atheroscelrosis

Question 1

definition of atherosclerosis

Answer 1

A chronic inflammatory disease of the intima of large and medium-sized arteries, characterised by formation of atheromatous plaques (atheromas) containing lipids, inflammatory cells, and fibrous tissue.

Question 2

6 phases of pathogenesis of atherosclerosis

Answer 2

1. endothelial injury/dysfunction
2. LDL entry and oxygenation
3. monocyte adhesion and migration
4. inflammation and cytokine release
5. smooth muscle migration and proliferation
6. Plaque formation

Question 3

causes of endothelial injury causing athersclerosis

Answer 3

HTN
smoking, diabetes, LDL, turbulent flow

Question 4

in atherosclerosis pathogenesis what do the macrophages do

Answer 4

macrophages ingest oxygenated LDL (oxLDL) an form FOAM cells

Question 5

what is a plaque made of

Answer 5

lipid core - foam cells, necrotic debris
fibrous cap - collagen, smooth muscle cells

Question 6

Histological hallmarks of atherosclerosis

Answer 6

Intimal thickening
Lipid core
Fibrous cap
Foam cells
Calcification (late stage)

Question 7

3 components of atherosclerotic plaques

Answer 7

1-cells including smooth muscle cells, macrophages and other leucocytes.

2-connective tissue extracellular matrix- including collagen, elastic fibres and proteoglycans.

3-intracellular and extracellular deposits.

Question 8

where is the thickening of the vessel in atherosclerosis

Answer 8

tunica intima

Question 9

what are the major risk factors for atherosclerosis

Answer 9

Increased lipids, cigarette smoking, hypertension, diabetes mellitus no matter the age group

Male gender is a risk factor, but only if all other risks are equal.
As women age and stop having their menses, their “age risk” equals that of men.
Family history is important- but the family risk factor becomes less relevant with age.

Question 10

In atherosclerosis, the cells at the centre of the plaque are?

Answer 10

Foam cells

Question 11

Endothelial cells anti-platelet effects

Answer 11

Intact endothelium prevents platelets and clotting factors from adhering to the thrombogenic extracellular matrix (ECM).
PGI2 (prostacyclin) and nitric oxide produced by the endothelial cells inhibit adhesion.
Both of these mediators are vasodilators and inhibit platelet aggregation.
Endothelial cells release ADPase that degrades ADP further inhibiting platelet aggregation.

Question 12

Endothelial cells anticoagulant effects

Answer 12

mediated by heparin like molecules, thrombomodulin and tissue factor pathway inhibitor.

Thrombomodulin binds to thrombin and converts it form a procoagulant to an anticoagulant via its ability to activate protein C.
Protein C inhibits factors Va and VIIIa.

Endothelium also produces co-factors for protein C and tissue factor pathway inhibitor (TFPI), which inhibits factors VIIa and Xa

Question 13

Endothelial fibrinolytic effects

Answer 13

endothelial cells synthesise tissue plasmin activator (t-PA) that cleaves plasminogen to plasmin which in turn cleaves fibrin to degrade thrombi

Question 14

What is responsible for binding of platelets to exposed extracellular matrix?

Answer 14

vWF

Question 15

What is the most significant early mechanism involved in increased vascular permeability?

Answer 15

endothelial cell contraction

Mechanisms of increased vascular permeability in acute inflammation include: Contraction of venule endothelium to form intercellular gaps (most common; immediate transient response)

Question 16

What is the most important independent risk factor in the development of atherosclerosis?

A Hypertension
B Genetics
C Body Mass Index
D Age

Answer 16

Genetics