Hematopoiesis

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Introduction

Hematopoiesis is the generation of all the cells of the blood - white blood cells, red blood cells, and platelets.

 

Cytokines and other hematopoietic growth factors are involved in specific steps of hematopoiesis.

These are generally glycoproteins acting in low concentrations, and are produced by stromal cells, monocytes, and lymphocytes.

Growth factors often act specifically, but they can also affect more than one lineage in similar or different ways. They can act synergistically or additively.

 

stem cell factor

 

 

Sites of Hematopoiesis

fetus:

infants: bone marrow of almost all bones

adults: vertebrae, ribs, sternum, skull, sacrum, pelvis, and end of femurs. There is progressive fatty replacement of marrow in other areas.

 

Fatty marrow is capable of reverting to hematopoiesis if necessary. The liver and spleen can also resume extramedullary hematopoiesis in some situations.

 

 

 

Specific Cell Lines

  • erythropoiesis
  • thrombopoiesis
  • granulopoiesis
  • lymphopoiesis
  • monocytopoiesis

Erythropoiesis

Erythropoiesis is controlled primarily by erythropoietin, but also GM-CSF, IL3, and IL11. Erythropoietin is released from kidney peritubular interstitial cells in response to oxygen levels.

 

EPO production increases in states of decreased tissue oxygen delivery. These included decreased Hb oxygenation (high altitudes, pulmonary dysfunction), hemoglobin levels (anemia), or hemoglobin affinity for oxygen (shift in oxygen dissociation curve). EPO expression increases logarithmically once levels fall below 120 g/L.

 

EPO levels are decreased by inflammatory cytokines such as TNF-a and TGFb. Drugs such as chemotherapy, cyclosporin A, and theophylline decrease EPO production.

 

EPO travels to the marrow, where it binds to EPO receptors on committed RBC precursors. Within hours, there is a noticable increase in DNA synthesis, followed by proliferation and differentiation. The full marrow response takes several days, with a detectable increase in hematocrit taking a week or more.

 

 

 

Cell cytoplasm changes from a deep basophilic RNA-rich substance to a substance

 

  • proerythroblast
  • basophilic erythroblast
  • polychromatic erythroblasts
  • orthochrmic erythroblasts
  • nuclear expulsion

3-4 x 109 EBC/kg are made each day.

RBCs survive an average of 120 days.

 

Erythropoiesis takes place in erythroid islands containing macrophages, which contain the iron the RBCs need and also eat the nuclei.

Reticulocytes leave the marrow and mature into RBCs.

 

 

 

 

Resources and References

 

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