also contains glucose and other dissolved nutrients. 1-liquid part Solids are: 1. Albumin. Glucose. - - 4 2. Fibrinogen. Sodium. 3. Calcium. Potassium. 4. Cholesterol. Magnesium. 5. Carbon dioxide. Oxygen. 6. Phosphorus. Many other products. Also there are such substances, like antibodies, hormones, complement and enzymes. 2-Cellular part (formed elements) a) Whole blood is (plasma and cells) b) The cells are forming about 45%. About half of blood volume is composed of blood cells: Red blood cells, which carry oxygen to the tissues White blood cells, which fight infections Platelets, smaller cells that help blood to clot - - 5 Cardiovascular system Blood is conducted through blood vessels (arteries and veins). Blood is prevented from clotting in the blood vessels by their smoothness, and the finely tuned balance of clotting factors. Cardiovascular system Definition: are all the organs in which the blood continuously circulating it is made up of three independent systems that work together: 1. The heart (cardiovascular); 2. lungs (pulmonary); and arteries, veins, coronary 3. And portal vessels (systemic), In the average human, about 7,572 liters of blood travel daily through about 96,560 kilometers of blood vessels Blood Flow Through the Heart 1. combines 2 circulatory systems Pulmonary circulation  primarily right side of heart  key = getting blood to lungs Systemic circulation  primarily left side of heart  key = getting blood to all other parts of body - - 6 Cardiovascular system Definition: are all the organs in which the blood continuously circulating Cardiovascular system parts: Consist of the following parts 1-Heart 2-Vesseles , consist of  Arteries  Arterioles = small arteries  Venoules = small veins  veins The heart  Definition: It is a muscular bag  Site: in the left part of the thorax  Function: continuously pumping the blood through all the organs of the body. 2.1- arteries  Definition they are thick walled tubes.  Function: carrying oxygenated blood away from the heart.  Type of blood: arterial blood with high percentage of oxygen (oxygenated blood  Sites: They lay below the muscular tissue and recognized by the pulse felling.  Arterioles: are the smallest vessels into which the arteries lead - - 7 2.2-Venoules: are the smallest vessels, considered the beginning of the veins, which collect the venous blood with Co2 and waste products Veins  Definition: they are thin walled vessels.  Function: carrying the blood into the heart and from there to the lungs etc. (deoxygenated)  Site: they lay below the skin directly and recognize by the sight and felt. 2.3-Capillaries:  Are the smallest blood vessels,  the end of the arteries and the beginning of the veins,  finding in the edges of the body’s (ears, fingers etc).  They form a network through all organs and tissues of the body. - - 8  Capillaries join arteries and vein  Nutrients and oxygen exchanged at cellular level Functions of Blood Vessels Arteries distribution of nutrients maintenance of blood pressure Veins takes waste products back to heart for circulation & disposal valves keep flow going in one direction Capillaries where internal respiration occurs i.e. the exchange of O2 & CO2 between vessel & cell where exchanges occur for nutrients, wastes, and fluids - - 9 Main functions of the blood 1-Transportation and distribution Transport the oxygen Transport the nutrients Transport the Waste products Transport hormones 2-Regulatory Function:  Regulate and maintain the pH of the blood between pH 7.35–7.45 (Buffer systems).  Regulate plasma osmotic pressure,  Regulate the temperature level of the body. 3-Protective function A. Control blood loss (Platelets) B. Fighting infections (leukocytes and antibodies) Blood gases level The gases in the blood are soluble, they are tow oxygen and carbon dioxide The blood according to their oxygen concentration divided into 1-arterial blood, contain high percentage of oxygen. 2-venous blood, contain high percentage of CO2. 