血脂检测临床应用的有关问题课件

1、Related problems on clinical application of plasma lipids assayProfessor zhou xin Department of Laboratory Medicine,Zhongnan hospital of wuhan university.Dr. Sheng-kai Yan , PhDDepartment of Laboratory Medicine, Peking Union Medical College HospitalAll kinds of lipids in plasma were called blood lip

2、ids 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 lipidsPlasma lipoproteinLDLLp(a)VLDLIDLHDLstruc

3、ture of lipoproteinClinical items for lipids detectiontotal cholesterol，TCtriglyceride，TGhigh density lipoprotein cholesterol，HDL-Clow density lipoprotein cholesterol，LDL-Capolipoprotein A1，ApoA1 apolipoprotein B，ApoBlipoprotein(a)The first four items were routine test ,and should be carried out in

4、healthy examinations Cinical items for lipids analysis (2)FFACerebroside esterceramideSphingenine SphingomyelinGalactode-cerebrosideGenotype ApoE genotype ApoCIII genotype ApoCII genotype Apo(a) genotype LDLR genotype VLDLR genotype HMGCoAR genotype SR genotypeCinical items for lipids analysis (3)Pr

5、eanalytical Factors Affecting Lipid Test Results 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) Behaviour factors (4)Alcohol abuseHDL-C, apoA,apoA （1.2 oz/d or 34g/d）Pri

6、mry 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 levelProper drinking red wine can decrease the level of Lp(a) .Immunosuppressive agentsCod

7、elcortone can increase the level of TC, LDL-C, HDL-C, TG, apoA and apoB.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 wa

8、s diverse in different nation and area. It has been suggested that 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

9、 .suggestions Adopt the standards of suggestions on prevention and cure lipid abnormality in china. Risk rateTC and CHD Plasma TC Medical decision level for lipid assay mmol/L(mg/dl)index china （1997） NCEP-ATP Serum TCSuitble leval 5.20(200) 5.20(200)margine increase 5.23-5.69(201-219) 5.20-6.21(200

10、-239)Increse 5.72(220) 6.24(240)Serum LDL-CSuitble leval 3.12(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-CSuitble leval 1.04(40) 1.56(60) Is a negative risk factor of CHDDecrese 0.91(35) 0.91(35) Is a risk factor of CHDSerum TGSuitble lev

11、al 1.70(150) 2.26(200)margine increase 2.26-4.52(200-400)Increse 1.70(150) 4.52(400) Unit conversion for clinical routine of lipid items (primitive unit legal unit)TC mg/dl 0.0259mmol/LTG 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/LapoB mg/dl 0.01 g/LLp(a

12、) mg/dl 10 mg/LThe application of clinical lipid assayDetecting 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 ,

13、 medicine and so on . The diagnosis of endrocrine excretion metabolic disorder The diagnosis of hereditary Lipids metabolic disorderHealth examinationClinical significance of lipid assay ( 1)The level of TC changed with the living condition, it increased with the age, but decreased lightly after 70

14、years old. It was higher in young and mid-aged men than 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 T

15、C was less than 4.5 mmol/L. The level of TC in CHD 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 TCPrimitivefamilial hypercholesterolemia（LDL-

16、R deficiency） mixed hyperlipoproteinemis familial hyper-high density lipoproteinemia （CETP deficiency）familial type hyperlipidemiasecondary ： endocrine disease： hypothyreosis、DM（especialy in coma）、cushing disease liver disease：emphraxis icterus、 hepatocarcinoma kidney disease：nephrotic syndrome、chro

17、nicity nephritis nephrotic、para-lipid nephrosisdrug-induced ;use of sterol agentPrimitive lackinglipoproteinemia hypo-lipoproteinemia lipoprotein deficiency familial LCAT deficiencysecondary：severe live disease：acute hepatic necrosis、cirrhosis of live endocrine disease ： hyperthyreosis、 severe dystr

18、ophy malabsorption syndrom severe anermia 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 ,

19、TG was absorbed and then circulating 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. Hypertriglyceridemiaprim

20、ary hypertriglyceridemia apoCdeficency LPL deficency familial hypertriglyceridemiaapoCdificencyprimary tyoe V hypertriglyceridemia famililial compated hyperlipidemiafamililial type hyperlipidemiaidiopsthic hypertriglyceridemia apoE abnomalityapoE deficency Secondary hypertriglyceridemiaautoimmue dis

21、ease thyroidhypofunctionalcohol abuse ,autoimmue disease drugobesity 、diabetes mellitusuraemia、oral contraceptiveThe 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 l

22、evel of the HDL-C.In CHD & 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 t

23、hey increased the risk 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 hi

24、gh), small dense LDL 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

25、 of lipid assay (5) Rich fatty and high calorie diet, seldom exercises and mental stress LDL-CThe 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 tar

26、get of prevention 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 atherosclerosisLp(a) increased Acut

