Biochemistry Lipids

Question 1

Lipoproteins: types

Answer 1

Bad (Non-HDL)

Good

Question 2

Bad (Non-HDL)

Answer 2

Chylomicron and Chylomicron remnant
VLDL Very low Density lipoprotein
IDL – Intermediate Density lipoprotein
LDL – Low density lipoprotein

Question 3

Good

Answer 3

HDL – High density Lipoprotein (cholesterol rich)

Question 4

IDL only present in

Answer 4

Significant amounts in disease – Type 3 hyperlipidaemia

→ Usually not present

Question 5

Chylomicron

Answer 5

Normally present after a meal

Abnormal in fasting state – Type 1 Hyperlipidaemia

Question 6

LDL calculation

Answer 6

TC – HDL – TG/2.2

Question 7

LDL cholesterol target

Answer 7

2 mmol/l

Question 8

NON HDL calculation

Answer 8

TC-HDL

Question 9

Non HDL target

Answer 9

2.5 mmol/l

Question 10

Bad non HDL includes

Answer 10

VLDL and LDL

Question 11

Total cholesterol includes

Answer 11

VLDL, LDL and HDL

Question 12

Metabolism of Exogenous and Endogenous Fat

Answer 12

1. Dietary fat is transported via chylomicrons across the epithelial wall.
2. Lip Lipase hydrolyses FFA
3. FFA (from triglyceride)
4. Chylomicrons and TG produce VLDL = produces IDL to LDL

Question 13

What can go wrong:

Answer 13

1. Eat too much → push too much through pathway
2. Overweight – over production of VLDL (liver)
3. Diabetes: over production
4. Smoke – LDL
5. Genetic – Familial hypercholestreamia

Question 14

HDL Metabolism:

Answer 14

➢ Apo A1 gathers Cholesterol from a peripheral (macrophages) (ABCA1 – gets energy for ATP – aids binding of cholesterol) produces HDL
➢ HDL is taken up by the liver in SRB1 (receptor ligand)
➢ High levels are good.

Question 15

Total Cholesterol
Normal/Average
Ideal/Target

Answer 15

5.9

<4

Question 16

Triglyceride
Normal/Average
Ideal/Target

Answer 16

<1.2

Question 17

HDL Cholesterol
Normal/Average
Ideal/Target

Answer 17

1. 2 (M) 1.4 (F)

1. 2-2

Question 18

LDL Cholesterol
Normal/Average
Ideal/Target

Answer 18

4

<2

Question 19

Non-HDL cholesterol
Normal/Average
Ideal/Target

Answer 19

4.5

<2.5

Question 20

Who to test

Answer 20

➢ CVD or at risk (family history; diabetes; age >50)

Question 21

Measuring TG’s vs total cholesterol process

Answer 21

➢ Fasting essential for accurate measurement of TG’s, but makes little difference to total cholesterol

Question 22

To calculate LDL

Answer 22

➢ Need fasting profile and TG <4 to calculate LDL

Question 23

To pick up mixed hyperlipidaemia

Answer 23

➢ MST measure full profile (Chol; Trig; HDL at least once before starting Rx –to pick up mixed hyperlipidaemia)

Question 24

Measuring Chol and HDL

Answer 24

➢ (and therefore Non-HSL cholesterol) on non-fasting sample

Question 25

Post trauma or MI

Answer 25

➢ NB Chol FALLS by -30% in 24 HRs for 3/12 months after MI

Question 26

Secondary Causes of High cholesterol measure first:

Answer 26

1. Glucose 2. LFT’s 3. U and E 4. TSH 5. Dipstick urine

Question 27

Cholesterol (High)

