Pathophysiology of Atheroma

Question 1

What is an atheroma also known as?

Answer 1

atherosclerosis

Question 2

What is an atheroma?

Answer 2

Formation of plaques in the intima of large and medium-sized arteries.

Question 3

What does atheroma lead to when the lumen of arteries is narrowed?

Answer 3

ischaemia

Question 4

What is a serious consequence from myocardial ischaemia due to atheroma?

Answer 4

angina

Question 5

What is myocardial ischaemia complicated by?

Answer 5

thromboembolism

Question 6

What is arteriosclerosis? (3)

What is it not? (1)

Answer 6

It is not the same as an atheroma.

It is an aged related change in muscular arteries. It presents with:

• smooth muscle hypertrophy
• reduplication of internal elastic laminae
• intimal fibrosis

These all lead to a decrease in diameter size.

Question 7

What sorts of ischaemia can be caused by arteriosclerosis?

4

Answer 7

• cardiac
• cerebral
• colonic
• renal

Question 8

When does arteriosclerosis become clinically apparent?

4

Answer 8

When CVS is further stressed by:

• haemorrhage
• major surgery
• infection
• shock

Question 9

What is the earliest lesion present in atheroma?

2

Answer 9

• a fatty streak

- yellow linear elevation of lipid-laden macrophages

Question 10

In what group of patients are fatty streaks found (earliest significant lesion of atheroma)?

Are they clinically significant?

Answer 10

young children

No - they may go away.

Question 11

What is the stage of atheroma prior to fully developed atheromatous plaque i.e. following initial fatty streak development?

(1)

Answer 11

• Early atheromatous plaque

Question 12

In what group of patients are early atheromatous plaques found?

Answer 12

young adults

Question 13

What are the characteristics of an early atheromatous plaque?

(2)

Answer 13

• smooth yellow patches in intima

- lipid-laden macrophages

Question 14

Describe the composition of a fully developed artheromatous plaque.

(3)

Answer 14

• Central lipid core
• fibrous tissue cap
• covered by arterial endothelium

Question 15

What does collagen in the fibrous cap of an atheromatous cap do?

What produces the collagen?

Answer 15

• provides structural strength to the structure

- smooth muscle

Question 16

Which inflammatory cells reside in the fibrous cap of a fully developed atheromatous plaque?

(3)

Answer 16

macrophages
T-lymphocytes
mast cells

Question 17

What is the core of an atheromatous plaque made from?

2

Answer 17

• cellular lipids

- debris from macrophages (died in plaque)

Question 18

What is often found around the rim of the atheromatous plaque?

Answer 18

foamy macrophages, due to uptake of lipoproteins by scavenger receptors

Question 19

What often forms in late development of artheromatous plaques?

Answer 19

dystrophic calcification

Question 20

Where are atheromatous plaques most likely to form?

What is specific about these places?

Answer 20

• at arterial branching points/bifurcations

- turbulent blood flow

Question 21

What are some features of complicated atheroma?

3

Answer 21

• haemorrhage into plaque = calcification

- plaque rupture/fissuring - thrombosis

Question 22

What is the most important risk factor form atheroma?

Answer 22

hypercholesterolaemia

Question 23

What is the congenital abnormality that can cause primary lipidaemia?

Answer 23

• lack of cell membrane receptors for LDL
• carriers affected (heterozygous)
• homozygous individuals affected more severely.

Question 24

What happens to patients homozygous for this type mutation?

3

Answer 24

• much less functional membrane receptors for LDL.
• very high cholesterol levels in the blood
• coronary artery atheroma in infancy/teens
• death

Question 25

What is the familial form of hyperlipidaemia called?

Answer 25

primary hyperlipidaemia

Question 26

What is the acquired form of hyperlipidaemia called?

Answer 26

secondary (idiopathic)

Question 27

What are some signs of major hyperlipidaemia? | 4

Answer 27

- premature corneal arcus - tendon xanthomata - xanthelasmata - FH of MI/atheroma

Question 28

What is corneal arcus?

Answer 28

an opaque ring forms around the margin of the cornea (common in elderly).

Question 29

What is tendon xanthomata? Where is it usually found?

Answer 29

- deposits of fat/foamy macrophages in the tendons | - usually of the knuckles and achilles

Question 30

What is xanthelasmata? Where is it usually found?

