Atherosclerosis

Atherosclerosis
is characterized by localized fibrous thickenings of the arterial wall associated with lipidinfiltrated plaques that may eventually calcify.

Atherosclerosis: A Progressive Process

Normal Fatty Streak Fibrous Plaque Occlusive Atherosclerotic Plaque Plaque Rupture/ Fissure & Thrombosis

Unstable Angina

MI Coronary Death Stroke Clinically Silent Effort Angina Claudication Critical Leg Ischemia

Increasing Age Courtesy of P Ganz.

Pathogenesis initial event is : Infiltration of lowdensity 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.

Atherosclerosis: A Progressive Process

Normal Fatty Streak Fibrous Plaque Occlusive Atherosclerotic Plaque Plaque Rupture/ Fissure & Thrombosis

Unstable Angina

MI Coronary Death Stroke Clinically Silent Effort Angina Claudication Critical Leg Ischemia

Increasing Age Courtesy of P Ganz.

Risk Factor
Male gender (and female after menopause) : Lack of LDLlowering 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, badrenergic 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 (ACS)

Dr Abdul Majid SpPD-KKV

Koroner normal Pasokan seimbang dengan kebutuhan

(aliran darah koroner) (kebutuhan miokard)

PJK Pasokan , tetap

kebutuhan

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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 10 20 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.

Plaque Rupture Leads to Thrombus Formation

Unstable Plaque Ruptured Plaque
Inflammatory Cells Thrombu Thrombu
s s Few SMCs
Activated Macropha ges

Thin Fibrous Cap Lipid Core

Loss 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 Formation

hiazarians Y et al. N Engl J Med. 2000;342:101-114.

Role of Platelets in Thrombus Formation in Acute Ischemic Events

Lipid Core

Atherosclerotic Vessel

Plaque Rupture

Platelet Adhesion, Activation, and Aggregation

Thrombus Formation

Thrombotic Occlusion

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

MI Stroke Vascular Death

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

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 normal Pasokan seimbang dengan kebutuhan

(aliran darah koroner) (kebutuhan miokard)

PJK Pasokan , tetap

kebutuhan

Pasokan tetap, kebutuhan

Patofisiologi SKA
Agregasi trombosit, akumulasi lipid & makrofag Plak stabil Injury & disfungsi endotel Hipertensi Merokok DM Dislipidemia Zat vasoaktif dll Disfungsi endotel Plak tak stabil disrupsi Trombosis akut APTS Oklusi koroner IMA Platelet & thrombin dependent vasoconstriction Vasokonstriksi

Atherosclerosis: A Progressive Process

Normal Fatty Streak Fibrous Plaque Occlusive Atherosclerotic Plaque Plaque Rupture/ Fissure & Thrombosis

Unstable Angina

MI Coronary Death Stroke Clinically Silent Effort Angina Claudication Critical Leg Ischemia

Increasing Age Courtesy of P Ganz.

Spectrum of Acute coronary syndromes

Acute Coronary Syndrome

No ST Elevation Non ST Elevation MI

ST Elevation

Unstable Angina

Myocardial Infarction Non Qw MI Qw MI

(NSTEMI) (STEMI)

Braunwald E et al. J Am Coll Cardiol 2000;36:9701062.

Cardiac serum marker in Acute Myocardial Infarction

Acute Coronary Syndrome

Ischemic Discomfort Unstable Symptoms
History Physical Exam

No ST-segment elevation

ST-segment elevation

ECG

Unstable angina

Non-Q AMI

Q-Wave AMI

Acute Reperfusion

Plaque Rupture with Thrombosis

Thrombus Fibrous cap

1 mm

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

Lipid core

Let it beat!