Erythropoiesis

• Erythropoiesis is red blood cell

(erythrocyte) production.
• Erythropoiesis is one type of
hematopoiesis.
• Hematopoiesis is the body’s process of
making all three types of blood cells: red
blood cells (erythropoiesis), white blood
cells (leukopoiesis) and platelets
(thrombopoiesis).
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• On average, the body produces about 2.5
billion red cells/kg/day.
• Erythrocytes arise from a complex line of
cells, and their rate of production is tightly
regulated to ensure adequate but not
excessive numbers of red blood cells are
produced.

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• Problems with erythropoiesis result in
anemia, a condition that involves not
having enough red blood cells.
• Erythropoiesis starts before birth.
• After birth it takes place in the bone
marrow.

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• In children, erythropoiesis can occur in the
bone marrow of most bones.
• Bone marrow is the spongy tissue
inside/center of your bones
• There are 2 types of bone marrow
– Red Marrow – Contains blood stem cells that
can differentiate into RBC, WBC or Platelets
– Yellow Marrow – Made of Fat
• However, in adults, it only occurs in the
bone marrow of the vertebrae, cranium,
ribs, sternum, pelvis and epiphysis of long
bones.

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 Fetal erythropoiesis
• The location of erythropoiesis changes as a
fetus develops during pregnancy.
– Week three: Erythropoiesis begins in the yolk
sac. The yolk sac is the structure that nourishes
the developing embryo.
– Months two and three: Erythropoiesis occurs in
a fetus’s liver and spleen.
– Month five: Erythropoiesis occurs in the
fetus’s bone marrow.
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 Erythropoiesis
• Occurs in the red bone marrow
• Active marrow in adult is found in the flat
bones of:
– Pelvis-34 %
– Vertebrae-28%
– Cranium and mandible-13%
– Sternum and ribs-10%
– Epiphysis of long bones-4-8%
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 Site of Hematopoiesis
After birth During fetal life
Active (red) BM: 1) Yolk sac:
2) Liver & Spleen:
In infancy & childhood 3) Bone marrow (BM):

In adult
 Medullary and extra-medullary
erythropoiesis
• “Medullary” refers to the bone marrow.
• Medullary erythropoiesis happens in the
bone marrow, while extra-medullary
erythropoiesis happens outside your bone
marrow.

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• Extramedullary erythropoiesis is normal
during fetal development.
• During adulthood, extramedullary
erythropoiesis is often a sign of a disease
or conditions affecting the bone marrow.
• Certain diseases cause erythropoiesis to
occur outside the bone marrow, within the
spleen or liver.
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 Stages of erythropoiesis
• For erythropoiesis, an originator cell called
the haemocytoblast a pluripotent
hematopoietic stem cell (HSC) matures
into a fully mature red blood cell, or
erythrocyte.
• The cell advances through a series of
differentiation stages for fully maturation
to occur.
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Lineage Cells of Hematopoiesis- HSCs
Hematopoietic
Stem Cells
o Each type of blood cell (HSC)

(red blood cells, white

blood cells and
platelets) begins as an
hematopoietic stem
cell
(HSC)/haemocytoblast
o Hemopoietic Stem
Cells are divided into:

1. Myeloid stem cells or

2. Lymphoid stem cells

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 • For a red blood cell to eventually form,
an HSC becomes a multipotent stem cell
or common myeloid progenitor (CMP)
cell.
• A CMP may mature into a red blood cell,
platelet or some types of white blood
cells.

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 Erythropoiesis

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• A common myeloid progenitor (CMP) cell
that eventually becomes a red blood cell
develops into a unipotent stem cell called
megakaryocyte-erythroid progenitor cell
(MEP).
• Once it’s developed into a MEP, the cell is
now on track to become a red blood cell.

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• It progresses through the following stages as it
develops:
– Pronormoblast/Proerythroblast.
– A basophilic or early normoblast/Erythroblast.
– A polychromatophilic or intermediate
normoblast
– An orthochromatic or late normoblast (Nucleus
is expelled)
– Reticulocyte (Cells contain RNA and are also
called "immature red blood cells")
– Erythrocyte (fully mature red blood cell).
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 Stages of Erythropoiesis

 Pronormoblast/Proerythroblast

 Basophilic Erythroblast

 Intermidiate normoblast

 Late normoblast

 Reticulocyte

 Erythrocyte 17
• The cell is released from the bone marrow
after the late normoblast stage and so in
newly circulating red blood cells there are
about 1% reticulocytes.
• After one to two days, these ultimately
become "erythrocytes" or mature red blood
cells.

