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1、Related problems on clinical application of plasma lipids assay,Professor zhou xin Department of Laboratory Medicine, Zhongnan hospital of wuhan university. Dr. Sheng-kai Yan , PhD Department of Laboratory Medicine, Peking Union Medical College Hospital,All kinds of lipids in plasma were called bloo
2、d lipids Total cholesterol，TC free cholesterolcholesterol ester Neutral fattytriglyceride，(TG) non esterified fatty acid （free fatty acid ，FFA） phospholipid , glucolipid Lipids were insoluble in water ,they were transported in the form of lipoprotein,Plasma lipids,Plasma lipoprotein,LDL,Lp(a),VLDL,I
3、DL,HDL,structure of lipoprotein,Clinical items for lipids detection,total cholesterol，TC triglyceride，TG high density lipoprotein cholesterol，HDL-C low density lipoprotein cholesterol，LDL-C apolipoprotein A1，ApoA1 apolipoprotein B，ApoB lipoprotein(a) The first four items were routine test ,and shoul
4、d be carried out in healthy examinations,Cinical items for lipids analysis (2),FFA Cerebroside esterceramide Sphingenine Sphingomyelin Galactode-cerebroside,Genotype,ApoE genotype ApoCIII genotype ApoCII genotype Apo(a) genotype LDLR genotype VLDLR genotype HMGCoAR genotype SR genotype,Cinical items
5、 for lipids analysis (3),Preanalytical Factors Affecting Lipid Test Results,The following factors may cause preanalytical variations,Biological factors Individual biological variations, gender, age, and race, etc. Life-style factors diet, obesity, smoking, stress, alcohol, and coffee intake, and exe
6、rcise, etc.,Behaviour factors (1),Diet The food containing abundant unsaturated fatty acid can decrease the level of TC, LDL-C, apoB and TG. The food containing abundant saturated fatty acid can elevate TC, LDL-C . The food containing abundant fiber can reduce the leval of TC. The levels of LDL-C an
7、d Lp(a) in vegetarians were lower (37, 35 respectively) than non-vegetarians, while HDL-C were higher than that of 12.,Behaviour factors (2),Obesity TG，TC and LDL-C HDL-C Lost weight TG （40） TC（ 10 ） LDL-C （ 10 ） HDL-C （ 10 ） ,Smoking TG, LDL-C and Lp(a) apoA and HDL-C HDL-C ,Behaviour factors (3),B
8、ehaviour factors (4),Alcohol abuse HDL-C, apoA,apoA （1.2 oz/d or 34g/d） Primry hypertriglyceridemia with mild drinking can lead to the level of TG increased further . Alcohol has different effects on Lp(a) from other lipids . at the begin Lp(a) 33% six weeks later Lp(a) back to initial level Proper
9、drinking red wine can decrease the level of Lp(a) .,Behaviour factors (5),Coffee TC and LDL-C apoA, apoA, apoB and HDL-C seemed not be affected. Tension TC Hospitalization HDL-C and apoA( 10) ,Behaviour factors (6),Exercise TG、LDL-C and apoB HDL-C and apoA The degree was related to the kinds of spor
10、ts and intensity. Intense exercises can increase the level of HDL-C obviously. Moderate regular exercises was a ideal way to decrease the level of blood lipid. Normal exercises have no influences on the level of Lp(a) ，while intense physical activity can increase the level of Lp(a) by 1015.,Clinical
11、 factors therapeutic drugs (1),Antihypertensive agents for example thiagine（diuresis drug）can increase the level of TC, LDL-C, TG and apoB by 12%、 20%,7%, 20% respectively , decrease the leval of apoAI and HDL-C by 6% and 16% . Beta-neg（ receptor blocker ） can increase the level of TG and decrease t
12、he leval of HDL-C. Estrogen Oral taking contraceptive with progesterone can increase the leval of TC and LDL-C,and decrease the leval of HDL-C . Estrin treatment can decrease the leval of Lp(a) by 50% .,Immunosuppressive agents Codelcortone can increase the level of TC, LDL-C, HDL-C, TG, apoA and ap
