00:01
Microcytic anemia is here.
00:03
We’ll take a look at alpha
and beta thalassemias.
00:05
Keep in mind now that we are dealing
with the globin portion of hemoglobin.
00:10
What do I mean by that?
Well, when you’re dealing with hemoglobin,
what we looked at, microcytic anemia
as dealing with the heme portion.
00:17
So therefore, we dealt
with iron studies, right?
And by that, the big prototype
for microcytic, of course,
is being your iron
deficiency anemia.
00:27
And we also looked at anemia of chronic
disease which deals with chronicity.
00:31
And we also looked
sideroblastic anemia.
00:33
Remember, in all 3 of those microcytic
anemias, we looked at iron studies
and each one was a
tad bit different.
00:40
Once you’ve completely mastered the iron
studies for those 3 microcytic anemias,
it is only then that
you have permission
to come into your thalassemias
and dealing with the globin.
00:50
Is that clear?
Okay.
00:52
So here, that’s difficult for us
to control the genes, isn’t it?
Especially when there is mutation of,
and hopefully the type of genes that we
have inherited from our parents and such,
gave us the right genes so
that we can transition from
the normal fetal hemoglobin
to our adult hemoglobin.
01:09
Now what’s really convenient
about the name fetal and adult
is the first letter of
each one of those words.
01:16
F – fetal.
01:18
Therefore, we have hemoglobin F.
01:20
Now, what you will have to memorize then
is the type of genes that are
comprising your fetal hemoglobin.
01:29
If you want, you might want to use --
Well, you have alphas and
you have “gugu gaga”.
01:34
What does that mean?
That means your gamma if that helps you.
01:37
So alphas and gammas,
maybe “go gugu gaga”.
01:40
And then as an adult, “A.”
Use the A and
that’s hemoglobin A
And that will be A’s and B’s,
meaning to say alphas and betas.
01:47
Okay, keep those mind.
01:48
We have a few more that we have
to go through as we proceed.
01:51
Now, our topic here brings
us to alpha thalassemia.
01:55
I don’t care what kind of
hemoglobin that you have,
hemoglobin A, hemoglobin A2, hemoglobin
F, hemoglobin S, hemoglobin C,
so on and so forth.
02:02
Every single one of those of hemoglobins
have an alpha, alpha, alpha in them.
02:06
Keep that in mind,
that becomes important
for us later on
when we do a type of electrophoresis
called hemoglobin electrophoresis.
02:13
Next,
well, we have four alleles
of alphas on each gene.
02:20
What does that mean?
I want you to take a look at the
bottom portion of this picture here
and you'll notice that there are four.
02:27
And by that, we mean that you get
two from mama and two from papa.
02:31
So we have a total of 4.
02:33
What are going to do?
We are going to do target practice.
02:36
Ready?
Bring out your gun.
02:38
You knock out one alpha, that gives
you one kind of alpha thalassemia.
02:42
It’s called silent.
02:45
Next,
knocked out two, that’s
alpha thalassemia trait.
02:51
Take the T in trait and then know that
you knocked out two alpha alleles, T and T.
02:57
Let’s stop there for now
and as you can imagine,
you’re going to knock out
each one of these alphas.
03:02
How many do you have total?
Four,
which means that technically you can have
four very variants of alpha thalassemia.
03:09
Is that clear?
Once again, what about these hemoglobins
where every single hemoglobin,
the once that are important
for us, ladies and gentlemen,
will be hemoglobin A,
hemoglobin A2 and hemoglobin F.
03:21
That’s what we’re going
to be dealing with here.
03:23
The reason we are not going
to work with hemoglobin S,
what category of anemia
are we doing here?
Good,
Microcytic.
03:31
Where do you think
hemoglobin S belongs to?
Tell me about hemoglobin S?
That’s sickle cell.
03:37
Isn’t that hemolysis?
There is no hemolysis here in
microcytic anemia, well, in general.
03:44
Okay, but when you think
massive hemolytic anemias,
such as sickle cell, that
comes in our normocytic, okay?
So that discussion of sickle
cell is not going to even be had
here in this section for microcytic.
