00:01
Hello.
00:02
In the second lecture
in our series on hematology,
we're going to look at the
physiology and function
of some of the major blood cells.
00:11
And the learning outcomes that
we'll be getting from this lecture
are as follows.
00:16
We'll look at red cell production,
and how that's regulated by
erythropoietin.
00:22
We will explore how red cells
contain hemoglobin,
and how that helps them
to carry oxygen to tissue.
00:30
We will look at the subsets
of white cells
which play specific roles
in protection against infection.
00:36
And we'll explore how lymphocytes
mediate the function
of the immune system.
00:42
And find out
how neutrophils are critical
in the first line of defense
against bacteria and fungi.
00:49
In this lecture, we're not
going to focus on platelets,
because they're the subject
of a later lecture
on blood clotting.
00:56
Let's look at red cells
in a little bit more detail.
00:59
By far, the most common cell
within the blood.
01:05
Red blood cells
derive of course
from a nucleated cell
within the bone marrow.
01:10
And the first cell that's
committed to forming red cells
is the erythroblast.
01:15
And there are rare forms
of leukemia,
are in fact
derived from these cells.
01:21
Now, red cells are packed
with hemoglobin.
01:24
And they carry oxygen to tissue.
01:27
The reason that we've
evolved red cells
is it allows hemoglobin
to be packaged effectively
within these blood cells,
rather than being free
within the blood.
01:40
Now the major production
of red cells
is through this hormone
called erythropoietin.
01:45
I will explore the regulation
of erythropoietin in some detail.
01:50
On the right, you'll see a lovely
scanning electron micrograph
of red cells.
01:54
And you'll see that classic
biconcave discs structure
of the red cell,
which allows it to be flexible
and flow through the capillaries
as well as diffusing oxygen
into tissues.
02:10
Now hematologist
can't stop making blood films.
02:12
And there you'll see a blood film
on the right,
and you'll see how red cells
look down the microscope.
02:19
And you'll see the characteristic
pale center because of their shape.
02:25
They're around seven microns
in diameter,
and a highly flexible structures
with the biconcave shape.
02:33
Now, some red cells in the blood
are very young
because they've just come out
of the bone marrow.
02:40
And we call those reticulocytes.
02:43
Now, they carry a lot of RNA.
02:45
And that RNA gradually gets degraded
over two or three days.
02:50
And the final red cell
then becomes apparent.
02:55
So you'll see on the left
that reticulocytes
can live for two or three days
normally within the blood
around 2% of the red cells
are reticulocytes.
03:05
And we can detect them
by staining,
what we call a supravital staining
with this wonderful dye
called brilliant crystal blue.
03:14
And you'll see on the right, those
cells with the intense blue stain,
those are reticulocytes.
03:21
There's an awful lot
in that picture
and many more than we'd find
in your own blood, I'm sure.
03:27
Now, as well as being
physiologically important
reticulocytes are important
clinically,
because they can give us a guide
as to the type of anemia
that we may be dealing with
in a patient.
03:39
Because if the reticulocyte count
is increased,
it shows that the patient's
bone marrow is very active
and pouring out a lot of red cells
into the blood.
03:50
Whereas, if we can't find
many reticulocytes,
it means that there's a problem
with the production of red cells
from the bone marrow.
03:58
So when we discuss anemia
in later lectures,
you can see why the reticulocyte
count is a very useful test
for trying to understand
the etiology of the anemia.
04:10
Now, the production of red cells
is described by the erythropoiesis.
04:17
And again, it's represented
by those blue cells.
04:22
Normoblasts have a nucleus.
04:24
But then as they themselves
differentiate,
the nucleus is objective.
04:30
And that stage that reticulocytes
can be released into the blood.
04:35
Now, we don't know why the nucleus
is ejected in red cell production,
but it may be that
that allows more room
for hemoglobin production.
04:45
And that has been selected
during evolution
as a very effective way
to increase oxygen transport
within the blood.
04:54
Now the regulation of this process
of hemopoiesis
is really control through this
protein called
erythropoietin or EPO.
05:07
This hormone EPO is produced largely
from the kidney.
05:12
Again, very surprising finding
of the kidney
should be regulating
our blood production.
05:18
But if cells in the kidney
detect that the blood is hypoxic
in any way,
they will then release
erythropoietin into the blood.
05:29
Erythropoietin circulate
to the bone marrow,
and it stimulates the production
of red cells.
05:36
As you can probably imagine,
EPO, erythropoietin levels
are increased.
05:41
And people who are short of oxygen
for instance,
those who live at high altitude
or patients who
have lung disease,
or perhaps smoke.
05:51
And you'll see
on the right there
representation of
the stimuli to hypoxia
factors such as
anemia
or low atmospheric
oxygen tension.
06:04
That hypoxia is detected
by the kidney
and erythropoietin is produced.
06:12
Erythropoietin
stimulates hemopoiesis
through a number of mechanisms.
06:17
It increases the
differentiation pathway
through erythropoiesis
to make more
erythropoietic cells,
to accelerate cell division
and it accelerates
the release of cells
into the blood.
06:33
That can usually address
the hypoxia,
of course, the negative feedback
loop is established.
06:41
Erythropoietin,
it's actually very useful
molecule for clinical therapy
and we can use it to stimulate
hemopoiesis in patients
with some forms of anemia.