Our first discussion in great detail will
be neutrophilic leucocytosis.
Remember, please, a normal count of neutrophilic
or WBC count should be between 4,500 to 11,000.
So, now you've noticed that your patient has
an increase in WBC count, but specifically
here, it's a neutrophilic count.
You have an absolute neutrophilic count greater
than 7,000, where the normal limit of your
neutrophil should be between 2,200 and 5,600.
If you remember-If you remember that, that's
up to you.
At least know normal WBC count between 4,500-11,000.
Here we have an absolute neutrophil count
being above 7,000.
When are you going to bring in neutrophils?
We had an entire section in which we briefly
breezed through acute inflammation, where
we talked about how you are then going to
bring about, well, remember, circulating pool,
marginating pool, we talked about rolling,
adhesion, transmigration, chemotaxis and fibrocytosis.
Neutrophilic leucocytosis seen in acute inflammation,
especially bacteria, infection-wise.
Sterile, well, you know about myocardial infarction.
If your patient's suffering from acute myocardial
infarction, one of the first cells that you're
going to bring in during acute, acute type
of myocardial infarction, once again, will
And remember, around the-around the third
day or so, the neutrophils will then undergo
apoptosis being replaced by monocytes or macrophages.
The most common drug to, then, cause neutrophilic
leucocytosis would be corticosteroids in which
it then causes demargination.
What that means to you is that it inhibits
the adhesion molecules so that you have decreased
marginating pool, neutrophil – increase
in circulating pool.
Keep in mind that whenever you do a CBC and
you're looking for a WBC count, in this case
a neutrophil count, then you'll always going
to measure the circulating pool.
Cytokines stimulation, well, we have something
like interleukin 17 which is then going to
stimulate the bone marrow, maybe secondary
to the acute inflammation.
You require more, more, more of these neutrophils
that then come out of the bone marrow.
Interleukin 17 is an important one.
In addition, when there's going to be such
increased activity of your bone marrow, you
can only expect, well, apart from the neutrophils
that are coming out, which are normally segmented,
that you might have a little bit of baby cells
coming out as well.
And by baby cells, I don't mean blast and
I'm not talking about hyper-segmented per
se, but I'm definitely talking about band
There's every possibility that during acute,
acute inflammation with neutrophilic leucocytosis
when there is increased regrouping of neutrophils
from the bone marrow, that you might actually
be recruiting in addition to neutrophils,
well, increased churning out of band cells
Hope that's clear.
This is called the left shift in pathology.
It used to be, back in the day, that if you
were to then talk about maturity of cells
and go from left to right, left to right;
left to be very, very, very, very, very primitive
cells and then as you read literally your
cell in pathology, you would find that the
cells are moving from left to right meaning
primitive or immature to mature.
When there's neutrophilic leucocytosis, you're
going to have more of a left shift more of
band cells that are coming into circulation.
That you would expect to see.
Corticosteroids, we talked about this earlier,
that it causes demargination, inhibits the
adhesion of neutrophil.
Remember the steps of adhesion?
What kind of factors are involved in adhesion?
We're talking about adhesion molecules such
as integrins, it then binds to your adhesion
molecules either VCAM or ICAM.
Here we have an extreme case of neutrophilic
An extreme case.
Maybe neutrophilic leucocytosis caused by
Maybe it was acute myocardial infarction.
And if that's the case, then yes, you would
find your neutrophilic count to be above 7,000.
And you find your WBC count to be elevated.
An extreme case of what we're looking at here.
Your patient, maybe young child, has lymphoid
hyperplasia taking place.
And the young child’s holding on down in
the right lower quadrant.
Number one differential and with that type
of histology that I gave you, lymphoid hyperplasia,
no doubt it's appendicitis.
The appendicitis now maybe diagnosed may too
late and appendicitis now ruptured.
Maybe you have a female who's pregnant.
And now, at this point, she's exposed to the
outside world, especially her urethra.
Urethra is very, very, now, quite small because
of the increased pressure from the pregnancy
and the fact that the size of the urethra
is always smaller in a female compared to
All of this making it very, very easy or increase
in susceptibility for urinary tract infection.
At some point in time, however, and now your
pregnant woman starts getting into the realm
Bacteraemia, septicaemia and [Inaudible 00:05:08]
It’s two extreme cases of really, really
When you have such diagnosis of perforated
appendicitis or sepsis, you're going to be
recruiting so many neutrophils.
You have a WBC count at being above 50,000.
Think about what your normal WBC count is.
It's 4,500 to 11,000.
So, now, we have it at being 50,000.
But, why do we call this leukemoid reaction?
Because it looks like leukaemia, but it's
"Oid", the suffix, means “appears as".
It appears as leukaemia.
Your discussion with leukaemia, you’ll understand
that you are going to find increased count,
but that-those cells that you're going to
find in leukaemia, they're not functioning,
excuse me, they're not functioning properly.
