Anal ysi s of t he Aci d- Base Bal ance i n Ar t er i al Bl ood Pl asma of El der l y Pat i ent s
Masaj i Mochi zuki
Emer i t us Pr of es s or of Yamagat a Uni v er s i t y, Yamagat a, J apan Ger i at r i c Res pi r at or y Res ear ch Cent er , Ni s hi mar uyama Hos pi t al ,
Chuo- Ku, Sappor o, J apan
(Accept ed Febr uar y 14, 2008 ) ABSTRACT
Addr es s f or Cor r es pondenc e :Mas aj i Moc hi zuki , Mi nami - 11, Ni s hi - 20, 4- 23, Chuo- Ku, Sappor o 064- 0811 Japan
We have pr e vi ous l y f ound t hat i n t he nor mal bl ood, whe r e a me t abol i c c ompone nt of pH, pH
o, was i gnor e d, a r e s pi r at or y c ompone nt , pH* , was gi ve n by a l i ne ar l ogar i t hmi c f unc t i on of Pc o
2, ; pH
owas t he n obt ai ne d by s ubt r ac t i ng pH* f r om t he me as ur e d val ue f or pH. Anal ys i s of t he ac i d ‐ bas e i mbal anc e was gr e at l y f ac i l i t at e d by t hi s di vi s i on of pH i nt o i t s me t abol i c and r e s pi r at or y c ompone nt s . I n ar t e r i al bl ood of e l de r l y pat i e nt s , t he r e gr e s s i on f unc t i ons of pH and pH* agai ns t pH
owe r e l i ne ar . Pc o
2was al s o l i ne ar l y r e l at e d t o pH
o, whe r e as pH* s howe d a r e c i pr oc al r e l at i on t o pH
o. I t was t he n e s t abl i s hi e d t hat about 26% of pH
owas c ompe ns at e d f or by t he c hange i n pH* , s o t he c hange i n pH was l i mi t e d t o 74% of t he c hange i n pH
o. Si nc e pH i s t he s um of pH* and pH
o, t he de vi at i ons of t he i ndi vi dual poi nt s of pH and pH* f r om t he r e s pe c t i ve r e gr e s s i on l i ne s be c ame e qual . De s i gnat i ng t he pH and pH* val ue s on t he r e s pe c t i ve r e gr e s s i on l i ne s by pH and pH* , pH -pH be c ame e qual t o pH* -pH* , be c aus e pH -pH* = pH -pH* .
Key wor ds : He nde r s on e quat i on, Re gr e s s i on anal ys i s , Cor r e l at i on r at i o, Me t abol i c Pc o
2c hange , Ve nt i l at i on/ Pe r f us i on r at i o.
I NTRODUCTI ON
pH i n bl ood pl as ma i s de t e r mi ne d by Pc o
2and [ HCO
3-] ac c or di ng t o t he He nde r s on e quat i on
1). As de s c r i be d pr e vi ous l y , we f ound
t hat at s t e ady s t at e i n vi vo bot h pH and [ HCO
3-] had a Pc o
2- de pe nde nt r e s pi r at or y c ompone nt and a me t abol i c c ompone nt
1),2),3). The r e s pi ar t or y c ompone nt of [ HCO
3-] , de s i gnat e d by [ HCO
3-] * , was gi ve n by an
e xpone nt i al e quat i on of Pc o
2. The Pc o
2- de pe nd-
e nt c ompone nt of pH, pH* , was gi ve n by s e t t i ng [ HCO
3-] * i n t he He nde r s on e quat i on by a l i ne ar l ogar i t hmi c f unc t i on of Pc o
2. The me t abol i c c ompone nt of [ HCO
3-] , [ HCO
3-]
o, was obt ai ne d by s ubt r ac t i ng [ HCO
3-] * f r om t he me as ur e d val ue f or [ HCO
3-] . Si mi l ar l y , t he me t abol i c c ompone nt of pH, pH
o, was obt ai ne d by s ubt r ac t i ng pH* f r om t he me as ur e d pH val ue . Thus , i t has be c ome pos s i bl e t o anal ys e t he ac i d- bas e i mbal anc e i n bl ood pl as ma by di vi di ng pH i nt o pH* and pH
o. Whe n pH
ode vi at e s f r om i t s nor mal l e ve l , c l os e t o z e r o, not onl y pH, but al s o Pc o
2c hange s i n pr opor t i on t o t he c hange i n pH
o. De s pi t e t he wi de s c at t e r i ng i n t he me as ur e d Pc o
2val ue s , t he r at i o of t he c hange i n pH* t o pH
ohas be e n as s e s s e d by r e gr e s s i on anal ys i s i n a numbe r of e l de r l y pat i e nt s .
