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.

General factors

Hypoxia erythropoietin

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.

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.

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

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.

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

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

ERYTHROPOEITIN

Stimuli for productionHypoxiaProducts of RBC destructionHigh altitudeAnemiaChronic lung or heart diseasesCatecholamines” neurotransmitters such as adrenaline and

dopamine.”

ProstaglandinsAndrogens

Inhibition

Blood transfusion

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.

Growth inducers/ Differentiation inducers

• Interleukin 1, 3, 6 (IL-3 is a growth inducer for all cell lines )

• CSF- E (colony stimulating factor – erythro)

Maturation factors

• Vitamin B 12• Folic acid

Dietary factors - IRON

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)

Sources of vitamin B12

16

Folic acid

• Green leafy vegetables , yeast, liver

• Function : maturation of RBC

18

IRON DEFICENCY ANEMIA