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Bài giảng DLS2_Gout_Thầy Tuấn Dũng
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"-I "•
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S«Aji~~~ sJi-th~VI ~- -----r chui. Cu1
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( / ~~5) n kt1::,~ c-kub c-r.' In',£~ c.ku'11~ ____ .
k.t:~_l- tor~ / \ Xa.t ~~ "J~f}~ c~~ ~b' ct•rcl t~· it Ceto
*
- {.1.1 1- . _., 1, .. / "'' ,.«.\'\on 1- ·c-i~nca -)h uoc. c \l t ca ... )~~., b" -)'-Ia~ cto~ j1o/ J.:.t<~ Jq- c-11:<&-o .'!!
R.6/ koc•fl ki 1,,-d ku·~~- ~J muol'\
/ 1' +I!) L ~ +~'P ..,fhf c-t~.,.c
~ I J.? t "'' _.~" ....
\/a(})CMRAJ
'~~' LI>L ~ ~~ ~~ C"->... ~ ctwt
"' ... . 0 StJ DVNG THU ·. C TRONG fli~U TRI seNH GOUT.
Figur~ I. The Gom (1799), ~;· thr: trrfisr }t~mrf Gillr.l)', dt>pirts :ht disr.:ue f',.J au ~t·il dermm aiiJtckhT .. ~;: toe.
TS. Nguyen Tuftn Diing
NQIDUNG
1. f)Qi r.tmng 2. B~nh sinh 3. Phan lo~i 4. Yeu to nguy CO'
5. Ch~n doan 6. Yeu to anh hU'&ng ket qua xet nghi~m 7. M¢t so di§m c~n IU'u y v§ b~nh gout B. Dien tien b~nh gout 9. Di§u t~ 10. Bien chl.fng b~nh gout 11. Cac kh6 khan khi di§u tri gout
p0;vuJv~ GUD~}-
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fllupn C(;ft;. t1tamr; JYF 1/35
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I I I f I I. ,I f._ I .II I ~ l .-. 1 1 11. C'Cl• A\Oei ,~,(_nor .x C\ I) Jt.n" e:.u" ''l.\0. ~ 1-a
~ ~'' A-c.hc:f G-o~.tr _ __ _ h - ( I _.f -lil "" Jl ( l • I ) n C\ q1""Ctu c ru. ~ em tjU'<tc ,,. e-n;- it
1· GOUT?
* Tay PhU'O'ng : giQt djch dQng l~i trong kh&p
*Dong PhU'O'ng : t~c nghen dU'ang kinh l~c lam sU'ng dau
dii' d(>i m(>t s6 kh&p (t~6~phOIJQ)
e=;I·C\,\ nhlic' ell> A"" ~ hon1. b~-' _k,,; ~ Vl'l f.t~~
• The disease of Kings and th~ Kl~f Dlsea~es •
6/hh (.!.\~ VIi"-. q If 'Jill
Yll"- U A(I <::-etc_ ,XCie>.l !le.r~ It
r.t. h~,h tuG ~~~C! ~·rii"l, ~ c--bt, nb{ =l,f cftc
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f ttL ft11d ~4 ( , C.<>
( 'l c:lrt c;r --HD l-. ,
I cxralll
I - r ~) T"ClVj~ I C.O c.f-tt1fl.1
LDL .. )
/ (c<Y (l~a~
I {, I I I -;fh OC\1 A>. C>C\ /..c.. ' cf ( Od-to cw-4hr-i1i ~ )
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..,-=---- /, gt ~Q..b(\~ J[ , 'Vlstm A.<.bor dC!?a -Jhop ( J<Jw.,tl'la-lo>c\
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R'-"'atold Aothrl*l$ vl,x."ro A'{ ""h rl.ctl'lq -;iM0 2.1 mllllo•. f ' J r
Ao>kylosl~g Spondylitis c.,{~<! t. b .:f 318,000 ~ (,<, I'
Arth~~ I ~~ "A V1 R...f() ,u.h clr ii\ 1\)l-"' "'t' I.JI..v\
nly t U• ft /6 Mol cit
~~ ~ v~~ 'Jotlr -t~o [acid uric]
· "* !(\,; (\~o [ C\c.tcl u.(r-c.1
I" I_ 9f /n( ~ {. 'X )'.0) ; \ .£1 ., C ,U) • '
> 3 "'<a/dl <6 6--7 7·8 8-9 >9 · Serum uric acid (mg!dl..)
Percent with gout
1$44 . . 45-64 .. ' 65+. : Age
http://www.medicine.ox.ac.uk/bandolier/booth/gout/prev.html
- f I A lcll\ h"'ltd \.. ~~\ ~0
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A I - ' ,1 I -1 / .tl t /lA&:[" {)' t' _ -1~=e - v Cj011r -Brj ')(9 A.ctc\t15:,o c:ct., ceu -7'l<.a nher~ ~> ;c,"'(
F H -fhl t ( C<> ( rf,~ ~ 0. ._,d ) "Vi. ct)l.l\'\ ' r ~~ ( ,/ ~~\, )<;;;,.) ~ \:. oO •hi£. -lhrt -7 a<r<lu:":_ ~~i.~~ 3'111 n«_d , / -~- )\a.c..c -> -\·n•J Aoc.. G\.c1 cl Uvl(, -> .;\a.o +~ ct[..
f I I hC\. vch nU'd£ 'PO ~o.Ji iltJO'c
1.1
rh~ c :1 11~ - < , _ 1 " j .. ,- J I I
"' -"7 M. c'\\1 C.l}l..flll f\Oq 2· eeNH SINH
)_.,. -,..A f /~Cil ~ Jfn ~ictt . I
i
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Normal
c \J.' ~ c\1'\ t.,ti\i.' ptl.l"if'l ..
70% renal excretion
j i j
I 8Gne. ere sums
Synovium ... f.._ _____ :r~·~·~. -~~ ) j • '"><.u,.,, crl,'tals / 1 1
, !'l • ( io a lop U$
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Gout
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D!i>\.. ~\·
ntestiiJe aruc,..l 1 .
