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ESA 2- Mechanisms of Disease > Atheroma > Flashcards

Atheroma Flashcards

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1
Q

What is an atheroma?

A

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

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2
Q

Where do atheromas happen?

A

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

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3
Q

Where is the fat deposited in an atheroma?

A

Can be on outside and inside wall

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4
Q

What is atherosclerosis?

A

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

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5
Q

What is arteriosclerosis?

A

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

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6
Q

What are the three macroscopic stages of an atheroma?

A

The fatty streak
The simple plaque
The complicated plaque

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7
Q

What causes the fatty streak?

A

Lipid deposits in the intima

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8
Q

How does the fatty streak appear macroscopically?

A

Yellow and slightly raised

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9
Q

What is the relationship between the fatty streak and atheroma?

A

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

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10
Q

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

A

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

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11
Q

How does the simple plaque appear macroscopically?

A

Raised yellow/white, with an irregular outline

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12
Q

What happens as simple plaques develop?

A

They enlarge and coalesce, eventually becoming complicated

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13
Q

What occurs when a complicated plaque has formed?

A

Thrombosis

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14
Q

Why do complicated plaques lead to thrombosis?

A

Because the plaque has an irregular surface, which disrupts flow

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15
Q

What can happen to a complicated plaque?

A

It may rupture
Can be haemorrhage into plaque
Calcification
Aneurysm formation

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16
Q

What happens when a complicated plaque ruptures?

A

It releases substances that cause thrombosis

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17
Q

What are the common sites of atheroma?

A 
Aorta, especially abdominal
 Coronary arteries
 Carotid arteries
 Cerebral arteries
 Leg arteries
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18
Q

What do early changes in atheroma include?

A

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

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19
Q

What do later changes in atheroma include?

A

Fibrosis
Necrosis
May be inflammatory cells
Cholesterol clefts

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20
Q

What are cholesterol clefts?

A

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

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21
Q

What is the eventual result of atheroma?

A

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

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22
Q

Why is there an ingrowth of blood vessels in atheroma?

A

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

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23
Q

What is plaque fissuring?

A

When the inside can move relative to the outside

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24
Q

What is the problem with plaque fissuring?

A

It allows for the release of materials that cause thrombosis

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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 ```

ESA 2- Mechanisms of Disease (11 decks)

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