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Case 4 > Lipids and Cardiovascular Disease > Flashcards

Lipids and Cardiovascular Disease Flashcards

1
Q

What are lipids chemically characterised by

A

Hydrophobic properties

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2
Q

Which lipids are relevant to CVD

A

Cholesterol, fatty acids, triacylglycerol (triacylceride) and phospholipids

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3
Q

What do and don’t lipids dissolve in

A

Dissolve in organic solvents (alcohols) but not aqueous solvents

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4
Q

What is cholesterol

A

An alcohol, multi-ring structure (free cholesterol) which possesses ester fatty links to fatty acids in the body

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5
Q

What does the fact that cholesterol in the body is amphiphilic and hydrophobic mean

A

It is completely insoluble

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6
Q

What do fatty acids differ in

A

Chain lengths and types of bonds

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7
Q

Describe liquid fatty acids

A

More polyunsaturated (more double bonds) meaning that they are less linear.

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8
Q

Describe solid fatty acids

A

They are saturated

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9
Q

Which fatty acids are essential

A

Eicosanoids which contain prostaglandins, thomboxanes and leukotriens. Alpha-linolenic acid (omega-3) and linoleic acid (omega-6) are essential fatty acids

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10
Q

What are trans fatty acids

A

Hydrogenated fats

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11
Q

How are trans fats produced

A

Synthetically by hydrogenation changes. The conformation change from cis to trans fatty acids seems to be harmful

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12
Q

What do trans fats do in the body

A

Raise levels of LDL and lower levels of HDL, therefore the use of trans fats is being reduced

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13
Q

What features do phosopholipids have in common with triglycerides

A

They have a glycerol backbone and two fatty acids (non-polar) but also have a phosphate group (polar)

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14
Q

What does polarity determine

A

How fats are distributed within circulation

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15
Q

How are fats transported

A

As lipoproteins

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16
Q

Describe the structure of lipoproteins

A

Shell and core. Inside the core there are hydrophobic lipids (cholesterol ester and triglyceride), inside the shell there are lipids with a polar component (phospholipids have phosphate group to outside, cholesterol have alcohol group to outside) which forms the shell on the outside which interacts with the plasma

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17
Q

Describe the protein component of lipoproteins

A

Protein component which are specialised proteins which are imbedded in the membrane and have a polar exterioir and non-polar interioir

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18
Q

How many major lipoproteins are there

A

5

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19
Q

How are the different lipoproteins defined

A

By their density, they precipitate to different extents depending on their composition

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20
Q

What are the most dense lipoproteins

A

HDL (high density lipoproteins)

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21
Q

What are the least dense lipoproteins

A

Chylomicrons

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22
Q

What is the major difference between HDL and chylomicrons

A

Chylomicrons are triglyceride and HDL are protein. Protein makes HDL dense and triglycerides make chylomicrons buoyant

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23
Q

Describe the proteins in HDL

A

Apo A1 receptor ligand

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24
Q

Describe the proteins in chylomicrons

A

Apo B48 receptor ligand (produced by splicing of messenger RNA)

