1 4 6

Conferences and Reviews

A P ract ical Ap p roach t o Acid- B ase D isorders
D iscu ssant
RI CH ARD J . H AB E R, MD
T h is discu ssion was sel ect edfrom t h e week l y st aff conferences in t h e D ep art m ent of Medicine, U niversit y of Cal ifornia, S an
F rancisco. T ak en from a t ranscrip t ion, it h as b een edit ed b y H om er A. B ou sh ey , MD , P rofessor of Medicine, and N at h an M.
B ass, MD , P h D , Associat e P rofessor of Medicine, u nder t h e direct ion of L l oy d H . S m it h , J r, MD , P rofessor of Medicine and
Associat e D ean in t h e S ch ool of Medicine.
E D I T O R' S N O T E : T h is discu ssion of acid- b ase disorders was
p resent ed at Medical G rand Rou nds at S an F rancisco G en-
eral H osp it al Medical Cent er and im p ressed t h e edit ors as
ou t l ining a cl inical l y u sefu l ap p roach t o a som et im es com p l i-
cat ed su b j ect .
ME RL E A. S AN D E , MD * : Acid- b ase dist u rb ances are com m on
in p at ient s adm it t ed t o ou r service and are som et im es confu s-
ing wh en t h ree p art ial l y offset t ing disorders are coincident
in t h e sam e p at ient . Recog niz ing im p ort ant u nderl y ing cl ini-
cal p rob l em s and init iat ing t h e p rop er t h erap y wil l b e en-
su red if one com b ines a sim p l e, discip l ined ap p roach t o
anal y z ing ch ang es in art erial b l ood g ases and el ect rol y t es
wit h focu sed correl at ion wit h t h e cl inical set t ing . Rich ard J .
H ab er, MD , Ch ief of t h e D ivision of G eneral I nt ernal Medi-
cine at S an F rancisco G eneral H osp it al , reviews h is ap -
p roach t o t h is im p ort ant t op ic.
RI CH ARD J . H AB E R, MD t : B ecau se of it s rep u t at ion for
com p l ex it y , acid- b ase anal y sis int im idat es m any p h y sicians.
I n real it y , acid- b ase dist u rb ances ob ey wel l - defined b io-
ch em ical and p h y siol og ic ru l es and are easil y recog niz ed
and int erp ret ed. I n t h is review I p resent a p ract ical , st ep -
wise ap p roach t o int erp ret ing dist u rb ances in b l ood g as and
el ect rol y t e val u es. T h e m et h od is sim p l e and does not re-
q u ire a nom og ram or com p l icat ed m at h em at ical form u l as,
y et it wil l ident ify cl inical l y im p ort ant acid- b ase disorders.
I st art wit h sim p l e p rob l em s and p roceed t o m ore com p l ex
ab norm al it ies.
D at a B ase
Assessing a p at ient ' s acid- b ase st at u s b eg ins wit h t h e
m easu rem ent of t h e art erial p H , p art ial p ressu re of carb on
diox ide, and b icarb onat e. B l ood g as anal y z ers direct l y m ea-
su re t h e p H and P co2 . T h e b icarb onat e val u e is cal cu l at ed
from t h e H enderson- H assel b al ch eq u at ion. A m ore direct
m easu rem ent of b icarb onat e is ob t ained from det erm ining
t h e t ot al venou s carb on diox ide. B ecau se of t h e dissociat ion
ch aract erist ics of carb onic acid at b ody p H , dissol ved carb on
diox ide is al m ost ex cl u sivel y in t h e form of b icarb onat e, and,
for p ract ical p u rp oses, t h e t ot al carb on diox ide cont ent is
* P rofessor and Ch air, D ep art m ent of Medicine, S an F rancisco G eneral H osp it al
Medical Cent er, U niversit y of Cal ifornia, S an F rancisco ( U CS F ) , S ch ool of Medicine.
t Ch ief, D ivision of G eneral I nt ernal Medicine; Assist ant Ch ief, Medical S ervices,
S an F rancisco G eneral H osp it al Medical Cent er; P rofessor, Cl inical Medicine, U CS F .
eq u ival ent ( + 3 m m ol p er l it er) t o t h e b icarb onat e concent ra-
t ion. I f a sim u l t aneou sl y det erm ined b l ood g as b icarb onat e
val u e and t ot al venou s carb on diox ide cont ent are su b st an-
t ial l y different , a second m easu rem ent is req u ired b efore
anal y sis can p roceed.
T erm s and D efinit ions
N orm al val u es for art erial p H , P co2 , and b icarb onat e and
val u es t h at define p rim ary acid- b ase disorders are g iven in
T ab l e 1 . I f t h e p H is l ess t h an norm al ( < 7 . 3 5 ) , t h e p at ient is
said t o b e acidem ic. I f t h e p H is g reat er t h an norm al
( > 7 . 4 5 ) , t h e p at ient is al k al em ic. N ot e t h e sep arat e t erm s
for p H t o al l ow for describ ing t h e net effect of m u l t ip l e
resp irat ory or m et ab ol ic ab norm al it ies.
I f t h e P co2 is l ower t h an norm al ( < 3 5 m m of m ercu ry )
and t h is is a p rim ary p rocess, t h en a resp irat ory al k al osis is
p resent . I f t h e P co2 is h ig h er t h an norm al ( > 4 5 m m of
m ercu ry ) and t h is is a p rim ary p rocess, t h en a resp irat ory
acidosis is p resent . I f t h e P co2 is ab norm al in com p ensat ion
for a p rim ary m et ab ol ic p rocess, t h e dist u rb ance is describ ed
as resp irat ory com p ensat ion- " m et ab ol ic acidosis wit h re-
sp irat ory com p ensat ion, " for ex am p l e.
