Ischemic Heart Disease,Angina,MI Flashcards
Pathogenesis
preexisting atherosclerotic occlusion of the coronary arteries and new superimposed thrombosis and/or vasospasm
LAD,LCX
RCA
Contributing elements
Inflammation(inception to plaque rupture
interaction of endothelial cells and circulating leukocytes, resulting in T cell and macrophage recruitment and activation
smooth muscles get activated
and superimposed on a lipid core
Thrombosis associated with an eroded or ruptured plaque
triggers the acute coronary syndromes.
partial luminal occlusion by a thrombus can compromise
blood flow sufficiently to cause a infarction of
the innermost zone of the myocardium (subendocardial
infarct). Organizing thrombi produce potent activators
of smooth muscle proliferation, which can contribute tosmall
emboli can be found in the distal intramyocardial circulation
(along with associated microinfarcts) at autopsy
of patients with unstable angina
the growth of atherosclerotic lesions
Vasoconstriction directly compromises lumen diameter;
moreover, by increasing local mechanical shear forces,
vessel spasm can potentiate plaque disruption
Circulating adrenergic agonists
• Locally released platelet contents
• Imbalance between endothelial cell–relaxing factors
(e.g., nitric oxide) and –contracting factors (e.g.,
endothelin) due to endothelial dysfunction
• Mediators
Acute Plaque Change
most patients, unstable angina, infarction, and sudden
cardiac death occur because of abrupt plaque change followed
by thrombosis—hence the term acute coronary
syndrome (
Plaques
most patients, unstable angina, infarction, and sudden
cardiac death occur because of abrupt plaque change followed
by thrombosis—hence the term acute coronary
syndrome (
Fibrous caps
Fibrous caps also are continuously remodeling; their
overall balance of collagen synthesis versus degradation
determines mechanical strength and plaque stability.
Collagen is produced by smooth muscle cells and
degraded by the action of metalloproteases elaborated
by macrophages. Consequently, atherosclerotic lesions
with a paucity of smooth muscle cells or large numbers
of inflammatory cells are vulnerable to rupture. Of
interest, statins (inhibitors of hydroxymethylglutaryl
Co-A reductase, a key enzyme in cholesterol synthesis)
can provide additional benefit in CAD and IHD by
reducing plaque inflammation and increasing plaque
stability, effects distinct from and their primary
cholesterol-lowering activity
Influences extrinsic to the plaque also are important
Influences extrinsic to the plaque also are important
Angina Pectoris
Intermittent chest pain
Typical or stable angina is predictable episodic chest pain
associated with particular levels of exertion or some
other increased demand (e.g., tachycardia)
Pain of angina pectoris
Typical or stable angina is predictable episodic chest pain
associated with particular levels of exertion or some
other increased demand (e.g., tachycardia
Prinzmetal
variant angina
Typical or stable angina is predictable episodic chest pain
associated with particular levels of exertion or some
other increased demand (e.g., tachycardia
Unstable angina
characterized
by increasingly frequent pain, precipitated by progressively
less exertion or even occurring at rest.
Unstable angina is associated with plaque disruption
and superimposed thrombosis, distal embolization of
the thrombus, and/or vasospasm; it can be a harbinger
of MI, portending complete vascular occlusion.
Heart attack/MI
is necrosis of the heart muscle resulting
from ischemia. The major underlying cause of IHD is atherosclerosis;
while MIs can occur at virtually any age, the
frequency rises progressively with aging and with increasing
risk factors for atherosclerosis
Sequence of events
atheromatous plaque is eroded or suddenly disrupted
by endothelial injury, intraplaque hemorrhage, or
mechanical forces, exposing subendothelial collagen
and necrotic plaque contents to the blood
atheromatous plaque is eroded or suddenly disrupted
by endothelial injury,
intraplaque hemorrhage, or
mechanical forces, exposing subendothelial collagen
and necrotic plaque contents to the blood
Activation of coagulation by exposure of tissue factor and
other mechanisms adds to the growing thrombus.
• Within minutes, the thrombus can evolve to completely
occlude the coronary artery lumen
Myocardial response
seconds of vascular obstruction, aerobic metabolism
ceases, leading to a drop in adenosine triphosphate
(ATP) and accumulation of potentially noxious metabolites
(e.g., lactic acid) in the cardiac myocytes. The functional
consequence is a rapid loss of contractility, occurring
within a minute or so of the onset of ischemia
Myocardial ischemia also contributes to arrhythmias,
probably by causing electrical instability (irritability) of
ischemic regions of the heart.
subendocardial regions of heart
