6. Maturation of reticulocytes to
RBCs in blood circulation (1-2
days)
Reticulocytes still
contain ribosomes
and elements of
endoplasmic
reticulum.
The RNA of the
ribosome can be
detected by cresyl
blue.
7. Reticulocyte count
A typical normal range
is 0.5-1.5 %.
Increase level of
reticulocytes as known
as reticulocytosis
10. Structure of EPO
Is a glycoprotein growth
factor (165 amino
acids) with high
carbohydrates content
which increase the
molecule’s stability in
the circulation
11. Erythropoietin (Epo)
Site of synthesis:
Peritubular
lining cells of
the renal cortex
Liver
Ito cells
EPO production
predominates
in the adult
EPO production
predominates in the
fetal and perinatal period
12. Factors which stimulate Epo
production:
Hypoxia of different genesis
Increase hemolyzates level (products of
RBCs destruction)
Anterior pituitary hormones: LH, FSH,
ACTH, TSH, GH
Androgens
13. Factors which decrease Epo
production
Estrogens decrease synthesis of Epo
This is why in females RBCs count is less
then in males.
15. Regulation of the EPO production
by blood oxygenation (feed-back)
O2
Oxygen
sensor
protein (heme-containing)
changes the
conformation
to Deoxy-form
HIF
(hypoxia inducible factor-1)
O2
Hydroxylation
of HIF
EPO gene transcription
EPO production
Proteosomal
degradation
EPO production
Oxygen
sensor
protein (heme-containing)
changes the
conformation
to Oxy-form
16. Effect of Epo
1. Epo induces proliferation and maturation
of erythroid progenitor cells (CFU-E and
BFU-E have receptors for EPO)
2. Epo increases release of reticulocytes
from the bone marrow
3. Epo stimulates absorption of hemoglobin
by suppressing hepcidin.
17. Role of hepcidin
Is peptide hormone
produced by the liver.
Increase iron storage
in cells
Prevents enterocytes
from secreting iron
into the hepatic portal
system
Antifungal and
antibacterial activities
20. Causes:
Causes of aplastic anemia usually bind
with damage of the stem cells in the bone
marrow:
Exposure to toxic substances
Cancer therapy
Autoimmune disease
Viral infection
21. Clinical signs
Due to
RBCs count platelets
count
WBCs
count
lack of energy
feeling of
tiredness, fatigue
prolonged
bleeding
frequent
nosebleeds
increased number
and severity
of infections
22. Hypoproliferative anemia (marrow
production defect)
Iron
deficiency
Epo
Anemia of chronic diseases:
(INF-gamma, TNF-beta-inflamatory
cytokines suppress the response of
the erythroid cells to EPO)
Anemia in renal disease
production of EPO)(
Endocrine deficiency states
(eg. Hypothyroidism -
hypometabolic state)
Protein starvation
Hypoproliferative anemia
25. Definition. Hemolytic anemias are defined as
decreased red cell mass resulting from an
increase rate of erythrocytes destruction.
Normal red cells have a lifespan 100-120
days.
At the end of this lifespan, both normal and
damaged cells are ‘recognized’ by
macrophages in the spleen and removed
from the circulation
26. In hemolytic anemia,
red cell lifespan is
shortened.
The bone marrow is
not able to produce
new RBCs quickly
to replace destroyed
RBCs
31. Composition of RBCs
membrane
50% of lipids
(help determine
membrane fluidity)
Phospholipids
cholesterol
50% of proteins
Integral Peripheral
(help determine
membrane integrity)
Band 3,
glycophorins
A and C)
Stomatin
(help determine
biconcave shape and
flexibility)
Ankyrin
Tropomyosin
Alpha and beta-
spectrin(form an
anion channel)
32. Diagram of the RBCs
membrane
3
A
A
stomatin C
4.1
ankyrin
actin
spectrin
(alpha)
spectrin
(beta)
outer
inner
lipid
bilayer
lipid
bilayer
lipid
bilayer
Polysaccharides
Tropomyosin
Adductin
33. Disease Defect of
proteins
Degree of
anemia
Shape of RBCs
Hereditary
spherocytosis
(HS)
α-spectrin Severe Spherocytes
Are not flexible
β-spectrin Mild
Ankyrin Mild
Hereditary
stomatocytosis
Stomatin
deficiency
Mild Cup-shaped
have one
surface
concave and
other side as
convex
Hereditary
elliptocytosis
Protein 4.1
deficiency
Mild Ovalocytosis
34. Clinical presentation:
Extravascular Hemolysis in the spleen.
Plasma hemoglobin is slightly raised.
Splenomegaly
UCB-emia and risk for jaundice and pigment
stones
Reticulocytosis (5-20%).
35. Osmotic fragility test is positive
When RBCs are exposed to a hypotonic
saline solution (<0.9%) only few normal
RBCs are hemolyzed.
But 50% of spherocytes lyses under this
conditions.
↓ ability of RBCs to extrude sodium →
retention of water → osmotic injury