TRUONG DAI HOC Y HA NOI HOA SINH LAM SANG (Séch déo tao Dai hoe Y) Chia bién: GS.TS. Ta Thanh Van Nagwya i Phiang at XNMb NHA XUAT BAN Y HOG HA NOI - 2043CHI DAO BIEN SOAN: ‘Trdg Dai hoe Y Ha NGi CHU BIEN: GS.TS. Ta Thanh Van NHUNG NGUOI BIEN SOAN: GS.TS. Ta Thanh Van PGS.TS. Nguyén Thi Ha PGS.TS. Dang Thi Ngoc Dung TS. Trin Thj Chi Mai THU KY BIEN SOAN: TS, Trin Thi Chi Mai ThS. Nguyén Thanh Hai ThS. Nguyén Ngoc Lan © Ban quyén thudc vé Trung Dai hoc Y Ha NGiLOI NOI DAU Thye hign Luat Giéo duc, BO Gido. duc va Bao tgo va BO Y té da ban hanh Chuong trinh khung dao tao dai hoc nganh Y té, Trudng Dai hoc Y Ha Noi da chi dong bién soan nhigu tai ligu phye vu cho céng tac day va hge cho cae cdc mén khoa hoc co ban, y hoc co sé va cée chuyén nginh thuée linh vye y hoc lam sing dua trén hung chuong tinh trén nhim timg buée xy dung bd séch chun cua trugmg phyc vu cho cOng tae dao tao ngudn nhan lye y té. Sach “Héa sinh lam sang” duge bién soan boi nhém céc nha khoa hgc giau kinh nghiém giang day va nghién etru khoa hoc thuge cdc linh vye Ha sinh va Héa sinh lam sang cia Truéng Bai hoe Y Ha Noi. Cuén sch nhim phyc vu dio tao dai hoc va sau dai hoc cua Truong Dai he Y Ha N6i theo chong trinh giéo duc chi tiét eta truvmg, Déng théi, cudn sach cing 1a tai ligu tham khdo cho céc bac si lam sang va cén lam sang ciing nhu eéc nha nghién tru trong linh vue y hgc. Séch “Héa sinh Idm séng” cung cap cho dc gia nhiing kién thife bénh hoc duéi céi nhin ciia mt nha héa sinh y hoe bao gm: (/) Qua trinh chuyén héa chat xay ra 6 cfc mé, eo quan cia co thé; (2) Co ché bénh hoe cling véi sy bién ddi ca céc chi s6 héa sinh trong suét qué trinh bénh ly; (3) Cc xét nghiém chan don, theo doi va tién long bénh. Thay mt nhém tic gid, ching tdi xin bay td sy biét on t6i cdc déng nghiép da danh thoi gian doe ban théo va gop ¥ chi tiét vé n6i dung cing nhur edch trinh bay. Loi cam on cling danh cho cdc cn b@ BO mén Héa sinh, BO mén Héa sinh lam séng thudc Khoa Kj thuat Y hoc, Truong Dai hoc Y Ha N6i va Nha xudt bin Y hoe da gitip 46 cde td gid trong qué trinh hoan thién cudn sch nay. Day 1a lan xudt bn dau tién nén chéc chan cudn sach con nhimg thiéu sét. Ching tdi mong mudn nhén duge ¥ kién déng gop cita ddng nghiép va cée dc gid dé chinh ly, bd sung va cp nbt cho séch duge hoan chinh hon trong nhémg lan xuat ban sau. Ha N6i, ngay 24 thang 8 nd 2012 GS.TS, Tg Thanh VanMYC LUC Loi ndi dau Chwong 1. Enzym hge lim sing 1. Enzym trong huyét thanh 2.Enzym co 3. Enzym gan 4, Enzym tuy 5. Enzym xuong Chwong 2. Réi loan chuyén héa carbohydrat 1. Dinh nghia va phan loai 2. Tom luge cdc dic diém chuyén hod carbohydrate 3. Diéu hoa ning 49 glucose mau 4, Tang glucose mau 5. Ha glucose mau 6. Cac réi loan chuyén hod carbohydrat bam sinh 7. Céc ky thuit phan tich glucose Chwong 3. Chuyén héa va réi logn chuyén béa lipoprotein 1. Lipid va lipoprotein 2. Chuyén hos ciia lipoprotein 3. R6i loan lipid mau Chwong 4. Acid amin, peptid va protein huyét thanh 1. Acid amin 2. Peptid va protein 3. Protein huyét thanh 4, Protein cit hé théng bé thé 5. Khang thé 3 9 Nguyén Thi Ha 9 12 16 20 2 22 Tran Thi Chi Mai 2 23 24 26 35 40 43 31 Nguyén Thi Ha 51 55 39 66 Ta Thanh Van 66 68 1 86 87Chwong 5. Chuyén héa chit khong va xwong 92 Dang Thi Ngoc Dung, Nguyén Ngoc Lan 1. Téng quan vé cht khong va xuong 2. Chuyén héa xuong 3. Canxi 4. Phosphat 5. Magie 6. Cac hormon digu hoa chuyén hod chat khoang ‘Chuong 6. Chuyén héa sit va porphyrin 92 92 95 101 105 108 113 Dang Thi Ngoc Dung, Nguyén Thanh Hai 1. Chuyén hod sit 2. R6i loan chuyén hod sit 3. Chuyén héa porphyrin 4, Réi loan chuyén héa porphyrin Chwong 7. Réi loan chuyén héa nude va cht dign gi 1, Nude 2. Natri 3. Kali 4.Clo 5. Khoang tréng anion 6. Magnesi 7. Ky thuat phan tich cdc chat dign giai Chuwong 8. Khi miu va thing bing acid-base 1. Céc khai nigm co ban 2. Diéu hoa thang bing acid-base 3. Oxy va sy trao di khi 4. Céc r6i loan thing bing acid-base 5. Thu thap va van chuyén miu bénh phim. 6. Kg thuat phan tich khi mau 113 118 122 126 129 Tran Thi Chi Mai 129 130 135 137 138 139 141 145 Tran Thi Chi Mai 146 147 149 153 160 163Chuong 9. Ce xét nghigm chan dodn bgnh tim-mgch 1. Lipid huyét tong 2. Trang thai huyét tuong 3. Theo dai sinh hoe bénh xo vita dgng mach 4. Theo dai sinh hoc bénh tang huyét 4p 5. Chin doén va theo di sinh hoc bénh nhdi mau co tim 6. Brain natridiuretic peptid Chwong 10. Héa sinh Him sing bénh gan-mat 1. Chite ning sinh ly 2. Cée xét nghiém danh gid chite nang gan 3. Mot sé bénh ly gan thudng gap Chwong 11. Héa sinh lm sing tuy va da day-rugt + ToHlod sith tay 2. Hod sinh daddy « 3. Hod sinh rugt Chwong 12. Héa sinh lain sing bgnli than-tiét nigu “1. Chite nang sinh'ly 2. Cae xét nghigm dan gid chiro ndng than 3. Mot sé bénh ly than thiteng gap ‘Chuong 13. Ving dwoi-dbi- 1. Viang dudi di 2. Tuyén ting 3. Tuyén yén 4, Cée r6i loan lam sang Chuong 14. Tuyén giap 1, Tuyén gidp 2. Cac xét nghiém danh gid chire nang tuyén giép 3. Cac bénh ly tuyén giép 166 Nguyén Thi Ha 166 in 172 172 173, 178 180 Ta Thanh Van 181 185 189 192 Tran Thi Chi Mai 192 201 203 206 Ta Thanh Van 206 215 223 225 Tran Thi Chi Mai 225 226 226 231 235 Tran Thj Chi Mai 235 239 244Chwong 15. Réi loan chuyén héa catecholamin 250 Déng Thi Ngoc Dung, Nguyén Ngoc Lan 1. C4u trac va chuyén hod catecholamin 250 2. Chite nang cia hé théng catecholamin 256 3. Ung dung lam sang 259 4, Dinh luong catecholamin 260 Chwong 16. Ddu dn ung thu 263 Ta Thanh Van 1. Lich sir phat hign cc d4u 4n ung thir 264 2. Ung dung lam sang 265 3. Higu qua va hudng dan lam sing 267 4. Céc déu an ung thu 269 Chwong 17. Hod sinh thai nghén 294 Déng Thi Ngoc Dung, Nguyén Thanh Hai 1. Cée giai doan mang thai 294 2. Bién déi trong qué trinh mang thai 295 3. Chan don va theo doi thai nghén dinh ky 301 Tai ligu tham khéo 307Chwong 1 ENZYM HOC LAM SANG MUC TIEU HOC TAP 1. Trinh bay duge nhiing déc diém chung ctia enzym huyét thanh, 2. Trinh bay duge ¥ nghia ldm sang cia mét sé enzym phé bién trong bénh ly cla m6 co, mé gan, mé tuy va mé xuong, Vige xéc dinh hoat 4 enzym trong céc dich sinh vat, dac biét trong mau, da g6p phan rét higu gua cho chan dodn, chan doan phan biét va theo doi diéu tri nhiéu bénh ly hac nhau, nhat la nhimg bénh néi khoa. Phan enzym hoc lm sang tap trung vao enzym cia nhimg bénh ve co, gan, tuy va tim-1a nhéing bénh phé bién trén lam sang. 1, ENZYM TRONG HUYET THANH Enzym trong huyét thanh gdm 2 nhém: ~ Nhém cée enzym huyét thanh cé chite nang: la nhimg enzym duge bai tiét vao mau va thyc hign cae chtte nang xtc téc cia ching trong mau; bao gdm: nhimg enzym cia qué trinh déng mau, LCAT (lecithin-cholesterol-acyltransferase), lipase,... — Nhém céc enzym huyét thanh khéng cé chite nang: 1 nhiing enzym duge bai tiét vao mau nhung khong hoat dong vi chung khéng c6 co chat trong huyét thanh. Néng dé cita cla nhimg enzym nay rat thép trong mau so véi ndng dé ciia ching trong cae m6. Logi enzym nay duge chia lam 2 phan nhém: (i) Céc enzym ngoai tiét, la nhing, enzym duoe bai tiét vao méu tir cdc mé, vi du: leucin aminopeptidase va phosphatase kiém ciia gan, lipase cia tuy, phosphatase acid cita tuyén tién ligt; (ii) Céc enzym cia té bao, nhimg enzym nay thudng t6n tai v6i ndng d6 rat thép hodc khong cé trong huyét thanh, hoat tinh cita ching tang trong huyét thanh khi cé sy tén thuong té bao. Nhimg enzym cé ngudn géc hao tuong té bao nhu lactat dehydrogenase (LDR), aldolase, alanin transaminase (ALT), aspartat transaminase (AST); nhimg enzym ngudn géc ty thé nhu glutamat dehydrogenase (GLDH); nhimg enzym ngudn géc lysosom nhu phosphatase Loai enzym nay rat duge quan tam trong chan doan chic nang va tinh trang bénh ly ca cde mé va eo quan, 1.1. Sy gidi phong enzym Enzym c6 m&t trong huyét thanh hod dén tir céc mé va t6 chite, hode la két qua tir sy bai tiét vao huyét tuong. Enzym cdc mé va t6 chite xtc tac hdu hét giai doan ctia cae qué trinh chuyén héa chinh cua té bao, noi ching hose dugc héa tan trong bio tuong té bao, ho&e duge gin véi cdu tritc bao.Mac dit nding 49 enzym trong té bao gép 1.000-10.000 ln so véi trong dich ngoai bao, nhung hoat 46 xtic tae rat thap cia enzym té bao van duge do luéng 6 co thé khoe manh, Co ché ciia sy giai phéng enzym van chua duge hiéu.biét day di. Nguyén nhan olla. ia.s gii phiéng bénh ly emzym| bao gdm: — Tén thuong tive tiép mang té bao, vi dy: do virus, do céc cht héa hoe. éu oxy va thiéu mau ca cdc mé va 16 chite. Sut gidi phéng enzym, bao gdm mic 46 va dién bién cia sy ting enzym trong huyét thanh, phy thude vao: (1) su chénh léch néng 46 enzym « trong va ngoai té bao, 2) noi khu tra trong té bao, vi du: noi khu tra trong gan ciing nhu trong duémg mét cla cia cde eo quan va nguyén nhdn gay thuong t6n co quan, (4) quy mé va tan suat ciia sy thidu hyt oxy trong mé va t6 chtte, (5) Tinh tham cia co quan va hoat dng chuyén héa cla co quan, 1.2, Sy ting hogt 49 cia enzym trong huyét thanh Tang hoat 49 enzym trong huyét thanh ting cé thé do: (1) sy tang vé s6 lung visho&e hoat tinh héa sinh hoc cua céc t8 bao & mé, vi du: ting hoat 46 ALP (Phosphatase kiém) trong giai doan tuéi truéng thinh do sy ting sé Iwong va hoat tinh cia té bao tly xuong, (2) sting sin sinh enzym cia cée té bao. m6, vi dy: sin xudt GGT (6-glutamyl transferase) tang béi cac té bao gan la két qua cia sy kich thich Ga té “bao nay’ do iby, thuiée barbiturate hoc phenytoin, (3) sy ton thuong té bao ciia ede rid do nhimg trang’ tii bénh ly, gay. hily hoai t8 bao-va giai-phéng enzym vao méu, (4) gidm d6 thanh Igc enzym. 11.3. Sy thanh Ipc enzym huyét thanh Nhting enzym c6 khSi lugng phan ti thap nhw a-amylase duoc bai tiét qua thin. Tuy nhign, phan lén enzym bj bat hoat trong huyét tuong va duge dua dén cae t8 bao cia 16 chite lign ving theo qué trinh endocytosis tre tiép qua receptor; tiép theo, ede enzym bj bé gy thinh peptid va acid amin, Nira di song cla nhiéu enzym la 24 + 48 gid (Bang 1.2) 1.4. Dinh Iwgng hoat 49 enzym voi enzym, nhidu khi khdng thé x4c dinh duge néng d6 thyc cia ching ma chi gidn tiép xc _dinh don vj hoat 46 cla enzym. Nhu vay, enzym duge. dinh long, trén co sé hoat tinh xtc tée. Hoat tinh xiic tac cita enzym duge biéu thi bang don vi déng hoc, bao gbm: — Bon vj quéc té (U = international Unit): Mét don vj quée té 1a lugng enzym xtie téie_mGt micromol (mol) co chat trong mét phiit. Hoat tinh xiie téc cla enzym trong mau thir duge biéu thi bang U/L, mU/L, KU/L. = Don vj Katal: Mot Katal la lugng enzym xiic tae sy bién déi hoan toan mot mol co chat trong m6t gidy. Hoat tinh xtc téc cha enzym trong mau thir thudng duge biéu thi bang pkatal/L. 10Bang 1.1, Nira di séng cilia cdc enzym huyét thanh Enzym Nira déi séng ‘ALP 3-7 ngay c-amylase 9-18 gid ALT (GPT) 50 gid ‘AST (GOT) 12-14 gio’ CHE 10 ngay cK 12 gio CK-MM 20 git CK-MB. 10 gi CK-BB 3 gid GLDH 16-18 gid GGT 3-4 ngay Lipase 7-14 90 Su chuyén déi: 1,0 pkatal/L = 60 U/L. (Céc phuomg php thudng diing dé dinh luong hoat 46 enzym la nhimg xét nghiém Ong hoc, ma sy thay di d6 hap thy mét d6 quang hoc cita chat chi thi trong mot don vi thoi gian duge sir dung dé do ludng tc d6 cua phan ting, tong tmg v6i hoat d> enzym trong diéu kign méi truéng enzym hoat dong véi tc 46 t6i da, nghia la diéu kign moi truing tin tai day di co chit va coenzym. Coenzym NADH" vi NADPH" thuéng duge ding 1a chat chi thi, Chét chi thj it ding hon 14 co chat hoae sn phim phan img (xét nghiém do mau). Cac két qua dinh Iugng hoat do enzym chi duge so sdnh véi nhau khi hoat 46 enzym duge do luring dudi nhtimg diéu kign giéng nhau. 1.5. Vai trd cia enzym trong chan doan Vigo lung hoat 46 enzym trong huyét thanh hode huyét tuong duge thie +hién nhim myc dich: Phat hign t6n thuong cia mé va té chite. Phat hign co quan géc bi t6n thuong. Phat hién mirc 6 tn thuong té bao (c6 kha nang hdi phuc hoac khong hdi phuc). Chan dodn bénh tiém an. Chan dean phan biét bénh bén trong cor quan (vj tri tén thurong té bao trong ec quan)... Céc théng tin chan doan can ctr vao: — Mite heat tinh cia enzym trong mau thi. Ml— Xéc dinh cdc logi hinh enzym (hoat d6 cdc enzym cé mat trong huyét thanh tai mét thoi diém). — Déinh gié hoat 46 cde enzym trong méi lién quan v6i nhau, vi du: tinh cdc ty Ig enzym. — Theo déi sy thay déi vé hoat d6 cac enzym. — Xéc dinh cdc isoenzym. Bang 1.2. Mot s6 enzym chinh ting dung trén lam sang Enzym ¥ nghia fam sang Acid phosphatase (ACP) Ung thy tuyén tién ligt ‘Alanine aminotransferase (ALT) Benh iy gan Aldolase (ALD) Benh Ij co x¥ong ‘Alkaline phosphatase (ALP) Benh Ij gan Benh Ij xong ‘Amylase (AMS) ‘viem tuy c&p ‘Angiotensin-converting enzyme (ACE) Diéu hoa huyét 4p mau Aspartate aminotransferase (AST) Nhdi mau co tim Benh ly gan Benh ly co xuong Creatine kinase (CK) Nhdi mau co tim Benh ly co xuong Elastase (E1) Sy thiéu hyt viem tuy man Glucose-6-phosphate dehydrogenase Thiéu mau huyét tan do thudc (G-6-PD) Glutamate dehydrogenase (GLD) Réi loan gan 8-Glutamyl-transferase (GGT) Réi loan gan Glycogen phosphorylase (GP) Nhéi mau co tim cdp_ Lactate dehydrogenase (LDH) Nhéi mau co tim Réi loan gan Ung thu Lipase (LPS) Vier tuy cp Trypsin (TRY) Viem tuy cdp 2. ENZYM CO Enzym thujc nhém nay bao gém creatin kinase (CK), lactat dehydrogenase (LDH), aldolase (ALD) va glycogen phosphorylase (GP). 122.1. Creatin kinase CK (EC 2.73.2; adenosine triphosphate: creatine N-phosphotransferase) la mot enzym dimer (82kDa), xiic tée phan img thufn nghjch phosphoryl héa creatin (Cr) bai ATP. Creatin pH9.0 Creatin phosphat SS + ATP pH67 ADP CK, Mg” Vé sinh ly hoc, khi co co, ATP bién thanh ADP, va CK xtc tac su t4i phosphoryl héa ADP thanh ATP sir dung creatin phosphat (CrP) nhu ngudn cung cap phosphat. pH tdi wu cho phan img (Cr + ATP > ADP + CrP) va phan tmg nguge lai (CrP + ADP — ATP + Cr) 14 9,0 va 6,7. G pH trung tinh, CrP 6 kha nang phosphoryl héa nhiéu lan cao hon ATP, kh ning ndy gitp cho phin img theo chiéu nguge ATP duge hinh thanh tir CrP. Phan img theo chiéu nguge xay ra nhanh gap 2 dén 6 lan hon phan img theo chiéu xu6i, phy thudc vao diéu kign phan img. Oi voi tat ca kinase, Mg” 1a ion hoat héa nbat thiét ciia cdc dang phitc hop ¢6 ATP va ADP. Khoang néng d6 t6i wu ota a Mg" rat hep, ngoai pham vi nay Mg™ la chat te ché, Nhiéu ion kim loai nhu Mn”, Ca**, Zn?* va Cu?" tre ché hoat tinh enzym. Bang 1.3. Hoat dé téi da cla CK va ty Ié cila cdc isoenzym trong céc mo Me Hoat 49 CK Isoenzym (%) bale ck-8B | CK-MB | CkK-MM Co xuong (t¥p |, co cham hoac soi 48) 50000 [<1 [3 97 ‘Co xuong (t¥p II, co nhanh hoac sqi tring) 50.000 <1 1 99 Tim 10000 |<, | 22 78 Nao 5000 | 400 «Jo 0 Co tron ng tieu hoa 5.000 | 96 1 3 Co tron bang quaig 4.000 | g2 6 2 CK la enzym dimer gdm 2 tiéu don vi, mdi tiéu don vj cé trong Iuong phan tir Khong 40.000. Céc tiéu don vj nay (B va M) la sn phim eta cée gen trén nhiém sic thé 14 va 19. Béi vi enzym hoat déng & dang dimer nén cé 3 dang isozym ciia CK tin tai: CK-BB (CK-1), CK-MB (CK-2) vi CK-MM (CK-3), Khu tri oa cdc isoenzym nay thay d6i trong céc mé (Bang 1.4). Tat ca 3 loai isoenzym duge tim thay trong bao tuong t€ bao; tuy nhién dang thir 4 khdc véi 3 dang trén vé mién dich hoc va 46 di chuyén dign di, 46 la isoenzym CK-Mt, khu trd gitta mang trong va mang ngoai ty thé, vi du 6 tim CK-Mt chiém 15% hoat d$ CK toan phan, Gen ma héa CK-Mt nim trén nhiém séc thé 15. Ngoai ra, hoat tinh CK cing dugc tim thay trong dang phan tir 1én — goi la macro- CK. Ky thuét xc dinh céc dang isoenzym CK 1a nhing ky thuat dic bigt, nhu: dign di & higu dign thé cao, sic ky long cao p (high-performance liquid chromatography, HPLC), sac ky tap trung (chromatofocusing) va ky thuat mign dich. 13Hoat d CK huyét thanh thay déi sinh ly theo gidi, tudi, khéi long co, hoat dong sinh ly. ¥nghia lam sang: Hoat a> CK huyét thanh ting trong tét ca céc bénh loan duémg ca. Trong loan during co tién trién (dae biét 14 bgnh Duchenne), hoat 46 CK huyét thanb tng cao nhat 6 dé tudi vi thanh nién va tho 4u (7 dén 10 tudi) va cé thé tang trong thoi gian dai trade khi bénh cé biéu hign lam sing. Hoat 49 CK huyét thanh giém & nhimg bénh nhan tudi cao va khi khéi tugng co edn chite nang bj gidm theo sy tién trién cia bénh. Khoang 50 én 80% ngudi phy nd Linh mang gen bénh Duchenne c6 hoat 49 CK huyét thanh tang. Hoat 49 CK cao trong vim co virus, viém da co va bénh co don thuan. Tuy nhién, trong nhiing bénh co do than kink, vi dy bénh nhuge co ning (myasthenia gravis), bénh xo img toin bd, bénh Parkinson, hoat 4 CK huyét thanh binh thuéng. Hogt 4 CK tng rat cao trong sét cao ac tinh. Co xuong bj bénh hoge bj tin thuong gay ting CK-MB trong mau tuin hoan, Trong ly gidi co van cép tinh do hoi chimg vii Idp, edu tric co bj phé hi nang né, hoat dg CK huyét thanh tang 200 ln so véi gidi han binh thudng, CK huyét thanh 6 thé ting rong nhiing tin thuong co khée nhur can thiép phdu thudt, tiém truyén trong co. Neoai ra, mét s6 thuéc eiing gay ting hoat 46 CK huyét thanh. Nhiing thay 48i eta hoat 4 CK va isozym CK-MB huyét thanh gp trong nhoi méu co tim, Mét s6 trang thai tim khéc cfing gay tang host dé CK va CK-MB huyét thanh, bao gdm: su khir rung co tim, phdu thudt d3t thong phéi tim va théng dng mach vanh, ghép tim, viém co tim va nhdi méu phdi. Hign nay, dé chén doan nhdi méu co tim cp, mot s6 xét nghiém khong enzym dic higu tim duge sir dung nhu troponin I hoge T. Hoat 49 CK huyét thanh cé méi lign quan nghich véi hoat dong tuyén gidp. Khoang 60% trudng hop suy gidp cé mitc ting trung binh cia hoat d§ CK cao hon 5 lan gid tri binh thudng, mic ting hoat dé CK cao nhat duge tim thdy gdp 15 lan gid tr binh thudng. Trong théi ky sinh 4é, hoat 49 CK toan phin trong méu ngudi me c6 thé ting 6 lan, CK-BB 06 thé ting & tré so sinh, dc biét khi nao bj tin thuong hoa tré so sinh c6 can ning thdp. Sy cé mat cia CK-BB trong mau, thug 6 néng d6 thap, trong 5 ngay dau sau sinh 6 tré. 2.2. Lactat dehydrogenase Lactat dehydrogenase (EC 1.1.1.27) la enzym vén chuyén hydro, xe tée phan mg oxy h6a L-lactat than pyruvat véi chat trung gian NAD" nhu chat nhén hydro, Day 1a phan tng thufin nghjch Lactatdehydrogenase pH8,8+9,8 L-Lactat + NAD" g=——— > Pyruvat + NADHH* pH 7,4 +7,8 14Enzym 6 trong long phan tit 134.000 va gm 4 peptid thude 2 loai M (hove A) va H (hoe B), méi loai chu sir kiém sodt gen khée nhau khu tri trén nhiém séc thé iva 12. Céc tiéu don vj tao thanh 5 isozym cla LDH, bao gm: LDH-1 (HHHH; Hy), LDH-2 (HHHM; HsM), LDH-3 (HHMM; HzM:), LDH-4 (HMMM; HM), LDH-5 (MMMM; Mz). Mat khde biét, isozym thir 6, LDH-X (cdn goi la LDH.) gdm 4 tiéu don vi X (hay C), c6 trong tinh hoan ngudi sau tui day thi. LDH thir 7, goi la LDH-6 cing duge tim thay trong huyét thanh cia nhing bénh nhén bj bénh tram trong. LDH cé trong tat ca t8 bao cia co thé va chi khu tri 6 bao tuong té bao. Nong d6 cla enzym trong cae mé khée nhau khoang 500 lan cao hon so véi trong huyét thanh, Boi vay, su thodt enzym tir khéi long nhé mé bi tén thuong sé lam ting c6 ¥ nghia hoat 4 LDH huyét thanh, Céc m6 khée nhau chtta dymg thinh phan isozym khée nhau, Co tim va hing cau c6 LDH-1 va LDH-2. Gan va-eg xuong e6 LDH-4 vi LDH-5. LDH trung gian tim thay 6 lich, phdi, té bao lympho va tiéu cdu, ¥ nghia lam sang: Bai sy phé bién ctia enzym & tat cd cde md, su tng hoat 49 LDH huyét thanh xay ra trong nhting treng thai bénh ly Khée nhau, nhu nhéi mau co tim, huyét tin va bénb ly gan, thin, phéi, co. Trong y van, LDH huyét thanh duge diing cho chan doan nhdi méu co tim, thigu méu huyét tan, u qua sin té bao mam budng trig, u té bao mam tinh hoan. Hoat 46 LDH duge ding trong theo doi bénh Hodgkin va u lym pho khéng Hodgkin. Sy tang hoat dd LDH huyét thanh duge dé cp trong cdc bénh ly gan, tuy nhién sy tang nay khdng nhiéu so véi su tang hogt 46 ciia cdc aminotransferase. Hoat d LDH ting dic bigt cao (10 lan so véi gié tri binh thuémg) trong gan bj nhiém dc kém vang da va giém nhe trong viém gan virus, ting bach cau don nhan nhiém khuan, Host 46 LDH binh thuémg hoge tang gidi han 2 Lin so véi binh thuémg trong xo gan, ving da tic mét. LDH-S huyét thanh ting dang ké & nhiig bénh nhan gan nguyén phat va thir phat do thiéu oxy, Bénh nhan mic bénh dc tinh c6 hoat 46 LDH huyét thanh ting, gm 70% bénh nan c6 di can gan, 20% dén 60% bénh nhan cé di cn ngodi gan. LDH-1 ting dang ké trong u té bio mam tinh hoan va budng trimg (61% truémg hop). 2.3. Aldolase Aldolase (EC 4.1.2.13; D-fiuctose-I,6-bisdiphosphate D-glyceraldehyde-3-phosphate- lyase; ALD) xée tée su phan cit D-fructose-1,6-diphosphat thanh D-glyceraldehyd-3- phosphat (GLAP) va dihydroxyaceton-phosphat (DAP), mot phan tmg quan trong cilia con dutmg duémg phan. j ALD la tetramer v6i cée tiéu dom vi duge xée din béi 3 gen. Hai trong cée gen nay sin sinh tiéu don vi A va B, xudt hign véi hoat tinh & hau hét cde m6, do vay mau hinh isozym phé bién nhat bao gdm ty 1é khéc nhau tiéu don vj A va B tao nén 5 thank vién homopolymer cita cdc isozym. Locus quyét dinh cdu tric tiéu don vi C hoat tinh & mé nao. 15¥nghia lim sang luong hogt 46 ALD huyét thanh c6 ¥ nghia lam sang trong bénh co xuong nguyén phat. Nhin chung, do ludng hoat 46 ALD giup ich cing nhimg két qua do lung céc enzym khée, nhu: AST, LDH va dic bigt CK. ALD duge sit dung thém eiing CK trong danh gid cdc mu hinh véi nghi ngo bénh ly vé co. 2.4, Glycogen phosphorylase Glycogen phosphorylase (EC 2.4.1.1; 1,4-alpha-D-glucan:orthophosphate alpha- D-glucosyltransferase; GP) gitt vai tr thiét yéu trong diéu hoa chuyén héa carbohydrat, xiie tée bude dau tién ota sy thodi héa glycogen thanh glucose-1-phosphat. Vai tr sinh Iy cha GP co a cung ep nhién ligu cho nhu céu ning lng cia m6 co. GP tn tai trong té bao co gin lién voi glycogen va hé théng ludi nguyén bao co, hinh thanh phite hop dai phan tt. Mite a9 lign két ctia GP véi phite hop nay phy thude vao trang thai chuyén héa cia eo. Khi m6 thiéu oxy, glycogen bi bé gy va mat di, GP bj hda tan va di chuyén tir thinh phan luéi nguyén bao co ngoai vi tryc tiép vao dich ngoai bao. GP 1a dimer véi 2 tiéu don vj. Trong cdc mé 6 ngudi cé 3 isozym GP: GP-LL, GP-MM va GP. BB. Co xuong cla ngudi truéng thanh chi cé6 GP-MM. GP-LL la isozym chi yéu trong gan va cée m6 khée; ngoai tr tim, co xuomg va nao. GL-BB la isozym chi yéu cia nao ngudi. G tim, isozym BB va MM tén tai nhung GP-BB IA isozym chinh cia co tim. ¥ nghta lam sang GP-BB 6 6 nhay hon CK va CK-MB trong chin dod t6n thuong oo cp tinh (AMD trong 3 dén 4 gic ddu sau tén thuong. Béi vay, GP la mét dau An sinh hoc quan trong trong chin don sém AMI. Tyong ty nhu cée protein clia bao twong khée nh myoglobin va CK-MB, GP-BB cé thé bj anh huéng dang ké béi sy thm sm cla bénh mach vanh lién quan dén nhéi mau, véi dinh ting cao va sém hon. Tuy nhién, GP-BB khéng phai la protein die higu ca tim va tinh dc higu nh mot déu én cho thuomg ton co tim cé gid han 3. ENZYM GAN 3.1, Aminotransferase Aminotransferase gm mét nhém cae enzym xtic tac sur chuyén héa cae acid amin thanh acid a-cetonic va ngugc lai bang céch vén chuyén nh6m amin. Aspartat aminotransferase (EC 2.6.1.1; L-aspartate:2-oxoglutarate aminotransferase; AST) va Alanin aminotransferase (EC 2.6.1.2; L-alanin:oxoglutarate aminotransferase; ALT) 6 ¥ nghia lam sang nhiéu nhat. Céc transaminase khu tri rng rai trong eo thé, AST tim thy dau tién 6 tim, gan, co xuong va than, ALT tim thay dau tién 6 gan va thin, véi s6 luong it hon so véi 6 tim va co xuong (Bang 1.5). ALT 6 bao tuong, AST duge tim thay & bao tuong va trong ty thé, Céc enzym cé cdu tric dimer véi 2 chudi polypeptid, vo khoang 400 acid amin,AST /F Bang 1.4. Hoat 46 Transaminase trong mot sé m6 & ngudi is6 lan gp so voi trong huyét thanh, tinh theo don vj U/L), AST ALT Tim’ 7800 450 Gan 7400 2850 Co xvong 5000 300 Than 4500 1200 Phéi 500 45 Héng cdu 15 2 Huyét thanh 1 4 VY nghia tam seng _ Bénh gan ld nguyén nhan quan trong nhdt gay ting hoat dO transaminase trong huyét thanh. Trong hau hét cdc bénh gan, hoat d6 ALT tang cao hon hoat 46 AST; ngoai ix vién gan do rugu, xo gan ya u gan. Trong viém gan virus va céc logi khdc cla bénh gan lién quan dén sy hoai tir té bao gan cdp tinh, néng 4 AST va ALT huyét thanh ting truéc khi céc hi chimg va dau hiéu lam sing xuat hign (vi dy; ving da). Hoat 46 ctia 2 enzym tng cao 100 lan hon ntta so véi gidi han binh thuéng. Dinh cia sy ting hoat dO xy ra trong khoang ngay thir 7 dén ngay thir 12, hogt 46 gim nhanh vé mie binh thong vao tuan thir 3 dén tuan thé 5 néu nhu khong cé cdc bién cé. Sy ting dai ding hoat 46 ALT trén 6 thang sau giai doan viém cp tinh la co sé 4 chan doan_viém gan man tinh. ALT cé thé binh thudng 6 15% dén 50% sO bénh nhan viém gan C man tinh. Bénh nhan viém gan C cp tinh, ALT phai duge theo dai dinh ky trong | dén 2 nam tiép cho dén khi vé binh thirong. Bite tranh cia viém gan nhiém déc khac voi viém gan nhiém tring. Gan bj tin thuong do acetaminophen cé dinh transaminase tang trén 85 lan so véi gidi, han trén & 90% truémg hop, hinh anh nay hiém gap trong viém gan virus. Hon ntta, hoat 46 AST va ALT cé dinh tang sém dién hinh va gidm nhanh, Viém gan nhiém mo khéng do rugu 1a nguyén nhan phé bién hon gay ting ‘transaminase so vii viém gan virus va do rugu. Nong d6 transaminase ting trong nhimg trudng hgp viém dung mat ngoai gan. Host d6 transaminase trong gan xo thay doi tay theo tinh trang cia qué trinh gan bj xo héa, tir 4 dén 5 lin cao hon giéi han trén véi ty sé AST/ALT >1. Sy ting hoat dO cia AST va ALT huyét thanh tir 2 dén 4 lan gap & nhimg bénh nhén carcinoma gan nguyén phat ho§c di cin, trong 46 AST ting cao hon ALT, tuy nhién hoat dé ciia ching thuring & mirc binh thuéng trong giai doan som cia ung thu gan, Sy ting trung binh hoae nhe ciia hoat 49 2 enzym cing gap sau str dung thude, yi dy céc thude chéng viém khéng steroid, thuéc khang sinh, thuéc d6ng kinb, cée chat tic ché hydroxymethylglutaryl-coenzym A reductase, hoje cdc opiat., Nhimg nguyén nhan it g§p hon gay tOn thuong gan man tinh bao gém bénh nhiém sét, bénh Wilson, viém gan tu mién, xo dudng mat nguyén phat, thiéu hut a)-antitrypsin. Hogt d§ AST va ALT huyét thanh ting trong qué trinh bénh chju anh huéng cia sy hap thy cua té bao gan. ALT 1a enzym dac hiéu hon cia gan. 7Sau AMI, hoat 49 AST huyét thanh tang can nghi ng’ do ndng d9 cao cla AST tai co tim. Hoat 49 AST efing ting trong bénh Duchenne, bénh viém da co, Néi chung, host 49 cia AST ty thé (m-AST) trong huyét thanh tang dang ké 6 bénh nhan c6 thodi héa va hoai tir té bao gan, Ty sé hoat 9 m-AST/AST toan phan rat c6 ich cho chén doan viém gan rugu. TY sé nay duéng nhu gitip xéc dinh r6 tinh trang té bao gan “typ hoai ti”. 