The document summarizes key aspects of haematopoiesis and erythropoiesis. It discusses how blood cells are formed from stem cells in the bone marrow, and the development and maturation of red blood cells. It also describes the structure and function of hemoglobin in transporting oxygen, factors regulating erythropoiesis including erythropoietin, and the lifespan and breakdown of red blood cells.

1. H A E M O P O I E S I S , R B C ’ S ,
E R Y T H R O P O I E S I S , L I F E S P A N ,
O X Y G E N T R A N S P O R T

2. DEVELOPMENT OF BLOOD CELLS- HAEMOPOIESIS

3. FORMATION OF BLOOD CELLS
RBC+ WBC+ platelets;
produced in BONE
MARROW
Blood cells originate
from single type
unspecialised cell-
STEM CELL
Stem cell divide to
form IMMATURE
RBC/WBC/platelets
Immature cells then
divide to form
MATURE CELLS
Stem Cell divide to
form- MYELOID and
LYMPHOID stem cells
Myeloid cells divide;
produce RBC,
PLATELETS, E, B, N, M
Lymphoid cells
differentiate into B &
T LYMPHOCYTES
B lymphocytes
develops in BONE
MARROW and migrate
to LYMPH NODES,
SPLEEN
T lymphocytes
develops in THYMUS
and migrate to other
lymph tissues
Where
E- Eosinophils
B- Basophils
N- Neutrophils
M- Monocytes

4. RED BLOOD CELLS/ERYTHROCYTES
• Most abundant blood cells.
• Shape- Biconcave discs and contain oxygen‐carrying protein called haemoglobin.
• Biconcave shape- Maintained by a network of proteins called SPECTRIN.
• Spectrin function- The network of protein allows the red blood cells to change shape as they
are transported through the blood vessel.
• The plasma membrane of a red blood cell is strong and flexible.
• There are approximately 4 million to 5.5 million red blood cells in each cubic millimetre of
blood.
• They are a pale buff colour that appears lighter in the centre.
• Young red blood cells contain a nucleus; however, the nucleus is absent in a mature red blood
cell and without any organelles such as mitochondria, thus increasing the oxygen‐carrying
capacity of the red blood cell.
• As red blood cells lack mitochondria to produce energy (adenosine triphosphate), they utilise
anaerobic respiration to produce energy and do not use any of the oxygen they are
transporting.
• Main function of haemoglobin- Transport oxygen and carbon dioxide, maintaining blood
pressure and blood flow.

5. HAEMOGLOBIN
• Haemoglobin is composed of a protein called globin bound to the
iron‐containing pigments called haem.
• Each globin molecule has four polypeptide chains consisting of two
alpha and two beta chains.
• Each haemoglobin molecule has four atoms of iron, and each atom of
iron transports one molecule of oxygen; therefore, one molecule of
haemoglobin transports four molecules of oxygen.
• There are approximately 250 million haemoglobin molecules in one red
blood cell; therefore, one red blood cell transports 1 billion molecules of
oxygen.
• At the capillary end, the haemoglobin releases the oxygen molecule into
the interstitial fluid, which is then transported into the cells.

7. ERYTHROCYTES – NORMAL VALUES
Measure Normal values
Erythrocyte count – number of erythrocytes per
litre, or cubic millilitre, (mm3) of blood
Male: 4.5 × 10 12/l to 6.5 × 10 12/l (4.5–6.5
million/mm3)
Female: 3.8 × 10 12/l to 5.8 ×10 12/l (3.8–5.8
million/mm3)
Packed cell volume (PCV, haematocrit) – the
volume of red cells in 1 l or mm3 of blood
0.40–0.55 l/l
Mean cell volume (MCV) – the volume of an
average cell, measured in femtolitres (1 fl = 10−15
litre)
80–96 fl
Haemoglobin – the weight of haemoglobin in whole
blood, measured in grams/100 ml blood
Male: 13–18 g/100 ml
Female: 11.5–16.5 g/100 ml
Mean cell haemoglobin (MCH) – the average
amount of haemoglobin per cell, measured in
picograms (1 pg = 10−12 gram)
27–32 pg/cell
Mean cell haemoglobin concentration (MCHC) –
the weight of haemoglobin in 100 ml of red cells
30–35 g/100 ml of red cells

8. SITES OF ERYTHROPOIESIS
• Early foetus- Yolk sac
• 2 – 5 months’ gestation- Liver and spleen
• About 5 months’ gestation- Bone marrow
• Children- Bone marrow of most bones
• Adults- Bone marrow of the vertebrae, ribs, sternum, sacrum, pelvis,
and proximal femur.
• When erythropoiesis is inadequate in the bone marrow, this can
trigger extramedullary haematopoiesis – i.e., haematopoiesis occurring
outside the marrow.
• This is commonly seen in hemoglobinopathies such as thalassemia and
myelofibrosis (type of bone marrow cancer).

