Hoa Sinh Hoc Mien Dich Trong Lam Sang_Y Ha Noi

7/30/2019 Hoa Sinh Hoc Mien Dich Trong Lam Sang_Y Ha Noi

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Ha sinh hc min dch

trong lm sng


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Trng i hc y h ni

Ha sinh hc min dchtrong lm sng

Nh xut bn y hc


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phn I: m u


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chng 1

i cngS qua v Ho sinh y hc v Ho sinh lm sng (HSLS) Ho sinh l mt ngnh Khoa hc nghin cu c

bn v ng dng cc i tng sng mc nguyn t v phn t - Ho sinh, nh tn gi bao hm ni dungho hc ca sinh hc, l s hi nhp ca 2 ngnh rng ln l Ho sinh hc v cc ngnh ca sinh hc. Trongnhng thp k qua, nh s tip thu c cc thnh tu to ln ca cc ngnh nhTin hc, vt l, ho l, sinh hchin i, in t v thng tin... Ho sinh pht trin nhanh chng, tin nhng bc di, to nhng kh nngphong ph cho nhiu ngnh khoa hc lin quan, cng nhau pht trin v thc y s ra i ca nhiu pht sinhmi nhiu thnh tu mi gn b mt thit vi sinh hc phn t, vi cng ngh sinh hc.

1. Ho sinh y hc. Ni chung, HSLS th hin c vai tr v v tr ca mnh mt cch xng dng, isu vo lnh vc nghin cu bn cht ca s sng con ngi, nghin cu bo v v khng ngng nng cao sckho, ko di tui th, phng chng cc bnh tt. L Khoa hc nghin cu v cu trc ca cc phn t sng,

nng ca chng cc t bo, cc dch sinh hc, s to thnh (tin bin, tng hp), vn chuyn, thoi bin(phn lng, ho ging), s chuyn ho ca chng v lin quan gia cc chuyn ho..., n khng ch dng cccu trc v cc phn ng chuyn ho m cn hng m ra cc quy lut chung cho php ni lin gia chng vkhm ph m ra cc hin tng cha bit hoc ca cc ngoi l mi, b xung cc c ch iu ho...

V nhvy, cc phng php k thut v sinh ho phi pht trin i t cc k thut c in v ho hc(s dng ng oong, buret, pipet... Thao tc tay nhng giai on u, vt ln bng cc phng php k thutho sinh hin ti, c hiu lc, c nhy cao nhcc phng php v sc k, v din di, v phn tch quang ph,siu ly tm, knh hin vi in t, cc phng php v min dch, v ng v phng x, v gen vi nhng trang bk thut hin i, t ng, c kh nng phn tch tinh vi, t lc kt qu ch biu th cao nht l mligam, 10-3 gth nay thng l microgam (, 10-6) ti ti mengam (ng, 10-9 picogam (pg, 1-12g)

Cc nghin cu Khoa hc ngy cng mc su hn, khng nhng cc c quan, t chc m mc tbo, cc thnh phn di t bo, ADN, gen, ghp gen... trong iu kin bnh thng v bt thng, bnh l.Trong nhng thp k qua, Ho sinh thm nhp vo nhiu ngnh Khoa hc v v c cc ngnh ny tip nhnnhmt cong c sc bn s gii quyt cc nhim v ca mnh,gp phn vo s tin b v cc thnh tu ca nhiungnh sinh hc - Phn ln cc gii thng ln, gii thng Nobel u c vai tr ca Ho sinh.

Ngnh Ho sinh y hc ni ring cng pht trin chuyn su, pht trin Ho sinh lm sng, Ho sinh mindch, Ho sinh Dc l, Ho sinh sinh dng, Ho sinh c hc, Ho sinh phng x, Ho sinh vi sinh, mi trng...

2. V Ho sinh lm sng: Vi nhim v vn dng cc kin thc, cc quy lut ho sinh phc v nghincu cc qu trnh bnh l t cn nguyn, bnh sinh,

cc yu t lm tiu chun chn on, theo di iu tr, tin lng bnh, hng o v tham gia vo cngtc iu tr... phc v cho lm sng, cho iu tr v d phng, sm v c hiu qu. Bng cc xt nghim thngngy v chuyn su c chnh xc, kp thi, ngy mt nng cao v s lng v cht lng, nhy, c hiu,bng cc bin php ho sinh iu tr v nng cao sc kho con ngi lm r cn nguyn nhiu bnh bm sinhbnh l phn t, gen ....

Cc xt nghim c th

c thc hin cc t b

o, cc th

nh phn d

i t b

o (ch yu l

khu vcnghin cu v ho sinh lm sng), cn thng xuyn ph bin l tin hnh cc dch sinh hc phc v cngtc thng ngy ca lm sng (ch yu l mu, nc tiu).

Bnh thng, nh bit, s nghin cu v ho sinh cc c th sng chng minh l thnh phn hohc ca chng lun bng dch trong mt gii hn no . Mt t bo sng bnh thng c mt s bng nh cons cc phn t ca mi cht chuyn ho (tng chng nh trng thi tnh) - Thc ra, n c nhng c ch iuho duy tr s bng nh y v s thay i ch xut hin.

1 - Khi cc t bo phi thch nghi vi s thay i cc iu kin mi trng quanh n.

V d: Khi mt t bo c s thc hin mt mnh lnh ca h thng thn kinh, tnh trng nng lng can thay i v cc cht chuyn ho c nhim v cung cp nng lng cng bin i (ATP, PCR,...)

2 - s trng thnh v pht trin - y l mt nguyn nhn quan trng.Trong qu trnh pht trin, cc t bo phi tng hp nhng lng ng k cc cht chuyn ho v s dng

chng c kh nng t phn chia.


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Cc t bo c nui dng bng cc cht chuyn ho cc dch sinh hc nhhuyt tng - Nhng ccdch sinh hc cng c c cc cht chuyn ho m cc t bo khng cn v c nhng cht cn thi loi.

Bnh thng th lun c mt lng cht no ca cc chuyn ho c ch ra khi t bo, qua mng t bo

ra ngoi bi cc l do khc nhau.2. hot ng ch tit ca cc t bo: to ra cc cht chuyn ho c ch cho cc t bo khc nhcc acid

bo khng ?? ho, cc cht to nng lng (ereatin), cc hortmon.. Qua , c th kt lun l thnh phn ho hcca cc dch sinh hc phn nh nhiu hay t hot ng chuyn ho c t bo, bnh thng th n n nh nhngn s thay i khi hot ng chuyn ho ca t bo thay i.

Vic sinh lng cc cht chuyn ho khc nhau c th cc t b o (khi c iu kin)hoc d thc hinhn l cc dch sinh hc, cho php thy c hnh nh v hot ng chuyn ho ca c th mt cch trungthnh - S hng nh ca nhiu thng s (hay cn c gi l hng s) ni ln l c th trng thi cn bngchuyn ho.

Bn cnh s thay i ca cc thng s sinh hc do vic thch nghi vi mi trng bn ngoi (c cc thayi sinh l), cn c th nhng thay i ln hn, qu mc mang tnh cht bnh l, c trng cho cc tnh trngbnh l. V vic nh lng mt hoc mt s thng s v ho sinh. Da trn mc thay i ca n gip ta nh

xt nh gi mt tnh trng bnh l ca c th hoc cc c quan c trng bi s khc nhau nhng thng s ,qua m pht hin chn on iu tr, theo di iu tr cng nh tin lng bnh, phc v cho lm sng (l ccni dung quan trng ca Ho sinh lm sng)

3. Vic s dng cc xt nghim ho sinh lm sng:

Khng k cc xt nghim vi cc k thut dng trong nghin cu s lng cc xt nghim ho sinh lmsng ngy cng nhiu, t tin, i hi vic s dng sao cho c hiu qu, tn km - Nhvy cn c kin thcv kinh nghim ca ngi thy thuc - chng ta bit ch ring cc xt nghim cc loi c t ng ho lnti trn di hng trm v xt nghim dng trong mi loi bnh cng kh nhiu, nht l cc xt nghim cao cpt tin.

V th khi dng phi c s la chn, ch nh phi hp b tr cc xt nghim mt cch khoa hc nhmsm pht hin gip chn on v chn on phn bit, theo di c din bin, tin tin ca bnh theo di nhgi kt qu vic s tr iu tr bnh - Vic s dng cc xt nghim phi da trn s c hiu v nhy ca xt

nghim i vi bnh vi giai on ca bnh.V d: trng hp nhi mu c tim cp, lc mi th nn dng crcatinkinase, izozym CKP-MB, Troponin

T, GoT (tng sm nhng ngy u).

Nhng nhng ngy sau th c gi tr li l xt nghim, LDH, X HBDH (cc enzyes ny c s tng ko dikhi nhi mu tn thng c tim)

Vi cc cn ti pht th c gi tr l nh lng CPK - izozym CPK-MB...

Cn phi hp vi in tm th hin s thay i ca sng Q

Tuy nhin cng cn lu v nhy ca sng Q mc du rt c hiu vi nhi mu c tim cp c thkhng bng CK.

3.1. Phn loi cch s dng cc xt nghim ho inh:

Da theo mc ch s dng cc xt nghim ngi ta c th phn ra vic dng cc xt nghim sng lc,

chn on v theo di iu tr.1 - Xt nghim sng lc: pht hin nhng ngi c cc yu t nguy him c mc bnh nhng khng

biu hin cc triu chng nhm:

- Pht hin v iu tr sm cc bnh tim n lm gim t l ngi mc bnh, phng chng cc bnh xhi, nguy him truyn nhim, phng nh, gim c t vong.

- Pht hin cc yu t nguy c c th can thip sm, ngn chn bnh khng xy ra hoc ngn chndi chng.

- i vi nhng bnh c tnh cht gia nh, xc nh cc thnh vin khng c biu hin bnh hay khngc yu t nguy c cung cp cho h li tvn v di truyn hc.

Vic thc hin xt nghim sng lc thng phi tn km, do vy cn cn nhc quyt nh v nn datheo cc nguyn tc hng dn sau:

a) V bnh tt:


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- Ph bin, ng tp trung c gng pht hin.

- T l bnh tt v t vong cao nu khng c iu tr - c sn phng php iu tr c hiu qu v chpnhn c lm thay i din bin t nhin ca bnh.

- C giai on tin chng c th pht hin v iu tr

- Pht hin v iu tr trong giai on tin triu s cho kt qu tt hn so vi vic iu tr trong giai ontriu chng.

b) V xt nghim:

- C th chp nhn c i vi bnh nhn

- Xt nghim nhy pht hin bnh nhng ngi c tin trin (m tnh gi t)

- Xt nghim c hiu loi tr bnh ngi bnh thng, kho mnh (t dng tnh gi).

c) V cng ng s nh lm xt nghim sng lc:

- C t l lu hnh bnh cao

- Tip cn c.

- C th ng thun cc xt nghim chn on v iu tr c khuyn co v sao.

2. Xt nghim chn on: xc nh hay loi tr bnh, nhm:

- Chn on xc nh bnh -

- Pht hin sm ngay sau khi bt u c cc du hiu, triu chng.

- Chn on phn bit.

- Xc nh cc giai on tin trin ca bnh.

3. Xt nghim theo di iu tr

Xt nghim thuc phm vi p dng ny nhm:

- nh gi khch quan v lng ho mc nng ca bnh v tm lng bnh.

- Theo di qu trnh din bin ca bnh (tin trin, n nh hay thuyn gim).

3.1. La chn hay iu chnh cch iu tr trnh ng c v m bo tc dng iu tr.

- Theo di p ng iu tr.

- pht hin s ti pht ca bnh.

3.2. Vn nh gi v la chn cc k thut xt nghim

Trong vic s dng cc k thut nh lng ho sinh lm sng thng c s cn nhc n cc yu t:

- n gin mc c th, tit kim, c li v thi gian v nhn lc.

- C nhy cn thit, nhn bit khi c s thay i cht t v nng , v hot tnh - sm pht hinkhi c bnh, khng c m tnh gi.

- C th pht hin c c nng mc kh thp, lng t.

- K thut n nh, chc chn tt, lp li c cc kt qu nn cng mt mu ch ging nhau hoc chgiao ng mc cho php

- Phng php phi chnh xc, cho cc kt qu khng qu khc bit gia cc phng xt nghim.

- K thut cn c hiu, ch xt nghim cht cn thm, khng chu nh h ng, tc ng ca cc chtkhc, phn t khc.

Kt qu xt nghim l dng tnh, bt phng cho php chn on xc nh c bnh cn nu kt qu lm tnh th cho php loi tr khng c bnh.

Thc t th him c mt xt nghim no dng trong lm sng l c hiu hon ton hoc c nhy honton v vy ngi thy thuc cn bit s dng phi hp cc xt nghim khng nhng v ho inh m c cc xtnghim cn lm sng khc.

3.3. Biu th kt qu xt nghim theo h thng n v quc t si (Systeme international)

Qua cc Hi ngh quc t v lnh vc o lng t 1957 thng nht quy nh 6 v quc t SI. l cc

n v c bn: mt (m) mpe (a) Candela (cd). Kilogram (Kg) Kelvin (K), giy (s) v c cc ... n v pascal (Pa).


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Newton (N).

Vi mi n v c bn hoc th n v tng ng c cc bi s v li bi s vi cc tip u ng v cck hiu c gii thiu trong bng di y:

S c m Tip u ng K hiu

1012 Tera T

109 Giga G

106 Mega M

103 Kilo K

n v c bn

103 Milli m

106 Micro

109 Nano n

1012 Pico p1015 Femto f

1018 Atto a

Ti Hi ngh ln th 14 "Poids et mesures" 1971 Paris chn Mole l n v SI th 7. Tip ti 1-1-1971, Lin on ho hc lm sng quc t gii thiu h thng n v mi thng nht biu th kt qu xtnghim v bt u a vo s dng, khc phc tnh trng nhiu n v khc nhau, cha khoa hc, kh chuyn iv i khi thiu s r rng.

