What does PAD stand for?
peripheral artery disease
What are the characteristics of an arterial thrombus?
- platelet rich 2. plaque rupture 3. areas of high flow 4. atherosclerosis, trauma, APLA 5. antiplatelet therapy
What do foam cells secrete and what is the relevance?
MMP- causes plaque to become unstable
A 70 year-old female with a history of hypercholesterolemia presents with intermittent substernal chest pain at rest and 2 mm of ST depression in the lateral leads of an ECG. The pain is improved with nitroglycerin, aspirin, an unfractionated heparin infusion, and a glycoprotein 2b/3a receptor inhibitor. Which of the following best describes the pathophysiology within the circumflex coronary artery?
The fibrous cap of a lipid-rich atherosclerotic plaque ruptured. The plaque was previously 50% obstructive but now a platelet-rich thrombus has formed on the exposed subendothelial components of the plaque such that the lesion is now 90% obstructive to blood (NSTEMI).
A 20 year-old female lives in Alaska and has no risk factors for atherosclerosis or thrombosis. In the winter, she develops ischemia of all fingers when exposed to cold. (This ischemia manifests as pain and symmetric color changes of her digits and is called Raynaud’s phenomenon.) What is the mechanism for this patient’s ischemia?
Nitric oxide synthase is expressed on the ____ side of the ____.
What is a vulnerable plaque?
lipid rich with a thin cap and many inflammatory cells
What is the common mechanism for angina?
a stable, obstructive lesion
Unhealthy vascular beds are in a state of _____.
Describe the characteristics of a venous thrombus.
- fibrin rich 2. RBCs 3. areas of stasis 4. genetic predisposition 5. environmental predisposition 6. treated with anticoagulation
What does an athroembolism from the carotid bifurcation cause? Where?
a stroke; brain and ophthalmic artery occlusion (blindness)
What do foam cells do?
- activate SM cells to induce their migration and proliferation 2. induce apoptosis of endothelial cells 3. cause fibrosis of the intima 4. perpetuate inflammation
Where do you listen for bruits?
at the carotid bifurcation (just below the jaw)
What best describes normal endothelial histology?
a monolayer of cells that comprises the intima, or innermost layer of a vessel wall, and is in direct contact with blood constituents within the vessel lumen
What can happen when a plaque ruptures?
either a thrombus is formed, causing an MI, or it heals but the lumen is narrowed b/c of a fibrous intima
A 76 year-old male with an abnormal exercise treadmill test (2 mm ST depression after walking for 5 minutes) experiences exertional chest discomfort every time he climbs 3 flights of stairs. The discomfort is relieved within 5 minutes of rest (typical angina). Which of the following best describes the pathophysiology within the culprit coronary artery?
There is an atherosclerotic plaque that is 70% obstructive. Coronary flow is limited with exercise but not at rest. Tx: nitrates, revasularization
NO causes vasodilation and also ______ when it diffuses into endothelial cells.
affects expression of inflammatory genes
How do stable plaques present?
angina or claudication upon exertion
How does a mac become a foam cell?
they ingest LDL
The same patient also experiences right calf discomfort when walking 3 blocks. The discomfort is relieved within 5 minutes of rest (typical claudication). Which of the following best describes the pathophysiology within the right superficial femoral artery?
There is an atherosclerotic plaque that is 70% obstructive. Blood flow is limited with exercise but not at rest.
NO causes _____-mediated vasodilation.
Large arteries – more elastin Smaller arteries – ______ Arterioles – more smooth muscle
If the MI is caused by a plaque rupture that results in a completely occlusive thrombus, it is called a _____ and is treated by _____.
How does leg claudication present?
pain or discomfort in the leg upon exertion; almost always in the calf
A 35 year-old female is taking oral contraceptives containing estrogen and has Factor V Leiden, a genetic predisposition to venous thrombosis. She develops an acutely edematous right leg. A duplex US shows a deep venous thrombosis of the right femoral vein. Before unfractionated heparin is started in the emergency department, she develops acute pleuritic chest pain and shortness of breath. A CT angiogram reveals an acute pulmonary embolism. What is the mechanism for the pulmonary embolism?
