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Erythropoiesis
1.
2.
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
17.
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.
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