Atherosclerosis Flashcards
Define atherosclerosis
Atherosclerosis: hardening of the arteries beginning in the intima due to build-up of fatty deposits and fibrous tissue
Asymptomatic artherosclerosis is also called ___, whereas symptomatic disease is called ___
Asymptomatic artherosclerosis is also called coronary artery disease, whereas symptomatic disease is called coronary heart disease/ischemic heart disease
Draw and describe the structure of arterial smooth muscle
**see image below**
The first appearance of artherosclerosis is ___ which is characterized by yellow discoloration on inner surface of an artery
T/F: This thing impedes blood flow
The first appearance of artherosclerosis is the fatty streak which is characterized by yellow discoloration on inner surface of an artery
Falsehood: The fatty streak does not impede blood flow
Another sign of artherosclerosis is ___ which develops over time and can impede blood flow when extra perfusion is needed
Another sign of artherosclerosis is the fibrous plaque which develops over time and can impede blood flow when extra perfusion is needed
Name some of the complications that can arise after the formation of a fibrous plaque (5)
Thrombosis
Plaque rupture
Hemorrhage
Wall weakening
Calcification
T/F: The endothelium is the largest organ in the body
Describe the origin of endothelial cells
Apparently this is true
Endothelial cells originate from the bone marrow (angioblast/embryonic endothelial progenitor cells)
The endothelium regulates various factors to maintain vascular hemostasis. What are some of these? (5)
Nitric oxide
Prostaglandins (prostacyclin, thromboxane)
Endothelial hyperpolarizing factor
Angiotensin I
C-type natriuretic peptide
Other factors that are regulated by the endothelium to balance blood fluidity and thrombosis include___
**see image below**
___ is a potent vasodilator that is also antithrombotic and inhibits smooth muscle migration and proliferation
Nitric oxide is a potent vasodilator that is also antithrombotic and inhibits smooth muscle migration and proliferation
In addition to NO, ___ and ___ are antithrombotic and promote vasodilation
In addition to NO, prostacyclin and bradykinin are antithrombotic and promote vasodilation
What thrombotic and vasoconstrictive substances are released by the endothelium?
Endothelin
Angiotensin II
Norepinephrine
What are the functions of vascular endothelium? (4)
The endothelium acts as a barrier to keep circulating LDL from going into the intima layer
Endothelium also secretes anti-clotting factors, dilates if we need more perfusion and can contract vascular smooth muscle
What are the consequences of having damaged endothelium/losing the endothelium?
If the endothelium is damaged/lost, circulating LDL can go into the intima, blood clots can form inside the vessel, blood vessels may constrict instead of dilating and smooth muscle might start migrating into the intima
The first step in the formation of an artherosclerotic plaque is ___
What triggers endothelial damage allowing for plaque formation?
The first step in the formation of an artherosclerotic plaque is the formation of the foam cell
Risk factors such as HTN, smoking, diabetes all can cause endothelial damage
In the development of foam cells, how do monocytes enter the intima layer?
The LDL molecules that break thru the damaged endothelium, become oxidized and induce cytokine production. Circulating monocytes then get stuck on the endothelium and get sucked into the intima layer
After monocytes get sucked into the intima during foam cell formation, what happens?
Monocytes then become macrophages and start eating the lipid particles >> foam cells
More and more foam cells start pushing thru the vascular wall >> formation of fatty streak
Summarize the formation of a foam cell
**see image below**
Following formation of foam cells in the fatty streak, a fibrous plaque develops. Draw and describe the development of the fibrous plaque
The foam cells release cytokines that recruit smooth muscle cells
The smooth muscle cells become activated and secrete growth factors, collagen and elastin
Cholesterol crystal form, the plaque calcifies and capillaries form
Summarize how a fibrous plaque forms from foam cells in fatty streak
Foam cells in fatty streak >> bunch of mechanisms in between >> smooth muscle cells migrate to intima >> sm muscle cell proliferation + production of extracellular matrix
Describe the effect of acetylcholine on vascular endothelial cells
Endothelial cells can be stimulated by acetylcholine which binds to the muscarinic receptor and release EDRF (nitric oxide) >> cyclic cGMP >> smooth muscle dilation
Describe the Furchgott phenomenon
Furchgott phenomenon:
stimulate blood vessel with intact endothelium >> vasodilation
Stimulate blood vessel with absent endothelium >> no dilation
Other molecules used to test endothelial function besides acetylcholine are __, ___ and shear stress
Other molecules used to test endothelial function besides acetylcholine are bradykinin, serotonin and shear stress
What explains the result in the coronary angiogram below?
The endothelium here is abnormal so stimulating the vessel with acetylcholine will cause blood vessel constriction instead of dilation
What factors improve endothelial function?
Lipid lowering agents
ACE inhibitors
Diabetic control
Statins
Exercise
Smoking cessation
**think about what the risk factors are and what one could do to improve them**
In which places can stable plaques inside a blood vessel rupture?
Usually at areas of low shear stress and branch points
Atherosclerosis usually starts in the ___ (large blood vessel)
Atherosclerosis usually starts in the aorta and proceesed to the coronary arteries, peripheral arteries and cerebral arteries
Describe Glagov’s coronary remodeling hypothesis
Coronary remodeling hypothesis: with more severe coronary artery disease, the lumen gets narrower and narrower as the blood vessel reaches its limit of expansion
Explain the concept of reverse remodeling that happens in diabetics with coronary artery disease
Reverse modeling: the vessel actually constricts inwards in pts with diabetes
Hard, fibrous plaques that build up over time are ___, whereas early plaques are ___
Hard, fibrous plaques that build up over time >> stable plaque
Early plaque >> soft/vulnerable plaque
What are the pathologies caused by a hard, fibrous plaque vs those caused a soft, vulnerable plaque?
Hard fibrous plaque has small lipid core, lots of connective tissue and a thick fibrous cap >> narrows vessel lumen and causes angina
A soft/unstable plaque has a large lipid core and a thi
n fibrous cap that can rupture >> can result in thrombus formation from rupture >> causes acute MI
Rupture of unstable plaques is mediated by ___ and usually happens in ___
Rupture of unstable plaques is mediated by inflammatory cells and usually happens in the shoulder region
What is the pathology below?
Stable plaque
What is the pathology below?
Vulnerable plaque
What is the pathology below?
Plaque rupture
What is the pathology below?
Thrombus occluding blood vessel
Another mechanism for plaque formation is ___ and is commonly ass’d with smoking, especially in women
Another mechanism for plaque formation is plaque erosion and is commonly ass’d with smoking, especially in women
Some complications that can arise from plaque formation include ___ (4)
If a plaque happens in the leg >> claudication, angina (happens in the chest)
Weakening of blood vessel wall >> aneurysm
Rupture of plaque/thrombosis >> MI
Fragmentation of plague/embolism >> embolic stroke, atherosclerotic renal failure
Below are two plaques. Which one is stable, which one is unstable?
What are some non-modifiable risk factors of coronary artery disease?
Family history of premature CHD
Age (increasing)
Being male
Genetic abnormalities
Name some modifiable risk factors of CHD (5)
Hyperlipidemia
HTN
Smoking
Diabetes
Obesity/Inactivity
What is the pathology below?
Truncal obesity (see below for ass’d conditions)
What are the qualifying factors for truncal obesity?
**see image**
