pathophysiology of vascular disease Flashcards
blood flow to donwstream tissue is inadequate if (2)
- perfusion pressure too low
2. resistance too high
vasculature fails to meet demands for increased blood flow if
resistance to flow can not be sufficiently lowered in order to increase flow
most important adaptive mechanism for PVD
collateral pathways
how does the body compensate for reduced blood flow caused by a blocked artery?
- dilation of arterioles distal to stenosis
- collateral artery formation
- reduced tissue metabolism
- increased oxygen extraction
progressive disease involving the development of arterial wall lesions. As they grow, these lesions may narrow or occlude the arterial lumen. Complex lesions may also become unstable and rupture, leading to acute coronary events, such as unstable angina, myocardial infarction, and stroke.
atherosclerosis
Turbulent flow and low shear stress leads to
endothelial injury and build-up of atherogenic material on the vessel wall.
High shear stress (I.e. post-stenotic dilatation) causes
vessel dilation
PVD becomes clinically apparent when diseased vessels become over _____ stenotic. Tandem lesions will cause greater symptoms.
50-70%
tight enough to have an impact on flow at rest or during increased demand
significant PVD
effort induced pain caused by accumulation of
- anaerobic metabolites
2. lactic acid and adenosine monophosphate
calf claudication, ischemic foot ulceration/gangrene
tibial atherosclerosis
calf claudication
supertifical femoral atherosclerosis
muscle ache, buttock/leg claudication, impotence
aortoiliac atherosclerosis
loss of neurological function, transient ischemic event, amaurosis fugax, stroke
carotid atherosclerosis
chest pain/discomfort, myocardial infarction, acute coronary syndrome, chronic stable angina
coronary atherosclerosis
do not alter resistance to blood flow and have no impact on flow
non-obstructive blockages
Blockages that do not restrict blood flow at rest but prevent flow increases needed meet increased demands (e.g. exertional angina)
Very tight blockages restrict flow at rest and at stress (e.g. rest pain)
obstructive blockages
Claudicants can have a wide range of ABI. Less than ______ is considered severe PVD.
0.4
Doppler systolic occlusion pressure at ankle versus arm measures pressure gradient between the two vascular beds at rest and with exercise (exercise increases flow (F))
ankle brachial index
increasing myocardial oxygen demand leads to (2)
- coronary vasodilation- decrease in resistance
2. increases coronary blood flow- increase in flow
cardiac stress test is done to
stress the coronary vascular bed
If the resistance cannot be sufficiently lowered to meet the requirements for coronary flow the heart becomes _____
ischemic
ection of radio-opaque contrast dye to create an image of the arterial lumen
Allows more direct measurement of blockage
Give limited information about how sufficient are the collaterals
contrast angiography
GOLD STANDARD
is useful for post operative follow up of bypass grafts and carotid endarterectom
-used to measure lumen area and the velocity of blood traveling across a stenosis which is proportional to the severity of the obstruction and the driving pressure.
Ultrasound
Wall tension (T) is proportional to
radius (R) and pressure (P or blood pressure).
Aneurysms form with ____________ particularly when the vascular radius is large (e.g. aorta) and the wall thickness is low.
increasing pressure (e.g. hypertension)
Wall tension is reduced by ______
increased blood vessel wall thickness.
Laplace’s law on risk of anuerysm
Risk of aneurysm rupture increases with size due to Laplace’s law
Defined as 50% or greater increase in diameter of vessel
arterial aneurysm
Ascending thoracic aortic aneurysm risk factors (4)
Hypertension
Marfan
Ehlors-Danlos
Bicuspid aortic valve associated aneurysm
Descending thoracic aortic aneurysm risk factors
2
Atherosclerosis
Hypertension
Abdominal aortic aneurysm
3
Infrarenal: 95%
Atherosclerosis
Hypertension
best imaging test for pre-operative planning. The thrombus seen adherent to the vessel wall in the aneurysmal aorta is common, and has no clinical significance.
CT
Spontaneous disruption of intima
“False channel” created within wall of aorta
Propagation of tear distally
May occlude branch vessels (viscera, extremities)
May lead to vascular rupture
Aorta, carotid arteries and coronary arteries are often sites
arterial dissection
Lipid infiltration and into vascular wall Macrophage activation Lipid oxidation Cellular proliferation Calcification, atheroma formation Responsive to LDL-C lowering
atherosclerosis
Plaque rupture Mural thrombus Arterial disease often platelet-dependent thrombus formation Responsive to anti-platelet therapy Aspirin P2Y12 blockers
thrombosis
ASCVD Pathogenesis: 1-2 Punch
- abnormal lipid metabolism
2. systemic inflammation
Atherogenic lipoproteins LDL VLDL/IDL Cholesterol Triglycerides
abn. lipid metabolism
Diabetes Obesity Tobacco Hypertension Age
systemic inflammation
Abnormal lipids (Dyslipidemia)
Elevated low density lipoprotein cholesterol (LDL-C)
Decreased high density lipoprotein cholesterol (HDL-C)
Elevated triglycerides, particularly with low HDL-C
Diabetes mellitus
Hypertension
Smoking tobacco products
Family history of premature coronary artery disease (CAD)
First degree male relatives < 55 years or females < 65 years.
Obesity and lack of exercise particularly in relation to Diabetes
Male sex
Advanced age
Others: Lipoprotein a (Lp(a))
risk factors for atherosclerotic CAD
Women develop ASCVD approximately 10 years after men following ______
menopause
Aspirin may be less effective at preventing ASCVD in women
true
The onset of ASCVD following menopause may be caused by the ______
loss of estrogen
- no benefits in replacement trials
monogenetic lipid disorders
- familial hyercholesterolemia
2. familial combined hyperlipidemia- Elevated triglycerides and LDL-C
_____ are remnant particles that started as VLDL and IDL and transport cholesterol and some triglycerides to tissues (forward cholesterol transport
Low Density Lipoproteins (LDL)
_______ transport cholesterol back to liver for disposal in bile (reverse cholesterol transport)
High Density Lipoproteins (HDL)
Derived from VLDL->IDL
Rich in esterified and non-esterified cholesterol
Protein: Apo B-100
Hydrophobic Core
Bind LDL-Receptor as well as scavenger receptors
Toxin to endothelium that incite blood vessel wall inflammation
“Bad Cholesterol”
LDL
Synthesized empty
Protein: Apo-A-I and –A-II
HDL particles pick-up cholesterol from tissues
Reverse cholesterol transport
CETP exchanges cholesterol between different lipoproteins
“Good cholesterol”
HDL
Genetic studies support a strong causal relationship between LDL-C levels ASCVD
yep
HMG-CoA Reductase Inhibitors
Statins:
High Intensity Statin used for
Secondary Prevention of ASCVD
Moderate Intensity Statin used for
Primary Prevention of ASCVD
aspirin
platelet inhibition
