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35 Cards in this Set
- Front
- Back
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What are the 3 clinical manifestations of atherosclerosis?
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1. Coronary heart disease
(angina, acute MI, sudden death, NSTEMI, etc) 2. Cerebrovascular disease (Stroke, TIA) 3. Peripheral arterial disease (Intermittent claudication, amputation) |
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The non-modifiable CHD risk factors are family history, age and sex. What are 7 modifiable risk factors of CHD?
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1. Dyslipidemia (↓HDL, ↑LDL, ↑TG)
2. Obesity 3. Smoking 4. HTN 5. DM 6. Sedentary lifestyle 7. Diet (also thrombogenic factors) |
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What is the primary lab value that is followed in order to prevent CHD?
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Serum LDL-C. A 10%↑ = 20%↑ in CHD risk.
Conversely, a 10%↓ in total cholesterol will = a 15% ↓ in CHD and 11% ↓ in total mortality |
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What is "good cholesterol"? Why is it considered good?
When HDL is low, what is high? What are the cut-offs for + and -- risk factors? |
HDL-C b/c it has a protective effect for atherosclerosis and CHD risk.
HDL tends to be low when TG are high. If HDL < 1.0 = major + risk factor If HLD > 1.55 = major -- risk factor |
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TG are related to what other serum marker?
What are very high levels of TG associated with? |
TG may be related to low HDL levels and highly atherogenic forms of LDL.
Optimal [TG] = < 1.7 mmol/L Very high [TG] (11.3mmol/L) is associated with pancreatitits |
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according to Canadian Lipid guidelines, what happens to the LDL cut-offs as you add CHD risk factors?
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As you add risk factors the LDL cut-offs go down.
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What are 3 functions of apolipoproteins?
What are the following associated with: Apo B Apo A1 |
1. Aid in lipid transport
2. Activate 3 enzymes of lipid metabolism 3. Bind to cell surface receptors Apo B: proportional to the # of LDL particles (can have diff # for the same [LDL] b/c droplets are diff sizes!) Apo A1: HDL |
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When would you measure Apo B and what does you use this value for?
What is the optimal value? |
Measure in ppl with moderate risk. Use to seperat higher and lower risk pt's with moderate ↑TGemia.
May be useful in determining CAD risk & Tx efficacy in pt's with metabolic disorder. Optimal < 0.9 g/L |
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When will CRP be elevated? Why?
What does it mean if it is moderately elevated in a person with normal cholesterol? |
In acute infections b/c it is involved in host-defence mechanisms.
If a pt has normal cholesterol but raised CRP - they may have the low-grade inflammation found in heart disease. ** can be used to predict future events but can NOT be used to monitor Tx or set guidelines |
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Arrange the following in order of size (from big to small):
LDL, IDL, HDL, VLDL, Chylomicron What Apo does each have? |
Chylomicron, VLDL, IDL, LDL, HDL
** size is inverse to density thus these are arranged in increasing density. CM - B48, C, E VLDL - B100, C, E IDL - B100, E LDL - B100 HDL - A, C, E |
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What is the exogenous pathway for lipoproteins? (ie how do they get from mouth to blood?)
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The enter the intestines, get absorbed into the lacteals and travel through the lymphatics until they re-join the venous circulation (they're too big to get into capillaries). Once in the blood they are rapidly hydrolyzed by Lipoprotein Lipase. Remnant particles are taken up by the liver.
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A homozyguous mutation in what receptor will produce familial hypercholesteremia?
What does the LRP receptor bind? |
LDL receptor:
The LRP receptor binds ApoE-rich CM and VLDL remnants (aka "remnant receptor"). It's localized to the liver. |
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What does the Lipoprotein Lipase do? Where is it found?
What does Hepatic Lipase do? |
LPL hydrolyzes TG, CM and VLDL at the surface of vascular endothelium.
Functions as both a lipase and phospholipase with IDL and HDL |
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What is the function of the followin apolipoproteins:
ApoA I ApoA II ApoB |
ApoA I: activates LCAT (converts free cholesterol into cholesteryl ester (a more hydrophobic form of cholesterol) which is then sequestered into the core of the HDL particle)
ApoA II: 2nd most abundant in HDL, can interfere with ApoA I ApoB: the only non-exchangeable one! |
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What is function of the following apolipoproteins:
ApoC - II ApoC - III ApoE |
ApoC - II: activates lipoprotein lipase
ApoC - III: inhibits lipoprotein lipase (high in diabetcs, interfering with lipid clearance) ApoE: important in the clearance of lipoproteins from circulation (the isoform of this will determins a person's ability to clear lipoproteins) |
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Dietary and biliary cholesterol combine to form luminal cholesterol. This is converted to ___a___ by ____.
How does "a" get into the cell? It then has 2 options what are those? |
Dietary and biliary cholesterol combine to form luminal cholesterol. This is converted to micellular cholesterol by bile acids. The cholesterol is then taken up via a cholesterol transporter. From there it can be esterfied and enter a CM or be excreted back into the lumen.
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Will cholesterol consumption affect de-novo synthesis in the body?
Is there a daily net gain or loss of cholesterol? What organ uses a lot of cholesterol? |
Yes - eat more and body will make a little less.
