WEBVTT

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Hello.

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Thank you so much for joining us today.

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My name is Doug Torres,
and I'm a human to pathologist.

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Today, I'm very excited to talk to you
about the morphology of red blood cells.

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And what we'll focus on today is a smear

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basics.

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Please read through the objectives
in brief.

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We will focus our presentation
on the morphologic aspects

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of assessment of red blood cells
in their peripheral blood smears.

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Will also be able to correlate
what we see in the smear

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to what we see on the CBC of that patient.

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We will discuss the pathogenesis
of certain abnormalities

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and what's important.

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We will also be able to link
what we see on the smear

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with some common morphologic conditions.

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So today we will focus on the basics.

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So let's start with what

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the, perfectly made
peripheral blood smear should look like.

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And this is the one that was prepared
by a very skillful laboratory scientist.

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Why do I think that this is a good smear?

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Well, first of all,
it has a well defined bullet shape.

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The application point or word, the
droplet of blood is place is right here.

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Then the scientist drags that, drop

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and creates this shape.

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What I'm looking for is that the edges,
the lateral edges of the smear,

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are still away
from the edges of the glass.

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And we have a very well defined end of
the smear, what we call feathered edge.

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Now, if we start looking
in the microscope,

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we will see that
the vast majority of the smear.

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All this area is what we call fake part.

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And it means that the, cells,
including red blood cells,

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will be so thickly distributed
there will be overlapping.

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So it will be very difficult for us to,

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appreciate morphology
here in the thick part.

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What I want to, pay your attention
is that, the white blood cells

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will be also so shriveled up, it's
going to be very difficult

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to see the nucleus versus
the cytoplasm of the cells.

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This is how we'll know that we are in
the wrong part of the smear.

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If we go further away,

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we will go to the monolayer
which is located right here.

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So the monolayer is called monolayer
for an obvious reason.

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The red blood cells
are actually not overlapping too much.

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They, form well, distributed pattern.

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And we even in lower power, we can see the
central pallor of those red blood cells.

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Also, if we pay attention to the white
blood cells, lymphocyte, in this case,

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we will be able to appreciate the nucleus
in the cytoplasm.

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However, if we decide to go further
into the feathered edge, we'll see

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that red blood cells will be more scars,

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and they will, lose their central pallor.

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Therefore, it's very important for us
not to go to further edge

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to assess red blood cell morphology,
as it may look quite different

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from the rest of this mirror.

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The normal
red blood cells in the monolayer,

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will have a round shape,
because they are by by concave disks.

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They will measure about 6.5 to 8 microns
in their diameter.

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It's very difficult
for us to appreciate the true,

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precise
size of the red blood cells in the smear.

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Therefore,
we need to find a reference point.

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Often we use small lymphocyte,
as seen in this illustration.

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As a reference point.

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As the nucleus of this lymphocyte
is about seven microns.

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If you look around that
the vast majority of our red blood cells

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will show size is quite comparable
to the nucleus of the, lymphocyte.

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Also, notice that

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in any normal peripheral blood smear,
there will be red blood cells

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that are slightly off, either
too small to large or have a funky shape.

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However,
if there's just a very few of them,

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they usually do not have
any clinical significance.

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Red blood cells are

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called red blood cells
because they contain hemoglobin,

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a very important pigment that gives
our blood red color in the smears.

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However,
we apply using this as a special stain

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that, stains, hemoglobin pink

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red blood
cells should have a central pallor,

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which is about one third of the size,
of the cell or diameter.

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The distribution of hemoglobin
within the cell should be, even

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and quite gradual.

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So having discussed
what the normal red blood cells look like,

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let's dive in and talk about the problems
with their distribution

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in our smear.

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I can assure you that this image
was taken in the monolayer.

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However,

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it does not look like a monolayer
because a lot of red blood cells overlap.

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It's also important to see that
this overlap

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has quite a distinct pattern

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that somewhat reminds the stack of coins.

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And this is what we call
the rule of formation.

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Rule of formation is actually an artifact
that can be seen quite often,

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especially when we are in the thicker
part of the smear.

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Therefore, for us to prove
that this is a true rule of formation,

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we have to make sure
that we're in the monolayer.

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In the center of this image
is a small lymphocyte.

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Once again, for the reference of the size
as well, to show you guys

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that we have nucleus and the cytoplasm,
that are very well appreciated here.

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So yes, we indeed are in the monolayer.

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So what does it mean
if we have a rule of formation?