13、oB. Ciclosporin can increase the level of TC, LDL-C, apoB，and decrease the level of Lp(a) . Tacrolimus FK506 can decrease the level of TC.,Clinical factors therapeutic drugs (2),The division of abnormal lipids level,The lipid level was diverse in different nation and area. It has been suggested that
14、 the level which can increase the risk of CHD obviously should serve as the division standard for abnormal level of lipid, meanwhile we claim to formulate the therapeutics destination and intervene the procedure according to the level . suggestions Adopt the standards of suggestions on prevention an
15、d cure lipid abnormality in china.,Risk rate,TC and CHD,Plasma TC,Medical decision level for lipid assay mmol/L(mg/dl),index china （1997） NCEP-ATP Serum TC Suitble leval 5.20(200) 5.20(200) margine increase 5.23-5.69(201-219) 5.20-6.21(200-239) Increse 5.72(220) 6.24(240) Serum LDL-C Suitble leval 3
16、.12(120) 3.38(130) margine increase 3.15-3.61(121-139) 3.38-4.13(130-159) Increse 3.64(140) 4.16(160) serum HDL-C Suitble leval 1.04(40) 1.56(60) Is a negative risk factor of CHD Decrese 0.91(35) 0.91(35) Is a risk factor of CHD Serum TG Suitble leval 1.70(150) 2.26(200) margine increase 2.26-4.52(2
17、00-400) Increse 1.70(150) 4.52(400),The classification of lipid level in ATP-III of the American National choleterol education project, mmol/L(mg/dl),LDL-C TC HDL-C TG leval judgement 6.24(240) 1.56(60) 2.265.64(200499) high 4.92(190) 5.65(500) very high 1.04(40) low JAMA,2001,285(19):24862497,Blood
18、 lipid mmol/L(mg/dl),Unit conversion for clinical routine of lipid items (primitive unit legal unit),TC mg/dl 0.0259mmol/L TG mg/dl 0.0113mmol/L HDL-C mg/dl 0.0259mmol/L LDL-C mg/dl 0.0259mmol/L apoAI mg/dl 0.01 g/L apoB mg/dl 0.01 g/L Lp(a) mg/dl 10 mg/L,The application of clinical lipid assay,Dete
19、cting and diagnosis hyperlipidemia in earlier period. Assisting in diagnosis of atherosclerosis. Evaluation of the risk of atherosclerosis disease , such as CHD and cerebral infarction. Monitoring and assessing the therapeutic efficacy of diet , medicine and so on . The diagnosis of endrocrine excre
20、tion metabolic disorder The diagnosis of hereditary Lipids metabolic disorder Health examination,Clinical significance of lipid assay ( 1),The level of TC changed with the living condition, it increased with the age, but decreased lightly after 70 years old. It was higher in young and mid-aged men t
21、han women ，but in old women it was higher than men. Hypercholesterolemia was an high risk factor of atherosclerosis, The higher the level of TC ,the earlier onset of CHD.,Clinical significance of lipid assay ( 2),The risk of CHD was lower when the TC was less than 4.5 mmol/L. The level of TC in CHD
22、patients was in the range of 5.0-6.5 mmol/L, The higher the level of TC , the earlier onset of CHD . When the cholesterol decrease by 1%, the risk of CHD may decrease by 2%。,Diseases affecting the level of TC,Primitive familial hypercholesterolemia（LDL-R deficiency） mixed hyperlipoproteinemis famili
23、al hyper-high density lipoproteinemia （CETP deficiency） familial type hyperlipidemia secondary ： endocrine disease： hypothyreosis、DM（especialy in coma）、cushing disease liver disease：emphraxis icterus、 hepatocarcinoma kidney disease：nephrotic syndrome、 chronicity nephritis nephrotic、para-lipid nephro
24、sis drug-induced ;use of sterol agent,Primitive lackinglipoproteinemia hypo-lipoproteinemia lipoprotein deficiency familial LCAT deficiency,secondary： severe live disease： acute hepatic necrosis、 cirrhosis of live endocrine disease ： hyperthyreosis、 severe dystrophy malabsorption syndrom severe aner
