Approach to Ac|d-8ase

D|sorders
naro|d M. Szer||p, MD IAC, ICC, IASN, INkI
Un|vers|ty of North 1exas nea|th Sc|ence Center


Iacu|ty D|sc|osures

CranL SupporL- SpecLral ulagnosucs, Lll Lllly
Learn|ng Cb[ecnves
Aer Lhls sesslon, learners wlll be able Lo:
1) 8ecognlze a slmple acld-base dlsLurbance
2) 8ecognlze a mlxed acld-base dlsLurbance
Approach to Ac|d-8ase
Penderson-Passelbalch (8osLon)
SLrong-lon ulerence (SLewarL)
8ase-excess (Copenhagen)
AlLhough each approach has lLs pros and cons,
because of lLs ease of use, Lhe Lradluonal Penderson -
Passelbalch approach wlll be used.
ML1A8CLIC ACIDCSIS
Penderson equauon

[P
+
] = k
x
([P
2
CC
3
]/[PCC
3
-
])

[P+] = 24

Passelbalch modlcauon

pP = pk
x
log[[PCC
3
-
]/ [S
CC
2
x
CC
2
]}

CC
2
PCC
3
-
pH 7.5 [H+] = 30
pH 7.4 [H+] = 40
pH 7.3 [H+] = 50
Approach to Ac|d-8ase
pP = pk + log[[PCC
3
-
]/ [S
CC
2
x
CC
2
]}

pP = k
a
+ Log

uoes noL mean LhaL pP ls physlcally deLermlned by
PCC
3
and
CC
2

rovldes false lmpresslon LhaL Lhe buer palr -
[PCC
3
-
]/[P
2
CC
3
] ls more lmporLanL Lhan oLher buers

SuggesLs LhaL [PCC
3
] ls an lndependenL varlable
Penderson Passelbalch equauon
PCC
3
-
0.03 x CC
2
{Buffer-Base Pair}
Approach to Ac|d-8ase
! uo PlsLory and hyslcal
! Measure pP, CC
2
, PCC
3
(v8C or A8C)
! CalculaLe Anlon Cap (CorrecL for Albumln)
! Apply Compensauon rules
" LxcepL for Chronlc resplraLory alkalosls compensauon never
correcLs Lo normal
" lf compensauon ls Loo much or Loo llule, Lhere ls a second
prlmary dlsLurbance
" When ln doubL use acld-base map
! CalculaLe delLa/delLa
Approach to Ac|d-8ase
PlsLory and hyslcal Clues
1. vomlung - meLabollc alkalosls
2. PlsLory of ulabeLes - meLabollc acldosls
3. PlsLory smoklng/CCu - resplraLory acldosls
4. PlsLory of Llver dlsease - resplraLory alkalosls
3. 8ecenL blnge drlnklng - meLabollc acldosls
6. ularrhea - meLabollc acldosls
7. 1achypnea - resplraLory alkalosls
8. PypoLenslon - meLabollc acldosls

Approach to Ac|d-8ase
MehLa AW, Lmmeu M. Approach Lo acld-base dlsorders. ln rlmer on kldney
ulseases. (3
Lh
edluon) Creenberg A ( Ld). Saunders Llsevler, hlladelphla, 2009
Approach to Ac|d-8ase
MehLa AW, Lmmeu M. Approach Lo acld-base dlsorders. ln rlmer on kldney
ulseases. (3
Lh
edluon) Creenberg A ( Ld). Saunders Llsevler, hlladelphla, 2009
Alkalemla (pP > 7.43)
Na
140
Cl
105
HCO
3

10
unmeasured anions
(Proteins, SO
4
, PO
4,
organic anions)
unmeasured
cations
(K, Ca, Mg)
{
Na
140
HCO
3

