Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

Cardiovascular system > Coronary Artery Disease and Atherosclerosis > Flashcards

Coronary Artery Disease and Atherosclerosis Flashcards

1
Q

Describe the expected burden of IHD

A

By 2020, will be the highest global killer. Increasing because of the epidemiological shift- developing countries have more westernised lifestyles.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

What is atherosclerosis

A

A progressive, inflammatory disease of large and medium sized arteries.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

Describe the areas of medicine that atherosclerosis involves

A 
Neurology
(cerebrovascular 
disease)
Cardiology
(coronary disease)
Cardiac 
Surgery
(revascularization)
Vascular
Surgery
(revascularization)
Endocrinology
(diabetes)
Metabolic medicine
(lipids)
Acute 
Medicine
(Heart attack
Stroke)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

What are the modifiable risk factors for atherosclerosis

A

Smoking
Lipid intake- can be controlled by pharmacological means and diet
Blood pressure- diet control (low salt) and medications
Diabetes- low sugar, lose weight, pharmacological (metformin, sulphonylurea)
Obesity- diet, exercise, drugs (lipid absorption, appetite, gastric bands)
Sedentary Lifestyle - exercise

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

What are the non-modifiable risk factors for atherosclerosis

A

Age- increased age increases number and severity of lesions
Sex- men are affected to a much greater extent than women, until the menopause when the incidence in women increases- cardioprotective effects of oestrogen.
Genetic background- at least 50% of risk.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

What are we concerned with in the clinic

A

Modifiable risk factors.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

Explain the interaction of the risk factors

A

Have a multiplicative effect

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

Describe the changes in the epidemiology over the past decade

A

Reduced hyperlipidaemia (statin treatment
Reduced hypertension (antihypertensive treatment
New improvements in diabetes treatment have doubtful effect on macrovascular disease
Increased obesity  Increased diabetes
Changing pathology of coronary thrombosis possibly related to altered risk factors

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

What are the clinical trials for SGLT2 inhibitors indicating

A

Diabetes drugs- still ongoing- little effect on microvascular disease.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

Where do atherosclerotic plaques tend to form

A

Bifurcations
Due to haemodynamic
Create eddys in blood- more turbulent flow in these areas.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

Describe the deposition of LDL

A

Low density lipoproteins (LDL) deposit in the subintimal space and binds to matrix proteoglycans.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

Describe the progression of atherosclerosis

A

lesion prone location- adaptive smooth muscle thickening following LDL deposition
Type 2 lesion- becomes inflammatory- population of foam cells (fat filled macrophages)
Type 3 -preatheroma- foam cells release fat as they die- small pools of extracellular lipid on artery wall
Type 4 (atheroma)- small pools of lipid coalesce to form necrotic core of extracellular lipid.
Type 5 (fibroatheroma)- fibrous thickening (collagen) lies over core, beneath the endothelium
Type 6 (complicated lesion)- if fibrous thickening not enough and cap cracks apart, triggering thrombus that can occlude artery

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

Describe the appearance of the type 6 lesion

A

Stratified appearance
As development is stepwise
Grows incrementally in small steps as you age.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

What does the stability of the plaque depend on

A

The stability of the plaque is dependent on the strength and thickness of the fibrous cap, which relies on the balance between inflammation and repair. If this balance is disturbed and inflammation predominates, the cap may become thinner, less stable and may rupture.
Counterintuitively, we want a thick, fibrous cap as it prevents MI.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

Where does the window of opportunity for lifestyle interventions lie

A

Intermediate and advanced lesions

lifestyle changes and risk factor management during intermediate/advanced lesion stage

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

Describe the clinical interventions for complicated plaques

A

Secondary prevention
Catheter based interventions
Revascularisation surgery
Treatment of heart failure

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

Describe percutaneous coronary intervention

A

Number of procedures to relieve stenosis in the coronary arteries.
Performed by the insertion of a catheter- usually via the femoral artery.
Balloon angioplasty: compresses the plaque; expands the lumen
Metal stent- positioned within the stenosis- expanding vessel walls and restoring vessel patency- should be coated with immuno-suppressive agents- to reduce the risk of re-stenosis.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