.;..!J~
Pyritnkilnes
w:ine
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Nitrogenous Bases of RNA
H'\, / H 0 H
Guan;ne II H
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eN/
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ctd-d .dl~h vi:· I .. Acid hoa RNA & DNA) ,
ldrc~ "'-Nucleotides
) j,Jl ~ Mononucleotides It- · I ·~
Purines ~ C tll~'t ~ I)
Pyrimidines <r- ( .Jh; ~ ltj C\ )
.~x::r o!"' 4.;
H,rf·' ·. "'-~,.......o., .
I ~
. i N ! H Purines
-01~0 .,. . Ti!'IMlNE f! DNA ~- j'
H li
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0 11!NA .,.
J' <\_._"uiN~ ~ ~
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OEOXYRU30SE;( ,· \. "'·
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RNA 11;'-';)-1 ti1-{'~
ott OH R!BO,SE
5
5/35
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~ CoQd\; c.~~ -7 n1 c~l\ .A~ .-h"J ef~va bC\.ch c.c£
-" • A. I. I I ..l_J\ <j 9 '\II)LtY\ -/' A<. Co -h:tc. .,.-Ill~
, , _ .~ 1-
1- Acid uric & n6ng d9 qua bao hOa se l~ng d<;>ng trong cac S~.Jn kh&p.
2- T~ bao mang ho~t djch (synoviocytes) tht,Yc bao tinh th~ acid uric va ph6ng thich cac ch~t trung gian h6a h9c gay viem nhU' Prostaglandin, enzyme cua lysosome, IL-1, ...
3 - Do h6a hU'&ng d9ng cac ch~t n~y loi keo va ho~t h6a cac b~ch ~u da nhan, b~ch ~u aO'n nhan (dii!i tht,Yc bao). Cac dii!i tht,Yc bao tieu huy cac tinh th~ urat va ph6ng thich leukotrien va cac ch~t trung gian gay viem lam n~ng them qua trinh vi om
/ <cJ-4crce-
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* lrc. -riY-·~ c\1.\n~ ~ NSAID 1
1o...,.-Clo.tafV\oQ.. , co(fic om 3- PHAN LOAI . . . . . . . . . -'7 €.
1 ..J, cbt_, -\h~\'j -(f~i;;.'(;, _.I ' I . o\ ,~ <{
nJI-.ll Co /rl.l~\.1 4ll<l -7 ).._ Gout nguyen phat (95%) - r6i loc;tn chuy~n h6a purin .
tc.l.~ dun1 cufchi c..\n. - r6i loc;tn trong si,J' dao thai
acid uric
(di truy~n . h(li chti'ng chuyen h6a va thll<'Yng xay
ra & nam gi&i tu6i !rung niem)
Gout thLI' phat (5%) do cac b~nh ly khac ho~c do sll'
d1,mg thu6c (nCr chi~m tY I~ cao)
.j,., Q~-lro~"- - ::> 1\ ~~ Ca<ll+ -> 1' la~oa tt n-c....
S ct" c-+B~ ~od .lri 1 _,c:q -fd ( . . '
~ ohc:U:; iht..t~~ - > rhc/ .-lh.~ tL -> t- ctcicl tt(ft_
6
6/35
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d. ~<Sn~ ~dr{ llac.f-ctl- -7 p11 tlc/.fl~ C}f"<'l~ -? ,&;' c! (jh..:~u- rn on ~ct~n· ura.t ( /YlSUr)
M~ dtt~ ..j.-dnd -{l)~T\\ ( Stk 1-"lg-'l)
4· Yi!U TO NGUY CO
~·- --~· ,,· .. --.. ~~_....,,
\ . ~~· . ;:e.
'. ~:::.~ ~'F~:%~~,
Risk factors and symptoms to avoid Gout coomonly strikes between the ages of30 and 50, usuaUy oca.rring il men aod; tess often., women in menopause. Avoidi1'1Q c»rtaln foods high in purine and keepiQg we;lght down are CO!ltrollab!e risk fadors.
Risky foods
Anchovies,~,..,.,...~ t>erringlsardines · •-..;,, ·· •
~~ Kidney, (!}.~· •
fiver1 .heart and 'V · . bfllln, gra\ies, . sweetbreads ,.. .
broths w.d COO: ~ .. .,..~~: Olrn!rrisk faclo<s include sudden - illne5s. crO<h des. joint irjuty and chemoih!!rapy
SOURce;s:A_rtru1t5-~0UI$bon.. !be Mmt .&.tar.U'ti-D1M£'4bl L"ITQnr~ •N>
.J. chi 0 -1-hd, ~<.td l,I.(\-C..
purirt.
J\ ..1._..\ I va:.' c:-1~4 ~UCt
, r 1 --::>- rna~ nU"oc
7
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7/35
/\... fJ A? A "7 ~ vonj kln '1\\C\O
.,
·. * bl~h R.L Lfr-cl )tuf-~ clun 1 ac.l d n i c oJio c. J.f
. -tJ- nhd"cJ acid nl~o-hnlc..
:· Je~,; Ja.rr. -L ~0 -Mld: ,:t,;cl 1M ft.
cl-.', i ' AJ.(opu rino Q.
+ { ('"'"'> ) 7clr1":! A\ etc lei tl<t C.. 1 . , .. f(_ ,. ., J.
' -......._ V<=>j 1'\}..1'\
ckn 'i Afi o pluinoX 4- h.,_~~
'jotd nWo':\ hi elw fer-1 J )\ 1 J., \, ). 7 .A
~~~" "~ tV-" tl•.q v'J fU'-0
}c.t~ f- Qu(l \ltlC. -7' )~ cliin~ il).lo puinaf -&--- ( ~ ' ~, _.,... v-o,, ~ / q,, C(l.\etl)
~ , / l'a."') ~C\.1'\ ')(tle1.~
b~<~ r~'
7 ) ' ,q!£191 ba., ·hJ1l-
' . bR.o pht "'-? ""' "":! M-n
r J.' Ill ~pr-d A1.~1-
. !f J. I
A1Curc.MllaQ ->- -b:t f~ "'.:''! AA-•'
:7 -lA~" caot~\- ~ .;\ ~~-C\
Cl~d oi~o~nrc. _;,clun·~r-8- IZL)irrd .b.y~
}.e.vo clopa.. _7 ;,\ii,, .l c. h6 .A ~ rt\
Risk Factors for the Dev elopment of Gout Ag in g
H~gher prevalence of gout and clinu:~lly significant hyperuricemia in higher age groups
~ 50
" . ; 0 " .., w g JS
... ~a
~ 2S
"' lS ~)
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~ 10 .. /'
·;-.......
