Bone Marrow & Hematopoiesis

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julieaburch
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83138
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Bone Marrow & Hematopoiesis
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2011-05-09 11:45:33
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Bone Marrow Hematopoiesis
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Bone Marrow & Hematopoiesis
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  1. These give rise to all lines of mature blood cells. They are self-renewing, cannot be specifically identified, and are detected by long-term colony growth or reconsitution of lethally irradiated animals.
    Pluripotent (Totipotent) Stem Cells
  2. About how many days does it take for maturation from stem cell to mature blood cell?
    About 10-14 days
  3. Where can Pluripotent Stem Cells be found? How can they be collected, and what are they used in?
    • Peripheral Blood and Cord Blood
    • Apheresis
    • Used in bone marrow transplantation
  4. What do stem cells give rise to? This is a progressive commitment to a single lineage, and is progressively more differentiated. These are more mitotically active than stem cells, but have less capacity for self-renewal.
    Committed Progenitor Cells
  5. What is the initial division of Hematopoietic Stem Cells (2)?
    • Common Myeloid Progenitor (CMP): give rise to all types of myeloid cells
    • Common Lymphoid Progenitor (CLP): gives rise to lymphocytes (both B-cells and T-cells)
  6. What cells do Common Myeloid Progenitors (CMPs) give rise to?
    • Granulocytes
    • Erythrocytes
    • Monocytes
    • Megakaryocytes
  7. What stage in the cell cyle are the majority of Pluripotent (Totipotent) Stem Cells found in?
    G0 phase
  8. In the first trimester, where does Hematopoiesis primarily take place?
    • Yolk Sac
    • Aorta-Gonadal-Mesoderm (AGM) Area
  9. In the second trimester, where does Hematopoiesis primarily take place?
    Predominantly in liver; less so in spleen
  10. In the third trimester, where does Hematopoiesis primarily take place?
    Bone Marrow hematopoiesis becomes predominant
  11. Post-natal, where does Hematopoiesis take place?
    Bone Marrow is only normal site
  12. These are proteins or glycoproteins that regulate hematopoiesis. They act on specific transmembrane receptors to activate intracellular signaling pathways. What is the end result?
    • Growth Factors
    • Result in DNA Transcription
  13. Many of the Growth Factor receptors are of what type? What are two of the major signaling pathways involved?
    • Protein Tyrosine Kinases
    • JAK & STAT
  14. What happens when a growth factor binds to its receptor?
    • Presence of the growth factor causes the growth factor receptors (which are normally separate and inactive) to dimerize; the JAK protein (a tyrosine kinase) becomes activated and phosphorylates the growth factor receptor; the STAT proteins become phosphorylated, form dimers and move to the nucleus where the dimer initiates DNA transcription.
    • There may be several levels of tyrosine kinases that get activated sequentially
  15. Hematopoietic Growth Factors are mostly produced in the bone marrow by what three types of cells? What two are produced outside of the bone marrow, and where are they produced?
    • Macrophages, T-cells, and Adventitial Cells
    • Erythropoietin: produced primarily in kidneys; small amount in liver
    • Thrombopoietin: produced primarily in liver; some in spleen and bone marrow
  16. What are the 4 main types of Growth Factors?
    • **Granulocyte Colony Stimulating Factor (G-CSF): Granulocytes
    • Granulocyte - Macrophage Colony Stimulating Factor (GM-CSF)
    • **Erythropoietin (EPO): Erythrocytes
    • **Thrombopoietin (TPO): Platelets
  17. Granulocyte Colony Stimulating Factor (G-CSF) is produced in the bone marrow by macrophages, T-cells, fibroblasts, and/or endothelial cells. They stimulate the production of granulocytes, and the function of mature cells. What are the two clinically available G-CSFs, and what are the therapeutic uses for them?
    • Neupogen & Neulasta
    • Granulocytopenia due to chemotherapy & other causes
    • Bone marrow transplantation
  18. The main site of production for Erythropoietin is where? What stimulates production? What is the clinically available EPO, and what are its clinical uses?
    • Kidneys
    • Production stimulated by renal ischemia or hypoxia
    • Procrit
    • Clinical Uses: anemia of renal failure, anemia of chronic disease, anemia of AIDS, & anemia of cancer chemotherapy
  19. Where is Thrombopoietin primarily produced? What two things does Thrombopoietin stimulate? What are the two clinically available TPOs, and what are their possible uses?
    • Liver
    • Stimulates megakaryocyte differentiation & platelet production
    • Promacta & Nplate
    • Possible Uses: thrombocytopenia, cancer chemotherapy, bone marrow transplantation
  20. What are the five granulocyte precursors?
    • Promyelocyte
    • Myelocyte (neutrophilic, eosinophilic, basophilic)
    • Metamyelocyte
    • Band Neutrophil
    • Segmented Neutrophil
  21. Identify the stage of Granulocyte Maturation:
    Promyelocyte (1st Stage)
  22. Identify the stage of Granulocyte Maturation:
    Neutrophilic Myelocyte (2nd Stage)
  23. Identify the Stage of Granulocyte Maturation:
    Neutrophilic Metamyelocyte (3rd Stage)
  24. Identify the stage of Granulocyte Maturation:
    Neutrophilic Band (4th Stage)
  25. Identify the stage of Granulocyte Maturation:
    Segmented Neutrophil (5th Stage)
  26. What types of neutrophils are normally seen in peripheral blood? What types should not be seen in normal blood smears?
    • Segmented & band neutrophils normal in peripheral blood; metamyelocytes occasionally seen with severe stress
    • Myelocytes and earlier forms should not be seen
  27. What are the five stages of Erythrocyte development?
    • Proerythroblast
    • Basopilic Erythroblast
    • Polychromatophilic Erythroblast
    • Orthochromatophilic Erythroblast
    • Reticulocyte
  28. Identify the stage of Erythrocyte development:
    Proerythroblast (1st Stage)
  29. Identify the stage of Erythrocyte development:
    Basophilic Erythroblast (2nd Stage)
  30. Identify the stage of Erythrocyte development:
    Polychromatophilic Erythroblast (3rd Stage)
  31. Identify the stage of Erythrocyte development:
    Orthochromic Erythroblast (4th Stage)
  32. Identify the stage of Erythrocyte development:
    Reticulocyte (5th Stage)
  33. What cell type are Platelets produced from? How does this occur?
    • Megakaryocytes
    • First stage: megakaryblast
    • Undergoes endomitosis 32-64n DNA content
    • Mature megakaryocyte -- particles of cytoplasm break off into sinuses as platelets (thrombocytes)
  34. Identify the cell below. What does it produce?
    • Megakaryocyte
    • Particles of cytoplasm break off into sinuses as platelets (thrombocytes)
  35. When nucleated RBCs and granulocyte precursors are found in peripheral blood, this is indicative of a space-occupying bone lesion in bone marrow. What is this called? This indicates abnormality in bone marrow. What are four potential problems, and what should be done?
    • Leukoerythroblastic Reaction
    • Fibrosis, Metastatic Neoplasm, Granulomas, Osteosclerosis
    • Indication for Bone Marrow Biopsy
  36. What type of growth factor are Neupogen and Neulasta? What are their clinical uses? How are they administered clinically? What are they contraindicated for?
    G-CSF