25、mia leukermia cancer,Cinical significance of lipid assay (2),The level of TG was related to race,age ,sex and Living condition .whats more , variation in the level of TG was obvious than the level of TC in the same individual and between individuals . After meal ,TG was absorbed and then circulating
26、 in the form of CM/VLDL in the blood .12 hours later after meal it was precluded, and the level of TG returned to initial level. TG existed in the blood circulation in the form of VLDL, if VLDL converts to sLDL,the risk of AS will increase.,Hypertriglyceridemia,primary hypertriglyceridemia,apoCdefic
27、ency LPL deficency,familial hypertriglyceridemia,apoCdificency primary tyoe V hypertriglyceridemia,famililial compated hyperlipidemia famililial type hyperlipidemia idiopsthic hypertriglyceridemia,apoE abnomality apoE deficency,Secondary hypertriglyceridemia,autoimmue disease,thyroidhypofunction,alc
28、ohol abuse ,autoimmue disease drug,obesity 、diabetes mellitus uraemia、oral contraceptive,The level of the ApoA1 in fasting serum of normal cohort was about 1.201.60g/L. Generally speaking, the serum level of ApoA1 could represent the HDL. It was positively correlated to the level of the HDL-C. In CH
29、D & CVD patients, the ApoA1 was lower. In familial hypertriglyceridemia, the HDL-C was usually lower, but the level of the ApoA1 was uncertain and it did not increase the risk of CHD. However, in familial combined hyperlipidemia, both the ApoA1 and HDL-C decreased lightly and they increased the risk
30、 of CHD.,Cinical significance of lipid assay (3),The level of the ApoB in fasting serum of normal cohort was about 0.80 1.20g/L. In general, the serum ApoB mainly represented the level of the LDL. It was positively correlated to LDL-C. In hypertriglyceridemia (the VLDL was very high), small dense LD
31、L increase ，ApoB was more and the cholesterol less, so we can see the level of LDL-C was not high ，but serum ApoB increased. So ApoB and LDL-C needed to be detected at the same time , it was helpful to clinical decision .,Cinical significance of lipid assay (4),Cinical significance of lipid assay (5
32、) Rich fatty and high calorie diet, seldom exercises and mental stress LDL-C The LDL belonged to the lipoprotein which could predipose to atherosclerosis. The high the level, the more the risk of atherosclerosis. The level of the serum LDL-C increased with age. LDL-C was the chief target of preventi
33、on of lipidemia abnormality.,The concentration of Lp(a) was regulated by gene. It was not affected by sex,age , drug and so on. Individual difference was obvious.（01000mg/L) Lp(a)300mg/L was abnormal (recommend) Lp(a) is an independent risk factor of atherosclerosis Lp(a) increased Acute phase react
34、ion : AMI, operation, acute wound 、acute inflammation, last stage of nephrosis，nephrotic syndrome，maglinant tumor except for liver cancer，pregnancy and so on.,Cinical significance of lipid assay (6),The risk of AS was higher in low HDL-C anemia. The lower the level of HDL-C , the higher the risk of
35、AS . When the HDL-C decreased by 1%, the risk of CHD might increase by 2%.,Cinical significance of lipid assay (7),Progression,Regression,?,?,?,?,?,?,HDL,LDL,VLDL,IDL,Lp(a),RLP,Im good,If treatable, were not that bad!,The Good,The Bad,The Ugly?,Plasma HDL-C level was affected by following diseases,s
36、econdary ： acute disease: AMI、operation, adustum、 acute inflamation diet with low fat and high sugar smoking, obesity hypomotility hormone decrease drug: receptor blocking phamacon,secondary ： alcohol abuse primary biliary cirhosis CETP activity increase HTGL activity decrease drug-induced： ACH、insu
