LIPID ABNORMALITIES

Physiology of lipid metabolism Triglycerides (Tg), cholesterol (both free and esterified), free fatty acids (FFA) and phospholipids (Pl) constitute the plasma lipids. Lipoproteins are complexes of lipids and proteins that are essential for the transport of cholesterol, triglycerides, and fat-soluble itamins !on-polar lipids(insoluble in "ater) li#e triglycerides (Tg) and cholesterol esters form the core "hile Pl and free cholesterol along "ith certain specific proteins called apoproteins (Apo) constitute $lipoproteins% (Lp). The lipoproteins ha e been classified into four ma&or classes, chylomicron ('m), ery lo" density lipoprotein ((L)L), lo" density lipoprotein (L)L) and high density lipoprotein (*)L). *)L is the smallest in si+e and (L)L is largest in si+e.

Apolipoproteins maintain structure of arious lipid particles and also help in their metabolism. ,.g -.//, - 01. LIPID-LIPOPROTEIN METABOLISM a) E oge!o"s lipid t#a!spo#t )ietary fat and cholesterol are incorporated into chylomicron, in the intestinal epithelial cells along "ith specific apoprotein. The 'm is then released into the lacteals and through the cisterna chyla-thoracic duct system enters into the circulation. At the capillary- tissue interface the en+yme LPL catalyses the brea#do"n of chylomicron and causes liberation of FFA and monoglycerides. The FFA is utilised for energy purposes or resynthesis of Tg in the adipose tissue "hile glycerol reaches the li er to be utilised for endogenous triglycerides synthesis. E!doge!o"s lipid t#a!spo#t

 'holesterol deri ed from exogenous lipid transport or synthesised by the li er

from non-cholesterol sources has three different fates. 2ome is secreted into the gut as such, "hile some gets con erted into bile acids and is then secreted so as to help in fat absorption from the gut. The rest is incorporated into (L)L for transportation and distribution to different tissues. The circulation and metabolism of (L)L molecules constitute the endogenous lipid transport. (L)L "ith shedding of the Tg load, the (L)L becomes smaller and less compact "ith cholesterol content becoming intermediate-density lipoprotein (3)L). 3)L is further metaboli+ed to L)L( lo" density lipoprotein) L)L is the end-product of (L)L metabolism.L)L is ery rich in cholesterol and most atherogenic.

Re$e#se %holeste#ol t#a!spo#t *)L secreted from the li er and gut, *)L is rich in Apo A.

*)L "hile interacting "ith peripheral tissue ac4uire cholesterol.this done in

presence of en+yme L'AT ( lecithin cholesterol acyl transferase). !et result is *)L is engaged in mobilising cholesterol from peripheral tissues to li er, a process "hich is re erse to both endogenous and exogenous lipid transport and so is called 5re erse cholesterol transport5.

&lassifi%atio!' .. Predominant hypercholesterolaemia 6. Predominant hypertriglyceridaemia

7. 8ixed *yperlipidaemia 9 both cholesterol and triglycerides are increased

Fredric#son classification is ery complicated. 3n this classification di ided lipid abnormalities into : groups. P#ima#y %a"ses Se%o!da#y &a"ses *ypothyroidism

Etiology Type (ype#%holeste#olaemi a

Familial hypercholesterolaemia *yperalphalipoproteinaemia

(ype#t#igly%e#idaemia

Lipoprotein lipase deficiency Familial hypertriglyceridaemia

!ephrotic syndrome 'hronic li er disease )iabetes mellitus 'ushing%s syndrome

)iabetes mellitus (type 6) 'hronic renal disease ,xcess alcohol retinoids, corticosteroids

)rugs (;-bloc#ers,

&li!i%al feat"#es' Asymtomatic, and accidentally detected due e aluation of )8, *T! or 'A). Patient may present "ith pancreatitis esp. familial hypertriglyceridemia. <anthomas 9 on Achilles tendon, platella and bac# of hand. <antholesma -- deposits around eye esp. upper eye lid. ,rupti e <anthomas 9 o er buttoc#s seen esp. in LPL deficiency patients. 'orneal arcus. Any patient "ho has presented "ith early onset of 'A) suspect familial lipid abnormalities. 8ost of the signs gi en abo e are more common in familial ariants than secondary causes. I!$estigatio!s' 2erum lipids should be as#ed on fasting (min. of 1*rs). This should include 9 Total cholesterol,L)L cholestrerol, *)L, T=. > L)L cholesterol ? Total cholesterol-(*)L @T=A:)

secondary causes of dyslipidemia ha e to be ruled out 9 sugars, LFT, TFT, urine

protein, BFT. C As# for drug history li#e beta-bloc#ers.

