Brainscape's Knowledge GenomeTM

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


See full index

brs (phase 1b) > (cardioresp) coronary heart disease & atherosclerosis > Flashcards

(cardioresp) coronary heart disease & atherosclerosis Flashcards

1
Q

how can risk factors be categorised?

A

modifiable risk factors

non-modifiable risk factors

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

what are the modifiable risk factors for atherosclerosis?

A

smoking

lipids intake

blood pressure

diabetes

obesity

sedentary lifestyle

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

what are the non-modifiable risk factors for atherosclerosis?

A

age

sex

genetic background

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

how can the risk factor of smoking be addressed and modified?

A

smoking cessation

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

how can the risk factor of lipid intake be addressed and modified?

A

antihyperlipidaemic agents

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

how can the risk factor of blood pressure be addressed and modified?

A

use ABCD

A = ACE inhibitors
B = Beta-blockers
(better for younger patients under 55 and ‘non-black’ patients)

C = Calcium channel blockers
D = Diuretics
(better for older patients and ‘black’ patients of all age)

= prescribed in such a way that if two are needed, another from the opposite group is prescribed e.g. A and C // B and D

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

how can the risk factor of diabetes be addressed and modified?

A

dietary advice, weight loss & lifestyle modifications

gastric surgery to achieve weight loss

metformin, sulphonylureas, insulin

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

how can the risk factor of obesity be addressed and modified?

A

increased exercise + lifestyle modifications

obesity can increase the risk of hyperlipidaemia, hypertension, diabetes

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

how can the risk factor of sedentary lifestyle be addressed and modified?

A

adopt a more active lifestyle w more exercise

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

explain risk factor multiplication

A

risk factors are multiplicative when they are combined

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

how has the epidemiology of coronary heart disease changed over the years and what does this indicate?

A

people are getting CHD much later

more people are dying of CHD but at a higher age

= people are living longer AND treatment has improved

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

which improvements in treatment have contributed to the changes in CHD epidemiology?

A

people get CHD later and live longer with it

positives
= reduced hyperlipidaemia (statin treatment)
= reduced hypertension (antihypertensive treatment)

negatives
= increased obesity so increased diabetes

miscellaneous
= new improvements in diabetes treatment have doubtful effect on macrovascular disease
= changing pathology of coronary thrombosis

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

which areas are most affected by atherosclerosis?

A

coronary arteries

cerebral arteries

carotid arteries (tends to occur at the carotid bifurcations)

iliac arteries (at the aortic bifurcations)

coronary tree (supplying the myocardium)

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

at which bifurcations is atherosclerosis likely?

A

carotid bifurcation

aortic bifurcation

coronary tree (supplying the myocardium)

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

why does atherosclerosis occur at branches and bends?

i.e. bifurcations

A

areas of low shear stress and disturbed, turbulent blood flow (vortices)

= low shear stress is pro-inflammatory, pro-thrombotic and stimulates SMC proliferation and reduced NO production

= collective contributes to the growth of the atherosclerotic lesion

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

describe the structure of the artery and its constituent layers

A

tunica intima (interna) = endothelium - subendothelium = internal elastic lamina

tunica media = smooth muscle cells

tunica adventitia = vasa vasorum, nerves

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

describe the layers of tunica intima

A

endothelium

subendothelium (i.e. subendothelial space)

internal elastic lamina

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

what does the tunic media consist of?

A

smooth muscle cells

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

what does the tunic adventitia consist of?

A

vasa vasorum, nerves

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

where does the atherosclerotic plaque develop?

A

in the subendothelial space

i.e. subintimal space

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

where do low-density lipoproteins deposit in the arterial wall and why?

A

deposit in the subintimal/subendothelial space and bind to the matrix proteoglycans

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

why do arterial walls have a high amount of muscle?

A

to maintain and resist blood pressure

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

why do arterial walls have a high amount of elastic?

A

to cope w the pulsatile pressure and stroke volume

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
24
Q

what is the function of the arterial endothelium?

A

separates the tissue walls from the blood

controls the vasodilation and vasoconstriction and therefore the blood pressure

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
25
Q

what are the names of the six stages of atherosclerosis progression?

A

coronary artery at lesion-prone location

type II lesion (fatty streak)

type III (preatheroma)

type IV (atheroma)

type V (fibroatheroma)

type VI (complicated lesion)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
26
Q

explain how an atherosclerotic plaque develops, from start to finish

A

1) endothelial damage due to hypertension/hyperglycaemia/hyperlipidaemia/smoking etc)
2) macrophages and LDL deposit in the subendothelial space; latter combines with free radicals from macrophages and forms oxLDL
3) oxLDL stimulates more macrophages to enter subendothelial space and engulf them
4) macrophages eventually engulf too many oxLDL molecules, leading to lipid overload and subsequent death (small pools of lipid)
5) as more macrophages die, more oxLDL & dead material accumulates to form extracellular lipid core
6) chemical signals released during lipid core formation cause SMC migration to wall off the lesion from the lumen (fibrous thickening)
7) complicated lesion = fibrous cap fissures/ruptures due to stress on endothelial wall and the atherosclerotic plaque components are exposed to the arterial blood leading to thrombogenesis

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
27
Q

what is a type II lesion and what key event characterises this step in atherosclerosis?

