Erythropoiesis and its regulation.

RBC life duration is 60-120 days (in males – on 10-20 days longer). They are formed in bone marrow from reticulocytes. At this stage reaching capillary wall is stretched, vessel is opened and Er are washed into blood stream, where they are transformed into young Er (normocytes) after 35-45 hours. Er die in liver, spleen. Destructed Er amount corresponds to formed Er amount. This closed system with all mass of Er circulating into organism received the name erythron.

Erythropoiesis regulation is performed by humoral and nervous-reflectory way. Humoral way is main and it’s more complicated. It includes 2 ways:

1. Specific - is linked with special substances - cytokines. Erythropoietin is the most essential among them from this point of view. This is polypeptide, produced in kidneys, uterus, salivary glands. Its amount is increased at:

· bleedings;

· low oxygen partial pressure;

· ascent to haltitude (in the mountains);

· muscular activity.

Action mechanism:

· stem cells transition into erythroblasts acceleration and enforcement;

· cellular mitosis increasing;

· interphase decreasing;

· normoblasts and reticulocytes maturation increasing;

· DNA, RNA and ferritin amount increasing in erythrocytic predecessors;

· circulation activation in erythroblastic bone-marrow insulas.

Other cytokines delt with erythropoiesis - haemopoeitines (they produce by leucocytes, macrophages and endotheliocytes):

· interleukines acting to bone-marrow;

· growth-stimulating factor;

· colony-stimulating factor;

· colony-forming factor.

2. Non-specific way – microelements, vitamines and hormones action.

a) Microelements:

· Iron is the most essential among them. It comes into bone-marrow from destructed erythrocytes (about 21 mg per day). But this amount is insufficient for normal erythropoiesis performance. Additional amount must be approximately 4 mg/day. 12-15 mg must come with water and food while normal urtilization in alimentary tract. If no – iron-deficient anaemia is observed (in pregnant, at stomach and intestine diseases). Ascorbic acid enforces iron absorbtion. Transferrin – special iron transporter – is located in intestinal mucosa; iron forms complex with protein ferritin in cells and is preserved in cells in such a form. Liver is main iron depot in organism.

· Copper provides iron mobilization from tissues and its utilization. Copper is utilized by bone-marrow and participate in haemoglobine synthesis. When copper absence RBC maturate only till reticulocytic stage.

· Cobalt is a haemoglobine constituent.

· Fluorum is erythropoiesis inhibitor, that’s why at its excess in environment (water, air, foods) anaemia may be developed.

b) Vitamines: of B-group are the most essential:

· B₁₂ (cyancobalamine) - haemopoiesis factor. It is synthesized by microorganisms, ray fungi and some weads. Cobalt is essential for cyancobalamine formation. This vitamine comes into human organism with liver, meat, eggs. This vitamine takes part in haemoglobine synthesis. It is accumulated into liver; its depot is very large (for 5-10 years).

· B₉ (folic acid) – is contained in plant food, liver, eggs. It participates in globine synthesis influencing on erythroblasts.

· B₆ (pyridoxine) catalyzes folic acid formation and cyancobalamine action.

· B₂ (rhibophlavine) participates in iron consumption, it also is necessary for haemoglobine synthesis.

· C (ascorbic acid) – encourages iron releasing from intestine and regulates haemoglobine synthesis.

· A (retinol) and E (tocopherol) – influence on haemopoietic tissue functions, protect Er membrane from free radicals action.

c) Hormones:

· Hypophyseal erythropoietical hormone, ACTH, STH - enforce erythropoiesis.

· Suprarenal glands – glucocorticoids, adrenaline - enforce erythropoiesis.

· Parathyroid - parathormone - enforces erythropoiesis.

· Female sexual organs – erythropoiesis weakening.

· Male sexual organs - enforce erythropoiesis.

Besides erythropoiesis activators there are also erythropoiesis inhibitors in blood.