27、e phase reaction : 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 t

28、he risk of AS .When the HDL-C decreased by 1%, the risk of CHD might increase by 2%.Cinical significance of lipid assay (7)ProgressionRegression?HDLLDLVLDLIDLLp(a)RLPIm goodIf treatable, were not that bad!The GoodThe BadThe Ugly?Plasma HDL-C level was affected by following diseasessecondary ：acute d

29、isease: AMI、operation, adustum、acute inflamationdiet with low fat and high sugarsmoking, obesity hypomotility hormone decreasedrug:receptor blocking phamacon secondary ： alcohol abuse primary biliary cirhosisCETP activity increase HTGL activity decrease drug-induced：ACH、insulin、estrogen、Micotinamide

30、 and its inductor 、HMG-CoA reductase blocker、chlorinated hydrocarbons primary ： Tanger desease LCAT deficiency apoAsbnormality familial hypercholesterolemia famililial compated hyperlipidemiaprimary ： CETP deficiency HTGL hypoactivity（macula opacity） apoA1 synthesis accenton HDL receptor abnormality

31、HDL-C decreasedHDL-C inceased hereditary Lipid metabolic disorder lipoprotein gene deficiency lipoprotein receptor gene deficiency lipid metabolic enzyme gene deficiency cytolysosome lipid metabolism enzyme gene deficiencyCinical significance of lipid assay (8)for instance : Lysosomal hydrolase here

32、ditary 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 of hydrolase,it worked so that it

33、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 lysosome contained about 50 kinds

34、 of hydrolase, such as protease, nuclease, glycosidase, lipase, phosphatase, phosphonolipidase and sulfatidase etc.鞘脂代谢Sphingolipid metabolismLysosomal lipids storage disordersdiseaseEnzymen defectStored lipidClinical symptom(Fucosidosis)(Fucosidase)gene locus : 1p34Cer-Glc-Gal-GalNAc-Gal-FucH-alloa

35、ntigen (H-lsoantigen) cerebrum degenerate，Convulsive tic，(Generalized gangliosidosis)(GM1-galactosidase)gene locus : 3pter-p21Cer-Glc-Gal(NeuAc)-GalNA-Gal(GM1Ganglioside)mental aphrenia ，skeleton deform hepatauxe，(Tay-Sachs disease)(Hexosaminidase A)gene locus : 15q13.1Cer-Glc-Gal(NeuAc)-GalNAc(GM2G

36、anglioside)mental aphrenia，acroisa amyastheniaMetachromatic leukodystrophy, MLD)(Arysulfatase A)gene locus : 10q21.1Cer-Gal-OSO3(3-suffogalactosyl-ceramide) mental aphrenia ，mental retardate in adult，demyelination(Krabbes disease)(-Galactosidase)gene locus : 14q31Cer-Gal(Galactosylceramide)mental ap

37、hrenia :nearly no myelin (Gaucher disease, GD)(-Glucosidase, -glu)gene locus: 1q21.1Cer-Glc(Glucosylceramidsplenohepatomegalia，Bone causticize ，mental retardate in youge child(Niemann-Pick disease)(Sphingomyelinase,ASM)gene locus: 11p15.1-p15.4Cer-_P-(Sphingomyelin)splenohepatomegalmental retardateD

38、ie in youge child(Farber disease,)(Ceramidase)Acyl-(Ceramide) Acyl- (Ceramide) NeuAc,(N-acetylneuraminic acid)；Cer， (ceramide)；Glc， (glucose)；Gal, (galactose)；Fuc， (fucose)； -enzyme action site 1. complete physical examination 2. cytological examination of marrow and peripheral blood cells mainly fi

39、nding the large foam cells. 3. determination of routine biochemical indicator especially the lipid level and functional examination of liver and kidney. Laboratory diagnosis of hereditary lysosomal lipids storage diseaseGaucher cell Niemann-Pick cell？ 4. lysosomal enzyme activity assayChitotriosidas

40、e, CT To identify diagnosis of Lipids Storage Disease Gaucher disease increased lightly Niemann-Pick disease more than 100 timesSphingomyelinase To confirm the diagnosis of Niemann-Pick disease.Glucocerebrosidase To Confirm the diagnosis of Gaucher disease. 5. High performance liquid chromatogram ,

41、HPLC To analyze the composition of lipids To detect the enzymes activity 6. Physical examination To check up the pathological changes of liver, spleen, skeleton and brain.7. Gene analysis If the basic mutations resulted in the substitution of amio acids or the nucleotide depletions and/or insertions

42、 were identified, you can get a final diagnosis.The lipid detection while the level of TC was normalSerum : TC=VLDL-C+LDL-C+HDL-Cfor instance：A and B were 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 0.9mm

43、ol/L LDL-C3.12 B. TC is normal HDL-C3.12So 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)LiverArteryTransportation of TCPhysiological functions of HDL and LDLTransportation of TC Non-HDL-C In ATP, non-HDL-C was recommend to

44、 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 efficiencyIn ATP, Patient , TG was in marginal (1.702.25mmol/L ), was suggested to change li

45、fe style ,and neednt to calculate non-HDL-C .The standard value and target value for hyperlipidimia received treatment (China 1997)AS (-) TC 5.72 mmol/LOther risk （ 220.0mg/dl ） factor(-) Ldl-c 3.64 mmol/L （ 140.0mg/dl ）AS (-) TC 5.2 mmol/L Other risk （ 200.0mg/dl ）factor(+) Ldl-c 3.12 mmol/L （ 120.