3-capillary blood, contain mixed blood because. Blood volume: Is the total volume of the plasma and the cells, in whole of the body. Blood volume in the circulatory system is the following according to the age Age Blood volume New born and infants About 200-300ml Children 1.0-2.5liter Adult male 5.0-6.0 liter Adult female 4.5-5.0 liter - - 10 Chapter 2 Hematopoietic Organs Definition: are all the organs which produce and developed the blood cells There is 2 types 1. -Hematopoietic organ in fetal life 2. -Hematopoietic organs in adult life Hematopoietic organ in fetal life 1. Yolk sac and Mesothelial layers of placenta 2. Liver and spleen and lymphoid tissues 3. Bone marrow from the 4th month Site of haemopoiesis During all Fetal life 0-2 months (yolk sac)  First semester 2-7 months (liver, spleen)  second semester 5-9 months (bone marrow)  Third semester The main Hematopoietic organs in adult life 1-Primary Hematopoietic organs 1. Bone Marrow 2. Thymus 2-Secondary Hematopoietic organs 1. Spleen 2. Lymph Nodes 3. Thymus 4. Other Secondary Organs RES is a part of the hematopoietic tissue that produces and forming blood cells. Because it’s have the same tissue with the bone marrow, - - 11 Hematopoietic organs in adult life 1-Primary Hematopoietic organs Consist of 1. Bone Marrow 2. Thymus - - 12 1-Bone marrow structure The marrow may be considered a large organ weighting from 1600-3700 gr. The bone marrow is made up of:  30-70% hematopoietic cells  Stromal cells including  fat cells  Mesenchymal stem cells  and fibrocytes, with extracellular connective tissue,  Sinusoidal and vascular spaces. Bone marrow secretion Stromal cells secrete several substances such as – growth factors necessary for stem cell survival. – secrete extracellular molecules such as collagen , glycoproteins and others Cell in the bone marrow 1-Hematopoietic cells consist about 30-70% from all the cells of the bone marrow From that 1-60-70% myeloid cells (White blood cells) 2-25-30% eryhtrocyte cells - - 13 Thymus The thymus which is a small, flat, bilobed organ Site.. found in the thorax, or chest cavity Weight… 30 g at birth, reaches about 35 g at puberty, and then gradually atrophies Function…. T cells develop their identifying characteristics 2-The reticuloendothelial system Abbreviation: RES Definition: RES is part of the hematopoietic tissues Properties Has the same tissue with the bone marrow, for that except the blood cells without reaction Function: 1-Take part in the developing of some hematopoietic cells - - 14 The secondary heamatopoietic organ - ( RES ) Consist of 1-Spleen The spleen (an organ in the upper abdomen that makes lymphocytes and filters old blood cells from the blood) 2-Lymph nodes…Small bean-shaped organs called lymph nodes. Clusters of lymph nodes are found –underarm, pelvis. Neck, and abdomen 3-The tonsils (an organ in the throat) are also part of the lymph system. 4-Intestine associated lymphoid tissue etc - - 15 The lymph system The lymph system is made up of thin tubes that branches like blood vessels, into all parts of the body. lymph vessels carry lymph, which is – a colorless, – watery fluid that – contains lymphocytes and lipids (chylomicron),O2,nutrients, protein, cancer cells, and dead or damaged cells - - 16 Chapter 3 Hematopoiesis Blood cells production introduction Blood cells production called hematopoiesis. 1-The main organs for hematopoiesis in all human life are 1. Liver and Spleen (prenatal period) 2. And the bone marrow (BM) (adult period) 2-The secondary hematopoietic organ called the reticuloendothelia system (RES) The first cell which produce all the other cells called Pluripotent stem cells (PSC) or hemocytoblasts 1-Totipotent means that the stem cell can give rise to any and all human tissue cells.  