-血脂检测临床应用的有关问题课件.ppt

1、 Plasma lipidsPlasma lipoproteinLDLLp(a)VLDLHDLstructure of lipoproteinClinical items for lipids detectionCinical items for lipids analysis(2)nFFAnCerebroside esterceramidenSphingenine SphingomyelinnGalactode-cerebrosideGenotype n ApoE genotype ApoCIII genotypen ApoCII genotype Apo(a)genotype n LDLR

2、 genotype VLDLR genotypen HMGCoAR genotype SR genotypeCinical items for lipids analysis(3)Behaviour factors(1)unsaturated fatty acid saturated fatty acid Behaviour factors(2)TG，TC and LDL-C HDL-C Lost weight TG（40）TC（10）LDL-C（10）HDL-C（10）TG,LDL-C and Lp(a)apoA and HDL-C HDL-C Behaviour factors(3)Beh

3、aviour factors(4)nHDL-C,apoA,apoA（1.2 oz/d or 34g/d）nPrimry hypertriglyceridemia with mild drinking can lead to the level of TG increased further.nAlcohol has different effects on Lp(a)from other lipids.at the begin Lp(a)33%six weeks later Lp(a)back to initial levelnProper drinking red wine can decr

4、ease the level of Lp(a).Behaviour factors(5)nCoffeeTC and LDL-C apoA,apoA,apoB and HDL-C seemed not be affected.nTension 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 sports and intensity.Intense exercises ca

5、n 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 factors therapeutic drugs(1)nfor example t

6、hiagine（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%.nBeta-neg（receptor blocker）can increase the level of TG and decrease the leval of HDL-C.nOral taking contraceptive with progesterone can increase the

7、leval of TC and LDL-C,and decrease the leval of HDL-C.nEstrin treatment can decrease the leval of Lp(a)by 50%.nImmunosuppressive agentClinical factors therapeutic drugs(2)The division of abnormal lipids level Risk rateTC and CHD Plasma TC Medical decision level for lipid assay mmol/L(mg/dl)The class

8、ification of lipid level in ATP-III of the American National choleterol education project,mmol/L(mg/dl)Blood lipid Unit conversion for clinical routine of lipid items (primitive unit legal unit)The application of clinical lipid assayClinical significance of lipid assay(1)Clinical significance of lip

9、id assay(2)Diseases affecting the level of TC Cinical significance of lipid assay(2)Hypertriglyceridemia drugnHowever,in familial combined hyperlipidemia,both the ApoA1 and HDL-C decreased lightly and they increased the risk of CHD.Cinical significance of lipid assay(3)Cinical significance of lipid

10、assay(4)Cinical significance of lipid assay(5)nephrotic syndrome，pregnancy and so onCinical significance of lipid assay(6)Cinical significance of lipid assay(7)?HDLLDLVLDLIDLLp(a)RLPIm goodIf treatable,were not that bad!Plasma HDL-C level was affected by following diseases hereditary Lipid metabolic

11、 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 hereditary defect ,phospholipid metabolism disorder were very c

12、ommon.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 can break down many kinds of endogenous and exogenous substan

13、ce,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 of hydrolase,such as protease,nuclease,glycosidase,lipase,phosph

14、atase,phosphonolipidase and sulfatidase etc.鞘脂代谢Sphingolipid metabolismLysosomal lipids storage disordersdiseaseClinical symptom(Fucosidosis)(Fucosidase)gene locus:1p34Cer-Glc-Gal-GalNAc-Gal-FucH-alloantigen(H-lsoantigen)cerebrum degenerate，Convulsive tic，(Generalized gangliosidosis)(GM1-galactosida

15、se)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(GM2Ganglioside)mental aphrenia，acroisa amyastheniaMetachromatic leukodystrophy,MLD)(Arysulfatase A)gene locus:

16、10q21.1Cer-Gal-OSO3(3-suffogalactosyl-ceramide)mental aphrenia，mental retardate in adult，demyelination(Krabbes disease)(-Galactosidase)gene locus:14q31 Cer-Gal(Galactosylceramide)mental aphrenia:nearly no myelin(Gaucher disease,GD)(-Glucosidase,-glu)gene locus:1q21.1Cer-Glc(Glucosylceramidsplenohepa

17、tomegalia，Bone causticize，mental retardate in youge child(Niemann-Pick disease)(Sphingomyelinase,ASM)gene locus:11p15.1-p15.4Cer-_P-(Sphingomyelin)splenohepatomegalmental retardateDie in youge child(Farber disease,)(Ceramidase)Acyl-(Ceramide)Acyl-(Ceramide)NeuAc,(N-acetylneuraminic acid)；Cer，(cerami

18、de)；Glc，(glucose)；Gal,(galactose)；Fuc，(fucose)；-enzyme action site plete 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 l

19、iver and kidney.Laboratory diagnosis of hereditary lysosomal lipids storage diseaseGaucher cell Niemann-Pick cell？4.lysosomal enzyme activity assayvChitotriosidase,CT To identify diagnosis of Lipids Storage Disease Gaucher disease increased lightly Niemann-Pick disease more than 100 timesvSphingomye

20、linase To confirm the diagnosis of Niemann-Pick disease.vGlucocerebrosidase 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

21、,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 were identified,you can get a final diagnosis.The lipid detection while the level of TC was normalLipoproteins which resulted in AS n CM and VLD

22、L remnantsn Modified LDLn Small dense LDL n Lp(a)LiverArteryTransportation of TCPhysiological functions of HDL and LDLTransportation of TC Non-HDL-C The standard value and target value for hyperlipidimia received treatment (China 1997)AS(-)Other risk factor(-)AS(-)factor(+)AS(+)The target value of T

23、LC and drug therapy in different kind of CHD (ATP 2001)Risk classification LDL-C LDL-C LDL-C target value onset of TLC considering drug treatmentCHD or other danger sign 20%）100mg/dl considering if drug treatment needed2 risk factor 10 years-risk 10%-20%10 years-risk 20%130mg/dl 130mg/dl 10 years-ri

24、sk 10%(01 risk factor 190mg/dl 160mg/dl 160mg/dl considering ifdrug treatment needed The target value and cutoff value for drug treatment and TLC at different risk in the modified ATP III based on recent evivence of clinical trials.NCEP Report.Circulation.2004:110;227-39Risk categary LDL-C goalonset

25、 of TLCconsidering drug treatmentSeveral incorrect conceptsReasonable selection and application of lipid items(1)Reasonable selection and Application of lipid items(2)Reasonable selection and Application of lipid items(3)HDL-C and ApoAI shoud not replace with each other LDL-C and ApoB shoud not substitute for each other Risk factors diagnostic criteria Administration of hyperlipidemia in children fasting conditions,hemoconcentration,use of anticoagulants and preservatives,capillary blood against venesection,and storage conditions of the specimen etc.