• Document: Blood cells, coagulation.
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Blood cells, coagulation. Teacher: Magdalena Gibas MD PhD Coll. Anatomicum, Święcicki Street no. 6, Dept. of Physiology I. Blood Cell Production A. Hemopoiesis - the production of formed elements of the blood. 1. Hemopoietic cells (those which produce blood) first appear in the yolk sac of the 2-week embryo. The highly cellular bone marrow becomes an active blood making site from about 20 weeks gestation and gradually increases its activity until it becomes the major site of production about 10 weeks later. 2. Beyond infancy, almost all formed elements are produced by myeloid hemopoiesis in the red bone marrow, and lymphocytes are produced in lymphoid organs by lymphoid hemopoiesis. 3. The pluripotential stem cell is defined as the precursor cell from which all erythrocytes, leukocytes, and megakaryocytes are derived (i.e. all blood cells have a common cell line of origin). B. Erythrocyte Production 1. Erythropoiesis produces erythrocytes at the rate of 2.5 million cells per second. 2. The proerythroblast (a committed cell) receives erythropoietin, which stimulates it to become an erythroblast. a. Erythropoietin is a glycoprotein. It is inactivated by the liver and excreted in the urine. It is now established that erythropoietin is formed within the kidney by the action of a renal erythropoietic factor erythrogenin on plasma protein, erythropoietinogen. b. Erythrogenin is present in the juxtaglomerular cells of the kidneys and is released into the blood in response to hypoxia in the renal arterial blood supply. 3. Erythroblasts multiply and synthesize hemoglobin, their nuclei degenerate, and the cells are then called reticulocytes. 4. Once reticulocytes leave the bone marrow and the remaining ER disappears, they are considered mature erythrocytes. 5. RBC (Red Blood Cell) count is managed by negative feedback. Hypoxia in tissues, or hypoxemia, triggers secretion of more erythropoietin from the kidneys, and red blood cell production increases. 6. One of the nutritional requirements for erythropoiesis is iron, which can only be absorbed in its ferrous (Fe2+) state in the small intestine. Ferrous ions bind to gastroferritin produced by the stomach and travel to the small intestine. They are absorbed into the blood and bound to a plasma protein called transferrin. 7. Transferrin carries the iron to bone marrow, liver, and other tissues. Bone marrow uses the iron to make hemoglobin; muscle cells use it for myoglobin; and other cells use it to make cytochromes. 8. The liver stores excess iron in the form of ferritin and hemosiderin. 9. Other nutrient requirements include folic acid and vitamin B12 for DNA synthesis, and copper and vitamin C that serve as cofactors for some of the enzymes that synthesize hemoglobin. 10. Various other factors can affect the rate of erythropoiesis by influencing erythropoietin production. Thyroid hormones, thyroid-stimulating hormone, adrenal cortical steroids adrenocorticotrophic hormone, and human growth hormone (HGH) all promote erythropoietin formation. C. Leukocyte Production 1. Leukopoiesis is the production of white blood cells; it begins when hemocytoblasts differentiate into three types of cells: B progenitors, T progenitors, or granulocyte- macrophage colony-forming units. 2. A variety of hormones stimulate the production of specific types of leukocytes in response to specific needs of the body. 3. Granulocytes and monocytes are stored in red bone marrow and released when needed. Lymphocytes begin developing in bone marrow, then migrate to lymphoid tissue to mature. D. Platelet Production 1. Platelet production (thrombopoiesis) begins when a hemocytoblast becomes a megakaryoblast. In response to thrombopoietin, the megakaryoblast develops into a huge megakaryocytic. Some of the megakaryocytic fragments become functional platelets. II. Erythrocytes A. Form and Function 1. The biconcave shape increases the cell's surface area and facilitates diffusion of O2 and CO2 into or out of the cell; the lack of nuclei and organelles contribute to increased haemoglobin content. 2. Their function is to: a. carry respiratory gases b. work as a buffer (Remember respiration? See biochemistry!!!) 2. Normal erythrocytes must be very flexible. They become deformed when flowing through capillaries and narrow slits in the spleen. All red blood cells have a limited life span of around 100 to 120 days. Aged RBC's are removed by the spleen, liver and the bone marrow. 3. Normal adult ranges: men 4.5 – 6.0 T/L; women 3.8 – 5.2 T/L B. Hemoglobin 1. Hemoglobin consists of four protein chains called globins. Two are alpha chains, and two are beta chains. Each chain is conjugated with a nonprotein heme group that binds oxygen to a ferrous ion at its center. 2. Carbon dioxide is transported bound to the globin portion of the hemoglobin. 3. Hemoglobin exists in several forms that differ in their structure and oxygen-carrying capacity. Fetal hemoglobin has a higher oxygen-binding capacity than adult hemoglobin, and thus can extract oxygen from the mother's blood. 4. The hemoglobin concentration is 13–17

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