10
Cl
120
}
} Lactate
15
Anion
Gap
10
Anion
Gap
25

Anion Gap
Acidosis
Hyperchloremic
Acidosis
Normal
Gap 10
Normal
Gap 10
Approach to Ac|d-base: An|on-gap
Approach to Ac|d-8ase
An|on-Gap
AC= na
+
- (PCC
3
-
+ Cl
-
)
normal AC 10 2
CorrecL for albumln
lor every 1 gm/dl decrease add 2.3 meq Lo AC
AC
cor
= na
+
- (PCC
3
-
+ Cl
-
) + (4 - Alb)2.3
Approach to Ac|d-8ase
Compensauon rules
MeLabollc Acldosls
CC
2
= 1.S(nCC
3
) + 8 2
CC
2
= lasL 2 dlglLs pP
CC
2
= PCC
3
+ 13
MeLabollc Alkalosls
CC
2
^ by 0.3-0.7 for each 1 meq ^
PCC
3
(usually noL >33-60)
Approach to Ac|d-8ase
Compensauon rules
8esplraLory Acldosls
AcuLe -- 1 meq ^ ln PCC
3
for every 10 mmPC
^CC
2
Chronlc - 3.3 meq ^ ln PCC
3
for every 10
mmPC ^CC
2

8esplraLory Alkalosls
AcuLe -- 2 meq j ln PCC
3
for every 10 mmPC
j ln CC
2

Chronlc -- 3 meq j ln PCC
3
for every 10 mmPC
j lnCC
2

Approach to Ac|d-8ase
uelLa-uelLa (!gap/!PCC
3
-
)
# Assumlng LhaL Lhe P
+
space ls equlvalenL Lo Lhe
PCC
3
-
space
# 1han for every 1 meq lncrease ln Lhe AC Lhere should
be a equal decrease ln Lhe PCC
3
-
Actua| An|on Gap - N| An|on Gap
N| nCC
3
-
- Actua| nCC
3
-

= 1
Approach to Ac|d-8ase
uelLa-uelLa (!gap/!PCC
3
-
)
lf greaLer Lhan 1 Lhan Lhere ls a concurrenL meLabollc alkalosls
lf less Lhan 1 Lhan Lhere ls a concurrenL hyperchloremlc
meLabollc acldosls
Actua| An|on Gap - N| An|on Gap
N| nCC
3
-
- Actua| nCC
3
-

= 1
Approach to Ac|d-8ase:
S|mp|e Metabo||c Ac|dos|s
Anlon Cap Pyperchloremlc
MeLabollc Acldosls
Approach to Ac|d-8ase:
An|on Gap Metabo||c Ac|dos|s
M ethanol
U remia
D iabetic or alcoholic ketoacidosis/ Drugs
P henformin/Paraldehyde/Pyroglutamic Acid/
Propylene Glycol
I nh/Iron
L actic acidosis ( L & D )
E thylene glycol
S alicylate
Approach to Ac|d-8ase:
An|on Gap Metabo||c Ac|dos|s
G lycols
O xoproline
L - lactic acidosis
D - lactic acidosis

