- Sau khi hép thu cdc monosacacrid phan Ién duge gitt lai & gan dudi dang glycogen dé can bang duéng huyét. Dd thu nhan loai monosaccarid nao nhung khi thoai hod glycogen gan chi dua vao mau mét loai la glucose - Glucose méu khuéch tén ty do qua thanh mach -> gian bao. Glucose thm dé dang vao mét 6 th ma khéng can sy 6 m&t cua insulin ( HC, tb gan,tb nfo). Hau hét cdc tb khée mu6n thu nh4n duge glucose doi héi phai cé insulin, nguén du thira dé tng hgp acid béo viaa Khi glucose mau > 1,6 g/l -> dao thai vao nuéc tiéu vi vugt qua kha ning ta Ong than 1.3 Chuyén hoa glucid ~ Vao tb glucose ( Fructose, galactose) duéi tac dung ctia enzym hexokinase chuyén thanh glucose 6 phosphat. Tuy theo nhu cau, logi th mA G6P cé thé di theo con dung sau + Thoai bién thanh acid pyruvic réi acetyl CoA vao chu trinh Kreb cung cp nang lugng, CO, va nude. + Khir phosphat gan cung cp lai glucose cho mau hp thu cia + Téng hgp thanh glycogen dy trit chi yéu 6 gan va co + Tham gia chu trinh pentose tgo acid béo xay ra ¢ gan va mé m@ voi su hd tra cia insulin. 1.4 Diéu hoa ein bing glucose mau. ~ Nong 46 glucose méu 6 ngudi khoé manh binh thuong lic déi la: 4,4- 6,1 mmol/l ( 80- 110 mg/dl). - Diu hoa can bling glucose méu nhiéu co ché phite tap, nhung quan trong nhat 1a vai tro ciia gan, hé théng ndi tiét, than kinh. 1.4.1 Vai tro diéu hoa cia ngi tiét: 6 2 nhém d6i lap nhau. - Hé lam gitim glucose méu + Insulin la hormone duy nhat cé tac dung ha glucose mau, né do té bao B cia dig tay bai tiét,+ Cae a.a, thé ketone, acid béo ty do huyét tuong, day X bj kich thich => tang tiét insulin. + Insulin 1am cho glucose vao té bao nhanh va lim giam tan tgo glucose tir glycogen, protid va lipid. - Hé lam tding glucose mau. + Adrenalin: kich thich tao AMP vong 6 tb dich, ting hoat hod enzyme phosphorylase 6 gan, tng thodi hod glycogen -> thanh glucose. + Glucagon: téc dyng tuong ty adrenalin nhung manh va kéo dai hon, né con kich thich phan huy mé ( do enzyme lipase durge hoat hoa béi AMP ving ). + Glucocorticoid . Ngan can glucose tham vao tb ( trir th nao). - Tang hogt hoa G6P -> ting giai phéng glucose 6 gan vao mau. . Ting tan tgo glucose tir protid + Thyroxin . Tang hap thu glucose 6 rudt. . Tang phan huy glucogen. +TSH . Tang hoai hoa glucogen do tre ché enzym Hexokinaze. . Hoat hod Insulinase. + Insulinase va KT chéng Insulin: tryc tiép huy Insulin. 1.4.2 Vai tro diéu hoa ciia thin kinh: - Kich thich san nao that IV gay tang dudng huyét. - V6 no, hé ¥ hung phan (hdi hGp, xiic dong, stress) gay ting during huyét ( do téc dung ciia Adrenalin) - Hai trung tam ( A va B) ciia ving nao dudi doi tham gia diéu hoa duéng huyét thong qua hormon.+ Trung tim A: g6m nhiing tb than kinh, kh6ng cé mit insulin van thu nhan duge glucose tir mau. Khi glucose mau giam duéi mie binh thudng -> trung tam A kich thich lam tang tiét glucagon, Adrenalin, ACTH... dé tang tao glucose. + Trung tm B: Dai dién cho tat c cdc tb cén Iai ctia co thé phai cé insulin méi thu nhan dugc glucose. Khi thiéu insulin trung tam B sé huy d6ng moi co ché ndi tiét lam glucose méu ting rét cao du thdm vao tb (g4p 4 ln so véi binh thuong). 2. R6i loan chuyén hoa Glucid. 