FACTORS NECESSARY FOR ERYTHROPOIESIS
Development and
maturation of erythrocytes require variety of factors, which are classified
into three categories:
1. General factors
2. Maturation factors
3. Factors necessary for hemoglobin
formation.
GENERAL FACTORS
General factors
necessary for erythropoiesis are:
i. Erythropoietin
ii. Thyroxine
iii. Hemopoietic
growth factors
iv. Vitamins.
i. Erythropoietin
Most important general factor for
erythropoiesis is the hormone called erythropoietin. It is also called
hemopoietin or erythrocyte stimulating
factor.
Chemistry
Erythropoietin is a
glycoprotein with 165 amino acids.
Source of secretion
Major quantity of
erythropoietin is secreted by peritubular capillaries of kidney. A small
quantity is also secreted from liver and brain.
Stimulant for
secretion
Hypoxia is the stimulant for the
secretion of erythropoietin.
Actions of
erythropoietin
Erythropoietin causes
formation and release of new RBCs into circulation. After secretion, it takes 4
to 5 days to show the action.
Erythropoietin
promotes the following processes:
a. Production of proerythroblasts
from CFU-E of the bone marrow
b. Development of proerythroblasts
into matured
RBCs through the
several stages – early normoblast, intermediate normoblast, late normoblast
and reticulocyte
c. Release of matured
erythrocytes into blood. Even some reticulocytes (immature erythrocytes) are
released along with
matured RBCs. Blood level of erythropoietin increases in anemia.
ii. Thyroxine
Being a general
metabolic hormone, thyroxine accelerates the process of erythropoiesis at many levels.
So, hyperthyroidism and polycythemia
are common.
iii. Hemopoietic
Growth Factors
Hemopoietic growth factors
or growth inducers are the interleukins and stem cell factor (steel factor).
Generally these factors induce the proliferation of PHSCs. Interleukins (IL)
are glycoproteins, which belong to the cytokines family.
Interleukins involved in
erythropoiesis:
a. Interleukin-3
(IL-3) secreted by T-cells
b. Interleukin-6
(IL-6) secreted by T-cells, endothelial cells and macrophages
c. Interleukin-11
(IL-11) secreted by osteoblast.
iv. Vitamins
Some vitamins are also necessary for
the process of erythropoiesis. Deficiency of these vitamins
cause
anemia associated with
other disorders. Vitamins
necessary for erythropoiesis:
a. Vitamin B: Its
deficiency causes anemia and pellagra (disease characterized by skin lesions,
diarrhea, weakness,
nervousness and dementia).
b. Vitamin C: Its
deficiency causes anemia and scurvy (ancient disease characterized by impaired collagen
synthesis resulting in rough skin, bleeding gum, loosening of teeth, poor
wound healing, bone pain, lethargy and emotional changes).
c. Vitamin D: Its
deficiency causes anemia and rickets
d. Vitamin E: Its
deficiency leads to anemia and malnutrition.
MATURATION FACTORS
Vitamin B12, intrinsic
factor and folic acid are necessary for the maturation of RBCs.
1. Vitamin B12
(Cyanocobalamin)
Vitamin B12 is the maturation
factor necessary for erythropoiesis.
Source
Vitamin B12 is called extrinsic
factor since
it is obtained mostly from diet. Its absorption from intestine
requires
the presence of intrinsic factor of Castle. Vitamin
B12 is
stored mostly in liver and in small quantity in muscle. When
necessary, it is transported to the bone marrow to promote
maturation of RBCs. It is also produced in the large intestine by the
intestinal flora.
Action
Vitamin B12 is
essential for synthesis of DNA in RBCs. Its deficiency leads to failure in
maturation of the cell and
reduction in the cell division. Also, the cells are larger
with fragile and weak cell membrane resulting in macrocytic anemia.
Deficiency of vitamin
B12 causes pernicious
anemia. So, vitamin B12 is called antipernicious factor.
2. Intrinsic
Factor of Castle
Intrinsic factor of castle is produced
in gastric mucosa by the parietal cells of the gastric glands. It is essential for
the absorption of vitamin B12 from intestine. In the absence
of intrinsic factor, vitamin B12 is not absorbed from intestine. This leads to
pernicious anemia.
Deficiency of
intrinsic factor occurs in:
i. Severe gastritis
ii. Ulcer
iii. Gastrectomy.
Hematinic principle
Hematinic principle is the principle
thought to be produced by the action of intrinsic factor on extrinsic
factor. It is also called or antianemia
principle. It
is a maturation factor.
3. Folic Acid
Folic acid is also
essential for maturation. It is required for the synthesis of DNA. In the
absence of folic acid, the synthesis of DNA decreases causing failure of maturation.
This leads to anemia in which the cells are larger and appear in megaloblastic
(proerythroblastic) stage. And, anemia due to folic acid deficiency is called megaloblastic
anemia.
FACTORS NECESSARY FOR
HEMOGLOBIN FORMATION
Various materials are essential for
the formation of hemoglobin in the RBCs. Deficiency of these
substances decreases the production of
hemoglobin leading to anemia.
Such factors are:
1. First class proteins and amino
acids: Proteins of high
biological value are essential for the formation
of hemoglobin. Amino acids derived
from these proteins are required for the synthesis of protein
part of hemoglobin, i.e. the globin.
2. Iron: Necessary
for the formation of heme part of the hemoglobin.
3. Copper: Necessary
for the absorption of iron from the gastrointestinal tract.
4. Cobalt and nickel: These
metals are essential for the utilization of iron during hemoglobin
formation.
5. Vitamins: Vitamin
C, riboflavin, nicotinic acid and pyridoxine are also essential for the
formation of
hemoglobin.
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