HEMATOPOIESES

DR. HIDELISA M. LOZADA

Hematopoiesis:

Process that determines the formation and

development of the cellular elements of the blood
Commences in embryonic yolk sac, early red blood
cells
After 6 weeks of gestation, fetal liver begins
producing primitive WBCs,RBCs,and Plts
Spleen becomes a secondary site of blood cells
production
Definitive long term site in the bone marrow

Hematopoiesis

Bone marrow becomes replaced by fat with age,

and is called yellow bone marrow
Active marrow sites, red bone marrow, in adult:
sternum, vertebrae, pelvis, ribs, and proximal
femur and humerus
Bone marrow samples obtained from the iliac crest
and sternum
Extramedullary hematopoiesis reestablish in fetal
sites under certain conditions as hemolytic anemia

Hematopoiesis
pluripotent stem cell
trilineage myeloid stem cell
lymphoid stem cell

committed stem cells

Definition of Terms

Hemopoiesis
Erythropoiesis
Leukopoiesis
Myeloid tissue
Lymphoid tissue

Definition of Terms

Hematopoietic stem cell

Lymphoid stem cell
Committed stem cells
Growth factors
Hematopoietic tissues

SCHEMA of ERYTHROPOIESIS

Hematopoietic Response
hypoxia

RBC

infection

granulocyte/monocyte

antigen

lymphocyte

hemorrhage

platelet

Normal Marrow Composition

unidentified or disintegrated cells

erythroid precursors
10%

Lymphocytes, monocytes

20%

10%

60%

granulocytes & precursors

Human blood smear

X 500

Formed elements

RBCs (erythrocytes)
WBCs (leukocytes)
Granulocytes
Agranulocytes

Blood smear
Light microscope
Stained

Hematopoiesis

Proliferative potential

differentiation

Development of Blood Cells

3 wk : formation of blood islands from yolk sac

6 wk : liver becomes hematopoietic organ
6-8 wk : spleen (until 8th month)
12-14wk : bone marrow (life-long)

MATURATION

SEQUENCE

SIZE
Immature cells are large &
becomes progressively smaller as
they mature

NUCLEUS
Young cells have large nucleus &
relatively large in relation to
cytoplasm
As the cells age,the absolute &
relative size of nucleus decreases

NUCLEAR CHROMATIN
Immature cells nuclear chromatin strands
contain DNA, has affinity for acidophilic
dye
As the nucleus ages, becomes more
intensely stained,and the color changes
from light red to dark blue

NUCLEAR CHROMATIN
Structure of nuclear chromatin is the most
reliable criterion for the age of the cell
Undifferentiated cells visible nuclear
chromatin strands.linear,lacelike,visible
strands

CYTOPLASM
In primitive cells ,cytoplasm is
largely blue & contains large
amounts of RNA, which has affinity
for the basic blue dye
As cytoplasmic structures &
secretory products are
manufactured , the cytoplasm
becomes more red than blue

NUCLEOLUS
Immature cells presence of nucleoli in
the nucleus
Nucleolus are small islands of cytoplasmic
materials,manufactured within the
nucleus,are signs of metabolic activity &
growth
Homogenous structure & color similar to
cytoplasm

ERYTHROPOIESIS

Erythropoiesis

erythropoietin-independent stage:
GM-CSF

marrow stromal cells

SCF

IL-3 (activated T-cells)

erythropoietin-dependent stage:
erythropoietin

hypoxia(liver, kidney)

Erythropoiesis

Production of red blood cells

Stem cells
proerythroblasts
early erythroblasts
intermediate
late
reticulocytes

Erythropoietin: Hormone to stimulate RBC production

Pronormoblast

Basophilic normoblast

Polychromatophilic normoblast

Orthochromatic normoblast

Reticulocyte

Normocyte

Nomenclature :Erythrocytic Stages of Maturation

RUBRIBLAST

NORMOBLAST

ERYTHROBLAST

Rubriblast

Pronormoblast

Proerythroblast

Prorubricyte

Basophilic normoblast

Basophilic erythroblast

Rubricyte

Polychromatophilic normoblast Polychromatic erythroblast

Metarubricyte

Orthrochromatic normoblast

Orthochromatic eryhtroblast

Reticulocyte *

Reticulocyte *

Reticulocyte

Erythrocyte

Erythrocyte

Erythrocyte

diffusely basophilic erythrocyte and

polychromatophilic erythrocyte are terms
sometimes applied to the reticulocyte, particularly
when seen on peripheral blood film.

PRONORMOBLAST
Earliest recognizable precursor
20 um diameter
Nucleus
Nucleoli
Cytoplasm - homogenous
,moderate in amount,
moderately basophilic , no
granules present, has highest
RNA content

BASOPHILIC NORMOBLAST
Size - somewhat smaller
N/C ratio 1/4 total area is
cytoplasm
Nuclear chromatin coarser w/
suggestive spoke of the wheel
pattern, parachromatin stains pink
Nucleoli
Cytoplasm beginning Hb
production..deeply basophilic owing
to abundance of RNA
Cell borders w/ pseudopodia

POLYCHROMATOPHILIC NORMOBLAST

Evident Hb production
Size
Nucleus - of area of cell
Nuclear chromatin stains intensely,
moderately condensed chromatin which is
sharply distinct from parachromatin
Cytoplasm - shows
polychromasia(mixtures of red staining Hb
w/ blue of RNA in varying shades of gray
Last stage capable of mitosis

ORTHOCHROMATIC NORMOBLAST
Full hemoglobinization
mitosis is no longer possible in this stage
Size
N/C ratio
Cytoplasm - more abundant Hb & fewer
ribosomes & remains slightly
polychromatophilic

Finally accompanied by cytoplasmic

contractions & undulations , the
nucleus & small rim of cytoplasm are
ejected from the orthochromatic
normoblast forming the
RETICULOCYTE
This after 3days forming 16
reticulocytes

RETICULOCYTE
Anucleated cell, which stains or airdried films with Romanowsky stains
Size larger than red cells , sticky
Remain in marrow for 1 -2 days
before released into the blood
Cytoplasm -stains polychromatophilic
due to retention of RNA , which
remains for few days

NORMOCYTE

Erythrocytes

7-8 m diameter
Biconcave disc shape

surface area
efficiency for diffusion of O2
& CO2

Erythrocytes

Flexible
Elastic
100-120 day life
span
Originate in bone
marrow

Basal Hematopoiesis

SCF

IL-6 GM-CSF

G-CSF

SCF: stem cell factor

GM-CSF: granulocyte-macrophage colony-stimulating factor
G-CSF: granulocyte colony-stimulating factor

Lifespan of blood cells

RBC

120 days

platelet

10 days

granulocytes

circ : 9 hours
tissue : days

lymphocyte

circ : variable (hours to years)

tissue : weeks to years

MEGALOBLASTIC MATURATION

Abnormal maturation of erythroid precursors that

occur in Vit B12 / Folic acid deficiency is known as
megaloblastic , and the abnormal eryhtroid cells
are called megaloblasts
Mechanism : impaired ability to synthesize DNA,
the intermitotic phase as well as mitotic phase is
prolonged. This results in enlarged cellsw/ nuclear
maturation lagging behind cytoplasmic maturation. (
cytonuclear dissociation )
Associated with Howell Jolly bodies