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  • 1. HEMOGLOBIN 1

2. INTRODUCTION The main function of red blood cell Transfer of O2 from lungs to tissue Transfer of CO2 from tissue to lungs To accomplish this function red cells has haemoglobin (Hb)Each red cell has 640 million molecules of Hb2 3. INTRODUCTION Haemoglobin(Hb), protein constituting 1/3 of the red blood cells found in the cytoplasm of erythrocytes Synthesisbegins in proerythroblast65% at erythroblast stage 35% at reticulocyte stage 3 4. STRUCTURE OF HEMOGLOBIN Hb is a spherical molecule consisting of 4 peptide subunits (globins) = quartenary structure Hb of adults (Hb A) is a tetramer consisting of 2 - and 2 globins each globin contains 1 heme group with a central Fe2+ ion (ferrous ion)4 5. SYNTHESIS OF HAEMOGLOBIN (HB) Haem & globin produced at two different sites in the cells Haem in mitochondria Globin in polyribosomes Well synchronized5 6. Synthesis of Hb: Hemoglobin synthesis begins in proerythroblast and continues slightly even into the reticulocyte stageSteps: 2 succinyl-coA + 2 glycine = pyrrole 4 pyrrole= protoporphyrin lx Protoporphyrin lx + Fe++ (iron) = Heme 1 Heme molecule + 1 polypeptide = hemoglobin chain (hemoglobin subunit) 4 hemoglobin chain = hemoglobin molecule (4 hemoglobin subunit) There are several slight variations in different subunit hemoglobin chain depending on the aminoacid composition of polypeptide portion The different types of chain are designated alpha chain, beta chain, gamma chain, and delta chain 2 alpha chain + 2 beta chain = hemoglobin A Each hemoglobin chain has 1 heme, so 4 hemoglobin chain in 1 hemoglobin molecule has 4 heme. One heme has one iron so 1 hemoglobin molecule has 4 iron atoms Each iron can bind with 1 molecule of oxygen ; so 1 molecule of Hb can transport 4 molecule of oxygen (8 oxygen atoms)6 7. SYNTHESIS OF HAEMOGLOBIN7 8. SYNTHESIS OF HAEM Protoporphyrin ring with an iron atom in centreThe main site is mitochondria as it contains ALASMature red cell does not contain mitochondria8 9. STRUCTURE OF HAEM9 10. SYNTHESIS OF GLOBIN10 11. SYNTHESIS OF GLOBIN Various types of globin combines with haem to form different haemoglobinEight functional globin chains, arranged in two clusters the - cluster (, , and globin E genes) on the short arm of chromosome 11 - cluster ( and globin Z genes) on the short arm of chromosome 16 11 12. Normal value Male:Range: 14-18gm/100ml of blood Average: 15.5 gm/100ml of bloodFemale:Range: 12-16.5 gm/100ml of blood Average: 14 gm/100ml of bloodAt birth:23 gm/100ml of bloodAt first year:10 gm/100ml of bloodMolecular weight: 64,45812 13. Hemoglobin consists of two parts a. Globin 96% b. Heme 4% Heme portion: Heme portion is synthesized mainly from acetic acid and glycine in the mitochondria Globin portion: Globin is composed of four large polypeptide chains. Globin is synthesized by ribosomes13 14. Function of hemoglobin: It is essential for transport of oxygen from lungs to the tissue and Carbondioxide from tissue to lungs It is an important blood buffer and helps to maintain pH of blood Various pigments of bile, stool, urine, etc are derived from it It acts a reservoir for protein and iron14 15. TRANSPORT OF O2 AND CO2 IN LUNGS15 16. TRANSPORT OF O2 AND CO2 IN TISSUES16 17. TYPES OF HEMOGLOBIN Adult Hb (Hb A) = 2 and 2 subunits HbA is the major form of Hb in adults and in children over 7 months. 1 HbA (2 , 2 ) is a minor form of Hb in adults. It forms only 2 3% of 2 atotal Hb A.Fetal Hb (Hb F) = 2 and 2 subunits - in fetus and newborn infants Hb F binds O2 at lower tension than Hb A Hb F has a higher affinity to O2 After birth, Hb F is replaced by Hb A during the first few months of life. Hb S in -globin chain Glu is replaced by Val = an abnormal Hb typical for sickle cell anemia 17 18. Types of hemoglobin (variation) A)Physiological variation: Normally there are three different types of hemoglobin 1.Fetal hemoglobin (HbF): It contains 2 and 2 polypeptide chain 2.Adult hemoglobin a.Hemoglobin A: It contains 2 and 2 polypeptide chain b.Hemoglobin A2 (HbA2): It contains 2 chain and 2 are replaced by 2 chain Hb AHbA2HbFAdult96%3%1%Neonate30%70% 18 19. B)Pathological hemoglobin:(SEC-D) 1.Hb S: Contains 2 and 2, but glutamic acid in 6th position is replaced by valine in (-chain) 2.Hb E: Contains 2 and 2, but glutamic acid in 26th position is replaced by lysine (in -chain) 3.Hb C: Contains 2 and 2, but glutamic acid in 6th position is replaced by lysine (in -chain) 4.Hb D (Punjab): Contains 2 and 2, but glutamic acid in 121st position is replaced by glutamine (in -chain) 19 20. DERIVATIVES OF HEMOGLOBIN Oxyhemoglobin (oxyHb) = Hb with O2Deoxyhemoglobin (deoxyHb) = Hb without O2Methemoglobin (metHb) contains Fe3+ instead of Fe2+ in heme groupsCarbonylhemoglobin (HbCO) CO binds to Fe2+ in heme in case of CO poisoning or smoking. CO has 200x higher affinity to Fe 2+ than O2. Carbaminohemoglobin (HbCO2) - CO2 is non-covalently bound to globin chain of Hb. HbCO2 transports CO2 in blood (about 23%). Glycohemoglobin (HbA1c) is formed spontaneously by nonenzymatic reaction with Glc. People with DM have more HbA1c than normal ( 7%). Measurement of blood HbA1c is useful to get info about long-term 20 control of glycemia. 