Arteriosclerosis Arteriosclerosis: is a generic term for thickeningand 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 personsolder than age 50.• The radiographically visible, often palpablecalcifications, do not encroach on vessel lumen.
o Arteriolosclerosis :• Affects small arteries and arterioles.• Two anatomic variants: hyaline and hyperplastic.• Both associated with thickening of vessel wallswith luminal narrowing that may cause downstreamischemic injury.• Most often associated with hypertension anddiabetes mellitus.
Atherosclerosis: Intimal lesions called atheromas; or atheromatousor fibrofatty plaques. Protrude into and obstruct vascular lumens andweaken the underlying media. Develop primarily in elastic arteries (aorta, carotid,and iliac arteries) and large and medium-sizedmuscular arteries (coronary and popliteal arteries). In small arteries atheromas can occlude lumensand cause ischemic injury.
Plaques can undergo disruption and precipitatethrombi. In large arteries, plaques encroach on subjacentmedia and weaken the affected vessel wallcausing aneurysms that may rupture. Extensive atheromas can be friable and shedemboli 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).
Morphology:Gross:An atheroma or atheromatous plaque:o Consists of a raised focal lesion initiating withinthe intima having a soft yellow core of lipid,covered by a firm white fibrous cap.o Appear white to whitish yellow and impinge onlumen of artery.o Vary in size from 0.3 to 1.5 cm in diameter , butsometimes coalesce to form larger masses.
This image shows Atheroscleosis of Aorta; the aorta was opned along theposterior wall . Numerous calcified and ulcerated yellow and whitish-yellowatherosclerotic plaques (arrows) dot the inner surface.
This is coronary atherosclerosis with the complication of hemorrhage intoatheromatous plaque, seen here in the center of the photograph. Suchhemorrhage acutely may narrow the arterial lumen.
Microscope:o Atherosclerotic plaque have three principalcomponents:(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 SMCsand relatively dense ECM.o Beneath and to side of cap (the shoulder) iscellular area consisting of macrophages, SMCs,and T lymphocytes.
The advanced lesion of atherosclerosis isat risk for following pathological changes:o Focal rupture, ulceration, or erosion:result in exposure of highly thrombogenicsubstances that induce thrombus formation.o Hemorrhage into plaque: especially in coronaryarteries, A contained hematoma may expandthe plaque or induce plaque rupture.
This is a normal coronary artery. The lumen is large, without any narrowing byatheromatous plaque. The muscular arterial wall is of normal proportion.
This microscopic cross section of the aorta shows a large overlying atheroma onthe left. Cholesterol clefts are numerous in this atheroma. The surface on the farleft shows ulceration and hemorrhage.
This is a high magnification of the aortic atheroma with foam cells andcholesterol clefts.
Epidemiology and risk factors:Age: atherosclerosis is not clinically evident untilmiddle age or later.Sex:o Males are much more prone than females.o After menopause the incidence increases, probablydue to decrease in natural estrogen levels.
Genetics:o Familial predisposition to atherosclerosis ismost likely polygenic.o Most commonly relates to familial clustering ofother risk factors such as hypertension or diabetes.o Less commonly it involves hereditary geneticderangements in lipoprotein metabolism thatresult in high blood lipid levels, such as familialhypercholesterolemia.
Hyperlipidemia:o Is a major risk factor for atherosclerosis,specifically hypercholesterolemia.o Hypercholesterolemia is sufficient to stimulate lesiondevelopment even if other risk factors are absent.o Low-density lipoprotein (LDL) cholesterol:act as a vehicle for delivery of cholesterol toperipheral tissues and associated with increased risk.
o In contrast, High-density lipoprotein(HDL)cholesterol: Mobilize cholesterol from atheromas to liver forexcretion in bile, hence its designation as "goodcholesterol.“ Therefore, the higher the level of HDL, the lower isthe risk. Exercise and moderate consumption of alcohol bothraise the HDL level. Whereas obesity and smoking lower it.
o High dietary intake of saturated fats present inegg yolk, animal fats, and butter raises theplasma cholesterol level.o Conversely, a diet low in saturated fats lowers theplasma cholesterol levels.o Omega-3 fatty acids ( abundant in fish oils ) arelikely beneficial.Hypertension:o major risk factor for atherosclerosis at all ages.Cigarette Smoking:o Cessation of smoking reduces the increased risksubstantially.
Diabetes Mellitus:o induces hypercholesterolemia.Other Factors:o Homocystinuria: a rare inborn error of metabolism.Hyperhomocystinemia: caused by low folate andvitamin B intake.o Markers of hemostatic function and inflammation:- those related to fibrinolysis (elevated plasminogenactivator inhibitor-1) inflammation (C-reactive protein).
o Lipoprotein-a: an altered form of LDL that containsapolipoprotein B-100 portion of LDL linked toapolipoprotein A. Increase the risk independentof 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 induceshypertension, diabetes, hypertriglyceridemia,and decreased HDL.
PATHOGENESIS : Chronic endothelial injury (usually subtle) yieldingincreased permeability, leukocyte adhesion, andthrombotic potential. Accumulation of lipoproteins (mainly LDL with itshigh cholesterol content) in vessel wall. Modification of lesional lipoproteins by oxidation. Adhesion of blood monocytes to endothelium,followed by their migration into intima and theirtransformation into macrophages and foam cells.
Adhesion of platelets. Release of factors from (activated platelets,macrophages, or vascular cells) that cause migrationof SMCs from media into intima. Proliferation of smooth muscle cells in intima,and elaboration of extracellular matrix, leading toaccumulation of collagen and proteoglycans. Accumulation of lipids both within the cells(macrophages and SMCs) and extracellularly.
Arteriolosclerosis:Hyaline arteriolosclerosisHyperplastic arteriolosclerosisMorphology:Hyaline Arteriolosclerosis:o Homogeneous , pink, hyaline thickening of wallsof arterioles with narrowing of lumen .o Encountered in elderly patients, whethernormotensive or hypertensive.o More severe in patients with hypertension.
o Common in diabetes as part of characteristicmicroangiography .o The lesions reflect leakage of plasma proteinsacross vascular endothelium and excessiveextracellular matrix production by SMCs secondaryto chronic hemodynamic stress of hypertensionor metabolic stress in diabetes that accentuatesendothelial cell injury.o Hyaline arteriolosclerosis is a major morphologiccharacteristic of benign nephrosclerosis.
Hyperplastic Arteriolosclerosis:o Characteristic of malignant hypertension(diastolic pressures usually over 120 mm Hg).o Onionskin concentric laminated thickening of wallsof arterioles with progressive narrowing of lumina.o Electron microscope: the laminations consist of SMCsand thickened and reduplicated basement membrane.
In contrast to acellular hyaline arteriolosclerosis, this is very cellular lesion.Smooth muscle cells are proliferating and undergoing hypertrophy in an attemptto cope with rapidly rising blood pressure. The lesions appear as thickenedconcentric rings of media and intima surrounding narrowed vascular lumina.This is hyperplastic arteriolosclerosis;