Atherosclerosis and Aneurysms Flashcards
T/F: Atherosclerosis can begin in childhood with the development of fatty streaks advancing with age
True
What is the typical cause of death due to atherosclerosis?
Ischemic heart disease (IHD)
What are (2) major predictors of atherosclerosis?
- HTN
- Hypercholesterolemia
Describe what atherosclerosis is.
- Lesions of the vascular intima called atheromas
- Atheromas impinge on vascular lumen (stenosis) and can suddenly rupture leading to occlusion
Occlusion –> ischemia + hypoxia
Weakening of the tunica media due to atherosclerosis can lead to what disorder?
Aneurysm
What is the pathogenesis of atherosclerosis?
- Chronic stress on endothelium leads to endothelial injury and dysfunction
- Leads to upregulation of ICAM-1 and VCAM-1
- Invasion of monocytes and lymphocytes through disrupted endothelial barrier
- Platelets adhere to endothelial (vessel) wall and release mediators
Plaque deposition along the arterial walls leads to what type of blood flow?
TURBULENT
How is the fibrous cap created during atherosclerosis?
- Platelets, macrophages, endothelial cells, and smooth muscle cells release growth factors
- Smooth muscle cells synthesize ECM including collagen that creates the fibrous cap
This is done to stabilize plaque
How are fatty streaks formed during atherosclerosis?
- Macrophages ingest oxidized LDL cholesterol and transform into foam cells
- Foam cells accumulate and turn into fatty streaks (early atherosclerotic lesions)
- Foam cells release cellular proteases and inflammatory cytokines
What is the basic structure of an atheromatous plaque?
- Fibrous cap: macrophages (foam cells), smooth muscle cells, and collagen & eastin
- Necrotic center: cholesterol crystals, foam cells, cell debris (garbage)
How do macrophages disrupt the integrity of the fibrous cap of an atheroma?
- Macrophages secrete matrix metalloproteinases leading to weakning of the fibrous cap
- This is due to breakdown of ECM via MMPs
- Minor stress leads to fibrous cap rupture (leading to thrombus
What is the molecule that antagonizes (balances) the activity of MMP?
Tissue inhibitor of MMP (Matrix metalloproteases)
Dysfunctional endothelial cells express adhesion molecules that stimulate what?
Leukocyte adhesion
Macrophages that take up oxidized LDL release what chemicals?
Inflammatory mediators
CRP is a strong independent risk factor for?
- MI
- Stroke
- PAD
- Sudden cardiac death
Even in apparently healthy individuals
Role of inflammation in atherosclerosis: INF-γ
Activation of macrophages, endothelial cells, and smooth muscle cells
Role of inflammation in atherosclerosis: IL-1
Recruitment and activation of macrophages & T-cells
Role of inflammation in atherosclerosis: ROS
LDL oxidation (macrophages ingest oxidized LDL)
Role of inflammation in atherosclerosis: MMPs
Breakdown of Extracellular matrix (ECM)
Role of inflammation in atherosclerosis: Platelets, macrophages, endothelial cells, and smooth muscle cells
- Secrete growth factors TGF, FGF, PDGF
- Leads to smooth muscle cell proliferation
What is a proven drug that treats the inflammatory response seen in atherosclerosis? What is its MOA?
- Canakinumab
- Targets IL-1
Compare a Stable plaque versus an Unstable plaque.
Stable Plaque
* Small lipid core w/ a thick fibrous cap
* Little inflammation w/o intraplaque hemorrhaging or rupture
* Reduction in blood flow during exertion
Unstable Plaque
* Large lipid core w/ a thin fibrous cap
* High inflammation w/ intraplaque hemorrhaging and rupture
* MMP –> degradation of collagen & fibrous components –> exposing of thrombogenic core –> thrombus formation and vessel occlusion
What is an extrinsic factor on plaques that can lead to instability?
HTN (increased BP)
What are the most commonly involved vessels in atherosclerosis?
- Abdominal Aorta
- Coronary Artery
- Popliteal Artery
- Internal Carotids
- Circle of Willis
Abundant Corona Pops In Circles
When does the risk of MI increase 5x?
