RBCs Hemoglobin VB12 PDF

# Red Blood Cells ## Number: - 5 million / mm3 in adult males - 4.5 million / mm in adult females - Newly born infant more than 5 million ## Shape: Circular, biconcave, non-nucleated discs ## Size: - 90-95 cubic micrometers in volume - Mean diameter 7.8 microns - 2.5 micrometers in thickness at...

# Red Blood Cells ## Number: - 5 million / mm3 in adult males - 4.5 million / mm in adult females - Newly born infant more than 5 million ## Shape: Circular, biconcave, non-nucleated discs ## Size: - 90-95 cubic micrometers in volume - Mean diameter 7.8 microns - 2.5 micrometers in thickness at the thickest point - 1 micrometer at center ## Biconcavity: Increases the surface area and allows the RBC to pass through narrow capillaries without rupture ## Areas of the Body That Produce Red Blood Cells: - **Origin:** site of formation - **Fetus:** - Early trimester yolk sac produce nucleated RBC - During the middle trimester of gestation, the liver, spleen and LN produce RBCs - During the last month or so of gestation and after birth RBCs are produced exclusively in the bone marrow - **Children:** bone marrow of all bones - **Adult by age 20yrs:** bone marrow of flat bones - (membranous bones) vertebrae, ribs, skull, sternum and ilia ## Functions of Red Blood Cells: - RBCs are responsible for most of the acid-base buffering power of whole blood - Transport large amounts of CO2 in the form of bicarbonate ion (HCO3-) from the tissues to the lungs, where it is reconverted to CO2 and expelled as a body waste product - If hemoglobin formation inside RBCs is deficient, the percentage of hemoglobin in the cells may fall, and the volume of the RBC may also decrease because of diminished hemoglobin to fill the cell # Genesis of All Blood Cells: - Blood cells begin their lives in the bone marrow from a single type of cell called the pluripotential hematopoietic stem cell, from which all the cells of the circulating blood are eventually derived. # Genesis of RBCs (Erythropoiesis) - Genesis of RBCs (erythropoiesis) and other blood cells needs: - Pluripotential Hematopoietic Stem Cells - Growth Inducers - Differentiation Inducers # Factors Affecting Erythropoiesis: ## 1. Hypoxia: - Tissue oxygenation is the most essential regulator of red blood cell production: how? - **Hypoxia** is the primary stimulus of erythropoiesis - It is due to the following factors: - Low blood volume - Anemia - Low hemoglobin - Poor blood flow - Pulmonary disease - Hypoxia leads to erythropoietin release from the kidney (90%) liver (10%) - Erythropoietin stimulates production of proerythroblast from hematopoietic stem cell ## 2. Hormones: - Androgens increase erythropoiesis by direct effect and indirect effect - Thyroid hormones, cortisone, stimulate general metabolism of all cells of the body including bone marrow cells ## 3. Diets: - Proteins formation of (globin part) - Vitamins (Vit B12, folic acid) (RBCs maturation) - Metals (Iron, copper, cobalt) # Genesis of RBCs: - Proerythroblast - Basophil erythroblast - Polychromatophil erythroblast - Orthochromatic erythroblast - Reticulocyte - Erythrocytes # Hemoglobin: - It is a protein inside the RBCs that carries 02 from the lungs to the tissues and CO2 from tissues to the lungs. - Synthesis of hemoglobin begins in the proerythroblasts and continues even into the reticulocyte stage of the RBCs - **HB Content:** average 15 gram / 100 ml, normal range 14-16g/100ml ## Structure: - Each HB molecule consists of 4 subunits. - Each subunit composed of heam group + polypeptide chain of amino acids (globin portion). - **Heam Group:** (ferrous (Fe++) iron + protoporphyrine ring) ## Hemoglobin Structure: - 2 alpha & 2 beta # Maturation of Red Blood Cells Requires Vitamin B12 (Cyanocobalamin) and Folic Acid: - These two vitamins are important for final maturation of the RBCs - Both of these vitamins are essential for the synthesis of DNA # Stages of Differentiation of Red Blood Cell: 1. Pluripotent hematopoietic stem cell in the bone marrow - In presence of **(erythropoietin)** 2. Pro erythroblast 3. Basophil erythroblast 4. Polychromatophil erythroblast 5. Orthochromatic erythroblast 6. Reticulocyte (1-2 days) 7. Mature erythrocyte # Function of RBCs: 1. Function of membrane to enclose hemoglobin 2. Function of contents: - Hemoglobin carry 02 and CO2 and act as a strong buffer system - Carbonic anhydrase enzyme catalyze the reversible reaction between CO2 and H2O to form carbonic acid # HB Types: - Depending on amino acid composition of polypeptide chains. ## Physiological types: 1. **HB-A:** Adult HB makes 98% of normal HB. Consists of 2 alpha 2 beta 2. **HB-F:** Present before birth. Consists of 2 alpha 2 gamma. 