Describe coronary artery bypass graft

A

The procedure uses autologous veins and/or arteries to bypass stenosis in coronary arteries.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

Describe the role of vascular endothelial cells

A 
surface for leukocyte recruitment 
Barrier function (e.g. to lipoproteins)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

Describe the roles of platelets

A

Thrombus generation

Cytokine and growth factor release - causing smooth muscle cell migration from the media to the intima

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

Describe the roles of monocytes/macrophages

A

Foam cell formation- macrophages take up oxidised LDL
Cytokine and growth factor release - monocyte and smooth muscle infiltration.
Major source of free radicals
Metalloproteinases- degrade fibre cap (cofactor is zinc)- more prone to thrombus.

22
Q

Describe the roles of the vascular smooth muscle cells

A

Migration and proliferation- move from media to the intima
Collagen synthesis
Remodelling & fibrous cap formation

23
Q

Describe the roles of T lymphocytes

A

Macrophage activation

24
Q

Describe the regulation of macrophages

A

Macrophage subtypes are regulated by combinations of transcription factors binding to regulatory sequences on DNA. However, we do not yet understand the regulation!

25
Q

Describe inflammatory macrophages

A

Adapted to kill microorganisms (germs

26
Q

Describe resident macrophages

A

Normally homeostatic - suppress inflammatory activity
Alveolar resident macrophages - surfactant lipid homeostasis
Osteoclasts - calcium and phosphate homeostasis
Spleen - iron homeostasis

27
Q

Describe the white cell response in atherosclerosis

A

Excessive and inappropriate

28
Q

Describe LDLs

A

‘Bad’ cholesterol - Synthesised in liver.

Carries cholesterol from liver to rest of the body including arteries.

29
Q

Describe HDLs

A

Good’ cholesterol

Carries cholesterol from ‘peripheral tissues’ including arteries back to liver (=“reverse cholesterol transport”)

30
Q

Describe oxidised/modified LDLs

A

Due to action of free radicals on LDL. (see later)
Not one single substance.
Families of highly inflammatory and toxic forms of LDL found in vessel walls.

31
Q

Describe the structure of lipoproteins

A 
Docking molecule ‘molecular addresses for fat delivery’ (apoprotein)
Lipid monolayer (like cell membrane) but one molecule thick
Cargo fat for fuel (triglycerides and cholesterol esters)
32
Q

Describe the modification of subendothelial LDLs

A

LDLs leak through the endothelial barrier by uncertain mechanisms
LDL is trapped by binding to sticky matrix carbohydrates (proteoglycans) in the sub-endothelial layer and becomes susceptible to modification
Best studied modification is oxidation - represents partial burning
LDL becomes oxidatively modified by free radicals. Oxidised LDL is phagocytosed by macrophages and stimulates chronic inflammation

33
Q

Describe familial hyperlipidaemia

A

Autosomal genetic disease.
Massively elevated cholesterol (20mmol/L).
Failure to clear LDL from blood.
Xanthomas and early atherosclerosis; if untreated fatal myocardial infarction before age 20
Failure to remove LDL from blood to liver.

34
Q

What is the LDL receptor and cholesterol synthesis regulated by

A 
LDL receptor (expression negatively regulated by intracellular cholesterol).
Cholesterol synthesis is also negatively regulated by cellular cholesterol. Led to the discovery of HMG-CoA reductase inhibitors (= “statins”) for lowering plasma cholesterol.
35
Q

What happens in LDLR-negative patients

A

In LDLR-negative patients, macrophages accumulate cholesterol
Deduced a second LDL receptor - not under feedback control - in atherosclerotic lesions. Called them ‘scavenger receptor’ since they hoover up chemically modified LDL.
Now known that scavenger receptors are a family of pathogen receptors that ‘accidentally’ bind OxLDL.