I f t h e art erial b icarb onat e l evel is l ess t h an norm al ( < 2 2
m m ol p er l it er) and t h is is a p rim ary ab norm al it y , a m et ab ol ic
acidosis is p resent . I f t h e b icarb onat e l evel is h ig h er t h an
norm al ( > 2 6 m m ol p er l it er) and t h is is a p rim ary p rocess, a
m et ab ol ic al k al osis is p resent . I f b icarb onat e l evel s are ab -
norm al in com p ensat ion for a p rim ary resp irat ory ab norm al -
it y , t h e dist u rb ance is cal l ed m et ab ol ic com p ensat ion.
Resp irat ory com p ensat ion for m et ab ol ic disorders is
rap id. F u l l m et ab ol ic com p ensat ion for resp irat ory dist u r-
b ances req u ires renal adj u st m ent and t ak es t h ree t o five day s.
S im p l e Acid- B ase D isorders
T h e first st ep in acid- b ase anal y sis is t o ident ify al l ab nor-
m al it ies in p H , P co2 , and b icarb onat e. T h e nex t is t o decide
wh ich ab norm al it ies are p rim ary and wh ich are com p ensa-
t ory . T ab l e 2 l ist s t h ree ru l es of t h u m b t o h el p in m ak ing t h is
det erm inat ion.
T h e first ru l e direct s u s t o l ook at t h e p H . W h ich ever side
of 7 . 4 0 t h e p H is on, t h e p rocess or p rocesses t h at cau sed it t o
sh ift t o t h at side are t h e p rim ary ab norm al it ies. I f t h e p H is
l ower t h an 7 . 4 0 , t h en an el evat ed P co2 ( resp irat ory acidosis)
or a l owered b icarb onat e ( m et ab ol ic acidosis) wou l d b e p ri-
( H ab er RJ : A p ract ical ap p roach t o acid- b ase disorders. W est J Med 1 9 9 1 Au g ; 1 5 5 : 1 4 6 - 1 5 1 )
Rep rint req u est s t o H om er A. B ou sh ey , MD , D ep art m ent of Medicine, U niversit y of Cal ifornia, S an F rancisco, S ch ool of Medicine, S an F rancisco, CA 9 4 1 4 3 .
T H I
T AB L E 1 . - P rim ary cAid- B ase D isorders-
P rim ary N orm al Rang e, P rim ary
V ariab l e D isorder Art erial G as D isorder
p H . . . . . . . . . . . . . . . . . . Acidem ia - 7 . 3 5 - 7 . 4 5 - Al k al em ia
P co2 ,
m m of m ercu ry . . . . . . . Resp irat ory al k al osis - 3 5 - 4 5 - Resp irat ory acidosis
B icarb onat e, m m ol / l it er . . . . Met ab ol ic acidosis 4 - 2 2 - 2 6 - Met ab ol ic al k al osis
T AB L E 2 . - Ru l es of T h u m b for Recog niz ing P rim ary Acid- B ase D isorders
W it h ou t U sing a N om og ram
Ru l e I
L ook at t h e p H . W h ich everside of 7 . 4 0 t h e p H is on, t h e p rocess t h at cau sed it t osh ift t o t h at side is t h e p rim ary
ab norm al it y
P rincip l e: T h e b ody does not fu l l y com p ensat e for p rim ary acid- b ase disorders
Ru l e 2
Cal cu l at e t h e anion g ap . I f t h e anion g ap is 2 0 m m ol p er l it er, t h ere is a p rim ary m et ab ol ic acidosis reg ardl ess
of p H or seru m b icarb onat e concent rat ion
P rincij l e: T h e b ody does not g enerat e a l arg e anion g ap t o com p ensat e for a p rim ary disorder
Ru l e 3
Cal cu l at e t h e ex cess anion g ap ( t h e t ot al anion g ap m inu s t h e norm al anion g ap [ 1 2 m m ol p er l it erD ) and add
t h isval u e t o t h e m easu red b icarb onat e concent rat ion; if t h e su m is g reat er t h an a norm al seru m b icarb onat e
( > 3 0 m m ol p er l it er, . t h ere is an u nderl y ing m et ab ol ic al k al osis; if t h e su m is l ess t h an a norm al b icarb onat e
( < 2 3 m m ol p er l it er) , t h ere is an u nderl y ing nonanion g ap m et ab ol ic acidosis
P rindp l e: 1 m m ol of u nm easu red acid t it rat es 1 m m ol of b icarb onat e ( + A anion g ap = - A I H C0 3 - 1 )
m ary ab norm al it ies. I f t h e p H is h ig h er t h an 7 . 4 0 , t h en a
l owered P co2 ( resp irat ory al k al osis) or a raised b icarb onat e
( m et ab ol ic al k al osis) wou l d b e p rim ary .
T h e p at h op h y siol og ic p rincip l e b eh ind t h is ru l e is t h at t h e
b ody does not fu l l y com p ensat e even for ch ronic acid- b ase
disorders. O ver t im e t h e p H ap p roach es b u t does not com -
p l et el y ret u rn t o norm al . T h is ob servat ion al l ows u s t o u se
t h e direct ion of p H ch ang e t o ident ify t h e p rim ary disorder.