46、0mg/dl ）AS (+) TC 4.68 mmol/L （ 180.0mg/dl ） Ldl-c 3.64 mmol/L （ 100.0mg/dl ）Drug therapyDietTarget valueTC 6.24 mmol/L（ 240.0mg/dl ） Ldl-c 4.16 mmol/L （ 160.0mg/dl ） TC 5.72 mmol/L（ 220.0mg/dl ） Ldl-c 3.64 mmol/L （ 140.0mg/dl ） TC 5.20 mmol/L（ 200.0mg/dl ） Ldl-c 3.12 mmol/L （ 120.0mg/dl ） TC 5.72 m

47、mol/L（ 220.0mg/dl ） Ldl-c 3.64 mmol/L （ 140.0mg/dl ） TC 5.2 0mmol/L（ 200.0mg/dl ） Ldl-c 3.12 mmol/L （ 140.0mg/dl ） TC 4.68 mmol/L（ 180.0mg/dl ） Ldl-c 2.60 mmol/L （ 100.0mg/dl ）The target value of TLC and drug therapy in different kind of CHD (ATP 2001)Risk classification LDL-C LDL-C LDL-C target val

48、ue onset of TLC considering drug treatmentCHD or other danger sign 20%） 100mg/dl 100.0mg/dl ） 2.59.3.36mmol/Lconsidering if drug treatment needed2 risk factor 3,36 mmol/L 3,36 mmol/L 10 years-risk 10%-20% ( 3,36 mmol/L)10 years-risk 20% 130mg/dl 130mg/dl 10 years-risk 10% ( 4,14 mmol/L ) 01 risk fac

49、tor 20%）100mg/dl ，(can select objective： 70mg/dl)especially patient with very high risk )100mg/dl100mg/dl(100mg/dl ;may regard medicine)milddling risk：2risk agent（10 years risk is 1020）130mg/dl( can select objective：100mg/dl130mg/dl#130mg/dl(100-129md/dL; ;may regard medicine)milddling risk ：2risk a

50、gent（10 year risk10%）130mg/dl130mg/dl160mg/dllow risk：01 risk agent160mg/dl160mg/dl190mg/dl(160-190mg/dl；;may regard medicine decresing LDL) pay attention to several problemsSeveral incorrect conceptsHDL-C HDL HDL-C is merely a part of HDL，but can reflect the HDL in the bloodnLDL-C LDLLDL-C is merel

51、y a part of LDL，but can reflect the LDL in the bloodReasonable selection and application of lipid itemsClinical routine lipids assay should include at least four items: TC, TG,HDL-C and LDL-C.Merely measured TC and TG cant reflect basic lipids levelSome cases were not suitable to calculate LDL-C by

52、Friedewald formula CM existed in plasma； TG 4.52mmol/L (400mg/dl)； Abnormal beta-lipoprotein existed type hyperlipidemia (HLP)(1)Reasonable selection and Application of lipid items(2)Cases needed to measure plasma ApoAI and ApoB ：Unsure if there were any risk factors in the patient with cardiovascul

53、ar or cerebrovascular disease, but the routine lipids items were normal.The youth and middle-aged men suffering from cardiovascular or cerebrovascular disease.Persons have the family histoty of early onset of AS.Family member with low ApoAI and high ApoB .Reasonable selection and Application of lipi

54、d items(3)Cases needed to measure plasma Lp(a)Unsure if there were any risk factors in the patient with cardiovascular or cerebrovascular disease, but the routine lipids items were normal.The youth and middle-aged men suffering from cardiovascular or cerebrovascular disease.Patients with the family

55、histoty of early onset of AS.Family member with high Lp(a) . HDL-C represented the metabolism status of cholesterol and transported by HDL. ApoAI can reflect the capacity of HDL, but increasing or decreasing of ApoAI was not in proportion to HDL-C.To measure the level of ApoAI and HDL-C at one time

56、was helpful to analyze the pathologic and physical status. ApoAI or HDL-C can not represent HDL , they were all necessary to be measured.HDL-C and ApoAI shoud not replace with each other LDL-C and ApoB shoud not substitute for each otherIn general , the level of ApoB can represent LDL,and it was a positive correlation with LDLC.LDL was a kind of lipoprotein which contained different size of particles and diverse compositions, and it can be divided into LDL1 ( type A) and LDL2 (type B).In hypertriglycerdemia, the