lipid disorders

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Disorders of Lipid Metabolism & Lipoproteins

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Cystic fibrosis ( CF ) Autosomal Recessive Disease Mutation of CFTR gene ( CF Trans-membrane Conductance Regulator)  chloride currency + Cl - in sweet ( Sweet Test) In pancreas, hydration  viscosity of pancreatic enzymes  stasis  pancreatic enz. deficiency  steatorrhoea (Loss of lipids in stool). Clinical Condition

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Obstructive biliary canals  loss of emulsification of lipids + loss of activation of lipases Jaundice + Steatorrhoea + Vitamin Deficiencies. In cystic fibrosis, chronic pancreatitis or obstructive pancreatic duct  Steatorrhoea. Ezetimibe , a drug further reduce cholesterol absorption by enterocytes. Orlistat , a drug used in ttt of obesity is an inhibitor of pancreatic lipase and colipase. Any cause of steatorrhoea  bulky, greasy and offensive stool. Digestion and absorption of all elements of chime will be affected due to coating effect of fat

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Accumulation of Polyenoic A Zellweger’s Neurodisorder

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Defective Carnitine Transporting System

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Defective ACAD Autosomal Recessive Most common FAO inborn errors ttt by CHO-rich diet Inherited Acute fatty liver in pregnancy Akee tree Jamaican Hypoglycin ttt by MCFA

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Fatty Liver From 4 to 40 % increase of lipid content of liver. Replacement by fibrosis if condition is prolonged. It is imbalance between lipid income into liver and lipid secreted from liver. ATP MTP PL Lipotropic Factors Proteins TG VLDL CHO Depot Toxins (CCl4, Chloroform or Arsenic …) Pr. Ө Alcohol  increase NADH/NAD  acetaldhyde  Acetyl CoA FA Ethionine traps ATP Vit. Def.

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Vitamins Deficiency: Folic & B12  methyl carriage  Choline syn. Pyridoxine  inositol syn. Lipositol Increased: Biotin  stimulate appetite + decreased inositol syn. PL (& PUFA) Lipotropic Factors TG VLDL CHO Depot Fatty Liver (Cont.) Methionine, Glycine & betaine

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RDS ( Respiratory Distress Syndrome) Lung collapse due to deficiency of special lecithin ( D iPalmityl P hos P hatidyl C holine, DPPC ), which contains C1 & C2 palmitic a. DPPC is called surfactant, essential for alveolar integrity as it reduces the surface tension and that helps gaseous exchange across the alveolar membrane Mutation of SP genes and ABC gene contribute the occurrence of RDS. Treatment: Corticosteroids DPPC local spray

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MDS ( Multiple Disseminated Sclerosis) Replacement of phospholipids in myelin sheath by glial tissue (Nerve Demyelination of white matter) Decreased sphingomyelin, glycolipids &EA Plasmalogen. CSF show Immunoglobulins, phospholipids & Chol.Ester. Treatment: Corticosteroids

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Sphingolipidosis Ceramide Glu Gal NAGLA NANA Glucosidase Globosidase HA- ase Gala-ase Gaucher’s Tay-Sachs Generalized Gangliosidosis

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Sphingolipidosis (Cont.) Choline P Sphingosine FA Ceramide Neiman-Pick Farber’s Sphingomyelin

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Thrombosis Endothelial Plaque PDGF Cytokines Proteases Endothelial Injury

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Ketosis Increased ketone bodies in blood (Ketonaemia > 3 mg/dl) and in urine (Ketonuria > 15 mg /day). Ketogenic conditions ( Decreased Insulin/Anti-insulin Ratio): - Starvation - DM - Low CHO + High Fat Diet - Severe Ms Exercise - Pregnancy Ketonuria is associated with loss of Na, K & NH 4 +  decreased HCO - in blood  Acidosis. Anti-ketogenics: CHO, Glycerol, Insulin and Proteins.

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Liver & Lipid Metabolism Lipogenesis VLDL assembly Ketogenesis Desaturation of FA Gluconeogenesis from Glycerol Phospholipids re-modulation (Lipoproteins synthesis , release and uptake. Activation (A), esterification (A&D) for storage & utilization (K)of Fat soluble vitamins. Cholesterol synthesis (& Vit D) and excretion .

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Desirable Lipid Levels in Adults Goal (mg/dl) * Lipid Less than 200 mg/dL Total cholesterol Less than 100 mg/dL Low-density lipoprotein (LDL) cholesterol More than 40 mg/dL High-density lipoprotein (HDL) cholesterol Less than 160 mg/dL Triglycerides Less than 2.8 Risk Factor (LDL/HDL)

Errors of Lipoprotein Metabolism:

Errors of Lipoprotein Metabolism Primary Hyperlipoproteinemia Type I: Apo-C II  LPL activity  TG Type II: Hyper β LP Apo-B100 Receptors LDL endocytosis ( (similar Wolman’s def. lysosmalCEase Type III: Dys β LP Apo-E  Broad Beta Band (LDL & IDL) Type IV: Hyper pre β LP Insulin Resistance  VLDL Type V: LCAT  RCT Discoid HDL Secondry Hyperlipoproteinemia : 20 % of Hyperlipaemia Diabetes Mellitus Hypothyroidism Nephrotic Syndrome Alcoholism Contraceptives Pancreatitis Obstructive Jaundice

Primary (Genetic) Causes of Low HDL-C:

Primary (Genetic) Causes of Low HDL-C ApoA-I  Complete apoA-I deficiency  ApoA-I mutations (e.g., ApoA-I Milano ) LCAT  Complete LCAT deficiency  Partial LCAT deficiency (fish-eye disease) ABC1  Tangier disease • Homozygous • Heterozygous  Familial hypoalphalipoproteinemia (some families)

Causes of High HDL-C:

Causes of High HDL-C CETP Defeciency  CETP Gene Mutations (AcD) Liver Lipase ( AR) Familial AD Hyper alpha Lipoproteinemia. Secondary Extensive regular aerobic exercise Regular substantial alcohol intake Estrogen replacement therapy Drugs  Phenytoin

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Classification BMI Normal / healthy /desirable weight 18.5-24.9 Overweight 25.0-29.9 Obesity I 30.0-34.9 Obesity II 35.0-39.9 Obesity III 40 or more

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Maintaining the Basal Metabolic Rate (metabolism) accounts for 60-75 per cent of daily energy expenditure in most people, while physical activity accounts for only 10-15 per cent

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Estimated relative risk (RR) of developing obesityassociated diseases in obese men and women as compared with people of healthy weight. For example, an obese man is more than five times as likely to develop type 2 diabetes as one who is not obese RR- WOMEN RR- MEN DISEASE 12.7 5.2 Diabetes type 2 4.2 2.6 Hypertension 3.2 1.5 Heart attack 2.7 3.0 Colon cancer 1.8 1.8 Angina 1.8 1.8 Gall bladder diseases 1.7 - Ovarian cancer 1.4 1.9 Osteoarthritis 1.3 1.3 Stroke

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Three medicines are currently authorised to aid weight loss in adults, and each of these works in a different way . Orlistat ( Roche) acts by reducing the absorption of fat from food . Sibutramine ( Abbott) helps to reduce food intake by acting on sites in the brain to increase and speed up feelings of 'being full' on eating . Rimonabant ( sanofi-aventis) acts by a different pathway, both in the brain and in other parts of the body, to increase feelings of fullness, control energy balance and affect the metabolism of glucose and fat in the body .

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Three main types of weight loss surgery are currently used : Gastric banding . Gastric bypass . Duodenal switch/biliopancreatic diversion .