Lipids and atherosclerosis Flashcards
what is atherosclerosis?
major risks factors?
arterial wall structure and function?
Figure 7 In order to understand AS, one must understand the structure and function of the artery.
The artery has three structural components:
adventitia (which carries blood and nerve supply to the artery itself);
media (comprised of smooth muscle, which controls vascular tone);
intima (a basement membrane covered by endothelium which regulates hemostasis, thrombosis, vascular tone and permeability).
The intima is the site of AS.
plaque formation, stage 1
fatty streak formation
Figure 10 Monocytes penetrate the intima and are transformed into macrophages and eventually cholesterol-rich foam cells. These activated macrophages scavenge and ingest oxidized low-density lipoprotein (LDL) in the subendothelial space. The progressive accumulation of lipids (intra- and extracellular) forms the fatty streak.
plaque formation - Stage 2
Fibrous Cap
Figure 11 The growing fatty streak eventually forms the lipid core, which becomes isolated by the progressive formation of a fibrous cap. The fibrous cap contains collagen, proteoglycans and activated smooth muscle cells. The sturdier the cap, the less likelihood there is of plaque rupture.
plaqe formation - stage 3?
Lipid core
Figure 12 Further lipid accumulation in the lipid core results in cell death (apoptosis).
plaque to thrombus?
Figure 13 The key event in transformation of a stable plaque to an unstable plaque is rupture, which results in either partial or complete occlusive thrombosis.
3 stages if atherosclerosis?
Atherosclerosis, the process underlying most CVD, has 3 distinct stages:
─ Initiation - during which lipids are deposited on the vessel wall
─ Progression - during which inflammation increases, plaque formation builds up in the intima, and fibrous caps are formed, increasing the potential for atheroma
─ Clinical disease - when complications result from stenosis or unstable plaque rupture, leading to myocardial infarction (MI), stroke, or death.1
LACT and ACAt found in?
LCAT - vessel
ACAT - cells
phosopholipid?
2 fatty acids and a phosophate group with alcohol derived group on the 3rd brach of glycerol
plamitic, oleic ad eicosapentaenoic?
c16, c18 and c20
saturated, monounsaturated and polyunsaturated
fredrickson classification?
1 - chylomicrons - creamy top
2 - LDL - clear
3 - IDL - turbid
4- VLDL - turbid
5 - chylomicrons and VLDL - creamy top and turbid
Familial hyperlipidemias are classified according to the Fredrickson classification which is based on the pattern of lipoproteins on electrophoresis or ultracentrifugation.[3] It was later adopted by the World Health Organization (WHO). It does not directly account for HDL, and it does not distinguish among the different genes that may be partially responsible for some of these conditions. It remains a popular system of classification, but is considered dated by many[who?].
plasma lipids?
Total Cholesterol
Total Triglyceride
HDL-cholesterol (measured)
LDL-cholesterol (calculated)
friedwald forumla?
LDL chol = Total chol – HDL chol – Trig/2.2
Fasting sample
Triglyceride < 4.5 mmol/L
LDL in familial hypercholesterolaemia?
deficiency of receptors
hetero - partial
homo - full
signs of hypercholesterolaemia?
chest scar from surgery
tendon xanthoma
corneal arcus
xanthelasma
what binds to LDL receptor?
apolipoprotain from LDL chylomicron
strucutreof a human plasma lipoprotein?
polar head groups of phospholipids
triglycerdes
cholesterol ester
cholesterol
metabolic syndrome?
reduced glucose tolerace
hyperinsulinemia
hypertension
viscral obesity
hemostatic disorder
lipid disorders - triglycerides elevated, LDL chol normal, HDL-C diminished.
Figure 61 The Metabolic Syndrome (‘Syndrome X’) is the pathological expression of the ‘susceptibility genotype’. It is a disease of the modern Western lifestyle characterized by truncal/visceral obesity, hypertension, hyperinsulinemia, reduced glucose tolerance, and a pro-coagulatory state.
visceral obesity and metabolic abdnomalities?
Figure 62 The Metabolic Syndrome is characterized by the following features of dyslipidemia:
high TGs;
increased small, dense LDL;
low HDL-cholesterol;
elevated apo B;
pro-inflammatory profile.
simvastatin?
glasgov’s remodeling hypothesis?
The new model of atherosclerosis was based on histological analysis of coronary artery sections reported by Glagov et al in 1987.1 The work they described showed that the early stages of disease were marked by plaque accumulation in the vessel wall, with subsequent enlargement of the EEM but no change in lumen size.
In Glagov’s original hypothesis, plaque development is extraluminal until the lesion occupies ≥40% of the area within the EEM. Only then does the lumen begin to shrink.
diet for hyperlipidaemia?
- Ideal body weight
- Total fat 30% energy
- Saturates 10%
- Alcohol limited for triglycerides
cholesterol dietary influences?
raised by SFA’s
reduced by omega-3’s, soluble fibre stanols/sterols)
dietary cholesterol (eggs, offal, shellfish) raise blood cholesterol slightly
triglycerides- dietary influences?
Alcohol
Sugar
Overweight
lipid lowering drugs?
Statins
Fibrates
Bile acid sequestrants
Cholesterol uptake inhibitors
Fish oil derivatives
Nicotinic acid (niacin)
statins?
Prava -
Fluva
Simva
Atorvo-
Rosuva-
Reduce LDL
Well tolerated
Proven reduction CAD
cholesterol biosynthesis?
Acetyl-CoA
HMG-CoA
HMG-CoA reductase
Mevalonate Cholesterol
side effects of statins?
Generally well tolerated
myositis (CK >5 uln)
liver disturbance (AST >3uln)
fibrates?
Clofibrate
Beza -
Feno -
Cipro -
Gemfibrozil
Action Stimulate lipoprotein lipase
Lower VLDL, LDL
Raise HDL
Pros- - Reduce LDL/HDL ratio
- Well tolerated
Cons - LDL lowering is slight
- outcome studies not clear cut
side efects of fibrates?
bile acid sequestrants?
Cholestyramine
Colestipol
Colesevelam
cholesterol uptake inhibitors?
Ezetimibe
Also plant sterol derivatives
(Benecol and Flora pro-active)
cholesterol production?
cholesterol absorption?
small bowel brush borders
coadministration
simvastatin and ezetimibe
fish oil derivatives?
prescribing?
(1)Cholesterol raised
First line : Statins
Second line : Ezetimibe or
Bile acid sequestrants
(2) Mixed hyperlipidaemia
Fibrates
Fish oil derivatives