Ac c or di ng t o t he He nde r s on e quat i on, pH
oi s gi ve n by a l ogar i t hmi c f unc t i on of t he r at i o [ HCO
3-]
o/ [ HCO
3-] * , i r r e s pe c t i ve of Pc o
23). Mor e ove r , s i nc e Pc o
2and pH* s howe d a Gaus s i an di s t r i but i on ar ound t he i r r e gr e s s i on l i ne s , t he me an r at i os of pH and pH* t o pH
owe r e gi ve n by t he i r r e s pe c t i ve c or r e l at i on r at i os agai ns t pH
o. The e xt e nt of t he i mbal anc e has l ong be e n r e c ogni z e d by t he c hange i n [ HCO
3-] f r om t he nor mal val ue . Si nc e [ HCO
3-] i s not l i ne ar l y r e l at e d t o pH, i t has be e n di f f i c ul t t o e val uat e t he c hange i n Pc o
2c onne c t e d wi t h t he me t abol i c c hange i n pH.
Howe ve r , t he pr e s e nt pape r s hows t he r e gr e s s i on f unc t i ons of pH and pH* ar e l i ne ar agai ns t pH
o, and t he me an r at i os c an be c al c ul at e d f r om t he c or r e l at i on r at i os . The c or r e l at i on r at i o of pH* t o pH
oi n ar t e r i al bl ood of e l de r l y par i e nt s was about -26% and t hat of t he me as ur e d pH t o pH
owas 74%.
Fur t he r mor e , t he de vi at i ons of i ndi vi dual val ue s of pH* and pH f r om t he r e s pe c t i ve
r e gr e s s i on f unc t i ons ar e e qual . De s i gnat i ng val ue s f or pH* and pH on t he r e gr e s s i on l i ne s by pH* and pH, t he di f f e r e nc e pH -pH* al s o be c ome s e qual t o pH
oMETHODS AND RESULTS
Al l t he c or r e l at i ons of pH and pH* agai ns t pH
owe r e c al c ul at e d on ar t e r i al bl ood s ampl e d f r om 215 e l de r l y pat i e nt s ( Tabl e 1) . The bl ood s ampl e s we r e obt ai ne d wi t h c ons e nt of al l t he pat i e nt s . The numbe r s of mal e and f e mal e pat i e nt s we r e 77 and 138, r e s pe c t i ve l y , and t he i r age s r ange d f r om 64 t o 97. The me an ± SD of t he age of mal e pat i e nt s was 82. 8 ± 7. 4 and t hat of t he f e mal e pat i e nt s was 83. 6 ± 6. 6.
Summar i z e d dat a f or pH, Pc o
2, [ HCO
3-] and ot he r r e l e vant par ame t e r s ( n=278) ar e s hown i n Tabl e 1. pH and Pc o
2we r e me as ur e d us i ng a bl ood gas anal ys e r ( Ci ba Cor ni ng 188) . [ HCO
3-] was c al c ul at e d f r om [ H
+] and Pc o
2us i ng t he He nde r s on e quat i on
1),4). pH* was c al c ul at e d by s e t t i ng Pc o
2i nt o t he f ol l owi ng e quat i on
1): pH* = 8. 285 -0. 543 l og Pc o
2. ( 1)
pH
owas obt ai ne d by s ubt r ac t i ng pH* f r om t he me as ur e d val ue f or pH. To c onf i r m t he val i di t y of pH
o, [ HCO
3-] * was c al c ul at e d ac c or di ng t o t he f ol l owi ng e quat i on:
[ HCO
3-] * = 4. 717 Pc o
2 0.457, ( mEq) . ( 2)
[ HCO
3-]
owas obt ai ne d by s ubt r ac t i ng [ HCO
3-] * f r om t he me as ur e d val ue of [ HCO
3-] . Fur t he r , s i nc e pH
oi s gi ve n by t he f ol l owi ng e quat i on
3):
pH
o= pH -pH*
= l og ( 1+ [ HCO
3-]
o/ [ HCO
3-] * ) , ( 3)
t he val i di t y of pH
owas r e adi l y r e c onf i r me d.
