Hyperlipidaemia and therapeutic approaches Flashcards
(30 cards)
hyperlipidaemia
is the term used to denote raised serum levels of one or more of total cholesterol (Tchol), low density lipoprotein cholesterol (LDL-C), Triglycerides (TGs) or both Tchol and TG (combined Hyperlipidaemia)
dislipidaemia
is a wider term that also includes low levels of high density lipoprotein cholesterol (HDL-C)
chylomicrons
transport TGs/cholesterol from intestine indirectly (via lymph) to the blood.
Veyr ow density lipoproteins VLDL
(liver synthesised) have a high TG content. The capillary enzyme lipoprotein lipase converts the VLDLs TGs to free fatty acids, used for either energy [in muscle or liver] or storage [in adipose tissue].
low density lipoproteins LDL
contain a high cholesterol content.
high density lipoproteins HDL
absorb and transport peripherally-mobilised cholesterol from cell breakdown to the liver (protective).
what does the body use lipids for
Energy storage Intracellular signalling Extracellular mediators/signalling (lipoprotein) Base for steroid hormone synthesis Vitamin D synthesis Cell membranes
excess carbs converted to what
triglycerides and transported to fat cells
main site of sytnhteis of cholesterol
liver
higher TAG( triglycerides) lower cholesterol
choylomicorns sourced where
intestines
Dietary Lipids inc chol and FFA emulsified by bile acids & transported within chylomicrons to the liver
Then circulated as chol and triglycerides to disuse inVLDL
Endothelial lipoprotein lipase (LPL) liberate FFA in adipose and muscle for storage or metabolism
Resulting LDL return to hepatocytes via LDL receptors or taken up by LDL receptors in extrahepatic tissue where they are oxidised and contribute to atherogenesis
HDL pool derived from chylomicrons from action of LPL and reverse cholesterol pathways return HDL to liver vis HDL receptors
Hypercholesterolemia
Elevated LDL-C
Dyslipidemia
Includes elevated triglycerides and low HDL-C
serum total cholesterol, LDL-C, triglycerides, apolipoprotein B, or lipoprotein(a) concentration >90th percentile
HDL-C or apolipoprotein A-I concentrations <10th percentile
why is dyslipidemia important
Promotes atherosclerosis-cholesterol plaques
Ischemic heart disease
Cerebrovascular disease
Peripheral vascular disease
LDL-C normal range
1.8-2.6 -3.3
total cholesterol desirable range
under 5.2 optimal under 4.4
triglycerides desirable range
1.1-1.7
HDL-C range
under 1
how do we diagnose high cholesterol
rings around eyes
Xanthomas are lesions on the skin containing cholesterol and fats. They are often associated with inherited disorders of lipid metabolism (inherited problems with the way that fats are broken down and used). Xanthomas are raised, waxy-appearing, frequently yellowish-colored skin lesions.
primary - eugenics as single gene
Secondary causes of dyslipidemia
Diet Obesity Diabetes (T1 and T2) Hypothyroidism Alcohol dependency CKD Nephrotic syndrome Drugs (glucocorticoids, anti-retrovirals, oral oestrogens, atypical antipsychotics) Cushings
How do we treat hyperlipidemia?
lifestyle - reduce total and saturated fats , weigh loss, exercise , plant sterols
this all lowers LDL-C and increases HDL-C
also use statins
what are statins
HMG-CoA reductase inhibitors (3-hydroxy-3-methylglutaryl coenzyme A)
Important enzyme in cholesterol synthesis
↑ LDL receptors →↑LDL Clearance
Ultimately eliminated in bile (significant re-uptake)
Dose and preparation dependent LDL-C reductions of 20-50%
PCSK9 inhibitors
Proprotein convertase subtilisin/kexin type 9 binds LDL receptors for degradation in hepatic cell lysosomes
Key determinant of LDL-c concentration
Blocking PCSK9 with a monoclonal antibody allows the LDL receptor to be recycled back to the cell membrane surface to continue LDL uptake from blood
Examples Evolocumab, Alirocumab (specialist rx only)
Ezetimibe
add on to statin therapy
Colestyramine and Colesevelam
Bile acid sequestrants
Modest reductions in cholesterol 10-24%
GI side effects limit use (nausea, cramps, bloating, diarrhoea, constipation)
Ineffective in FH