Answer 30

- cholesterol deposits under the skin | - usually around eyelids

Question 31

What are the main risk factors for atheroma i.e. for same cholesterol levels? (6)

Answer 31

``` Smoking Hypertension Diabetes mellitus Male Elderly ``` or of course increased cholesterol/lipid levels.

Question 32

What are less strong risk factors for atheroma? | 5

Answer 32

- obesity - sedentary lifestyle - low socioeconomic background - low birthweight - role of microorganisms

Question 33

What are the two main steps in the development of atheromatous plaques?`

Answer 33

1. injury to endothelial lining 2. chronic inflammation and healing response of vascular wall to agent causing injury This process repeated leads to atheromatous plaque development.

Question 34

Describe in detail the development of atheromatous plaques? | 8

Answer 34

1. Endothelial injury 2. LDL accumulates to vessel wall 3. Monocyte adhesion to endothelium → foamy macrophages in intima 4. Platelet adhesion 5. Platelet factor release 6. smooth muscle cell recruitment and proliferation 7. extracellular matrix production and T-cell recruitment 8. Lipid accumulation (extracellular and in foamy macrophages)

Question 35

What are some common causes of endothelial disturbance that can cause atheroma?

Answer 35

- haemodynamic disturbances (turbulent blood flow) | - hypercholesterolaemia

Question 36

How does hypercholesterolaemia cause endothelial damage?

Answer 36

increases local production of reactive oxygen species

Question 37

How does hypercholesterolaemia cause atheromatous plaques? | 4

Answer 37

1. lipoproteins (LDL) aggregate in intima 2. LDL modified by freeradicals produced by inflammatory cells 3. modified LDL taken up by macrophages = foamy macrophages 4. these are toxic to endothelial cells plus release growth factors (cytokines).

Question 38

How are injured endothelial cells functionally altered to bring about atheroma? (3)

Answer 38

- increased cell adhesion molecules (e.g. ICAM-1) - increased permeability for LDL - increased thrombogenicity

Question 39

___________ cells + ______ in the _______ layer = ________

Answer 39

inflammatory lipids intima plaques

Question 40

Describe the formation of an advanced atheromatous plaque. | 3

Answer 40

1. lipid-laden macrophages die through apoptosis = debris in lipid core. 2. inflammatory response. 3. smooth muscle proliferation, synthesis of collage, elastin and mucopolysaccharide = fibrous cap around lipid core.

Question 41

What is PDGF?

Answer 41

a group of molecules/ growth factors released from platelets.

Question 42

How do established plaques grow in volume? | 2

Answer 42

1. endothelial loss 2. microthrombi formed at denuded areas of plaque surface (smooth muscle proliferation and collagen deposition). 3. cycle repeats

Question 43

What is the main symptom of ileal, femoral or popilteal artery stenosis?

Answer 43

intermittent claudication

Question 44

What causes stable angina?

Answer 44

stenosed atheromatous coronary artery, small obstruction

Question 45

What is unstable angina? What causes unstable angina?

Answer 45

Ischaemic pain at rest. very severe stenosed atheromatous coronary artery

Question 46

What does long standing tissue ischaemia cause?

Answer 46

atrophy of the affected organ

Question 47

What are the major complications of atheroma? | 2

Answer 47

Acute atherothrombotic occlusion - rupture of plaque - total occlusion of artery

Question 48

What occurs when a plaque ruptures? | 2

Answer 48

- highly thrombotic contents released into blood | - activation of coagulation cascade and thrombotic occlusion in very short time.

Question 49

What happens when there is a total occlusion of an artery?

Answer 49

- irreversible ischaemia | - necrosis of tissue (infarct)

Question 50

The total occlusion of a coronary artery leads to what?

Answer 50

MI

Question 51

What causes a stroke?

Answer 51

total occlusion of the carotid or cerebral artery

Question 52

Total occlusion of ileal, femoral or popliteal arteries lead to what?

Answer 52

lower limb gangrene

Question 53

What can be a cause of small infarcts in organs distal to an atheromatous plaque?

Answer 53

small thrombus fragments can emolise and block smaller arteries when the large original plaque ruptures

Question 54

What can small emboli from atheromatous plaques cause if the block a coronary artery branch?

Answer 54

small foci of necrosis which can cause life-threatening arrhythmias

Question 55

What can debris from a carotid artery atheromatous plaque cause?

Answer 55

stroke, TIA, cerebral infarct

Question 56

What can happen when an atheromatous plaque slowly extends in to the media of the aorta and weakens it?

Answer 56

an aneurysm or sudden rupture causing retroperitoneal haemorrhage.

Question 57

What are the features of atheromatous plaques that give them a high risk of having thrombotic complications? (3)

Answer 57

- thin fibrous cap - large lipid core - prominent inflammation

Question 58

What are the approaches to prevent atheromatous plaques from forming? (5)

Answer 58

``` smoking cessation blood pressure control weight loss regular exercise dietary modifications ```

Question 59

What are the some general drugs used to prevent atheromatous plaques? (2)

Answer 59

1. Cholesterol lowering drugs | 2. Aspirin (inhibits platelet aggregation to decrease risk of thrombosis on established atheromatous plaques)