36
Q

What were scavenger receptors intended to bind to

A

Germs and not oxLDL

Hep B- actively protective- receptor binds to Hep B and not oxLDL

37
Q

Describe macrophage scavenger receptor A

A 
Known as CD204
Binds to oxidised LDL
Binds to Gram-positive bacteria like Staphylococci & Streptococci
Binds to dead cells
Cause inflammation and destruction
38
Q

Describe macrophage scavenger receptor B

A 
Known as CD36
Binds to oxidised LDL
Binds to malaria parasites
Binds to dead cells
safe clearance and reverse cholesterol transport
39
Q

Describe the macrophage function of generating free radicals

A

Macrophages have oxidative enzymes that can modify native LDL
a) NADPH Oxidase, for example superoxide O2-
b) Myeloperoxidase, for example, HOCl hypochlorous acid (bleach) from ROS + Cl-, HONOO Peroxynitrite.
Further oxidation- vicious cycle of positive feedback loop.
bleach secreted to walls to oxidise LDLs

40
Q

Describe the role of macrophages in Phagocytosing modified lipoproteins, & become foam cells

A

Macrophages accumulate modified LDLs to become enlarged foam cells

41
Q

Describe the role of macrophages in Expressing cytokine mediators that recruit monocytes

A

Plaque macrophages express inflammatory factors that are involved in monocyte recruitment.
Cytokines – protein immune hormones that activate endothelial cell adhesion molecules
VCAM-1 mediates tight monocyte binding
Atherosclerosis is reduced in mice without IL-1 or VCAM-1

Chemokines - small proteins chemoattractant to monocytes
Monocyte chemotactic protein-1 (MCP-1
MCP-1 binds to a monocyte G-protein coupled receptor CCR2.
Atherosclerosis is reduced in MCP-1 or CCR2 deficient mice.

42
Q

Describe the roles of macrophages in expressing chemo-attractants and growth factors for VSMC

A

Wound healing” role of the macrophage in atherosclerosis - Macrophages release complementary protein growth factors that recruit VSMC and stimulate them to proliferate and deposit extracellular matrix

Platelet derived growth factor
Vascular smooth muscle cell chemotaxis
Vascular smooth muscle cell survival
Vascular smooth muscle cell division (mitosis)

Transforming growth factor beta
Increased collagen synthesis
Matrix deposition

43
Q

Describe the difference between the normal and atherosclerotic media

A

 High Contractile filaments
Low Matrix deposition genes

 Low Contractile filaments
High Matrix deposition genes

44
Q

What are the metalloproteinases

A

Family of ~28 homologous enzymes.
Activate each other by proteolysis.
Degrade collagen.
Catalytic mechanism based on Zn.

45
Q

What may blood coagulation at the site of rupture lead to

A

Effect of plaque erosion/rupture - Blood coagulation at the site of rupture may lead to an occlusive thrombus and cessation of blood flow.
Plaque full of pro-coagulation factors
once it touches the blood it will thrombose
MI or stroke risk

46
Q

Describe ruptures plaques

A

macrophages mean fibrous cap becomes so thin that will break and rupture, allowing necrotic core to contact blood and cause thrombus formati

47
Q

Describe the characteristics of vulnerable plaques

A 
Large soft eccentric lipid-rich necrotic core
Increased VSMC apoptosis
Reduced VSMC & collagen content  
Thin fibrous cap
Infiltrate of activated 
macrophages expressing MMPs
48
Q

Describe macrophage apoptosis

A

OxLDL derived metabolites are toxic eg 7-keto-cholesterol
Macrophage foam cells have protective systems that maintain survival in face of toxic lipid loading
Once overwhelmed, macrophages die via apoptosis.
Release macrophage tissue factors and toxic lipids into the ‘central death zone’ called lipid necrotic core.
Thrombogenic and toxic material accumulates, walled off, until plaque rupture causes it to meet blood

49
Q

Describe NFkB

A 
Master regulator of inflammation
Activated by numerous inflammatory stimuli
Scavenger receptors
Toll-like receptors
Cytokine receptors
Switches on numerous inflammatory genes
Matrix metalloproteinases
Inducible nitric oxide synthase
50
Q

Summarise the role of NFkB

A

Integrator
Activates a variety of downstream mechanisms from a variety of different stimuli (switching on inflammatory genes (e.g. Matrix metalloproteinases and inducible nitric oxide synthase) - can be activated by many stimuli and coregulate multiple genes

51
Q

What can inflammation be

A

prothrombogenic

Cardiovascular system (19 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions