HAEMOPOIESIS
• Suresh Kr. Mahaseth
• Assistant Professor
• Dept. of MLT
• DSEU Dwarka Campus
HAEMOPOIESIS
• The hematopoietic system is the body's system responsible for
the production and development of blood cells.
• Hem-Blood Poises - Synthesis
• It includes the bone marrow, where blood cells are primarily
formed, as well as other organs and tissues like the spleen, lymph
nodes, and thymus, which also play roles in the maturation and
regulation of blood cells.
• General term for production of blood cells from Haemopoietic stem cell.
• It includes
Erytropoiesis
Leucopoiesis
Thrombopoiesis
.
• During the foetal production of blood cells occurs various body tissues , but mainly
in the liver & the marrow is the only tissue that continues to produce red cells.
• Haematopoiesis is production , development & Maturation of cellular elements of
Blood.
• This process referred to as haematopoiesis the constituents of the bloods are in a
state of between loss , regeneration & replacement this state of equilibrium is
known as Haematopoiesis.
• It consist of Production of
• 1. Erythrocytes ( Erythropoiesis )
• 2. Leucocytes ( Leucopoiesis )
• 3. Thrombocytes ( Thrombopoiesis )
•
Sites of Haemopoiesis
Before Birth - Foetus Yolk Sac - 0 – 2 (Months)
Liver , Spleen - 2 - 7 (Month )
After Birth - Bone Marrow
Bone
Marrow
RED marrow – active, found inside all
bones till the age of 20 years, most of it
replaced by yellow marrow. adult pattern of
marrow distribution - crani bones
vertebrae, pelvic al ,
upper endsbones,
of femur & humerus.
ribs, sternum
,
YELLOW marrow – inactive, filled with fatty
tissue, on demand become active
converted into red marrow producing
blood cells.
Haemopoetic stem
cells
• The blood cells begin their lives in the bone marrow from a single type of cell
called the pluripotential hematopoietic stem cell, from which all the cells of
the circulating blood are eventually derived.
• As these cells reproduce, a small portion of them remains exactly like the
original pluripotential cells and is retained in the bone marrow to maintain a
supply of these, although their numbers diminish with age.
• Most of the reproduced cells, however, differentiate to form the other cell
types.
• The intermediate stage cells are very much like the pluripotential stem cells,
even though they have already become committed to a particular line of cells
and are called committed stem cells.
• The different committed stem cells, when grown in culture, will produce
colonies of specific types of blood cells. A committed stem cell that produces
erythrocytes is called a colony-forming unit–erythrocyte, and the
abbreviation CFU-E is used to designate this type of stem cell. Likewise,
colony-forming units that form granulocytes and monocytes have the
designation CFU-GM, and so forth.
Stage of Development
All Pluripotent stem cell is the most primitive cell
which give rise to Myeloid as well as lymphocytic series
cells.
The Pluripotent stem cell then given rise to committed
stem cells . One type of committed stem cell produces
RBCs, Neutrophils, Eosinophils , Monocytes &
Platelets. The other type of committed stem cell
produces the Lymphocytes.
Cells committed to produce the myeloid series further
differentiate & form progenitor cells .
These are distinctly separate progenitor cells for RBC ,
Granulocytes , Monocytes & Platelets. Progenitor cells
are generally called colony forming unit (CFU) cells.
.
The first Progenitor cell for RBC is called Brust forming unit
Erythrocyte (BFU-E) .
The BFU-E undergoes further differentiation & produces
colony forming unit Erythrocytes (CFU-E).
From the Progenitor CFU-E , the Pronormoblast develops.
It is the first morphologically recognisable Precursor of RBC.
From Pronormoblast early normoblast develops which
in turn gives rise to intermediate normoblast .
From intermediate normoblast late normoblast
develops.
From late normoblast develops the reticulocyte. The
reticulocyte matures for one or two days in bone
marrow & then enters the peripheral blood .
The reticulocyte gives rise to the matured red blood
cell.
• Growth and reproduction of the different stem cells are controlled by
multiple proteins called growth inducers.
• Four major growth inducers have been described, each having
different characteristics. One of these, interleukin-3, promotes growth
and reproduction of virtually all the different types of committed stem
cells, whereas the others induce growth of only specific types of cells.
• The growth inducers promote growth but not differentiation of the cells.
• This is the function of another set of proteins called differentiation
inducers. Each of these causes one type of committed stem cell to
differentiate one or more steps toward a final adult blood cell.