•1e r~ ... ~;:,.:·-:: ..... _ ....... ~ .. ~d'~·---:--:~ -&- 1 a-~ , . -· ~~
.... ;-·· 65--7.1
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. .:.-- $.-.! -::- -- ~-:~
~ s a: ol-"'··;· ~ ~--»--: ~ a~ .. --~r-:---:-~2-
1990 1991 1991 199J 1~ 199) 1996 1113i 1~9a 1 ~99
Wolla<: o <I x . J Rhoum. 20 0.1:31(8):1582-1587.
~ Y~u t6 nguy CO' v~ Sl! phat tri~n b~nh gout theo tu6i
,.I _L~ \ ' ' l - ( /..a ) ~,oc. e'IOC.. ~~ je\t.l 6 v I< A I I J .l ~ -'-' J )I ~ "'"'a· A<-\ ,~,,"ca ~ ""ttl /
/ ~ - ? A-/ c- l
00'r.Cj /\.._ .\,·~" C • I .-1 (·--~"'1 . C6 f\~ f\~ "r:f
Ting san xu6t acid· urJ¢ / .
' "' ( ::\"~ I I .I ' ~ ~\c, 1,11GI.t'kl c 0 dl!, c{;~) Dinh dU'6'ng
Y~u t6 huyE§t h9c
Thu6c
YE§u t6 di truy~n
Y~u t6 khac
Th(rc an 9hi~u purin, nhi~u fructose
R6i IQarfsl! tang sinh tuy xU'ang, tang h6ng du
Thu6c tytotoxic, Vit B12
Thi~u h~,Jt Glucose-6-phosphate, thiE§u HPRT,
Nghi~n 11J'Q'U, ~ph~ . ~Y. n~r1J @!{;j ~cerid~atiJ/ hQat d¢ng qua m(rc ~ Uipr.
'7 :11::: c ~~~ c:lo~n -'(9';.,~ ;h?p acid t.lr'ic...
I ,J ..-1\ua:e~
.Giim bal tlit acid uric Cl thtn Thu6c Cyclosporin, lq.i ti~u thiazide, lqi ti~u quai, ethambutol,
aspirin)'~utfiaPJ l~vo.aopa,J~:Ui£Qt@9J .
' Th~n Cao ~uy~t ap, b¢nQ1th~n da nang, suy th~n man
Chuy~n h6a/n¢i tiM MM/nU'&c, nhi~m l lactic, suy giap, wang ~n giap,
YE§u t6 Khac ~ phL;'sarcoidj nhiem d¢c thai ky, nhi~m chi
_l _ -- _/ __ _ --
\ ,, '(A'. f.-.' A\. .1.-- II. " 0~· \ ' P"'" ~"" c..o -> T - •ao ~n,
-t}- b ~"..~ pa-fk."n ~0•'\. (. c-lun~ c:ha ,\~ n:\ )
(~>:' ,"6J c~ JJa:~~ 1-,cl c{o~ m;,l -..a C(QVcho..QI~ )
8
, , __ ' J ,, ~.~ -~ l f -~ 'J ~ A4 0 (1\ct\'\1 ~·rof > :JV l)< <>i ~ 'I.e c- oyn.f"'t 'l
-//\ b 1( .,..liJn<'( ~lt·Jc ch11-:'/ c/o;ct«11on -v--;- _f_c que< /l> cm _'f _,\c-;;. m~u: J:!V "-, r r
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.&: ~ Jz;.o -th a:-lA<-tcl u«G-
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( ~~'-~ ..rhn C ) ._hq
C ctfV\.
(l~'l, -~ r+f c~u 4 ~q,-
)c h til\ 1 .,.-h:r~ )
'y ,...
N wd~::;;a:~~
Gout va Sl,J' tieu thl) fructoz --J \ Rf 1 1~~ ~, _.fW{of(._ 1\;R_(,_ ~
10 ~ ~~ ~ b~~h 1ol.l+ "J-1" 1-t,.'O~ 0. ::1 ':...Vlt!l c -~ so~
0~ u.§ 40 (!IV) c £ -g_ 30 u E :::l ::1
~ C! 20 .c8 .~ :I:
PM cl "~ lOl l
<1/ u c
6 ~-~8 ........ .... ~
4 0.. ~ ..., ...... :::l 0 (!) .
0 0 1970 1976 1986 1996
Sucrose
Rho et al (2011)- USA £>.CH,OH ~,OH .
HO OH I 0 CH,oH
OH OH '---,-----' ~ G~ fNctose
I 1' """" .... .. , __ ..... """ , .... """ .. ... ....__ .....
~··- . " ' 'V' '--' .. (f
Thuoac la•m talng thaOI acid uric I n66uc tfeAu / ~-(~ c.hC\0\, r com.-
Acetahexamlde crtfa.t Meclofenamate
ACTH&GC Dlcumarol Merbazone
~II!PJI[InoiJ Diflunisal Phenylbutazone
Acid ascorbic §ti'Oijens) Phenolsulfophtaleln
Benzbromazon Glyceryl ProiJineciCIJ guaiacolate
Calcitonin Glycopyr..Oiate Sallcylates
Chloprothlxene Halogenate Sulpyrazole ,
M~ ~··1- -"7 .k\w,r~ b il.h .h~ ( on ith({ etil c.! ~-;,~ )c.l~,
I hnh e:tuc.l
( r
/-h.- 4 }4;111
~ + 1c_.._-<Yl .\ cv.J . ---:> ~ ~~let; a.~;A u..-R. j
9
9/35
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6 ' bn )u.n h~ " I A
c\o .3 n~l~\\ i\1\C\1\
J I ~I 11\ ~
Cl'l.<.. CO CU\ '
-+ A-5 1'
t-a-~ 1 P"ctf ~ 1(-t
I nuoc <:a ll\.
