Acid uric v bnh gout

1.CHUYN HO PURIN V S TO THNH ACID URIC Axit uric l sn phm cui cng ca qu trnh thoi bin purine. L mt acid yu nn thng b ion ha thnh mui urate ha tan trong huyt tng .i a s tn ti di dng monosodium urate. Gii hn ho tan ca mui urat khong 6,8 mg/dl nhit 37 0C. nng cao hn cc tinh th urate s b kt ta. Tuy nhin, trong mt s trng hp cc tinh th urate khng b kt ta, phi chng do nh hng ca mt s cht ha tan trong huyt thanh. Phn ln acid uric trong mu dng t do, ch khong <4% gn vi protein huyt thanh. Nng axit uric mu trung bnh nam: 5,1 1,0 mg/dl (420 mol/lt) n 4,0 1mg/dl (360 mol/lt). Khi nng axit uric mu vt qua gii hn trn c coi l c tng axit uric. Bnh thng qu trnh tng hp v bi tit axit uric trng thi cn bng. Tng lng axit uric trong c th c khong 1200 mg ( nam), 600 mg ( n) Khong 2/3 tng lng acid uric c tng hp mi v cng vi s lng tng t o thi ch yu qua thn. Trong nc tiu, acid uric ha tan d dng hn trong nc. pH nc tiu nh hng ln n s ha tan acid uric, bnh thng lng acid uric thi qua nc tiu l trn 800 mg/ngy. Do vy, pH cng kim cng thun li cho vic thi acid uric v ngc li nc tiu cng toan th kh khn cho vic o thi acid uric. - pH 5,0: Acid uric bo ha vi nng t 390-900 mol/L - pH 7,0: Acid uric bo ha vi nng t 9480-12000 mol/L CU TO ACID URIC

cu to ca acid uric

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Acid uric v bnh gout

S TM TT QU TRNH TNG HP ACID URIC NGI

S chuyn ho purine (theo Segmilla, Rosenblsom Kelley: 1967). S chuyn ho purine (theo Segmilla, Rosenblsom Kelley: 1967). 1: Amidophoribosyl ferase. 2: Hypoxanthine- Guanine phospho ribosyl Transferase. 3: Phosphoribosyl-Pyrophosphat Synthetase- (PRPP Synthetase). 4: Adenine-Phosphoribosyl transferase. 5: Adenosine deaminase. 6: Purine-Nucleoside Phosphorylase. 7: Nucleotidase. 8: Xanthine oxydase. 2. NGUYN NHN V PHN LOI TNG ACID URIC MU: Tng axit uric mu c th do: + Tng tng hp axit uric mu: c th do n nhiu thc n c cha purin, tng tng hp purin ni sinh, tng thoi bin nucleotite hoc phi hp. + Gim bi tit axit uric qua thn: c th do gim lc cu thn, gim tit urat ng thn hoc phi hp. + Phi hp 2 nguyn nhn k trn. 2.1. Tng tng hp axit uric: + Tng axit uric mu tin pht: Khng r nguyn nhn. Thiu HGPRT (mt phn hay ton b). Tng hot tnh men PRPP synthetase. + Tng axit uric mu th pht: n qu nhiu thc n c purine. Tng ti to nucleotite. Tng thoi ho ATP. Bnh d tr glycogen. Bnh c nng. Vin Gt www.benhgout.com

