Endothelium, Plaque Rupture and Vascular Injury

Question 1

What does PAD stand for?

Answer 1

peripheral artery disease

Question 1

What are the characteristics of an arterial thrombus?

Answer 1

1. platelet rich 2. plaque rupture 3. areas of high flow 4. atherosclerosis, trauma, APLA 5. antiplatelet therapy

Question 2

What do foam cells secrete and what is the relevance?

Answer 2

MMP- causes plaque to become unstable

Question 3

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?

Answer 3

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).

Question 3

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?

Answer 3

Vasospasm.

Question 4

Nitric oxide synthase is expressed on the ____ side of the ____.

Answer 4

luminal; epi

Question 4

What is a vulnerable plaque?

Answer 4

lipid rich with a thin cap and many inflammatory cells

Question 4

What is the common mechanism for angina?

Answer 4

a stable, obstructive lesion

Question 5

Unhealthy vascular beds are in a state of _____.

Answer 5

inflammation

Question 5

Describe the characteristics of a venous thrombus.

Answer 5

1. fibrin rich 2. RBCs 3. areas of stasis 4. genetic predisposition 5. environmental predisposition 6. treated with anticoagulation

Question 6

What does an athroembolism from the carotid bifurcation cause? Where?

Answer 6

a stroke; brain and ophthalmic artery occlusion (blindness)

Question 7

What do foam cells do?

Answer 7

1. activate SM cells to induce their migration and proliferation 2. induce apoptosis of endothelial cells 3. cause fibrosis of the intima 4. perpetuate inflammation

Question 7

Where do you listen for bruits?

Answer 7

at the carotid bifurcation (just below the jaw)

Question 9

What best describes normal endothelial histology?

Answer 9

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

Question 10

What can happen when a plaque ruptures?

Answer 10

either a thrombus is formed, causing an MI, or it heals but the lumen is narrowed b/c of a fibrous intima

Question 11

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?

Answer 11

There is an atherosclerotic plaque that is 70% obstructive. Coronary flow is limited with exercise but not at rest. Tx: nitrates, revasularization

Question 11

NO causes vasodilation and also ______ when it diffuses into endothelial cells.

Answer 11

affects expression of inflammatory genes

Question 12

How do stable plaques present?

Answer 12

angina or claudication upon exertion

Question 13

How does a mac become a foam cell?

Answer 13

they ingest LDL

Question 15

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?

Answer 15

There is an atherosclerotic plaque that is 70% obstructive. Blood flow is limited with exercise but not at rest.

Question 16

NO causes _____-mediated vasodilation.

Answer 16

cGMP

Question 18

Large arteries – more elastin Smaller arteries – ______ Arterioles – more smooth muscle

Answer 18

more collagen

Question 19

If the MI is caused by a plaque rupture that results in a completely occlusive thrombus, it is called a _____ and is treated by _____.

Answer 19

STEMI; recanalization

Question 20

How does leg claudication present?

Answer 20

pain or discomfort in the leg upon exertion; almost always in the calf

Question 21

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?

Answer 21

There has been thromboembolism. The deep venous thrombosis migrated to the pulmonary arteries.

Question 22

What is the common mechanism for a stroke?

Answer 22

1. athroembolism of a carotid bifurcation lesion 2. thromboembolism from the L atrial appendage in A-fib

Question 23

Large arteries – more elastin Smaller arteries – more collagen Arterioles – more _____

Answer 23

smooth muscle

Question 24

What is venous thromboembolic disease?

Answer 24

blood clots in the veins— DVTs and PEs

Question 25

If the MI is caused by a plaque rupture that results in a non-occlusive thrombosis, it is called a _____ and is treated by ____.

Answer 25

NSTEMI; anticoagulation/vasodilators

Question 27

What occurs in the abnormal endothelium?

Answer 27

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.

Question 29

Large arteries – ______ Smaller arteries – more collagen Arterioles – more smooth muscle

Answer 29

more elastin

Question 30

What is the common mechanism for claudication?

Answer 30

a stable, obstructive plaque that is >70% occlusive

Question 32

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?

Answer 32

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.

Question 33

What is the common mechanism for acute limb ischemia

Answer 33

usually a thrombotic event- acute- obstructs blood flow- can be atheroembolism or thromboembolism

Question 34

What is the common mechanism for an MI?

Answer 34

ruptured plaque ==> in-situ thrombosis

Question 35

What is a stable plaque?

Answer 35

rich in fibrous tissue, calcified, low lipid content, inflammation, and apoptosis

Question 36

_____ is expressed on the luminal side of the epi.

Answer 36

NO synthase

Question 38

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?

Answer 38

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).

Question 39

Normal paracrine and endocrine functions of the endothelium include?

Answer 39

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.)

Question 40

What are the 2 manifestations of PAD?

Answer 40

1. claudiacation 2. acute limb ischemia

Question 41

NO is synthesized from the aa, ____.

Answer 41

arginine

Question 42

What molecules does the endothelium express that regulates thrombus formation?

Answer 42

1. heparin sulfate 2. thrombin 3. NO 4. platelet activation factor 5. prostacyclin

Question 43

What molecules to endothelial cells express that allow inflammatory cells to enter the intima?

Answer 43

selectins and CAMs

Question 44

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?

Answer 44

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.