Ma!ageme!t' Lipid-lo"ering therapies ha e a #ey role in the secondary and primary pre ention of cardio ascular diseases. A) Dieta#y a!d life-style This is the cornerstone of therapy in the management of hyperlipidaemias.

Deight reduction and maintenance of near normal body "eight is desirable esp for
hypertriglyceridemia. The lipid-lo"ering diet should aim at reducing the total fat inta#e to 7/ per cent along "ith reduction of saturated fat to less than ./ per cent of daily calorie re4uirement, 3ncrease consumption of cardioprotecti e and nutrient-dense foods such as egetables, unrefined carbohydrates, fish, pulses, legumes, fruit. 2upplementary inta#e of foods containing lipid-lo"ering nutrients such as n-7 fatty acids, dietary fibre and plant sterols Besponse to diet is usually apparent "ithin 7-0 "ee#s.

,xplanation, encouragement and other measures should be underta#en to reinforce

patient compliance B) Pha#ma%ologi%al t#eatme!t Lipid ab!o#mality *ypercholesterolemia *ypertriglyceridemia Mi ed (ype#lipidaemia D#"g of %hoi%e 2tatins Fibrates 2tatins @ Fibrates

(M) &o Red"%tase I!hibito#s *stati!s) E+g 2ima astatin (:-./mg) Ator astatin (:-./mg). 8.E.A 9 3nhibits cholesterol synthesis. 2ide effects 9 increase in li er en+ymes, 8yositis. '.3 9 pregnancy and lactation and li er disorders. ,ib#i% a%id de#i$ati$es' ,.g =emfibrocil, finofibrate, -en+afibrate. 8.E.A 9 decrease the hepatic triglyceride synthesis. 2ide effects 9 8yositis, nausea and impotence. '.3 9 se ere renal and hepatic dysfunction. &holeste#ol Bi!di!g #esi!s' ,.g 9 'holestyramine and cholestipol. 8.E.A 9 Anion exchange resins.

 2ide effects 9 nausea and flatulence and abdominal bloating. Ni%oti!i% a%id de#i$ati$es' 8.E.A 9 inhibit lipid synthesis in the li er. 2ide effects 9 headache, rashes, abnormal LFT. '.3 9 pregnancy, breast-feeding. Omega - fatty a%ids*fish oils)' 8.E.A 9 ,icosapentaenoic acid (,PA) and docosahexaenoic acid ()*A) comprise approximately 7/F of the fatty acids in fish oil. ,PA and )*A are potent inhibitors of (L)L T= formation. 2ide effects 9 nausea and belching. &holeste#ol abso#ptio! i!hibito#s,.g -e+etimibe These inhibit the intestinal mucosal transporter that absorbs dietary and biliary cholesterol. 8echanism of action is synergistic "ith the effect of statins. 2o generally used in combination "ith statins. Mo!ito#i!g of the#apy The effect of drug therapy can be assessed after G "ee#s. 'H and li er function ha e to be regularly assessed.

Ta#get $al"es of lipids The#ape"ti% )oal. mg/dL

Primary TargetI L)L 'holesterol J.// J.7/ J.G/ 2econdary TargetI !on-*)L 'holesterolC (T.'hol-*)L) J.7/ J.G/ J.L/

'A) and 'A) ris# e4ui alentsC 8ultiple (6@) ris# factors Kero to . ris# factor

Cclinical forms of non-coronary atherosclerotic ascular disease (peripheral arterial disease, abdominal aortic aneurysm, clinical carotid artery disease), diabetes