3.2. Glutamat dehydrogenase Glutamat dehydrogenase (EC. 1.4.1.3; L-glutamate: NAD(P) oxidoreductase; GLDH) la enzym ty thé duge tim thdy chi yéu 6 gan, co tim va than, véi s6 Iuong nhé & cde mé kha nhu nao, eo xuong va té bao lympho. GLDH a enzym gin Zn, gdm 6 chudi polypeptid. Enzym xic téc sw chuyén hydro tir L-glutamat hinh thanh 2-oxoglutarat. GLDH bi tre ché bai céc ion kim logi nhur Ag" va Hg", béi mét sé téc nhan chelat héa va bai L-thyroxin, ¥ nghia lam sang GLDH tang trong huyét thanh cia bénh nhén bj thuong tin té bao gan. Hoat 46 4-5 lan trong viém gan man, ting 2 lin trong xo gan. GLDH ting rit cao trong im dc halothane va mot s6 déc t6 khéc. Chia khéa chdn dodn phan biét 1a xée dinh noi khu tr trong co quan va trong té bao cia enzym. LA enzym dic higu cia ty thé, GLDH dupe giai phéng tir nhimg té bao bi hoai tu; boi vay, khi so sénh bénh ly viém, va trong diéu kign nay, sy giai phéng enzym bao tuong, nhu ALT, véi sé Iugng déng ké. Hai enzym m-AST, GLDH c6 gid tri trong viée xée dinh mite 49 khéc ligt cia sy pha huy té bao gan. GLDH cé ndng dé cao & ving trung tam cia tigu thay gan hon & ving ngoai vi. Su phan bé nay trai nguge véi ALT. Boi vay, sy gidi phong GLDH cho biét trudc tinh trang hoai tir ving trung tam tiéu thiy gan. 3.3. Alkaline phosphatase Alkaline phosphatase (EC 3.1.3.1; orthophosphoric-monoester phosphohydrolase; ALP). ALP ¢6 trong hu hét cdc co quan ciia co thé va dac biét gin voi mang va bé mat cc té bao cia niém mac rugt non va ong lugn gan cia than, trong xuong (tao cét bao), gan va rau thai. Mac dit chic nang chuyén héa cia enzym chua biét, nhung chic chin ALP gan lién v6i sy van chuyén lipid rut non va van chuyén canxi & xuong. ALP e6 trong huyét thanh ngudi trudng thanh khée manh ¢6 ngudn géc chinh tir gan, mOt nira hoat tinh cia ALP dén tir xuong, M@t s6 lugng nhé ALP cia rugt non cling cé mat trong huyét thanh cita cdc c4 thé nhom mau B hoje O. ¥ nghta lam sang Sy ting hoat 46 ALP huyét thanh bit nguén phé bién tir mgt hoe hai co quan: gan va xuong, Do luéng hoat d§ ALP huyét thanh nhim khdo sét bénh ly gan-mat va bénh ly xuong lién quan dén hoat tinh ting cia tao cbt bao 18_Dap img ca gan d6i v6i bat ky téc mat do nguyén shan gy ting ting hyp ALP bai té bio gan. Mot s6 enzym méi hinh thanh di vao vang tun hodn, gay ting hoat 46 ALP trong huyét thanh. Sy ting hoat 46 dang ké (hon 3 lan) trong téc duémg mat ngoai gan (vi dy: s6i hay ung thu dau tuy) nhigu hon so véi tic duéng m§t trong gan. Hoat tinh enzym trong huyét thanh cé thé ting gdp 10 dén 12 lin so véi gidi han trén va thug tr vé bink thurng sau phdu thuét tic mat. Sy ting tuong ty trén bénh nhan ung th gan nguyén phat hoge ung thu di cn thit phét. Bénh gan téc dng dén té bao nhu m6 gan nhu viém gan nhiém khudn, hoat 46 ALP ting trung binh (dudi 3 lin) hoge khéng tng. Hoat d6 ALP cé thé ting trong phan img véi thude. Hoat d9 ALP ting 2-3 lin so v6i gia tri binh thuimg o6 thé thay & phy ntr mang thai thang thir 3, c6 nguén géc tir rau thai. Tang hoat 6 ALP huyét thanh cé thé mang tinh gia dinh do ning 49 ALP ciia rudt non tang cao. Tang tam thai, ting nhe ctia ALP huyét thanh 6 tré nh6, cé thé gdm thé gan va xuong. Két qua phan tich isozym cia ALP huyét thanh cho biét isozym ctia rau thai xudt hién trong huyét thanh bénh nhan mac bénh dc tinh. 3.4, Gamma-Glutamyt Transferase Pepidase 1a enzym xtic téc sy thily phan chudi peptid thanh cac acid amin hoae peptid mach ngin hon, M@t s6 enzym gift vai tr xiie tée sy van chuyén acid amin tr peptid nay dén peptid khéc. Gamma-Glutamyl Transferase (EC 2.3.3.2; 6-glutamyl- peptide: amino acid 8-glutamyl-transferase; GGT) xtc téc su van chuyén nhém 6- glutamyl tir peptid va hgp chat chira né dén cht nhan. Chdt nhfn 8-glutamyl La co chat, GGT cé 6 éng hign gan cia than, gan, tuy va rudt. Enzym c6 trong bao tuong {(microsom), nhung phén doan lin hon khu tri mang té bao va o6 thé van chuyén cdc acid amin va peptid vao trong té bao qua mang té bio dudi dang 8-glutamyl peptid. N6 fing lién quan dén chuyén héa glutathion. Hoat 4 GGT huyét thanh c6 ngudn géc ban dau tir gan, ¥ nghia lam sang Mée di GGT 6 néng d6 cao nhét & t6 chic than, nhumg hoat 46 GGT huyét thanh ¢6 nguén géc ban dau tir hé théng gan-mat. GGT 1a chi diém nhay ddi voi cde bénh ly gan mét. Tae mat trong gan hode sau gan cé hogt d$ GGT huyét thanh ting 5 dén 30 lan gidi han trén. Hoat 4) GGT tang cao cing tim thdy trén nhiing bénh nhan ung thu gan nguyén phat hoc thir phat (di can), trong trudng hgp nay nhimg thay doi ciia GGT huyét than xy ra sém hon var rét hon so véi cée enzym gan khée. Sy tang trung binh (2-5 lin binh thutng) trong viém gan nhiém khuan. Hoat 46 GG huyét thanh tang trong nhiém déc he trong viém tuy man tinh va ung thu tyy (lién quan én sy tic mét trong gan), tang 5 dén 15 lan gidi han trén. Tang host & GGT cling thiy & ngudi viém gan do ruqu va chi yéu 6 ngudi nghign nugu. Heat 46 GGT huyét thanh ting khi sir dung mét sO thude nhu phenobarbital. Thude va rugu anh hug dén cdu tric microsom ctia té bao gan. ‘Trong AMI, hoat 4 GGT huyét thanh hau nhw binh thurdng, c6 thé tang nhe is4, ENZYM TUY 4.1, Amylase A-amylase (EC 3.2.1.1; 1,4-a-D glucan glucanohydrolase; AMY) 18 enzym thiy phan, xtic tic sy thiy phan lién két 1,4-a-glucosid trong polysaccarid. Ca polyglucan mach thing va polyglucen mach nhénh nh amylopectin, glycogen déu bj thiy phan, nhung véi cée ty 1é khée nhau. Enzym huyét thanh c6 ngudn géc tir tuy (P-AMY) va tuyén nude bot (S-AMY) ¥ nghia lam sang Hogt €9 AMY huyét thanh thép va hing dinh. Hoat 49 ting cao trong viém tuy cp va viém tuyén nude bot. Trong viém tuy cp, hoat dé ting cia AMY xay ra trong vong 5 dén 8 gid cia sy khoi phat hOi ching, hoat dé AMY tré vé binh thuing vao ngay thir 3 hode 4, thuémg gap hoat dé AMY ting 4-6 lan so v6i gidi han trén va dat nong 46 tdi da trong 12 dén 72 gid. Mite 46 tang hoat 46 ciia enzym Kkh6ng lién quan én sy khac bigt vé tinh chat phite tap cla mé tuy, tuy nhién, su ting cao cla hoat dé enzym chi ré tinh trang viém tuy cdp. Sy thanh loc AMY ra khoi hé tuan hoan 1a con duong bai tiét cia than qua nude tiéu, sir tang hoat do AMY huyét thanh sé dan dén tang hoat 46 AMY trong nuéc tiéu. Sy ting hoat 46 enzym trong nude tiéu cao hon va kéo dai hon so véi trong huyét thanh. Bénh ly dudmg dn mét, vi du: viém tii mat, gay tng khong 4 Lin hoat dg AMY huyét thanh. Trong thiéu nang thén, hoat dé AMY huyét thanh tang tong img véi swt suy giim chite nang cia than. Tang AMY mu cfing xudt hién trong bénh Iy khéi u. Kadi u 6 phdi hoge & budng trimg gay ting hoat 46 AMY huyét thanh. 4.2. Lipase Lipase cia ngudi (EC 3.1.1.3; triacylglycerol acylhydrolase; LPS) 18 mot glycoprotein chudi don, trong luong tr 48.000. Néng do LPS & tuyén tuy vao Khoang 5000 lan Ién hoa 6 cdc m6 khéc va sy chénh léch gitta tuyén tuy véi huyét thanh vio khoang 20.000 lan. Trong hoat dong xiic tée cia lipase, svt ed mat cia mudi mat va chat cng téc cofactor (colipase) 1A can thi Hiiu hét lipase trong huyét thanh e6 ngudn géc tr tuy, mot lung nho dugc bai tiét- boi tuyén nude bot duéi lubi, da day, phdi va niém mgc ruét non. LPS ige d& dang qua cdu thén, Yughia lam sang Do luong hoat d6 LPS huyét than nhim chin dodn viém tay edp. D6 nhay va 46 dic higu vao khoang 80% dén 10%. Sau tan cng viém tuy cdp, hoat 46 LPS huyét thanh tng trong ving 4-8 gid, dat dinh khong 24 gid va gidm trong khong 8-14 ngay. Néng d6 tang cla LPS cé thé kéo dai hon, mite ting cao 06 thé gap 2-50 An gidi han. Mite dé tang hoat d6 LPS huyét thanh khéng ty 16 voi mute d6 viém cdp cha ty. ‘Viém tuy cép d6i khi gap khé khan trong chan dodn, béi vi trigu chimg cia viém cdc co quan khéc trong 6 bung cling cé thé tong ty, vi du: thing da day, loét ta trang, 20ob me! te rudt non,.. Trong chan doén phan bigt, sy tang hogt 49 LPS huyét thanh gap 5 in gidi han la chan dodn dac higu cita sy ting hoat 40 LPS huyét thanh. Tac éng din tuy béi soi hoge ung thu tuy 6 thé gay tang hoat do LPS huyét thanh, né phy thude vao vj tri te va phan mé ty cdn chite nang. Nhtmg bénh nhan cé mife loc cau thn gidm cling ting hoat 4 LPS huyét thanh, béi, véy hoat 46 LPS huyét thanh cao g6p phan chan dodn bénh than. Nhimg bénh nhan diéu tr] thudc opiat 6 thé 6 hoat d6 LPS huyét thanh tang (do co thit co Oddi). 5. ENZYM XUONG Enzym xuong duge sin sinh true tigp tir tg cbt bao (ALP cia xvomg) va hy e6t bao (tartrate-resistant acid phosphatase) Alkaline phosphatase (ALP xwong) Dang isozym ALP cia xuong, gan va thin déu duge tng hop bai mét gen. ALP xuong duge téng hgp tir tao cét bao. Enzym nay la chi diém tuyét voi cia hoat dong hinh thinh hé xuong. ¥ nghia lam sang Trong cae bénh ly cla xuong, néng 4 ALP xuong cao nhat trong bénh Paget (bién dang xuong), bai d6 1a két qua hoat déng cia tao cét bio. Thiéu vitamin D, ndng 46 ALP ting 2-4 lan so véi binh thug va gidm cham trong qué trinh diéu tr]. Cudng sip trang nguyén phat va thr phat gay tang trung binh hoe nhe hoat 4 ALP huyét thanh, Nong d9 ALP tang cao trén nhimg bénh nhan ung thu xuong, Nong 46 ALP ting nhe 5 nhtmg ngudi bj loang xuong, khéng phu thude vao tudi. Giai dogn phat inh ly cia xuong cé hoat 46 ALP huyét thanh ting, do vay, hoat 46 ALP trong huyét thanh tré dang lén cao hon 1,5-7 lan so véi ngudi truéng thanh va dat dinh cao nif sém hon & nam, CAU HOI ON TAP Trinh bay nhiing co sé khoa hoc cia vige dinh luong hoat d6 enzym huyét thanh, Trinh bay ¥ nghia lm sang cia mét sé enzym chinh cua mé co. Trinh bay ¥ nghia lm sang cla mét sé enzym chinh trong mé gan. Trinh bay ¥ nghia lam sing cia amylase va lipase ctia mo tuy. soe ee Trinh bay f nghfa kim sing cia alkalin phosphatase cita m6 xuong. 21Chirong 2 ROI LOAN CHUYEN HOA CARBOHYDRAT myc TIEU HOC TAP 1. Dinh nghia duoc carbohydrat, phan logi va mé té duoc ba nhém chinh cia carbohydrat. Trinh bay duege lire a3 cde con cheng chuyén héa carbohydrat va ¥ nghiia ciia ching: duong phén, chu trinh pentose, tan tao ducing, thodi héa va téng hop glycogen. M6 té dugc nguén géc, cdc yéu 16 diéu hoa néng dé glucose mdu. M6 ta duge sinh ly bénh cita ha glucose mdu, tang glucose méu va méi lién quan ciia ede xét nghiém voi cde tink trang bénk | M6 tai dune mBt 36 die diém ldm sing chink, dic diém xét nghiém ciia mbt sé bénh réi loan chuyén héa carbohydrat bdm sinh: galactosemia, khéng dung nap fructose, te glycogen, réi loan chuyén héa mucopolysaccarid. Trinh bay dage ede nguyén ly ky thudt, loai mdu bénh phim duge lea chon, cée uu nhuge diém cia céc phueong phdp phan tich glucose. Trinh bay duege ede kj thudt phan tich thé ceton. Ké tén duge céc kj thudt ste dung dinh lugng HbAle vat ting dung ldm sing ctia xét nghiém. NS Aw w 2 pM Carbohydrat va céc sin phdm dj héa clia ching 1a nguén cung cp ning luong quan trong cho co thé con ngudi. Mac dit ca ba nhém carbohydrat, protein va lipid déu duge co thé sir dung la nguén cung cdp ning lugng, carbohydrat la nguén cung cdp niing Iugng chinh cho nao, héng cu va té bao ving mac. 1, DINH NGHIA VA PHAN LOAL Carbohydrat la céc dain xuit aldehyd ho§c ceton ciia cdc polyalcol. Carbohydrat duoc phan lim ba nhém chinh: 1.1, Monosaccarid Monosaccarid 14 eée dug don, chita Ot nhém aldehyd hoe ceton va 6 hai hay nhiéu hon hai nhém hydroxyl. Céng thie phan tir la (CH2O)n, n = 3 ho§e lén hon. Céc monosaccarid chita nhém aldehyd goi la aldose, chia nhém ceton goi la cetose. Cie hexose, dac biét la D-glucose la monosaccarid hay gip nhét trong ty nhién, Phén én cde monosaccarid trong ty nhién cé céu hinh D. 22‘Vi cée monosaccarid chira céc nhém aldehyd hoac ceton ty do, chting c6 thé khir cae téc nhan oxy héa nhu Cu", ferricyanid hoge hydroperroxid. Trong phan img nay, monosacearid bj oxy héa thanh acid tuong img. Dac tinh nay 1a co’ so cho cdc ky thuat phan tich glucose. 1.2. Oligosacearid Oligosaccarid gdm mét sé monosaccarid lién két véi nhau bang lién két glycosid. Oligosaccarid don gidn nhat va hay gap nhat trong ty nhién 1a disaccarid. Disaccarid hay gp trong ty nhién [a saccarose (dutg mia), lactose (dung cé trong sita) va maltose. 1.3, Polysaccarid Polysaccarid gdm nhiéu monosaccarid lién két véi nhau bing lién két glycosid. Polysaccarid hay quan trong nhat trong ty nhién 1a tinh b9t, carbohydrat dy tri cba thye vat, va glycogen, carbohydrat dir trtt chinh cua déng vat. 2. TOM LUQC BAC DIEM CHUYEN HOA CARBOHYDRAT Carbohydrat 1a m6t trong ba thanh phan chinh trong thie an cia con ngudi. Trude khi duge hap thu va sir dung, ching phai durge thoai héa thanh cde monosaccarid. Qua trinh nay xy ra trong éng tiéu héa, Pau tién, amylase nuéc bot thiy phan tinh bét tao thanh céc dextrin va maltose. Khi dén da day, pH acid ciia dich vi sé bat hoat amylase nude bot. Téi rugt, pH kiém va amylase cla tuy sé tiéu héa tinh bét va glycogen thinh maltose, Maltose, lactose hay saccarose sé bj thily phan béi cdc disaccaridase cita niém mac rut tgo thanh cae monosaccarid: glucose, galactose va fructose. Céc monosaccarid dugc hp thu qua thanh rut vao mau va chuyén tdi gan qua hé théng tinh mach ctra. Vi glucose 1 monosaccarid duge co thé sit dung dé cung cdp nang lugng, galactose va fructose duge chuyén thanh glucose bdi céc enzym cita gan. Dau tién, glucose duge phosphoryl héa thanh glucose-6- phosphat duéi tic dung ciia hexokinase. Glucose-6-phosphat la trung tm cho ba con durémg chuyén héa ciia glucose. Néu co thé cn ning wong, glucose duge thodi héa thinh CO2 va nude, cung 4p ATP. Qué trinh chuyén glucose thanh pyruvat goi la con duémg duéng phan, xay ra o bao tuong cita té bao, khéng cin oxy va cung cdp 2 ATP/mét phan tir glucose. Pyruvat cé thé chuyén thénh lactat trong diéu kién yém Khi, Trong diéu kién 4i khi, pyruvat sé duge chuyén vao ty thé, dugc khir carboxyl va oxy héa dé tao thanh acetyl CoA. Acetyl CoA di vao chu tinh acid citric, dét chay hoan thanh CO; va nude, va tao 12 ATP/phan tir acetylCoA. Oxy héa hoan toan mét phan tir glucose cung cdp 38 ATP. M6t con durmg khée oxy héa glucose Li con duimg hexose monophosphat, cdn goi la chu trinh pentose. Trong con dudmg nay, glucose-6-phosphat duoc chuyén thanh ribose-5- phosphat va tao NADPH. NADPH 1a ngudn niing Iuong cho cdc phan img dng hoa nhu sinh tng hop acid béo, steroid; gitip bao v¢ té bao chéng lai tac nhan oxy héa. 23‘Néu glucose khéng cin dé cung cp ning lugng cho co thé, ngay lap the n6 sé duge dy tir & gan dudi dang glycogen. Sinh tng hop glycogen xAy ra khi ndng 49 glucose méu tng cao nh sau bita an. Khi néng d6 glucose mau gidm xuéng, glycogen phan ly thanh glucose. Qué trinh sinh tng hop va thodi héa glycogen & gan la co ché quan trong trong diéu héa ndng 49 glucose mau. Glycogen cing duge ting hop va dy trir 6 co, tuy nhién chi c6 glycogen & gan méi phan ly dé cung cép glucose cho mau vi & co Khong ¢é glucose-6-phosphatase. Tan tao glucose 14 mt con duémg quan trong trong duy tri ndng a6 glucose mau, dac bigt khi d6i kéo dai. Tén tao glucose la sinh tng hgp glucose tir cdc nguén khong phai lé carbohydrat, vi dy nhu acid amin, lactat, glycerol tao ra tir thodi héa triglycerid. 3. DIEU HOA NONG BQ GLUCOSE MAU Néng d6 glucose trong mau tuong di hing dinh trong céc didu kign binh thudng. Khi doi, sw gidm ndng d glucose o6 thé tranh duge nhi phan ly glycogen. Khi déi kéo dai hom, tan tg0 glucose tr nén quan trong trong cung cp glucose cho méu. Khi glucose méu ting, sinh ting hop glycogen tir glucose dién ra. Cae con dung chuyén héa nay duge diéu hoa bing cdc co ché nhay bén, nhwr tre ché nguge va kiém soat boi hormon, lim cho ndng 46 glucose mau 6 trong mét khoang hep din no hay doi. Gan, tuy va cdc tuyéa néi tiét khéc tham gia kiém sodt ndng d9 glucose mau. Khi déi, gan phén ly glycogen dy tr dé cung cép glucose ty do cho méu. Khi déi kéo dai hon mot ngay, glucose dugc ting hop tir cdc nguén khac tai gan va mét phan nh 6 than, Hai hormon chinh tham gia digu hda glucose mau la insulin va glucagon, déu do tuy sin xu, 06 téc dung d6i Iép nhau, Céc hormon khée eting gép phan tham gia diéu hoa glucose, cho phép co thé thich tmg véi nhiing d0i hdi gia ting vé glucose hoge tin tai khi d6i kéo dai. Chuing con cho phép dy tit ndng long duéi dang lipid khi thite an cung cp du thita. 3.1. Insulin Insulin la hormon protein do té bao beta cia dao tuy sin xudt khi ndng 49 glucose mau ting cao. Day la hormon duy nhét lam giém glucose mau. Tae dng cia insulin la ting tinh tham cia mang véi glucose, vi vay lam tang cu’ng vin chuyén glucose vao gan, co, mé mé. Insulin cdn téc dOng trén chuyén héa glucose trong té bao: ting tao glycogen, lipid va protein, tang chuyén héa glucose theo con duémg duémg phan. Bai tiét insulin duge kiém soat béi ndng dé glucose mau. Khi ndng 6 glucose mau ting, insulin duge bai tiét. Néng 49 glucose mau gidm ite ché gidi phéng insulin. Insulin duge tng hop dudi dang preproinsulin, 14 mt chudi polypeptid; sau Khi cit di mot doan peptid dan duéng tao thanh proinsulin. Proinsulin dugc chuyén thanh insulin hoat dong nhé téc dyng ciia peptidase dc higu, insulin tao thinh ¢6 2 chudi A va B néi voi nhau béi 2 cdu ndi disulfur, doan peptid & gitta goi IA peptid C. Peptid C va insulin duge gidi phéng vao mau véi néng 4 tuong duong, vi vay ndng dé insulin tyong duong vai ndng d6 peptid C. 24HN opti) chal B tin higu Prercinsln Proinauin Instn Hinh 2.1. Sy tao thanh insulin 3.2. Glucagon va céc hormon khac Glucagon 18 hormon polypeptid do té bao alpha cia dao tuy bai tiét khi ndng 46 glucose méu gidm.. Day 1a hormon chinh gay ting nhanh ndng d6 glucose méu. Glucagon téc dung bing céch tang phén ly glycogen va tan tao glucose & gan, nhung Khéng c6 anh hudng dén glycogen 6 co. Bang 2.1. Tac dung cit c&c hormon trén ndng dd glucose mau Hormon Ngudn géc ‘Tae d6ng trén Co ché tac dung hormon glucose mau Insulin TébaoB daotuy | | Tang van chuyén glucose vao té bao Tang tao glycogen, lipid Tang dung phan, giém phan ly glycogen Glucagon TébaoAdaotuy | t ‘Tang phan ly glycogen Tang tan tao glucose Tang tgo thé ceton, thoai héa protein Epinephrin | Tay thong than | + Tang phan ly glycogen Thyroxin Tuyén giap 1 khong y nghta | Tang phan ly glycogen GH Tuyén yén truoc | t ‘B6i khang véi insulin ACTH Tuyén yen trvoe | t 6i khéng v6i insulin Cortisot Vethuong than | 7 Tang tan tgo glucose, ai khang véi tac dung cila insulin Somatostatin | Té bao D dao tuy, | Tae dung khong | Uo ché giai phéng insulin va glucagon métsémokhac | nhidu Somatomedin | Gan Tac dyng khong | Tac dung giéng insulin nhieu 25Epinephrin (Adrenalin) 14 hormon cia tiy thugng thén, lam ting glucose méu bing ttc ché bai tiét insulin, ting phan ly glycogen. Epinephrin sii phong khi c6 stress tinh thin ho&c thé Iue, lam tang nhanh chéng glucose cho nhu cau nang Iuong, ding thdi cdn tang phan hay lipid, ting nhip tim, huyét 4p va mét sé téc dung sinh ly khéc. Glucocorticoid, chi yéu 1a cortisol, do tuyén vd thugng thn sin xudt, ¢6 tée dung lam ting glucose mau bling céch lam ting tén tao glucose, gidm van chuyén glucose tir mau vao té bao. Ching cé tac dung 46i Khang véi insulin trén mét sé chuyén héa, déi hi duge goi la céc hormon gay dai thao duéng (diabetogenic hormone), Adrenocorticotropic hormone (ACTH), cdn goi [a corticotropin, 1a hormon polypeptid cia tuyén yén truée, lam ting glucose méu béi déi khang téc dung véi insulin. GH (Growth hormone), cdn ggi 1a somatotropin, 14 hormon polypeptid cita tuyén yén trude. Tac déng cia GH d6i khdng véi insulin, lm tang glucose mau bang giém ‘van chuyén glucose vao té bao va ting phan ly glycogen & gan. Taytoxin (14) la hormon tuyén giép, o6 tic dung lam ting glucose mau bing ech lim tang phan ly glycogen, ting tn tgo dug, tng hp thu glucose 6 rut. Bénh nhan curing gidp cé thé giam dung nap glucose nhung glucose méu khi déi thuong binh thuong. Mac di T4 lim ting glucose mau nhung vai trd cita n6 trong diéu hda glucose mau khéng dang ké, Somatostatin la hormon polypeptid, chi yéu do té bao D cita dao twy san xudt, NO ito ché bai tiét insulin va glucagon, vi vay diéu hoa téc dng tuong hd ca hai hormon nay. Vai trd khng nhiéu trong diéu hda glucose mau. Somatomedin a céc peptid do gan sin xuAt duéi tac dOng kich thich cla GH, bao gdm somatomedin A, C va insulin-like growth factor I va Il. Vai trd cia ching kich thich sy ting truéng, cé téc dung gidng insulin 6 m6t vai md nhu mé m6. 4, TANG GLUCOSE MAU (Hyperglycemia) 4,1. Dinh nghia dai thio duimg ai théo duomg (DTD) la hoi chimg réi loan chuyén héa v6i su ting glucose méu do thiéu tuyét d4i hode tuong d6i insulin. Sy thiéu hut insulin anh huéng t6i chuyén hoa carbohydat, protein, lipid va gay ra cdc ri loan hang dinh ni moi nude va dign gai. Te vong ¢6 thé do sy mét bi chayén héa cép tinh, c6n ri loan chuyén héa man tinh gay ra cée thay di du tric va chic nang m6t céch thudng xuyén va khéng thé dio nguge cia cée 16 bao trong co thé, trong dé hé thong mach méu dc bigt nhay cém. Su thay adi nay din dén céc bién chimg man tinh cla bénh DTD. Cée bién chimg man tinh ctia DT bao gdm bénh mach mau Ién (VXDM tién trién), bénh mach méu nhé (vi mach): 6 mit, gay chay méu va thoai hod vong mac (diabetic retinopathy), duc thuy tinh thé; tén thuong thin gy suy thén va tén thuong cdc day thin kinh ngoai bién (peripheral neuropathy). 