chang gung university department of medical biotechnology clinical hematology rbc 2 : erythropoesis...
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Chang Gung UniversityDepartment of Medical Biotechnology
Clinical Hematology
RBC 2 : Erythropoesis & RBC Senescence
Dr. Daniel Tsun-Yee Chiu
Spring, 2012
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
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.
Hematopoiesis
Fig.1.2 Diagrammatic representation of the bone marrow pluripotent stem cell and the cell lines that arise from it.
Hematopoiesis
Fig.1.7 A diagram of the role of growth factors in normal haemppoiesis.
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
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
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
Erythropoiesis
• The differentiation and proliferation of RBC.
(erythroblast)
(Basophilic erythroblast)
(Orthochromatic erythroblast)
Differentiation
Erythopoietin reaposiveness
Globin mRNA sythesis
Hgb sythesis
Stem cell pool
myeloblast megakaryoblast
unipotentialmultipotential
unipotential-erythopoitin responsive
CFU-S
BFU-E
CFU-E
5 days
120 days
Regulation of erythropoiesis and the Production of erythropoietin
Kinetics of erythropoiesis
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
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
Red cell life spanSingle-age (Cohort) Label Mixed-age Label
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
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
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
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