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Well, the rule, forms when,
the plasma has too much protein.

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And very often we see,

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rulo, in, in a, infection

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as well as some B-cell malignancies,
for example, plasma cell myeloma.

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This is actually a smear from, 
patients with plasma cell myeloma.

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And the amount of approaching
this patient was very high

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that it also gave a blue
tint to the background

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of this smear.

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In contrast, there's another,

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common type of abnormal red blood
cell distribution.

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This is what we call a red blood
cell agglutination.

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We see here that the red blood cells
are sticking to each other,

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and they do not really distribute,
nicely, as we see in the monolayer.

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Unlike in, Rouleau formation,
this agglutination

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usually looks very unorganized,
sometimes compared

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to the bunch of grapes.

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Now, to help us

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distinguish Rouleau from agglutination,
which is very important,

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we also need to understand
why those phenomena, occur.

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So in normal condition,
the red blood cells have negative charges

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which help them to stay repelled
from each other.

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They really do
not like to touch each other. Rule.

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Or as we said, is a consequence
of increased proteins in this serum.

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And some proteins,
with positive charge would coat red

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blood cells very evenly decreasing.

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That differences in charge.

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Therefore, red blood cells
will start tending to stick to each other.

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And because they're sticking,

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to their larger surfaces,
it will appear as a stack of coins.

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Agglutination is
associated with the presence of antibodies

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that are targeting antigens
on the surface of a red blood cells.

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In this image,
I actually included IgG as the most common

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type of antibody
associated with agglutination

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and as you see, the same, 
pentameter of AGM can link different

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red blood cells together,
forming this large,

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body of a gluconate.

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Another abnormal, distribution pattern

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that is not very often
seen is cryo globule anemia.

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In this particular smear, one can see that

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the red blood cells
have a very bizarre distribution.

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Some of them also show strange contours.

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And at first it's really difficult
to understand why is it happening.

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But if we look a little bit closer,
we will be able to see a very pale

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stained, bluish, aggregates

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of, homogenous material.

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So this is, what we call cryo globulin.

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Cryo globulin, by
definition, is immunoglobulin

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that tends to precipitate at temperatures,
lower than your body temperature.

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So when the specimen, is drawn
from the human body, and as it cools down,

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this proteins will precipitate, forming,

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these, aggregates.

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Sometimes we also can appreciate,

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cryo precipitate
being engulfed by the neutrophils.

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What's

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important to know about cryo globulins
is that it often interferes

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with hematology analyzers
because as a simple

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IG this passes through hematology
analyzer.

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The particles of cryo globulin
will be read as a cellular material,

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and depending on how big they are,
they can be counted as leukocytes,

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therefore increasing
the leukocyte number, which is not true.

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It can be read as a red blood cells
or sometimes even as a platelet.

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A one way to circumvent

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this morphologic, problem
is to actually read the specimen.

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And as we

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heat it to the room temperature, the, 
cryo globulins will tend to dissolve.

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So this is when we can run hematology
analyzer.

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And also we make a peripheral blood smear

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in terms of, different associations,
when we see cryo globulins,

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it is, noteworthy,

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that some lymphomas, hepatitis C,

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some other, conditions
that are associated with inflammation,

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either infectious inflammation or immune
inflammation can give us this pattern.

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Now let's

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focus, with the problems with size
and the color of red blood cells.

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But first of all, let's remark,
let's be reminded of, different

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CBC parameters that can be, correlated
with the red blood cell morphology.

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Among those will be we have to be very
clear about the three most important ones.

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Those are MCV mean corpuscular volume,

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which shows the volume of the red blood

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cells as it passes the analyzer.

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So, MCV correlates

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with the size of red blood
cells in the smear.

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For example, when we have small red blood
cells in the smear,

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we probably should expect low MCV
in the CBC.

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Alternatively, if our red blood cells
become larger in the smear,

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we will see it on CBC
as an increased mean corpuscular volume.

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The next parameter is McMinn
corpuscular hemoglobin concentration

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that shows how much hemoglobin

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a red blood cell
has related to its volume.

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So if, our normal red blood
cells have normal mixy,

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then if we have pale
red blood cells with low hemoglobin,

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then we'll also expect
to see a low MCQ in this on the CBC.

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And the third parameter

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is RW which stands for red blood
cell distribution width.

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And it shows how much of a difference

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there is in the red blood cell size
within a particular specimen.

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So normally we have some variability
as we saw in one of our slides.

