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ESA 2- Mechanisms of Disease > Atheroma > Flashcards

Flashcards in Atheroma Deck (98):
1

What is an atheroma?

An accumulation of intracellular and extracellular lipid in the intima and media or large and medium sized arteries

2

Where do atheromas happen?

On the inside of the arteries, and spreads through the wall

3

Where is the fat deposited in an atheroma?

Can be on outside and inside wall

4

What is atherosclerosis?

The thickening and hardening of arterial walls as a consequence of atheoma

5

What is arteriosclerosis?

The thickening of walls of arteries and arterioles, usually as a result of hypertension or diabetes mellitus

6

What are the three macroscopic stages of an atheroma?

The fatty streak 
The simple plaque 
The complicated plaque

7

What causes the fatty streak?

Lipid deposits in the intima

8

How does the fatty streak appear macroscopically?

Yellow and slightly raised

9

What is the relationship between the fatty streak and atheroma?

Somewhat debatable- generally regarded as the precursor, but some people disagree

10

Why do some people dispute that the fatty streak is the precursor to atheroma?

Fatty streak may be seen in populations that don’t progress to atherosclerosis. 
Some discussion about anatomical position of fatty streak compared to atherosclerosis

11

How does the simple plaque appear macroscopically?

Raised yellow/white, with an irregular outline

12

What happens as simple plaques develop?

They enlarge and coalesce, eventually becoming complicated

13

What occurs when a complicated plaque has formed?

Thrombosis

14

Why do complicated plaques lead to thrombosis?

Because the plaque has an irregular surface, which disrupts flow

15

What can happen to a complicated plaque?

It may rupture 
Can be haemorrhage into plaque 
Calcification 
Aneurysm formation

16

What happens when a complicated plaque ruptures?

It releases substances that cause thrombosis

17

What are the common sites of atheroma?

Aorta, especially abdominal 
Coronary arteries 
Carotid arteries 
Cerebral arteries
Leg arteries

18

What do early changes in atheroma include?

Proliferation of smooth muscle cells
Accumulation of foam cells and extracellular lipid, either in or between cells
The matrix of the cell may be substantially changed from normal

19

What do later changes in atheroma include?

Fibrosis
Necrosis 
May be inflammatory cells 
Cholesterol clefts

20

What are cholesterol clefts?

Where cholesterol crystals are laid down, there are needle shaped crystals of cholesterol that are soluble, so when solvents are used they are dissolved, leaving clefts

21

What is the eventual result of atheroma?

Disruption of the internal elastic lamina, with damage that extends into the media. 
Ingrowth of blood vessels 
Plaque fissuring

22

Why is there an ingrowth of blood vessels in atheroma?

Because whenever there is damage/inflammation, there is always a vascular response

23

What is plaque fissuring?

When the inside can move relative to the outside

24

What is the problem with plaque fissuring?

It allows for the release of materials that cause thrombosis

25

What are the clinical effects of atheroma?

Ischaemic heart disease 
Cerebral ischaemia 
Mesenteric ischaemia 
Peripheral vascular disease

26

What is ischaemic heart disease?

The process of atheroma reducing flow of blood with or without thrombotic occlusion of arteries

27

What can ischaemic heart disease lead to?

Sudden death 
Myocardial infarction 
Angina pectoris 
Arrhythmias 
Cardiac failure

28

Why does ischaemic heart disease cause cardiac failure?

Causes scarring of the heart so it can’t function properly

29

What may be seen in cardiac failure caused by ischaemic heart disease?

Swollen arteries, scarring

30

What is cerebral ischaemia a result of?

Atherosclerosis in cerebral or carotid vessels

31

What can cerebral ischaemia lead to?

Transient ischaemic attack 
Cerebral infarction (stroke)
Multi-infarct dementia 
Can undergo secondary haemorrhages 
Abdominal aortic aneurysm

32

When may someone undergo secondary cerebral haemorrhages?

