Haematology - 3 .Year Students - Dr. Burhan A. Mohammed

Haematology______ 3th .Year Students __ _ Dr.
Burhan A. Mohammed ERYTHROPOIESIS (Formation of Red blood cells)

Erythropoiesis is the formation of erythrocytes from committed progenitor cells through
a process of mitotic growth and maturation. The first recognizable erythyroid cell in the
bone marrow is the proerythroblast or pronormoblast, which on Wright or Giemsa stain
is a large cell with basophilic cytoplasm and an immature nuclear chromatin pattern.
Subsequent cell divisions give rise to basophilic, polychromatophilic, and finally
orthochromatophilic normoblasts, which are no longer capable of mitosis. During this
maturation process a progressive loss of cytoplasmic RNA occurs as the product of
protein synthesis, hemoglobin, accumulates within the cell; as a result the color of the
cytoplasm evolves from blue to gray to pink.
At the same time the nuclear chromatin pattern becomes more compact tan clumped
until, at the level of the orthochromatophilic normoblast, there remains only a small
dense nucleus, which is finally ejected from the cell. The resulting anucleate
erythrocyte still contains some RNA and is recognizable as a reticulocyte when the
RNA is precipitated and stained with dyes such as new methylene blue.
Normally, reticulocytes remain within the bone marrow for approximately 2 days as
they continue to accumulate hemoglobin and lose some of their RNA.
The reticulocyte then enters the peripheral blood, were, after about one more day, it
loses its residual RNA and some of its excessive plasma membrane and becomes
indistinguishable form adult erythrocytes. Under normal conditions the transit time
from the pronormoblast to the reticulocyte entering the peripheral blood is about 5 days.
Morphology of the red cells and their precursors
A. Pronormoblast (Rubriblast)
Pronormoblast is the earliest morphologically recognizable red cell precursor, 20-25µm

in diameter.
Nucleus: large, round to oval and contains 0-2 light bluish, indistinct nucleoli.
The chromatin forms a delicate network giving the nucleus a reticular appearance.
Cytoplasm: there is a narrow (about 2µm) rim of dark blue cytoplasm. There may be
a perinuclear halo. The nuclear/cytoplasm ratio is about 8:1.
B. Basophilic Normoblast
Size: 16-18µm in diameter
Nucleus: round or oval and smaller than in the previous stage. The chromatin forms
delicate clumps so that its pattern appears to be denser and coarser than that seen in the
Pronormoblast. No nucleoli are seen.
Cytoplasm: slightly wider ring of deep blue cytoplasm than in the Pronormoblast and
there is a perinuclear halo. The nuclear/cytoplasm ratio is about 6:1.
C. Polychromatophilic Normoblast

Nucleus: smaller than in the previous cell, has a thick membrane, and contains coarse
chromatin masses.
Cytoplasm: as the nucleus is shrinking the band of cytoplasm is widening.
It has a lilac (polychromatic) tint because of beginning of hemoglobinization.
The nuclear cytoplasmic ratio varies from 2:1 to 4:1.
D. Orthochromatic Normoblast
Size: 10-12µm in diameter.

Nucleus: small and central or eccentric with condensed homogeneous structure less
chromatin. It is ultimately lost by extrusion.
Cytoplasm: a wide rim of pink cytoplasm surrounds the shrinking nucleus.
The entire cell is somewhat smaller than the Polychromatophilic Normoblast.
The nuclear / cytoplasmic ratio varies from 1:2-1:3.
E. Reticulocyte
After the expulsion of the nucleus a large somewhat basophilic a nuclear cell remains
which when stained with new methylene blue, is seen to contain a network of bluish
granules. This network is responsible for the name of the cell and consists of
precipitated ribosomes. As the bone marrow reticulocyte matures the network becomes
smaller, finer, thinner, and finally within 3 days disappears. About 1% of reticulocytes
enter the peripheral circulation.
Nucleus: the reticulocyte does not contain a nucleus.
Cytoplasm: faintly basophilic (blue).
F. Mature erythrocyte
Cytoplasm: biconcave, orange-pink with a pale staining center occupying one-third of
the cell area.
Regulation of Erythropoiesis
Erythropoietic activity is regulated by the hormone erythropoietin which in turn is
regulated by the level of tissue oxygen. Erythropoietin is a heavily glycosylated
hormone (40% carbohydrate) with a polypeptide of 165 amino acids. Normally, 90% of
the hormone is produced in the peritubular (juxtaglomerular) complex of the kidneys
and 10% in the liver and elsewhere. There are no preformed stores of erythropoietin and
the stimulus to the production of the hormone is the oxygen tension in the tissues
(including the kidneys). When there is tissue air hypoxia due to:
-Low blood hemoglobin levels (e.g., anemia)
- Imped oxygen release from hemoglobin for some structural or metabolic
- defects (e.g., the hemoglobinopathies)
- Poor blood flow as in severe circulatory defects.
- Low atmospheric oxygen (e.g., high altitude)
Erythropoietin production increases and this stimulates erythropoiesis by increasing the
number of progenitor cells committed to erythropoiesis.
Erythropoietin accelerates nearly every stage of red cell production:
• It increases the rate at which the committed stem cells divide and differentiate
• It increases the rate of cell division
• It speeds up the incorporation of iron into the developing red cells
• It shortens the time cell maturation, and
• It hastens the entry of reticulocytes into the peripheral circulation Similarly, increased
oxygen supply to the tissues due to:
• Increased red cell mass (e.g., polycythemia)
• Ability of hemoglobin to release oxygen to the tissues more readily than normal
reduces the erythropoietin drive.
Ineffective erythropoiesis/Intramedullary hemolysis
Erythropoiesis is not entirely efficient since 10-15% of erythropoiesis in a normal bone
marrow is ineffective, i.e., the developing erythroblasts die within the marrow without
producing mature cells. Together with their hemoglobin, they are ingested by
macrophages. This process is substantially increased in a number of anemias.
Megaloblastic Erythropoiesis
Megaloblasts are pathologic cells that are not present in the normal adult bone marrow,
their appearance being caused by a deficiency in vitamin B12 or folic acid or both
leading to defective DNA synthesis. In Megaloblastic erythropoiesis, the nucleus and
cytoplasm do not mature at the same rate so that nuclear maturation lags behind
cytoplasmic hemoglobinization. This nuclear lag appears to be caused by interference
with DNA synthesis while RNA and protein synthesis continue at a normal rate. The
end stage of Megaloblastic maturation is the megalocyte which is abnormally large in
size (9-12µm in diameter)

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Haematology____ 3th .Year Students _ Dr.

Burhan A. Mohammed ERYTHROPOIESIS (Formation of Red blood cells)

Pronormoblast is the earliest morphologically recognizable red cell precursor, 20-25µm

Size: 12-14µm in diameter

Size: 10-12µm in diameter.

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