atherosclerosis Flashcards
describe the structure of the normal arterial vessel WALL
- tunica intima (innermost, next to lumen, simple squamous)
- tunica media (smooth muscle layer)
- adventitia (outermost)
4 components of an atherosclerosis plaque
Lipid
Necrotic core
Connective tissue
Fibrous “cap
what are the 3 main headings to plaque formation mechanism
- damage to endothelial wall
- LDLs begin formation of fatty streak
- plaque growth
list non-modifiable risk factors for atherosclerosis
Age
Gender
Race
Family History
type 1 diabetes
list modifiable risk factors for atherosclerosis
Smoker
Lack of exercise
Weight
(Borderline) Diabetes (type 2)
Hypertension
High cholesterol
why is smoking a risk factor for atherosclerosis?
Releases free radicals, nicotine + CO into the body/blood → These damage endothelial cells → increased risk of plaque formation
why is hypertension a risk factor for atherosclerosis?
Increased pressure →increased damage of the vessel wall → increased risk of plaque formation
why is poorly controlled Diabetes a risk factor for atherosclerosis?
High glucose levels in the blood
Increased Free radicals leads to Increased oxidation of LDLs
Loss of nitric oxide (NO) , Which normally allows relaxation of vessel + increased flow
Promotes platelet aggregation
why is High cholesterol levels a risk factor for atherosclerosis?
High LDLs
Can pass in and out of the arterial wall in excess, accumulates in arterial wall,
undergoes oxidation….
plaque formation etc
why is obesity a risk factor for atherosclerosis?
Increases proinflammatory cytokines levels
More LDLs
why is a lack of exercise a risk factor for atherosclerosis?
exercise helps rebalance of low- and high-density lipoproteins
Reduces blood pressure
Therefore lack of exercise can lead to high levels of LDLs, hypertension, obesity
why is age a risk factor for atherosclerosis?
?
Risk increases with age as plaque builds up over time
The trend shows: If fatty streaks develop in 20s, these don’t establish into plaques until 30-50s, and only in you 40s-80s do these plaques cause compilations such as thrombosis or angina
why is race/ethnicity a risk factor for atherosclerosis?
Certain ethnic minority groups are at greater risk of heart disease
Rates of cardiovascular disease (CVD) and diabetes are higher among Black and South Asian groups in the UK
why is family history a risk factor for atherosclerosis?
Lipid levels, hypertension and diabetes, all appear to have an inheritable component.
what are primary preventative measures for atherosclerosis?
Exercise more
- Helps rebalance of low- and high-density lipoproteins
- Reduces blood pressure
Eat more healthily
- Less salt + sat fats
- Less sugar- diabetes risk
Stop smoking
- Less free radicals, nicotine + CO into the body/blood
- Therefore less damage endothelial cells
what are secondary preventions for atherosclerosis?
Statin
- to help lower the level of low-density lipoprotein (LDL) cholesterol in the blood.
Antihypertensives:
Calcium channel blockers (CCB) eg. Nifedipine
ACE inhibitors (ACEi) eg. ramipril
angiotensin receptor blockers (ARB) eg. Candesartan
Diuretics eg. chlorthalidone
Beta blockers eg. propranolol
Diabetes control:
- Eg. Metformin medication
Social and green prescribing
- Weight loss groups
- Gym vouchers
- Join a walking group
Define the term ‘co-benefits’ in relation to health and climate change?
Co-benefits:the positive effects that a policy or measure aimed at one objective might have on other objectives
Implementation of climate policies has many co benefits including reducing health risks
Climate change and health are interlinked, for instance, measures to prevent air pollution will also help breathing quality
what is the most accepted theory on the mechanism of atherosclerosis plaque formation
the endothelial damage theory
explain step 2 of plaque formation:
- endothelial wall damage
Due to high levels of LDLs in blood stream (hyperlipidemia)
Smoking or air pollution (free radicals)
High cholesterol
Hypertension - causes physical injury
Turbulent blood flow, for example, where arteries branch
Chronically elevated blood glucose levels
explain step 2 of plaque formation:
- LDLs begin formation of fatty streak
Dysfunctional endothelial cells allow Low density lipoproteins (LDLs) to move from lumen into tunica intima layer
The Dysfunctional cells release reactive oxygen species (eg. metalloproteases) which oxidise the LDLs
Oxidised LDLs cannot leave the intima, they are trapped
Dysfunctional endothelial cells + oxidised LDLs trigger endothelial cells to express adhesion molecules for WBCs (monocytes + T helper cells)
These monocytes attach and move into intima where they are now called macrophages
Macrophages have scavenger receptors that will engulf the oxidised LDLs to become a foam cell ( a macrophage containing lipids, essential to inflammation)
A fatty streak has formed
explain step 3 of plaque formation:
- Plaque growth
Foam cells release products, then die and release their contents. this forms the fibrous cap, the bulk of the plaque and increases inflammation.
Products released:
- chemokines, to attract more macrophages
- IGF-1 ( a growth factor), that causes smooth muscle cells to proliferate and migrate from the media to the intima layer. These cells make collagen, which forms a hard, fibrous cap to the plaque
- proinflammatory cytokines and reactive oxygen species increase inflammation
- When the foam cells die they release lipid content, containing DNA materials which attract neutrophils to the site of Inflammation
what 2 other factors increase plaque growth
- increased blood supply to plaque
- T cells
- they bind onto endothelial cells
- enter plaque area
- are activated by macrophages to release IFN-Y
- this promotes inflammation and activates endothelial cells to attract more WBCs
- as a result inflammation increases and plaque grows
