Dyslipidemia & Atherosclerosis Flashcards
What is atherosclerosis?
An inflammatory disease characterized by thickening and hardening of the arterial wall. Affects large and medium sized arteries.
‘Athere’ = fatty
‘sclerosis’ = hardening and stiffening
What are atheromas?
Fatty/fibrous plaques that develop in arterial walls that result in decreased perfusion, ischemia and infarction.
What are the key arteries affected by atherosclerosis?
- Coronary (coronary artery disease = CAD)
- Carotid, vertebral, cerebral (cerebrovascular disease)
- Abdominal aorta (aortic aneurysm)
- Iliac, femoral, popliteal (peripheral artery disease = PAD)
- Renal (renal artery stenosis)
What are fatty streaks?
A non-clinical lesion and the earliest sign of atherosclerosis.
Develops in the tunica intima of artery walls.
Thin and flat = do not block the artery lumen or disturb blood flow
Present in aorta and coronary arteries before age 20.
It is a yellow accumulation of foam cells (oxidized LDL + macrophages) and T lymphocytes in the lining of an artery.
What is a fibrous plaque?
The advanced lesion.
Development is slow = 20-40 years before clinically evident.
Persistent injury, inflammation, and lipid infiltration = the plaque enlarges and grows into the artery lumen.
Why are hypertension and dyslipidemia risk factors for atherosclerosis?
Hypertension causes mechanical injury to endothelial cells which can lead to vascular proliferation. Can also increase the permeability of LDL to the intima of the blood vessel. High angiotensin II levels associated with hypertension is pro-inflammatory (stimulates the production of inflammatory cytokines).
Dyslipidemia can lead to LDL oxidation and internalization, which can contribute to endothelial dysfunction. Can also decrease the bioavailability of nitric oxide which can lead to vasoconstriction.
Which layer of the artery wall is affected by atherosclerosis?
The tunica intima (inner coat) which consists of the endothelial cells, connective tissue and internal elastic membrane.
Describe the pathogenesis of atherosclerosis.
- Lesion initiation (response to injury or response to retention theories).
- LDL deposition on injured area.
- FOAM cells = oxidized LDL + macrophages
- Fibrous plaque development and smooth muscle hypertrophy
- vasodi;ation capacity decreases
- plaque calsifies with time, fissures easily, pieces of plaque break off - travel = emoblism
In lesion initiation, what is the ‘response to injury’ hypothesis?
Endothelial injury or dysfunction (causing inflammation) is the triggering even tin the development of atherosclerosis.
Chronic endothelial injury:
- HTN
- Tobacco use
- Hyperlipidemia
- Hyperhomocysteinemia
- Diabetes
- Infections
- Toxins
Inflammation causes:
1) endothelial cell retraction allowing the infiltration of LDLs
2) recruits WBCs to the area
Supported by observations of atheromas in areas of turbulent flow (branching points, tight bends)
In lesion initiation, what is the ‘response to retention’ theory?
Proposes that the entry and retention of LDLs in susceptible areas of the arterial wall is the initiating event in atherosclerosis.
Trapped LDLs are oxidized by free radicals, which in turn cause endothelial injury and inflammation.
Describe how fatty streaks develop.
- Endothelial injury causes inflammation.
- LDLs infiltrate the intima layer across the leaky endothelium.
- trapped LDLs are oxidized by free radicals
- Monocytes are recruited, enter the intima, are converted to macrophages (& release free radicals)
- Macrophages ingest oxidized LDLs forming foam cells
- an accumulation of foam cells forms the fatty streak
What are the steps in fibrous plaque development?
- Foam cells secrete factors that stimulate the migration of smooth muscle cells from the tunica media to the intima.
- Smooth muscle cells proliferate, engulf oxidized LDLs, migrate over the fatty streak, and produce collagen.
- The fibrous plaque composed of a lipid core (foam cells, cholesterol and cell debris) and fibrous cap (smooth muscle cells and collagen) develops.
What is a stable atherosclerotic plaque?
- thick fibrous cap and a small, fatty core
- may slowly cause narrowing
- obstruct blood flow, but do not tend to form thrombi
-implicated in stable angina
What is an unstable (vulnerable) atherosclerotic plaque?
- Thin fibrous cap and a large, fatty core (soft)
- Vulnerable to rupture, platelet aggregation, and thrombus formation
- implicated in unstable angina and acute MI
In an MI, what is the difference between non-ST and ST elevation?
non-ST = partial blockage by thrombus
ST = full blockage by thrombus
