Red Blood Cell Production (Erythropoiesis) and Survival
Key Points:
To understand mechanisms of RBC production and factor affecting mean red cell life
span
Discuss origin and regulation of RBC production
Explain importance of iron, vitamin B12 and folate in RBC production
Outline deficiencies of haematinics (drug that increases Hb) and their effects
Discuss RBC survival and intrinsic factors affecting survival
Erythropoiesis
Erythropoiesis starts of in the bone marrow with a stem cell (haemocytoblast) and it
goes through a number of stages under the influence of cytokines.
Stem cell -> CFU-GEMM (colony forming unit – granulocyte, erythrocyte, monocyte,
megakaryocyte) under influence of IL-3 and GM-CSF (granulocyte macrophage colony
stimulating factor)
CFU-GEMM -> BFU-E (burst forming unit erythroid) under influence of IL-3 and GM-
CSF
BFU-E -> CFU-E (colony forming unit E) under influence of IL-3
The CFU-E then differentiates into the proerythroblast (which is the first recognisable
RBC), the sequence is shown below
Proerythroblast -> Basophil (early) erythroblast -> Polychromatophil (late)
erythroblast -> Orthochromatic erythroblast/normoblast (nucleus extruded)->
Reticulocyte (no nucleus) -> Erythrocyte
We start of with the stem cell, which becomes the proerthroblast. Then when we have
the early (basophilic) erythoblast we have “Phase 1” occurring in the cell which is
ribosome synthesis.
Then once it differentiates into the late (polychromatophil) erythroblast haemoglobin
starts to accumulate in the cell as it is synthesised.
In the normoblast stage the nucleus gets extruded and we get the reticulocyte which
has no nucleus (Hb is still being formed from left over mRNA). Eventually we get the
fully developed erythrocyte.
, The main hormone that regulates erythropoiesis is erythropoietin (EPO).
Erythropoietin is a glycosylated polypeptide hormone, 90% is produced by the kidneys
(and is only produced when needed, it is not stored).
Erythropoietin stimuluates the bone marrow to produce red blood cells and its major
stimulus for EPO production is reduced O2 blood tensions detected while the blood
passes through the kidney tissues.
The low blood O2 will stimulate EPO production from peritubular interstitial cells of
outer cortex and will then act on the late BFU-E, CFU-E and pronormoblast stages
which have receptors on the surface for EPO.
Hence anything that causes low levels of O2 in the blood e.g. high altitude, renal issues,
[Hb] issues will stimulate EPO secretion.
Components for RBC production include-
-Haemocytoblast
-Iron and globin
-Vitamin B12 and folic acid
-Along with EPO to stimulate
=1012 RBC/day
Haemoglobin Synthesis
65% of Hb is synthesised in the erythoblast and 35% at the reticulocyte stage!
The haem synthesis mainly occurs in the mitochondria while the globin synthesis
occurs on polyribosomes in the cytoplasm
The rates of haem and globin synthesis are carefully coordinated to ensure optimal
efficiency of Hb synthesis.
Key Points:
To understand mechanisms of RBC production and factor affecting mean red cell life
span
Discuss origin and regulation of RBC production
Explain importance of iron, vitamin B12 and folate in RBC production
Outline deficiencies of haematinics (drug that increases Hb) and their effects
Discuss RBC survival and intrinsic factors affecting survival
Erythropoiesis
Erythropoiesis starts of in the bone marrow with a stem cell (haemocytoblast) and it
goes through a number of stages under the influence of cytokines.
Stem cell -> CFU-GEMM (colony forming unit – granulocyte, erythrocyte, monocyte,
megakaryocyte) under influence of IL-3 and GM-CSF (granulocyte macrophage colony
stimulating factor)
CFU-GEMM -> BFU-E (burst forming unit erythroid) under influence of IL-3 and GM-
CSF
BFU-E -> CFU-E (colony forming unit E) under influence of IL-3
The CFU-E then differentiates into the proerythroblast (which is the first recognisable
RBC), the sequence is shown below
Proerythroblast -> Basophil (early) erythroblast -> Polychromatophil (late)
erythroblast -> Orthochromatic erythroblast/normoblast (nucleus extruded)->
Reticulocyte (no nucleus) -> Erythrocyte
We start of with the stem cell, which becomes the proerthroblast. Then when we have
the early (basophilic) erythoblast we have “Phase 1” occurring in the cell which is
ribosome synthesis.
Then once it differentiates into the late (polychromatophil) erythroblast haemoglobin
starts to accumulate in the cell as it is synthesised.
In the normoblast stage the nucleus gets extruded and we get the reticulocyte which
has no nucleus (Hb is still being formed from left over mRNA). Eventually we get the
fully developed erythrocyte.
, The main hormone that regulates erythropoiesis is erythropoietin (EPO).
Erythropoietin is a glycosylated polypeptide hormone, 90% is produced by the kidneys
(and is only produced when needed, it is not stored).
Erythropoietin stimuluates the bone marrow to produce red blood cells and its major
stimulus for EPO production is reduced O2 blood tensions detected while the blood
passes through the kidney tissues.
The low blood O2 will stimulate EPO production from peritubular interstitial cells of
outer cortex and will then act on the late BFU-E, CFU-E and pronormoblast stages
which have receptors on the surface for EPO.
Hence anything that causes low levels of O2 in the blood e.g. high altitude, renal issues,
[Hb] issues will stimulate EPO secretion.
Components for RBC production include-
-Haemocytoblast
-Iron and globin
-Vitamin B12 and folic acid
-Along with EPO to stimulate
=1012 RBC/day
Haemoglobin Synthesis
65% of Hb is synthesised in the erythoblast and 35% at the reticulocyte stage!
The haem synthesis mainly occurs in the mitochondria while the globin synthesis
occurs on polyribosomes in the cytoplasm
The rates of haem and globin synthesis are carefully coordinated to ensure optimal
efficiency of Hb synthesis.
