1. Arteriosclerosis
 Arteriosclerosis: is a generic term for thickening
and loss of elasticity of arterial walls.
 Three patterns:
o Atherosclerosis: most frequent and important pattern.
o Mönckeberg medial calcific sclerosis:
• Calcific deposits in muscular arteries in persons
older than age 50.
• The radiographically visible, often palpable
calcifications, do not encroach on vessel lumen.

2. o Arteriolosclerosis :
• Affects small arteries and arterioles.
• Two anatomic variants: hyaline and hyperplastic.
• Both associated with thickening of vessel walls
with luminal narrowing that may cause downstream
ischemic injury.
• Most often associated with hypertension and
diabetes mellitus.

3. Atherosclerosis:
 Intimal lesions called atheromas; or atheromatous
or fibrofatty plaques.
 Protrude into and obstruct vascular lumens and
weaken the underlying media.
 Develop primarily in elastic arteries (aorta, carotid,
and iliac arteries) and large and medium-sized
muscular arteries (coronary and popliteal arteries).
 In small arteries atheromas can occlude lumens
and cause ischemic injury.

4.  Plaques can undergo disruption and precipitate
thrombi.
 In large arteries, plaques encroach on subjacent
media and weaken the affected vessel wall
causing aneurysms that may rupture.
 Extensive atheromas can be friable and shed
emboli into distal circulation.
 Major consequences of atherosclerosis are:
o Myocardial infarction (heart attack).
o Cerebral infarction(stroke).
o Aortic aneurysms.
o Peripheral vascular disease (gangrene of legs).

5. Morphology:
Gross:
An atheroma or atheromatous plaque:
o Consists of a raised focal lesion initiating within
the intima having a soft yellow core of lipid,
covered by a firm white fibrous cap.
o Appear white to whitish yellow and impinge on
lumen of artery.
o Vary in size from 0.3 to 1.5 cm in diameter , but
sometimes coalesce to form larger masses.

6. This image shows Atheroscleosis of Aorta; the aorta was opned along the
posterior wall . Numerous calcified and ulcerated yellow and whitish-yellow
atherosclerotic plaques (arrows) dot the inner surface.

7. This is coronary atherosclerosis with the complication of hemorrhage into
atheromatous plaque, seen here in the center of the photograph. Such
hemorrhage acutely may narrow the arterial lumen.

8. Microscope:
o Atherosclerotic plaque have three principal
components:
(1) Cells: SMCs, macrophages, and other leukocytes.
(2) ECM: collagen, elastic fibers, and proteoglycans.
(3) Intracellular and extracellular lipid.
o The superficial fibrous cap is composed of SMCs
and relatively dense ECM.
o Beneath and to side of cap (the shoulder) is
cellular area consisting of macrophages, SMCs,
and T lymphocytes.

9.  The advanced lesion of atherosclerosis is
at risk for following pathological changes:
o Focal rupture, ulceration, or erosion:
result in exposure of highly thrombogenic
substances that induce thrombus formation.
o Hemorrhage into plaque: especially in coronary
arteries, A contained hematoma may expand
the plaque or induce plaque rupture.

11. This is a normal coronary artery. The lumen is large, without any narrowing by
atheromatous plaque. The muscular arterial wall is of normal proportion.

14. This microscopic cross section of the aorta shows a large overlying atheroma on
the left. Cholesterol clefts are numerous in this atheroma. The surface on the far
left shows ulceration and hemorrhage.

15. This is a high magnification of the aortic atheroma with foam cells and
cholesterol clefts.

16. Epidemiology and risk factors:
Age: atherosclerosis is not clinically evident until
middle age or later.
Sex:
o Males are much more prone than females.
o After menopause the incidence increases, probably
due to decrease in natural estrogen levels.

17. Genetics:
o Familial predisposition to atherosclerosis is
most likely polygenic.
o Most commonly relates to familial clustering of
other risk factors such as hypertension or diabetes.
o Less commonly it involves hereditary genetic
derangements in lipoprotein metabolism that
result in high blood lipid levels, such as familial
hypercholesterolemia.