    Used to treat Neutopenia --> stimulates the bone marrow to increase production of neutrophils. Causes of neutropenia include chemotherapy and bone marrow transplantation

    Administered by injection

    • The most commonly observed adverse effect is mild-to-moderate bone pain after repeated administration and local skin reactions at the site of
    • injection. Persons with sickle cell disorders may suffer sickle cell crisis after receiving Neupogen. Other adverse effects include spleen rupture, serious allergic reactions (including a rash over the whole body,
    • shortness of breath, wheezing, dizziness, swelling around the mouth or eyes, fast pulse, and sweating), alveolar hemorrhage, acute respiratory distress syndrome (ARDS), and hemoptysis.

    Should not be used in patients with known hypersensitivity to E. coli-derived proteins
  37. What type of clinical growth factor is Procrit? What is its clinical indications? How can it be administered? What are the potential side effects?
    Erythropoietin (epoitin alpha)

    Used to treat anemia of renal failure, anemia of chronic disease, anemia of AIDS, & anemia of cancer chemotherapy

    Administered through injection

    • Common side effects include high blood pressure, headache, joint-pain and clotting at the injection site. Rare cases of stinging at the injection site, skin rash and flu-like symptoms (joint and muscle pain) have occurred within a few hours following administration. More serious side effects, including allergic reactions,
    • seizures and thrombotic events (e.g., heart attacks, strokes, and pulmonary embolism) rarely occur. Chronic self-administration of the drug by two individuals caused increases in blood hemoglobin and hematocrit to abnormally high levels, resulting in dyspnea and abdominal pain
  38. What type of growth factor is Promacta and Nplate? What are their clinical uses? How are they administered? What are the potential side effects?
    Thrombopoietin

    Thrombocytopenia, Cancer Chemotherapy, and Bone Marrow Transplantation

    Subcutaneous Injection

    Potentially serious side-effects may develop, including myalgia, joint and extremity discomfort, insomnia, thrombocytosis, which may lead to potentially fatal clots, and bone marrow fibrosis, the latter which may result in an unsafe decrease in the red blood count.

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