Aterioskleorisi & PJK_CVS-K33

8/2/2019 Aterioskleorisi & PJK_CVS-K33

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Atherosclerosis


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Atherosclerosis

is characterized by localized

fibrous thickenings of the arterialwall associated with lipid-infiltrated plaques that may

eventually calcify.


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NormalNormal

FattyFattyStreakStreak

FibrousFibrousPlaquePlaque

OcclusiveOcclusiveAtheroscleroticAtherosclerotic

PlaquePlaque

PlaquePlaqueRupture/Rupture/Fissure &Fissure &

ThrombosisThrombosis

MIMI

StrokeStroke

Critical LegCritical LegIschemiaIschemia

Clinically SilentClinically Silent

CoronaryCoronary

DeathDeath

Increasing AgeIncreasing Age

Effort AnginaEffort Angina

ClaudicationClaudication

UnstableUnstableAnginaAngina

Atherosclerosis: A Progressive Process

Courtesy of P Ganz.


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Pathogenesis initial event is : Infiltration of low-

density lipoproteins (LDL) into the sub

endothelial region. endothelium is subject toshearstress, tendency to be pulled along or

deformed by flowing blood.


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LDL are oxidized or altered in other

ways, then taken up by macrophages,forming foam cells.

foam cells form fatty streaks.

in the first decade of life, the streaksappear in the aorta, in the seconddecade in the coronary arteries, and

in the third and fourth decades in thecerebral arteries.


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Vascular smooth muscle cells in the

vicinity of foam cells are stimulatedand move from the media to theintima, where they proliferate, laydown collagen and other matrixmolecules, and contribute to the bulkof the lesion.

Smooth muscle cells also take upoxidized LDL and become foam cells.


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As plaques mature, a fibrous capforms over them.

plaques with defective or brokencaps are most prone to rupture.

The lesions alone may distort vesselsto the point that they are occluded,but it is usually rupture or ulceration

of plaques that triggers thrombosis,blocking blood flow.


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NormalNormal

FattyFatty

StreakStreakFibrousFibrous

PlaquePlaque


PlaquePlaque



MIMI

StrokeStroke



CoronaryCoronary

DeathDeath




UnstableUnstableAnginaAngina


Courtesy of P Ganz.


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Risk Factor

Male gender (and female aftermenopause) : Lack of LDL-lowering effect of estrogens;

estrogens probably act byincreasing the number of LDLreceptors in the liver.

Family history of ischemicheart disease, stroke :Probably multiple genetic

mechanisms.


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Primary hyperlipidemia andSecondary hyperlipidemia(Increased circulating triglyceridesproduced by diuretics, b-adrenergic blocking drugs, excessalcohol intake)

Cigarette smoking: Probablycarbon monoxide-induced hypoxicinjury to endothelial cells.


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Hypertension: Increased shearstress, with damage toendothelium.

Diabetes mellitus (types 1 and 2):Decreased hepatic removal of LDLfrom the circulation; increasedglycosylation of collagen, which

increases LDL binding to bloodvessel walls.


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Obesity, particularly abdominalobesity:

Nephrotic syndrome: Increased

hepatic production of lipids andlipoprotein(a).

Hypothyroidism: Decreased

formation of LDL receptors in theliver.


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PathophysiologyAcute Coronary

Syndrome

( A C S )

Dr Abdul Majid SpPD-KKV
http://www.harthosp.org/cardi/images/beat_heart.gif


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Koroner normal

Pasokan seimbang dengan kebutuhan

(aliran darah koroner) (kebutuhan miokard)

PJK Pasokan , kebutuhan

tetap

Pasokan tetap, kebutuhan


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When flow through a coronary arteryis reduced to the point that themyocardium it supplies becomes

hypoxic, "P factor" accumulates andangina pectoris develops .

If the myocardial ischemia is severeand prolonged, irreversible changes

occur in the muscle, and the result ismyocardial infarction.


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Partially occluded coronary arteriescan be constricted further byvasospasm, producing myocardial

infarction. The most common cause of

myocardial infarction is rupture ofan atherosclerotic plaque, or

hemorrhage into it, which triggersthe formation of a coronaryoccluding clot at the site of theplaque.