Resp irat ory Al k al osis
Consider a p at ient wit h a p H of 7 . 5 0 , a P co2 of 2 9 m m of
m ercu ry , and a b icarb onat e concent rat ion of 2 2 m m ol p er
l it er. B ecau se t h e p at ient is al k al em ic, t h e l ow P co2 is a
p rim ary dist u rb ance and a resp irat ory al k al osis is p resent .
T h e l ack of m et ab ol ic com p ensat ion- t h at is, t h e norm al
b icarb onat e- indicat es t h at t h e disorder is acu t e. T h e cau ses
of acu t e resp irat ory al k al osis are l ist ed in T ab l e 3 . W h y m ak e
su ch a l ist ?
Acid- b ase dist u rb ances are m anifest at ions of u nderl y ing
cl inical disorders. I dent ify ing a p rim ary acid- b ase ab nor-
m al it y - in t h is case, resp irat ory al k al osis- ident ifies a dis-
order cau sed b y onl y a l im it ed nu m b er of disease p rocesses.
E st ab l ish ing a sp ecific diag nosis is cl inical l y im p ort ant b e-
cau se t reat m ent is b est aim ed at correct ing t h e u nderl y ing
cau se of t h e acid- b ase ab norm al it y rat h er t h an at correct ing
t h e ab norm al it y p er se.
Resp irat ory Acidosis
W h at ab ou t a p at ient wit h a p H of 7 . 2 5 , a P co2 of 6 0 m m
of m ercu ry , and a b icarb onat e of 2 6 m m ol p er l it er? T h is
p erson is acidem ic wit h an increased P co2 and a norm al
b icarb onat e: a resp irat ory acidosis wit h no evidence of m et a-
b ol ic com p ensat ion. T h e cau ses of acu t e resp irat ory acidosis
are l ist ed in T ab l e 4 .
W h at if t h e nex t p at ient p resent ed wit h a p H of 7 . 3 4 , a
P co2 of 6 0 m m of m ercu ry , and a b icarb onat e of 3 1 m m ol p er
l it er ( T ab l e 5 ) ? I n t h is p erson, b ot h t h e P co2 and t h e b icarb on-
at e l evel s are el evat ed, t wo ab norm al it ies wit h op p osit e ef-
fect s on p H . W h ich one is p rim ary and wh ich com p ensat ory ?
B ecau se t h e p H is l ower t h an 7 . 4 0 , t h e p rim ary disorder is
st il l a resp irat ory acidosis. T h e el evat ed b icarb onat e ( and
near- norm al p H ) indicat es t h at m et ab ol ic com p ensat ion h as
occu rred and t h at t h e acidosis is ch ronic.
D ifferent iat ing acu t e from ch ronic resp irat ory acidosis
h as im p ort ant cl inical im p l icat ions. Acu t e resp irat ory acido-
sis is a m edical em erg ency t h at m ay req u ire em erg ent int u b a-
t ion and m ech anical vent il at ion, wh ereas ch ronic resp irat ory
acidosis is oft en a cl inical l y st ab l e condit ion. At t ent ion t o t h e
p H and b icarb onat e val u es wil l different iat e acu t e from
ch ronic h y p ovent il at ion.
Met ab ol ic Al k al osis
Assess t h e fol l owing b l ood g as com b inat ion: p H 7 . 5 0 ,
P co2 4 8 m m of m ercu ry , and b icarb onat e l evel 3 6 m m ol p er
l it er. B ecau se t h e p at ient is al k al em ic, t h e el evat ed b icarb on-
at e l evel is t h e p rim ary ab norm al it y and t h e p at ient h as a
m et ab ol ic al k al osis wit h resp irat ory com p ensat ion. Al -
t h ou g h t h e p art ial carb on diox ide p ressu re is a p owerfu l res-
p irat ory st im u l u s, it m ay rise m odest l y in com p ensat ion for a
m et ab ol ic al k al osis. A P co2 in ex cess of 5 5 m m of m ercu ry is
u nl ik el y t o b e sol el y com p ensat ory , h owever, and an addi-
t ional p rim ary resp irat ory ab norm al it y sh ou l d b e sou g h t . " ' 2
T AB L E 3 . - Acu t e Resp irat or Al k al osis
Art erial G os V al u e I nt erp rt at ion
p H . 7 . 5 0 Al k al em ia-
P co2 * . 2 9 m m of m ercu ry Resp irat ory al k al osis
H CO 3 - . 2 2 m m ol / l it er N orm al H C0 3 -
Cau ses
Anx iet y
H y p ox ia
L u ng disease wit h or wit h ou t h y p ox ia
Cent ral nervou s sy st em disease
D ru g u se- sal icy l at es, cat ech ol am ines, p rog est erone
P reg nancy
S ep sis
H ep at ic encep h al op at h y
Mech anical vent il at ion
I h is is t h e p rim ary ab norm al it y .
T H E W E S T E RN J O U RN AL O F ME D I CI N E
*
AU G U S T 1 9 9 1
-
1 5 5
-
2 1 4 7
ACI D - B AS E D I S O RD E RS
T h e cau ses of m et ab ol ic al k al osis can b e divided int o t h ose
associat ed wit h a decreased ex t racel l u l ar vol u m e, or t h e
p ost h y p ercap nic st at e ( l ow u rinary ch l oride l evel ) , and t h ose
associat ed wit h a norm al or increased ex t racel l u l ar vol u m e
or recent diu ret ic u se ( norm al or h ig h u rinary ch l oride l evel ) ,
as l ist ed in T ab l e 6 . Measu ring t h e u rinary ch l oride l evel is
t h e p referred m et h od for assessing t h e renal resp onse t o cir-
cu l at ing vol u m e in p at ient s wit h m et ab ol ic al k al osis; t h e u ri-
nary sodiu m concent rat ion is l ess rel iab l e as a g u ide, for t h e
renal t h resh ol d for b icarb onat e m ay b e ex ceeded and sodiu m
sp il l ed as t h e b icarb onat e cat ion even in a p at ient wh o is
vol u m e dep l et ed.