/
.. \"" () ~(~So~ an clw Gl
/ A - "'1dh.,.. c ~"~ ddf)
b - ~:L =!.Jo r11d- ( ;;:1-tn~ "A"'~.:.. , safb ~,,f«M a£ __ ) ----"" c Co r.fico·t.d
5- CHAN aoAN
I (;,!,0<;,
/" ~· I
"'"' # ; _,
/
cs 1 / 1 I I I ·h / ( ~/ { J. •> fl f I L ,f I r f • T !hOC\\ I\"'C•C\ 4t< Of Xu q l· mi,~:.~ cJ J,..Qt. t~,OI op Cf\U1 ,.W:t
1 I , I .1. I V ( I Il L ..u t~.or ~o, , Jrqn'J , c.~,-
.t, ,' r v ,:. on,_ illaL~.l~~ , c~---. A I I ( ' II. I I ,f • A I \ • ,
-f;; "vi llll\ c6, A_( I' op \11 SL tlL \'\ o n ~ J r }
. A- / ., I _,J ,, * q 0 ut ( Vl PY\ i ,kh tr( 1 bat~~ ~"<il ) - Lam sang
Gout c6 d~c di§m Ia m9t trong nhO>ng b~nh dU'Q'C
ch~n doan qu_a khai thac Q_~nh sll'
Gout dU'Q'c righi nga khi bjnh nhan khai c6 nhO>ng can
viem dau kh&p l~p di l~p l~i & kh&p ~- Ke d6 Ia kh&p , I ,_ A / I I ' ..1 A[ 1. - ·I
.1: h~ ' ~. (\t!O !l c (I C<I'l Ccu .Ail 1:11 .,;Trur ' [)..14') co c an va go1. ~ ·
Gout thU'ang chi bi m6i l~n m9t kh&p trong khi &
nhO>ng b~nh khac nhU' lupus, viem da kh&p d~ng th~p.
thU'ang bi nhi§u kh&p cung m9t luc.
10
10/35
. ' ~ -
· ,
....
lil:==:.;:..
Gout Attack l ocations
Ft1s• toe evef'!~l~l ly aft'e<n:d In~ o11~tvld"~~'!"~90':'t
/ ~ c~ l ~~ "'.' f mer/ dt· ( [o.crd UtrG 1/ C~n 13m sang / ~)
Nam
NiP
Nbng dQ acid uric trong nLP&c ti~u I 24 gia
250-800 .{mg} I 24 giiY
250-750 mg /24 giiY
1.5-4.8.(ymQj}/24
1.5-4.5 mcmol/ 24 giiY
- Gia trj nay c6 thll thay a6i theo ph6ng thi nghi~m
- K~t qua xet nghi~m trong v6ng 1 - 2 ngay
11
11/35
I
E)inO ~~~ M~t~rr
ltl{l,lj~~· ll~~t~
,.. .! _\ _,.7 h ,..n ..Li / (I C}l~l\ f.cit. ~o'l . elK- c u.n .;-r l) o n
Can lam sang ~ - /
- ·est c6 gia tri nhatt~gUtla xet nghiem tinh the acid
uric l~y dU'Q'C khi chQc kh&p. Ho~c tinh th~ urate & tophi
va baa kh&p viem. (dn thiE§t trong ch~n d6an phan bi~t
v&i viem kh&p do nhCrng tinh th~ khac gQi Ia gia gut, viem
kh&p trong binh v~y nE§n, viem da kh&p d~ng th~p va ngay
ca nhi§m trung.
- X-quang d6i khi c6 fch va c6 th~ chi ra si,J' lang dQng
nhCI'ng tinh th~ tophi va t6n thU'O'ng XU'O'ng do viem kh&p
nhi§u lcln. X-quang cung c6 tac d1,mg thea doi nhCrng anh
hU'&ng cua gut man tfnh len kh&p
~ ·"'' ~.
F
aou.t : c h oc. d , I
.,-(t~h _-f.&, Of?
12
12/35
~ ~ . ......
liwJ,c. tl\"1~ ·'I I "I }lu -,~o ..J
~~ ~ltiJu
NhiPng tUiu chi ch§n doan benh gout
1- 51! xu§t hi~n tinh th~ urat trong ho~t djch va/ho~c
2- Tophi c6 ch(Fa tinh th~ urat va/ho~c
3- St.J' hi~n di~n cua 6 trong s6 nhfrng bi~u hi~n sau :
- DQ't viem kh&p dp
- SlPng viem xay ra trong vong m(lt ngay
- Viem m(lt kh&p dan d(lc
- Do & kh&p
- Dau va Slfng kh&p ng6n chan xu~t hi~n Jan d.lu tien
- Dau m(lt ben kh&p ng6n chan xu~t
- Dau m(lt ben khQ-p cb chan
- C6 d~u hi~u cua tophi
- Tang acid uric huy~t
- Ch(Fng c(F slfng kh&p ttl k~t qua chvp X-quang
- Ch(Fng c(F u nang XlfO'ng dlP&i svn khong -X quang
- K~t qua nuoi dy hqat djch am tinh trong dqt viem dp
k J, oc;
6- M(>t s6 y~u t6 anh huang d~n vi~c bi~n lu~n k~t qua xet nghi~m
~--$-1(, v4tn~4.2.
