Atheroma Flashcards Preview

Mechanisms of Disease > Atheroma > Flashcards

Flashcards in Atheroma Deck (14):
1

What is an atheroma

An atheroma is the accumulation of intracellular and extracellular lipid in the media and intima of large and medium sized arteries. Atherosclerosis is the thickening and hardening of the walls as a result of atheroma. Arteriosclerosis is the thickening of the walls of smaller arteries due to hypertension and diabetes Mellitus.

2

What are the 3 stages of an atheroma?

1. The fatty streak – lipid deposits in the intima, they are pale yellow in colour and slightly raised however the relationship between these and atheroma is somewhat debatable
2. Simple plaque – much more raised, yellow/white in colour, widely distributed and have irregular outlines and slowly merge together
3. Complicated plaque – thrombosis appears, haemorrhage into the plaque and calcification begins (may show up in x-ray) – may result in aneurysm

3

What arteries most commonly have atheroma formation?

Most common arteries for atheroma are the aorta especially the abdominal, coronary, carotid, cerebral and leg arteries.

4

Describe the microscopical changes seen in atheroma formation

Microscopically the early changes seen are the proliferation of smooth muscle cells and accumulation of foam cells and extracellular lipid. Later on we get fibrosis, necrosis and formation of cholesterol clefts and either the presence or absence of inflammatory cells. We also get disruption of internal elastic lamina (effecting compliance) which extends to the media and the ingrowth of blood vessels and finally the plaque may fissure into the lumen.

5

What effect does atheroma formation have?

• Ischaemic heart diseases such as – myocardial infarction, angina pectoris, arrhythmias, cardiac failure and sudden death
• Cerebral ischaemia - transient ischaemic attack, cerebral infarction (stroke) and multi-infarct dementia
• Mesenteric ischaemia – ischaemic colitis, malabsorption and intestinal infarction
• Peripheral vascular disease – intermittent claudication, leriche syndrome, ischaemic rest pain and gangrene

6

What causes aneurysms to form?

Aneurysms form when the walls of the artery become weakened and as a result bulges out due to the high pressure. Because this creates abnormal flow and abnormal vessel wall this leads to thrombus formation inside the vessel.

7

Describe some atheroma risk factors

• Age – although small plateau at top
• Gender – men more than woman until menopause
• Hyperlipidaemia – LDL most significant i.e LDL receptor mutations and polymorphisms of the apolipoprotein E leads to genetic markers i.e. familial hyperlipidaemia – corneal arcus, tendon xanthomas and xanthelasmas
• Cigarette smoking – mode of action uncertain but effects the coagulation system, reduced PG12 and increase platelet aggregation
• Hypertension
• Diabetes Mellitus – doubles IHD risk, related to hyperlipidaemia and hypertension
• Alcohol – often associated with other risk factors such as smoking but smaller amounts of alcohol may be protective
• Infection – potentially a link with certain bacteria such as chlamydia pneumoniae, helicobacter pylori and cytomegalovirus

lack of exercise, obesity, soft water, oral contraceptive, and stress/personality type.

8

Describe the role of Endothelial cells in atheroma formation

Endothelial cells – have a key role in haemostasis, altered permeability to lipoproteins and the production of collagen and stimulation of proliferation and migration of smooth muscle cells

9

Describe the role of plaetlet cells in atheroma formation

Platelets – key role in haemostasis and stimulate proliferation of migration of smooth muscle cells (PDGF)

10

Describe the role of smooth muscle cells in atheroma formation

Smooth muscle cells – take up LDL and other lipids to become foam cells and synthesise collage and proteoglycans both of which are present in excess in atheroma

11

Describe the role of Macrophages cells in atheroma formation

Macrophages – oxidise LDL, take up lipids to become foam cells, secrete proteases which modify matrix and stimulate the proliferation and migration of smooth muscle cells

12

Describe the role of Lymphocytes in atheroma formation

Lymphocytes – TNF may affect lipoprotein metabolism and they stimulate proliferation and migration of smooth muscle cells

13

Describe the role of 6. Neutrophils in atheroma formation

Neutrophils – secrete proteases leading to continued local damage and inflammation

14

What is the unifying hypothesis for atheroma formation?

• Endothelial injury due to raised LDL, toxins (e.g. cigarette smoke) hypertension and haemodynamic stress
• This damage causes platelet adhesion PDGF release, SMC proliferation and migration, accumulation of lipid, LDL oxidation and uptake of lipid by SMC and macrophages
• Stimulated SMC produce matrix material, foam cells secrete cytokines causing further SMC stimulation and recruitment of other inflammatory cells