Atherosclerosis Flashcards by Rebekah Agunede

What is arteriosclerosis?

Thickening and hardening of walls of arteries and arterioles
Usually as a result of hypertension or diabetes mellitus
often associated with loss of elasticity

(umbrella term)

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What can arteriosclerosis result in? (3)

Poor tissue perfusion
Inelastic/weak vessels (leading to aneurysm)
Increased risk of thrombus formation

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What is atherosclerosis?

Accumulation of intracellular and extracellular lipid in the intima and media of the large and medium sized arteries

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What is an atheroma?

Necrotic core of the atherosclerotic plaque. The thickening and hardening of arterial wall as a consequence of atherosclerosis.

Atherosclerosis - disease process

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What are 3 macroscopic features of atherosclerosis?

Fatty streak
Simple plaque
Complicated plaque

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What are the macroscopic features of fatty streak? (3)

Lipid deposits in intima
Yellow
Slightly Raised

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What are the macroscopic features of a simple plaque?”

Yellow/white
Raised (even more raised than fatty streak)
Irregular outline
Widely distributed
Enlarge and coalesce/become more prominent

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What are the macroscopic features of a complicated plaque?

Thrombosis
Haemorrhage into plaque
Calcification
Aneurysm formation

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Common sites for atherosclerosis

Aorta (ABDOMINAL)
Coronary arteries
Carotid arteries
Cerebral arteries
Leg arteries

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Normal arterial structure

Intima 
Internal elastic lamina
Media (muscular)
External elastic lamina
Adventitia

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What happens early on in atherosclerosis?

Proliferation of smooth muscle cells and foam cells

Extracellular lipid

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Later changes in atherosclerosis

Fibrosis
necrosis
cholesterol clefts (holes)
+- inflammatory cells

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Later vessel changes atherosclerosis

Internal elastic lamina disrupted
damage to media
ingrowth of BV
Plaque fissuring

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Clinical effects of atherosclerosis

Ischaemic heart disease
Cerebral Ischaemia 
Mesenteric ischaemia
Peripheral vascular disease
Aortic aneurysm

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Ischaemic heart disease can lead to…

MI, death, angina pectoris, arrythmias, cardiac failure

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Cerebral ischaemia can lead to

Transient ischaemic attack (mini stroke)
Cerebral infarct (stroke)
Multi infarct dementia

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Mesenteric ischaemia can lead to…

Ischaemic colitis
Malabsorption
Intestinal infarction

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Peripheral vascular disease can lead to…

Intermittent claudication (calf pain on exercise)
Leriche syndrome
Ischaemic rest pain
gangrene

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What is leriche syndrome?

Pain in buttocks
Impotence
(from ischaemia of iliac arteries)

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Risk factors atherosclerosis

Age
Gender
Hyperlipidaemia (LDL high)
Smoking
Hypertension
Diabetes mellitus
Alcohol
Infection 
Oral contraceptive

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Gender for atherosclerosis

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Men affected more than women until menopause

Oestrogen is protective

Apo E and atheroscelrosis

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Genetic variations in Apo E = changes in LDL levels

caused by polymorphisms of genes (can be used as risk markers)

Physical signs of familial hyperlipidaemia

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Corneal arcus
Tendon Xanthoma (nodules)
Xanthalasma (yellow fatty eye deposits)

Problems with smoking

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Risk factor for ischaemic heart disease
activates coagulation
reduced prostaglandins
increased aggregation of platelets

Why is hypertension a risk for IHD?

Endothelilal damage from raised pressure?

Diabetes mellitus risks

Increase risk of IHD Cerebrovascular and peripheral vascular disease (no protective effect for premenopausal women if have diabetes)

Alcohol risk of IHD

Greater than 5 units per day = increased risk | Smaller amounts protective

Infections causing atherosclerosis

Chlamydia pneumoniae Helicobacter pylori Cytomegalovirus

Broad risk factors Atherosclerosis

Lack of exercise Obesity Stress/personality Genetic predisposition

What can cause genetic predisposition for atherosclerosis?

Variations in apolipoprotein metabolism | Variation in apolipoprotein receptors

Theories of atherosclerosis

Thrombogenic Insudation Monoclonal Reaction to injury

Thrombogenic theory (1852 Rokitansky)

plaques are formed by repeated thrombi Lipid derived from thrombi Overlying fibrous cap

Insudation theory (1856 Virchow)

Endothelial injury inflammation increased permeability to lipid from plasma

Reaction to injury hypothesis (1972 Ross and Glomset)

Endothelial injury hypercholesterolaemia = endothelial damage injury increases permeability allows platelet adhesion monocytes penetrate smooth muscle cells proliferate

Reaction to injury (1986 Ross)

Endothelial injury is subtle (undetectable visibly) | Oxidised LDL may cause damage to endothelium

Monoclonal hypothesis (Benditt and Benditt)

Smooth muscle cell proliferation = crucial monoclonal plaques - benign tumours? viral causes

Process of atherosclerosis

Thrombosis Lipid accumulation Production of intercellular matrix Interactions between cell types

Cells involved in atherosclerosis

``` Endothelial cells Platelets Smooth muscle cells Macrophages Lymphocytes & Neutrophils ```

Endothelial cells roll in atehrosclerosis

Haemostasis Altered permeability to lipoproteins Produce collagen Stimulate proliferation and migration of SMC (EGF)

Platelet role in atherosclerosis

Haemostasis | Stimulate proliferation and migration of SMC (PDGF)

Smooth muscle cells role in atherosclerosis

Take up LDL and lipid Become foam cells Synthesise collagen and proteoglycans

Macrophages role in atherosclerosis

Oxidise LDL Become foam cells (engulf lipid) Secrete proteases = modify matrix Stimulate proliferation and migration of SMC

Lymphocytes role in atherosclerosis

Produce TNF Affect lipoprotein metabolism Stimulate proliferation and migration of SMC

Neutrophils role in atherosclerosis

Secrete proteases = local damage and inflammation

Unified hypothesis

Endothelial damage Effects of injury SMC stimulated and produce matrix

Why does endothetlial damage occur?

Raised LDL Toxins (smoking) Hypertension haemodynamic stress

What does endothelial injury cause?

Platelet adhesion ``` PDGF release = SMC proliferation and migration Accumulation of lipid LDL oxidation (lipid uptake by macrophages and SMC) ``` Migration of monocytes to intima

What do foam cells do?

Secrete cytokines = further SMC stimulation recruitment of other inflammatory cells

Prevention of atherosclerosis

``` No smoking Treat hypertension/diabetes mellitus Not too much alcohol Regular exercise/weight control Lipid lowering drugs ```

What can arteriosclerosis result in?

- Poor perfusion - Inelastic/weak vessels (leading to aneurysm) - Increased risk of thrombus formation

Atherosclerosis Flashcards

(50 cards)