atherosclerosis

Question 1

what are the 3 layers of arteries

Answer 1

tunica intima
tunica media
tunica adventitia
the three layers communicate to form a system that regulates its function.

Question 2

describe the intima

Answer 2

endothelial cells linked by tight junctions lying on a basement membrane.
resistant to apoptosis and rarely divide

Question 3

describe the media

Answer 3

layers of perforated elastic laminae with smooth muscle cells in between.
bound by the internal and external elastic laminae

Question 4

describe the adventitia

Answer 4

consists of connective tissue and contains fibroblasts, leucocytes, nerves, lymphatics and its vasa vasorum

Question 5

describe large arteries

Answer 5

prominent elastic laminae in the media. so called elastic arteries. elastic recoil aids continuous flow

Question 6

describe medium sized arteries and small

Answer 6

eg coronary.

classified as muscular arteries since the media is largely smooth muscle but little elastic.

Question 7

define atherosclerosis

Answer 7

a disease of the intima of large and medium sized arteries. focal thickenings of intima called plawues are formed which are deposits of fibrous tissues and lipids.

Question 8

define arteriosclerosis

Answer 8

loss of elasticity and physical hardening of the arterial wall from any cause. often accompanied by calcification. one cause is atherosclerosis.

Question 9

name an epidemiological study that looked at the risk factors for atherosclerosis

Answer 9

the Framingham study

Question 10

4 major positive risk factors for atherosclerosis

Answer 10

• hyperlipidaemia
• cigarette smoking
• hypertension
• diabetes mellitus

Question 11

10 minor positive risk factors for atherosclerosis

Answer 11

1 - old age
2 - family history (polygenic inheritance)
3 - male gender (oestrogens may protect in premenopause)
4 - high sat fat diet
5 - stressful and sedentary lifestyles
6 - obesity 
7 - excess alcohol 
8 - low birth weight
9 - low socioeconomic status
10 - possibly infections like chlamidya

Question 12

3 negative risk factors for atherosclerosis

Answer 12

1 - high levels of circulating HDLs
2 - moderate alcohol consumption of 2units a day
3 - cardiovascular fitness.

Question 13

general structure of lipoproteins

Answer 13

a lipid core of triglycerides, cholesterol, cholesterol esters and phospholipids surrounded by apolipoproteins

Question 14

what do lipoproteins do

Answer 14

transfer the lipids they carry into cells through 2 receptor systems

Question 15

what are the 2 uptake systems for lipids carried by lipoproteins

Answer 15

1 - LDL receptor pathway - most active in hepatocytes. responsible for cholesterol breakdown. underactivity leads to hypercholesterolaemia.

2 - scavenger receptor pathway - used by macrophages to take up modified lipoproteins (eg oxidised in atherosclerotic plaques). pathway is unregulated and so leads to uncontrolled accumilation of cholesterol so macrophages - foam cells then burst.

Question 16

what’s dyslipoproteinaemia?

Answer 16

a collective name for an abnormality in the constitution or concentration of lipoproteins in the blood. can be inherited - familial hypercholesterolaemia. or secondary to other disease (diabetes mellitus or hypothyroidism)

Question 17

what types of dyslipoproteinaemia predispose for atherosclerosis

Answer 17

• increased: cholesterol, total triglycerides, LDL and lipoprotein a.
  especially cholesterol - one study suggested a 10% drop in serum levels may result in a 15% drop in deaths due to CHD.
• decreased HDL

Question 18

3 atheroscerotic mice studies

Answer 18

1 - deficient in lipoprotein component of apoE or for the LDL receptor results in fast dev of atherosc.

2 - deficient in scavenger receptors SR-A or CD36 caused modest drop in atherosclerotic lesions.

3 - those that cannot store cholesterol due to deficiency in acyl-cholesterol acyl transferase (ACAT) also have a reduction in atherosclerotic lesions.

Question 19

atherosclerosis pathogenesis overview

Answer 19

several interacting processes. ost components of cell wall disrupted. initiates chronic inflammation.

