1. Chang Gung University
Department of Medical Biotechnology
Clinical Hematology
RBC 2 : Erythropoesis & RBC
Senescence
Dr. Daniel Tsun-Yee Chiu
Spring, 2012

2. Part I : Erythropoiesis
I. Definition of erythropoiesis : Production of red cells
II. Site(s) of erythropoiesis
1. Fetal period
2. After-birth
III. Biological processes involved in erythropoiesis
1. Differentiation
2. Proliferation
3. Biosynthetic activities, hemoglobin synthesis in particular
4. Maturation: nuclear extrusion
IV. Kinetics of erythropoiesis

3. Red Cell Production
The Production of red cells, known as erythropoiesis,
is a developmental system fundamentally under genetic
control but modulated and regulated by the interaction of
humoral, cellular, and molecular processes. These must
be understood if there is to be full elucidation of any of
the pathological processes which afflict the red cell
system.

4. Hematopoiesis
Fig.1.2 Diagrammatic representation of the bone marrow pluripotent
stem cell and the cell lines that arise from it.

5. Hematopoiesis
Fig.1.7 A diagram of the role of growth factors in normal haemppoiesis.

6. Part I : Erythropoiesis
I. Definition of erythropoiesis : Production of red cells
II. Site(s) of erythropoiesis
1. Fetal period
2. After-birth
III. Biological processes involved in erythropoiesis
1. Differentiation
2. Proliferation
3. Biosynthetic activities, hemoglobin synthesis in particular
4. Maturation: nuclear extrusion
IV. Kinetics of erythropoiesis

7. Site(s) of erythropoiesis
Organ of
erythropoiesis
Fetal period Kinds of blood cells
Yolk sac 2~9 week RBC
liver 9~24 week RBC, myelocyte, platelet
spleen 10~24 week RBC, myelocyte, platelet
Lymph node 8 week~after birth lymphocyte
Bone marrow 10 week~after birth RBC, myelocyte, platelet

8. Part I : Erythropoiesis
I. Definition of erythropoiesis : Production of red cells
II. Site(s) of erythropoiesis
1. Fetal period
2. After-birth
III. Biological processes involved in erythropoiesis
1. Differentiation
2. Proliferation
3. Biosynthetic activities, hemoglobin synthesis in particular
4. Maturation: nuclear extrusion
IV. Kinetics of erythropoiesis

9. Erythropoiesis
• The differentiation and proliferation of RBC.
(erythroblast)
(Basophilic erythroblast)
(Orthochromatic
erythroblast)

10. Differentiation
Erythopoietin
reaposiveness
Globin mRNA
sythesis
Hgb
sythesis
Stem cell
pool
myeloblast megakaryoblast
unipotential
multipotential
unipotential-erythopoitin
responsive
CFU-S
BFU-E
CFU-E
5 days
120 days

12. Regulation of erythropoiesis and
the Production of erythropoietin

13. Kinetics of erythropoiesis

14. V. Regulation of erythropoiesis: Cytokines
1. Erythropoietin (EPO)
2. Burst promoting Activity (BPA)
3. Iron availability
4. Other regulatiory factors (eg. Androgenic steroids)
VI. Required reading
“ Essential Haematology " by Hoffbrand & Pettit . pp 12-15
VII. Additional References
1. Rifkind et al. "Fundamental of Hematology" 3rd ed., pp 1-19, 1986
2. Jandl J. "Blood---Textbook of Hematology" pp 49-53, 1987
Part I : Erythropoiesis

16. Part II : Red Cell Destruction
(Senescence)
I. Red cell life span : about 120 days
Methods of measuring RBC life span :
1. Single-age (Cohort) label
2. Mixed-age label
II. Routes of Destruction and Major determinants of destruction
1. Spleenic entrapment --- Deformability
2. Monocyte/Macrophage --- Surface Antigenicity
3. Osmotic lysis --- Permeability

17. Red cell life span
Single-age (Cohort) Label Mixed-age Label

18. Part II : Red Cell Destruction
(Senescence)
I. Red cell life span : about 120 days
Methods of measuring RBC life span :
1. Single-age (Cohort) label
2. Mixed-age label
II. Routes of Destruction and Major determinants of destruction
1. Spleenic entrapment --- Deformability
2. Monocyte/Macrophage --- Surface Antigenicity
3. Osmotic lysis --- Permeability

19. Red cell deformablity
A. Factors affecting red cell deformability
1. Cytoplasmic viscosity
2. Intracellular rubbish
3. Membrane rigidity
4. Surface to volume ratio
B. Techniques to measure red cell deformability
1. filtration
2. micropipette
3. ektacytometry

20. Part II : Red Cell Destruction
(Senescence)
III. Possible underlying mechanism (s)
1. Metabolic depletion theory
2. Mechanical shear stress
3. Changes in surface properties induced by endothelial cells
4. Oxidative damage theory
IV. Required Reading
Jandl J. “Blood---Text book of Hematology" pp 91-96, 1987
V. Additional Reference
Rifkind et al. "Fundamental of Hematology" pp 1-19, 1986