there's a history in your family of this disease,
you're more likely to get it as well.
Let's talk about pathogenesis—that is, the
abnormal physiology and anatomy that goes
in along with this disease. So here, we see
a little cartoon showing you one of these
early atherosclerotic plaques that can occur
even in children or in young adults and develop,
eventually, into big, thick inflammatory atherosclerotic
plaques. You can see that there is a thickening
of the endothelial layer. You can see that
there's also development of scar tissue with
a necrotic core, with dead cells in the center.
And these dead cells often contain lipids—that
is, LDL cholesterol—that macrophages (which
are a defense cell in the bloodstream, a white
cell) have come to try and capture and dissolve.
Unfortunately, they don't dissolve it, and
in fact, what it does is it kills these macrophages,
and that just increases the inflammatory process—the
scar tissuing—and increases the size of
the atherosclerotic lesion.
You can see that there's a fibrous cap overlying
this. When the fibrous cap is thick, the lumen,
or the channel of the artery, gets smaller,
but it doesn't rupture. When the fibrous cap
on top is very thin, it can rupture, blood
clot can form, and the artery can actually
occlude totally, resulting in infarction or
necrosis (death of tissue) downstream. And
you see, in this little cartoon, you can see
that the materials that are in the fibrous
cap, the infiltrating macrophages and also
lymphocytes that are drawn in by the inflammation.
And you can see that the epithelium on the
surface is still intact, but if the fibrous
layer (as I said before) is thin, that can
rupture, and a blood clot can form that can
cause infarction, or death of tissue, from
no blood flow getting through the obstruction.
So atherosclerosis usually starts as mild.
The endothelium (the thin layer on… in…
that's right on… next to the channel of
the artery) gets damaged. Factors such as
high blood pressure and cigarette smoke damage
the endothelium, and this allows the LDL cholesterol—often,
the oxidized form—to get underneath and
into the wall of the artery, where it starts
the inflammatory process. One advances to
moderate atherosclerosis, where the inflammatory
response, the white cells coming in, trying
to ingest the LDL cholesterol, dying, forming
a great stimulus to scar tissue formation
and further arrival of LDL cholesterol in
Finally, in the healing process, calcium salts
can occur, and actually, the artery can become
rock-hard for… almost with bone formation
and, of course, lots of scar tissue. The artery
loses elasticity, the channel narrows, and
blood flow is impaired. In the most severe
form, there is severe restriction of blood
flow through the artery. Often, this can lead…
this can make high blood pressure even worse,
and the, of course, increase in the blood
pressure can promote formation of more plaques.
And eventually it's even possible for an area
where the plaque ruptures and a blood clot
forms and the artery is totally obstructed.
And that's what happens in a heart attack,
or a myocardial infarction. Here, we see three
examples. You can see mild atherosclerosis
in the top, moderate in the middle, and very
severe at the bottom. The bottom one has lots
of calcification, lots of scar tissue. You
can also see the yellow color; that's from
the deposition of cholesterol in the artery
There are also sudden occlusions of the artery.
As I mentioned, it can happen when a plaque
ruptures, but it can also happen when there
is an embolus—that is, a blood clot that
forms somewhere in the heart. And I gave examples,
during the basic lecture, of blood clots forming
in the left atrium during atrial fibrillation.
Blood clots can also form on prosthetic, or
plastic and steel, heart valves. Sometimes,
in a rare circumstance, fat can actually get
into the bloodstream and embolize. Or air—particularly
during procedures or during some sort of trauma—air
can get in. And when any of those things block
an artery, no blood flow gets through, and
there is necrosis, or death of tissue. Remember
the term thrombus? That's a blood clot that
forms on a vessel wall: could be in the venous
side, can be on the arterial side, can be
in the left atrium. And when that thrombus
breaks off and flows in the bloodstream and
causes mischief somewhere downstream, it's
called an embolus. The diagnosis is made because
of signs of restricted blood flow in an area.
For example, if there had been a blood clot
in the left atrium that suddenly went to the
brain, the patient would have sudden symptoms
of a stroke. The therapy is aimed at restoring
blood flow. It can be done by removing the
clot, either surgically or with catheters
or by giving so-called clot busters, or drugs
that dissolve the blood clot.
Here is an example of atheroma under the microscope.