Acid uric v bnh gout

2.2. Gim bi tit axit uric: + Tng axit uric mu tin pht. Khng r nguyn nhn. + Tng axit uric mu th pht: . Suy thn. . c ch bi tit urat ng thn. . Tng ti hp thu urat ng thn. + C ch cha xc nh r: . Tng huyt p . Cng chc nng tuyn cn gip . Mt s thuc lm tng axit uric mu (cyclosporine, pyrazinamide, ethambutol, liu thp aspirin). . Bnh thn do nhim c ch. 2.3. Tng axit uric mu do nguyn nhn phi hp: + Lm dng ru. + Thiu oxy v gim bo ho oxy t chc. + Thiu ht glucose-6-phosphatase. + Thiu ht fructose-1-phosphate-aldolase. 2.4. Cc quan nim mi v gen Ti Anh quc, s ngi mc phi bnh gt tng hng nm v nguyn nhn c cho l v h n ung khng iu .Tuy nhin, mt cuc th nghim gene trn mt mu hn 12 ngn ngi, c cng b trn tp ch Nature Genetics, pht hin rng mt gene c th l nguyn nhn a n s gia tng ny. Cc nh nghin cu thuc n v MRC Human Genetics Unit, ti thnh ph Edinburgh, ni rng gene ny v cht protein m gene kim sot, c th mt ngy no l ch nghin cu ch to ra thuc mi tr bnh ny.Mt s ngi c nguy c cao hn hoc thp hn mc phi bnh gt ty theo gene m h tha hng Trong mt c th khe mnh, acid uric, mt cht ph thi xut hin trong mu, c thn lc ra v thi khi c th qua ng nc tiu.Tuy nhin, mt s ngi, thn khng lm c chc nng ny mt cch trit , v acid uric tch t trong mu, kt thnh tinh th cc khp xng v dn n tnh trng vim, gy au nhc cho ngi bnh. Cc khoa hc gia ti n v MRC Human Genetics nghin cu v bnh ny v khm ph ra rng gene vi k hiu SLC2A , c th lm cho c th kh thi cht acid uric ra khi mu. Gio s Alan Wright, hin ang hng dn cng trnh nghin cu ny, ni: Gene ny l mt nhn t then cht trong vic chuyn ti acid uric qua cc vng khc nhau ca thn. ng nghip ca ng l gio s Harry Campbell ni : Mt s ngi c nguy c cao hn hoc thp hn mc phi bnh gt ty theo gene m h tha hng. Pht hin ny s gip cho vic pht trin cc phng thc tt hn chn on bnh gt. 2.5. Lin quan gia axit uric vi ung ru bia Vin Gt www.benhgout.com

Acid uric v bnh gout

Ung nhiu ru bia lm tng d ho cc nucleotid c nhn purin, lm tng d ha ATP thnh AMP gy tng sn xut axit uric. Ru cn c th gy mt nc v lm tng axit lactic mu. Khi ung ru cng vi cc n th mt mt bn thn ru b sung mt lng purin, mt khc cn hn ch bi tit urat qua nc tiu, to iu kn gi li purin ca thc n v tng qu trnh tinh th ho cc urat nc tiu v t bo. 3.TNG ACID URIC L YU T NGUY C TRC TIP CA BNH GT 3.1.T l mc bnh Tng acid uric mu gp 2-13% ngi ln - Ch c < 10% c biu hin bnh gt phi iu tr. C n 90% trng hp tng acid uric n thun khng triu chng (Hyperucicemia) - Tuy nhin ngi ta thy acid uric mu bnh thng 30% bnh nhn gt cp - Mc acid uric mu cng cao th nguy c mc bnh gt cng cao. - T l mc bnh gt ngy cng gia tng trn ton th gii. Tc gi Roddy v CS tng hp bo co cc nguyn nhn chnh gy bnh gt ti EULAR 2008 nh sau: + Tng lng tiu th bia ,ru cng ng + Tng s dng Thiazide v aspirin trong cc bnh l tim mch + Tng s dng ch n giu purin + Gia tng cc bnh l chuyn ha v bo ph + Gia tng t l ngi gi > 65 tui, c s lin quan n thoi ha khp + Gia tng v ko di cuc sng ca cc bnh nhn suy thn mn. 3.2. C ch lng ng axit uric C ch ch yu l do tng axit uric mu ko di, c th c hng lot phn ng thch nghi nhm gim axit uric trong mu bng cch: tng bi tit qua thn, lng ng mui urat trong cc t chc nh: mng hot dch, da, k thn, gn Dn n s bin i v hnh thi hc cc t chc ny. Tng axit uric trong dch khp dn n kt ta thnh cc tinh th hnh kim gy tn thng sn, mng hot dch, bao khp. Qua ch sn b tn thng cc tinh th xm nhp xung tn lp xng di sn, hnh thnh cc ht tophi, gy ph hu xng di dng khuyt xng hnh cu. Vim mng hot dch, tng sinh mng hot dch, thm nhim cc t bo lympho l tn thng th pht. S lng ng cc tinh th t chc to thnh cc ht tophi kch thc to nh khc nhau. Lng ng tinh th urat k thn dn n tn thng thn nh si thn, vim thn k, x ha cu thn. Tn thng lan rng dn n suy thn, tng huyt p. y l yu t tin lng quan trng. Vin Gt www.benhgout.com