There has been thromboembolism. The deep venous thrombosis migrated to the pulmonary arteries.
What is the common mechanism for a stroke?
- athroembolism of a carotid bifurcation lesion 2. thromboembolism from the L atrial appendage in A-fib
Large arteries – more elastin Smaller arteries – more collagen Arterioles – more _____
What is venous thromboembolic disease?
blood clots in the veins— DVTs and PEs
If the MI is caused by a plaque rupture that results in a non-occlusive thrombosis, it is called a _____ and is treated by ____.
What occurs in the abnormal endothelium?
a) Increased permeability to lipoprotein particles. b) Increased expression of cell adhesion molecules and increased secretion of inflammatory cytokines (TNF-alpha, TGF-beta, IL-1) resulting in increased leukocyte recruitment. c) Decreased release of nitric oxide and prostacyclin which predisposes to vasoconstriction, platelet activation, and thrombosis.
Large arteries – ______ Smaller arteries – more collagen Arterioles – more smooth muscle
What is the common mechanism for claudication?
a stable, obstructive plaque that is >70% occlusive
An 80 year-old male with a history of atrial fibrillation is unable to tolerate anticoagulation with warfarin due to gastrointestinal bleeding. He develops sudden onset of pain in his right foot. His right foot is also pale and cool to the touch compared to the contralateral lower extremity. There are no pulses in the right foot. Which of the following is MOST LIKELY to describe the pathophysiology within the right popliteal artery?
There has been thromboembolization. For example, a thrombus from the left atrial appendage formed due to this patient’s atrial fibrillation and lack of anticoagulation. The left atrial appendage thrombus has migrated to the right popliteal artery to obstruct blood flow acutely. Because it is an acute event, there has not been time for collaterals to develop to prevent ischemia.
What is the common mechanism for acute limb ischemia
usually a thrombotic event- acute- obstructs blood flow- can be atheroembolism or thromboembolism
What is the common mechanism for an MI?
ruptured plaque ==> in-situ thrombosis
What is a stable plaque?
rich in fibrous tissue, calcified, low lipid content, inflammation, and apoptosis
_____ is expressed on the luminal side of the epi.
A 61 year-old male with a history of hypercholesterolemia presents with severe substernal chest pain at rest and 3 mm of ST elevation in the anterior leads of an ECG. The pain is NOT relieved by nitroglycerin, aspirin, or an unfractionated heparin infusion. Which of the following best describes the most likely pathophysiology within the left anterior descending coronary artery?
The fibrous cap of a lipid-rich atherosclerotic plaque ruptured. The plaque was previously 50% obstructive but now a platelet-rich thrombus has formed on the exposed subendothelial components of the plaque such that the lesion is now 100% obstructive to blood flow (STEMI).
Normal paracrine and endocrine functions of the endothelium include?
a) Defend against thrombosis. (For example, by producing antithrombotic molecules such as heparans and tissue plasminogen activator.) b) Provide anti-inflammatory properties. (For example, by downregulating expression of cell adhesion molecules thereby decreasing leukocyte recruitment.) c) Promote vasodilatation (For example, by secreting vasodilatory molecules such as nitric oxide and prostacyclin.)
What are the 2 manifestations of PAD?
- claudiacation 2. acute limb ischemia
NO is synthesized from the aa, ____.
What molecules does the endothelium express that regulates thrombus formation?
- heparin sulfate 2. thrombin 3. NO 4. platelet activation factor 5. prostacyclin
What molecules to endothelial cells express that allow inflammatory cells to enter the intima?
selectins and CAMs
A 79 year-old female has sudden loss of vision in the right eye. A duplex ultrasound of the carotid arteries reveals a 50% right internal carotid artery stenosis. The neurologist on call states that this carotid stenosis likely is the cause of this patient’s stroke. What is the most likely mechanism for this adverse clinical event?
There has been atheroembolism. For example, a portion of an atherosclerotic plaque has migrated from the right internal carotid lesion into the right ophthalmic artery to obstructive blood flow acutely. The only manifestation of the event is right eye vision loss because the embolism did not involve other cerebral arteries.