Hemopoiesis

• Hemopoiesis


  The process of blood cell formation

  
• Hemopoiesis is initiated in early embryonic development
• Hemopoiesis

  1. Hematopoietic cells generated in yolk sac as blood islands in 3rd week of gestation

  2. Primitive red blood cells (erythroblasts) first blood cells formed in first 2-8 weeks of life

  3. Liver becomes major site of hematopoiesis in 2nd-5th month of gestation

  4. Granular types of leukocytes appear

  5. Bone marrow begins to function in blood cell production in 4th month of gestation

  6. Bone marrow becomes primary site of hematopoiesis after 5th fetal month

  
• Pluripotent hematopoietic stem cell


  Bone marrow stem cell believed to be where all blood cells arise

  
• Pluripotent stem cell


  • Can produce all blood cell types
  • Proliferate and form two major cell lineages: lymphoid cells and myeloid cells

  
• Progenitor/precursor cells


  Pluripotent stem cells give rise to daughter cells with restricted potentials
• Types of progenitor/precursor cells

  • CFU-erythrocytes (CFU-E)
  • CFU-megakaryocytes (CFU-Meg)
  • CFU-granulocytes-monocytes (CFU-GM)
  • CFU-lymphocytes of all types (CFU-L)
• Hematopoietic growth factors (CSF)


  • Also called hematopoietins (poietins)
  • Have overlapping functions in stimulating proliferation, supporting differentiation, and enhancing functions of hematopoietic cells

  
• Hematopoietic growth factors

  • Erythropoietin
  • IL-3
  • G-CSF
  • M-CSF
  • GM-CSF

  
• Red bone marrow


  Blood-forming red bone marrow
• Yellow bone marrow


  Filled with adipocytes
• In newborns, all bone marrow is red and active in blood cell production
• In conditions like severe bleeding or hypoxia, yellow marrow reverts to red
• Components of red bone marrow

  • Stroma - meshwork of reticular/adventitial cells and reticular fibers
  • Hematopoietic cords or islands of cells
  • Sinusoidal capillaries
  • Matrix of collagen type I, proteoglycans, fibronectin, and laminin
• Erythropoietic islands


  Specialized niches in which erythroid precursors proliferate, differentiate, and enucleate
• Erythroid cells account for 5-38% of nucleated cells in normal bone marrow
• Proerythroblast


  First recognizable cell in erythroid series, with loose chromatin, nucleoli, and basophilic cytoplasm

  
• Basophilic erythroblast


  More strongly basophilic cytoplasm and condensed nucleus with no visible nucleolus
• Polychromatophilic erythroblast


  Reduced cell volume, regions of basophilia and acidophilia, heterochromatin granules in checkerboard pattern
• Orthochromatophilic erythroblast


  Nucleus becomes small and dense, no longer capable of mitosis, more abundant hemoglobin and fewer polyribosomes
• Polychromatophilic erythrocyte


  Nucleus and small rim of cytoplasm ejected from orthochromatophilic erythroblast, retains some RNA
• Polychromatophilic erythrocytes constitute 1-2% of total RBC count
• Myeloid cells


  Account for 23-85% of nucleated cells in normal bone marrow
• Neutrophils in bone marrow


  Reside in proliferating pool and maturation storage pool
• Myeloblast


  Most immature recognizable myeloid cell, with finely dispersed chromatin and faint nucleoli

  
• Promyelocyte


  Characterized by basophilic cytoplasm and azurophilic granules
• Myelocyte


  Gradual increase of specific granules
• Metamyelocyte


  Specific granules occupy most of cytoplasm, nuclei condense further
• Mature granulocyte


  Final stage of granulocyte development
• Functional compartments of neutrophils

  Circulating, marginating, and storage pools
• Increase in circulating neutrophils does not necessarily imply increased production
• Bacterial infections cause neutrophilia due to increased production and shorter cell lifespan
• Monoblast


  Committed progenitor cell identical to myeloblast in morphology

  
• Promonocyte


  Large cell with basophilic cytoplasm and slightly indented nucleus, divides twice to become monocyte
• Monocyte


  Rich in RER, extensive Golgi, contains primary lysosomes, function as macrophages in tissues
• Lymphocytes and plasma cells produced in lymphoid follicles

  
• Lymphocytes typically account for 1-5% of nucleated cells in normal bone marrow
• Lymphoblast


  First identifiable progenitor of lymphoid cells, divides 2-3 times

  
• Prolymphocyte


  Smaller than lymphoblast, more condensed chromatin, no T or B cell surface markers
• T lymphocytes


  Acquire full attributes in the thymus, predominant lymphocyte in lymphoid organs