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In some situations

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when we have a lot of smaller red blood
cells, larger red blood cells are red.

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Red blood
cell distribution with will be increased.

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So we will talk about high RTW.

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So the first abnormality here
is what we call microsite ptosis.

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This is when our red blood
cells are smaller than we expect.

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So by definition
microsite ptosis is considered

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when we have, decrease

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in our red blood cell size
by at least two standard deviations.

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So they would be about six microns
as opposed to seven microns.

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And if we look at the CBC,
those cells will

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cause lower MCV,
usually less than 80 ventilators.

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And as you see

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here, a lot of red blood
cells in the smear

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actually are smaller
than the nucleus of the lymphocyte.

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We can grade microsite ptosis

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when we see more than ten,
but less than 20% of micro size.

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We can say that two

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plus microsite tells us in that
there's more than 20% of those cells.

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Then, we call it, three
plus microsite ptosis.

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Microsite ptosis is usually associated
with conditions that

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cause decreased production of hemoglobin.

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Therefore,

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there's not much we can put into each red
blood cells, making them smaller.

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The main, causes of decreased
hemoglobin is iron

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deficiency, because iron is very important
for human globin.

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And alternatively
we can have a genetic defect

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in hemoglobin gene synthesis,
which we call thalassemia.

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So both iron deficiency and thalassemia
will often present with microsite ptosis.

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But if our red blood cells

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are larger than expected,
we would call that macro psychosis.

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In in macro, say ptosis,
the CBC will show us increased

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MCV, usually more than 100 ventilators.

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And morphologically we'll see large cells

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that are more than eight
microns in diameter here.

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I actually do not have any lymphocyte
to show you.

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However, I hope you appreciate that
a lot of cells in this field

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are larger than your normal counterparts.

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Macro sites can be somewhat oval

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like in this case or round,
and this can be a very important

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observation as to show what possible
causes, to this macro psychosis.

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There is, for example, overall macro size
as in this case

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can be associated with B12 deficiency,
with Foley deficiency

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as well as some clonal conditions,
for example myelodysplastic syndrome,

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00:14:46.886 --> 00:14:50.189
also with chronic infection
in the plastic anemia,

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00:14:51.323 --> 00:14:52.057
round macro

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00:14:52.057 --> 00:14:55.494
sites
are more commonly seen in liver problems,

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00:14:55.895 --> 00:14:58.964
in patients with hypothyroidism and hyper

242
00:14:58.964 --> 00:15:01.967
spleen ism.

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00:15:03.335 --> 00:15:05.271
The next observation always

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00:15:05.271 --> 00:15:08.974
we can see in the peripheral blood
is polychromatic like red blood cells.

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00:15:10.409 --> 00:15:13.112
This is a field from a patient who is,

246
00:15:13.112 --> 00:15:16.815
who has quite
a lot of those larger cells.

247
00:15:18.050 --> 00:15:21.654
Some of them have retained central pallor
and some don't.

248
00:15:22.121 --> 00:15:26.492
And as you see here, the those large cells
actually have a bluish hue

249
00:15:27.159 --> 00:15:30.596
so polychromatic, like red blood cells or,
very young

250
00:15:30.596 --> 00:15:34.400
red blood cells
just barely, came out of the bone marrow.

251
00:15:34.900 --> 00:15:39.838
So if we stain them with a special way,
we call it super vital stain, we will see

252
00:15:39.838 --> 00:15:44.476
that those cells have a lot of retained
RNA which give them bluish hue.

253
00:15:45.077 --> 00:15:48.080
Therefore,
the vast majority of polychromatic

254
00:15:48.347 --> 00:15:52.584
red blood cells
actually, represent, reticular sites.

255
00:15:53.652 --> 00:15:56.789
So reticular size, being
the youngest mature form of red blood

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00:15:56.789 --> 00:16:00.459
cell, can give us a lot of information
about what is happening to the patient.

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00:16:01.327 --> 00:16:03.629
In normal condition, about

258
00:16:03.629 --> 00:16:06.966
1% of red blood cells are polychromatic,
like red blood cells.

259
00:16:07.433 --> 00:16:10.903
However, if we see quite a lot of them,
like in this case,

260
00:16:12.371 --> 00:16:15.174
that may mean that the bone marrow
is really trying

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00:16:15.174 --> 00:16:18.177
to make more and more out of cells
very fast.

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00:16:18.744 --> 00:16:22.014
That happens when the bone marrow
regenerates from some insult,

263
00:16:22.014 --> 00:16:26.051
for example, iron deficiency
that is treated with iron.