264.2. Phan logi dai thao dong DTD typ 1: (OTD phy thuéc insulin) do sy thiéu hut tuyét déi insulin béi phd huy té bao B ciia dao tuy, co ché tu mién, chua r6 nguyén nhan, DTD typ 2: (DTD khong phy thude insulin) do sw phéi hgp gitta khang insulin va suy gidm tuong déi insulin, insulin khOng di dap img nhu cdu gia ting do sy khéng insulin, Céc typ khée: Tén thong gen vé chitc nding té bao beta. Tén thong gen vé tac dung ctia insulin: bdt thudng vé tdc dung qua receptor. Bénh tuy ngoai tiét dén dén réi loan chite nang té bao B wong adi hay tuyét doi: — Cat tuy. — Viém tuy man tinh hode tai phét. = U tan sinh, — Xo hod nang. — Nhiém sic t6 sit. — Viém tuy nang hod. ~ Réi loan viém/tham nhiém khdc. Bang 2.2. Cac tiéu chudn phan biét TO typ 1 v6i typ 2 sit Dac diém Typ1 Typ 2 1__| Tudi khdi phat <30 >30 2 __| Th trang Gay ‘Thuong béo phil 3___| Cach khéibenh Ram ro Tw tir, khong r6 rang 4 Dai nhiéu, khat nuéc Ro ret {tro ret 5 An nhiéu, sat can co Khong phé bién 6 _| Tang ceton mau thueng o6 Thuong khong 7 __| insulin huyét wong Thap hoac khong c6 | Binh throng hoac tang 8 _| Le thug insulin co Khong) 9 | Glucagon huyét tong Tang Binh thuéng 10 _| Khang thé khang tiéu dao co Khong 11 _| Lién quan 16i khang nguyén HLA | DR3, DRA Khong 12__| Bénh si gia ainh Khong phd bién Thuong gap Cac bénh ngi tiét: tang khéng insulin, gidim bai tiée insulin hode cd hai: — Chi yéu lam ting khang insulin: to dau chi, hdi chimg Cushing, u tiét glucagon, cuing gidp. 2— Chi yéu lam giam bai tiét insulin: u tiét somatostatin, u tiét aldosteron. — Téc dong khang va bai tiét: u té bao wa crom (pheochromocytoma). Do thudc hay hod chat: — Chi yéu gay ting khang: glucocorticoid, hormon tuyén giap. — Chi yéu gay gidm bai tiét: vacor, pentamidin, cyclosporin, acid nicotinic, diazoxid, chen beta giao cdm, thiazzid, dilantin, c-interferon. Nhiém khudn: phd hu), viém té bao beta — Rubella bam sinh. — Bénh quai bi. = Nhiém coxsackie. Cée dang bénh te mién khéc: — Hoi chig “sti — Khang thé khang receptor insulin. — Dang khéc. DTD thai nghén: DTD khéi phat trong khi mang thai. Thug khoi sau khi sinh con, khoang 50% tré thanh DTD typ 2. Giém dung ngp glucose (Impaired glucose tolerance): néng 49 glucose méu cao hon binh thuong nhung duéi nguong chan dodn dai thio dudng. Nhing bénh nhin nay mite glucose mau cé thé tr vé binh thudng, nhung cé nguy co cao bj DTD. man”, 4.3. Cac thay adi chuyén hod trong dai thao dwong Trong DTD, sy gidm insulin gay ra céc thay di chuyén hoa binh thudng (Hinh 2.2). Vi thiéu insulin nén sy van chuyén glucose tir mau vao cac té bao co, mé m& giam; din dén ndng 46 glucose mau ting cao. Khi ndng d@ glucose méu ting cao vugt qué kha nang tai hdp thu cia than, glucose sé bj bai tiét ra nude tiéu. Tinh trang nay goi 14 glucose nigu, Vi nude sé bai tiét theo glucose nén bénh nhan DTD khéng duge diéu tr) sé c6 cdc trigu ching khat va déi. Triéu chimg dac trmg cia bénh 1a dai nhidu, uéng nhiéu va an nhidu. Con dutng dudmg phan bj ite ché, sy thodi hod glycogen thanh glucose tang, sw phan gidi lipid va tan tgo duémg tang. Sw dj hod acid amin va acid béo tang dan dén lugng acetyl CoA tang. Acetyl CoA khéng di vao chu trinh tricarboxylic ma duge chuyén thanh cholesterol va thé ceton (acid acetoacetic, acid B-hydroxybutyric va aceton). Sy tng tao thé ceton dan dén trang thai nhiém ceton: néng dé ceton trong mau tng cao vA trong nudc tiéu cé thé ceton. Aceton 1a chat bay hoi, c6 thé xudt hign trong hoi thé gay ra dic diém hoi thé cd mii ceton. Sy ting tao cdc acid cetonic gay tinh 28BTt trang nhiém acid (pH méu gid). Dé bit lai sy gidm pH nay, bicarbonat trong hé dém bicarbonat tac dung véi H' tao CO, va HzO. Sy gidm néng 6 bicarbonat gay nhiém acid chuyén hod. Trung tam hé hdp bj kich thich gay thé nhanh va sau, lam ting dio thai CO, qua phéi. Hén mé cé thé xay ra, cn diéu tri nhanh chong bing insulin dé ngin chain tir vong. Mau Gan Glucose Glucose - 6 - phosphat + ADP Glucose ; 1 - phosphat Ribosse -5-phosphat + ‘glycogen Tilose phosphat NADPH synthe Phosphorviase If Glycogen Lactat—» Pyruval + NADH + ATP. IS ‘Acid béoSp Acetyl CoA — Acid amin co, 2 Chu trinh - = Thd ceton oft Ho, Thé cetort acid etic ie Cholesterol’ Cholesterol Hinh 2.2. Cac thay ddi chuyén hoa d&c trung trong dai thao duéng. 4.4. Céc xét nghigm chin doin va theo d6i déi théo dung 4.4.1. Cac xét nghifm phat hign bgnk DTD Glucose nigu Trong DTD glucose xuét hién trong nude tiéu khi glucose méu vugt qué nguong tai hap thu cua thén, ‘igudng t4i hdp thu ciia thén binh thudng IA 160 dén 180 me/dL. (8,9 dén 10 mmol/L). G ngudi dinh thudng glucose nigu khong 0,5 mmol/24 gid, xét nghigm thong thung khéng phat hién dugc. D6 nhay cla xét nghiém khéng cao, c6 thé tang 46 nhay cach lay nuée tiéu sau an. Glucose niéu tir lau da duge ding lim xét aghigm sing loc DTD va hudng dan diéu tr insulia, nhung vai trd eta xét nghigém nay ngay cang giam béi syr sir dung ngay cdng nhiéu xét nghiém ty do dudng huyét c4 nhan {self-monitoring of blood glucose). Glucose méungéu nhién Méu toan phan tinh mach > 10 mmoV/L, (180mg/dL) hoe huyét tuong > 11,1 mmoV/L (200 mg/dL.) 1 déu higu eta BT. Néu tri s6 thdp hon (7,8 mmol/L) thi cin lam thém nghiém phép tng duong huyét bing duémg udng 29Glucose méu khi abi 6 ngudi binh thudng, glucose huyét tuong khi déi (10-16 gid nhin an) tir 4,4-5,0 mmol/L (80-90 mg/dL), gid trj ting theo tudi Glucose huyét tuong khi d6i> 7,0 mmol/L it nhdt tir hai lan tré lén la DTD. Néng d6 glucose mau tinh mach th4p hon mau mao mach, mau toan phan thip hon trong huyét trong khoang tir 10-15% (cing mét mau méu). Bang 2.3. Bién luan cdc tri 6 ndng d6 glucose mau khi déi Glucose mau toan phan Glucose huyét Bign luan khi d6i twong khi déi <4,4 mmol <5,6 mmovL. Loai try BTD (49 mg/dL) (<100 mg/dL) 4,4-5,5 mmol. 5,6-6,4 mmol. Xéc sudt It, khong can km nghigm phap (79-99 mg/dL) (100-116 mg/at) _| "ng glucose mau bang duéng ubng 5,6- 6,6 mmol/L 65-7,0 Cn lam nghiém phap tang glucose mau (100-119 mg/at bang duéng uéng mmoliL, (197-126 mg/dL) 26,7 mmol 27,0 mmol/L. erp (2 120 mg/dL) (2126 mg/dL) Glucose mau sau an 2 gid: La thir nghiém don gian, tién hanh dinh lugng glucose huyét twong sau khi bénh nhan an 2 gid, bita an c6 khoang 100 g carbohydrat cling v6i cdc thinh phan khéc. Glucose huyét tuong > 11,1 mmol/L 1a chi diém cia DTD. Gia tri < 6,7 mmol/L duge xem nhu binh thuéng. Mac di thir nghiém don gin nhung rat khé dé kiém soat thanh phan bia an, théi gian biia n va su hdp thu thite an. Nghigm phdp ting glucose mdu bang dung udng (Oral glucose tolerance test- OGTT) Nghigm phép nay duge ding dé khang dinh chan doan DTD & nhimg ngudi 6 glucose huyét trong khi d6i cao hon binh thong nhung nhé hon 7,0 mmol/L. Thir nghiém bao gém vigc dinh hong mét loat cac ndng 46 glucose huyét tuong 6 cdc théi diém truéc va sau udng glucose. Chudn bi bénh nhén. — Khéng tién hank nghiém phdp & nhing bénh nhan ¢6 bénh ly cdp tinh. — Khéng ding céc thudc nhém glucocorticoid, thudc Igi nigu, thudc chen beta giao cam ft nhat 3 ngay truéc khi lam nghiém phap. 30— Bénh nhén nén duy tri hoat d6ng thé lye binh thudng, an uéng binh thudng (bita an chifa it nhit 150 g carbohydrat) 3 ngay truéc khi kim nghiém phap. — Nghiém phép nén tién hanh vao budi sang sau khi bénh nhfn da nhin an 10 dén. 16 gid. Nghi ngoi 30 phut truée khi tién hanh nghiém phap. Tién hanh nghiém phdp: ~ Lay mau dé dinh lugng glucose lie ai. — Cho bénh nhan uéng 75 g glucose hoa trong nude trong ving 5 phiit; dink luong glucose mau 6 céc thai diém 30, 60, 90 va 120 phat sau uéng, Tré em udng 1,75 g/kg cn nang. Trong théi gian lam thir nghiém, bénh nhan nghi ngoi, khong hut thuéc. © ngudi binh thug, glucose mau tang lén dén khoang 8,3 mmol/L (150 mg/dL) trong vong 30 dén 60 phat sau udng va sau dé gidm xudng do sur bai tiét insulin dudi tac dong kich thich cia sy gia ting néng 49 glucose mau. Nong 4 glucose méu 06 xu hhuéng gidm xudng thp hon glucose méu khi d6i mt it trude khi téc dung ciia insulin mat di réi sau d6 id vé binh thudng trong khoang 3 gid. O bgnh nhin DTD, ndng 46 glucose méu ting cao hon & ngudi binh thudmg va tre vé mic dO truée khi udng mét céch cham chap. ‘Nong d6 glucose huyét tong > 11,1 mmol/L 6 thdi diém 2 h va mot thoi diém nao do tir 0 dén 2 gids thi duge chan dodn la DTD. J x0 é Tang glucose mau jm i ry Binh thong fim ee B so 3 Ha glucose mau 0 1 2 3 4 8 Thdi gian sau uéng glucose (gid) Hinh 2.3. fy¢ng cong dung nap glucose & nguéi binh thydng va ngudi DTD Bang 2.4, Cac gid tri chan doan cia OGTT theo khuyén cdo cla WHO (1985) Glucose mau toan phan Glucose huyét twong mmol/L(mg/dL) mmol/L (mg/dL) Tinh mach Mao mach Tinh mach Mao mach eT Khi doi | 26,7 (120) 26,7 (120) 27,8 (140) 27,8 (140) * Sau 2h | 2 10,0 (189) 2 14,1 (200) 2 11,1 (200) 2 11,1 (200) IGT Khi doi] < 6,7 (120) <6,7 (120) <7,8 (140) <7,8 (140) Sau 2h | 6,7 (120)-<10,0 (180) | 7,8 (140)-<11,1 (200) | 7,8(140-< 11,1 200) | 7:8 (140 < 11,1 (200) 31Nghiém phdp ting glucose méu dieing tiém tinh mgch (Intravenuos glucose tolerance test- IVGTT) Burge tién hanh & nhimg bénh nhéin kém hap thu hay khong cd kha ning dung nap carbohydrat duéng uéng. Tiém tinh mgch glucose véi liéu 0,5 g/kg cn nang. Dinh luong glucose mau 10 phut 1 lan trong vong 1 git. Thuong dinh lugng ca insulin kem theo. Bang 2.8. Tiéu chudn chan doan DTD Glucose huyét twong oT. Glucose khi di" 27,0 mmol/L. (126 mg/dL) 2 gid sau thi nghiém dung nap glucose dudng uéng 214.1 mmol/L (200 mg/dL) 75 g* (75 g ofal glucose tclerance test) hode glucose mau gu nhién khi cé trigu chiing cla BTB* BTO thai nghén: Sang Ic: (1 gig sau 89 g OGTT) 27,8 mmol/L (140 mg/dL) Chan doan (100g OGTT)(it nhat 2 gid tri bat thudng) Luc 46% 25,8 mmol/L (105 mg/dL) 1910 210,6 mmol/L (190 mg/dL) 2gi0 29,2 mmol/L (165 mg/dL) 3gi0 28,1 mmol/L (145 mg/dL) ‘Gidm dung nap glucose (Impaired glucose tolerance- IGT) Lac ai <7,0 mmoVL (126 mg/dL) Va 2 gid sau 75 g OGTT* 7,8-14,Ammol/L (440-200 mg/dL) Glucose mau khi d6i khéng binlh thug (Impaired fasting glucose- IFG) Lac oi" * Phai dug khang dinh bang xét nghiém Iai 6,1-6,9 mmol/L (110- 125 mg/dL) 4.4.2, Cie xét nghiém phan bigt DTD typ 1 va typ 2 Dink legng insulin Ngudi binh thudng i ndng d6 insulin trong khoang 10-20 wU/ ml. Ngudi béo phi Khf déi insulin > 30 2U/ ml. Bénh nhan DTD typ 1 insulin thdp hoe khéng cd, DTD typ 2 thé béo ndng dé insulin hoae cao hon ngudi béo hodc binh thudng. Dinh long peptid C Luong peptid C tuong duong véi lugng insulin do tuy bai tidt. Viée dinh Ivong peptid C c6 téc dung phin biét DTD typ 1 véi typ 2. O nhimg bénh nhin DTD dug diéu trj bang insulin, vige dinh hong peptid C cho biét lung insulin tong mau cé 32ngudn géc néi hay agoai sinh. Peptid C cé thé dinh Iuong khi déi, sau bita an chuan hay sau khi kich thich bing glucagon; tat ca déu c6 gid tri dénh gid chite nang cia té bao B tuy ndi tiét. Nghigm phép glucagon: Tiém tinh mach 1 mg glucogon khi d6i, sau 6 phit dy mau dinh lugng peptid C. Bang 2.6. Y nghia cia ndng 46 peptid C trong thiy nghiém glucagon Trang thai co ban Sau tiém glucagon 6 phit Yanghia >1,8ng/L (0,5 nmol) _ | >2,9 ng/L-(0,8 nmol) TO typ2 <0,7 ug/l (0,2 nmolL) | <1,0 pg/L. (0,3 nmolL) TO typ 1 0,7-1,8 pg/k. Khong tang Khéng dura ra durgc két luan nao (0,2-0,5 nmol) 4.4.3, Clic xét nghi¢m theo doi BT Glycohemoglobin Hb ngudi truimg thanh binh thudng bao gm HbA (95-97%), HbAz (<3%) va HbF (< 1%). Mét lrgng nhé HbA bj glycosyl hod tao thinh glycohemoglobin. HbA, duge tao thanh do sur glycosyl hod nhém amin ty do cia valin & dau N tén cia chudi beta véi cdc carbohydrat khae nhau. Ngoai ra sur glycosyl hod cén xay ra ¢ cde nhém amin tyr do khée trong phan tt Hb. Tat ca cdc loai Hb bj glycosyl hod duge goi la glycohemoglobin. eae ‘san pdm, —K, lucose + Ke, schiff Ks, san phdém _" , San phim tan coreg base" Amador! tng, glan oa ——» “Ghyooy hee Ho NHR CH-NHER | v V ‘7 yee ¢ ¢ a Ho, oH AL (CHOM), + NHL-R (CHOH), == (CHOH,- on Ho 6 HO | Y cHoH HOH cHOH HO Hinh 2.4, Sy hinh thanh céc s&n phdm glycosyl hod HbA, binh thuéng tir 5-7%, bao gdm: HbAja, HbA, va HbAjc. HbA gin voi fructose 1,6-diphosphat tao HbA:a1, gin voi glucose-6-phosphat tgo thanh HbAy2, gin voi fructose-6-phosphat tao HbAtp, gin véi glucose tao HbAj.. HbAr. chiém 75-80% lugng HbA, (4-6%). Bénh nhan DTD c6 ty 1 HbA, cao hon binh thang. Dai song héng cau binh thudng 1a 120 ngay, phan tmg glycosyl hod xay ra ty 1é thudn véi nong 48 glucose trong méu, vi vay xét nghiém ty 1 HbA, hay HbA), 1a chi diém cho ndng 46 glucose mau trung binh trong giai doan 2 thing trude d6, Day la xét nghiém hiu ich cho vigc theo doi diéu trj bénh nhan DTD, dy béo nguy co bién chimg. 33Bang 2.7. Danh php oa cdc loai glycohemoglobin HbAo 90% Phan HbA khéng bj glycosyl hoa HbA, 5-7% | HbA bi glycosyl hoa nhém amin ty do ctia valin 6 dau N 9! = HbAve tan cua chudi B ea glycosyl hoa v6i fructose 1,6-diphosphat HDA vas glycosyl hoa véi glucose -6-phosphat oi glycosyl hod v6i fructose -6-phosphat eae glycosyl hod véi glucose, chiém 75-80% HbAt Cé rat nhiéu phuong phdp khdc nhau ding dé do ty 1¢ HbA: sic ky di lc, sic ky trao d6i ion, dién di, mién dich. Gid tri quy chiéu phy thugc vao phuong phap xét nghiém va hoa chat thude thir. Cée bénh ly vé Hb c6 thé lam cho cdc két qua xét nghigm vé glycohemoglobin sai Iéch vi cée Hb bénh ly ¢6 thé anh huéng dén phuong phap xét nghiém. Hon nita, cde bénh ly nay thudng gy giam sinh hong cdu hay tan huyét, din dén khé 6 thé phan tich két qua clia xét nghiém glycohemoglobin. Trong céc truémg hop nay, ching ta c6 thé ding xét nghiém fructosamin dé thay thé. Fructosamin Céc protein huyé: thanh gin vi glucose trong phan tng glycosyl hod tao fructosamin. Vi albumin la protein cé nhiéu nhét trong huyét thanh nén sy do luong fructosamin chi yéu la do Iugng albumin bj glycosyl hod. Thoi gian ban huy cia albumin 1a 2-3 tudn nén fructosamin 14 xét nghiém danh gid sy kiém sodt néng 46 glucose trong khoang 3 tudn trudc 46 Microalbumin nigu DTD gay ra nhimg bién ddi 6 than din dén bénh than do DTD. Bién chimg nay hinh thanh trong nhiéu nim va cé thé lam cham sy tién trién cia né bing su kiém soat t6t néng 49 glucose méu. Dau higu sém cila bénh than trong DTD la sy tang bai tiét albumin trong nuéc tiéu. Sy dinh long microalbumin nigu cho phép chin doan bién chimg than giai doan sém, truée khi xudt hién protein nigu. Nong d@ albumin nigu vi jurgng tir 20 dén 300 mg/24 gid, protein nigu> 0,5 g/24 gid. Khuyén céo sing loc DTD — Ngudi lén khéng cé trigu chimg, khong mang thai: glucose méu khi di duge dang hiéu hon 1A OGTT. — Sang loc tét ca ngwai lon tir 45 tudi tro 1én ft nhdt 3 nam 1 Lan, — Ngudi lén, khong trigu chimg, khéng mang thai véi ft nht mdt trong cdc bidu ign duéi day phai xét nghiém 6 lita tudi tré hon va tin sé nhiéu hon: 34Béo phi (BMI >27 kg/m’). ‘Thé hé thtr nhat ca gia dinh cé ngudi DTD. Nhém ching ngudi od nguy co cao. Sinh con > 4 kg. Cé tién sir TD thai nghén Tang huyét 4p. + HDL <35 hode triglycerid > 250 mg/dL. + IGT hay IFG 6 lan xét nghiém truéc. — Phy nt c6 thai: 50g OGTT véi két qua sau 1 gid 6 tuan thir 24-28 cia thai ky (néu truée 46 44 bj DTD thai nghén, nén xét nghiém sém hon). Néu sing loc so bd duong tinh, lam tip 100g OGTT 3 gid. +e et + + 5. HA GLUCOSE MAU (HYPOGLYCEMIA) Néng dé glucose mau binh thudng duge diéu hoa trong gidi han rdt hep, phan anh su phu thude hodn toan cia nfo vao glucose cho chuyén hod cung cdp nang long. ‘Nguoi khée manh binh thuong cé ndng dO glucose huyét tong tir 60-90 mg/dL (3,3-5,0 mmol/L) sau m6t dém nhin 46i, chi ting nhe lén dén 120-130 mg/dL. (6,7-7,2 mmol/L) sau mét bita in hin hop. Cé mét hé théng diéu hoa dé dam bao su hing dinh ndi méi ctia glucose, réi loan hé théng nay cé thé dan dén giam glucose mau, mite d6 tram trong dU gay ra thim hoa hodc cdc biéu hién nhe nhang kim bd qua sy chit y 1am sing. Céc trigu chimg khéng dc higu cia gidm glucose méu géy khé khan cho chin dodn. Tuy nhién, nhing tién b@ trong hiu biét vé co ché diéu hoa glucose 6 mite 49 sinh If va mic 46 phan tir cung cp cde phuong tign hiu ich gitip cho cae nha lam sing chan doan duge nguyén nhan cua ha glucose méu. 5.1. Binh nghia Ning 46 glucose huyét tuong dudi 50 mg/dL (2,8 mmol/L) 6 ngudi lén duge xem nhu hg glucose méu, tuy nhién khong xéc Ip duge mét gid tri tuyét 46i nao mot céch tin cy. Phu ntr khoé manh cé thé ndng 46 glucose xudng téi 25-30 mg/dL (1,4-1,7 mmol/L) sau 72 gid nhin déi, nhiéu khi tré so sinh glucose huyét tuong thip dén 30 mg/dl (1,7 mmol/L) van binh thudng. Tuy nhién, phan Ién céc téc gid nhat tri ring tré em c6 ndng d6 glucose huyét tuong duéi 50 mg/dL nén duge theo doi cin thin, chan dodn va can thigp diéu tri nén bit dau 6 ndng 49 dudi 40 mg/dL. (2,24 mmol/L). Vi nao khdng c6 kha nang dy trit glucose cfing nhu kha nang tan tao glucose, nang lugng cung cdp cho hoat déng cia nao phan Ién do glucose tir mau cung cp. Téc 9 van chuyén glucose qua hang rio mau nao bai GLUTI (Glucose Transporter 1) ca0 hon téc d6 chuyén hod glucose 6 nfo trong diéu kign binh thudng. Khi ndng d6 glucose 35méu gidm xuéng dudi mite 6 bao d6ng, téc d6 van chuyén glucose vao ndo giam. Sy gidm glucose mau lam nao va cé thé ca gan tro nén nhay cam, hoat hod dong thac giai phong céc hormon lam tang glucose mau. Nguéng glucose méu gay gidi phéng cdc hormon gay tang glucose mau & ngudi khoé manh 1a khoang tir 60-70 mg/dL (3,3-3,9 mmol/L). 5.2, Cae dau higu va trigu chimg Céc trigu chimg khong dic higu, cé thé nhim Jan véi nhidu trigu chimg co ning khdc gay khé khan cho chén doan. Céc trigu chimg cita ha glucose mau chi yéu 14 cde dau higu cua hé than kinh trung wong va hé than kinh giao cam. Cée trigu chitng than kinh Dau dau, 1a ln, ngi lim, mat ¥ thite, hn mé. Céc tn thuong nao khéng hdi phuc hoc tir vong c6 thé xay ra néu ha glucose mdu va hén mé kéo dai. Cac trigu ching kick thich than kink giao céim Sy gidm nhanh glucose méu kich thich giai phéng adrenalin gay céc trigu chimg nhu va mé héi, yéu, run rdy, nén, d6i, mach nhanh, khé chiu 6 ving thugng vi. Cae déu higu va trigu ching khée Bén canh cée trigu chimg than kinh trung wong va than kinh giao cam, ha glucose miu cp c6n e6 ede dau higu Khéc, Thay di huyét déng hoc bao gbm nhip tim nhanb, ting ha Luong tim, thay d6i trén dign tim (T det, khong Q-T kéo dai), c6 thé loan nhip tim. Céc thay déi hod sinh tuy thude nguyén nhén gay ha glucose méu. 5.3. Phan logi Ha glucose mau khéng phai la mét bénh ma la mét chi diém cho sy réi loan hing dinh ngi méi cia glucose, Khi hg glucose mau duge xac dinh, nguyén nhan cia n6 phai duge tim ra, Ha glucose méu cé thé phan loai lam 3 nhém sau: ha glucose méu khi déi (fasting hypoglycemia), ha glucose méu phan img (reactive hypoglycemia) va ha glucose mau do kich thich (induced hypoglycemia). Mac dit cdc bénh nhan ha glucose mau khi d6i 6 thé 6 trigu chimg sau an, nhtmg bénh nhan ha glucose méu phan img khOng bao gid 6 trigu chimg khi di. Mot céch thite khac 48 phan biét la cde biéu hign lam sang cua ha glucose mau khi doi hau nhu khéng cai thign néu khong ¢6 can thiép, trong khi bénh nhan ha glucose mau phan img luén khdi khéng can sir dung thite an. Ha glucose mau khi doi 1a sy mat cn bang hing dinh n6i méi glucose din dén ha glucose mau khi khéng an (46i). Ha glucose mau khi d6i luén la bénh ly. Trong ha glucose méu phan img, bénk: nhan cé trigu chimg lam sing sau an va nong dé glucose huyét tvong lic dé 1a duéi 45-50 mg/dL (2,5-2,8 mmol/L). Cée bénh nin ha glucose méu phan tmg hiém khi e6 triéu chimg than kin, glucose huyét twong néi chung khéng dudi 40 mg/dL, giai doan ha glucose mau thuéng ngén. 36Nguoi binh thudmg khi déi, ede hormon va co chat thay ddi dé duy tri ndng 46 glucose mau binh thudng (ngin chin sur ha glucose mau). Sy giam ndng d6 glucose mau mét it (gidm 5-10 mg/dL.) hay lugng calo dua vao giém lam giam néng 46 insulin huyét tuong. Sy giam ndng 46 insulin huyét tuong 1a thay d6i hormon chu yéu din dén ting tao glucose ¢ gan va giam sir dung glucose & co, mé m@, két qua la néng d6 glucose méu tré vé binh thuéng. Bang 2.8. Phan logi ha glucose mau |. Ha glucose mau khi déi: A. NOi tidt: 1. Tang bai tiét insulin hoc insulin-like factor: a. kh6i u ti6u dao tang bai tit insulin bb. tang sinh tiéu dao (adenomatosis, ...) c. c4c khéi u ngoai tuy 2. Suy gidm oc hormon di khdng v6i insulin: a. Suy tuyén yen b. Suy ACTH hay GH . Benh Addison B.Gan: 1. Benh t glycogen 2. Bénh bam sinh thiéu hut enzym tan tao glucose: 3. Hogi tir gan cp: do dc t6, viérm gan virus, hoi chéeng Reye 4. Suy tim sung huyét C. Thiéu hyt co chat cia sy tn tao glucose: 1. C6 thai, cho con ba 2. Gidm glucose mau nhiém ceton & tré em 3. Suy thén man tinh 4. Suy dinh duéng nang 5, Benh xir6 nigu D. KhOng 16 rang: 1. Hi ching ty min insulin 2. Suy giam carnitin hé thong 3. Tang insulin ha glucose mau 6 tré em. II, Ha glucose mau phan tng: A. Phan tng chire nang B. Thre an Il, Ha glucose mau do kich thich: A. Insulin va sulfonylure B. Do rvgu C. Do thuée ae4+ Glucose mau va Tho8e | calo dua vio INSULIN | ——~ 1 Huy dong acid amin Phan ly glycogen + Phan hu lipid ~ Cac enzym tan tao a 4 San xuat glucose 4 Sir dung glucose (Gan) GN 4 (m6 mé, co) Glucose mau binh thuéng Hinh 2.5, Sy didu hoa hang dinh ndi méi glucose khi d6i 5.4. Cée xét nghiém dénh gid ha glucose mau 5.4.1. Glucose huyét trong Su giam ndng 46 glucose huyét twong 1a tiéu chuan bat bude dé chin don ha glucose mau, Nang 46 glucose binh thug tai thdi diém xay ra cdc trigu chimg loai trix hg glucose mau va cn phai tim ede nguyén nhén khdc. 5.4.2, Insulin huyét twong Xét nghigm dinh lugng insulin gip ich cho vige chin don ting tiét qué mie insulin gay ha glucose mau khi d6i. Xét nghiém nay la dénh gid ban dau véi tat c cdc bénh nhan ha glucose miu khi déi. Nong 49 insulin sau mét dém nhjn d6i nhin chung 1a duéi 10 wU/ml, nhung & ngudi béo phi hay sau truyén glucose c6 thé cao hon. Céc phuong phap mién dich hod phat quang (immunochemiluminometric assays-ICMA) dae higu véi insulin va khéng 6 phan img chéo véi proinsulin, 49 nhay 6 mite duéi_1 U/ml, nén néng d@ insulin cao hom binh thurong tir 2-3 wU/ml 06 thé dt nhay a8 chin doan chimg ting tiét insulin. Nén xét nghigm dBng thai ca glucose huyét twong dé c6 thé phan tich méi lién quan v6i ndngd6 insulin, 161 hat 1a trong cling mét mau mau, Vi néng dé glucose méu c6 téc dung diéu hoa sy bai tiét insulin, binh thuong néng 49 glucose mau thap phai tuong img véi nng 49 insulin thdp. Trude day thug sir dung ty s6 insulin/glucose dé danh gid chimg ting tiét insulin (hyperinsulinism). Binh thuémg ty sé nay < 0,03 (insulin tinh theo don vj U/ml, glucose don vj mg/dL). Tuy nhién gid tri chan dodn cia chi s6 nay c6 han, chi nén xem nhu mét goi ¥. Khi ca glucose va insulin duge dinh 38lugng ding théi trong thir nghiém nhjn d6i thi kha ning chin dodn chimg ting tiét insulin cua ty s6 nay tang lén, 5.4.3, Peptid C Xée dinh peptid C 1a xét nghiém co ban dé phén biét ting insulin n6i sinh hay ngogi sinh, Vi insulin va peptid C duge té bao beta bai tiét voi s6 phan tir trong duong nhau, hai peptid nay cé tinh mién dich khée nhau, t6c d6 thanh thai peptid C chém hon insulin; nén, su ting néng d6 peptid C khi déi 1a chi diém cho sy tang bai tiét ciia té bao beta. 5.4.4, Proinsulin Binh thudng proinsulin chiém duéi 20% téng luong insulin cé tinh phan img mién dich trong huyét tuong. Trong mdt vai trang thdi, bao gdm ca cdc khéi u cia tiéu dao, proinsulin chiém t6i hon 70% . Nhimg bénh nhén suy thn va nhimg thinh vién cia gia dinh mic chimg ting proinsulin Linh tinh, ndng 46 proinsulin cing tang. Viée inh lung proinsulin khéng thé la xét nghigm duy nhat chin dodn phan biét cdc trang thai bénh ly nay. Can luu ¥ 1a proinsulin c6 phan tmg chéo véi peptid C trong hau hét cde phuong phap mign dich phéng xa (RIA) dinh luong peptid C, phuong phap xéc dinh proinsulin bang HPLC hay mign dich héa phat quang (ICMA) dic hiéu hon. 5.4.5. Thit nghiém nhjn abi kéo dai ‘Xét nghiém dang tin cdy nhat chan doan nguyén nhan ha glucose mau khi déi 1a thir nghiém nhjn doi kéo dai ¢6 theo déi va kiém sodt 6 bénh vign, o6 thé t6i 72 gid. Nguyen 1y: sy hing dinh ni méi cia glucose duge duy tri bai hé théng hormon, trong 46 cé insulin va glucagon. Néu hé théng nay réi loan, vi dy chtmg tang tiét insulin, ndng d9 irsulin mau ting khi glucose mau giam. Viéc nhin d6i t6i 72 gid gay ha glucose mau va nguyén nhan cua ha glucose mau cé thé xdc dinh duge bing cach xét nghiém céc mau mdu trong khi bi ha glucose mau. Tién hanh: ~ Bénh nan nhin déi, ngimg diing cdc thudc. — Buoge udng céc dé udng khéng cé nang luong va cafein. — Bénh nhén nén hoat déng thé lye binh thudng khi thite. — Dinh lugng glucose, peptid C, insulin va cé thé ca proinsulin 6 gid mét lan téi khi glucose mau < 60 mg/dL (3,3mmol/L) thi cir 1-2 gid lay mau dé xét nghiém. — Néu bénk nhan cé trigu chimg ciia ha glucose mau va glucose huyét tuong < 45 mg/dL thi ngimg nghiém phdp. — Két thc thir nghiém, dinh luong glucose, peptid C, insulin va cé thé ca proinsulin, f-hydroxybutyrat trong cling m6t méu, tiép theo tiém tinh mach Img glucagon va dinh Iugng glucose sau 10, 20 va 30 phut. 39— Néu nghi ngi suy gidm cortisol, GH hay glucagon, cc hormon nay edn duge dinh luong khi bat dau va két thie thir nghiém. — O tré em, théi gian nhin déi phy thudc tudi. Téi da la 12 gid 6 tré < 1 tudi va khéng kéo dai hon 24 git tré lén hon. Déinh gid két qué: Binh thudmg khi glucose huyét twong < 60 mg/dL thi insulin < 6mU/L (36 pmol/L), peptid C < 0,7 pg/L (0,2 pmol/L) va proinsulin < 25ng/L (3 pmol/L). Néu glucose mau giém ma insulin va peptid C lén hon hode bing céc gid tri néi trén thi goi y C6 kh6i u tiéu dao (insulinoma). Néu trong ving 72 giés ma glucose huyét tuong khong gidm xuéng dudi 45 mg/dL (2,5mmol/L) va insulin < mU/L (36 pmol/L), peptid C < 0,7 pg/L (0,2 pmol/L) thi logi trir insulinoma. 