S6) Atherosclerosis Flashcards

1
Q

What is an atheroma?

A

Atheroma is the accumulation of intracellular and extracellular lipid in the intima and media of large and medium sized arteries

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2
Q

What is atherosclerosis?

A

Atherosclerosis is the thickening and hardening of arterial walls as a consequence of an atheroma

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3
Q

What is arteriosclerosis?

A

Arteriosclerosis is the thickening and hardening of arteries and arterioles due to conditions such as hypertension and diabetes mellitus

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4
Q

Identify three macroscopic features of atherosclerosis

A
  • The fatty streak
  • The simple plaque
  • The complicated plaque
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5
Q

Describe the appearance of the fatty streak

A
  • Lipid deposits in intima
  • Yellow, slightly raised
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6
Q

Describe the appearance of the simple plaque

A
  • Raised yellow/white
  • Irregular outline
  • Widely distributed
  • Enlarged and coalesce
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7
Q

Describe the appearance of the complicated plaque

A
  • Thrombosis
  • Haemorrhage into plaque
  • Calcification
  • Aneurysm formation
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8
Q

Identify five common sites for atherosclerosis

A
  • Aorta (especially abdominal)
  • Coronary arteries
  • Carotid arteries
  • Cerebral arteries
  • Leg arteries
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9
Q

Describe normal arterial structure

A
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10
Q

Describe the microscopic appearance of the early changes in atherosclerosis

A
  • Proliferation of smooth muscle cells
  • Accumulation of foam cells
  • Extracellular lipid deposition
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11
Q

Describe the microscopic appearance of the later changes in atherosclerosis

A
  • Fibrosis & necrosis
  • Cholesterol clefts
  • Disruption of internal elastic lamina
  • Ingrowth of blood vessels
  • Plaque fissuring (could lead to thrombosis)
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12
Q

Identify 5 clinical effects of atherosclerosis

A
  • Ischaemic Heart Disease
  • Cerebral ischaemia
  • Mesenteric ischaemia
  • Peripheral vascular disease
  • Abdominal Aortic Aneurysm
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13
Q

Identify 5 complications of Ischaemic Heart Disease due to severe atherosclerosis in the heart

A
  • Sudden death
  • Myocardial infarction
  • Angina pectoris
  • Arrhythmias
  • Cardiac failure
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14
Q

Identify 3 complications of cerebral ischaemia due to severe atherosclerosis in the brain

A
  • Transient ischaemic attack
  • Cerebral infarction (stroke)
  • Multi-infarct dementia
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15
Q

Identify 3 complications of mesenteric ischemia due to severe atherosclerosis in the colon

A
  • Ischaemic colitis
  • Malabsorption
  • Intestinal infarction
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16
Q

Identify 3 complications of peripheral vascular disease due to severe atherosclerosis in the peripheries

A
  • Intermittent claudication
  • Ischaemic rest pain
  • Gangrene
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17
Q

What are the possible reasons for the genetic predisposition to atherosclerosis?

A
  • Variations in apolipoprotein metabolism
  • Variations in apolipoprotein receptors
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18
Q

Identify four theories / hypotheses explaining the pathogenesis of atherosclerosis

A
  • Thrombogenic theory
  • Insudation theory
  • Monoclonal hypothesis
  • Reaction to injury hypothesis
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19
Q

How does the thrombogenic / encrustation hypothesis explain the possible mechanisms of atherogenesis?

A
  • Plaques formed by repeated thrombi
  • Lipid derived from thrombi
  • Overlying fibrous cap
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20
Q

How does the insudation hypothesis explain the possible mechanisms of atherogenesis?

A
  • Endothelial injury
  • Inflammation
  • Increased permeability to lipid from plasma
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21
Q

How does the monoclonal hypothesis explain the possible mechanisms of atherogenesis?

A
  • Crucial role for smooth muscle proliferation
  • Each plaque is monoclonal
  • Might represent abnormal growth control
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22
Q

How does the reaction to injury hypothesis explain the possible mechanisms of atherogenesis?

A
  • Endothelial injury may be very subtle and be undetectable visually
  • LDL, especially oxidised, may damage endothelium
23
Q

Identify the four processes involved in atherogenesis

A
  • Thrombosis
  • Lipid accumulation
  • Production of intercellular matrix
  • Interaction between cell types
24
Q

Identify the six cells involved in atherogenesis

A
  • Endothelial cells
  • Platelets
  • Smooth muscle cells
  • Macrophages
  • Lymphocytes
  • Neutrophils
25
Q

Describe the role of endothelial cells in atherogenesis

A
  • Altered permeability to lipoproteins
  • Production of collagen
  • Stimulation of proliferation and migration of smooth muscle cells
26
Q

Describe the role of platelets in atherogenesis

A

Stimulate proliferation and migration of smooth muscle cells (PDGF)

27
Q

Describe the role of smooth muscle cells in atherogenesis

A
  • Take up LDL and other lipid to become foam cells
  • Synthesis collagen and proteoglycans
28
Q

Describe the role of macrophages in atherogenesis

A
  • Oxidise LDL
  • Take up lipids to become foam cells
  • Secrete proteases which modify matrix
  • Stimulate proliferation and migration of smooth muscle cells
29
Q

Describe the role of lymphocytes in atherogenesis

A
  • TNF may affect lipoprotein metabolism
  • Stimulate proliferation and migration of smooth muscle cells
30
Q

