1. HEMOGLOBIN (Hb) Structure of Hb The red, oxygen-carrying pigment in the red blood cells is hemoglobin, a protein with a molecular weight of 64,450.Hb is a globular molecule made up of 4 subunits. Each subunit contains a heme conjugated Each subunit contains a heme conjugated to a polypeptide (globin) i.e. Hb molecule to a polypeptide (globin) i.e. Hb molecule consists of 4 protein chains and 4 heme groups. consists of 4 protein chains and 4 heme groups. Each protein, called globin, is bound to one heme.

3. Normal Hb concentration in the blood : The average normal Hb content of blood is 16g/dl in men and 14g/dl in women. O2 carrying capacity of the blood : One gram of Hb can bind with 1.34 ml of O2. Whole blood in healthy adults contains 15g of Hb per dl of blood thus. O2 capacity of blood = 1.34 mL O2 x gHb/dl. of blood. = 1.34 ml O2/gHb x 15gHb/dl = 20.1 ml O2 combine with Hb /dl blood. The heme portion of Hb molecule is synthesized from glycine and succinyl-CoA in mitochondria and globin in ribosomes

6. Structure of Heme:heme is a chemical structure made up of a porphyrin ring with an iron atom inserted in the center. Each heme is a red- pigment molecule containing one iron atom. The porphyrin is made up of 4 pyrrole rings. synthesis of heme takes place in the mitochondria.

9. Formation of Hemoglobin The heme portion of the Hb is synthesized mainly from: Acetic acid is changed in the Krebs cycle into succinyl-CoA

10. Structure of globin:The globin portion of the Hb is a protein (simple polypeptide chains made up of amino acids). There are two Paris of polypeptides in each Hb molecule, two of the subunits contain one type of polypeptides the other two contain another type of polypeptides. There are two Paris of polypeptides in each Hb molecule, two of the subunits contain one type of polypeptides the other two contain another type of polypeptides. Synthesis of globin takes place in the polyribosomes. Synthesis of globin takes place in the polyribosomes. 1.Alpha chain(α) contain 141 amino acid residues. 2. Beta chain(β) contain146 amino acid residues. 3.Delta chain(δ) contain also 146 a.a. residues but differ from β chains by 10 a.a. residues. 4.gamma chain(γ) also contain 146 a. a. residues,differ from β chain by 39 a.a. residues. 2. Beta chain(β) contain146 amino acid residues. 3.Delta chain(δ) contain also 146 a.a. residues but differ from β chains by 10 a.a. residues. 4.gamma chain(γ) also contain 146 a. a. residues,differ from β chain by 39 a.a. residues.

13. different types of normal Hb: 1.Embryonic Hb: this Hb occur early in gestation: Gower 1. Gower 2. Portland. Embryonic Hb is replaced by: 2.Fetal Hb (HbF α 2 γ 2 ) : which consist of two alpha– chains and two gamma – chains. Before birth, fetal Hb is gradually replaced by HbA. HbF has more affinity to oxygen than HbA because gamma chains combine to 2,3,DPG less avidly than HbA which have 2 beta chains. 3.Adult Hb (HbA α 2 β 2 ): there are two types: HbA1: made up of two alpha chains + two beta chains. accounts for 97.5% of the total HbA. HbA2 ( α 2 δ 2) : which consists of two alpha chains & two delta chains 2.5% of adult Hb is HbA2. Glycosylated Hb (HbA1c): consists of a minor variation of HbA1. It differs from normal HbA1 in that if has a molecule of glucose attached to the N -terminal valine of each beta - chains. attached to the N -terminal valine of each beta - chains. The normal level of HbA1c in adults is 5% of adult hemoglobin. In diabetes mellitus the level of HbA1c is elevated.

15. Reactions of Hb : 1- Reaction of Hb with O2(oxygenation): 1- Reaction of Hb with O2(oxygenation): Hb4 + O 2 Hb4O 2 Hb4O 2 + O 2 Hb4O 4 Hb4O 4 + O 2 Hb4O 6 Hb4O 6 + O 2 Hb4O 8 oxyhemoglobin oxyhemoglobindeoxyhemoglobin O 2 attached to Fe +2 (ferrous iron) in the heme.

