The topic now is Pulmonary Hypertension.
As simple as it may seem, it's the fact that
you have to dive into quite a bit of detail
and the reason for that is because there has
been so much research on this over the years
because of sequelae of right-sided heart failure,
cor pulmonale and death, that now, at this
point, we know how to, first, identify normal,
completely analyze the pathology through WHO
classifications and every single class you
will have to know, there's four of
them and then management.
To begin with, Pulmonary Hypertension, defined
as, well, the big one here that you want to
know is greater than 25mmHg at rest. So, how
would you go about, perhaps, measuring this?
How about a right heart catheterization?
So, here, when you catheterize the right side
and you get from the right ventricle and moved
up to you pulmonary artery. Alright, can you
picture that? Good. Right ventricle, you have
a pressure of approximately 2, very passive,
but then you start getting to pulmonary artery,
the pressure increases to approximately 10,
but at rest, if you find that the pulmonary
arterial pressure is greater than 25, guaranteed,
your patient has Pulmonary Hypertension.
But what caused this? Well, let's continue.
The Pulmonary Hypertension may result in arteriosclerosis.
What does that mean? Imagine when there is
an increase in tension, then what's going
to happen? Is this arteriolar is this
an arteriole? That is your first question,
isn't it? Always. Whenever you deal with blood
vessels, you want to try to break it up into
the arteries and arterioles and then that
will then give you the respected diagnosis.
Here, it is arteriosclerosis, most likely,
hyaline type. Then you have medial hypertrophy,
intima fibrosis of pulmonary arteries and
by that we mean that, here is my intima, there
is my media and so, those are two major layers
of the blood vessels that are being affected.
There will be medial hypertrophy and intimal
fibrosis, causing what, please? Increased
narrowing of the pulmonary arteries. Now,
the clinical course includes severe respiratory
distress. Whenever there is problem with the
pulmonary artery and there is increased resistance
or pressure you are then going to feel this
in the right ventricle resulting in right
ventricle hypertrophy (RVH) and unfortunately,
getting into severe failure, cor pulmonale.
Now, this is what I was referring to earlier,
with the WHO classification of Pulmonary Hypertension.
I am going to give you a brief description
for every single class that you absolutely
must know because the way that you approach
this or clinical vignettes, I will show you,
will be a class by class.
Begin with Class I. Now, we
will begin, chronological order, by
Class I. Clinically however, you will begin
this a little bit different. Why? Keep it
in mind. If it is familial, very difficult
to sometime figure this out immediately, isn't
it? So, it is easier to actually perform certain
tests that are a lot faster to rule things
out, Class II, III and IV, so then you would
highly suspect Class I. Let’s put it that
way. Once more, this is
familial. What does that
mean to you? Once upon a time, known as your
primary Pulmonary Hypertension, get away from
that, idiopathic pulmonary arterial hypertension
is a much better descriptive name. Majority
of these will be familial. Okay. That means
that there is no secondary effect. There is
no hypoxia in which there is there's pulmonary vasoconstriction.
There is no heart disease causing pulmonary
arterial hypertension and there is no thromboembolic
episode, chronically, resulting in increased
pulmonary hypertension. Right? This is familial.
So, it is actually faster and more effective
to rule out, and we will go through each one,
I,II,III and IV, and then to see as to whether
or not Type 1, in fact, is your proper
diagnosis. Now, what do you want to
know about familial? Oh, it's an inactivation
mutation of a particular gene called your
bone morphogenic protein-receptor-2. Know
the entire name. I'm sorry, you must. The
abbreviation is BMPR2. R is Receptor. BMP
is bone morphogenic protein. What does it
do? It normally inhibits the vascular smooth
muscle proliferation and so, therefore if
you have such a mutation, where you inactivate
the gene, which normally controls the proliferation,
where am I? Blood vessel. And so therefore,
if you remove this suppressor, you have increased
proliferation, end up having pulmonary arterial
hypertension. Prognosis, poor.
Okay, now, important causes include drugs
such as amphetamines, cocaine, connective
tissue disorders, HIV, portal hypertension
and congenital heart disease and schistosomiasis.
If I were you, I would take a look at each
one of these differentials. How do you rule them
out? Your patient is an addict. Your patient
has scleroderma. Do you remember a topic when
we had scleroderma and it was the continuum
of fibrosis that you are paying attention
to and it’s a fact that we had crust and
we had systemic type and so, therefore, if
it is fibrosis that you are dealing with,
then it is the fact that you are, at first,
having non-specific changes and then your
usual interstitial pneumonitis which we as
pathologist, are then going to describe it
as. Are we clear? Okay.
HIV, immuno-compromised. How do you rule out
something that’s causing liver injury? Check
out your liver function test. Are we clear?
That’s important. Rule things out.