5.4.6, Chie xét nghibm khée Céc thir nghigm udng arginin hay leucin, tiém tinh mach tolbutamid, glucagon hay canxi nhin chung cé it gia tri trong chan dodn phin biét. Glucagon néng 46 cao 1a yéu t6 kich thich bai tiét insulin truc tiép. Cac khdi u té bao tiéu dao dic biét nhgy trong dép img véi glucagon in vitro. Bénh nhdn insulinoma 6 thé tang bai tiét qué mite insulin sau tiém tinh mach Img glucagon. Nong d@ insulin t6i da sau tiém 5 phut binh thudng 1a duéi 150 U/ml, mOt s6 bénh nhan u tiéu dao c6 thé c6 néng 46 1én hon giéi han trén vai Lin. 6. CAC ROL LOAN CHUYEN HOA CARBOHYDRAT BAM SINH 6.1. Bénh tr glycogen (Glycogen storage diseases) Bénh t glycogen bao gdm mét nhém cdc r6i loan di truyén do thiéu hyt mot hay nhiéu enzym lién quan dén chuyén héa glycogen. Cac bat thudng nay cé thé biéu hién nhu céc bénh ly cla gan, tim, co xuong. Cé hon 10 typ bénh, tuy nhién mét sé typ rat hiém gap. Typ I hay bénh von Gierke la mét trong céc r6i loan hay hap nhét. Nguyén nhin do thiéu hyt hodc khéng cé glucose -6-phosphatase & gan. Tré mic bénh thdp bé, bung rit to do gan to, gidm glucose mdu ning, ting acid lactic mau, ting lipid mau. Co thé chan dodn bang thir nghiém tiém glucagon hode epinephrin. Chan doan xéc dinh tit cd cdc typ bénh phai dya vao do hogt 46 enzym cua m6 thiéu hut va sinh thiét mé ton thuong. 40Bang 2.9. Cac bénh glycogen ‘Typ bénh Enzym thiéu hyt u hign lam sang 1(Bénh von Gierke) | Giucose-6-phosphatase Gan rt to, ha glucose mau nang, nhiém toan acid lactic, tang lipid mau, cham lon II (Bénh Pompe) A-1,4-Glucosidase Tré em: tim to, yu co, chét sm Ngudi lon: ybu co Il (Benh Cori) Amylo-1,6-Glucosidase Gan to, yéu co, ha glucose mau (enzyme cat nhanh) IV (Bénh Andersen) a-1,4-Glucan: a-1,4-Glucan, | Gan to, xo gan, cham lon, chét som 6-glucosyl transferase (enzym gn nhanh) V(Bénh McArdle) | Phosphorylase co Chuot rit Sau tap thé duc, mot niva s6 bénh nhan c6 myoglobin niéu VI (Bénh Hers) Phosphorylase gan Gan to, biéu hign lam sang nhe Vil (Benh Tauri) Phosphofructokinase co Chudt rit sau tap thé duc, mot sb benh nhan c6 myoglobin niu vil Adenyl kinase Co cing, mat nude, catecholamin nigu cao, chét khi cén du tho K Phosphorylase b kinase Gan to, néng 46 glycogen trong gan ting x Kinase phy thudc AMP véng | Gan to 6.2. Réi loan chuyén hod galactose Réi loan ckuyén héa galactose (galactosemia) 14 mot bénh di truyén hiém gap, bénh nhan khéng chuyén héa duge galactose do thiéu hut hogc khéng c6 mot trong ba enzym chuyén héa galactose. Ba enzym dé 1a galactokinase, galactose-1-phosphat uridin tranferase va UDP galactose-4-epimerase. Bénh galactosemia cé dién 1a do thiéu hut transferase, Thiéu hut galactose-1- phosphat uridyl transferase ‘Vi galactose c6 trong thanh phn lactose cia sita, nén tré bi galactosemia cd dién duge chan doan khi con nhi nhi. Sau khi n stta, xudt hién nn, tiéu chay, xo gan, duc thily tinh thé, cham phat trién tinh than. Tré cham Ién va c6 thé tir vong néu khéng duge igu tri bing stta nhan tao khong chifa lactose. : Chin dodn galactosemia dya vao sy phat hién galactose trong nude tiéu hode huyét thanh, khang dinh chan doan bing do hoat d9 glactose-1-phosphat uridyl 41transferase trong hdng cdu. Chuong trinh sang loc galactosemia dya trén do hoat dé transferase trong héng cdu. Thiéu hut UDP galactose-4-epimerase R6i loan rét hiém gap, biéu hign lam sang tong ty nu thiéu hut transferase. Thiéu hut galactokinase Biéu hién chi yéu cia bénh 1a duc thay tinh thé do ling dong galactitol 6 thé thiy tinh. Chin doan xéc dinh: khéng cé galactokinase trong hong cau va hoat dé transferase binh thuong. 6.3. R6i logan chuyén hod fructose Fructose cé thé xuét hién trong nude tiéu sau an hoa qua, mt ong, xi r6, trudng hop nay khong cé ¥ nghia lém sing. Fructose 6 trong nude tiéu bénh nhan réi loan chuyén héa fructose do thiéu hut enzym can thiét cho chuyén héa fructose. C6 ba nhom r6i loan chuyén héa fructose, tat cd déu di truyén lin nhiém sic thé thudng. Khéng dung nap fructose do di truyén do thiéw hut enzym fructose I-phosphat aldolase, gay t dong fructose-I-phosphat trong té bao. Khi an hoa qué hoe sin phém chita dudng saccarose, tré xudt hign nén, giém glucose méu, gan to, cham Ién, Chan dodn dua vao tim thay fructose trong nude tiéu, gidm glucose va phosphat mau sau Khi lam thir nghiém dung nap fructose dug tinh mach. Thiéu hut fructose-1,6-diphosphatase, enzym can thiét cho chuyén pyruvat thanh glucose, lam tré gidm glucose khi déi, nhiém acid lactic, gan to, tién lung rat xdu. Fructose nigu (Fructosuria) 1a bénh lanh tinh do thiéu hut fructokinase cua gan, dc trang boi su tang cao fructose mau va nudc tiéu sau khi an fructose ho§e saccarose. Diu quan trong 1a khéng duge nham lan réi loan nay véi ddi dudng. Dinh hong glucose bing cdc ky thudt dic higu hoc khéng dac hiéu dé xéc dinh dé 1a fructose hay glucose cé thé hiu ich. 6.4, Bénh t mucopolysacearid (Mucopolysaccharide storage diseases) Mucopolysaccharid la thanh phan cdu tric ciia sun, xuong, da, céc mé lién két khdc. Cdu tao gém rdt nhiéu cdc don vi la cdc disaccarid (hexosamin va acid uronic, hexosamin thuéng acetyl héa va gin nhém sulfat). Ching duge thodi héa béi céc enzym cia lysosom. Bénh tt mucopolysaccarid (Mucopolysaccharidoses) la cdc réi loan di truyén do thiéu hut mét ho&c vai enzym thoai héa cia lysosom. Mucopolysaccarid (Glycosaminoglycan) tich ty trong cc mé khéc nhau va bai tiét trong nude tiéu. Ba nhém mucopolysaccarid cé lién quan 14 dermatan sulfat, heparan sulfat va keratan sulfat. H@i chimg Hurler la nguyén mu cho cde bénh mucopolysaccaridose. Bénh tién trién nang né v6i dae diém dye gide mac, tir vong thudmg trude 10 tudi, Tré bj bénh 06 b9 mat thd, bat thudng xuong, cham phat trién va gan léch to. Xét nghiém bao gdm 42sang lge mucopolysaccarid nigu, dinh Iuong acid hexuronie, dign di xée dinh fe thanh phin mucopolysaccarid nude tiéu, Chin doin xée dinh bing tryc tiép do hogt a enzym nghi nghd trong bach cau hoe nguyén bao sqi nudi cy. 7. CAC KY THUAT PHAN TICH GLUCOSE 7.1. Phan tich glucose huyét tong va dich nfo tiy 7.1.1. Mau bénh pham Trong qua kh, dinh lugng glucose thudng sit dung m&u mau toan phin. Ngay nay, huyét thanh hoac huyét tuong 1a cdc loai mau duge Iya chon. Tuy nhién, vige sir dung mau toan phin lai tro nén quan trong vi céc thiét bj do dudng huyét tai nha ding mau toan phan, Glucose huyét thanh hoc huyét tong cao hon mau toan phan 10 dén 15% vi su khée nhau vé ham Iugng nude gitta hai ogi mau bénh phim. Glucose phan bd déu gitta té bao mau va huyét tuong, nhung mau toan phan véi hematocrit binh thudng chi chita khoang 89% long nuéc khi so sinh véi cling mét thé tich huyét tong. C6 mét vai uu thé cia viée sir dung huyét thanh hay huyét tuong dinh long glucose so véi méu toan phan, Trude hét, huyét thanh va huyét tong thich hop cho cdc ky thuat ty déng. Tiép nita, hematocrit khéng anh huéng dén glucose huyét thanh hay huyét tuong, trong khi sy ting hematocrit lim giam glucose mau toan phan do lung nude trong mau gidm. Héng cau cting chira cae chat khir khong phdi glucose khdc, 6 thé anh huéng dén viée dinh lwong glucose ding phuong phap khir, Cudi cing, sir dung huyét twong hay huyét thanh khdng can chat bao quan. Trong mau toan phan, glucose bi chuyén héa béi hong cdu, bach cdu, tiu cau va bat ctr vi khudn nao nhiém vao, vi vay néng d6 glucose gidm v6i tée 46 12%/gid & nhiét 4} phing. Qué trinh dung phan c6 thé bi tee ché bing cach cho thém sodium fluorid yao mau bénh phim. Céc ion fluorid ttc ché enzym: enolase va fructose-1,6- diphosphatase, ngin chan qué trinh duéng phan. Ching edn tte ché dong mau bing cach gin canxi, nhung déng méu cé thé xay ra sau vai gid. Do vay, hn hgp fluorid- oxalat thudng duge diing. lodoacetat cing c6 thé duge ding nhu tic nhén chéng phan hiy glucose. Né tre ché phosphoglyceraldehyd dehydrogenase cia qué trinh duéng phan. V6i ce chat bao quan nay, glucose én dinh 24 gid trong méu toan phan & nhiét phong. Cac cht bao quan nay cé thé tre ché mét sO phan (mg enzym, lam cho mau bénh phim khéng thé ding cho mét sé xét nghiém khac, vi dy dinh lugng uré bang phuong phdp urease. Khi khong ding chat bao quan, huyét thanh hodc huyét tuong can duge tach khéi té bao trong vong 1 gid sau khi ldy mau, Sau khi tach, glucose trong huyét thanh hode huyét tuong dn dinh toi 8 gid & nhiét dd 25°C va 72 h 6 4°C néu mau khong con té bao va khong nhiém vi khudn. 3Huyét thanh ho&e huyét tuong mau tinh mach duge str dung cho phan tich glucose. Khi d6i, glucose trong m4u mao mach va dng mach cao hon trong méu tinh mach khoang 0,2 mmol/L. Khi mau bénh phim duge lay 15 dén 90 phut sau thir nghiém carbohydrat, ndng d6 glucose méu mao mach cao hon méu tinh mach 1,8 mmol/L. Vi vay, mau cdn duge thu thép tir mt nguén duy nhit trong thir nghiém dung nap glucose. Vi DNT thudng nhiém khuan hodc céc té bao khac, luén phai dinh lrgng glucose ngay hoe phai bdo quan vi chat chéng phan hiy duéng. 7.1.2, Ce phucong phdp C6 thé six dung cing m6t phuong phép dé dinh Iuong glucose trong mau va DNT. Céc phuong phap dinh luong cé thé dugc xép thanh 2 loai: héa hoc va enzym. Phuong php enzym dic higu hon phutong phdp héa hoc. Phan lén cde phuong phép hoa hoc hign khong con duge sir dung vi thiéu dic higu, chim va kh6ng higu qua, nhung sé duge trinh bay tém tit dé gidi thigu lich str. Plurong phép héa hoc Oxy héa kine: cde phuong phap héa hoc cit dya trén ky thuat oxy héa khir, Trong ‘méi trudng kiém, glucose khir ion déng hai (Cu) thanh ion ding mét (Cu’). Trong méi trudng kiém, dang enol cla glucose chiém uu thé, lién két ddi va dign tich 4m c6 mat trong anion enol lim glucose 14 chét khit. Vi glucose, fructose vA mannose chi khéc nhau & nguyén tir carbon thir hai, tt cd ching déu tao cling dang enendiol va déu duge do bing cdc phuong phép dya trén tinh khir cua glucose. Céc chat khir khong phai dung nhu acid uric, acid ascorbic va creatinin cing sé duge do khi ding phuong phap nay. Sy khéc nhau vé 49 dic higu ciia phurong phép khir phy thudc vao chat nhiéu duge Joai bé higu qua nhu thé nao khi khtr protein va mau sinh ra cla phan (mg. Trong phuong phap Somogyi-Nelson, protein duge két tha bing bari hydroxid va kém sulfat, chat sinh mau trong thudc thir 1a arsenomolybdat bi khir thinh hop chat molybdat mau xanh da tri béi ion Cu’. Day 1a ky thuat oxy héa khur dic hiéu nhat vi acid uric va creatinin d6 duge két tia véi protein. Phuong phip Folin-Wu sir dung gc acid tungstic va thuéc thir mau phosphomolybdat nhung thiéu dic higu vi céc Khir khéc khéng phai duong cé trong dich loc. Trong phuong phép ferricyanid kiém, glucose khir ferricyanid mau vang thanh ferrocyanid khong mau, duge ding dinh lugng glucose trong céc may tr dong nhumg van bj nhiéu boi chat kh. A-toluidin la phuong phdp héa hoc dac hiéu nhdt, tuy nhién rat déc do A-toluidin hign duge xem la chat gay ung thu. Phuong phép enzym Cae phuong phap enzym sir dung céc enzym lam thuéc thir dé tang tinh dac hiéu phan img véi glucose. Cée phuong phép nay dinh lugng glucose thye chér khéng phai céc chat khit. Day 1a cde phuong phap phé bién nhat dang duge sir dung hign nay vi tién 44hanh nhanh va don gian, dé dang ty d6ng héa, sir dung mét Iugng nhé mau va dic hiéu cao. Ba phuong phap enzym la hexokinase, glucose oxidase va glucose dehydrogenase, trong dé hexokinese dugc xem la phutong phap quy chiéu. Phuong phép Hexokinase: Nguyén Ii ciia phuong phap: Hexokinase Glucose + ATP > Glucose-6-phosphat + ADP GePD Glucose-6-phosphate + NADP" -> 6-Phosphogluconat + NADPH + H+ Hexokinase (HK) xtc tée phan ting phosphoryl héa glucose béi ATP tao glucose- 6- phosphat va ADP. Phan tg thir hai glucose-6-phosphate dehydrogenase (G6PDH) xtic tae sy oxy héa glucose-6-phosphat boi NADP* dé tao NADPH. Sy tang mat 46 quang NADPH duge do tai bude song 340 nm va ty Ig thudn véi néng 46 glucose trong méu thir. Khi G6PDH cua ndm thi coenzym str dung la NADP*, khi G6PDH tia vi khuan thi NAD* duge sir dung. Phuong phép quy chiéu HK sir dung dich loc khéng chia protein lam mau thir, nung phuong phip nay mat nhigu thoi gian d6i voi cOng vige thu’mg quy. Huyét thanh hoge huyét tuwong cé thé sir dung true tiép véi vige tring mau tai bude séng 340 nm dé higu chinh cdc chat nhiéu h4p thy anh sang tai 340 nm. Dé tiét kiém thai gian, nhiéu phng xét nghigm khéng chay mu tring, vi vay két qu dat duge cao hon so voi phuong phap quy chiéu mét chit. Sy két hgp tinh dic higu cia HK va G6PDH han ché cdc yéu té nhigu carbohyrat khac. HK phosphoryl h6a ca fructose va mannose nhumg cae dudng nay 06 trong mau v6i ndng a9 khong dit cao dé gay nhiéu, Huyét tan anh huéng dén phuong phdp nay vi héng cdu cd G6PDH va 6- phosphogluconat dehydrogenase, cd 2 enzym sir dung NADP* lam co chat. Phan Ion cae phuong phap hiéa nay ding enzym vi khudn 4é gidm nhiéu do huyét tan, Ca huyét tuong va huyét thanh cé thé sir dung lam miu thir, Sodium fluorid va cdc chat chéng déng nhu heparin, EDTA, oxalate Khong anh huéng én phuong phap. Vige tring miu thudng bj bé qua sé gay anh hudng nhiéu khi mau huyét tan 13, vang da, duc. Nhuge diém chinh cia phuong phdp la gid thanh cao. Phuong phap HK ciing c6 thé sit dung m9t chat chi thi nhu phenazine methosulfat (PMS) va iodonitrotetrazolium (INT) dé mat 46 quang 06 thé do duge & viing kha kién. INT bj khtr boi NADPH dé tao sin phim mau c6 46 hap thy Anh séng cue dai tai 320nm. Phuong phdp glucose oxidase Glucose oxidase Brglucose +02 —>D-Gluconic acid + H,0, 45Glucose oxidase (GOD) dic higu cao véi beta-glucose. Dung dich glucose trong nude & trang thai cn bing chita 1/3 alpha D glucose va 2/3 beta D glucose. Vi vay, diéu quan trong la dung dich glucose chudn sir dung trong phuong phap nay can it nhat 2 git 48 dat trang thai cn bang. Vi beta glucose bi oxy héa béi glucose oxidase, alpha glucose chuyén thanh dang beta bai dinh luat khdi lugng. Phuong phép glucose oxidase di khi chita enzym mutarotase dé Lam nhanh tién trinh nay. Nong 46 glucose ty 1g thudn voi lugng oxy tiéu thy hoe HO. sinh ra, ca hai c6 thé do duge. H,02 c6 thé do bang ech kep 46i v6i phan img chi thi peroxidase. H,0> + Chat sinh mau dang khir —» Chit mau dang oxy héa + H2O Phan tmg nay kém dic higu so véi phan (mg glucose oxidase. Nhiéu chat khit trong huyét thanh nh acid uric, acid ascorbic, bilirubin va glutathion tre ché phn tmg bdi canh tranh voi chat sinh mau trong phan tmg v6i H2O2; do dé lam két qua thap gia tao. Cae chét nhugm nhy 3-methyl-2-benzolinon hydrazon (MBTH) cing voi N,N- dimethylaniline (DMA) (phuong phép Gochman) ho%e 4-aminophenazon cing voi phenol (Phuong phép Trinder) la it bj nhiéu bdi creatinin, acid uric, ho&c hemoglobin. Céc két qua thap c6 thé gap néu phan img nhiém catalase vi catalase phan hiy H02. Thudn Ioi chinh cia phuong phap glucose oxidase la gia thanh thdp. HO, tao thanh tir phan img xiie tae béi GOD cé thé do bang nhieu ky thuat khéc nhau, Trong phuong phap str dung héa chét khd (Vitros 250, Ortho Clinical Diagnostic), H:O2 phan mg véi chat sinh mau tao san pham mau. Cuémg 46 mau duge do & bude séng 540 nm bing anh sang phan xa. Nhiéu thiét bj chm séc tai ch3 (POCT-point of care testing), bao gdm ca may do khi mau, sir dung phuong phép GOD dinh lugng glucose. Trong cac thiét bj nay, cathod bac va anod bach kim duge bao quanh bai dung dich din ly va nhidu lép mang tai dau nhé. Mang nay bao gdm mot lép ngoai tham glucose, lép gitta chita GOD duge cé dinh, lop trong thm véi hydrogen peroxid, H2Oz duge van chuyén qua mang trong téi dign cue duong bach kim va duge oxy héa. Ding dign sinh ra ty 1é thudin voi Luong H202, vi vay ty Ig v6i lwong glucose trong méu thir, Dé hoan thinh mgch dién, phan mg 6 cyc fm chuyén hai Ag’ (AgCl) thanh Ag véi mdi phan tir H2O> bi oxy héa. Phuong phép glucose dehydrogenase (GDH) Nguyén ly: a B-D-Glucose + NAD* -> D-Glucono-A-lacton + NADH +H Mutarotase duge cho vao hén hgp phan tmg dé chuyén dang alpha sang beta. Phan img duge do tai 340 nm duéi dang dng hoc hoge do diém cudi. GDH duge phan lap tir Bacillus cereus rét dic higu v6i glucose, két qua cla phuong phép nay tuong déng véi phuong php HK. 46yoeus 7.1.3. Glucose djch nao tuy Néng d6 glucose dich nao tiy (DNT) khong 60-75% trong huyét tuong (2,2-3,9 mmol/L). Glucose DNT can bing véi huyét tuong, tuy nhién thép hon huyét tuong vi glucose duge sir dyng béi hé than kinh trung wong va vi su yan chuyén tang cudng qua mang ndi mé béi chat van chuyén dac higu khéng gian. Phai mat 2 dén 3 gid’ su thay déi glucose huyét tuong méi gay ra thay déi glucose DNT. ‘Sy ting ndng dd glucose DNT khong cé y nghia lam sang nhiéu, thing chi phan anh sy ting glucose mau. Sy gia ting glucose DNT khong ty 1¢ thufin véi glucose mau. V6i ndng d6 glucose huyét tuong 44,7 mmol/L hode cao hon, glucose DNT chi khong 30-40% mite glucose huyét tong. Giam glucose DNT thuong cé ¥ nghia trong chan dodn viém mang nfo do lao, vi khuan, nam; gidm glucose mau, cdc u than kinh trung wong. Sy gidm glucose trong cdc trudng hop nay la do giam vn chuyén glucose tir mau vao DNT, ting sir dung glucose bai mé than kinh, tng sir dung glucose béi vi Khudin, bach edu hoe cdc té bao méi sinh trong DNT nhiém bénh. Vi cé thé cé cdc vi khudn hay té bao trong DNT, didu quan trong la can phai phén tich m&u bénh phim ngay lap ttre hoe bao quan DNT béi cde chat tre ché phan hiy dudng. Nong dé glucose huyét tuong nén duge dinh luong cing lic voi DNT dé gitp phan tich két qua glucose DNT. Ca glucose huyét tuong va DNT duge do luéng bang cng mt phuong phép. 7.2. Phan tich glucose nwéc tiéu Glucose xuét hién trong nude tiéu trong mét sé trang thai bénh nhw di thio dung. Cac dung khac cé thé xudt hign trong nude tiéu nhw galactose trong bénh galactosemia, Nude tiéu c&n duge phan tich glucose ngay lap tire vi nude tiéu chita vi khudn va cde té bao khéc 06 thé lam gidm glucose béi qué trinh duéng phfn. Glucose trong nude tiéu 24 gid c6 thé duoc béo quan bing thém acid acetic hoc sodium benzoat vao dung cy chira nude tiéu truée khi bit dau thu thap. Cé thé dinh tinh hoac dinh long glucose niéu. Dé dinh tinh glucose nigu, cé thé ding phuong phép Benedict phat hién cdc during c6 tinh chat khit. Glucose va cae chat khir khde c6 thé khir ion Cu** thinh Cu’, tao thinh CuOH mau vang ho&e CuO dé gach két tia. Vién Clinitest img dung nguyén li nay. Phuong phap nay khéng dic higu voi glucose vi tét cd cde duéng khir khdc (galactose, fructose, maltose, lactose, xylose, ribose, arabinose) déu phan img. Cac chat Khir khac nhu acid ascorbic, acid uric, creatinin ciing dong gép dang ké vao ting long céc chat khit cé mit trong nude tiéu. Phuong phép diing que nhting (dipstick) a8 sang loc glucose trong nude tiéu dya trén phuong phép GOD v6i chit sinh mau. Phuong phap nay dic higu véi glucose va 47nhay hon phuong phdp Khir. Két qua 4m tinh gid c6 thé do acid uric hay ascorbic tte ché phan img. Duong tinh gia khi nude tiéu nhiém hydrogen peroxid hodc cdc tac nhén oxy héa manh nhw hypochlorit. Dinh lugng glucose nigu cé thé sir dung ky thugt HK hoge GOD do t6e 49 tiéu thy oxy tiéu thy tuong ty nhu trong huyét thanh. Phuong phép GOD ding phn img H202- peroxidase khéng thé sir dung vi néng 46 cao ctta cdc chat nhu acid uric sé lam nhiéu phan img va gay két qua thdp gid tao, Nuéc tiéu thudng duge pha loang véi nude truée khi dinh lugng. 7.3. Thé ceton ‘Thé ceton bao gém acid acetoacetic, beta hydroxybutyric, aceton. Ching c6 trong mau véi ty 1¢ tuong img 1 20%, 78% va 2%. Tao thé ceton qua mic gay ting néng 46 trong mau va tang bai xudt trong nude tiéu, gap trong nhin déi kéo dai hoc dai th4o dudng khéng kiém soat. Khéng 6 phuong phdp nao ding xdc dinh thé ceton trong mau hay nude tiéu phan (ing véi ca ba chit. Cac kj thudt str dung nitroprussid la thuémg ding nhat dé ban inh lugng thé ceton trong mau va nuéc tiéu. Acetoacetat va aceton tao san pham mau tim khi phan img véi nitroprussiat trong m6i trudng kiém. Phan img ctia nitroprussiat ‘véi acetoacetat nhay hon véi aceton tir 15-20 lin, khéng xay ra v6i betahydroxybutyrat. Phai sir dung cdc mAu nudc tiéu va huyét thanh, huyét tong tuoi, khéng huyét tan. Acetoacetat va betahydroxybutyrat trong mau cé thé duge dinh Iugng bang ky thudt enzym dae }- hydroxybutyrat dehydrogenase (B-HBD). NADH +H’ + Acetoacetat_ «+ Beta-hydroxybutyrat + NAD" Tai pH 7, phan tmg xay ra theo chiéu tir trai sang phai, ndng d9 acetoacetat duge do bai su gidm mét 46 quang cia NADH tai 340 nm. Tai pH 8,5 dén 9, phan ting xay ra theo chiéu tir phai sang tréi, ndng 46 beta-hydroxybutyrat duge do bai sy tang mat 45 quang cla NADH tai 340 nm. Binh thuong ndng 46 acetoacetat va beta-hydroxybutyrat duéi 3 mg/dl (0,3 mmol/L). 