Session 6 ILO's Atheroslerosis Flashcards
Define arteriosclerosis, atherosclerosis and atheroma
Atheroma = accumulation of intracellular and extracellular lipid in intima and media of medium and large sized arteries
Arteriosclerosis = thickening and hardening of arterial walls usually due to hypertension or diabetes
Atherosclerosis = thickening and hardening of arterial walls due to atheroma
Describe the variable macroscopic appearances of atherosclerosis
- Fatty streak (3)
- Lipid deposits in the intima
- Yellow and slightly raised
- Relationship to atherosclerosis is somewhat debatable - Simple plaque (4)
- Yellow/white and raised
- Irregular outline
- Widely distributed
- Enlarge and coalesce - Complicated plaque (4)
- Thrombosis
- Haemorrhage into the plaque
- Calcification
- Aneurysm formation
Describe the microscopic appearances of atherosclerosis
Early stage: (3)
- Proliferation of smooth muscle cells
- Foam cells accumulate (macrophages carrying lipid)
- Extracellular lipid (so lipid inside and outside cells)
Larger stage: (7)
- Fibrosis
- Necrosis
- Cholesterol clefts
- +/- inflammatory cells (lymphocytes, neutrophils)
- Disrupts internal elastic lamina
- Damage extends into media
- Plaque fissuring
Identify modifiable and non-modifiable risk factors for the development of atherosclerosis
Modifiable:
- Smoking
- Alcohol
- Hypertension
- Hyperlipidaemia
- Diabetes Mellitus
Non-modifiable:
- Age
- Gender
- Geography
- Ethnicity
- Genetic predisposition/family history
Identify interventions to prevent and manage atherosclerotic disease
- Stop smoking
- Manage diabetes mellitus
- Control hypertension
- Reduce fat intake
- Lipid lowering drugs
- Increase exercise and weight management
(6)
However, some people will still develop atherscleorsis!
Describe and understand the cells involved in the formation of an atherosclerotic plaque.
Endothelial cells, platelets, smooth muscle cells, macrophages, lymphocytes, neutrophils.
Recognise the common sites of atherosclerosis and the sequelae/complications of atheroma at these sites.
- ischaemic heart disease (heart)
- Cerebral ischaemia (brain)
- Mesenteric ischaemia (intestines)
- Peripheral vascular disease (peripheries)
- Abdominal aortic aneurysm (stomach)
5 common sites of atherosclerosis:
- Aorta (especially abdominal)
- Coronary arteries
- Carotid arteries
- Cerebral arteries
- Leg arteries
Explain the cellular events and proposed theories that lead to the formation of atherosclerotic lesions LEARN
4 OLD theories for atherosclerosis pathogensis:
- Thrombogenic theory
- Plaques formed by repeated thrombi
- Lipid derived from thrombi
- overlying it, a fibrous cap developed - Insudation theory
- endothelial injury
- leads to inflammation
- increased permeability to lipids from plasma to get into arterial walls - Reaction to injury
- plaque forms due to endothelial injury
- increases permeability and allows for platelet adhesion
- monocytes enter endothelium
- smooth muscle cells proliferate and migrate - Monoclonal hypothesis = generally not accepted
- Smooth muscle proliferation is needed for formation of APL
- each plaque is monoclonal
- Each plaque represented a single clone of cells
is each plaque a benign tumour, might represent abnormal growth control?
- could atherosclerosis have a viral aetiology?
3 NEWER theories!
- Unifying hypothesis 1
Endothelial injury due to:
- Toxins, hypertension, haemodynamic stress - Unifying hypothesis 2
Endothelial injury causes:
- Platelet adhesion, PDGF release, smooth muscle proliferation, migration
- Accumulation of lipid, LDL oxidation, uptake of lipid by smooth muscle and macrophages
- Migration of monocytes into the intima - Unifying hypothesis 3
- Stimulated smooth muscle cells produce matrix material
- Foam cells secrete cytokines (causes further smooth muscle proliferation and inflammation cell recruitment)
