Hello, welcome to this lecture on disorders
of the red cell. Learning outcomes that you
will gain from this lecture include these
four points. Red cell disorders are some of
the most common diseases in the world. Anaemia
can result from many different conditions
such as iron deficiency, haemoglobinopathy
and chronic infection. Haemolytic anaemia
occurs when the red recall lifespan is reduced
and increased numbers of red cells are seen
in polycythemia, which may result from a myeloproliferative
disease or response to hypoxia.
Let us start with the red cell itself and
here is a very familiar electron micrograph
of red cells showing a biconcave shape. Red
cells derive from erythroblasts in the bone
marrow. They are packed with haemoglobin and
they carry oxygen deep into tissues.
The production of these cells is regulated by an erythropoietin
and they do not have a nucleus, so their lifespan
is limited and is around 120 days. Anaemia
is very common throughout the world.
It can be defined as a reduction in the haemoglobin
level within the blood, but remember that
this must taken in relation to two factors.
One is the age of the patient and the other
is the gender. Let us look at that table on
the right, which shows typical haemoglobin
concentrations at different ages. If you look
at the mean haemoglobin column, at birth cord
blood has a high haemoglobin concentration
around 165 g/L. Then the green line of one
month shows this is already fallen to 140
g/L. In the first few weeks of life, there
is a lot of breakdown of red cells within the
blood and change of the globin to a different form.
At six months to 2 years, you will see
a relatively a haemoglobin concentration,
120 g/L, which then starts to increase at
the age of 12 to 18 to around 114.
Then look at adults right at the bottom and you will
see the characteristic difference between
females and males in haemoglobin concentration
with males having an increment of around 15
g/L due to the fact on anabolic male hormones.
Now the symptoms of anaemia include a range
of things including tiredness, shortness of
breath, poor concentration, palpitations because
the heart is beating fast and vigorously and
of course colour is a sign that somebody may
be anaemic. A good method for approaching
the classification of anaemia is through analysis
of the red cell volume. So let us now take
a look at that in a little more detail.
Here we see the classification of anaemia
based on the mean cell volume. So, on the
blue row, you will see the anaemia type, microcytic
hypochromic. Those are small cells with low
levels of haemoglobin. Here we have two subsets
of disease that we will discuss in more detail,
iron deficiency and thalassemia. In the middle,
we have normal size cell, normocytic and normochromic.
These are due to chronic infection, renal
disease and marrow disease and may also include
haemolytic anaemia whereas on the right we
have macrocytic anaemia, large red cells with
a raised MCV. We will see later on how these
are normally secondary to vitamin deficiency
particularly vitamin B12 and folic deficiency.
Let us take the first of these and that is
an iron deficiency. First we have to consider
the physiology of iron within your body.
Iron is one of the most common elements in the
crust of the earth and yet we only have around
4 or 5 g of iron within our body. There is
also no mechanism for regulating the excretion
of iron and so we have to be very careful
how much iron we absorb. We now think that
this is the case because iron can be quite
toxic in excess and it can even lead to damage
of DNA and so the absorption of iron is controlled
to levels that we just need to maintain normal
physiological function. On the right, the
diagram shows where this iron is held within
the body and you will see that 70 percent
is incorporated into haemoglobin with 25 percent
stood in the reticuloendothelial system. Minor
fractions are circulating within the blood.
This is a representation of iron regulation
and we can see at the top our intake of iron
is around 10 to 20 mg per day in our food.
There are two major forms of iron that we
encounter in our diet, heme iron comes in
meat products and that is relatively well
absorbed whereas nonheme iron is more tricky
for our body to absorb. In the stomach, much
of this iron is reduced into the ferrous Fe2+
form and that helps absorption and you will
see that absorption occurs in the upper small
intestine. But on the left-hand side of the
slide, you will see much of this is absorbed
into mucosal cells and then shed for excretion
perhaps a milligram a day whereas around a
mg goes into the blood stream and there is
absorbed and is used in an erythropoiesis.
So what is iron used for? It is used largely
for making haemoglobin. Let us just look at
how our cells make haemoglobin and you will
see that is a representation of a mitochondrion
on the left and at the top of the mitochondria,
you will see glycine and succinyl CoA and
those are the first derivatives that come
together to form the constituents of the haem.
The delta-ALA enzyme, aminolevulinic acid
is a great limiting step here and it produces
through intermediates protoporphyrin, which
is very interesting flat planar molecule and
you will see that comes out of the mitochondria
links with iron and forms haem and of course
haem needs globin and globin you see comes
in the top right as amino acids forming these
chains of 141 or 146 amino acids long.
As we bring haem and globin together, we form
the haemoglobin, which is so densely concentrated
within red cells. When we look later at haemolytic
anaemias, we will take this process and reverse
and see how haemoglobin is degraded and how
they can lead to some of the symptoms of haemolytic
anaemia. Iron deficiency is one of the most common
findings in people around the globe and the
major cause is chronic blood loss particularly through menstruation.
Women women who are premenopausal
having regular menstruation are very commonly
iron deficient. It can also be the result
of gastro intestinal malignancy or inflammation.
That is very important because if you see
a man who has iron deficiency anaemia clearly
they cannot be menstruation that is a warning
sign also in a postmenopausal woman.
You must think if there is a gastrointestinal cause
perhaps a colonic tumour or even a gastric
tumour. Those should be investigated in most
cases. Dietary deficiency of iron is actually
quite uncommon and malabsorption can occur
and, of course, the celiac disease is an important
consideration there, but they are relatively
less common when actually chronic blood loss.
The treatment to iron deficiency is usually
relatively easy and ends with an oral iron
source, which should be around for over 100
years that is one of the cheapest tablets
you can possibly buy. Now some people cannot
tolerate oral iron. It can lead to some
gastrointestinal upset and so intravenous iron can also
be given and this is really very well tolerated
now. Now on the right, there is a blood film
of a person with iron deficiency and you can
see how those cells fit those two criteria
that we described microcytic that is more,
hypochromic that polyhemoglobanised, you see
very pale staining cells and another feature
is pencil cells, very long thin cells as you
can see in one or two places.