2.1 Réi loan duéng mau: 2.1.1 Gi glucose miu: Khi néng 46 glucose méu < 4,4 mmol/l. - Neuyén nhéi + Cung cp thiéu khau phan an hang ngay : di. + RI kha nang hap thu glucid. Thiéu enzym tiéu glucid cia tuy va rudt. - Gidm dign tich hép thy 6 ru6t: cét doan rust, thc, viém rudt 126 dc, viém rudt man tinh. - Gidm qué trinh phosphoryl hod 6 tb thanh ru - Thiéu bam sinh mét sé men lam khéng hap thu duge galactoza, fructoza: tré khéng chju duge sta, nén sau khi bi, tiéu chay, suy dinh dudng, +RL kha nang dy trir - Gan gidm kha ning dy trir glucid: viém gan, xo gan. - Thiéu bam sinh mét sé enzym thodi hod glucose nhwr phosphorylase... Jam gan bi tf dong glucose, thiéu G6P. + Tang mite tiéu thy: co ca, run co ( chéng rét), sét, ung thur.. + RL digu hoa cita mét s6 hé TK- néi tiét: cudng phé &, te ché © -> gidm tiét cde ndi tiét t6 06 te dung lam tang glucose mu hodc ting tiét insulin, + Than gidm kha ning tdi hap thu glucose do RL qué trinh phosphoryl hoa 6 tb éng than (bam sinh) -> dai duéng do than.+ U tb B cia dao tuy (u than tuy) Lam tang tiét insulin gay ha durong mau kjch phat > d& di vao hén mé. - Hau qué: + Glucose mau < 4,4 mmol/l ( 80mg/dl), tim dap nhanh do tang tiét adrenalin, thiéu glucose mu > thiéu GOP trong tb => phat sinh cém gide déi. + Glucose mau <3,3 mmol/l ( 60 mg/dl) > hé bi KT -> ting tiét cathecholamin -> tac dung 1én mach ngoai bién lam co manh -> da bénh nhan xanh nhgt, téc dung lén tim lam tim d§p nhanh, manh, héi hp, danh trdng ngyc, va mé héi ( do tuyén mé hoi bj kich thich), gian dong tir (hoa mat, md mat) Ngoai ra ngudi bénh cé biéu hién mét moi, nhite dau ( trung tam 6 nao thiéu oxy). + Glucose mau < 2,5 mmol/l ( 50mg/dI: khéng cAp ciru kip thoi > tén thuong TKTW ( RL cam gide, thi gide nhw chéng mt, ao gidc, nhin déi, nhin ba, RL ngén ngit néi liu lu6i, khong ra tiéng ..., RL van dng run ray, mat phdi hgp dOng téc, co git, hon mé...). 2.1.2 Tang glucose miu: Khi luong glucose méu litc 46i > 7,0 mmol/l (126 me/dl) - Nguyén nhan: + Xay ra trong va sau bita an nhat a khi an nhiéu dudng thiéu vitamin B,-> & tré acid Pyruvie (By la ¢6 enzym eda nhiéu enzym gitt vai trd khir carboxyl, oxy hod acid Pyruvic va acid cetoglutaric) > khéng vao dugc chu trinh Krebs, + Unnio, trung tm B kém nhay cdm véi insulin ( tudi gia). + Do n@i tiét: gim hode thiéu insulinase, c6 KT chéng insulin, - Hau qua: + Tang glucose mau it déc cho tb, nhung lam ting 4p lye tham théu -> khat nuée, tiga nhiéu, mat Na’, K*. Khi long glucose méu qu cao vugt qué nguéng hap thy cla than -> glucose nigu [ nguéng glucose ciia than 10 mmol/l, (180 mg/dl) J. + Tang glucose do RL not tiét ( RL bai tiét Insulin) > RL chuyén hod glucid trim trong -> gap trong bénh tiéu duong. vee2.2 Bénh tiéu dudng. Tir thé ki XI y van da mé td mot bénh la, voi 4 trigu chimg chinh: An nhiéu, uéng nhiéu, dai nhidu, gay nhiéu, V8 sau nha quan sat thdy kién bu vao bai nuéc tiéu, nén them trigu ching nuéc tiéu ngot -> tén chinh thie la bénh tiéu dung. 2.2.1 Bénh nguyén va phan loai bénh tiéu duong. - Phan loai bénh tiéu ducong. + Dai duéng typ I phy thugc insulin (IDDM: Insulin Dependent Diabetes Mellitus) theo phan loai OMS 1980: chiém 5-10% thug thiéu hut insulin tuyét déi. * Bai duéng typ II khéng phy thude insulin ( NIDDM: Non Insulin