Normal Hemopoiesis
Ahmad Sh. Silmi
Msc Haematology, FIBMS
Lifespan and production of blood cells
Cell type
Red Cells
Neutrophils
Platelets
Lymphocytes
Approximate
lifespan
Production
rate
cells/day
Production
rate
cells/sec
Production
rate Kg/year
100 days
2 x 1011
2.3 million
7.3
t½ 6 hours
3 x 1010
350,000
10.9
7 days
1 x 1011
1.2 million
4.6
t½ 10 days
1 x 1010
116,000
3.7
Annual total
26.5 Kg
So our body is in a continuous dynamic and a very
rapid cell turnover to be able to live.
HOW ?
It’s the Stem Cell !
HEMOPOIESIS: INTRO
Hemo: Referring to blood cells
Poiesis: “The development or production of”
The word Hemopoiesis refers to the
production & development of all the blood
cells:



Erythrocytes: Erythropoiesis
Leucocytes: Leucopoiesis
Thrombocytes: Thrombopoiesis.
HEMOPOIESIS
Hemopoiesis depends on 3 important
components:
 the bone marrow stroma (Local control)
 the hemopoietic stem and progenitor cells
 the hemopoietic growth factors (Humoral
control)
STEM CELL THEORY
The dazzling array of all the blood cells are
produced by the bone marrow.
They all come from a single class of primitive
mother cells called as:
PLURIPOTENT STEM CELLS.
These cells give rise to blood cells of:


Myeloid series: Cells arising mainly from the
bone marrow.
Lymphoid series: cells arising from lymphoid
tissues.
STEM CELLS
These cells have extensive proliferative
capacity and also the:


Ability to give rise to new stem cells (Self
Renewal)
Ability to differentiate into any blood cells
lines (Pluripotency)
They grow and develop in the bone marrow.
The bone marrow & spleen form a supporting
system, called the
“hemopoietic microenvironment”
STEM CELLS: Types
Pluripotent Stem cells:



Has a diameter of 18 – 23 μ.
Giving rise to: both Myeloid and Lymphoid series of cells
Capable of extensive self-renewal.
Myeloid Stem cells: Generate myeloid cells:



Erythrocytes
Granulocytes: PMNs, Eosinophils & Basophils.
Thrombocytes.
Lymphoid Stem cells: Giving rise only to:

Lymphocytes: T type mainly.
Routes a stem cell can take
self-renew
differentiate
Self renewal of stem cells
Symmetric cell division
Asymmetric cell division
Stem cells divide asymmetrically
Non-stem cells divide symmetrically
Rules of Normal Cell Proliferation
1
2
3
Stem cells self renew--immortal
non-stem cells have finite life span
But also when it is required : Stem cells divide
symmetrically to restore stem cell quantity
Stem cells symmetric cell division
CLONAL HEMOPOIESIS
MULTIPLICATION
COMMITTMENT
COMMITTED
STEM CELL
STEM CELL
MULTIPLICATION
COMMITTED
STEM CELL
CFU: COLONY
FORMING UNIT
CLONAL HEMOPOIESIS:
COLONY FORMING UNIT
(Contd)
(CFU)
MORPHOLOGICALLY
RECOGNIZABLE
MATURE BLOOD CELLS
END CELLS: FINITE LIFE SPAN
INTERMEDIATE
BLAST CELLS
Properties of stem cells
1. Self renewal
2. Hierarchy
3. Extensive proliferative capacity
4. Cell cycle status
5. Surface Markers
6. Interact with microenvironment
Stem Cell Hierarchy
Stem Cell Progression Is Associated By
Changes In:
- Specific cell markers
- Receptors
- Adhesion molecules
- Chromatin openness
- Access to epigenetic transcription
factors and loss of proliferative
potential.
SITES OF HEMOPOIESIS
Yolk
sac
Liver
and spleen
Bone
marrow
–Gradual replacement of
active (red) marrow by
inactive (fatty) tissue
–Expansion can occur
during increased need
for cell production
SITES OF HEMOPOIESIS
Active Hemopoietic
marrow is found,
in children
throughout the:

Axial skeleton:





