Blood Lipids 2024-2025 Past Paper PDF

Blood Lipids Dr Ross Pallett HCPC Biomedical Scientist: BS71638 [email protected]  Preparation For this lecture you’ll need… Biochemistry/Metabolism Eat a pizza afterwards (it’s active revision!) ...

Blood Lipids Dr Ross Pallett HCPC Biomedical Scientist: BS71638 [email protected]  Preparation For this lecture you’ll need… Biochemistry/Metabolism Eat a pizza afterwards (it’s active revision!)  Aim and Objectives Aim To introduce to you the blood lipids Following this lecture you should be able to: 1. Understand lipid biochemistry and metabolism 2. Describe the lipid disorders and clinical disease 3. Understand the role of the Clinical Biochemistry laboratory in analysing blood lipids 4. Explain the treatment of dyslipidaemia Essential to life! Structural components of cells Metabolic Lipids and Hormone pathways Energy Storage  Major groups of lipids Glycerol Long C chain backbone with 3 with COOH FA residues Fatty Acids Triglycerides Metabolic fuels stored as Energy source trigylcerides Lipids Cholesterol Lipoproteins Lipid and Diet and liver apoprotein Essential component of Solubility cell membranes  Apoproteins Q. How do you transport insoluble lipids into the hydrophilic environment of the blood? Marry them to a protein! (Apoprotein) Multifunctional protein: A A1, A2, A4 and Intestine and liver Maintain structural integrity of the lipoproteins A5 B B48 and B100 Intestine (B48) and Liver (B100) Regulate enzymes acting on lipoproteins C C1, C2 and C3 Liver Receptor recognition E E2, E3 and E4 Intestine, Liver and Macrophage Defects cause dyslipidaemia  Lipoproteins Marriage between a lipid and an apoprotein Three roles: 1. Interorgan fuel 2. Distribution 3. Maintain cholesterol pool The apoprotein determines the lipoprotein class  Key lipoprotein classes… Variation in: Triglycerides, Cholesterol, Phospholipids and Apoproteins 1. Chylomicrons 2. VLDL 3. LDL 4. HDL Composition 86% Triglyceride 86% Triglyceride 6% Triglyceride 4% Triglyceride 5% Cholesterol 5% Cholesterol 50% Cholesterol 17% Cholesterol 7% Phospholipid 7% Phospholipid 22% Phospholipid 25% Phospholipid 2% Protein 2% Protein 22% Protein 55% Protein Major A1, B48, C2 and E B100, C2 and E B100 A1 and A2 apolipoproteins Mean Diameter 500 43 22 8 (nm) Density 0.93 0.95 – 1.006 1.019-1.063 1.063-1.210 (g/mL) Function Main carrier of dietary Main carrier of Main carrier of Protective triglycerides endogenously cholesterol produced triglycerides Phospholipid and protein percentage Mean diameter Extra reading: IDL  Exogenous Pathway - Chylomicrons 1. Chylomicrons Microsomal triacylglycerol transfer protein (MTP) Composition 86% Triglyceride Diet Chylomicrons ApoB-48 5% Cholesterol 7% Phospholipid 2% Protein Triglycerides ApoC3 ApoE Major apolipoproteins A1, B48, C2 and E Mean Diameter (nm) 500 Via lymphatic system into the blood ApoC1 Density 0.93 (g/mL) Chylomicrons ApoC2 Function Main carrier of dietary triglycerides Activates lipoprotein lipase Shed ApoC2 Tissue lipoprotein lipases Free Fatty Acids Chylomicron remnants Endocytosis via ApoE and remnant chylomicron receptors Enters cells/tissues  Endogenous Pathway - VLDL Microsomal triacylglycerol 2. VLDL transfer protein (MTP) 86% Triglyceride Triglycerides VLDL ApoB-100 5% Cholesterol 7% Phospholipid Synthesised by the liver 2% Protein B100, C2 and E Secreted into the circulation 43 0.95 – 1.006 ApoC3 ApoE Main carrier of endogenously produced triglycerides ApoC1 VLDL Shed Reach peripheral tissues Endocytosis via ApoE ApoC2 Activates lipoprotein lipase ApoC2 