Dependent Diabetes Mellitus) theo phan loai OMS 1980: Chiém chi yéu 85-90% téng sé BN, thiéu hut insulin tuong déi. + Céc typ dai dutng dic biét khée: khiém khuyét vé gen lign quan tdi tb B hay hoat dong cia insulin, dai duéng 6 ngudi tré, khoi phat 6 tudi trudng thanh (MODY: Maturity onset Diabetes of youth), bénh tuyén tuy ngoai tiét (xo nang tuy...). H/c cushing, nguyén nhan do hoa chat hay thuéc (thud didu tri HIV/ AIDS). * Dai dudng thai ky: chiém 3-5% phy nit c6 thai, dai dudng trong thoi gian mang thai, da sé tré vé binh thudng sau sinh nhung 30-60% phat trién thanh dai duong sau d6. - Bénh nguyén: * Dai dung typ I (kém san xudt insulin), * Bénh c6 tinh chat di truyén r6 rét: phét hién 0,2- 0,5% s6 ngudi trong quan thé. Néu gia dinh 6 cha hotic me mc bénh thi con cdi o6 nguy co mac 8-10%, néu ca cha va me déu mac €6 t6i 40% con cai mic bénh, Gen lién quan HLA- DR3, HLA-D4 va DQW-8, gen Khang lA HLA- DRW2, B7. + Cae yéu t6 méi trudng: virus (rubella, quai bj...), mot s6 déc 6 gay thodi bién tb B, dic biet la hop chat 06 chit nito (nitrit,nitrat,..), + Cée yéu t6 MD: phat hign ffong mau bénh nhén 6 KT chéng tb B va hodc chéng insulin, va hodc chéng thy thé insulin, * Ddi duong typ It:+ Yéu t6 di truyén: lign 6i : lién quan véi nhing bién ddi di truyén trén nha gut ee ii truyén trén nhanh ngfn cia NST XI, rat + Yéu t6 méi tru rong rat quan trong, tac déng vao ngoai canh oé thé lam bénh xuét hién mudn ( ché 46 én tap, gidm bé Ef " ( 16 &n, luyén tp, giam béo). Khéi phat bénh 6 ngudi > 40 tudi ( chit yéu 50- 60 tudi), béo phi, it van dong Fk FROG aoe ; R6i loan ae insulin; 25% bn dai dudng c6 gidm tiét insulin, 25% khéng gidm tiét va 50% cén lai tang tiét insulin. Do cée nguyén nhén ngoai tuy gay ra ( c6 thé tang tiét eae hormon lam tng glucose mau nhu glucocorticoid, ACTH...) , u v6 thugng thén + Khang insulin; gidm hode mat tinh nhay cém ciia co quan dich voi insulin (co ché chua 16 rang) 2.2.2 Bénh sinh a. Co ché bénh sinh ctia dai duéng typI _ Thiéu insulin tuyét déi do tb B cia dao tuy bj ton thuong gay nén. hau qua cia sy pha huy th B cia dio tuy ty mign gay hau hét cdc trudng hop dai durong typl - Nguyén nhan ban dau gay qua trinh ty mign dich va pha huy tb B dio tuy chua r6, cde yeu 18 méi trudng bén ngoai nhu VR quai bj, rubela, 6 thé 1a yéu td ban dau gay pha huy va tang qua trinh phé huy cdc tb nay _ Mot 86 it tnrdmg hop dai dudng typ! Khong tim thdy nguyén nhan, khéng cé lién quan HLA, nhung cé yéu t6 di truyén rat ro b. Co ché bénh sinh cia dai dwong pl ~ pai dudng typlll lién quan dén su thiéu hut insulin tuong 46i do RL tiét insulin va hién tugng khang insulin né 6 lién quan mat thiét v6i nhau va déu xdy ra trude khi xudt hién biéu hién lam sang, - Bénh nhan dai during typll khéng thira e&n > gidm tiét insulin 1a chinh, Thita cén tinh trang khang insulin la chinh + Réi loan tiét insulin+ Trong giai doan dau a8 by tee to: n: a an dau dé bi trir lai hién tong khéng insulin -> 43 - insulin ho&e tang khéi lugng eda tuy > dao tuy ting cudng bai tiét + Giai doan sau néu au vin tié : glucose mau van tiép tue ting > kha ning tiét insulin dap img véi glucose ngay cang giam sit ie + Dai dudng typll cé6 bidu hién 1a i i pel u hign lam sang