The only totipotent cells in human development are the fertilized egg 2-Pluripotent =Totipotent 3- Multipotent  restricted to a limited range of cell types  For example, there are multipotent stem cells in the bone marrow that can give rise to red cells, white cells and platelets - - 17 Hematopoietic stem and progenitor ells Definition: They are cells which give new generation of cells, and existing in the bone marrow exclusively and they are: 1-Pluripotent stem cells (PSC) or hemohistoblast 2-Myeloid stem cell (MSC)p 3-Lymphoid stem cell (LSC) MSC and LSC also called Progenitor cells, Committed cells  The sources of the hematopoietic stem cells are the mesenchymal cells of the yolk sac and they are - - 18 Pluripotent stem cells (PSC) or (hemohistoblast cells – HSCs ) Properties Pluripotent stem cells has the following properties Sources: 1. bone marrow of adults, 2. umbilical cord blood 3. peripheral blood Properties 1- Self-renewal  Has the ability to renew its selves 2-Multipotentiality  Can produce another cells (pluripotent cells ) 3-Mothers of all blood cells 4-Existing mainly in the bone marrow - - 19 Hematopoiesis in the human life the hematopoiesis is different as follow 1-Hematopoiesis in fetus (prenatal 1-Hematopoiesis in fetus (prenatal period) period) 1-First trimester start early in the fetus, and could be 2-Second trimester 3-Third trimester: derived to three anatomic stages: First stage First trimester Name: Mesoblastic stage Site: Yolk sac and Mesothelial layers of placenta Period 0-2 months - - 20 Second stage Second trimester Name: Hepatic stage Site: Liver and spleen and lymphoid tissues Period 2-7 months Third stage Third trimester Name: Myeloid stage Site: Bone marrow from the 4th month learn to be the main normal heamatopoietic organ in childhood and adult life. Period 5-9 months Written By -Dr.Abdulrazzaq Othman Alagbare -M.Bhc.MSc.Lecturer of hematology 21 Hematopoiesis during infancy Hematopoiesis During childhood And adult life : up to about 4 years of age  During infancy: all  Erythropoiesis becomes gradually restricted marrow cavities are active in erythropoiesis (almost to flat bones as; all the bones of the body ) AND CALLED "Red skull, vertebrae, sternum, Ribs and pelvic bones, in Marrow". addition to ends of long bones.  The shafts of long bones become populated by fat AND CALLED "yellow marrow" - - 22 Types of hematopoiesis 1. Intramedullary hematopoiesis. It is normal and occur only in the bone marrow 2. Extramedullary hematopoiesis. describes hematopoiesis outside the bone marrow environment, primarily the liver and spleen. (it is abnormal)  Extramedullary hematopoiesis may occur in fetal hematopoietic tissue (liver and spleen) of an adult when the bone marrow cannot meet the physiologic needs of the tissues Hematopoiesis At birth, liver and spleen stop hematopoietic activity. Bone marrow now becomes active site of hematopoiesis - - 23 Progenitor cells What are progenitor cells?  They are the first cells which produce from the stem cell  They also called: hematopoietic or committed cells  They are two, MYELOID and LYMPHOID stem cells  has a tendency to differentiate into a specific type of cell, but is already more specific than a stem cell and is pushed to differentiate into its "target" cell 1-Myeloid stem cell (MSC) 1. Exist in the bone marrow 2. Produce the cells called Myeloid group or myeloid sera 2- Lymphoid stem cell (LSC) 1. Exist in the bone marrow 2. Produce the cell called Lymphoid group or Lymphoid sera Stem cells culture CFU-S refers to the pluripotent stem cells that can differentiate into all types of blood cells. CFU-S divides into two lineages: 1. the lymphoid precursor (CFU- LSC) 2. and the myeloid precursor (CFU- GEMM) Progenitor cells culture In culture media the progenitor cells are defined as colony forming unit (CFU). Each of the CFUs in turn can produce a colony of one hematopoietic lineage under appropriate growth conditions - - 24 The myeloid stem cell - colony forming unit (CFU). The cells which produced from the MSC and existing in the peripheral blood are CFU-myeloid stem cell include the following cells - CFU-GEMM A. CFU-E -- Eryhtrocytes B. CFU-GM I. Granulocytes (neutrophils, basophils, eosinophils) II. Monocytes and macrophages C. CFU-M -- Megakaryocytes (Platelets) Colony-forming unit lymphocyte (CFU-L) The cells