Acid uric v bnh gout

4. ACID URIC L YU T NGUY C C LP CA BNH TIM MCH Tng acid uric l yu t nguy c cho bnh tim mch v l yu t nguy c c lp ca t vong tim mch. Tuy nhin c quan im tri chiu nh sau: Trong nghin cu Framingham, mc d nng acid uric c tng quan vi bnh tim mch ph n, nhng sau khi hiu chnh theo cc yu t nguy c khc v s dng li tiu th s tng quan khng c ngha. Ngc li d liu ca NHANES 1 cho thy c mi tng quan mnh v c lp ca nng acid uric vi t vong tim mch. Mi tng quan mnh n so vi nam, ngi da en hn ngi da trng, v ngi trn 45 tui. S khc bit v kt qu ca 2 nghin cu c gii thch l do dn s khc nhau, trong nghin cu Framingham dn s tuyn chn a s l ngi da trng v tng lp trung lu, trong khi NHANES 1 ly ton b dn s chung l ngi M. Ngoi ra t l t vong ton b ca NHANES cao gn gp i so vi nghin cu Framingham, iu ny mt ln na khng nh s khc bit v dn s chn nghin cu. Ti sao acid uric khng lun lun l yu t nguy c c lp tim mch qua cc nghin cu? Nu acid uric gy ra bnh tim mch l do hu qu ca tng huyt p v suy thn th acid uric khng c xem l c lp vi tng huyt p v suy thn khi nh gi yu t nguy c tim mch. Trong th nghim SHEP, li tiu lm gim nguy c t vong tim mch ngi ln tui, tuy nhin phn tch di nhm cho thy tc dng bo v mt i khi iu tr li tiu cho bnh nhn c tng acid uric. Do mi lin quan gia acid uric vi bin c tim mch s gim i khi c tng huyt p hoc s dng li tiu. Mt nguyn nhn khc l do c tnh chng oxy ha ca acid uric. Mi lin quan gia acid uric v bin c tim mch theo hnh ch J, trong phn thp nht l t phn v th hai. iu ny c th c gii thch bi khi nng acid uric qu thp th tc dng chng oxy ha gim cng s gy bin c tim mch, cn khi nng acid uric qu cao s nh hng ln mch mu v huyt p gy bin c tim mch. Mi tng quan acid uric vi bnh l tim mch cng nh t vong do tim mch c xc nh trong cc nhm dn s nghin cu bao gm nhng ngi khe mnh cho n nhng bnh nhn i tho ng, suy tim, bnh mch vnh, tng huyt p. Bnh nhn tng huyt p vi tng acid uric s c nguy c bnh mch vnh, bnh mch no gp 3-5 ln so vi khng tng acid uric. Bnh nhn suy tim, tng acid uric c gi tr tin on t vong. Bnh nhn bnh mch vnh tng acid uric c nguy c t vong tng gp 5 ln. Vi mi mc tng 1mg/dl acid uric tng ng vi tng 26% t vong. bnh nhn i tho ng tp 2 c tng acid uric, tn sut t qu v t vong chung cng nh t vong do t qu u gia tng. Rt nhiu cc nghin cu cho thy acid uric l yu t nguy c c lp cho bnh tim mch sau khi hiu chnh. Do cho n hin nay, acid uric vn ng vai tr trong c ch bnh sinh ca bnh tim mch, bnh tng huyt p v bnh thn. Gi thuyt trn cn c ng h bi nghin cu cho thy tr em c tng acid uric s c nguy c bnh tng huyt p khi trng thnh v khi pht tng huyt p kh sm. 5. CC BNH L C TH I KM VI TNG ACID URIC V BNH GOUT 5.1. BO PH: C s lin quan gia trng lng c th v nng acid uric mu. T l bnh gout tng r rt nhng ngi c trng lng c th tng trn 10 %. Bo ph lm tng tng hp acid uric mu v lm gim thi acid uric niu, kt hp ca c 2 nguyn Vin Gt www.benhgout.com

