Blood and Vascular Diseases Dr Stephen Lam Department of Pharmacology College of Medicine East Room 761 413 5928 sclam uic edu Anemias 1 Body Contents of Iron Structure of Hemoglobin 2 The Heme Group Iron Absorption Ferritin a large protein for iron storage Hemosiderin aggregated ferritin Iron storage sites hepatocytes reticuloendothelial system muscle minor Iron absorption duodenum and jejunum Ferrous Fe2 Ferric Fe3 Transferrin iron transport 3 Pathway of Iron Absorption Daily Iron Intake and Absorption 4 Iron Deficiency Dietary intake of iron not adequate to meet normal requirements Conditions producing an increased requirements of iron because of iron loss Interference of iron absorption Therapy for Iron Deficiency Oral therapy Drug of Choice ferrous sulfate administered under fasting Side effects heart burn nausea upper gastric discomfort constipation diarrhea antidote deferoxamine Parenteral therapy Drug iron dextran injection im or iv Side effects im long term discomfort local discoloration of skin malignant changes iv serious anaphylactic reactions 5 Vitamin B12 and Folate Metabolism Vitamin B12 and Folate Metabolism 6 Hematological Responses of Vitamin B12 and Folate Therapy Vitamin B12 Cobalamin 7 Vitamin B12 Absorption Release from food Binds to intrinsic factor Absorbed through ileum Transport to blood Binds transcobalamin II Target tissue bone marrow liver Intrinsic Factor Vitamin B12 Complex 8 Vitamin B12 Deficiency Gastric achlorhydria and decreased intrinsic factor due to gastric atrophy and gastric surgery Panacreatic disorders Antibodies to intrinsic factor vitamin B12 complex Bacterial overgrowth and intestinal parasites prevent vitamin B12 from reaching the ileum Damaged ileal mucosa Congenital defects in transcobalamin II Vitamin B12 Therapy Oral preparations to supplement deficient diet to prevent vitamin B12 deficiency Cyanocobalamin injection given by intramuscular and subcutaneous routes never intravenously 9 Folate pteroylglutamic acid Folate Absorption Release from food Hydrolyzed reduced and methylated Absorbed through duodenum and jejunum Transport to blood folate binding protein Target tissues Liver to bile reabsorption enterohepatic cycle 10 Folate Deficiency Malnutrition Acute and chronic alcoholism Defect in folate enterohepatic cycle Small intestinal diseases Defects in folate binding protein Vitamin B12 deficiency Folate Therapy Oral preparations Folic acid drug of choice Folic acid injection Problems with absorption Do NOT use folic acid to treat vitamin B12 deficiency 11 Hematopoiesis Hematopoietic and Lymphopoietic Growth Factors Glycoproteins produced by marrow cells and peripheral tissues Active at low concentrations Act on more than one committed stem cells Synergism Networking Act on several points during cell proliferation and differentiation 12 Erythropoietin Stimulates proliferation maturation and hemoglobin formation by CFU E Stimulates the release of reticulocytes Acts synergistically with IL 3 and GM CSF A glycoprotein 34 kDa Binds to the erythropoietin receptor and activates signal transduction processes Produced primarily by the kidney Deficiency in anephric patients Erythropoietin Therapy Recombinant erythropoietin epoetin alpha Administered parenterally half life 10 h 50 100 units kg 3 times weekly for patients with chronic renal failure Titrate dosage by hematocrit measurements No significant allergic reactions Mild adverse effects lower dosage Iron vitamin B12 folate deficiency 13 Myeloid Growth Factors Colony stimulating Factors Glycoproteins that stimulate the proliferation of one or more myeloid cell lines Recombinant GM CSF G CSF IL 3 M CSF CSF 1 SCF thrombopoietin are available GM CSF and G CSF are used for treatments of neutropenia Administered subcutaneously or intravenously Short half life Adverse effects bone pain malaise flulike symptoms more seriously vessel defects 14
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