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Flashcards in MoD Session 6 Deck (137):
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What is atheroma?

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

1

What is atherosclerosis?

Thickening and hardening of arterial walls as a consequence of atheroma

2

What is arteriosclerosis?

Thickening of the walls of arteries and arterioles usually from hypertension or DM

3

Is atherosclerosis or arteriosclerosis the same as atheroma?

Atherosclerosis

4

What is the normal arterial structure?

Endothelium
Subendothelial connective tissue
Internal elastic lamina
Muscular media
External elastic lamina
Adventitia

5

How does the muscular media change as you move to arteries closer to the heart?

More elastin and less smooth muscle

6

What is the fatty streak in atheroma?

Lipid deposits in the intima which give rise to a yellow, slightly raised tissue

7

Why is the relationship of the fatty streak not direct to the atheroma?

Location of lesions in intima is not identical to the most severe atherosclerosis

8

What is the simple plaque in atheroma formation?

Individual lesions enlarge and coalesce to form widely distributed, irregularly outlined, raised yellow/white tissue

9

What is the complicated plaque in atheroma formation?

Haemorrhage into the thrombotic plaque by invading BV from the adventitia can cause it to rupture
Calcification of the plaque can further stiffen arterial walls
Aneurysm forms if there is a loss of elastic tissue

10

Where are common sites of atheroma?

Leg arteries
Aorta - below superior mesenteric and above renal arteries
Coronary arteries
Carotid arteries
Cerebral arteries

11

What does the severity of atheroma depend on?

Anatomical site

12

What are the three early microscopic features of atheroma?

Proliferation of smooth muscle cells
Accumulation of foam cells
Extracellular lipid

13

What are the later microscopic features of atheroma?

Fibrosis
Necrosis
Cholesterol clefts from crystals
+/- inflammatory cells
Disruption of internal elastic lamina
Damage through to media
Ingrowth of BV
Plaque fissuring

14

What leads to haemorrhage of plaque and subsequent occlusion of the artery?

Ingrowth of BV

15

How do cholesterol clefts appear histiologically?

As gaps as cholesterol dissolves during fixation

16

What is the structure of atheroma?

Endothelium
Smooth muscle cell
Lipid
Matrix

17

What is present in variable amounts in different atheromas?

Lipid - some hardly have any

18

What happens over time to an atheroma?

Matures by fibrosis
Replaces smooth muscle

19

What are the possible clinical effects of atheroma?

Ischaemic heart disease
Cerebral ischaemia
Mesenteric ischaemia
Peripheral vascular disease
Abdominal aortic aneurysm

20

Name some consequences of ischaemic heart disease.

Sudden death
Myocardial infarction
Angina pectoris
Arrhythmias
Cardiac failure

21

How is an old MI seen in the heart?

Pale tissue in heart wall

22

How does atheroma cause cerebral ischaemia?

Atheroma in carotid arteries causes turbulent flow --> thrombus --> embolism --> trapped in cerebral arteries

23

What are the sequelae of cerebral ischaemia?

Transient ischaemic attack
Cerebral infarction
Multi infarct dementia

24

What can be a further complication of cerebral infarction?

Can haemorrhage causing extra damage to tissues which is visible

25

Which artery is mesenteric ischaemia particularly seen in?

Superior mesenteric

26

What can mesenteric ischaemia cause?

Ischaemic colitis
Malabsorption
Intestinal infarction

27

Why is mesenteric ischaemia hard to recover in the elderly which is where it is most commonly seen?

Due to loss of GI function

28

Can the superior mesenteric artery be removed if it has become ischaemic?

Yes if BP is normal, no if BP is high

29

What is intermittent claudication?

Pain in calf upon exercise due to relative ischaemia which is relieved by rest but has a decreased claudication distance after

30

What is intermittent claudication a type of?

Peripheral vascular disease

31

What develops after intermittent claudication in the peripheral vascular disease pathway?

Ischaemic rest pain

32

What I s the final stage in the pathway of peripheral vascular disease?

Gangrene

33

What is Leriche syndrome?