1. - i vi cc cht l Mol hoc cc di n v Mol:

millimol (mmol) = 10-3 mol

micromol ( mol) = 10-6 mol

nanomol (nmol) = 10-9picomol (pmol) = 10-12

2 - i vi th tch l lt hoc di n v lt:

decilit (dl) = 10-1l

millilit (ml) = 10-3l

microlit (ml) = 10-6l

nanolit (nl) = 10-9l

picolit (pl) = 10-12l

femtolit(fl) = 10-15l

3 - i vi nng l mol hoc cc di n v mol trong lt (biu th nng dung dch hoc cht xt

nghim).Cc di n v ch chn ti a l 3 con s v du phy biu th cc kt qu xt nghim, phn tch:

V d: thay vo 0,402 mmol ta vit 402 mol

3200 mmol ta vit 3,20 mol

Khi s dng vi cc cht cc dch sinh hc nc tiu, mt, cc cht khc... phn cn c th tnh ra molhoc di n v mol trong 24 gi.

Ngoi ra, khng dng t l phn trm m dng cc s l ca n v nh 50% thay bng 0,5 v 15% thaybng 0,15.

4 - Phn ch thch

Vi cc cnzym, thay dn cc n v c ca cc tc gi cn dng v thng nht quy v n v quc t IU.

HU (n v quc t) bng 1 mol c cht b phn hu trong mt pht iu kin tt nht ( c quy nh).

1 mIU (mili n v quc t) = 10-3 IU


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n v IU tuy quen dng nhng hin nay li chuyn sang n v mi SI l Katal (Kat).

Kat l lng enzym xc tc s bin i mt mol c cht trong mt giy (s) trong iu kin xt nghim quynh:

1 Kat = 1 mol/s

Cc n v di dng sinh ho lm sng:

Microkat pKat = 106 Kat = lng enzym xc tc s bin i 1 micromol c cht/1"

nanoKat nKat = 109 Kat = lng enzym xc tc s bin i namomol c cht/1".

- Vi cc cht l mt tp hp cc cht nht nh nhng cng tn ti vi cc t l c th thay i nhprotidlipid... th vn dng cc n v c ang dng: g/l.

- Chuyn i gia cc h thng n v:

Da vo hai cng thc chnh chuyn mmol/l sang mg/l hoc ngc

mg/l = mmol/l x Phn t lng

T cc cng thc ny s tnh cc h s chuyn i ra n v SI v c trong vic chuyn ra mEp.

C th dng cc cng thc chuyn i di y:

Gi tr cn tm Gi tr c Tnh chuyn di

Mol

gG

Mol =Phn t lng

Ep hoc ho tr = Ep/Ho tr

Eq hoc ho tr

g Ho trEp = g

phn t lng

Mol = Mol. Ho tr

g Mol g = Mol.Phn t lng

Ho tr Phn t lng= Ep.

Ho tr

mg/l 1000 x g/lmmol/l = =

phn t lng phn t lng

Di Ep (Equivalent) l Ep (milliequivalent) = 103 Ep thng vn dng tnh nng cht in gii (tronglt).

Vi cc kh c tnh theo n v Pa (Pascal) thuc h thng n v SI, l n v p lc. n v dng trcy l mmhg trong cc xt nghim pO2 PcO2 1mmHg = 0.113 KPa - 1KPa = 7,5 mmHg

Ch thch: xt nghim c th cn cc kt qu theo n v c thng dng- n v ngoi SI cn c s dng

V thi gian: Pht (mc), gi (h), ngy (d)

V th tch: Lt (l) dm3.10-3m3

V di: ngstrom 0,1 mm.10-10 m


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Bng qui i theo n v quc t

Cc cht sinh-ho Quy i ra mol/l Quy i ra g/l, mEq/lI. Mu

Acid ascorbic mg/1 x 5.68 (mol) mol/l x 0,176 (mg)

Acid folic mg/l x 2,27 (nmol) mnol/l x 0,441 (mg)

Acid lactic mg/l x 1,1 x 10-3 nmol/l x 90,1 (mg)

(mmol)

Acid pyruvic mg/l x 11,4 (mol) mol/l x 88 x 10-3 (mg)

Acid uric mg/1 x 5,95 (mol) mol/l x 0,168 (mg)

Amoniac mg/l x 58,8 (mol) mol/l x 0,168 (mg)

BEI, PBIg/l x 7,87 (nmol)

nmol/l x 0,127 (mg)

Bilirubin mg/l x 1,71 (mol) mol/l x 0,585 (mg)

Calci mEg/l x 0,5 (mmol) mmol /l x 2 (mEq)

Ch mg/l x 4,826 (mol) mol/l x 0,207 (mg)

Clo mg/l x 1 (mmol) mmol /l x 1 (mEq)

Cholesterol g/l x 2,58 (mmol) mmol /l x 0,387 (q)

Creatinin mg/l x 8,85 (mol) mol/l x 0,113 (mg)

ng (Cu) mg/l x 15,7 (mol) mol/l x 0,0635 (mg)

Fibrinogen g/l x 0,340 (mol) mol/l x 2,94 (g)

Glucose g/l x 5,56 (mmol) mmol/l x 0,18 (g)

Huyt sc t g/lx62,1x10-3 mmol) mmol/l x 16,11 (g)

Kali mEq/l x 1 (mmol) mmol/l x 1 (mEq)

Magi mEq/l x 0,5 (mmol) mmol/l x 2 (mEq)

Natri mEq/l x 1 (mmol) mmol/l x 1 (mEq)

Phospholipid g/l x 1,29 (mmol) mmol/l x 0,774 (g)

Phospho v c mg/l x 32,3x10-3 (mmol) mmol/l x 31 (mg)

St mg/l x 17,9 (mol) mol/l x 55,8 10-3 (mg)

Testosteron g/l x 3,47 (nmol) nmol/l x 0,288 (g)

Thyroxin g/l x 1,29 (nmol) nmol/l x 0,777 (g)

Triglycerid g/l x 1,14 (mmol) mmol/l x 0,875 (g)Ur g/l x 16,6 (mmol) mmol/l x 60X10-3 (g)

Vitamin A g/l x 3,5x10-3 (mol) mol/l x 286(ng)

B12 ng/l x 0,737(pmol) pmol/l x 1,355(ng)

E mg/l x 2,40 (mol) mol/l x 0,416(mg)

II Nc tiu

(24 gi)

Adrenalin g x 5,46(nmol) nmol x 0,183(g)

5-HIAA mg x 5,24(mol) mol/l x 0,191(mg)

Acid urc mg x 5,95 x 10-3(mmol) mmol/l x 168 (mg)


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Cc cht sinh-ho Quy i ra mol/l Quy i ra g/l, mEq/l

Aldosteron g x 2,77(nmol) nmol x 0,364(g)

Amoniac g x 58,8 (mmol) mmol x 0,017(g)

Calci mEq x 0,5 (mmol) mmol x 2(mEq)

Creatin mg x 7,63(mol) mol x 0,131(mg)

Creatinin g x 8,85(mol) mol x 0,113(g)

ng (Cu) g x 15,7 (nmol) nmol x 0,0635(g)

DHA mg x 3,46(mol) mol x 0,288(mg)

Kali mEq x 1(mmol) mmol x 1(mEq)

Magi mEq x 0,5(mmol) mmol x 2(mEq)

Natri mEq x 1(mmol) mmol x 1(mEq)

Nor-adrenalin g x 5,92(nmol) nmol x 0,169(g)Estradiol g x 3,68(nmol) nmol x 0,272(g)

Estron g x 3,47 (nmol) nmol x0,270(g)

Phospho g x 32 (mmol) mmol x 32,2x10-3(g)

Pregnandiol mg x 3,13 (mol) mol x 0,320(mg)

17-OHCS mg x 2,76(mol) mol x 0,362 (mg)

17-cetosteroid mg x3,47(mol) mol x 0,288(mg)

Ur g x 16,6 (mmol) mmol x 60X10-3(mg)

VMA mg x 5,04 (mol) mol x 0,198(mg)

4. V thng k trong Ho sinh y hc v Ho sinh lm sng:

Trong Ho sinh thng p dng loi thng k so snh (so snh mt mu ny vi mt mu hoc nhiu mukhc, so snh mt mu nghin cu vi mt chun, nghin cu nhng mi tng quan gia cc mu...) v dngloi thng k m t ( ???), d kin thu thp c m t bng ho (hoc ton hc)

Nghin cu thng c tin hnh trn mt tp hp (???) mt nhm tiu biu i din tch ra, chn lc rat mt tp hp - Thc t th kim khi c iu kin nghin cu c ton b mt tp hp m ch c iu kinnghin cu mt vi mu trong tp hp ri t a ra nhng nhn nh c ngha cho c tp hp. Vic chnmu l ht sc quan trng. Tu theo tnh cht nghin cu m xc nh cc ch tiu chn vi mu cho thch hp -Cn ch ti cc yu t nh tui, gii ngh nghip, mi trng sng, sinh hot v chn sao cho mu ng l tiu

biu cho tp hp, mu p ng c ch tiu c bn ca cng trnh nghin cu.Cc ch tiu nh gi trong Ho sinh y hc thng c th biu th di cc dng d liu sau.

- D liu nh lng (quantitative data)

- D liu nh tnh (qualitative data)

- D liu bn nh lng (sem quantitative data)

+ D liu nh lng: Cc d liu th hin bng nhng con s, bin thin lin tc (continusus) hoc ri rc(discretc)

Nhng con s bin thin lin tc gi l bin s lin tc (continuone variable) hoc bin thin khng lintc th gi l bin s ri rc - Bin s trong thng k l mt b cc s hiu v mt ch tiu nghin cu no vta c th phn bit bin s c lp (independent varicble) v bin s ph thuc (???). Vic xc nh l c lphay ph thuc cng ch l tng i tu theo yu cu ca nghin cu.

+ Cc d liu nh tnh, bn nh lng cng c s dng trong ton thng k nhng khng nhiu.


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T cc d liu c a vo thng k tnh ton hoc dng my tnh (comfutor) c ci t my mt phnmm, chng trnh STATA c th gii quyt c tt c cc bi ton trong thng k y hc. c im ca STATAl linh hot - Ngi s dng c th thm bt, thay i tu theo yu cu, c th nhp s liu thnh lp (file) hoc

tnh nhanh bng cch trc tip ( ??? ) v dng thun tin.Di y xin ni qua v thng k m t, loi thng k thng p dng trong Ho sinh, dng vi mu

nghin cu nh lng, bn nh lng hoc nh tnh - Thng k m t l bc c bn v cng l bc khi uca nhiu cng trnh tnh ton thng k cc vic phi lm l:

1 - Chn c t ( esSinator) trong hng chc, hng trm s liu thu nhn c, cn tm ra s no tiu biu,i din nht, lc t - C nhiu loi c t trong nghin cu c tnh nh lng nhng hay dng nht ltrung bnh cng (mean) ri n trung v (median).

2 - Kho st s phn b: Mt dy s c coi l phn b chun nu trung bnh cng, trung v v "mt"(made) cng v tr chnh gia (mt biu th s no gp nhiu nht).

- Vi mu nghin cu c dng phn b chun th dng trung bnh cng l hp l v thun tin. Trung bnhcng (x) c trng cho kt qu ca cc php o tun theo lut Garess x..... Xi = gi tr thu c ca mi ln o.

n = s ln o

Tng s.

Nu phn b lch v mt bn (phi hoc tri) th khng nn dng trung bnh cng m dng trung v lthch hp v trung v khng tnh n nhng s liu qu nh hoc qu ln.

nh gi s phn b bng my tnh ta dng mt s thut ton trong chng trnh STATA.

3 - Tm cc s ngoi l (outliers): Trong nghin cu y sinh hc s liu c th bin ng kh ln lm sailch kt qu nghin cu, nhng trng hp c gi l ngoi l, chng ta c php loi b nu thy cn thitv hu ch.

4 - Tnh tn mn (spread) - tn mn cng ln th trung bnh cng cng t gi tr tiu biu. V vycn xc nh tn mn ca dy s liu - tn mn c nh gi bng 1 tham s: lch chun (Stadardeviation - SD-), sai chun (Standar error) nu ch thng k m t th ch cn tnh lch chun - Nu munt mu nghin cu suy ra cho c tp hp th phi tnh sai chun. Cng thc tnh lch chun SD - nh sau:

SD = Trng hp dng c t l trung v th tn mn c nh gi bng t phn di (laner quartile), tphn trn (nyper quartih) v khong lin t phn (interpuartile)

5 - Khong tin cy (Confidence interval - CI).

Trong y hc thng dng khong tin cy 95%

6 - xc sut (Probability- B -) v tin cy (Confidence level - CL).

Trong y thng dng xc sut 5% ( Pc = 0,05) c ngha l chp nhn 5% khng ph hp vi kt lun - khini xc sut 5% c ngha l tin cy t mc 95% - Nu xc sut l 1% th tin cy l 99%.

Vi cch dng my tnh thoe chng trnh STATA c th gip ta nhanh chng tnh trung bnh cng, lch chun, sai chun, khong tin cy hoc tnh trung v, t phn, v ng phn b chun, pht hin ngoi l,v th ct... trong thng k m t mu nghin cu c c tnh nh lng, mt mu, hai mu, so snh... v y khng cp ti thng k v tnh ton khc.


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Tn s

0

5

10

75 80 85

A

b

Nng o c

ng cong kiu Gauss

(nh lng cng mt phn t 100 ln)

A - nh lng tt

B - chnh xc km

M c M c M c

mmollog log

mmol

A b C

Tn s

S phn b ca mt tp hp dng tham chiu.

A - Phn b bnh thng

B- Phn b khng i xng (trng hp cho huyt tng) tr thnh logmo... thC.


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5. V cht lng xt nghim tt nht, chnh xc nht bao gi cng phi l mc tiu phn u ca miphng xt nghim cht lng xt nghim ph thuc vo nhiu yu t.

- Trang b phng tin ho cht, t my xt nghim, cc dng c phng th nghim cho n nc ct, hocht ( tinh khit) thi hn s dng cho php) lu, bo qun.

- K thut nh lng c p dng.

- Chun b, ly bnh phm, bo qun bnh phm xt nghim.

- Thc hin vic nh lng, thao tc v qui trnh k thut.

mi khu u c s lu ring m bo c cht lng (QA ???0 v khi chng ta ni v cht lngthng ch dnh cho ni v kt qu xt nghim nh mt sn phm ca mt qu trnh sn xut ca phng xtnghim. Vic kim tra cht lng (QS -Quality conirol) nhm m bo cht lng xt nghim, xc thc (???)v tin cy (??) ca xt nghim. Qu trnh m bo cht lng phi tin hnh t khu:

- Chun b s thc hin xt nghim: v bnh nhn, bnh phm, v my mc, dng c, ho cht mu th,v th tc...