No - amount of cholesterol eaten/synthesized = amount excreted The adrenal gland! B/c it needs a lot to make all of it's steroid hormones. |
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What type of oils are solid at room temperature?
What type of oil do plants contain? |
Saturated! These are also linked to heart disease (have no double bonds).
Unsaturated oils - they have 1 to 6 double bonds and are liquids at room temp. |
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What is the precursor of Arachidonic acid?
What arachidonic acid do? |
Linoleic acid (18:2). Arachidonic acid (20:4) will give rise to eicosinoids and these regulate iflammatory and immune systems. (omega 6)
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What is an example of an omega 3 poly-unsaturated oil? Where is it found and what does it do?
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18:3 which ---> EPA (20:5) --> DHA (22:6)
Found in fish oils, flax and canola Important for neural development. |
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What effect do unsaturated fats have on LDL and HDL?
What do LDL and HDL do (respectively)? |
Unsaturated fats will raise the LDL and lower the HDL = BAD!
LDL will deposit in arterial walls HDL serves to remove cholesterol from circulation |
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What are the 5 functions/effects of high insulin?
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1. Will cause ++ glucose to enter cells (excess will be converted to fat)
2. Will stimulate ACC and the production of Malonyl CoA 3. Activates pyruvate deHnase to produce Acetyl CoA (malonyl precursor) 4. Profoundly inhibit the enzyme that breaks down fatty acids 5. Stimulates FA synthesis |
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Where does VLDL come from? What does it do?
What other particles does it become? |
The liver of course! VLDL has B, E, C. The VLDL floats around in the blood handing out fat to all the tissue. It does so by binding to LPL (the LPL is activated by C-II). In doing so it becomes IDL whose ApoE is recognized by hepatic lipase. It is further fat-depleted and is no LDL.
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Hepatic metabolism of LDL depends on what 3 things?
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- the LDL receptors (Apo B/E) *
- the activating abilities of C-II - the integrity of the ApoB100 which binds to the receptor. * defective in FH |
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What are the 2 broad categories for disorders of LDL/VLDL metabolism?
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1. overproduction from the liver (metabolic syndrome & DM II)
2. Decreased clearance d/t a problem with the LDL receptor or ApoB |
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What is the difference between HDL that comes from the liver and HDL that comes from the intestine?
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Liver --> HDL has Apo A -1 and ApoA-2
Gut --> HDL has only Apo A-1 ** the more Apo A-2 you have the less active you are!! |
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Describe the pathway of "reverse cholesterol transport"
What is the significance of CETP in this pway? |
Squoidal or nascent HDL will go around scavenging CE from cells/tissue (uses ABC-A1) until it becomes a mature HDL particle (LCAT), at which point it binds SR-B1 receptor and the CE it has gathered is taken into the liver, processed and released in Bile.
CETP is bad b/c it transfers CE out of the HDL and into the IDL/VLDL (potential drug target) |
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What are the characteristic dyslipidemias of insulin resistance?
- HDL - TG - VLDL -LDL (qualitatively) |
HDL = low (b/c excess VLDL sucks it all up!)
TG = super high! VLDL = HIGH LDL = get smaller and more dense [LDL] might be normal but ApoB will be higher |
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Where is the "vomiting centre" in the brain? what's it called and how does it work?
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The "area postrema" - it's a part of the brain stem, but is outside of the BBB and can thus detect noxious stimuli in the blood and alert the vomiting centre!
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What are the 3 standard drugs for heartburn? how do they work?
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1. Antacids - buffer gastric pH
2. H2 Blockers - blocks histamine's affects on parietal cells "--tidine" * use intermittently! 3. Proton-pump inhibitors: blocks the activated pumps that are at the membrane by binding irreversibly ("---azole") |
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What are the 3 standard drugs for GI related chest pain? How does each drug work?
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1. Smooth msk relaxants - block voltage-gated L-Ca channels (have cardiac SE & limited efficacy)
2. Anticholinergics (Buscopan) - blocks muscarinic (Ach) receptors (blocks stimulatory effects) *contraindicated in glaucoma 3. Psychotropics - TCA's (more effective) and SSRI's for visceral hyperalgesia |
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What does metoclopramide do? What is the mechanism of it's 2 actions?
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1. Anti-emetic: d/t it's antagonist activity at D2 receptors in the chemoreceptor trigger zone
2. Pro-kinetic: mediated by muscarinic activity, D2 receptor antagonist and 5-HT4 receptor agonist activity. |
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What does Domperidone do? HOw?
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Domperidone will not cross the BBB but will still act as a dopamine antagonist. Speeds gastric emptying which may contribute to it's anti-emetic effects. (will raise prolactin levels)
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What is erythromyocin used for? What does it do microscopically and macroscopically?
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Used as a prokinetic b/c it acts on motilin receptors of SMC and ACh neurons. WIll initiate MMC in upper gut = increased gastric emptying and decreased fundic volume.
** use actuely |
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What is the biochemical mechanism of Cisapride? What affect does this have on the GI system?
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It's a "parasympath-o-mimetic" which acts as a serotonin 5-HT4 receptor agonist. Stimulation of the serotonin receptors ↑ACh release in the enteric nervous system.
It ↑s muscle tone in the esophageal sphincter and ↑s gastric emptying. ** serious cardiac SE therefore compassionate use ONLY! |