3. **HB-A2:** Contributes to about 2% of normal HB. Consists of 2 alpha 2 sigma. ## Pathological Types: 1. **HB-S:** 2 abnormal B chains. When the RBC expose to low 02 it leads to precipitation of HB inside the RBCs making them sickle in shape and leads to sickle cell anemia. 2. **HB-H:** - No alpha chain 4 B chains (alpha thalassemia) - No B chains 4 ALPHA (B thalassemia) # Forms of Hb (Reactions): - Depended mainly on the heam portion of hemoglobin and divided into: ## Normal Forms: 1. **Oxy HB:** HB + 02 each HB molecule attached to 4 O2 molecules. 2. **Carb amino HB:** In which CO2 attached to protein part of HB (Hb + CO2) ## Abnormal Forms: 1. **Carboxy HB:** HB+CO (carbon monoxide) compete O2 CHERRY RED. 2. **Met HB:** HB - **STRONG OXIDATION:** Fe++ to Fe+++ - Met Hb is brown color - Enzyme NADH methemoglubin reductase maintain iron in FERRUS state. - Hereditary methemoglubin # Hemoglobin: (Hem + Globin) 1. **Globin:** Amino acids used for protein synthesis 2. **Heam:** Fe++ used in HB synthesis or **bilirubin** unconjugated in the plasma. 3. **Liver:** Conjugated bilirubin. 4. **Intestine:** Stercobilinogen - 1/3 reabsorbed again - 2/3 pass with stool # Iron Metabolism: - Daily intake 10-20 mg. - The amount absorbed is equal only to the losses. - Daily loss: 1mg in males, 2mg in females. - Daily needs: 1mg in males, 2mg in females. - Thus, the amount of iron absorbed is normally about 3-10% of the amount ingested. - Most of the iron in the diet is in the ferric (Fe3+) form, whereas it is the ferrous (Fe2+) form that is absorbed # Absorption, Transport, Utilization, and Storage: ## Absorption: - Fe+++ is reduced to Fe++ by vit C and HCL in food - Fe++ combine with Apo transferrin in bile to form transferrin - Transferrin then releases its Fe++ to the blood. ## Transport: - Fe++ in the blood combined with apotransferrin in the blood to form transferrin. - Transferrin transports iron to its utilization and storage sites. ## Regulation of total body Iron: - Total iron is regulated by alteration of intestinal absorption rate because there is no iron excretion. - No more Apo transferrin in the plasma to combine with Fe++. - Decrease formation of apotransferrin in the liver leads to a decrease of its level in the bile and plasma. ## Excess iron: - Excess iron is transported by transferrin for storage in the liver. - Excess iron then combines with Apo ferritin to form ferritin which releases its Fe++ back to the plasma where the body is needed. ## So..... - Metabolic pathway of iron is a closed loop in which little iron is lost consequently little iron is needed. # Heamosiderosis: - Heamosiderosis is a disease when excess amount of iron is stored in an extremely insoluble form called **hemosiderin**, leading to damage to the storing cells # Vitamin B12 (Cyanocobalamin) - (Extrinsic factor)(Anti pernicious anemia factor) - Normal daily requirement: 1-2 ug / day - Liver stores about 3000 ug (3mg) of vit B12 which equals to the body's needs for 5 years. - Manifestation of vit B12 appear after about 5 years of deficient intake. ## Absorption: - Vit B12 in food + glycoprotein secreted by the parietal cells in gastric mucosa **(intrinsic factor)** (Vit B12-IF complex) bind to receptors in terminal ileum, enter the intestinal cells, and are released to the blood. ## Transport: - Transcobalamin to liver and bone marrow ## Utilization: - By bone marrow # Absorption of Vitamin B12: - Diagram showcasing the process of Vitamin B12 absorption.