Atheroma Formation And Atherosclerosis Flashcards
Atheroma define
Abnormal accumulation of fatty material in the inner wall (intima) of the artery
Atherosclerosis define:
Fat deposition in the walls of medium-sized and large arteries; progressive thickening and hardening of the arterial wall
Atherosclerosis around the body: coronary arteries
Coronary artery/heart disease: angina (chest pain) and myocardial infarction (heart attacks)
Atherosclerosis around the body: cerebral arteries
Cerebral vascular disease : transient ischemic attacks and stroke
Atherosclerosis around the body: peripheral arteries
Peripheral vascular disease : claudication (pain in lower limbs when walking) ; gangrene (due to lower limb ischaemia)
Risk factors of atherosclerosis : modifiable
High bp
High cholesterol
T2 diabetes
Obesity
Exercise
Smoking
Risk factors of atherosclerosis : non- modifiable
Age
Ethnicity
Gender
Family history
LDL vs HDL
LDL- BAD cholesterol
HDL - GOOD cholesterol
Timeline of atherosclerosis
Foam cells
Fatty streak
Intermediate lesion
Atheroma
Fibrous PLAQUE
Complicated. Lesion /rupture
TIA transient ischemic attack linked to?
High levels of LDL cholesterol in the body
Fatty collection =Leads to injury and inflammation
Inflammation in atherosclerosis explain
Present during all stages of atherosclerosis
Response to injury hypothesis : atherosclerosis
Chronic inflammatory and healing response of arterial wall to endothelial injury
Atherosclerosis progression:
- Endothelial dysfunction
- Endothelial injury
- Accumulation of cholesterol
- Formation of fibrous cap
- Plaque rupture
What is happening at stage 1 of atherosclerosis progression: endothelial dysfunction
Single layer of endothelial cells ; provide barrier
Decreased NO production = increased permeability = disruption of endothelial lining
What is happening at stage 2 of atherosclerosis progression: endothelial injury
Injured of endothelium initiates and inflammatory response
=increased expression of adhesion molecules
Monocytes attach and migrate into vessel wall
What is happening at stage 3 of atherosclerosis progression: Accumulation of cholesterol
LDL cholesterol enters the vessel wall
Monocytes-macrophages-foam cell
Fatty streak
T lymphocytes accumulate
What is happening at stage 4 of atherosclerosis progression: fIBROUS CAP
Inflammatory state
Cytokines and growth factors get released from macrophages, platelets and endothelial cells
=cause proliferation and migration of SMCs-form fibrous cap overlaying fatty core
What forms fibrous cap?
Cytokines and growth factor released= causing proliferation and migration of SMCs
Late stage atherosclerotic plaque structure
Fibrous cap
Necrotic core
Media
Necrotic core consists of?
Apoptotic cells, debris, cholesterol crystals, foam cells, calcium
Media consists of?
SMC proliferation
Lesion diversity : stenosis vs non-stenotic
Stenotic- thick cap, quite stable, few immune cells
Non-stenotic- thin cap, highly unstable, mainly immune cells
What is happening at stage 5 of atherosclerosis progression:plaque rupture
Inflammation and immune cells promote plaque rupture
Rupture of the fibrous cap exposes the core of blood stream
Platelets are activated: coagulation cascade
Formation of blood clot (thrombus)
Atherosclerosis treatment:
prevent it or its complication by targeting modifiable risk factors : hyperlipidaemia+hypertension + diabetes + smoking
Target obstructed arteries
How might you prevent atherosclerosis or its complication by targeting modifiable risk factors
hyperlipidaemia- lipid lowering drugs (statins)
hypertension- lower blood pressure (anti-hypertensive drugs)
diabetes - lower blood sugar
Smoking- stop smoking
How might you prevent atherosclerosis or its complication by targeting obstructed arteries ?
Coronary artery obstruction: stents , thrombolysis
Statins work by?
Lowers cholesterol by competitive inhibition of HMG-CoA reductase (enzyme that catalyses the conversion of HMG-CoA to mevalonate )
