Atherosclerosis

DSOBriain
April2007

Atherosclerosis
Arteriosclerosis(hardeningofthearteries)
3types:
1. Atherosclerosis(athero=porridge)plaquesof
lipidandfibroustissueinvesselwall
Lessimportantformsofarteriosclerosis
2.Medialcalcification(Monckeberg)
3.Smallvessel(arteriolosclerosis)hyalineorhyperplastic

AtheromatousPlaque,
Macroscopic
Distribution:Abdominalaorta>coronary>popliteal>descending
thoracic>internalcarotid>circleofWillis.
Spared:upperextremities,renal,mesenteric(exceptostia).

Fibrouscap(white),deeperportion(grumous,yellow).
315mmdiameter,raised,coalesce.
Scantytonumerous

AtheromatousPlaque
Histology
Fibrouscap:Smoothmuscle,WBC,connectivetissue,
collagen,elastic,proteoglycan.
Core:lipiddebris,cholesterol,cholesterolesters,foam
cells(smoothmuscleandmacrophage),fibrin,plasma
proteins,Tcells.
Periphery:neovascularisation,chronicinflammation.

EffectsofAtheromatous
Plaque

Differenteffectsinnarrow(coronary)andwide(aorta)vessels
Clinicallysilent
Mostplaqueshavenoeffect.
Calcification:Identifyonimaging.
Complicatedplaques
Fissure
Ulcerate:atheroemboli.
Thrombose:occlude,embolise
Haemorrhage:occlude.
Consequences
Stenose:Ischaemia,atrophy.
Occlude(bythrombusorhaemorrhage):Infarct.
Aneurysm:pressureeffects,leak(rupture)

Fattystreak
Possibleprecursorofatheroma.

Spot(1mm),Streak(1x10mm).

Composition:Macrophagesfilledwithlipid(foamcells)latersmoothmuscle
cellswithlipiddroplets,extracellularlipid,Tlymphocytes,proteoglycans,
collagen,elastin.
Incidence:Morefrequentwithhighmilk/fatdiet:
10%firstdecade,30%thirddecade,
Mayrecede,persistorconverttofibrousplaque
Distribution:Aortaunlikeatheroma,Coronaryarterieslikeatheroma.

IntimalCushion
Whiteareasofdiffuseintimalthickeningcomposedof
intimalsmoothmuscleandmatrix(littlecollagen,no
lipid),gelatinouslesion.
Degenerateeffectofbloodpressureandtime.
Butoccuratostia(atheromasites).

MonckebergsCalcificMedial
Sclerosis

Calcificationofmediumorsmall
arteries
Bothsexes,over50
Arteries:Femoral,radial,ulnar,genital.
Cause:vasotonicfactors,adrenaline,
nicotine.
Effect:none,visibleinimaging

Arteriolosclerosis

Hyalinechangeinvesselwalls.

Pathogenesisplasmaleakage,smoothmusclematrix.
Associationshypertension,diabetes,age.

Benignhyalinenarrowing.
Hyperplasticonionskin(fibrinoidnecrosis).
Sites:Kidney,gallbladder,intestine,periadrenal,pancreatic.

TheoriesofAtherogenesis
Virchowimbibation
(lipidtheories)

Rokitanskyencrustation
(thrombotictheories)

AtherosclerosisRiskFactors
Hyperlipidemia.

LDL(lowdensitylipoprotein)

Hypertension:160/95Vs140/90,RiskX5.Increases:Atheroma,IHD,CVD.Riskdecreases
withtherapy.
Cigarettes:MoreAS,moresuddendeath,Riskincreasedby70200%.Decreasesaftercessation.
Diabetes:MoreAS,MIx2,IncreasedCVD,PVDriskincreasedx8150.
Other:Physicalactivity,stress,obesity,oralcontraceptives,hyperuricemia,highcarbohydrate
intake,male,age,familyhistory,homocystinemia.
MultipleFactors:

Morethanadditive.

NOTE:IHDischaemicheartdisease,CVDcerebrovasculardisease,PVDperipheralvascular
diseaseASatherosclerosis,MImyocardialinfarction,

RoleoflipidinAtherosclerosis
1.Foundinplaque
2.Experimentallyraisedlipid>AS
3.Hyperlipidemias>AS
4.Populationswithhighlipids>highAS
rate
5.TreathyperlipidemiadecreaseAS.

