Dr. Doaa Mustafa Histology lec.

10-11

FORMATION OF BLOOD CELLS (HEMOPOIESIS)

Hemopoiesis (hematopoiesis) includes:

1. Erythropoiesis: development of red blood cells.

2. Leukopoiesis: development of white blood cells.
3. Thrombopoiesis: development of platelets.

Blood cells have a limited life span; they are continuously

produced and destroyed. The ultimate objective of hemopoiesis is
to maintain a constant level of the different cell types found in the
peripheral blood.

Both the human erythrocyte (life span of 120 days) and the
platelet (life span of 10 days) spend their entire life in the
circulating blood. Leukocytes, however, migrate out of the
circulation shortly after entering it from the bone marrow and
spend most of their variable life spans (and perform all of their
functions) in the tissues.

In the adult, erythrocytes, granulocytes, monocytes, and platelets

are formed in the red bone marrow; lymphocytes are also formed
in the red bone marrow and in the lymphatic tissues.

Leukocytes are subclassified into two general groups. The basis

for this division is the presence or absence of prominent specific
granules in the cytoplasm

1. Granulocytes (neutrophils, eosinophils, and basophils)

2. agranulocytes (lymphocytes and monocytes)

Hemopoiesis is initiated in early embryonic development.

During fetal life, both erythrocytes and leukocytes are formed in

several organs before the differentiation of the bone marrow.

1. Yolk-sac phase: begins in the third week of gestation and is

characterized by the formation of “blood islands” in the wall
of the yolk sac of the embryo.
2. Hepatic phase: The liver is the major blood-forming organ in
the fetus during the second trimester.
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Dr. Doaa Mustafa Histology lec.10-11

3. Bone marrow phase: involves the bone marrow (and other

lymphatic tissues) and begins during the second trimester
of pregnancy.
4. After birth: hemopoiesis takes place only in the red bone
marrow and some lymphatic tissues, as in the adult.

Monophyletic Theory of Hemopoiesis

The hemopoietic stem cell (HSC) is capable not only of

differentiating into all the blood cell lineages but also of self-
renewal (i.e., the pool of stem cells is self-sustaining).

HSCs have the potential to repair tissues under pathologic

conditions (e.g., ischemic injury, organ failure).

A hemopoietic stem cell (HSC) in the bone marrow gives rise

to multiple colonies of progenitor stem cells.

In the bone marrow, descendants of the HSC differentiate into two

major colonies of multipotential progenitor cells:

1- common myeloid progenitor (CMP) cells

2- common lymphoid progenitor (CLP) cells.

1- common myeloid progenitor (CMP) cells, differentiate into :

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Dr. Doaa Mustafa Histology lec.10-11

A.Megakaryocyte/erythrocyte progenitor (MEP) cells: These

give rise to

❖ megakaryocyte-committed progenitor cells

❖ erythrocyte- committed progenitor cells that give rise to the

erythrocyte

B.Granulocyte/monocyte progenitor cells: These cells then give

rise to the neutrophil progenitors ,which differentiate into the
neutrophil.

C.eosinophil progenitors (EoP), cells that give rise to

eosinophils;
D.basophil/mast cell progenitors (BMCP) that give rise either to
basophil progenitor cells (BaP) in the bone marrow or MCPs in
the gastrointestinal mucosa
E.monocyte progenitors (MoP) that develop toward monocyte
lineages.
F.dendritic cells (DCs), which are professional antigen-presenting
cells.

2.common lymphoid progenitor (CLP) cells are capable of

differentiating into :

❖ T cells

❖ B cells

❖ natural killer (NK) cells.

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Dr. Doaa Mustafa Histology lec.10-11

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Dr. Doaa Mustafa Histology lec.10-11

BONE MARROW

Red bone marrow lies entirely within the spaces of bone,

medullary cavity of young long bones, and spaces of spongy bone.

Bone marrow consists of blood vessels, specialized units of

blood vessels called sinusoids, and a sponge-like network of
hemopoietic cells .

The bone marrow sinusoidal system is a closed circulation

system; newly formed blood cells must penetrate the endothelium
to enter the circulation.

Bone marrow not active in blood cell formation contains

predominately adipose cells, giving it the appearance of adipose
tissue.

Inactive bone marrow is 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.

The yellow bone marrow retains its hemopoietic potential,

however, and when necessary, as after severe loss of blood, it can
revert to red bone marrow 5
Dr. Doaa Mustafa Histology lec.10-11

Development of Erythrocytes (Erythropoiesis)

Erythrocyte development starts from Common Myeloid Progenitor

cells that, under the influence of erythropoietin transform into
erythropoietin-sensitive erythrocyte-committed progenitors
(ErPs) that give rise to the proerythroblast.

1. The first microscopically recognizable precursor cell in

erythropoiesis is called the proerythroblast.
2. The basophilic erythroblast is smaller than the
proerythroblast, from which it arises by mitotic division.
3. The polychromatophilic erythroblast shows both acidophilic
and basophilic staining of cytoplasm.
4. The orthochromatophilic erythroblast (normoblast) is
recognized by its increased acidophilic cytoplasm and dense
nucleus.
5. The polychromatophilic erythrocyte has extruded its
nucleus.