·NCr c6 ham IU'Q'ng acid uri~p hanna~-------- v'h., C 1 cJlaJpuotM..e_
• M9t s6 thu6c c6 th§ lam tang ho.;lc giam n6ng d9 acid uric
• U6ng thiJ'c u6ng c6 c6n trong thai gian l~y m~u , c6 th§
lam giam IU'qng acid uric trong nU'&c ti§u
• Ky thu~t l§y m~u (khong du IU'qng nU'&c ti§u)
• V~n d9ng qua miJ'c hay ch§ d9 an giau purine
• Ch§t can quang (X-quang) c6 th§ lam tang acid uric I nU'&c
ti§u
13
13/35
( Scrl TA'>5 . )
7- Mc}t so dieu can IU'u y 1. Ham IU'qng acid uric I mau tang cao chU'a h~n da bi b~nh
gout, nhU'ng n6 Ia ti~n d~ cua b~nh gout. "necessary, but not sufficient"
2. Dlv b~nh nhan suy th~n I sci th~n. c6 th~ dU'Q'C di~u tri ngay bc1ng allopurinol, cho du ham IU'qng acid uric mau
1 th§p A~~ h:~, /: 1~u~~ ~~k 'fho~ e/
3. C6 th~ do acid uric tron{mau ho~c trong nU'&c ti~u 4. # 10% sci th~n Ia do acid uric. Vl sci nay c6 mau tr~ng
hay vang nen se g~p kh6 khan khi chvp x-quang. Sci urat hlnh thanh khi pH nU'&c ti~u th§p (acid). Ngt.fai bi b~nh gout cOng d~ bi sci th~n
5. Ham IU'qng urate I nU'&c ti~u c6 th~ tang cao trong khi di~u ~ri "h6a tri li~u" cho b~nh nhan ung thU'
6. LU'qng urat nU'&c ti~u > 750 mg 124 gi6' : san xu§t qua m(fc "overproducer", dn di~u tri bc1ng allopurinol
7. LU'qng urat nU'&c ti~u < 750 mg 124 gia : dao thai kern 1 "u nderexcretor"' c§n di~u tri bc1ng probeneci~ ch~l- lctl~l 1' .*O:o ih· ~
8. B~nh nhan bi hc;it tophy ho~c sci urat & th~n phai di~u tri bc1ng thu6c rna khong c§n d~ y d~n ham IU'qng urat c6 tang cao hay khong
-tt~ -i.e ,AqJ· c b{ )<0.~ bqck~
~ I .A I . I / ~' - t 1_ Q ~1 ....1:..... I l. ,_ 11... ,v I ~? l- L ) f ).) / '
vl lZ-01 .u.~'{)f Cof v q rna~ nn.., 1 o~ c'o,!lfl Ce<c.- '1111•1 ,~TJJ!. tl...-c;n- c; JNn.op, xucn~, n'\a rd~71 1
_\t\~ J.c'ho{ -6.? tl~<i";.h co..{ u cue ~& ~~· L;; J,at- +orh\. ' ~cS b~h J{h...,·r' c'O ~o«r,
..-· .. ~,
/
~
14
14/35
• j; UV\ II.J> I>" ~t-J _:a
' . 'Yn~ '-"' q 7)):l ... tt .if" t,\"t\1..\ / I ~I -,
()~;) ,y
['!m fil"'] ~ ~?IA.I
tv~) \~J>~r
L:'-----
~no a HNiB YO~ Nill~ NiiO ·8
,. . .
15/35
I--
Ac,c\ unc
/ Ac c./~ A;. c-\., J-; .,-~lq "\lltl- 1< ~o' b!L~~ ~out-/ 17 .L/ II . .
C<> cl ,;l V
U(!Co. ~ t_ ::> A.lfarY~Oil'\... --t~"'11' 1'~
Diet and nudeetide turnover . l . ~ I A
).VI ::t ~ m ~ '1"0."' 'note a,..-J, ~t•f< -llw~ "j"'oo fQ{c:;:~.,-\cs\ n.. \ Xanthine
• 'XBnihine oxidase
Allantoin Unease Urate - Excretory mechanisms NOTIJ.oi serum te\lel UJlnary: ~·-
HumBn: 4--6- r~/s:P. (f!I,D-3?0 J.iM) Sa~tre!ntest!nat 20~ tJ'.00....,:<1mp.;i (eflltM)
t t Hyperuricemia Hyperuriro$Uria
t t t Urate crystal Pro-o~idant Uric acid crystals
oopos~ion (gout) {cardiovascular (renal calculi) .,......._, effects?) ·
Dien ti~n chung cua b~nh
Tang acid uric mau dan thu~n Hyperuricemia
Can viem kh&p gout c~p
Khoang each gill'a cac can viem kh&p gout c~p
Viem kh&p gout man
[ ctt'icfu.r<..J
1' C'o.o
Acute Goutty Arthritis
lntercritical gout, Interval gout
Chronic Goutty Arthritis
.I
P" .-t'":i.n ch~h
A--C\u clo ~au. I-
b [)ih ~i': cu~ b/(11, Cjq-t~-t 1ua 4 cjrC\\ cfuao r u-P - R.. - r
~
16
16/35
..
•·
•
.;..' ~.,!' A\.
/ Q Ol\ ~ en> c\l. I c; til'~ C. 1\'\ aM . I CQ6
'
7 ln~nsity of P11.in
L 1AI ~ A Tn~'tl d\u~'}-
c >t,Yt.llt1.()r; ...,~-"!
Progression of Gout
Thisf)eriod could~ S yea~
orionger
~~res bo~ome longer and more seve~
lntercritical periods growsho~er
o t.. I ).C. h CCI.IIJ C"C:tc.~ ()(
I .AI
J,J't-, ( A-dvall~cl tjou.+-)
\u V I - { .J!·'? h' 11 ( ( t .,J Lll " 11 t· l rn«.r c as f, <~cJ.» sa 'l.j ?in"' ~f c o (.. u.. .;~ J J . -
Cnc. C.<>~ 9 nui cop ( ...Jh..;~ 11h:A. /;; j tOO~
1) Tang acid uric mau dan thuan
• Khong c6 tri~u chtPng chi c6 k~t qua tang acid uric
trong XN c~n lam sang
Phat hi~n nhi~u nam tr~&c khi xay ra CO'n gout cap
• Nam (tu6i d~y thi) nll' (tu6i man kinh)
'i •' !> I " ') /"' 0 1\j ~a ,\. tl.k~\,
17
17/35
..
--
~·
__ I 'l"''~ · r-~· ~x:-~,_!.~J,~1~ ____ _J 4"i, ~"~l(~Jr L.... I I ,I
Co~ 2~ ol'-'~ ~CU]~ ~OM
{/"' .,k. ~ .fu·1 1 1\\Y\-\ (), pa.raa.kroJ2,
_ f 1
.AI • ( lin~ ~l xv:o~.
.Jf_l -~1._-_. -'1. Wt· ~ 'lh-\'1
k ~i~ ct·UJ' / (J ~r; ' l ).c!. J
.A. I .A ( ,f Octt ~I )(\..&11}
.p
0 ~ 11
A'\<1'~ ~liD
I I · ~~ )Cu'n~.
