2. To achieve these functions the red cell
has several unique properties….
Function
The primary function of the erythrocyte is the
carriage of oxygen from the lungs to the
tissues and CO2 from the tissues to the lungs.
The red cell also plays an important role in pH
buffering of the blood.
Lifespan: Because the fully developed
red blood cell has no nucleus the cell
cannot divide or repair itself. The lifespan
is therefore relatively short (120 days).
Image: scanning electron microscope of red
blood cell
Haemoglobin content: unique to the red
cell, it is this metaloprotein molecule
which is pivotal in red cell development
and Oxygen transport due to its affinity
for O2.
Biconcave shape: increases surface
area available for gaseous exchange.
Flexibility: the red cell is
7.8 m across and 1.7
m thick and yet it is
able to fit through
capillaries of only 5 m
diameter. This is in-part
due to the flexible
membrane and
shedding of the
nucleus.
Strength: it has a strong
but flexible membrane
able to withstand the
recurrent shear forces
involved in the
circulation of blood.
3. Erythropoiesis
An erythrocyte is a fully developed, mature red blood cell. The adult human makes
approximately 1012 new erythrocytes every day by the process of erythropoiesis. This is a
complex process that occurs within the bone marrow. Before an erythrocyte arrives fully
functioning into the blood stream it must develop from a stem cell through an important
number of stages..
3. EPO continues to
stimulate primitive
erythroid cells (red
blood cells) in the
bone marrow and
induce maturation.
2. EPO stimulates stem
cells within the bone
marrow which
differentiate into
erythroid precursors.
START HERE
1: Erythropoietin (EPO), a growth
factor, is synthesized primarily
(90%) from peritubular cells of the
kidneys (renal cortex).
Macrophages surround and supply
iron to these erythroprogenitor cells
that become erythroblastic islands.
Stem
cells
Bone marrow
Erythroid
precursors
As with much human
physiology, this system
works via a feedback
mechanism.
Red blood cells in
circulation
erythropoietin
Kidney
FINISH HERE
4. There is no store of EPO. The production of erythropoietin is
triggered by tissue hypoxia (oxygen tension sensed within the
tubules of the kidney) and stops when oxygen levels are normal.
4. Hypoxia is the major stimulant for increased EPO
production
Chronic renal disease / bilateral nephrectomy will reduce or stop the production of EPO.
It’s absence or reduction causes anaemia through reduced red cell production. Anaemia
due to EPO deficiency will be normocytic in morphology; i.e. the red cell will be a normal
shape and size but reduced in number.
Stem
cells
Bone marrow Erythroid
precursors
Stem
cells
Bone marrow Erythroid
precursors
erythropoietin
erythropoietin
Kidney
Kidney
In chronic states of anaemia the opposite may occur. The chronic hypoxic state increases production
of EPO. This leads to an increase in the proportion of erythroblasts, expansion and eventually fatty
deposition within the bone marrow.
5. Key point!
Red cell precursors and the sequence of erythropoiesis
Reticulocytes are an important cell in haematology as they increase in number following a
haemorrhage, haemolytic anaemia or from treatment of a haematinic deficiency. They provide
an excellent measure of red cell production. In normal blood there is usually about 1 reticulocyte :
100 erythrocytes.
marrow
Pronormoblast: This is the earliest and largest cell with a
large nucleus and no haemoglobin.
Normoblasts: these cells go through a large number of
progressive changes. Fundamentally they reduce in
cell size but increase the haemoglobin concentration
in the cytoplasm.
The nucleus proportionally
decreases until it is extruded before the cell is released
in to the blood.
3.4. Reticulocytes: Considered the “teenagers” of the
the life cycle! This is the FINAL stage of development
before full maturation. These cells are now anucleate
and contain roughly 25% of the final haemoglobin
total. They reside mostly in the marrow but in healthy
individuals a small number can be found in the
peripheral blood. They contain some cell organelles.
blood
Sequence: amplification and
maturation of the erythrocyte
2.2
3.5 Erythrocyte:
after 1 week the mature
erythrocyte emerges with no organelles and high
haemoglobin content.
6. Erthropoiesis is also regulated by the availability of
haematinics
2.4
• So what exactly are the haematinics? These are the key micronutrients that must be present if a red
blood cell and its haemogoblin are to develop in a normal fashion.