• Formation of the growth inducers and differentiation inducers is itself
controlled by factors outside the bone marrow. For instance, in the case
of erythrocytes (red blood cells), exposure of the blood to low oxygen
for a long time results in growth induction, differentiation, and
production of greatly increased numbers of erythrocytes.
• In the case of some of the white blood cells, infectious diseases
cause growth, differentiation, and eventual formation of specific types of
white blood cells that are needed to combat each infection.
Haemopoetic stem
cells
Stem cell
(pluripotent)
Stem cells
Stem cells
myloied Lymphoid series
series
Formation
of
RBCs,Granulocytes,Monocy Formation of
tes &
Lymphocytes
platelets
Cell
Renewal
Progenitor cells – in between committed
stem cells & blast cells.
Eg. Progenitor of erythrocytic series
Blast cells –immature cells found in the early
stages of development, normally not found
in peripheral blood but only in bone
marrow
Eg. erythroblast, myeloblast,
megakaryoblast, lymphoblast,
monoblast
Erythropoiesis
The term erythropoiesis means the generation of
erythrocytes.
Erythro - Red , Poiesis - Formation
Up to the 3rd month of the intrauterine life
erythropoiesis occurs in the mesoderm of yolk sac.
Between the 3rd month and the 5th month of
intrauterine life, erythropoiesis occurs in the liver and
spleen.
This stage is called the 'hepatic stage’ of erythropoiesis.
From the 5th month red bone marrow begins to produce
erythrocytes. This phase is called 'myeloid phase'.
Stages of Development
The development of a mature erythrocyte is
through several stages of division and
differentiation. There are controversies
regarding the details but following details
represent the consensus thinking.
A pluripotent stem cell is the most primitive
cell which gives rise to myeloid as well as
lymphocytic series cells.
The pluripotent stem cell then gives rise to
committed stem cells. One type of committed
stem cell produces RBCs, neutrophils,
eosinophils, monocytes, and platelets (cell of
the myeloid series). The other type of
committed stem cell produces the
lymphocytes.
Cells committed to produce the myeloid series, further differentiate
and form 'progenitor cells’. There are distinctly separate progenitor
cells for RBC, granulocytes, monocytes and platelets. Progenitor
cells are generally called colony forming unit (CFU) cells.
The first progenitor cell for RBC is called burst forming unit
erythrocyte (BFU-E). The BFU-E undergoes further differentiation
and produces colony forming unit erythrocyte (CFU-E).
From the progenitor CFU-E, the pronormoblast develops. It is the
first morphologically recognisable precursor of RBC.
From pronormoblast 'early normoblast' (large basophilic
normoblast) develops, which in turn, gives rise to 'intermediate
normoblast' (or polychromatophilic normoblast). From intermediate
normoblast 'late normoblast' (or orthochromatic normoblast)
develops.
From late normoblast develops the 'reticulocyte'. The reticulocyte
matures for one or two days in bone marrow and then enters the
peripheral blood. The reticulocyte gives rise to the matured red
blood cell.
Erythropoiesis: Genesis of RBC
• The first cell that can be identified as belonging to the red blood cell series is the proerythroblast.
Under appropriate stimulation, large numbers of these cells are formed from the CFU-E stem cells.
• Once the proerythroblast has been formed, it divides multiple times, eventually forming many mature
red blood cells. The first-generation cells are called basophil erythroblasts because they stain with basic
dyes; the cell at this time has accumulated very little hemoglobin.
• In the succeeding generations, the cells become filled with hemoglobin to a concentration of about 34
per cent, the nucleus condenses to a small size, and its final remnant is absorbed or extruded from the
cell.
• At the same time, the endoplasmic reticulum is also reabsorbed. The cell at this stage is called a
reticulocyte because it still contains a small amount of basophilic material, consisting of remnants of the
Golgi apparatus, mitochondria, and a few other cytoplasmic organelles.
• During this reticulocyte stage, the cells pass from the bone marrow into the blood capillaries by
diapedesis (squeezing through the pores of the capillary membrane).
• The remaining basophilic material in the reticulocyte normally disappears within 1 to 2 days, and the
cell is then a mature erythrocyte. Because of the short life of the reticulocytes, their concentration
among all the red cells of the blood is normally slightly less than 1 per cent.
Regulation of Red Blood Cell Production—
Role of Erythropoietin
• The total mass of red blood cells in the circulatory system is
regulated
within narrow limits, so that
(1)an adequate number of red cells is always available to
provide sufficient transport of oxygen from the lungs to the
tissues, yet
(2) the cells do not become so numerous that they impede
blood flow.
Tissue Oxygenation Is the Most Essential Regulator of Red
Blood Cell Production
• Any condition that causes the quantity of oxygen transported to the
tissues to decrease ordinarily increases the rate of red blood cell
production.
