Regulation of Erythropoiesis

Dr Ghulam Mustafa

Regulation of Erythropoiesis Importance Factors affecting Erythropoiesis

Tissue Oxygenation Anemia, High Altitudes, Cardiac failure, Resp Problem ERYTHROPOITEN

VitaminsMetalsProteinsHormonesOther factors/Conditions

Normal RBC Count

Importance:

Must Not fall

To supply oxygen from lungs to tissues

Must Not rise

Blood viscosity may increase

May impede blood flow

Factors affecting Erythropoiesis

1. Tissue Oxygenation

2. Vitamins

3. Metals

4. Proteins

5. Hormones

1. Tissue Oxygenation – Most

Important Regulator of Erythropoiesis ANY CONDITION Decrease Tissue

Oxygenation Increase Erythropoiesis

Anemia

Immediately Increase RBCs production

Bone marrow destruction:

Hyperplasia of remaining cells

Increase production of RBCs

High altitudes:Partial pressure of oxygen in air lessDecrease in oxygen transport to tissuesTissue hypoxiaResult?

Cardiac FailureInefficient pumping by heartDecreased blood flow to peripheral vesselsTissue hypoxiaResult?

Lung diseases:Failure of oxygen absorption in LungsBlood carries less OxygenTissue hypoxiaResult?

All conditions have one common problem

HYPOXIA

ERYTHROPOIETIN

Erythropoietin

Glycoprotein Mol weight 34000 Sites of production

KidneysLiverBrain, Uterus

If Erythropoiten production reducedEffect of Hypoxia?

Stimulants of Erythropoiten production:

RENAL MECHANISMAnemic blood to kidney

Less oxygen supplied

Renal tubular cells - High O2 consuming

Stimulates production of Erythropoiten

NON RENAL MECHANISM

Hypoxia in other parts – Non renal sensorNor epinephrine, epinephrine, prostaglandins

In Renal failure?

Formation of Erythropoiten Erythrogenin – Renal Erythropoitic factor Erythropoitinogen

Alpha globulinSubstrate for Erythropoiten

Stimulants of Erythrogenin HypoxiacAMP NADHemosylates

Role of EP in Erythropoiesis

Formed in response to Hypoxia within minutes

RBC production in 5 days

Erythropoiten

Stimulates Proerythroblasts formation

Causes cells to pass through various stages

of Erythropoiesis rapidly

Recombinant Erythropoiten

Anemia – Renal Failure Blood doping

Erythropoiten - AthletesRunning – Increase Oxygen demandBreathlessnessERYTHROPOITEN – Increase RBC’sLess dyspnea

DNA Recombinant Technique

2. Vitamins

Vit B12 & Folic acid

Essential for formation of thymidine triphosphate

Essential building block of DNA

Diminished DNAFailure of nuclear maturation

Inadequate Erythropoiesis

Vitamin C Potentiate the effect of Folic acid Also helpful in Iron

Absorption Reducing Ferric to ferrous form

Pyridoxine: Coenzyme for condensation of Glycine and

succinyl-CoA

Riboflavin and Pantothenic acid Heme formation Cell growth and division

2. Minerals Iron Copper

CeruloplasminNecessary for Iron transfer from storage sites

Bone marrow, Liver and Spleen

CobaltForms a part of Vitamin B12

Nickel and Manganese

3. Proteins

Adequate protein diet essential

Formation of Globin

Protein deficiency

Kwashiorkor

Prisoners

Protein losing Enteropathies

Renal disease- Proteinuria

4. Hormones

Testosterone

Growth hormone

Thyroid hormone

Cortisol

Adrenocorticotrophic hormone ACTH

5. Other Conditions Stimulating Erythropoiesis Exercise Excitement Menstruation Pregnancy Menopause

More RBC Count in fetal lifeHbF – Binds more oxygen

Regulation of Erythropoiesis Importance

Factors affecting Erythropoiesis

1 Tissue Oxygenation

Anemia, High Altitudes, Cardiac failure, Resp Problem

ERYTHROPOITEN

Site of production

Stimulants for production

Mechanism of production

Role in Erythropoiesis

2 VitaminsVit B12 and Folic acidPyridoxineVitamin CRiboflavin and Pantothenic acid

3 Metals Iron, Cu, Co, Ni, Mn

4 Proteins5 Hormones

GH, TH, CORTISOL, TESTOSTERONE, ACTH

5 Other conditions affecting…..

If  you complain about your transport

system, What about them?