Atherosclerosis

Question 1

What is atherosclerosis ?

Answer 1

Gruel; hardness to elastic and medium-large arteries

Question 2

What is an atheroma ?

Answer 2

Intimal fibrous cap
Central core rich in lipids

Question 3

Clinical Significance of Atherosclerosis

Answer 3

IN 2016 - atherosclerosis was related to the top 2 causes of death

Although death rates from heart and circulatory diseases have fallen and plateoud from 1969 to 2017.

Question 4

Describe features of symptomatic atherosclerosis

Answer 4

Contributes to 1/2 of all deaths (western world)

Question 5

State some clinical conditions linked to atherosclerosis

Answer 5

MI
Stroke
Aneurysm
Peripheral Vascular Disease

Question 6

How has the peak of deaths from atherosclerosis reduced from 1963 to the 2000’s ?

Answer 6

Improved methods of treatment
Prevention of recurrences
Prevention of atherosclerosis

50% decreased death rate heart attack
70% decreased death rate stroke

Question 7

Risk Factors for atherosclerosis

Answer 7

Age
Sex
Genetics
Hyperlipidaemia
Hypertension
Smoking
Diabetes Mellitus

Question 8

Hyperlipidaemia

Answer 8

Elevated concentrations of lipids/fats in the blood. (LDL)

One of the most prevalent risk factors contributing to the evolution of atherosclerosis.

Question 9

What does hyperlipidaemia cause ?

Answer 9

Impairs endothelial function
Accumulates within intima
Causes oxidative modification of LDL

Question 10

Describe oxidative modification of LDL

Answer 10

Inhibits the motility of macrophages

Stimulates the release of cytokines

Cytotoxic to endothelial and smooth muscle cells

Chemotactic centre for monocytes

Question 11

State the stages of atherosclerosis

Answer 11

Initiation/ Formation Stage (subclinical)
Adaptation stage (subclinical)
Clinical Stage

Question 12

How is atherosclerosis developed ?

Answer 12

Chronic endothelial injury/ dysfunction
Role of Lipids -
Role of macrophages
Smooth muscle proliferation
Formation of a fibro-lipid plaque
Injury to the plaque - thrombus formation

Question 13

Describe chronic endothelial injury / dysfunction risk factors

Answer 13

Haemodynamic disturbances
Hypercholesterolemia
Hypertension
Smoking
Toxins
Viruses
Immune Reactions

Question 14

What happens when endothelial cells are injured ?

Answer 14

This creates gaps in between endothelial cells
IN these gaps you get monocytes
Monocytes adhere to the endothelium

Question 15

State the steps leading to atherosclerosis

Answer 15

Chronic Endothelial injury

Endothelial dysfunction (monocyte adhesion and immigration)

Smooth muscle emigration from media to intima
(macrophage activation)

Macrophages and smooth muscle cells engulf lipid

Smooth muscle proliferation, collagen and other ECM deposition, extracellular lipid

Question 16

What does endothelial dysfunction lead to ?

Answer 16

Increased endothelial permeability

Increased leukocyte adhesion

Increased monocyte adhesion and migration

Question 17

Yellow dots

Answer 17

Low density cholesterol

Question 18

Monocytes

Answer 18

Monocytes pass through the endothelium and change themselves into macrophages, eating away oxidised LDL.

Question 19

Function of macrophages

Answer 19

Macrophages eat away, phagocyte oxidised LDL

Question 20

Role of macrophages

What do they secrete ?

Answer 20

Engulf oxidised LDL = foam cells

Secrete :

• IL1 (interleukin 1)
• TNF (tumor necrosis factor)
• MCP1
• Growth factors
• INterferon

Question 21

Fatty streak

Answer 21

Accumulation of LDL
Raised streak of yellow

Question 22

Foam cells

Answer 22

Macrophages that phagocytes oxidised LDL

Question 23

Role of smooth muscles proliferation

Answer 23

Collagen and ECM deposition

Fatty streak —> Mature fibro-fatty atheroma

Question 24

What happens once macrophages / foam cells die ?

Answer 24

The LDL cholesterol in the cytoplasm will form crystals.

All cholesterol forms a lipid debris centre.

Question 25

Summary of atheroma formation

Answer 25

Monocytes adhere and emigrate into the tunica intima. Monocytes change into macrophages In addition to monocytes, LDL also goes into the tunica intima and becomes oxidised . Macrophages phagocytose, oxidise LDL This forms foam cells and these cells produce granules which further attracts more monocytes. Foam cells and granules cause migration of smooth muscle cells from the tunica media to the intima. These muscle cells produce collagen, forming the fibrous caps. Eventually the foam cells die and form cholesterol crystals in the centre

Question 26

Describe the morphology of atheromatous plaque

Answer 26

Patchy and raised white to yellow 0.3-1.5 cm Core of lipid Fibrous cap

Question 26

Where are atheroma commonly found ?

Answer 26

Abdominal aorta Coronary Arteries Popliteal arteries - back of leg Descending thoracic aorta Internal carotid arteries Vessels of the circle of Willis

Question 27

Most common site of atheroma ?

Answer 27

Abdominal aorta

Question 28

Atheroma in coronary artery

Answer 28

Contributes to heart attacks

Question 29

Vessels of the Circle of Willis

Answer 29

Circuit of the blood vessels in the brain Patient could have a stroke due to blockage

Question 30

How do complicated lesions look like ?

Answer 30

Calcification Rupture or ulceration Haemorrhage Thrombosis Aneurysmal dilation

Question 31

What are fatty streaks precursors to ?

Answer 31

Plaques

Question 32

Fatty streaks morphology

Answer 32

Foam cells and T lymphocytes Elongated streaks 1cm or longer Fatty dots <1mm

Question 33

Where are fatty dots found ?

Answer 33

IN the aorta, present before the age of 1 in everyone In coronary artery from adolescence

Question 34

If there are complications, what can atherosclerosis lead to ?

Answer 34

Thrombosis Calcification Aneurysmal dilation Ischaemic Events

Question 35

Describe what happens in the preclinical phase

Answer 35

Normal artery Fatty streak Fibrofatty plaque Advanced/ vulnerable plaque

Question 36

Describe what happens in the clinical phase

Answer 36

Aneurysm and Rupture Occlusion by thrombosis Critical stenosis (progressive plaque growth)

Question 37

Primary prevention of atherosclerosis

Answer 37

Stop smoking Control hypertension Weight reduction Lowering total LDL Reduce calories intake

Question 38

Secondary prevention of atherosclerosis

Answer 38

Prevent complication Antiplatelet drugs in thrombosis Lower blood lipid levels

Question 39

What do smooth muscle cells produce ?

Answer 39

Collagen

Question 40

What is the white parts found in the left ventricle ?

Answer 40

Fibrous scar tissue - could be due to myocardial infarction.

Question 41

Why may the thyroid appear white ?

Answer 41

Auto-immune thyroiditis