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