Question 20

6 key changes in vessel walls in atherosclerosis

Answer 20

1 - endothelial cell injury or dysfunction
2 - monocyte migration into plaque and maturation to macrophages
3 - smooth muscle cell activation
4 - lipoprotein infiltration
5 - t-lymphocyte migration into the plaque
6 - platelet adherence

Question 21

causes and results of endothelial damage/dysfunction in atherosclerosis

Answer 21

causes - haemodynamic forces, chemical insults, cytokines.

results - altered permeability (so lipid infiltration), adhesion molecules expression (selectins, VCAM-1, ICAM-1) chemokine/mitogn expression (MCP-1, IL1, IL8, M-CSF) so leukocyte infiltration, activation of thrombosis

Question 22

cause of monocyte recruitment in atherosclerosis, effect?

Answer 22

cause - chemotaxis, adhesion, migration into intima, maturation to macrophage.

result - increase chemokine expression, present antigen to T cells, activate endothelial cells, oxidise and scavenge lipids, activate smooth muscle cells (PDGF, ROS), modify matrix with collagenase, promote coagulation (tissue factor)

Question 23

what caused smooth muscle activation in the media and what results

Answer 23

macrophages, platelets and endothelial cells all produce growth factors (PDGF, FGF) and ROS that activate SMCs.

result - proliferation, migration to intima, change from contractile to synthetic (ECM producing) phenotype. secrete ECM and enzymes for matrix remodelling.

Question 24

what oxidises lipoproteins in plaques

Answer 24

ROS and enzymes from platelets, macrophages and endothelial cells.

Question 25

what do oxidised lipoproteins do

Answer 25

1- macrophage chemoattractants
2 - phagocytosed by macrophages -foam cells
3 - stim various cells to secrete cytokines and growth factors
4 - induce dysfunction/apoptosis in SM, macrophages, and endothelium
5 - may be immunogenic
6 - inhibit plasminogen activation

Question 26

evidence for relevant role of lipoproteins

Answer 26

1 - anti-oxidants ie vitamin E and NO inhibit their oxidation and also reduce the risk of myocardial infarc

2 - cholesterol lowering drugs (eg statins) decrease freq of coronary artery atherosclerosis

Question 27

result of T lymphocyte migration into the plaque

Answer 27

may recognise oxidised lipoproteins as antigens and hence activate immune responses inc cytotoxic killing of cells in the plaque. may be the cause of necrotic areas.

Question 28

role of platelets in early and advanced lesions

Answer 28

early - evidence they adhere transiently to dysfunctional endothelium, release PDGF to activate SMCs.

advanced - if plaques ulcerate or rupture then they are involved in thrombosis

Question 29

4 stages of atherosclerotic lesions

Answer 29

1 - isolated monocytes - from soon after birth
2 - fatty streaks or dots
3 - fibro-fatty plaques
4 - complicated plaques

Question 30

describe fatty streaks

Answer 30

common by second decade of life. clusters of lipid laden SMCs and foam cells. no sig pathological effects

Question 31

describe fibrofatty plaques

Answer 31

principally in abdominal aorta, coronary arteries, carotids, circle of willis. 3rd or 4th decade in men, later in women.

-raised yellow/white plaques. possibly atrophy of media. 3 regions in the intima:

1 - fibrous cap - collagen, SMCs, macrophages, T cells
2 - lipid core - foam cells, necrosis and extracellular lipid in more advanced lesions
3 - shoulder of the cap - foam cells, SCs, t cells and angiogenesis.

Question 32

describe complicated plawues

Answer 32

• may become calcified
• may expand if new vessels haemorrhage
• may rupture or ulcerate, particularly if rich in leucocytes or angiogenesis. embolism.
• aneurysm due to thinning of the media and fragmentation of the elastic laminae.

Question 33

what is diffuse intimal thickening

Answer 33

separate from atherosclerosis but can coexist. build up of SMCs, collagen and elastin due to advancing age, hypertension and chronic inflam.

Question 34

atherosclerosis death?

Answer 34

its complications cause about 50% of all deaths in the western world.

Question 35

the problem with atherosclerosis

Answer 35

its silent and progressive, only becoming symptomatic when somehting serious happens - rupture, ahemorrhage or embolism.

Question 36

different results of atherosclerosis in small and large vessels?

Answer 36

small - gradual stenosis or occlusion

large - embolisation of thrombus formed on plaque, aneurysm.

Question 37

5 most clinically important results of atherosclerosis

Answer 37

1 - ischaemic heart disease (angina, MI, heart failure)
2 - peripheral vascular disease (intermittent claudication, gangrene)
3 - cerebrovascular disease (transient ischaemia, infarc, stroke)
4 - aneurysm (esp abdominal aorta)
5 - renal failure