302 Lipid disorders and metabolic syndrome Flashcards

1
Q

Describe the structure of a lipoprotein

A

They have a central hydrophobic core of non-polar lipids (mostly cholesterol esters and triglycerides) surrounded by a hydrophilic membrane

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2
Q

What are lipoproteins?

A

A water soluble version of a lipid

-formed when apolipoproteins and other amphipathic molecules surround a lipid to make it water soluble

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3
Q

What are the 5 major classes of lipoprotein

A

Chylomicrons (CM)
Very low density lipoprotein (VLDL)
Intermediate density lipoprotein (IDL)
Low density lipoprotein (LDL)
High density lipoprotein (HDL)

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4
Q

Why do lipoproteins vary in size and flotation density?

A

Triglyceride content
Cholesterol content
Apo-lipoprotein content
Stage in circulation through the body

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5
Q

What is the function of lipoprotein lipase?

A

It breaks down the fatty acids in both the exogenous and endogenous pathway

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6
Q

What happens to the endogenous lipid cycle during fasting?

A

Lipids are stored away from the liver and exported as VLDL

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7
Q

Which lipid delivers cholesterol to peripheral tissues?

A

LDL

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8
Q

Which enzyme is the target for statins?

A

HMG CoA reductase

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9
Q

What is the function of N-SREBP?

A

It’s a transcription factor that helps regulate cholesterol synthesis

It causes more receptors to be formed that will bring more LDL into the cell

It’s turned on when cholesterol is low

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10
Q

Where are HDL particles secreted?

A

In the intestines and the liver

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11
Q

Why is HDL considered protective?

A

It goes into the lipid plaques created, takes up some cholesterol and takes it to the liver to be recycled and disposed of

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12
Q

What is the endogenous pathway of lipid metabolism?

A

VLDL is formed in the liver from triglycerides and cholesterol esters. These can be hydrolysed by lipoprotein lipase to form IDL or VLDL remnants

VLDL remnants are cleared from the circulation or incorporated into LDL

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13
Q

What is the exogenous pathway of lipid metabolism?

A

Dietary cholesterol and fatty acids are absorbed. Triglycerides are formed in the intestinal cell from free fatty acids and glycerol and cholesterol is esterified

Triglycerides and cholesterol combine to form chylomicrons

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14
Q

Where are dietary lipids stored?

A

In adipose tissue following absorption

Some is used for energy in muscles

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15
Q

How do lipid from the exogenous lipid pathway enter systemic circulation?

A

They are secreted into the lymphatic system as chylomicrons and then enter the systemic circulation via the thoracic duct

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16
Q

Where is lipoprotein lipase found?

A

-On the surface of cells that line capillaries
-Within muscles
-In adipose tissue

17
Q

What is hepatic lipase?

A

It contributes to the regulation of triglycerides

18
Q

What is the co-factor for lipoprotein lipase?

19
Q

What are the substrates for Lipoprotein lipase?

A

Chylomicron and VLDL

20
Q

What regulates lipoprotein lipase?

A

Feeding, fasting, and exercise

21
Q

What are the substrates for hepatic lipase?

A

IDL, HDL, and LDL

22
Q

In which tissues does lipoprotein lipase work in?

A

In the adipose tissue and skeletal muscle

23
Q

What is the optimal serum cholesterol level?

A

<5.0 mmol/L

24
Q

What is the healthy limit for serum triyglicerides?

A

1.7 mmol/L (fasting)

25
What is the lower limit of serum HDL?
Men: 0.9 mmol/L Women: 1.2 mmol/L
26
What is familial hypercholesterolaemia (FM)
An autosomal dominant disorder of lipid metabolism Features: -Raised blood cholesterol (especially LDL) -Tendon and skin xanthomata -Arcus senilis
27
What is Arcus senilis?
A ring of cholesterol around the iris
28
What is the difference between heterozygous and homozygous familial hypercholesterolaemia (FH)?
Homozygous is a lot more severe
29
What are the mutations that cause familial hypercholesterolaemia (FH)?
APOB - The protein that binds to LDL PCSK9 - A protein involved in receptor degradation LDLR - LDL receptor (most common)
30
What are some secondary dyslipidaemias that cause hypertriglyceridaemia?
Obesity Diabetes mellitus Excess alcohol Renal failure Gout Drug treatment (thiazides, beta blockers, retinoic acid derivatives, oestrogen therapy)
31
What are some secondary dyslipidaemias that causes hypercholesterolaemia?
Hypothyroidism Nephrotic syndrome High saturated fat diet Cholestatic liver disease Anorexia nervosa
32
Which fat increases cardiovascular risk?
Visceral fat
33
What is metabolic syndrome?
A collection of risk factors for cardiovascular disease -Reduced glucose tolerance -Visceral obesity -Haemostatic disorders -Hyperinsulinemia -Hypertension -Lipid disorders
34
When is a person said to have metabolic syndrome?
Waist circumference Men (Europid) > 94 cm (> 90 in S Asians) Women (Europid) > 80 cm (> 80 in S Asians) Plus any two of: Fasting Serum Triglycerides 1.7 mmol/L or treatment Serum HDL-cholesterol Men < 1.03 mmol/L Women < 1.29 mmol/L Blood pressure -130/85 mm Hg or treatment Fasting glucose - 5.6 mmol/L or diagnosis of DM
35
What is visceral/ ectopic fat a risk factor for?
Heart disease -Heart failure, valve diseases, arrhythmias Brain -Stroke, Brain size, cognitive function, dementia Respiratory -Sleep apnoea Cancers Diabetets Others -Bone density, PCOS, HIV
36
What is the Q risk 2 score for?
Identifies who is at risk of coronary disease
37
What are some drug treatments for dyslipdaemias?
-Statins (HMGCoA reductase inhibitor) -Bile acid sequestrant (Bind bile salts) -Cholesterol absorption inhibitor Eg. Ezetimibs -PCSK inhibitor (block LDLR catabolism) -Fibric acid derivatives (LPL stimulation) -Fish oil (ω3-FAs) (Reduced hepatic synthesis)