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Flashcards in Biochemistry Lipids Deck (59):
1

Lipoproteins: types

Bad (Non-HDL)

Good

2

Bad (Non-HDL)

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

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Good

HDL – High density Lipoprotein (cholesterol rich)

4

IDL only present in

Significant amounts in disease – Type 3 hyperlipidaemia
→ Usually not present

5

Chylomicron

Normally present after a meal
Abnormal in fasting state – Type 1 Hyperlipidaemia

6

LDL calculation

TC – HDL – TG/2.2

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LDL cholesterol target

2 mmol/l

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NON HDL calculation

TC-HDL

9

Non HDL target

2.5 mmol/l

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Bad non HDL includes

VLDL and LDL

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Total cholesterol includes

VLDL, LDL and HDL

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Metabolism of Exogenous and Endogenous Fat

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

13

What can go wrong:

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

14

HDL Metabolism:

➢ 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.

15

Total Cholesterol
Normal/Average
Ideal/Target

5.9
<4

16

Triglyceride
Normal/Average
Ideal/Target

<1.2

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HDL Cholesterol
Normal/Average
Ideal/Target

1.2 (M) 1.4 (F)
1.2-2

18

LDL Cholesterol
Normal/Average
Ideal/Target

4
<2

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Non-HDL cholesterol
Normal/Average
Ideal/Target

4.5
<2.5

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Who to test

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

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Measuring TG’s vs total cholesterol process

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

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To calculate LDL

➢ Need fasting profile and TG <4 to calculate LDL

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To pick up mixed hyperlipidaemia

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

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Measuring Chol and HDL

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

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Post trauma or MI

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

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Secondary Causes of High cholesterol measure first:

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

27

Cholesterol (High)

Accelerated atherosclerosis

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Low HDL leads to

Accelerated atherosclerosis

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Triglyceride

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

30

Secondary Causes of High cholesterol

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

31

Test before treating

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

32

Primary (Monogenic) Hyperlipidaemia

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

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Familial Hypercholestraemia: Genetics

Autosomal dominant, 1:500

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Familial Hypercholestraemia:Cholesterol typical levels

>7.5

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Familial Hypercholestraemia: Triglyceride levels

Normal

36

Familial Hypercholestraemia: Defect seen in one of the following genes

LDL receptor
Apo B
PcSK9 defect (breakdown role)

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Familial Hypercholestraemia:Signs

Tendon xanthomata
Corneal arcus

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Familial Hypercholestraemia: CHD event by and in

50% CHD events by age of 55 if untreated

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Familial Hypercholestraemia:Diagnosis in

25% of patients

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Familial Hypercholestraemia: Prognosis

Normal lifespan with treatment

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Familial Hypercholestraemia: Rx

Diet and statins

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Familial Combined Hyperlipidaemia:Genetics

Autosomal dominant

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Familial Combined Hyperlipidaemia:Cholesterol levels

Typically 5-10 mmol/L

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Familial Combined Hyperlipidaemia:Triglyceride levels

5-10 mmol/L

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Familial Combined Hyperlipidaemia:Prognosis

Aggressive CHD in middle age

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Familial Combined Hyperlipidaemia:Treatment

statins

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Type 3 Hyperlipideamia: Cholesterol levels

5-15 mmol/L

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Type 3 Hyperlipideamia: Causes/Genetics

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

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Type 3 Hyperlipideamia: Signs

Palmar crease xanthomata
Periheral vascular disease also

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Type 3 Hyperlipideamia: Consequences

CHD
PVD

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Type 3 Hyperlipideamia: Treatment

Statin and /or Fibrates

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Type 3 Hyperlipideamia:Epi

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

53

High Triglyceride: Triglyceride levels

>10 mmol/L

54

High Triglyceride:Pathology

Lipoprotein lipase deficiency (Type 1 hyperlipideamia)

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High Triglyceride: Signs

Eruptive xanthomata
Lipaemia retinalis

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High Triglyceride: Risk of

Acute pancreatitis

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High Triglyceride: Treatment

Fibrates

58

Drug treatment:

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

59

Drugs In Development:

➢ 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)

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