Athlerosclerosis Flashcards

(44 cards)

1
Q

Define atherosclerosis

A

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

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

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

Define arteriosclerosis

A

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

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

What are the macroscopic features of atherosclerosis?

A

Fatty streak

Simple plaque

Complicated plaque

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

What is a fatty streak?

A

Lipid deposits in intima

Yellow, slightly raised

Relationship to atherosclerosis somewhat debatable but, seen as precursors for it.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

What is a simple plaque?

A

raised yellow / white

Irregular outline

Widely distribute

Enlarge and coalesce

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

What is a complicated plaque?

A

Thrombosis

Haemorrhage into plaque

Calcification - Can see on x-rays

Aneurysm formation - expansion of artery

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

What are some common sites of atherosclerosis?

A
  • Aorta - particularly abdominal (renal and could go into iliac)
  • Coronary arteries
  • Carotid arteries
  • Cerebral arteries
  • Leg arteries
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

What is normal arterial structure?

A
  • Endothelium
  • Sub-endothelial CT
  • Internal elastic lamina (closer to heart, more elastic and muscle)
  • Muscular media
  • External elastic lamina
  • Adventitia
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

Microscopic features of atherosclerosis (early changes)

A

Early changes:

  • Proliferation of smooth muscle cells
  • Accumulation of foam cells
  • Extracellular lipid
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

Microscopic features of atherosclerosis (later changes)

A

Later changes:

  • Fibrosis
  • Necrosis
  • Cholesterol clefts - where cholesterol was
  • +/- inflammatory cells
  • Disruption of internal elastic lamina
  • Damage extends into media
  • Ingrowth of blood vessels - leaky, can lead to haemorrhage
  • Plaque fissuring
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

What are the clinical effects of atherosclerosis?

A
  • Ischaemic heart disease
  • Sudden death
  • Myocardial infarction
  • Angina pectoris (chest pain on exertion - goes away when rested)
  • Arrhythmias
  • Cardiac failure - due to fibrosis.
  • Manifest as shortness of breath and pulmonary oedema.
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

What are the clinical effects of athlerosclerosis in the brain?

A

Cerebral ischaemia

  • Transient ischaemic attach (TIA - mini stroke as resolve in 24hrs)
  • Cerebral infarction (stroke) - thrombus in cerebral artery or thromboembolus
  • Multi-infarct dementia
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

Clinical effects of atherosclerosis of the bowel

A

Mesenteric ischaemia

  • Ischaemic colitis
  • Malabsorption
  • Intestinal infarction
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

What are the clinical effects of peripheral vascular disease?

A
  • Arms are rare so usually legs
  • Intermittent claudication - distance can walk before pain in calf.
  • Leriche syndrome (blockage of abdominal aorta as it goes to common iliac arteries.)
  • Ischaemic rest pain - when worse
  • Gangrene - once tissue has infarcted.
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

Why do people get athleroscleosis?

A
  • Age - slowly progressive throughout adult life. Risk factors operate over years
  • Gender - males more affected than females as women are protected relatively before menopause. There is a presumed hormonal basis
  • Hyperlipidaemia
  • Cigarette smoking
  • Hypertension
  • Diabetes mellitus
  • Alcohol
  • Infection
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

Why does hyperlipidaemia cause athlerosclerosis?

A
  • High plasma cholesterol associated with athlerosclerosis
  • LDL most significant
  • HDL protective
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

Lipid metabolism

A
  • Lipid in the blood is carried on lipoproteins
  • Lipoproteins carry cholestrol and triglycerides (TG)
  • Hydrophobic lipid core
  • Hydrophilic outer later of phospholipid and apolipoprotein (A-E)
  • Chylomicrons - Transport lipid from intestine to liver
  • LDL - Rich in cholestrol and carries to choletrol to non-liver cells.
  • VLDL - Carry cholestrol and TG to liver. TG removed leaving LDL.
  • HDL - Carry cholestrol from periphery back to liver
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

Apolipoprotein E

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.
  • Polymorphisms can be used as risk markers for atherosclerosis
19
Q

Familial Hyperlipidaemia

A

Genetically determined abnormalities of lipoproteins

Lead to early development of atherosclerosis

Associated physical signs:

  • Arcus (A thin, whitish circle around the iris; normal finding in old people.)
  • Tendon xanthoma (deposits of cholestrol)
  • xanthelasma (depositions of cholestrol)
20
Q

How does cigarette smoking cause atherosclerosis?

