Atherosclerosis Flashcards
what is the innermost later of an artery called and what does it consist of?
Tunica Intima, consists of the endothelium, subendothelial layer and elastic membrane
what is the inner lining of the tunica called and what is it?
It is called the endothelium
it is a continuous thromboresistant layer between the blood and potentially thrombogenic subendothelial tissue
what is the function of the endothelium of an artery
Modulates tone, growth, hemostasis and inflammation throughout circulatory system
what is the middle layer of an artery called and what does it consist of?
- Tunica Media
- Consists of smooth muscle cells and an elastic membrane
what is the outer layer of an artery called and what does it consist of?
- tunica externa / tunica adventitia
- Composed of extracellular matrix with fibroblasts, mast cells and nerve terminals
what are the functions of the tunica intimia, media and externa
- Tunica intima creates the pathway for oxygenated blood to be carried to the site of perfusion
- Tunica media is comprised of smooth muscle that dilates and constricts in response to cardiac output needs
- Tunica externa / adventitia connects arteries to other structures in the body
what is the word break down of atherosclerosis
- athero = porridge, soft, fatty, gruel-like (refers to soft lipid-rich material in the center of atheroma)
- sclerosis = hard, scarring. (refers to connective tissue in the plaques)
what is atherosclerosis
- A pathologic process that causes disease of the coronary, cerebral, and peripheral arteries
how does atherosclerosis begin
with the development of “fatty streaks” within arterial walls.
can develop as early as childhood!!!
what are the 6 histological steps of atherosclerosis
- Fatty streak formation
- Fibrous cap development
- Disruption of the vasa vasorum
- Proliferation of the fibrous plaque
- Development of an advanced lesion
- Intraplaque hemorrhage
histological development of atherosclerotic plaque can help us understand the adverse events that occur in CHF
what causes the formation of fatty streaks in atherosclerosis
- focal thickening of the intima d/t accumulation of foam cells and extracellular matrix.
- Lipids accumulate, creating the fatty streak
- fatty streaks may also contain T lymphocytes
what is biglycan?
a specific protein created by the coronary arteries that can trap VLDL and LDL
what are foam cells
lipid laden macrophages
( in notes, slide 14)
describe the process of fatty streak formation
- Vascular injury precipitates monocyte binding to endothelium
- Monocytes cross endothelium and become activated tissue macrophages
- Macrophages “eat” oxidized LDL, becoming foam cells
- T cells release cytokines, which further activates macrophages and cause smooth muscle cells to proliferate
- Smooth muscle cells move to subendothelial space, producing collagen and taking up LDL, adding to foam cell accumulation
what is a fibrous cap
- A dense, collagen-based layer of connective tissue that covers the well-defined lipid core of an atherosclerotic plaque
- this provides further stability to the atherosclerotic plaque
what is the vasa vasorum and what does it do?
- A network of micro-vessels originating from tunica adventitia of large arteries
- Serve to provide oxygen and nutrients to outer layers of arterial wall
how is the vasa vasorum disrupted with atherosclerotic plaque?
- as plaque expands, it creates its own thin-walled microvasculature. this increases the risk of microvascular hemorrhage, leading to progression of atherosclerosis
What causes the development of fibrous plaque? what is this plaque made of
the accumulation of connective tissue.
this plaque is made up of lipid-containing smooth muscle cells and an extracellular lipid pool
what characterizes advanced lesions
Characterized by a necrotic lipid–rich core and calcified regions that develop over time
what is the difference between positive and negative remodeling of coronary arteries in response to atheroma formation
what is an intaplaque hemorrhage
- a result of plaque neovascularization
- this is a critical event that leads to acceleratedd plaque progression, instability, and ischemic vascular events
What are four factors that contribute to the pathogenesis of atherosclerosis
- endothelial dysfunction
- inflammatory and immunologic factors
- plaque rupture or erosion
- risk factors for development of disease
what is the initial step in development of atherosclerosis
endothelial vasodilator dysfunction
occurs d/t loss of endothelial-derived nitric oxide
what precipitates endothelial vasodilator dysfunction
oxidized LDL
what is endothelial dysfunction associated with
Hypercholesterolemia
Diabetes
Hypertension
Cigarette smoking
what are ways to improve endothelial vasodilator dysfunction
Correct HLD (diet or statins which increases bioavailability of nitric oxide)
ACEI if HTN present
High doses of antioxidants (Vitamin C, flavonoids)
what is the role of inflammation in the pathogenesis of atherosclerosis
- macrophages “eat” oxidized LDL.
