PROCESS OF FORMATION OF RBC

1. DR NILESH KATE
MBBS,MD
ASSOCIATE PROF
DEPT. OF PHYSIOLOGY
ERYTHROPOIESIS.

2. OBJECTIVES
 Sites of haemopoiesis.
 Blood cell precursors.
 Control of haemopoiesis.
 Stages of erythropoiesis.
 Regulation of erythropoiesis
 Factors necessary for erythropoiesis
Monday, December 7, 2015

3. HAEMOPOIESIS.
 Process of development
of blood cells.
 Erythropoiesis –
development of RBC
 Leucopoiesis –
Development of WBC
 Thrombopoiesis –
Development of
platelets.
Monday, December 7, 2015

4. SITES OF HAEMOPOIESIS.
 First 2 months of
gestation – yolk sac.
 3rd
month onwards –
liver 7 spleen.
 20th
week onwards –
till birth - bone
marrow.
Monday, December 7, 2015

5. SITES OF HAEMOPOIESIS.
 In Young Children – axial
skeleton & bones of extremities
i.e. Red Bone marrow.
 With fatty replacement it
becomes Yellow Bone Marrow.
 In Adults – axial skeleton &
proximal extremities of long
bones.
 In Pathological conditions –
extra medullary haemopoiesis
i.e liver & spleen resumes .
Monday, December 7, 2015

6. BLOOD CELL PRECURSORS.
 The stem cells –
Monophyletic Theory.
 All originate from PHSC,
Pleuripotent
Hamopoietic Stem Cell.
 Fundamental
properties
 Self replication.
 Differentiation &
commitment.
Monday, December 7, 2015

7. BLOOD CELL PRECURSORS.
 Progenitor cells.
 Pleuripotent progenitor
cells
 Lymphoid stem cell –
Lymphocytes.
 Myeloid stem cell.
 Granulocyte – Monocyte
progenitor.
 Erythroid progenitor.
 Megakaryocyte Progenitor.
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8. FEATURES OF PROGENITOR
CELLS.
 Progenitor cells form
group of cells called Clones
so also called CFU-colony
forming units.
 CFU-GEMM – Granulocyte,
Erythroid, Megakaryocyte
& Macrophages.
 BFU-E – Burst forming
units Erythroid.
 CFU-E - Erythroid
 CFU-Ba – Basophil.
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9. CONTROL OF HAEMOPOIESIS.
 Mainly by Hamopoietic
Growth Factors i.e.
Cytokines.
 These are called Colony
Stimulating Factors (CSF)
 CSF-G
 CSF-M
 CSF-GM
 Interleukins – for
Lymphocyte precursor.
 Erythropoietin
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10. Monday, December 7, 2015

11. STAGES OF ERYTHROPOIESIS.
 Pronormoblast
 Early normoblast
(Basophilic)
 Intermediate
normoblast
(Polychromatic)
 Late normoblast
(orthochromatic)
 Reticulocyte.
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12. Monday, December 7, 2015
STAGES OF ERYTHROPOIESIS.

13. Monday, December 7, 2015
CELLS/FEATURES SIZE CYTOPLASM NUCLEUS
HAEMOGLOB
IN
MITOSIS
PRONORMOBLAS
T
15-20
μm
BASOPHILIC
LARGE WITH
RETICULAR
FORMATION
ABSENT SEEN
EARLY
12-
16μm
BASOPHILIC
LARGE,NUCL
EOLI
DISAPPEARE
D.
ABSENT SEEN
INTERMEDIATE
10-
14μm
POLYCHROM
ATIC
CONDENSED APPEARS PRESENT
LATE 8-10μm
ACIDOPHILI
C
SMALL
PYKNOTIC
INCREASES ABSENT
RETICULOCYTE
7-
7.5μm
RETICULUM
LIKE
ABSENT INCREASES ABSENT

14. MATURATION OF RETICULOCYTE
TO ERYTHROCYTES.
 Reticulocyte – juvenile red cells
without nucleus but contains
ribosomal RNA so can synthesize Hb.
 Mature Red cells maturation in
spleen, lost Ribosomes, Mitochondria.
 Reticulocyte in Infants -2-6%, Adults
0.5-2%.
 Slightly basophilic hue in cytoplasm
& can stain with new Methelene Blue
or Brilliant Cresyl Blue
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15. SUMMARY OF CHANGES.
Cell Duration Size Nucleus
Hb
synthesis
Cytoplas
m
staining
Mitosis
Reticuloc
yte
0-5 DAYS 7-7.5 μm
Condens
es,
pyknotic
Present
Basophili
c-
polychro
matic -
acidophil
ic
Only
upto
intermed
iate
normobl
ast
RBC 2 DAYS 7 μm Absent Absent
acidophil
ic
Absent
only cell
matures.
Monday, December 7, 2015