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• The RBC’s carry oxygen from the lungs to
the tissue.
• They also move carbon dioxide from the
tissues to the lungs (to be exhaled).
• Essential for the maturation of red blood
cells are iron, Vitamin B12 (cobalamin) and
Vitamin B9 (folate).
• Lack of either causes maturation failure in
the process of erythropoiesis
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 Erythropoiesis

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 Erythropoiesis

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• During the maturation process, the overall
size of the erythroid precursor cell
decreases
• The nucleus is initially large in size and
contains open chromatin.
• As red blood cells mature, the size of the
nucleus decreases, until it finally disappears
with the condensation of the chromatin
material.
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• It takes 1 week for a red blood cell to fully
mature.
• Red blood cells live for approximately 120
days.
• The body’s sensitivity to oxygen levels
regulates erythropoiesis.
• If the tissues don’t have enough oxygen
(hypoxia), the body ramps up red blood cell
production.
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• More red blood cells mean there’s more
oxygen flowing to the tissues and cells.
• A hormone called erythropoietin (EPO)
triggers erythropoiesis.
• Hormones are chemical messengers that
coordinate essential body functions.
• The kidneys and liver secret's EPO.

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 Regulation of erythropoiesis
• A negative feedback loop involving
erythropoietin helps regulate the process of
erythropoiesis so that, in non-disease states,
the production of red blood cells is equal to
the destruction of red blood cells
• and the red blood cell number is sufficient
to sustain adequate tissue oxygen levels but
not high as to cause thrombosis, or stroke.
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• Erythropoietin is bound to circulating red
blood cells protein
• Low circulating numbers lead to a
relatively high level of unbound
erythropoietin, which stimulates RBC
production in the bone marrow.

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 EPO Release Process
• The process can be summarized as follows:
1. The tissues lack oxygen because the red
blood cells are low.
2. There is a reduced partial pressure of
oxygen (pO2) in the kidney, which is
detected by the renal interstitial
peritubular cells.

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 3. The kidneys secrete more EPO in
response.
4. EPO stimulates the bone marrow to
make more red blood cells- This hormone
stimulates proliferation and differentiation
of red cell precursors

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 4. The kidneys detect an increase in
hemoglobin, a key protein in red blood
cells, and increased pO2 thus secrete less
EPO in response
5. The body achieves a balance
(homeostasis) with the right amount of red
blood cells.

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• The kidneys constantly secrete low levels
of EPO to keep red blood cell production
in check.
• Every day, about 1% of the red blood
cells are lost.
• Erythropoiesis replaces the red blood cells
that have reached the end of their lifespan.
• However, the kidneys may secrete more or
less EPO in response to conditions or
injuries affecting the red blood cell levels.

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 Types of erythropoiesis

1. Microcytic erythropoiesis
• This is where cells are produced being
smaller in size. It happens because of disease
conditions e.g. iron deficiency anaemia,
thalassaemia etc.

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 2. Macrocytic erythropoiesis
• Cells are produced being larger in size

due to abnormal conditions e.g. vitamin B 12 /

Folic acid deficiency. Also in haemolytic
anaemia.
3. Normocytic / normoblastic erythropoiesis.
• It gives rise to normal red blood cells.
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 Conditions impacting
erythropoiesis
• Many conditions can affect the body’s
ability to make and regulate red blood cells.
Lung diseases
• Asthma.
• Chronic obstructive pulmonary disease
(COPD).
• Bronchitis
• Etc.
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Chronic Kidney Disease
• Chronic kidney disease often causes
anemia.
• In the damaged kidney, there is a reduced
basal level EPO production and a reduced
response to hypoxia leading to anemia.
• To counteract this, patients can be given
EPO injections
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Cancers affecting the blood or bone marrow
– Leukemia.
– Lymphoma.
– Myeloma.
– Myeloproliferative disorders
Other factors
– Nutritional deficiencies (Iron, Vit B12, folate)
– High altitudes (The body secretes more EPO in
response to the decreased oxygen at high
altitudes)
– Increased physical activity
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 Drug Doping
• Exogenous EPO can be used as a
performance-enhancing drug among
athletes.
• By stimulating increased red blood cell
production, it increases the amount of
haemoglobin available for oxygen-binding,
thus improving the oxygen supply to
muscles.
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 Thank you

March 2, 2024