Hemopoiesis

lec.4
BY
Dr. Suhair Majeed
2020-2021
 Hemopoiesis
*Mature blood cells have a relatively short life span and
must be continuously replaced with new cells from precursors
developing during hemopoiesis .
* In the early embryo these blood cells arise in the yolk
sac mesoderm.
*In the second trimester, hemopoiesis occurs primarily in
the developing liver, with the spleen playing a minor role .
* Skeletal elements begin to ossify and bone marrow
develops in their medullary cavities, and in the third trimester
marrow of specific bones becomes the major hemopoietic
organ.
Cont.
*During childhood and adult life, erythrocytes,
granulocytes, monocytes, and platelets continue to from stem
cells located in bone marrow.

*The origin and maturation of these cells are termed,

erythropoiesis , granulopoiesis, monocytopoiesis, and
thrombocytopoiesis.

* lymphopoiesis occurs in the marrow and in the

lymphoid organs to which precursor cells migrate from
marrow.
 Stem Cells

* Stem cells are pluripotent cells capable of asymmetric

division and self-renewal.
* Some of their daughter cells form specific, irreversibly
committed progenitor cells, and other daughter cells remain as
a small pool of slowly dividing stem cells.
 Hemopoietic Stem Cells
*All blood cells arise from a single type of pluripotent
hemopoietic stem cell in the bone marrow that can give rise to all
blood cell types .
*These pluripotent stem cells proliferate slowly and give rise to
two major lineages of progenitor cells with restricted to produce
specific blood cells:
1- lymphoid progenitor cells (lymphocytes)
2- myeloid progenitor cells
*Myeloid cells include granulocytes, monocytes, erythrocytes,
and megakaryocytes.
* The lymphoid progenitor cells migrate from the bone marrow to
the thymus or the lymph nodes, spleen, and other lymphoid structures,
where they proliferate and differentiate.
 Bone Marrow
*Bone marrow is found in the medullary canals of long
bones and in the small cavities of cancellous bone, with two
types :
- blood-forming red bone marrow, whose color is produced
by an abundance of blood and hemopoietic cells,
- yellow bone marrow, which is filled with adipocytes that
exclude most hemopoietic cells.
* In the newborn all bone marrow is red and active in blood
cell production, but as the child grows, most of the marrow
changes gradually to the yellow variety.
* Under certain conditions, such as severe bleeding or
hypoxia, yellow marrow returns to red.
 Red Bone Marrow
*Red bone marrow contains a reticular connective tissue
stroma , hemopoietic cords or islands of cells, and sinusoidal
capillaries.
* The stroma is a meshwork of specialized fibroblastic cells
called stromal cells (also called reticular cells) and a delicate web of
reticular fibers supporting the hemopoietic cells and macrophages.
* The matrix of bone marrow also contains collagen type I,
proteoglycans, fibronectin, and laminin, they interacting with integrins
to bind cells to the matrix.
Cont.

* Red marrow is also a site where older, defective

erythrocytes undergo phagocytosis by macrophages, which
then reprocess heme-bound iron for delivery to the differentiating
erythrocytes.

*Between the hematopoietic cords run the sinusoids,

which have discontinuous endothelium, through which newly
differentiated blood cells and platelets enter the circulation .
Stromal Cells Or Reticular Cells
* Are stellate in shape , and are in contact with each other through
their processes.

* Their Functions :

1- act as a meshwork to support and protect hemopoietic

cells.

2- formation of reticular fibers.

3- phagocytosis

4- they transfer to adipocytes by accumulating lipid in their

cytoplasm.
 Bone Marrow
megakaryocyte

erthyroblastic islet

endothelium

Adipose cells
sinusoid
 Bone Marrow

sinusoid

Erythroblast islets

megakaryocyte
 Bone Marrow Barrier
* The blood vessels of the bone marrow constitute
a barrier, inhibiting immature blood cells from leaving the
marrow.

* Only mature blood cells contain membrane proteins

such as aquaporin and glycophorin , that are required to attach
to and pass the blood vessel endothelium.