M ethanol
A spirin
R enal failure
K etoacidosis
Lacnc Ac|dos|s
Lacuc Acldosls
$ LacLaLe > 3 mmol/L
$ pP < 7.33
$ Anlon gap lnsensluve
$ AssoclaLed wlLh a worse prognosls
(especlally when noL rapldly cleared)
Lacnc Ac|dos|s
Lacnc Ac|dos|s
1ype A
Inadequate nssue oxygenanon
1ype 8
Adequate nssue oxygenanon
1here |s ohen an over|ap
lncreased lacLaLe producuon
decreased lacLaLe uullzauon
Lacnc Ac|dos|s
Etiology of Lactic Acidosis
Drugs
$ biquanides
$ nucleoside analogs
$ propylene glycol
$ propofol
$ !-agonists
$ linezolid
$ aspirin
$ cocaine
Lacnc Ac|dos|s:
ropy|ene G|yco|
1-2 propaned|o|
P CP P
CP - C - C - C - P
P P P
30 unchanged
Alcohol
dehydogenase
Lactate
Lacnc Ac|dos|s:
ropy|ene g|yco|
ropy|ene G|yco|
% Common veh|c|e for numerous drugs
$ Lorazepam,
$ ulazepam,
$ nlLroglycerln
$ henyLoln
$ LLomldaLe
$ 1rlmeLhoprlm-sulfameLhoxazole
$ Sllver sulfadlazlne
Clue:
Csmolal gap
An|on Gap Ac|dos|s
Low Mo|ecu|ar We|ght A|coho|s
MeLabollc acldosls
Csmolal gap ( measured osmolallLy - calculaLed osmolallLy
*
>
10)
*
calculated osmolality = 2 x Na + BUN/2.8 + Glucose/18 + ethanol/4.6
Time &
An|on Gap Ac|dos|s
Low Mo|ecu|ar We|ght A|coho|s
LLhylene glycol & oxallc acld
uecreased MS
8enal lallure
CxalaLe crysLals
MeLhanol& formlc acld
uecreased MS
vlsual dlsLurbances (papllllus)
Acidosis secondary to the metabolism of
alcohol by alcohol dehydrogenase
An|on gap ac|dos|s: treatment
1. 1reaL underlylng cause
2. 8eplace 8uer (conLroverslal)
3. Pemodlalysls
An|on Gap Ac|dos|s
Low Mo|ecu|ar We|ght A|coho|s
1reaLmenL:
Alcohol or fomeplzole !"#$%&'& )#* +,"#-#, .&-/.*#0&1+2&3
ulalysls
Acetam|nophen: Metabo||c ac|dos|s

Acetominophen
N-acetyl benzoquinonimine
Glutathione
"-glutamylcysteine synthase
Cysteine
L-Glutamate
"-glutamylcysteine
Glutathione
Glycine
5-Oxoproline
Pyperchloremlc MeLabollc Acldosls
Renal
Non-Renal
Decreased
renal NH4
+

excretion
Na
50
Cl
135
nP4
73
CLher
anlons
k
43
Na
50
Cl
80
nP4
20
CLher
anlons
k
43
Normal NH4
excretion
Decreased NH4
excretion
N
e
g
a
t
i
v
e


a
n
i
o
n

g
a
p

p
o
s
i
t
i
v
e


a
n
i
o
n

g
a
p

Ur|ne An|on Gap
urlne anlon gap (u
na
+ u
k
) - u
cl
lndlrecL measure of urlne nP
4
+
Lxcreuon
of
organlc anlons
uefecL ln
PCC
3
-
reclamauon
uefecL ln
P
+
secreuon
lnadequaLe
nP
3
producuon
LxLra-renal
Loss of base
Acld load
1oluene lngesuon
ulabeuc keLoacldosls
roxlmal 81A ulsLal 81A
8enal fallure
PypoaldosLeronlsm
PA
ularrhea
ancreauc sLula
ureLeral dlverslons
nP4Cl/PCL
naCl
load
Fractional
Excretion
HCO3 >15%
Urine pH > 5.5
Positive Urine AG

