Clinical pathophys of endothelium Flashcards
normal endothelium is (3 things)
1) anti-inflamm
2) anti-thrombotic
3) vasodilatory
what is endothelium
single cellular layer lining blood/lymph vessles, heart, and other cavities
what does internal elastic lamina separate
intima and media
what does external elastic lamina separate
media and adventitia
tunica intima made of
endothleium + thin layer connective tissue
tunica media made of
vascular smooth muscle + connective tissue
tunica adventitia made of
loose connective tissue
distinguish large arteries, smaller arteries, and arterioles
large arteries = more elastin
smaller arteries = more collagen
arterioles = more smooth muscle
activated endothelium
1) permeable to macrophages and monocytes
2) incr inflammatory cytokins
3) incr leukocyte adhesion molecules
4) incr vasodilatory molec
5) incr antithrombotic molec
activated smooth muscle
1) incr inflammatory cytokines
2) incr ECM syntheiss
3) incr migration and proliferation into subintima
where is nitric oxide synthase expressed
on luminal side of endothelium
where does NO diffuse to?
smooth muscle in media
fxns of NO synthase
1) responds to multiple stimuli
2) make NO from arginine
3) cGMP-mediated vasodilation
what generates inflammatory state?
decr NO due to oxid stress
what are inflammatory molecules
in endothelium
1) selectins
2) cell adhesion molec
3) cytokines
what is process of forming atherosclerotic plaque
1) monocytes enter intima
2) macrophage engulf foam cells
3) smooth muscle activ/migr, apoptosis, fibrosis, ongoing inflamm
stages of atherosclerotic plaque
1) fatty streak
2) plaque progression
3) plaque disruption if lose endothelial cap
fibrous cap in atherosclerotic
Foam cells
MMP = degrade fibrous cap over atherosclerotic plaque
compare vulnerable vs. stable plaque
vulnerable plaque
1) less fibr tissue
2) less calcified
3) more lipid content
4) more inflamm
5) more apoptosis
much of thrombosis is regulated by _____ on ____
regulated by molec expressed
on surface of or secreted by endothelium
examples of molec expressed on or secreted by endothelium
1) hep sulfate/thrombin
2) NO/platelet activ
3) prostacyclin
risk factors for coronary atherosclerotic plaque formation
requires 3 risk factor
1) HTN
2) hyperlipidemia
3) smoking
4) diabetes
5) age
CAD can cause
1) MI
2) unstable angina
3) myocardial infarction
Renal artery disease can cause
1) atheroembolic renal disease
2) renal artery stenosis
peripheral artery disease can cause
1) limb claudication
2) limb ischemia
mechanism of ischemia
stroke
atheroembolism from carotid bifurcation lesion
thromboembolism from LAtrial appendage with a-fib
mechanism of ischemia
myocardial infarction
thromboembolism
mechanism of ischemia
angina
ruptured plaque, in situ thrombosis
mechanism of ischemia
claudication
trauma
in situ thrombosis
mechanism of ischemia
acute limb ischemia
stable obstructive plaque
mechanism of ischemia
pulmonary embolism
vasospasm
mechanism of ischemia
raynaud’s phenomenon
vasospasm
for stroke, what is unique about the source lesion?
source lesion doesn’t need to be obstructive ( embolizes to brain
with stroke
what is common artery?
ophthalmic artery (1st branch off carotid artery)
what are common effects of CAD?
1) myocardial infarction
2) chronic stable angina
what is mechanism behind MI in CAD?
1) rupture plaque
2) in-situ thrombosis (don’t have to be obstructive before rupture)
normal stress test
what is mechanism behind angina in CAD?
stable, obstructive (>70% reduction diameter) lesion
abnormal stress test
how to treat non-occlusive plaque rupture and thrombosis?
1) some flow but intermittent occlusion/embol
2) STABILIZE WITH ANTICOAG/VASODILATOR
present with NSTEMI
how to treat occlusive plaque rupture?
1) no flow down artery
2) emergency and RECANALIZE
administer thrombolytics or coronary angiogram/plasty/stent
which has positive serum biomarkers + ST depression +/- T wave inversion
NSTEMI
which has occlusive thrombus + ST elevation + biomarkers
STEMI
WHAT ARE clinical manifestation of peripheral artery disease?
claudication
acute limb ischemia
what does claudication and acute limb ischemia mean?
peripheral artery disease
what does MI and chronic stable angina indicate?
coronary artery disease
mechanism behind claudication in peripheral artery disease
1) obstructive (>70% diam reduction), STABLE PLAQUE
mechanism behind acute limb ischemia in peripheral artery disease
1) obstruct blood flow before develop collaterals
2) ~ atheroemboli (AAA) or thromboemboli (A-fib)
what is acute limb ischemia rarely due to?
rarely in-situ thrombosis
compare stable vs unstable/vulnerable plaques
stable plaque
1) less biol active
2) cause angina and claudication (exertional ischemia) if obstructive (>70% diam reduction)
3) less likely to cause thrombotic/embolic
vulnerable
2) more likely cause MI/stroke
what are common manifestation of venous thromboembolic disease?
1) DVT
2) PE
what do DVT and PE indicate underlying?
venous thrombosis different than arterial thrombosis
a
a
a
a
compare venous and arterial thrombosis
major component of clot
venous = fibrin rich
arterial = platelet rich
compare venous and arterial thrombosis
occur from …
venous = RBC
arterial = plaque rupture
compare venous and arterial thrombosis
found in areas of ?
venous = areas of stasis
arterial = areas of high flow
compare venous and arterial thrombosis
predisposing factors?
venous = genetic, environmental
arterial = atherosclerosis, trauma, anti-phospholipid antibody
compare venous and arterial thrombosis
treatment?
venous = anticoagulation
arterial = antiplatelet
WHAT IS PRIMARY RAYNAUD’S
- vasospasm in digital arteries of fingers or toes
- brought on with cold
- managed with lifestyle or vasodilators
WHAT IS SECONDARY RAYNAUD’S
- PT HAS SCLERODERMA, LEUKEMIA OR LYMPHOMA
Pain at rest that won’t improve with meds
STEMI
–> due to?
fibrous cap of atherosclerotic plaque rupture
50% occlusive –> now 100% obstrucitve to blood flow
NSTEMI
due to?
ruptured plaque has thrombus not completely obstructive ~90%
ST depression on exercise treadmill
chest pain with exertion relieved at rest (angina) due to?
atherosclerotic plaque 70% + obstructive
myocardium receives adequate flow at rest but not with exercise
how to treat angina (pain with exertion)
1) control BP
2) long acting nitrates to dilate
3) revascularized
angina + right calf discomfort with exertion relieved with rest (claudication)
–> patho in right superficial femoral?
atherosclerotic plaque 70% obstructive
blood flow limited with exercise not at rest
Hx Afib
sudden pain in right foot –> cool and no pulse
–> patho in right popliteal artery
due to thromboembolism
thrombus from left atrial appendage d/t a-fib and lack of anticoag
migrated to right popl artery; acute so no time for collaterals
sudden loss of vision in right eye
50% right internal carotid artery stenosis
atheroembolism
plaque migrate from right internal carotid to right ophthlamic artery
only manifests as right eye loss b/c did not involve other cerebral arteries