Val ue s f or pH
o( pH -pH* ) we r e di s t r i but e d f r om -0. 16 t o 0. 14. The val ue s f e l l i nt o t hr e e gr oups : an ac i dot i c gr oup ( 56 s ampl e s ) , whe r e pH
owas l e s s t han -0. 02, an al kal ot i c gr oup ( 136 s ampl e s ) , whe r e pH
owas gr e at e r t han 0. 02 and a nor mal gr oup ( 86 s ampl e s ) . Ove r 50% of t he me as ur e d pH val ue s we r e al kal ot i c , whe r e as about 20% we r e ac i dot i c .
I n t he al kal ot i c gr oup t he me an Pc o
2was hi ghe r and t he me an pH* was l owe r t han i n t he ot he r gr oups , i ndi c at i ng t hat t he c hange i n pH* was oppos i t e i n s i gn t o t hat of pH
o= pH - pH* .
Cor r e l at i ons of pH and pH* agai ns t pH
oThe c or r e l at i on c oe f f i c i e nt and t he r e gr e s - s i on f unc t i on we r e c al c ul at e d us i ng Kal e i d Gr aph Sof t war e ( Syne r gy) . Fi g. 1 s hows pH - 7. 4 pl ot t e d agai ns t pH
oi n ar t e r i al bl ood s ampl e d f r om t he e l de r l y pat i e nt s s hown i n Tabl e 1. The c or r e l at i on c oe f f i c i e nt was 0. 78 and t he r e gr e s s i on f unc t i on ( pH) was l i ne ar as
s hown by t he i nt e r r upt e d l i ne . The c hange i n pH was about 74% of pH
oas s hown by t he f ol l owi ng e quat i on:
pH = 7. 439 + 0. 74 pH
o. ( 4)
The me an ± SD of t he de vi at i on of i ndi vi dual poi nt s f or pH f r om t he r e gr e s s i on l i ne pH was 0. 01 ± 0. 030.
I n Fi g. 2, pH* -7. 4 i s pl ot t e d agai ns t pH
o. The c or r e l at i on c oe f f i c i e nt was 0. 39 and t he r e gr e s s i on f unc t i on ( pH* ) s hown by t he i nt e r r upt e d l i ne was l i ne ar as f ol l ows :
pH* = 7. 439 - 0. 26 pH
o. ( 5)
Fr om Eqs . ( 4) and ( 5) , i t i s s e e n t hat about 26%
of t he c hange i n pH
owas c ompe ns at e d f or by t he c hange i n pH* . Fr om t he de f i ni t i on of pH
ot he f ol l owi ng e quat i on was de r i ve d:
pH
o= pH - pH* . ( 6) Fr om Eqs . ( 4) , ( 5) and ( 6) t he f ol l owi ng Tabl e 1. Summar i z e d dat a f or pH, Pc o
2, [ HCO
3-] and ot he r r e l e vant par ame t e r s i n ar t e r i al bl ood s ampl e d f r om 215 ac i dot i c , nor mal and al kal ot i c e l de r l y pat i e nt s .
