Haematopoiesis Jones

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EVELYN HONE COLLEGE OF

APPLIED ARTS AND COMMERCE

NAME : KASHIMU JONES KASAMIKA

STUDENT ID : 16600045

COURSE : HAEMATOLOGY

LECTURER : MR MULILO

TASK : ASSIGNMENT ONE

DUE DATE : 12 TH APRIL, 2017


QUESTION : HAEMATOPOIESIS

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INTRODUCTION

Haemapoiesis is the process that describes how the cellular components of blood are
formed, that is the blood cells proliferation , maturation and entry into the blood stream.
Haemopoiesis occurs in a stable microenvironment provided by the stromal matrix on which the
stem cells grow and divide. This microenvironment provides the presence of fat cells, fibroblasts
and macrophages on a bed of endothelial cells.
Haemopoiesis starts with a pluripotent stem cell that can give rise to the separate cell
lineages. Haemopoiesis essentially encompasses the formation of Erythrocytes (red blood cells)
in the process called erythropoiesis. The formation of leukocytes (white blood cells) this process
is called leukopoiesis and the formation of thrombocytes (platelets) this process is known as
thrombopoiesis.
The pluripotent stem cell is the first in a sequence of regular and orderly steps that cells
undergo as they grow and mature. The pluripotent stem cells may mature along morphologically
and functionally diverse lines depending on the stimuli and mediators conditions and these
include erythropoietin, interleukin and colony-stimulating factors to mention just but a few. The
maturation of the stem cell may lead to the production of other stem cells and self-regenerating
factors that are responsible for maintaining the original numbers of the cells.
Secondly the stem cells may take another rout as they mature giving rise to two main
directions. The first one being committed to the lymphoid cell line for lymphopoiesis and the
second one being committed to the development and progression of the multipotent stem cell
which has the ability of bringing up processes such as leukopoiesis which is the formation of
white blood cells, erythropoiesis (the formation of red blood cells) and thrombopoiesis
(formation of platelets).
The pluripotent stem cell has the capacity for continuous self- reproduction and
proliferation and the ability to differentiate into progenitor cells for each cell line.
This proliferation is controlled by regulatory factors known as cytokines. Cytokines are cell
signalling molecules that aid cell to cell communication in immune responses and stimulate the
movement of cells towards sites of inflammation, infection and trauma as well as the regulation
of blood cells production.

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In fetal life the process of haemapoiesis occurs first in the embryonic yolk sac, meaning
all the blood cells are synthesized from this embryonic yolk sac. The second site that is
predominant for haemopoiesis in the second trimester of fetal life is the liver. Starting from the
seventh month the process of haemopoiesis is taken over by the bone marrow. The bone marrow
continues with this process till someone is an adult. This makes the bone marrow the most
predominant sit for haemopoiesis.
In the first four years of life, almost all marrow cavities contain haematopoietic tissue,
which is known as red marrow. The quantity of this haematopoietic tissue decreases and is
replaced by fat which is known as yellow marrow as one grow (age). In adults the red marrow is
limited to the axial skeleton and long bones. In the presence of defective or insufficient
haemapoiesis in the bone marrow, expansion of the red marrow may occur. When this happens
Haemopoiesis can occur in other organs such as the liver and the spleen. This is what is known
as extra-medullary haemapoiesis.

In the bone marrow the process of haemapoiesis occurs in the extravascular region of the
red bone marrow which comprises of the fine supporting reticulin framework interspersed with
vascular channels and the developing marrow cells. There is a single layer of endothelial cells
that tends to separate the extravascular marrow potion from the intravascular compartment.
When the hemopoietic marrow cells are mature and ready to circulate in the peripheral blood, the
cells leave the marrow parenchyma by passing through fine "windows" in the endothelial cells
and emerge into the venous sinuses joining the peripheral circulation

The diagram bellow shows the process of haemapoiesis or haematopoiesis. It shows


the different cell linage that arise from the pluripotent stem cell. That is the Myeloid stem
cell and Lymphoid stem cell.

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The diagram below shows the maturation and development of blood cells from the myeloid
stem cell and lymphoid stem cell.

