Lecture 13.

ATHEROSCLEROSIS

DEFINITION

Atherosclerosis is a specific form of arteriosclerosis affecting primarily the intima of large and
medium-sized muscular arteries and is characterised by fibrofatty plaques or atheromas. The term
atherosclerosis is derived from athero- (meaning porridge) referring to the soft lipid-rich material
in the centre of atheroma, and sclerosis (scarring) referring to connective tissue in the plaques.
Atherosclerosis is the commonest and the most important of the arterial diseases. Though any
large and medium-sized artery may be involved in atherosclerosis, the most commonly affected
are the aorta, the coronary and the cerebral arterial systems. Therefore, the major clinical
syndromes resulting from ischemia due to atherosclerosis are the myocardial infarcts (heart
attacks) and the cerebral infarcts (strokes); other less common sequelae are peripheral vascular
disease, aneurysmal dilatation due to weakened arterial wall, chronic ischemic heart disease,
ischemic encephalopathy and mesenteric occlusion.

PATHOLOGIC CHANGES
The clinical disease states due to luminal narrowing in atherosclerosis are caused by fully devel-
oped atheromatous plaques and complicated plaques. However, early lesions in the form of
diffuse intimal thickening, fatty streaks and gelatinous lesions are often the forerunners in the
evolution of atherosclerotic lesions.
1. INTIMAL THICKENING. Fibromuscular thickening of the intima of arteries may be a part
of atherosclerotic process, particularly rapid during the first two decades of life. Grossly, the le-
sions may appear as small white areas of intimal cushion at the bifurcation and branching of
arteries, or may appear as 'diffuse intimal thickening'. Microscopically, the lesions consist of
smooth muscle cells, fibrous tissue, some collagen but no lipid.
2. FATTY STREAKS. Fatty streaks of the intima by themselves are harmless but may be the
precursor lesions of atheromatous plaques. They are seen in all races of the world and begin to
appear in the first year of life. However, they are uncommon in older persons and are probably
absorbed. They are especially prominent in the aorta and other major arteries, more often on the
posterior wall than the anterior wall. Grossly, the lesions may appear as flat or slightly elevated
and yellow. They may be either in the form of small, multiple dots, about 1 mm in size, or in the
form of elongated, beaded streaks. Microscopically, fatty streaks lying under the endothelium are
composed of closely-packed foam cells, lipid-containing elongated smooth muscle cells and a
few lymphoid cells. Small amount of extracellular lipid, collagen and proteoglycans are also
present.
3. GELATINOUS LESIONS. Gelatinous lesions develop in the intima of the aorta and other
major arteries in the first few months of life. Like fatty streaks, they may also be precursors of
plaques. They are round or oval, circumscribed grey elevations, about 1 cm in diameter.
Microscopically, gelationous lesions are foci of increased ground substance in the intima with
thinned overlying endothelium.
4. ATHEROMATOUS PLAQUES. A fully developed atherosclerotic lesion is called
atheromatous plaque, also called fibrous plaque, fibrofatty plaque or atheroma. Unlike fatty
streaks, atheromatous plaques are selective in different geographic locations and races and are
seen in advanced age. These lesions may develop from progression of early lesions of the
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atherosclerosis described above. Most often and most severely affected is the abdominal aorta,
though smaller lesions may be seen in descending thoracic aorta and aortic arch. The major
branches of the aorta around the ostia are often severely involved, especially the iliac, femoral,
carotid, coronary, and cerebral arteries. Grossly, atheromatous plaques are white to yellowish-
white lesions, varying in diameter from 1 -2 cms and raised on the surface by a few millimeters to
a centrimeter in thickness. Cut section of the plaque reveals the luminal surface as a firm, white
fibrous cap and a central core composed of yellow to yellow-white, soft, porridge-like material
and hence the name atheroma. Microscopically, the appearance of plaque varies depending upon
the age of the lesion. However, the following features are invariably present:
The superficial luminal part of fibrous cap is covered by endothelium, and is composed of
smooth muscle cells, dense connective tissue and extracellular matrix containing proteoglycans
and collagen.
The cellular area under the fibrous cap is comprised by a mixture of macrophages, foam cells,
lymphocytes and a few smooth muscle cells which may contain lipid.
The deeper central soft core consists of extracellular lipid material, cholesterol clefts, fibrin,
necrotic debris and lipid-laden foam cells.
In older and more advanced lesions, the collagen in the fibrous cap may be dense and
hyalinised, smooth muscle cells may be atrophic and foam cells are fewer.
5. COMPLICATED PLAQUES. Various pathologic changes that occur in fully-developed
atheromatous plaques are called the complicated lesions. These account for the most serious
harmful effects of atherosclerosis and even death. These changes include calcification, ulceration,
thrombosis, haemorrhage and aneurismal dilatation. It is not uncommon to see more than one
form of complication in a plaque.
i) Calcification. Calcification occurs more commonly in advanced atheromatous plaques, espe-
cially in the aorta and coronaries. The diseased intima cracks like an egg-shell when the vessel is
incised and opened. Microscopically, the calcium salts are deposited in the vicinity of necrotic
area and in the soft lipid pool deep in the thickened intima. This form of atherosclerotic intimal
calcification differs from Monckeberg's medial calcine arteriosclerosis that affects only the tunica
media.
ii) Ulceration. The layers covering the soft pultaceous material of an atheroma may ulcerate as a
result of haemodynamic forces of mechanical trauma. This results in discharge of emboli com-
posed of lipid material and debris into the blood stream, leaving a shallow, ragged ulcer with yel-
low lipid debris in the base of the ulcer. Occasionally, atheromatous plaque in a coronary artery
may suddenly rupture into the arterial lumen forcibly and cause thromboembolic occlusion.
iii) Thrombosis. The ulcerated plaque and the areas of endothelial damage are vulnerable sites
for formation of superimposed thrombi. These thrombi may get dislodged to become emboli and
lodge elsewhere in the circulation, or may get organised and incorporated into the arterial wall
as mural thrombi. Mural thrombi may become occlusive thrombi which may subsequently
recanalise.
iv) Haemorrhage. Intimal haemorrhage may occur in an atheromatous plaque either from the
blood in the vascular lumen through an ulcerated plaque, or from rupture of thin-walled
capillaries that vascularise the atheroma from adventitial vasa vasorsum. Haemorrhage is a
particularly common complication in coronary arteries. The haematoma formed at the site
contains numerous haemosiderin-laden macrophages.

