Robbins 9th ed - Chapter 11 - Blood Vessels - Atherosclerosis (1)

Question 1

Describe the basic structure of an atherosclerotic plaque.

Answer 1

On the surface of the internal elastic lamina, there is a necrotic core of cellular debris, cholesterol, foam cells and calcium. On the luminal surface of this necrotic core, there is a fibrous cap, made of smooth muscle cells, macrophages, foam cells, lymphocytes, collagen, elastin, proteoglycans and neovascularisation.

Question 2

Atherosclerosis is a process occurring in which layer of arteries?

Answer 2

Intima

Question 3

Which vessels can be affected by atherosclerosis?

Answer 3

Large and medium arteries.

Question 4

Describe the constitutional risk factors of atherosclerosis.

Answer 4

Constitutional (non-modifiable) risk factors include Genetics, Age and Gender.
Genetics: Positive FHx
Age: Between the ages of 40 and 60, risk increases 5-fold
Gender: Pre-menopausal women have lower rates than similar aged men, but post-menopausal women have higher rates than similar aged men.

Question 5

Name the five steps in the pathogenesis of atherosclerosis.

Answer 5

1. Chronic endothelial “injury”
2. Endothelial dysfunction
3. Macrophage activation, Smooth muscle recruitment
4. Macrophages and smooth muscle cells engulf lipid
5. Smooth muscle proliferation, ECM deposition, deposition of extracellular lipid

Question 6

What are foam cells?

Answer 6

Macrophages that have engulfed excess lipids.

Question 7

Describe the two most common factors that trigger step 1 of the pathogenesis of atherosclerosis: Chronic endothelial “injury”.

Answer 7

Endothelial damage progresses over time in response to these two most important triggers:

• Hypercholesterolaemia
• Haemodynamic disturbances (turbulent flow, e.g. at branching points)

Question 8

Describe some secondary risk factors that may trigger step 1 of the pathogenesis of atherosclerosis: Chronic endothelial “injury”.

Answer 8

Endothelial damage progresses over time in response to these triggers:

• Chronic inflammation, inflammatory mediators, ROS
• Toxins from cigarette smoke
• Homocysteine
• Toxins, viruses, immune reactions, etc

Question 9

Describe what happens in step 2 of the pathogenesis of atherosclerosis: Endothelial dysfunction.

Answer 9

The endothelial layer develops increased permeability. Monocytes from the lumen adhere and migrate through, as do platelets.

Question 10

Describe what happens in step 3 of the pathogenesis of atherosclerosis: Macrophage activation + Smooth muscle recruitment.

Answer 10

Macrophages become activated. Smooth muscle cells migrate from the media to the intima.

Question 11

Explain which vessels are affected by atherosclerosis, from most common to least common.

Answer 11

Abdominal aorta, Coronary arteries, Popliteal arteries, Descending thoracic aorta, Internal carotid arteries, Circle of Willis.

Question 12

Describe the (six) potential consequences of an atherosclerotic plaque.

Answer 12

1) Plaque rupture, exposing highly thrombogenic plaque constituents
2) Haemorrhage into the atheroma, expanding its size
3) Thromboembolism from elsewhere, lodging in the narrowed lumen of the plaque
4) Medial thinning (wall weakening) –> aneurysm
5) Progressive plaque growth –> critical stenosis
6) Calcification

Question 13

What is the difference in the composition of stable plaques and vulnerable plaques?

Answer 13

Stable plaques have a dense fibrous cap. Vulnerable plaques have thin fibrous caps and large lipid cores. If plaques develop slowly over time, they undergo remodeling to withstand the shear forces of the blood flow, and become stable plaques.