AM L3 Thrombosis and diabetes Flashcards

1
Q

What is plaque erosion?

A

focal areas of endothelium become denuded (stripped) and expose underlying connective tissue

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2
Q

MMPs are ____-dependent ____.

A

zinc dependent endopeptidases

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3
Q

Role of MMPs in plaque erosion?

A

degrade components of the extracellular matrix and basement membrane

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4
Q

2 main ways plaque erosion occurs?

A
  1. endothelial cell desquamation (scraping off) due to lysis of the extracellular matrix (caused by MMPs)
  2. endothelial cell death (including apoptosis)
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5
Q

MMPs subdivided into….

A

5 classes including collagenases, gelatinases and stromelysins

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6
Q

How does plaque erosion cause thrombosis?

A

The basement membrane is exposed, including collagen. This is prothrombotic. Platelet aggregation is trigger which can result in thrombosis.

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7
Q

Where does the thrombos lie in plaque erosion?

A

On top of the fibrous cap

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8
Q

Plaque rupture is….

A

a structural defect (gap) in the fibrous cap that separates the necrotic lipid core of an ATS plaque from the lumen, resulting in exposure of the necrotic core to the blood.

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9
Q

Trauma activates which clotting pathway

A

Extrinsic.

Activates VIIa.

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10
Q

The plaque expresses high levels of ….

A

tissue factor.

This results in the clotting cascade being activated when the legionis ruptured as large amounts are exposed.

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11
Q

Markers of vulnerable plaques

5

A

Large lipid core (>50% volume of plaque)
High density of macrophages
Low density of smooth muscle cells in the cap
High Tissue Factor content
Thin cap in which the collagen structure is disorganised

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12
Q

Why is high density of macrophages a risk factor?

A

Express tissue factor and MMPs.

Risky, particularly at the edges

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13
Q

If the thrombosis is in the surface of the plaque it is as a result of….

A

Superficial erosion

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14
Q

If the thrombosis is coming out of the necrotic lesion it is as a result of….

A

Rupture of the fibrous cap

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15
Q

Plaque rupture accounts for …. of fatal MI in men

Plaque erosion accounts for …. of MI in women

A

80%
50%
So basically it is very bad

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16
Q

What is a risk factor

A

something that changes your chances of having a disease.

May be modifiable or fixed

17
Q

Modifiable risk factors in terms of LDL and HDL

A

Raised LDL

Low HCL

18
Q

Modifiable risk factors include

A
Diabetes
Obesity
Hypertension
Smoking
Physical inactivity
19
Q

Is homocysteine modifiable or fixed risk factor?

A

Elements of both - diet can change the level

20
Q

What is the leading cause of mortality in diabetes?

A

CHD (50% of all deaths)

21
Q

How does the body respond to an increase in blood glucose?

A

beta islet cells of the pancreas produce insulin

this causes adipocytes, liver and muscle to take up glucose

22
Q

How does the body respond to a decrease in blood glucose?

A

Pancreatic alpha cells produce glucagon.

Causes liver to increase ketone synth, gluconeogenesis and glycogenolysis

23
Q

What process is stopped in type 1 diabetes?

A

Pancreatic beta cells don’t produce insulin

24
Q

What process is stopped in type 2 diabetes?

A

Response to circulating insulin

25
Diabetes causes ....(4)... thus increasing cardiovascular risk
increase endothelial dysfunction increase blood viscosity increase blood coagulation secondary dyslipidemia
26
Most complications of diabetes arise from
damage to blood vessels
27
ATS is accelerated in diabetes particularly in what 3 arteries?
coronary, carotid and femoral | macrovascular damage
28
Microvascular damage of diabetes occurs where? (3)
Retina, kidney, nervous system
29
Hyperglycemia causes ....(4) ... resulting in endothelial dysfuntion
Constriction Growth promotion Pro-thrombosis Pro-inflammation
30
Endothelial dysfunction is...
imbalance between the production of vasoconstricting and vasorelaxing mediators
31
Sign of endothelial dysfunciton
decreased production of nitric oxide
32
enzyme that produces nitric oxide?
phosphorylated eNOS (endothelial nitric oxide synthase)
33
what is necessary to maintain the enzyme that makes NO
insulin is needed to activate AKt kinase this phosphorylates eNOS to make it active this produces NO
34
unphosphorylated eNOS causes....
``` endothelial dysfunction (via: reduced blood flow thrombosis inflammation neointima formation) ```
35
low NO also results in
``` more ROS more NADPH (precursor) ```
36
what happens in mice with insulin receptor knock out?
decreased eNOS and impaired endothelial vasodilator funciton. Impaired NO bioavailability and defects in PI3kinase/Akt system, what ever that is ....