HISTOLOGY 1.8.: HEMATOPOIESIS
I. 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.
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
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
Blood cells are produced in the hematopoietic compartment and
reach the bloodstream by crossing the wall of vascular sinuses.
Adventitial 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.
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)
Lymphoid stem cells
Lymphocytes
myeloid stem cells (multipotent)
erythrocytic
granulocytic
monocytic
(They are all unipotent cell types)
megakaryocytic
Hematopoietic and stromal stem cell differentiation
CFU-E (Colony-forming unit-erythrocyte)
(Rubriblast)
16-22 mm
(Metarubricyte)
12-15 mm
(Rubricyte)
14-18 mm
(Prorubricyte)
10-12 mm
Erythron: mass of circulating erythrocytes + marrow erythropoietic tissue
Efficacy of erythropoiesis in a dog: 1 million/second
Erythroblastic islands: group of erythrocytic cells within the bone marrow
organized around a macrophage (more mature ones at the periphery).
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 chromatin
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
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
15-18 mm
10-15 mm
18-22 mm
Myeloblast:
ovoid or spherical cell, spherical euchromatic nucleus,
light blue cytoplasm.
Promyelocyte: larger, similar nucleus,more cytoplasm, with azurophilic
granules.
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
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.
Formation of monocytes: monocytopoesis
CFU-M: monocyte progenitor (common ancestor with neutrophils)
Monoblast
Promonocyte
Monocyte
Azurophilic granules Final shape and size of nucleus
Monocytes reside in the blood stream for 24 hours, then enter
the connective tissue as CT macrophages.
Their development is still not fully understood.
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)
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.
Lymphopoiesis
Lymphoid stem cells:
pre-B-lymphocyte
pre-T-lymphocyte
B-lymphoblast
T-lymphoblast
B-lymphocyte
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
Thank you for your attention!