16. REGULATION OF ERYTHROPOIESIS
 Erythropoietin –
Glycoprotein with
molecular wt 34000.
 Site of formation-
 85% - epithelial linings of
peritubular capillaries.
 15% - liver & cells of
tissue macrophage
system.
Monday, December 7, 2015

17. ERYTHROPOIETIN
 Stimulus for secretion.
 Mainly hypoxia –
causes release of Renal
Erythropoietic Factor –
acts on Plasma alpha
globulin
Erythropoietinogen –
form Erythropoietin
Monday, December 7, 2015

18. ERYTHROPOIETIN
 Actions
 Main effect on stem
cells – differentiation
 Promote Hb synthesis
 Promotes every stage
 Promotes release of
RBC from Bone
Marrow to Peripheral
Circulation.
Monday, December 7, 2015

19. FACTORS AFFECTING
ERYTHROPOIETIN
 Increase secretion
 Hormones – Androgen ,
Thyroxine, GH, ACTH,
Prolactin, Adrenocortical
Steroids.
 Haemolysates – products
of RBC destruction.
 Nucleotides –
cAMP,NAD,NADP
 Vasoconstrictor drugs –
that causes renal hypoxia
 Decrease secretion.
 Adenosine antagonists
– Theophylline.
 Oestrogen – decreases
synthesis of Globin &
depressing
erythropoietic
response to hypoxia.
Monday, December 7, 2015

20. Monday, December 7, 2015

21. FACTORS NECESSARY FOR
ERYTHROPOIESIS
 General factors.
 Special maturation
factors.
 Haemoglobinization
factors.
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22. GENERAL FACTORS.
 Optimum levels of
hormone
Erythropoietin &
efficient feedback
mechanism
controlling
erythropoietin.
Monday, December 7, 2015

23. SPECIAL MATURATION FACTORS.
 Vit B 12
(extrinsic factor)
 Folic acid
 Intrinsic factor
of Castle.
Monday, December 7, 2015

24. VIT B 12 (EXTRINSIC FACTOR)
 Vit B12 –
Cyanocobalamin or
extrinsic factor.
 Daily need – 1-2 μg.
 Sources – Milk, Meat,
Liver of Animals
 Also synthesized by
bacterial Flora.
Monday, December 7, 2015

25. VIT B 12 (EXTRINSIC FACTOR)
 ABSORPTION – need
Intrinsic Factor Of Castle , a
glycoprotein secreted by
parietal cells of gastric
mucosa.
 With it form Intrinsic
Factor- Cyanocobalamin
complex
 Bound to sp receptors in
ileum & absorbed by
Endocytosis.
Monday, December 7, 2015

26. VIT B 12 (EXTRINSIC FACTOR)
 TRANSPORT – in blood transported by combining
with Transcobalamin-II
 STORAGE – In liver & Muscle
 ROLE – required for synthesis of DNA & maturation
of nucleus & cell.
Monday, December 7, 2015

27. FOLIC ACID
 Folic acid –
Pteroylglutamic acid.
 Daily requirement –
100 μg.
 Sources – leafy veg,
pulses, yeasts, liver.
 From breakdown of
Polyglutamate to
Monoglutamates.
Monday, December 7, 2015

28. ROLE OF FOLIC
ACID IN DNA
SYNTHESIS.
Monday, December 7, 2015
Polyglutamates in food
Monoglutamates
Plasma Methyl tetrahydrofolate
TetraHydrofolate (THF)
Formyl THF(Folinic Acid)
5,10 methylene THF
Dihydrofolate
Uridine
Monophosphate
D Thymidine Monophosphate
Dihydro reductase

29. INTRINSIC FACTOR OF CASTLE.
 Intrinsic factor of
Castle is formed by
Gastric Cells.
 Deficiency if intrinsic
factor occurs in
autoimmune cause of
failure of secretion of
IF. ( Addisonian
Pernicious Anaemia)
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30.  Thank you.
Monday, December 7, 2015