Hematopoiesis

Fetal Hematopoiesis

1. Mesoblastic (yolk sac) phase
   • From 19th day of gestation to 2-3 months
   • Primitive RBCs formed intravascularly
   • Three embryonic hemoglobins produced with very high O2 affinity
     • Hb-Gower 1
     • Hb-Gower 2
     • Hb-Portland
2. Hepatic phase
   • From 5-7 weeks gestation, declining until birth
   • Liver and spleen produce initially produce cells, eventually continuing in thymus, placenta, kidney, lymph nodes, and bone marrow
   • Cells produced extravascularly
   • All cell types produced
   • Hemoglobin-F primarily produced (high O2 affinity), some adult hemoglobins (Hb-A) may begin formation
3. Myeloid (medullary) phase
   • From 4-5 months onwards
   • Bone marrow primary site of hematopoiesis
     • Mostly active (red) marrow at birth
   • All cell types produced
   • Hemoglobin F and Hemoglobin A produced

Adult Hematopoiesis

• Primarily occurs in bone marrow (all cell types)
  • Also produced in lymph nodes, spleen, liver, and thymus
• Red marrow: hematopoietically active
  • 50:50 ratio of active cells to apidose in red marrow
• Yellow marrow: hematopoietically inactive
  • Can revert to red marrow when there is need for more blood cells
• At birth and early childhood, all bones contain red marrow
  • Over time, red marrow replaced with adipose tissue (yellow marrow)
  • At 5-7 years, regression begins with adipose tissue dominating
• Active red marrow located more interior-ly (skull, spine, sterum, ribs, pelvis, proximal ends of long bones, etc.)
• In times of extreme stress, other sites can resume producing blood cells (extramedullary hematopoiesis)
  • Liver, spleen, thymus, lymph nodes, etc.

Bone Structure

• Exterior surrounded by cortical bone layer
• Interior contains cavities
  • Trabecular bone, consists of connecting structures
  • Hematopoietic tissue, adipose tissue, and blood vessels are present within the gaps in bone trabeculae
• Red marrow arranged into cords/sheets of cells that are held together by connective tissues
  • Contains variety of blood cell types at various stages of maturation
    • Erythrocytic islands sequester iron for RBC production, located near vessels
    • Megakaryocytes release fragments (platelets)
    • Granulocytes move towards vasculature as they mature
  • Release of cells stimulated by cytokines, and is tightly controlled
  • Also contains apidocytes and other supporting cells (connective tissue, endothelial cells of blood vessels, stromal cells regulating nutrients, other cells secreting signalling cytokines, etc.)
• Yellow marrow adipocytes present throughout red marrow