A
  • Don’t know - effect coagulation system, reduced Prostaglanin I2, Incresed platelet aggregation.
  • Powerful risk factor for IHD
  • Risk falls after giving up.
21
Q

Hypertension and atherosclerosis

A
  • Strong link between IHD and high systolic / diastolic BP
  • Mechanism uncertain
  • Maybe endothelial damage caused by raised pressure.
22
Q

Atherosclerosis and diabetes Mellitus

A
  • DM doubles IHD risk.
  • Protective effect in premenopausal women lost
  • DM also associated with high risk of carebrovascular and peripheral vascular disease
  • It is maybe related to hylerlipidaemia?
23
Q

Atherosclerosis - Alcohol Consumption

A

Over 5 units per day is associated with increased risk of IHD

Alcohol consumption after associated with other risk factors e.g. smoking and high BP but still an independent risk factor.

Smaller amounts of alcohol may be protective.

24
Q

Atherosclerosis-Infection

A
  • Chlamydia pneumoniae
  • Helicobacter pylori
  • Cyromegalovirus

All look at but no hard evidence.

25
Atherosclerosis - Other Risk Factors
* Lack of exercise * Obesity * Soft water * Oral contraceptives * Stress and personality type?
26
Atherosclerosis - Genetic Predisposition
Familial predisposition well known Possibly due to: * variations in apolipoprotein metabolism * variations in apolipoprotein receptors
27
What are the theories as to how atherosclerosis develops?
* Thrombogenic theory * Isudation theory - Movement from lumen into the wall * Monoclonal hypothesis * Reaction to injury hypothesis
28
The thrombogenic theory of atherosclerosis
Though that plagues formed by repeated thrombi. Lipids derived from thrombi Overlying fibrous cap.
29
Insudation theory of atherosclerosis
Endothelial injury causes inflammation. This makes the vessel leaky and allows lipid from the plasma into wall and develop.
30
Reaction to injury hypothesis
Plaques form in response to endothelial injury Hypercholestrolaemia leads to endothelial damage in experimental animals Injury increases permeability and allows platelet adhesion. Monocytes penetrate endothelium Smooth muscle cells proliferate and migrate. Endothelial injury may be very subtle and be undetectable visually. LDL, especially oxidised, may damage endothelium.
31
The monoclonal hypothesis
Aside, not widely accepted Crucial role for smooth muscle proliferation Each plaque is monoclonal Might represent abnormal growth control
32
What are the stages of atherosclerosis?
Thrombosis Lipid accumulation Production of intercellular matrix Interactions between cell types
33
What cells are involved in atherosclerosis?
Endothelial cells Platelets Smooth muscle cells (become foam cells) Macrophages Lymphocytes Neutrophils
34
Endothelial cells in Atherosclerosis
Key role in haemostasis Altered permeability to lipoproteins Production of collagen Stimulation of proliferation and migration of smooth muscle cells.
35
Platelets in atherosclerosis
Key role in haemostasis Stimulate proliferation and migration of smooth muscle cells (PDGF - platelet derived growth factor)
36
Smooth muscle cells in atherosclerosis
Take up LDL and other lipid to become foam cells Synthesise collagen and proteoglycans
37
Macrophages in atherosclerosis
Oxidise LDL Take up lipids to become foam cells Secrete proteases which modify matrix Stimulate proliferation and migration of smooth muscle cells.
38
Lymphocytes in atherosclerosis
TNF May affect lipoprotein metabolism. Stimulate proliferation and migration of smooth muscle cells.
39
Neutrophils in atherosclerosis
Secrete proteases leading to continued local damage and inflammation
40
What causes endothelial injury?
Endothelial injury due to: Raised LDL ‘Toxins; e.g. cigarette smoke. Hypertension Haemodynamic stress
41
What are the consequences of endothelial injury?
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
42
What are final things cause atherosclerosis?
Stimulated SMC (smooth muscle cells) produce matrix material Foam cells secrete cytokines causing: * Further SMC stimulation * Recruitment of other inflammatory cells
43
How do you prevent atherosclerosis?
No smoking Reduce fat intake (ish.. not matter too much if good fat metabolism) Treat hypertension Not too much alcohol Regular exercise / weight control BUT, some people will still develop atherosclerosis!
44
What interventions can reduce the risk of atherosclerosis?
* Stop smoking * Modify diet * Treat hypertension * Treat diabetes * Lipid lowering drugs