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The pluripotent stem cell gives rise to the Myeloid stem cell and the Lymphoid stem cell
lineages. The Myeloid stem cell is multipotent and hence it differentiates into the Myeloblast and
Pronormoblast. The Myeloblast give rise to the following cells through different levels of
maturation and division and these are Basophils, Eosinophils and Neutrophils. These are
collectively known as Polymorphonuclear Leucocytes (granulocytes). The pronormoblast gives
rise to erythrocytes (red blood cells). The myeloid stem cell also gives rise to monocytes and
platelets (thrombocytes). The Lymphoid stem cell gives rise to the lymphocytes.

1.0 LEUCOPOIESIS
This is the process in which leucocytes (white blood cells) are formed from the
haematopoietic stem cells in the bone marrow. Leucopoiesis is comprised of Granulopoiesis,
Lymphopoiesis and Monocytopoiesis. Granulopoiesis is the formation of white blood cells called
granulocytes (basophils, eosinophils and neutrophils). Lymphopoiesis is the formation of white
blood cells called lymphocyts. Monocytopoiesis is the process in which monocytes are produced.

Leukopoiesis is hormonally stimulated by two families of cytokines (hematopoietic


factors) – interleukins and colony-stimulating factors (CSFs). Interleukins are numbered for
example IL-1, IL-2 etc, while colony-stimulating factors (CSFs) are named for the white blood
cells they stimulate for example granulocyte-CSF which stimulates granulocytes. The main
source for cytokines are the macrophages and T cells.

The above mentioned haematopoietic processes are discussed below.

GRANULOPOIESIS
Granulopoiesis is the formation of granulocytes within the bone marrow. It is controlled
by a number of substances including granulocyte colony stimulating factors. This hematopoiesis
process involves the synthesis of white blood cells which have the presence of granules in their
cytoplasm hence the name granulocytes. The blood cells produced by the process of
granulopoiesis include basophils, eosinophils and neutrophils.

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Basophils, eosinophils and neutrophils undergo similar stages of maturation and
developmental stages. These developmental stages of maturation happens in a well regulated
sequence that give rise to the desirable white blood cells.

The following are the stages of granulopoiesis. The pluripotential hemopoietic stem cell
differentiates into the myeloblast. The myeloblast develops into promyelocyte. This
promyelocyte gives rise to the basophilic myelocyte, eosinophilic myelocyte and neutrophilic
myelocyte. The myelocyte gives rise to the metamyelocyte. The band cell which is also known
as the stab cell arises from the metamyelocyte. The band cell develops and matures into
granulocytes which are the basophils, eosinophils and neutrophils.

It is important to note that the myelocyte stage is the first stage where cell-specific
maturation appears.

In most cases the average time interval from the initiation point of granulopoiesis to the
time when mature granulocytes enter into the circulating blood stream is about 10 to 13 days.
The mature granulocytes remains in the circulation for only about 10 to 14 hours before they can
enter the tissue. When they enter the tissue they perform their phagocytic functions and soon
after that they die.

NEUTROPHILS
Neutrophils are a type of white blood cell responsible for fighting infections in the body. They
are the first line of defense. Neutrophils are part of the innate immune system of the body.
Neutrophils follow the following sequence in their maturation.
Myeloblast  Promyelocyte  Neutrophilic Myelocyte  Metamyelocyte (Juvenile
cell)  Band Granulocyte (Stab Cell) Segmented granulocyte (mature granulocyte)
1. MYELOBLAST
The myeloblast is an early precursor cell which has a round shape and a diameter of
about 20-25m. It has got a round or oval shaped nucleus which is also large and
eccentric. Its nuclear membrane is quite thin. The ratio of the nucleus to the cytoplasm is
7:1 this means that it has reduced or small cytoplasmic mass. Its cytoplasm lacks granules
and it stains basophilic (bluish).

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2. PROMYELOCYTE
This is the next stage in the maturation of neutrophils characterized by the presence of
numerous azurophillic primary granules in cytoplasm that contain different enzymes. The
cytoplasm is pale blue staining and relatively occupies more space as compared to the
myeloblast. Its nucleus is surrounded by a thin membrane and is eccentrically located,
having an oval shape too. The promyelocyte is about 15-20m in diameter and oval in
shape.

