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• HISTOLOGY 1.8. HEMATOPOIESIS
• Prenatal
• Blood cell generation begins in the wall of the
  yolk sac during
• intrauterine life primitive erythroblasts
  derive from mesenchyme.
• Later the hematopoietic cells migrate to the
  liver.
• Then the bone marrow, spleen, lymph nodes and
  thymus of the
• embryo are seeded with hematopoietic stem cells
  from the liver
• and become engaged with hematopoiesis.

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II. Postnatal hematopoiesis The major site of
hematopoiesis is the bone marrow, it also
persists in the liver and spleen for a few weeks
after birth (potential is retained). Early in
life all the marrow is active, with age the
demand for blood cells decreases red marrow is
replaced by resting yellow marrow. Red bone
marrow is present in the adult animal sternum
vertebrae ribs skull pelvis epiphyses of
long bones
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Structure of the bone marrow The hematopoietic
compartment consists of irregular anastomosing
cords that lie between vascular sinuses. The
marrow lacks lymphatic vessels Innervation
vasomotor nerves around the blood vessels
Bone marrow smear
Bone marrow in sternum
Hematopoietic compartment
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Blood cells are produced in the hematopoietic
compartment and reach the bloodstream by
crossing the wall of vascular sinuses. Adventitia
l reticular cells meshwork that support
hematopoietic cells and provide special
microenvironment that influence the development
of the various stem cells. They may fill with
fat and transform into adipose cells when
hematopoiesis decreases. Marrow hematopoiesis
is most active in areas close to the
bone. Erythropoietic cells and megakaryocytes
are close to vascular sinuses. Granulopoietic
cells are deep within the cords, away from the
vascular sinuses.
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Hematopoietic stem cells Undifferentiated
cells are generally larger than mature cells,
they have large euchromatic nuclei (large
nuclear-to-cytoplasmic ratio). The marrow
contains several types of self-replicating stem
cells. Their morphology resembles that of
lymphocytes, but their proliferating capacity
differs pluripotent multipotent stem
cells unipotent
Embryonic yolk sac, fetal liver,spleen, bone
marrow primitive stem cells (pluripotent) Lym
phoid stem cells myeloid stem cells
(multipotent) Lymphocytes erythrocytic granulocy
tic monocytic megakaryocytic (They are all
unipotent cell types)
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Hematopoietic and stromal stem cell
differentiation
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BFU-E (burst-forming unit-erythrocyte) CFU-E
(Colony-forming unit-erythrocyte)
(Rubriblast)
(Metarubricyte)
(Rubricyte)
(Prorubricyte)
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Erythron mass of circulating erythrocytes
marrow erythropoietic tissue Efficacy of
erythropoiesis in a dog 1 million/second Erythro
blastic islands group of erythrocytic cells
within the bone marrow organized around a
macrophage (more mature ones at the periphery).
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1. Rubriblast (arrow) largest, with deep blue
cytoplasm and round euchromatic nucleus 2.
Prorubricyte (arrowhead) Similar, but smaller, no
nucleoli
4. Metarubricyte the smallest nucleated
erythrocyte with picnotic nucleus
4.
3.
3. Basophilic rubricyte nucleus with clumped
chormatin
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Reticulocyte
Mature mammalian erythrocytes
Erythrocyte kinetics Development of rubriblasts
to mature erythrocytes 5.-7 days Reticulocytes
normally 1-2 days maturation within the bone
marrow Regulation of erythrocyte formation
cellular and humoral factors erythropoietin
key-molecule produced in the kidney
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Granulopoiesis Occurs in clusters away from the
vascular sinuses in the midportion of the
hematopoietic compartment of the marrow CFU-GM
colony-forming units-granulocyte-monocyte
(bipotent) Neutrophil and /or monocyte
progenitor cells
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Myeloblast ovoid or spherical cell, spherical
euchromatic nucleus, light blue
cytoplasm. Promyelocyte larger, similar
nucleus,more cytoplasm, with azurophilic granule
s. Myelocyte spherical to slightly indented
nucleus, some chromatin condensation, specific
and azurophilic granules. Specific granules
indicate the type of granulocyte to
be developed. Metamyelocyte indented,
kidney-shaped heterochromatic nucleus,
specific granules have their characteristic
colours. Band-form further nuclear indentation,
C,-S,-V-shaped nuclei. Mature forms marked
segmented nuclei and specific granules
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Granulocyte kinetics Compartments of
granulocytic cells proliferative (mitotic)
with myeloblasts, promyelocytes,
myelocytes maturative (postmitotic) with
metamyelocytes, band neutrophils reserve
(storage) with mature neutrophils Production
time for granulocytes 5-7 days Compartments of
blood neutrophils circulating (6-14 hours)
marginating Total neutrophil pool in the
blood is replaced at least twice a day. The
production and kinetics of eosinophils, basophils
and monocytes are similar to those of neutrophils.
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Thrombopoiesis CFU-MK colony-forming
unit-megakaryocyte large spherical
euchromatic nucleus Megakaryoblast undergoes
endomitosis, thus, only the nucleus
divides Promegakaryocyte multilobed nucleus, lot
of cytoplasm Megakaryocyte largest hematopoietic
cell in the marrow (40-100 mm)
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Platelet kinetics Platelets are produced by
fragmentation of the megakaryocytic cytoplasm
along demarcation membranes. Place of
megakaryocytes in the bone marrow against the
sinus wall. They shed their platelets directly
into the bloodstream, or extend their cytoplasmic
projections through the endothelium into the
sinus lumen. Life span of platelets 9-12 days
in domestic species. Place of storage
spleen Regulation of platelet formation local
regulatory factors and thrombopoietin produced
in the kidney.
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Lymphopoiesis Lymphoid stem cells
pre-B-lymphocyte B-lymphoblast B-lymphocyte p
re-T-lymphocyte T-lymphoblast T-lymphocyte Stem
cells derive from the bone marrow. Maturation
process for B-lymphocytes bone marrow, GALT
(bursa-equivalent organs) Maturation
process for T-lymphocytes thymus