Met ab ol ic Acidosis
N ex t consider a p at ient wit h a p H of 7 . 2 0 , a P co2 of 2 1
m m of m ercu ry , and a b icarb onat e l evel of 8 m m ol p er l it er.
T h e p at ient is acidem ic; t h erefore, t h e l ow b icarb onat e is t h e
p rim ary ab norm al it y and a m et ab ol ic acidosis wit h resp ira-
t ory com p ensat ion is p resent . T o h el p in dist ing u ish ing t h e
cau se, m et ab ol ic acidoses are com m onl y divided int o t h ose
wit h and t h ose wit h ou t an anion g ap . B ecau se t h e seru m
p ot assiu m cont rib u t es l it t l e t o t h e t ot al ex t racel l u l ar el ect ro-
l y t e p ool , t h e anion g ap is t radit ional l y cal cu l at ed b y ex -
cl u ding t h e p ot assiu m val u e and su b t ract ing t h e su m of t h e
ch l oride and b icarb onat e ( t ot al carb on diox ide) l evel s from
t h e sodiu m concent rat ion. I n t h e l it erat u re, t h e norm al anion
g ap is rep ort ed as 1 2 + 2 ( m ean + S D ) m m ol p er l it er, 3 ' 4
al t h ou g h t h e norm al rang e m ay b e l ower wh en m easu red on
t h e newest g enerat ion of au t oanal y z ers. 4 T h e cau ses of anion
g ap and nong ap acidosis are l ist ed in T ab l e 7 .
Mix ed Acid- B ase D isorders
I n each of t h e p reviou s ex am p l es, we h ave assu m ed t h at
onl y one p rim ary ab norm al it y is p resent . I n real l ife, h ow-
ever, p at ient s oft en h ave m ore t h an one disorder.
Mix ed acid- b ase disorders can b e ident ified b y det erm in-
ing t h e ex p ect ed com p ensat ory resp onse t o a g iven ch ang e in
t h e p rim ary ab norm al it y and assu m ing t h at any val u e t h at
fal l s ou t side t h is rang e rep resent s an addit ional p rim ary dis-
order. S u ch 9 5 % confidence b ands are t h e b asis for com -
m onl y u sed nom og ram s' and for t h e m at h em at ical form u l as
p op u l ariz ed b y N arins and E m m et t . 3 U nfort u nat el y , m at h e-
m at ical eq u at ions, esp ecial l y ones t h at are different for acu t e
and ch ronic disorders, can b e difficu l t t o m em oriz e. N om o-
g ram s are sim p l e t o u se b u t can fu rt h er m y st ify acid- b ase
anal y sis b y p roviding answers wit h ou t necessaril y req u iring
an u nderst anding of t h e rel evant p at h op h y siol og y . A sim p l er
al t ernat ive, wh ich wil l ident ify m ost cl inical l y im p ort ant dis-
orders, is ou t l ined in T ab l e 2 .
W e h ave al ready discu ssed t h e first ru l e of t h u m b t h at
direct s u s t o l ook at t h e p H t o det erm ine wh ich ab norm al it y is
p rim ary if m ore t h an one ab norm al it y is p resent . T h e second
ru l e inst ru ct s u s t o det erm ine t h e seru m el ect rol y t e val u es-
sodiu m , ch l oride, and t ot al carb on diox ide- and t o cal cu l at e
t h e anion g ap . I f t h e anion g ap is 2 0 m m ol p er l it er or g reat er,
t h en a m et ab ol ic acidosis is p resent reg ardl ess of t h e p H or
seru m b icarb onat e concent rat ion.
T h e p h y siol og ic p rincip l e b eh ind t h is assert ion is t h at t h e
b ody does not g enerat e a l arg e anion g ap t o com p ensat e even
for a ch ronic al k al osis. T h erefore, a su b st ant ial increase in
u nm easu red anions indicat es a p rim ary disorder, a m et ab ol ic
acidosis, reg ardl ess of t h e p H or t h e b icarb onat e concent ra-
t ion. T h ree l ines of evidence su p p ort t h is st at em ent . F irst , an
anion g ap of g reat er t h an 2 0 m m ol p er l it er is m ore t h an 4
st andard deviat ions from t h e m ean and t h erefore is u nl ik el y
t o b e du e t o ch ance. 3 4 S econd, al t h ou g h a m odest increase in
t h e anion g ap occu rs in p at ient s wit h m et ab ol ic or resp irat ory
al k al osis du e p rim aril y t o an increase in t h e neg at ive ch arg e
of seru m p rot eins, even in severe al k al osis t h is increase is
al m ost never g reat er t h an 2 0 m m ol p er l it er. 1 6 - 8 L ast , a
sp ecific cau se for an increased anion g ap can b e fou nd in
fewer t h an 3 0 % of p at ient s wit h a g ap g reat er t h an 1 2 m m ol
p er l it er b u t l ess t h an 2 0 m m ol p er l it er, as com p ared wit h
7 7 % of t h ose wit h a g ap of 2 0 m m ol p er l it er or g reat er and al l
of t h ose wit h a g ap of m ore t h an 3 0 m m ol p er l it er ( T ab l e 8 ) . 9
T h u s, an anion g ap of g reat er t h an 2 0 m m ol p er l it er is h ig h l y
p redict ive of t h e p resence of an ident ifiab l e m et ab ol ic acido-
sis. T h e g reat er t h e anion g ap , t h e m ore l ik el y it is t h at a
sp ecific m et ab ol ic acidosis wil l b e fou nd.