03:57
Let’s continue.
03:58
There are two alpha
globin genes, as I said,
on chromosome 16 from each
parent for a total of four alleles.
04:06
Let's continue.
04:07
So what are we going to do?
Nice little table here for you to
knock out each alpha, alpha, alpha.
04:12
And as we do so,
I’m going to give you the important
associations and symptoms
and, really, epidemiology
of your patient.
04:22
And if you have understood those three
things about the alpha thalassemias,
you’re in fantastic shape.
04:28
First, if you knock out one alpha,
that is going to be silent.
04:33
And so therefore, clinical
manifestation asymptomatic, let it go.
04:37
Clear?
You’re not going to be tested on
things that are asymptomatic.
04:41
If the patient is not going to suffer,
then the patient is not going
to come into the clinic.
04:46
Know about it,
know that it exist
and please don’t get confused
with silent and trait.
04:52
That I beg of you.
04:53
Many students end up doing that.
04:55
I asked them about two and they’ll
tell me silent and that’s not true.
04:59
So T means two,
T means trait.
05:03
Do not confuse that with silent at all.
05:05
Now let’s move on
to trait though.
05:08
Now with trait, let me show you how
to interpret what I have given you.
05:11
Very important in the second row here
for you to interpret the genotype
because it actually tells you of what
kind of ethnicity, believe it or not.
05:19
Okay.
05:20
So second row,
the first genotype pattern
that you see there,
you see two dash lines together, a slash
and then two Greek alpha symbols, okay?
And what that represents is
that you have two alleles
that are missing
from the same gene.
05:40
Same.
05:40
In biochemistry, when something
is missing from the same,
the pattern that you see
there is called cis.
05:46
So if you want cis, same
and by cis, it’s C-I-S.
05:52
Correct?
So here, the cis pattern of
alpha thalassemia trait, unbelievably,
do you have any idea as to
what population this would be?
Good,
This would be more
about the Far East.
06:05
And more about Chinese, and that type of
population when you have cis pattern.
06:09
Unbelievable, right?
Next, by definition, what does trait mean?
Two alleles that have gone
awry or not missing, mutated.
06:18
In the second pattern that
you see here for trait,
you have one allele missing
from each side of the slash.
06:25
So that means, one
allele from the mother
and one allele from the father
is missing for a total of two.
06:31
This type of pattern in
biochemistry is known as?
Good.
06:35
Trans pattern.
06:36
So the trans pattern
is another ethnicity.
06:39
And this is more likely
to be found in African.
06:42
Is that clear?
So that is how important it is for
you to know the actual pattern
of the alleles that are missing from that
particular gene for alpha thalassemia trait.
06:51
Okay, now,
at rest, the patient most
likely will be asymptomatic.
06:55
However, upon exertion,
then what happens?
Well maybe at this point, the
hemoglobin is a little compromised
and is not able to properly
provide the oxygen
that is required for
normal activity.
07:08
Is that clear?
There might be mild anemia.
07:11
Once again, Asia and by Asia, you
might be thinking about Malaysia.
07:15
You might be thinking Singapore,
the Far East - cis pattern.
07:20
Trans – African.
07:22
Let’s go into another type
here of alpha thalassemia.
07:24
Now things get a little bit
more dangerous, it really does.
07:28
So I told you earlier that
every single hemoglobin
relevant to us right now has alpha
allele 2 and an alpha globin, right?
And the three major ones
that you want to know here,
hemoglobin A, hemoglobin A2 and
then hemoglobin F (fetal).
07:44
Let’s go into now the
genetic patterns.
07:46
I will say it, introduce them.
07:48
Hopefully, you know it and
then we’ll keep reinforcing.
07:51
We said that as a
fetus, what is it?
Alpha and gamma.
07:53
All jokes aside, okay?
Alpha and gamma.
07:56
Hemoglobin A will be A’s and B’s
and that will be alphas and betas.
07:59
And then you have to know hemoglobin
A2 which is alpha and delta.
08:02
Is that clear?
You have to know that and
I’ll tell you why later.
08:06
Now to begin, if you
have HbH disease,
this is a hemoglobin that is
going to be produced in excess.