Cranium
Ribs.
Sternum
Vertebrae
Pelvis
Appendicular
skeleton:
• Bones of the
Upper &
Lower
limbs
In Adults active
hemopoietic marrow is
found only in:
•The axial skeleton
•The proximal ends
of the appendicular
skeleton.
Sites of Hemopoiesis
Hemopoiesis starts as early as yolk sac development.
2-3 weeks after fertilization 3 layers are developed (ecto,
meso, and endoderm)
Hemoangioblast which is derived from the mesoderm
Hemoangioblast
Endothelial stem cell
Hemopoietic stem cell
Will develop to Blood vessels
will develop to Blood cells
In the embryo
 2 week old embryo, hematopoiesis begins in yolk
sac.
THE 1ST CELL TO BE PRODUCED IS
erythrocytes
 By 2 month old fetus, granulocyte and
megakaryocyte production.
 4th month, lymphocytes production.
 5th month, monocytes produced.
CONTINUED…..
In the 3rd to 7th month of fetal life Hemopoietic stem cells
will migrate to the liver and spleen, where hemopoiesis
starts there and hemopoiesis is still mainly erythropoietic
in nature, with minimal granulopoiesis
The bone marrow (BM)
The stem cells then migrate to the bone marrow
(BM) where hemopoiesis starts and continue
all over the life. In the bone marrow all types
of blood cells are formed which include:
RBCS
Granulocytes: Neutrophils, Eosinophils, Basophils
Lymphocytes
Monocytes and macrophages
Platelets
Extramedullary Hemopoiesis
When required, yellow marrow can be replaced by
red marrow.
Liver & spleen can aslo resumed.
This will multiply the production by 6.
Remark that Hemopoiesis within the marrow is
called intramedullary or medullary hemopoiesis
Stages in haemopoietic cell
development
Cell hierarchy (Haemopoiesis schematic
representation)
Hematopoietic Inductive
Microenvironment
Why hemopoietic cells reside in the bone
marrow
The stromal matrix plays an important role in presenting
growth factors and nutrients to developing blood cells.
The most immature cells have receptors which bind them to
proteoglycan molecules on the matrix and to receptors on the
stromal cells (i.e. macrophages, fibroblasts, fat cells and
endothelial cells)
There are lineage specific regions ( "niches" ) which provide the
molecular basis for homing of transplanted stem cells.
The unique supportive microenvironment stem cell niche
- regulates proliferation and differentiation
- supports survival and inhibits apoptosis
Similar principles apply to malignant stem cells in myeloid
leukemias
The sinusoids are lined with specialized endothelial cells which play
an important role by producing factors which regulate growth
and differentiation.
Interaction of stromal cells, growth
factors and haemopoietic cells
Stromal Cells of BM
Endothelial cells
Fat cells
Fibroblasts
Lymphocytes
Macrophage
Haemopoietic growth factors
Haemopoietic growth factors
The haemopoeitic growth factors are glycoprotein hormones
that regulate the proliferation and differentiation of
haemopoietic progenitor cells and the function of mature
blood cells.
T lymphocytes, monocytes, marcrophages and stromal cells
are the major sources of growth factors except for
erythropoietin, 90% of which is synthesized in the kidney
and thrombopoietin, made largely in liver.
Haemopoietic growth factors
Overview
Regulate growth and differentiation
- a family of glycoproteins with clinical utility
- with different specificities
- with different origins
- bind to cognate receptors on progenitor cells
- act locally or at a distance
- regulate proliferation and differentiation
- prevent apoptosis
- enhance function of some end stage cells
eg. GM-CSF enhances PMN function....,
Adhesion molecules /integrins
Haemopoietic growth factors
GM-CSF
 Granulocyte-Macrophage colony stimulating
factor
M-CSF
 Macrophage colony stimulating factor
Erythropoietin
 Erythropoiesis stimulating hormone
(These factors have the capacity to stimulate the proliferation of
their target progenitor cells when used as a sole source of
stimulation)
Thrombopoietin
 Stimulates megakaryopoiesis
Haemopoietic growth factors
Cytokines