Free Fatty Acids Acquires cholesterol IDL Removal of remaining triglycerides and cholesterol ester substitution Enters cells/tissues ATHEROGENIC: Cholesterol rich: CAN LDL PENETRATE VASCULAR ENDOTHELIUM  Endogenous Pathway - LDL 3. LDL LDL ApoB-100 6% Triglyceride 50% Cholesterol LDL Receptor 22% Phospholipid 22% Protein B100 22 1.019-1.063 Main carrier of cholesterol LDL receptor binds to apoB100 Its expression is regulated by intracellular cholesterol concentrations Mediates cellular uptake of intact LDL Mutations can result in severe inherited forms of hypercholesterolemia  HDL 4. HDL 4% Triglyceride 17% Cholesterol HDL ApoA1 25% Phospholipid 55% Protein A1 and A2 8 1.063-1.210 Protective Free cholesterol HDL is involved in the reverse transport of cholesterol Mops up free cholesterol SRB1-HDL Complex Binds to Scavenger receptor type B1 (SRB1) on hepatocytes Cholesterol excretion via bile  Dyslipidaemia Abnormally elevated levels of lipids and/or lipoproteins within the blood WHO (Fredrickson) classification for primary hyperlipidaemia Phenotype Lipoprotein Increased Lipid Plasma Occurrence Elevated Fraction Appearance 1 Chylomicrons Triglycerides Creamy top layer Rare 2a LDL Total Cholesterol Clear Common 2b LDL & VLDL Triglycerides Clear or Turbid Most Common Total Cholesterol 3 IDL Triglycerides Clear, cloudy or Rare Total Cholesterol milky 4 VLDL Triglycerides Clear, cloudy or Common milky 5 Chylomicrons & Triglycerides Creamy Rare VLDL  Classification Hypercholesterolaemia Primary Secondary Familial Familial defective Diabetes mellitus Renal disease Hypercholesterolaemia ApoB100 Autosomal recessive Sitosterolaemia Anorexia nervosa Liver disease hypercholesterolaemia  Familial Hypercholesterolaemia Autosomal dominant LDL receptor Prevalence: 1 in 500 Tendon xanthomas  Classification Hypertriglyceridaemia Primary Secondary Familial combined Lipoprotein lipase Pancreatitis SLE hyperlipidaemia deficiency Familial endogenous Apoprotein E Alcohol Pregnancy hypertriglyceridaemia polymorphisms  Familial Combined Hyperlipidaemia Autosomal dominant Overproduction of VLDL Prevalence: 1 in 100 Increased Triglycerides (and cholesterol)  Atheroma and Atherosclerosis Atheromas – lipid rich lumps in the inner lining of arteries Movement of Monocyte infiltration Rupture of the Injury to the blood cholesterol into the and the conversion atherosclerotic vessel subendothelium and to foam cells plaque media of the artery Laboratory Tests Family History Disease/ Illnesses Patient History Patient Assessment BMI Diagnosis Examination Measure Waist Laboratory Tests Blood Pressure  Specimen Requirements 1. Phlebotomy Check patient & sample details match 2. Correct sample collection tubes SST (Biochemistry) K-EDTA (Haematology) Patient has fasted ([triglyceride] affected and its used for LDL reporting  1. Total Cholesterol Enzymatic assay Three-stages: Cholesterol esterase Stage 1: Cholesterol esters + H2O Cholesterol + Fatty Acids Cholesterol oxidase Stage 2: Cholesterol + O2 Cholest-4-en-3-one + H2O2 Stage 3: Hydrogen peroxide reacts with phenol and peroxidase to oxidise colourless 4-aminophenazone Colour intensity of the product is directly proportional to the cholesterol concentration Normal range: 1.20 mmol/L  4. Calculating LDL Friedewald equation: [LDL Cholesterol] = [Total Cholesterol] – [HDL Cholesterol] - ([Triacylglycerol]/2.2) Problems: Assumes most circulating triglycerides are in VLDL Assumes that the triglyceride : VLDL ratio is 5:1 Should not be used when triglyceride concentration >4.52 mmol/L Normal range: