This document summarizes the regulation and production of erythropoietin (EPO) and factors involved in erythropoiesis. EPO is produced mainly in the kidney and promotes red blood cell formation in the bone marrow. Its production is stimulated by hypoxia and regulated by oxygen sensors in the kidney and liver. EPO increases red blood cell production by promoting progenitor cell production, shortening maturation time, and promoting early reticulocyte release. Other general and maturation factors involved in erythropoiesis include growth inducers, vitamins B12 and folic acid, iron, copper, and proteins for hemoglobin and heme synthesis.

2. Regulation of erythropoiesis
 General factors
- Hypoxia  erythropoietin
- Growth inducers
- Vitamins
 Maturation factors
- Vitamin B 12
- Folic acid
 Factors necessary for hemoglobin production
- Vitamin C Helps in iron absorption (Fe+++  Fe++)
- Proteins  Amino Acids for globin synthesis
- Iron & copper  Heme synthesis
- calcium, bile salts, cobalt & nickel.

3. General factors
Hypoxia  erythropoietin

4. EPO
• Erythropoietin (EPO) is a hormone produced
by the kidney that promotes the formation of
red blood cells by the bone marrow. The
kidney cells that make erythropoietin are
sensitive to low oxygen levels in the blood
that travels through the kidney.

5. Erythropoietin (EPO) facts
• Erythropoietin (EPO) is a hormone produced by the
kidney.
• Erythropoietin promotes the formation of red blood
cells by the bone marrow.
• The erythropoietin hormone level can be detected and
measured in the blood (the EPO test). 4 up to 24 mU/m
• Measurement of the blood erythropoietin level can be
used to detect certain medical conditions.
• Erythropoietin can be synthesized and used as a
treatment of some forms of anemia.
• Erythropoietin has been misused as a performance-
enhancing drug by some athletes.

6. ERYTHROPOIETIN
• Glycoprotein MW-34000 (165 AA residues)
Formation
• 85% formed in endothelial cells of the
peritubular capillaries of the renal tubules.
• 15% formed in liver, hepatic cells & Kupffer
cells.
Breakdown
 In liver. Half life is 5hours

7. Function
• Erythropoietin stimulates the bone marrow to
produce more red blood cells. The resulting rise
in red cells increases the oxygen-carrying capacity
of the blood.
• As the prime regulator of red cell production,
erythropoietin's major functions are to:
• Promote the development of red blood cells.
• Initiate the synthesis of hemoglobin, the
molecule within red blood cells that transports
oxygen.

8. uses
• uses of erythropoietin may include treatment
of anemia related to the medication AZT (used
to treatAIDS), anemia caused
by chemotherapy, anemia caused by
dysfunctional bone marrow (where the blood
cells are made), and anemia associated
with cancer

9. Regulation of erythropoietin secretion
• O2 sensor (heme protein) in kidney & liver
• Deoxy & oxy form of O2 sensor
• HYPOXIA INDUCIBLE FACTOR-1 (HIF-1)
• Erythropoietin gene
• Erythropoietin mRNA
• Erythropoietin
• 2-3 days to increase RBC count

10. ERYTHROPOEITIN
Stimuli for production
Hypoxia
Products of RBC destruction
High altitude
Anemia
Chronic lung or heart diseases
Catecholamines” neurotransmitters such as
adrenaline and dopamine.”
Prostaglandins
Androgens
Inhibition
 Blood transfusion

11. Functions of Erythropoietin
• Erythropoietin increases
• RBC production in 3
ways:
– Promotes pronormoblast
production
– Shortens the transition
time through the
normoblast stage
– Promotes the early
release of reticulocytes.

13. Growth inducers/ Differentiation inducers
• Interleukin 1, 3, 6 (IL-3 is a growth inducer for
all cell lines )
• CSF- E (colony stimulating factor – erythro)

14. Maturation factors
• Vitamin B 12
• Folic acid
Dietary factors - IRON

15. Vit B-12
• Source : only animal tissues
• Absorption from ileum
• Functions
• Promotes maturation of RBCs (plays an
important role in folic acid synthesis of nucleic
acid-DNA)

16. Sources of vitamin B12
16

17. Folic acid
• Green leafy vegetables , yeast, liver
• Function : maturation of RBC

18. 18

20. IRON DEFICENCY ANEMIA