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Blood Facts ERYTHROPOIESIS
ERYTHROPOIESIS In embryo the 1st RBCs arise in the yolk sac Liver assumes major role in RBC formation during 2nd month of intrauterine life During 5th month the spleen is dominant producer, but this activity rapidly subsides Erythropoiesis takes place in red bone marrow about 5th month In certain blood diseases and following massive hemorrhage, blood formation may revert back to the liver and spleen At birth all bones are filled with red marrow Red marrow of long bones is gradually replaced by fatty, yellow marrow Becomes more fat laden in elderly - explains their difficulty in regenerating lost blood In adult, red marrow is limited to bones of skull (diploe), clavicles, vertebrae, sternum, ribs, pelvis and proximal ends of humerus and femur RBCs are formed in the red bone marrow from nucleated cells known as hemocytoblasts or stem cells Stem cells go through several stages of development during which nucleus becomes smaller and disappears as hemoglobin content increases Also lose organelles (mitochondria) Hemocytoblast -- rubriblast -- prorubricyte -- rubricyte (begins to synthesize hemoglobin) -- metarubricyte (maximum hemoglobin synthesis) -- reticulocyte 3-5 days from hemocytoblast to reticulocyte Newly formed RBCs when they leave the bone marrow and enter the blood are called reticulocytes Contain a netlike reticulum that represents endoplasmic reticulum Lose nuclei by extrusion Become erythrocytes within 1 - 2 days after release from bone marrow Approximately 0.5 to 1.5% of RBCs in normal blood are reticulocytes A count less than 0.5% indicates a slowdown in RBC formation Due to nutritional or pernicious anemia or to kidney disease and too little erythropoietin A count higher than 1.5% indicates an acceleration in RBC formation For example, following treatment for anemia, oxygen deficiency or cancer in bone marrow-also occurs in hemolytic anemia For complete maturation of RBCs vitamin B12 is necessary (also folic acid which is used in synthesis of DNA) Intrinsic factor, secreted by parietal cells of stomach, promotes absorption of vitamin B12 in ileum Vitamin B12 is stored in liver, liberated as needed, and is carried in blood to bone marrow where it functions to complete maturation of RBCs Proteins, several vitamins, folic acid, copper, cobalt and iron are essential for RBC formation Reticuloendothelial cells (macrophages in liver, spleen (especially) and bone marrow phagocytose RBCs Spleen is “red blood cell graveyard” Estimate that 1/15 of RBCs are removed from circulation each day Hemoglobin is broken down into heme and globin Approximately 65% of body’s Fe supply (approx 4,000 mg) is in hemoglobin Heme is decomposed into hemosiderin (contains Fe) and biliverdin (green) Biliverdin is reduced to bilirubin Bilirubin is carried by plasma to liver where it is excreted in bile into intestine where it is metabolized to urobilinogen. Most urobilinogen leaves in feces as brown pigment, stercobilin Because free Fe is toxic it is stored inside cells as protein-bound complexes such as ferritin and hemosiderin Hemosiderin (Fe) is stored in liver Fe is combined with a transport protein, transferrin, and carried to red bone marrow where most is used over again in RBC synthesis Small amounts of Fe are lost each day in feces, urine and perspiration Average daily loss is 0.9 mg in men and 1.7 mg in women (more due to menstrual losses) About 2 million RBCs are produced each second-this rate can be increased up to 10X The rate of production speeds up if the number of RBCs decreases or if tissue hypoxia (oxygen deficiency) develops (at high altitude or in chronic lung diseases) These conditions stimulate the kidneys to release an enzyme, renal erythropoietic factor, that converts a plasma protein into the hormone erythropoietin which stimulates the bone marrow to produce RBCs Erythropoietin is also released from the liver but to a lesser extent The kidneys fail to produce erythropoietin in renal dialysis patients-as a result they have have half the RBC count of a normal person and are treated with recombinant (genetically engineered erythropoietin At high altitude the concentration of erythropoietin in the blood rises and the rate of RBC formation rises sharply after 2 days to a maximum in 5 days Fluosol - DA is a blood (hemoglobin) substitute Slippery, white liquid with a very high capacity for 02 Used in CO poisoning, sickle-cell anemia, strokes, heart attacks and burns
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