19
700
When pipes get
clogged
, it is usually
because we’ve dumped something
down the drain that shouldn’t be
there—a greasy mass or a hairball.
Sometimes, pipes get blocked when
something is growing inside them
(tree roots, for example), trapping the
normal sludge coming through (see top
photo). In
arteriosclerosis
, the walls
of our arteries become thicker and
stiffer, and
hypertension
results. In
atherosclerosis
, the most common
form of arteriosclerosis, small patchy
thickenings called
atheromas
form that
can intrude into the vessel lumen, making
it easy for
arterial spasms
or a
roaming
blood clot
to close the vessel
completely.
Although all arteries are susceptible to
atherosclerosis, those most often affected
are the aorta and the coronary and carotid
arteries.
Onset and Stages
Atherosclerosis indirectly causes half of
the deaths in the Western world. How
does this scourge of blood vessels come
about? The development of a full-blown
atheroma is believed to occur in several
stages.
1. The endothelium is injured.
According to the
response to injury
hypothesis
, the initial event is damage
to the tunica intima caused by
bloodborne chemicals, hypertension,
components of cigarette smoke, or
viral or bacterial infections. Researchers
suspect that almost any type of
chronic infection—even periodontal
problems—could set the stage for
atherosclerosis. How a bacterium such
as
Chlamydophila pneumoniae
(found
in some plaques) triggers atheroma
development is not completely
understood, but we know that any
injury to the endothelium sets off the
alarm summoning the immune system
and the inflammatory process to repair
the damage.
2. Lipids accumulate and oxidize in
the tunica intima.
Injured endothelial
cells release chemotactic agents and
growth (mitosis-inducing) factors,
and begin to transport and modify
lipids picked up from the blood,
particularly low-density lipoproteins
(LDLs) that deliver cholesterol to
tissue cells via the bloodstream. This
accumulated LDL oxidizes in the hostile
inflammatory environment. This not
only damages neighboring cells, but
also acts as a chemotactic agent,
attracting macrophages. Some of these
macrophages become so engorged with
LDLs that they are transformed into
lipid-laden
foam cells
. Accumulating
foam cells form a
fatty streak
, the first
visible sign of an atheroma.
3. Smooth muscle cells proliferate and
a fibrous cap forms.
Smooth muscle
cells migrate from the tunica media
and deposit collagen and elastic fibers,
thickening the intima and producing
fibrous lesions with a core of dead
and dying foam cells called
fibrous
or
atherosclerotic plaques
. At first the
vessel walls accommodate the growing
plaque by expanding outward, but
eventually these fatty mounds begin
to protrude into the vessel lumen,
producing full-blown atherosclerosis
(see bottom photo).
4. The plaque becomes unstable.
As the plaque continues to enlarge,
the cells at its center die. Calcium
is deposited, and collagen fiber
production by smooth muscle cells
declines. Now called a
complicated
plaque
, it is unstable and prone to
rupture.
Consequences
The presence of plaques stiffens artery
walls and results in
hypertension
. The
increased pressure stresses the plaques,
making them even more unstable.
Plaques also constrict the vessel and cause
the arterial walls to fray and ulcerate,
conditions that encourage blood sludging
and backup, platelet adhesion, and
thrombus formation.
Two other factors also promote
thrombus formation: (1) Endothelial cells
damaged by plaques release less nitric
oxide and prostacyclin—chemicals that
would otherwise promote vasodilation and
inhibit platelet aggregation. (2)
Lipoprotein
(a)
, an altered form of LDL found in some
individuals, inhibits fibrinolysis by competing
with plasminogen.
Plaque formation increases the risk
of myocardial infarction, strokes, and
aneurysms, and is responsible for the pain
(angina) that occurs when heart muscle
is ischemic. We often think of large
complicated plaques as being the culprits
for heart attacks and strokes, but plaques
of any size may rupture and form a clot.
At least one-third of all heart attacks are
caused by plaques too small to be seen
on traditional angiograms. They cause no
warning symptoms, and victims appear
perfectly healthy until they drop dead!
One goal of current research is to find
ways to identify these vulnerable plaques.
Risk Factors
Why are some of us so troubled by
atherosclerosis while others are seemingly
immune to its ravages? A large number
of interacting risk factors determine the
progress of atheroma development. Risk
factors include increasing age, male sex,
a family history of atherosclerosis, high
blood cholesterol, hypertension, cigarette
smoking, lack of exercise, diabetes,
obesity, stress, and intake of trans fats.
A growing body of evidence links
systemic inflammation with the formation
Atherosclerosis? Get Out the Cardiovascular Dra
¯ no
A
C L O S E R
LOOK
Top
A pipe clogged by accumulated
deposits.
Bottom
Atherosclerotic plaques
nearly close a human artery.
previous page 734 Human Anatomy and Physiology (9th ed ) 2012 read online next page 736 Human Anatomy and Physiology (9th ed ) 2012 read online Home Toggle text on/off