6 ndng 46 nay, cde thir nghiém dinh tinh sing loc véi nitroprussiat cho két qua am tinh. 7.4, Hemoglobin glycosyl héa (Glycosylated Hb hoc Glycated Hb, Glycohemoglobin) Miu bénh phim: méu duge chéng déng bing EDTA, heparin hay fluorid, Mau toan phan c6 thé bao quan 4-8°C trong 1 tuan, dich hemolysat cé thé dn dinh 4-7 ngay & 4°C va 30 ngay 6 -70°C. Tuy nhién, tinh én dinh cé thé con dic hiéu phuong php. Méu toan phan cé thé én 1 nam 6 -70°C. Hin tai, céc phuong phép dinh rong HbAIc 6 thé chia lam 2 nhém Ién dya trén céich thite phan tach Hb glycosyl héa va Hb Khong bi glycosyl héa. Su phan téch o6 thé dya trén sur kha nhau vé dién tich, tinh phan tmg héa hoc va edu tric. 48Cofen | Cééc phuong phdp dua trén sy khdc nhau vé dién tich Stic ki trao di ion-sic ky léng higu nang cao (HPLC) phan tich eéc loai Hb dyva trén sir khée nhau vé dign tich ca chting. Mau duge bom ty dng hoe bing tay vao cbt 6 chita resin hoge gel c6 cae nhém chite dign tich trai déu véi chat phan tich, Dung dich dém véi lye ion ting dan chay qua cét, day cdc loai Hb ra. Cée phin Hb duge phén tach lan lugt di qua dau do, mat 46 quang duge do bing quang phd ké. Phin mém tich hop sé xirIy sé ligu va tinh todn két qua. Céec thiét bj hign nay sit dung méu ton phan va c6 ca b6 phan tron lac mAu, pha long va bom mu ty déng. HPLC Ia phutong phap 6 d9 chinh xac cao va cé kha nang phat hién sy c6 mat ciia cdc bién thé cita Hb. Dign di phn téch céc loai Hb dya trén sy khéc nhau vé dign tich, mau thir duge dat trén gel agarose, dat trong mét dign tring, céc logi Hb di chuyén va duge phan tich. Sau dign di, cdc bang duoc doc béi densitometer va so sénh véi chudn dé dinh iugng. Nam 2007, Higp hdi cdc nha bénh hoc My (CAP) téng két khong thy phong xét nghigm nao dinh lugng GHb (hemoglobin glycosyl hoa) bing phuong phap dién di. Phuong phép dua trén sur khée nhau vé cdu trie Sde ky di luc: borat duoc gin cé dinh trén mOt matrix tro, khéng tan. Borat tuong téc chon loe véi cée nhém cis-diol e6 mit trong cde phan tir duimg nhur glucose dé t90 lign két dbng héa trj chat nhumg thugn nghich. GHb s€ duge git lai, trong khi Hb khéng. glycosyl héa sé bj rita giai bang dém. Tac nhan héa tan chita diol nhu sorbital duge ding dé day GHb ra. C4 hai loai Hb duge phat hign bang phuong phdp quang phé tai bude séng 414 nm, Phuong phap nay dinh lugng tong luong GHb. Mién dich: str dyng khang thé nhin biét cdc nhom tan amin duge glycosyl héa cla chudi beta. Cac pkuong phép cé trén thj trudng hién nay sir dung ngung két latex-khang thé hoc min dich do 46 duc. Enzym: méu toan phan duge tao dich huyét tén, sau 46 due thiy phin béi protease. Valin glycosyl héa ld co chat cia enzym fructosyl valin oxidase. Hydrogen peroxid duge tgo thanh tir phan (mg trén sé bi phan hiy bdi peroxidase véi sy tham gia ciia chat sinh mau. Mau tao thanh sé ty 1é thudn véi ndng 49 GHb. TOM TAT Carbohydrat la céc aldehyd ho§e ceton véi hai hay nhiéu nhém hydroxyl. Ching duge phan thanh ba logi: monosaccarid, oligosaccarid va polysaccarid. Monosacccarid quan trong va phé bign nhét trong ty nhién 1a duémg sau carbon D-glucose. D-glucose li durémg hima hinh trong mau. Glucose mau cé ngubn géc tir glucid thie an, phan ly glycogen dy trit 6 gan, tir chuyén déi cdc hexose khéc thinh glucose 6 gan, tan tgo glucose tit acid amin, lactat. Glucose 14 nguén nhién ligu chinh cho céic mo tir khi d6i kéo dai, Néng 46 glucose mau duge diéu hda chat ché béi céc qué trinh chuyén héa va hormon. (Cc ri loan chuyén hoa carbonhydrate6 thé lam nding 46 glucose mau ting hoge gidm, Déi thao duémg la nguyén nhan hay gap nhat va trim trong nbdt gy ting glucose méu. 49 i ' | | | | | | | |Phat hign, dinh lugng glucose trong méu, nude tiéu ld céng cy quan trong trong chan doan va theo di bénh nhén dai thdo dudng, Céc ky thuat hay diing nhat dé dink lugng glucose la ky thudt enzym (glucose oxidase va hexokinase) vi ching dc higu v6i glucose. Hb glycosyl héa durge tao thanh tir phan tig lién hgp glucose véi nhom amin t@n ciia Hb bang phan tng khéng enzym. Bay la mot chi diém quy trong dénh gid ndng d6 glucose trong vong hai thang va do dé rit c6 ich trong quan ly bénh nhan dai thao during, CAU HO! ON TAP . Trinh bay nguén géc, cdc yéu t6 diéu hoa ndng d9 glucose mau. . Trinh bay céc xét nghiém hod sinh trong chén doén dai thao duémg. . Trinh bay cée xét nghiém hoa sinh ding phan biét dai thao dudng typ 1 va typ 2. . Trinh bay cée xét nghiém hod sinh trong theo doi diéu tri va tién Iugng dai théo duong. Trinh bay céc xét nghiém hod sinh sir dung danh gia ha glucose mau. 6. M6 ta mét sé dic diém lam sang chinh, dic diém xét nghiém cba mét sé bénh. r6i loan chuyén héa carbohydrat bam sinh: galactosemia, khéng dung nap fructose, tr glycogen, réi loan chuyén héa mucopolysaccarid. Rene 7. Trinh bay cée nguyén ly ky thudt, loai mu bénh phim duge Iya chon, ede wu nhuge diém cia céc phuong phép phan tich glucose. 8, Trinh bay céc ky thugt phan tich thé ceton, 9. Ké tén céc ky thudt sir dung dinh Iuong HbA Ic. 50Chuong 3 CHUYEN HOA VA ROI LOAN CHUYEN HOA LIPOPROTEIN Muc TIEU Hoc TAP 1. Trinh bay doc thanh phan héa hoc va cdu trie ctia lipoprotein trong mau. 2. Trinh bay duge cde dang lipoprotein trong mdu: dae diém va vai tré sinh hoc ctia timng loai. 3. Trinh bay duoc con duéng chuyén héa ctia lipid ngogi sinh trong mau. 4, Trinh bay duge con dudng chuyén héa cita lipid ndi sinh trong mau. 5. Trinh bay duoc cdc thé réi loan lipid mdu tién phat. 1, LIPID VA LIPOPROTEIN LA. Li Lipid chinh o6 mat trong huyét tuong 1a acid béo, triglycerid, cholesterol va phospholipid. M61 s6 thanh phan khdc cia lipid c6 kha ning héa tan trong huyét tuong va cé mat véi sé rong it hon rét nhiéu nhung gitt vai trd sinh ly quan trong, bao gm cae hormon steroid, cdc vitamin tan trong md. Nhing tharh phn trén khéng tan trong nude, boi vay lipid age van chuyén trong huyét trong bang céch lién két véi protein. Albumin la chat van chuyén chinh cia cae acid béo ty do. Céc thanh phan lipid khée gin véi protein tao thanh phite hop lipoprotein dé uu théng trong mau. mau 1.2. Thanh phan va edu tric ciia lipoprotein Lipoprotein 14 nhimg phan wr hinh cau bao gém phan Idi khong phan cyc 1a triglycerid va cholesterol este héa, phan vé bao quanh a phospholipid, cholesterol va protein ~ apolipoprotein (hay apoprotein). Phin v6 dim bio tink tan ca lipoprotein trong huyét tong, van chuyén cdc lipid khéng tan. Apoprotein (apo): La thanh phin protein cha lipoprotein. Theo danh phép cla Alaupovic, apoprotein duge goi tén bing mot chit s6 cai cta bang cht c4i (A, B, C, D va E d6i_véi cde apo chink). Chtt cai nay duge thém vao sau nd mot s6 La mA (Al, All...) khi cling mdt ho apo c6 sur thay 4éi edu tric bée 1. Apo ciing 6 nhtng hinh thai dudi cdu trie nay (ALI, AL2,...) duge xée dinh béi nhting thay déi ciia sy di chuyén trén dign di, lién quan dén su thay di phan acid sialic trong phan tt apo. Céc apoprotein c6 nhiéu chite nang quan trong: 51pid phan ove fea ne (Phospholipid, cholesterol, apoproteins) Lipid khéng phan ove (triglycerd, cholesterol este) Hinh 3.1. Mé hinh cdu trac cia lipoprotein — Chite nang héa tan: nh sy c6 mat cla apo ma cée lipoprotein héa tan duge trong nude va do vay, né duge van chuyén trong mau va bach huyét. Nhu vay, apo vita, C6 chite ning cdu tric vita c6 chite nang vén chuyén, Ty Ié protein trong thanh phan céu tao cdng cao thi tinh tan trong nude cia lipoprotein cang cao. Néu tinh tan bj réi loan hoe sy van chuyén lipoprotein bi cham tré sé dan dén tinh trang i dong cée phan tir giau lipid-mét trong nhimg yéu t6 gay xo vita déng mach. — Chite nding nhan dign: cdc phan tir protein trong cdu trac cia lipoprotein cé chite ning nhfn dién céc receptor & mang té bao. Théng qua ede receptor dic higu, cae lipoprotein mang nhiing apo tong img méi cé thé vao trong té bao. Vi dy: apoB cia LDL duge cdc receptor ctta mang nhan dién dé dua LDL vao trong té bao. — Chite neing diéu héa: cée apo cé chite ning hoat héa ho&c kim him mét sé enzym chuyén héa lipoprotein, vi dy: apoAI hoat héa enzym LCAT (lecithin-cholesterol acyltransferase), apoCII hoat héa enzym lipoprotein lipase, apoCIII tre ché lipoprotein lipase. Cc apo 6 nhiéu logi va duge phan bé khdc nhau trong céc lipoprotein khéc nhau, 1.3. Phan logi cia lipoprotein Lipoprotein duge phan loai bang 2 cach: dign di hoac siéu ly tam. 1.3.1. Phan logi bang phicong phdp dign di Bang dign di, lipoprotein huyét tong duge tach thanh 4 thanh phan: — alipoprotein — lipoprotein Tién B lipoprotein ' Chylomicron. 521.3.2. Phan logi bing phuong phdp siéu ly tam Bang phuong phép nay lipoprotein huyét tuong duge phan chia dya trén ty trong cia chting theo siéu ly tm phan doan. Dd lng ciia céc logi lipoprotein khi siéu ly tam ty 16 nghich véi tr Lugng lipid. = Chylomicron (CM): 06 ty trong < 0,96, la nhiing hat m6 nhii twong héa lo limg trong huyét tuong va duge tao thinh dc nhét béi cdc té bao mang rut. Chylomicron chi cé mat trong thdi gian ngin & huyét tuong, sau bita in gidu mG va lam cho huyét tuong cé mau dye, tring nhu sita. Chylomicron bién mat sau an vai giér va boi vay, huyét tuong cua nguéi binh thuémg khi doi phai trong. Chylomicron chita cha yéu la triglycerid. Chite ning chinh cia chylomicron la van chuyén triglycerid va cholesterol ngoai sinh (tir thite an) t6i gan. ~ Lipoprotein 0§ trong rdt thdp: (very low density lipoprotein-VLDL) 6 ty trong 0.96-1.006, duge tgo thanh & té bdo gan va la dang van chuyén triglycerid ni sinh-duge ting hop & gan-véo hé tuin hodn, VLDL chita nhigu triglycerid, van chuyén hon 90% triglycerid ndi sinh. ~ Lipoprotein 0} trong thdp: (low density lipoprotein-LDL) ¢6 ty trong 1.006- 1,063, 14 san phdm thodi héa cia VLDL trong mau, LDL chtra nhiéu cholesterol. Chit nang chinh cla LDL 1a van chuyén phan lén cholesterol tir mau téi céc mé dé sit dung. LDL duge gin vio receptor dac higu & mang té bao, rdi duge dua vao trong té bao. Néng 49 LDL trong huyét tuong tir 3.38 dén 4.16 mmol/l. ~ Lipoprotein t trong trung gian: (intermediate density lipoprotein-IDL) 18 logi lipoprotein cé ty trong 6 gitta VLDL va LDL, con goi la VLDL tin du IDL 06 trong mau tudn hoan v6i sé lugng nhé nhung cé thé tich ly khi cé r4i loan bénh ly vé chuyén héa ciia lipoprotein. Bang 1 - Cac lagi lipoprotein chinh trong huyét tong nguéi Ea ‘chylomicrons VLDL 1L Bl pen . Hinh 3.2. Cac loai lipoprotein trong huyét tong ngudi = Lipoprotein 3 trong cao: (high density lipoprotein-HDL) c6 ty trong 1,063- 1,210, duge tng hop & gan, mOt phan duge téng hp 6 rudt va mgt phAn do chuyén héa ciia VLDL trong méu ngoai vi. HDLI c6 ty trong 1,063-1,085, HDL2 cé ty trong 1,085-1.120, HDL3 cé ty trong 1,120-1,210. HDL chita nhieu protein, chite nang chinh cia HDL la van chuyén nguge céc phan tir cholesterol tir cde m6 ngoai vi vé gan. Tai gan, cholesterol duge thoai héa thanh acid m§t va duge dio thai qua duémg mat. O ngudi, HDL ting dan theo tudi. Sau tuéi day thi, HDL & n®t cao hon & nam, Ham Iuong ELHDL ty 1é nghich véi trong lugng co thé, voi ham long triglycerid mau. HDL ting & ngudi tap luyén thé duc thé thao va nang hoat dng. Binh thuémg, HDL >1,17 mmol/l 6 nam va >1,43 mmol/l 6 nit. idu quan trong a cdc thanh phan cia lipoprotein ru théng 14 khéng hang dinh, ching & trang thai nang dong véi sy thay d6i lién tiép gitta cdc ndng 4 voi nhau cia nhimg thanh phan nay. Lipoprotein (a) hay Lp(a) la lipoprotein khong xép loai véi chic ning chua biét 16, Lp(a) c6 kich thuée va sé Iugng lon hon LDL nhung cé thanh phan cdu tao tuong ty LDL ngoai trir c6 thém mt phan tir apoprotein (a) trong cée phén tir apo B-100. Apo(a) gan giéng nhu plasminogen. Néng 49 Lp(a) huyét tong thay d6i gitta cdc cé thé trong Khoang 0 + 100 mg/dL. Sy tang cla Lp(a) nhu 1a yéu t6 nguy co ca bénh mach vanh. Bang 3.4. Chire nang cia céc apoprotein chii yéu ‘Apoprotein Chigc nang chinh Ad Cofactor clia leat (trong HDL) All ‘Chat hoat héa lipase cla gan Tham gia cu tric HDL B-100 Tham gia cau tric LDL va VLDL Lign két voi receptor B48 ‘Tham gia cau tric cm Ci Cofactor cla leat? cal Chat hoat héa lipoprotein lipase (LPL) Cul Uc ché sy thanh loc CM va nhGng phan tl tan du E Lign k&t v6i receptor Bang 3.2. Phan loai va ac tinh cla cdc lipoprotein Lipoprotein] Tytrong | Swéng | Dichuyén | Ngudngéc | Chirc nang chinh (aim!) kinh aign di (rm) ‘CM <0,96 500 ‘Diém = xuat | Rudt van chuyén: phat triglycerid ngoai sinh [voor 10,960-1,006 43 | Tiénbeta | Gan Van chuyén triglycerid_ngi sinh IDL 1,007-1,01¢ 27 ‘San pham| Chat tién than cia chuyén héa cia | LDL LOL LDL 1,020-1,063 22 Beta ‘San pham Van chuyén chuyén héa ciia | cholesterol VLDL (qua IDL) HOL 1,064-1,210 8 Alpha Gan, rudt van chuyén san phdm cholesterol chuyén héa cla | tro ve CM, VLDL 542. CHUYEN HOA CUA LIPOPROTEIN Chuyén héa cia lipid uu hanh da duge biét rét 15. Bao gdm 2 con dudng: chuyén héa cia lipid ngogi sinh va chuyén héa cia lipid n6i sinh. 2.1. Chuyén héa cita lipid mau ngoai sink Con dudng chuyén héa nay lién quan dén lipid thite an. Sau Khi an thite an chifa nhigu mé, CM duge téng hop & té bao rudt nhdim van chuyén triglycerid va cholesterol do thire an cung cp dén céc md khée nhau ca co thé. TE bao biéu mé cia niém mec rudt t4i ting hop triglycerid tir glycerol, acid béo va monoglycerid duce hp thu sau qué trinh tiéu héa; ddng thoi phan doan protein hoge apoprotein duge téng hop 6 té bio biéu m6 niém mac rugt. Phite hop cua lipid va protein nay tao nén CM. CM duge hap thu qua mang day, vao mach bach huyét, qua dng neve vio hé wan hoan & hgp Iuu tinh mach cdnh va tinh mach du6i don dé t6i mo m@ va co. Trong hg tuin hoan, CM dat duge céu trie 6n dinh, Mat khée, m6t phan lipid thige an vao trye tép tinh mech cita dé t6i gan, dé la ede acid béo chudi ngin (gém 10- 12 nguyén tir carbon); ching lu hanh trong mau dudi dang cdc acid béo ty do va khong tham gia thanh phin cia CM. CM bao gim gin 90% triglycerid, 5% phospholipid, 3% cholesterol, 2% protein (apoprotein chinh duge ting hop 6 té bao nigm mac rudt 1A apoA va apoB-48; apoC-II va apoE 6 néng 46 rat thép, duge van chuyén dén CM tir HDL). Trong mau tudn hoan CM cé théi gian ban hay vai phit, Qué trinh thanh loc CM ra khdi mau tuan hoan dién ra theo nhiéu giai doan. ~ Bung kinh cla CM khéng cho phép né di qua ndi:mac cla mach méu, 46 la ly do tai sao ting CM mau khéng gay via xo dong mach. Triglycerid chju téc dung ctia enzym lipoprotein lipase (LPL) c6 6 bé mat té bao ngi mac mao mach cla mé md, co xutong, co tim va tuyén vi dé giai phéng cdc acid béo tyr do vao nhing t6 chite nay; hoge duge sir dung nhu co chat sinh nang Iugng, hodc sau dé Iai duge este héa thanh triglycerid dy trit tai cdc mé nay. LPL duge hoat héa bai apoC-II. . — Boi vi triglycerid duge chuyén doi tir CM dui tae dung tia LPL nén CM tre: nén nhé hon (goi la CM tan dur). Cholesterol, phospholipid, apoA va apoC-II duge giai phéng va chuyén dén HDL; ngugc Iai cholesterol este héa duge van chuyén dén CM tan du tir HDL. Nhu vay, CM tan du 06 lugng triglycerid giém nhumg duge lim gidu cholesterol este, su thay déi nay tgo diéu kién thudn Igi cho vige gn bat phan tir tin dur vao té bio gan nhi receptor dae higu ciia apoB-48 va apoE 6 té bao nhu mé gan va CM tan dir duge thanb loc khéi mau tuan hoan. — Tai gan, phan tir tan dur durge thodi héa hoan toan tai lysosom. Cholesterol durge gidi phong; mgt phn cholesterol duge sit dung 4@ tng hop acid mat va dio thai theo durimg mat xudng ru6t non; mot phin cholesterol cing triglycerid tgo thanh VLDL eiia gan, réi vao hé tudn hoan dé bat ddu con duéng van chuyén hay chuyén héa lipid ni sinh (cbn goi 18 chuyén héa lipid 6 mach méu). 55Mot digu dang chit ¥ 1a trong giai doan hp thu, néu luong acid béo nhieu thi 6 bao niém mac rudt téng hyp CM; nhung trong giai dogn sau hap thu, t8 bao biéu mo. niém mac rudt sé tong hyp VLDL va HDL. Thanh phan VLDL nay gin giéng VLDL cia gan va chiém khong 10% tng s6 VLDL huyét tuong. ‘Té bao co” M6 mo <= SP oe Ti ee Ce q D aout we raves 5 | pupe ge ‘con duréng néi sinh Me VLDL S. Q goai vi tan dy LDL receptor (gén apo E18) Remmant receptor (gn apo E) p60 ty do Tébaoco Mme Hinh 3.3, Chuyén héa cia lipid mau ngoai sinh 2.2. Chuyén héa ca lipid mau ngi sinh Con dudng nay lién quan dén lipid chi yéu cé ngudn géc tir gan. VLDL gidu triglycerid duge tao thanh & gan (90%) va m6t phan tir rut (10%) vao méu, dén céc m6 ngoai vi va tai dé, triglycerid tiép tue bi thiy phan dudi tac dung cia LPL. Phospholipid, cholesterol ty do va apoprotein (apoC va mgt phin apoE) duge gidi phéng tir bé mat cia VLDL va chuyén dén HDL; ching tré thanh nhimg phan tir IDL. Cholesterol duge van chuyén dén HDL va duge este héa, cholesterol este héa duge van chuyén tré vé IDL. Enzym LCAT (Lecithin-Cholesterol Acyltransferase) tg0.ra 75%- 90% cholesterol este trong huyét tuong, phan cholesterol este con lai trong huyét tuong do gan hode rugt tao nén nh enzym ACAT (Acyl-Cholesterol Acyltransferase) ciia té bao gan va té bao niém mac rudt. Do vay, su thiéu hyt LCAT sé gay réi loan chuyén. héa cita lipoprotein. 56M6t phan IDL tré lai gan, gin vao receptor dic hiéu ciia LDL (goi la receptor B.E, 6 kha ning lién két v6i apoB-100 va apoE) 6 mang té bao, nhung hau hét IDL bj lay di triglycerid do tae dung cia lipase gan va chuyén thinh LDL véi thanh phin chinh la cholesterol este, apoB-100. Nhu vay, & trang thai binh thudng, chi cé mOt lugng rt nhé IDL trong huyét tuong, bai vi ching di chuyén thinh LDL. Cac LDL sé gin vao receptor dac higu & mang té bao gan ( 70% receptor cla LDL & gan) va 6 mang té bao cia cdc mé khdc. LDL sat nhép véi receptor va chju tac dung cla enzym protease dé phan hiy thanh céc acid amin, cholesterol este,... Sau 46 cholesterol este chuyén thanh cholesterol ty do, Cholesterol ty do c6 3 tae dung co ban la: (1) Gidm hoat tinh cia HMG-CoA reductase (hydroxyl-methyl-glutaryl-CoA), tre ché sy téng hyp cholesterol trong té bao; (2) Hoat héa enzym ACAT dé chuyén cholesterol tyr do thanh cholesterol este va cing voi cae yéu té khéc, gitp sy tao thanh cholesterol este cia mang va trong té bao; (3) Lam giam sé lugng receptor cla LDL & mang té bao qua con dudng feedback 4m tinh. ‘Voi nhimg téc dung trén, qua trinh diéu héa gitta su tong hop cholesterol tir cdc acetyl- CoA trong té bao va sy xuyén thdm (dm thyc) cia LDL vao trong té bao duge xac lap. Binh thudng, LDL duge phan hiy trong té bao nhd cdc receptor ciia né & mang té bao. Khi c6 sw sai sét vé chat Iugng cia receptor LDL (khi an ché 46 qua nhiéu cholesterol va lipid bo héa) hod sw sai sét vé sé Iugng cua receptor LDL (khi bj bénh tang cholesterol méu gia dinh typ If), cc LDL sé tdn tai lau trong huyét tuong, thi gian ban huy cia chiing kéo dai, chting bi bién déi (bj oxy héa, bi acetyl héa hoac bj glycosyl héa...) vi duge nhan biét boi mét loai receptor dac higu & dai thue bio. Tom lai, LDL gitt vai trd chinh trong sy van chuyén cholesterol dén té bao gan va té bao md. ngoai vi Bai nude CChotestert ects mat (chylomicron Cchyomiceon Yan do Cholesterol Upeprten ‘thie an Rugtnon | ——> Con dung ngos Tandy -Crovatoret Con dung ngi sinh saci mat 0% ine ors a ere © recor 10k apo wor an eee 5 LoL bién a’: BQ inn Hinh 3.4. Chuyén héa lipid mau ndi sinh va sy tao thanh LDL huyét tongVige ldy di LDL bbi dai thye bao trong thanh déng mach la sy kién quan trong cia qué trinh bénh ly vita xo déng mach. Dai thyte bio bi tr dong cholesterol este sé tre thanh “té bao bot” - mét thanh phn dn dén vita xo dong mach. 6 tré so sinh, ndng 46 LDL huyét tuong thip hon nhiéu so véi ngudi trréng thanh. Néng 46 LDL ting trong thoi ky nién thiéu va dat tdi da sau day thi. HDL duge tng hgp ban dau 6 gan va véi sé Ingng it hon 6 té bao rudt non (HDL. méi sinh) bao gdm phospholipid, cholesterol, apoB, va apoA. HDL méi sinh cé hinh dia, Trong mau toan phan, HDL duge lam giau thém apoC va apoA-I tit céc lipoprotein khée va tir cde t8 chtte ngoai gan. Cholesterol duge este héa boi LCAT trong HDL méi sinh, Cholesterol este xm nhap vao bén trong HDL va ede HDL hic nay tre nén 06 edu tric hinh cu, bao gdm mét nhn giau cholesterol este va mOt lop vo chita phospholipid 6 cye va cdc apoprotein; mat khc, apoE duge chuyén dén VLDL, hinh thanh HDL3 1bi dén HDL2. Cholesterol este duge van chuyén tir HDL3 dén cde phan tir tan du (CM tan du va IDL) song song véi viée nh§n thém triglycerid. Sau dé, cholesterol este trong CM tan du va IDL dug té bao gan ldy di va bai tiét theo mat sau khi chuyén héa thanh acid mat. HDL méi sinh tinh dia 7a) Fe. Mé ngoal vi <= {a thy bao Ccrytomicron ‘an dy Chylomicron —_ fp) —| vubLtandy LoL holesterol tr do CE = Cholesterol ester © 11 receptor (gin epo EB) Remnant receptor (gin apo E) © HDL receptor {nhén biét apo A) LCAT= lectia-chlesterol acyltransferase Hinh 3.8. Con dudng van chuyén cholsterol "tro va" HDL2 giau triglycerid duge chuyén tre Iai thinh HDL3 bing céch phan hy triglycerid béi_enzym lipase gan va mét s6 HDL2 duge loai khdi h@ tuan hoan, gin bait vio gan boi receptor dic higu cla apoA-I. 58HDL cé 2 vai tro thiét yéu: ay La nguon cung cap apoprotein cho CM va VLDL; (2) Van chuyén cholesterol “tra vé", léy cholesterol tir cée té bio Ido hoa vi cdc lipoprotein khée, van chuyén ching dén céc phin tir tan du, rdi duge gén bat tai gan dé ‘bai tiét theo mat. Tém Igi, nhitng dic tinh co ban cia chuyén héa lipoprotein la: ~ Triglycerid thite an duge van_chuyén trong CM dén cfc mo. Tai ede mé, triglycerid c6 thé duge sit dung nhu nguén cung cp ning long hoge dy tri. __ = Triglycerid ni sinh duge téng hop & gan, ri duge van chuyén trong VLDL én céc mé nhw nguén sinh nang Luong hoge dy tri. — Cholesterol do gan ting hop (ndi sinh) duge van chuyén dén cde mé trong LDL -san phdm thoai héa cla VLDL. Cholesterol tir thie an (ngoai sinh) duge dua dén gan trong CM tan du. ~ HDL liy cholesterol tr t8 bao ngoai vi va tir eée lipoprotein khée, rdi durge este hda béi LCAT. Cholesterol este duge van chuyén dén cée phan tir tin dur va roi duge dura én gan. Tai gan, cholesterol duge bai tiét theo mat sau khi chuyén héa thanh acid mat. — Tinh chat va chite nang ca céc lipoprotein duge quyét dinh béi céc protein ciia ching - 46 1 nhiing apoprotein tham gia trong cu tric ciia cc lipoprotein, chting c6 vai trd van chuyén lipid trong mau va 06 thé la ligand d4i véi receptor ca mét s6 lipoprotein hhoje la cofactor ctia mt s6 enzym thiy phan lipid (LPL). Céc receptor 6 bé mat té bio cing déng gép vai trd quan trong trong chuyén héa lipoprotein huyét tuong. 