Relative ischaemia in the iliac artery

34

What are the S/S of Leriche syndrome?

Pain in buttock
Impotence
Decreased/absent femoral pulse

35

What happens to the collateral vessels in Leriche syndrome?

They increase in number to maintain oxygen supply

36

How does atheroma lead to abdominal aortic aneurysm?

Atheroma causes loss of elastic tissue --> abnormal BV wall and flow --> thrombus

37

When does an abdominal aortic aneurysm rupture?

When the wall stretches and is not thick enough to support the increased diameter of the aorta

38

What can increase the risk of atheroma formation?

Oral contraceptives
Age
Gender
Infection
Hyperlipidaemia
Cigarette smoking
Hypertension
DM
Obesity
Alcohol
Stress and personality type
Lack of exercise
Soft water

39

Which gender has the higher risk of atheroma formation?

Male up until menopause

40

Which three pathogens have been linked with an increase in risk of atheroma formation?

Chlamydia pneumoniae
Helicobacter pylori
Cytomegalovirus

41

Which lipid is most significant in the risk of atheroma formation?

LDL

42

What is the suggested method by which cigarette smoking increases risk of atheroma formation?

Decreases prostaglandin 2 levels
Increases platelet aggregation
Causes hypercoaguable blood

43

What is a powerful risk factor for IHD?

Cigarette smoking

44

How may hypertension increase risk of atheroma formation?

Causes endothelial damage from high pressure

45

By how much does having DM increase the risk of IHD?

2x

46

What is lost in premenopausal women with DMD?

Protective effect against atheroma formation

47

Why are all sizes of BV compromised in DM?

Small vessels are compromised by arteriosclerosis

48

Other than IHD, what else does DM increase the risk of?

Cerebro-vascular disease
Peripheral vascular disease

49

How many units of alcohol per day increases IHD risk?

>5 units per day

50

What effect can small amounts of alcohol have on the pathogenesis of atheroma formation?

May be protective

51

How is lipid transported in the blood?

On lipoproteins

52

What do lipoproteins carry?

Cholesterol
TAGs

53

What is the structure of a lipoprotein?

Hydrophilic outer phospholipid layer and apolipoprotein (A-E) layer

54

What is the function of chylomicrons?

Transport lipid from intestine to liver

55

What is the function of LDL?

Rich in cholesterol to carry it to non-liver cells

56

What is the function of VLDL?

Carry cholesterol and TAGs from liver so TAGs can be removed to leave LDL behind

57

What is the function of HDL?

Carry cholesterol from periphery back to liver

58

Genetic variations on what are associated with changes in LDL levels?

Apo E

59

What allows there to be at least 6 Apo E phenotypes possible?

Polymorphisms of the genes involved

60

What can be used as risk markers for atheroma?

Polymorphisms of Apo E genes

61

What causes familial predisposition to atheroma?

Variations in apolipoprotein metabolism and/or receptors

62

What is familial hyperlipidaemia?

Genetically determined abnormalities of lipoproteins leading to early development of atheroma

63

How do the relative consequences for heterozygotes and homozygotes in familial hyperlipidaemia compare?

Heterozygotes are less severely affected
Homozygotes often have MI before 25 y.o.

64

What are visible signs of familial hyperlipidaemia?

Corneal arcus
Xanthelasma
Xanthomas

65

What forms xanthomas?

Foamy macrophages sitting in the dermis, especially on tendons

66

What are the four possible mechanisms for atheroma formation?

Thrombogenic/encrustation theory
Insudation theory
Reaction to injury hypothesis
Monoclonal hypothesis

67

How are atheroma formed in the thrombogenic/encrustation theory?

Plaques are formed by repeated thrombi and lipid from the thrombi forms an overlying fibrous cap

68

How is atheroma formed by the insudation theory?

Endothelial injury causes inflammation which increases permeability of lipid through intima from plasma

69

What are the two mechanisms proposed by the reaction to injury hypothesis in atheroma formation?