Describe the role of neutrophils in atherogenesis

A

Secrete proteases leading to continued local damage and inflammation

31
Q

Outline the Unifying Hypothesis 1

A

Endothelial injury occurs due to:

  • Raised LDL
  • Toxins e.g. cigarette smoke
  • Hypertension
  • Haemodynamic stress
32
Q

Outline the Unifying Hypothesis 2

A

Endothelial injury causes:

  • Platelet adhesion, PDGF release, SMC proliferation and migration
  • Insudation of lipid, LDL oxidation, uptake of lipid by SMC and macrophages
  • Migration of monocytes into intima
33
Q

Outline the Unifying Hypothesis 3

A
  • Stimulated SMC produce matrix material
  • Foam cells secrete cytokines causing further SMC stimulation and the recruitment of other inflammatory cells
34
Q

Identify 10 risk factors for atherosclerosis

A
  • Diabetes Mellitus
  • Infection
  • Smoking
  • Hypertension
  • Hyperlipidaemia
  • Gender
  • Age
  • Familial hyperlipidaemia
  • Alcohol consumption
  • Apolipoproteins E genotype

Mnemonic: DISHH GAFAA

35
Q

Discuss the epidemiology of atherosclerosis in light of Diabetes Mellitus

A
  • DM also associated with high risk of IHD, cerebrovascular and peripheral vascular disease
  • DM is related to hyperlipidaemia and hypertension
36
Q

Which infections increase the likelihood of atherosclerosis?

A
  • Chlamydia pneumoniae
  • Helicobacter pylori
  • Cytomegalovirus
37
Q

Discuss the epidemiology of atherosclerosis, in light of smoking

A
  • Powerful risk factor for IHD
  • Mode of action uncertain – coagulation system, reduced PGI2, increased platelet aggregation
38
Q

Discuss the epidemiology of atherosclerosis, in light of hypertension

A
  • Strong link with IHD
  • Mechanism uncertain – endothelial damage caused by raised pressure
39
Q

Discuss the epidemiology of atherosclerosis, in light of hyperlipidaemia

A

High plasma cholesterol associated with atherosclerosis:

  • LDL most significant
  • HDL is protective
40
Q

Discuss the epidemiology of atherosclerosis, in light of gender

A

Women protected relatively before menopause (resumed hormonal basis)

41
Q

Discuss the epidemiology of atherosclerosis, in light of age

A
  • Slowly progressive throughout adult life
  • Risk factors operate over years
42
Q

Discuss the epidemiology of atherosclerosis, in light of familial hyperlipidaemia

A

Genetically determined abnormalities of lipoproteins leads to early development of atherosclerosis

43
Q

Discuss the epidemiology of atherosclerosis, in light of alcohol consumption

A
  • >5 units /day associated with increased risk of IHD
  • Often associated with other risk factors e.g. smoking and high BP
44
Q

Discuss the epidemiology of atherosclerosis, in light of apolipoproteins E genotype

A
  • Genetic variations in Apo E are associated with changes in LDL levels
  • Polymorphisms of the genes involved lead to at least 6 Apo E phenotypes and can be used as risk markers for atherosclerosis
45
Q

How can atherosclerosis be prevented?

A
  • Sensible alcohol intake
  • Regular exercise and control of weight
  • Reduce fat intake
  • Treat hypertension
  • No smoking
46
Q

Identify the steps that can be taken for disease intervention in atherosclerosis

A
  • Stop smoking
  • Treat hypertension
  • Treat diabetes mellitus
  • Lipid lowering drugs where needed
47
Q

What is a transient ischaemic attack?

A
  • A TIA (aka “mini stroke”) is a brief episode of neurological dysfunction caused by a temporary disruption in cerebral blood flow (ischaemia without infarction)
  • It presents with sudden symptoms similar to a stroke e.g. speech and visual disturbance, and numbness or weakness in the face, arms and legs
48
Q

What is a stroke?

A

A stroke is a rapid onset of cerebral deficit (usually focal) lasting more than 24 hours or leading to death, with no cause apparent other than a vascular one

49
Q

What is an ischaemic stroke?

A

An ischaemic stroke is a stroke secondary to a reduction or cessation of blood flow to a localised area of brain due to arterial occlusion or hypoperfusion

50
Q

Describe four causes of an ischaemic stroke

A
  • Embolisation from a distant source
  • In situ thrombus on an atherosclerotic plaque
  • Inflammation of blood vessels (infectious/non-infectious vasculitis)
  • Hypoperfusion i.e. severe hypotension
51
Q

Where might the embolus have come from in an ischaemic stroke?

A
  • Cardiac mural thrombi (MI & AF)
  • Thromboemboli from carotid arteries, aortic arch or vertebral arteries
  • Calcific material / vegetations from heart valves
  • Fragments of atrial myxoma
52
Q

What is a haemorrhagic stroke?

A

A haemorrhagic stroke is a stroke secondary to bursting of a blood vessel, often seen in hypertension

53
Q

What is a berry aneurysm?

A
  • A berry aneurysm is a common form of intracranial aneurysm which is congenital or secondary to blood vessel injury (not atherosclerosis)
  • They commonly occur within the circle of Willis and the adjacent arteries and thus, blood accumulates in the subarachnoid space