Dr Suria Abdul Aziz

Department of Pathology

UKMMC

Define haemopoiesis

Sites of haemopoiesis

Relate the properties of pluripotent haemopoietic

stem cells to its functions.

Describe normal haempoiesis ( include the regulation

of haemopoiesis

Erythropoiesis

Granulopoiesis & Lymphopoiesis

Thrombopoiesis

Haematopoiesis / haemopoiesis (from Ancient

Greek: haima -blood; poiesis -to make);

Formation of blood cellular components (red

cells, white cells and platelets) from

pluripotent haemopoietic stem cells in the living

body.

Human embryo - 1st 3

weeks of gestation

Haemopoiesis begins in yolk

sac.

This cluster forms red blood

cells and endothelial cells,

which line the blood vessels.

From Wikipedia, the free encyclopedia

Liver is the primary source

of foetal cells

From 6 weeks until 6-7

months of foetal life

ceases at 40 weeks LSB

• lit some blood (like make

some blood)
hence liver, spleen, BM

Spleen

Produces blood cells @ 10

weeks

Continues throughout 2nd

trimester

Bone Marrow

Starts to produce blood cells @ 20 weeks

Become the sole source of blood cells by 40 weeks

During normal childhood and adult life

Bone marrow is the only sites of Bone Marrow

haemopoiesis

Infants

All bones are active haemopoietic

areas. (red marrow)

Children

Progressive fatty replacement of

marrow of long bones. (yellow

marrow)

Adults

Red marrow becomes restricted to

proximal ends of long bones, and

flat bones such as sternum, ribs,

sacrum & pelvis and vertebrae.

50% of these haemopoietic areas

consist of fat

Red marrow Yellow marrow

mainly of haemopoietic tissue mainly made up of fat cells

At birth, all red marrow. Yellow marrow is found in

With age, progressive the medullary cavity of

conversion to yellow marrow; long bones.

(in adult BM~50% is red

marrow) In severe blood loss or chronic

anameia,

mainly found in •yellow marrow can be revert

flat bones, such as the pelvis,

back to red marrow to increase

sternum, cranium, ribs, vertebrae

and scapulae, and blood cell production.

in the cancellous ("spongy") •Liver & spleen may resume

material at the epiphyseal ends of their foetal haemopoietic

long bones such as the femur and function (called extramedullary

humerus haemopoiesis)

Unidentified or disintegrated cells Erythroid precursors

Lymphocytes, monocytes

10%

20%

10%

60%

Granulocytes & precursors

Important elements for haemopoiesis :

Haemopoietic stem cells

Microenvironment

Bone marrow stroma

Growth factors

Stimulation

Haemopoiesis starts with a pluripotent

haemopoietic stem cells

Rare, 1 in 20 million nucleated cells in bone marrow

Pluripotent haemopoietic Proliferative

stem cells capable of : Potential

1. Self-renewal the marrow

cellularity remains constant Differentiation

in a normal healthy steady

state.

2. Cell differentiation to

committed haemopoietic

progenitor cells which are

restricted in their

developmental potential.

Bone marrow forms a suitable environment for stem

cells survival, growth and development.

It is composed of : af me

stromal cells (adipocytes, fibroblasts, endothelial

cells and macrophages)

Secrete extracellular molecules to form an extracellular
matrix
Secrete several growth factors for stem cell survival
a microvascular network.
Are Glycoprotein hormones
that:
regulate proliferation and
differentiation of haemopoietic
progenitor cells

stimulate cell proliferation,

differentiation and maturation.

prevent apoptosis

affect the function of mature

cells.
Haemopoietic growth factors & their site of action
Pluripotent cells can give
rise to all of the cell types
that make up the body;
embryonic stem cells are To maintain the pool of
considered pluripotent.
SC Fiction (lots of
facts hence pluri)
Multipotent cells can develop
into more than one cell type,
pluripotent and
but are more limited than
pluripotent cells; adult stem
multipotent progenitor
cells and cord blood stem
cells are considered
cells
3G -> IL3, G-CSF multipotent
Sex (6) GaMes -> IL6, GM-CSF
at Toilet -> Thrombopoietin

Multitasking hence multi potential

To increase the production of
Progenitors are typically the
descendants of stem cells, 1 or more cell lines to meet
only they are more
constrained in their
MET IG -> get 5 followers differentiation potential or
the body’s need.
capacity for self-renewal,
and are often more limited in
(instagram must be committed)
both senses.