T AB L E 4 . - Acu t e Resp irat ory Acidosis
X Art erial G as V al u e I nt erp ret at ion 0
p H . . . . . . . . . . . . . . . . 2 5 Acidem ia
P co2 . . . . . 6 0 m m of m ercu ry Resp irat ory acidosis
H CO 3 - . 2 6 m m ol / l it er N orm al H CO 3 -
Cau ses
Cent ral nervou s sy st em ( CN S ) dep ression- dru g s, CN S event
N eu rom u scu l ar disorders- m y op at h ies, neu rop at h ies
Acu t e airway ob st ru ct ion- u p p er airway , l ary ng osp asm , b ronch o-
sp asm
S evere p neu m onia or p u l m onary edem a
I m p aired l u ng m ot ion- h em ot h orax , p neu m ot h orax
T h oracic cag e inj u ry - fl ail ch est
V ent il at or dy sfu nct ion
T h is is t h e p rim ary ab nirm al it y .
T AB L E 5 . - Ch ronic Resp irat ory Acidosis W it h
Met ab ol ic Com p ensat ion
Art eriol G as V al u e I nt erp ret at ion
p H . . 7 . 3 4
P co2 * . . . . . . . 6 0 m m of m ercu ry Resp irat ory acidosis
H CO . . 3 - . . . . 3 1 m m ol / l it er Met ab ol ic com p ensat ion
Cau ses
Ch ronic l u ng disease- ob st ru ct ive or rest rict ive
Ch ronic neu rom u scu l ar disorders
Ch ronic resp irat ory cent er dep ression- cent ral h y p ovent il at ion
' T h is is t h e p rim ary ab norm al it y .
T AB L E 6 . - Met ab ol ic Al k al 0 si W it h
Resp irat ot y Com p ensdt ion
Art erial G as V al u e I nt erp ret at ion
p H . . 7 . 5 0 Al k al em ia
P c2 . . . 4 8 m m of m ercu ry Resp irat ory cm p ensat ion.
H CO 3 - * . . 3 6 m m ol / l it er Met b ol ic al k al osis
Cou ses
rina Ch l oride L evel L ow C U rinary Ch l orideL evel N rm al or H ig h
V om it ing , nasog ast ric E x cess m nineral ocort icoid ~ act ivit y
su ct ion Cu sh ing ' s sy ndrom e, Conn' s sy n-
D iu ret ic u se in p ast drom e, ex og enou s st eroids, l icoricefr
P ost h y p ercaP na ing est ion, increased j renin st at es:
B art t er' s sy ndrom e
Cu rrent or recent diu ret ic u se
E x cess al k al i adm inist rat ion
Refeeding al k al osis
I h is is t h e p rim ary ab norm al it y .
1 4 8
T H E W E S T E RN J O U RN AL O F ME D I CI N E * AU G U S T 1 9 9 1 * 1 5 5 * 2 1 4 9
I f t h e anion g ap is increased, t h en t h e t h ird ru l e inst ru ct s
u s t o cal cu l at e t h e ex cess anion g ap - t h e t ot al anion g ap
m inu s t h e norm al anion g ap ( 1 2 m m ol p er l it er) - and add
t h is val u e t o t h e m easu red b icarb onat e concent rat ion ( t ot al
venou s carb on diox ide cont ent ) . I f t h e su m of t h e ex cess
anion g ap and t h e m easu red b icarb onat e is g reat er t h an a
norm al seru m b icarb onat e concent rat ion ( norm al rang e, 2 3
t o 3 0 m m ol p er l it er) , t h en an u nderl y ing m et ab ol ic al k al osis
is p resent reg ardl ess of t h e p H or m easu red b icarb onat e
val u e. I f t h e su m is l ess t h an a norm al b icarb onat e concent ra-
t ion, t h en an u nderl y ing nong ap m et ab ol ic acidosis is
p resent .
T h e p h y siol og ic b asis for t h is st at em ent is t h at for each
m il l im ol e of acid t it rat ed b y t h e carb onic acid b u ffer sy st em ,
1 m m ol of b icarb onat e is l ost t h rou g h conversion t o carb on
diox ide and wat er and 1 m m ol of t h e sodiu m sal t of t h e
u nm easu red acid is form ed. B ecau se each m il l im ol ar de-
crease in b icarb onat e is accom p anied b y a m il l im ol ar in-
crease in t h e anion g ap , t h e su m of t h e new ( ex cess) anion g ap
and t h e rem aining ( m easu red) b icarb onat e val u e sh ou l d b e
eq u al t o a norm al b icarb onat e concent rat ion. T h ese rel at ion-
sh ip s are sch em at ical l y p resent ed in F ig u re 1 . I f t h e su m of
t h e ex cess anion g ap and t h e m easu red b icarb onat e val u e
ex ceeds t h e norm al b icarb onat e concent rat ion, t h en an addi-
t ional disorder ( a m et ab ol ic al k al osis) h as added b icarb onat e
t o t h e ex t racel l u l ar sp ace. I f t h e su m is l ess t h an norm al , t h en
an addit ional p rocess ( a nonanion g ap m et ab ol ic acidosis)
h as cau sed g ast roint est inal or renal l oss of b icarb onat e. P u b -
l ish ed rep ort s indicat e t h at t h is recip rocal rel at ionsh ip b e-
t ween t h e increase in anion g ap ( and org anic acid sal t ) and t h e
decrease in seru m b icarb onat e concent rat ion is act u al l y ob -
served in u ncom p l icat ed org anic acidosest 0 - 1 8 b u t t h at t h e
one- for- one rel at ionsh ip is al t ered if t h ere is su p erim p osed
vom it ing 1 0 1 9 ' 2 0 or renal l oss of b icarb onat e. I 5 I - 7 T h ese dat a
su g g est t h at al t h ou g h t h e b ody ' s t it rat ion of acid rep resent s a
com p l ex int erp l ay of m u l t ip l e b u ffering sy st em s, b ecau se
b icarb onat e rem ains t h e m aj or ex t racel l u l ar b u ffer over a
wide rang e of p H , 2 1 ou r ru l e is em p irical l y correct and cl ini-
cal l y u sefu l .
