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Def. It is the synthesis of RBC’s.
•
In the embryo occurs in the yolk
sac.
In the fetus, erythrocytes are
formed in the liver and spleen.
After birth, erythropoiesis is
restricted to the red bone marrow.
Factors affecting erythropoiesis
1. Oxygen supply to the tissues and role
of erythropoietin.
2. State of hemopoietic organs.
3. Hormones.
4. Diet.
Conditions that decrease O2 supply to the tissues
increases the rate of production of erythrocytes as
occurs in:
• High altitude
•Increase demands for O2 in atheletes
• Chronic respiratory disease e.g. COPD.
• Anemia
• Prolonged heart failure.
1. Oxygen supply to the tissues and role of
erythropoietin
Erythropoietin hormone
Nature : Glycolipid.
M.W. : 35000
 Concentration : Low
 Half life: 5 hours Source
1. During fetal life : Liver
2. Adult
• 85- 90 % by endothelial cells of peritubular
capillaries in the kidney.
• 10 - 15 % by tissue macrophages of the
liver (Kupffer cells).
Mechanism of action:
Stem cell
Erythropoietin acts on specific receptors on stem cells
mitosis
Erythroblast Mature erythrocyte
Erythropoietin causing speeding up of all the stages of
development of proerythroblasts into mature erythrocytes
Stimulation of secretion:
 Factors increasing erythropoietin secretion:
(i) Hypoxia
(ii) Androgens
(iii) Growth Hormone
(iv) Catecholamines
(v) Prostaglandins
 Factors inhibiting erythropoietin secretion:
(i) Estrogen
(ii) Theophylline
EPO stimulation & action:
2. State of hemopoietic organs:
1. Healthy bone marrow:
•A healthy bone marrow is essential for the
production of erythrocytes.
•When bone marrow is destroyed by ionizing
irradiation or drugs, aplastic anemia occurs.
2. State of liver & bone marrow:
2. Healthy liver:
 The liver is essential for erythrpoiesis
because it is the site of :
• Formation of the globin portion of hemoglobin.
• Formation of 10 - 15 % of erythropoietin hormone.
• Storage of iron, vitamin B12, folic acid & copper.
3. Hormonal factors
1. Erythropoietin hormone.
2. Androgens: stimulate erythropoietin secretion.
3. Thyroid hormones:
 Stimulate the metabolism of all body cells.
 Hypothyroidism is associated with anemia
while hyperthyroidism is associated with
polycythaemia.
3. Hormonal factors, cont.
4. Glucocorticoids:
 Stimulate the general metabolism and also
stimulate the bone marrow to produce
more RBCs.
In Addison’s disease (hypofunction of
adrenal cortex) anemia present, while in
Cushing’s disease (hyperfunction of
adrenal cortex) polycythaemia present.
3. Hormonal factors, cont.
5. Pituitary gland:
 Affects erythropoiesis both directly
and indirectly through the action of
several hormones.
4. Dietary factors
 The following are essential for adequate erythropoiesis
1. Proteins.
2. Minerals:
 Iron
 Copper and cobalt as Co-factors for formation of
Hb.
 Cobalt as a part of vit. B12.
3. Vitamins:
 Vitamin C, Vitamin B12, Folic acid.
 Totipotential stem cells- convert into any
tissue type
 Pluripotent stem cell- Pluripotent
hematopoeitic stem cell
 Committed stem cells- CFU E, CFU G, CFU
M, etc
Stem cells
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.
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)
Figure19.6
How RBC Developed ?
15-20µm- basophilic cytoplasm,
nucleus with nucleoli.
14-17µm-mitosis, basophilic
cytoplasm, nucleoli disappears.
10-15µm-’POLYCHROMASIA’
Hb appears, nucleus condenses.
7-10µm- PYKNOTIC
Nucleus Extrusion, Hb
7.3µm- Reticulum of basophilic
material in the cytoplasm.
7.2µm- Mature red cell with Hb.
ERYTHROPOIESIS STAGES
CHANGES DURING ERYTHROPOIESIS
 Cells of CFU-E pass through different stages and
finally become the matured RBCs.
 During these stages four important changes are
noticed.
1. Reduction in size of the cell (from the diameter of
25 to 7.2 µ)
2. Disappearance of nucleoli and nucleus
3. Appearance of hemoglobin
4. Change in the staining properties of the cytoplasm.
3
2
Proerythroblast
or
pronormoblast
Basophilic
erythroblast or
Early Normoblast
Polychromatophilic
(or intermediate)
Erythroblast or
Normoblast
Dividing
Polychromatophilic
Erythroblast or
Normoblast
Orthochromatic
(Acidophilic)
erythroblast
Or Late
Erythroblast
Orthochromatic
erythroblast
Extruding
Nucleus
ReticulocyteMature
Erythrocyte
1 3 4
5 567
2
CHANGES DURING ERYTHROPOIESIS
Important eventsStages of Erythropoiesis
Synthesis of Hb startsProerythroblast
Nuclei disappearEarly Erythroblast
Hb starts appearingIntermediate Erythroblast
Nucleus disappearsLate Erythroblast
Reticulumformed. Cells enter
into capillary from site of
production
Reticulocyte
Reticulum disappears. Cell attain
Biconcavity
Mature RBC
ERYTHROKINETICS
 Number is constant normally as their life span is
120 days approximately.
 Differentiation phase: from pronormoblast to
reticulocyte phase- 5 days
 Maturation phase: from reticulocyte to mature
RBC- 2 days
 10-15% of erythroid precursors never mature and
are destroyed.