Al kal ot i c gr oup Nor mal pH gr oup
Ac i dot i c gr oup
pH
o>0. 02
-0. 02 < pH
o<0. 02 pH
o<-0. 02
Sampl e s and pat i e nt s
f e mal e mal e
f e mal e mal e
f e mal e mal e
80 56
53 33
38 18
No of s ampl e s
56 32
44 27
38 18
No of s ubj e c t s
83. 1 ± 5. 9 82. 0 ± 7. 6
84. 2 ± 7. 2 84. 9 ± 7. 6
83. 6 ± 6. 9 81. 3 ± 6. 9
Me an age ± SD Par ame t e r s obt ai ne d
7. 480 ± 0. 040 7. 442 ± 0. 030
7. 404 ± 0. 044 pH
39. 28 ± 5. 19 36. 29 ± 4. 23
34. 33 ± 4. 57 Pc o
228. 94 ± 3. 06 24. 44 ± 1. 30
21. 30 ± 2. 29 [ HCO
3-]
25. 19 ± 1. 53 24. 30 ± 1. 31
23. 67 ± 1. 47 [ HCO
3-] *
7. 422 ± 0. 032 7. 440 ± 0. 028
7. 453 ± 0. 033 pH*
0. 059 ± 0. 032 0. 002 ± 0. 010
-0. 050 ± 0. 035
pH
oe quat i on was t he n obt ai ne d:
pH -pH* = pH -pH* = pH
o. ( 7)
Eq. ( 7) s t at e s t hat t he de vi at i on of pH f r om i t s r e gr e s s i on l i ne , i . e . , pH -pH al ways e qual s t he de vi at i on of pH* f r om i t s r e gr e s s i on l i ne , i . e . , pH* -pH* .
Fi gur e 3 s hows t he c or r e l at i on of Pc o
2agai ns t pH
o, whe r e t he c or r e l at i on c oe f f i c i e nt was 0. 402. The r e gr e s s i on f unc t i on ( Pc o
2) was appr oxi mat e l y gi ve n by t he f ol l owi ng l i ne ar e quat i on:
Pc o
2= 36. 48 + 40. 3 pH
o, ( mmHg) . ( 8)
The me an ± SD of t he de vi at i on of i ndi vi dual poi nt s of Pc o
2f r om Pc o
2was 0. 15 ± 4. 71 mmHg.
Cor r e l at i ons of [ HCO
3-]
oand [ HCO
3-] * agai ns t pH
oThe r at i o [ HCO
3-] / [ HCO
3-] * at t he s ame
Pc o
2obt ai ne d f r om t he He nde r s on e quat i on i s f r e e f r om Pc o
2. Si nc e pH
oi s gi ve n by l og( [ HCO
3-] / [ HCO
3-] * , as s hown i n Eq. ( 3) , pH
oal s o be c ome s f r e e f r om Pc o
2. To de mon- s t r at e t hat pH
owas i nde pe nde nt of Pc o
2, t he c or r e l at i on of [ HCO
3-]
oagai ns t pH
owas c al c ul at e d i n t he ar t e r i al bl ood. The i nt e r - r upt e d l i ne i n Fi g. 4 s hows [ HCO
3-]
oc al c ul at e d f r om pH
ous i ng t he f ol l owi ng e quat i on:
[ HCO
3-]
o= 24. 63 ( l og
-1pH
o-1) , ( mEq) , ( 9)
24. 63 mEq i n t he above e quat i on i s t he me an val ue f or [ HCO
3-] * i n t he ar t e r i al bl ood. Al l t he me as ur e d val ue s of [ HCO
3-]
owe r e di s t r i but e d c l os e l y r ound t he t he or e t i c al val ue i ndi c at e d by t he i nt e r r upt e d l i ne , s ugge s t i ng t hat t he r e l at i ons hi p be t we e n pH
oand [ HCO
3-]
owas uni nf l ue nc e d by Pc o
2. The t hi n das he d l i ne i n Fi g. 4 i ndi c at e s t he c hange i n [ HCO
3-] * c al c ul at e d f r om Pc o
2gi ve n by Eq. ( 8) . The magni t ude of t he c hange i n [ HCO
3-] * was about 20% of t hat i n [ HCO
3-]
o.
Fi gur e 5 s hows t he c hange s i n pH* and
Fi g. 1. pH -7. 4 pl ot t e d agai ns t t he me t abol i c c ompone nt of pH ( pH
o= pH -pH*) i n ar t e r i al bl ood of t he e l de r l y pat i e nt s . The i nt e r r upt e d l i ne i s t he r e gr e s s i on l i ne and t he t wo das he d l i ne s s how t he s t andar d de vi at i on of i ndi vi dual pH val ue s f r om t he r e gr e s s i on l i ne .
Fi g. 2. pH* -7. 4 pl ot t e d agai ns t pH
o( pH -
pH*) i n ar t e r i al bl ood of t he e l de r l y pat i e nt s .
