HEMOPOIESIS &

ERYTHROPOIESIS
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.
Begins in the 20
th
week of life in the fetal liver &
spleen, continues in the bone marrow till young
adulthood & beyond!
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
Active Hemopoietic
marrow is found, in
children throughout
the:
Axial skeleton:
Cranium
Ribs.
Sternum
Vertebrae
Pelvis
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.
CLONAL HEMOPOIESIS
PLURIPOTENT STEM CELL
STEM CELL
MULTIPLICATION
COMMITTMENT
COMMITTED
STEM CELL
COMMITTED
STEM CELL
MULTIPLICATION
PROGENITOR
CELL
CFU: COLONY
FORMING UNIT
CLONAL HEMOPOIESIS: (Contd)
COLONY FORMING UNIT
(CFU)
INTERMEDIATE
BLAST CELLS
MATURE BLOOD CELLS
END CELLS: FINITE LIFE SPAN
MORPHOLOGICALLY
RECOGNIZABLE
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
Pluripotent Stem cells:
Has a diameter of 18 23 .
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.
STEM CELLS: Types
PROGENITOR CELLS
Committed stem cells lose their capacity for
self-renewal.
They become irreversibly committed.
These cells are termed as Progenitor cells
They are regulated by certain hormones or
substances so that they can:
Proliferate
Undergo Maturation.
CELL LINE REGULATORS
CELL LINE REGULATOR
ERYTHROID: BFU-E:

CFU : E
BURST PROMOTING ACTIVITY

ERYTHROPOIETIN
GRANULOCYTE-MONOCYTE:
CFU-GM
COLONY STIMULATING
FACTOR(CSF)
MEGAKARYOCYTES: CFU-M MEGAKARYOCYTIC
STIMULATING ACTIVITY
MEGAKARYOCYTES THROMBOPOIETIN
BLOOD CELLS: DEVELOPMENT
PROGENITOR
CELLS
LYMPHOID
CELLS
PRO
NORMOBLAST
MEGA
KARYOBLAST
MYELOBLAST MONOBLAST
LYMPHOCYTES ERYTHROCYTES THROMBOCYTES GRANULOCYTES
MONOCYTES
ERYTHROPOIESIS:
SITES/PHASES
INTRAUTERINE LIFE:
INTRAVASCULAR PHASE: Upto 3
rd
month of
Intra Uterine Life.
Endothelial cells = = = RBCs
HEPATIC PHASE: 3
rd
to 5
th
month IUL
Liver & Spleen
nRBCs from Mesenchymal cells.
MYELOID PHASE: From 5
th
month of IUL
onwards.

POST NATAL LIFE:
CHILDREN:
Predominantly Red Bone Marrow of skeleton:
Axial &
Appendicular.
ADULTS:
Red Bone Marrow of Axial Skeleton.
ERYTHROPOIESIS: SITES/PHASES
contd.
PROERYTHROBLAST
BASOPHILIC
ERYTHROBLAST
POLYCHROMATOPHILIC
ERYTHROBLAST
ORTHOCHROMATIC
ERYTHROBLAST
RETICULOCYTE
MATURE ERYTHROCYTES
ERYTHROPOIESIS
FACTORS REGULATING
ERYTHROPOIESIS
SINGLE MOST IMPORTANT REGULATOR:
TISSUE OXYGENATION
BURST PROMOTING ACTIVITY
ERYTHROPOIETIN
IRON
VITAMINS:
Vitamin B
12
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
B
12
: 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.
ERYTHROPOIESIS: SEQUENTIAL CHANGES
I II III IV V
VI
P
R
O
N
O
R
M
O
B
L
A
S
T
E
A
R
L
Y
N
B
L
A
S
T
I
N
T
E
R
N
B
L
A
S
T
L
A
T
E
N
B
L
A
S
T
R
E
T
I
C
U
L
O
C
Y
T
E
M
A
T
U
R
E
R
B
C
MITOCHONDRIA
BASOPHILIA
HEMOGLOBIN
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)
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.

ERYTHROID PROGENITOR CELLS
Normoblastic Precursors
PROERYTHROBLAST:
Large cell: 15 20 Microns in diameter.
Cytoplasm is deep violet-blue staining
Has no Hemoglobin.
Large nucleus 12 Microns occupies 3/4
th
of the
cell volume.
Nucleus has fine stippled reticulum & many
nucleoli.

EARLY 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:
Has a diameter of 10 14 Microns.
Shows active Mitosis.
Increased Hemoglobin content in the
cytoplasm
Cytoplasm is Polychromatophilic.
Normoblastic Precursors
LATE NORMOBLAST:
Diameter is 7 10 Microns.
Nucleus shrinks with condensed
chromatin.
Appears like a Cartwheel
Cytoplasm has a Eosinophilic appearance.
Normoblastic Precursors
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 B
12
Normoblastic Precursors
MATURE ERYTHROCYTE:
Biconcave disc.
No nucleus.
About One-third filled with Hemoglobin.
Normoblastic Precursors
Regulation of Erythropoiesis
CFU E

Proerythroblasts
Mature Erythrocytes

Tissue Oxygenation
Factors decreasing:
Hypovolemia
Anemia
Poor blood flow
Pulmonary Disease
ERYTHROPOIETIN
Decreases
Stimulates
An example
of a
Negative
feed back
mechanism
HEMOPOIESIS: REVIEW I
Hemopoiesis: Production of blood
cells.
Site: Predominantly in the Bone
Marrow.
Both axial & appendicular skeletons.
Erythropoiesis: Production of
Erythrocytes.
Leucopoiesis: Production of
Leucocytes.
Thrombopoiesis: Production of
Thrombocytes.

HEMOPOIESIS: REVIEW II
Cell lines:
Pluripotent Stem Cell
Progenitor Stem Cells: Committed
Proerythroblasts
Myeloblasts
Monoblasts
Lymphoid cells
Megakaryoblasts