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Cardiovascular System > Atherosclerosis > Flashcards

Flashcards in Atherosclerosis Deck (24):
1

Atherosclerosis

Disease affecting the innermost layer of large and medium sized arteries. Appears as focal thickenings called 'plaques', which are deposits of fibrous tissues and lipids.

Thought to contribute to 50% of deaths in the western world

2

What layer of the endothelium wall is affected in atherosclerosis

The Tunica intima.
Contains
-endothelial cells(in contract w intra-vascular cells): involved in BP and inflammation, separated by tight junctions,

-Scattered myointimal cells

-BM: presents growth factors, anchors cells, with a IEL

3

Tunica Media of arteries

an EEL and smooth muscle cells
SM: regulates flow by contraction, and stabilise EC by secreting ECM and activating TGF-beta

4

What do the Elastic Lamina Layers look like in a histology section?

Pink and wavy

5

Tunica Adventitia of the arteries

Connective Tissue: fibroblasts, nerves, leucocytes, lymphatics, blood vessels (vasovasora)

6

How is the exact structure of arteries dependent on their size?

Large arteries > exposed to high-pulsitile pressures > have prominent elastic laminae and are called "elastic arteries"

Medium Sized arteries > media largely composed of SM cells > "muscular arteries

7

Muscular arteries

eg) coronary arteries
-Media largely composed of SM fibres
-Few elastic fibres
-Separate Int/Ext elastic Laminae

8

Large elastic arteries

eg) Aorta, common carotid
-Media contains prominent elastic laminae
-Int/Ext Elastic laminae continuous
-Exposed to high pulsitile pressure
-Elastic recoil assist w continuous flow

9

Arterioles

Small branches within tissues

10

Clinically risk factors ____ and are therefore _______

Clinically risk factors synergise and are therefore considered together

11

Main Positive Risk Factors of Atheroscelorsis (increase disease risk)

-Hyperlipidaemia: (inc lipids in blood, especially cholesterol)
-Cigarette smoking
-Hypertension
-Diabetes mellitus

**advancing age

12

Additional + risk factors of Atheroscelrosis

Family history (polygenic inheritance)
Male
High sat-fat diet
Stressful & sedentary lifestyle
Obesity & metabolic syndromes
Excess alcohol consumption
Low birth weight
Low Socioeconomic status
Infections

13

What is a risk factor that can be BOTH + and -??

A little alcohol is +
A lot of alcohol is -

Theory is alcohol has some antioxidants

14

Negative Risk factors for Atherosclerosis (decrease risk)

High levels of HDL
Moderate alcohol consumption
Cardiovascular fitness

15

Lipoproteins as powerful risk modifiers for Atherosclerosis

Lipoproteins: lipid core, surrounded by a protein coat (apolipoproteins)
Abnormal blood levels of lipoproteins may alter atherosclerosis risk.

-Cholesterol greatly increases risk
whereas
HDL > decreased risk
LDL > increased risk

16

Whats the pathogenesis of Atherosclerosis

Several theories, but the precise process in uncertain.

Initiation: may involve endothelial cell injury
Progression: is an example of chronic inflammation

1) Endothelial cell injury
2) Leukocyte Migration
3) Smooth Muscle activation and migration
4) Lipoprotein infiltration

17

Endothelial cell injury. Caused by?

Thought to be one of the most important initiators of atherosclerosis

Caused by a combo of injuries or stresses: haemodynamic force of blood(hypertension), chemical insults (smoking, lipids), cytokines

Caused most predominantly at BV junctions

18

Endothelial cell injury may lead to...

-Altered permeability (lipid infiltration)
-Adhesion and activation of leucocytes (due to enhance expression of chemokines and adhesion molecule)
-Activation of thrombosis (turn on blood clot formation)
-In addition endothelial progenitors are recruited

Gradually plaque begins to build up under endothelial cells

19

Leukocyte Migration into the developing plaque

Type of chronic inflammation

1) Circulating monocytes adhere to endothelial cells and enter the atherosclerotic lesion

2) They then differentiate into macrophages

3) Once in the plaque, they ingest large amounts of oxidised lipoproteins which give them a foamy appearance > "foam cells"

4) When they die by necrosis (or apoptosism), their contents including lipoproteins, spill into the extracellular space. (potent activation of inflamm)

20

Smooth muscle cell activation and migration

1) macrophages, platelets and endothelial cells produce growth factors that activate vascular smooth muscle cells

2) Once activated, SM cells proliferate and migrate into the tunica intima from the tunica media
**accelerated by failure of the IEL


Activated SM:
produces cyto/chemo kines that activated leukocytes
take up lipids
produce ECM proteins

21

Lipoprotein infiltration and oxidation

LP's become oxidised in plaques. When Endothelial cell is damaged LDL can infiltrate, and is a risk of oxidisation by ROS.

Oxidised lipoproteins:
-attract monocytes > macrophages which injest LDL and form foam cells, as they cannot breakdown the LDL
-stimulate several cell types to release cytokines, inflamm mediators and ROS, growth factors
These cause more dysfunction, inflammation and apoptosis in smooth muscle cells, macrophages and endothelial cells. A viscous cycle


***IEL may be a protective barrier

22

Draw an atheroma lesion

....

23

Pre-clinical to clinical phase of atherosclerosis

Silent phase,
Normal artery progression to an advanced plaque UNTIL they suddenly cause symptoms due to rupture, haemorrhage, thrombosis or dissection.

24

Clinical consequences of atherosclerosis

Myocardial infarction
Peripheral vascular disease
Cerebrovascular disease (strokes)