ATHEROMATOUS PLAQUE
In those with a genetic predisposition to atherosclerosis and/or
persons who eat excessive quantities of cholesterol & other fats, large
quantities of cholesterol gradually become deposited beneath the intima at many
points in the arteries. Later these areas of deposits become invaded by fibrous
tissue, and then become calcified. The net result is the development of atherosclerotic
plaques that protrude into the vessels and either block or partially block the
blood flow
A very common site for the development of atherosclerotic
plaques is the first few centimetres of the coronary arteries possibly due to
exposure to stresses of turbulent blood flows.
Vascular Atheroma Types
§
May appear
on aorta by age of 10
§
Consist of:
i)
lipid laden
macrophages [foam cells]
ii)
lipid
filled smooth muscle cells
§
Grossly
appear as an area of yellow discolouration
§
Bulk of lipid
in form of cholesterol
§
Over time
may convert into fibrous plaques
Fatty
streak response-to-injury hypothesis:
INJURY to endothelium
secondary to increase in plasma LDL (ie cholesterol)
> 1) changes in surface characteristics of
endothelium
2) changes to circulating
monocytes
> increased adhesion of
monocytes to endothelium in arteries
> monocytes migrate
subendothelially
> monocytes convert
into macrophages
> macrophages take up
lipid [foam cells]
In a hypercholesterolemic state:
> large amounts of
lipid enter subendothelium
> fatty streaks
B]Uncomplicated atheromatous plaque
§
Advanced
lesion of atherosclerosis is called fibrous
plaque
§
Fibrous
plaques are grossly white in appearance
§
May
protrude into the lumen of the artery & compromise blood flow
§
Lesion
consists of:
i)
large
numbers of intimal smooth muscle cells
ii)
numerous
macrophages
§
The
proliferated smooth muscle cells are surrounded by collagen, elastin &
proteoglycans
§
In the
hypercholesterolemic patient:
i)
smooth
muscle & macrophage cells may also contain lipid in form of cholesterol
ii)
lipid may
deposit in connective tissue
§
Fibrous
plaques are covered by a fibrous cap
Uncomplicated atheromatous plaque response-to-injury hypothesis:
1)
INJURY to endothelium
2° hypertension, toxins, immunological, viruses
> increase turnover of
endothelial cell
> increased production
of growth factors by endothelial cells
> stimulate migration
of smooth muscle from media into intima
> further release of growth factors by smooth muscle
> fibrous plaque
production & further lesion progression
2)
Fatty streak scenario:
a) Release of growth factors from macrophages & damaged endothelial
cells
> stimulate migration
of smooth muscle from media into intima
> further release of growth factors by smooth muscle
> fibrous plaque
production & further lesion progression
b) Release of injurious
substances from macrophages
(used normally against
toxins & microbes)
> injure endothelium
> lose overlying
endothelium
> platelet adherence
> platelets now a
further source of growth factors
> fibrous plaque
production & further lesion progression
C] Complicated atheromatous lesion
- When
fibrous plaque becomes involved with thrombus, haemorrhage, &/or
calcification is called a complicated
lesion
Calcium tends to
precipitate with the lipids developing calcified
plaques
Atheromatous plaque complications
1)
Arteriosclerosis
- Fibrous
plaque ± calcium > extremely hard arteries
- Arteriosclerotic
arteries lose distensibility + have degenerate areas> easily ruptured
2)
Thrombus/ emboli
- Atheromatous
plaques often protrude through intima into blood vessel lumen
- Protruding
surface of the atheromatous plaques are often rough
> resultant thrombus or
emboli formation
> occlude artery
3)
Intra atheroma haemorrhage
- Haemorrhage
within atheroma from vaso vasorum or from endothelial surface >
occlude artery
eg As the blood flow is impeded by degenerative vascular changes, there is more opportunity for platelets to catch & rupture of the rough edges of the fatty plaques. Clotting subsequently occurs, and a small clot or thrombus begins to develop. To the extent that the thrombus increases in size, it can eventually cause total obstruction of the artery
