MMBS, MMED (Path),MAACB, MACTM, MACRRM
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1 Dr Mere Kende MMBS, MMED (Path),MAACB, MACTM, MACRRM Lecturer- SMSH
2 Brief Overview of Lipids What is dyslipidemia? Classification of hyperlipidemia Primary vs secondary hyperlipidemia Hypercholesterolaemia & Hypertriglyceridemia Diagnosis & Treatment 5mins Video References
3 Constituents of living cells Primary source of energy, precursors for steroid, hormones PGs,& leukotrienes Important structural components of cell membranes Components of bile for digestion
4 Fatty Acids Triacylglycerols (TRIGLYCERIDES) Cholesterols (sterols) Sterol esters Phospholipids Bile acids
5 FAT
6 Mader. Human Biology, 7 th Edition
7
8 Hydrophobic End Hydrophilic End
9 Relative insolubility in water Most lipids except Phospholipids are hydrophobic Has to be packaged as lipoproteins in specific protein complexes (apo-proteins) for transport in plasma FFA (>18Carbon) is transported in albumin
10 Mader. Human Biology, 7 th Edition
11 Mader. Human Biology, 7 th Edition
12 Mader. Human Biology, 7 th Edition
13 Mader. Human Biology, 7 th Edition
14
15 Are apo-protein + packaged lipids Make lipids water soluble for transport in plasma Carry varying amounts of fat to different tissues Apo-proteins are enzyme co-factors, structural proteins & ligands for receptor recognition
16 Chylomicrons (Diet TRIG) VLDL (Liver TRIG) LDL (Liver) IDL (Tissues form VLDL) HDL (liver) Chylomicron remnants (Tissue from chylomicrons) Lipoprotein (a)
17 Harrison s Principle of Internal Medicine 17 th Ed
18 Harper s illustrated Biochemistry 26 th Ed, 2003
19 Triglycerides (triacyl glcerol) Free Cholesterol & Cholesteryl esters Phospholipids FFA (small)
20 A. Despopoulous, S. Silbenagl. Colour Atlas of Physiology, 5 th Edition
21 Chylomicrons (TRIG)- apob48- supplied in DIET VLDL (TRIG)-ApoB100,E,C synthesis : Liver + GIT LDL derived from VLDL in liver, Apo B100 transport CHO to peripheral tissues HDLC Apo A,E & C transport CHO to liver for excretion
22 Harper s Ilustrated Biochemistry 26 th Ed, 2003
23
24 Refers to abnormal metabolism of lipoproteins/lipids Hypolipoproteinemia Hyperlipidemia Tangier s Disease
25 Refers to high cholesterol or high triglycerides Primary/Genetic/Familial Causes Secondary: Diabetes, hypothyroid, nephrotic syndrome Obesity Oral contraceptives steroids Combined cause/polygenic
26 Acute Coronary Syndrome Stroke Peripheral Vessel Disease (claudication)
27 Atlas of clinical Diagnosis, 2 nd Edition
28 ABC of Dermatology, BMJ Pub, 4 th Edition Atlas of clinical Diagnosis, 2 nd Edition
29
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35 Cardiovascular Risk Assessment TOO MANY NOT GOOD Overweight Diabetes Over-weight Diabetes Hypertension Cholesterol HIGHEST RISK Smoking NORMAL RISK
36 Isolated high cholesterol (CHO) Isolated high triglycerides (TRIG) Combined elevation of both CHO & TRIG
37 Inherited Due to various defects in catabolism of lipoprotein include defective transport proteins (apo-proteins), receptors and ligands for receptors (apo E) Early onset of CVD/stroke (<40y old) Acute pancreatitis (+ very high TRIG) Xanthomas (skin, tendons, extensor surfaces, eyelids) Family members with hyperlipidemia/early CVD deaths
38 Type I------V Based on type of lipoprotein elevated Results in elevation of cholesterol or triglycerides or both
39 Familial hyperlipoproteinemia
40 Autosomal dominant Defect in LDL receptors/apo B100 Isolated high CHO- almost due to raised LDL Normal TG CVD Risk 25x >normal after 30 Family history of early death/cvd, Heterozygous >9mmol/L; symptoms at 30-40y; CVD at 50/60y Homozygous >15mmol/L; early CVD; die before 20y
41 Tendon xanthomas (most commonly of the Achilles tendons and the extensor tendons of the knuckles), tuberous xanthomas (softer,painless nodules on the ankles and buttocks), & xanthelasmas (deposits on the eyelids) are common.
