ERYTHROPOIESIS

Dr. Niranjan Murthy

Assistant Prof of Physiology
SSMC, Tumkur
• It is the process of development,
differentiation and maturation of
RBCs from primitive stem cells

• Monophyletic and polyphyletic theory

• Things to learn:- Site, Stages,

Duration, Regulating factors, Clinical
abnormalities
 Sites of erythropoiesis
• Mesoblastic stage-
in the yolk sac
Starts at 2 weeks of intrauterine life
intravascular
• Hepatic stage-
2-7 months
Both liver and spleen
• Myeloid stage
 Myeloid stage
• Occurs in bone marrow

• Starts at 5 months of fetal life and

takes over completely at birth

• Red bone marrow of all bones

• Late adult life, red marrow of flat

bones
 Stem cells
• 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
Microenvironment
Stages of erythropoiesis
Pronormoblast

Early normoblast

Intermediate normoblast

Late normoblast

Reticulocyte

Erythrocyte
ERYTHROPOIESIS

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 is maximum.

7.3µm- Reticulum of basophilic

material in the cytoplasm.

7.2µm- Mature red cell with Hb.

Pronormoblast
•15-20 microns
•Mitosis present
•Nucleus with
multiple nucleoli
•Basophilic
cytoplasm
with
polyribosomes
Basophilic normoblast
• Large nucleus
• Basophilic
cytoplasm
• Active mitosis
• Slight reduction
in size
Polychromatophilic
normoblast
• Chromatin lumps
• Hb starts appearing
• Reduced mitoses
Orthochromatic normoblast
• Small and pyknotic
nucleus
• Eosinophilic
cytoplasm
• Mitoses absent
Reticulocyte
• Reticular nuclear
fragments
• Nucleus extruded
• Slightly larger than
RBCs
 Duration
Differentiation phase: from
pronormoblast to reticulocyte phase-
5 days

Maturation phase: from reticulocyte to

RBC- 2 days
 Regulation of erythropoiesis

1. Tissue
Oxygenation
 Erythropoietin
• Glycoprotein with 165 amino acids,
4 oligosaccharide chains
and molecular weight of 34,000
• Production- 85% by peritubular
capillary bed interstitial cells(Kidney)
and 15% by perivenous hepatocytes(
Liver)
• Also seen in brain, salivary glands,
uterus, oviducts
Factors increasing erythropoietin
secretion:
2 Hypoxia
3 Androgens
4 Growth Hormone
5 Catecholamines
6 Prostaglandins
Factors inhibiting erythropoietin
secretion:
8 Estrogen
9 Theophylline
Action of Erythropoietin:
2. Formation of Pronormoblast from
stem cell
3. Speeds up the differentiation
through various stages of
erythropoiesis

Mechanism of Action:
• Formation of ALA synthetase
• Activation of Adenylyl Cyclase
• Synthesis of transferrin receptors
Erythropoietin receptors:
Member of cytokine superfamily
Receptor has Tyrosine kinase activity
 Maturation factors
Vitamin B12 and Folic acid:
• Essential for DNA synthesis
(Thymidine triphosphate)
• Abnormal and diminished DNA
• Failure of division and maturation
• Macrocytic / Megaloblastic anemia
 Pernicious Anemia
Intrinsic factor of Castle- secreted by
oxyntic cells of gastric mucosa
Essential for absorption of Vitamin B12
by enteric route
 Other Factors
• Cobalt
• Copper
• Proteins
• Vitamin C
 Clinical Aspects
Anemias: Reduced RBC count /
reduced Hb concentration

Polycythemia: Increased RBC count

• Polycythemia vera
• Secondary polycythemia- due to
hypoxia