Congenital heart disease. What kind of a test
might you want to perform on a patient to
rule out congenital heart disease? Good. A
Cardiac MRI or a Cardiac Magnetic Resonance
test. Clear? Schistosomiasis.
Well, that might be history.
Maybe patient came from North Africa, Egypt
specifically. That type of region where the
patient might have been exposed
to Schistosoma. That’s Class I.
Move on to Class II, please. Now Class
II, the way that I have thought about this
and the way that maybe might help you, Class
II, is there any way that you could
possibly think of your heart having two sides?
Would that perhaps help you? Okay. The
reason I say that is, Type 2, or Class II,
excuse me, type of Pulmonary Hypertension
is going to be trouble in your pulmonary blood
vessels secondary to the heart, secondary
to the heart. Are we clear? So, pay attention
to that and so, if it helps you to think of
the heart as having two sides. And
let’s say that you have right
ventricle hypertrophy and you have to start
on the left side. So, if you have left-sided
heart failure, then you might back up into
pulmonary veins. Right? You further back
up into pulmonary capillary, pulmonary artery.
So, therefore, here, the Pulmonary Hypertension
was due to a left ventricle heart disease.
That’s Class II. How would you rule this
out? Maybe something as simple as E & E. What
are these? Echocardiogram, EKG. Alrighty?
Okay, let’s go on to talk about Class III.
Now, Class III type of Pulmonary Hypertension
and all of these, ladies and gentlemen, you
really must know in detail. Okay. So, I am
not wasting your time. With Class III, it
is actual lung disease that took place primarily.
In Type 1, the majority of a more familial,
but then you also had drugs and other habits
or diseases, but then here, if it’s Type
3, it is primary lung parenchymal disease
of all of which COPD would be the most common.
Okay. Now, along with COPD, say that your
patient is suffering from hypoxia, now, what’s
the state of your pulmonary blood vessels?
It is called, remember, one of the big exceptions,
when there is hypoxia in which blood vessels
constrict would be hypoxic vasoconstriction
and nowadays, in current day practice, your
patients very well might be obese and
so, therefore, you are thinking about obstructive
sleep apnea, and then, of course, high-altitude
residence. Here once again, because of low
barometric pressure, thus resulting in decreased
FiO2, you find your patient having hypoxic
vasoconstriction. That’s Class III.
Then we go into Class IV. Class IV, if it
helps you any further, you need
to remember, this is a thromboembolic
disease causing a Pulmonary Hypertension.
So, we had a discussion about PE and all the
different ways in which you might then develop
a PE. The most common of which would be your
DVT, right? But, keep in mind though that
you can also have embolization from different
sources. We talked about the amniotic fluid
emboli, we talked about the gas emboli, the
fat emboli, all depending as to the situation.
Anyhow, so there is a thromboembolic disorder
and what I was trying to say is, if you
want to perhaps think of four and how would
you say that perhaps in Latin, it would
be tetra. Alright, it's tetra. Think of it as
being thromboembolic. So, give yourself whatever
you need to do to distinguish Class I through
Class IV. Try to do it now and get an
understanding and keep coming back
and keep applying test. So, let's
do that now, once again.
We ruled out our heart issue if you had maybe
normal EKG and normal Echo. That’s good
enough for you right now. If it’s Class
III, well, you take a look at the chest X-ray
and say that this was pneumonia, alright,
or it was COPD, you would expect there to
be quite a bit of marking on your X-ray, wouldn’t
you? So, this would then obviously tell you
that I have a serious problem with my lung
primarily and therefore causing vasoconstriction
or perhaps increased Pulmonary Hypertension.
And with Class IV, you tell me, what would
be effective in terms of ruling out, perhaps,
something like a DVT and such? You are thinking
about a VQ scan. okay. A VQ Scan. Remember,
you don’t want to get into a PE. If you
get into a PE then it will be a spiral
CT, right? So, a VQ scan will perhaps help
you for ruling out, effectively, a chronic thromboembolic
disease. Now, there are multifactorial.
Some would say that this is a Class V, whatever.
Here you go. Hematologic, systemic,
metabolic disorders. These are the other ones
that really don’t fit into Class I through
Class IV. And the reason that this is important
is now the approach, the approach of Pulmonary
Hypertension. The Pulmonary Hypertension,
it's much easier for you to rule out effectively
Class II. What is that? Where is my problem?
How is that causing Pulmonary Hypertension?
The heart. Secondary Pulmonary Hypertension.
Next. Class III. How would you effectively
rule that out? A relatively unremarkable chest
X-ray. And then Class IV, maybe a normal VQ
scan. You rule out II, III and
IV. What are you really left with right now?
Good. Class I. And so, then you start thinking
about your genes such as BMPR2, Bone Morphogenic
Protein-2, maybe drugs and so on and so forth.
Are we clear?
So, this is “Pulmonary Hypertension”,
Classes I through IV. I would be very, very
familiar with that table.