A

type II lesion = fatty streak formation

= macrophage foam cell formation

(oxLDL is ingested by macrophages that subsequently form foam cells)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
28
Q

what is a type III lesion and what key event characterises this step in atherosclerosis?

A

type III lesion = preatheroma

some foam cells die due to lipid overload and release their lipid contents

= forming small extracellular pools of lipid

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
29
Q

what is a type IV lesion and what key event characterises this step in atherosclerosis?

A

type IV lesion = atheroma

most/all foam cells die due to lipid overload and multiple small pool os lipid coalesce to form a large lipid core

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
30
Q

what is a type V lesion and what key event characterises this step in atherosclerosis?

A

type V lesion = fibroatheroma

smooth muscle cells migrate to the luminal surface of the lipid core and form a fibrous cap (fibrous thickening!)

= barrier bw atherosclerotic plaque and arterial blood

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
31
Q

what is a type VI lesion and what key event characterises this step in atherosclerosis?

A

type VI lesion = complicated lesion

rupture of atherosclerotic plaque due to damage to fibrous cap (fissure, hematoma, thrombus)

= release of plaque contents into blood stimulating thrombogenesis

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
32
Q

what is the main growth mechanism of atherosclerosis from type I to type IV lesions?

A

growth due to lipid addition

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
33
Q

what is the main growth mechanism of atherosclerosis from type V to type VI lesions?

A

type V = smooth muscle and collagen increase

type VI = thrombus formation or haematoma

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
34
Q

when is the window of opportunity for primary prevention?

A

intermediate and advanced lesions

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
35
Q

what forms of primary prevention occur in the intermediate-advanced lesion stage??

A

Life-style changes

Risk factor management

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
36
Q

what are two complications that can occur as a result of atherosclerosis?

A

stenosis

plaque rupture

(due to occlusion of an artery = subsequent ischaemia, infarction OR due to extensive growth of lipid cores)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
37
Q

what clinical interventions are carried out in the complicated lesion stage of atherosclerosis?

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
38
Q

name the 5 main cells involved in atherosclerosis

A

vascular endothelial cells

monocyte-macrophages

vascular smooth muscle cells

platelets

T lymphocytes

39
Q

what are the two main functions of vascular endothelial cells in atherosclerosis?

A

1) barrier function (e.g. against LDL)
2) leukocyte recruitment

(also involved in blood pressure control)

40
Q

what are the main functions of monocyte-macrophages in atherosclerosis?

A

1) foam cell formation
2) release free radicals and metalloproteinases
3) release inflammatory cytokines and growth factors

41
Q

what are the main functions of vascular smooth muscle cells in atherosclerosis?

A

1) migration, proliferation and formation of the fibrous cap (remodelling)
2) collagen synthesis

42
Q

what are the main functions of platelets in atherosclerosis?

A

thrombus generation

3) release inflammatory cytokines and growth factors

43
Q

what are the main functions of T lymohocytess in atherosclerosis?

A

activate macrophages

44
Q

explain how fibrous cap thickness in atherosclerosis can cause either unstable angina or myocardial infarction

A

if fibrous cap is thick = plaque is stable, can narrow lumen BUT does not stop blood flow (unstable angina)

BUT

if thin capped = atherosclerotic plaques are thought to be more prone to rupture into lumen, blocking blood flow leading to thrombus formation (myocardial infarction)

45
Q

differentiate between a thrombus and an embolus

A

thrombus = blood clot that forms in a vein

embolus = usually part of a blood clot that has chipped off, that moves through the blood vessels until it reaches a vessel that is too small to let it pass

46
Q

define thromboembolism

A

an embolus that breaks off a thrombus (blood clot)

47
Q

what are MACEs?

A

major adverse cardiovascular events

48
Q

which type of treatment during clinical trials resulted in fewer major adverse cardiovascular events (MACE)?

A

(CANTOS trial)

= anti-IL1 antibody

49
Q

why is IL-1 significant to the pathogenesis of atherosclerosis?

A

cholesterol crystals trigger macrophage/inflammatory cells of plaque to release more IL-1

50
Q

which CD macrophage protein is appears brown-dyed?

A

CD68

51
Q

why is foam cell debris (i.e. atherosclerotic plaque) dangerous?

A

contains toxic, thrombogenic molecules that can cause thrombus formation on exposure to blood

52
Q

what is the main inflammatory cell of atherosclerosis?

A

macrophages, derived from blood monocytes

53
Q

how are macrophage subtypes regulated?

A

combinations of transcription factors binding to regulatory sequences on DNA

54
Q

what are the two types of macrophages?

A

inflammatory macrophages

resident macrophages

55
Q

what is the function of inflammatory macrophages?

A

phagocytose pathogens

56
Q

what is the function of resident macrophages?

A

maintain normal homeostatic mechanisms + suppress inflammatory activity

57
Q

give examples of three types of resident macrophages

A

lung alveolar macrophages

osteoclasts

reticuloendothelial macrophages

58
Q

what is the function of alveolar macrophages?