IL 1 (Interleukin 1)
IL 3
IL 4
IL 5
IL 6
IL 9
IL 11
TGF-β
SCF (Stem cell factor, also known as kit-ligand)
Cytokines have no (e.g IL-1) or little (SCF) capacity to stimulate cell
proliferation on their own, but are able to synergise with other
cytokines to recruit nine cells into proliferation
Role of growth factors in normal
haemopoiesis
Order of blood cell formation
1:STEM CELLS
2: Progenitor cells may be mutli-potential, bipotential or uni-potential
3: Precursor cells, or also called maturing cells
4: Terminally differentiated cells Mature cells
Precursor cells
Precursor cells
Precursor cells
Precursor cells
Stem Cells
 Stem Cells: undifferentiated cells that give rise to all
of the bone marrow cells.
 Only 0.5% of all marrow nucleated cells.
 Multipotential precursors.
 High self-renewal – give rise to daughter stem cells
that are exact replicas of the parent cell.
 Not morphologically distinguishable At any time,
the majority of stem cells (95%) are out of the cell
cycle (they are in G0 mode/phase, also called
quiescent).
 The current phenotype is: CD34+CD38-Lin-HLADR-Rh123Dull
Progenitor cells of the BM
 Stem cells which undergo differentiation.
 Limited self-renewal ability.
 Multipotential but Gradually they become
unilineage or committed progenitor cell.
 ~3% of total nucleated hematopoietic cells
of bone marrow
Progenitor cells of the BM
 Form colonies of cells in semisolid media in vitro –
described as colony forming units (CFU).
 CFU-GEMM (granulocytic, erythrocytic,
monocytic,megakaryocytic,CFU-GM,CFU-Mk, etc. )
 Survival and differentiation of progenitor cells
influenced by growth regulatory glycoproteins,
called cytokines – include interleukins, colony
stimulating factors
Morphology of stem cells and progenitor
cells
Stem cells & progenitor cells are not
recognized morphologically but all
look like small mononuclear
lymphocytes
Maturing blood cells
1-
Majority of cells (>95%)
2- lose adherence receptors, become deformable.
3- migrate through cytoplasm of lining endothelial
cell to enter sinusoids.
4. Platelets are the exception.
Megakaryocytes form part of the sinusoidal
wall. They form long processes of proplatelets
which fragment into nascent platelets.
Regulation of Haemopoiesis
There
should be a balance between cell production and cell death except at
the times of requirement
Regulation of Haemopoiesis
Local environmental control
Stromal cell mediated Haemopoiesis
Apoptosis
Haemopoietic
growth factors (Humoral regulation)
Regulation of Haemopoiesis

Immunoglobulin superfamily - Growth Factor Receptors
(GFr) bind to cognate "ligand" to initiate signal transduction
( GF binds to extracellular domain of GFr, alters
configuration of cytoplasmic domain, causes
phosphorylation of a tyrosine kinase and initiates the signal
that is ultimately transmitted to the nucleus.)

Selectins are involved in:
a) inflammatory and immune responses
b) platelet adhesion and activation

Integrins - control traffic and specific cell functions
- adhere to matrix niches
- release from marrow
- homing of lymphocytes and stem cells etc.
Apoptosis
important for homeostasis
Hematopoietic cells are programmed
to self destruct but can be rescued
from apoptosis by:
specific growth factors
certain gene products
specific antigen
some viruses eg EBV
Mechanism of apoptosis
Apoptosis, Continue
Defects in the apoptotic pathway are very important in
causing diseases such as chronic lymphocytic leukemia
(CLL), and in enhancing resistance to chemotherapy in
malignancy.
Induction of apoptosis is a therapeutic strategy in
resistant CLL
Inappropriate apoptosis is a disease mechanism in
myelodysplasyic syndromes.
Apoptosis is induced by chemotherapy, and resistance to
chemotherapy is associated with blocked apoptosis.
Assessment of hemopoiesis
Hemopoiesis can be assessed clinically by;
1- (FBC, CBC= complete blood count) on
peripheral blood.
2- Bone marrow Aspiration also allows
assessment of the later stages of
maturation of hemopoietic cells.
3- Bone marrow Trephine Biopsy
provides a core of bone and bone
marrow to show architecture.
Bone marrow Aspiration
Bone marrow aspiration
Hypercellular
Normocellular
Hypocellular
The M:E ratio
Myeloid to Erythroid ratio in the bone
marrow
Is called M:E ratio
Normally it is 3-4:1
Normal Blood Cells
ERYTHROPOIESIS
PROERYTHROBLAST
BASOPHILIC
ERYTHROBLAST
POLYCHROMATOPHILIC
ERYTHROBLAST
ORTHOCHROMATIC
ERYTHROBLAST
RETICULOCYTE
MATURE ERYTHROCYTES
Stages in Red cell (erythroid)
Maturation
Proerythroblast
Basophilic
erythroblast
Polychromatic
erythroblast
(two examples)
Orthochromic
erythroblast
ERYTHROID PROGENITOR
CELLS
BFU-E: Burst Forming Unit – Erythrocyte:
 Give rise each to thousands of nucleated
erythroid precursor cells, in vitro.