- Thc hin xt nghim (trong c k thut nh lng)

- Kt qu v phn tch kt qu, s dng kt qu.

Vic kim tra cht lng cng cn h thng nh vy nhng tu theo yu cu ni dung cn gii quyt mc s tp trung vo nhng vn cn c quan tm m quyt nh.

cng tc kim tra cht lng c th l thng xuyn nh k nhm duy tr v nng cao cht lng xtnghim, uy tn ca phong xt nghim hoc l khi c bt thng v kt qu xt nghim (do pht hin ca ngilm k thut, k phiu hoc thng tin t lm sng..) c nghi ng vi s chnh xc ca xt nghim.

Hnh thc v phng php kim tra c th l:

1 - Ni kim cht lng (Internal quality control IQC)

y l vic kim tra trong ni b phng xt nghim, nhm thng xuyn theo di cht lng ca cng tcxt nghim.

2 - Ngoi kim cht l

ng (Exlomasl quality control - EQC hoc Interlaboratong quality control).

Tn s

Nng Nng

Tn s

A C

Nng

Tn s

b So snh tp hp tham chiu vi tp hp

ngi m:A - Hon ton khc bit

B -C mt vng ph ln nhau. Vng nykhng c gi tr s dng

C - Khng s dng c.


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Hnh thc ny c p dng phi hp vic kim tra cht lng gia cc phng xt nghim, vi mt laboqui chiu, loi tr tnh trng ch quan trong KICL ca mi labo.

Hi dung l kim tra chnh xc ca xt nghim, xc thc ca xt nghim.

(Xem tip di c cp trong mt phn ring).

1 - Vai tr ca cc xt nghim ho sinh trong lm sng

2 - Kim tra cht lng ti cc phng xt nghim lm sng)

Hnh thc Ngoi kim cht lng c th c t chc theo nh k, c ngha i vi vic phn u nng cao cht lng xt nghim cp ??? dch v y t nhsang lm nhiu nc pht trin.

Vic nh gi chnh xc ca kt qu xt nghim thng dng cc ch s.

Trung bnh cng (x), lch chun (SD-6) h s bin thin (CV ???)

Vic nh gi xc thc l mt vic kh, xem xt da vo s sai khc vi gi tr thc v s sai khc nycng nh cng tt. Gi tr thc thng da vo dung dch mu chun hoc huyt thanh kim tra c bit rnng do mt labo quy chiu xc nh, c bnh thng v bnh l.

Vic kim ta cht l

ng th

ng xuyn h

ng ng

y. Kim tra chnh xc ca xt nghim.Mi phng xt nghim cn thc hin mi ngy t nht mt ln vi mu chng. Mu ny c th lu -Thc t, c th thu gp t cc huyt thanh kim tra, c dng vo cc l nh v c ng kh - Hng ngy, khidng n l no th ngi ta ly mt lng nc ct xc nh ho tan v s dng. Vic tin hnh nh lngtrn huyt thanh ny c lm cng vi huyt thanh bnh nhn trong cng iu kin v cng thi gian -Kt qus c a vo th theo di v nh gi, phn tch. trc tung l tng hp (hm lng, nng ) v trchonh l thi gian (ngy).

Nu kt qu hng ngy c lp li, s th hin th nhmt ng ngay nu ta ni cc im li.

Kt qu y c th a vo lm theo cch thng k mi thng v nhvy c th kim tra s lp li c kthut - Mt phng xt nghim tt phi c th hin ng ngang trn th vi mi mt cht nh lng hoc thng k tng ng. Cng c th dng cch ny s nh gi mt b phn ca phng xt nghim.

0.200

0 10 20 30

a

b

0.200

Bng chm kt qu nh lnghng ngy ca mt k thut t theodi kim tra nh gi cht lng.

A - Cc kt qu tt

B - Chnh sai ca k thut t ngy

th 13.

iu kin cn thit vic kim tra cht lng thng xuyn hng ngy c kt qu l bao gi cng phim bo c c huyt thanh mu chng tng t.

Vic sn xut huyt thanh mu chng tng "l vi cht lng tt cung cp c thc hin bngphng php cng ngh. V vy l vn c gii quyt v khng cn l vic kh khn nh lc phi thu gp

huyt thanh lm theo cch th cng.

10 20 30 ngy

ngy

Nng o c(mmol)


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Vn cn cn phi lu l bo qun sao cho tt cht lng c bit vi nhng cht km bn vng nhcc enzym th c th s dng cng mt l sn xut trong c nm. Thng cc huyt thanh mu chng c boqun 200C.

y l phng php kim tra dng cho Ni kim cht lng, cho php sch gi cc kt qu s lp li cacc nh lng trong mt phng xt nghim nht nh m khng dng em so snh vi kt qu ca cc labo khcc.

Khi c kt qu bt thng, ngoi mc giao ng cho php phi tm nguyn nhn gy ra s mt chnhxc, khc phc nguyn nhn gy cc sai s , l sai s th bo hin nhin, sai s ngu nhin hay sai s h thng.


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chng 2

vic ly cc bnh phm, cht th xt nghimVic ly cc cht th xt nghim c tt, s m bo cho vic xt nghim v cc kt qu xt nghim

c tt, chnh xc.

Hin nay, tu ni, tu trng hp vic ly mu xt nghim l do cc bnh phng lm ri a n cc labohoc ly mu trc tip labo. D trng hp no cng cn thng nht theo cc hng dn thng nht t cyu cu cc xt nghim chnh xc.

1. Ly mu xt nghim: Cn bit l vic xt nghim cn tin hnh vi ton phn, huyt thanh hoc huyttng - Nu l huyt tng th phi chng ng v chng ng bng cht g l theo yu cu ca xt nghim.

Trng hp cn xt nghim trn cc thnh phn hu hnh (v d choliesterase hng cu) th cng phichn cht chng ng cho ph hp - Cc cht chng ng thng dng theo nhsau:

1 Heparin (di dng mui ammoni, Li, Na, K) - Dng 25 IU cho 1 mm mu - Huyt tng chng ngbng Heparin c th gy nhiu cho xt nghim do gy v hng cu nh - Khng nn dng trong xt nghimPhosgihatase acid- cn lu l cc heparin th trng c th gp li khng c tht tinh khit v nn chn loiHeprin dng cho xt nghim.

2. Nacitrat: 5mg/ml mu - Tc dng chng ng bng cch kt gn vi ion Ca2+ - cng c cc bt tinnhOxalat (ni di, Dung dch ACD (acid citric -citrat - dextrose) gm: acid citric 47g, tri Natri citrat 1H2O160 g, gluose 250g trong 1000 ml nc - chng ng dng 0,15 mg ACD cho 1 ml mu - Dung dch ny dng sbo qun hng cu.

3. Oxalat (mui Na, li, K) c ch ng mu do phc hp vi cc ion Ca2+. Thng dng dung dch NaOxalat khan 200g do ho long l 1% cho 1 ml mu - Sai s gy ra cht chng ng Oxalat th phi xy kh nhit di 800C trnh b phn hu, mt tc dng.

Khi c mt Oxalat, nc trong hng cu thot vo huyt tng gy mt sai s ho long vo khong 5%,

c i vi hematocrit - Mt khc, nng cao c th gy v hng cu - cui cng, cc ion )xalat lm thay iPh mu, khng cho php nh lng Ca, cc ion Na, Li hoc K (v mi Oxalat) cng nh khng cho php thchin nh hot ca mt s enzym.

4. Fluorua (dng mi Na) - Dng 2 mg cho 1ml my, vi tc dng chng ng v chng s phn huGlucose do c ch mt s ynzym phn hu ng qua tc dng vi Mg2+ mt ion cn thit cho hot ng camt s enzym phn hu ng Fluorua thng dng cho xt nghim nh lng ng mu. Tc dng chngng ca Pluorua (lin kt vi Ion Ca2+) yu nn cn c s kt hp vi Oxalat.

Chng ng bng Fluorua th khng c dng trong nh lng ur bn urease.

5. EDTA (ethylen diamin tetracetic acid) dng mui dinatri hoc dipotassic - phc hp vi Ca2+ v ngntr s ng mu. Dng 2mg EDTA cho 1ml mu.

Khng dng trong nh lng Ca mu, mt s enzym corulo plosmin, phosphatase kim (b c ch),Phosphatase acid (c hot ho), v bilirubin (c ch phn ng diazo).

1.1. Vic tch ly huyt tng:

Mu sau khi chng ng, cn c sch sm bng ly tm ( gia tc t 1000 - 3000g; 1800 g - 4000vng/pht) s sch cc huyt cu v s trnh cc vt hu huyt, c bit trng hp nh lng Kali mu. Nu cs thot Kali t huyt cu s gy sai s ln.

Bt li ca vic phi a thm cc cht chng ng vo l c th gy nhiu cho xt nghim mt s cht(xem thm phn cc cht chng ng)

Vic nh lng fibrinogen phi lm trn huyt tng.

1.2. Vic tch ly huyt thanh

Mu ly ra, khng dng cht chng ng, c th bt u ng trong vng vi pht v thn ch tit huytthanh (khng c fibrinogen) ri em ly tm trong vng 2y - gn hoc ht ly huyt thanh chuyn sang 1 ngnghim khc lm cc xt nghim - Ci li ca vic s dng huyt thanh l khng ng li c nh huyt

tng v trong nhng trng hp c tng s ng huyt tng, nu nh khi dng cc my t ng thc hin


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cc xt nghim, huyt tng c th b ng cc ng dn ca cc vi qun v gy sai s hoc tc - Cng cci bt li l ly huyt thanh th phi ko di thi gian tip xc gia dch th ca mu v cc huyt cu c th cthay i no qua li v c th c nguy c gy v hng cu.

1.3. Dng mu ton phn: y l trng hp vi mt s cht nng huyt tng cng gn ging nh hng cu - V d nhGluose v Ur- ch khc l huyt tng nc chim khong 93% cn mu ton phnl khong 81%. V vy cc cht trn huyt tng cao hn mu ton phn mt cht, 1,12 ln.

2. Nhng iu cn ch khi ly mu xt nghim:

Tu theo yu cu cht cn xt nghim m c th ly mu:

-ng mch (s nh lng cc thng s v kh mu, v cn bng acid - base)

- Tnh mch (thng dng nht i vi hu ht cc xt nghim).

- Mao mch (dng vi cc xt nghim ch cn t mu, ly mu bng cch chn u ngn tay, di tai hocgt chn - c bit vi cc nh nhi -)

2.1. Chun b bnh nhn trc khi ly mu xt nghim.

-Bnh nhn trng thi sinh l t nhin, ngh ngi, nm di th dn, khng c vn ng mnh - Vnng c th gy tng cc enzym nh creatinphosphoKinase, lactardehydrogenase, GOT... hoc tng cc cht nhacid lactic.

Cng thng c th lm tng Catecholarmin...

- n ba n chiu hm trc xong, t sau khng c n g thm cho ti lc ly mu xt nghim snghm sau - (Thi gian nhn i l 12 h) - Vic ly mu thng nn vo khong 7-8gi sng (vo mt gi nhtnh, bui sng dy, khng n ung g), s trnh s thay i theo thi im trong ngy ca mt s cht nh cchomon thng thn, cortisol...

Nu nh c n trc ly mu xt nghim th gy tng nhiu cht nh ng, triglycenid, phosphat vc th nhiu cht khc na nhbilarubin, cholestrerol, Kali, calri, wat, Protein, phosphatase kim... nn cn trnhly mu xt nghim sau khi n.

2.2. K thut khi ly mu:

- Gar ch nn va phi, khng qu cht, vn cm nhn c mch quay, trnh gy nhng thay i giahng cu v huyt tng.

- Trnh tt c cc tnh trng gy hu huyt v cc thnh phn cc cht huyt cu nu vo huyt tng slm thay i thnh phn huyt tng v mu ca hemoglobin c bit s c th nh hng ti nhiu nh lngtheo phng php so mu - Cc iu c th cn lu l:

-St trng: V l thuyt th tt c cc cht dng st trng d nh te, cn... u c th gy hu huyt - Vvy ngi ta c s hng dn thm l sau , dng bng thm nc mi sinh l v trng lau li - Tuy nhintrong thc t thng ch l ch mt cht cho kh cht st trng ri ly mu.

- Khi ly mu khng dng bm tim ht qu mnh hoc p piston bm qu mnh, v gy cc thay imnh, t ngt v p lc c th lm v hoc thot ra khi hng cu cc cht c trong n.

- Nu mu cha dng ti, cn bo qun th cn nhanh chng ly tm tch huyt thanh hoc huyt tng,ri lnh 40C hoc - 200C tu theo yu cu.

- Vi cc cht nh lng l cc cht km bn vng cng cn nhanh chng s vo v c th chuynnhanh ti phng xt nghim - nhit 40C trong khong thi gian ngn th cng cha gy nh hng g ngk.

- Nu bnh phm (mu) cn c vn chuyn th cn tch ring hng cu trc v rung lc c th gy huhuyt.

2.3. Ngoi ra cng cn bit l hin nay th trng nhng loi ng ng mu chun b sn:

- Loi c cc cht chng ng vi nhng ch dn, k hiu thun li cho vic s dng ly my chngng, huyt tng, huyt cu.

- Loi ng ly huyt thanh (c cc ht nh Ploicthylen hoc nhng ng chn khng ht mu v phnlp SST)

2.4. Vic bo qun huyt thanh:

Nu bo qun huyt thanh ch dng ngn ngy th ch lnh 40C.


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Nu bo qun huyt thanh dng di ngy th cn lnh su hn -200C.

Thi gian cho php vi mi cht, c bit cc hormon, cc enzym c nhng theo di v quy nh ring(xem thm cc phn lin quan).

Mt s cht khng n nh nhLactat, Pyrurat... th nn nt nghim ngay - Nu cn li th cn x l,loi b protein sm bng acid trcloracetic hoc acid periloric trc. Ngoi ra cng phi c y nt kn hoctrnh nh sng vi mt s cht nhbiliubrin...

3. Vic ly nc tiu xt nghim:

Nu l xt nghim nh tnh mt s cht thng c th lm vi mt mu nc tiu ti, bt k ly xonglm ngay.

Khi i tiu nn b mt cht phn u ri ly phn tip theo xt nghim.

