Exam 2: Ch 18 Blood Vessel Disorders & Cholesterol Flashcards
3 layers of a blood vessel
tunica externa
tunica media (smooth muscle activity)
tunica intima (only layer capillaries have)
endothelial cells
simple squamous epithelium that lines cardiovascular system
maintains selectively permeable barrier in brain
regulates clotting, inflammation, vessel reactivity
influences growth of smooth muscle
how do endothelial cells regulate clotting
produces thrombogenic factors and prevents platelet adhesion
how do endothelial cells regulate vessel reactivity
produce dilators (NO)
produce constrictors (ACE)
endothelial dysfunction (plaques)
reversible changes in response to environmental stimuli
modulate blood flow (NO, ACE)
regulate SMC proliferation (growth factors)
regulate inflammation (produce IL)
vascular SMCs
can constrict and relax
synthesize collagen
migrate and proliferate
lipids are transported in the blood as…
lipoproteins
chylomicrons: carry triglycerides and cholesterol from intestine to tissues and liver
VLDL: main carrier of triglycerides
LDL: main carrier of cholesterol
hypercholesterolemia means
high blood lipids
risk factor for MI and stroke
VLDL
made in liver from cholesterol
deliver triglycerides to tissues…becomes cholesterol rich IDL
lipoprotein and apoprotein structures
micelles
hydrophilic outside, hydrophobic core
apolipoproteins
Proteins that bind lipids
control fate of lipids b/c receptors
activate enzymes for lipoprotein metabolism (remove lipids from lipoproteins)
recognized by tissue cell receptors – endocytosis takes in lipoproteins
chylomicrons
synthesized in cells of sm. intestinal wall
Carry dietary triglycerides and cholesterol from intestines to tissues and liver
Exogenous pathway
exogenous lipid transport
chylomicrons transfer triglycerides to cells for storage and energy use
remnant (cholesterol rich) chylomicrons taken up by liver
cholesterol used to make VLDL or is excreted in bile acid
the liver makes and releases ____ & _____
VLDL, HDL
endogenous lipid transport
VLDL delivers triglycerides to tissues, turns into cholesterol rich IDL
IDL recycled to VLDL by liver or to LDL in circulation
LDL in blood taken up by LDLr if low
LDL scavenged by macrophages and monocytes in tissues and into blood vessel walls if high –> plaque
low LDLr leads to
high circulatory LDL –> plaque
HDL
returns cholesterol from peripheral tissues to the liver…requires ABCA1
exercise increases HDL
smoking decreases HDL
ABCA1
ATP binding cassette transporter A, class 1
transports cholesterol out of vessel wall cells
genetic defect = Tangier disease (low HDL)
a low HDL is indicative of
early atherosclerosis
type 1 familial hyperchylomicronemia is high in..
french-americans
high chylomicrons means deficiency in LPL (lipoprotein lipase) or apo cells
hypercholesterolemia diagnoses and causes
Dx: LDL based on fasting blood sample every 5 yrs (20+ older)
causes: deit, co-morbidities like diabetes mellitus, meds, genetics
calculate total cholesterol
LDL + HDL + tF/S
genetic basis of hypercholesterolemia
LDLr gene abnormality
heterozygoes have LDLs of 250-500 mg/dl (1st heart attack in 30s)
homozygotes have LDLs of ~1000 mg/dl (see fat in blood)
xanthomas and atherosclerosis common
heart attack in 20s
treatment of hypercholesterolemia
not based on LDL goals
risk reduction
statins
how do statins work
higher intake of LDL causes it to decrease
less cholesterol production in liver causes higher LDL receptors
ASCVD
atherosclerotic cardiovascular disease
how are statins perscribed
moderate to high for people with clinical ASCVD
no ASCVD but LDL > 190 mg/dl
DM w/o ASCVD regardless of LDL or 10-yr risk
10-yr risk > 7.5% regardless of LDL, DM
other CHD risk factors
smoking
HTN
low HDL
DM
non modifiable CHD risk
family history
age
males > 45
females > 55 (post-menopausal)
diet therapy for cholesterol
lower calories, sat fat, cholesterol
higher fruits, veggies, fish
used for 3 months before starting meds
statins
HMG CoA inhibitors, block cholesterol syn. in liver –> upregulate LDLr
bile acid resins bind bile acids in intestine
nicotinic acid and fibrates block VLDL syn.
heart attack and plaques
plaques lead to rupture
clot forms at rupture site… hole in endothelium
some artery locations are more likely to accumulate…
plaques
atherosclerosis
Thickened artery wall due to plaque
Preference for medium to large arteries –> CHD is one type
fibrous plaques at ~20 take decades for disease to develop
CHD death rates
low since 1960 but CHD remains #1 killer in US
risk factors for atherosclerosis
hypercholesterolemia #1
HTN (stress injury to edothelium), smoking (chemical injury), obesity
aging
family history
C-reactive protein
marker of systemic inflammation (CHD is an inflammatory process)
anti-inflammatory effect so less plaque forms
homocysteine
methionine metabolite in animal protein
damages endothelium and stimulates clotting
Vit B breaks down, but do not decrease risk
lipoprotein A
Altered LDL
Increases cholesterol delivery to injured blood vessels
increases risk of CHD
fatty streak
yellow lines in tunica intima of major arteries
composed of SMC filled with cholesterol and macrophages –> foam cells (fatty macrophages
present from ~20yr old
fibrous plaque
fibrous cap over lipids and necrotic core
reduce flow in vessel
rupture and suddenly occlude vessel
inhibition of NO by oxidized LDL lowers vasodilation
what happens in fibrous plaques
LDL infiltrates to subendothelial space
monocytes bind to site of endothelial injury and enter space to oxidize LDL (which is toxic to endothelium)
what happens when LDL is oxidized by monocytes in fibrous plaques
rapid uptake by monocytes
inhibition of NO release
stimulation of cytokine release from T cells
cytokine release in fibrous plaques stimulated by monocytes oxidizing LDL
activate monocytes to differentiate into macrophages
SMC proliferation
macrophages take up…
LDL to form foam cells
SMC in fibrous plaques
lay down collagen in plaque
take up LDL to form foam cells
atherosclerotic occlusive disease (peripheral artery disease)
commonly affect lower extremities
same risk factors as atherosclerosis…smoking really bad
intermittent claudication
intermittent claudication
pain when walking, atrophy of skin, blanching when leg elevated
occurs when vessels > 50% occluded
Dx. tibial:brachial systolic BP ratio less than .9, ultrasound, CT, MRI
Rx. ASA, surgery, reduce CHD risk
thromboangitis obliterans (Buerger disease)
vasculitis that causes thrombus formation
effects medium sized arteries of foot and hand
smoking and genetics
Dx: similar to intermittent claudication
Rx: stop smoking, sympathectomy
Raynaud’s disease
arterial vasospasm in arteries of fingers
pallor and cold followed by hyperemia
cause ulceration and gangrene
Primary Raynaud’s disease–no known cause
overactive SNS
most common in healthy young women
triggered by cold or strong emotion
Secondary Raynaud’s disease
Associated with previous vessel injury like frostbite
Trauma from use of vibrating tools
diagnosis of Raynaud’s disease
cold to trigger
treatment of Raynau’s disease
eliminate triggers (cold)
quit smoking
calcium channel blockers
alpha-blockers
avoid stress