264
00:16:26.452 --> 00:16:31.323
Sometimes it's a massive blood loss
and the bone marrow tries to recover.

265
00:16:32.091 --> 00:16:36.428
However, in other situations,
when we expect to have high number

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00:16:36.428 --> 00:16:41.433
of polychromatic like red blood cells
and we don't see them, that may mean that

267
00:16:41.433 --> 00:16:45.237
the bone marrow is just tired
and it cannot produce as many of those

268
00:16:45.237 --> 00:16:46.939
red blood cells as needed.

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00:16:46.939 --> 00:16:49.942
That happens in aplastic anemia,
myeloid dysplastic syndrome,

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00:16:50.342 --> 00:16:52.244
and, other conditions.

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00:16:54.880 --> 00:16:57.282
Hyperkalemia is when our red blood

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00:16:57.282 --> 00:17:01.120
cells, become very pale,
and that paleness

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00:17:01.120 --> 00:17:05.190
is due to very low concentration
of hemoglobin within those cells.

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00:17:06.558 --> 00:17:10.195
Usually hyperkalemia is appreciated
when the central pallor

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00:17:10.596 --> 00:17:14.066
in the red blood cell is more than one
third of its diameter.

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00:17:14.066 --> 00:17:17.102
For example,
this cells that I'm showing with a cursor,

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00:17:17.269 --> 00:17:20.272
or here either at the higher power.

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00:17:21.774 --> 00:17:24.610
So, hyperkalemia is obviously associated

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00:17:24.610 --> 00:17:27.946
with decreased hemoglobin content
within the red blood cell.

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00:17:28.414 --> 00:17:32.584
And as we've already discussed, it can be,
commonly seen in iron deficiency

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00:17:32.584 --> 00:17:35.587
and thalassemia.

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00:17:36.455 --> 00:17:38.957
And more difficult pattern to recognize

283
00:17:38.957 --> 00:17:42.594
is what we call
dimorphic population of red blood cell.

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00:17:43.395 --> 00:17:46.331
In this case, one can appreciate

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00:17:46.331 --> 00:17:49.334
that there's
two different subsets of red blood cells.

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00:17:49.535 --> 00:17:51.870
Some of them

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00:17:51.870 --> 00:17:56.442
with a yellow mark
are smaller with a larger central pallor.

288
00:17:56.442 --> 00:18:00.913
So this is what we call micro acidic hyper
chromic red blood cells.

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00:18:01.647 --> 00:18:02.448
The others

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00:18:03.449 --> 00:18:04.249
are marked with

291
00:18:04.249 --> 00:18:08.487
below have normal size
and normal amount of hemoglobin.

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00:18:08.487 --> 00:18:11.490
So that would be normal
and normal. Chronic.

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00:18:11.890 --> 00:18:13.725
So this pattern usually represents

294
00:18:13.725 --> 00:18:17.196
that we have two different subsets
of red blood cells.

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00:18:17.996 --> 00:18:19.932
One of the subset can be from a patient.

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00:18:19.932 --> 00:18:23.602
For example if one has iron deficiency
and they have micro

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00:18:23.836 --> 00:18:26.839
hyper chromic red blood cells
and they get transfused,

298
00:18:27.372 --> 00:18:31.410
the transfused portion
will show, more normal morphology.

299
00:18:32.311 --> 00:18:36.815
Sometimes you can also,
manifest clonal hematopoiesis.

300
00:18:36.815 --> 00:18:40.719
So the bone marrow has several clones
that produces slightly different red

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00:18:40.719 --> 00:18:42.087
blood cells.

302
00:18:42.087 --> 00:18:44.723
Some congenital anemia can also give,

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00:18:44.723 --> 00:18:47.793
this look and other conditions as well.

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00:18:48.827 --> 00:18:52.664
An interesting observation
that we can correlate with the Murphy

305
00:18:52.664 --> 00:18:59.238
population is the m CV graph
that comes from the hematology analyzer.

306
00:19:00.038 --> 00:19:04.109
If you look at the median number
produced by the analyzer,

307
00:19:04.276 --> 00:19:07.946
it usually does not represent
the dimorphic population

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00:19:07.946 --> 00:19:12.484
as it will give us the mean,
the mean value.

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00:19:12.951 --> 00:19:18.123
However, if we look at the graph that is
usually it's usually has one peak.