9. STAGES OF ERYTHROPOIESIS
Haemocytoblast (multipotent
haematopoietic stem cell)
Differentiate into common
myeloid progenitor cells
(CMPC)
1st CMPC
become normoblasts
(erythroblasts)- present in
Bone Marrow
2nd mature into reticulocytes
(immature RBCs)- lose their
nucleus and released into the
peripheral circulation
3rd mature into erythrocytes
(fully mature RBCs)- lose
their remaining organelles

10. FACTORS AFFECTING ERYTHROPOIESIS
• Erythropoietin and Iron- Iron is a crucial mineral required for haemoglobin
production. Lack of erythropoietin (seen most commonly in renal failure) can result
in reticulocytopenia and anaemia.
• Maturation factors such as B12 and folate are key components of DNA synthesis.
Deficiency of either results in megaloblastic anaemia.
• Vitamin B12 is also called the extrinsic factor. Parietal cells of the stomach lining
produce the intrinsic factor, a chemical that combines with the vitamin B12 in food
to prevent its digestion and promote its absorption in the small intestine.
• A deficiency of either vitamin B12 or the intrinsic factor results in pernicious
anaemia.
• Androgens and thyroxine also exert a stimulatory effect on erythropoiesis.
• Copper and pyridoxine are key components of iron incorporation into haem;
deficiency of either can result in sideroblastic anaemia.

11. CONTD….
• Protein and iron are necessary to synthesize haemoglobin and become
part of it.
• Copper is part of some enzymes involved in haemoglobin synthesis.
• Vitamins folic acid and B12 are required for DNA synthesis in the stem
cells of the red bone marrow.
• A chemical from the Parietal cells of the stomach lining (Intrinsic factor)
combines with the vitamin B12 (Extrinsic factor) in food to prevent its
digestion and promote its absorption in the small intestine.

12. LIFE SPAN
• Red blood cells live for approximately 120 days.
• As they reach this age, they become fragile and are removed from circulation by
cells of the tissue macrophage system (formerly called the reticuloendothelial or RE
system).
• The organs that contain macrophages (literally, “big eaters”) are the liver, spleen,
and red bone marrow.
• The old RBCs are phagocytized and digested by macrophages, and the iron they
contained is put into the blood to be returned to the red bone marrow to be used for
the synthesis of new haemoglobin.
• If not needed immediately for this purpose, excess iron is stored in the liver.
• The iron of RBCs is recycled over and over again.
• The globin or protein portion of the haemoglobin molecule is also recycled. It is
digested to its amino acids, which may then be used to synthesize new proteins.
• Another part of the haemoglobin molecule is the heme portion, which cannot be
recycled and is a waste product.

13. CONTD….
• The heme is converted to bilirubin by macrophages.
• The liver removes bilirubin from circulation and excretes it into bile; bilirubin is a
bile pigment.
• Bile is secreted by the liver into the duodenum and passes through the small
intestine and colon, so bilirubin is eliminated in faeces and gives faeces their
characteristic brown color.
• In the colon some bilirubin is changed to urobilinogen by the colon bacteria.
• Some urobilinogen may be absorbed into the blood, but it is changed to urobilin
and excreted by the kidneys in urine.
• If bilirubin is not excreted properly, perhaps because of liver disease such as
hepatitis, it remains in the blood.
• This may cause jaundice, a condition in which the whites of the eyes appear
yellow.

14. Life cycle of red blood cells

15. OXYGEN TRANSPORT THROUGH RBCs
• Oxygen is one of the substances transported with the assistance of red blood cells.
• The red blood cells contain a pigment called haemoglobin, each molecule of which binds four
oxygen molecules to form Oxyhaemoglobin.
• The oxygen molecules are carried to individual cells in the body tissue where they are
released.
• The binding of oxygen is a reversible reaction.
• Hb + 4O2 ⇌ Hb.4O2
• At high oxygen concentrations oxyhaemoglobin forms, but at low oxygen concentrations
oxyhaemoglobin dissociates to haemoglobin and oxygen.
• The balance can be shown by an oxygen dissociation curve for oxyhaemoglobin.
• The curve shows that:
• • at relatively low oxygen concentrations, there is uncombined haemoglobin in the blood and
little or no oxyhaemoglobin, e.g. in body tissue.
• • at relatively high oxygen concentrations, there is little or no uncombined haemoglobin in the
blood; it is in the form of oxyhaemoglobin, e.g. in the lungs.