37、lin、estrogen、 Micotinamide and its inductor 、 HMG-CoA reductase blocker、 chlorinated hydrocarbons,primary ： Tanger desease LCAT deficiency apoAsbnormality familial hypercholesterolemia famililial compated hyperlipidemia,primary ： CETP deficiency HTGL hypoactivity（macula opacity） apoA1 synthesis acce
38、nton HDL receptor abnormality,HDL-C decreased,HDL-C inceased,hereditary Lipid metabolic disorder lipoprotein gene deficiency lipoprotein receptor gene deficiency lipid metabolic enzyme gene deficiency cytolysosome lipid metabolism enzyme gene deficiency,Cinical significance of lipid assay (8),for in
39、stance : Lysosomal hydrolase hereditary defect , phospholipid metabolism disorder were very common.,Gene analysis of lysosomal storage disease,The Structure and Function of Lysosome Lysosome was such a kind of organelle like a film in the cell, with a cystiform structure,and it contained many kinds
40、of hydrolase,it worked so that it can break down many kinds of endogenous and exogenous substance, so it was also considered as a peptic in the cell. Phospholipid could be divided into glycerophospholipide and sphingolipid; the latter could be divided into sphingomyelin and glycosylsphingolipid. The
41、 lysosome contained about 50 kinds of hydrolase, such as protease, nuclease, glycosidase, lipase, phosphatase, phosphonolipidase and sulfatidase etc.,鞘脂代谢,Sphingolipid metabolism,Lysosomal lipids storage disorders,NeuAc,(N-acetylneuraminic acid)； Cer， (ceramide)； Glc， (glucose)； Gal, (galactose)； Fu
42、c， (fucose)； -enzyme action site,1. complete physical examination 2. cytological examination of marrow and peripheral blood cells mainly finding the large foam cells. 3. determination of routine biochemical indicator especially the lipid level and functional examination of liver and kidney.,Laborato
43、ry diagnosis of hereditary lysosomal lipids storage disease,Gaucher cell,Niemann-Pick cell？,4. lysosomal enzyme activity assay Chitotriosidase, CT To identify diagnosis of Lipids Storage Disease Gaucher disease increased lightly Niemann-Pick disease more than 100 times Sphingomyelinase To confirm th
44、e diagnosis of Niemann-Pick disease. Glucocerebrosidase To Confirm the diagnosis of Gaucher disease.,5. High performance liquid chromatogram , HPLC To analyze the composition of lipids To detect the enzymes activity 6. Physical examination To check up the pathological changes of liver, spleen, skele
45、ton and brain. 7. Gene analysis If the basic mutations resulted in the substitution of amio acids or the nucleotide depletions and/or insertions were identified, you can get a final diagnosis.,The lipid detection while the level of TC was normal,Serum : TC=VLDL-C+LDL-C+HDL-C for instance：A and B wer
46、e two person taken healthy examination TC=VLDL-C+LDL-C+HDL-C A. TC = 0.5 + 2.9 + 1.7 = 5.1 B. TC= 0.6 + 3.7 + 0.8 = 5.1 A. TC is normal HDL-C 0.9mmol/L LDL-C3.12 So B have a higher risk of AS than A.,Lipoproteins which resulted in AS,CM and VLDL remnants Modified LDL Small dense LDL Lp(a),Liver,Arte
47、ry,Transportation of TC,Physiological functions of HDL and LDL,Transportation of TC,Non-HDL-C,In ATP, non-HDL-C was recommend to regard as a second treatment target for high TG patient. When the chief treatment target arrived, while the level of TG was still high(TG 2.26 mmol/L ), non-HDL-C should be assisted in minitoring therapeutic efficiency In ATP, Patient , TG was in marginal (1.702.25mmol/L ), was suggested to change life style ,and neednt to calculate non-HDL-C .,The