A

take up lung surfactant + reduce lung surface tension

59
Q

what is the function of osteoclast macrophages?

A

bone resorption to regulate serum calcium levels

60
Q

what is the function of reticuloendothelial macrophages?

A

iron homeostasis by recycling old, damaged erythrocytes

61
Q

what can inflammation of the spleen lead to?

A

anaemia

= due to impaired iron homeostasis

62
Q

what is the function of LDL and where is it found?

A

synthesised in the liver

= carries cholesterol from liver to rest of the body including arteries

63
Q

what is the function of HDL?

A

synthesised in the liver/small intestine

carries cholesterol from ‘peripheral tissues’ including arteries back to liver

= reverse cholesterol transport

64
Q

what is the function of oxLDL and where is it found?

A

found in vessel wall

= highly inflammatory and toxic forms of LDL which forms due to action of free radicals on LDL (released by active macrophages)

65
Q

where is cholesterol abnormally deposited?

A

in the arterial intima

66
Q

what are the docking molecules of lipoproteins that assist with lipid binding?

A

apoproteins

67
Q

what are contained within LDL micelles?

A

cholesterol esters

68
Q

what is the fate of LDL cholesterol within the sub-endothelial space?

A

binds to matrix proteoglycans and forms a cholesterol-proteoglycan complex

= at a greater risk of modification

69
Q

what extracellular matrix protein binds to LDL cholesterol in the sub-endothelial space?

A

matrix proteoglycans

70
Q

how does proteoglycan-cholesterol binding influence oxidation?

A

increases susceptibility to modification

71
Q

how is the proteoglycan-cholesterol complex modified?

A

modified by free radicals released by activated macrophages

72
Q

what is the fate of the modified LDL?

A

phagocytosis by macrophages leading to foam cell formation

73
Q

what is familial hyperlipidaemia?

A

autosomal dominant condition

that presents w massively elevated serum cholesterol levels

74
Q

what are cholesterol levels in familial hyperlipidaemia?

A

approx >20 mmol/L

much higher than normal levels of 1-5 mmol/L

75
Q

why does familial hyperlipidaemia occur?

A

defect/mutation of the LDL receptor of hepatocytes

= failure to clear LDL from the blood

76
Q

how does familial hyperlipidaemia present?

A

xanthomas (yellow plaques)

increased number of atherosclerotic plaques

77
Q

explain the pathophysiology of familial hyperlipidaemia

A

genetic mutation causes defect in LDL receptor on hepatocyte surface

1) reduced uptake of serum cholesterol into hepatocytes

= reduced cellular cholesterol concentration
= reduced inhibition of HMG-CoA reductase
= increased cholesterol synthesis
= further increases serum cholesterol levels

78
Q

which cell structure has impaired functioning in FH?

A

LDL receptor of hepatocytes

79
Q

what is the LDL receptor responsible for?

A

stimulates endocytosis of cholesterol and subsequent reduction in cellular cholesterol synthesis

80
Q

which enzyme is inhibited due to increased uptake of extracellular cholesterol and what is the implication of this?

A

HMG-CoA reductase (key in cholesterol biosynthesis)

= reduced cellular cholesterol biosynthesis

81
Q

which receptors are sensitive to extracellular serum cholesterol?

A

LDL cholesterol

82
Q

what can be deduced by the fact that in LDL-R negative patients, macrophages still continue to accumulate cholesterol?

A

macrophages, in atherosclerotic plaques, have a secondary LDL receptor!

= takes up oxLDL (‘scavenger receptor’)

83
Q

in which cells does cholesterol synthesis occur?

A

hepatocytes

84
Q

on which cells are LDLRs found?

A

hepatocytes

85
Q

what are the two effects of an LDL receptor mutation?

A

1) reduced sensitivity to serum cholesterol levels

2) reduced inhibition of cellular cholesterol synthesis

86
Q

true of false: LDLs are characterised by the presence of a lipid bilayer?

A

false

= lipid monolayer!

87
Q

why are extremely high levels of HDL cholesterol harmful?

A

extremely high levels of HDL will promote CVD instead

above 2.5 mmol/L

88
Q

how are macrophage scavenger receptors different to LDL receptors?

A

scavenger = not under negative feedback, take up oxLDL

LDL = under negative feedback, take up LDL

89
Q

what are the two types of macrophage scavenger receptors?

A

macrophage scavenger receptor A

macrophage scavenger receptor B

90
Q

what is another term for macrophage scavenger receptor A?

A

MSR-A

= CD204

91
Q

what is another term for macrophage scavenger receptor A?

A

MSR-B

= CD36

92
Q

what does MSR-A bind to?

A

oxidised LDL
dead cells

gram-positive bacteria (e.g. Staphylococcus, Streptococcus)

93
Q

what does MSR-B bind to?

A

oxidised LDL
dead cells

malarial parasites

94
Q

what are the two fates of oxLDL once it is taken up by macrophages?

A

1) stimulates inflammation

2) modified and returned to HDL to be transported back into the liver via reverse cholesterol transport

brs (phase 1b) (71 decks)

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