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25
Describe the proteins in LDL
Apo B100 receptor ligand
26
Describe the proteins in VLDL
ApoCII cofactor lipoprotein lipase
27
Describe the proteins in IDL
ApoE receptor ligand
28
What is the function of chylomicrons
Transport triglycerides from the digestive system in the gut to the liver
29
How are chylomicrons absorbed into the liver
Through lacteals
30
What does the liver do with the triglycerides in chylomicrons
Makes VLDL
31
What is the function of VLDL
Transports triglyceride from the liver to the tissue
32
What is IDL
A remnant from chylomicrons
33
What is VLD
An intermediate between chylomicrons and LDL
34
What is the function of LDL
Transports cholesterol from the liver to tissues
35
What is the function of HDL
Transports cholesterol from the tissues back to the liver (reverse cholesterol transport)
36
What are the 3 main lipid pathways
Exogenous pathway, endogenous pathway and reverse cholesterol pathway
37
Describe the exogenous pathway
Chylomicrons are produced from triglycerides in the gut and the circulate through capillaries once absorbed into the circulation. Triglyceride is taken up by enzyme lipoprotein lipase and bind to free fatty acid which becomes adipose tissue. Triglycerides are lost leaving chylomicron remnants which is taken back up into the liver and is recycled
38
Describe the endogenous pathway
Occurs internally from the liver. The liver synthesises VLDL which is a triglyceride rich lipoprotein. Triglyceride then leaves the circulation by the action of the enzyme lipoprotein lipase. VLDL then becomes IDL. IDL then is converted to LDL after being taken up in the liver via the enzyme hepatic lipase. The LDL then transports cholesterol to tissue, particularly muscle and other tissues that require cholesterol
39
Describe the reverse cholesterol pathway
Empty HDL picks up cholesterol from tissues, particularly muscle, and transports it back to the liver in a process called reverse cholesterol transport pathway
40
What are lipids a risk factor for
Atherosclerosis
41
What cores do atherosclerotic plaques have
Lipid cores
42
What is the evidence for lipids and CVD
Pathology, epidemiology, inborn errors, effects of treatment
43
Describe the formation and course of plaques
The process of atherosclerosis takes years. To begin with there is endothelial damage then a fatty streak forms then a plaque forms with a lipid core. Plaques tend to rupture as they are large and have a lipid core
44
Describe a grade I plaque
Foam cells
45
Describe a grade II plaque
Fatty streak
46
Describe a grade III plaque
Extracellular fatty streak
47
Describe a grade IV plaque
Lipid core
48
Describe a grade V plaque
Atherosclerotic plaque lipid core embedded in fibrosis
49
Describe a grade VI plaque
Complicated atherosclerotic plaque (plaque rupture, thrombosis, haemorrhage)
50
What does HDL appear to be
Protective against CHD or is a marker of something else which is protective
51
What is familial hypercholesterolaemia
An inborn error which affects LDL receptors
52
What happens if you have no LDL receptors (FH homozygotic)
You develop heart disease as a child
53
What happens if you have one copy the LDL receptor gene (FH heterozygotic)
You have half the number of receptors meaning that you have a significant risk of developing CVD
54
What is FH a model disorder for
Cell surface receptors, receptor mediated endocytosis and atherosclerosis
55
What is an LDL receptor
A transmembrane protein with an LDL binding component
56
Describe the action of LDL receptors
APOB of the LDL binds to the receptor which results in LDL being removed from the blood. LDL is broken down which releases cholesterol carried by LDL
57
What is cholesterol released from LDL converted to
Bile, then excreted
58
What does the LDL receptor recycle
PCSK9
59
Describe the dominancy of FH
It is autosomal dominant
60
When does FH occur
When there is a mutation in the LDL receptor pathway
61
When does CHD usually develop in those with FH
Around 20 years early
62
What treatment is effective in reducing CVD
Statins
63
What are the clinical signs of FH
Corneal arcus, xanthelasma, tendon xanthoma. The clinical signgs of FH are due to hypercholesterolemia
64
Why do we treat hyperlipidaemia
To reduce CHD rates
65
What are effective in reducing high cholesterol
Statins
66
How do statins work
They limit the activity of HMG-CoA reductase and therefore inhibit cholesterol synthesis. The decrease in cholesterol means that cells upregulate cholesterol receptors and therefore remove cholesterol from circulation
67
Via what mechanism do statins act
Competitive inhibition
68
What are the 4 different statins available in the UK
Atorvastatin, simvastatin, pravastatin and rosuvastatin
69
What statin is used in children
Pravastatin
70
Which statin is the most intensive and expensive
Rosuvastatin
71
What is a possible side effect of statins
Myositis (inflammation and degeneration of muscle tissue)
72
Who needs to take statins
Anyone whose risk is more than 10% for the next 10 years
73
What are other lipid lower drugs
Fibrates, bile acid sequestrants, cholesterol uptake inhibitors, cholesterol ester transfer protein inhibitors (all more specialist)
74
Who gets the highest benefit from statins
Patients who have already had a heart attack and are using statins as a secondary prevention
75
What do statins do to plaques
Stabilise plaques and prevent them from rupturing

Case 4 (7 decks)

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