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what is atherosclerosis?
- arterial wall hardening and loss of elasticity by the build up of plaque
- plaque beneath the tunica interna of arteries
what do atherosclerosis plaques do?
obstruct vessels, reducing or blocking blood flow
Describe the 3 main components of atherosclerosis plaque.
- cells: smooth muscle cells, macrophages, other leukocytes
- extracellular matrix: collagen, elastic fibers
- Cholesterol particles: lipoproteins
- fibrous cap made of smooth muscle cells
what is a key factor in plaque formation?
lipids are hydrophobic so they need to be modified for transport in blood. How is this done?
they combine with proteins forming lipoproteins
what is the function of lipoproteins?
transport vehicles for cholesterol and triglycerides
Describe the composition of lipoproteins. (2)
- contain hydrophobic core: with insoluble triglycerides and cholesterol
- hydrophilic surface monolayer: coating phospholipids and proteins (apoproteins)
what are the 4 major kinds of lipoproteins and categorize which are "good" and "bad" cholesterol.
- chlymicrons: bad
- Very-low-density lipoproteins (VLDL): bad
- low-density-lipoproteins (LDL): bad
- high-density-lipoproteins (LDL): bad
- high-density-lipoproteins (HDL) : good
what are 2 ways that lipoproteins enter the bloodstream?
- exogenous pathway
- endogenous pathway
One of the ways lipoproteins enters the bloodstream is through the exogenous pathway, describe this pathway. (3)
- refers to dietary intake of lipids
- absorbed by intestine and packaged as chylomicrons
- fats removed from circulation by receptors and remnants travel to liver for final absorption
One of the ways lipoproteins enters the bloodstream is through the endogenous pathway, describe this pathway.
refers to lipoproteins secreted by the liver into the blood
what are the lipoproteins in the endogenous pathway?
VLDLs (very low density proteins)
describe the structure if VLDLs. what is its primary function.
- high triglycerides, small amounts of phospholipids and cholesterol
- function is to transport triglycerides to peripheral tissues
what are the 2 types of lipoproteins in the endogenous pathway?
- LDLs - low density lipoproteins (bad cholesterol)
- HDLs - high density lipoproteins
Describe the structure of LDLs and what is its's primary function?
- contain very few triglycerides, a few more lipoproteins andn lots and lots of cholesterol primary function is to deliver cholesterol to peripheral tissue
what happens when there is too many LDLs in circulation?
can be taken up by "unauthorized tissues" such as the arterial walls
what is the lipid hypothesis of atherosclerosis?
states that LDL circulating in the blood are oxidized by free radicals (ROS) to form oxidized-LDL that damage the arterial wall and stimulate influx of macrophages and other immune cells
what are foam cells?
macrophages that consume oxidized-LDLs in vast numbers
what is the "response to injury" hypothesis? what does it result in?
- suggests that atherosclerosis is a chronic inflammatory response due to injury to the endothelial lining of the artery
- results in smooth muscle proliferation and adhesion and infiltration of the wound by macrophages and other inflammatory cells
what are some signs that can lead to the progression of atherosclerosis? (4)
- earliest sign is presence of fatty streaks
- fibrous plaque formation
- plaque rapture and thrombosis
what is a fatty streak?
yellow, flat areas full of foam cells in the endothelial layer of an artery
what are the 3 steps for the initial phase of atherosclerosis plaque formation?
- 1. adhesion of blood leukocytes to activated enodthelial monolayer
- 2. directed migration of the bound leukocytes into the intima
- 3. maturation of monocytes into macrophages and their uptake of lipid, yielding foam cells
what are the 3 steps in the progression of lesion-fibrous plaque formation?
- 1. migration of SMCs from the media to the intima
- 2. extracellular lipid accumulation in central region of a plaque
- 3. proliferation of SMC and heightened synthesis of extrecellular matrix macromolecules (collagen, elastin) forms fibrous cap
what are the 3 steps in the progression of lesion-fibrous plaque rapture and thrombosis?
- 1. plaque continues to grow, narrowing lumen, may develop calcification
- 2.plaques fibrous cap fractures and plaque projects into lumen disrupting smooth flow of blood
- 3.resulting turbulence slows flow and may also strip away endothelial cells, which leads to clot(thrombus) formation
Hypertension contributes to ____________ damage.
what are the non-modifiable risk factors for atherosclerosis? (3)
- increasing age
- familial traits
what are the 7 modifiable risk factors for atherosclerosis?
- cigarette smoking
- physical inactivity
- stress and personality
what are some possible outcomes and major damage due to atherosclerosis?
- vessels can rapture leading to hemorrhage
- clot can beak off (embolus formation) and obstruct smaller vessels
- acute blockage of an artery will cause ischemic necrosis
- growth of plaque can weaken artery wall, leading to aneurysm (bulge in arterial wall)
the consequence of atherosclerosis in the central nervous system (CNS) is __________.
the consequence of atherosclerosis in the peripheral circulation is ____________________.
peripheral arterial disease (gangrene)
the consequence of atherosclerosis in the coronary arteries is__________________.
CHD: angina pectoris, myocardial infraction
Cardiovascular mortality-30-50% of all deaths in _________________.
what are some simple changes you can make to prevent atherosclerosis? (3)
- eat heart-healthy diet
- be active and exercise
- stop smoking
what are 3 mechanical therapies for atherosclerosis?
- vein and artery bypass grafting
- balloon angioplasty
how does the coronary bypass surgery for atherosclerosis work?
cut a artery/vein from usually the leg and attached to block section creating another passage for blood to flow through.
how does balloon angioplasty surgery for atherosclerosis work?
- balloon catheter with inflated balloon is sent into obstructed area in the artery
- when balloon is inflated, it stretched arterial wall and squashes atherosclerotic plaque
- after complete catheter is withdrawn
how does stenting, a mechanical therapy, for atherosclerosis work?
insertion of cylindrical metal strut that expands the lumen
what is primary prevention?
action taken prior to the onset of disease, which removes the possibility that the disease will ever occur
what are 3 advantages and disadvantages of prevention through high risk strategy?
- advantages: intervention appropriate to individual at risk
- cost-effective use of limited resources
- high ratio of benefits to risks
- disadvantages: difficulties and costs of screening
- not radical: does not alter the underlying causes of the disease
- behaviourally inappropriate
what are 3 advantages and disadvantages of prevention through population (mass) strategy?
- advantages: radical (attempts to remove the underlying causes that make the disease common)
- large potential for population
- behaviourally appropriate
- Disadvantage: small benefit to individual
- poor motivation of subject/physician
- low benefit: risk ratio