* Hematopoietic stem cells may also cross the bone

marrow barrier, and may thus be collected from blood .
 Yellow Bone Marrow

* Bone marrow not active in blood cell formation contains

predominately adipose cells, giving it the appearance of
adipose tissue, called yellow bone marrow.

* It is the chief form of bone marrow in the medullary

cavity of adult bones that are no longer hemopoietically active,
such as the long bones of the arms, legs, fingers, and toes.

* In these bones, the red bone marrow has been replaced

completely by fat.
Cont.

* active bone marrow in adults—as in ribs, vertebrae,

pelvis, and shoulder girdle—about half of the bone marrow
space is occupied by adipose tissue and half by hemopoietic
tissue.

* The yellow bone marrow retains its hemopoietic

potential, when necessary, as after severe loss of blood, it can
revert to red bone marrow .
 Maturation Of Erythrocytes
* Erythropoiesis involves three to five cell divisions between the
progenitor cell stage and the release of functional cells into the
circulation.
* The erythropoietin, produced by the kidneys, is essential for
erythrocyte production.
1-The erythroid progenitor cell is the proerythroblast, a large
cell with rounded nucleus and basophilic cytoplasm.
2- The next stage is Basophilic erythroblast (basophilic
normoblasts) has :
- condensed nucleus
- strongly basophilic cytoplasm because of free
ribosomes and polyribosomes (involved in the synthesis of
hemoglobin ).
Proerythroblast basophilic erythroblast
Cont.
3- polychromatophilic erythroblast ( polychromatophilic
normoblasts) :
-in this stage, cell volume is reduced, polyribosomes
decrease, and some cytoplasmic areas begin to be filled with
hemoglobin,(mixed color cytoplasm , purplish blue to grey) .
4- Orthochromatophilic erythroblasts (also called
normoblasts).
* Incapable of cell division
* At this stage the cytoplasm is completely
hemoglobinized and appeared eosinophilic
* the nucleus is eccentrically located , then extruded from
the cell with a thin rim of cytoplasm
Polychromatic Erythroblast
Orthochromatic Erythroblast
CONT.
5- Reticulocyte :
- It’s formed when the nucleus is extruded from the
normoblast .
- Named reticulocyte ,because the clustering of
polyribosomes forms a reticular network.
- Can carry oxygen and enter the blood stream ,
- These cells enter the circulation (where they may
constitute 1% of the red blood cells), quickly lose all
polyribosomes, and mature as erythrocytes.
6- Erythrocyte :
-The final product of erythropoiesis is the erythrocyte ,and
it’s released from bone marrow into the circulation .
Reticulocyte
Stages Of Erythropoiesis
 Granulopoiesis
* Granulopoiesis involves cytoplasmic changes dominated by
synthesis of proteins for the azurophilic granules and specific
granules.

* In sections of bone marrow cords of granulopoietic cells can be

distinguished from erythropoietic cords by their granule-filled
cytoplasm .

1- The myeloblast

- is the most immature recognizable cell, has ovoid nucleus,

basophilic cytoplasm due to abundance of RER and ribosomes .
 Bone Marrow

Granulopoiesis

Erythropoiesis
Myeloblast
 2-Promyelocyte

* Are the product of myeloblast division

*Usually grow larger than their progenitor cells

*Nucleus is eccentric .

* basophilic cytoplasm containing azurophilic granules

(lysosomal enzymes ).
 Promyelocyte

promyelocyte
 3-Myelocytes

* The first visible sign of differentiation in lineages for the

three types of granulocytes is the appearance of specific
granules and the developing Myelocytes can be distinguished
into 3 types:

1- neutrophilic myelocyte

2- acidophilic melocyte

3- basophilic myelocyte
Myelocyte
 4-Metamyelocytes
* It is the stage at which neutrophil, eosinophil, and
basophil lines can be clearly identified by the presence of
numerous specific granules .

* Nucleus slowly take on a kidney -bean shape.