Nu l xt nghim nh lng, mt cht no th khng th tin lm trn mt th tch nc tiukhng xc nh v nhvy khng c ngha m phi tun th cc qui nh - Nc tiu ly phi trong mt khongthi gian nht nh (3h, 6h hoc 24h...), dng c ng nc tiu phi sch, cn th phi c bo qun lnh viho cht s trnh s phn hu ca cc cht cn xt nghim, hn ch s pht trin ca cc vi khun, hoc kt qu

ca mt cht. Tt nhin l

cc cht bo qun phi khng

c gy nhiu cho phn ng phn tch v

sau phic lc u v o th tch.

Vic ly nc tiu 24h thng khng d dng c s chnh xc (v d phi ly c nc tiu trc v ktthc i i tin). m bo cho vic xt nghim tt nn thc hin theo mt qui trnh nhsau:

3.1. Chun b cho vic ly nc tiu:

Tu theo cn thit i vi cht xt nghim m bnh nhn phi tun th mt quy nh v n ung v dngthuc nht nh .

V d: Khng n chui tiu, bnh ngt, c vani, ung thuc... khi ly nc tiu nh lng VMA(Vanyl mandelic acid) hoc trng hp xt nghim acid uric th khng n nhiu m (protid nhn tht c bp)chocolat. ..

3.2. Ly nc tiu 24h

Sng thc dy (v d l 7h sng) i tiu tht ht, b i v bt u tnh t gi ny thu gp tt c nc tiucho n 7 h sng hm sau. Gi l nc tiu 24 h.

Nc tiu c bo qun lnh v ho cht tu yu cu - Lc hoc khuy u tng lng nc tiu 24h.

o, ghi li th tch v ong khong 50 ml nc tiu lm xt nghim v cn xt nghim sm - kt quc tnh vi lng nc tiu 24h.

V vic thu gp nc tiu 24h kh m bo chnh xc, ngi ta thng nh lng thm creatinin niu lmt cht c bi xut hng ngy ca mt ngi hu nh hng nh kim tra li s lng nc tiu cthu gp mt cch gin tip c c chnh xc khng? Tuy nhin cng cn nhc li l lng cretinin niu c thc s thay i theo khi lng c bp, tui, tnh trng ca thn mc du vn c dng mt cch th i lmchng cho s bi niu.

3.3 V vic dng cht bo qun vi nc tiu:

- Vic bo qun nc tiu Thng l cc hn Kali acid Phosphat, na benzoat, Na, bicarbonat, Metheamin,

oxyd thu ngn .Hn hp bo qun gii phng ra formol, h thp pH nc tiu, dit khun dng c c cho xt nghim

ho inh v vi sinh.

V trong thnh phn c c nati Kali nn khng dng cho nh lng Natri, Kali khi bo qun bng hnhp ny.

- Formalin: Dng bo qun c nhng c bt li l nng cao s ta ur v c ch mt s phn ngdng enzym nh thanh th dng esterase tm bch cu.

- Dung dch Hoc l 6 mol/l: dng 10 ml acid ho nc tiu, a pH xung di 3 bo qun nctiu 24h. Thng dng cho cc nh lng Cali, cc steroid, VMA - Bt li l gy ta urat v khng dng chonh lng acid uric - Dng acid boric cng gy ta acid uric.

- Thymol, chloroforon: dng bo qun c ci bt li l phi xt nghim ngay , nhiu trng hp li thhin l khng c tc dng v l ngun gy nhiu cho mt s phn ng phn tch - V vy nhiu ni khng dngna.


19/186

- Toluen: l mt dung mi hu c, d chy, lin quan n an ton lao ng phng th nghim.

Toluen c s dng to mt mng mng trn mt, chng cc vi khun nhng khng c tc dng vicc vi khun k kh - Cng t c s dng.

- Natri Carlonat: dng bo qun Porphyrin v arobilinogen vi lng 5g Natricarbonat cho nc tiu 24h.

4. Vic ly cc dch sinh hc khc

Cc dch sinh hc khc c ly xt nghim khi thc hin cc nghim php ly dch v, dch t tr ng,dch mt, khi ly dch no tu hoc cc dch bt thng, bnh l nh dch mng bng (c chng), mng phi,mng tim hoc dch bng chc d nhm phc v cho chn on iu tr hoc nghin cu.

C th l xt nghim thnh phn cc cht, cc t bo, phn bit dch thm, dch tit...

Tu trng hp c th kt hp, vic ly dch xt nghim thng do lm sng lm gi ti v c s trao itrc labo c s chun b.

5. Vic ly cc t chc xt nghim:

mt s ni c ly t chc khi m hoc sinh thit (da, d dy, gan, nghi khi u...) xt nghim theonhng yu cu chuyn su cc lab c bit - c th lc n y vic mi ch l lc mi bt u nhng l phngphp c ngha vi sau ny.

Cng vic cn c s phi hp bn bn chun b trc gia lm sng vlab khi tin hnh lab c thxt nghim ngay c. C nhng trng hp cn phi qua cc bc nui cy t bo hoc cc k thut phc tphn v sinh hc phn t.

C nhng trng hp, t chc ly ra cn c ng lnh ngay trong huyt carbonic.

6. Vic ly phn xt nghim:

Cn c l kh, sch, y np - Tu yu cu cht cn xt nghim m c hng dn ring. Thng ly phn phn gia hoc c nghi ng bt thng, bnh l: c mu, mt, cht nhy hoc nghin cu nh gi v tiu hotip thu cc cht dinh dng glucid, lipid, Protid...

Vic ly phn xt nghim nhiu khi cng cn phi c s chun b v n ung v dng thuc. V nhtrng hp cn pht hin mu phn do xut huyt ng tiu ho th trc 3 ngy lm xt nghim khng n

tht, c, rau qu c cha cht dip lc, chui c cha Peroxydase, ngng khng dng cc thuc c Fe, Cu.


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nghim cp cu mt nhiu tin nn phi c s la chn khi ch nh.

4. Vic tr li kt qu ca phng xt nghim ti thy thuc.

Kt qu tr li phi d c, trnh c cc sai ln do vit ghi khng r (con s, cc n v) - Tt hn l cphn t ghi my hoc c nh my.

Ngi k tr li kt qu thng nn l ngi cn b v y c trch nhim, c th kim tra cht lng xtnghim v pht hin cc yu t sai st lm hng kt qu, c s i chiu theo di kt qu nhng ln xt nghimln trc nu c. - Phn ln nhng nguyn nhn sai st thng l do s sao chp vit tay thiu cn thn.

Cn ghi chp y r rng cc con s, n v... (theo mu) v cht xt nghim, huyt thanh, huyttng nhng mch, tnh mch. Trong iu kin hin nay th nn tr li kt qu xt nghim bng h thng nv c v c n v mi (n v SI)

5. Vn phn tch cc kt qu xt nghim

Vi mt kt qu chc chn, chnh xc em i chiu vi bng gi tr bnh thng, ta c th thy ngayc l bnh thng, tng hoc gim - Phn tch cc nguyn nhn tng gim, l thay i c tnh cht sinh lhoc bnh l - Cn lu cc thuc s dng, kt qu tc ng i vi c th c lin quan n xt nghim ri i

n chn on - khu ny nhiu khi s rt c ch nu nhc c s trao i ca thy thuc lm sng vi thythuc sinh ho.6. Mt vn cng phi ni qua, mc d khng th c th v ph thuc v o trang b k thut v phng

tin ho cht... l gi tin phi chi tr cho cc xt nghim theo thi im m ngn qu v ngi bnh phi gnhchu, c bo him.

Chng 4Vai tr cc xt nghim ho sinh trong lm sngTSKH. Nguyn Ch Ph

M u:

Ho sinh lm sng c vai tr rt quan trng trong cc hot ng lm sng hng ngy, ng thi gp phnkhng nh trong nghin cu sng to nhm khng ngng nng cao nhng hiu bit v bnh tt, tm kim cc giiphp nng cao cht lng chn on, iu tr v tin lng bnh.

1. Nhng lnh vc tc ng ca Ho sinh lm sng.

1.1. Xt nghim sng lc

* Xt nghim sng lc nhm pht hin nhng ngi c cc yu t nguy c mc bnh, nhng khng biuhin cc triu chng.

* ngha ca sng hc:

- Pht hin v

iu tr sm bnh tt tim n gip cho gim t l bnh tt v t vong.- Pht hin cc yu t nguy c cho php can thip sm, ngn chn bnh khng cho xy ra, hoc ngn

chn di chng.

- i vi nhng bnh c tnh gia nh: xt nghip sng hc cho php xc nh nhng thnh vin khng cbiu hin bnh, hay khng c yu t nguy c, cung cp cho h li tvn di truyn hc.

* Nn quyt nh lm xt nghim sng hc trong nhng trng hp no?

Vic quyt nh lm xt nghim sng hc nn da theo mt nguyn tc hng dn, nh tm tt bng 1.

1.2. Xt nghim chn on.

* Xt nghim chn on c dng xc nh hay loi trs c mt ca mt s bnh nhng ngikhng c triu chng.

* ngha ca xt nghim chn on:- Chn on xc nh.


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- Chn on sm, ngay sau khi bt u cc triu chng hay du hiu.

- Chn on phn bit.

- Xc nh cc giai on tin trin ca bnh.

1.3. Xt nghim theo di bnh nhn.

Xt nghim thuc phm vi p dng ny nhm mc ch:

- nh gi khch quan v lng ho mc nng_ ca bnh; v tin lng_ bnh.

- Theo di qu trnh din bin ca bnh (tin trin, n nh hay thuyn gim).

- La chn hay iu chnh cch iu tr trnh ng c, v m bo tc dng iu tr

- Theo di p ng iu tr

- Pht hin s ti pht bnh

Bng 1- Nguyn tc s dng xt nghim sng hc

c im ca bnh:

1.Ph bin, ng tp trung c gng pht hin.

2.T l bnh tt v t vong cao nu khng c iu tr.

3.C sn phng php iu tr hiu qu v chp nhn c lm thay i din bin t nhin ca bnh.

4.C giai on tin chng c th pht hin v iu tr.

5.Pht hin v iu tr trong giai on tin triu s cho kt qu tt hn so vi vic iu tr trong giai ontriu chng.

c im xt nghim.

1.C th chp nhn c i vi bnh nhn.

2. nhy pht hin bnh nhng ngi c tin triu (m tnh gi: t).

3. c hiu loi tr bnh ngi kho mnh (t dng tnh gi).

c im ca cng ng d nh lm xt nghim sng lc

1.T l lu hnh bnh cao.

2.Tip cn c.

3.C th ng thun cc xt nghim chn on v iu tr c khuyn co v sau.

2. Mt s vn thng gp trong khi s dng cc xt nghim

2.1. nhy ca cc xt nghim (sensitivity)

nhy ca mt test th hin kh nng dng tnh ca n nu nhbnh c tht.

Mt xt nghim cho kt qu d

ng tnh mi bnh nhn th c nhy 100% (khng c kt qu mtnh gi)

Mt xt nghim c nhy hon ho nhvy cho php loi tr chn on bnh, nu kt quca n lmtnh.

2.2. c hiu (specificity)

c hiu th hin kh nng m tnh ca mt xt nghim nu nh bnh ang nghin cu bng xtnghim ny lkhng c.

Mt xt nghim cho kt qu m tnh tt c cc bnh nhn khng mang bnh s c c hiu honton ( c hiu 100%).

Mt xt nghim c c hiu hon ton cho php chn on xc nh nu kt qu xt nghim dngtnh (bt thng).

V d, Creatine Kinase (CK) l xt nghim nhy i vi hoi t do thiu mu ca c tim.


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Nu CK bnh thng trong thi gian 24 - 48h sau khi au ngc, th c th loi tr nhi mu c tim ctim cp.

Nhng CK li khng c hiu lm (nhiu nguyn nhn khc cng lm cho CK bt thng).

Tri li, cc sng Q mi trn in tm th rt c hiu, gip chn on xc nh nhi mu c tim cp.Nhng c li khng nhy lm, v nhi mu c tim cp c th xut hin ngay c khi khng c sng Q.

Trn thc t, khng c mt xt nghim labo no dng trong lm sng c nhy hon ton hay chiu hon ton.

2.3. Dng tnh gi v m tnh gi

- Kt qu dng tnh gi xy ra khi mt kt quxt nghim dng tnh (bt thng) m ngi c th likhng c bnh.

T l dng tnh gi i vi mt xt nghim l yu t b sung ca tnh c hiu ca n. Dng tnh gi= (1 - c hiu).

- Kt qu m tnh gi xy ra khi mt xt nghim cho kt qu m tnh (bnh thng) m ngi c th limang bnh.

T l m tnh gi i vi mt xt nghim l yu t b sung vo nhy ca n. m tnh gi = (1 - nhy).

2.4. Gi tr tin lng ca mt xt nghim.

2.4.1. Gi t tin lng dng tnh (positive predictive value - PPV)

- Gi tr tin lng dng tnh ca mt test cho bit kh nng b bnh ca mt ngi c xt nghim khikt qa dng tnh.

- Gi tr tin lng dng tnh lin quan n nhy ca test

- T l bo ng gi (false - alarm rate) ca mt test l: yu t b sung ca gi tr tin lng dng tnh (= 1 - PPV)

2.4.2. Gi tr tin lng m tnh (negative predictive value - NPV)

- Gi tr tin lng m tnh ca mt test cho bit kh nng khng b bnh ca ngi c th nu testm tnh.

- Gi tr tin lng m tnh lin quan n c hiu ca test.

- T l trn an gi to (false - reassurance rate) l yu t b sung ca gi tr tin lng m tnh (NPV)(= 1 - NPV).

4.3.2. Cch tnh cc gi tr tin lng (bng 2)

Bng 2 - Cc mi quan h gia bnh v cc kt qu xt nghim.

Bnh

Xt nghimC Khng

Dng tnh a b

m tnh c d

a nhy = x 100%

a + c

d c hiu = x 100%

b + d

a


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Gi tr tin lng dng tnh = x 100%a + b

dGi tr tin lng m tnh = x 100%

c + d

cT l m tnh gi = x 100%

a + c

bT l dng tnh gi = x 100%

b + d

bT l bo ng gi = x 100%

a + b

cT l trn an gi = x 100%

c + d

3. La chn v gii thch cc kt qu xt nghim3.1. nh l ca Bayes

Gi tr tin l

ng (d

ng tnh v

m tnh) ca mt test lin quan khng nhng vi c im ca test m

cn lin quan vi qun th ngi c xt nghim (t l hin nhim ca bnh - prevalence). Ngha l ngi thythuc cn cn nhc khng nhng v tnh khng chc chn vn c ca xt nghim, m cn phi tnh n c xcsut ( c bit hoc c on) ca s hin hu bnh.

