metabolic 4: lipid disorders

Question 1

what are the sources of lipids?

Answer 1

Sources of Lipids
Exogenous: From the gut to tissues – ingested lipids
Endogenous: From the liver to tissues – synthesised lipids

Question 2

what are the 5 classes of lipoprotein ?

Answer 2

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

Question 3

describe the endogenous lipid cycle

Answer 3

Lipids synthesised in the liver when more CHO available than needed for energy and glycogen storage.
Lipid needs to be stored away from the liver
They are exported as VLDL
Synthesis of Triglyceride
Export as VLDL
Take up particles when triglyceride removed
LDL delivers cholesterol to peripheral cells

Question 4

describe the exogenous lipid cycle

Answer 4

Dietary lipids are largely stored in adipose tissue following absorption although some is used for energy in muscle
Cholesterol and fatty acids from digestion are absorbed into intestinal mucosa cells
Re-esterified to cholesterol esters and triglyceride and packaged with phospholipids and lipoproteins
Secreted into the lymphatic system as chylomicrons
Enter the system circulation via the thoracic duct
Lipoprotein lipase from capillary walls hydrolyses triglyceride to fatty acids and glycerol
Fatty acids taken up by adipose or muscle cells
Glycerol is processed by the liver – re-utilised to make TG or converted to glucose
The chylomicron remnant is taken up by the LDL receptors on the liver

Question 5

what is the role of the liver in the exogenous pathway?

Answer 5

The liver produces both the bile acids and cholesterol involved in the creation of micelles for lipid absorption from the gut

The liver also takes up chylomicron remnant particles when most of the triglyceride has been removed

Question 6

what are the healthy limits for a lipid profile ?

Answer 6

An optimal serum cholesterol level is 5.0 mmol/L in individuals without cardiovascular disease

The upper limit of normality for fasting serum triglycerides is 1.7 mmol/L

The lower limit of normality for serum HDL-C is 0.9 mmol/L in men and 1.2 mmol/L in women

Question 7

what are the signs of a primary dyslipidaemia ?

Answer 7

Exclude secondary causes of dyslipidaemia first
Often a family history of early cardiovascular disease
May be monogenic, or polygenic
May still respond to lifestyle modification
May be due to mutations of proteins associated with lipid metabolism

Question 8

what are the features of familial hypercholestolaemia

Answer 8

Autosomal dominant disorder of lipid metabolism
One mutant gene is enough!
Affects up to 1 in 200 in UK population
Features:
Raised blood cholesterol (specifically low density lipoprotein cholesterol)
Tendon and skin xanthomata (deposits of cholesterol)

Question 9

what genes are involved in FH?

Answer 9

APOB
the protein that binds to the LDL receptor 9 mutations described
PCSK9
a protein involved in receptor degradation 6 mutations described
LDLR
Over 1000 mutations spread throughout gene described

Question 10

what makes up the metabolic syndrome?

Answer 10

1) visceral obesity
2) hyperinsulinaemia
3) hemostatic disorders
4) HTN
5) reduce glucose tolerance
6) lipid disorder

Question 11

list risk factors for CHD

Answer 11

obesity 
HTN
inflammation
Socio-economic status 
smoking 
genetic component 
high lipids

Question 12

what score is used in primary care for CVD risk?

Answer 12

QRISK2

is there a QRISK3 coming?

Question 13

list some treatment options for dyslipidaemia

Answer 13

statins 
bile acid sequestrant 
cholesterol absorption inhibitor 
PCSK inhibitors 
fibric acid derivatives 
fish oil

Question 14

mechanism of statins?

Answer 14

HMG-coA reducatase inhibitor

Question 15

mechanism of PCSK9 inhibitors

Answer 15

Inhibiting PCSK9, thereby blocking PCSK9–LDL-R interaction, increases LDL-R expression and increases LDL-C clearance