(NGM) Lipid Metabolism & Lipid Disoders.pdf

Department of Pathology LIPID METABOLISM AND LIPID DISORDERS Nichole Anne G. Maceda, MD August 13, 2024 Lecturer  OUTLINE Lipid Disorders 01 Lipid Metabolism 02 - Lipoprotein Classes...

Department of Pathology LIPID METABOLISM AND LIPID DISORDERS Nichole Anne G. Maceda, MD August 13, 2024 Lecturer  OUTLINE Lipid Disorders 01 Lipid Metabolism 02 - Lipoprotein Classes - Lipid Digestion - Dyslipidemia 03 Reading Assignments - Fredrickson Classification for Inherited Hyperlipidemias 01 Lipid Metabolism  01 Fats Essential part of the Diet Contribute to Taste and Texture of foods Major source of Energy Help absorb essential Vitamins Can be converted to other molecules like Prostaglandins 01 Lipid Molecular Structure 01 Fats  01 Lipoprotein Complex particles that have a central hydrophobic core of non-polar lipids Functions: Play a key role in the absorption and transport of dietary lipids by the small intestine Transport of lipids from the liver to peripheral tissues Transport of lipids from peripheral tissues to the liver and intestine (reverse cholesterol transport) 01 Lipoprotein Classes 01 Lipoprotein Classes 01 Lipid Digestion 01 Lipid Digestion 01 Lipid Digestion 01 Lipid Digestion 01 Lipid Digestion  01 Chylomicrons Large structures with a core of triglycerides and cholesterol Outer membrane made up of phospholipids, interspersed with proteins called apolipoproteins Makes it water-soluble so that it can travel in the aqueous environment of the body 01 Lipid Digestion 01 Lipid Digestion Lipoprotein Lipase 01 Lipid Digestion Hepatocyte Internalization 01 Lipid Digestion  01 Lipid Digestion LPL - Lipoprotein Lipase IDL - Intermediate Density Lipoprotein Free Fatty Acids  01 Lipid Digestion LPL - Lipoprotein Lipase IDL - Intermediate Density Lipoprotein 02 Lipid Disorders  02 Dyslipidemia Abnormal blood levels of Cholesterols, Triglycerides and/or Lipoprotein Elevated lipids in the blood Hyperlipidemia (HLD) (elevated cholesterol, triglycerides, and/or lipoproteins) Hyperlipoprotenemia Elevated levels of LDL, VLDL Elevated total cholesterol Hypercholesterolemia (> 200 mg/dL) Elevated triglyceride levels Hypertriglyceridemia (> 150 mg/dL)  02 Dyslipidemia Abnormal blood levels of Cholesterols, Triglycerides and/or Lipoprotein Types Primary (Familial) Secondary (Acquired) Prevalence increases with age Men > Women Major risk factor for Coronary Artery Disease Increased risk of developing Atherosclerosis  02 Dyslipidemia: Causes Primary (Familial) Secondary (Acquired) Polygenic inheritance Lifestyle Obesity Cigarette smoking Heavy alcohol use Classified according to the Systemic Illness Fredrickson phenotype Diabetes mellitus Cholestatic liver disease Nephrotic syndrome Chronic liver disease Hypothyroidism Depression Psoriasis Medications Thiazide diuretics Beta-blockers Oral estrogens Protease inhibitors 02 Atherosclerosis: Fatty Streak Phase Adhesion of blood leukocytes to the activated endothelial monolayer  02 Atherosclerosis: Plaque Progression & Stabilization Generous Fibrous Cap composed of Layers of: Smooth Muscle Cells Stable Plaque Collagen Proteoglycans Elastin Migration of Smooth Muscle Cells Heightened synthesis of extracellular matrix macromolecules such as Collagen 02 Atherosclerosis: Thrombus Formation 02 Atherosclerosis 02 Fredrickson Classification for Inherited Hyperlipidemias (HLP)  02 Fredrickson Classification: Type I HLP ApoC-II protein - Activates the enzyme lipoprotein lipase in capillaries which hydrolyzes triglycerides and thus provides free fatty acids for cells  02 Fredrickson Classification: Type 2 Apolipoprotein B-100 (Apo B-100) - Necessary for the assembly and secretion of VLDL PCSK9 gene - Provides instructions for making a protein that helps regulate the amount of cholesterol in the bloodstream  02 Fredrickson Classification: Type 3 HLP (Dysbetalipoproteinemia) Palmar Xanthomas ApoE - interacts significantly with the low-density lipoprotein receptor (LDLR), which is essential for the normal processing (catabolism) of triglyceride-rich lipoproteins acids for cells 02 Fredrickson Classification: Type 4 HLP  02 Fredrickson Classification: Type 5 HLP ApoA5 - decreases plasma triglycerides by enhancing lipoprotein lipase-mediated triglyceride hydrolysis 03 Reading Assignment  03 Reading Assignment 1. What is Reverse Cholesterol Transport? 2. Read on the following diseases: Tangier Disease Lecithin:Cholesterol Acyltransferase (LCAT) deficiency Isolated Low HDL-C 3. What are Friedewald & Delong’s Equations?  QUICK REVIEW 04 QUESTIONS:  QUESTION NO. 1 In familial β- dyslipoproteinemia (type III hyperlipoproteinemia), which lipoprotein accumulates? a. CHYLOMICRONS b. LDL c. VLDL d. IDL  QUESTION NO. 2 Which of the following mechanisms accounts for the elevated plasma level of β lipoproteins seen in familial hypercholesterolemia (Type II hyperlipoproteinemia)? a. ApoC-II activated lipase deficiency b. ApoE3 deficiency c. ApoB-100 receptor defect d. Mutation in APOC2  Department of Pathology Lipid Metabolism and Lipid Disorders - End of Slide -