Atheroscleorsis Flashcards
What is atherosclerosis?
Thickens of artery walls, less elasticity
Artery diameter decrease beucase of the build up of plaques on the inner walls.
Arteries are very elastic and have a strong ability to change the diameter and be able to widen. Less elastic decreases the ability to dilate –> what occurs is atherosclerosis.
Irreversible
Can be a silent condition
What are atherosclerotic plaques made of?
Lipids, calcium, cellular debris
Macrophages transformed into foam cells
Smooth muscle cells
Causes damaged endothelium
Plaque formation is irreversible, some surgery can reduce size but doesn’t eliminate the damage.
Lifestyle interventions cannot get rid of the plaque.
Who are at risk?
- Ageing
- Smoking –> can lead to damage in the endothelial cells
- High fat (LDL) diet
- Lack of exercise
- Being overweight or obese –> endothelial cell damage
- Drinking lots of alcohol
- Family history
- Being south Asian, African or African-Caribbean
Other conditions - Hypertension
- High cholesterol
- Diabetes –> endothelial cell damage
How does atherosclerosis link to blood pressure?
Blood pressure is regulated by cardiac output and peripheral resistance
Cardiac output –> heart rate + stroke volume
Peripheral resistance –> arteriole radius + blood viscosity
Atherosclerosis decrease the size of the lumen in a blood vessel causing higher blood pressure. Causes a change in peripheral resistance.
High blood pressure is a consequence of atherosclerosis
What can cause the development of atherosclerosis?
- Oxidative stress
- Inflammation
- Fibrosis
Central to the whole process is a dysfunction of the endothelial cells which line the blood cells
What maintains endothelial function?
Nitric oxide –> vasodilator
Endothelin 1 –> vasoconstrictor
What can causes endothelial cells to release nitric oxide?
Endothelial cells release nitric oxide (vasodilator) in response to
- Mechanical stimuli –> blood flow, increased when there is a higher cardiac output and stroke volume as the heart is working harder during exercise. Will cause an increase in nitric oxide to cause blood vessels to widen, especially those vessels that go to muscles. In other parts of the body the opposite will happen. Endothelin 1 will increase to constrict other vessels such as digestive organs
- Hormones
The end result is the blood vessels dilate, pre-capillary sphincters open and blood flow matches metabolic demand
How is nitric oxide produced?
What is the NOS pathway? mechanism?
NOS pathway - enzymatic pathway
Acetylcholine
Cytokine
Mechanical stimulus (most common) –>
|
Increased phosphorylation of Endothelial nitric oxide synthase (eNOS) –>
|
Activated eNOS and causes a reduction in L-Arginine (amino acid) which cause Nitric Oxide release –>
|
Nitric oxide diffuses to the medium layer where there are lots of smooth muscle cells –>
|
NO activates a cascade response of proteins which causes medium-layer relaxation –>
|
The relaxation facilitated artery expansion and it increases the size –>
|
Vasodilation occurs
NO inhibits the production of endothelin 1 in endothelial cells.
Digestive organs receive less blood flow to reduce NO production
What is the mechanism of Endothelin 1?
Growth factors
Cytokines
Stress
Hypoxia
|
Activation of pre-endothelin 1
|
Activate Endothelin-1
|
Down regulate nitric oxide
|
Diffuse to middle layer
|
Down regulate cGMP
|
Constriction of blood vessels (Vasoconstriction)
What is the relationship between atherosclerosis and NO and ET-1?
Dysregulated mechanisms
Lower capacity to form NO (expand blood vessels)
HIgher ability to form ET-1 (constrict blood vessels)
Reducing blood vessel elasticity causing blood pressure to increase.
What is dyslipidemia?
A heterogeneous group of disorders charatersied by abnormal levels of circulating lipids and lipoproteins. The abnormalities include elevations in cholesterol, triglycerides or a combination of the 2.
What are lipoproteins?
Provide energy from fat in adipose tissue and muscle
Describe the development of atherosclerosis
- Damage/ lesion to the endothelium
- smoking (tobacco compounds can dysregulate endothelial cells)
- high levels of blood glucose
- high levels of LDL
- high blood pressure
Atherosclerotic plaque can form - Endothelial dysfunction, less effective to produce NO and ET-1
- Translocation of LDL into the Tunica Intima. LDL becomes oxidised and produce free radicals
- Macrophages move to tunica intima to try to get rid of LDL molecules are they aren’t meant to be there. Free radicals signal the macrophages
- Macrophages eat the LDL and form foam cells (macrophages that contain large quantities of LDL)
- Foam cells formed chronically, accumulation can stimulate accumulation of smooth muscle from medium layer to the internal layer
- Movement of muscle cells reduces elasticity, as it grows it reduces the diameter of the lumen
- Forms a fibrous cap/ atherosclerotic plaque
What happens if the plaque ruptures?
A clot will be released
Ischaemia –> plaque breaks and goes to other parts of the body
In the heart the diameter of the blood vessels is usually large enough to cope with the clot, but if it travels to the brain that is when problems can happen.
Can block capillaries
Can cause a stroke
Thrombus
What is the calcium score?
Imaging with contrast that can show calcium deposits, a score than be used to detect the amount of plaque.
Coronary artery calcium.
0 –> no evidence of plaque
1-10 –> minimal coronary artery plaque
11-100 –> mild
101-400 –> moderate
>400 –> extensive
