Biochemistry Lipids Flashcards
Lipoproteins: types
Bad (Non-HDL)
Good
Bad (Non-HDL)
Chylomicron and Chylomicron remnant
VLDL Very low Density lipoprotein
IDL – Intermediate Density lipoprotein
LDL – Low density lipoprotein
Good
HDL – High density Lipoprotein (cholesterol rich)
IDL only present in
Significant amounts in disease – Type 3 hyperlipidaemia
→ Usually not present
Chylomicron
Normally present after a meal
Abnormal in fasting state – Type 1 Hyperlipidaemia
LDL calculation
TC – HDL – TG/2.2
LDL cholesterol target
2 mmol/l
NON HDL calculation
TC-HDL
Non HDL target
2.5 mmol/l
Bad non HDL includes
VLDL and LDL
Total cholesterol includes
VLDL, LDL and HDL
Metabolism of Exogenous and Endogenous Fat
- Dietary fat is transported via chylomicrons across the epithelial wall.
- Lip Lipase hydrolyses FFA
- FFA (from triglyceride)
- Chylomicrons and TG produce VLDL = produces IDL to LDL
What can go wrong:
- Eat too much → push too much through pathway
- Overweight – over production of VLDL (liver)
- Diabetes: over production
- Smoke – LDL
- Genetic – Familial hypercholestreamia
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.
Total Cholesterol
Normal/Average
Ideal/Target
5.9
<4
Triglyceride
Normal/Average
Ideal/Target
<1.2
HDL Cholesterol
Normal/Average
Ideal/Target
- 2 (M) 1.4 (F)
1. 2-2
LDL Cholesterol
Normal/Average
Ideal/Target
4
<2
Non-HDL cholesterol
Normal/Average
Ideal/Target
4.5
<2.5
Who to test
➢ CVD or at risk (family history; diabetes; age >50)
Measuring TG’s vs total cholesterol process
➢ Fasting essential for accurate measurement of TG’s, but makes little difference to total cholesterol
To calculate LDL
➢ Need fasting profile and TG <4 to calculate LDL
To pick up mixed hyperlipidaemia
➢ MST measure full profile (Chol; Trig; HDL at least once before starting Rx –to pick up mixed hyperlipidaemia)
Measuring Chol and HDL
➢ (and therefore Non-HSL cholesterol) on non-fasting sample
Post trauma or MI
➢ NB Chol FALLS by -30% in 24 HRs for 3/12 months after MI
Secondary Causes of High cholesterol measure first:
- Glucose
- LFT’s
- U and E
- TSH
- Dipstick urine
Cholesterol (High)
Accelerated atherosclerosis
Low HDL leads to
Accelerated atherosclerosis
Triglyceride
2-10 mmol/l – accelerated atherosclerosis
>10 mmol/L – acute pancreatitis
Secondary Causes of High cholesterol
Diabetes Liver disease Renal disease ➢ Nephrotic syndrome Hypothyroidism Alcohol HIV Anorexia Drugs: ➢ Ani retrovirals ➢ Retinoids ➢ Steroids (anabolic) ➢ Antidepressants ➢ Pscyhotrophics
Test before treating
- Glucose
- LFT’s
- U and E
- TSH
- Dipstick urine
Primary (Monogenic) Hyperlipidaemia
➢ Familial Hypercholestraemia
➢ Familial combined hyperlipidaemia
➢ Type III hyperlipidaemia
➢ Severe Hypertriglyceride
Familial Hypercholestraemia: Genetics
Autosomal dominant, 1:500
Familial Hypercholestraemia:Cholesterol typical levels
> 7.5
Familial Hypercholestraemia: Triglyceride levels
Normal
Familial Hypercholestraemia: Defect seen in one of the following genes
LDL receptor
Apo B
PcSK9 defect (breakdown role)
Familial Hypercholestraemia:Signs
Tendon xanthomata
Corneal arcus
Familial Hypercholestraemia: CHD event by and in
50% CHD events by age of 55 if untreated
Familial Hypercholestraemia:Diagnosis in
25% of patients
Familial Hypercholestraemia: Prognosis
Normal lifespan with treatment
Familial Hypercholestraemia: Rx
Diet and statins
Familial Combined Hyperlipidaemia:Genetics
Autosomal dominant
Familial Combined Hyperlipidaemia:Cholesterol levels
Typically 5-10 mmol/L
Familial Combined Hyperlipidaemia:Triglyceride levels
5-10 mmol/L
Familial Combined Hyperlipidaemia:Prognosis
Aggressive CHD in middle age
Familial Combined Hyperlipidaemia:Treatment
statins
Type 3 Hyperlipideamia: Cholesterol levels
5-15 mmol/L
Type 3 Hyperlipideamia: Causes/Genetics
Apo E2:E2 plus (doesn’t bind to receptor normally)
Alcohol XS or poor diet
Type 3 Hyperlipideamia: Signs
Palmar crease xanthomata
Periheral vascular disease also
Type 3 Hyperlipideamia: Consequences
CHD
PVD
Type 3 Hyperlipideamia: Treatment
Statin and /or Fibrates
Type 3 Hyperlipideamia:Epi
Rare (need another factor e.g. diabetes/poor diet) to trigger process
High Triglyceride: Triglyceride levels
> 10 mmol/L
High Triglyceride:Pathology
Lipoprotein lipase deficiency (Type 1 hyperlipideamia)
High Triglyceride: Signs
Eruptive xanthomata
Lipaemia retinalis
High Triglyceride: Risk of
Acute pancreatitis
High Triglyceride: Treatment
Fibrates
Drug treatment:
- HMGCoA reductase inhibitors (Statins)
- Fibrates
- Cholesterol absorption inhibitor (Ezetimibe) (2nd line for high cholesterol)
- Fish oils (Omacor) (2nd line high triglyceride)
- Bile acid sequestrants
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)