/
/
. n~<>~ chcih ccc.{ I l k hd'p okt~ ~c , I
2) Can gout cap
Chi belt d~u xuilt hi~n can gout cAp khi n6ng d{l acid uric a nam l 1 ~ ·~_ 1 1-f lfl- . .:.' /1-':1 (>7mg/dl) Vel nfi' (>6md/dl) \:, .;~ 11\lO." rncu c\liO - .;!. )LIRJ.,j £ <feW }!IOI
. 21 ' ~ ' CO'n gout dAu th~n thlJ'C1ng xay ra d9t ng9t vao ban dem : rat dati (y m9t ng6n -( 6i., . chan cai (y m9t ben 'chan, trong khi ng6n chan cai chan ben kia khong dau gi ca.
Trong vai giC1, ng6n chan cai SU'ng to dAn, ll'ng do va n6ng len. £>au nh(Jtc
tang dAn. M~n. khan trai gilPO.ng d~p len chan dau cling lam b~nh nhan kh6 chju,
b~nh nhan bl!c t(Jtc khi c6 SIJ' CQ xat tren ban chan dau. MC1i nhin c6 th~ lAm
tlJ'O.ng Ia c6 ap xe iY ng6n chan cai.
* Kern thea ngU'eri b~nh c6 th~ s6t, ret run, m~t moi, ...
* Cac y~u t6 thu~n lqi : ron viem kh&p ~P thU'erng xuat hi~n sau khi an u6ng qua mile, u6ng
fU'Q'U, gang sllc, bi l;;mh d¢t ngl)t, ch~n thU'O'ng, ph<lu thu~t. nhiem khu<ln, ... lam cho cac phan tiY
acid uric lang d<;>ng & cac t6 chile.
3) Khoang each giD'a cac can viem kh&p gout cap
(lntercritica/ gout, Interval gout) :
*Acid uric tang va c6 SI,J' hi~n di~n tinh th~ MSU
* Hoan toan yen l~ng, kh&p khoi hoan toan
* Khoang each gili'a can dau tien va can thll' hai c6 th~ tU.
vai thang d~n vai nam, th~m chi > 10 nam.
* Cang v~ sau khoang each nay cang ngan l~i. Cac CO'n
viem kh&p cap xay ra lien ti~p Va kh6ng khi nao d(l't CO'n.
( vel : o2v f,~ff-__.. ' .-.'
- ;>- Sa.nl hit
3v /o39 ' , €/)-" I ht£u fot - /$ct11Jf'C
18
18/35
. "' ~ .
Thai gian tw can gout c&p Tyl~
1 nam 62%
1-2 'nam 16%
2-5 nam 11%
5-10 nam 6%
> 10 nam 7% ---- - -
~----~~-----------;?L~:::::__1ffO~ll.+~n'\et~ '-h~~ }_;I j,c&,_,• X'-' ; f
4) Vi em kh&p gout marf Jc, 4 h. ~ h +orR, (Chronic Goutty Arthritis I Chronic Tophaceous Gout)
* Viem nhi~u khap, c6 thil d6i xwng, bi~n d~ng khap, teo
CO',CWng khap ...
* Cac Cl)C u (tophus) iY sl)n vfmh tai, iY ph§n m~m cc;tnh khap,
(y quanh khap (ng6n chan, khuyu tai, c& chan, g6i, ng6n tay ... ) do acid
uric l~ng dQng iY khap va t& chwc ph§n m~m quanh khap.
Kich thlJ'ac cac ct.Jc u tw vai mm d~n vai em, khong dau, dlJ'ai
lap da m6ng c6 th~ nhin thay c~n t~ng. Nhi~u trlJ'6tng hgp cac Cl)C u
nay bi va, xi ra mc}t chat tr~ng nhlJ' phan, chinh Ia cac tinh thil mu6i
urat, do cac acid uric l~ng dQng ma nhi~u nglJ'6ti tlJ'iYng l§m d6 Ia mu.
19
c
19/35
·' -
OG
ll:I.L n~IG ·6
~ ~~ -· .. ~
!
/ -20/35
• '·
'.~ .
h«-ih -~y{ hL"n~
fr'iiu._ \ cvef~ymi n£ ~ ~ 1\5 ~ }3-£ -M~,~r
I O-< t d utf-c' a. ";-c~ lhf( I
! f *~1 a..c.l J l\llC..
A ...\r ol\~ IY\ 0
1 h~\1 1Cll ~
Uri f ctSL
( pyo lhru...c\d
Co~c.. llli c.irt..
F.!=--
Prob•~&d --? -f b-o lncr~a$C!:$ ex.c~don of uriC add In urt.ne
NSAI~ortl'cost•rokls r~uces ~#oflnfl~tnm~tl9f1
I (
f:: ~~(._~t•'
-4-
U'lC. =7 cJio.+"iY'V
iC
Ji ' I' I R-: c.vu, j), .
L\ Co~clti C.I~ =f'}T vc!/ cc/ t:' /:/- / ta/ ))ao 71oi RetE/ .,.fa.( ...fv~' !!
[!] I Rx: NSAIDs
Acu1
(Adapted from Neogi, 2011) la'rl
I
}-
f<f"j J,_of ct~:( J Uric_ 1 ck' 00.1'\ )(ct rrlhif\...(.._
( t1ilovu ,: roo f) I
ref UtfL
(\let /tt co;, 3 %
21
21/35
~
[.
.,
1
-
2
)
M1,1c dich di@u tri :
1 - Kh&ng ch§ cac dqt viem kh&p gout c~p ( Co~chicin)
2 - Lam h~ va duy tri acid uric milu & mlrc cho phOp (1o pu nno.Q )
3 - Ki~m soat t&t cac b~nh kern theo
Kh6ng chi\ cac Colchicin - alkaloid tir toi dqc, ngqt ngh~o dQ1 viem kh6'p - TDP : tieu chay, non, dau bl}ng • Dung dai ngay co th~ che d~u s'! I~ng cap -
dqng MSU I kh6'p gay nen Sl! mit ciinh giac i'r bn
NSAIDs
Corticoids Sir dl}ng trong tnrimg hQl> bn khong dung nl_lp colchicin hay NSAIDs KQ k.ha quan nhlfng d~ tai phat khi nglfng thu6c, I~ thu{)c corticoid. lhrimg sir dl}ng : tl_li ch6 I toan than
Paracetamol Giamdau
Lam hl_l vaduy Chang t6ng hQ'P acid Allopurinol tri ham llfQ'Ilg uric Febuxostat (*) aicd uric Tang thai acid uric Probenecid i'r muc cho phep [Uricouric agentl Sulfinpyrazon
Benzbromarone Fenofibrat Losartan
Tieu acid uric (**) Uricase: Uricozyme® (Aspergillus Oavus)
(Urate oxydase) Rasburicase (***) PEGylated uricase
/ ~ ·~
/
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22/35
' •·
"<·
-• ·
1 KHONG CHa cAc 9Q'T VI aM KH6'P
GOUT CAP
'"'
Nguyen tcic : cfmg nhanh cang t6t
Thu6c siP d~;~ng :
Colchicin
Khang viem khong steroid: indomethacin, diclofenac, naproxenKhang
viem steroid : prednisolon, metylprednisolon
Nghi ngO'i, h<;~n ch~ v~n dqng khi kh&p SlPng dau
23
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,.