3.2. p dng:* loi trmt bnh vi mc chc chn, nn ch nh mt xt nghim rt nhy (cho t kt qu m

tnh gi).

* xc nh chun on vi yu cu tin cy cn mt test rt c hiu (cho t kt qu dng tnh gi)

Khi la chon mttest nhy loi trhay mt test c hiu xc nh chn on, trc ht ngi thythuc phi c onxem liu mc tiu chn on l kh c th tn ti hay c th tn ti. Bng 3 tm tt mt shng dn dng cc test

Bng 3 - Mt s hng dn s dng xt nghim labo

1.Trc khi ch nh mt xt nghim, hy c on t l hin hu ca bnh. Nh gii thch kt qu xtnghim vi t l ny.

2.Khi mt bnh c rt nhiu kh nng l khng tn ti, th mt kt qu dng tnh s lun l dng tnhgi.

3.Khi mt bnh rt c th tn ti, th kt qu xt nghim m tnh s lun lun l kt qu m tnh gi.

4.Vic loi tr mt bnh cn c kt qu m tnh ca mt xt nghim c nhy cao (t m tnh gi). Hys dng gi tr ca mt kt qu xt nghim m tnh

5.Vic xc nh mt bnh i hi kt qu dng tnh ca mt bnh c c hiu cao (t dng tnh gi).Hy s dng gi tr ca mt kt qu xt nghim dng tnh.

6.Hy t hi xem liu kt qu xt nghim c th lm thay i chn on ca anh hay lm thay i s theodi bnh khng? Nu khng, th dng ch nh xt nghim


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7. lm gim nguy c ca kt qu dng tnh gi, hy hn ch dng cc xt nghim sng lc cho nhngtrng hp c cc nguy c hay cc biu hin khc c th lm tng t l i vi bnh.

8.i vi cc bnh khng ph bin, hy gii hn vic sng lc hay xt nghim vo cc trng hp cc p

dng sau y:- Bnh quan trng cn pht hin (hay khng b st).

- Bnh c th iu tr c v c iu kin iu tr.

- Xt nghim c nhy v c hiu cao.

- C cch phn bit dng tnh tht v dng tnh gi.

9.Khi nh gi nhng i hi v cc xt nghim chn on mi, hy t hi:

- Test nhy nh th no i vi cc trng hp tin triu chng hay ch c triu chng ti thiu.

- Xt nghim c hay cho kt qu dng tnh gi nhng ngi c nhng bnh khc m biu hin cc triuchng hay du hiu tng t, c bit l cc bnh c lin quan cht ch.

* c on t l bnh trc xt nghim (pretest likelihood) trnh sai lm hay gp ca cc thy thuc l kt lun c bnh da trn kt qu xt nghim dng tnh,

nhng thc ra li khng c bnh, thy thuc cn phi c on s b v t l bnh trc khi yu cu lm xtnghim.

- Khi t l bnh trc xt nghim cao, th mt kt quxt nghim dng tnh gip cho xc nh chn on:song mt kt qu m tnh khng mong mun li khng th loi tr chn on.

Khi t l trc test thp, mt kt qa m tnh s gip loi tr chn on; nhng mt kt qu dng tnhkhng mong mun li khng c ngha xc nh

Xt nghim c ch nhtlkhi chn on thc skhng chn chn (t l trc xt nghim khong 50%).

Cc xt nghim labo ch ng gp t mt khi vic chn on xc nh cc k t kh nng xy ra hoc lhu nh chc chn.

3.3. Phn nh ranh gii cc kt qu bnh thng v bt thng: cut-off pointTrong thc hnh xt nghim, hu ht cc xt nghim nh lng u cho nhng gi tr c dng phn b

hnh chung (phn b Gauss). V, rt nhiu trng hp, i vi mt xt nghim no , cc gi tr o cca ngi bnh thng v gi tr thu c ngi bnh thng c mt khu vc trng nhau (xem H.1). Do ,ngi lm cng tc xt nghim cn xc nh im ct (cut - off point) phn nh ranh gii bnh thng vbnh l.


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Sitngcxtnghim

Kt qu xt nghim

Khng bnh C bnh

A B C

H1 - S phn b cc kt qu bnh thng v bnh l

Phn tch

Vic xc nh cut - off point gia cc kt qa xt nghim bnh thng v bt thng th hin mi quanh gia nhy v c hiu.

Nu chn A lm im ct, th: tt c cc bnh nhn c gi tr bn phi A u l bt thng. Do : xtnghim c nhy 100%, nhng c hiu thp. im chn ny thch hp cho mc tiu sng lc hay loi trbnh

Nu chn C lm im ct, th: mi bnh nhn c gi tr bn phi C l c kt qu bt thng. Do : xtnghim c c hiu 100% nhng nhy thp. im chn ny thch hp cho vicxc nh chn on i vitrng hp nghi ng.

i vi hu ht cc xt nghim, thng chn im B, vo khong gia A v C. Vic khng nh v tr caB tu thuc l do lm xt nghim v vo tm quan trng ca cc kt qu dng tnh gi v m tnh gi.

i vi hu ht cc xt nghim, cc gi tr bnh thng c xc nh bao gm vng gi tr 2 lchchun ca gi tr trung bnh (X ). Gi tr tham chiu thay i theo phng php k thut, phng xt nghim,cch ly v bo bnh phm. Mun c kt qu xt nghim tin cy, mi labo cn phi thc hin tt vic mbo cht lng xt nghim theo nhng quy chun nht nh.

Chng 5

kim tra cht lng ti cc phng xt nghim lm sng(*)m u

Cht lng ng ngha vi "xut sc: v "thng hng". Mi phng xt nghim lm sng u phi phnu cung cp dch v y t tt nht thng qua cc kt qu xt nghim c cht l ng cao. Trn thc t, d c cgng n my i na, mi labo vn phi chp nhn mt s kin km chnh xc (imprecision) v km xc thc(inaccuracy) mt mc no trong hot ng xt nghim.

Mt labo c nng lc phi gi cho s km chnh xc/km xc thc mc thp nht. Mun vy, cnphi thc hin nghim tc cc hot ng m bo cht lng (quality assurance, QA) v kim tra cht lng

* Tin s Khoa hc Nguyn Ch Phi


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(quality control, QC)

1. Kh i nim v m bo cht lng vkim tra cht lng

1.1. m bo cht l

ng (QA)QA l mt h thng y cc ng li, phng php v thc hnh cn phi lm m bo tin cyv xc thc ca phng php xt nghim.

1.2. Kim tra cht lng (QC)

QC l mt h thng cc phng php v thc hnh cn phi lm theo di v nh gi cht lng caqu trnh xt nghim, nhm m bo xc thc (accuracy) v tin cy (reliability).

2. m bo cht lng phng xt nghim lm sng.

2.1. Mc tiu ca hot ng QA.

QA i khi cn c biu t di nhng thut ng khc nhng mang ngha tng t nh:

- Ci thin cht lng (quality improvement, QI)

- Ci thin cht lng lin tc (continuous quality improvement, CQI)

- Qun l cht lng ton din (total quality management, TQM)

Mc tiu ca QA l m bo tin cy v xc thc cc hot ng ca labo, thng qua mt h thngcu trc c hiu lc, bao gm cc ng li, phng php, t chc v thc hnh ph hp.

H thng ni trn c theo di v nh gi bng cc cng c theo di v nh gi (monitor, indicator).

2.2. Phm vi qun l ca QA

QA qun l cc hot ng ch yu ca labo nhm thc y v to iu kin labo t c cc mc tiucht lng v uy tn vng chc.

Phm vi qun l ca QA c th chia lm 3 lnh vc:

* Qun l cc hot ng trc phn tch (Preanalytic phase), bao gm:

- Ch nh xt nghim

- Chun b bnh nhn

- Ly mu xt nghim

- nh du bnh phm

- Bo qun bnh phm

- Vn chuyn bnh phm

- Loi b bnh phm

- Thng tin phc v xt nghim

* Qun l cc hot ng phn tch, bao gm:

- Thc hin xt nghim

- a ra kt qu xt nghim

* Qun l sau phn tch bao gm:

- Phn tch kt qu

- nh gi ngha lm sng kt qu

- a ra cc bo co

- Gii quyt khiu ni v phn nn.

Trong lnh vc qun l hot ng phn tch, QA s dng chin lc rt quan trng v kim tra cht lng(quality control QC).

Nhvy, trong thc hnh, QC l mt b phn ca QA, mt b phn khng th thiu c i vi mi laboc tn nhim cao. Mi hot ng QA v QC nhm mang li cc kt qu xt nghim t ti yu cu lm s ng, rtxp x gi tr thc.

2.3. Hai thnh phn c bn ca QA.


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Hai thnh phn c bn m bo tnh kh thi cho QA l chng trnh QA v cc cm nang QA.

* Chng trnh QA:

Chng trnh QA to nn mt h thng qun l cht lng ca labo. Chng trnh ny tn ti v c tuchnh thch hp vi s pht trin ca labo. Chng trnh phi c vit thnh vn bn; thng bao gm cc nidung ch yu sau y:

- Qun l xt nghim

- nh gi hot ng kim tra cht lng

- nh gi k nng xt nghim

- So snh vi kt qu xt nghim

- Mi quan h gia kt qu xt nghim v bnh nhn

- nh gi nhn lc.

- Trao i thng tin gia hot ng labo v hot ng lm sng

- Qun l thc mc/than phin.

- Tho lun ni b labo- Xy dng cc bn gi

* Cm nang QA.

Cm nang QA bao gm mt h thng ti liu c bn son sp v xp thch hp hng dn vic thchin cc ni dung ca chng trnh QA.

Cm nang QA cng y v chi tit cng c th gip cho labo thc hin c hiu qu chng trnh QA.

3. Kim tra cht lng (QC)

Hot ng QC ca mt labo din ra hng ngy theo nhng quy trnh thch hp nhm m bo chc chnrng qu trnh xt nghim ca labo c th cung cp cc kt qu c chnh xc v xc thc dt n nhng yucu lm sng v xp x gi tr thc. Hot ng QC gip ngi qun l labo pht hin cc vn pht sinh kpthi sa cha, nng cao hiu qu chuyn mn v hiu qu kinh t cho cc hot ng labo.

3.1. Cc yu t c nh hng n kt qu phn tch ca cc labo.

C nhiu yu t nh hng n cc khu ca qu trnh xt nghim, gy nn tnh km chnh xc(imprecision) v km xc thc (inaccuracy) ca labo. Mt labo c uy tn phi lun lun phn u lm cho tnhkm chnh xc v tnh km xc thc mc thp nht.

Cc yu t gy nn tnh km chnh xc v tnh km xc thc ni trn c gi l ci sai s theo thut ngthng k.

- Sai s hin nhin (sai d th bo, gross error)

Sai s ny gy nn do nhng li th bo d nhn thy mt s khu thc h nh xt nghim, nh: x lmu xt nghim, s dng pipet, ong thuc th, chn bc sng o quang...

- Sai s ngu nhin (random errors)

Sai s ngu nhin l

m cho cc gi tr phn tch ca mt mu xt nghim lp li nhiu ln trong cng mtiu kin, b phn tn nhiu hay t ch khng th cho mt gi tr duy nht. Sai s ngu nhin tc ng v o chnh xc ca kt qu phn tch.

C th hn ch sai s ny bng cch dng my phn tch tt v ho cht xt nghim c cht lng cao.

- Sai s h thng (systematic error).

Sai s h thng gy nn nhng xu hng bt thng ca cc gi tr phn tch (lun lun thp hn hoc lunlun cao hn so vi gi tr trng i).

Nhng sai s ny thng gy nn bi nhng yu km khng c pht hin kp thi m vn cho chng canthip mt cch h thng vo qu trnh xt nghim; chng hn:

+ Thuc th hng

+ iu chnh nhit khng chnh xc

+ Pipet c khuyt tt


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+ My o khng c cn chnh tt...

Sai s h thng tc ng vo xc thc ca php phn tch.

3.2. Mt vi khi nim thng k dng trong vic kim tra cht lng (QC)

* Trung bnh cng (X) v Trung v (Median, Me).

Khi xc nh nng ca mt thng s xt nghim trong mt mu xt nghim nht nh (mu, ...) tathng o lp li nhiu ln v nhn thy cc gi tr thu c c tnh phn tn mc ln hay nh.

S phn tn ni trn c th phn b theo hai dng: phn b chun (biu th bng ng cong Gauss) vphn b khng chun.

Trung bnh cng (x) c trng cho kt qu ca cc php o tun theo lut Gauss.

Xi: Gi tr thu c ca mi ln oX = : Tng

nn: s ln o

Trong phn b khng chun, gi tr c trng cho php o l Trung v (median, Me). Me l gi tr o c nm

ti v tr chnh gia dy s o c sp xp theo th t t nh ti ln.* lch chun (Standard deviation, SD)

2

Sd =n - 1

(x1 - x)

Cc gi tr o tun theo lut phn phi Gauss c phn b theo t l sau:

X SD: Chim 68.26% (thng dng 68%)

X 2SD: Chim 95,44% (thng dng 95%(

X 3SD: Chim 99,74% (thng dng 99,7)

- Trng hp cc gi tr o c phn b khng theo lut chun th khong 95% bao gm cc gi tr nm

trong phm vi t 2,5% dy s n 95% dy s th t (dy th t xp t nh n ln ca cc kt qu o).* H s phn tn (Coefficient of variation, CV)

SD

CV = x 100X


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H s phn tn quan h vi X theo biu sau:

Cv

%

15

10

5

100 200 X[ ]

Biu ny l-u rng khi so snh CV ca 2 my o hay 2 labo khc nhau, hoc khong gia hai ph-ng php phn tch, cn phi

xem cc kt qu c trong nhng khong nng t-ng t khng.

