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Phys. Exam 2 Arteriosclerosis
Arteriosclerosis
60
Physiology
Graduate
10/16/2010

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Term
Atherosclerosis is:
Definition
- hardening of arteries
- more than half of the deaths in the U.S. result from this
- 300 billion dollars per year
Term
number one killer in country:
Definition
coronary heart disease
Term
atherosclerosis can cause:
Definition
- infarct
- stroke
- gangrene
- aneurysm
Term
summary of progression of events with atherosclerosis:
Definition
- fatty streak> fibrous plaque > calcification complicated lesion: hemorrhage, ulceration, thrombosis
Term
62% of men and 46% of women have a MI or die before aware of their coronary artery disease.
Definition
Term
coronary fatty streaks are the ___ lesions. ___ ____ are the later lesions that induce the formation of clots leading to a stroke or heart attack.
Definition
- initial
- coronary atheromas
Term
later lesions of atherosclerosis that lead to clot formation, heart attack, and stroke?
Definition
- coronary atheroma
Term
1 in 6 teenagers has atheroma.
Definition
Term
Three components of the atherosclerotic process:
Definition
- dyslipoproteinemia
- inflammation
- thrombosis

smoking is a huge contributor
Term
lipid roles:
Definition
part of triglyceride for energy storage, cholesterol is essential membrane component in order to generate new cells and tissues, primary importance for developing individuals carried by lipoprotein, cholesterol is also used as a hormone precursor and its also a precursor for bile acids for lipid digestion and absorption
Term
chylomicrons tranpsort triglycerides to __ or ___ tissue.
Definition
- adipose
- muscle
Term
lipoproteins can be abnormal due to ___ or ___.
Definition
- amount
- composition
Term
In the initial fatty streak phase of atherosclerosis ___ ___ ___ form.
Definition
- macrophage foam cells
Term
In the plaque stage ___ ___ ___ accumulate and a __ ___ forms.
Definition
- macrophage foam cells accumulate
- necrotic core forms
Term
In the plaque stage ___ ___ ___ accumulate and a __ ___ forms
Definition
- macrophage foam cells accumulate
- necrotic core forms
Term
fatty streak> macrophage foam cells form> plaque stage where foam cells accumulate and necrotic core develops> rupture of endothelium and occlusive blood clot formation
Definition
Term
Pathophysiological contributors to endothelial dysfunction:
Definition
- lipids
- LDL
- Diabetes
- Hypertension
- Smoking
- Homocysteine
- estrogen withdrawal
Term
Prevention strategies for atherosclerosis are based on the assessment of modifiable risk factors including:
Definition
- hypertension
- smoking
- high cholesterol
Term
high cholesterol is strongly associated with coronary death.
Definition
Term
sequence of events with plaque formation and arteriosclerosis:
Definition
In intima of tissue:
- macrophages interact with and take up oxidized LDL forming foam cells filled with cholesterol ester
- foam cells irritate the artery and promote proliferation of muscle cells
- irritation results in deposition of cholesterol ester > platelets and cellular debris accumulate
Term
explain HDL:
Definition
- good cholesterol
- takes cholesterol out of macrophages and artery
- has antioxidant effect that prevents LDL from being oxidized
- has anti-inflammatory effect to counteract inflammation that can lead to arteriosclerosis
Term
main target for cholesterol lowing drugs:
Definition
- lower LDL
Term
lipoproteins transport what?
Definition
- cholesterol
- triglycerides
- phospholipids
Term
Lipoproteins are spherical macromolecules consisting of a core of triglycerides and cholesteryl esters surrounded by an outer shell of cholesterol and phospholipids and apolipoproteins.
Definition
Term
how to precipitate out lipoproteins:
Definition
- human plasma + Na/K bromide
- centrifuge for 36 hours at 40,000x g
- from top to bottom: chylomicrons>VLDL> LDL> HDL> free fatty acids and albumin
Term
describe chylomicrons:
Definition
- core lipid: triglycerides
- function: transport dietary triglycerides to liver, muscle, and adipose tissue
Term
describe VLDL:
Definition
- core lipid: triglycerides
- function: transports endogenously (liver) synthesized triglycerides to adipose and muscle tissues
Term
describe LDL:
Definition
- core: cholesterol esters
- function: transport of cholesterol to peripheral and liver cells
- ATHEROGENIC
Term
describe HDL:
Definition
- core lipid: chosterol esters
- function: transport cholesterol from peripheral tissues to the liver.
- ANTI-ATHEROGENIC
Term
___ is the only organ that is able to eliminate cholesterol by converting it to ___ ___ that can be excreted through the intestinal system. This is why we need ___ to do reverse cholesterol transport to the liver.
Definition
- Liver
- bile acids
- HDL
Term
Only a small portion of the cholesterol molecule is available for energy, this portion is called ___ __.
Definition
- Proprionyl-CoA
Term
ALL ORGANS CAN DO ENDOGENOUS SYNTHESIS OF CHOLESTEROL, BUT ONLY LIVER CAN GET RID OF IT BY MAKING IT INTO BILE ACIDS TO BE EXCRETED.
Definition
Term
total amount of bile acid traficcing aka bile acid lost is about ___ grams or __%.
Definition
10 grams
10 %
Term
cholesterol balance is essential for normal cell activity and is mantained through
