Summary: Episode 33: Listen to this science content review and learn its format for your own audio notes. Hematopoietic Agents Notice how these show notes are arranged: a list review of hematopoietic agents (that cause red blood cell production), core text review, and an audio version. This fits into the Mastermind Study System after you have attended lecture, read the material once, and are reviewing your notes and organizing them for the first time: MCAT Study Notes: 1. Growth Factors 2. Erythropoietin 3. GCSF – granulocyte colony stimulating factor 4. GMCSF – granulocyte/macrophage colony stimulating factor 5. Thrombopoietin 6. Folic Acid 7. Iron 8. Ferrous Sulfate 9. Iron Dextran 10. Desferoxamine 11. Cobalamin – Vit B12 Growth Factors General Initiation – Stem cell factor, IL-3, and GMCSF stimulate marrow stem cells to proliferate and form burst forming units and colony-forming units Differentiation – stimulated by growth factors for each of the major cell lines 1. RBCs – Erythropoietin 2. Platelets – Thrombopoietin 3. Granulocytes – Granulocyte colony-stimulating factor (G-CSF) 4. Monocytes/Macrophages – Monocyte/Macrophage stimulating factor (CSF-1 or M-CSF) Erythropoietin glycoprotein produced in the kidney acts synergistically with IL-3 and GMCSF Hypoxia – stimulates the synthesis and secretion of erythropoietin (adenosine A2-receptor, cAMP) Causes 1. increase in the rate of mitosis of BFU-E and CFU-E 2. increase in release of reticulocytes from the marrow 3. induces hemoglobin formation requires adequate supply of iron Therapeutic uses 1) progressive or chronic renal failure 2) anemia of patients with AIDS being treated with AZT 3) Anemia caused by cancer chemo 4) Preoperatively to permit storage of larger volumes of bloods 5) Anemia in myelodysplasia Side Effects 1) hypertension and seizures Myeloid Growth Factors GMCSF, GCSF, IL-3, CSF-1, M-CSF Clinical investigations ongoing for: 1) nonneoplastic diseases or malignancies that interfere with marrow production 2) neutropenia caused by chemo 3) augmentation of host defenses against infection 4) harvesting of peripheral blood stem cells Thrombopoietin preliminary clinical studies now improves the platelet count following chemo induced thrombocytopenia IRON General absence of iron – microcytic, hypochromic anemia essential forms of iron – hemoglobin, myoglobin, cytochromes, and nonheme iron-dependent enzymes Absorption – almost exclusively in the duodenum and jejunum Ø enterocyte regulates the absorption based on need Ø DCT-1 (divalent cation transporter-1) involved in transport of iron from the gut lumen to the enterocyte increased in iron deficiency Ø HFE control enterocyte iron and DCP-1 levels defective in hereditary hemochromatosis Ø Normal absorption – 1 mg/day in male, 1.4 mg/day in female Transport – bound in blood to transferrin Excess storage Ø RE system and hepatocytes as ferritin or hemosiderin Body store of iron is highly conserved – no active excretion of iron Pharmacology Oral Ferrous Sulfate – treatment of choice for iron deficiency Ø remember dosage based on amount of elemental iron content Ascorbic Acid – increases the absorption of iron by reducing the iron from ferric to the ferrous form. Optimal absorption occurs when dosage occurs in a fasting state Side Effects Ø GI distress, heartburn, nausea, upper abdominal pain Iron poisoning rare in adults – due to “mucosal block” children do not have mucosal block 4 distinct phases of acute iron toxicity 1) vomiting and hemorrhagic gastritis followed by hypotension and lethargy 2) up to 12 hr quiescent period – looks improved 3) 12-24 horus post-ingestion – life-threatening events Ø coma Ø pulmonary ede[...]