3. NEUTROPHILIC MYELOCYTE
At this stage the oval nucleus becomes indented and still remains eccentric. The
secondary granules become prominent. The cytoplasm stains light pink. The ratio of the
nucleus to the cytoplasm is about 2:1. It has got a round shape and a diameter of about
14-18μm. At this level cell specific maturation is observed.

4. METAMYELOCYTE
This is the last stage of granulocyte development where mitotic division is experienced.
The developmental stages that follow after this are caused my maturation and non-
division. At this stage the granules are becoming more concentrated within the cell and
the nucleus gets to be more lobulated and appear in a kidney shape. The nuclear
membrane tends to be more heavy and thick. The cytoplasm stains pale or pink and is
much more abundant. It is round in shape bearing a diameter of 12-14μm.

5. BAND GRANULOCYTE
The band granulocyte also known as the stab cell are the youngest granulocytes that are
normally found in the peripheral blood. They develop from the bone marrow through
further lobulation (formation of more lobes) of its nucleus. The cytoplasm contains
specific and a few non-specific granules and is pink or colorless. This cell has got more
cytoplasm occupying the space than the nucleus and this gives a ratio of the nucleus to
the cytoplasm as 1:2. The nucleus is U-shaped, elongated and curved which may have
one or two twists. The size of the stab cell is normally 10-12μm in diameter.

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6. SEGMENTED GRANULOCYTE (MATURE GRANULOCYTE)
At this stage we have the mature neutrophils which are ready to join the circulation
system in order to fight various types of infections that may invade the body systems. The
nucleus is characterized by heavy, thick chromatin masses. It is also eccentric. The
nucleus is multi lobulated having about 2-5 lobes which are connected or linked to each
other by the thin bridges of chromatin membrane. The cytoplasm is quite abundant and
slightly eosinophilic that is pinkish. This gives a nuclear/cytoplasmic ratio of 1:2.
The neutrophilic granules present in this cell have got a fine texture and do not overlay
the nucleus. The diameter of the cell is 10-12μm.

EOSINOPHILS
Eosinophils are white blood cells and are part of the innate immune system of the body.
They are responsible in the fighting of allergic reactions and combating helminthic
infections. Eosinophils are slightly larger than neutrophils and they have a diameter of
12-14m. The nucleus has got two lobes which are arranged in a spectacle manner.
Eosinophils mature in the same manner as the neutrophils as they develop from
the same cell lineage. The following is the sequence followed in summary form.
Myeloblast  Promyelocyte  Eosinophilic Myelocyte  Metamyelocyte
(Juvenile cell)  Band Granulocyte (Stab Cell) Segmented granulocyte (mature
granulocyte). The mature eosinophil contains granules which are uniform in size, they
are large but do not still cover the nucleus. This granules are orange-pink in color.

BASOPHILS
Basophils mature in the same why as neutrophils do. The key stage in their maturation is
when the basophilic myelocyte is formed. This signifies and specifies a cell as basophil.
Basophiles have a kidney shaped nucleus which contains less chromatin and it is often
covered by the granules present in the cytoplasm. Their granules stain deep purple/blue.
They also contain chemical mediates that come into play during inflammation. These are
histamine and heparin. Basophils have a diameter of between 10-12μm. Basophils are
generally smaller than eosinophils.

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2.0 LYMPHOPOIESIS

Lymphopoiesis is a haematopoietic process that arise from the lymphoid stem cell as the
progenitor cells. Lymphocytes are a type of white blood cells. Lymphopoiesis is the process that
involves the production, development and maturation of lymphocytes. Cells that develop and rise
from this process include B-lymphocytes (B cells), T-lymphocytes (T cells) and the Natural
Killer (NK cells). The B cell lymphopoiesis is completed in the bone marrow, whereas
T cell lymphopoiesis occurs in the thymus. Lymphocytes have large round/oval nuclei that
occupies most of the cell with little cytoplasm. The nucleus will stain dark purple or blue when it
is exposed to a certain stain called Wright’s stain. The B cells ultimately differentiate into
morphologically distinct, antibody-producing cells called plasma cells.
The maturation and development of lymphocytes follows this cell lineage. The
lymphoblast develops into the prolymphocyte which then gives rise to the lymphocytes.
Lymphoblast  Prolymphocyte  Lymphocytes.
The diagram below shows the process of lymphopoiesis.