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v) Aneurysm formation. Though atherosclerosis is primarily an intimal disease, advanced
lesions are associated with secondary changes in the media and adventitia. The changes in media
include atrophy and thinning of the media and fragmentation of internal elastic lamina. The
adventitia undergoes fibrosis and some inflammatory changes. These changes cause weakening in
the arterial wall resulting in aneurysmal dilatation.
CLINICAL EFFECTS
The clinical effects of atherosclerosis depend upon the size and type of arteries affected. In
general, the clinical effects result from the following:
1. Slow luminal narrowing causing ischaemia and atrophy.
2. Sudden luminal occlusion causing infarction necrosis.
3. Propagation of plaque by formation of thrombi and emboli.
4. Formation of aneurysmal dilatation and eventual rupture.
Large arteries affected most often are the aorta, renal, mesenteric and carotids, whereas the
medium-and small-sized arteries frequently involved are the coronaries, cerebrals and arteries of
the lower limbs. Accordingly, the symptomatic atherosclerotic disease involves most often the
heart, brain, kidneys, small intestine and lower extremities. Some of the important effects are
listed below:
i) AortaAneurysm formation, thrombosis and embolisation to other organs.
ii) HeartMyocardial infarction, ischaemic heart disease.
iii) Brainchronic ischaemic brain damage, cerebral infarction.
iv) Small intestineischaemic bowel disease, infarction.
vi) Lower extremitiesIntermittent claudication, gangrene.

Subject XIII. An atherosclerosis. Subject XIV. Ischemic heart disease (IHD)

To learn macroscopic specimens:

429. Atherosclerosis of aorta.

There are a lot of atherosclerotic plaques on the intima of aorta at different stages of development. Some
of them are motley contain lipids, others like mother-of-pearl (due to sclerosis). There are also
ulcerated plaques, with yellowish-white masses in the bottom (atheromatosis), parietal thrombosis and
calcification of plaque.

43. Atherosclerosis of aorta.

26. Infarct of papillary muscles with a breaking.

A dim variegated tissue with breaking of papillary muscle are distributed in the left ventricle of heart.

408. Myocardial infarction with the parietal thrombus.

There is dim variegated lesion at the sectioned surface of heart left ventricle. Wall of left ventricle is thin.
The endocard in the region of necrosis is covered with parietal thrombus.

