Hoffbrand, A.V., Moss, P.A.H. and Pettit, J.E., 2006. Essential Haematology. 5th edition.

UK: Blackwell Publishing Ltd.

1. Erythropoiesis Regulated by erythropoietin. Erythropoietin gene has hypoxia-response element at 3 end. Heavily glycosylated PP. Normally, 90% produced in peritubular interstitial cells of kidney and 10% in liver + elsewhere. No preformed stores and stimulus to erythropoietin production is oxygen tension in tissues of kidney. Therefore, EPO production increases in anaemia, when Hb for some metabolic/structural reason cant give up O2 normally, when atmospheric O2 is low/when defective cardiac/pulmonary function/damage to renal circulation affects O2 delivery to kidney. EPO stimulates erythropoiesis by increasing number of progenitor cells committed to erythropoiesis. Transcription factors GATA-1 and FOG-1 activated by EPO receptor stimulation and are important in enhancing expression of erythroidspecific genes and also enhancing expression of anti-apoptotic genes and of transferrin receptor. Late precursors which have EPO receptors are stimulated to proliferate, differentiate and produce Hb. % erythroid cells in marrow increases and, in chronic state, theres anatomical expansion of erythropoiesis into fatty marrow and sometimes into extramedullary sites.

Conversely, increased O2 supply to tissues (greater O2 unloading efficiency/increased RBC mass) reduces drive for erythropoiesis. Tissue hypoxia also stimulates new blood vessel formation by vascular endothelial growth factor (VEGF).

2. Granulopoiesis Formed in the bone marrow from a common precursor (myeloblast).

3. Haemoglobin synthesis Red cells main job is to carry oxygen to tissues and return waste carbon dioxide to the lungs. Hb achieves these purposes. 640 mn Hb molecules/RBC.