Outline

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Outline

• review blood cells
• discuss hematopoiesis
• stages
• sites
• terms to know
• what are stem cells
• cell differentiation
• requirements for hematopoiesis
• CSFs
• erythropoietin

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HematopoiesisSeptember 13 15, 2006

• Hematopoiesis learning objectives
• Able to
• 1. List fetal and adult sites of hematopoiesis.
• 2. Discuss two unique characteristics of stem
  cells.
• 3. Use the following terms to describe
  hematopoiesis Hematopoietic stem cells,
  committed stem cells, differentiated end-stage
  cells.
• 4. Discuss requirements for normal hematopoiesis.

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• 5. Define the terms ineffective erythropoiesis
  and extramedullary hematopoiesis and give
  examples of their occurrence.
• 6. Discuss reasons for bone marrow examination
  including indications for aspirates and trephine
  biopsies. Calculate and interpret
  myeloiderythroid ratios (ME ratios).
• 7. Recognize, describe and name all stages of
  development of bone marrow and peripheral blood
  cells including erythropoiesis, granulopoiesis,
  and thrombopoiesis.

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Hematopoiesis in the Embryo

• Germ Layers in the yolk sac
• 1. endo- or ento- derm
• 2. mesoderm -blood cells, vessels, bone,
  connective tissue
• 3. ectoderm

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Stages of Hematopoiesis
1. Mesoblastic Stage - (yolk sac) blood islands
form primitive erythroblasts 2. Hepatic
Stage megakaryocytes, granulocytes, lymphocytes
monocytes appear 3. Medullary Stage bone marrow
takes over production
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Hematopoietic Sites

• pelvis
• ribs
• skull
• vertebrae
• long bones

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Overall Bone Structure

• periosteum

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Requirements for Hematopoiesis

• Adequate micro-environment (stroma)
• fibroblasts
• macrophages (histiocytes)
• adipose cells (FAT)
• endothelial cells
• Normal stem cells
• nutrients (i.e. iron, vitamin B12, folate)
• hematopoietic growth factors and cytokines
• feedback inhibition mechanisms

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Colony Stimulating Factors

• regulate hematopoiesis by mediating
• Progenitor cells
• proliferation
• differentiation
• maturation
• Mature cells
• survival
• function

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Colony Stimulating Factors
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Effect of CSFs
CFU-L pluripotential blast
colony-forming cell self renew lymphocyte
IL3 GMCSF CFU-GEMM self renew
GMCSF IL3 IL3 GMCSF IL3 BFU-E CFU-GM
CFU-Eo CFU-Bas CFU-Meg IL3 GMCSF
IL3 GMCSF CFU-E CFU-G CFU-M
GMCSF IL3 GMCSF IL3
EPO GMCSF
GMCSF erythrocyte neutrophil monocyte
eosinophil basophil megakaryocyte

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Actions of Erythropoietin

• 1. Stimulates proliferation of committed
  erythroid stem cells.
• 2. Regulates the rate of Erythropoiesis.
• 3. Increases the size of the marrow sinusoids.

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Regulation of Erythropoiesis

• Bone marrow
• Stem cells BFU-E CFU-E erythroid
  precursors
• Erythropoietin Red cell mass
  atmospheric O2
• cardio-pulm. func.
• blood volume
• hemoglobin conc.
• O2 affinity
• renal vascular O2
  endothelium sensor adapted from Jandl page
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