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When myocardial cells actually die,

they leak enzymes into thecirculation, and measuring the rises inserum enzymes and isoenzymesproduced by infarcted myocardial

cells also plays an important role inthe diagnosis of myocardial infarction.

The enzymes most commonlymeasured today are the MB isomer ofcreatine kinase (CK-MB), troponin T,and troponin I.


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Mechanism ofAtherosclerosis


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ACS: physiopathology


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at rest, to produce cellular ischemia

arterial lumen must be decreased to 90%

when exercise, a 50% reduction in lumen

size can lead to symptoms.

In unstable angina, fissuring of the

atherosclerotic plaque can lead to platelet

accumulation and transient episodes of

thrombotic occlusion, usually lasting 1020 minutes.


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platelet release of vasoconstrictivefactors such as thromboxane A2 or

serotonin and endothelial dysfunctionmay cause vasoconstriction and

contribute to decreased flow.

In myocardial infarction, deeparterial injury from plaque rupture

may cause formation of a relativelyfixed and persistent thrombus.


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Thin Fibrous CapThin Fibrous CapLipid CoreLipid Core

Unstable Plaque

ThrombuThrombussThrombuThrombuss

InflammatoryInflammatory

CellsCells

FewSMCs

ActivatedActivated

MacrophaMacrophagesges

Ruptured Plaque

Plaque Rupture Leads to Thrombus Formation

Loss of the extracellular matrix and cellular necrosis dueto the inflammatory response appear to be the key

mediators for plaque rupture


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Plaque Rupture Leads to Thrombus Formation

hiazarians Y et al. N En l J Med. 2000 342:101-114.


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Role of Platelets in ThrombusFormation

in Acute Ischemic Events

AtheroscleroticVessel

PlaqueRupture

Platelet Adhesion,Activation, and

Aggregation

ThrombusFormation

ThromboticOcclusion

MIStroke

VascularDeath

LipidCore

Schafer AISchafer AI. Am J Med. Am J Med..1996;101:199209.1996;101:199209.

Vessel wall injury Plaque rupture Exposure of subendothelial collagen andother platelet-adhering ligands


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a cross-section of the coronary artery. Most of its wall is filled

with smooth muscle cells that can contract and relax.

atherosclerotic plaque( consists of cholesterol, inflammatory cells,

and fibrosis, and it reduces the space for blood flow in the artery.)

Nitroglycerin dilates constricted arteries. A spasm can suddenly develop in an atheroscleroticcoronary artery ( angina pectoris)


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Koroner normal

Pasokan seimbang dengan kebutuhan

(aliran darah koroner) (kebutuhan miokard)

PJK Pasokan , kebutuhan

tetap

Pasokan tetap, kebutuhan


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Patofisiologi SKA

Injury &

disfungsi endotel

Plak takstabil

HipertensiMerokok

DM

Dislipidemia

Zat vasoaktif

dll

VasokonstriksiDisfungsi endotel

Platelet & thrombin

dependent vasoconstriction

Agregasi trombosit,

akumulasi lipid & makrofag

disrupsi

Oklusi koroner

Trombosis akut

APTS

IMA

Plak stabil


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NormalNormal

FattyFatty

StreakStreak

FibrousFibrous

PlaquePlaque


PlaquePlaque



MIMI

StrokeStroke



CoronaryCoronary

DeathDeath




UnstableUnstable

AnginaAngina


Courtesy of P Ganz.


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Spectrum of Acute coronary syndromes

Acute Coronary Syndrome

No ST Elevation ST Elevation

Unstable Angina Myocardial Infarction

Non Qw MI Qw MI(NSTEMI) (STEMI)

Non ST Elevation MI

Braunwald E et al. J Am Coll Cardiol2000;36:9701062.


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Cardiac serum marker in Acute Myocardial Infarction


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Acute CoronarySyndrome

Ischemic Discomfort

Unstable Symptoms

No ST-segment

elevation

ST-segment

elevation

Unstable Non-Q Q-Wave

angina AMI AMI

ECG

AcuteReperfusion

History

Physical Exam


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Plaque Rupture with Thrombosis

ThrombusFibrous cap

1 mm

Lipid core

Illustration courtesy of Frederick J. Schoen,M.D., Ph.D.


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Let it

b t!

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Aterioskleorisi & PJK_CVS-K33