khi tb B cla dao tuy bi tin thuong, khéng da dua glucose mau vé gi han binh thudng va su suy gidm tb B dign ra mét céch tir tir i Reaches, eae 5 Nguyén nhan dan dén giam tiét insulin ciia tb B cd thé do di truyén, yéu t6 TK. Chua khang dinh duge gen nao déng vai trd quyét dinh + Ngoai ra sy suy giam tb B dao tuy cdn do déc t6 * Khang insulin: giam hay mit tinh nhay cam cia co quan dich véi insulin 1a khiém khuyét chinh trong dai dursng typ IT + La nguyén nhan gidn tiép lam suy chite nang bai tiét insulin etia tb B dao tuy + Khang insulin chu yéu do bat thuéng trong con duéng truyén tin higu nGi bao cia insulin sau khi né gn vao reseptor 2.2.3 Co ché ctia cdc biéu hién lam sang trong déi duong Glucose mau ting cao: do glucose khéng duge insulin hé trg 48 qua mang tb. Déng thai thiéu insulin > gan thodi hoa glycogen, ting huy dong mé va giém tng hop lipid => hu qua ~ An nhiéu: thiéu insulin > thiéu nang lugng va G6P giém -> trung tim 4éi bj kich thfch > cam gide d6i thing xuyén - Khét va udng nhiéu: néng 46 glucose mau tang cao -> tang dp lye thém théu mau - Déi nhigu: do can tre su hdp thu nude & éng than va glucose mau tang cao vugt qua ngudng than nén nudc tiéu cé dudng -> gay da nigu thdm théu => dai nhieu - Gay nhanh * Thiéu GOP + Protid khéng duge téng hop, edn bi thoai bién nén ean bing nito am| + Chu trinh pentose ngimg tré khon, acid béo + acetylCoA * San phim thodi méu cang ting 8 tong hop duge lipid, mat khéc lipid bj thoai hoa > hoa Pe duge trung tam B phan ing ting tao duéng méi > glucose ~> duong mat theo nuséc tigu ngay cang nhiéu _ Be Sa hats Aare én nhan hén mé, hoi thé cé mai ceton: do thiéu G6P nén thiéu acid pyruvic va acid estrGale 1am cho chu trinh kreb quay cham , vi vay acetylCoA i dong va duge tring hgp thanh thé ceton ~ Cholesterol ting dé gay xo via mach, phi gai thi, NMCT, hoai tir chi kém suy gidm MD va suy kiét toan than * Hau qua - Nhiém toan ceton: xy ra & bn dai duéng typ I do thiéu insulin tuyét d6i gay tang glucose mau, ting phan huy protid, lipid > ting tich luy mau acetyl CoA khéng vao chu trinh krebs -> chuyén thanh cdc thé ceton ( trir aceton) 1a acid manh -> pH méu gidm -> nhiém acid chuyén hod mat bu, RI nude dign gidi trong va ngoai tb, ddng thoi gay nhiém doc TK => bn hn mé, tut HA - H6n mé do tang dp luc thdm thdu mau hay xdy ra & bn dai duéng typ I + Tang glucose méu: Itic dau tang 4p lye tham théu ngogi bao -> kéo nude ra ngoai > gay mat nuéc trong tb + Tang glucose m4u -> da niéu tham thau va tinh trang ting théng khi (do nhiém acid) > mat nue ngoai tb => gidm cung cAp mau cho nao -> HA tut > hon mé - Nhiém khudn: glucose mau tang cao -> gidm strc dé khang, giam tao KT, gidm kha nang thy bao vi thiéu nang long => tao diéu kién thuan Igi cho cdc VSV phat trién (lién cau, ty cau, truc khuan lao..) -> bn dai dudng thudng bj myn nhot, loét hoai ti, lao phéi - Tén thuong thodi hod TK, mach mau + Do tb TK tich luy dung cén sorbitol, Fructose -> do qué trinh tham thau thy déng va bat thuong cia glucose mét each thir phat ( do glucose mu man tinh)mang day, ting tinh t cholesterol méu, ting HA, suy vanh, bénh ly vong mac ( xudt huyét vong mac, phi vong mac...), bénh ly vé TK ( liét day TK, tn thong TK ngoai bién)