19. Reaction of Hb with CO2: CO2 is combine amino group of the globin molecule & not with iron atom and form carbamino hemoglobin (carbamino-Hb). 3- CO reacts with Hb to form carboxyhemoglobin (carbon monoxyhemoglobin). Cigarette smoke also contains CO and the blood of smokers contain 5% - 15% carboxyHb. Carbon monoxide is a poisonous substance. 4- When the blood is exposed to various drug and other oxidizing agents in vitro or in vivo, the ferrous iron (Fe ++ ) in the hemoglobin molecule is converted to ferric iron (Fe +++ ) forming methemoglobin (metHb). 4- When the blood is exposed to various drug and other oxidizing agents in vitro or in vivo, the ferrous iron (Fe ++ ) in the hemoglobin molecule is converted to ferric iron (Fe +++ ) forming methemoglobin (metHb).

21. Formation of methemoglobin methemoglobin is a type of hemoglobin that contain ferric iron rather than ferrous. (oxidation of iron). Met-hemoglobin is useless as O2 carrier. A small amount of met-hemoglobin is present in the blood of normal individuals =0.3 g/dl OR 1.7% of total Hb. Increased met-hemoglobin result in met-hemoglobinemia. Causes : Oxidant drugs ex. Anti- malaria{ chloroquine and primaquine }or antibacterial drugs or certain food as fava- beans that cause oxidation of iron. The presence of NADH-met-hemoglobin reductase system convert Fe +3 to Fe +2. congenital deficiency of this enzyme result in met-hemoglobinemia. Formation of methemoglobin methemoglobin is a type of hemoglobin that contain ferric iron rather than ferrous. (oxidation of iron). Met-hemoglobin is useless as O2 carrier. A small amount of met-hemoglobin is present in the blood of normal individuals =0.3 g/dl OR 1.7% of total Hb. Increased met-hemoglobin result in met-hemoglobinemia. Causes : Oxidant drugs ex. Anti- malaria{ chloroquine and primaquine }or antibacterial drugs or certain food as fava- beans that cause oxidation of iron. The presence of NADH-met-hemoglobin reductase system convert Fe +3 to Fe +2. congenital deficiency of this enzyme result in met-hemoglobinemia.

23. Hemoglobin Position on β polypeptide chain of Hb 1 2 3 4 5 * 6 --------------------- 146 HbA (normal) HbS(sickle cell) Glutamic acid Valine The erythrocyte contain an abnormal type of Hb called HbS. When this Hb is exposed to hypoxia, it precipitates into long crystals inside the erythrocyte which give it the appearance of a sickle rather than a biconcave disc.

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31. Jaundice (Icterus) Is ayellowish coloration of the skin, mucous membrane & sclera of the eyes by bile pigments;associated with hyperbilirubinemia (increase in the concentration of bilirubin in the plasma & interstitial spaces). The normal total plasma bilirubin concentration is 0.2-0.8mg/dl(0.5 mg/dl), jaundice is usually detected clinically when the total plasma bilirubin level exceed 2mg/dl. Types of jaundice: 1- Pre-hepatic (hemolytic jaundice) ex. Sickle cell anemia, hereditary spherocytosis, hemolytic disease of new born(ABO or Rh incompatibility). 2-Hepatic jaundice: Damaged liver cells ex. Viral hepatitis. 3-Post-hepatic jaundice (obstructive): Gall stones, carcinoma of the head of the pancreas.

33. Types of Anemias 1- Blood loss anemia:Iron deficiency 2- Aplastic anemia : Pancytopenia. 3- Megaloblastic anemia(B12,Folic,IF). 4- Hemolytic anemias: A.Hereditary spherocytosis. 5-sickle cell anemia. 6- Thalassemia (cooleys anemia) 7-Erythroblastosis fetalis (HDN).

37. Effects of anemia on function of the circulatory system 1-Viscosity fall as low as 1.5 OF H2O. 2-Resistance decreases. 3- Cardiac output increases. 4-Hypoxia causes dilation of the peripheral tissue blood vessels increasing cardiac output more giving normal quantity of O2 to the tissues. 5-During exercise there is increasing tissue demand for oxygen, extreme tissue hypoxia result in acute cardiac failure

39. Effect of polycythemia on the circulatory system 1- viscosity increases. 2-Blood flow in peripheral vessels decreases. 3- Rate of venous return to the heart decreases. But 4- Blood volume increases, this increase venous return (cardiac filling & cardiac output remains normal) these 2 factors(3 & 4) neutralize each other. Arterial blood pressure is normal, but in 1/3 is elevated. The color of the skin is bluish (cyanotic),because the color of deoxygenated Hb masks the red color of oxygenated Hb.