310
00:19:18.357 --> 00:19:20.859
In this situation we have two peaks.

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00:19:20.859 --> 00:19:25.164
Each peak will correspond
to a certain population here.

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00:19:25.164 --> 00:19:26.431
For example, this peak.

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00:19:30.035 --> 00:19:32.604
Corresponds to the micro erythrocytes.

314
00:19:32.604 --> 00:19:35.607
And this one most likely represents
not acidic

315
00:19:35.707 --> 00:19:38.710
erythrocytes.

316
00:19:42.581 --> 00:19:42.948
Well,

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00:19:42.948 --> 00:19:45.951
having discussed all of this,
let's jump to the challenge.

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00:19:46.385 --> 00:19:50.322
So our first challenge is
why don't we call it sends you this image

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00:19:51.056 --> 00:19:54.259
because they see
some potential abnormalities.

320
00:19:54.259 --> 00:19:56.695
So they just want to consulted with you.

321
00:19:56.695 --> 00:19:58.597
What is the problem here.

322
00:19:58.597 --> 00:20:02.334
Maybe the patient has increased AGM
the target red blood cells.

323
00:20:03.502 --> 00:20:06.505
Perhaps the patient has increased
overall proteins

324
00:20:06.738 --> 00:20:09.741
in their serum.

325
00:20:09.908 --> 00:20:14.346
Maybe there is an immunoglobulin
that precipitates at room temperature.

326
00:20:14.680 --> 00:20:17.749
Or perhaps we are in the wrong
part of the smear.

327
00:20:21.420 --> 00:20:24.523
So answer D
would be the most likely answer.

328
00:20:27.226 --> 00:20:30.162
As we look at the white blood cells,

329
00:20:30.162 --> 00:20:33.532
the morphology is really difficult
to appreciate,

330
00:20:33.899 --> 00:20:37.903
which is indicative of us being
in the thick parts, a part of the smear.

331
00:20:38.470 --> 00:20:41.907
The distribution of the red blood cells
with a lot of overlapping

332
00:20:42.174 --> 00:20:45.277
is also compatible
with, thick part of the smear.

333
00:20:45.811 --> 00:20:49.848
The main distractor in this situation
is rule of formation, right?

334
00:20:50.182 --> 00:20:54.319
Because if you think that it's
not the thick part of the smear

335
00:20:54.319 --> 00:20:58.690
that the distribution of red blood
cells will be most compatible with flow.

336
00:20:58.690 --> 00:21:00.459
And as we talk, as we said,

337
00:21:00.459 --> 00:21:05.297
rule low is due to increased,
overall proteins in the serum.

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00:21:08.033 --> 00:21:09.568
Challenge to

339
00:21:09.568 --> 00:21:13.572
let's look at the smear from a patient
with a history of iron deficiency

340
00:21:13.805 --> 00:21:16.608
and try to predict what the CBC

341
00:21:16.608 --> 00:21:19.611
parameters that come from
the analyzers will be.

342
00:21:20.145 --> 00:21:26.118
So the first question,
if we look at MCV mean corpuscular volume,

343
00:21:26.785 --> 00:21:29.254
would we expect it to be normal

344
00:21:29.254 --> 00:21:32.257
decreased or increased.

345
00:21:33.792 --> 00:21:35.827
And the correct answer is decreased.

346
00:21:35.827 --> 00:21:38.664
As you remember MCV corresponds

347
00:21:38.664 --> 00:21:41.667
to the size of the red blood cell

348
00:21:41.867 --> 00:21:43.635
in our situation,

349
00:21:43.635 --> 00:21:47.172
as we use lymphocyte as a reference guide,
quite

350
00:21:47.172 --> 00:21:49.274
a lot of red blood
cells are actually smaller

351
00:21:49.274 --> 00:21:53.111
than the nucleus of this lymphocytes,
consistent with micro ptosis.

352
00:21:53.345 --> 00:21:56.048
So MCV will be decreased.

353
00:21:56.048 --> 00:21:58.417
Next question what about MSI?

354
00:21:58.417 --> 00:22:00.852
Each and MSI.

355
00:22:00.852 --> 00:22:03.522
Would that be normal decreased

356
00:22:03.522 --> 00:22:06.525
or maybe increased.

357
00:22:07.059 --> 00:22:09.695
And the correct answer is also decreased.

358
00:22:09.695 --> 00:22:12.464
And CRH and Amca actually measure

359
00:22:12.464 --> 00:22:15.534
the amount of hemoglobin
without a red line. So

360
00:22:17.269 --> 00:22:21.073
and in this situation
our red blood cells are very pale.