3. ROI LOAN LIPID MAU 3.1. Céc yéu t6 anh huong dén mau Khi méi sinh, ndng 49 cholesterol huyét tuong rat th4p (cholesterol toan phan < 2,6 mmol/L, LDL-cholesterol <1,0 mmoV/L). Nam dau tién cia cuge dai c6 mét dinh ting cia cholesterol huyét tong, nhung trong thoi ky nién thiéu cholesterol huyét tuong khéng vugt qué 4,1 mmol/L. Tai nhiing nude c6 ddi séng sung tic, nong 46 cholesterol trong quin thé din cu tang sém trong giai doan dau cua tudi thanh nién. Nong 46 cholesterol huyét tong ting 1a yéu t6 nguy co chinh cia bénh mach van. Méi Jign quan gitta ndng dé cholesterol va ty 1é tit vong do bénh mach vanh la duémg cong di én, ty 1é tir vong ting gap déi khi néng d6 cholesterol 1a 5,2 + 6,5 mmol/L va ting gap 4 lan khi ndng dé cholesterol trong khoang 5,2 + 7,8 mmol/L, néu néng dé cholesterol < 5,2 mmol/L thi duéng cong cia ty Ié tir vong sé rat thdp tuy khong bing phing. Véi nhiing cé thé cé thém céc yéu t6 nguy co khac nhu hut thuéc, duéng cong cua ty 1é tir vong déc hon. Sy lién quan gitta ndng 46 cholesterol huyét tuong (dic biét 14 LDL-cholesterol) va nguy co cao ciia bénh mach vanh 1a chic chan; trdi lai, c6 sy tn tai mdi lién quan nghich dao gitta HDL-cholesterol va nguy co bénh mach vanh. Nhiéu yéu t6 anh huéng dén ham lugng cia HDL va LDL-cholesterol trong huyét tong. 59TY'6 nguy co enh mach vanh 26 39 62 65 78 Cholesterol huyét trong (gral) Hinh 3.6. Méi lién quan gitra benh mach vanh va cholesterol huyét tong Sy tang triglycerid mau ciing la yéu t6 nguy co cia bénh mach vanh (gap nhiéu 6 nf gidi hon & nam gigi), mac di it quan trong hon, Sy tng triglycerid mau ty thude vao nhiing phan tir LDL giau triglycerid o6 mat d6 day dc va nh (LDL-III). LDL nay lign quan mAt thiét dén dai théo dung typ 2 va c6 ¥ nghia dic bigt vi nhimg phan ti nay xudt hién nhiéu & mang vita xo dong mach hon céc typ LDL khéc. Néng 46 triglycerid huyét twong >10 mmol/L din dén nguy co gay viém tuy. Triglycerid va HDL-cholesterol, cholesterol toan phan trong huyét tuong 6 thé do Iuong dé dang & céc phing xét nghiém. LDL-cholesterol c6 thé dugc tinh toan theo céng thitc sau day: LDL-Chol. (mmol/L) = Chol.toan phin-(HDL-Chol. + Triglycerid/2,2). Céng thite trén khéng cé gid tri néu triglycerid vugt qua 4,5 mmol/1 Bang 3.3. Cac yéu t6 anh hudng trén lipoprotein huyét tvong Cac you t6 HDL-Chol LDL-Chol Triglycerid Gidi tinh Nam > ni NO= nam No < nam Tudi Tang nhe & nov Tang Tang Tha duc Tang Giam iam C6 thei Giam - Tang Noghign requ Tang - Tang Estrogen ndi sinh Tang iam Tang 3.2. Réi loan lipid mau Khi cé r6i loan vé lipid mau thi cdc thanh phan lipoprotein huyét tuong cling thay di, Tang lipid mau thuémg do ting cholesterol vayhoge tang glycerid trong céc loai lipoprotein. CAc réi loan lipoprotein cé thé do di truyén hoac do ché 46 an khéng hgp ly. 60‘Tang lipid méu va réi loan céc thanh phan lipoprotein huyét tuong 6 thé la thit phat do cdc qué trinh bénh 1y dan dén nhw hoi chimg than hu, suy than, dai thdo duéng, viém tuy, goutte ode do diéu tr] voi m6t s6 thudc kéo dai. 3.2.1, Réi logn lipid mau thit phat Bénh iy Réi loan lipid Réi loan lipoprotein ‘ai thao duong Te VLDL, HDL (Chylomicron) Hi ching than hu Chol. (TS) LDL, (VLDL) Tang ure mau 1 VLDL, HDL Suy giép trang Chol. (6) LDL, (VLDL) Benh gan tac nghén Chol Lpx Nghién gu To VLDL, (Chylomicron) Dung thuéc tranh thai Te VLDL, HDL Thudc tre ché beta -giao cam | TS VLDL, HDL, Isotreinion (13-cis-nicotinic acid) Ts VLDL, (Chylomicron), HDL LpX = lipoprotein giau cholesterol bat thug 3.2.2, R6i logn lipid mau tién phat Theo Fredrickson (1965) cdc bién adi lipid mau va thinh phan cita né duge chia thanh 5 typ trong d6 typ II chia thanh typ Hla va IIb . Phan loai réi toan lipid va lipoprotein mau theo Fredrickson Typ 1 Na tb m Vv v Cholesterol t tt tt t BT f Triglycerid ttt BT ae tt tt ttt Lipoprotein yom | qTlDL TLOL tL | qvoL | qvLDL 1VLOL +cM Tang trighycerid mdu ngng typ Iva typ V Triglycerid mau c6 thé >11mmol/L (bink thung <2,3 mmol/L), HDL thip, c6 thé thdy vang nhdi - d6 1a ede u nh nhé (kich thud tinh bing mm), mau vang bo, thudng thay 6 phan cao cia than minh va trir 6 mat. Thé dién hinh c6 kém gan Va léch to, be nhin, nhiém mé. Bién chimg ning la viém tuy cdp tinh. Trong thé nay, huyét thanh tring duc nhu stta, néu dé yén mét éng huyét thanh & 4°C trong 24 gid sé thdy mét lop kem néi 6 phan trén cia éng, tuong img véi lp CM. 61‘Tang triglycerid méu typ I rét nhay cam véi mé ngoai sinh, bénh di truyén lan trén nhiém sic thé thuéng; do réi loan hoat tinh cua lipoprotein lipase, ho&c réi loan enzym, hode réi loan chat hoat héa sinh hoc cua enzym-apoC Il, dn dén hau qua la cham qué trinh thodi héa cla CM va gay tich ly CM, hoac cé thé do gan gan bat true tiép cdc VLDL. Can lu ¥ ring cé mét thé tang CM mau hiém gap do tin tai mét chat te ché lipoprotein lipase lu harh trong méu. Phan biét typ I va typ V: trong typ I, cholesterol binh thutng hodc thdp; trong typ V, cholesterol tng cao do sur c6 mat cée VLDL chtta cholesterol. ‘Typ V tién phat rat hiém gap, typ V thir phat hay gap trong con tang lipid mau cia typ IV (gay ra do rugu, didu trj corticoid, dai thao duéng nang,...). Tang cholesterol don thudn typ Ha ‘Tang cholesterol don thudn typ Ha cé 2 thé: thé da gen va thé di truyén tri nhiém se thong. Thé da gen: do khuyét tit cha receptor LDL; ¢é 2 hin thai ddng hop tir va di hop tit, v6i cdc kigu lang dong cholesterol: vong cung mau tring quanh gide mac, ban vang & phia géc trong ca mi irén ho&e mi duéi, u vang gén Achille va gan co dudi cée ngén tay, u vang phdng duéi da dac higu cho thé tng cholesterol mau déng hop tir. Tan suit ciia thé dj hgp tir 1a 1/500 tré so sinh, tin sudt cia thé dérig hop tir 1a 1/1000.000 tré so” sinh. Véi thé déng hop tir, sing sét sau 20 tudi la trudng hop ngogi 1é néu khong durge didu tri, mang vita xo rat lon & géc dong mach ché gay hep dong mach chi va phai diéu tri ngoai khoa, mang vita xo nay lan téa dén 16 déng mach vanh va diéu nay giai thich ring: trong phan Ién céc truéng hop, biéu hién dau tién 1a chét d6t ngét. Hinh thai thé dj hop ti c6 tién Iugng tdt hon, ede tai bién mach mau xudt hign sau 30 tudi, néu khong duge didu trj thi 50% sé bénh nhén sé chét vi bénh tim thiéu mau cuc bd trude 60 tudi. Néng dé cholesterol mau thudng gap trong thé dj hyp ti la 10,4mmol/L va trong thé ding hop tr la 15,6-36,4 mmol/L (binh thudng la 3,9-5,2 mmol/L), triglycerid va HDL 6 gidi han binh thudng (HDL-C >0,9mmol/L). Cholesterol mau ting do LDL ting (binh thudng LDL <4,0mmol/L). Naw vay, apoA-I binh thuong nhung apoB-100 ting nhidu song song véi sy ting LDL-C. Nguyén nhfn ciia bénh 1a do dt bién gen ma héa receptor cia LDL nam trén nhiém sic thé sé 19. Hign nay, nguéi ta da nhan biét duge hon 150 dét bién gen, trong 46 c6 71 d6t bién gen di duoc nhan biét & mite phan tir. Ngudi binh thudng co 100% receptor cia LDL & mang (4 bao (70% receptor c6 & mang té bao gan), ngudi bj bénh thé dj hgp tir c6 50% receptor LDL (ngudsi bénh nay nhgn tir cha hose me mot gen bénh ly ma héa receptor LDL), ngudi bj bénh thé ding hop tir khong 6 receptor LDL (ngudi bénh nay nhin hai gen bénh ly ma héa receptor LDL tir cha va me). Thé gia dinh di truyén tr6i nhiém scc thé binh thiedng: thé nay do d6t bién apoB- 100. ApoB-100 ld mét chudi polypeptid gdm 4536 acid amin, duge ma héa boi mot gen 62nam trén nhiém sac thé s6 2. Sy dét bién nay & vi tri 3500, gay su giam gin bat LDL vao té bao voi sy tang cholesterol vira phai va ting LDL, bénh dng mach vanh xudt hign sém. Tan sudt ciia bénh Iy nay gan bang tin sudt cita chimg tang cholesterol mau do khuyét tat cila receptor LDL. Tang lipid méu typ Hb La thé tang lipid mau hén hop, ting glycerid va ting cholesterol mau, c6 ling dong & vong xung quanh giée mac va ban ving. Tang lipid mau typ IIb thuong kém theo r6i loan chuyén héa glucid, ting acid uric méu, tang huyét 4p. Thé nay 14 di san kép ciia 2 thé réi loan lipid mau typ Ila va typ IV, ngudi bénh c6 cha hode me bi bénh tang cholesterol don thuan typ Ila va tang triglycerid don thudn. Céc réi loan vé lipoprotein huyét tuong rat thay déi, huyét thanh khi d6i thi dye véi ting cholesterol, tng LDL, ting apoB-100, ting triglycecid ctia VLDL, giam HDL va gidm apoA-I. Tang lipid mau typ II Thé bénh ly nay hiém gap (1/10.000 ngudsi), bénh thuong duge phat hién sau tudi 20, nhimg thé & tré em thi rat nang. Ngudi bénh cé huyét thanh duc, cholesterol toan phan ting, triglycerid mau tang va tang IDL-diém nay dic trung cho typ II. Sinh bénk hoc: dudi tac dung cia enzym LPL, cde VLDL bj rit dan triglycerid va bién déi thanh IDL, cic IDL gin voi receptor ctia apoE va apoB trén mang té bao gan, sau 46 enzym lipase gan dua IDL tré lai hé tudn hoan duéi hinh thai LDL, cée LDL duéi dang LDL nay sé gin vao receptor tia apoE va apoB trén mang té bao ngoai bién. ‘Nhu vay, apoE cé vai trd trong sy thoi héa IDL. ApoE la polypeptid gdm 299 acid amin va tin tai duéi 3 dang apoE-II, apoE-IIl, apoE-IV véi sy khée nhau béi acid amin & vj tri 112 va 158, cdc déng phn nay duge xdc dinh trén 3 allen ¢ cing mét vj tri tai nhiém sdc thé. Acid amin ApoE ApoE-Ii ApoE-V 86112 Cystein Cystein Arginin 86158 Cystein Arginin Arginin ApoE cé 6 phenotyp & ngudi, trong 46 3 phenotyp déng hop tir (E-II & E-Il, E-Il & Ell, ELV & E-IV) va 3 phenotyp dj hop tir (B-I & E-lI, E-Il & E-IV, E-IIl & E-IV). Ai luc ciia cde déng phan apoE véi receptor apoB va apoE & mang té bao la khéc nhau, ai luc ciia apoE-III va apoE-IV la binh thug, 4i lye cla apoE-II la thdp. Nhiing ngudi mac chimg ting lipid mau typ Ill thi luén c6 m6t kiéu hinh E-IVE-Il, do vay swt thodi héa cia IDL cham, kiéu hinh E-IVE-II khong du gay ting lipid mau (1% dan sé 6 kiéu hinh nay va phn 1én nhtng cé thé nay lipid mau khong ting). Kiéu hinh nay gy bénh ly khi cé kém theo sy tang ting hgp apoB-cé thé do bat thuéng khdc vé gen hodc ¢6 thé do béo phi hodc do ché d6 an ubng khong hop ly. 63Tang triglycerid méu typ IV ‘Thé nay thudng khSng cé trigu chimg lam sang, duge phat hién trong didu tra vé di truyén, Sy tang triglycerid mau typ IV nhay cm véi nugu, cdc logi glucid, cde chat béo va tinh trang béo phi, Triglycerid mau >11,0-16,Smmol/L, cholesterol mau thudng binh thuong hode tang (cholesterol nay trong thinh phan cia VLDL), mite tang cia cholesterol luén thdp hon ro rét so véi mite ting triglycerid mau, HDL thdp tuong img v6i mite ting triglycerid méu. Khée véi ting lipid mau typ Ib, ting triglycerid mu n6i sinh typ TV cé dc tinh sinh vita xo yéu. Diéu nay durge giai thich rang: o6 sy phdi hop cia triglycerid mau ting cao v6i HDL thap (huéng sinh vita xo) va LDL thép (huéng bao vé chéng vita xo). Tang lipid méu typ IV c6 thé la bénh di truyén don gen tri (khodng 10% sb bénh nhn) hodc thiéu gen. V8 bénh sinh, ngudi ta cho rang cé sy phéi hop cia 2 co ché chinh; (1) sy ting sin xudt VLDL, nguyén nhan c6 thé do khang insulin ¢ ngoai bién va cudng insulin (6 ngudi béo phi), cng insulin gy phan hiy lipid & ngoai bién va acid béo dé din vé gan, cudng insulin lam cho gan ting hop acid béo tir glucose, ting ting hop triglycerid va tang VLDL; (2) viée ding qué nhiéu rugu, sy thodi héa rugu 6 gan lam gidm ty 1g NAD*/NADH, giam thodi héa acid béo va ting tng hop triglycerid va VLDL, sit gidm thodi héa acid béo thudng di kém theo tn thuong hogt tinh cla LPL. Trong thé bénh nay, ngudi ta da hiéu 16 vai trd cia cdc yéu t6 méi trudng nhung vai trd cha gen van chua duge sang to. 3.2.3, Cée r6i logn lipid mau khée Téng alpha-lipoprotein huyét twong Nhidu nghién ctru cho thy ring: tang HDL huyét tuong c6 téc dung bao vé chéng lai qué trinh gay vita xo trong céc bénh tim mach. Trong thu t, mot s6 trudng hop 6 HDL huyét twong ting cao nhung van di kem vita xo dong mach. Neguyén nhén c6 thé do tae nghén qué trinh thodi hoa cla HDL, gay ting HDL ¢ trong huyét twong, vi dy nhur khi c6 bénh ly cta enzym lipase gan; tang HDL bénb nban suy gidp nhumg khOng han ché duge sy phat trién cua cdc tén thuong vita xo. Hg alpha-tipoprotein huyét ueong Bénh Tangier ld m§t bénh hiém gp, di truyén theo kiéu ding gen tri. Cac bénh han dng hgp ti c6 triglycerid mau ting vita phai nhumg thiéu hyt trim trong HDL. Cac bénh nhan dj hgp cé néag 46 HDL va apoA-I ha thap khong 50% so voi gid tri binh thuémg. Bénh ly nay do ting manh qué trinh thodi héa cia HDL va apoA-I, khong bat thurng vé cau tric ca apoA-L.CAU HOI ON TAP ea Bw Dinh nghia, thanh phan va cdu tric cita lipoprotein huyét tuong. Trinh bay danh phap va céc chite nang ciia apolipoprotein. Trinh bay phan loai lipoprotein huyét tuong. Néu die diém sinh hoc va ‘hing chire nang chinh cia timg loai lipoprotein huyét tuong. Trinh bay con dung chuyén héa lipid ngoai sinh trong mau. ‘Trinh bay con dudng chuyén héa lipid mau ngi sinh trong mau. ‘Trinh bay ¥6i loan lipid mau tién phat typ I va V. ‘Trinh bay réi loan lipid mau tién phat typ Ha va typ IIb. Trinh bay réi loan lipid mau tién phat typ III va typ IV. 65Chuong 4 ACID AMIN, PEPTID VA PROTEIN HUYET THANH MYC TIEU HOC TAP 1. Nim duege chuyén héa, ting dung lam sing va cde phuong phap dinh luong acid amin. 2. Néim deve tinh chdt ea ba eta peptid, protein va ing dung eta ching 3. Néim duge thanh phén protein huyét thanh, chite néing vat mot s6 thay déi bénh If va cdc xét nghiém chén dodn. Acid amin, peptid va protein déng vai tro cue ky quan trong trong mgi qua trinh sinh hoc. Acid amin 1a don vj edu tric co ban ciia céc phan tir protein. Nhiéu dt bién gen lam thay déi trinh tw protein, qua d6 lim thay déi t6c 49 sinh tong hop, bai tiét ho&c chuyén héa protein citing hw chite nang cia chiing. Cé nhiéu bénh ly di truyén gay ra sur roi loan chuyén héa acid amin. Con ngudi cé khodng trén 50,000 loai protein khéc nhau va sé protein trong mot té bao khodng 3000 dén 5000. Chi trong huyét thanh cing c6 Khong 1400 protein da duge xée dinh. Mét s6 protein chi xuat hién va liu théng & timg giai dogn phat trién ‘sat dinh cia cé thé hog chi trong tinh trang sinh ly hoge bénh ly nao 46. Nhiéu protein. 18 protein céu tric cia té bao hog Ia thanh phin ca t6 chire lién két. Céc protein nay chi ting cao khi.cée, té bao bi tach Khdi md, noi ching cu tri. Mét s6:protein khéc tén tai 6 dang héa tan 6 trong té bao hog dich ngoai bao. Mat s6 protein hda tan 6 trong té ‘bdo thodi ra dich ngoai bao khi cdc té bao bj ton thong. Mét s6 protein cé thé thoat vao trong mau, hog ra ngoti nude tiéu & mic 06 thé phat hign duge. $6 lung cée protein ign hon sé lygng gen ma héa ching rat nhiéu do qué trinh biér ddi sau phién ma. Sy bién d6i sau phién ma c6 thé lim cho cée phan tir protein hode cé chire naiig chuyén bigt, Hoge sé bi thodi héa, Cac phan tir protein khéng chi da dang vé s6 Iugng ma con Kine bigt vé ndng 8, sy phdn bb, che nang, thinh phan cing nhur edu tric trong nhimg diéu kign sinh ly binh thing hodc tinh trang bénh ly. 1, ACID AMIN Acid amin 1a don vj cdu tric eo ban cia protein. Vige xée dinh ndng d6 cae acid amin nay trong céc dich sinh hoc 1a muec tiéu ctia cdc nghién ctu co ban nhim phye vy chan dodn xéc dinh céc tinh trang bénh ly cing nhu bénh ly di trayén. 1.1, Chuyén héa G trang thai khée manh, ngudn cung cp cdc acid amin cho qué trinh sinh tong hop protein trong co thé la tir thife &n, Mac di da s6 céc acid amin cé thé duge tong hop in vivo, 8 dén 10 trong s6 22 cde acid amin thudng gap khéng thé duge tng hop & dong vat c6 vi. Do vay cée acid amin nay duge coi 18 acid amin can thiét duge cung cap 66thong qua ché do an dé duy tri stte Khioe va phat trién, G hg tiéu héa, ede enzym thity phan protein thanh céc acid amin sau dé duge hap thu vao mau. Gan va mét s6 co quan khdc sit dung ngudn acid amin dé téng hop thinh protein cia huyét tong va protein ngi bao. Gan va thin cling déng vai trd. chuyén héa acid amin bing phan ing chuyén amin ya Khir amin, Khic amin tgo ra NH," va chat nay nhanh chéng duge str dung dé sinh tong hop ure dé bai tiét ra ngoai nude tiéu,-Acid amin trong mau duge loc qua ming cdu than song binh thuéng lai duge téi hap thu 6 éng thin nho hé thing van chuyén bio héa (saturate transport systems). Chinh vi vay, ndng 49 acid amin cao trong mau sé din dén viéc dao thai ra ngoai nuéc tiéu (aminoaciduria). Trong nhing truéng hgp binh thuéng, acid amin nigu xudt hién khi lugng protein dua vao co thé vugt qua nhu cau. Co ché téi hap thu acid amin & éng thén chua duge hiéu 6 hoan toan mie, di day 1a cor ché van chuyén tich cue phu thude vao ede chat van chuyén & mang va ndng 6 Na’. Cé 4 hé thong van chuyén khéc nhau d& duge xéc dinh cho 4 nhém acid amin: nhom acid amin trung tinh, nhém acid amin kiém, nhém prolin, hydroxyprolin, glycin va nhém acid amin dicarboxylic. M@t so acid amin e6 thé duge van chuyén bang 2 hg thong song thudmg bao gid cing c6 hé 6 tinh dc hiéu cao hon va hé cé tinh dac hiéu thip hon. M6t s6 acid amin nhu cystathionin va homocystein khéng duge tai hap thu mot céch higu qua 6 dng than do vay chti yéu 1a bj dao thai sau khi duge loc & cu than. Co ché téi hip thu & dng thén duge hiéu 16 théng qua cic nghién ciru vé hgi chimg acid amin nigu. Cé 3 nguyén nhan géy ra hoi chimg nay: (1) acid amin nigu xuat hign khi ndng 49 cic acid amin huyét thanh qué nguong thén (qué khé ning tai hap thu ciia dng than); (2) acid amin nigu xudt hign Khi néng d6 acid amin & huyét thanh binh thudmg song hé théng van chuyén c6 tn thuong hoge [a bam sinh ho§e li mac phai; (3) hi chimg acid amin nigu do khéng c6 nguéng than. Bénh gay ra do thn thuong di truyén, ning d@ acid amin trong mau binh thug va tat ca cdc acid amin déu in & ngoai mide tiéu. Vi du cho trudmg hop nay 14 hoi chimg homoeystein nigu: cde acid amin xuat hign ngoai nude tiéu khéng phai do céc tn thuong bam sinh hay mic phai ma do sy bio hda cae acid amin & dng than gay qué kha nang tai hap thu cla ng than. Néng d6 acid amin cao trong nhimg ngay dau tién ciia cuge adi, dic biét 1a 6 tre so sinh non. Tuy nhién, néng 46 acid amin lai thdp & nhimg tré e6 cn nang thdp do dinh duéng kh6ng dui khi cdn 6 trong tir cung ngudi me. Ning d9 acid amin & ngudi me thép trong mira du cia thai ky. O ngudi truéng thanh, ndng 46 homocytein lién quan dén nguy co bénh ly tim mach. Néng d6 acid amin trong huyét thanh thay d6i khoang 30% trong ngiy. Do vay mau xét nghiém cin ldy vio mét thdi diém cy thé trong moi ngay. Gid trj acid amin huyét thanh cao nhit vao budi trua va thdp nhat va sang sém. Sy bién déi nay 06 gid tri khi phan tich dé xéc dinh cdc bénh ly di loan chuyén héa thé di hop tu. Trong nude tiéu ngudi trudng thanh, phan doan glycin 1a chit yéu, va sau dé 1a alanin, serin, glutamin va histidin, con I-methylhistidin thi chiém mét luong nhé hon. 0 mt s6 miu nude tiéu binh thudng, taurin lai chiém phan chi yéu con trong mot s6 trudng hgp khac thi acid B-aminoisobutyric Iai la chit yeu. 67Trong dich nao thy (CSF) néng 46 da s6 cde acid amin thép hon so véi huyét thanh mie di téc 46 vin chuyén acid amin vao trong hé thn kinh trung wong cao. TY 18 mi acid amin gitta huyét thanh va dich nao tiy khéc nhau do ching c6 hé thong van chuyén khée nhau, Cée té bao 6 ndng 9 acid amin cao gdp 10 lan so véi huyét thanh. Co ché dé duy ti nong 46 khéc biét nay hign chua duge biét ro song cé 1é né lién quan én vai trd cla hé théng enzym dic higu cha mang t& bao. * 1.2. Ung dyng Him sang HOi chimg acid amin nigu c6 thé la tién phat hoge thir phat. Bénh tién phat l& do t6n thuong hé di truyén va duge goi la hdi chimg réi loan chuyén héa bam sinh, Céc sai sét nay c6 thé tai mt vi tri nao dé ciia con dudng chuyén h6a acid amin ode & chd nao 46 cia hé théng t4i hdp thu & éng than. Hi chimg acid amin nigu thir phat c6 thé do bénb ly tai céc co quan nhw gan, noi dién ra qué trinh chuyén héa acid amin hod cé thé tai than, noi xay ra qué trinh tdi hép thu acid amin 6 cdc dng than, hoaic cting 6 thé do tinh trang suy dinh dudng, 1.3, Phan tich acid amin Cé nhiéu quy trinh xdc dinh acid amin trong céc mau sinh hhge. C6 thé chia thanh 3 nhom cae xét nghiém phan tich acid amin dya vao muc dich chan doan tinh trang r6i wan acid amin bénh ly: — Xét nghigm sang ioe: séc ky lop méng (TLC), test 1én mau nude tidu, test vi sinh Guthrie, Xét nghiém dinh hong dé theo doi higu qua diéu tri hoge dé chan doan xae dinh: sie ky long higu nang cao (HPLC), sac ky trao déi ion. Véi mot s6 acid amin, 06 thé ap dung ky thuat xét nghiém dinh Iuong theo nguyén tic héa hoe. — Xét nghiém dinh danh cdc acid amin hodc chat chuyén héa. 2. PEPTID VA PROTEIN Lién két peptid duge hinh thanh siita nhém a-amin cia acid amin nay véi nhém a-carboxyl eia acid amin bén canh. Chudi peotid ngén goi lA tripeptid, tetrapeptid hogc pentapeptid,...Glutathion 14 mot vi dy déi véi tripeptid gdm glutamin (Glu), cystein (Cys) va glycin (Gly). Hormon oxytocin va vasopressin déu 14 nonapeptid. Chudi peptid €6 5 acid amin duge goi la oligopeptid, va chudi dai hon (6-30 acid amin) thi duge goi 1a polypeptid. Khi sé acid amin qua 40 (MW khoang 000 Da) thi dugc goi la protein. ‘Cum tir proteose va pepton li nhing san phim thiy phin cia protein va gdm cée polypeptid én va céc protein nay khdc véi cdc protein thye su la ching khong bi ta béi nhigt 6. Nhigu logi peptid duge tgo ra trong qué trinh thiy phan protein & dung tiéu héa hodc trong phong thi nghigm. 68Protein c6 4 bic cdu tréc: edu trie bac 1, bac 2, bac 3 va edu tre bie 4. KY thuat nhiéu xa tia X la ky thuat dau tién duge sir dung d8 xac dinh céc bac cdu trite cia protein. Gan day, nhiéu céc ky thuat IY hoe, hoa hoe va sinh hoe da duge sir dung dé xay dung co sé dt ligu vé cau trie protein. Cac ky thudt genomic va proteomic chic chiin sé déng gp vai trd quan trong trong viée xéc dinh sé long cdc chudi protein, Mét sé protein c6 cde thanh phin phi protein (prosthetic group) trong céu tric phan tl, Céc protein nay thuéng duge goi 1a protein gin két (conjugated protein) va duge phan logi theo dic tinh cla nhém phi protein nhu: metalloprotein, glycoprotein, hoe mucoptotein, phosphoprotein,...Ca glycoprotein va mucoprotein déu lién két véi gc phi protein la carbohydrat song ty Ié phan tram cia carbohydrat khéc nhau: 15% di v6i glycoprotein va 15%-75% di v6i mucoprotein, Nhiéu protein 6 chita cdc chat gin két (ligand) c6 chite nang van chuyén nhu lipid, hormon, ion kim logi,...Céc protein gin két khi loai bo phan gin két thi duge goi la apoprotein (vi dy lipoprotein khi loai bo lipid thi duge goi 1d apolipoprotein va ceruloplasmin khi khong cé ddng thi goi 1a apoceruloplasmin). Hau hét cdc protein img dyng trong linh vye héa lam sang dau 1a cdc protein chu nhu hemoglobin, enzym va cae protein huyét thanh (trir fibrinogen). Céc protein hinh cu toan ven c6 rat it hod khéng cé khong khong gian danh cho cdc phan tir nuée 6 bén trong cdu trac phn tir ma chi yéu chi cé cdc géc R kj nude. Mat khéo, da s6 cdc goc R phan cyc nim & bé mat cia phén tr protein, noi xay ra cde hoat déng chite nang ctia phan tir protein nay cing nhu quyét dinh tinh chat ly héa cia ching (46 héa tan, tinh acid hoac kiém), Da sé cdc protein cau déu kém bén vig va duy tri hoat tinh sinh hgc cla minh trong m6t gidi han hep vé nhiét 46 cing nhu pH, 6 diéu kign ma cdu tric phan tir cha ching bén nt. Chi cin & Khoang nhiét 46 65-70°C trong thoi gian ngin hoge & pH bat Joi thi cde protein nay sé bj bién tinh, két tha va mét host tinh sinh hoe. Cée protein bj bin tinh mat cau mic bic 4 trong khi edu tric bac 1 vin durge duy tri. G trang théi bién tinh nh (thay d6i pH hoge e6 mat mot s6 chat nhur ure thi da s6 ede protein tro nén kém bén vig song hoat tinh sinh hoc c6 thé duge phyc hdi néu ching da dua vé diéu kign kh6ng bién tinh ban du. Nhiéu dae tinh cla protein duge tmg dung trong cdc ky thudt phan tich, dinh danh, xéc dinh dc tinh sinh hoc nhu: — Kich thuce phan tir: img dung trong cdc ky thuat tham tich, siéu loc bing mang v6i kich thuée céc I6 loc khéc nhau, sic ky loc gel hode siéu ly tém phan tich theo ti trong. ~ Kha nang hda tan: phu thuge vao pH, lye ion, nhiét 46 va hing sé dién méi cia dung méi. Céc dc tinh nay duge img dung 4é phan tach cdc protein trong mét hén hop. ~ Dién tich: pH anh hudng dén dign tich bé mat cla phan tir protein, Tinh chat nay duge tmg dung cho céc ky thudt dign di phan téch hode dign di 6 diém ding dién hay sic ki trao dai ion. 69Bang 4.1. Dc diém cia cdc protein huyét thanh Vang [Protein Thei | pl Mw | Ky thuat phan tich | Choe ning aign gian ban (daltons) di hay Protein gn | 12 gid. 21.000 | IN, IT, RID van chuyén retinol (RBP) retinol, tao phic voi TTR Transthyretin §[48gio | 4,7 | §4.980 | IN, IT, RID van chuyén (TR) hormon _ giap trang, RBP ‘Albumin 15-19 [4-58 | 66.300 | IN, IT, RID Protein van ngay chuyén, duy th ap, lye thdm thdu a; | ay-antitrypsin [4ngay [48 | 51.000 | IN, IT Ung ché (AT) protease a,-acid Sngay | 2,7-4 | 40.000 | IN, IT, RID Gan thude glycoprotein mang ign (AAG) duong, homon a,-fetoprotein 69.000 | RIA, EIA, phan cyc | Protein bao (AFP) huynh quang thai a2 Haptoglobin 2ngay | 4,1 85.000- | IN, IT Gan (Hp, HAP) 840.000 hemoglobin a Sngay [54 | 720.000 IN, IT, RID Uc che Magroglobulin protease (AMG) Ceruloplasmin [4,Sngay | 4,4 | 132.000 | IN, IT, RID, phuong | Chéng oxy (CER) hap enzym, héa Bi Transferrin (TA) | 7 ngay 79.600 __| IN, IT, RID ‘Van chuyén sat ce 206.000 _| IN, IT, RID BO thé | Bz Cs 180.000 _| IN, IT, RID Bé thé Be 11.800 | RIA, EIA Ding éanh gia microglobutin chiro nang éng (8MG) than Y IgG 24ngay | 6-7,3 | 144.000- | IN, IT ‘Khang thé 450.000 IgA 6 ngay 460.000 _| IN, IT. Khang thé. IgM ‘S ngay 900.000 | Bo 46 duc, c6 dinh | Khang thé mién dich Protein phan 6.2 | 115.000 | RID, RIA, IN, IT Chéng nhiém tng C (CRP) Khudn khéng, dac higu, foal bé-manh vo tébao Chu thich: IN, do 6 dyc min dich; IT, khuéch tan mién dich; RID, khuéch tan min dich huéng tam; RIA, mién dich phéng xa. 70Helen hth/Abuniy | = Dé hap thy véi cde vat ligu tro: cdc vat ligu nay c6 bé mat rong dé tuong tac v6i cdc protein nhu than hoat tinh, cdc chat khéng phan cyc théng qua cdc tuong tac kj nude. Tinh chat nay duge img dung trong céc kf thuat sic ky ki nude. Sy hap phy con xay ra déi véi cae chat phan cye nhu silica, alumina ho&c hydroxyapatid théng qua tuong tac ion hodc lién két hydro, Dac tinh nay cting duge img dung trong cdc ky thuat sic ky. — Gan dic higu véi khang thé, coenzym hode receptor cita hormon. Dic tinh duy nhat ciia protein la cé kha nang gin dic higu voi khang thé. Day 1a nguyén tic cla cic kg thuat héa mign dich. Protein ciing cé thé phan tach ra khdi hn hop nhé séc ky Ai lye trong dé khang thé khang protein dic higu nay duge gin véi chat gi 3, PROTEIN HUYET THANH Ba sé cdc protein trir khang thé va cdc protein hormon, déu duge tong hop 6 gan. Céc protein nay duge té bao gan téng hop va bai tiét vao méu qua tinh mach cita, Céc protein nay Iuu théng trong méu, gitta mau va khodng gian bio. Sy liu thong ca cde protein nay khéng chi nh khuéch tan thy d6ng tai cde vj tri ndi ca té bao noi mac ma con théng qua co ché van chuyén tich cue, 4m bio va bai tiét. Nhé co ché van chuyén nay ma dich ngoai long mach thudng chi chita mt lugng nhé céc protein huyét thanh. Céc dich khdc nhau thi khéc nhau vé sé lugng, thanh phan, ty 1é cfing nhu dac tinh sinh hoc cila céc protein. Mai truéng hop bénh ly cu thé thi sé cé sir thay déi protein huyét thanh dc trung cla minh. ‘Téc a9 sinh ting hop protein huyét thanh 6 té bao gan bj anh hung béi tinh trang cia bénh nan, Mét s6 hormon steroid anh huéng dén néng dé mét sé protein huyét thanh. Chinh vi vay, ndng d9 cia mét sé protein huyét thanh trong mét s6 truong hop bénh ly cy thé c6 thé bj anh hudng boi tinh trang cc hormon steroid cita bénh nhan fing nhw tinh trang viém cap. Mét sé protein thudc chét phan img pha cép (acute phase reactants: APR) nhu o1- antitrypsin (AAT), al-acid glycoprotein (AAG), haptoglobin (Hp), ceruloplasmin, C4, C3 procanxitonin (PCT), va amyloid huyét thanh A (SAA). Céc protein nay ting & hau hét cde trudng hop viém va duge goi 18 APR duong tinh, Mét sé protein khée nhu transthyretin (prealbumin) albumin, va transferrin thi Iai gidm trong cée trudng hep viém va duge goi la phan tmg pha ep am tinh. Phan img pha ep la phin ime khong ac hiéu véi qué trinh viém, cfing tuong ty nhu sét hay tang s6 Iuong bach cau. Sy thay di trén 1a do giai phong cdc cytokin ti vj tri tén thuong. 