- This releases inflammatory substances, cytokines, and growth factors leading to further plaque proliferation
is chronic or active inflammation associated with stable plaques
chronic.
active inflammation is assocaited with unstable and ruptured plaques
what is silent plaque erosion/rupture
- no acute symptoms occur
- characterized by repeated ruptures and thrombosis followed by wound healing
- leads to increased plaque burden, progression of vessel stenosis, and negative arterial remodeling
what regions of circulation correlate with what presentations/complications when affected by atherosclerosis
- Coronaries – MI, angina
- CNS – Stroke, TIA
- Periphery – Claudication, limb ischemia/poor healing, aneurysms
- Renal Arteries – RAS
- GI – mesenteric ischemia
why is it important to manage atherosclerosis
beucase its the #1 cause of death in the US and wordwideeeeee
what is the first sign of heart disease in 40-50% of US adults with CHD
sudden death :(
prevalence of CHD increases with…
ageee!
how common are silent heart attacks?
1 in 5 heart attacks are silent
what are diseases that have the same risks as CHD
- Clinical coronary heart disease (CHD)
- Symptomatic carotid artery disease
- Peripheral arterial disease (PAD)
- Abdominal aortic aneurysm (AAA)
- Diabetes mellitus
- Chronic kidney disease (CKD)
what are modifiable risk factors for atherosclerosis/CHD
- Cigarette smoking
- Dyslipidemias (↑LDL or ↓HDL)
- HTN
- DM
- Obesity
- Sedentary Lifestyle
what are unmodifiable risk factors for Atherosclerosis/CHD
- Premature CHD in 1st degree relative (age <55 in men, <65 in women)
- Age (men ≥ 45 y/o, women ≥ 55 y/o)
- Male sex
what are “other” risk factors for atherosclerosis/CHD
- High serum levels of C-reactive protein (CRP)
- High Triglycerides (esp in women)
- Sleep apnea
- Stress
- Persistent Heavy Alcohol Use
- Elevated Homocysteine levels
how much does heart disease risk increase with smoking?
increases risk by 2-4x.
on average smokers die 10 years earlier than non smokers!
what is the number one preventable cause of death and illness in the US
cigarette smokinh
According to WHO, one year after quitting, risk of CHD can decrease by 50%
how does smoking promote atherosclerosis
by increasing platelet adhesiveness, raised endothelial permeability, SNS stimulation by nicotine
How does hyperlipidemia (specifically hypercholesterolemia) increase atherosclerosis/CHD risk
- atherosclerotic plaques contain cholesterol and cholesterol esters!
- risk increases progressively increases as LDL increases and HDL declines
- hypercholesterolemia = higher mortality rate from CHD
- cholesterol lowering drugs and diet changes will reduce the risk of CHD
what populations will benefit with the use of a statin in regards to decreasing risk of CHD
- Individuals with clinical ASCVD (secondary prevention)
- Individuals with primary elevations of LDL–C ≥190 mg/dL
- Individuals 40-75 yrs with DM and LDL–C 70 to 189 mg/dL w/out clinical ASCVD
- Individuals w/out clinical ASCVD or DM who are 40-75 yrs with LDL–C 70-189 mg/dL and have an estimated 10-year ASCVD risk of >7.5%
How does hypertension increase the risk of atheroclerosis/CHD
- causes mechanical injury to the arterial wall
- increases the heart’s workload causing heart muscle to thicken and stiffen
- endothelial injury resulting from persistent high BP leads to plaque formation as per response the the injury hypothesis.
How does DM increase the risk of atherosclerosis/CHD
- CHD develops at an earlier age for DM people
- even if glucose is under control, DM increases risk of heart disease and stroke. (risk greater if sugar uncontrolled)
- 65% of DM patients die from heart/vessel disease
How does age and gender factor into the risk for atherosclerosis/CHD
- higher incidence and severity in men (occurs earlier, increased risk after 45)
- lower incidence in women, esp premenopausal. (risk increase at 55, although still lower than men)
what can increase the risk of CV events in a postmenopausal woman
hormone replacement therapy
how does familial and genetic factors affect risks for atherosclerosis/CHF
- CHD in male first degree relative <55 years; CHD in female first degree relative <65 years increases risk of CHD.
- hereditary genetic derangements of lipoprotein metabolism predispose the individuals to high blood lipid level and familial hypercholesterolemia
- fam hx of DM, HTN and HLD may secondarily increase risk of CHD
how do racial and ethnic factors affect risk of development of atherosclerosis/CHD
- African americans have more severe HTN than caucasions and a higher risk of heart disease
- Heart disease risk is also higher among Mexican Americans, American Indians, native Hawaiians, and some Asian Americans
Partly due to higher rates of obesity and diabetes
what 6 factors go into determining the risk of atherosclerotic cardiovascular disease
- age and gender
- diabetes
- race
- smoking
- cholesterol
- BP
NOt sure if we have to know all the USPSTF stuff, but maybe look at it. its slides 59-63. i feel like we do have to know it, but i havent made those cards yet.
yayyyyy doneso