3.3. Mt s im ch yu trong thc hnh kim tra cht lng ho sinhlm sng (HSLS)

3.3.1. Ni kim cht lng (NKCL) v ngoi kim cht lng (NgKCL) HSLS.

* Ni kim cht lng HSLS (NKCL HSLS)

m bo cht lng ca nhng kt qu xt nghim ca mi labo, hot ng phn tch ca bn thnlabo cn c theo di v nh gi thng xuyn bi nhng hot ng kim tra cht lng. l NKCKHSLS (Internal QC, IQC).

* Ngoi kim cht lng HSL (NgKCL HSLS)

lm tng thm tinh thn trch nhim ca mi labo i vi vic t chc thc hin kim tra cht l ngxt nghim ng thi loi tr c tnh trng ch quan i vi cht lng ca mi labo, hot ng KTCL cnc t chc phi hp gia mt s labo, c bit l phi hp KTCL vi mt labo quy chiu.

Hot ng phi hp KTCL nh vy goi l ngoi kim cht lng (NgKCL) (External QC, EQC,Interlaboratory QC)

3.3.2. Thc hnh NKCL HSLS

3.3.2.1. Cc ch tiu nh gi cht lng xt nghim

* chnh xc (precision)

. C nhiu cch nh ngha chnh xc trong KTCL HSLS. chnh xc cho bit mc lp li, sging nhau ca cc gi tr thu c trong php phn tch lp li nhiu ln i vi cng mt mu xt nghim.

. nh gi chnh xc ca kt qu xt nghim, thng dng cc ch s sau:

- Gi tr trung bnh cng (X )

- lch chun (SD, )

- H s phn tn (CV)Cc ch s ny c tnh t nhng kt qu KTCL cho mi thng s xt nghim (Parameters)

* xc thc (accuracy)

- Gi tr thc lgi tr thc ca cht cn o.

Trn thc t, khng bao gi c th t c xc thc, m ch c th c gng tip cn n vi mtmc chnh lch cng nh cng tt. Mc chnh lch (sai lch) gia gi tr thc (X0) vi gi tr thu ctrong KTCL phn nh km xc thc (inaccuracy) ca kt qu xt nghim, k hiu bng d tnh ra %.

d: km xc thcX0 - X

d = x 100X0

X : Gi tr trung bnh cng thu c trong KTCL

X0 : Tr s thc

3.3.2.2. Kim tra chnh xc ca xt nghim


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* Quy trnh:

Tu theo iu kin ca labo, c th thc hin linh hot quy trnh xt nghim kim tra cht lng. Quytrnh sau y c th p dng cho nhiu labo:

- Mi lot XN bnh phm u phi kim tra chnh xc (k c khi ch lm 1 XN).

- Nu s XN trong mt lot qu nhiu th t 2 XN KTCL: mt lot u v mt cui.

- Nu phn tch nhiu lot XN th c sau 10-20 XN bnh phm li l m 1 XN kim tra cht lng. Mi xtnghim KTCL c thc hin vi mt mu huyt thanh kim tra thch hp cho kt qu xt nghim t ng ngvi cc thng s cn KTCL. Ghi li cc kt qu ny sau mt thi gian c s liu, tnh ra cc ch s ctrng cho chnh xc (X , CV), ri xy dng mt biu theo di v nh gi chnh xc. Dng biu ca chung nht l biu levy-jennings (xem hnh v)

Trn s ny, trc X c dt tnh ngy thng; trc Y t cc gi tr KTCL, cc gii hn ISD, 2SD cbiu th r rng.

Huyt thanh kim tra dng kim tra chnh xc thuc cc loi sau y: khng bit trc nng , bittrc nng , hay t to bng thu gom cc huyt thanh d trong qu trnh xt nghim.

+3sd

+2sd

+1sd

-1sd

-2sd

-3sd

Gi tr trng iGi trKtra

N

Biu Levy - Jennings*Phn tch kt qu kim tra chnh xc

- Phng php thng thng

- -c chp nhn nu kt qu nm trong khong tin cy (t X - 2 n X + 2 )

- Thn trng nu c 1-2 kt qu nm ngoi gii hn tin cy nhng tron phm vi X 3 (khong bo ng)

- Khng chp nhn khi:

- Nu kt qu nm ngoi khong bo ng

- 7 gi tr kim tra lin tip u nm mt pha ca gi tr trung bnh.

- 7 gi tr kim tra lin tip c xu hng tng ln hoc gim xung lin tc.

- Ngoi ra, phi nh gi cht lng thng qua CV v SD xem xt s phn tn ca cc gi tr KTCL.

- Phng php phn tch ca Westguard (Westguard Multirule technique).

gy 1 2 3 4 5....

X


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Phng php ny a ra 5 trng hp khng chp nhn kt qu xt nghim:

- Lut 1: 3S: Mt kt qu kim tra vt gii hn X 3

- Lut 2: SD: Hai kt qu lin tc cng vt qu gii hn X -2 hay X +2- Lut R: 4S: Mt kt qu kim tra vt gii hn X +2 , v mt kt qu vt gii hn X -2- Lut 4: 1S: 4 kt qu kim tra lin tip cng vt qu gii hn X + 1 hay cng vt qu gii hn X -1

- Lut 10: mean: 10 kt qu kim tra lin tip cng ri vo mt pha ca gi tr trung bnh.

Kt qu cch phn tch thng thng vi phn tch theo lut Westguard s mang li nhng kt qu nhgi chnh xc kh tin cy.

3.3.2.3. Kim tra xc thc ca kt qu xt nghim

* Huyt thanh kim tra xc thc thuc loi bit r nng , do mt s labo quy chiu xc nh. Chai loi huyt thanh tng ng vi hai mc nng (bnh thng v bnh l) ca cht cn nh lng.

* Kt qu xt nghim kim tra xc thc cn c ghi li tnh ra gi tr X, ri so snh vi gi tr thc(X0) tnh ra km xc thc (d%).

* Phn tch xc thc tnh c so vi xc thc cho php i vi mi thng s tng ng cng mtphng php nh lng.

4. Cp tn ch cho phng xt nghim lm sng, tiu chun cht lng ISO.

4.1. Cp tn ch cho phng xt nghim lm sng.

mt s nc, hot ng ca mt s h thng labo lm sng (pathology, clinical laboratory) chu skim sot v nh gi ca nhng c quan chc nng. Nu c cp tn ch ca cc c quan ny th labo xem nhc php v c xc nhn ca nh nc v cht lng v quyn cung cp dch v xt nghim.

Hoa K c hai t chc c u tn c cp tn ch thuc loi ny:* Hi ng cp tn ch cho cc c quan y t (The Joint Commission on Accreditation of Health care

organizations, JCAHO). Hi ng mu nh gi v cp tn ch cho 18.000 t chc y t v chng trnh ca Ho

K. Nm 1998, JCAHO cho ra cun cm nang cp tn ch i vi cc dch v labo lm s

ng v

bnh hc(Comprehensive Accreditation Manual for Pathology and Clinical laboratory Services, CAMPCLS).

* Hi cc nh bnh hc lm sng M (American Society of clinical Pathologists, ASCP) c thnh lpnm 1922; sau thnh lp Trng o to cc nh bnh hc M (College of American Pathologists, CAP). Viccp tn ch ca CAP c th c chp nhn t cc yu cu m bo cht lng (QA) v c cp bng nhnc lin bang hay bang.

4.2. Chng trnh ISO 9000.

y l nhng chng trnh QA c bit. ISO 9000 l mt loi hnh ghi nhn v cp chng ch cho cquan t c nhng tiu chun QA nht nh.

Trong s cc chng trnh ISO 9000, th chng trnh ISO 9002, ban hnh nm 1994 v "cc h thngcht lng - m hnh m bo cht lng trong sn xut, lp t v lm dch v"; cha cc ni dung c th pdng cho cc c quan y t, v thng c cc labo la chn.

Kt lunm bo cht lng (QA) ni chung v kim tra cht lng (QC) ni ring c vai tr quyt nh trong

vic gi vng cht lng v uy tn ca cc labo lm sng.

Thng qua cc hot ng ni kim cht lng hng ngy v ngoi kim cht lng nh k, cc labo lmsng phn u t n chnh xc v xc thc cao nht ca cc dch v xt nghim.

Vic xy dng cc quy ch v QA v QC, tin ti xy dng cc quy ch kim tra v cp chng ch chocc labo lm sng bt u tr thnh nhng yu cu bc thit i vi cc nh qun l cc dch v y t trong giaion mi ca ngnh y t nc nh.


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chng 6

Ho sinh hc h thng mng v vn chuyn qua mngTSKH Nguyn Ch Phi

1.Khi qut v mt s c im ho sinh ca t bo c nhn (Eukaryoticcell).

Cc t bo eukaryot u c nhn cha nhim sc th (chromosomes) v -c bc bi mng nhn. Nhim sc th l nhng thnhphn ng-ng tp c t chc ca cc gien.

Cc t bo prokaryot l nhng t chc n bo, bao gm vi khun. Cc t bo ny khng c nhn v thiumt s bo quan khc nhau so vi t bo eukaryot.

1.1. Kch thc t bo:

Cc t bo ng vt c ng knh khong 10-20 m.1.2. Cu trc bn trong t bo:

1.2.1. Nhn

Nhn t bo c bc bi 2 mng: mng trong quyt nh khi nhn; v mng ngoi lun lun gn linvi li ni nguyn sinh trong bo tng (cytoplasmic endoplasmic reticulum (ES)).

H thng mng nhn cn -c gi l lp v quanh nhn (perinuclear envelop).

Khong khng gian gia mng trong v mng ngoi th thng vi lng ca li ni nguyn sinh (ER).

Ti mt s im ca b mt nhn, mng trong v mng ngoi t hp vo nhau, to thnh cc l nhn(nuclear pores) trao i cht gia nhn v bo tng.

Hu htDNA ca t bo u trong nhn dng phc hpDNA - Protein, gi lChromation. Chromatin

c t chc th

nh nhng vt th d

i v

khng lin tc, d

y khong 25mm,

c gi l

Chromosom (nhim scth).

DNA cha thng tin di truyn ca t bo

* Bn trong nhn c hch nhn (nucleolus), giuRNA

Ni dung hch nhn c mt hay nhiu chromosom, gi l c quan t chc hch nhn (nucleolarorganizer), ti y, fRNA (RNA ribosom) c to thnh.

Khu vc ngoi hch nhn ca nhn t bo c gi lnhn bo tng.

Trong nhn bo tng, c mt gia nh nh ca cc Protein dng si, g lLamin. Cc si ny gn DNAvo mng nhn.

1.2.2. H thng mng trong bo tng

*Li ni nguyn sinh (ER): l h thng mng bn trong t bo rng nht ca t bo eukaryot.

Li ni nguyn sinh c gn (studded) cc ribosom; nhng li ni nguyn sinh nhn (smooth ER) thkhng gn.

-ER nhn

L ni tng hp v chuyn ho phospholipid v acid bo.

ER nhn cha mt s enzym kh c cc carcinogen hay cc chtPesticidbng cch lm cho chngtan trong nc v nh s d o thi. iu ny c th gii thch ti sao mt s t bo, nh t bo gan c nhiuER hn cc loi t bo khc.

- ER g gh:

C nhiu trong cc t bo sn xut cc hormon peptid (nhInsulin), v cc protein (nhkhng th).

Cc ribosom gn vo ER g gh sn sinh protein, to thnh mt phn cc mng t bo v bo quan.

Phc hp rRNA-mRNA bm vo eR g gh, v lun lun y chui peptid ang ko di i qua mt l


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vo lng trung tm (central lumen) ca ER. Ti , chui Peptid ngng tp li (aggregate) trc khi vn chuynn ni no trong t bo, hoc vo khoang ngoi t bo.

* B my Golgi:

L mt h thng cc ti c lm dt ra (flattened) v cc mng nhn (Smooth membrane).

Li ny chuyn cc tin lipid (lipid precursors) v carbohydrat n cc protein tp nn cc lipoproteinv glycoprotein. Qu trnh th hai c gi lglycosylation, cn thit cho vic vn chuyn protein qua mng botng (plasma membrane).

Golgi cng to ra nhiu mng bo mi, di dng cc ti (vesicle); , cc hormon, tin hormon v mts enzym c "bao gi" (packaged) v c chuyn i t t bo (exported from the cell).

B my Golig cng to ra cc mng cho cc bo quan (organelles) nhperoxisome v lysosom.

* Lysosom:

L cc bo quan c mt mngduy nht, cha cc enzym thu phn loi acid trong mi trng acid (pH 5).

Cc hydrolase lm thoi ho cc polyme nh DNA, RNA v protein thnh nhng n v monome cachng

Mng lysosom khng cho cc phn t ln v nh thm qua )impermeable); cc phn t ny -c vn chuyn qua mng nh cc chttrung gian c hiu (specific mediators).

S thiu ht di truyn ca mt s enzym lysosom - B-N- hexosaminidase, quan trng trong s thay c imi. (turnover) ca mt Protein mng (GM2) dn n bnhTay-Sachs.

Trong bnh ny, Protein GM2 tch t trong cc t bo thn kinh ang pht trin, dn n cht vo tuikhong 5 nm.

*Peroxisom

L cc bo quan nh cha cc Enzym s dng O2 oxy ho acid uric D-amono acid v mt s 2 -Hydroxy qcid; v sn sinh hydroperoxyd (H2O2)

Hydro peroxyd chuyn (trong peroxisom) thnh nc (H2O) v O2 nhcatalase.

Nhvy, peroxisom bo v t bo khi c H2O2, mt cht oxy ho mnh.- Peroxisom cng cha cc enzym quan trng trong chuyn ho lipid. Cc enzym khc nhau gia cc t

bo v thay i do iu kin ca t bo.

- Khong c cc .peroxisom trong no, thn, gan v c xng dn n bnh autosoma ln him gp - hichng Zellweger (Zellweger syndrome) - lm cho tr cht trong vng 6 thng sau sinh.

* Mitochndria (Ty lp th):

- L nh my nng lng ca t bo (energy powerhouses).

y l loi bo quan to, khong 7 m di 0,5 - 1,0 m ng knh, v c th chim ti 25% bo tng.- N c c mng trong v mng ngoi. Mng ngoi cho cc phn t ln n 10 kDa i qua, cn mng trong th t thm hn.

Mng trong c nhiu cu trc cun (infoldings), hay l Cristae; n protrude vo khng gian bn trong, hayl mng (matrix).