The i nt e r r upt e d l i ne i s t he r e gr e s s i on l i ne and
t he t wo das he d l i ne s s how t he s t andar d
de vi at i on of i ndi vi dual pH* val ue s f r om t he
r e gr e s s i on l i ne .
[ HCO
3-] * de pi c t e d agai ns t pH
o( l owe r abs c i s s a) and Pc o
2( uppe r abs c i s s a) , us i ng Eqs . ( 2) , ( 5) and ( 8) . [ HCO
3-] * and Pc o
2i nc r e as e d t oge t he r wi t h an i nc r e as e i n pH
o, whi l e pH* s howe d a r e c i pr oc al c hange t o t hat i n pH
o, de mons t r at - i ng t hat t he i nf l ue nc e of pH
oon pH i s r e duc e d by t he r e c i pr oc al c hange i n pH* . Fr om t hi s dat a t he e xt e nt of t he c ompe ns at or y i nf l ue nc e of pH* was t ake n t o be about 26%.
DI SCUSSI ON
I n t he pr e c e di ng pape r
3)r e gr e s s i on anal ys e s of pH and Pc o
2i n e l de r l y pat i e nt s we r e made agai ns t [ HCO
3-]
o, but not pH
o, t o quant i f y t he c ompe ns at or y c hange of pH* . Howe ve r , s i nc e t he i r r e gr e s s i on f unc t i ons we r e not l i ne ar , t he c or r e l at i on r at i o of pH* t o pH
oc oul d not r e adi l y be r e c ogni z e d. To de r i ve a l i ne ar r e l at i ons hi p be t we e n pH, pH* and Pc o
2, we at t e mpt e d t o c al c ul at e t he r e gr e s s i on f unc t i ons of pH, pH* and Pc o
2agai ns t pH
oi n a numbe r of t he e l de r l y pat i e nt s . As s hown i n Fi gs . 1 and 2, pH and pH* we r e l i ne ar l y c or r e l at e d agai ns t pH
o. The r e gr e s s i on c oe f f i c i e nt of pH agai ns t pH
owas 0. 74 as gi ve n by Eq. ( 4) and t hat of pH* was -0. 26 as gi ve n by Eq. ( 5) . Mor e ove r , t he r e gr e s s i on f unc t i on of Pc o
2agai ns t pH
owas al s o l i ne ar agai ns t pH
oas gi ve n by Eq. ( 8) . By di vi di ng pH i nt o r e s pi r at or y and me t abol i c c ompone nt s , an ac c ur at e me as ur e of t he ac i d- bas e i mbal anc e c oul d be obt ai ne d.
Ge ne r al l y , Pc o
2i n ar t e r i al bl ood i s c ont r ol l e d by r e s pi r at or y f ac t or s , s uc h as t he ve nt i l at i on/
pe r f us i on r at i o or t he Comr oe r at i o
5). Fi gur e 1
Fi g. 4. [ HCO
3-]
opl ot t e d agai ns t pH
o. The i nt e r r upt e d l i ne s hows t he t he or e t i c al val ue f or [ HCO
3-]
o= 24. 63 ( l og
-1pH
o-1) , 24. 63 ( mEq) be i ng t he me an val ue of [ HCO
3-] *. The das he d l i ne i s t he r e gr e s s i on l i ne of [ HCO
3-] * -24. 41 ( mEq) agai ns t pH
ous i ng t he val ue s de r i ve d f r om Eq. ( 8)
Fi g. 5. pH* -7. 439 ( △ pH*) and [ HCO
3-] * - 24. 41 ( △ [ HCO
3-] *, mEq) c al c ul at e d agai ns t pH
oand Pc o
2by us i ng Eqs . ( 2) , ( 5) and ( 8) . Fi g. 3. Pc o
2pl ot t e d agai ns t pH
oi n ar t e r i al
bl ood of t he e l de r l y pat i e nt s . The i nt e r r upt e d
l i ne i s t he r e gr e s s i one l i ne and t he t wo das he d
l i ne s s how t he s t andar d de vi at i on of i ndi vi dual
Pc o
2val ue s f r om t he r e gr e s s i on l i ne .