42
43 Yellow, creamy & elevated papule
44 Large subcutaneous tumor adherent to the Achilles Tendon.
45
46 Phenotype I (AR) IIa (AD) IIb LP high chylo LDL LDL & VLDL III (AD) Chylo remnants & IDL IV (AD) VLDL V (AR) Chylo & VLDL TRIG >9++ < >9++ CHO <6 > / Plasma milky clear clear turbid turbid milky xanthomas Eruptive, buttocks Knee/ elbow none Palmar, tendon none pancreatitis yes no no no no yes IHD no Yes ++ Yes++ Yes++ -/+ -+ PVD no yes yes yes -/+ -/+ Gene defect LPL, apocii LDL R/ B100? Apo E2/E2 Apo A- V? yes Apo A- V?
47 Diabetes Mellitus (high TRIG+/- CHO) Nephrotic syndrome (high CHO) Severe Hypothyroidism (high CHO) Cushing s Syndrome (TRIG) Obesity (TRIG) OCP (TRIG) Cholestasis/Obstructive Jaundice (high CHO)
48 High CHO and LDLC No identifiable mode of inheritance?environmental & poorly understood genetics Diet alone can control CHO in some patients
49 Total cholesterol LDL cholesterol (LDLC) HDL cholesterol (HDL) Ratio of LDL:HDLC Triglycerides Apo-lipoproteins A & B Lipoprotein (a)
50 Measured after an overnight fast. Creamy layer in tube non-fasting/defect in chylomicron metabolism Plasma is usually clear when TG levels are <4.5 mmol/l (<400 mg/dl) & cloudy when levels are higher
51 Clinical- early CVD, very high CHO, xanthomas Many diagnosed incidentally Laboratory Total cholesterol Triglycerides LDLC & HDLC Ratio LDLC:HDLC Others: Small dense LDLC Apo A and B Lipoprotein (a) & lipoprotein electrophoresis
52 Normal TRIG level > 2.3 mmol/l (> 200 mg/dl). Normal Total cholesterol <5.5mmol/L HDL Cholesterol Good cholesterol <1mmol/L ---Bad LDLC Bad cholesterol >2.5mmol/L Bad
53 Over-weight /Obesity Hypertension Diabetes Mellitus Heart Disease
54 Lifestyle changes (Weight Loss /diet/exercise) Medication Lower Cholesterol & Triglycerides Treat secondary problems
55 Lifestyle Changes (smoking/alcohol/drug) Weight loss BMI= wt (kg)/ht x ht (m) IBW= [ 25 x ht x ht] (m) Acceptable IBW= IBW + 10% of IBW Low fat Diet Exercise (3omins /day) Manage existing Risk factors (DM)
56 Fish, canola oil & flaxseeds (Omega 3) Olive oil Nuts (unsaturated Fatty Acids) Peanuts, walnuts, almonds, hazelnuts High Fibre (oat meal, oat bran, kidney beans, apples, pears) Green Leafy Vegetables
57 Adapted from Lullman Color Atlas of Pharmacology 2000
58 HMG co-enzyme reductase (statins)-block Cholesterol synthesis) Simvastatin, pravastatin, atorvastatains, lovastains Cholesterol absorption inhibitors (enhances excretion) ezitimibe Bile acid sequestrant (Increase LDLC excretion) Cholestyramine, cholestipol & cholesvelem Nicotinic acid (increases LDLC & TRIG excretion) Clofibrates (Increase LDLC excretion & Increase HDLC) Gemfibrozil & fenofibrozil Fish Oil (Omega 3)---decreases TRIG
59 What Does Diabetes Do.mp4
60 ESC Koay & N Walmsley: A primer of Chemical Pathology 1996 Harrisons Principle of Internal Medicine 17 th Edition PJ. Gallagher, GA Tanner. Medical Physiology, 2 nd edition A. Despopoulous, S. Silbenagl. Colour Atlas of Physiology, 5 th Edition
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