10. lipid disorders.pdf

lipid disorders Q. what’s one of the risk factors for ↑ cardiovascular mortality? ◦hyperlipidemia atherosclerotic cardiovascular disease can be prevented Q. what’s the major lipids in plasma? ◦FA ◦TAG ◦sterols ◦phospholipids Q. ho...

lipid disorders Q. what’s one of the risk factors for ↑ cardiovascular mortality? ◦hyperlipidemia atherosclerotic cardiovascular disease can be prevented Q. what’s the major lipids in plasma? ◦FA ◦TAG ◦sterols ◦phospholipids Q. how can we transport lipid in plasma if they're insoluble in water? ◦by associating it w/ a protein (Albumin & lipoproteins) lipoprotein has hydrophobic center & hydrophilic coat triglycerides (TG) & cholesterol ester cholesterol are amphipathic oh molecules phospholipids Apolipoproteins lipid transport ① Chylomicron (dietary lipids) ③ HDL (cholesterol) mucosal cells → peripheral peripheral tissues to liver tissues and finally → liver (in liver = metabolism & storage) ② VLDL / LDL (lipid synthesized in liver) liver → the peripheral tissues Q. what are the functions of apolipoproteins? ◦a component of lipoproteins ◦ligands (for receptors) ◦cofactors (for enzymes) Lipid disorder ◦primary hyperlipidemia (genetics) → appear early in life ◦secondary hyperlipidemia (there’s another disorder in the body that caused ↑ lipid levels ) Rare causes of hypo-lipoprotenmia Abeta-lipoproteinemia ◦Caused by defect in synthesis of apo B ◦this causes absence of LDL, VLDL & CM in plasma ◦Clinical manifestation: ‣ Fat malabsorption ‣ Retinitis pigmentosa ‣ Ataxic neuropathy Hypo-beta-lipoproteinemia ◦caused by apo B deficiency ◦Characterized by low LDL, VLDL & CM levels ◦decreased ASCVD risk Alpha-Lipoprotein Deficiency or Tangier’s disease ◦cuz of increase Apo A-1 catabolism ◦Low HDL-C levels activates LCAT & in HDL structure ◦Hyperplastic, orange tonsils  Primary Causes of Lipoprotein Abnormalities Signs Reasons Symptoms Familial Hypercholesterolemia Autosomal dominant condition defect in LDL receptor that -xantherlasma → chol High cholesterol from early reduce the uptake & deposition in eyelid childhood catabolism of LDL particles Normal TG -MI → especially in young ppl -corneal arcus lipidus → u have whitish thing around the iris -tendon xanthomas → accumulation on fat on/within the tendon Familial Dysbetalipoproteinemia Increased levels of IDL, CM Apo E-2/E-2 phenotype remnants o (not normal) Tubero-eruptive Xanthomas Increased TG and CHOL & appear on bony o obesity prominences o hypothyroidisms o diabetes and alcohol Familial combined Elevated VLDL overproduction of VLDL by live -Cutaneous manifestations hyperlipidemia Elevated CHOL and TG → leading to high LDL secretion -Increased risk of coronary artery disease Familial hypertriglyceridemia Markedly elevated VLDL -Increased risk of coronary Normal LDL artery disease -Increased risk of pancreatitis Familial chylomicronaemia ↑ chylomicrons in the blood LPL deficiency -Eruptive xanthomas (it’s normally metabolised by LPL) Apo CII deficiency (LPL activator) -Recurrent abdominal pain due to pancreatitis  What does the laboratory actually check in a Lipid Profile? How to Calculate LDL Cholesterol? Total choilesterol, HDL-C & triglycerides are measured A full lipid profile consists of: directly in the lab – Total Cholesterol – Triglycerides LDL can be calculated using a specific equation – HDL cholesterol – LDL cholesterol– (calculated) LDL-C = Total Cholesterol – (HDL-C + TG/2.2) – Apo A1 – Apo B we only use it when lower If TG is > 4.5 mmol/L then this formula is not accurate Compare values with “desirable” reference values & LDL must be measured directly in the lab Classification of lipid levels Triglycerides mmol/L HDL cholesterol mmol/L Total cholesterol mmol/L LDL cholesterol mmol/L < 5.2 Desirable < 2.6 Optimal p < 1.69 Normal < 1.03 (males) Near Low Borderline Border line < 1.3 (females) 5.2-6.2 2.6-3.3 optima/Above 1.7-2.3 high high optimal Borderline 2.3-4.5 High 3.3-4.1 high ≥ 1.55 High ≥ 6.2 High 4.1-4.9 High ≥ 5.6 Very high ≥ 4.9 Very high Reasons for checking the lipid profile 1) Assess the risk for cardiovascular and cerebrovascular disease 2) Assess risk for pancreatitis