which produced from the LSC and existing in the peripheral blood are I. T- Lymphocytes II. B -Lymphocytes III. N-Killer cells The myeloid stem cell The cells which produced from the MSC and existing in the peripheral blood are 1-Erythrocytes ( Red blood cells ) 2-Granular cells 3-Monocytes 3-Platelets or Thrombocytes The lymphoid stem cell The cells which produced from the LSC and existing in the peripheral blood are  Lymphocytes – T-Lymphocyte – B-Lymphocyte - - 25 Regulation of hematopoiesis For blood cells production needs  regulation and control to produce  adequate cells and no more than the normal needs, for that there are many factors do that. They called  Hemopoietic growth factors  colonies stimulated factors (CSF)  or cytokines Haemopoietic growth factors 1. Chemical nature: glycoprotein hormones 2. Source: from all the body cells (T –lymphocytes, monocytes, kidney, liver, hematopoietic cells) 3. Action: stimulate, regulate and maintain the blood cells Proliferation, Differentiation , Maturation and function - - 26 Action: stimulate, regulate and maintain the blood cells 1. Proliferation, 2. Differentiation , 3. Maturation 4. and functional activation 5. Apoptosis it is the programmed death of the cells Haemopoietic growth factors These factors have the capacity to stimulate the proliferation of their target progenitor cells when used as a sole source of stimulation The most important are SCF=Stem Cell Factor --Act on pluripotential stem cells Tpo= Thrombopoietin  platelets Epo= Erythropoietin Erythrocytes IL= Interleukin GM-CSF= Granulocyte Macrophage-colony stimulating factor M-CSF= Macrophage-colony stimulating factor --. Monocytes G-CSF= Granulocyte-colony stimulating factor - - 27 Chapter 4 Types of hematopoiesis: 1. Erythropoiesis: red cells 2. Granulopoiesis: granulocytes 3. Megakaryopoiesis: megakaryocytes Erythropoiesis Definition: it is a process of erythrocytes production. Erythropoiesis produces 2.5 million RBCs/second from stem cells (hemocytoblasts) in bone marrow Production site: 1- RBC Formation before birth A. Mesoblastic stage  Nucleated RBCs B. Hepatic stage  all blood cells C. Myeloid stage  all blood cells RBC Formation after birth 1. From the birth up to 5years old  All the bones produce blood cells (long bones and sternum) 2. After the 5th years only in  Vertebrae, Sternum, Ribs, and Ilium. - - 28 G Synthesis requirements for RBC production needs  Iron  Protein  Vitamin B12 and B6 Folic acid and Vitamin C and E  Copper (for cofactors for enzymes synthesizing RBCs)  Erythropoietin hormone (EPO) Erythropoietin hormone (EPO)  Nature: Glycoprotein  Human erythropoietin is a 193-amino acid glycoprotein.  The responsible gene located on the chromosome 7  Sources : 90% from the kidneys and 10% from the liver  Activity: stimulate and regulate the bone marrow to produce erythrocytes Regulation of erythropoiesis The erythrocytes production regulated by 1-Erythropoietin hormone (EPO) 2-Level of oxygen in the tissues Stimuli for erythropoiesis  Low levels of O2 increase production of erythrocytes  Increase in exercise  Hemorrhaging - - 29 Erythrocytes Maturation steps are Erythrocytes consist 10-30% of all hematopooietic cells in the bone marrow Production Site: only in the bone marrow Target: synthesis of 1. Hemoglobin (Hb) 2. Enzymes such as  Glucose 6 dehydrogenase phosphate (G6PD)  and pyruvate kinase (PK) Period: about 8-10 days Erythrocytes Maturation sequence of the formation of red blood cells (Erythropoiesis) Pronormoblast Early normoblast Intermediate normoblast late normoblast Reticulocyte mature Erythrocyte - - 30 1) Pronormoblast:- 2) Early - normoblast:- No hemoglobin  Nucleoli disappear Nucleus 12 um  Hemoglobin starts appearing – Little Contain nucleoli Hb ((3) Intermediate - normoblast:- 4) Late -normoblast:-  Cytoplasm deep blue  Increase in  Nucleus smaller-pyknosis RNA  And Nuclear extrusion  Increase Hemoglobin synthesis - - 31 (5) Reticulocyte:-  Remnant of RNA  Synthesizing proteins and Hb continue 34%  Consist about 1 % of Red Cells  Reticulocytes contain ribonucleic acid (RNA) for 4 days; normally, the first 3 days are spent in the marrow and fourth in the blood (6) Erythrocytes:-  Round, biconcave, disc shaped.  