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