21. Amount of oxygen that can be carried by Hb: Average Hb in Men: 16 gm/dl Women: 14 gm/dl Each gram of pure hemoglobin is capable of combining with 1.39 ml of oxygen Therefore In men: 100 ml of blood contains 16 gm of hemoglobin So 100 ml of blood contains 16 x 1.39 ml of oxygen = 21 ml of oxygen So in men: 100 ml of blood (16 gm Hb) can carry 21 ml of oxygen In female: 100 ml of blood contains 16 gm of hemoglobin So 100 ml of blood contains 14 x 1.39 ml of oxygen = 19 ml of oxygen So in women: 100 ml of blood (14 gm Hb) can carry 19 ml of oxygen21 22. What would happen if hemoglobin were present freely in plasma? Normally, all of Hb is contained within RBC, only a minute amount (about 3 mg%) being present in the plasma. If Hb were freely present in plasma 1.It would increase viscosity of blood (thus rising BP) 2.It would increase colloidal osmotic pressure (thus affecting fluid exchange) 3.It would pass quickly through glomerular membrane and excreted out through urine.22 23. Why RBC (Hb) is lower in female? 1.As because estrogen have an inhibitory effect on the secretion of erythropoietin, which is the major regulator of erythropoiesis. 2 .Testosterone is males have a stimulatory action on the secretion of erythropoietin Menstrual loss of blood in female is not the cause of lower level of RBC (Hb)Why RBC (Hb) is more in newborn? The newborn has been living in a state of relative hypoxia and hypoxia is a very potent stimulus for erythropoietin secretion. As age advances, Hb levels decrease and adult level are reached in a few year.23 24. Fate of RBC Life span of RBC is 120 days. After 120 days RBC becomes fragile, so they become destroyed when they pass through tight spot of circulation or in reticuloendothelial cell of liver, spleen, lymph node, and bone marrow. After destruction (rupture) of RBC, Hb is released from them 1.Hemoglobin is phagocytised by RE cell and converted into heme and globin Hemoglobin HemeGlobin2.Globin is degraded into aminoacid. These aminoacids are liberated into plasma and are stored as aminoacid pool. 3.Heme is broken down into Fe (iron) and straight chain of 4-pyrrole ring (choleglobin) Heme Festraight chain of 4-pyrrole ringFe (iron) is bound to plasma protein transferrin and transported to the bone marrow for further production of Hb or store in liver or other tissue as ferritin and transferrin24 25. 4. Straight chain of 4-pyrrole ring is converted to biliverdin straight chain of 4-pyrrole ring biliverdin biliverdin reductase bilirubin This bilirubin is released from RE cells into plasma 5. This bilirubin now binds with plasma protein albumin to form unconjugated bilirubin (water insoluble) This unconjugated bilirubin now enters into liver Here a. 80% conjugate with uridine diphosphate (UDP) glucoronide to form (mono- and dibilirubin glucoronide) b. 10% conjugate with sulphate and 10% with other This forms conjugated bilirubin (water soluble) Enzyme: Glucoronyl transferase25 26. 6. Now this conjugated bilirubin is transported via bile duct into duodenum where theyare converted into urobilinogen by intestinal bacteria. These urobilinogen a.Some of these urobilinogen are later converted to stercobilinogen and excreted through stool. When this stercobilinogen is exposed to external air. It is oxidized to stercobilin b.Some of these urobilinogen are reabsorbed by enterohepatic circulation. From it they reach the systemic circulation and finally into kidney. This urobilinogen is excreted through urine. When urobilinogen is exposed to air it is oxidized into urobilin.26 27. Fate of RBC (Bilirubin metabolism)27 28. The red cell absolute value 1)PCV (packed cell volume) or hematocrit (Hct): It is fraction of volume of blood occupied by RBC. Average: 45%2)Mean corpuscular volume (MCV): The MCV is the average or mean volume of a single red blood cell expressed in cubic micrometer (cubic microns) Formula:Hct x 10 RBC count in million/mm3 =45 x 10 = 90 um3 5 3 Range: 76-96 um /fl (femtoliter)28 29. 3) MCH (Mean corpuscular hemoglobin): The MCH is the average hemoglobin content (weight of Hb) in a single RBC expressed in picogram (micro-microgram, uug) Formula:Hb in gram in 100 ml of blood x10 Red cell counts in million/mm3 15 x10 5 = 30 picogram (pg)Normal range: 27-32 pg29 30. 4)MCHC (Mean corpuscular hemoglobin concentration): The MCHC represents the relationship between the red cell volume and its degree or percentage saturation with hemoglobin,that is how many parts or volumes of red cell are occupied by Hb. It represents the average concentration of Hb in the red cells The MCHC does not take into consideration the RBC counts, but represents the actual

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