..
Colchicin ToOi iioac : Colchicum autumnale L. Liliaceae
Ngout ngoeOo : Gloriosa superba L.
0
COLCHICINE
N~CH3 0
ToQi noac : Colchicum autumna/e L. Liliaceae
..
/
24
24/35
.•.
1'.
"
Ngout ngoeOo : Gloriosa superba L
C , h 1 ' \_ <J 9 "- I! I b _I , I ..> ) , . • -" ac : }\~ ~ ~ ~i f'.jcli\ c.a." rhctl'\ .l.'dn c ~:o, o -.~u .. ., / ~.Al A
Ng6?linhit 1;~ fa.n con J...-
2mg - 1 mg - 1 mg ... (moi 2 gia d~n khi giam dau, max 6mg/ngay)
Ngay thCf hai, ba
Ngay thCF tlJ'
each 2 :
Ngay 1: 3vien
Ngay 2: 2 vien
Ngay 3: 1 vien
: 1 mg X 2 laim (sau khi aen) SoU ,L.l.i c\~
: 0,5 mg x 21aan (sau khi aen) sa.u .kl\,ct~ ~
.Xt~ Jl~~..r-
Sang- Chi~u -@l Sang @ ·
@ bd~ budc.. f hG'.t (! n "' · - 1 A'' "'' p..i .U\ vc\.0 'Jl\01 \01
-Ji Co~ C1~ ve:i:'o bet~ I cr.;..~
25
25/35
.\
..
J
1
1
I 1
Chu -y: Li~u gay a¢c : >= 1 o mg
Li~u gay ch~t : 40 mg .
l\~ +t: efov ,k~~~ 9ucf ~ ~ill/.,~~
~~:;:;- Colchlmax : + tiemonium ((/ -It ol-C\1.\ o~~, k ,o'l)
A :-) -\ha..lih r'\ + opium ( (l'tt'~ <h ~ c:.hai) !
,_;;.. r~ht\t ,~.u: -k -+ Co ~chiCI'n ( -4- ~ot.'-t ) P 1r f • . ., f~ ~ e~ ... \~ (1:-~o :.
c\a..~ bl\~ . ~.L, ~~rc.), . ..
C,(cu; "" ).' oZ:-Ih\(l(.
Colchicin
TU'ang tac thu&c THU6C P. HQ'P cacHE XlrTRi
ARV ARV U>c ch~ Giam li~u colchicin Atazanavir, Darunavir Fosamprenavir,
CYP3A4 lndinavir ,Lopinavir/ritonavir Nclfinovir, Soquinovir Trpranavir
'"' J::::-rc,y / I ( ~ rl'Al-l b£ '-..... ~''"'""
• Clarithromycin Crc ch~ Giam li~u colchicin c-l() \,~ {; 'CU'l
\ul-n
)
o2__ -\-h ~.,, .;': C. c e:, •w1-
•L . ..<f dl '1'11\,\0 c.
>y~<l l~~ tH;I~
C.o nG\ z of..· ::r:-hcv-
/
jA I
6 'Dllo'} Ghu'\ ~
• Cyclosporine CYPA4 (d~c bi$1 & b$nhnhan • Diltiazem suy gan I suy th~n) • Erythromycin
~·'"' '."' • ltraconazole (Colchicin dflO thai 10-20% • Ketoconazole qua duimg th~n)
• Verapamil • NU'&c bU'&i,
Colchicin Cyclosporine Crc ch~ bam Giam li~u colchicin ketoconazole P-glyco protein (d~c bi$t & b$nhnhan protease inhibitors suy gan I suy th~n) tarcolimus. (P-glycoprotein efflux
pumps)
C {J I . ,I IL ,.1 - ... -o_,tC, iCin v o1 ~"''liCJC.. na.o C.eu\
? ' .;. ~ -j ' r 1J.W\ I.(..U 1 11150~1 -·lrl( ?."
[ c.oJ ci,;CI., J
26
@ A?-i -1-h ro, t;r\ b _ t-1 -fh ('0 ffl 'a(.;" c ' Di (Jr" z.. .. vn. cl. !Ce_hco!"Cl. Z.o.fc...
' ' /- '
,-
26/35
..
....
·'
NON-STEROID & STEROID
Phenylbutazone (63%) - Oxybutazone (23%)- DX hydroxyl (14%)
Indomethacin
50 mg x 31~n. ngay ti~p theo x 21~n
LuiDafllt.ari. C)IH)4Cl"'O,~: -~·
C'Ht 0
Prednisolon : 40 mg/ngay Metylprednisolon : 20-40 mg I khoup
( x 3-5 ngay), ngU'ng sau 10-14N
Predniwlcme C21Hu0s AY.:~ou
o·)_~J.
2
Msthylpredbisolone C12R"O'
Oil
LAM ~VA DUY TRl ACID URIC MAU
a MUC CHO PHEP
27
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.. '
.-
...
/ ·1' C\cldur'IC .. ?
.\Cl.m o. ~...-c\ llr'\C: ..
I 1 \ Enalapril - Losartan - lrbesartan & GOUT
(ACEi) ( A~b)
Urk:acld(pmOUU • end dtreauncm Uric acld(pmoi/U"' end d treatrnont
Enolaprll Lcsanan50mg Looanan100mg
C Wi.irzner et al. Journal of Hypertension 200119: 1855-1860.
a) Ch6ng t6ng hO'p acid uric :
DU'cmg nqoai sinh : hc;m ch~ cac thfrc an chfra nhi~u purin
nhU': tim gan, 6c, ...