Hypercholesteroleamia causes endothelial injury stimulating platelet adhesion and increased permeability so plaque forms whilst monocytes penetrate endothelium causing smooth muscle cells to proliferate and migrate
LDL, especially oxidised causes visually undetectable endothelial injury

70

What is the monoclonal hypothesis in atheroma formation?

Smooth muscle proliferation --> monoclonal tumour (plaque)

71

What questions can be raised about the monoclonal tumour formed in the monoclonal hypothesis of atheroma formation?

Benign?
Abnormal growth control?
Viral aetiology?

72

What processes are involved in atheroma?

Thrombosis
Lipid accumulation in lesions
Production of abnormal ECM (fibrosis)
Interactions b/w cell types

73

What cells may interact at different stages of atheroma?

Neutrophils
Lymphocytes
Macrophages
Smooth muscle
Platelets
Endothelial cells

74

What do neutrophils do during atheroma?

Secrete proteases causing continued local damage and inflammation

75

What do lymphocytes do during atheroma?

Secrete TNF which may affect lipoprotein metabolism
Stimulate proliferation and migration of smooth muscle cells

76

What do macrophages do during atheroma?

Oxidise LDL
Take up lipid to form foam cells
Secrete proteases which modify matrix
Stimulate proliferation and migration of smooth muscle

77

What do smooth muscle cells do in atheroma?

Take up LDL and other lipids to form foam cells
Synthesise collagen and proteoglycans

78

What do platelets do in atheroma?

Haemostasis
PDGF stimulates proliferation and migration of smooth muscle cells

79

What do endothelial cells do in atheroma?

Haemostasis
Altered permeability to lipoproteins
Secrete collagen
Stimulate proliferation and migration of smooth muscle cells

80

What is the unifying hypothesis for atheroma formation?

Endothelial injury leads to:
Platelet adhesion
PDGF release
Smooth muscle cell proliferation, migration and production of matrix
Insudation of lipid by smooth muscle cells and macrophages

81

What are the possible causes of endothelial injury in the unifying hypothesis of atheroma formation?

High LDL levels
Toxins e.g. cigarette smoke
Hypertension
Haemodynamic stress which varies in different areas of circulation

82

What may macrophages possibly do in the unifying hypothesis of atheroma formation?

LDL oxidation

83

What do the cytokines secreted by foam cells in the unifying hypothesis of atheroma formation do?

Cause further smooth muscle cell stimulation
Recruit other inflammatory cells

84

Where do monocytes migrate to in the unifying hypothesis of atheroma formation?

Intima

85

What can be done to try and prevent atheroma formation?

Not too much alcohol
No smoking
Lower fat intake
Control weight w/regular exercise
Treat hypertension

86

What interventions are used after a clinical event caused by atheroma?

Statins to decrease lipid levels
Stop smoking
Modify diet
Treat hypertension
Treat diabetes

87

Is atherosclerosis seen in veins?

Nope

88

What percentage of lumen occlusion is required to significantly affect flow through an artery?

70-80%

89

Which three diseases cause decrease in arterial elasticity thus causing arteriosclerosis?

Atherosclerosis
Arteriolosclerosis
Monkeberg's disease

90

Which arteries does atherosclerosis affect?

Medium and large sized

91

How does atherosclerosis progress?

Begins in intima producing plaques filled with necrotic gruel-like material

92

What is arteriolosclerosis?

Hardening of the arterioles affecting the small arteries

93

Describe the connection b/w arteriolosclerosis and atherosclerosis.

Little or none

94

What is arteriolosclerosis usually secondary to?

Severe hypertension

95

Which arterioles does arteriolosclerosis particularly affect?

Those of the kidney

96

What is Monkeberg's disease?

Uncommon calcification of the media of large arteries

97

What is the approximate diameter of the basic lesion (plaque) seen in atherosclerosis?

1 cm

98

What causes the endothelium to bulge in the pathogenesis of atherosclerosis?

Crowded foam cells

99

What happens in the final stage in the pathogenesis of atherosclerosis?

Necrosis in the plaque followed by development of cholesterol crystals, calcification and vascularisation from the adventitia

100

What is the key event in the pathogenesis of atherosclerosis?

