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INTRODUCTION

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OBJECTIVES

After studying this chapter, you should be able to:

  • Understand the concept of stem cells and their importance.

  • Explain why red blood cells are reliant on glucose for energy.

  • Describe the roles of erythropoietin, thrombopoietin, and other cytokines in the production of red blood cells and platelets.

  • Describe the enzyme systems that protect heme iron from oxidation and reduce methemoglobin.

  • Identify the major components of the erythrocyte cytoskeleton.

  • Summarize the causes of the major disorders affecting red blood cells.

  • Describe the major function of erythrocyte band 3 protein.

  • Know the biochemical bases of the ABO blood group substances.

  • List the major components contained in the dense granules and α-granules in platelets.

  • Describe the molecular bases of immune thrombocytopenic purpura and von Willebrand disease.

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BIOMEDICAL IMPORTANCE

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The evolution of a diverse array of freely circulating blood cells was critical to the development of animal life. The packaging of hemoglobin and carbonic anhydrase inside specialized cells called erythrocytes greatly amplified the capacity of circulating blood to carry oxygen to and carbon dioxide away from peripheral tissues. Anemia, a deficiency in the level of circulating hemoglobin (<120-130 g/L), compromises health by reducing the ability of the blood to supply tissues with adequate levels of oxygen. Anemia can arise from a variety of causes that include genetic abnormalities (eg, sickle cell trait, pernicious anemia), excessive bleeding, insufficiencies of dietary iron or vitamin B12, or the lysis of red blood cells by invading pathogens (eg, malaria). Platelets help staunch the outflow of blood from damaged tissues. Deficits in platelet number or function increase a patient’s vulnerability to hemorrhage by reducing the speed of formation and structural integrity of protective clots. As is the case for anemia, a low platelet count, known as thrombocytopenia, can be triggered by a range of factors that include bacterial infection, sulfa-containing antibiotics and certain other medications, or autoimmune reactions such as idiopathic thrombocytopenic purpura. Other pathophysiologic syndromes, such as von Willebrand disease and Glanzmann thrombasthenia, are caused by genetic mutations that impair platelet adherence or aggregation rather than their abundance.

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RED BLOOD CELLS DERIVE FROM HEMATOPOIETIC STEM CELLS

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Both red blood cells and platelets turn over at a relatively high rate. Hence, replacements are constantly being produced from precursor stem cells. Stem cells possess a unique capacity both to produce unaltered daughter cells (self-renewal) and to generate a diverse range of specialized cell types (potency). Broadly speaking, stem cells therefore can be considered to exist in an undifferentiated state. Stem cells may be totipotent (capable of producing all the cells in an organism), pluripotent (able to differentiate into cells of any of the three germ layers), multipotent (produce only cells of a closely related family) or unipotent (produce only one type of cell). Stem cells are also classified as embryonic or adult. Since adult stem cells are more limited in their capacity to differentiate, intensive efforts are being directed toward overcoming this restriction.

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Differentiation of hematopoietic stem cells is regulated by a set of secreted glycoproteins called cytokines. Stem cell factor and several colony stimulating factors collaborate ...

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