RiskofAtherosclerosis
High:RaisedLDL(70%cholesterol),triglycerideand
VLDL.
Low:RaisedHDL.
Riskincreaseswithincreasedcholesterollevel(riskx5
withcholesterolincrease220to265)
Increasedintakecholesterolandtriglyceridesincreases
serumcholesterol.
Omega3fattyacids(fish)protective

HowHyperlipidemiamay
damageintima
MoreserumLDL,morecellularpenetration.
LDLwithproteoglycanaviduptake.
LDLmodifiedlysosomaluptake.
LDLdirectlydamagesendothelialcell.
Oxidisedlipoproteins:Endothelialinjury,smooth
muscleinjury,foamcellsscavengerreceptor,
chemotactic.

Intimaldysfunction
Cause:Mechanical,Haemodynamicstress,Immune
complex,Radiation,Chemotherapy.

Association:Hypertension,Stress,Cigarettes.
Effect:Increasedintimalpermeability,adhesion,
smoothmuscleproliferation,atheroma(if
hyperlipidemia)

Macrophage
Family:Monocyte,histiocyte,macrophage,epithelioidcell,giant
cell,granuloma
Monocytesadhere,migrate,phagocytose
HavescavengerreceptormodifiedVLDLreceptor(Lipid
internalised,hydrolysed,esterified>lipiddroplet).
Monocytesproduce:IL1,TNF(increasedadhesion),chemotaxis
factors,toxicO2,PDGF,TGFbeta>smoothmuscle

Smoothmuscleproliferation
Origin:Frommedia(ormyointima)
Stimulus:PDGF(fromplatelets,macrophages,
endothelialandsmoothmusclecells),FGF,EGF,
TGF.
Inhibit:Heparin,TGFB.

Result:Smoothmusclecellsproduce
extracellularmatrixandfoamcells
(atheroma)

ArterialInjury
Permeabilityincreases.
Adhesionofplatelets,monocytes
Factorsreleased
Smoothmusclemigratestointima,proliferatesandproduces
extracellularmatrix,collagen,elastin,proteoglycans
Monocytesphagocytose
Lipiddeposited

OtherTheoriesof
Atherogenesis
Primarysmoothmuscleproliferation:monoclonal
growth(asaformofleiomyoma)
Cause:Exogenous(hydrocarbon,virus),
endogenous(cholesterol)
Experimentally:PlaquesinMarekchickenvirus,
anthracycline,herpesmRNAinplaque

IschaemicHeartDisease
Epidemic
Causes80%ofcardiacmortality

PeakedinUSin1960s,40%declinesince
DifferentpatternsinsomeWestern
countries
Causeofdecline:Changinglifestyle(diet,
smoking,exercise)

Bettertherapy(CCU,thrombolysis,
arrhythmiatherapy,CABG,angioplasty)

AtheroscleroticCoronaryArtery
Disease:
ClinicalSyndromes

SilentInfarct
AnginaPectoris
MyocardialInfarct
ChronicIschaemicHeartDisease
SuddenDeath

AtheroscleroticCoronaryArtery
Disease:
ClinicalSyndromes

SilentInfarct
AnginaPectoris
MyocardialInfarct
ChronicIschaemicHeartDisease
SuddenDeath

Aneurysms
Localisedabnormaldilationofvessel.
Types:Saccular,fusiform,cylindroid,dissection.
Complications:Pressure,thrombus,rupture.
Aetiology:Atherosclerosis,cysticmedialnecrosis,syphilis,trauma
(arteriovenousaneurysm),PAN,infections,(mycotic),congenital
(berry).

AtheroscleroticAneurysm

Malesof50+,frequently(50%)hypertensive
Abdominalaorta(betweenrenalarteryandaorticbiforcation).(Thoracic
aorta,renal,mesentericarteries)

Complications;
Rupture(if>6cm,50%rupturein10years)
surgicalmortality50%(unruptured5%)
Compressionureter,vertebrae
Occlusion(thrombus,pressure)
Embolism
Abdominalmass

Atherosclerosis
Peripheralvasculardisease

Pain(claudication)
Ischaemicchanges
Gangrene
Generalatheromarisk
factors
But100timesmore
frequentindiabetes

Atherosclerosis
Mesentericischaemia
Coeliac,superior
mesentericartery)
Aymptomatic
Intestinalangina(pain
afterfood)
Intestinalischaemia
Bloodydiarrhoea
Infarction/gangrene
obstruction

Athersclerosis
Cerebrovasculardisease

Thrombosis(embolism,
haemorrhageareother
importfactorsinstroke)
Sitesofthrombotic
occlusion:carotid
bifurcation,middle
cerebralandbasilar
arteries)
Transientischaemicattack
(TIA),cerebrovascular
accident(CVA),(stroke)