Diameter 7.8 um.  Can deform easily. Transfer of RBC to Circulation RBC transfers into the peripheral blood by (Diapedesis) Diapedesis: Process by which Erythrocytes come out of blood vessel wall a) Pores of vessel wall are smaller than cells b) Small portion of the cell squeezes through the pores Maturation effect on the Erythrocytes production 1-synthesis of hemoglobin 2-Synthesis of the main enzymes (G6PD and PK) 3-Loss of the nucleus in the late normoblast step RBC properties in the peripheral blood 1. Non nucleated 2. Flexible biconcave disc 3. lives 100-120 days in the circulation. 4. Function transport of 02 to the tissue and remove the CO2 5. Aged red cells removed by the spleen - - 32 Chapter 5 Leukopoiesis  Leukopoiesis in general means the state of the production, development, differentiation of all white blood cells Types  1-Granulopoiesis  production of white blood cells which contain granules in their cytoplasm  2-Lymphopoiesis (Non Granular cells production):  production of white blood cells which not contain granules in their cytoplasm Committed cells of Leukopoiesis 1-Myeloid stem cell (MSC) or colony forming unit CFU-GEMM a) CFU-G: granular, I. CFU-Neutrophil II. CFU-Eosinophil III. CFU-Basophil b) CFU-E: erythrocyte c) CFU-M: monocyte d) CFU-M: megacaryocyte) 2-Lymphoid stem cell (CFU-LSC), which give the lymphocytes I. T - lymphocytes II. B – lymphocytes III. Natural Killer cells - - 33 1-Granulopoiesi Definition: is the production of all granular cells which existing in the peripheral blood and contain granules in their cytoplasm Source: from the myeloid stem cell (MSC) in the Bone marrow Site of production: The main production site of the granular cells is the bone marrow Granulopoiesis-Regulation: Regulated mainly by the following growth factors: - The gene responsible for encoding the granulocyte colony stimulating factor CSF (G-CSF) is on the chromosome 17 1-Granulocyte CSF (G-CSF) 2-Granulocyte-macrophage CSF (GM-CSF), 3-Group of interleukines or haemopoietin Action of growth factors 1. Stimulate proliferation 2. Differentiation 3. Affect the function of the mature cells on which they act - - 34 Granulopoiesis The most important changes In the myelocyte stage become clear cut, when the differentiation into one of the granular cell type will become (Neutrophil, Eosinophil or Basophil) The most important changes which taken place during their maturation, are 1-Nucleus  Separated into lobes or segments 2-Cytoplasm  Granules appear in the cytoplasm. - - 35 Granulopoiesis maturation steps are 1-Myeloblast: It has a large nucleus with fine chromatin, 2–5 nucleoli and scanty pale blue cytoplasm without granules ) 2-Promyelocyte 1. Slightly larger than a myeloblast and less clear nucleoli. 2. Cytoplasm contains both azurophilic granules and characteristic neutrophilic granules) 3-Myelocyte 1. Smaller than a promyelocyte, 2. the nucleus is usually oval and without nucleoli. 3. cytoplasm contains azurophilic and neutrophilic granules. 4. Separate myelocytes of the neutrophil, eosinophil and basophil series can be identified - - 36 4-Metamyelocyte The nucleus is indented (U-shaped) and the cytoplasm is pale pink and contains neutrophilic granules 5-Band Neutrophil (stab form): Similar to the metamyelocyte but with a curved or coiled, often S shape ,nucleus (without clear lobes), 6-Neutrophil : The nucleus has 3 (occasionally 4 or 5) clear lobes, separated by chromatin threads. The cytoplasm is pale staining and contains neutrophilic i.e. mauve staining granules. - - 37 The Monocytic Series Origin of development:  The bone marrow, It is part of the myeloid sera Development steps are the following  1-MyeloMonocytoblast --Pro Monocyte Monocyte  Control mechanism of Monocyte production mainly by the following growth factor:  GM-CSF: For regulation and stimulation of granulocytes and monocytes  M-CSF : For regulation and stimulation exclusively of monocytes Types of granular cells in the peripheral blood  Normal neutrophils with 3-4 lobes  Band form with tow lobes  Polysegment neutrophil or (PMNs) over 5 lobes  Eosinophil 2 lobes  Basophils 2 lobes invisible - - 38 Thrombocytes Production Thrombocytes Production Thrombocytes or platelets produced only from the bone marrow as part of myeloid group Regulation Thrombocytes regulated by 1-thrombopoietin hormone (TPO). 