Pathology - Atherosclerosis

Question 1

What is atherosclerosis?

Answer 1

The accumulation of intracellular and extracellular lipid in the intima and media of large/medium arteries leading to thickening and hardening of arterial walls

Question 2

What is arteriosclerosis?

Answer 2

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

Question 3

What is the same given to a yellow, slightly raised lipid deposit in the lumen of an artery?

Answer 3

Fatty streak

Question 4

How does a simple plaque appear in the lumen?

Answer 4

Raised yellow/white, irregular outline, widely distributed, can enlarge and coalesce

Question 5

Why is a complicated plaque more dangerous than a simple plaque?

Answer 5

• can lead to thrombosis
• can lead to haemorrhage into plaque
• can lead to calcification of arteries
• may cause aneurysm formation

Question 6

Give some common sites of atherosclerosis

Answer 6

Aorta (especially abdominal), coronary arteries, carotid arteries, cerebral arteries, leg arteries

Question 7

What are the EALRY microscopic features of atherosclerosis?

Answer 7

Proliferation of smooth muscle cells, accumulation of foam cells, extracellular lipid

Question 8

What are the ADVANCED microscopic features of atherosclerosis?

Answer 8

Fibrosis, necrosis, cholesterol clefts, inflammatory cells, disruption of internal elastic lamina, damage extends into media, ingrowth of blood vessels, plaque fissuring

Question 9

Give some clinical effects of atherosclerosis which relate to ischaemic heart disease

Answer 9

Ischaemic heart disease:

• sudden death
• myocardial infarction
• angina pectoris
• arrhyhmias
• cardiac failure

Question 10

Give some clinical effects of atherosclerosis which relate to cerebral ischaemia

Answer 10

• transient ischaemic attack
• cerebral infarction
• multi-infarct dementia

Question 11

Give some effects of atherosclerosis which relate to mesenteric ischaemia

Answer 11

Ischaemic colitis, malabsorption, intestinal infarction

Question 12

Give some clinical effects of atherosclerosis which relate to peripheral vascular disease

Answer 12

• intermittent claudication
• Leriche syndrome
• ischaemic rest pain
• gangrene

Question 13

Give some pre-disposing factors for atherosclerosis

Answer 13

• age (risk increases as get older)
• gender (women protected before menopause)
• hyperlipidaemia (high plasma cholesterol associated with atherosclerosis)
• cigarette smoking
• hypertension (possibly due to endothelial damage caused by raised pressure)
• diabetes mellitus
• alcohol
• infection (chlamydia pneumoniae, H. Pylori, cytomegalovirus)
• lack of exercise/obesity
• soft water
• oral contraceptives
• stress (uncertain)

Question 14

How is atherosclerosis associated with apolipoprotein E?

Answer 14

• genetic variations in Apo E are associated with changes in LDL levels
• polymorphisms of these genes can be used as risk markers for atherosclerosis

Question 15

Give some physical signs of familial hyperlipidaemia

Answer 15

• corneal arcus
• tendon xanthomas
• xanthelasma

Question 16

What was the thrombogenic theory of atherosclerosis?

Answer 16

Plaques formed by repeated thrombi, lipid is derived from these. Overlying fibrous cap forms

Question 17

What was the insulation theory of atherosclerosis?

Answer 17

Endothelial injury leads to inflammation and increased permeability to lipid from plasma

Question 18

What is the reaction to injury hypothesis of atherosclerosis?

Answer 18

• plaques form in response to endothelial injury
• injury increases permeability and allows platelet adhesion
• monocytes penetrate endothelium
• smooth muscle cells proliferate there and migrate

Question 19

What is the monoclonal hypothesis of plaque formation?

Answer 19

Each plaque is monoclonal, so they may represent abnormal growth control - could be a benign tumour

Question 20

Which cell types are involved in atherosclerosis?

Answer 20

• endothelial cells
• platelets
• smooth muscle cells
• macrophages
• lymphocytes
• neutrophils

Question 21

What is the role of endothelial cells in atherosclerosis?

Answer 21

• altered permeability to lipoproteins
• production of collagen
• stimulation of proliferation/migration of smooth muscle cells

Question 22

What is the role of platelets in atherosclerosis?

Answer 22

Stimulate proliferation and migration of smooth muscle cells

Question 23

What is the role of smooth muscle cells in atherosclerosis?

Answer 23

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

Question 24

What are the roles of macrophages in atherosclerosis?

Answer 24

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

Question 25

What are the roles of lymphocytes in atherosclerosis?

Answer 25

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

Question 26

What is the role of neutrophils in atherosclerosis?

Answer 26

Secrete proteases leading to continued local damage and inflammation

Question 27

What methods can be used to help prevent atherosclerosis?

Answer 27

- no smoking - reduce fat intake - treat hypertension - not too much alcohol - regular exercise/weight control

Question 28

What interventions can be used to help prevent a high risk individual from developing atherosclerosis?

Answer 28

- stop smoking - modify diet - treat hypertension - treat diabetes - lipid lowering drugs

Question 29

What is the unifying hypothesis of atherosclerosis?

Answer 29

Endothelial injury (due to raised LDL, toxins, hypertension, haemodynamic stress) causes platelet adhesion, PDGF release, SMC proliferation/migration, migration of monocytes into intima and a few other events. Stimulated SMC produce matrix material. Foam cells secrete cytokines causing further SMC stimulation and recruitment of other inflammatory cells