Hematopoiesis

Jul 10, 2024

Hematopoiesis

Overview

  • Mature blood cells have a limited lifespan and must be continuously replaced.
  • This process is called hematopoiesis and occurs in the red bone marrow.
  • All blood cells derive from hematopoietic stem cells (HSCs).

Hematopoietic Stem Cells (HSCs)

  • HSCs are multipotent and can differentiate into all types of blood cells.
  • They maintain their numbers in the bone marrow through constant multiplication.
  • Blood cell formation from HSCs involves several intermediate progenitors and is regulated by cytokines.

Role of Cytokines

  • Cytokines are signaling molecules that control:
    • Proliferation
    • Differentiation
    • Survival or death of progenitors
  • Maintain steady-state levels of blood cells in normal situations.
  • Induce production of specific cell types in response to stimuli (e.g., blood loss).

Differentiation Process

  • Begins when progenitor cells develop surface receptors for specific stimulating factors.
  • Cells lose their potency and become committed to a certain cell type.

Production of Red Blood Cells (RBCs)

  • Stimulated by erythropoietin (EPO).
  • Differentiation involves:
    • Reduced size
    • Increased number
    • Hemoglobin production
    • Loss of nucleus
  • EPO is produced by the liver during fetal development and by the kidneys in adulthood.
  • Low levels of EPO compensate for normal RBC turnover.
  • Increased EPO secretion in response to hypoxemia (e.g., blood loss) leads to higher RBC production.
  • People at high altitudes and athletes have higher RBC counts due to lower oxygen levels and elevated oxygen demand, respectively.

Production of Granulocytes and Macrophages

  • Controlled by colony-stimulating factors (CSFs).
  • Maintained at constant levels by low CSFs, but increase greatly upon infection.
  • CSFs are secreted by lymphocytes and macrophages, and can be produced by various organ or cell types.
  • Can increase a thousand-fold in response to infection indicators like bacterial endotoxins.

Production of Platelets

  • Stimulated by thrombopoietin (TPO).
  • TPO is secreted by the kidneys and liver.
  • Leads to formation of megakaryocytes, which give rise to platelets.
  • Platelets are fragments of megakaryocyte cytoplasm.
  • Production regulated by negative feedback: low platelet levels promote production, while high levels inhibit it.