Welcome.
In the next set of slides and sessions,
we're going to talk about a very important cause of pathology,
that is atherosclerosis.
And the most common complication related to atherosclerosis,
which is infarction,
the death of tissues that are being now blocked
because of a vascular occlusion.
Atherosclerosis is going to be a major cause
of morbidity and mortality around the world.
Much more than 50% of people will ultimately die as a result
of coronary artery disease,
or stroke related to atherosclerosis.
So with that preface, let's get started.
Here's the roadmap.
And we're going to have a number of blocks after this
as we work our way through the various aspects of atherosclerosis.
We'll talk about risk factors,
we'll talk about how a plaque actually gets formed.
We will talk about how the plaque looks
and the complications related to that morphology.
It's not just simply a plaque.
But in fact, how it is assembled,
that will have implications for outcomes.
We'll talk about how we can diagnose and potentially treat atherosclerotic disease.
And then finally, we'll talk about complications.
That's our roadmap.
Lots of fun along the way.
First, an overview of atherosclerosis.
Now, what is atherosclerosis?
Let's start with your typical arterial wall.
And we're starting mostly with arteries
because atherosclerosis is typically
predominantly a disease of arteries.
Not a veins, although you can get venous atherosclerosis
under some circumstances.
You've learned in your basic anatomy
and your basic physiology,
how vessels are assembled,
there is an outer layer of loose connective tissue,
and fat, that's called the adventitia.
The next layer in is the media.
And it's largely composed of smooth muscle cells
with a little bit of extracellular matrix.
And that smooth muscle media
is going to be an important source of tone and integrity to the vessel wall.
So when I talk about tone,
it that smooth muscle relaxes,
the wall dilates.
If that smooth muscle contracts,
the wall constricts.
And we can control blood pressure in that way,
we can control flow into the tissues in that way.
The next layer in from the smooth muscle media
is going to be the intima.
And the intima usually has very little connective tissue.
And it's basically an endothelium sitting on a basement membrane,
and just a little bit of extracellular matrix.
That's the normal situation, and that's the normal vessel.
Now let's do atherosclerosis.
And in atherosclerosis, we have an artery
that has been narrowed by an atherosclerotic plaque.
Well, it still doesn't tell us what that's about.
But atherosclerosis,
the name is actually quite good.
It comes from the Greek,
the athero actually means gruels like
gruel as in porridge or oatmeal like
and the central core,
the atheromatous core and an atherosclerotic plaque is fat,
and necrotic debris,
old red cells, a whole variety things, it's kind of a mush,
and it looks a little bit like gruel,
hence that,
was the name that was given to it.
The sclerosis part is scarring.
So atherosclerosis is scarring, overlying gruel,
and that is the typical atherosclerotic plaque.
Now, sometimes we have more fibrous scarring in the fibrous cap,
composed of extracellular matrix and smooth muscle cells.
And sometimes we have less.
And sometimes we have a big old atheromatous core
with lots of necrotic debris and fat and cholesterol,
and sometimes not so much.
So the relative components of the fibrous cap versus atheromatous core
will also determine kind of the outcomes associated with atherosclerotic plaque.
Now, there are multiple players that are in here.
And this very broad kind of overview captures those.
So dysfunctional endothelium,
on the surface is going to be a major driver
for the production of atherosclerosis.
And we'll talk about that when we talk about risk factors,
and we talk about how a plaque is formed.
So endothelium over an atherosclerotic plaque, not normal.
It's an unhappy endothelium.
It's prothrombotic. It's pro-inflammatory,
it's dysfunctional.
We have recruited smooth muscle cells,
and the smooth muscle cells have come largely from the media,
they can also come from circulating precursors
and those smooth muscle cells
that are part of the atherosclerotic plaque and scar
are also important players in the process.
And the last important player in this are macrophages,
elements of innate immunity.
So, for many, many years,
we thought of atherosclerosis as a fat related disease,
a cholesterol driven process.
In fact, now we know that it's really largely driven
by innate immunity by macrophage activation and recruitment.
Okay, so we've got kind of the general feeling for
what an atherosclerotic gruel and scar plaque is all about.
So why is atherosclerosis so bad?
Well, in small vessels,
this is showing a coronary angiogram,
we have small vessel occlusion,
remember that plaque is growing, growing, growing in it is blocking blood flow.
So in a coronary and a small vessel,
maybe 50 60% of the vessel lumen
is blocked by the growth of this plaque.
And now we're not getting adequate flow into the distal vasculature.
So the two areas are indicating areas,
of narrowing in the coronary.
In larger vessels,
atherosclerosis can lead to abnormal endothelial cell function
leading to thrombosis,
but can also lead to the production of plaques,
which are friable,
they break up.
So what we're looking at here is an aorta.
Off to the left would be the head down to the right would be the legs.
And this lumen of the aorta is filled up with chromous,
friable,
thrombus,
platelets and fibrin
and inflammatory debris and necrotic debris.
And all of this is because of atherosclerosis,
that had led to very easily fragmented plaque
in the lumen of this large vessel.
Another complication associated with larger vessels as well
is that the recruitment of the macrophages
as part of the atherosclerotic plaque growth
is also going to lead to the production of proteases
that are going to degrade extracellular matrix of the media.
So we're looking at in an angiogram reconstruction.
Again, at the top would be the head
and at the bottom are going to be the legs
and there is this kind of bulbous dilation
just above the iliac bifurcation.
This is an abdominal aortic aneurysm
occurring as a result of the recruitment of macrophages
into the area of a growing atherosclerotic plaque
and those macrophages elaborating elastases
that break down the matrix and cause the wall to thin
and therefore dilate.
As we talked about, in our thrombosis
and hemostasis,
sessions,
that abnormal bulbous dilation
also causes aberrant flow
and as part of Virchow's triad, we'll get a thrombus in that.
So here's why atherosclerosis is so bad,
small vessels, we block them large vessels,
we get friable atherosclerotic plaque
and vessel wall destruction and aneurism.
With that, we've had our overview,
and I look forward to seeing you again
when we talk about all the details
related to the development of atherosclerosis.