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LYMPHOBLAST
The Lymphoblast is the immature white blood cell that gives rise to a type of
immune cells known as a lymphocytes. The nucleus contains moderately fine chromatin (readily
stainable nuclear material) and has a well-defined nuclear membrane. There are one or two
nucleoli, and the cytoplasm is small or moderate in amount. The nucleus is oval and it is
centrally located. The size of the lymphoblast is about 15-20μm in diameter. The cytoplasm does
not contain granules and it appears sky blue which even forms a thin perinuclear ring.

PROLYMPHOCYTE
A prolymphocyte is a white blood cell with a certain state of cellular differentiation in the
process of lymphocytopoiesis. This cell of the lymphocytic series is the intermediate cell
between the lymphoblast and the lymphocyte. It measures about 14-18μm in diameter. The
nucleus of the prolymphocyte appears slightly indented and oval. Condensed chromatin is
observed in a mosaic format. Its cytoplasm appears homogeneous.

LYMPHOCYTES
Lymphocytes are a type of white blood cells. Its nucleus will stain dark purple or
blue when it is exposed to a certain stain called Wright’s stain. There are two categories of
lymphocytes and these are small lymphocytes (T-lymphocytes) and big lymphocytes (B-
lymphocytes)
The small lymphocytes measure about 7-10m in diameter, they have a pal blue staining
cytoplasm and they are the predominant forms in blood.
The big lymphocytes measure about 12-14m in diameter. They contain a little pall
nucleus. They have more cytoplasm that stains blue.

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3.0 MONOCYTOPOIESIS
Monocytopoiesis is the process which leads to the production of monocytes and
subsequently, macrophages. It can be induced by macrophage colony-stimulating factor.
The monoblast develops into the promonocyte which eventually matures into monocytes.

MONOBLAST
Monoblasts are large cells, with round to oval nuclei and abundant cytoplasm. The monoblast
has a relatively large amount of cytoplasm which stains pal blue. It has got an oval nucleus and a
diameter of about 15-25μm.

PROMONOCYTE
A promonocyte (or premonocyte) is a cell arising from a monoblast and developing into a
monocyte. This cell is capable of mitotic division. It is about 15-20μm in diameter. It contains
abundant cytoplasm which stains gray-blue. The nucleus is quite large, grooved and convoluted.

MONOCYTE
Monocytes are a type of white blood cells, or leukocyte. They are the largest type of leukocyte
and can differentiate into macrophages and myeloid lineage dendritic cells. Monocytes have
abundant cytoplasm which stains gray-blue. The nucleus is centrally and at times eccentric
having a kidney shape and often lobulated. It measures about 14-18μm in diameter.

4.0 THROMBOPOIESIS
Thrombopoiesis refers to the process of thrombocyte (platelet) generation. Thromobocytes are
ligations of the cytoplasm from megakaryocytes. A single megakaryocyte can give rise to
thousands of thrombocytes. The stages of thrombopoiesis include the following, Megakaryoblast
developing into Promegakaryocyte and this developing into Granular Megakaryocyte. The
granular megakaryocyte gives rise to Platelets. Platelets are responsible for blood clotting.

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MEGAKARYOBLAST
A megakaryoblast is a precursor cell to a promegakaryocyte, which becomes
a megakaryocyte during haematopoiesis. It is the beginning of the thrombocytic series.
This cell is smaller than its mature forms. Its diameter ranges with 10-30 m. it has a large single
nucleus which is also oval. Its cytoplasm forms a scanty, bluish, patchy, irregular ring around the
nucleus.

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PROMEGAKARYOCYTE
A promegakaryocyte is a precursor cell for the megakaryocyte, it arises from a megakaryoblast
cell. its bigger than the megakaryoblast having a diameter of between 20-50 m. A large
prominent, poly-lobulated nucleus is present. Clumping is usually observed due to the chromatin.
Its cytoplasm appear blue.