18. Hyperlipidemia:
o Is a major risk factor for atherosclerosis,
specifically hypercholesterolemia.
o Hypercholesterolemia is sufficient to stimulate lesion
development even if other risk factors are absent.
o Low-density lipoprotein (LDL) cholesterol:
act as a vehicle for delivery of cholesterol to
peripheral tissues and associated with increased risk.

19. o In contrast, High-density lipoprotein(HDL)cholesterol:
 Mobilize cholesterol from atheromas to liver for
excretion in bile, hence its designation as "good
cholesterol.“
 Therefore, the higher the level of HDL, the lower is
the risk.
 Exercise and moderate consumption of alcohol both
raise the HDL level.
 Whereas obesity and smoking lower it.

20. o High dietary intake of saturated fats present in
egg yolk, animal fats, and butter raises the
plasma cholesterol level.
o Conversely, a diet low in saturated fats lowers the
plasma cholesterol levels.
o Omega-3 fatty acids ( abundant in fish oils ) are
likely beneficial.
Hypertension:
o major risk factor for atherosclerosis at all ages.
Cigarette Smoking:
o Cessation of smoking reduces the increased risk
substantially.

21. Diabetes Mellitus:
o induces hypercholesterolemia.
Other Factors:
o Homocystinuria: a rare inborn error of metabolism.
Hyperhomocystinemia: caused by low folate and
vitamin B intake.
o Markers of hemostatic function and inflammation:-
 those related to fibrinolysis (elevated plasminogen
activator inhibitor-1)
 inflammation (C-reactive protein).

22. o Lipoprotein-a: an altered form of LDL that contains
apolipoprotein B-100 portion of LDL linked to
apolipoprotein A. Increase the risk independent
of the level of total cholesterol or LDL.
Factors associated with a less pronounced risk include:
o Lack of exercise.
o Stressful life style.
o Weight gain: largely because obesity induces
hypertension, diabetes, hypertriglyceridemia,
and decreased HDL.

23. PATHOGENESIS :
 Chronic endothelial injury (usually subtle) yielding
increased permeability, leukocyte adhesion, and
thrombotic potential.
 Accumulation of lipoproteins (mainly LDL with its
high cholesterol content) in vessel wall.
 Modification of lesional lipoproteins by oxidation.
 Adhesion of blood monocytes to endothelium,
followed by their migration into intima and their
transformation into macrophages and foam cells.

24.  Adhesion of platelets.
 Release of factors from (activated platelets,
macrophages, or vascular cells) that cause migration
of SMCs from media into intima.
 Proliferation of smooth muscle cells in intima,
and elaboration of extracellular matrix, leading to
accumulation of collagen and proteoglycans.
 Accumulation of lipids both within the cells
(macrophages and SMCs) and extracellularly.

25. Arteriolosclerosis:
Hyaline arteriolosclerosis
Hyperplastic arteriolosclerosis
Morphology:
Hyaline Arteriolosclerosis:
o Homogeneous , pink, hyaline thickening of walls
of arterioles with narrowing of lumen .
o Encountered in elderly patients, whether
normotensive or hypertensive.
o More severe in patients with hypertension.

26. o Common in diabetes as part of characteristic
microangiography .
o The lesions reflect leakage of plasma proteins
across vascular endothelium and excessive
extracellular matrix production by SMCs secondary
to chronic hemodynamic stress of hypertension
or metabolic stress in diabetes that accentuates
endothelial cell injury.
o Hyaline arteriolosclerosis is a major morphologic
characteristic of benign nephrosclerosis.

29. Hyperplastic Arteriolosclerosis:
o Characteristic of malignant hypertension
(diastolic pressures usually over 120 mm Hg).
o Onionskin concentric laminated thickening of walls
of arterioles with progressive narrowing of lumina.
o Electron microscope: the laminations consist of SMCs
and thickened and reduplicated basement membrane.

30. In contrast to acellular hyaline arteriolosclerosis, this is very cellular lesion.
Smooth muscle cells are proliferating and undergoing hypertrophy in an attempt
to cope with rapidly rising blood pressure. The lesions appear as thickened
concentric rings of media and intima surrounding narrowed vascular lumina.
This is hyperplastic arteriolosclerosis;