- Hemopoiesis is the process where mature blood cells are continuously replaced by stem cell progeny produced in hemopoietic organs like the bone marrow. - In early embryogenesis and during fetal development, hemopoiesis occurs first in the yolk sac, then the liver, and later primarily in the bone marrow. - After birth, the major types of blood cells are derived from stem cells located in the bone marrow, which is the primary site of hemopoiesis through childhood and adulthood.

1. Hemopoiesis
Department Of General Histology

2. Introduction
• Mature blood cells have a relatively short life span and must be
continuously replaced with stem cell progeny produced in the
hemopoietic (Gr. haima, blood, + poiesis, a making) organs. In the
earliest phase of human embryogenesis, blood cells arise from the yolk sac
mesoderm. In the second trimester, hemopoiesis (also called
hematopoiesis) occurs primarily in the developing liver, with the spleen also
playing a role. Skeletal elements begin to ossify and bone marrow develops
in their medullary cavities, so that, in the third trimester, bone marrow
increasingly becomes the major hemopoietic organ.
• After birth and on into childhood, erythrocytes, granulocytes, monocytes,
and platelets are derived from stem cells located in bone marrow. The
origin and maturation of these cells are termed, respectively,
erythropoiesis (Gr. erythros, red, + poiesis), granulopoiesis,
monocytopoiesis, and thrombocytopoiesis. Development of the
major types of lymphocytes by lymphopoiesis occurs in the marrow and
in the lymphoid organs to which precursor cells migrate, as discussed in
Chapter 14.
• Before reaching maturity and being released into the circulation, blood cells
go through specific stages of differentiation and maturation. Because these
processes are continuous, cells with characteristics that lie between the
various stages are frequently encountered in smears of blood or bone
marrow.

4. Main characteristics of five
hemopoietic growth factors (colony-
stimulating factors, CSF).

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6. Red bone marrow (active in
hemopoiesis) Red bone marrow contains adipocytes but
is also active in hemopoiesis, with several
cell lineages usually present. It can be
examined histologically in sections of
bones or in biopsies, but its cells can also
be studied in smears. Marrow consists of
capillary sinusoids running through a
stroma of specialized, fibroblastic
reticular cells and an ECM meshwork.
Reticular cells secrete various colony-
stimulating factors and the stroma forms
the microenvironment for hemopoietic
stem cell maintenance, proliferation, and
differentiation. This section of red bone
marrow shows some of its components.
Sinusoid capillaries (S) containing
erythrocytes are surrounded by stroma
containing adipocytes (A) and islands or
cords (C) of hemopoietic cells. Sinusoidal
endothelial cells (one nucleus at E) are
very thin. Most reticular cells and cells of
the hemopoietic lineages are difficult to
identify with certainty in routinely stained
sections of marrow.

7. Sinusoidal endothelium in active
marrow

8. Summary of erythrocyte maturation

9. Erythropoiesis: Major erythrocyte
precursors
(a): Micrographs showing a very large and scarce proerythro-blast (P), a slightly
smaller basophilic erythroblast (B) with very basophilic cytoplasm, typical and late
polychromatophilic erythroblasts (Pe and LPe) with both basophilic and
acidophilic cytoplasmic regions, and a small orthochromatophilic erythroblast (Oe)
with cytoplasm nearly like that of the mature erythrocytes in the field.

10. Micrograph containing
reticulocytes (arrows) that have
not yet completely lost the
polyribosomes used to
synthesize globin, as
demonstrated by a stain for
RNA. X1400. Brilliant cresyl
blue.

11. Granulopoiesis: Formation of
granules

12. Developing erythrocytes and
granulocytes in marrow.
Precursor cells of different
hemopoietic lineages develop
side by side with some
intermingling as various cell
islands or cords in the bone
marrow. Plastic section of red
bone marrow showing mitotic
figures (arrows), a plasma cell
(arrowhead), and fairly distinct
regions of erythropoiesis and
granulopoiesis. Most immature
granulocytes are in the
myelocyte stage: their
cytoplasm contains large, dark-
stained azurophilic granules and
small, less darkly stained
specific granules. X400. Giemsa.

13. Granulopoiesis: Major granulocyte
precursors.
Two micrographs from smears of bone marrow showing
the major cells of the neutrophilic granulocyte lineage.
Typical precursor cells shown are labeled as follows:
myeloblast (MB); promyelocyte (1); myelocytes (2); late
myelocyte (3); metamyelocytes (4); stab or band cells
(5); nearly mature segmented neutrophil (6). Some of
the early stages show faint nucleoli (N). Inset:
Eosinophilic myelocytes (EM) and metamytelocytes
(EMm) with their specific granules having distinctly
different staining. These and cells of the basophilic
lineage are similar to developing neutrophils, except for
their specific staining granules and lack of the stab cell
form. Also seen among the erythrocytes of these
marrow smears are some orthochromatophilic
erythroblasts (Oe), a small lymphocyte (L), and a cell in
mitosis (arrow). All X1400. Wright.

14. Neutrophilic myelocyte
At the myelocyte stage lysosomes
(azurophilic granules) have formed and
production of specific secretory granules is
underway. This micrograph shows
ultrastructurally a peroxidase-stained
section of a neutrophilic myelocyte with
cytoplasm containing both large,
peroxidase-positive azurophilic granules
(AG) and smaller specific granules (SG),
which do not stain for peroxidase. The
peroxidase reaction product is present only
in mature azurophilic granules and is not
seen in the rough ER (RER) or Golgi
cisternae (GC), which are located around
the centriole (C) near the nucleus (N).

15. Functional compartments of
neutrophils

16. Megakaryoblast and megakaryocytes
Megakaryoblasts (Mb) are very large, fairly
rare cells in bone marrow, with very
basophilic cytoplasm. X1400. Wright.

17. Megakaryoblasts undergo endomitosis
(DNA replication without intervening cell
divisions), becoming polyploid as they
differentiate into megakaryocytes (M).
These cells are even larger, but with
cytoplasm that is less intensely basophilic.
X1400. Wright.

18. Micrograph section of bone marrow
megakaryocyte (M) shown near sinusoids
(S). X400. Giemsa. Megakaryocytes
produce all the characteristic components
of platelets (membrane vesicles, specific
granules, marginal microtubule bundles,
etc) and in a complex process extend many
long, branching pseudopodia-like
projections called proplatelets, from the
ends of which platelets are pinched off
almost fully formed.

19. Megakaryocyte ultrastructure
TEM analysis of a megakaryocyte during platelet
formation showing a lobulated nucleus (N),
numerous cytoplasmic granules (G), and an
extensive system of demarcation membranes (D)
through the cytoplasm. Once believed to be
perforations along which platelets were shed from
the cells, this membrane system is now considered
a reservoir of membrane used during elongation of
the numerous proplatelets which extend from the
megakaryocyte surface. X10,000.

20. Thank you for attention!