Stromal cells are the major source of growth factors except

for erythropoietin (90% synthesized in kidney) and Erythropoesis (mostly in
kidney) hence mostly
thrombopoietin (largely made in the liver). people with kidney failure
suffers anaemia
 Hypoxia RBC

Infection granulocyte/monocyte

Antigen lymphocyte

Haemorrhage platelet
Production of red blood cells
(erythrocytes)
Substance needed for erythropoiesis:
Iron: haem part of haemoglobin
Vitamins B12 and folic acid: DNA synthesis
Vit C: folate metabolism, facilitates iron absorption
Vit B6 (pyridoxine): co-enzyme in synthesis of haem.
Protein: protein of the red cell membranes, globin
part of haemoglobin.
Hormones: Erythropoietin, stem cell factor, IL3, GM-
CSF, androgens, thyroid hormone.
Thyroid hormones, adrenal cortical steroids,
adrenocorticotrophic hormone, and human growth
hormone (HGH) - promote erythropoietin formation and
so enhance erythropoiesis
However, very high doses of steroid hormones seem to inhibit
erythropoiesis.
guys naturally better in sport
than girls hence androgens
stimulate and E2 depress

Androgens (male hormones) stimulate and oestrogens

(female hormones) depress the erythropoietic response.
In addition to the effects of menstrual blood loss, this effect
may explain why women tend to have a lower haemoglobin
concentration and red cell count than men.

Erythropoietin is also produced by a variety of tumours

of both renal and other tissues.
 Peter Build Pillow On
Pluripotential stem cells Red Elephant
(imagine elephant injured
lots of blood red colour,
pillow to comfort ->
erythropoiesis)
This orthochromatic Reticulocyte
erythroblast will then Contain reticular networks
extrude its nucleus and of polyribosomes, still
enter the circulation synthesize haemoglobin.
Proerythroblast Larger than mature
red cells
Spends 1 – 2 days in
circulation before
maturing (RNA
First cell that is recognizable completely lost).
as specifically leading down
Orthochromatic
the red cell pathway erythroblast
Erythrocyte As reticulocytes
loose their
The cytoplasm polyribosomes
Basophilic eventually becomes they become
erythroblast more eosinophilic mature red
blood cells

Polychromatophilic Non-nucleated
erythroblast The cell will continue to biconcave disc
become smaller shape
Development progresses, the throughout development.
nucleus becomes smaller and As the cell begins to
the cytoplasm more produce hemoglobin, the
basophilic, due to the cytoplasm attracts both
presence of ribosomes basic and eosin stains,
Mature red blood cells develop from
pluripotential stem cells.
Takes about 7 days and involves 3-4 mitotic cell
divisions
Each stem cell gives rise to 8 or 16 cells.
Mature red cells are non-nucleated, biconcave disc,
lifespan 120 days

It is regulated by the hormone erythropoietin

(90% produced by kidney, 10% by liver).
Granulocytes three types of white blood cell.
Namely neutrophils, basophils and eosinophils.

Neutrophils Eosinophils Basophils

Granulocytes constitute 40-80% of the haemopoietic

cells in the normal bone marrow.

After birth and into adulthood, granulopoiesis occurs in

the red marrow.
 Myeloblast
Myelo -> sounds
like MILO hence
The myeloblast is the first gRAN, ran for
health
recognizable cell of the
granulopoiesis.
Promyelocyte
The myeloblast enlarges and
differientiates to the
promyelocyte.
specific granules begin to
appear
eosinophilic granules in the
Granulocytes include
neutrophilic, eosinophilic,

eosinophilic leucocytes,
and
basophilic granulocytes

basophilic granules in the

basophilic granulocytes and Leucocytes ->

neutrophilic granules in the

lymphocytes,
granulocytes,

neutrophilic leucocytes. monocytes, and

macrophages
Majority of granulopoiesis in the normal marrow
consists of neutrophilic leucocytes.

% of eosinophilic leucocytes and basophilic

leucocytes usually do not exceed 5% and 1%
respectively.

a,b,c,d,e take a=1, b=2 hence e=5

Eosinophilic -> x exceed 5%
Basophilic -> x exceed 1%
bass -> the muscial instrument least people play -> hence 1%
Monocytes are produced in the bone
marrow from precursors, the monoblast
and promonocyte.

Growth factors involve are GM-CSF and

M-CSF As long as got M->
monocyte

Mature cells have a life in blood of gM-csf

approximately 3-8 hours M-csf

Monocytes are actively phagocytic (engulf

other cells) and, on migration into the
tissues, they mature into larger cells
called macrophages, which can survive in
the tissues for long periods.