Reduced RBC count / reduced Hb
concentration
Increased RBC count
 Polycythemia vera
 Secondary polycythemia- due to hypoxia
Erythropoiesis
Erythropoiesis

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Erythropoiesis

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  • 3. Def. It is the synthesis of RBC’s. • In the embryo occurs in the yolk sac. In the fetus, erythrocytes are formed in the liver and spleen. After birth, erythropoiesis is restricted to the red bone marrow.
  • 4. Factors affecting erythropoiesis 1. Oxygen supply to the tissues and role of erythropoietin. 2. State of hemopoietic organs. 3. Hormones. 4. Diet.
  • 5. Conditions that decrease O2 supply to the tissues increases the rate of production of erythrocytes as occurs in: • High altitude •Increase demands for O2 in atheletes • Chronic respiratory disease e.g. COPD. • Anemia • Prolonged heart failure. 1. Oxygen supply to the tissues and role of erythropoietin
  • 6. Erythropoietin hormone Nature : Glycolipid. M.W. : 35000  Concentration : Low  Half life: 5 hours Source 1. During fetal life : Liver 2. Adult • 85- 90 % by endothelial cells of peritubular capillaries in the kidney. • 10 - 15 % by tissue macrophages of the liver (Kupffer cells).
  • 7. Mechanism of action: Stem cell Erythropoietin acts on specific receptors on stem cells mitosis Erythroblast Mature erythrocyte Erythropoietin causing speeding up of all the stages of development of proerythroblasts into mature erythrocytes
  • 8. Stimulation of secretion:  Factors increasing erythropoietin secretion: (i) Hypoxia (ii) Androgens (iii) Growth Hormone (iv) Catecholamines (v) Prostaglandins  Factors inhibiting erythropoietin secretion: (i) Estrogen (ii) Theophylline
  • 10. 2. State of hemopoietic organs: 1. Healthy bone marrow: •A healthy bone marrow is essential for the production of erythrocytes. •When bone marrow is destroyed by ionizing irradiation or drugs, aplastic anemia occurs.
  • 11. 2. State of liver & bone marrow: 2. Healthy liver:  The liver is essential for erythrpoiesis because it is the site of : • Formation of the globin portion of hemoglobin. • Formation of 10 - 15 % of erythropoietin hormone. • Storage of iron, vitamin B12, folic acid & copper.
  • 12. 3. Hormonal factors 1. Erythropoietin hormone. 2. Androgens: stimulate erythropoietin secretion. 3. Thyroid hormones:  Stimulate the metabolism of all body cells.  Hypothyroidism is associated with anemia while hyperthyroidism is associated with polycythaemia.
  • 13. 3. Hormonal factors, cont. 4. Glucocorticoids:  Stimulate the general metabolism and also stimulate the bone marrow to produce more RBCs. In Addison’s disease (hypofunction of adrenal cortex) anemia present, while in Cushing’s disease (hyperfunction of adrenal cortex) polycythaemia present.
  • 14. 3. Hormonal factors, cont. 5. Pituitary gland:  Affects erythropoiesis both directly and indirectly through the action of several hormones.
  • 15. 4. Dietary factors  The following are essential for adequate erythropoiesis 1. Proteins. 2. Minerals:  Iron  Copper and cobalt as Co-factors for formation of Hb.  Cobalt as a part of vit. B12. 3. Vitamins:  Vitamin C, Vitamin B12, Folic acid.
  • 16.  Totipotential stem cells- convert into any tissue type  Pluripotent stem cell- Pluripotent hematopoeitic stem cell  Committed stem cells- CFU E, CFU G, CFU M, etc Stem cells
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  • 18. 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.
  • 19. 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)
  • 21. 15-20µm- basophilic cytoplasm, nucleus with nucleoli. 14-17µm-mitosis, basophilic cytoplasm, nucleoli disappears. 10-15µm-’POLYCHROMASIA’ Hb appears, nucleus condenses. 7-10µm- PYKNOTIC Nucleus Extrusion, Hb 7.3µm- Reticulum of basophilic material in the cytoplasm. 7.2µm- Mature red cell with Hb. ERYTHROPOIESIS STAGES
  • 22. CHANGES DURING ERYTHROPOIESIS  Cells of CFU-E pass through different stages and finally become the matured RBCs.  During these stages four important changes are noticed. 1. Reduction in size of the cell (from the diameter of 25 to 7.2 µ) 2. Disappearance of nucleoli and nucleus 3. Appearance of hemoglobin 4. Change in the staining properties of the cytoplasm.
  • 23. 3 2 Proerythroblast or pronormoblast Basophilic erythroblast or Early Normoblast Polychromatophilic (or intermediate) Erythroblast or Normoblast Dividing Polychromatophilic Erythroblast or Normoblast Orthochromatic (Acidophilic) erythroblast Or Late Erythroblast Orthochromatic erythroblast Extruding Nucleus ReticulocyteMature Erythrocyte 1 3 4 5 567 2
  • 24. CHANGES DURING ERYTHROPOIESIS Important eventsStages of Erythropoiesis Synthesis of Hb startsProerythroblast Nuclei disappearEarly Erythroblast Hb starts appearingIntermediate Erythroblast Nucleus disappearsLate Erythroblast Reticulumformed. Cells enter into capillary from site of production Reticulocyte Reticulum disappears. Cell attain Biconcavity Mature RBC
  • 25. ERYTHROKINETICS  Number is constant normally as their life span is 120 days approximately.  Differentiation phase: from pronormoblast to reticulocyte phase- 5 days  Maturation phase: from reticulocyte to mature RBC- 2 days  10-15% of erythroid precursors never mature and are destroyed.
  • 26. Reduced RBC count / reduced Hb concentration Increased RBC count  Polycythemia vera  Secondary polycythemia- due to hypoxia