Resp irat ory Al k al osis and Met ab ol ic Acidosis
Consider a p at ient wit h a p H of 7 . 5 0 , a P co2 of 2 0 m m of
m ercu ry , a b icarb onat e concent rat ion of 1 5 m m ol p er l it er, a
sodiu m concent rat ion of 1 4 0 m m ol p er l it er, and a ch l oride
l evel of 1 0 3 m m ol p er l it er. T h is p erson is al k al em ic wit h a
l ow P co2 and a l ow b icarb onat e concent rat ion. B ecau se t h e
p H is h ig h , t h e l ow P co2 rep resent s a p rim ary disorder, and a
resp irat ory al k al osis is p resent . At first insp ect ion, t h e l ow
b icarb onat e l evel ap p ears t o b e in m et ab ol ic com p ensat ion
for a ch ronic al k al osis. F ol l ow t h e second ru l e, h owever, and
cal cu l at e t h e anion g ap : 1 4 0 - ( 1 0 3 + 1 5 ) = 2 2 m m ol p er
l it er. A g ap of 2 2 m m ol p er l it er is g reat er t h an wou l d b e
ex p ect ed sol el y in com p ensat ion for a ch ronic al k al osis and
su g g est s t h at a second p rim ary disorder, an anion g ap m et a-
b ol ic acidosis, is al so p resent . I f t h e anion g ap h ad not b een
cal cu l at ed, t h e u nderl y ing m et ab ol ic acidosis wou l d h ave
b een m issed. N ow, p roceed t o t h e t h ird ru l e and cal cu l at e t h e
ex cess anion g ap : 2 2 - 1 2 = 1 0 m m ol p er l it er, and add it t o
t h e m easu red b icarb onat e l evel : 1 5 m m ol p er l it er. T h e su m ,
2 5 m m ol p er l it er, is norm al , indicat ing t h at no fu rt h er p ri-
norm al norm al
an ion g ap anion g ap
ex cess
anion g ap
H 0 0 3 H CO
E
E
N a C1 0 1 -
N orm al Met ab ol ic
Acidosis
( anion g ap )
F ig u re 1 . - T h e g rap h sh ows t h e effect of u nm easu red acid on t h e b icarb onat e
concent rat ion, anion g ap , and ex cess anion g ap . Anion g ap
=
[ N a+ ]
- ( [ Cl I - +
[ H CO 3 - ] ) ; ex cess anion g ap
=
t ot al anion g ap
- norm al anion g ap ( 1 2 m m ol /
l it er) .
T AB L E 7 . - Met ab ol ic Acidosis W it h Resp irat ory
Com p ensat ion
Art eriol G as val u e I nt erp ret at ion
p H . . 7 . 2 0 Acidem ia
P co2 . . 2 1 m m of m ercu ry Resp irat ory com p ensat ion
H CO 3 - - * . . . . . 8 m m ol / l it er Met ab ol ic acidosis
Anion g ap = sodiu m - ch l oride +
b icarb onat e
N orm al = 1 2 2 ( S D ) m m ol / l it er
Cou ses
N onanion G ap Anion G ap
G I b icarb onat e l oss Ket oacidosis
D iarrh ea D iab et ic
U ret eral diversions Al coh ol ic
Renal b icarb onat e l oss Renal fail u re
Renal t u b u l ar acidosis L act ic acidosis
E arl y renal fail u re
Carb onic anh y drase inh ib it ors Rh ab dom y ol y sis
Al dost erone inh ib it ors T ox ins
H y droch l oric acid adm inist rat ion
E t h y l eneol y l o
P ost h y p ocap nia P aral deh y de
S al icy l at es
G l g ast roint est inal
T h is is t h e p rim ary ab norm al it y .
T AB L E 8 . - T h e Rel at ion B et ween L evel of Anion G ap and
B ioch em ical D iag noses in 5 1 P at ient s
W it h ou t Renal F ail u re*
B ioch em ical l y Confirm ed
Anion G ap , P at ient s, O rg anic Acidosis P resent ,
m m ol / l it er N o. N o. %
1 7 - 1 9 7 2 2 9
2 0 - 2 4 2 0 1 3 6 5
2 5 - 2 9 1 5 1 2 8 0
3 0 - 4 5 9 9 1 0 0
> 2 0 4 4 3 4 7 7
' Adap t ed from G ab ow et al . 9
T H E W E S T E RN J O U RN AL O F ME D I CI N E
o
AU G U S T 1 9 9 1
o
1 5 5
- 9
2 1 4 9
ACI D - B AS E D I S O RD E RS
m ary ab norm al it ies are p resent . T h is p at ient h ad ing est ed a
l arg e q u ant it y of asp irin and disp l ay ed t h e cent ral l y m ediat ed
resp irat ory al k al osis and t h e anion g ap m et ab ol ic acidosis
associat ed wit h sal icy l at e overdose. 2 2 Resp irat ory al k al osis
and m et ab ol ic acidosis, h owever, can occu r t og et h er in a
variet y of rel at ed and u nrel at ed cl inical condit ions ( T ab l es
3 and 7 ) .
