02/23g Atherosclerosis Flashcards
What are the progressive steps to forming an atherosclerotic lesion?
1) Begin with fatty streaks (lipid-filled myointimal cells) that start forming within 20 years
2) Progress to fibrous plaques, when a subendothelial cap forms over extracellular lipid
3) Plaques with erosion, intramural hemorrhage, thrombus, and/or calcification qualify as complicated plaques
What are common sites of atherosclerotic plaque formation?
*Larger vessels and branch points* Abdominal aorta and iliac arteries Proximal coronary arteries Thoracic aorta Internal carotid and cerebral artery
What are uncommon sites of atherosclerotic plaque formation?
Subclavian arteries
Axillary arteries
Renal arteries
Superior mesenteric and celiac arteries
What are the major risk factors for atherosclerosis that cannot be changed?
Genetics
Male
Age (older than 55)
What are the major risk factors for atherosclerosis that CAN be changed?
Tobacco use
Hypertension
Lipidemias
Diabetes mellitus
What laboratory test result is correlated with a higher risk of adverse coronary events? What does it indicate?
High C-Reactive Protein (CRP), an acute phase reactant
Indicates ongoing inflammation
What can you do to reduce your CRP levels and risk of a coronary event?
Adjust lifestyle
Medications (statins)
Which is a stronger predictor for coronary artery disease - high CRP or high cholesterol?
High CRP
What are three models of the pathogenesis of atherosclerosis?
Intimal injury and repair model - response to injury hypothesis
Mural thrombosis and organization model - thrombogenic or encrustation hypothesis
Monoclonal proliferation model - monoclonal hypothesis
What are the possible ‘injuries’ in the Injury and Repair Model?
Hyperlipidemia Hypertension and shear stress Tobacco abuse Inflammatory state Microorganisms/viruses (CMV, adenovirus)
What are the effects of the injury in the Injury and Repair Model?
Accumulation of lipids and free radicals
Release of cytokines and chemokines
Necrosis/apoptosis and thrombosis
Fibrosis
What cells are involved in the Injury and Repair Model?
Smooth muscle cells Macrophages Endothelial cells WBCs Platelets
What role to Toll-like receptors play in the progression of atherosclerosis?
TLRs can be stimulated by endogenous ligands
Respond by affecting lipid transport, affecting macrophage uptake and release, interacting with oxidized lipoproteins, and upregulating cytokines
May also stimulate arterial remodeling to accommodate progressing atherosclerosis
What conditions are caused by luminal narrowing in clinical atherosclerosis?
Critical stenosis and episodic ischemia
What are the symptoms of episodic ischemia?
Angina pectoris
Transient ischemic attacks with possible emboli
Intermittent claudication (cramping while walking)
Renovascular hypertension
Mesenteric ischemia
What is acute arterial occlusion? What is the most common cause?
Sudden significant or total obstruction of the lumen of an artery
Most commonly caused by a thrombus superimposed over a plaque rupture/erosion site
What is a vulnerable plaque?
A plaque that is more likely to rupture and cause thrombosis
What qualities make a plaque vulnerable to rupture?
Large atheromatous core Thin fibrous cap/increased cap tension Inflammation or foam cells in fibrous cap Matrix metalloproteases Cap fatigue/stress
Which type of plaque is more likely to cause clinical effects - an obstructive plaque, or a vulnerable plaque?
A vulnerable plaque
What is the purpose of a stress test? What are its limitations?
To demonstrate symptoms of flow restriction when requirements are increased
To demonstrate ischemia due to critical stenosis through exercise or pharmacoloy
Limited because it only predicts severity of stenosis, not plaque vulnerability
What are some other complications of atherosclerosis?
Thrombosis
Aneurysms
Aortic dissection
What is an aneurysm?
An area of weakness in the wall of a blood vessel that typically results in bulging due to arterial blood pressure
What factors can put you at risk for an aneurysm?
Congenital/genetic - polycystic kidney disease, Marfan syndrome
Atherosclerosis
Infectious disease
Autoimmune disorders - lupus, arthritis
What factors can put you at risk for aortic dissection?
Cystic medial necrosis - loss of elastin fibers and smooth muscle, and replacement with ground substance
Marfan syndrome
Hypertensive injury (cocaine abuse)