These cells form the mononuclear

phagocytic cells of the reticuloendothelial
system in bone marrow, liver, spleen and
lymph nodes.
Lymphopoiesis constitute 5-20% of the bone marrow cells.

NK cell

Hematopoietic Pluripotent Lymphoid T lymphocyte

stem cell stem cell stem cell

B lymphocyte

All lymphocytes originate from a common lymphoid

progenitor before differentiating into their distinct
lymphocyte types.
Primary lymphoid organs
Bone marrow
Liver
Red bone marrow
Thymus

Thymus
(In foetus: yolk sac, liver and spleen)
*Spleen (both, but primary in
foetus!)

Secondary lymphoid organs

Lymph nodes
Spleen
Diffuse lymphoid tissues of the alimentary and
respiratory tracts. Mucosa Associated Lymphoid Tissue (MALT)
Lymphocytes are produced in bone marrow and
thymus from primitive precursors, the
lymphoblasts and prolymphocytes.
Pro-B cells become pre-B cells when they express membrane m chains
with surrogate light chains in the pre-B receptor

The cell divides into precursors pro-B and pre-T

cells, which develop into the stage of the mature
B- and T-lymphocyte.
Following maturation, the lymphocytes enter the
circulation and peripheral lymphoid organs (e.g the
secondary lymphoid organ

spleen and lymph nodes) where they survey for

invading pathogens and/or tumour cells
The lymphocytes differentiate further after
exposure to an antigen; they form effector and
memory lymphocytes.
Effector lymphocytes function to eliminate the
antigen, either by releasing antibodies (in the case of
B cells), cytotoxic granules (cytotoxic T cells) or by
signaling to other cells of the immune system (helper
T cells).
Memory cells remain in the peripheral tissues and
circulation for an extended time ready to respond to
the same antigen upon future exposure.

Life span for lymphocytes ranging from days to

weeks.
MATURE LEUCOCYTES

eosinophil -> EYE (hence 2

eyes - 2 lobes)

proton, electron, neutron

there's 3 hence (3 lobes) base -> very dark sound
hence filled with many
dots2 and darker

NEUTROPHILS EOSINOPHILS BASOPHILS

BASOPHILS

LYMPHOCYTES
MONOCYTES
Platelets are produced in bone
marrow.
Mega car -> big car
causing injury hence
need to stop blood so

Megakaryoblast arises by a thrombopoiesis

process of differentiation from

the haemopoietic stem cell and
mature to megakaryocyte in 10
days.
Hamopoietic stem cell -> Megakaryoblast -> Megakaryocyte

The cytoplasm of the

megakaryocyte fragments at the
edge of the cell that is called
platelet budding.
 Platelets produced in BM, thrombopoietin syntheiszed in liver (the
regulation)

Formation of platelets is controlled by

thrombopoietin (synthesized in the liver).
Thrombopoietin increases the number of
megakaryocytes, their maturation and the
release of platelets.
At any one time, about 2/3 of the body's
platelets are circulating in the blood and 1/3
are pooled in the spleen. There is constant
exchange between the two populations.
The life span of platelets is between 8 and 12
days. They are destroyed by macrophages,
mainly in the spleen and also in the liver.
Normal haemopoiesis is necessary for the survival of a
human

Important elements for haemopoiesis are

pluripotent haemopoietic stem cells and
haemopoietic growth factors (bone marrow stroma) .
Stimulation of haemopoiesis
 Nucleus Cytoplasm Life
Erythrocytes nil pink 120 days
Neutron (hence both positive and negative equal -> pink blue like the
positive negative bacteria), neutral hence half a day almost 10 hrs
Neutrophil 2-5 lobes pink-blue granules 10 hours
Sounds like base (low key hence very dark sound - dark granules)
Basophil 2-5 lobes dark granules 2.5 days
Sin (bad thing hence red in colour -> the lowest life
Eosinophil 2 lobes red granules span 4-5 hours
cause bad people should die early, sinned
hence mankind separated from God -> only 2 lobes)

Monocyte oval/indented fine vacuoles, scanty Months

granules
Lymphocyte round/oval clear cytoplasm, days-weeks
Lymph (helps filter hence clear)
scanty granules
Platelet nil fine granules
plate (for food hence it is FINE.. imagine rice as
granules.. if eat in banana leaf then not fine) -
7-10 days
elimination method hence monocyte and lymphocyte
scanty granules