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Where ?
o Yolk sac early weeks of embryonic life o Middle trimester of gestation mainly liver, but also @ spleen and lymph nodes o ast month of gestation !or so" and after birth bone marrow o #ntil the age of five all bones produce $%&s o 'fter the age of twenty long bones cease $%& production

(our ma)or developments in the process of Erythropoiesis *

o $eduction in cell si+e o ,ncrease in cell number o -ynthesis of .aemoglobin o oss of nucleus and most of other organelles

Erythropoietin *
o /roduced by kidney in response to hypo0ia
o .ypo0ia o o o o 'ccumulation ,ncrease in Erythropoietin production .,( ! .ypo0ia1,nducible (actor " unable to be degraded

o E/2 stimulates only committed stem cells o

Erythroid progenitors *
o %(#1E *
o 3amed for their abilities to give rise to multiclustered colonies !erythroid bursts" of haemoglobin containing cells o &ells missing from proliferation are less differentiated than those of &(#1E thus re4uiring more time to mature o ess sensitive to E/2 than &(#1E o /resence of common surface antigens of early progenitors, as &567, &566 !properties more similar to those of pluripotent stem cells and progenitor cells committed to non1erythroid lineages"

o &(#1E *
o E0hibit properties more similar to erythroid precursor cells rather than to those of %(#1E o imited proliferative potential o E04uisitely sensitive to E/2 o %ereft of cell surface antigens of early progenitors, as &567, &566 o ack of self1renewal ability o /ositive influences from 8rowth factors 93(, 98(, interferon which e0press negative influences in %(#1E o E0presses Erythroid specific glycoprotein, glycophorin ', and $h antigens

Erythroid precursors *
o Erythroid maturation se4uences *
o /roliferation parameters ! id est rates of 53' and $3' synthesis" and cell si+e decreases o 'ccumulation of erythroid specific proteins heme and globin o 'daptation of characteristic morphology

%asophilic erythroblasts * production of huge numbers of ribosomes /olychromatic erythroblast * blue stain : pink stain !.b" 2rthochromatic erythroblast * o /ink stain of .b and e)ects most of its organelles o Enucleation inactive, dense nucleus moves to one side of the cell and is e0truded encased by a thin cytoplasmic layer e0pelled macrophage ingestion; $eticuloyte Erythrocyte * $eticulocytes minus remnants of ribosomes ! degraded by intracellular en+ymes "

'lterations in 4uantity and 4uality of membrane proteins *

o <imentin, one of the membrane glycoproteins, is lost at the late erythroblasts stages facillitates enucleation o /revention of cytoskeletal assembly at these early stages may secure more membrane fluidity and cell motility needed during proliferative phase of differentiation

E/2 receptors peaks at the &(#1 E=proerythroblast level and progressively declines when cells mature further, undetectable @ reticulocytes Erythroid progenitors are distinguished from other marrow progenitors by the presence of high levels of transferrin receptors
o /eak level * &(#1E and erythroid precursors, lower level on reticulocytes o 'fter reticulocyte stage, receptors are shed as small lipid vesicles

<itamin %>? and folic acid * re4uired for the formation of thymidine phosphate essential building blocks of 53' acking of <itamin %>? and folic acid results in maturation failure

-ources *
o .ematology * %asic /rinciples and /ractice @th Ed .offman o 9e0tbook of Medical /hysiology >>th Ed 8uyon and .all o .uman 'natomy and /hysiology Ath Ed Marieb and .oehn o 'natomy and /hysiology* #nity of (orm and (unction @th Ed 1 -aladin