Undergo some changes to become the
Colony Forming Units-Erythrocyte (CFU-E)
Regulator: Burst Promoting Activity (BPA)
ERYTHROID PROGENITOR
CELLS
CFU-E: Colony Forming Unit- Erythrocyte:




Well differentiated erythroid progenitor cell.
Present only in the Red Bone Marrow.
Can form upto 64 nucleated erythroid precursor
cells.
Regulator: Erythropoietin.
Both these Progenitor cells cannot be
distinguished except by in vitro culture
methods.
Normoblastic
Precursors
PROERYTHROBLAST:


Large cell: 15 – 20 Microns in diameter.
Cytoplasm is deep violet-blue staining
Has no Hemoglobin.
 Large nucleus 12 Microns occupies
3/4th of the cell volume.
 Nucleus has fine stippled reticulum &
many nucleoli.

Normoblastic
Precursors
EARLY NORMOBLAST:(BASOPHILIC
NORMOBLAST)
–
–
–
–
Smaller in size.
Shows active Mitosis.
No nucleoli in the nucleus.
Fine chromatin network with few condensation
nodes found.
– Hemoglobin begins to form.
– Cytoplasm still Basophilic.
Normoblastic
Precursors
INTERMEDIATE NORMOBLAST:
(POLYCHROMATOPHILIC NORMOBLAST)
– Has a diameter of 10 – 14 Microns.
– Shows active Mitosis.
– Increased Hemoglobin content in the
cytoplasm
– Cytoplasm is Polychromatophilic.
Normoblastic
Precursors
LATE NORMOBLAST:
(ORTHOCHROMIC NORMOBLAST)
– Diameter is 7 – 10 Microns.
– Nucleus shrinks with condensed
chromatin.
– Appears like a “Cartwheel”
– Cytoplasm has a Eosinophilic appearance.
RETICULOCYTE
– The penultimate stage cell.
– Has a fine network of reticulum like a
heavy wreath or as clumps of dots
– This is the remnant of the basophilic
cytoplasm, comprising RNA.
– In the Neonates, Count is 2 – 6/Cu.mm.
– Falls to <1 in the first week of life.
– Reticulocytosis is the first change seen
in patients treated with Vit B12
MATURE ERYTHROCYTE
– Biconcave disc.
– No nucleus.
– About One-third filled with Hemoglobin.
Erythropoiesis
 4 mitotic divisions between pronormoblast and
orthochromic normoblast stage.
 Thus giving rise 16 RBCs.
 But not all of the 16 will be good RBCs, some are bad and
will be destroyed, these destroyed cells is called ineffective
erythropoiesis.
 2 – 7 days for pronormoblast to mature into orthochromic
normoblast
 1 more day to extrude the nucleus from the orthochromic
normoblast.
 Reticulocyte further matures for 2 – 3 days in bone marrow
before it is released into the peripheral blood.
 Red cell has life span of 120 days in peripheral blood.
Phases of Erythropoiesis
FACTORS REGULATING
ERYTHROPOIESIS
SINGLE MOST IMPORTANT REGULATOR:
“TISSUE OXYGENATION”
BURST PROMOTING ACTIVITY
ERYTHROPOIETIN
IRON
VITAMINS:
– Vitamin B12
– Folic Acid
MISCELLANEOUS
ERYTHROPOIETIN
A hormone produced by the Kidney.
A circulating Glycoprotein
Nowadays available as Synthetic Epoietin
Acts mainly on CFU – E.
Increases the number of:
– Nucleated precursors in the marrow.
– Reticulocytes & Mature Erythrocytes in the
blood.
VITAMINS
B12: Cyanocobalamine & Folic Acid:
– Is also called Extrinsic Factor of Castle.
– Needs the Intrinsic Factor from the Gastric
juice for absorption from Small Intestine.
– Deficiency causes Pernicious (When IF is
missing) or Megaloblastic Anemia.
– Stimulates Erythropoiesis
– Is found in meat & diary products.
IRON
Essential for the synthesis of Hemoglobin.
Deficiency causes Microcytic, Hypochromic
Anemia.
The MCV, Color Index & MCH are low.
Regulation of Erythropoiesis
Stimulates
CFU – E
Proerythroblasts
ERYTHROPOIETIN
Mature Erythrocytes
Tissue Oxygenation
Factors decreasing:


Hypovolemia
Anemia
Poor blood flow
Pulmonary Disease

An example of a
Negative feed back
mechanism
Erythropoietin (Epo)
As its name suggests, EPO stimulates growth of
Erythrocytes, and its function include:
 Activates stem cells of bone marrow to differentiate into
pronormoblasts.
 Shortening cell cycle.
 Decrease maturation time.
 Increases rate of mitosis and maturation process.
 Increases rate of hemoglobin production.
 Causes increased rate of reticulocyte release into the
peripheral blood, (normally the reticulocyte when it is
released to the peripheral blood it need only one day to
mature to RBC, but here they will be released
prematurely into peripheral blood, thus they need more
than one day to mature to mature RBC.
 Prevent apoptosis.
EPO receptors
Found on surface on bone marrow erythroid
progenitor and precursor cells.
The highest number of EPO receptors is seen
on the CFU-E and the pronormoblasts.
The number of EPO receptors per cell
gradually decreases during erythroid cell
differentiation, and studies have shown that the
reticulocyte and mature erythrocyte do not
contain EPO receptors
EPO Receptor
Divided into extracellular,
transmembrane, and cytoplasmic
domains.
The cytoplasmic domain has terminal
that contains both positive and negative
growth-regulatory domains.
After EPO binding, EPOR
homodimarizes and JAK-2
phosphorylates itself, so EPOR and other
proteins like STAT-5 initiate the cascade
of proliferative signals.
Granulopoiesis
E
Granulocytes
Neutrophils
Eosinophils
Basophils
Only mature cells are present in
peripheral blood
N
B
Stages in Granulocyte
Maturation
Blast cell
Promyelocyte Myelocyte Metamyelocyte Band cell Segmented
Neutrophil
Neutrophil Maturation - Myeloblast
Cells in the BM proliferation pool take 24-48
hours for a single cell cycle
Less than 1% of the normal BM compartment is
composed of myeloblasts
Large, 15-20 um in size
Delicate nucleus with prominent nucleoli
Small amount of cytoplasm with rough
endoplasmic reticulum, a developing Golgi
apparatus and an increasing number of
azurophilic granules
Neutrophil Maturation - Myeloblast
Cytochemical staining shows presence of
myeloperoxidase which is required for
intracellular kills
Killing function is the first to be
operational in the neutrophil cell line
Myeloblast is incapable of motility,
adhesion and phagocytosis and is
therefore nonfunctional
Neutrophil Maturation - Promyelocyte
After a few days in the blast stage, the cell
becomes a promyelocyte
1-5% of BM compartment composed of
promyelocytes
Size is variable and may exceed 20 um, so
may be larger than myeloblast
Nuclear chromatin may be delicate or may
show slight clumping
Nuceloli begin to fade
Stages in Granulocyte
Maturation
Blast cell
Promyelocyte Myelocyte Metamyelocyte Band cell
Segmented
Neutrophil
Neutrophil Maturation - Myelocyte
Production and accumulation of neutrophilic
granules is characteristic of the myelocyte
The myelocyte is the last cell of the BM
compartment capable of mitosis
Myelocytes demonstrate morphologic variability as
this development stage lasts from 4-5 days and
cause alterations in the staining characteristics of
the cell
Neutrophil Maturation - Myelocyte
Smaller in size than the promyelocyte (12-18 um)
Less than 10% of BM compartment is made up of
myelocytes
Nucleus is round to oval with a flattened side near the
now well-developed Golgi apparatus
Nuclear chromatin shows clumping
Nucleoli no longer visible
Stages in Granulocyte
Maturation
Blast cell
Promyelocyte Myelocyte Metamyelocyte Band cell Segmented
Neutrophil
Neutrophil Maturation - Myelocyte
Secondary granules stain pink causing a
“dawn of neutrophilia” or pink blush
within the cytoplasm
Compounds such as alkaline phosphatase
begin to concentrate in the cell
The cell acquires some motility
Granulopoiesis
Notice change in
granules color
Neutrophilic Maturation - Metamyelocyte
13-22 % of BM compartment
10-15 um in size
Not seen in normal PB
Not fully functional, part of the maturation
component of the marrow
Neutrophilic Maturation - Band
The band is a transitional form that exists in both
the PB and the BM and considered part of both
the maturation and storage pools
Up to 40% of the WBCs of the BM are bands
Represents the “almost mature” neutrophil having
full motility, active adhesion properties, and some