• These major micronutrients, provided in a balanced diet, are iron, vitamin B12 and folate
• A deficiency in any one of these micronutrients can result in anaemia through impaired red
cell production within the bone marrow
• Assessing haematinic status is key to the investigation of the cause of anaemia
Iron:
At the centre of the haem molecule is an atom of iron which binds oxygen in a reversible
manner. Haemoglobin concentration in the developing red cell is a rate limiting step for
erythropoiesis. In iron deficiency, red cells undergo more divisions than normal and, as a result,
are smaller (microcytic) and have a reduced haemoglobin content (hypochromic). Iron
deficiency is the leading cause of anaemia worldwide.
Vitamin B12 (cobalamin) and folate (pteroylglutamic acid):
These are key building blocks for DNA synthesis and essential for cell mitosis. DNA synthesis is
reduced in all cells that are deficient in either folate or vitamin B12. The bone marrow is the
factory for blood cell production. In haematinic deficiency, DNA replication is limited and
hence the number of possible cell divisions is reduced leading to larger red cells being
discharged into the blood i.e. less DNA, less divisions and larger cells. This leads to enlarged,
misshapen cells or megaloblasts in the marrow and macrocytic red cells in the blood.
8. Hb
Structure of human hemoglobin. The proteins 2α and 2 β subunits .
The iron-containing haem groups is attached to each chain.
1g/dl Hb; 200 mg of iron is needed.
Reticuloendothelial cells
Apoferritin + Fe3+
Ferritin
Haemosiderin
10. Dietary source of Iron
• Liver, egg yolk, dry beans, dry fruits, wheat,
germ, meat, fish spinach, banana, apple.
11. The normal iron cycle
Iron deficiency can be identified best by assessing the appearances of the red cells
on a blood film.
Iron is a key constituent of haemoglobin (60-70% of total body
iron is stored here) and it’s availability is essential for
erythropoiesis. In iron deficiency, there are more divisions of red
cells during erythropoiesis than normal. As a result the red cells
are smaller (microcytic) and have a reduced haemoglobin content
(hypochromic).
Soluble transferrin receptors,
sTfR are on the red cell surface.
These are increased in iron
deficiency.
Red blood
cells
In iron deficient states, bone marrow
iron is reduced.
Erythroid bone
marrow
(normoblasts)
Some iron binds to
apoferritin to form
ferritin, a storage
compound.
Reticuloendothelial
system;
Spleen & macrophages
Liver
2. Iron is then attached
to a protein, transferrin
in the serum (plasma),
where it is transported to
the bone marrow for
haemoglobin synthesis.
Serum
transferrin
Fe
Duodenum
3. Dying red cells
are recycled by
macrophages in
the spleen and
iron is recycled
into the plasma
for further use.
1. Iron is absorbed from the
small intestine in the ferrous
state (Fe2+; approx. 1mg/day).
12. Preparations of IRON
• Ferrous are rapidly absorbed
• Ferrous sulphate (20-30% iron): 200 mg tab,
cheapest but has metallic taste.
• Ferrous gluconate (12% iron): Ferronicum, 300
mg tab
• Other are ferrous succinate, iron choline
citerate, iron calcium complex etc
13. • Sustain releasing preparations not rational
and expensive
• Liquid formulations stain teeth.
• 200 mg elemental iron produces hemopoietic
effect.
• Abs better empty stomach.
14. Injectables
• Injectables are recommended: when oral is not
tolerated, failure to absorb iron, non compliance,
severe deficiency with chronic bleeding .
• The ionised salts of iron cant be used parentrally
as they cause protein precipitation.
• Egs Iron-dextran (50 mg/ml ele. iron), can be
given by any route.
• Iron sorbitol citric acid complex (50 mg iron/ml),
used only IM
19. Iron Poisoning
• Acute poisoning: 10-20 mg iron tab or liquid
prepn. May cause serious toxicity in children.
• Symptoms: Vomiting, abdominal pain,
lethargy, cyanosis, convulsions, shock and CVS
failure.
• Treatment: induce vomiting, give egg yolk or
milk, desferrioxamine (5-10 g) in 100 ml saline.
• EDTA is used to chellate iron.
