MoD Session 6 Flashcards
0
Q
What is atherosclerosis?
A
Thickening and hardening of arterial walls as a consequence of atheroma
1
Q
What is atheroma?
A
Accumulation of intracellular and extracellular lipid in the intima and media of large and medium sized arteries
2
Q
What is arteriosclerosis?
A
Thickening of the walls of arteries and arterioles usually from hypertension or DM
3
Q
Is atherosclerosis or arteriosclerosis the same as atheroma?
A
Atherosclerosis
4
Q
What is the normal arterial structure?
A
Endothelium Subendothelial connective tissue Internal elastic lamina Muscular media External elastic lamina Adventitia
5
Q
How does the muscular media change as you move to arteries closer to the heart?
A
More elastin and less smooth muscle
6
Q
What is the fatty streak in atheroma?
A
Lipid deposits in the intima which give rise to a yellow, slightly raised tissue
7
Q
Why is the relationship of the fatty streak not direct to the atheroma?
A
Location of lesions in intima is not identical to the most severe atherosclerosis
8
Q
What is the simple plaque in atheroma formation?
A
Individual lesions enlarge and coalesce to form widely distributed, irregularly outlined, raised yellow/white tissue
9
Q
What is the complicated plaque in atheroma formation?
A
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
Q
Where are common sites of atheroma?
A
Leg arteries Aorta - below superior mesenteric and above renal arteries Coronary arteries Carotid arteries Cerebral arteries
11
Q
What does the severity of atheroma depend on?
A
Anatomical site
12
Q
What are the three early microscopic features of atheroma?
A
Proliferation of smooth muscle cells
Accumulation of foam cells
Extracellular lipid
13
Q
What are the later microscopic features of atheroma?
A
Fibrosis Necrosis Cholesterol clefts from crystals \+/- inflammatory cells Disruption of internal elastic lamina Damage through to media Ingrowth of BV Plaque fissuring
14
Q
What leads to haemorrhage of plaque and subsequent occlusion of the artery?
A
Ingrowth of BV
15
Q
How do cholesterol clefts appear histiologically?
A
As gaps as cholesterol dissolves during fixation
16
Q
What is the structure of atheroma?
A
Endothelium
Smooth muscle cell
Lipid
Matrix
17
Q
What is present in variable amounts in different atheromas?
A
Lipid - some hardly have any
18
Q
What happens over time to an atheroma?
A
Matures by fibrosis
Replaces smooth muscle
19
Q
What are the possible clinical effects of atheroma?
A
Ischaemic heart disease Cerebral ischaemia Mesenteric ischaemia Peripheral vascular disease Abdominal aortic aneurysm
20
Q
Name some consequences of ischaemic heart disease.
A
Sudden death Myocardial infarction Angina pectoris Arrhythmias Cardiac failure
21
Q
How is an old MI seen in the heart?
A
Pale tissue in heart wall
22
Q
How does atheroma cause cerebral ischaemia?
A
Atheroma in carotid arteries causes turbulent flow –> thrombus –> embolism –> trapped in cerebral arteries
23
Q
What are the sequelae of cerebral ischaemia?
A
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
