MoD S6 - Atherosclerosis

Question 1

What is an atheroma?

Answer 1

Accumulation of intracellular and extracellular lipid in the intima and media of large to medium sized arteries

Question 2

Outline the differences between atherosclerosis and arteriosclerosis

Answer 2

Atherosclerosis is the thickening and hardening of arterial walls as a consequence of atheroma whereas arteriosclerosis is the thickening of walls of arteries and arterioles due to hypertension and diabetes mellitus

Question 3

Outline the events leading to the formation of atherosclerotic lesions

Answer 3

• Chronic endothelial injury
• Endothelial dysfunction with platelet adhesion and monocyte accumulation
• Release of cytokines and growth factors
• Smooth muscle emigration from tunica media to intima
• Macrophages and smooth muscle cells engulf lipids to form foam cells
• Smooth muscle proliferation, collagen and matrix deposition

Question 4

What are the three different macroscopic appearances of atherosclerosis?

Answer 4

Fatty streaks, simple plaque and complicated plaque

Question 5

Describe the differences in appearance of fatty streak, simple and complicated plaque

Answer 5

Fatty streak - yellow lipid deposits in intima, raised

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

Complicated - Thrombosis, haemorrhage, calcification, aneurysm formation

Question 6

What are the early microscopic changes seen in atherosclerosis?

Answer 6

• Proliferation of smooth muscle
• Accumulation of foam cells
• Extracellular lipid

Question 7

List some possible consequences of ischaemic heart disease

Answer 7

Sudden death, MI, angina pectoris, arrhythmias, cardiac failure

Question 8

List some possible consequences of cerebral ischaemia

Answer 8

Transient ischaemic attacks, cerebral infarction, Multi‐infarct dementia

Question 9

What are the later microscopic changes seen in atherosclerosis?

Answer 9

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

Question 10

How does multi‐infarct dementia differ from Alzheimer’s?

Answer 10

Due to vascular problems opposed to neurological

Question 11

List some possible consequences of mesenteric ischaemia

Answer 11

Ischaemic colitis, malabsorption, intestinal infarction

Question 12

How would a patient with peripheral vascular disease present and how may this progress if left untreated?

Answer 12

Intermittent claudication

Develops into gangrene

Question 13

How does intermittent claudication differ from Leriche syndrome?

Answer 13

IC‐ pain in the calf muscles

LS‐ pain in buttocks, may also present with impotence

Question 14

How can abdominal aortic aneurysm result in death?

Answer 14

Ruptures causing haemorrhage resulting in hypovolemic shock

Question 15

What are the potential genetic risk factors for atherosclerosis?

Answer 15

Apolipoprotein E genotype, familial hyperlipidaemia

Question 16

Outline the main concepts involved in the insudation theory?

Answer 16

Endothelial injury occurs causing inflammation and subsequent increased permeability to lipid from the plasma

Question 17

What is the monoclonal hypothesis? (Benditt and Benditt)

Answer 17

Smooth muscle cells proliferate and each plaque that forms is monoclonal

Example of abnormal growth control

Each plaque is a benign tumour

Question 18

What possible aetiology for atherogenesis does the monoclonal hypothesis lead to?

Answer 18

Possible viral link

Question 19

List the main cells involved in atherogenesis and their roles

Answer 19

Endothelial‐ haemostasis, altered permeability to lipoproteins, secretion of collagen, stimulation of proliferation and migration of SMC

Macrophages‐ oxidise LDL, take up lipids and become foam cells, secrete proteases which modify extracellular matrix, stimulate proliferation and migration of SMC

Platelets‐ haemostasis, stimulate proliferation and migration of SMC

Lymphocytes‐ TNF interferes with lipid metabolism, stimulation of proliferation and migration of SMC

Neutrophils‐ secrete proteases leading to continued local damage and inflammation

SMC‐ take up LDL to make foam cells, synthesise collagen and proteoglycans

Question 20

Outline the main concepts of the Reaction to Injury Hypothesis (Aka insudation)

Answer 20

• Plaque forms due to endothelial injury
• Hyperlipidaemia causes endothelial damage
• Results in increased permeability to lipid and platelet aggregation
• Monocytes migrate in and form foam cells
• SMC migrate and proliferate

Question 21

What later additions were made to the Reaction to Injury hypothesis?

Answer 21

Endothelial damage may be subtle and hard to see, oxidised LDL may be responsible for endothelial damage

Question 22

Outline the unifying hypothesis and what theories contribute to this one overall hypothesis

Answer 22

Thrombogenic theory, insudation theory, monoclonal hypothesis and response to injury hypothesis

Endothelial injury occurs due to:
● toxins, hypertension, raised LDL, haemodynamic stress

Endothelial injury then results in:
● platelet aggregation, PDGF production, SMC migration and proliferation
● Insudation of lipids, oxidation of LDL, foam cells form from SMC and macrophages
● Migration of monocytes into intima

Stimulated SMC produced intercellular matrix

Foam cells secrete cytokines causing:
● further SMC stimulation, recruitment of other inflammatory cells

Question 23

What interventions would be used in atherosclerosis?

Answer 23

Stop smoking, modify diet, lipid lowering drugs, treat hypertension, treat diabetes

Question 24

Why is cigarette smoking a risk factor for atheroma?

Answer 24

Increased risk of IHD

Believed to be due to coagulation system (decreased PGI2, increased platelet aggregation)

Question 25

How is diabetes mellitus a risk factor for atheroma formation?

Answer 25

Link to IHD, increased risk of cerebrovascular and peripheral vascular damage, related to hyperlipidaemia and hypertension

Question 26

List the possible infections that result in atheroma

Answer 26

Chlamydia, helicobacter pylori, cytomegalovirus