Guided learning- Atherosclerosis

Question 1

Describe the normal structure of blood vessels

Reference layers of the vascular wall, its component parts and how this may differ between arteries and veins.

Answer 1

• Normal blood vessels are composed of three vascular layers:
  
  • Tunica Intima- Inner layer:
    
    • ​Endothelium: Single layer of squamous epithelium lying on top of…
    • Basal lamina- thin extracellular layer consists of collagen, proteoglycans and glycoprotein.
    • Underlying the basal lamina is the Subendothelial layer. Consists of connective tissue and in arteries and arterioles it contains a sheet like layer of inner elastic layer called the internal elastic membrane.
  • Tunica Media- Middle layer:
    
    • ​Consists of circumferentially arranged smooth muscle cells interspersed with elastin, reticular fibres (type 3 collagen from reticular cells) and proteoglycans.
    • In arteries this layer is thick and extends from the internal elastic membrane to the external elastic membrane.
    • External elastic membrane surrounds the smooth muscle layer and separates the SMC’s from the tunica adventitia.
  • Tunica Adventitia- Outer layer:
    
    • ​Formed of longitudinal collagen and elastic fibres.

Question 2

What are the differences between arteries and veins?

Answer 2

• Arteries
  
  • specialised to convey blood at high blood pressures, therefore have a much thicker wall with higher content of vascular smooth muscle and elastin.
  • Maintains blood pressure and withstands pulsatile flow of blood.
  • Lumen is narrow compared to veins.
• Veins
  
  • ​ are distensible thin walled vessels with less smooth muscle and elastin, mainly fibrous tissue.
  • Specialised for return of blood to heart at low pressure, valves for one way flow.
  • Wide lumen to provide less resistance to flow.
  • High capacitance.

Question 3

Describe the structure of arterioles

Answer 3

• Tunica intima has thin layer of endothelium and subendothelium.
• Internal elastic membrane is fenestrated and thin
• only 1-2 layers of smooth muscle in their tunica media.
• Tunica adventia is a thin sheath
• Ratio of wall thickness to lumen diameter increases to allow more precise regulation of intravascular pressure

Question 4

What defines a large or elastic artery?

What arteries are included?

Answer 4

• A large or elastic artery is an artery with a large amount of collagen and elastin in its tunica media that means it is able to stretch in response to each pulse of blood.
• Aorta, Pulmonary trunk - and main branches:
  
  • Subclavian, brachiocephalic trunk, common carotids
  • Common iliac arteries

Question 5

why is it difficult to classify medium or muscular arteries?

Describe any potential differences between medium/ muscular arteries and large/small arteries

Answer 5

• Difficult to classify between large/ elastic arteries and medium/muscular arteries as they tend to have intermediate features of both large and small arteries.
• Medium arteries tend to have thinner tunica intima compared to elastic/ large arteries and the internal elastic lamina and external elastic lamina more prominent.
• Elastic/ large arteries tend to have prominent tunica media with many elastic layers interspersed with the smooth muscle, hard to distinguish between internal elastic layer and tunica media.
• small arteries and arterioles have a thin endothelial and subendothelial layer. Less smooth muscle than medium/ muscular arteries.

Question 6

How can we distinguish between small arteries and arterioles?

Answer 6

• By the number of smooth muscle cell layers in the tunica media.
• Generally in small arteries there are up to 8 smooth muscle cell layers
• In arterioles there are only 1- 2 smooth muscle cell layers.

Question 7

Describe the layers of this elastic artery

Answer 7

• Tunica intima with its endothelium, basal lamina and subendothelium and internal elastic membrane
• Tunica media with circumferentially arranged smooth muscle cells layered with elastin fibres, reticular fibres and collagen that form a lamellar arrangement.
• The external elastic membrane which separates the tunica media from the tunica adventitia
• The tunica adventitia consisting of collagen and some elastin fibres, vasa vasorum (blood vessels) and nerves.

Question 8

Describe the layer of this muscular/ medium artery

Note: cannot see tunica intimal layers of endothelium and basal lamina.

Answer 8

• Starting at the lumen- see the wavy internal elastic layer/membrane
• Tunica media- lots of smooth muscle cells interspersed with collagen and elastin fibres.
• Well defined external elastic membrane
• Tunica adventitia with collagen and some elastin fibres

Question 9

What is the endothelium?

What is endothelial activation?

Answer 9

A single layer of continuous squamous epithelium that lines the entire vascular tree and regulates many aspects of blood and blood vessel function.

Endothelial activation describes the process in which various stimuli induce a response in the endothelium. Endothelial activation is known to play a part in many vascular diseases.

Question 10

Describe 5 functions of the endothelium

Answer 10

1. Maintenence of selective permeability barrier- allow selective movement small/large molecules between tissues and blood and vice versa depending on size and charge.
2. Anti-thrombogenic barrier- under normal circumstances endothelium are antithrobogenic, do not support adherence of platelets/ thrombus formation. When damaged they release prothrombogenic factors such as VWF and collagen.
3. Modulate blood flow and vascular resistance- release vasodilators (NO, Prostacyclin) and vasoconstrictors (endothelin, thromboxane A2, prostaglandin H2) that act on VSM cells to modulate lumen and resistance.
4. Modulate immune responses- by expressing adhesion molecules and receptors for lymphocytes.
5. Oxidation of lipoproteins - LDL’s with high cholesterol content and vLDL’s oxidised by free radicals produced by endothelial cells.

Question 11

What normal and pathological processes are vascular smooth muscle cells involved in?