Met ab ol ic Acidosis and Met ab ol ic Al k al osis
T h e fol l owing ex am p l e is adap t ed from a l ect u re b y Rob -
ert N arins, MD : p H 7 . 4 0 , P co2 4 0 m m of m ercu ry , b icarb on-
at e 2 4 m m ol p er l it er, sodiu m 1 4 5 m m ol p er l it er, and
ch l oride 1 0 0 m m ol p er l it er. T h is is a seem ing l y norm al set of
val u es u nt il t h e anion g ap is cal cu l at ed: 1 4 5 - ( 1 0 0 + 2 4 ) =
2 1 m m ol p er l it er. T h e increased g ap defines a m et ab ol ic
acidosis even t h ou g h t h e p H is norm al . N ow cal cu l at e t h e
ex cess anion g ap : 2 1 - 1 2 = 9 m m ol p er l it er, and add it t o
t h e m easu red b icarb onat e: 2 4 m m ol p er l it er. T h e su m , 3 3
m m ol p er l it er, is h ig h er t h an a norm al b icarb onat e concen-
t rat ion, indicat ing a m et ab ol ic al k al osis is al so p resent .
T h ese l ab orat ory val u es are from a p at ient wit h ch ronic renal
fail u re ( cau sing t h e m et ab ol ic acidosis) wh o b eg an vom it ing
( h ence t h e m et ab ol ic al k al osis) as h is u rem ia worsened. T h e
acu t e al k al osis of vom it ing offset t h e ch ronic acidosis of renal
fail u re, resu l t ing in . * norm al p H . W it h ou t a sy st em at ic ap -
p roach t o acid- b ase disorders, incl u ding cal cu l at ion of t h e
anion g ap and of t h e ex cess anion g ap , t h ese m ix ed acid- b ase
disorders cou l d easil y h ave b een overl ook ed.
Resp irat ory Al k al osis, Met ab ol ic Acidosis, and
Met ab ol ic Al k al osis
Anal y z e t h e fol l owing b l ood g as and el ect rol y t e val u es:
p H 7 . 5 0 , P co2 2 0 m m of m ercu ry , b icarb onat e 1 5 m m ol p er
l it er, sodiu m 1 4 5 m m ol p er l it er, and ch l oride 1 0 0 m m ol p er
l it er. T h e p H is h ig h , t h e P co2 and b icarb onat e val u es are l ow,
and t h ere is an increased anion g ap . B ecau se t h e p H is ab ove
7 . 4 0 , t h e l ow P co2 is a p rim ary ab norm al it y , and t h e p at ient
h as a resp irat ory al k al osis. B ecau se t h e anion g ap is el evat ed
( 3 0 m m ol p er l it er) , a m et ab ol ic acidosis is al so p resent .
B ecau se t h e su m of t h e ex cess anion g ap ( 1 8 m m ol p er l it er)
and t h e m easu red b icarb onat e ( 1 5 m m ol p er l it er) is g reat er
t h an a norm al b icarb onat e concent rat ion, t h e p at ient al so h as
a m et ab ol ic al k al osis. T h e near- norm al p H refl ect s t h e com -
p et ing effect s of t h ese t h ree p rim ary disorders. T h is p erson
h ad a h ist ory of vom it ing ( t h e m et ab ol ic al k al osis) , evidence
of al coh ol ic k et oacidosis ( cau sing m et ab ol ic acidosis) , and
finding s com p at ib l e wit h a b act erial p neu m onia ( h ence t h e
resp irat ory al k al osis) . T h ese t h ree indep endent disorders can
occu r concu rrent l y in ot h er cl inical set t ing s ( T ab l es 3 , 6 , and
7 ) . F ou r p rim ary acid- b ase disorders cannot coex ist , as a
p at ient cannot h y p ovent il at e and h y p ervent il at e at t h e sam e
t im e.
Resp irat ory Acidosis, Met ab ol ic Acidosis, and
Met ab ol ic Al k al osis
W h at if a p at ient p resent s wit h a p H of 7 . 1 0 , a P co2 of 5 0
m m of m ercu ry , a b icarb onat e l evel of 1 5 m m ol p er l it er, a
sodiu m l evel of 1 4 5 m m ol p er l it er, and a ch l oride l evel of
1 0 0 m m ol p er l it er? T h e p erson is acidem ic wit h an el evat ed
P co2 , a l owered b icarb onat e, and an increased anion g ap ( 3 0
m m ol p er l it er) . B ecau se t h e p H is l ow, t h e increased P co2
( resp irat ory acidosis) and decreased b icarb onat e ( m et ab ol ic
acidosis) are b ot h p rim ary disorders. T h e anion g ap is in-
creased; t h erefore, t h e m et ab ol ic acidosis is of t h e anion g ap
variet y . B ecau se t h e su m of t h e ex cess anion g ap ( 1 8 m m ol
p er l it er) and t h e m easu red b icarb onat e ( 1 5 m m ol p er l it er) is
g reat er t h an t h e norm al b icarb onat e concent rat ion, a m et a-
b ol ic al k al osis is al so p resent : t h ree p rim ary disorders. T h is
p at ient p resent ed in an ob t u nded st at e ( resp irat ory acidosis) ,
wit h a h ist ory of vom it ing ( m et ab ol ic al k al osis) and l ab ora-
t ory finding s consist ent wit h diab et ic k et oacidosis ( m et a-
b ol ic acidosis) .