Cc enzym h hp protrude t mng trong vo trong mng (matrix), cng nh- l nhng enzym xc tc s sn xut ATP t ADP vphosphat v c. Mng -c np y enzym chuyn acetyl coenzymA (CoA) thnh CO2

Nhiu c cht, nhATP, ADP, Citrat v phosphat cn chuyn dch vo - ra mitohondria, khng th i quamng mt cch th ng c. Chng c chuyn ch theo nhng knh do ccProtein permease m ra.

Trong Matrix l mt s bn copy ca mt phn t DNA nh m ho cho mt s Protein then cht camng mitochondria. Nhng hu ht cc Protein mitochondria c sn xut bi cc ribosom bo tng, s dngmRNA c ngun gc trong nhn t bo.

*Cytokeleton:

- L mt mng li (network) cc tm mng (filaments) v cc ng nh (micro - tubules); n gi cho tbo c hnh dng, vn chuyn, phn bo, meiosis, v di ng t bo (motility).

- Cc ng nh (microtubules) cu to bi cc polyme ca Protein tubulin.

. t nht c 3 Protein ho c hc (mechanochemical proteins) - Kinesin, dynesin, v myosin - chuyn


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nng lng ho hc thnh nng lng c hc, c trong Cytoskeleton.

* Cytosol: ti y, cc phn ng din ra. N cha cc thnh phn ho tan

- Ribosom: Xem ch-ng tng hp Protein.

H.1. T bo Eukaryot

- Peroxisomes: cn gi l Microbodies, l nhng c quan n gn mng, ni thc hin cc phn ng oxyho peroxid hydro

" L mng cc si actin ng vai tr ch yu to dng t bo.

2. Cu trc ca mng. Cu trc Lipid ca mng

2.1. Chc nng ca mng lipid

- To nn hnh dng ca t bo v cc bo quan

- Kim sot vic trao i cc cht ho tan: N+, K+, CL- gia mi trng bn trong v mi trng bnngoi mng.

- To thnh cc v tr din ra cc phn ng ho hc. V d: s phosphoryl oxy ho din ra trn mang ti lpth...

- Lm v tr cho cc c quan truyn thng tin ho hc; nh: cc hormon, cc c quan dn truyn thn kinh.

Cc receptor ca cc c quan dn truyn ny nh v ngay trn mng bo.- ng vai tr trong qu trnh tng tc/nhn din t bo - t bo.

- To thun li cho s c ng t bo (cellular locomotion).

2.2. Cu trc ca cc mng

Tt c cc mng sinh hc u c dy khong 5 - 10 nm,cu to bi Protein v lipid. T l gia haithnh phn ny thay i tu theo ngun gc.

Cu trc ca mng ng vt c v

Cc mng ca ng vt c v c bit giu phospholipid v cholesterol.- Phospholipid c tnh cht amphipathic: trong cng mt phn t c c phn -a n-c v phn k n-c. S t-ng tc k n-c gia ccchui acyl ca cc phn t lipid to thnh mt lp phospholipid kp. Lp ny l mt tm 2 lp phospholipid c cc u phn cch-ng vo n-c, cn cc chui acyl bo th to thnh min trong k n-c (H.2)


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a nc

K nc

a nc

H.2 - Cu trc mng

Khi lc trn phospholipid vi n-c, chng to thnh cc ht hnh cu (micelle); cc chui acyl bo h-ng tch xa khi n-c (H.3)

H.3 - Ht micel

* Lp lipid kp -c ph c hai mt bi cc phn t protein theo m hnh "khm trai" (fluidmosaicmoden). (H.4).

Protein kt

hp m

ng

Protein xenci mng

Protein mcvo mng

H.4 Cu trc khm trai ca mng

Bn thn lipid v mt s protein chuyn dch "quanh qun" (around) trong tm keo .

* Cc Protein mngc mt s vai tr nht nh

- Vn chuyn cc phn t i qua mng

- ng vai tr receptor ca cc c quan truyn thng tin ho hc, nhcc hormon

- To nn nhng tng tc t bo - t bo thng qua cc chui, hydrat carbon phn nhnh ca chng.

- To nn kh nng nhn bit khng nguyn

- Hot ng nh

nhng enzym


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Cc Protein c th cxen ci, gn chc vo mng; hoc kt hp, treolng lo vo mng, v c th rira bng cch x l nh (H.4)

Cc Protein xen ci c th c "mc vo" mng bng cu ni ng ho tr chng hn, bng cch lin kt

u tn cng carboxy ca Protein v glycopholipid ca mng.- Nhiu Protein xen ci khng tan trong nc, c t hp trong mng, v c gi bi 3 lc ch yu:

+ Tng tc ion vi cc cu phn cc.

+ Tng tc k nc vi min trong lipid

+ Tng tc c bit vi Cholesteron hay vi phn t khc ca mng. Hu ht cc Protein xen ci trikhp (span) lp lipid kp v c nhng vng phn cc c hai u ca Protein.

2.3. Ho hc mng

Mng t bo c to thnh bi Protein, lipid, v nhng lng thay i ca glycolipid v glcycoProtein(H.5), (Bng 1)

Bng 1. Thnh phn ho hc ca mngMng Protein(%) Lipid (%) Carbohydrat (%)

Gan chut nht 44 52 4

Mng trong Mitochondria 76 24 0

Myelin 18 79 3

Hng cu 49 43 8

2.3.1. Lipid:Ba loi lipid chnh trong mng cc t bo c nhn (eukaryotic): cholesterol, sphingolipid vphosphoglycerid.

2.3.1.1. Phospholyceris:

L thnh phn lipid ch yu ca mng. Hai phosphoglycerid phong ph nht l:

- Lecithin (phosphotidyl choline)

- Cephalin (phosphatidylethanolamine

2.3.1.2. Sphingolipid:

L nhng phn t amphipahtic ("lng tnh"), gm cc acid bo chui di vi mt cu ni amid, to nnu phn cc. Hp cht ny c gi lceramin. Glycosphingolipidc mu ng (gluco hoc galactose) gnvo ceramid

Cc cerebrosid l nhng v d ca glycosphingolipid.

Galacto cerebosidl cc cerebosid c yu tm thy trong h thng thn kinh trung ng.

2.3.1.3. Cholesterol

L mt phn t "rn", an xen (intercalate) gia cc phospholipid trong mng. Vng steroid nc tngtc vi cc chui acyl bo ca phospholipid mng.

37 C, trong t bo c nhn, cholesterol lm hn ch tnh th dch (fluidity) ca mng. Nhng ncng gi cho mng khng tr nn km "ht dch" nhit thp, bng cch ngn cc chui khng gn vo nhau.

Tnh th dch ca mng ph thuc khng ch vo hm l-ng cholesterol, m cn ph thuc nhit v cu to lipid.

Tnh th dch c khi ng bi cc acid bo khng bo ho. C bng chng rng ch n c th nhhng n th dch trong cc mng ca mt t bo.

Lipid mng


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Cholesterol Sphingolipid Phosphoglycerid

Cephalin Lecitin

Hnh 5. Thnh phn ho hc ca mng

2.4. Mng hng cu

2.4.1. Mng tng bo ca hng cu tng i d tch khi cc thnh phn cu to khc.

Cc thnh phn lipid c phn b khng i xng (asymmetricallydistributed) cho qua mng, tri vi

s phn b i xng trong cc micelle. Cephalin chim

u th lp lipid trong. Tnh khng i xng n

y

cduy tr bi s chuyn ng o ngc ca phospholipid cho qua mng, c s tr gip ca cc Protein mng vduy tr nng lng chuyn ho.

S chuyn ng "flip - flop" khng c xc tc (uncatalysed) ca sphingolipid v phosphoglycerid choqua mng th chm do hng chuyn ng n cc u phn cc khng o vo cc u k nc kp(hydrophoboc billyer). S chuyn ng ny cn n mt s ngy hoc tun l.

2.4.2. Mng hng cu cha mt glycoprotein xen cI (intergral glycoprotein):Glycophorin

Glycophorn cha 131 acid amin v tri khp mng; ng thi cn c mt Protein khc gi l"bng3"(band 3), v linh ng ca n trn in di gel polyacrylamid. Bng 3 gm 900 acid amin, c th c vai trtrong s khuch tn ca hydro carbonat (HCO3, v Cl qua mng. N gn vo Protein ngoi bin trong Cytosol(bo tng) - ankyrin. Ankyrin li gn vo spectrin. Spectrin v ankyrin l nhng thnh phn ca sytoskeletonhng cu.

Cytoskelrton*

cho php hng cu bin dng khi i qua cc mao mch nhoe; v tre li hnh dng ban u(hai mt lm) trong cc iu kin khng g b.

3. Chc nng vn chuyn ca mng

3.1. S vn chuyn qua mng

3.1.1 S thm chn lc

Mng c th thm cc cht ho tan mt cch chn lc nhm mc ch:

- Duy tr hng ro i vi mi trng ngoi bo

- m bo cho cc phn t cn thit i vo trong t bo (lipid, glucose v acit amin), v a cc cht thira khi t bo.

- Duy tr grsdient ( chnh) ion qua mng.

Cc b

o quan trong t b

o cng c th c cc m

ng thm chn lc. M

ng lysosom gi cho nng ionH+ cao hn nng trong cytosol (bo tng) 1000 - 10 000 ln

3.1.2. Vn chuyn th ng, vn chuyn tch cc (active) hay vn chuyn c tr gip (facilitatedtransport)

3.1.2.1 Vn chuyn th ng

Vn chuyn th ngl s vn chuyn ca mt phn t hay mt ion xung mt vng chnh nng haychnh in ho (electronchemicalgradient).

y c th l mt skhuych tn n thun, nh l mt cch i qua mng bo tng ca cc cht khnhO2 v CO2, hoc ca cc phn t n gin nhetanol (H.6)

* Cytskeleton l b khung c sinh hc; gm 3 loi Protein c bit l nhng n v ho tan, hay cu trc dng si, hoc cu trc hnh ng,cc vi si, si trung gian, v cc ng li ti.


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Tc (fd)

(d)

nng H.6 - Vn chuyn th ng (khuych tn, d)v khuych tn c tr gip (fd).

Trong khuych tn n gin, mt phn t nh c ho tan trong dch ngoi bo nay li ho tan trongmng, ri li ho tan vo trong dch ni bo. Qu trnh ny khng c hiu. Yu t hn ch tc i vo mngca phn t ltnh k nc ca n (hydrophobicity), ngha l tnh tan trong du. Tc khuych tn qua mng

kp phospholipid t l vi tnh k nc (hydrophobicity). N cng t l vi chnh nng qua mng(concentrationgradient).

3.1.2.2. S khuych tn c tr gip (facilitated diffusion) (H.6)

y l vn s chuyn nhanh ca cc phn t qua mng c s gip ca cc Protein mng c hiu - gil ccpermease.

Qu trnh ny c tnh c hiu, nhanh hn khuch tn n thun, v c tc vn chuyn ti a.

3.1.2.3.Vn chuyn tch cc (activetransport)

Vn chuyn tch cc l s vn chuyn ca cc ion hay phn t qua mng chng li s chnh nng ; dng nng l-ng nh thuphn ATP. (H.7)

ATP

ADN + Pi (active transport)

H.7 Vn chuyn tch cc.

* Vn chuyn ion tch cc : c 3 loi chnh:- Bm Na+/K+ - adenosin triphosphatase (ATPase).

Bm ny vn chuyn Na+ i ra v K+ i vo

- Bm Calci, cn gi l bm Ca2+ - ATPase.

Bm ny dn Ca2+ ngoi t bo hoc t Cytosol vo trong mng sarcoplamic

- Bm proton (H+)

Cc chnh ion (ion gradients) to ra nh s vn chuyn tch cc c th c cp i vi s vn chuyn

tch cc ca cc phn t, nh trong trng hp vn chuyn mt s acid amin v vn chuyn ng (vn chuyn


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Phn t cvn chuyn

tch cc "th cp")

3.1.2.4. ng vn chuyn (Cotransport)

ng vn chuyn ca mt ion hay phn t cp i vi mt ion c ng vn chuyn.

*Symportl s vn chuyn ng thi ca 2 yu t c vn chuyn theo cng mt hng (H.8)

*Antiportl s vn chuyn ng thi theo cc hng i ngc (H.8)

* Uniportl qu trnh vn chuyn khng cp i vi mt ion c ng vn chuyn (H.8)

Phn t cng V/C

Uniport Symport Antiport

Bm

3Na+2K+

V tr K+

V tr Ouabain

Bn ngoi

Bn trong

V tr xc tc i viATP

V tr Na+

3Na+2K+ATP

ADP + Pi (Phos

Carbohydrat

phat v c)

Na+

/K - ATPase+

Na +/K - ATPase+

H.8 - ng vn chuyn

ng vn chuyn c th xy ra trong qu trnh khuych tn c tr gip hay trong khi vn chuyn tchcc.

Glucose c th c vn chuyn nh khuych tn tr gip simport(H.9)

3Na+ 2K+

Na+

3Na+ 2K+Na+

Glucose

Bn ngoi

Yu t V/Cglucose

Bn trong

H.9 Vn chuyn glucose qua mng (C ch simport, ph thuc Na+)

Cl- v HCO3- c vn chuyn qua mng hng cu bng mt c ch bm khuych tn tr gip antiportgi l band 3. Bng 3 bm Cl- v HCO3- theo hng i ngc nhau; hng vn chuyn tu thuc vo gradientnng prevailing, (H.10)


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H.10 - Vn chuyn Cl- v HCO3- c ch antiport

3.2 Vn nng lng trong vn chuyn tch cc

* Vn chuyn tch cc i hi nng lng sinh ra do s thu phn ATP thnh ADP, cp i vi vic bmcc ion i khng li gradient nng ca chng.

* Ging nh s khuych tn tr gip, vn chuyn tch cc c tnh chtc hiu, c ng hc bo ho, vc th b c ch.

V d, s vn chuyn Na+/K+ - ATPase. y l h thng enzym antiport (antiporter enzyme) i hi ccion Na+, K+ v

G2+ (H.11) v c trong mi t bo ng vt; c bit c nng cao trong cc t chc d b kch (thnkinh, c), v trong nhng t bo tham gia tch cc vo s vn chuyn Na+ qua mng bo tng, nh cc t bothn v tuyn nc bt.

* Enzym ATPase:

l mt phn t Oligomer, cu to bi2 tiu n v () v 110kDa, v 2tiu n v ()55kDa l glycoprotein.

