cholesterol, atheroma, CHD Flashcards
LDL levels are raised by (3)
cigarette smoking, coffee, stress
Majority of cholesterol is
LDL
Cholesterol largely responsible for atheroma formation
LDL
Cholesterol which prevents atheroma
HDL
Functions of cholesterol (6)
lipid precursor for other steroids, important in cell growth and division, regulation of sexual function, regulation of tissue metabolism, mineral balance and formation of bile salts
proportion of cholesterol made in liver
1/4
cholesterol is poorly absorbed by
gut
cholesterol is carried in blood as part of
lipoprotein
HDL formation begins in
liver
HDL begins as
empty collapsed protein shell
HDLs travel in blood picking up
cholesterol and phospholipids
After picking up cholesterol and phospholipids, HDL
returns to liver and cholesterol is removed
chylomicrons form in
absorptive cells of small intestine
chylomicrons travel from small intestine through ….. to blood
lymphatic system
chylomicrons are hydrolysed to monoglycerides and free fatty acids to travel through capillary walls into adipocytes before being resynthesised into
triglycerides
VLDLs are produced by
liver
VLDLs transport lipids to adipose tissue for storage where they become
LDLs
liver compensates for …………. of cholesterol
dietary intake
changes in diet can reduce serum cholesterol by
5% max
Fatty acid intake can reduce cholesterol level by
15-20%
2 other forms of synthesis of cholesterol
glycolysis (acetyl CoA) or beta-oxidation of other lipids
exercise reduces sensitivity of right atrium to …….. and so heart secretes less …… and blood volume …… meaning more cholesterol is transported by HDLs to …….
blood pressure; atrial natriuretic peptide; increases; liver
familial hypercholesterolaemia due to (2)
low number LDL receptors, altered function/structure of receptors
familial hypercholesterolaemia is most common type of ……… (1/500)
hyperlipidaemia
in familial hypercholesterolaemia, LDL levels are in excess of
190
LDL receptor gene on chromosome
19
familial hypercholesterolaemia alleles exhibit
incomplete dominance
symptoms of familial hypercholesterolaemia (5)
xanthomas, xanthelasmas, arcus senilis, obesity, symptoms of atherosclerosis
xanthoma =
fatty, cholesterol-rich deposits in skin
xanthelasma =
fatty deposits on eyelid
arcus senilis =
white ring around cornea
atheroma =
accumulation of intracellular and extracellular lipid in INTIMA of large and medium arteries
3 stages of atheroma formation
fatty streak, simple plaque, complicated plaque
arteriosclerosis =
thickening of arterial walls, usually due to diabetes / hypertension
causes of atherosclerosis (5)
high BP, high cholesterol, smoking, high blood sugar, heart disease - angina
risk factors of atherosclerosis (15)
smoking, male, menopause, diet, alcohol, obesity, familial hyperlipidaemia, acquired hyperlipidaemia, diabetes, lack of exercise, type A personality, stress, infection, soft water, oral contraceptives
ATHEROMA FORMATION: (1) micelles absorbed into intestinal mucosa > converted to ……
chylomicrons
ATHEROMA FORMATION: (2) chylomicrons absorbed by ……… and travel through thoracic duct to be distributed throughout the body
lacteals
ATHEROMA FORMATION: (3) ………… ………. hydrolyses chylomicrons into fatty acids and monoglycerides which are released into intestinal fluid to be absorbed by adipocytes and skleletal muscle
lipoprotein lipase
ATHEROMA FORMATION: (4) liver absorbs chylomicron and removes triglyceride > combines with ……….. (alters surface protein)
cholesterol
ATHEROMA FORMATION: (5) Capillary endothelial cells contain LDL receptors and absorb LDLs in ………. coated vesicles
clathrin
ATHEROMA FORMATION: (6) Excess levels of cholesterol inhibit cholesterol and LDL receptor synthesis > LDL uptake reduced > cholesterol ……… promoted
storage
ATHEROMA FORMATION: (7) Circulatory monocytes remove ………. and become saturated with ………… droplets
lipoproteins; lipid
ATHEROMA FORMATION: (8) Saturated monocytes form ….. cells which attach to endothelial walls of blood vessels
foam
ATHEROMA FORMATION: (9) Once foam cells attached to endothelial walls of blood vessels, they release cytokines which stimulate stimulate smooth muscle cells near the tunica ………… to divide causing the walls to thicken
intima
ATHEROMA FORMATION: (10) Other monocytes invade the area and ……….. lipids forming an atherosclerotic ……. and ……..
phagocytise; plaque; stenosis
LDLs secrete ……. which prevents normal migration of macrophages out of arteries
netrin-I
coronary atherosclerosis is a complex …….. process
inflammatory
coronary atherosclerosis is the accumulation of lipids, macrophages and …… ……… cells
smooth muscle
ATHEROGENESIS: (1) atherogenesis follows endothelial …….. with increased permeability to and accumulation of ………. lipoproteins
dysfunction; oxidised
ATHEROGENESIS: (2) oxidised lipoproteins taken up by macrophages at ………. ….. within endothelium
focal sites
ATHEROGENESIS: (3) these macrophages form lipid-laden ….. …… which form a fatty …..
foam cells; streak
ATHEROGENESIS: (4) fatty streak progresses with extracellular lipid within endothelium to form a ………… plaque
transitional
ATHEROGENESIS: (5) monocytes, macrophages and damaged endothelium release ….. which promote further accumulation of macrophages and smooth muscle cell migration and ……….
cytokines; proliferation
ATHEROGENESIS: (6) collagen is produced in large quantities by ……… ………. and events accumulate finally forming a ……… ……..
smooth muscle; fibrolipid plaque
There are two mechanisms a thrombosis can develop on a plaque:
superficial endothelial injury, deep endothelial fissuring
superficial endothelial injury = denudation of endothelial covering of plaque exposing the subendocardial …. ……. ………. and allowing platelet adhesion due to reaction with …..
connective tissue matrix; collagen
deep endothelial fissuring = advanced plaque with ….. core formed because plaque cap tears allowing …. to enter. Core now has lamellar lipid surfaces, …… …… produced by macrophages and exposed ….. which makes it highly …..
lipid; blood; tissue factor; collagen; thrombogenic
total cholesterol ratio should not exceed
5
ideal cholesterol ratio
1.0-3.5
when calculating cardiovascular risk, what is cut off for high risk?
20+%
when calculating cardiovascular risk, what is cut off for moderate risk?
10-20%
when calculating cardiovascular risk, what is cut off for low risk?
<10%