phagocytic ability
Neutrophilic Maturation - Band
Band forms begin to produce tertiary granules
Membrane maturity shows changes in cytoskeleton, surface
charge and presence of receptors for complement
Once entered into the PB, account for less than 6% of
circulating WBCs
10-15 um in size
Found in marginating and circulating pools of the PB
Neutrophilic Maturation - PMN
This cell’s nucleus continues to indent until thin strands of
membrane and heterochromatin form into segments, hence
it is also called a “seg”
Polymorphonuclear means “many-shaped nucleus”,
describing the varied nuclear shapes
Cell is completely functional and spend time in the storage
pool of the BM as well as marginating and circulating
pools of the PB
50-70% of circulating WBCs of PB
Neutrophilic Maturation - PMN
PMNs spend their life performing phagocytosis and
pinocytosis
Phagocytosis involves larger material and can be
observed with light microscopy, pinocytosis
involves small material (liquids) and is observed
with EM
Both of these function can be performed in the
circulation of the blood stream or in the tissues
Neutrophil kinetics
Monocyte/Macrophage Maturation
Monocyte/Macrophage cells mature from monoblast to
promonocyte to blood monocyte to free and fixed
macrophages, but the mechanism of commitment is not
well understood.
Granular content vary considerably with more than 50
secretory compounds having been identified.
PB monocytes demonstrate morphologic variability
Aggressive motility and adherence may distort the monocytes
during PB smear preparation
Monocyte/Macrophage Maturation
Monocyte nucleus is indented or curved with
chromatin that is lacy with small clumps
Typically the largest cell in the PB
Cytoplasm is filled with minute granules that
produce a cloudy appearance
Cytoplasmic membrane may be irregular, pseudopods
and phagocytic vacuoles may be evident
Monocyte/Macrophage Maturation
Lymphocytes
The only human WBCs whose site of development is not
just BM, but also tissues referred to as primary and
secondary lymphoid organs
In humans, the primary lymphoid organs are the thymus
and bone marrow, the secondary organs include the
spleen, Peyer’s patches of the GI tract, the
Waldermyer ring of the tonsils and adenoids, the
lymph nodes and modules scattered throughout the
body
Lymphocytes
Lymphocytes circulate throughout the body in both PB and
lymph which act as carrier streams to bring the
lymphocytes to sites of activity
Lymphocytes migrate from thoracic duct through vessel
endothelium to lymph nodes to blood stream and back.
Lymphocytes are categorized in a variety of ways and may
be short-lived or long-lived cells
Lymphocytes may produce antibodies or lymphokines and
have different surface charges, densities and antigen
receptors.
Lymphocytes - Development
The PSC results in a stem cell for the lymphoid cell
(CFU-L) as a result of hormonal stimuli
The CFU-L matures in several environments
Thymus and BM give rise to lymphocytes, foster
differentiation and are indepentendent of antigenic
stimulation
Lymphocytes - Development
Lymphocyte % in the PB varies, depending on age.
Children under the age of 4 have a higher proportion
of lymphocytes in the PB than do adults
Lymphocytes are the second most common WBC of
the PB making up 20-40% of WBCs.
20-35% of circulating lymphocytes are B cells
Lymphocytes - Maturation
Lymphoblast to prolymphocyte
Lymphoblast is small, 10-18 um
Round to oval nucleus
Loose chromatin with one or more active nucleoli
Scanty cytoplasm
Prolymphocyte difficult to distinguish, subtle changes, more
clumped chromatin, lessening nucleolar priminence,
change in thickness of the nuclear membrane
Lymphopoiesis
Thrombopoiesis
Platelet play a major role
in primary hemostasis
Life span 7-10 days
Production, fragmentation
of cytoplasm
Megakaryocytes undergoes
endomitotic division
1/3 in spleen
The role of cytokines
in
Megakaryocytopoiesis
The effect of IL-1on target cells & Tissues
Summary
Normal haemopoiesis is necessary for the survival
It is under the control of multiple factors
Normal bone marrow environment is necessary for normal
haemopoiesis
Decreased production results in cytopenias
Hematopoiesis
Just notice
general trends,
Don’t memorize
Maturation Sequence
Notice general
trends,
Don’t memorize
Monophyletic theory of cell
formation