Hyperlipoproteinemia

Hyperlipoproteinemia

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  Rida Nisar Pharm.D
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  Plasma lipids aretransported in the form of complexes called lipoproteins. Metabolic disorders that involve elevations in any lipoprotein species are termed as hyperlipoproteinemias or hyperlipidemias.
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  Lipid metabolism canbe divided into two basic pathways: the exogenous pathway, which is associated with the metabolism of exogenous (dietary) lipids , and the endogenous pathway, which is associated with the metabolism of endogenously produced lipids
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   After digestionenterocytes absorb the fatty acids and cholesterol from the lumen of the gut, re-esterify them to glycerol and secrete them in chilomicron.  the CM enter the venous circulation at the subclavian vein. In the systemic circulation the CM acquire many apoproteins from HDL. Muscle and adipose tissue synthesise LPL that attaches to proteoglycans on the endothelial cells. ApoCII on the CM activates LPL in these vascular beds and it digests triglyceride to fatty acids. The core of the CM diminishes in volume, and excessive surface area forming HDL.  The CM remnants bind to hepatic receptors (LDLR as well as LDLR like lipoprotein) by virtue of apoE.
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   The liverassembles fatty acids into triglycerides for export in VLDL. Triglyceride, CE, phospholipids and un-esterified cholesterol are blended into a VLDL particle before secretion into the venous circulation.  Circulating VLDL undergoes similar metabolism to CM forming VLDL remnants under the action of LPL. These remnants are cleared from the circulation by virtue of apoE-binding hepatic receptors. However, almost half of the VLDL remnants are further metabolised by HL to LDL. The LDL particles contain only apoB100 and this is now in the appropriate conformation for binding to the LDLR.
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   Hyperlipoproteinemia canbe a primary or secondary condition. Primary hyperlipoproteinemia is often genetic. It’s a result of a defect or mutation in lipoproteins. These changes result in problems with accumulation of lipids in your body. Secondary hyperlipoproteinemia is the result of other health conditions that lead to high levels of lipids in your body. These include:  diabetes  hypothyroidism  pancreatitis  use of certain drugs, such as contraceptives and steroids  certain lifestyle choices
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  Mechanism dylipidemia PathphysiologyCause plasma lipoprotein pattern Increased production Increased VLDL production Familial hypertriglyceridemia Decreased LPL activity,high VLDL production Genetic Type IV and V Polygenic hypercholsetrolemia Multifactorial Type II A, II B and IV Familial combined hyperlipidemia VLDL overproduction Multifactorial Defective removal Decreased LDL removal Familial hypercholestrolemia Defective or absent LDL receptors Genetic Type II A and II B Familial defective apoB- 100 LDL receptor binding decreased due to defective Apo B Genetic Abnormal LPL function Familial LPL deffeciency mutation in gene:No expression Genetic Type I, IV and V Familial Apo C-II defeciency mutation in gene:No expression Genetic Decreased remnant removal Dysbetalipoproteinemia Mutation in ApoE that serves as ligand for binding to hepatic reeceptors Multifactorial Type III
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   Type I:In these individuals elevated chylomicrons are found due to lipoprotein lipase or Apo CII deficiency, causing elevated levels of triglycerides.  Type IIa: In these individuals elevated LDL cholesterol and total cholesterol are observed mostly due to genetic defects.  Type IIb: In these individuals elevated LDL and VLDL are seen as observed in individuals with familial combined hyperlipidemia. Both cholesterol and triglyceride levels may be elevated.  Type III: is a recessively inherited disorder These individuals have elevated IDL, Both cholesterol and triglyceride levels may be elevated.  Type IV: These individuals have elevated VLDL , As a result, triglyceride levels are elevated. Type IV disorder also may be due to secondary causes such as diabetes and nephrotic syndrome.  Type V: These individuals have elevated VLDL and chylomicrons causing elevated triglycerides.
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   Lipid depositsare the main symptom of hyperlipoproteinemia. the location of lipid deposits can help to determine the type. Some lipid deposits, called xanthomas, are yellow and crusty. They occur on your skin.  Other signs and symptoms of hyperlipoproteinemia include:  Pancreatitis  abdominal pain  enlarged liver or spleen  lipid deposits or xanthomas  family history of heart disease  family history of diabetes  heart attack  stroke
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   The majorclinical sequelae of hyperlipidemias are acute pancreatitis and atherosclerosis which eventually leads to coronary heart disease.
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   Hyperlipidemia isthe most important risk factor for atherosclerosis ,which is the leading cause of death for both genders. characterized by the accumulation of lipids, cholesterol and calcium and the development of fibrous plaques within the walls of large and medium arteries  Low Density Lipoprotein (LDL) is pro-atherogenic. Hence high levels of LDL increase “Coronary Heart Disease” (CHD) risk. High density lipoprotein (HDL) is anti-atherogenic. Hence low levels of HDL also increases CHD risk.
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   Coronary heartdisease (CHD) is the cause of about half of all deaths in the United States. The incidence of CHD is correlated with elevated levels of low-density lipoprotein (LDL) cholesterol and triacylglycerols and with low levels of high- density lipoprotein (HDL) cholesterol.  characterized by the accumulation of lipid and the formation of fibrous plaqueswithin the wall of the arteries resulting in narrowing of the the arteries that supply blood to the myocardium, and results in limiting blood flow and insufficient amounts of oxygen to meet the needs of the heart.
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   The mechanismby which hypertriglyceridemia induces pancreatitis is not clear, but it has been suggested that serum triglycerides are hydrolyzed by the action of pancreatic lipase, leading to excessive production of free fatty acids, which are toxic to the pancreas
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   MI isa condition which occurs when blood and oxygen supplies are partially or completely blocked from flowing in one or more cardiac arteries, resulting in damage or death of heart cells. The occlusion may be due to ruptured atherosclerotic plaque.
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   Stroke isthe fourth leading cause of death. Usually strokes occur due to blockage of an artery by a blood clot or a piece of atherosclerotic plaque that breaks loose in a small vessel within the brain.
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  Normal and abnormallipid and lipoprotein metabolism,A D MARAIS, MB ChB, FCP (SA) Head, Lipidology Division of Internal Medicine, Groote Schuur Hospital and University of Cape Town Health Science Faculty and MRC Cape Heart Group  https://www.healthline.com/health/hyperlipoproteinemia  Lipids and disorders of lipoprotein metabolism  Graham R. Bayly, inClinical Biochemistry: Metabolic and Clinical Aspects (Third Edition), 2014  A Review Article on Hyperlipidemia: Types, Treatments and New Drug  Targets  Ghassan F. Shattat  College of Science and Health Professions, King Saud Bin Abdulaziz University for Health Sciences, Riyadh, Saudi Arabia.  Hyperlipidemia Background and Progress Isam Karam¹*, Ya Jun Yang² and Jian Yong Li²  An Update on Hyperlipiclemia and its Management  Riaz A. Memon ( Department of Physiology and Pharmacology, Faculty of Health Sciences, The Aga Khan University, Karachi. )