GRANULAR MEGAKARYOCYTE
. A megakaryocyte ("large-nucleus cell") is a large bone marrow cell with a large lobulated
nucleus responsible for the production of blood thrombocytes (platelets), which are necessary for
normal blood clotting. The majority of the megakaryocytes of a bone marrow are in stage III
which is characterized by progressive nuclear condensation. The beginning of platelet formation
within the cytoplasm. This is a giant cell which measures about 30-100μm in diameter and is the
largest cell found in the bone marrow. It contains a large amount of polychromatic cytoplasm
produces blunt, smooth, pseudopodia-like projections that contain aggregates of azurophilic
granules surrounded by pale halos. These structures give rise to platelets at the periphery of the
megakaryocytes.

PLATELETS
Platelets which are also called thrombocytes are a component of blood whose function along
with the coagulation factors is to stop bleeding by clumping and clotting blood vessel
injuries. Platelets have no cell nucleus. They are small colorless disc-shaped fragments
of cytoplasm that are derived from the megakaryocytes of the bone marrow. They enter the blood
circulation in order to perform there functions. They are found in large numbers in the blood.
They measure about 1-4μm in diameter.

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This diagram shows the process of thrombopoiesis.

5.0 ERYTHROPOIESIS
This is the process that refers to the development and maturation of erythrocytes which are also
known as red blood cells. The diagram shows the summary of erythropoiesis.

REGULATION OF HAEMATOPOIESIS.
Haematopopoiesis is regulated by haemopoietic growth factors and glycoprotein hormones.
These are heterogeneous group of cytokines that stimulate the progenitor cells and induce
proliferation and maturation. They are glycoproteins synthesized by variety of cells in marrow.
They bind to specific receptors on the surface of various cells of the hematopoietic system.

Thrombopoietin is a glycoprotein hormone produced mainly by liver and kidney that


regulates the production of platelets in bone marrow. It stimulates the production and
differentiation of Megakaryocytes.

GM-CSF are Produced by fibroblasts, stromal cells, T-lymphocytes and endothelial cells.
They stimulate progenitors for granulocytes, monocytes and erythrocytes.

Eryhtropoietin is responsible stimulation of the production of red blood cells.

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CONCLUSION
Haemapoiesis (haematopoiesis) is the process that refers to the formation, development
and maturation of all blood cells arising from the pluripotent stem cell in the bone marrow.

Haemopoiesis starts with a pluripotent stem cell that can give rise to the separate cell lineages.
Haemopoiesis essentially encompasses the formation of Erythrocytes (red blood cells) in the
process called erythropoiesis. The formation of leukocytes (white blood cells) this process is
called leukopoiesis and the formation of thrombocytes (platelets) this process is known as
thrombopoiesis.

Haemapoiesis is essential in the maintenance of the blood cells in the body. This shows
that haemapoiesis has the homeostasis function in the maintenance of the numbers of the blood
cells by keeping them within the normal ranges.

Blood cells have got a programmed cell death which is known as apoptosis. Apoptosis is
a regulated process of physiological cell death in which cells are triggered to activate
intracellular proteins that lead to the death of the cells. Morphologically it is characterized by cell
shrinkage, condensation of the nuclear chromatin, fragmentation of the nucleus and cleavage of
DNA at internucleosomal sites. Apoptosis is an important process for maintaining tissue
homoeostasis in homeostasis and lymphocyte development.

. The following are the sites for haematopoiesis the yolk sac , liver, spleen and the bone
marrow. In adults the bone marrow is the site for haematopoiesis. Haemapoiesis is a well-
regulated process by hormones, growth factors and cytokines.

The different forms of the process of haematopoiesis are essential in the formation and
maintaining of blood cells effectively without comprications.

These processes have to be regulated in order to avoid different types of blood cancers
and other hematological conditions which may be life threatening.

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REFERENCES
1. Hall, Roger and Malia, Robert G. Medical Laboratory Hematology. Butterworths and
Co. 1984.
2. Hayhoe, F.G.J. and Flemans R.J. A Color Atlas of Hematological Cytology. 3rd
Edition Wolfe Publishing Ltd. 1992.
3. www.nature.com/subjects/lymphopoiesis
4. https://www.britannica.com/science/lymphoblast
5. http://www.interactive-biology.com/3998/lymphopoiesis-the-development-of-
lymphocytes/
6. https://en.wikipedia.org/wiki/Basophil

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