1.anemic condition due to hemorrhage or any other condition
2.destruction of major portions of the bone marrow by any means
3.At very high altitudes, where the quantity of oxygen in the air is greatly
decreased
4.Various diseases of the circulation that cause decreased blood flow
through the peripheral vessels, and particularly those that cause failure
of oxygen absorption by the blood as it passes through the lungs
Tissue hypoxia resulting from these above conditions
increases red cell production, with a resultant increase in hematocrit and
usually total blood volume as well.
Function of the erythropoietin mechanism to increase production of
red
blood cells when tissue oxygenation decreases.
Erythropoietin Stimulates Red Cell
Production, and
Its Formation increases in Response to
Hypoxia.
• In the absence of erythropoietin, hypoxia has little or no effect
stimulating
in red blood cell production. But when the erythropoietin
system is functional, hypoxia causes a marked increase in erythropoietin
production, and the erythropoietin in turn enhances red blood cell
production until the hypoxia is relieved.
• Renal as well as nonrenal sensor sends signal to the kidneys (renal
tubular epithelial cells) to produce & secrete the erythropoietin under
low oxygen state.
• Erythropoietin a glycoprotein hormone with a molecular weight of about
34,000.
• In the normal person, about 90 per cent of all erythropoietin is formed in
the kidneys; the remainder is formed mainly in the liver.
• Both norepinephrine and epinephrine and prostaglandins stimulate
erythropoietin production.
Leucopoiesis: (Genesis of White Blood
Cells)
Leukocytes
:
• The leukocytes, also called white blood cells, are the mobile
units of the body’s protective system. They are formed
partially in the bone marrow (granulocytes and monocytes
and a few lymphocytes) and partially in the lymph tissue
(lymphocytes and plasma cells). After formation, they are
transported in the blood to different parts of the body where
they are needed.
Genesis of the White Blood Cells
• Apart from those cells committed to form red blood cells, two
major
lymphocytic
lineages of lineages.
white blood cells are formed, the myelocyticand the
• The granulocytes and monocytes are formed only in the bone
marrow. plasma cells are produced mainly in the
• lymphogenous various
Lymphocytes tissues—especially
and the lymph glands, spleen, thymus,
tonsils, and various pockets of lymphoid tissue.
• The white blood cells formed in the bone marrow are stored within the
marrow until they are needed in the circulatory system. Then, when the
need arises, various factors cause them to be released.
• The lymphocytes are mostly stored in the various lymphoid tissues,
except for a small number that are temporarily being transported in the
blood.
1, myeloblast;
2,promyelocyte;
3,
megakaryocyte;
4, neutrophil
myelocyte;
5, young neutrophil metamyelocyte;
6,“band” neutrophil
metamyelocyte; 7,
polymorphonuclear neutrophil;
8, eosinophil myelocyte;
9,eosinophil metamyelocyte;
10,polymorphonuclear
eosinophil; 11, basophil
myelocyte;
12, polymorphonuclearbasophil;
13–16,stages of monocyte
formation
Genesis of white blood cells. The different cells of the myelocyte
series.
Control of White Blood Cell
Production
• The cause of the increased production of granulocytes and monocytes
by the bone marrow is mainly the three colony-stimulating factors, one
of which, GM-CSF (granulocyte-monocyte colony-stimulating factor),
stimulates both granulocyte and monocyte production; the other two, G-
CSF (granulocyte colony-stimulating factor) and M-CSF (monocyte colony-
stimulating factor), stimulate granulocyte and monocyte production,
respectively.
• These factors are formed by activated macrophage cells in the inflamed
tissues
• This combination of TNF (tumor necrosis factor), IL-1 (interleukin-1) , and
colony-stimulating factors provides a powerful feedback mechanism that
begins with tissue inflammation and proceeds to formation of large
numbers of defensive white blood cells that help remove the cause of
the inflammation.
Control of bone marrow production of granulocytes and monocyte- macrophages in
response
to multiple growth factors released from activated macrophages in an inflamed tissue.
Thrombopoiesis : Genesis of
Platelets
Platelets
• Platelets (also called thrombocytes) are minute discs 1 to 4 micrometers
in diameter.
• They are formed in the bone marrow from megakaryocytes, which are
extremely large cells of the hematopoietic series in the marrow.
• The megakaryocytes fragment into the minute platelets either in the
bone marrow or soon after entering the blood, especially as they
squeeze through capillaries.
• The normal concentration of platelets in the blood is between 150,000
and 300,000 per microliter