Acid uric v bnh gout

nhn gy tng acid uric mu. Theo cc thng k gn y, 50 % bnh nhn gout c d cn trn 20 % trng lng c th. 5.2. TNG LIPIDE MU: S kt hp gia tng TG mu v tng acid uric mu c xc nh chc chn. C n 80 % ngi tng TG mu c s phi hp ca tng acid uric mu, v khong 50%-70% bnh nhn gout c km tng TG mu. bnh nhn gout, ngoi s ri lon ca thnh phn TG, ngi ta cn nhn thy c s ri lon ca HDL, mt loi lipoprotein c li, c tnh bo v i vi c th. S lin quan gia gout v ri lon lipid mu chnh l mt phn ca hi chng chuyn ho bao gm tng BMI, bo ph vng bng, tng TG, gim HDL, tng huyt p, tiu ng, tnh trng khng insulin v nguy c b bnh mch vnh. Tng acid uric mu kt hp vi bo ph vng bng l nhm nguy c cao ca bnh tim mch c lin quan n s khng insulin. 5.3. I THO NG: Bnh l i tho ng, c bit l i tho ng typ 2 l bnh l thng gp i km vi Gout. Bnh l i tho ng nm trong hi chng ri lon chuyn ho chung. Bnh c c trng bi s tng ng huyt, m nguyn nhn chnh do thiu ht Insulin tuyt i hoc tng i. Bnh l i tho ng bnh nhn Gout thng do s khng Insulin. Vic kt hp nhiu bnh lm cho vic iu tr gp kh khn, i hi phi kt hp tt iu tr nhiu bnh cng mt lc, v mt ch dinh dng hp l 5.4. TNG HUYT P: Tng acid uric mu c pht hin 22 38 % bnh nhn tng huyt p khng c iu tr. T l bnh gout trong dn s tng huyt p l 2 12 %. Mc d t l tng acid uric mu tng i tng tng huyt p nhng khng c s lin quan gia acid uric mu v tr s huyt p. C 25 50 % bnh nhn gout c km tng huyt p, ch yu cc bnh nhn bo ph. Nguyn nhn gy nn mi lin h gia bnh gout v tng huyt p hin nay cha c bit r. 5.5. NHI MU C TIM: nhng bnh nhn tng acid uric mu c 20,1% b hi chng chuyn ha, trong khi bnh nhn khng tng acid uric mu th con s ny l 15,3%. ng thi, tng acid uric mu c lin quan vi tng nguy c nhi mu c tim v t t do tim nhng bnh nhn c hi chng chuyn ha. 5.6. Va x ng mch: Cc nghin cu gn y ch r mi lin quan gia gout v x m ng mch. Tuy vy tng acid uric mu khng phi l yu t nguy c trc tip ca bnh mch vnh. Tng huyt p, tiu ng, x m ng mch lin quan nhiu n tnh trng bo ph hn l lin quan n s tng acid uric mu. bnh nhn gout, cc yu t nguy c ca bnh mch vnh nh tng huyt p, bo ph, khng insulin, tng TG mu gp phn lm tng s lin quan gia acid uric mu v x m ng mch. Cc yu t Vin Gt www.benhgout.com

Acid uric v bnh gout

nguy c ny t n lm tng nguy c ca bnh tim mch, v nh vy, acid uric mu ch gin tip lm tng nguy c t t do bnh tim mch thng qua vic kt hp vi cc bnh l c nguy c cao ni trn. Ti liu tham kho: 1. Trn Ngc n, T Diu Yn. Biu hin lm sng cu 121 trng hp Gt iu tr ti Bnh vin Bch mai (1985 1994). Hi ngh ton quc ln th III v cc bnh thp khp. lt thng 3 nm 1996. 2. on Vn (2009). Bnh gt. Bnh hc ni khoa-HVQY.tr 39 3. H Th Ngc Dung, Chu Ngc Hoa. (2009). Nng acid uric huyt thanh bnh nhn tng huyt p. Y hc thnh ph H Ch Minh, 13, 41-46. 4. Chu Ngc Hoa, L Hoi Nam. (2009). Kho st nng acid uric huyt thanh bnh nhn tng huyt p v ngi bnh thng. Y hc thnh ph H Ch Minh, 13, 87-91. 5. Hong Quc Ha. (2007). Kho st nng acid uric mu bnh nhn tng huyt p. Y hc thnh ph H Ch Minh, 11, 39-43. 6. L Anh Th v CS. c dim ca 254 bnh nhn Gout iu tr ti Bnh vin Ch Ry 1999 2001. i hi Thp khp hc ton quc, Nha trang 8/2002 7. L Anh Th (2012). Cp nht chn on v iu tr bnh gt. Cp nht kin thc iu tr bnh l c xng khp.Tr 48 8. Textbook of Rheumatology (2009) -08th ed. 9. Alderman, M. H. (2007). Podagra, Uric acid and cardiovascular disease. Circulation, 116, 880-883. 10. Feig, D. I. (2008). Uric acid and cardiovascular risk. The new England journal of medicine, 359, 1811-1821. 11. Melinda K. Kutzing, B. L. F. (2007). Altered uric acid levels and disease states The journal of pharmacology and experimental therapeutics, 324, 1-7. 12. MY Nadkar, V. J. (2008). Serum uric acid in acute myocardial infarction. JAPI, 56, 759-762. 13. Richard J. Johnson, D.-H. K. (2003). Is there a pathogenetic for uric acid in hypertension and cardiovascular and renal disease? Hypertension, 41, 1183-1190. 14. Sanghamitra Pati, P. K. S. (2004). The role of uric acid in cardiovascular disease and its clinical implications. Orissa Journal of Medical Biochesmistry, 1, 39-43. 15. Viazzi, F. (2006). Serum uric acid as a risk factor for cardiovascular and renal disease: an old controversy revived. The journal of clinical hypertension, 8, 510-518. Bs Nguyn Vn Dng Vin Gt Tp H Ch Minh

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