pathogenesis of acute coronary syndromes
DESCRIPTION
This presentation was prepared & done on the request by the board certified Consultant Cardiologist, Dr.(Mrs). Nimali Fernando, MDTRANSCRIPT
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