Robbins pg. 374-382 Flashcards
Why would cardiac function be strictly dependent upon the continuous flow of
oxygenated blood through the coronary arteries?
Because cardiac myocytes generate energy almost exclusively through mitochondrial oxidative phosphorylation
In more than 90% of cases, IHD is a consequence of what?
reduced coronary blood flow secondary to obstructive atherosclerotic vascular disease
Thus, unless otherwise specified, IHD usually is synonymous with coronary artery disease (CAD).
Less frequently, IHD can result from what other things?
increased demand (e.g., with increased heart rate or hypertension);
diminished blood volume (e.g., with hypotension or shock);
diminished oxygenation (e.g., due to pneumonia or CHF); or
diminished oxygen-carrying capacity (e.g., due to anemia or CO poisoning)
The clinical presentation of IHD may include what symptoms?
- angina pectoris
- acute MI
- sudden cardiac death
What are the types of angina pectoris?
Ischemia induces pain but is insufficient to cause myocyte death.
Angina can be stable (occurring predictably at certain levels of exertion), can be caused by vessel spasm (Prinzmetal angina), or can be unstable (occurring with progressively less exertion or even at rest).
What does the term acute coronary syndrome mean?
refers to any of the
three catastrophic manifestations of IHD—unstable angina,
acute MI, and SCD.
Clinically significant plaques contributing to IHD can be located anywhere but tend to occur where?
within the first several centimeters of the LAD and LCX, and along the entire length of the RCA
What is the basis of critical stenosis?
Critical stenosis refers to the percentage of coronary occlusion needed to produce symptoms of IHD upon exertion. Typically, the critical stenosis is around 70% occlusion. At this point, symptoms are typically only present upon exertion and present as chest pain (stable angina)
When does stable angina transition to unstable angina?
A fixed stenosis that occludes 90% or more of a vascular lumen can lead to inadequate coronary blood flow with symptoms even at rest. This is termed unstable angina
Is the rate at which atherosclerotic stenosis develops an important factor in the potential of the plaque to cause IHD?
Yes, typically with slow developing occlusion, other coronary arteries have time to provide collateral perfusion to the heart
What does atherosclerosis begin with?
interaction of endothelial cells and circulating leukocytes driven by INFLAMMATION, resulting in T cell and macrophage recruitment and activation
metallo-proteinases secreted by macrophages can destabilize plaques
What is the most direct cause of chest pain with angina pectoris?
The pain probably is a
consequence of the ischemia-induced release of adenosine, bradykinin, and other molecules that stimulate the autonomic afferents.
How does stable angina (chest pain upon exertion) present clinically?
The pain is classically described as a crushing or squeezing substernal
sensation, that can radiate down the left arm or to the left jaw (referred pain).
How is stable angina typically treated?
The pain usually is relieved by rest (reducing demand) or by drugs such as nitroglycerin, a vasodilator that increases coronary perfusion.
What is Prinzmetal (variable) angina?
occurs at rest and is causedmby coronary artery spasm. Although such spasms typically occur on or near existing atherosclerotic plaques, completely normal vessel can be affected.
Prinzmetal angina typically responds promptly to vasodilators such as nitroglycerin and calcium channel blockers.
What is an MI?
Myocardial infarction (MI), also commonly referred to as “heart attack,” is necrosis of heart muscle resulting from ischemia
The vast majority of MIs are caused by what?
acute coronary artery thrombosis
In most instances,
disruption of preexisting atherosclerotic plaque serves as the nidus for thrombus generation, vascular occlusion, and subsequent transmural infarction of the downstream myocardium.
In a typical MI, the following
sequence of events takes place:
• An atheromatous plaque is suddenly disrupted by intraplaque hemorrhage or mechanical forces, exposing subendothelial collagen and necrotic plaque contents to the blood.
• Platelets adhere, aggregate, and are activated, releasing
thromboxane A2, adenosine diphosphate (ADP), and serotonin—causing further platelet aggregation and vasospasm
• Within minutes, the thrombus can evolve to completely occlude the coronary artery lumen.
Can a thrombus inducing MI clear without intervention?
Yes it is fairly common (25% range) through lysis of the thrombus or relaxation of spasm.
Does the myocardial structure respond to ischemia?
Within seconds of vascular obstruction, aerobic glycolysis ceases, leading to a drop in ATP and accumulation of potentially noxious metabolites (e.g., lactic acid) in the cardiac
myocytes.
What is the functional consequence of aerobic glycolysis cessation?
The functional consequence is a rapid loss of contractility, which occurs within 1 minute or so of the onset of ischemia.
Ultrastructural changes (including myofibrillar relaxation, glycogen depletion, cell and mitochondrial swelling-makes cells red) also become rapidly apparent.
Are the early changes of ischemia reversible?
Yes, only severe ischemia lasting at least 20 to 40 minutes causes irreversible damage and myocyte death leading to coagulation necrosis. With longer periods of ischemia, vessel injury ensues, leading to microvascular thrombosis.
