RT Book, Section
A1 Prchal, Josef T.
A1 Thiagarajan, Perumal
A2 Kaushansky, Kenneth
A2 Lichtman, Marshall A.
A2 Prchal, Josef T.
A2 Levi, Marcel M.
A2 Press, Oliver W.
A2 Burns, Linda J.
A2 Caligiuri, Michael
SR Print(0)
ID 1121091421
T1 Erythropoiesis
T2 Williams Hematology, 9e
YR 2015
FD 2015
PB McGraw-Hill Education
PP New York, NY
SN 9780071833004
LK accessmedicine.mhmedical.com/content.aspx?aid=1121091421
RD 2024/04/19
AB SUMMARYProduction  of  red  cells  or  erythropoiesis,  is  a  tightly  regulated  process  by  which  hematopoietic  stem  cells  differentiate  into  erythroid  progenitors  and  then  mature  into  red  cells.  Erythropoiesis  generates  approximately  2  ×  1011  new  erythrocytes  to  replace  the  2  ×  1011  red  cells  (approximately  1  percent  of  the  total  red  cell  mass)  removed  from  the  circulation  each  day.  Red  cell  production  increases  several  fold  after  blood  loss  or  hemolysis.  When  one  of  the  progeny  of  the  multipotential  hematopoietic  stem  becomes  committed  to  the  erythroid  lineage,  this  early  erythroid  progenitor  undergoes  a  series  of  divisions  and  concurrent  maturation  that  eventually  result  in  morphologically  recognizable  erythroblasts.  After  expulsion  of  the  nucleus,  a  macrocyte  (polychromatophilic  when  stained  by  Wright  stain,  or  a  reticulocyte  if  stained  with  new  methylene  blue)  leaves  the  marrow.  During  the  first  24  hours  in  the  circulation,  reticulocytes  lose  their  residual  organelles  (mitochondria  and  ribosomes)  through  an  autophagic  process  and  undergoes  reconditioning  of  the  membrane  to  become  mature  red  blood  cells  with  a  morphology  of  a  biconcave  disc.  Erythropoiesis  is  controlled  by  transcription  factors  and  cytokines,  the  principal  ones  being  GATA  1  and  erythropoietin  (EPO),  which  influence  the  rate  of  lineage  commitment,  proliferation,  apoptosis,  differentiation,  and  number  of  divisions  from  the  earliest  progenitor  to  late  erythroblasts.  The  number  of  red  cells  produced  varies  in  response  to  tissue  oxygenation  that  determines  the  level  of  the  transcription  factors,  hypoxia-inducible  factors  (HIF),  HIF-1  and  HIF-2,  the  principal  regulators  of  the  response  to  hypoxia.  HIFs  modulate  erythropoiesis  by  regulation  of  EPO  production,  by  direct  EPO-independent  mechanism(s)  and  facilitating  iron  availability.