Focal accumulation of look and cells beneath the endothelium forming a raised, flat plaque 1-2 mm thick

101

Where can plaque formation in atherosclerosis be a major obstacle to flow?

Coronary arteries

102

How long does the process of plaque formation in atherosclerosis in humans take?

Many years

103

What favours lipid deposition and plaque formation?

Areas of disturbed flow

104

How can a plaque in atheroma formation become ulcerated?

Fibrous cap eroded from underneath exposing core

105

What can cause spasm at the site of a plaque?

Thrombi releasing vasoconstrictors

106

What can happen if the exposed atheroma in a plaque complication breaks up?

It can shed atheromatous emboli

107

What can develop in and around a plaque making the artery even stiffer?

Calcification

108

What plaque complication is seen in cerebral arteries and is especially associated with hypertension?

Rupture of the atherosclerotic artery and bleeding secondary to weakening of the medial layer

109

What are dilatations in veins called?

Varices

110

What is a saccular aneurysm?

Weakening of an artery wall shaped like a sac

111

What can prevent the bursting of a saccular aneurysm?

Lining/filling by thrombus

112

What diameter can saccular aneurysms reach in the aorta?

10-15 cm

113

What are fusiform anuerysms?

Aneurysms shaped like a spindle

114

How do dissecting aneurysms occur?

Inner layer of arterial wall tears open --> blood enters tear --> media separates into two layers --> blood sometimes reenters lumen through second tear

115

Where do dissecting aneurysms occur?

Virtually only in aorta and its major branches

116

What is the survival of dissecting anuerysms like?

Rare

117

At what point does atherosclerosis stop being a totally silent disease?

Symptoms secondary to plaque comic actions arise

118

How do macrophages cause oxidation of LDL?

Produce toxic oxygen species

119

What stage of the morphological appearance of atheroma is seen in children?

Fatty streaks

120

In which type of arteries are atherosclerotic plaques seen?

Elastic
Medium and large sized muscular

121

What range of diameter do atheromatous plaques occupy?

0.3-1.5 cm

122

Where do symptoms of severe atherosclerosis usually occur?

Heart
Brain
Kidney
Legs

123

How do statins reduce risk of atheroma formation?

Inhibit HMG CoA reductase which is required for cholesterol biosynthesis in the liver

124

Why is premature vascular disease seen in homocystinuria?

Due to high levels of circulating homocysteine

125

Why can low folate or vitamin B intake cause premature vascular disease?

Causes raised levels of homocysteine

126

How can geography be linked to atheroma development?

Ubiquitous among developed nations
Lower incidence in South America, Africa and Asia
Migrants who immigrate to high risk locations and adopt new lifestyles and diet have same risk as the new location

127

How can genetic variations causing higher levels of angiotensin converting enzyme be a risk marker for atheroma formation?

Higher levels result in hypertension

128

What is the difference between primary and secondary prevention in atherosclerosis?

Primary = in people who have never had complications
Secondary = in people who have had events

129

What interventions can be used in atherosclerosis?

Lipid lowering drugs
Aspirin prophylaxis
Thrombolysis
Angioplasty
Stents
CABG
Control of arrhythmias

130

What level of anti-oxidant intake should be avoided to decrease risk of atherosclerosis?

Low

131

What is found in vegetable and seed oils, soya beans, saffron, sunflower, cereal and nuts which has a possible protective role?

Vitamin E (antioxidant)

132

What oils should be used for cooking to decrease the risk of a high atherosclerosis-risk patient?

Monounsaturated (olive) and polyunsaturated (sunflower, soya)

133

Which foods can be avoided to reduce dietary cholesterol?

Liver
Offal
Fish roes

134

What type of sugar should be consumed to reduce atherosclerosis risk?

Unrefined not simple

135

Which foods high in soluble fibre reduce circulating lipid?

Pulses
Legumes
Root/leafy vegetables
Unprocessed cereals

136

What produces secondary hyperlipidaemia?

Excess alcohol intake