I nt erest ing l y , ident ical b l ood g as val u es cou l d occu r in a
p at ient wit h ch ronic resp irat ory acidosis and m et ab ol ic com -
p ensat ion in wh om an acu t e anion g ap m et ab ol ic acidosis
devel op ed. Al t h ou g h t h e p H , P co2 , and b icarb onat e val u es
wou l d b e t h e sam e in b ot h t h ese p at ient s, cl inical correl at ion
wou l d readil y different iat e b et ween t h e t wo. As is t h e case
for ot h er diag nost ic t est s, acid- b ase ab norm al it ies cannot b e
p rop erl y int erp ret ed wit h ou t k nowl edg e of t h e cl inical
cont ex t .
Anion G ap and N onanion G ap Met ab ol ic Acidoses
Consider a p at ient wit h t h e fol l owing val u es: p H 7 . 1 5 ,
P co2 1 5 m m of m ercu ry , b icarb onat e l evel 5 m m ol p er l it er,
sodiu m l evel 1 4 0 m m ol p er l it er, and ch l oride val u e 1 1 0
m m ol p er l it er. T h e p at ient is acidem ic wit h a l ow P co2 , a l ow
b icarb onat e, and an increased anion g ap ( 2 5 m m ol p er l it er) .
At first g l ance, t h is p at ient h as a sim p l e anion g ap m et ab ol ic
acidosis wit h resp irat ory com p ensat ion. T h e su m , h owever,
of t h e ex cess anion g ap ( 1 3 m m ol p er l it er) , and t h e m easu red
b icarb onat e ( 5 m m ol p er l it er) is l ower t h an t h e norm al b icar-
b onat e concent rat ion, su g g est ing t h at addit ional g ast roint es-
t inal or renal l oss of b icarb onat e h as occu rred and t h at b ot h
an anion g ap and a nonanion g ap m et ab ol ic acidosis are
p resent . D iab et ic k et oacidosis was resp onsib l e for t h e anion
g ap acidosis in t h is p at ient . T h e nonanion g ap ( h y p er-
ch l orem ic) acidosis is t h at p h enom enon ob served in t h e
recovery p h ase of diab et ic k et oacidosis du e t o fail u re t o re-
g enerat e b icarb onat e from k et oacids l ost in t h e u rine. 1 5 - 1 7 I f
t h e su m of t h e ex cess anion g ap and t h e m easu red b icarb on-
at e h ad not b een cal cu l at ed, t h e u nderl y ing nong ap acidosis
wou l d not h ave b een ap p reciat ed.
Concl u sions
Acid- b ase dist u rb ances are not difficu l t t o anal y z e if ap -
p roach ed in a sy st em at ic m anner. F irst , assess t h e p at ient ' s
cl inical st at u s. A p rop er int erp ret at ion of l ab orat ory resu l t s
req u ires k nowl edg e of t h e cl inical set t ing . S econd, det er-
m ine b l ood g as val u es and ident ify al l ab norm al it ies in
p H ,
P co2 , and b icarb onat e l evel . T h ird, det erm ine wh ich ab nor-
m al it ies are p rim ary and wh ich are com p ensat ory b ased on
t h e p H . I f t h e p H is l ess t h an 7 . 4 0 , t h en a resp irat ory or
m et ab ol ic acidosis is p rim ary . I f t h e p H is g reat er t h an 7 . 4 0 ,
t h en a resp irat ory or m et ab ol ic al k al osis is p rim ary . N ex t ,
m easu re t h e seru m el ect rol y t es- sodiu m , ch l oride, and t ot al
carb on diox ide concent rat ions- and cal cu l at e t h e anion g ap .
I f t h e anion g ap is 2 0 m m ol p er l it er or g reat er, t h en a m et a-
b ol ic acidosis is p resent reg ardl ess of t h e p H or seru m b icar-
b onat e concent rat ion. I f t h e anion g ap is increased, t h en
cal cu l at e t h e ex cess anion g ap ( t h e t ot al anion g ap m inu s t h e
norm al anion g ap [ 1 2 m m ol p er l it er] ) and add t h is val u e t o
t h e m easu red b icarb onat e. I f t h e su m is g reat er t h an a norm al
seru m b icarb onat e ( > 3 0 m m ol p er l it er) , t h en an u nderl y ing
m et ab ol ic al k al osis is p resent . I f t h e su m is l ess t h an a norm al
b icarb onat e ( < 2 3 m m ol p er l it er) , t h en an u nderl y ing non-
1 5 0
T H E W E S T E RN J O U RN AL O F ME D I CI N E * AU G U S T 1 9 9 1 * 1 5 5 * 2
anion g ap acidosis is p resent . L ast , det erm ine t h e cau se of
each p rim ary disorder t h at h as b een ident ified and b eg in
cau se- sp ecific t h erap y . T h is ap p roach wil l al l ow even com -
p l ex acid- b ase disorders t o b e recog niz ed and wil l p rovide a
cl inical l y rel evant fram ework for u nderst anding acid- b ase
h om eost asis.
RE F E RE N CE S
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t h e recovery p h ase
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1 5 1