Consequently, polychromatophilic erythrocytes are also (and

more commonly) called reticulocytes. In normal blood,
reticulocytes constitute about 1% to 2% of the total erythrocyte
count. However, if increased numbers of erythrocytes enter the
bloodstream (as during increased erythropoiesis to compensate
for blood loss), the number of reticulocytes increases

Nearly all erythrocytes are released into the circulation as soon as

they are formed; bone marrow is not a storage site for
erythrocytes.

Erythrocyte formation and release are regulated by

erythropoietin, a glycoprotein hormone synthesized and
secreted by the kidney in response to decreased blood oxygen
concentration.

Erythrocytes have a life span of about 120 days in humans.

When erythrocytes are about 4 months (_120 days) old, they

become senile. The macrophage system of the spleen, bone
marrow, and liver phagocytoses and degrades the senile
erythrocytes.
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Dr. Doaa Mustafa Histology lec.10-11

Development of Thrombocytes (Thrombopoiesis)

Each day, bone marrow of a healthy adult produces about 1x1011

platelets, a number that can increase 10-fold in time of increased
demand.

Thrombocytes (Platelets) are produced in the bone marrow

under stimulation by thrombopoietin, a glycoprotein hormone
produced by liver and kidney

1. Common myeloid progenitor (CMP) cells as the erythroid and

myeloid series. a CMP stem cell differentiates into

2. Bipotent megakaryocyte/erythrocyte progenitor (MEP) cell.

Further development proceeds toward

3. Unipotent megakaryocyte-committed progenitor (MKP) cell,

which further develops into

4. Megakaryoblast.

5. Platelet-producing megakaryocyte

Thrombocytopenia (a low blood platelet count) is an important

clinical problem in the management of patients with immune-
system disorders and cancer (i.e., leukemia). It increases the risk
of bleeding.

Development of Granulocytes (Granulopoiesis)

Granulocytes originate from the common myeloid progenitor

(CMP) stem cell, which differentiates into granulocyte/monocyte
progenitors (GMPs) which then produce granulocytes
(neutrophils, eosinophils, and basophils) and monocytes.

The neutrophil progenitor (NoP) undergoes six morphologically

identifiable stages in the process of maturation

Eosinophils and basophils undergo a morphologic maturation

similar to that of neutrophils.
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Dr. Doaa Mustafa Histology lec.10-11

1. Myeloblasts are the first recognizable cells that begin the

process of granulopoiesis.
2. Promyelocytes are the only cells to produce azurophilic
granules.
3. Recognition of the neutrophil, eosinophil, and basophil lines is
possible only in the next stage—the myelocyte— when specific
(secondary) and tertiary granules begin to form.
4. The metamyelocyte is the stage at which neutrophil,
eosinophil, and basophil lines can be clearly identified by the
presence of numerous specific granules.
5. mature neutrophil, also called a polymorphonuclear
neutrophil or segmented neutrophil.

Although the percentage of band cells in the circulation is almost

always low (0% to 3%), it may increase in acute or chronic
inflammation and infection.

Granulopoiesis in the bone marrow takes about 2 weeks.

Neutrophils live for 1 to 2 days in the connective tissue, after

which they are destroyed by apoptosis and are subsequently
engulfed by macrophages.

Also, large numbers of neutrophils are lost by migration into the

lumen of the gastrointestinal tract from which they are discharged
with the feces.

Bone marrow maintains a large reserve of fully functional

neutrophils ready to replace or supplement circulating neutrophils
at times of increased demand.

This bone marrow reserve pool constantly releases neutrophils

into the circulation.

A reservoir of neutrophils is also present in the vascular

compartment. This reserve consists of a freely circulating pool
and a marginated pool, with the latter contained in small blood
vessels.
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Dr. Doaa Mustafa Histology lec.10-11

Development of Monocytes

Monocytes are produced in the bone marrow from a CMP stem

cell that can mature into a monocyte or another of the three
granulocytic cell lines.
In addition, CMP gives rise to dendritic cells.
The transformation of MoPs to monocytes takes about 55 hours
monocytes remain in the circulation for only about 16 hours
before emigrating to the tissues where they differentiate into
tissue macrophages.
Their subsequent life span is not yet fully understood.

Development of Lymphocytes (Lymphopoiesis)

Although lymphocytes continuously proliferate in the peripheral

lymphatic organs, the bone marrow remains the primary site of
lymphopoiesis in humans.
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1. T- Lymphocytes
The differentiation of pluripotent HSCs toward common
lymphoid progenitor (CLP) cells. Progeny of the CLP cells
that express GATA-3 transcription factor are T lymphocytes.
These cells that express GATA-3 leave the bone marrow as
pre–T lymphocytes and travel to the thymus, where they
complete their differentiation and thymic cell education. They
then enter the circulation as long-lived, small T lymphocytes.
2. B-Lymphocytes
Another transcription factor, Pax5, activates B-cell–specific
genes in CLP cells destined to become B lymphocytes.
3. Natural Killer Cells
Although a number of transcription factors have been identified
in the development of lymphoid cell lineages, little is known
about factors that may influence development and lineage
commitment of NK cells.

The bone marrow is the main NK cell–producing organ. However,

recent studies suggest that lymph nodes or fetal thymus may also
contain NK-progenitor cells.

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