2-The responsible gene existing on the chromosome 3 2-Interleukin 6 affect the proliferation and maturation of megakaryoyte Platelets existing in the peripheral blood as non-nucleated small particles. Platelets production a) Formed in the bone marrow b) Megakaryocytes fragment in bone marrow c) Smaller fragments are known as platelets (or thrombocytes) I. Platelets then pass into the blood II. Very important for blood clotting The steps of platelets production --Megakaryocytoblast  Megakaryocyte Platelet - - 39 2-The non-Granular cells (Lymphoid Group) Lymphoid stem cells:  These divide to form lymphoid progenitor cells which differentiate into B & T lymphocytes.  Early development of B lymphocytes takes place in the bone marrow and lymphoid tissues,  and development of T lymphocytes in the thymus Origin: 1-bone marrow and thymus 2-lymphoid tissue (spleen, lymphnodes,) Lymphoid group regulation  Regulated by: Inter-Leukines (IL 1 up to 21). Development steps Development steps are the following Lymphocytoblast  Prolymphocyte  Lymphocytes (T and B lymphocytes) Regulation: by interleukin (IL)-1 and IL-6 - - 40 Plasma cells  They are type of B lymphocyte  Their function to produce antibodies after B cells stimulation with antigen  Origin: Bone marrow not found in the peripheral blood 1- Plasma blast:- 2- Proplasma cells: 3- Plasma cells -This appearance is not found in peripheral blood only in the bone marrow Diagram of blood cells production - - 41 Peripheral blood cells - - 42 Changes during cells maturation - - 43 Chapter 6 Spleen structure and Function Spleen- introduction The spleen has an important role in the function of the haemopoietic and immune systems. About spleen 1. Site: located on the left side of the body under the rib cage 2. Weight: 150-250 g 3. length of between 5 and 13 cm 4. Shape: fist-shaped, soft in texture 5. Blood Quantity: The spleen, is a rich organ of blood a filled organ, receives 5% of blood per minute, 6. Palpitation: normally not palpitated Functions of the Spleen 1-Filter and remove any abnormal blood cells (remove the RNA ruminant of reticulocytes ). 2-produce blood cells in fetal life 3- participate in the Immune function 4- storage place for the blood cells - - 44 Red blood cell membrane development and function Introduction RBC proprieties The mature RBC  They lack nuclei  Contain two main enzymes (G6PD and PK)  Its main content is the hemoglobin (Hb)  Survive 120 days  No capacity to synthesize protein  Capable of a limited metabolism  Its main function is blood gases exchanges  They must maintain a high internal concentration of potassium and low internal concentration of sodium  They must be flexible to pass through small capillaries Red cell membrane The red cell membrane comprises OF 1. A lipid bilayer, 2. Integral membrane proteins 3. A membrane skeleton Approximately  50% of the membrane is protein,  20% phospholipids,  20% cholesterol molecules  10% is carbohydrate - - 45 Red cell membrane structure-proteins Proteins are either peripheral or integral, that include αlfa (α) and beta (β)  spectrin,  ankyrin,  protein 4.1  and actin. Proteins importance: Maintaining the biconcave shape of RBC What cause the proteins defects? abnormalities of shape of the red cell membrane (e.g. hereditary spherocytosis and elliptocytosis) - - 46 Deformability and elasticity are crucial (vital) properties of the red cell membrane, which must be able to extend is surface area up to 117% to accommodate its passage through arterioles and capillary space Red cell