08:13
Because take a look at how many
alpha alleles you're missing here.
08:17
You have three dash lines total.
08:19
You’re missing three alpha alleles.
08:21
That’s major.
08:22
By that, I mean that
is devastating.
08:25
Meaning to say that you’re not going
to produce too much hemoglobin A.
08:28
You can’t even produce
too much hemoglobin F,
nor can you produce too
much hemoglobin A2
because each one of them
had alpha, alpha, alpha.
08:35
And you’re missing three alleles
from both of the genes in total.
08:40
This is not a good situation.
08:42
This is not a good situation.
So what does the body do?
Well, remember the body always find to
compensate, compensate, compensate.
08:47
What are we talking about here?
Alpha thalassemia, not beta.
08:51
Why am I bringing that up?
Because if you start losing the
alpha, guess what the body does?
The body is very resourceful,
at least trying to be.
08:58
And so what does it upregulate?
You need that hemoglobin A.
09:02
What does that hemoglobin A mean?
Alphas and beta.
09:05
Clear?
So if you start losing your alpha, what
do you think the body is going to do?
Upregulate beta, beta, beta.
09:13
Unfortunately, once you start
losing three alpha alleles,
your body starts producing more betas.
09:19
And when four of these betas,
which should never have a pattern
of beta-beta, beta-beta, right?
It should be alphas and betas.
09:25
But if you have 4 betas put together
and aggregating or precipitating,
this then forms a completely different
pathologic hemoglobin called HbH.
09:35
You’ve heard of HbH disease,
what you’ll have to do
please is memorize four beta
that you’re forming with three alphas
missing, then forms hemoglobin H.
09:46
Now, what you’ll have to do later on is memorize
another one called hemoglobin Bart’s.
09:49
We’ll do that later,
step by step by step.
09:52
Here, you’re going to have
either intermediate at best
to severe chronic anemia.
09:59
Stop!
What does that mean?
If over a period of time
you have chronic anemia
and end up forming a weird or bizarre
hemoglobin, where are you right now?
What do you mean where are you?
You’re in the RBC, right?
And you formed a weird
hemoglobin like an HbH,
this is unrecognizable by the body.
10:18
The RBCs then rendered as
being an alien or an invader.
10:23
So that’s interesting.
10:25
So where is this RBC going to go?
Where is the grave site of an RBC?
Good.
10:29
The spleen, right?
But if you have a bizarre HbH in your RBC,
you’re going to be transported
to the spleen like that.
10:38
And over a long period of time, chronic,
when you start destroying your RBCs, guess
what that patient is going to have?
You tell me.
10:44
This is the same stuff that you’ve
been learning for years now.
10:47
This is extravascular hemolysis.
10:49
The spleen is destroying your RBC.
10:52
They are going to destroy your hemoglobin.
10:53
What are you going to
release into circulation?
Good.
10:56
Unconjugated bilirubin.
10:57
This unconjugated bilirubin
will give you what color?
Yellow jaundice or icterus
around the eyes or mucosa.
11:04
And you end up having what kind
of stones in the gallbladder?
Good.
11:07
Pigment stones.
11:08
Is that clear?
Interesting, isn’t it?
Do you see as to how big, big, big
time it is for you to know HbH disease
and the fact that you’re
missing three alleles?
Look how much of a difference it makes you
go from two to three missing alleles.
11:21
And then what about 4?
My goodness.
11:23
If you’re missing four alleles,
unfortunately the fetus is dead.
11:28
So you’re looking at an intrauterine
death, that’s unfortunate.
11:31
And the reason for that is, well,
you can’t even form hemoglobin F.
11:35
Can you?
You can’t form any hemoglobin
because all alphas are not present.
11:39
So this is more or less
hydrops fetalis, anasarca.
11:42
There’s going to be massive, massive what’s
known as high output cardiac failure.
11:46
No hemoglobin in the fetus.
11:49
Do you see how significant that is, okay?
All four.
11:52
And for the most part, here you
go, here's your presentation.
11:54
If you know this table well, you’ve
understood alpha thalassemia.
11:58
Let us now fill in the gaps.