Between 40-60 yo
Accumulation of vascular injury
T/F: Estrogen therapy in post-menapausal women has been shown to decrease cardiovascular risk
False, it has not shown any benefit
What age group appears to be protected from cardiovascular disease when age-matched with the other population?
Females
What is the cigarette/day evaluated to increase cardiovascular mortality significantly?
10 cigarettes/day
* Males: 20%
* Females: 30%
What are the (5) factors of metabolic syndrome?
- HTN
- Waistline (M: 40”; F: 35”)
- Low HDL (M: < 40 mg/dL; F: 50 mg/dL)
- High Tg > 150 mg/dL
- FBG > 100 mg/dL
What is a rare inborn error of metabolism that results in elevated levels of circulating homocysteine and is associated with premature vascular disease?
Hyperhomocysteinemia
What is a hematoma?
Abnormal collection of blood outside of a vessel
What are aneurysms?
Abnormal dilations of arteries defined as a ≥50% increase in arterial diameter compared to normal
Compare a true aneurysm versus a false aneurysm.
True aneurysm
* Involves all 3 layers of artery (intima, media, adventitia)
False aneurysm
* Bulging pulsatile mass
* Local hematoma
The infrarenal aorta relies on what to acquire nutrients?
Nutrient diffusion from abdominal aorta
* has a poorly developed vaso vasorum (vessels dedicated to it)
What is the pathogenesis of aneurysms due to atherosclerosis?
- Atherosclerosis leads to thickening of intima
- Increases distance that O2 and nutrients diffuse to reach the tunica media
- Activates macrophages leading to MMP secretion and ECM degradation
What is the pathogenesis of aneurysms due to systemic HTN?
- Systemic HTN leads to hyaline arteriosclerosis resulting in lumenal stenosis leading to decreased supply of O2 and nutrient delivery to the tunica media
- Increased shear stress leading to endothelial injury and atherosclerosis
What is the pathogenesis of aneurysms due to tertiary syphilis?
- Tertiary syphilis leads to inflammation of vasa vasorum of the thoracic aorta leading to tunica media ischemia
- Leads to smooth muscle cell, elastic fiber, and ECM loss
What is the pathogenesis of aneurysms due to infections?
- Microorganisms seed vessel wall
- Suppuration and inflammation that leads to tunica media destruction causing rapid dilation and rupture of the vessel wall
What is the pathogenesis of aneurysms due to Marfan Syndrome?
- Inability to sequester endogenously produced TGF-β
- Fragmentation of elastic lamina and fibrosis
- Abnormal TGF-β siganling leads to defective elastin and collagen synthesis
- Diminished ECM contents and aneurysmal dilation
What is the pathogenesis of aneurysms due to Ehlers-Danlos Syndrome?
Defective Type III collagen leading to thin skin, arterial rupture and easy bruising
Where is Type I Collagen found?
One BITE
* Bones
* Eyes
* Teeth
* Ears
Where is Type II Collagen found?
CarTWOlage = Type II collagen
Cartilage
Where is Type III collagen found?
Three = Reticulin fibers
* vessels, uterus, granulation tissue
Where is Type IV Collagen found?
Four = Floor
* Basement membrane
* Lens
When does the USPSTF recommend screening for abdominal aortic aneurysm (AAA)?
1-time screening
Males 65-75 yo who have smoked
Where do abdominal aortic aneurysms typically occur?
Between renal arteries and the aortic bifurcation
* Decreased collagen content
What type of inflammation characterizes abdominal aortic aneurysms?
Transmural inflammation
Degradation of elastin & collagen by MMP & loss of smooth muscle
What is the sizing standard of thoracic aortic aneurysms?
≥3 cm
What are some common risk factors for thoracic aortic aneurysms?
- HTN, smoking, age
- Tertiary syphilis
- Bicuspid aortic valve
- Connective tissue disease (e.g., Marfans; Ehlers-Danlos)
What occurs in cystic medial degeneration?
Accumulation of mucopolysaccharides in the tunica media of vessels leading to a loss of muscle and elastic fibers
Non-inflammatory
How can a thoracic aortic aneurysm present?
- Respiratory or feeding difficulties due to airway or esophageal compression
- Persistent cough from irritation of the recurrent laryngeal nerves
How may an abdominal aortic aneurysm present?
During PE as a palpable, puslatile, non-tender abdominal mass
