2. Erythropoiesis
■ Erythropoiesis is the process of red blood
cells formation
■ Daily replacement of 0.8–1% of all
circulating red cells in the body.
■ Occur over a period of 7 days.
■ Erythropoiesis starts from the pluripotent
hemopoietic stem cell through the CFU-
GEMM, BFU-E, CFU-E to the first recognizable
precursor in the BM (Pronormoblast).
6. Erythropoiesis
▪ 4 mitotic divisions between pronormoblast and
orthochromic normoblast stage.
▪ Thus giving rise 16 RBCs.
▪ But not all of the 16 will be good RBCs, some are bad
and will be destroyed, these destroyed cells is called
ineffective erythropoiesis.
▪ 4– 5 days for pronormoblast to mature into
Reticulocyte.
▪ Reticulocyte further matures for 2 – 3 days in bone
marrow before it is released into the peripheral blood.
▪ Red cell has life span of 120 days in peripheral blood.
7. Each pluripotent stem cell produces one
million (106) red cells by 20 division
Single pronormoblast gives rise to 16 red
cells
Hemoglobin synthesis begins in the
pronormoblast and ends in the reticulocyte.
Normally, nucleated red cells are not
appeared in the peripheral blood and only
present in the BM
Origin and development
8. Morphologic Changes in Erythropoiesis
Immature > Mature
Large cells,
gorgeous
basophilic
cytoplasm
Small cells, with red (eosinophilic) cytoplasm
Large,
violet-blue
nucleus
Small, dark blue-black nucleus
Fine
chromatin
(see
nucleoli)
coarser, then pyknotic nucleus (eventually extruded)
Basophilic
erythroblast
Proerythroblast* erythroblast
Ortho-
Polychromatophilic
chromatophilic
erythroblast
Reticulocyte
Mature
red cell
10. Proerythroblast:
Large cell, deep violet-blue staining cytoplasm,
very fine chromatin.
Proerythroblast
Large cell: 15 – 20 Microns in diameter.
Nucleus has fine stippled reticulum & many
nucleoli.
11. Basophilic erythroblast:
a little smaller, with more condensed chromatin and
darker cytoplasm..
EARLY
NORMOBLAST:
(BASOPHILIC
NORMOBLAST)
12. Polychromatic erythroblasts:
even more condensed chromatin, cytoplasm grey-blue
(has a little hemoglobin)
Increased
Hemoglobin
content in the
cytoplasm
Cytoplasm is
Polychromatophilic
.
Intermediate
normoblast:
(polychromatophilic
normoblast)
13. Orthochromatic erythroblast:
chromatin very condensed, cytoplasm is grey-pink-
lavender (has more hemoglobin)
LATE
NORMOBLAST:
(ORTHOCHROMIC
NORMOBLAST)
Cytoplasm has
a Eosinophilic
appearance.
15. Erythrocyte: (Red Blood
Cell, Discocyte)
RBCs Properties
■ Biconcave disc shape: to increase surface area (30% more
surface).
■ Diameter: 6.0-8.0 μm, 1.2-2.5 µm thick,
■ Anucleate (no nucleus): so, no cell division
■ No mitochondria or other organelles: - no protein synthesis,
can generate energy (2ATP) by anaerobic glycolysis.
■ Flexible and deformable: Can change shape to pass through
microcirculation (3.5 μm diameter) to transport O2.
■ Life-span 120 days, travels 480 km (300miles), then
elimination from circulation by RES.
17. Erythrocyte function and
Normal Range
■ Erythrocyte function
– Carrying hemoglobin into close contact
with tissues for successful gaseous
exchange
■ Normal range:
– Males: 4.5–6.5 million cells/ μL of blood.
– Females: 3.9-5.6 million cells/ μL of blood.
18. Erythrocyte fate
■ Red cell has no nucleus, so it is unable to synthesis
enzymes to maintain its function.
■ During its lifespan (120 days), it undergoes to the
process of aging.
■ At the end of its lifespan, it becomes old where
certain glycolytic enzymes decreased in activity.
■ Decrease energy production
■ Loss of flexibility and becomes rigid
■ Unable to pass through the microcirculation
■ Removed from the circulation by the macrophages
especially in the BM, spleen and liver
21. Erythropoietin:
■ Erythropoietin (EPO) is a regulated
hormone of erythropoiesis
■ Secreted by peritubular capillaries of kidney
(90%).
■ Small quantity also secreted from brain and
liver (10%).
■ Hypoxia is the stimulant of erythropoietin.
22.
23. Hypoxia→Kidney→EPO BFU-
E
CFU-E
↑NewRBCproduction
pronomoblast
Control of erythrocyte
production
▪ Every day 1% of red cells is removed from
the circulation because their old age
▪ This lowering oxygen level in the kidney
tissues and stimulates EPO production
↓O2 tension←↓RBC(oldRBC)←(Feedback) ↑O2 tension
24. Erythropoietin (Epo)
As its name suggests, EPO stimulates growth of
Erythrocytes, and its function include:
▪ Activates stem cells of bone marrow to differentiate
into pronormoblasts.
▪ Decrease maturation time.
▪ Increases rate of mitosis and maturation process.
▪ Increases rate of hemoglobin production.
▪ Increased rate of reticulocyte release prematurely into
the peripheral blood.
▪ Prevent apoptosis.
25. EPO receptors
▪ Found on surface on bone marrow erythroid
progenitor and precursor cells.
▪ The highest number of EPO receptors is seen
on the CFU-E and the pronormoblasts.
▪ The number of EPO receptors per cell gradually
decreases during erythroid cell differentiation,
and studies have shown that the reticulocyte
and mature erythrocyte do not contain EPO
receptors