16. CONTD….
Note- Oxygen dissociation curves can be used to illustrate Le Chatelier's Principle which states
that a system in dynamic equilibrium responds to any stress by restoring the equilibrium.
 For example shifts in the position of the curve occur as a result of the concentration of CO2
or changes in pH.

17. THE EFFECT OF CARBON DIOXIDE IN THE BLOOD
• Haemoglobin can also bind carbon dioxide, but to a lesser extent to form
Carbaminohaemoglobin.
• Some carbon dioxide is carried in this form to the lungs from respiring tissues.
• The presence of carbon dioxide helps the release of oxygen from haemoglobin. This is
known as the Bohr effect.
• This can be seen by comparing the oxygen dissociation curves when there is less carbon
dioxide present and when there is more carbon dioxide in the blood.
An increase in oxygen affinity
results in the curve shifting to
the left, whereas a decrease in
oxygen affinity results in the curve
shifting to the right.

18. CONTD….
• When carbon dioxide diffuses into the blood plasma and then into the red blood
cells (erythrocytes) in the presence of the catalyst carbonic anhydrase, most CO2
reacts with water in the erythrocytes, and the following dynamic equilibrium is
established
• H2O + CO2 ⇌ H2CO3
• Carbonic acid, H2CO3, dissociates to form hydrogen ions and hydrogencarbonate
ions. This is also a reversible reaction and undissociated carbonic acid, hydrogen
ions and hydrogencarbonate ions exist in dynamic equilibrium with one another
• H2CO3 ⇌ H+ + HCO3
-
• Inside the erythrocytes negatively charged HCO3- ions diffuse from the cytoplasm
to the plasma. This is balanced by diffusion of chloride ions, Cl-, in the opposite
direction, maintaining the balance of negative and positive ions either side. This is
called the 'chloride shift'.
• The dissociation of carbonic acid increases the acidity of the blood (decreases its
pH).

19. CONTD…..
• Hydrogen ions, H+, then react with oxyhaemoglobin to release bound
oxygen and reduce the blood's acidity.
• This buffering action allows large quantities of carbonic acid to be carried in
the blood without major changes in blood pH.
• Hb.4O2 + H+ ⇌ HHb+ + 4O2

20. CONTD….
• It is this reversible reaction that accounts for the Bohr effect. Carbon
dioxide is a waste product of respiration and its concentration is high in the
respiring cell and so it is here that haemoglobin releases oxygen.
• Now the haemoglobin is strongly attracted to carbon dioxide molecules.
• Carbon dioxide is removed to reduce its concentration in the cell and is
transported to the lungs were its concentration is lower.
• This process is continuous since the oxygen concentration is always higher
than the carbon dioxide concentration in the lungs.
• The opposite is true in respiring cells.

21. FACTORS AFFECTING OXYGEN AFFINITY
1. pH/pCO2 – When H+/pCO2 increases and pH decreases, Hb affinity for oxygen
decreases. This is known as the Bohr effect. Inversely, when H+/pCO2 decreases and pH
increases, the affinity of haemoglobin for oxygen increases.
2. 2,3-diphosphoglycerate (2,3-DPG) – 2,3-DPG, sometimes referred to as 2,3-BPG, is a
chemical found in red blood cells from the glucose metabolic pathway.
• 2,3-DPG binds to the beta chains of haemoglobin, so increased 2,3-DPG levels result in it
binding to haemoglobin, decreasing the affinity of haemoglobin for oxygen.
• Conversely, when there are decreased 2,3-DPG levels, e.g in states of decreased tissue
metabolism, there are fewer 2,3-DPG molecules binding to haemoglobin. This means there
are more opportunities for it to bind and therefore, it has a higher affinity for oxygen.
3. Temperature – At increased temperatures, for example in active muscles, there is an
increase in heat production which decreases the affinity of haemoglobin for oxygen. At
decreased temperatures, e.g. in states of decreased tissue metabolism, there is
decreased heat production and the affinity of haemoglobin for oxygen increases.

22. CONTD….
4. Erythropoietin (EPO) - It is a glycoprotein hormone, naturally produced by the
peritubular cells of the kidney, that stimulates red blood cell production. Renal cortex
peritubular cells produce most EPO in the human body. PO2 directly regulates EPO
production. The lower the pO2, the greater the production of EPO.

23. CONTROL OF ERYTHROPOIESIS: THE ROLE OF
ERYTHROPOIETIN
Tissue hypoxia
Kidney secrete
erythropoietin into the blood
Bone marrow increases
erythropoiesis
RBCs number rise
Increased blood-oxygen
carrying capacity; reverses
tissue hypoxia
-