6. Atherosclerosis Flashcards
What is arteriosclerosis?
Arteriosclerosis = hardening of the arteries. In this condition the walls of arteries are thickened and lose their elasticity. It includes atherosclerosis, arteriolosclerosis.
What is atherosclerosis?
The accumulation of intracellular and extracellular lipid in the intima and media of large and medium sized arteries
What is a fatty streak?
Lipid deposits in the intima, is not raised and does not effect blood flow
What is the macroscopic appearance of a fatty streak?
yellow, slightly raised area - does not impede blood flow, not raised
What is the macroscopic appearance of a simple plaque?
Raised yellow/white area with an irregular outline, enlarge and coalesce
What happens in a compliated plaque?
calcification, thrombosis, aneurysm formation, haemorrhage and expansion of plaque
What blood vessels does atherosclerosis affect?
Arteries only
How does athersclerosis lead to death?
Leads to stenosis of the arterial lumen and can result in myocardial infarction and stroke
What are the common sites for atherosclerosis?
Elastic arteries- aorta, carotid and iliac arteries
Large and medium sized muscular arteries-coronary and popliteal arteries
Commoner in the abdominal rather than the thoracic aorta.
What is arteriolosclerosis?
Hardening of the arterioles - usually due to hypertension and diabetes mellitus.
What is an atheroma?
Atheroma is the necrotic core of the atherosclerotic plaque. It consists of dead cells, debris and cholesterol crystals.
What are the 3 basic components of a plaque?
- Cells – macrophages, leucocytes, smooth muscle cells
- Intra- and extracellular lipid
- Extracellular matrix – collagen, elastin, proteoglycans.
What is the microscopic appearance of a fatty streak?
Intimal foam cells, some smooth muscle cells and some extracellular lipid.
What is the microscopic appearance of a plaque?
fibrosis, necrosis, cholesterol clefts, disruption of the internal elastic lamina, extension into the media and ingrowth of small vessels from the adventitia.
What is an aneurysm?
local dilatations of an artery due to weakening of the arterial wall
What are the effects of severe atherosclerosis in the coronary arteries?
myocardial infarction, chronic ischaemic heart disease, arrhythmias, cardiac failure and sudden cardiac death,
What are the effects of severe atherosclerosis in cerebral arteries?
Cerebeal ischaemia -
Cerebral infarction (stroke)
Transient ischaemic attack (mini-stroke)
What are the consequences of mesenteric ischaemia?
Ischaemic colitis
Malabsorption
Intestinal infarction
What are the consequences of peripheral vascular disease?
Intermittent claudication - blood supply to legs
Ischaemic rest pain
Gangrene
What are the risk factors for atherosclerosis?
Smoking Hypertension Age - progressive Gender - women protected before menopause Hyperlipidaemia Alcohol Diabetes mellitus Infection
What atherosclerosis prevention measures and interventions would you recommend to patients?
Stop smoking Decrease fat intake Treat hypertension Aspirin Sensible alcohol intake Exercise and weight control Treat diabetes Lipid lowering drugs if needed
What cells are involved in plaque formation?
Endothelial cells Platelets SM cells Macrophages Lymphocytes Neutrophils
What are complications of aortic aneurysms?
Rupture - hypovolaemic shock
Thrombus formation
Embolism
How does thrombomodulin prevent thrombosis?
Thrombomodulin binds to any locally formed thrombin and this complex initiates the anti‐coagulant effects of protein C and protein S
How much does a lumen have to be occluded in order to significantly affect blood supply?
70-80%
What is arteriolosclerosis?
Hardening of the arterioles, usually secondary to severe hypertension or diabetes mellitus.
Where is a common site of arteriolosclerosis?
Kidney arterioles
Briefly outline the events that lead to plaque formation.
- Chronic endothelial insult
- Lipid and monocytes cross endothelium and enter intima. Oxidised and form foam cells.
- SM cells migrate from media to intima and proliferate.
- Plaque grows - SM and foam cell proliferation. Fibrous cap formed.
- Cells in centre undergo necrosis, cholesterol crystals appear, angiogenesis from adventitia, calcification.
When fibrosis occur in plaque formation?
Collagen, elastin and other matrix proteins form a fibrous cap.
What are cholesterol clefts?
Holes where cholesterol has been removed during tissue processing
Aneurysm usually occurs secondary to _________.
Atherosclerosis
What are the 2 major complications of an aortic aneurysm?
Rupture and haemorrhage
Thrombus formation/emboli
What is aortic dissection?
The inner layer of arterial wall tears open, blood enters and separates the media into 2 layers. Tear fills and can occlude artery.
What are the 3 proposed mechanisms of atherosclerosis?
- Response to injury hypothesis
- Encrustation hypothesis
- Monoclonal hypothesis
What is the response to injury hypothesis?
Atherosclerosis is a chronic inflammatory response of the arterial wall initiated by injury to the endothelium.
Progression by interaction between modified lipoproteins, macrophages, T cells and cells in arterial wall.
What is the encrustation hypothesis?
Plaques are formed by repeated thrombi overlying thrombi. Lipid core derived from thrombi.
What is the monoclonal hypothesis?
Each plaque is monoclonal. Is each plaque a benign tumour? Could it be induced by viruses?
What role do endothelial cells have in atherosclerosis?
- Altered permeability to lipoproteins
- Collagen production
- Stimulation of proliferation and migration of SM cells
What role do platelets play in atherosclerosis?
Stimulate proliferation and migration of SM cells - PDGF
What role do SM cells play in atherosclerosis?
- Take up LDL to form foam cells
- Synthesise collagen and proteoglycans
What role do macrophages play in atherosclerosis?
- Oxidise LDL
- Take up lipids to become foam cells
- Secrete proteases that modify matrix
- Stimulate proliferation and migration of SM cells
What role do lymphocytes play in atherosclerosis?
- TNF may affect lipoprotein metabolism
- Stimulate proliferation and migration of SM cells
What role do neutrophils play in atherosclerosis?
- Secrete proteases leading to continued local damage and inflammation
What can cause endothelial injury and initiate plaque formation?
Hypertension
Toxins - cigarette smoke
Raised LDL
What role do foam cells play in plaque progression?
Secrete cytokines which cause further SMC stimulation and recruit other inflammatory cells
