K33 - Arteriosklerosis & PJK (Fisiologi).ppt

Atherosclerosis

Atherosclerosisis characterized by localized fibrous thickenings of the arterial wall associated with lipid-infiltrated plaques that may eventually calcify.

NormalFatty StreakFibrous PlaqueOcclusive Atherosclerotic PlaquePlaque Rupture/ Fissure & ThrombosisMIStrokeCritical Leg IschemiaClinically SilentCoronary DeathIncreasing AgeEffort AnginaClaudicationUnstableAnginaAtherosclerosis: A Progressive ProcessCourtesy of P Ganz.

Pathogenesisinitial event is : Infiltration of low-density lipoproteins (LDL) into the sub endothelial region. endothelium is subject to shear stress, tendency to be pulled along or deformed by flowing blood.

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 streaks appear in the aorta, in the second decade in the coronary arteries, and in the third and fourth decades in the cerebral arteries.

Vascular smooth muscle cells in the vicinity of foam cells are stimulated and move from the media to the intima, where they proliferate, lay down collagen and other matrix molecules, and contribute to the bulk of the lesion. Smooth muscle cells also take up oxidized LDL and become foam cells.

As plaques mature, a fibrous cap forms over them. plaques with defective or broken caps are most prone to rupture. The lesions alone may distort vessels to the point that they are occluded, but it is usually rupture or ulceration of plaques that triggers thrombosis, blocking blood flow.

NormalFatty StreakFibrous PlaqueOcclusive Atherosclerotic PlaquePlaque Rupture/ Fissure & ThrombosisMIStrokeCritical Leg IschemiaClinically SilentCoronary DeathIncreasing AgeEffort AnginaClaudicationUnstableAnginaAtherosclerosis: A Progressive ProcessCourtesy of P Ganz.

Risk FactorMale gender (and female after menopause) : Lack of LDL-lowering effect of estrogens; estrogens probably act by increasing the number of LDL receptors in the liver.Family history of ischemic heart disease, stroke : Probably multiple genetic mechanisms.

Primary hyperlipidemia and Secondary hyperlipidemia (Increased circulating triglycerides produced by diuretics, b-adrenergic blocking drugs, excess alcohol intake)Cigarette smoking: Probably carbon monoxide-induced hypoxic injury to endothelial cells.

Hypertension: Increased shear stress, with damage to endothelium.Diabetes mellitus (types 1 and 2): Decreased hepatic removal of LDL from the circulation; increased glycosylation of collagen, which increases LDL binding to blood vessel walls.

Obesity, particularly abdominal obesity:Nephrotic syndrome: Increased hepatic production of lipids and lipoprotein(a).Hypothyroidism: Decreased formation of LDL receptors in the liver.

Pathophysiology Acute Coronary Syndrome( A C S )Dr Abdul Majid SpPD-KKV

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PJK Pasokan , kebutuhan tetap

Pasokan tetap, kebutuhan

When flow through a coronary artery is reduced to the point that the myocardium it supplies becomes hypoxic, "P factor" accumulates and angina pectoris develops .If the myocardial ischemia is severe and prolonged, irreversible changes occur in the muscle, and the result is myocardial infarction.

Partially occluded coronary arteries can be constricted further by vasospasm, producing myocardial infarction. The most common cause of myocardial infarction is rupture of an atherosclerotic plaque, or hemorrhage into it, which triggers the formation of a coronary occluding clot at the site of the plaque.

When myocardial cells actually die, they leak enzymes into the circulation, and measuring the rises in serum enzymes and isoenzymes produced by infarcted myocardial cells also plays an important role in the diagnosis of myocardial infarction. The enzymes most commonly measured today are the MB isomer of creatine kinase (CK-MB), troponin T, and troponin I.

Mechanism of Atherosclerosis

ACS: physiopathology

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.

platelet release of vasoconstrictive factors such as thromboxane A2 or serotonin and endothelial dysfunction may cause vasoconstriction and contribute to decreased flow.In myocardial infarction, deep arterial injury from plaque rupture may cause formation of a relatively fixed and persistent thrombus.

Thin Fibrous CapLipid CoreUnstable PlaqueThrombusInflammatory CellsFew SMCsActivated MacrophagesRuptured PlaquePlaque Rupture Leads to Thrombus FormationLoss of the extracellular matrix and cellular necrosis due to the inflammatory response appear to be the key mediators for plaque rupture

Plaque Rupture Leads to Thrombus FormationYeghiazarians Y et al. N Engl J Med. 2000;342:101-114.

Role of Platelets in Thrombus Formation in Acute Ischemic EventsAtherosclerotic VesselPlaque RupturePlatelet Adhesion,Activation, and AggregationThrombus FormationThrombotic OcclusionLipid CoreSchafer AI. Am J Med. 1996;101:199209.Vessel wall injury Plaque rupture Exposure of subendothelial collagen and other platelet-adhering ligands

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 atherosclerotic coronary artery ( angina pectoris)

Koroner normalPasokan seimbang dengan kebutuhan (aliran darah koroner)(kebutuhan miokard)

PJK Pasokan , kebutuhan tetap

Pasokan tetap, kebutuhan

Patofisiologi SKAInjury &disfungsi endotelPlak tak stabilHipertensiMerokokDMDislipidemia Zat vasoaktif dll VasokonstriksiDisfungsi endotelPlatelet & thrombindependent vasoconstrictionAgregasi trombosit, akumulasi lipid & makrofagdisrupsiOklusi koronerTrombosis akutAPTS IMAPlak stabil

NormalFatty StreakFibrous PlaqueOcclusive Atherosclerotic PlaquePlaque Rupture/ Fissure & ThrombosisMIStrokeCritical Leg IschemiaClinically SilentCoronary DeathIncreasing AgeEffort AnginaClaudicationUnstableAnginaAtherosclerosis: A Progressive ProcessCourtesy of P Ganz.

Spectrum of Acute coronary syndromes Acute Coronary SyndromeNo ST ElevationST ElevationUnstable AnginaMyocardial InfarctionNon Qw MI Qw MI(NSTEMI) (STEMI)Non ST Elevation MIBraunwald E et al. J Am Coll Cardiol 2000;36:9701062.

Cardiac serum marker in Acute Myocardial Infarction

Acute Coronary SyndromeIschemic Discomfort Unstable SymptomsNo ST-segment elevation ST-segment elevationUnstable Non-QQ-Wave angina AMI AMIECGAcute ReperfusionHistory Physical Exam

Plaque Rupture with ThrombosisThrombusFibrous cap1 mmLipid coreIllustration courtesy of Frederick J. Schoen, M.D., Ph.D.

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