59. Myocardial infarction.

The dim, variegated lesion 5x6 cm in sizes is at the posterior wall of heart left ventricle. Thrombus
obdurate the lumen of coronary artery.

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87. Ischemic infarctions of kidney and spleen.
White colour lesions of necrosis are distributed under capsule of kidney and spleen. Triangular lesion is
seen on the spleen section with the top at the gate of the organ and the base under the capsule.

80. Infarction of kidneys.

There are generalised pale lesions of necrosis under the capsule of kidney.

382. Ischemic infarction of brain.

Greyish-brown in colour mollities of brain lesion is seen in the top of brain section.

35. Gangrene of colon.

Necrotic part of colon is black colour and dim.

45. Mural (nonocclusive) thrombus of aorta.

The densely thrombus with irregular and rough surface is attached to the intimae of ulcerated aorta. There
are head, body and tail of the thrombus.

320. Scars after the infarction of kidney.

The retractions of the lesions are visible under capsule of the kidney.

519. Aortic aneurysm with laminated mural thrombus.

Laminated mural thrombus is seen in the expanded part of aorta (aneurysm).

404. Transmural myocardial infarction.

The dull region is seen under the epicardium in the field of septum and anterior wall of left ventricle.

394. Chronic aneurysm of heart with parietal thrombus.

There is parietal thrombus on the inducardium of heart left ventricle posterior wall. The apex of heart is
elongated in the healed infarct region due to formation of thin, non-elastic scar tissue.

116. Transmural myocardial infarction with parietal thrombus.

The heart myocardium of left ventricle is dull and motley with red parietal thrombus on endocardium.

497. Micro foci of cardiosclerosis.

There are whitish coloured lucid foci in the section of the myocardium.

497. Diffuse myocardial fibrosis.

The left ventricular wall generally shows foci of grey-white fibrosis in brown myocardium.

Study of microscopic specimens:

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93. Atherosclerosis of aorta. Fatty streaks stage (colouring by Sudan).
The intima of aorta is thickened and yellowish colour due to absorption of cholesterol, its esters and
plasma proteins. Fatty streaks lying under the endothelium are composed of closely-packed foam cells,
lipid-containing elongated smooth muscle cells and a few lymphoid cells. Blue coloured regions represent
zones of dystrophic calcification.
Indicate in the figure:
1 lipid accumulation in smooth mussels cells and foam cells,
2 zone of calcification.

41. Atherosclerosis of aorta. Complicated plaques - calcification.

The calcium salts are deposited in the fibrous atheromatous plaque area deep in the thickened intima.
Indicate in the figure: 1 - atheromatous plaque,
2 calcification.

11. Thrombosis of coronary arteria of heart.

An occlusive white thrombus is seen in the lumen of coronary arteria with initial signs of organization. (An
occlusive thrombus is the reason for myocardial infarction).

21. Infarction of myocard with parietal thrombosis.

The muscle fibres are dispossessed of nuclei (karyolysis) in zone of infarction. There is aggregation of
leucocytes - demarcation inflammation between necrotic muscle fibres and normal muscles.

57. Postmyocardial infarction cardiosclerosis.

Young connective tissue replaced the centre of necrosis in myocardium infarction, rich with vessels,
fibroblasts and thin collagen fibres (scars). Survived cardiomyocites are hypertrophied.
Indicate in the figure:
1 site of cardiosclerosis,
2 - hypertrophied cardiomyocites.

127. Ischemic infarction of brain

There are resorbtive obesity of glial macrophages in the zone of ischemic infarction of brain.
Large round cells are inside the cavity after necrosis of brain tissue (cyst). Macrophages contain lipids in
cytoplasm. (The visible vacuoles in the places of lipids are due to lipids dilution in alcohol at hematoxylin -
eosine colouration). These microglial cells have phagocytic function to remove the disintegrated lipid rich
products of brain. They are called as "grainy balls".

The literature

1. .., ... Pathological anatomy. 1993, page 75, 98, 268-292.

2. Classification, terms and verbiages of concepts on pathological anatomy, (Manual).
3. Harsh Mohan .Textbook of Pathology. 4th Edition, page 254-262, 288-299.
4. Robbins. Pathologic basis of disease. 1999, page 40, 79, 129, 498-509, 551, 554-564.