3.1, Protein toin phin Trong huyé: thanh, protein toan phan dao d9ng trong khoang tir 73,10 + 6,06 g/L. Chite nang cia protein La duy tri 4p sudt keo trong huyét thanh. Téc dyng cua 4p sudt keo 1 ngan chan sy mét dich tir md. Lugng protein toan phan trong huyét thanh bi anh huéng boi tinh trang dinh duéng, chite n&ing gan, than, réi loan chuyén héa va mét s6 ntinh trang bénh Ly. Trj sé protein toan phan it c6 gid tri trén lm sang song tri sé cla cde phan doan protein dic higu thi dao dng nhiéu va chinh sy thay ddi nay méi o6 gid tri chan don. Khi mét nuéc thi tt ca cde phan doan protein trong huyét thanh déu tng gay ra hi ching tang protein. Sy mét nude cé thé bi gay ra béi gidm hap thu hoac la ting su mat nude trong m6t s6 bgnh nhu: Addison, dai thao duéng hoa Ia tiéu chay nang. Trong giai doan khéi phat clia bénh u ty xuong c6 sy gia ting cia mt phan dogn protein gay ra syt tang tri s6 protein toan phan trong huyét thanh, Nguyén nhin gay ra giam protein huyét thanh cé thé do ting sy mat protein ho&c so gidm cung cdp protein do déi hay gidm hép thu. Trong hi chtmg viém than, mat protein 1a do albumin bi thodt ra ngoai cdc éng than bj tén thuong. Ngoai ra mat protein cdn cé thé do mat méu trong chdn thurong, trong bong nang hay do truyén dich nhanh hon so véi viéc bd sung protein. 3.2. Albumin Albumin 6 trong lugng phan tir khoiing 66,3 kDa va chiém khodng hon mot nira luong protein toan phan. Albumin cé cu tric hinh edu va 1a thanh phan chi yéu trong cdc dich ngoai long mach nhu dich nao tiy, nude tiéu, nude di, dich ke. Albumin chi la mét chubdi polypeptid, $80 acid amin véi 17 cdu néi S-S n6i phan ‘tr tgo nén nhiéu cdu trie vong. Chi cé 1 nhom SH ty do 6 vj tri acid amin 34. Day la mét trong sé it protein huyét thanh khéng cé gin véi carbohydrat. Albumin rt bén, cé d6 4m dién cao 6 pH sinh ly va dé tan trong nude. Albumin duge tng hop béi cae té bao nhu mé gan trir & giai dogn dau cla qua trinh bao thai thi duge tong hgp béi noain hoang. Téc 46 sinh tng hop albumin truée hét duge diéu hda bai 4p sudt keo va sau dé 1a t5e d6 ging héa cia protein. Céc cytokin viém lim giam sinh téng hop albumin. Théi gian ban hoy (half life) cia albumin huyét thanh la 15-19 ngay. 3.2.1. Chite nang Chite nang cia albumin la duy tri ép sudt keo trong va ngoai long mach. Sir c6 mat cia cic géc mang dign trén bé mat phan tir cling nhu cée vj tri gin dic higu nhu céc ion, g6¢ kj nude cho phép albumin cé kha nang gin va van chuyén mét sé long ln cde hop chat kém hoa tan nhu acid béo, bilirubin, céc hormon, canxi, kim logi, thude va vitamin. Albumin con déng vai tro cung cap ngudn acid amin cho céc m6 ngoai vi Albumin van chuyén cdc acid amin tir hé tiéu héa dén cdc mé va co quan va chinh ban than albumin ciing 14 ngudn cung cap acid amin cho cdc mé va co quan nay. Ngoai ra albumin cin cé mét sé chite nang kha nhu: 1a thanh phan quan trong cia hg théng chéng oxy héa cua huyét thanh; déng vai tr nhw hé dém dac biét 1a trong diéu kign kh6ng sinh ly; khi gin v6i glycoprotein 6 mang té bao ndi mac albumin lam ting tinh tham cita mang 4éi v6i céc protein nhé ma cdc protein nay déng vai trd quan trong d6i véi chuyén héa 6 ngoai ong mach; lam gidm dép tmg viém ciia tigu cdu va bach cau ‘trung tinh. 723.2.2. ¥ nghia lim sang Albumin tang trong cdc trudng hop mat nude cdp. Luu ¥ ring sy thay déi dp sudt keo sé diéu chinh rat nhanh qué‘trinh sinh tong hop albumin. Albumin huyét thanh giam trong cdc trudng hgp giam tng hgp hod ting gidng héa hodc két hop ca 2. Giam téng hop cé thé do bénh ly di truyén (analbuminemia) hoic do méc phai (qué trinh viém). H6i chimg albumin huyét thanh thdp (analbuminemia) la bénh ly di truyén tri lién quan dén nhiém sic thé thudng. Gen ma héa albumin nim trén nhanh dai cia nhiém sic thé sé 4 gan vi tri cia a-fetoprotein. Chi cé khoang 20 gia dinh cé hi chimg albumin huyét thanh thdp di truyén di duge céng bé. Nhing thanh vign trong gia dink nay cé néng d6 albumin huyét thanh chi 0,5 g/L (chi khoang 1% so v6i binh thuéng). Trigu climg lam sang ciia nhimg bénh nhan nay hiu nhu binh thuémg ngoai biéu hién phi (thuong xudt hién sau tudi 40), va rdi loan chuyén héa lipid. Mot sé trigu chimg cita héi ching nay ciing da duge mé ta nhu: cao huyét 4p, lodng xuong, u she t6 vang,... Mae di cé biéu hign réi loan chuyén héa lipid nhumg cdc bénh nhan nay Khdng c6 nguy co xo vita déng mach. Cé khodng hon 80 alen lién quan dén sy thay ddi cdu tric albumin song khéng im thay déi néng d6 albumin huyét thanh. TAt ca cae trudng hop nay déu 1a di truyén tri va duge goi la bisalbuminemia va duge phat hién ho dign di albumin huyét thanh, Tuy nhién, khi phan tich két qua dién di cho cde bénh nhan nay hét site than trong vi albumin huyét thanh thudng gin két v6i thudc, cdc chat chuyén héa...nén.d@ lam thay d6i dign tich va anh huéng dén sy di chuyén trong dign trudng. Théng thug la Alb A, & ngudi Chau Au da tring phd bién la Alb B (1/1000- 1/10000 tay thude vao ngudn géc). Alb B di chuyén nhanh hon vé cue 4m do cé sy thay thé Glu thanh Lys. Da sé cdc isoform cia albumin la binh thuéng mac di mét sé thé c6 sy bat thudng trong viée gin voi thyroxin (T4). Mét sé thé albumin bi glycosyl héa nhu Alb Redhill va Alb Casebrook thay déi dic tinh lién két véi acid béo. Gidm albumin huyét thanh thudng gap trong bénh gan (do gidm san xudt), bénh vé than (do ting sy dao thai) va c6 thé gap trong hdi chimg giém albumin do di truyén, do albumin khong duge san xuat. Ngoai ra ciing thuéng gap trong cdc trong hop viem cp hay man tinh, suy dinh duéng. 3.2.3. Kj thugt xét nghigm Voi cdc mu huyét thanh: sir dyng ky thudt tr déng gin véi chdt lén mau (bromeresol green hay purple) sau 6 xAc dinh d6 h4p thy quang hoc. Ai lye cia cde chat mau nay véi albumin cao hon nhiéu so véi cée protein khéc nén tinh dac higu cua ¥é{ nghiém s& cao hon hin néu ching ta chi chon t6c 49 gn két ban dau (giai doan sém nhét), Sir dung ky chuat lén mau don c6 thé gay ra sai sO thira khi dinh Ixgng albumin vi fibrinogen va heparin cing tham gia phan img mau nay. C6 thé khde phyc bang ky thuat Jén mau d6i. Cac chat c6 kha nding lién két véi albumin nhu thudc, céc chét chuyén héa nhung it anh hudng dén phan img lén mau trit khi ndng 46 cia ching qué cao. K¥ thuat ign di két hop véi dinh hong protein toan phan la kf thudt dinh long albumin it chinh 2Bxée va khong duoe khuyén céo sit dung. Céc ky thugt héa mign dich dic bigt Ia ky thuat do 49 due mign dich thi chinh xéc hon nhiu so véi cdc ky thugt 48 ligt ke & trén, Véi cdc mau nude tidu: sit dung ky thuat két tia hoge bang nhiét 46 trong mdi trudng acid hode tia bing acid (acid sulfosalicylic). Tuy nhién, khi sng loc thi nguéi ta thudng ding test thir nhanh (cé nguéng phat hign khodng 200-300 mg/L). Ngay nay 6 Jogi test nhanh phat hién microalbumin nigu. Céc ky thuft héa min djch giip phat hign nhanh va chinh xéc ndng d6 thdp albumin trong nue tiéu. V6i mau dich nao tly: str dung ky thuat mién dich do dé duc. Albumin trong huyét thanh ngudi Ién trong khoang tudi 20-60 1a 35-52 g/L (3,5- 5,2 g/dL). Khoang thdi gian 20-30 tuan cia thoi ky thai nghén, ndng 46 albumin dat tuong duong véi mite cia ngudi truéng thinh. Albumin huyét thanh gidm nhe & cong déng dan cu sng & ving khi hau cn nhiét déi hode ving nhiét d6i. Diéu nay 6 thé do tang néng 46 immunoglobulin thir phat sau nhiém ky sinh tring 3.3. Alpha-1-acid glycoprotein (Orosomucoid) Alpha-l-acid glycoprotein (AAG) la glycoprotein huyét thanh dau tién duge phan lap 6 dang tinh khiét dé xdc dinh dc tinh phan tir, AAG cé trong luong phan tir vao Khoang 40 kDa, 1a mt chudi polypeptid c6 181 acid amin chia mét ty 18 cao carbohydrat (45%) va sé Iuong lén cdc géc acid sialic (11-12%). Dac diém nay tao cho AAG cé d6 dign tich 4m rét Ion va kha nang tan trong nude cao va tinh da dang phan tir rat lén, AAG duge tng hgp 6 gan, song bach clu hat va bach cdu don nhén cling tham gia tong hop dé bai tiét vao trong huyét thanh trong trudng hop nhiém khudin hhuyét. Thoi gian ban hiy cia AAG huyét thanh 1a 3 ngay. Khi thodi héa, AAG truée hét bi loai bé géc acid sialic béi receptor asialoglycoprotein. Khi bi loai bé géc acid sialic thi thoi gian ban huy cia AAG chi cdn vai phiit. 3.3.1, Chite ning Nhiéu chite nang cia AAG 48 duge cng bé song chite ming that sy ca protein nay thi chua duge biét 6. AAG thude nh6m lipocalin bao gdm cée protein gin véi céic chat tan trong lipid va cé trinh ty acic amin kha giéng nhau. Thudc nhém nay bao gbm: protein gin retinol, B-lactoglobin, danrglobin, a-microglobulin, bikunin, chudi ciia bd thé Cy va inter-a-trypsin inhibitor. AAG cé kha nding gin va bat hogt m6t s6 Iugng lon cée hop chat tan trong lipid trong dé phai ké dén progesteron va céc hormon khéc, gin v6i chit déi khdng progesteron RU486. AAG con gin véi nhiéu logi thudc nhw propranolol quinidin chlorpromazin, cocain va benzodiazepin. Da s6 cdc xét nghiém dinh Iugng thuéc trong méu la dinh lugng thude toan phan chit khOng phai phn thude do. O nhimg tring hop AAG ting thir cép nhu trong dap ting pha cp hay Khi diéu trj bing corticosteroid thi viée bd sung thém thudc 1a quan trong (nham ting thém ndng 49 thudc trong mau) dé bi lai phan thudc bj gin voi AAG. 74Chire nang khéc cia AAG bao gém: tte ché dép img mién dich, giam qua trinh thuc bao, ttc ché két tap tiéu cau, tre ché phan bao, ttc ché ciia virus va ky sinh tring. Thém vio 46 AAG cén tte ché sy hinh thanh sgi collagen, 1a cofactor ciia lipoprotein lipase va tham gia diéu hda qué trinh van chuyén albumin va mét s6 hgp chat dai phan ‘ir qua mao mach thong qua dé tich dign am Ién cia AAG. 3.3.2. ¥ nghia lam sang AAG ting trong huyét thanh lién quan téi nhiéu bénh ly nhw trong viém, tén thuong mé va hormon trj ligu. Dac biét & dap tng pha cdp, AAG huyét thanh ting 3-4 lan trong nhimng truémg hop viém hodc hay hoai mé va thudng dat trj s6 t6i da vao ngay thir 3 dén ngay thir 5, AAG tang duéi sy anh huéng cia céc hormon glucocorticoid hodc 1a tri ligu (diéu tr bang prednison hay dexamethason) hodc 1a 6 cdc bénh ly nhu hi chimg Cushing. AAG giam 6 tat ca nhimg trudng hop gay gidm protein trong huyét thanh (hdi chimg thén hu hode hdi chimg da day rugt. Estrogen Lim cho sy ting hop va ndng 49 AAG huyét thanh giam. AAG cé thé t6n tai trong huyét thanh & dang da hinh thai lién quan toi céc dang khdc nhau cia chudi polypeptid. Day la thé di truyén tri lién quan dén nhiém se thé thuémg. Cé 3 gen ma héa AAG 6 vi tri 9q34.3 nim gan cdc thanh vién khac thudc nhém lipocain. Gen ma héa 6 vi tri ORM1 chiém 2/3 ciia sinh téng hop AAG va chiém da sé trong cdc thé AAG. San phim cia ORM1 va ORM2 cé thé duoc phan tach dé ding nh ign di ding din AAG sau khi loai bé acid sialic véi su cé mat cia ure. Sy tn tai cla cdc thé AAG khéng cé ¥ nghia trén lam sing. 3. KS thugt xét nghigm AAG ludn duge xét nghiém cing haptoglobin vi phan img pha cdp va cée téc déng cia hormon déu anh huéng dén 2 protein nay. Mac dit AAG 1a mét trong nhimg protein cé ndng 49 cao nhét trong ving qj-globulin & nhimg ky thuét dign di thuéng quy song protein nay thudng khong bat mau thude nhudm tét vi cé long lén nhém CHO. Protein nay cé thé dé dang quan sat nhé periodic acid-Schiff hod cdc thuée nhudm carbohydrat. AAG ¢6 thé dugc dinh lugng bing cdc kf thudt héa mién dich trong 46 06 ky thuat mign dich do d6 dye. Ning do AAG 6 ngudsi thanh nién va nguis lon 1a 0,5-1,2 g/L (50-120 mg/dL). Nong d9 AAG khi tré mdi sinh chi bing 20-30% ngudi trung thank va dat chi s6 xp xd nguoi truéng than khi 6-12 thang tuéi. 3.4. Alpha-I-antitrypsin Alpha-1-antitrypsin (AAT) cin duge goi 1a alpha-1-anti protease thudc nhém chat tte ché serine protease va phan lén dugc téng hop 6 gan. AAT la mdt chudi polypeptid 6 394 acid amin véi trong luong phan tir khoang $1 kDa. 153.4.1. Chate ning AAT thug nh6m serpin (serine protease inhibitor), déng vai trd 1a co chat va hinh thanh phife hgp tetrahedral véi trang tim hoat dng cia serine protease va khéa trung tam nay lai. M@t sé thanh vién khée thuge nhém nay nhu: proteinase inhibitor al- antichymotrypsin , e-antiplasmin, antithrombin Il, heparin cofactor TI va Cy inhibitor, thyroxine-binding globulin va mét s6 protein Khéc. AAT c6 ndng 46 cao thir 2 vé mat Khdi Iurgng trong s6 cdc chat ite ché proteinase 6 trong huyét thanh (sau AMG). Tuy nhién, AAT cé kh6i lugng chi bing 7% AMG nén AAT cé ndng dé phan tir cao nhat trong s6 cae cht tre ché proteinase huyét thanh, Vi c6 kich thuéc nhé nén AAT c6 kha ning di dén moi dich trong co thé trong khi AMG chi 6 trong long mach, AAT la cht Ge ché quan trong nhét déi voi elastase ciia tiéu cu lién quan chat che t6i qua trinh thye bao. Enzym nay phan tig véi elastin 6 té bao ndi mac cia thanh mgch, nhanh phé quan. AAT do vay déng vai tré quan trong trong vige ngin can sy mat tinh dan hdi cia phdi va phOng ngita khi phé thing. AAT cdn ngan cin sy pha hiy mé lién két gay ra do elastase giai phéng tir bach cdu 6 ving viém. AAT bit hoat céc protease cita bach cdu trung tinh, kallikrein, renin, urokinase, plasmin va thrombin. 3.4.2, ¥ nghta lam sang AAT ting trong phan img pha cdp, thudng ting sau 24h va dat mite d6 cao nhat & ngay thir 3 va ngay thir 4. Céc cytokin dac biét 1a IL6 kich thich sy ting hop AAT. ‘Viém gan cing lam tang AAT trong huyét thanh ma khéng Lim ting cae hgp cht khae ‘tong phan img pha cdp. Estrogen kich thich tng hgp AAT do vay AAT ting & giai doan cudi thai ky. AAT gidm trong cde trudng hop bénh ly do tén thuong gen. Gen ma hoa AAT nim 6 14q32.1 cita nhiém séc thé, gan vj tri gen ma héa chudi nfng ciia khdng thé va serpin a -antichmotrypsin, protein C inhibitor va corticosteroid-binding globulin. C6 téi 75 thé di truyén AAT Khéc nhau duge goi 14 Pi tir B dén Z theo thit ty gidm dan tdc 46 di chuyén trong dign trudng. Trong dé B la gan eye duong nhat. Pi Z thudng gap 6 eng ding dain cu Bic Au cin Pi S thi lai phd bién & ngudi song & Tay Nam Au. Thiéu hut AAT do tn thuong gen (Pi Z hay thé khéng 6 AAT) dé d&n dén bénh khi phé thiing. Bénh thudng khéi phat sém (20-40 tui) & nhiing truéng hop Pi ZZ. Nguyén nhén cia cn bénh hi phé thing nay 1a do elastin bj tiéu hi bdi elastase ciia bach cau. Bénh tang cuéng khi khéng khi bj 6 nhiém ho&e 6 nhing bénh nan hiit thude 14. Thiéu hut AAT cén lién quan dén cée bénh ly cua gan nhu viém, xo gan, tr mat bam sinh, ung thy gan. U mét bam sinh chiém khodng 11% céc trudng hgp tré Pi ZZ 6 They Bién, Bénh thuémg xuét hign & tré vao tudn thir 3 dén tun thir 8. AAT con giém trong nhting truéng hop do tang sit dung (hdi chimg suy h6 hap so sinh, viém gan so sinh, viém tuy cdp) hay do mt qua duémg nude tiéu (hi chimg than iz) hode dung tiéu hoa, 763.4.3, KY thud xét nghigm Vige dinh lrong AAT cé thé duge tién hanh bang dién di boi khoang 90% vet ctia a-1 globulin chirh 1a protein nay. Ngoai ra ¢6 2 protein khée eiing vj tri trong ty la AAG va a-lipoprotein. Tuy nhién, 2 protein nay khéng bit mau thude nhudm tét do c6 nhiéu nhém CHO va lipid. Mét sé thé AAT cé thé duge nhan biét nho ky thudt dién di do c6 téc 46 di chuyén khée nhau. AAT con cb thé duge dinh lugng sit dung ky thuat héa min dich va ky thugt mién dich do 46 dye. Céc dang phan tir cha AAT duge xéc dinh boi dign di & diém ding dign. Néng 49 AAT trong huyét thanh 1a 0,9-2,0 g/L (90-200 mg/dL) va én dinh trong sudt cudc dai, tir khi sinh ra dén khi gia. AAT 6 nif cao hon nam mét chit. Tré so sinh 6 AAT cao hon ngudsi lon mét chit, c6 1é do anh hudng cita estrogen cén lai cia me. 3.5, Alpha-2-macroglobulin Alpha-2-macroglobulin (AMG) 1a mét trong nhting protein cé khdi lung phan tir lon nhdt (725 kDa) va la chat tre ché nhiéu nhém protease nhu: serin, cystein, ion kim loai & trung tém thay phan protein. AMG 6 4 chudi popypeptid gidng hét nhau t20 thanh 2 cp dimer lién két v6i nhau bing cdu néi disulfid. Trong khi 2 chudi lién két véi nnhau bing cdu ndi khOng eng héa trj. Cau tric dimer la thé hoat déng, do vay phan tir AMG cé kha nang lién két véi 2 phan tir protease. AMG duge ting hgp & gan. Thoi gian ban huy cia AMG la vai ngay trong khi ciia dimer chi vai phuit. 3.5.1, Chite nang AMG lién quan dén sy tre ché cae enzym cla hé Kinin, bé thé, dong mau va phan hiy fibrin, Cac chét oxy héa lam hoat tinh AMG giim do téc dung pha hity cdu tric tetramer thanh céu tric dimer mét hogt tinh, AMG 6 chite nang van chuyén nhieu logi peptid nho hur cytokin va cde yéu t6 phat trién (insulin va hormon phat trién), cation héa tri 2, dc biét 18 kém. AMG con tham gia diéu hda dap img mién dich va viém. 3.5.2. ¥ nghic lam sang AMG huyét thanh ting dudi sy téc dng cia hormon (estrogen) do vay AMG & nit cao hon so véi nam gidi ciing tudi. AMG & tré em cao gdp 3 lin ngudi Ion. AMG tng & hdi chtmg than hu do phan tmg tang téng hop bi cia co thé déi véi cdc protein bj mt ra ngoai nuéc tiéu. AMG giim 6 nhing trudng hop do bénh ly cla gen, Gen ma hoa AMG nim 6 vi tri 12p12-13 trén nhiém sac thé. Thudng gap cdc trudng hyp thiéu AMG thé di hop tir, Khi d6 c6 mét lugng bang nhau AMG binh thudng va d6t bién cing tdn tai trong huyét thanh bénh nhan, ee3.5.3. KY thugt xét nghigm AMG Ia thanh pha chi yéu cla ving y-globulin khi dign di. Me do thé cia AMG khéng phan téch duge & ky thudt dién di thong thudng song thé AMG binh thudng gan cy am hon do né da phan tg véi hod 1a cdc protease hoe 1a cdc chat Ai nhan va bj mat lién két thiol ester. Dya vio dae diém nay ma chiing ta c6 thé xée dinh mite dé bat hoat cla AMG in vitro hoac in vivo (nhw trong bénh cia tuyén tuy), AMG due dinh lugng dua vao ky thugt mign dich khuéch tan hay do d6 tan xa. Vige dinh lugng AMG trong nude tiéu c6 thé ding dé phan biét dai ra protein hay dai mau, AMG 6 ngudi Ién la 1,3-3,0 g/L (130-300 mg/dL). Nang 49 AMG & tré em cao gdp 2 ngudi lén (cao nhat & tré 2-4 tudi), néng d6 6 nit cao hon nam gidi cing tudi Khoding 20-30% sau tudi 40. 3.6. Alphal-fetoprotein Alphal-Fetoprotein (AFP) la mét glycoprotein c6 | chuéi polypeptid va khoang 4% carbohydrat véi khéi long phan tir i 70kDa. 3.6.1, Chute nang AFP 1a mét protein chinh ciia huyét thanh bao thai, dugc téng hop 6 gan bao thai, tii nofin hoang va m6t s6 co quan khdc cla bao thai, Nong 49 AFP huyét thanh bao thai cao nat & trong 3 thang dau cia thai ky sau dé giam dan. Khi tré méi sinh, ndng 46 AFP chi cén lai 1%, sau 18 thang thi chi con 2 ng/mL. Nong d6 AFP trong mau me dat cyte dai & tuan thir 30 ca thai ki. AFP c6 kha nang gin va bat hoat estrogen, c6 1é dé bao vé thai khdi ndng dé cao hormon nay trong mau me. 3.6.2, ¥ nghta lam sang Dinh lugng AFP trong dich 4i va trong mau me gitip sang loc di tat bam sinh va bat thudng nhiém séc thé thai nhi. Tang AFP mau me cé thé tang trong nhimg truéng hop cé dj tat & dng than kinh hodc thanh bung thai nhi, da thai, thai nhi nhé, thai chét hun, hay tinh sai tudi thai Trisomy 21 hay trisomy 18 lién quan dén AFP thdp 6 mau me. AFP con duge sit dung lam dau 4n déi véi ung thu gan va ung thu nguyén bao nudi. APP 6 tré méi sinh <5 mg/L va é tré trén 18 thing <2 pg/L. 3.7. Betay-microglobulin Betag-microglobulin (BMG) 14 mt protein ‘cé trong long phan tir nho (11,8 kDa) cé trén bé mat cita cdc té bao c6 nhan, dac biét 1a té bao lympho B va mét sd té bao ung thu. 78BMG la chudi nhe cita khang nguyén bach cdu ngudi gdm 1 chudi polypeptid voi 1 cu disulfid ngi phan tir. Do ¢6 kich thuiéé hd nén BMG dé ding dude Ioe qué cau than song chi dudi 1% dirge bai tiét-ra ngoai mude tiéu. Thai gian bin hiy ca BMG trong huyét thanh chi 107 phut. Néng 46 BMG trong huyét thanh phan dnb ty 1 sin xudt va chit nang cila cau than trong viée lgc va tai hap thu protein. BMG con duge ding nhu mét ddu An ung thu dc biét 1a trong vic chuan dodn ung thw bach cau va la m6t test nhay cho viée danh gid chite nang than, BMG duge dinh Iuong nhé ky thuat mién dich phéng xa (RIA), mién dich khuéch tan. Lugng BMG trong huyét thanh dao déng trong khoang 0,7-3,4 mg/dL va trong nude tiéu 1a 0-300 pg/L. 3.8. C-reactive protein C-reactive protein (CRP) duge téng hep & gan, gdm c6 5 chudi polypeptid giéng h@t nhau, khéng bj glycosyl héa va lién két véi nhau bang lién két khng ong héa tri. CRP gin v6i khéng chi polysaccharid cita vi khudn, ndm, ky sinh tring ma cdn cd voi phosphorylcholir, phosphatidylcholin, cée anion trong digu kign khong cb Ca". Khi e6 mat cla Ca’, CRP cé kha nang gin v6i polycation nhu histon. 3.8.1. Chite nding CRP ta mot chét quan trong ca hg théng bao vé khong dic higu ciia eo thé d6i voi qué trinh vigm, de bigt la bénh truyén nhiém. CRP gin véi cde thanh phan vi cia t& bao dé hoat héa con dug bé thé kinh dién Cla, tang qué trinh thye bao théng qua receptor C3b, Tuy ghién, phite hop CRP gin voi yéu tb H, mot yéu t6 tre ché b6 thé, am gidm ‘sy. hogt héa cdc thanh'phan mugni (C5 dén C9) va diéu ha nguge dong ‘héng qua con dung thay thé khée. “06 the gi cdng’B6 ofc'thé DNA ota RP va bidy hign thigu hut do di truyén song chua od phat hign bat thudng’vé gen: 3.8.2. ¥ nghia lim sing CRP 1a mot trong nhimg protein ting cao & phan img pha ep, Trong mot sé trudng hop nhu: nhéi méu co tim, tress, viém nhiém, chan thuong, phdu thugt... néng 4 CRP 06 thé wing t6i 2000 Lan. Khi nbiém khudn CRP ting cao hon so véi nhiém virus. Khi viém, CRP bat dau ting sau 6-12h va t6i da khodng 48 gid, Mite d6 ting ty 16 thudn véi mite dg tn thurong cia m6, Mau cudng rén c6 CRP thap (1-35 g/dL), song khi nhiém khudn thai nhi thi cé thé tang t6i 26 my/dL. 3.8.3, KP thude xét nghigm CRP duge dinh Iuong bang kf thudt min dich enzym (EIA) hay ky thuat do d6 tan xa. Nong 46 CRP trong huyét thanh