Where dying tissues start to degenerate

33

How does mesenteric ischaemia often present?

Rectal bleeding
Maybe abdominal pain

34

What can mesenteric ischaemia lead to?

Ischaemic colitis 
Malabsorption 
Intestinal infarction

35

What is an acute intestinal infarction more likely to be caused by?

Thrombus or embolus

36

Where are intenstinal infarctions most common?

In superior mesenteric artery

37

What is peripheral vascular disease?

Atherosclerosis affecting vessels supplying the legs

38

What can peripheral vascular disease lead to?

Intermittent claudication 
Leriche syndrome 
Ischaemic rest pain 
Gangrene

39

What is intermittent claudication?

Pain in legs because of reduced blood supply

40

What happens to claudication distance as time goes on?

It gets shorter

41

What is meant by claudication distance?

How long can walk for before gets too painful

42

What is Leriche syndrome?

Buttock claudication

43

What is Leriche syndrome often associated with?

Impotence

44

What is ischaemic rest pain?

When muscles hurt even when not exercising

45

What causes gangrene?

No oxygen supply to tissue

46

Why is gangrene problematic when amputating?

Needs to heal, but that increases oxygen demand, causing further gangrene, so need amputation stump in good, healthy tissue

47

How can the clinical affect of peripheral vascular disease be delayed?

The development of a collateral channel

48

What are the risk factors for atheroma?

Age 
Gender 
Hyperlipidaemia 
Cigarette smoking
Hypertension
Diabetes mellitus 
Alcohol 
Infection 
Lack of exercise
Obesity 
Soft water
Oral contraceptive
Stress and personality type

49

How does age affect the risk of atheroma?

The older you are, the more likely you are to have it, until you get to right at the top of the age range (because people living that long are likely not to have atheroma, or they wouldn’t have lived that long)

50

Why does risk of atheroma increase with age?

Because risk factors operative over years, building up

51

How does gender affect the risk of atheroma?

Men are at a high risk than women, until the menopause where women catch up

52

How is hyperlipidaemia associated with atheroma?

High plasma cholesterol associated with atheroma

53

How do the different types of cholesterol impact on the risk of atheroma?

LDL most significant risk of the types
HDL protecting

54

What happens to the risk of atheroma after giving up smoking?

It falls

55

Why does cigarette smoking increase the risk of atheroma?

Mode of action uncertain, but possible causes are- 
Changes to coagulation system 
Reduced PGI2
Increased platelet aggregation

56

What is strongly linked to high systolic/diastolic BP?

IHD

57

Why does hypertension cause IHD?

Mechanism uncertain, but could be due to endothelial damage caused by raised pressure

58

By how much does diabetes mellitus increase the risk of atheroma?

Doubles it

59

Why does diabetes mellitus increase the risk of atheroma?

Protective effect in premenopausal women lost
Could be related to hyperlipidaemia and hypertension

60

What else is diabetes mellitus associated with high risk of?

Cerebrovascular and peripheral vascular disease

61

How much alcohol is associated with high risk of atheroma?

>5 units a day

62

What other risk factors is alcohol associated with?

Smoking
High BP

63

What effect can small amount of alcohol have on risk of atheroma?

Can be protecting

64

How is lipid carried in the blood?

On lipoproteins

65

What do lipoproteins carry?

Cholesterol and triglycerides

66

What do lipoproteins consist of?

Hydrophobic lipid core
Hydrophilic outer layer of phospholipid and apolipoprotein (A-E)

67

What do chylomicrons do?

Transport lipid from intestine to liver

68

What do VLDL do?

Carry cholesterol and TG from liver, and TG is removed leaving LDL

69

What is LDL rich in?

Cholesterol

70

What do LDLs do?

Carry cholesterol to non-liver cells

71

What do HDLs do?

Carry cholesterol from periphery back to liver

72

What are genetic variations in ApoE associated with?

