Erythropoiesis

lectures series in basic hematology

3. Def. It is the synthesisofRBC’s.
•
In the embryo occurs in the yolk
sac.
Inthe fetus, erythrocytes are
formed in the liver andspleen.
After birth, erythropoiesis is
restricted to the red bonemarrow.

4. Factors affectingerythropoiesis
1.Oxygensupplytothe tissues and role
of erythropoietin.
2.State of hemopoieticorgans.
3.Hormones.
4.Diet.

5. Conditions that decrease O2 supply to the tissues
increases the rate of production of erythrocytes as
occursin:
•High altitude
•Increase demands for O
2 inatheletes
•Chronic respiratory disease e.g.COPD.
•Anemia
•Prolonged heartfailure.
1. Oxygensupplytothe tissues and role of
erythropoietin

6. Erythropoietin hormone
Nature :Glycolipid.
M.W.: 35000
Concentration : Low
Halflife: 5hours Source
1.During fetal life : Liver
2.Adult
•85-90% by endothelial cells ofperitubular
capillaries in thekidney.
•10 -15 %by tissue macrophages of the
liver (Kupffer cells).

7. Mechanism ofaction:
Stemcell
Erythropoietin acts on specific receptors on stemcells
mitosis
Erythroblast
Matureerythrocyte
Erythropoietin causing speeding up of all the stages of
development of proerythroblasts into matureerythrocytes

8. Stimulation ofsecretion:
Factors increasing erythropoietinsecretion:
(i)Hypoxia
(ii)Androgens
(iii)GrowthHormone
(iv)Catecholamines
(v)Prostaglandins
Factors inhibiting erythropoietinsecretion:
(i)Estrogen
(ii)Theophylline

9. EPO stimulation & action:

10. 2. State of hemopoieticorgans:
1. Healthy bonemarrow:
•A healthy bone marrow is essential for the
production oferythrocytes.
•When bone marrow is destroyed by ionizing
irradiation or drugs, aplasticanemia occurs.

11. 2. State of liver & bonemarrow:
2. Healthy liver:
The liver is essential forerythrpoiesis
because it is the site of:
•Formation of the globinportion ofhemoglobin.
•Formation of 10 -15 % of erythropoietinhormone.
•Storage of iron, vitaminB12, 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:
Stimulatethegeneralmetabolismandalso
stimulatethebonemarrowtoproduce
moreRBCs.
InAddison’sdisease(hypofunctionof
adrenalcortex)anemiapresent,whilein
Cushing’sdisease(hyperfunctionof
adrenalcortex)polycythaemiapresent.

14. 3. Hormonal factors, cont.
5.Pituitarygland:
Affectserythropoiesisbothdirectly
andindirectlythroughtheactionof
severalhormones.

15. 4. Dietary factors
The following are essential for adequateerythropoiesis
1.Proteins.
2.Minerals:
Iron
Copper and cobalt as Co-factors for formation of
Hb.
Cobalt as a part of vit.B
12.
3. Vitamins:
VitaminC, VitaminB
12,Folicacid.

16. Totipotentialstem cells-convert into any
tissuetype
Pluripotentstem cell-Pluripotent
hematopoeiticstemcell
Committedstemcells-CFUE,CFUG,CFU
M,etc
Stem cells

18. PROGENITORCELLS
Committed stem cells lose their capacity
for self-renewal.
They become irreversiblycommitted.
These cells are termed as “Progenitor
cells”
They are regulated by certain hormones
orsubstances so that theycan:
Proliferate
UndergoMaturation.

19. ERYTHROID PROGENITOR CELLS
BFU-E: Burst Forming Unit –Erythrocyte:
Give rise each to thousands ofnucleated
erythroidprecursor cells, invitro.
Undergo some changes to become theColony
Forming Units-Erythrocyte(CFU-E)
Regulator: Burst Promoting Activity(BPA)

20. Figure19.6
How RBCDeveloped ?

21. 15-20µm-basophilic cytoplasm,
nucleus withnucleoli.
14-17µm-mitosis, basophilic
cytoplasm,nucleolidisappears.
10-15µm-’POLYCHROMASIA ’
Hb appears, nucleuscondenses.
7-10µm-PYKNOTIC
NucleusExtrusion, Hb
7.3µm-Reticulum of basophilic
material in thecytoplasm.
7.2µm-Mature red cell withHb.
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 nucleoliand 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
Reticulocyte
Mature
Erythrocyte
1 3 4
5 567
2

24. CHANGES DURING ERYTHROPOIESIS
Important eventsStages of Erythropoiesis
Synthesisof HbstartsProerythroblast
Nuclei disappearEarlyErythroblast
Hbstarts 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
120days approximately.
Differentiation phase: from pronormoblastto
reticulocytephase-5days
Maturation phase: from reticulocytetomature
RBC-2days
10-15% of erythroidprecursors never mature and
are destroyed.

26. Reduced RBC count / reduced Hb
concentration
Increased RBCcount
Polycythemiavera
Secondary polycythemia-due tohypoxia