* Metamyelocyte is distinguished from a myelocyte by

incipient lobe formation .

* it is followed by the band stage and then the

segmented stage.
Metamyelocyte
5-Band stage
* Represent further development of Metamyelocytes .
* The beginnings of segmentation may be visible, but the
constriction should never cut more than two – thirds of the way
across the nucleus .

6- Segmented Stage
* represent final stage in the lineage .
* Nuclear segments are connected by narrow chromatin bridges.
* Cytoplasm is soft pink to colorless.
Band Cell
Development Of Granulocytes
Cont.
* The stages of maturation of eosinophil granulocytes
are the same as for the neutrophil.

* Specific eosinophil granules appear at the myelocyte

stage and are identifiable soon after they appear.

* The granules may have a purple-blue color, becoming

more orange as the cell matures.

Basophil granulocytes :

also pass through the same maturational sequences

 Thrombopoiesis
*Megakaryocytes differentiate from myeloid stem cell
and are responsible for production of platelets.

* Three stages of maturation of megakaryocytes :

1- Basophilic stage

2- Granular stage

3- Mature stage
Cont.
1-Basophilic stage,

megakaryocyte is small, has diploid nucleus and abundant

basophilic cytoplasm

2.Granular stage,

the nucleus is more polypoid (resembling polyp), cytoplasm is

more eosinophilic and granular

3.Mature stage,

megakaryocyte is very large, with approx 16-32 nuclei, abundance

of granular cytoplasm. It undergoes shedding to form platelets.
 Megakaryocytes
* Reside in bone marrow .
* Cytoplasm with granules is pinched off from
megakaryocytes to form thrombocytes .

Regulation
Thrombopoietin:
* is a glycoprotein hormone produced mainly by liver
that regulates the production of platelets in bone marrow.
* It stimulates the production and differentiation of
Megakaryocytes.
Megakaryocyte

megakaryocyte
 Maturation Of Agranulocytes
*The precursor cells of monocytes and lymphocytes do not show
specific cytoplasmic granules or nuclear lobulation .

Monopoiesis
* The monoblast is a committed progenitor cell that is identical
to the myeloblast in its morphology.
* Further differentiation leads to the promonocyte, a large cell with
a basophilic cytoplasm and a large nucleus.
* Promonocytes divide twice as they develop into monocytes.
Cont.
* it’s cytoplasm contain, an extensive Golgi complex
and granule condensation .

* These granules are primary lysosomes, which are

observed as fine azurophilic granules in blood monocytes.

* Mature monocytes enter the bloodstream, circulate

for about 8 hours, and then enter the connective tissues,where
they mature into macrophages and function for several months.
 Lymphopoiesis
*The first identifiable progenitor of lymphoid cells is the
lymphoblast, a large cell capable of dividing two or three
times to form lymphocytes .
*As lymphocytes develop ,their nuclei become smaller,
and cell size decreases.
* In the bone marrow and in the thymus, these cells
synthesize the specific cell surface proteins that characterize
B or T lymphocytes.
* Mature and functionally active B and T cells are
larger than newly formed lymphocytes.
*lymphocytes acquire special cell surface and other
proteins during differentiation that can be detected by
immunocytochemical techniques and used to isolate the
specific lymphocytic types.
Cont.

* lymphocyte progenitor cells originate in the bone marrow.

Some of these lymphocytes migrate to the thymus, where they
acquire the properties of T lymphocytes.
* T lymphocytes populate specific regions of peripheral
lymphoid organs.
* Other bone marrow lymphocytes differentiate into B
lymphocytes in the bone marrow and then migrate to
peripheral lymphoid organs, where they reside in, and multiply
within their own niches.
 Medical Application
* Leukemias are malignant clones of leukocyte
precursors.

* they occur in :

1- lymphoid tissue (lymphocytic leukemias)

2- bone marrow (myelogenous and monocytic

leukemias)

* in these diseases , there is usually a release of large

numbers of immature cells into the blood .
Thank you