DU'cmg noi sinh : giam t6ng hgp acid uric b~ng ch~t frc ch~
xanthin oxydase (Allopurinol - Zyloric, Zyloprim)
Allopurinol C5fi.J'l.&.O
0
H)\---r l __ Jl .. /~
N N I
H
, '
28
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CoPc~l t.>', -> 't"''~ J.cu. ~>--{hJ""t c6f AJlo rtlt1oo.Q -> -cya·~ atrcllltfL - / 4 goLl+ I'Y\~
IAdenin I I Guanin I l
Adenosin
! I Hypoxanthin I · • I Xanthin 1--• Acid uric
xo . xo Xanthin { Co Qck~~~, . ph~t'J!p
Allopurinol t.oxydase Af1op' t{(IQ.R.
/ caotLt c~p ~Co chit.\~ b \C~ mo: ~~ ef-~ diio~ /t.florUtt~{, do i J-/r(-'-.,. J r' fit r: u.f ~~~-- [ acTJ ll<le-1 _.,.. xu~.!. )t,'.!n co'11 01 altr
'd0"-1 O''-Cl" 0 A- ...uop~~c'lna.(. (I 1. ,? ) • A _, 1 ' v ra 1')!.(.1.( '\l;..V\ '}rri"} cull 'Jo·~+ eel{/->
• -1-h f -{d_ / A_ojiJ vel,/
Nguyen tac sll' dung Allopurinol (Zyloric, Zyloprim) : ,. J 1 • • 1
_ t_O . c tl• u., <Jif"cM ~ vcu
- khong sll' dl)ng trong dQ'l viem c&p, trong 3 tuAn dAu nen k~t 4t\cfn' ~ "kv~'q r
h9'p v&i cac thu6c d~ ngll'a can gout c&p I ~cw c:lo' cof·11~ ciiio}-
- Biit d~u (y li~u th&p (100mg/ngay) va tang d~n t&i li~u di~u tri I A-llo (I'll ;f\ I.e (t6i da 800 mg/ ngay) sao cho acid uric mau < 300f.A.moi/L (hay < 5 mgt
dL) - Sll' dl)ng lien tl)c, khong ngiit quang
- Chu y khi ph6i hap thu6c
*Allopurinol lam tang n6ng 119 cua Theophyllin
*Allopurinol/am tang tac d!mg cua cac thu6c thai acid uric va
ng1J'9'C l<;~i
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·.
L 'fl,tkfen~
b) Taeng thaUi acid uric khoUi co thea (URICOURIC AGENT)
Probenecid: kh6oi d~u 250 mg/ ngay, tang li~u t6i da 1g x 21An/ N
Probenecid CuHuNO-'S
CH CH CH -D-'' l 2 2'NSO . 1 \ COOH
/ 2 CHaCH2CH2 · -
Sulfinpyrazon : kh6oi d~u 50 mgt ngay, tang li~u t6i da 200 mg I ngay
rJis 0 N / CJ16
Sulfinpyrazone ·y··' r( CnHuN201S . u-~ ft ~
SCH2CH2 0
f I. ( ;\" ~ co .hnt, c,{,R-IJ\'\
Ki~m hoa m.PO<c ti~u : ch~ de) an nhi~u rau xanh, dung thu6c
(NaHC03, Acetazolamide) (
3% 1.--..-"J flllo't
~ cr- cf-; IC r-CU-\
, .. -.
/
1\ClO u.l~~ .:f:c. )
Chi djnh Uri~ouric a,.gent khi nao? [ o c< d «~'i { 1 / <>24-l < -11JO,J.-( lcM)~ ;:1.-c\.o -the\., a<ld Uil"c:) /
Juo-H\C\~/ 1. Tang a c. uric mau do giam ~:HM acid uric
2~ Tu6i < 60 + "kJ~ !\ on~ -;lh~V\ 1 ~~~~j 3. Chll'c nang th~n con t6t GFR >80mllphut
4. Khong c6 ti~n can soi th~n
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,,
c) Thuoac tieau acid uric (Urate oxydase)
CX too Asp~gillus flavus : URICOZYME~
n f1 r- 'tr
Acid uric --+ allantoine
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XO. --;;-- AAopuii!>OI \ -----.. _ 1 E~tic Oi<ida!ioo
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So;.~r;:o Na! C1m Pract On:ol C 2006 Natuf'tl PuN:ltHn~ Group
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Nong do acid uric va thuc u6ng c6 cafein
Serum uric acid {Jimoi/L)
ro Cttf!J C<> I le\c"l 1'
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320
310
300
290
280
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Thai gian 1988-1994, tG~i My- SO IU'qng 14.000, tu6i > 20 LoG~i tn:r : gout ho~c dang-dung allopurinol, thai ac.uric
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Frequency (servings per day)
http://www.medicine.ox.ac.uklbandolier/band161/b161-7.html
NEN KHONG NEN I H~N CHE
An Rau Phu t~ng (gan, th~n, long, ti~t Tnl'ng, sfra ft beo, canh, ... ) phomat, yaourt, Th!t Thit (tr~u bo, heo, ct'Pu, ... ) triing Haisan 86 sung calci Thfrc an chua
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Dau oliu, dau hU'&ng diJ'O'ng
U6ng Nhi~u nU'&c RU'Q'U, bia NU'&c + NaHC03 (3%)
i
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tan ph~ kh&p, . ..
Lien quan d~n SOi th~n, th~n lP nlFQoC, Tang huy~t ap, tai bi~n Th~n IP mti, suy th~n. m~ch mau nao, nh6i mau
CO' tim
Lien quan d~n di~u Ch&n doan nh&m v&i Khang sinh tri viem kh&p nhi~m Kh3ng viem
khu&n
Lien qua'! d~n NSAID T6n thlFO'ng nhi~u CO' dung thuoc quan (mau, th~n. tieu
h6a, .. )
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Saturation threshold: 0.42 mM
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Flg. 20-13 Hypoxanthine, xanthine, allop!Jrlnql and alloxanlhine are water soluble
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