Answer 11

• Participate in normal vascular repair as well as pathological process of atherosclerosis

Question 12

When stimulated by various factors (e.g. cytokines, oxygen free radicals) how do Vascular smooth muscle cells respond?

Answer 12

• They can release growth factors and cytokines
• They can proliferate
• They can stimulate the release of matrix materials such as collagen, elastin and proteoglycans.

Question 13

Define arteriosclerosis

Answer 13

Chronic disease with abnormal thickening and hardening of the arterial walls with a resulting loss of elasticity.

Question 14

Define Atherosclerosis

Answer 14

Atherosclerosis is a specific type of arteriosclerosis. It refers to the buildup of fat, cholesterol and other substances within the artery wall that leads to plaque formation that can limit blood flow.

Question 15

What is the most common type of acquired abnormality in blood vessels?

Answer 15

Atherosclerotic lesions are the most common acquired abnormality of blood vessels.

Question 16

What are common complications of atherosclerosis?

Answer 16

• Angina
• Acute coronary syndrome ( unstable angina, Myocardial infarction both STEMI and NSTEMI).
• Stroke
• Gangrene of limbs

Question 17

What is arteriolosclerosis?

What patients does it commonly effect?

Answer 17

Abnormal hardening of small arteries and arterioles that can lead to downstream ischaemic injury.

Often seen in patients with hypertension and diabetes.

Question 18

What starts the initial process of atherosclerosis? Where does this occur?

Answer 18

• The initial process of atherosclerosis starts in the tunica intima, often in large elastic arteries after endothelial damage.
• Damage to the endothelium leads to endothelial dysfunction which can be caused by a number of factors:
  
  • High LDL/Cholesterol/Hyperlipidaemia
  • Hyperglycaemia (Diabetes)
  • Hypertension
  • Increased toxins from smoking (nicotine)
  • Viral and bacterial infections

Question 19

Describe the intial stages of atherosclerosis up to the formation of a fatty streak.

Answer 19

• Endothelial damage leading to endothelial dysfunction.
• Dysfunctional endothelium are more permeable to LDL cholesterol
• Increased permeability allows LDL to enter the tunica intima and starts to accumulate.
• Endothelial dysfunction also leads to the production of oxygen free radicals which oxidise LDL.
• Oxidised LDL leads to endothelial activation- expression of chemoattractant factors and adherence molecules for white blood cells.
• Leads to leukocyte adhesion (T cells) and monocyte adhesion and emigration into the tunica intima.
• Oxidised LDL activates infiltrating monocytes which differentiate into macrophages
• Macrophages phagocytose oxidised LDL into the cell and slowly transform into large foam cells- spongey appearance of cytoplasma with lipid containing vesicles.
• Foam cells produce variety of cytokines and growth factors that stimulate infiltration and proliferation of SMC’s from the media.
• Foam cells and infiltrated T cells form initial atherosclerotic lesion or fatty streak.

Question 20

Describe the later stages of atherosclerosis from the formation of the fatty streak to rupture.

Answer 20

• Activated foam cells secrete growth factors and cytokines that leads to recruitment and the proliferation of smooth muscle cells and fibroblasts from the tunica media.
• SMC’s and fibroblasts migrate over the fatty streak and proliferate forming a fibrous cap over the fatty streak which continues to grow with further infiltration of WBC’S, LDL which becomes oxLDL and formation of foam cells.
• Fibrous cap now encloses lipid rich necrotic core composed of lysed foam cells that release cholesterol crystals, foam cells and oxLDL.
• Forms the Fibrofatty plaque and as the plaque grows it begins to occlude the artery.
• Smooth muscle cells in response to cytokines starts to deposit ECM and collagen further stregthening the cap.
• Inflammatory cells such as macrophages release matrix metalloproteinases that degrade collagen and ECM.
• Imbalance between matrix deposition and degradation occurs leading to breakdown of the ECM deposited by VSMC’s in fibrous capsule.
• Fibrous capsule weakens and eventually can rupture
• Exposure of highly thrombogenic material to blood, leading to thrombus formation and occlusion of the artery.

Question 21

What is shown by the arrows?

Would this cause significant flow disturbance?

Answer 21

• Arrows point to fatty streak formation, shows infiltrated monocytes that have become macrophages that have become foam cells in the tunica intima.
• This would not cause significant flow disturbance as it is minimally raised.

Question 22

What is shown in the image?

Answer 22

Macroscopic fatty streak formation in the aorta, seen as yellow, flat area of discoloration

Question 23

What is shown by the arrow in this image?

Answer 23

Image shows an atheromatous fibrous plaque that has formed in the aorta. Evident as atheromatous plaques show as white to yellow raised lesions with intimal thickening and lipid accumulation.

Question 24

What is shown in this image?

Answer 24

Two ruptured atheromatous plaques, thrombus shown as red brown colour

Question 25

Which vessels are most commonly affected in atherosclerosis?

What regions of the body are commonly affected and what conditions are seen?

Answer 25

Large elastic arteries such as aorta/pulmonary trunk/ common carotids/ subclavian/ common iliac

Medium/ muscular arteries such as coronary arteries, renal arteries, popliteal.

Regions commonly affected are brain, heart, lower extremities, kidneys.

Conditions associated:

• Myocardial infarction
• Cerebral infarction (Stroke)
• Gangrene
• Reno-vascular disease
• Aortic aneurysms

Question 26

What are three clinical outcomes of continued plaque development?

Answer 26

1. Complete occlusion of the artery - can lead to hypoperfusion injury
2. Plaque rupture and thrombosis - occlusion, embolisation or resolution
3. Destruction of underlying vessel wall, aneurysm and vessel rupture.