Whereas if it's leukemoid reaction, sepsis
and a perforated appendicitis, the neutrophils
that you're recruiting, they're all functioning.
My point is this – what is a laboratory
test that you know of that assists the functionality
of your neutrophil?
That's called leukocyte alkaline phosphatase.
LAP, LAP, LAP.
You might have memorised this before, but
sometimes you get this confused perhaps.
From now on, you won't.
And leukemoid reaction, which is not a leukaemia,
but a severe, extreme case of an infection
perhaps, you're going to have all this recruitment
of neutrophils and they're functioning and
therefore, your LAP will be sky high in leukemoid
Whereas if it's chronic myelogenous leukaemia,
could you find an increase in count?
Sure, you can.
But, those are cancer cells.
Cancer cells aren't working properly.
Chronic myelogenous leukaemia, you find your
LAP to be decreased.
We'll talk about that one more time when we
get into CML.
The second extreme case will be the following.
Now, let's say that your patient has a molecular
pathology and molecular mechanism of jack
two-step pathway, jack two-step pathway.
Upon reticular stain or trichrome stain of
the bone marrow, you end up finding all this
Think about the bone marrow, please.
It should be nice and empty.
Not empty, but should be more open, huh?
Cancellous bone, should be spongy, should
have fat globules.
Normally, a little bit.
And then, of course, you have your stem cells.
But, instead of finding a little bit of fat
vacuoles and such within the bone marrow,
now you find tons of fibrosis in the bone
Or maybe, perhaps, your patient has a breast
And with breast cancer, let's say invasive
lobular breast cancer.
And breast cancer loves to spread.
Metastasis, any metastasises to the bone marrow.
So, now, you have a space-occupying lesion
within the bone marrow.
You have fibrosis within the bone marrow occupying
The normal stem cells that should be in it
now are being displaced.
Those baby cells that you find in the bone
You know about megakaryocytes, you know about
your nucleated RBCs, you know about your blast.
Now, these cells in the bone marrow are then
being displaced, pushed out of the bone marrow,
have you, by space-occupying lesion, let it
be metastasis from a cancer.
I give you breast, breast cancer.
Number two, maybe it's myelofibrosis, which
is a peripheral myeloid disorder.
So, when such issues take place, you're going
to displace-displace the blastic cells into
Welcome to our picture of leuko(WBC)erythro(RBC)blast(baby)
So, we have all these baby WBCs, baby RBCs
How can you confirm this?
If you take a look at the peripheral blood
smear, you find RBCs that are nucleated.
Pause there for a second.
Understand significance of what I just said.
Hmm, an RBC that's nucleated in peripheral
That's a baby.
You should never have an RBC nucleated in
your peripheral blood smear.
But if you do, highly differential, what then
is causing the space- reaction?
Yet another extreme case of neutrophilic leucocytosis.
Increase in immature WBCs including myeloblasts.
Where are you finding these?
In your peripheral blood smear.
Caused by infiltrated bone marrow disease
or multiple fractures.
Can you see the common denominator between
the last two statements?
The bone marrow is being infiltrated by whom?
Oh, fibrosis or breast cancer by metastasis.
Or what if the patient had multiple, multiple,
Obviously now, the bone marrow is going to
release immature cells into circulation – welcome
to our second extreme case of neutrophilic
leucocytosis, known as a leukoerythroblastic
picture or reaction.
Now, the extreme case is here, leukemoid reaction.
What I'm trying to show you is the following:
a leukemoid reaction – we talked how, well,
looks like leukaemia, but it's not.
There is no anaemia, thrombocytopenia, but
there is going to be an increased number of-of
blast and by that, we mean the following:
looks like leukaemia.
Meaning to say that your patient here is not
going to be suffering from dead bone marrow.
Because of leukemoid.
What's the only thing that you're bringing
out from the bone marrow?
But, the patient is not going to have the
leukemic symptoms of anaemia, thrombocytopenia
or perhaps increased number of blast.
The only type of cells that you might find
would be maybe bands and such in leukemoid
In leukoerythroblastic picture, if you’re
going to take a look at the picture here,
we have tear drops cells.
We have NRBC, which stands for nucleated RBCs.
And what-And what this basically means is
Well, before we move on, this is a peripheral
blood smear picture and what ends up happening
is that if there is a bone marrow infiltration,
maybe due to myelofibrosis or metastasis to
the bone maybe, perhaps, from a breast cancer.
Now, you have a space-occupying lesion within
the bone marrow.
The RBCs will be squeezed out and then, as
it does, it hurts and it's making me cry.
It's a tear drop cell.
Literally, squeezing out of the bone marrow.
It's tear drop cell.
And nucleated RBC, that's a baby.
Take a look at the-the blast that you see
up in the top there and it's a metamyelocyte.
All these are blasts.
This is leukoerythroblastic picture.