Pathogenesis of ACSs

ACSs

• May result from new superimposed thrombosis on a pre-existing ("fixed") atherosclerotic occlusion and/or vasospasm of one or more coronary arteries.

Role of Acute Plaque Changes

• In most patients, unstable angina, infarction, and many cases of SCD all occur because of abrupt plaque change followed by thrombosis.

• Hence the term acute coronary syndrome.

Acute Plaque Changes

Acute Coronary Syndromes

Rupture, fissuring, or ulceration Exposing

Highly thrombogenic plaque constituents

Underlying subendothelial

basement membrane

Hemorrhage into the core of plaques

Expansion of plaque volume

Worsening of the luminal occlusion

Plaque rupture

Events that trigger the abrupt plaque changes

• Rupture reflects the inability of a plaque to withstand mechanical stresses.

• Triggers may be intrinsic or extrinsic

Intrinsic factors

• Large atheromatous core

• Thickness of the fibrous cap

Extrinsic factors

• Adrenergic stimulation • Intense emotional stress

Integrity of the Plaque

collagen synthesis

collagen degradation

Fibrous caps are continuously remodeling

Collagen produced by smooth muscle cells

Collagen degraded by the action of metalloproteinases (macrophages)

Role of Inflammation

• Inflammation plays an essential role at all stages of atherosclerosis

• What’s the contribution of Inflammation to acute coronary syndromes…?

Inflammation Neutrophil infiltration

Release of metalloproteinases

Breakdown of collagen in the

fibrous cap

Plaque destabilization &

rupture

Role of Thrombus

• Formation of a thrombus on a disrupted atherosclerotic plaque

• Significant rapid stenosis• Complete occlusion of the coronary arteries• Mural thrombus in a coronary artery can also

embolize• Small fragments of thrombotic material• Small infarcts

Acute Myocardial Infarction• Ischemic necrosis of a part of the myocardium• In a typical MI,

Within minutes the thrombus can evolve to completely occlude the coronary lumen of the coronary vessel

Vasospasm (platelet aggregation and mediator release)

Other mediators activate the extrinsic pathway of coagulation

Release potent secondary aggregators(thromboxane A2, adenosine diphosphate, and serotonin)

Platelets adhere, aggregate, become activated

A sudden disruption of an atheromatous plaque

Acute Myocardial Infarction

Ischemia Death of myocardium

Electrical instability of the myocardium

Arrhythmias (ventricular fibrillation)

Reduction in the contractility of the myocardium

Reduction in the ejection fraction & increase in end systolic volume &

pressure (Heart failure)

Or a fatal mechanical failure

• Irreversible injury of ischemic myocytes first occurs in the subendocardial zone (STEMI)

• With more prolonged ischemia• Involve progressively more of the transmural

thickness (NSTEMI)

Myocardial Infarction