Answer 27

Accelerated atherosclerosis

Question 28

Low HDL leads to

Answer 28

Accelerated atherosclerosis

Question 29

Triglyceride

Answer 29

2-10 mmol/l – accelerated atherosclerosis | >10 mmol/L – acute pancreatitis

Question 30

Secondary Causes of High cholesterol

Answer 30

``` Diabetes Liver disease Renal disease ➢ Nephrotic syndrome Hypothyroidism Alcohol HIV Anorexia Drugs: ➢ Ani retrovirals ➢ Retinoids ➢ Steroids (anabolic) ➢ Antidepressants ➢ Pscyhotrophics ```

Question 31

Test before treating

Answer 31

1. Glucose 2. LFT’s 3. U and E 4. TSH 5. Dipstick urine

Question 32

Primary (Monogenic) Hyperlipidaemia

Answer 32

➢ Familial Hypercholestraemia ➢ Familial combined hyperlipidaemia ➢ Type III hyperlipidaemia ➢ Severe Hypertriglyceride

Question 33

Familial Hypercholestraemia: Genetics

Answer 33

Autosomal dominant, 1:500

Question 34

Familial Hypercholestraemia:Cholesterol typical levels

Answer 34

>7.5

Question 35

Familial Hypercholestraemia: Triglyceride levels

Answer 35

Normal

Question 36

Familial Hypercholestraemia: Defect seen in one of the following genes

Answer 36

LDL receptor Apo B PcSK9 defect (breakdown role)

Question 37

Familial Hypercholestraemia:Signs

Answer 37

Tendon xanthomata | Corneal arcus

Question 38

Familial Hypercholestraemia: CHD event by and in

Answer 38

50% CHD events by age of 55 if untreated

Question 39

Familial Hypercholestraemia:Diagnosis in

Answer 39

25% of patients

Question 40

Familial Hypercholestraemia: Prognosis

Answer 40

Normal lifespan with treatment

Question 41

Familial Hypercholestraemia: Rx

Answer 41

Diet and statins

Question 42

Familial Combined Hyperlipidaemia:Genetics

Answer 42

Autosomal dominant

Question 43

Familial Combined Hyperlipidaemia:Cholesterol levels

Answer 43

Typically 5-10 mmol/L

Question 44

Familial Combined Hyperlipidaemia:Triglyceride levels

Answer 44

5-10 mmol/L

Question 45

Familial Combined Hyperlipidaemia:Prognosis

Answer 45

Aggressive CHD in middle age

Question 46

Familial Combined Hyperlipidaemia:Treatment

Answer 46

statins

Question 47

Type 3 Hyperlipideamia: Cholesterol levels

Answer 47

5-15 mmol/L

Question 48

Type 3 Hyperlipideamia: Causes/Genetics

Answer 48

Apo E2:E2 plus (doesn’t bind to receptor normally) | Alcohol XS or poor diet

Question 49

Type 3 Hyperlipideamia: Signs

Answer 49

Palmar crease xanthomata | Periheral vascular disease also

Question 50

Type 3 Hyperlipideamia: Consequences

Answer 50

CHD | PVD

Question 51

Type 3 Hyperlipideamia: Treatment

Answer 51

Statin and /or Fibrates

Question 52

Type 3 Hyperlipideamia:Epi

Answer 52

Rare (need another factor e.g. diabetes/poor diet) to trigger process

Question 53

High Triglyceride: Triglyceride levels

Answer 53

>10 mmol/L

Question 54

High Triglyceride:Pathology

Answer 54

Lipoprotein lipase deficiency (Type 1 hyperlipideamia)

Question 55

High Triglyceride: Signs

Answer 55

Eruptive xanthomata | Lipaemia retinalis

Question 56

High Triglyceride: Risk of

Answer 56

Acute pancreatitis

Question 57

High Triglyceride: Treatment

Answer 57

Fibrates

Question 58

Drug treatment:

Answer 58

1. HMGCoA reductase inhibitors (Statins) 2. Fibrates 3. Cholesterol absorption inhibitor (Ezetimibe) (2nd line for high cholesterol) 4. Fish oils (Omacor) (2nd line high triglyceride) 5. Bile acid sequestrants

Question 59

Drugs In Development:

Answer 59

➢ MTP inhibitors (reduce VLDL synthesis) – homozygous hypercholestraemia ➢ Glybera (Lipoprotein lipase gene replacement) – for patients with severe recurrent pancreatitis ➢ CETP inhibitors (raise HDL) ➢ PCSK9 inhibitors (increase LDL clearance)