metabolism Because the mature red cell has no nuclear or mitochondrial organs for metabolizing fatty or amino acids. For that it gets all of its energy from the breakdown of glucose. The RBC get the energy mainly from tow enzymes inside it 1-G6PD enzyme 2- pyruvate kinase enzyme (PK) 1-The Embden-Meyerhof pathway 1. Use the G6PD enzyme as source of glucose 2. Provide 90% of the cellular ATP 3. It is anaerobic 2-The hexose monophosphate shunt 1. using the pyruvate kinase enzyme (PK) as source of energy 2. provides 5% to 10% of the ATP 3. It is aerobic ATP is important to A. Protect the membrane from damage B. Regulate the movement of electrolytes C. Keep hemoglobin in the reduced (Fe2) state) D. Produce 2,3 DPG enzyme The importance of 2,3 DPG enzyme: oxygen loading and unloading - - 47 Chapter 7 Requirements for Red Blood Cell Production 1. Erythropoeitin (EPO) 2. Proteins, required for globin synthesis 3. Iron 4. Vitamin B12 and folic acid 5. Vitamin B6 6. Vitamin C 7. Thyroid hormones, estrogens and androgens Iron Introduction Iron is essential to life for synthesis 1. Hemoglobin 2. Myoglobin 3. Enzymes Iron sources 1-foods such as meat, eggs, fishes 2-drugs Iron forms in the body: 1-Fe2 active ferrous (Fe2 ) 2-Fe3 - ferric (Fe3 ) - - 48 Differences between Fe2 and Fe 3 1. Fe2: it is active, it is toxic, exist inside the RBC 2. Fe3: non active , non-toxic , exist in the storage organs 2. Daily intake ( 1 mg ) s balanced against small daily losses (1 mg ) 3. Only 5-10 % or about 1.0 mg of dietary iron is absorbed as ferrous iron (Fe++), 4. The women needs more iron daily (monthly lose by menstruation period) Diurnal iron variation: It is the case of level of the iron in the body. In the morning the serum iron is higher, and lower in the afternoon Iron excretion: Minimal amount (1mg) is loss by fecal or urinary excretion as well as through sweating and desquamating skin. Iron metabolism Iron metabolism needs three proteins All the proteins are 1. Specific protein 2. Production site: Liver They are 1. Apoferritin  transport the iron from the intestine to the plasma (Fe3) 2. Transfeerin  binding with the iron and transport it to the different organs for uses or storage (Fe2) 3. Ferritin  the main protein for iron storage (Fe3) - - 49 Iron storage Storage irons occur in two forms-  Quantity : about 1-2 g  Forms storage are 1. ferritin 2. and hemosiderin Ferritin Ferritin is normally predominant protein for iron storage and store it at: 1-Bone marrow (the main place for iron storage) 2-Liver 3-Kidneys and spleen Iron storage -Hemosidern 2-Hemosidern  When the main storage organs are full with iron  the iron storage as small oxide granules of ferritin called “Hemosiderin” in different organs such as  Heart  Lungs  Skin. etc - - 50 Iron recycled After the RBC death the :  Iron is recycled and reused to produce new RBC  Free iron in the body not exist  Free iron is very toxic Total iron in the body Total iron in the body 4 to 5 grams of iron about 2.5 g is contained in the hemoglobin 2 gram binding as storage iron with the ferritine 400 mg in the myoglobin) or cytochromes enzymes etc Hemoglobin Fe 2.5 g Ferritin & Hemosiderin 2 gram Myoglobin Fe 300 mg Cytochromes; enzymes 100 mg Total Body Iron 4,900 g - - 51 Summary points  Iron is essential metal for life  Iron existing in the body on two forms  Fe2 is active iron existing inside the Hb  Fe3 non active and existing in the storage  The main iron storage organs are B, marrow, liver, kidneys and spleen  Three proteins take place in the iron metabolism  Apoferitine transport iron (Fe3) into plasma  Transfeering transport iron (Fe2) into bone marrow to make RBC  Ferritine storage the iron in the form Fe3  The excess iron storage in the tissue as ferritine called hemosiderine  Free iron in the plasma not exist  The free iron is high toxic and must be removed from the plasma  Daily iron intake is 1 mg and losing 1mg  Diurnal variation of iron is high in the morning low afternoon  The iron excreted by the stool, urine and sweating - -