Trong khi ATP thu phn, tiu n v () c phosphoryl ho kh phosphoryl ti mu aspartate c hiu to thnh mt () -aspartaylphosphat.

S phosphoryl ho i hi Na+ v g2+, nhng khng cn K+. S kh phosphoryl ho (dephosphorylation)li i hi K+, m khng cn Na+

Phc hp Protein c m t di hai dng cu trc hnh lin quan n mc nng lng. Do vy,ATPase c gn tn l [E1- E2 - typetransporter] (c quan vn chuyn E1 - E2) (H.11)

Bm ATPse b c ch bi cc glucosid h-ng tim (Cardiotinicglycosides), bao gm digoxin v Ouabain.

Do tnh d tan trong n-c . Ouabain -c s dng rng ri nh gi bm.

ATP ADP

E1 E1 - PNa+ Mg+

E2 E2 - P

Pi

H.11 - E1 - E2 - type transporter. Yu t vn chuyn loi E1 - E2 (ATPase)

3.3. S vn chuyn glucose.

S vn chuyn glucose l mt v d v s kt hp c khuych tn tr gip vvn chuyn tch cc. Qutrnh u s dng c ch untiport; qu trnh th hai dng c ch symport.


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3.3.1. Glucose c th vn chuyn vo hng cu bng khuych tn tr gip. Hng s Michaelis (Km) chos thu np glucose vo trong hng cu khong 1,5 mmol/l (ngha l, ti nng ny ca glucose, 50% cc phnt pemease sn c s c gn vo cc phn t glucose).

V nng glucose trong mu ngi vo khong 4 - 6 mmol/l, nn s thu np glucose vo trong hng cus din ra cc tc thc s ti a.

Permease c tnh cht c hiu, bi v dng L - isome ca glucose c vn chuyn khng ng k votrong hng cu .

D - galactose v D - Mannose li c vn chuyn, nhng i hi nhng nng cao hn lm bo homt na h thng vn chuyn.

Mt khi vo bn trong t bo, glucose s c phosphoryl ho v khng th ra khi t bo c na.

- Permease i vi glucose cn c gi tn l D - hexose permase. N chnh l Protein xen ci vo mng(integral membrane Protein), c phn t lng 45 k Da.

3.3.2. Glucose cng c th c vn chuyn nh h thng symport ph thuc Na+ Na+ - dependentsymport system) (H.9)

3Na+ 2K+

Na+

3Na+

2K+Na+

Glucose

Bn ngoi

Yu t V/Cglucose

Bn trong

H.9 - Vn chuyn glucose qua mng (C ch symport, ph thuc Na+)

* H thng ny c trong cc mng bo tng ca cc t chc, bao gm ng thn v lin bo rut.

Mt phn t glucose c vn chuyn i khng vi gradient nng ca n, v mt ion Na+ c vnchuyn xung (moved down) Gradient nng ca n bng c ch khuych tn tr gip(facilitated diffusion).Nhng, cui cng h thng cng c dn n bm Na+/K+ - ATPase. Do , h thng Symport l h thng vnchuyn tch cc th cp.

Acid amin cn c vn chuyn nhvy.

3.4. Bm Ca2+

Bm Ca2+ l mt bm vn chuyn tch cc thuc loi E1 - E2. N l mt Protein mng xen ci (integralmembrane Protein),c phosphiryl ho trn mt mu aspartmyl trong khi vn chuyn Ca2+.

Hai ion Ca2+ c vn chuyn i vi mi phn t ATP b thu phn. Trong cc t bo c nhn, Ca2+gn vo Protein gn Ca2+ (Calcium - binding Protein), gi l calmodulin; v phc hp gn vo bm Ca2+.

Cn c cc Protein gn Ca2+ khc, bao gm troponin C v paralbumin.

4. receptor v yu t truyn tin th cp

4.1. Truyn thng ho hc (chemican communication)

4.1.1 Pht tn hiu ni tit

*S pht tn hiu ni tit(endocrin signalling) xy ra khi cc t bo/c quan gii phng cc cht ho hchay hormon vo dng mu i n cc t bo hay c quan ch; cc c quan ny nhn din chng thng quacc receptor c hiu (receptor + cm th quan).

* Receptor l nhng protein trn mng bo tng hoc bn trong t bo. Receptor c cc v tr nhndin v gn hormon. Phn ng gn gy nn mt sbin i trong receptor, cho php n truyn thng tin gn

hormon trn t bo.


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C-terminal

N-terminal

H.12 Cu trc in hnh ca receptorgn Protein Gvi 7 vng xon xuyn mng

(v d: adrenergic receptor)4.2 H thng tn hiu th hai

4.2.1. Protein G

Protein G l mt Protein xen ci gn cht vo mng pha bo tng. N gn GTP (guanosine triphosphat)vi i lc cao.

Protein G cu to bi 3 tiu n v: ().() v () (trng lng phn t ln lt vo khong 42, 35, 10 kDa)

Tiu n v () c th gn GDP (guanosinen diphosphat) v GTP. (H.13)

4.2.2. Adenylate cyclase

y l Protein th 3 xen ci mng. n c mt v tr gn ATP trn b mt pha bo tng ca mng.

Khi enzym c hot ho s chuyn ATP thnh AMP vng (cAMP) (H.13)

Khi khng c hormon,Protein G gn GDP v adenylate cyclase b bt hot. Nhng khi hormon gn vo vtr gn ca n trn receptor b thay i v gn Protein G. GDP ri ra, nhng cho GTP gn vo.

Sau , Protein G phn ly thnh cc tiu n v G() v G(). Tiu n v G() gn vo adenylate cyclase lmcho enzym c hot ho v chuyn ATP thnh cAMP.

aCMP c gi ltn hiu th hai


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H.13 Hot ho receptor (R) ca Adenylate Cyclase

S hot ho adenylate c kt thc nhanh chng bng s thu phn GTP thnh GDP, dn n ti lp lih thng cho s kch thch tip theo.

4.2.3. Protein kinase

- Trong t bo. cAMP khi ng cc qu trnhphosphoryl ho Protein bng cch gn voProteinkinase

Khi cANP gn vo, kinase phn ly thnh 2 tiu n v: mt iu ho v mt xc tc (H.14). Sau ,kianse c th phosphoryl ho cc Protein khc bng cch chuyn nhm phophat tn cng ca ATP cho cc muserin, threonin hay tyrosin ca Protein c cht.

Kt qu cui cng ca qu trnh ny l cc sn phm to thnh nh cc qu trnh hot ng ca cckinase, nh:

S phosphoryl ho glycogen trong gan v c, s thu phn ca triacylglycerol thnh acid bo v

glyceroltrong cc t bo m, hay s tng hp cc hormon steroid v thng thn.


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H.14 Hot ng ca Protein kinase

- Dy chuyn ny l h thng cc k hiu qu i vi skhuych i tnhiu; bi v vic gn mt phn tadrenalin duy nht dn n s hot ho cc phn t adenylate cyclase, v to ra nhiu phn t cAMP. (H.15)

H.15 Nguyn tc khuych i tn hiu

4.2.4 Protein G c ch (Inhibitory G Proteins)

- Protein G c ch cng c trong mng. Chng c hot ho c chvic sn xut cAMP.

Chng c hot ho bi cc hormon v receptor khc.

Cc Protein G ny c cc tiu n v G() nhng tiu n v G() th khc - gi l G().

G() gn GTP khi c hot ho, nhng c ch adenylate cyclase.

V d, adrenalin thng qua () - receptor ca n, kch thch sn xut cAMP; trong khi , adenosin dntruyn thn kinh (neurotransmitter adenosine), thng qua receptor ca n - Alreceptor- , li c ch sn xutcAMP, nhng adenoisne A2 - receptor li kch thch sn xut cAMP.

Ch : choleratoxin, do vi khun vibrio cholerae sn xut, hot ho khng thun nghch G(), lm cho nkhng th thu phn GTP thnh GDP, dn n cAMP tng cao lin tc trong lin bo rut, lm ngp Na+ vH2O vo trong mng rut ((intestinal lumen), a chy nng v c th cht do mt nc.

4.2.5. V d khc v c quan truyn tin th 2 (second messenger): inositol triphosphate (ip3 vdiacylglycerol (dag) Ip3 v DAG sinh ra do s hot ho receptor mng bi hormon, chng hn thng qua tcng ca adrenalin ln () 0 receptor, hay l tc ng ca cht dn truyn thn kinh acetycholin(neurotransmitteracetyl choline) trn receptor holinergic muscarinic.

(muscarinic cholinergicreceptors). Receptor c hot ho gn vo Protein G mng, dn n hot

ho enzym gn m

ng phosphatlipace C (PLC), l

m thu phnphosphatidyl - inositon - 4,5 biphosphate (PIP2)cho ra DAG v IP3


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IP3 khuych tn vo cutosol v gn vo 1 receptor trn ER, lm gii phng Ca2+ t do vo trong botng. Cc ion gip cho nhng qu trnh ni bo nhqu trnh exocytosis hay qu trnh ng phn.

5. Cc receptor ni bo v cc cht i khng receptor

5.1. Receptor ni bo

5.1.1 Cc Protein recepotr trong ni bo

Cc Protein recepotr ni bo gn cc hormon a lipid (lipohilic hormoner); hormon ny i qua mng tbo mt cch d dng.

Cc recepotr ni bo i vi steroid,vitamin D v hormon tuyn gip to thnh mt b phn ca siu gianh recepotr (recepotr superfamily). Cc thnh phn ca gia nh ny gn vo Chromatin ca nhn v tc ngvo qu trnh sao chp m(transcription) (H.6)

H.16a Recepotr ni bo

5.1.1.1. C ch ho recepotr (h,16b)

* C ch hot ho recepotr ni bo bi hormon vn cha c bit r; nhng c bng chng cho thyrng, trng thi bt hot th recepotr c gn vo ccprotien shock nhit(HSP 90). Con s 90 ch kch thcca Protein. Thut ng "shock nhit" ni ngun gc vic pht hin ra Protein ny sau khi lm shock t bo bngnhit; mc d ngy nay bit rng chng c c nhng t chc khng b shock nhvy.

- C mt h HSP lin quan n bnh tt, st, thiu mu, tui tc, v qu trnh vim. Mt s HSP cng lchaperon phn t (molecularchaperoner)

Molecular chaperones l nhng phn t Protein gip cho vic cun ca nhiu Protein mi tng hp.Molecular choperones gn vo Protein mi sinh khng cho n kt vn trong t bo, v lm trung gian cho qutrnh cun Protein thnh trng thi nguyn vn.

- Khi hormon gn vo recepotr, HSP 90 ri ra khi recepotr. v Protein recepotr to thnh ccHormon -recepotr gn vo c v tr c hiu trn DAN, gi l ccyu t p ng hormon (hormone response elemeents -HREs), ngc dng t cc v tr khi u. Ngi ta bit c nhiu on deoxynucleotid ca HIEs.

Cc recepotr i vi hormon sinh dc, v i vi glucocorticoidnh cortisol, th kt hp vi HSPs.Nhng cc recepotr i vi hormon Thyroid v vitamin D li khng. Hnh nhchng kt hp vi HREs th khng

c hormon.


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- Trong khi tt c cc trng hp , qu trnh hot ho recepotr u bao gm sphosphoeyl ho recepotr.

H.16b C ch hot ho ni bo

5.1.1.2 Bn cht ca recepotr.

Cc thnh vin ca siu gia nh recepotr ni bo cha 3 vng ch yu.

* Vng 1: l mt domain gn DNA, to thnh bi hai "ngn tay km" (Zune fingers), mi ngn mang 1ion km (Zn2+) (H.17)

H.17 Recepotr ni bo

Vng ny giu Cystein v cc acid amin kim. g tay km th nht quytnh tnh cht gn c hiu carecepotr vo DNA; cn ngn tay kia gi bn vng recepotr, m bo :yu t p ng" trn DNA.

* Vng 2 v 3 ca recepotr quyt nh tnh cht c hiu hormon ca phn ng gn.

Vng mt c bo tn rt cao (highly conserved)trong cc thnh vin ca siu gia nh, cn nhng vnggn hormon t ra km thun nht hn nhiu (H. 18)


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H.18 Cc thnh vin ca siu gia nh steroid - recepotr. Cc ch s nhng khi ghi trong hnhcho thy cc on acid amin thun nht vi glucpcorticoid - recepotr (%)

5.2 i khng recepotr. (recepotr 0antagonism).

5.2.1. S i khng v c ch tc dng

*tnh c hiu ca phn ng gn gia ligandc tc dng lm yu hoc ngn tc dng ca ligand.

Cc thuc phong b recepotr c vai tr ln trong iu tr, v d:

-Thuc phong b () - recepotr: nhpropanolol dng iu tr cc ri lon tim mch- Thuc chng ung th (anticancer): nhtamoxifen c ch gn hormon sinh dc oestradiol vo ni bo

ca n; c dng trong mt s th ung thv.

* Cc cht i khng c th c phong b tc dng ca hormon bng cch gn trc tip vo recepotr, haytheo cch gin tip.

Theo ngn ng dc l kinh in, ligand hot ho recepotr c gi lagonist, cn ligand phong b tcdng ca agonnist c gi lantagonist(agonist: cht tc dng, antagonist: cht phn tc dng).

5.2.2. S i khng recepotr mng (H.19)

* Hnh m t aginist 1 gn vo v tr ca n gy nn phn ng, cn antagonist 1 gn vo v tr d khnggian (allosteric site) trn recepotr v c ch tc dng ca agonist 1.

V d mt cp agonit - antagonist gp trong trng hp cht dn truyn thn kinh (neurotransmitter)

glutamate.Glutamate bm vo v tr gn ca n m cc knh ion.Antagonist

2 - aminiphosphonovalrrate gn vo v tr d khng gian trn cng mt recepotr ca glutamate.

* Trng hp khc (Agonist 2); cn c hai phn t agonist 2 gn vo recepotr gy nn mt phn ng .Antagonist 2 phong b bng cch chim ch

V d, trng hp agonist acetylcholin> Acetylcholin gn vo 2 v tr trn recepotr nicotinic (nicotinicrecepotr) trn cc si c vn (skeletal muscle fibres). Antagonist

Hoa Sinh Hoc Mien Dich Trong Lam Sang_Y Ha Noi

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