Haematology
Haemopoiesis
Site of haeomopoiesis:
- First few weeks of gestation: yolk sac = main site.
- Definitive haemopoiesis derives from a population of stem cells first observed on the dorsal aorta, termed the AGM
region (aorto-gonads-mesonephros) region- these common precursors of endothelial and haemopoietic cells
(haemangioblasts) are believed to seed the liver, spleen and bone marrow.
- From 6 weeks until 6-7 months of fetal life, the liver and spleen are the major haemopoietic organs, and continue to
produce blood cells until about 2 weeks after birth.
- Bone marrow = most important site from 6-7 months of fetal life.
- During normal childhood and adult life, the marrow = the only source of new blood cells. The developing cells are
situated outside the bone marrow sinuses; mature cells are released into the sinus spaces, the narrow microcirculation
and into the general circulation.
- In infancy, all bone marrow = haemopoietic; during childhood there is progressive fatty replacement of marrow
throughout the long bones, so that in adult life, haemopoietic marrow is confined to the central skeleton, and
proximal ends of femur and humerus
- Even in these haemopoietic areas, approximately 50% of the marrow consists of fat; remaining fatty marrow is
capable of reversion to haemopoiesis and in many diseases there is also expansion of haemopoiesis down the
long bones.
- Liver and spleen can resume their fetal haemoopietic role.
Haemopoiesis (blood cell formation) arises from pluripotent stem cells in the bone marrow.
Stem cells give rise to progenitor cells, which after cell divisions and differentiation, form red cells, granulocytes (neutrophils,
eosinophils, basophils), monocytes, platelets and B and T-lymphocytes.
Haematopoietic tissue occupies about 50% of the marrow space in normal adult marrow.
Haeomopoeisis in adults: confined to central skeleton; in infants and young children it extends down the long bones of the arms and
legs.
HAEMOPOIETIC STEM AND PROGENITOR CELLS
Haemopoiesis starts with a pluripotent stem cell that can
self-renew, but also give rise to separate cell lineages;
these cells are able to repopulate a bone marrow from
which all stem cells have been eliminated by lethal
irradiation/chemotherapy.
This haemopoietic stem cell is rare - 1:20,000,000
nucleated cells in the bone marrow.
- CD34+ and CD38-
- negative for lineage markers
- Has appearance of small/medium-sized lymphocytes
- Cells reside in ‘niches’
- Cell differentiation occurs from stem cell via
committed haemopoietic progenitors which are
restricted in their developmental potential.
Mixed myeloid progenitor (colony forming unit CFU-
GEMM): gives rise to granulocytes, erythrocytes,
monocytes and megakaryocytes.
Bone marrow = primary site of origin of lymphocytes
which differentiate from a common lymphoid precursor.
Stem cell has capability for self-renewal: marrow
cellularity remains consent in a normal healthy steady
state; considerable amplification in system as one stem
cell —> 10^6 mature blood cells following 20 cell divisions
Precursor cells are capable of responding to haemopoietic growth factors with increased production of one or other cell
line when the need arises.
HAEMATOLOGY - 1
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