Changes in LDL levels

73

What do polymorphisms of genes involved in lipid metabolism lead to?

At least 6 ApoE phenotypes

74

How can polymorphisms of genes involved in lipid metabolisms be used?

As risk markers for atheromas

75

What is familial hyperlipidaemia?

Genetically determined abnormalities of lipoproteins

76

What does familial hyperlipidaemia lead to?

Early development of atheroma

77

What are the associated physical signs of familial hyperlipidaemia?

Arcus
Tendon xanthomas
Xanthelasma

78

What is a corneal arcus?

A ring around the iris due to lipid

79

What is an xanthalasma?

A small accumulate of fat in skin and subcutaneous tissue

80

What could genetic predisposition to atheroma be due to?

Variations in apolipoprotein metabolism 
Variations in apolipoprotein receptors

81

What are the theories of pathogenesis of atheroma?

Thrombogenic theroy 
Insudation theory 
Reaction to injury hypothesis 
Monoclonal hypothesis

82

What is thrombogenic theory?

Plaques formed by repeated thrombi. Lipid derived from
thrombi. Overlying fibrous cap.

83

What is insudation theory?

Endothelial injury. Inflammation. Increased
permeability to lipid from plasma

84

What is the reaction to injury hypothesis?

Plaques form in response to endothelial injury.
Hypercholesterolemia leads to endothelial damage in experimental animals.
Injury increases permeability and allows platelet adhesion. Monocytes penetrate
endothelium. Smooth muscle cells proliferate and migrate.


Amended to say that endothelial injury may be very
subtle and undetectable visually and that LDL, especially oxidised, may damage
endothelium

85

What is the monoclonal hypothesis?

Crucial role for smooth muscle proliferation. Each
plaque is monoclonal. Might represent abnormal growth control. Each plaque
could be benign tumour, or atheroma could have viral aetiology.

86

What processes are involved in atheroma?

Thrombosis 
Lipid accumulation 
Production of intercellular matrix
Interactions between cell types

87

What cells are involved in atheroma?

Endothelial cells 
Platelets
Smooth muscle cells 
Macrophages 
Lymphocytes
Neutrophils

88

What is the role of endothelial cells in atheroma?

Key role in haemostasis 
Alter their permeability to lipoproteins 
Produce collagen 
Stimulate proliferation and migration of smooth muscle cells

89

What is the role of platelets in atheroma?

Key role in haemostasis 
Stimulate proliferation and migration of smooth muscle cells

90

How do platelets stimulate the proliferation and migration of smooth muscle cells?

Using PDGF

91

What is the role of smooth muscle cells in atheroma?

Take up LDL and other lipids to become foam cells
Synthesis collagen and other proteoglycans

92

What is the role of macrophages in atheroma?

Oxidise LDL
Secrete proteases
Stimulate proliferation and migration of smooth muscle cells

93

What do the proteases secreted by macrophages do?

Modify the matrix

94

What is the role of lymphocytes in atheroma?

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

95

What is the role of neutrophils in atheroma?

Secrete proteases leading to continued local damage and inflammation

96

What is the unified atheroma hypothesis?

Endothelial injury occurs due to-
Raised LDL
Toxins, e.g. cigarette smoke
Hypertension
Haemodynamic stress

Endothelial injury causes-
Platelet adhesion
PDGF release
Smooth muscle proliferation and migration
Insudation of lipid
LDL oxidation
Uptake of lipid by smooth muscle cells and macrophages
Migration of monocytes into intima

Stimulated smooth muscle cells produce matrix material, and foam cells secrete cytokines, causing further smooth muscle stimulation and recruitment of inflammatory cells

97

How can atheroma be prevented?

No smoking
Reduce fat intake
Treat hypertension 
Reduce alcohol intake
Regular exercise 
Weight control

98

What interventions can be made to help with atheroma?

Stop smoking 
Modify diet 
Treat hypertension 
Treat diabetes 
Lipid lowering drugs