Definition
- hepatic activity
- extrahepatic activity
Term
The general concept of cholesterol balance is well established. A typical human metabolizes approximately 1,200 mg of cholesterol per day. On a modestly restricted diet, 300 mg of this cholesterol will be absorbed from the diet and 900 mg will be synthesized.
Every cell in every organ of the body requires the constant movement of cholesterol through the Golgi network, into specialized structures of the cell membrane, and onto the caveola and other structures.1 Therefore, cholesterol is constantly synthesized by the extrahepatic organs, circulated to the cells for processing, then removed from the cell surface by adenosine triphosphate binding cassette-1 (ABCA-1) transporters.2 It is then carried by HDL to the liver, where it is taken up by the scavenger receptor class B, type I (SR-BI) pathway,3 metabolized, and excreted. In every species, including the primate, the level of circulating LDL-C depends on the LDL-receptor activity in the liver.4
Definition
Term
a typical human metabolizes ___ mg of cholesterol a day.
Definition
1200
- 300 absorbed from diet
- 900 synthesized in body
Term
every cell in body requires constant movement of cholesterol through __ __.
Definition
golgi network and on to calveoli
Term
cholesterol is constantly being synthesized by ___ tissues, ciruclated to cells for procesing, then removed from the cell surface by ___ and ___ transporters. Then it is carried to the liver by ___, where the scavenger __ __ __, type I SRBI pathway metabolizes it, and then its excreted
Definition
- extrahepatic
- ATP cassete I, ABCA transporters
- HDL
- receptor class B
Term
In every species, the level of circulating LDL-C depends on what?
Definition
- LDL receptor activity in the liver
Term
cholesterol is converted to steroid hormones in the __ ___ and in the ___.
Definition
- adrenal cortex
- gonads
Term
cholesterol is converted to bile acids in the ___.
Definition
liver
Term
Interhepatic circulation:
Definition
- circulation of bile acids back to the liver
- about 1 gram per day does this
Term
LDL not made in the liver. VLDL is made in the liver and it circulates and the ___ ___ on endothelial lining of capillaries depletes the triglyceride load, so you have ___. LDL is the major cholesterol carrier to tissues.
Definition
- lipoprotein lipase
- LDL
Term
adults have a lower demand for cholesterol and their cholesterol is almost entirely taken up by bile acid synthesis.
Definition
Term
cholesterol synthesis from acetyl-coA requires ___ steps and ___ ATP.
Definition
- 33 steps
- 18 ATP
Term
what is the rate limiting step in cholesterol biosynthesis:
Definition
- HMG CoA reductase
Term
HMG COA reductase is the rate limiting step with cholesterol synthesis b/c this enzyme is inhibited by one of the products it produces, ____. This enzyme is also regulated by ___/____. So once enough of its product has been made, this enzyme will be inhibited.
Definition
- squalene
- phosphorylation/dephosphorylation
Term
LDL receptors are in ___ __ ___. LDL interacts with the receptor> LDL is internalized into cell> LDL get dismanteled in the lysosome releasing amino acids and breaking cholesterol ester apart> cholesterol accumulates in the ER membrane and sends out signals> signals affect cholesterol trafficing by three ways, list them:
Definition
- clatharin coated pits
build up cholesterol in ER membrane sends out the following signals:
- decreased HMG-CoA reductase
- increased ACAT and cholesterol oleate
- decreased LDL receptors
Term
LDL receptor pathway is designed to make sure that enough cholesterol is availble, and that there is no overloading. This is done be regulation of:
Definition
- hmg coa reductase
- LDL receptors
Term
The liver makes VLDL. IDL and LDL are made in blood by endothelial lipoprotein lipase. Liver has receptors for IDL and LDL.
Definition
Term
homozygotes with familial hypercholesterolemia have LDL ___ times normal.
Definition
10 times normal
Term
familial hypercholesterolemia is due to defective or absent __ ___.
Definition
LDL receptors
Term
treatment of familial hypercholesterolemia:
Definition
Coadministration of :

- cholesterol absorption inhibitor (CAI)like ezetimibe- prevents cholesterol absorption from diet
- statin- prevents cholesterol synthesis
Term
statins may effectively counter the upregulation of cholesterol synthesis caused by CAIs, and CAIs may reduce the cholesterol content of chylomicrons.3
Definition
Term
Hetero for familial hypercholesterolemia have cholesterol in 4-500s. Homozygotes have cholesterol around 1000.
Definition
Term
Statins upregulate ___ ____ and decrease ___ __ ___ so that synthesis is shut off and only source of cholesterol is from the plasma. Statins also moderately increase __ but no one is sure how.
Definition
- LDL receptors
- HMG CoA reductase
- HDL
Term
common to treat high cholesterol with statins and bile acid sequestrants.
Definition
Term
Even if LDL is high, if ___ is also high, then the risk is almost the same as having a low LDL.
Definition
- HDL
Term
Low __ is an independent predictor of CHD risk even when LDL is low.
Definition
- HDL
Term
___ should also be treated when treating arteriosclerosis or CHD.
Definition
- inflammation
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