Erythropoiesis Flashcards
describe the stages of erythropoiesis and how is it regulated
Erythropoiesis is the process of formation of Red Blood Cells from primitive stem cells.
Sites
In Fetus: Yolk sac (up to 3months), liver and spleen(3-6 months)and bone
marrow (after 6 months)
Adults: Flat bones like sternum, ribs, vertebrae, pelvic bones etc
Stages:
1.Pleuripotent hemopoietic stem cell is most primitive cell in the bone marrow and is capable of forming all types of blood cells. It is large (18-30 microns) cell with large nucleus and thin rim of deep blue cytoplasm.
2.Committed Stem Cell of myeloid series: is formed by differentiation of pleuripotent cell and is capable, of forming RBC s, granulocytes, monocytes and megakaryocyte. Has same appearance as pleuripotent cell. A committed stem cell that produces erythrocytes is called a colony forming unit erythrocytes (CFU-E)
3. Progenitor cells: Can form only RBCs
a) burst forming unit Erythrocyte (BFU-E) cell: So called because it forms bursts
of RBCs in tissue culture. It gives rise to a large number of CFU-E cells.
b)Colony forming Unit Erythrocyte (CFU-E) cell: Forms colonies of RBCs in tissue culture. These progenitor cells differentiate to form Pronormoblasts.
4. Pronormoblast (Proerythroblast): First morphologically recognizable cell belonging to RBC series. It is a
large (15-20 microns)cell with scanty deep blue cytoplasm. Nucleus shows prominent nucleoli and chromatin
reticulum.
5.Early normoblast (Basophil erythroblast) : Formed by multiplication of pronormoblast. It is a similiar cell but the nucleoli disappear and cytoplasm becomes lighter.
6.Intermediate normoblast (Polychromatic erythroblast (Polychromatophil erythroblast) :10-15 microns in diameter. There is condensation of nuclear chromatin. Hemoglobin (acidophilic) appears in cytoplasm (eosinophilic) which becomes polychromatophilic.
7.Late normoblast(Orthochromatic erythroblast): Smaller (7-12 microns)in size. Nucleus becomes smaller and
deeply stained i.e. pyknotic nucleus. Later the nucleus disappear(Karyorrhexis). Hemoglobin content increases and cytoplasm becomes eosinophilic. The cell looses capacity to divide.
8. Reticulocyte : no nucleus. Supravital staining shown network like appearance due to remains of basophilic cytoplasm and organelles, some reticulocytes escape into circulation(1% RBCs)
9. Mature RBC:7.5 microns in diameter, fully hemoglobinised reticulum disappears. Enters circulation.
Regulation
Erythropoiesis is precisely regulated in accordance with the oxygen needs of the tissue.
Various condition like blood loss, cardiac failure, pulmonary diseases, high altitude and anemia reduce oxygen delivery to tissues and thus produce hypoxia.
In such conditions, kidney and liver cells secrete a substance called Renal erythropoeitic Factor which acts on
a plasma protein called Erythropoietinogen to form a glycoprotein hormone called Erythropoietin. Erythropoietin then stimulates erythropoiesis by-
1. Promotes conversion of pleuripotent cells into committed stem cells of myeloid series.
2. Conversion of CFU-E cells into pronormoblasts.
3. Accelerates maturation process.
4. Stimulates haemoglobin synthesis.
In addition, burst promoting activity (BPA) produced by monocytes and lymphocytes also stimulates
Erythropoiesis.
in absence of erythropoietin hypoxia has little to no effect to stimulate rbc production.
erythropoietin
- 90% in kidneys
- rest in liver
- renal tissue hypoxia
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inc in hypoxia inducible factor 1 (HIF-1)
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induce erythropoietin genes - other factors also affect erythropoietin production - norepinephrine epinephrine and several of the prostaglandins
factors affecting erythropoiesis.
Erythropoiesis is the process of formation of RBCs from primitive stem cells.
Various factors essential for erythropoiesis are
- Erythropoietin :
Erythropoietin not only stimulates erythropoiesis in hypoxia but its
normal circulating levels are essential for normal erythropoiesis. Chronic
renal diseases are associated with anemia due to failure of production of
normal amount of erythropoietin.
Formation: In conditions of hypoxia cells of kidneys and liver produce
renal erythropoietic factor which acts on plasma Erythropoietinogen to
form erythropoietin.
Actions: Stimulates maturation of CFU-E cells into pronormoblasts and
hastens synthesis of hemoglobin - Dietary Protein and Energy
- Vitamin B12 (Cynocobalamin): It is essential for synthesis of DNA in
erythropoiesis. It helps in conversion of deoxyuridilate to deoxythymidilate and also acts as donor of methyl group in cellular reactions.
Source: Meat, milk, liver.
Daily requirements: 1-3 micrograms.
For the absorption of B12 (extrinsic factor), an intrinsic factor is produced by parietal cells in gastric mucosa is essential.
In B12 deficiency due to defective DNA synthesis, there is failure of multiplication as well as maturation of cells leading to formation of large abnormal cells called megaloblasts which produce macrocytes. normal oxygen carrying capacity but their fragility causes them to have a short life - Folic acid: Along with Vit B12 (folic acid) is essential for synthesis of DNA. Therefore deficiencies of folic acid
also causes maturation failure anemia.
Source- Vegetables, fruits, meat.
Daily requirement-50 micrograms. - Iron :It is essential for synthesis of haem part of hemoglobin. Iron in ferrous state combines with protoporphyrin IX to form haem. Oxygen is transported, attached to one of the covalent bonds of ferrous atom in the hemoglobin molecule.
Source: meat, peas, leafy vegetables, jaggery.
Daily requirement:Males-1mg; Females-2mg
Absorption of iron is facilitated by a protein called Apotransferrin present in the bile. Deficiency of iron (absolute or relative)causes defective hemoglobin synthesis and leads to microcytic
hypochromic anemia. - Vit B6 (pyridoxine) and Vit C (ascorbic acid): These are essential for erythropoiesis because of their role in cellular enzymatic reactions and Vit C keeps the iron in ferrous form.
- Copper, Cobalt and manganese : these are essential because they act as components of various co-enzymes in cellular reactions(catalysts).
- Hormones like thyroxine and cortisol have stimulating effect on erythropoiesis either because of their protein anabolic effect or by stimulating production of erythropoietin. Myxoedema is associated with anaemia.
- Bile Salts: Essential for absorption of metals.
- Riboflavin
- Niacin
- Vitamin A
- Vitamin E
Maturation Failure
- deficiency of either vit b12 or folic acid causes maturation Failure in the process of erythropoiesis
- due to their deficiency, erythroblastic cells will fail to proliferate rapidly and will produce mainly larger than normal red cells called macrocytes
- these cells will have normal o2 carrying capacity but have short life span, 1/2 of the normal
Maturation Failure Anemia - Pernicious Anemia
Maturation Failure due to poor absorption of vit b12
- will cause pernicious anemia
- role od intrinsic factor in absorption of b12
a) binds tightly with b12
b) protects b12 from different secretions
c) intrinsic factor binds with specific receptor sites on brush border membranes of mucosal cells in ileum
d) vit b12 is taken by pinocytosis carrying intrinsic factor together - each day body needs only 1-3 mg of b12 and liver and other tissues have 1000 times stored.
- therefore 3-4mg defective vit b12 absorption are usually required to cause maturation failure anemia.
