Erythropoiesis Production of red blood cells Erythropoiesis Yolk

Erythropoiesis (Production of red blood cells)

Erythropoiesis • Yolk sac in embryonic life • Spleen & liver and lymph nodes in middle trimester of pregnancy, early fetal life • Red Bone marrow of all the bones in late fetal life and early childhood until age of 5 years. • The marrow of the long bones, except for the proximal portions of humeri and tibiae, becomes fatty, produce no more RBCs after 20 yrs.

• Beyond this age , red cells are produced in membranous bones such as sternum, vertebrae, ribs and ilia.

Erythrogenesis in bone marrow

Erythropoiesis • Erythrocytes are derived from committed erythroid proginator → series of mitotic divisions and maturation phases. • Erythropoietin, (kidneys) → stimulates erythropoiesis → proliferation of the committed stem cells and differentiation of erythrocytes

• Blood cells are derived from pleuripotential hematopoietic stem cell. • A small portion remain exactly like the original pleuripotential cells. • When these cells become committed to form a particular line of cells , these are called committed stem cells. • A committed stem cell that produces erythrocytes is called a CFU-E.

PHSC & blood cells

Stages of Erythropoiesis • • Pluripotential hemopoietic stem cell Committed stem cell (CFU-E) Proerythroblast Basophilic erythroblast Poly chromatophilic erythroblast Orthochromatic erythroblast Reticulocyte Erythrocyte

Erythropoiesis

Erythropoiesis • Tissue hypoxia (lack of oxygen) is the main stimulus for erythropoietin production. • Nucleated red cell precursors in the bone marrow are collectively called erythroblasts. • RBCs that have matured to the nonnucleated stage gain entry to the peripheral blood. • Once the cells have lost their nuclei they are called erythrocytes.

Erythropoiesis • Young erythrocytes that contain residual RNA are called reticulocytes. • Bone marrow erythroblast proliferation and maturation occurs in an orderly and well defined sequence. – gradual decrease in cell size, – condensation and eventual expulsion of the nucleus – an increase in hemoglobin production.

Erythropoiesis • Reticulocytes enter into the peripheral blood → maturation into erythrocytes within 24 hours. • 1% reticulocytes in the peripheral smear • More in new born babies. – Visualized by staining with methylene blue – Remnants of the ribosomes on the endoplasmic reticulum may be visualized

Erythropoiesis

Erythrocyte kinetics • The normal erythrocyte concentration varies with age, sex, and geographic location. – ↑ RBC count at birth which – Decreases until the age of 2 -3 months -physiologic anemia due to low erythropoietin production. – ↑RBC count to adult levels at about 14 years of age. – Males have higher RBC counts because testosterone stimulates erythropoietin production. – High altitude →↓ partial pressure of O 2 → ↑ erythropoietin → ↑ RBC

Hypoxia and erythrogenesis

Requirements for normal erythropoiesis • Vitamin B 12 is required (Synthesis of DNA, maturation) • Folic Acid is required (Synthesis of DNA, maturation) – Both are required for Thymidine triphosphate • • • Iron Proper porphyrin synthesis Proper globin chain synthesis Cobalt Copper Zinc

• Vit B 12 and FA are req for the formation of thymidine triphosphate , one of the essential building blocks of DNA. • Failure of nuclear maturation and cell division. • Proerythrocytes fail to proliferate rapidly and produce larger than normal RBCs called macrocytes, shape is oval, large, irregular and fragile. • Hb content is normal , life span short.

- - MATURATION FAILURE DUE TO POOR ABSORPTION OF B 12 pernicious anemia, atrophic gastritis. Parietal cells of gastric glands produce IF IF+ B 12 IF binds to specific receptor sites on the brush border membrane of the mucosal cells in the ileum. Lack of IF causes faulty absorption of B 12. Sprue, vit B 12 and folic acid not absorbed.

Factors influencing erythropoiesis • Growth inducers (interleukin-3), growth and reprod of all types of comitted stem cells. • Differentiation inducers cause one type of comitted stem cell to differentiate. • Erythropoietin • Hypoxia →↑ Renal erythropoietic factor →↑ Erythropoietin →↑ Growth inducers & differentiation inducers →↑erythrogenesis. • Low Oxygen for a long time results in growth induction, differentiation and production of large no. of erythrocytes eg. cardiac failure, high altitude. • Testosterone, Cortisol.

Erythropoiesis – Normally 1 -15% of the RBCs die during maturation. – Erythroblasts normally spend 4 -7 days proliferating and maturing in the bone marrow. – The stages of maturation from the most immature to the most mature are:

Proerythroblast

Basophilic Erythroblast

Polychromatophilic Erythroblast

Orthochromic Erythroblast

Reticulocyte

Mature erythrocyte

Erythropoiesis

Erythropoiesis • Normal lifespan 100 -120 days • Old RBCs are removed by the spleen.

The RBC membrane • Semi-permeable lipid bilayer • Supported by a protein cytoskeleton (contains both integral and peripheral proteins). • Extensive damage cannot be repaired • The mature cells lack enzymes and cellular organelles necessary to synthesize new lipid or protein.

Cellular Energetics – RBCs generate energy almost exclusively from the anaerobic breakdown of glucose.

Polycythemia • An increase in RBC mass is called polycythemia and it may lead to an increase in blood viscosity. • Polycythemia – Relative polycythemia due to decreased plasma volume e. g. in dehydration. – Absolute polycythemia due to actual increase in RBC mass. • This may occur in disorders that prevent adequate tissue oxygenation

Polycythemia • Secondary polycythemia – Individuals living at high altitudes have increased RBC levels because of the decreased partial pressure of O 2 at high altitudes which leads to decreased O 2 saturation. • Polycythemia vera – Uncontrolled proliferation/production/cancer of RBC

Choose the best response, During the middle trimester of gestation, which is the main organ for production of RBCs a)Bone marrow b)Liver c)Lymph nodes