You might also like

• Triệu Chứng Học Ngoại Khoa Y Dược TP Hồ Chí Minh - - Trường ĐH Y Khoa Vinh VMU

  

  Document408 pages

  Triệu Chứng Học Ngoại Khoa Y Dược TP Hồ Chí Minh - - Trường ĐH Y Khoa Vinh VMU

  Vmu Share

  100% (8)
• Đau bụng cấp 2

  

  Document60 pages

  Đau bụng cấp 2

  Vmu Share

  No ratings yet
• Xử lý vết thương

  

  Document44 pages

  Xử lý vết thương

  Vmu Share

  100% (1)
• • Magazines
  • Podcasts
  • Sheet music
• Đau bụng cấp

  

  Document41 pages

  Đau bụng cấp

  Vmu Share

  100% (1)
• Sổ Tay Từ Vựng y Học - Tiếng Anh Lê Nguyệt CLB Y KHOA TRẺ Y KHOA VINH

  

  Document23 pages

  Sổ Tay Từ Vựng y Học - Tiếng Anh Lê Nguyệt CLB Y KHOA TRẺ Y KHOA VINH

  Vmu Share

  No ratings yet
• Joint Dislocation CLB Y KHOA TRẺ Y KHOA VINH

  

  Document25 pages

  Joint Dislocation CLB Y KHOA TRẺ Y KHOA VINH

  Vmu Share

  No ratings yet
• Tiếp Cận Và Xử Trí Bệnh Nhân Hôn Mê CLB Y KHOA TRẺ Y KHOA VINH

  

  Document33 pages

  Tiếp Cận Và Xử Trí Bệnh Nhân Hôn Mê CLB Y KHOA TRẺ Y KHOA VINH

  Vmu Share

  No ratings yet
• Phôi Thai Học Người ĐH Y Hà Nội - - Trường ĐH Y Khoa Vinh VMU

  

  Document636 pages

  Phôi Thai Học Người ĐH Y Hà Nội - - Trường ĐH Y Khoa Vinh VMU

  Vmu Share

  100% (1)
• Tiếp cận - Xử trí BN chấn thương

  

  Document18 pages

  Tiếp cận - Xử trí BN chấn thương

  Vmu Share

  No ratings yet
• Kháng Kháng Sinh

  

  Document18 pages

  Kháng Kháng Sinh

  Vmu Share

  No ratings yet
• Bệnh Học Nội Khoa Y Dược TP Hồ Chí Minh - - Trường ĐH Y Khoa Vinh VMU

  

  Document480 pages

  Bệnh Học Nội Khoa Y Dược TP Hồ Chí Minh - - Trường ĐH Y Khoa Vinh VMU

  Vmu Share

  50% (2)
• Bệnh Học Nội Khoa ĐH Y Hà Nội Tập 1 - - Trường ĐH Y Khoa Vinh VMU

  

  Document498 pages

  Bệnh Học Nội Khoa ĐH Y Hà Nội Tập 1 - - Trường ĐH Y Khoa Vinh VMU

  Vmu Share

  No ratings yet
• Nội Khoa Cơ Sở Tập 2 ĐH Y Hà Nội - - Trường ĐH Y Khoa Vinh VMU

  

  Document418 pages

  Nội Khoa Cơ Sở Tập 2 ĐH Y Hà Nội - - Trường ĐH Y Khoa Vinh VMU

  Vmu Share

  No ratings yet
• Giải Phẫu Bệnh Bộ Y Tế - - Trường ĐH Y Khoa Vinh VMU

  

  Document556 pages

  Giải Phẫu Bệnh Bộ Y Tế - - Trường ĐH Y Khoa Vinh VMU

  Vmu Share

  50% (2)
• Bệnh Học Niệu Khoa ĐH Y Dược TP Hồ Chí Minh - Trường ĐH Y Khoa Vinh VMU

  

  Document242 pages

  Bệnh Học Niệu Khoa ĐH Y Dược TP Hồ Chí Minh - Trường ĐH Y Khoa Vinh VMU

  Vmu Share

  No ratings yet
• Bệnh Học Nội Khoa ĐH Y Hà Nội Tập 2 - - Trường ĐH Y Khoa Vinh VMU

  

  Document614 pages

  Bệnh Học Nội Khoa ĐH Y Hà Nội Tập 2 - - Trường ĐH Y Khoa Vinh VMU

  Vmu Share

  100% (1)
• Triệu Chứng Học Nội Khoa Y Dược TP Hồ Chí Minh - - Trường ĐH Y Khoa Vinh VMU

  

  Document238 pages

  Triệu Chứng Học Nội Khoa Y Dược TP Hồ Chí Minh - - Trường ĐH Y Khoa Vinh VMU

  Vmu Share

  No ratings yet
• Thực Tập Sinh Lý Học Học Viện Quân Y - - Trường ĐH Y Khoa Vinh VMU

  

  Document154 pages

  Thực Tập Sinh Lý Học Học Viện Quân Y - - Trường ĐH Y Khoa Vinh VMU

  Vmu Share

  No ratings yet
• Thực Tập Hoa Sinh

  

  Document210 pages

  Thực Tập Hoa Sinh

  Sen Sophorn

  100% (1)
• Phôi Thai Học Người ĐH Y Dược TP HCM - - Trường ĐH Y Khoa Vinh VMU

  

  Document138 pages

  Phôi Thai Học Người ĐH Y Dược TP HCM - - Trường ĐH Y Khoa Vinh VMU

  Vmu Share

  100% (1)