s hows t hat t he me an pH val ue i nc r e as e d f r om 7. 36 by 0. 20, whi l e i n Fi g. 2 pH* de c r e as e d f r om 7. 463 by -0. 056, as pH
oi nc r e as e d f r om -0. 1 t o 0. 12. Taki ng i nt o ac c ount t hat t he magni t ude of t he c hange i n pH
owas muc h gr e at e r t han t hat of pH* and t hat t he c hange i n pH* was r e c i pr oc al of t hat i n pH
o, t he c hange i n ve nt i l at i on s e e me d t o be i ni t i at e d by t he c hange i n pH
o, not i n Pc o
2. I n ot he r wor ds , t he c hange i n Pc o
2appe ar s t o be a r e s ul t , not a c aus e of t he c hange i n ve nt i l at i on.
Thus , s e t t i ng Pc o
2on i t s r e gr e s s i on l i ne agai ns t pH
o( Eq. ( 8) i nt o t he e quat i on f or t he Comr oe r at i o
5), t he e f f e c t of pH
oon t he pul monar y ve nt i l at i on was c al c ul at e d as f ol l ows :
V
●A/ Q
●C= ( Cvc o
2- Cac o
2) / ( 4. 23 + 4. 67 pH
o) . ( 10)
( Cvc o
2- Cac o
2) of Eq. ( 10) i s t he ve nous - ar t e r i al CO
2di f f e r e nc e ( vol %) . Fi gur e 6 s hows t wo c ur ve s f or t he V
A/
●
Q
Cr at i o agai ns t pH
o●
( l owe r abs c i s s a) and pH ( uppe r abs c i s s a) .
( Cvc o
2-Cac o
2) i n t he uppe r and l owe r c ur ve s was t ake n t o be r e s pe c t i ve l y 4. 2 and 4. 0 vol %.
The V
●A/ Q
●Cr at i o de c r e as e d hype r bol i c al l y as pH
oi nc r e as e d.
As s e e n i n Fi g. 2, pH* s howe d a Gaus s i an di s t r i but i on ar ound i t s r e gr e s s i on l i ne agai ns t pH
oand, as gi ve n by Eq. ( 5) , t he r e gr e s s i on c oe f f i c i e nt of pH* agai ns t pH
owas -0. 26. Thi s s ugge s t s t hat t he r e s pons e of r e s pi r at or y f unc t i on t o t he c hange i n pH
owas i de nt i c al among i ndi vi dual pat i e nt s . Fur t he r mor e , be c aus e t he c hange i n pH* was r e c i pr oc al t o t hat i n pH
o, and pH was t he s um of pH
oand pH* , t he pH di f f e r e nc e , pH -pH* , was al ways e qual t o pH -pH* = pH
o, as gi ve n by Eq. ( 7) . Thi s s e e ms t o be at t r i but abl e t o t he f ac t t hat Pc o
2or pH* was e ve nl y di s t r i but e d, among i ndi vi dual bl ood s ampl e s , ar ound t he i r r e s pe c - t i ve r e gr e s s i on f unc t i ons agai ns t pH
o.
Ove r - al l , t he anal yt i c al me t hod of di vi di ng pH and [ HCO
3-] i nt o r e s pi r at or y and me t a- bol i c c ompone nt s may he l p t o obt ai n a pr e s i c e i nf or mat i on about t he r e l at i ons hi p be t we e n par ame t e r s r e l at e d t o t he ac i d- bas e bal anc e .
Acknowl edgement
The aut hor i s i nde bt e d t o Dr Ann Si l ve r , Cambr i dge , UK, f or he r he l pf ul c omme nt s and f or r e vi s i ng t he manus c r i pt . He i s al s o i nde bt e d t o Dr Kyui c hi Ni i z e ki , Yone z awa, Japan, f or hi s c or di al s uppor t wi t h r e gr e s s i on anal ys i s .
REFERENCES
1 . Moc hi z uki M: Anal ys i s of bi c ar bonat e c onc e nt r at i on i n human bl ood pl as ma at s t e ady s t at e i n vi vo . Yamagat a Me d. J . 2004; 22: 9- 24 2 . Moc hi z uki M: Anal ys i s of pH i n bl ood
pl as ma at s t e ady s t at e i n vi vo. Yamagat a Me d J . Fi g. 6. The ve nt i l at i on- pe r f us i on r at i o V
●A/ Q
C●