361
00:22:21.073 --> 00:22:24.042
It means that we are dealing
with hyperkalemia,

362
00:22:24.309 --> 00:22:28.780
which corresponds to decreased MSI
and or ehm CHC.

363
00:22:29.881 --> 00:22:30.349
All right.

364
00:22:30.349 --> 00:22:35.487
Next parameter red blood cell distribution
with do we expect it to be normal

365
00:22:35.987 --> 00:22:38.990
decreased or increased.

366
00:22:40.625 --> 00:22:43.628
And the answer
yes is going to be increased

367
00:22:43.628 --> 00:22:47.065
because the smear shows that the red blood
cells,

368
00:22:47.999 --> 00:22:53.171
have quite, 
quite a different size to them.

369
00:22:53.171 --> 00:22:55.907
We have very small forms.
We have larger forms.

370
00:22:55.907 --> 00:22:59.411
So the distribution of those shapes
of those sizes,

371
00:22:59.611 --> 00:23:02.881
to be precise, is going to be way
higher than we expect to.

372
00:23:02.881 --> 00:23:05.617
The RTW is increased.

373
00:23:05.617 --> 00:23:07.652
And the last question,

374
00:23:07.652 --> 00:23:11.323
if we look at the raw data
of the red blood cell volume curve,

375
00:23:12.190 --> 00:23:17.562
would we expect it
to be one peak curve or two peak curve?

376
00:23:20.532 --> 00:23:20.766
And the

377
00:23:20.766 --> 00:23:24.169
answer
we're probably going to see multiple peaks

378
00:23:24.536 --> 00:23:27.773
because as you see here, we are dealing

379
00:23:27.939 --> 00:23:30.942
with a dimorphic population.

380
00:23:31.276 --> 00:23:34.713
Many of those red blood
cells are going to be micro acidic

381
00:23:35.614 --> 00:23:38.483
with a subset of them being normal acidic.

382
00:23:38.483 --> 00:23:41.720
So multiple peaks
is probably the most likely pattern.

383
00:23:43.255 --> 00:23:44.456
Okay.

384
00:23:44.456 --> 00:23:44.823
All right.

385
00:23:44.823 --> 00:23:47.893
To summarize what we see
in this peripheral blood smear is

386
00:23:48.360 --> 00:23:50.896
there is micro acidic hyper
chromic anemia.

387
00:23:50.896 --> 00:23:55.033
Of course we if we can show that there's
decreased hemoglobin with increased

388
00:23:55.033 --> 00:23:59.070
and dissociate ptosis and dimorphic
red blood cell population.

389
00:24:00.071 --> 00:24:03.041
And I've noticed that polychrome
is not significant.

390
00:24:03.909 --> 00:24:08.213
So, how can we translate it
into the clinical, facet?

391
00:24:08.547 --> 00:24:10.682
What can we say about this patient.

392
00:24:10.682 --> 00:24:13.685
So because we know that the patient
has a history of iron deficiency,

393
00:24:14.186 --> 00:24:17.689
this patient's anemia is most likely due
to energy efficiency.

394
00:24:17.689 --> 00:24:23.361
And as we said,
micro doses and hyperkalemia quite, often

395
00:24:23.361 --> 00:24:27.632
seen in error deficiency,
the patient has been likely transfused.

396
00:24:27.833 --> 00:24:31.570
That would explain why the population,
why the,

397
00:24:31.570 --> 00:24:35.173
why there's that,
de morphic pattern to the smear.

398
00:24:35.507 --> 00:24:38.376
And also it's very unlikely
that the patient is effectively

399
00:24:38.376 --> 00:24:43.582
treated with iron because we do not see
much of the recovery bone marrow

400
00:24:43.748 --> 00:24:47.652
by virtue of very low number
of polychromatic like red blood cells.

401
00:24:48.753 --> 00:24:49.087
All right.

402
00:24:49.087 --> 00:24:52.224
Just to summarize, today we talked about

403
00:24:52.224 --> 00:24:55.227
how to prepare good, beautiful Bosnia.

404
00:24:55.694 --> 00:24:59.531
We talked about most common causes
of abnormal red blood cell distribution.

405
00:25:00.232 --> 00:25:04.569
And we also touched base on red blood
cell changes in size and color.

406
00:25:04.936 --> 00:25:05.737
Thank you so much.