Students tend to have
a hard time with
normocytic anemia only
because of the organization.
So it’s exactly what we will focus
upon initially with the overview.
This will be the largest
category of anemias.
Here, the MCV will, in fact, be
between 80-100, perfectly normal.
Next, what do you do once you have
a patient who gives you the symptoms
of each of one of these diseases
that we will go through
and the MCV has 80-100.
Well, next you check to see
as to whether or not the bone
marrow in fact is working properly.
How do you know?
Well the bone marrow if
it’s working properly
and the RBCs are being
or there is massive hemolysis,
either through intra or
now, please understand the bone
marrow is going to do what?
Churn, churn, churn more
reticulocytes into circulation.
So therefore, in clinical practice, we call
this reticulocyte production index or RPI.
For you, you want to
know RPI, so be it,
but it’s equivalent to the concept
of increasing reticulocyte.
So therefore, the two on the right
that you’re looking at here,
the magic number is a corrected
reticulocyte being greater than 3%.
All it means is that the RBCs are being
destroyed either within the vasculature,
intra or extravasculature
mainly the spleen
in which now the bone marrow
is increasing or compensating
and increasing the
production of reticulocytes,
concept number 1.
Concept number 2 will do the opposite.
What if you have a condition in which
the bone marrow has been shut down?
Such as, well, maybe your patient
was taking chemotherapy.
Maybe chloramphenicol, maybe there is a
concomitant infection parvovirus B19.
If that is the case, your bone
marrow, in fact, is being shut down.
And so therefore, how in the world could
the bone marrow produce any reticulocytes?
It does not.
And so therefore, you would have a decreased
RPI or reticulocyte production index.
And here, the magic number is corrected
reticulocyte count of less than 3%.
These are concept that you want
to make sure that you have down.
Now, one little thing that I want
to point to you before we move on
is that couple of anemias
can occur at the same time.
coming off the discussion of both
microcytic and macrocytic anemias,
Well, the microscopic anemia that
you might be thinking about being,
well, quite common,
is iron deficiency.
And if you have a type of
then you’re going to then release
hemoglobin into the urine
along with the hemoglobin there
goes the iron, doesn't it?
So you might have concomitant
iron deficiency as well.
Now, which one of these is
hemolytic or non-hemolytic
that may result in
Good, the hemolytic.
RBCs are dying and as they do so,
well, the bone marrow is now churning
out increase amounts of reticulocytes.
And therefore, we have
Would you give me the size of reticulocyte
when compared to a mature RBC?
It is larger.
So what is that going
to give you with MCV?
Greater than 100,
every possibility that you
might have a nonmegaloblastic
Are we seeing this
at this point?
Let’s continue to the overview.
Now continuing from the
previous slide, on your left,
you will notice that your
reticulocytosis is not increased,
magic number less than
3% for corrected.
And if you take a look
at the differentials,
I will give you the ones
that were obvious here.
We have aplastic anemia due
to many, many reasons,
or renal disease if
the kidneys are dead
then you do not have
EPO or erythropoietin
and so therefore, who's
not functioning properly?
The bone marrow.
And then, let's say that you had
malignancy such as breast cancer.
And if it's breast cancer, then there is every
possibility that it might then metastasize
into your bone marrow, therefore really
impeding the development of an RBC.
So you can see here clearly that your
patient is in fact suffering from anemia,
but the bone marrow might be shut
down or is not working properly.
And so therefore, is going to present with
normocytic non-hemolytic type of anemia.
Now in addition to that,
we’ll walk through in greater detail the
blood loss being acute, less than 1 week.
And what that means, is that when you’re
having blood loss, it’s whole blood
and so therefore, you’re losing
RBCs and you’re losing your plasma.
So therefore, in terms of the
symptoms might be there obviously.
But in terms of actually looking
at the anemia and the MCV,
it will be perfectly normal.
Less than 1 week becomes very
important for us and you’ll see why.
And the early stage of both anemia of
chronic disease and iron deficiency
could be normocytic.
So early on, but interesting enough,
the anemia of chronic disease,
normocytic will perhaps even
persist even into the long run.
So remember I told you about --
Can you think of anemia of chronic disease?
Last time we talked about that was
chronicity, chronicity, chronicity.
You have that acute phase
reactant known as hepcidin
which then blocks release of
your iron from your ferritin.
So that is going to be non-hemolytic.
Under hemolysis and hemolytic, well --
here both take a look at
Magic number corrected
reticulocyte greater than 3%.
And what you will do next, if you want,
is maybe divide this into intrinsic
and extrinsic, but I can assure you
that is not really going to
give you clinical features.
What question that you need
to ask yourself that truly
gives you the clinical features for all
hemolytic anemias, both intrinsic and extrinsic
and I’ll give you the definition later
is whether or not this
hemolysis was intravascular
Let me give you one big
intravascular type of hemolysis.
If you go under membrane
and actually, what you might want to do
here is maybe create a mnemonic called MAD.
M is membrane defect hemolysis.
A is abnormal hemoglobins.
And D is deficiency of enzymes.
And we’ll go through each and
every single one of these
as we then peruse through our
various types of pathologies.
But I told I will give you one major
intravascular hemolysis here.
This is PNH, paroxysmal
And pretty much, the name tells
that it’s intravascular.
you tell me, where is hemoglobin
supposed to go normally
for its complete metabolism
To the spleen, right?
And so therefore, the heme will then
be further broken down to biliverdin
and then your indirect
and the globin will then be recycled.
We can’t breakdown globin.
That’s your genes.
So that would have to be spleen
So how is it that you
end up hemoglobinuria?
If the blood vessel then
destroys your RBC intravascular,
your blood vessel normally cannot
metabolize your hemoglobin
all the way down into
your indirect bilirubin.
So therefore, you’re going to
have quite a bit of hemoglobin
that is being released into circulation.
Are you with me? Are
you picturing this?
This hemoglobin is then going to
be delivered to the glomerulus
where it then passes through, welcome to red
urine or hemoglobinuria, intravascular.
What if it was external
If it is extravascular hemolysis, I am
going to give you the prototype here
under abnormal hemoglobin.
Not to mention, we’re going to
go to a little bit more detail
with hemoglobin C as well.
We have to.
But sickle disease, is that homo
or heterozygous type of pattern?
Good, it’s homozygous.
Homozygous is always more dangerous.
So let’s say that you have an African-American
child who has sickle cell disease.
And well you know the symptoms
like acute chest pain,
maybe there is going to be
difficulty with vision,
so on and so forth.
And if you take a look at the
eyes, well you'll find icterus,
What is icterus and perhaps
yellowing of the skin?
That’s jaundice, isn’t it?
All of this is --
What kind of substance is this?
This is indirect unconjugated bilirubin.
So sickle cell disease,
you would know that upon exertion of
the child, exercising or whatever,
that now, all of a sudden,
the RBC becomes sickled.
Really bad, right?
Sickled, gets polymerized
is what it's called.
And when it becomes sickled, then it’s
taken to the spleen, splenomegaly.
Welcome to extravascular.
The spleen is then going to remove
the RBCs out of the vasculature
and then it will further
break things down.
And welcome to
The question that you want to ask
yourself, on the right side,
for intrinsic and extrinsic,
more importantly is
is my disease intravascular or
is my disease extravascular?
And we’ll go through the details as
to membrane, abnormal hemoglobin
and deficiency of enzyme
and then we’ll walk through
the extrinsic part
where it includes our micro and
macroangiopathic type of hemolytic anemia.
So those become
important for us.