Lect 1- Atherosclerosis Flashcards
Atherosclerosis
disease of the ARTERIES (NOT veins)
characterized by intimal lesions (atheromas, atherosclerotic plaques)
How do vessels look in atherosclerosis?
accumulation of lipid in coronary artery (fatty streaks)
Aorta is usually smooth (key in preventing thrombosis) to provide vessels with environment where you can have laminar blood flow but in atherosclerosis they are not smooth
Response-to-injury hypothesis
Injury to the blood vessels/ endothelial injury
Changes that you see in blood vessel looks a little like a response you would see in normal healing
Interaction b/w lipoproteins and certain immune cells (monocytes and T-cells)
Pathogenic events in atherosclerosis
Multi-factorial set of events that causes it but don’t know what actually causes the inflammation
High levels of certain lipoproteins, Endothelial injury, accumulation of LDL, up-regulation of certain molecules inside cells (adhesion molecules)
Monocytes adhere to endothelial cells and squeeze in between cells to enter and become macrophages
Plts also adhere
Atheroma development
Endothelial injury –> Monocytes and plts adhere to endothelium –> monocytes getting across barrier and becoming macrophages –> macrophages can phagocyte lipo-particles –> called foam cells –> Smooth muscle cells can go from media to intima –> phentotype change (cannot divide/proliferate or produce ECM proteins); can only contract/relax
Recruitment of smooth muscle cells coming from circulation
What happens when LDL is oxidized?
changes it in a way that it can interact with both LDL and scavenger receptors so more LDL can get into the cell (normal LDL receptors are usually highly regulated)
What is a foam cell?
When a macrophage engulfs a lipo-particle inside the atheroma
What can cause endothelial injury/ dysfunction?
hyperlipidemia, HTN, smoking, toxins, hemodynamic factors, immune rxns, viruses
What happens when smooth muscle cells migrate from the media to the intima?
phentotype change (can divide/proliferate or produce ECM proteins); cannot only contract/relax
Rupture and thrombosis of atheroma
• All the substances that are inside will be exposed to blood → thrombus formation
○ Sometimes the thrombus is small enough that it can be incorporated into vessel → no bad clinical impact
○ Other times, the thrombus can grow and occlude the entire blood vessel
*Important if it happens in blood vessels that supply brain and heart blood
What is the most common cause of MI?
thrombotic occlusion of coronary artery
Microvessels in atheromatous plaque
as plaque advances, complex network of microvessels develop
bad since you don’t want more blood vessels cause it will increase inflammatory response and higher risk of MI
may serve as portals for entry and exit of WBC
Calcification
• Deposit of calcium
• Arteries become very stiff and hard (rigid) and cannot respond to changes in BP
Recapitulates many aspects of bone formation
Manifestations of atheroma
- No symptoms (since it is a chronic process)
- compensatory enlargement
- stenotic occlusive disease
- ectasia, aneurysms (caused by weakening of blood vessel wall)
- thrombosis and rupture
Myocardial infarction
Necrosis of certain portion of the myocardium
Angina pectoris
insufficient blood flow to the heart muscle from narrowing of coronary artery
chest pain
Do not usually have occlusion of blood vessel but you will have stenosis
Intermittent claudication
arteries become narrowed (from buildup of fatty substances) and blood flow decreases
pain in calves after exercise which goes away during rest
Blood vessels rupturing inside the brain
hemorrhagic stroke
what kind of stroke results from stenosis of blood vessels in brain
ischemic stroke
mesenteric ischemia
in abdominal cavity
• If this happens, then needs surgical resection of ischemic fragment of intestine
○ Dark part= necrotic part
○ Connect the remaining healthy tissue together
• Necrotic part will rupture w/o surgery and substances will go into abdominal cavity –> peritonitis –> death
• Clinical emergency= pt needs to go to operation quickly
ectasia, aneurysm
abdominal aorta has advanced lesions
If it ruptures, then the pt dies in a few minutes from brain damage (Dramatic hypotension/ hemorrhagic shock)
epidemiology of atherosclerosis
MAJOR CAUSE OF DEATH IN DEVELOPED SOCIETIES
not so much in 3rd world
causes coronary artery disease
constitutional risk factors for atherosclerosis
Cannot be changed
- Age= as we age more, risk increases
- Gender= more in men at first b/c women are protected until menopause, then they become more vulnerable
- Family history= genes equals higher risk
acquired risk factors for atherosclerosis
Risk factors work synergistically (Combine 2 risk factors, it will increase risk several fold higher than just one risk factor)
- Hyperlipidemia/ Hypercholesterolemia= Can also be familial; can also be assoc with obesity
- HTN
- cigarette smoking
- diabetes