Negative
Urine AG
Urine pH < 5.5
(pH maybe > 5.5)
Positive Urine AG
High urine osmole gap
nyperch|orem|c Metabo||c Ac|dos|s
nyperch|orem|c Metabo||c Ac|dos|s:
1reatment
1. 1reaL underlylng cause
2. 8ase replacemenL
Metabo||c A|ka|os|s
Cenerauon hase
Loss of P
+
or galn of base
MalnLenance hase
uecrease renal PCC
3
-
excreuon
uecreased Cl8
volume depleuon
PyperaldosLeronlsm
uecreased Chlorlde
Pypokalemla
Metabo||c A|ka|os|s
Chlorlde responslve Chlorlde 8eslsLanL
leCl < 1
vomlung
uluresls
leCl > 1
PyperaldosLeronlsm
Pypokalemla
Metabo||c A|ka|os|s
1reaLmenL
Chlorlde repleuon
oLasslum repleuon
SplronolacLone/eplerenone
AceLazolamlde
0.1 n PCL
kesp|ratory Ac|dos|s
uecreased venulauon
CenLral (narcoucs)
ChesL Wall (paln)
ulaphragm ( myopaLhy)
lncreased dead space
kesp|ratory A|ka|os|s
lncreased venulauon
CenLral
Sepsls
SallcylaLes
regnancy
Llver dlsease
Pypoxla
M|xed Ac|d-8ase D|sorders
When Lo suspecL
1. pP normal wlLh abnormal CC2 or PCC3
2. Acldemla wlLh low PCC2 hlgh CC2
3. uelLa:uelLa > 1.2
4. Alkalemla wlLh hlgh PCC3 and low CC2
3. Compensauon noL approprlaLe
Case 1
A 32-year-old man ls admlued Lo Lhe lnLenslve care unlL
wlLh pneumonla and sepuc shock. Cver Lhe pasL 4 days, he
has had lncreaslng shorLness of breaLh and fever. Pe has
hyperLenslon. Medlcauons are amlodlplne and
hydrochloroLhlazlde.
Cn physlcal examlnauon, LemperaLure ls 38.8 C, pulse raLe
ls 110/mln, resplraLory raLe ls 22/mln, and blood pressure ls
83/30 mm Pg. Cardlac examlnauon reveals a grade 2/6
sysLollc murmur. Cn pulmonary examlnauon, Lhere are
crackles over Lhe enure rlghL lung eld. 1here ls Lrace pedal
edema.
Case 1
LaboraLory SLudles
Clucose 113 mg/dL
8lood urea nlLrogen 22 mg/dL (
Creaunlne 1.4 mg/dL
Sodlum 136 meq/L
oLasslum 4.8 meq/L
Chlorlde 103 meq/L
8lcarbonaLe 11 meq/L
Albumln 3.8 g/dL
pP 7.0 CC
2
46 mm Pg C
2
31 mm Pg
Case 1
Whlch of Lhe followlng condluons ls mosL llkely presenL ln
Lhls pauenL?
A. Anlon gap meLabollc acldosls
8. Mlxed non-anlon gap meLabollc acldosls and
resplraLory acldosls
C. Mlxed anlon gap meLabollc acldosls and resplraLory
alkalosls
u. Mlxed anlon gap meLabollc acldosls and resplraLory
acldosls
L. Mlxed non-anlon gap meLabollc acldosls and
resplraLory alkalosls
Case 2
A 47 year old male wlLh a hlsLory of alcohol abuse and
clrrhosls presenLs Lo Lu c/o n/v and abdomlnal paln.
Pe had been drlnklng heavlly unul 1 day prlor Lo
presenLauon when because of Lhe abdomlnal paln and
nauseas he dlsconunued alcohol consumpuon.
Cn exam he appears lll.
vS: 8 110/60 106 88 24 1 37
Skln: + [aundlce, splder LelanglecLaslas
Case 2
Labs:
na 136 k 3.2 Cl 90 PCC3 23
A8C pP 7.47 CC2 33
Case 2
WhaL ls Lhe acld base dlsLurbance
A. MeLabollc Acldosls
8. 8esplraLory Alkalosls
C. MeLabollc Acldosls/8esplraLory Alkalosls
u. MeLabollc Acldosls/MeLabollc Alkalosls/8esplraLory
Alkalosls
L. Can noL lnLerpreL due Lo lab error
Case 3
A 32-year-old man wlLh a hlsLory of chronlc alcohol
abuse presenLs Lo Lhe Lmergency ueparLmenL
confused and aglLaLed. hyslcal exam reveals
LemperaLure 38
o
C, pulse 112 bpm and blood
pressure 164/100. Pe ls orlenLed x 1. LxcepL for
mlld hepauc Lenderness Lhe remalnder of Lhe exam
ls normal.
Case 3
Admlsslon labs:
W8C 16.1 hemoglobln 11.4 plaLeleLs 108 k
na 136 k 3.3 Cl 104 PCC
3
26 8un 8
Creaunlne 1.0

Pe ls LreaLed wlLh Mvl and Lhlamlne and admlued
Lo Lhe lCu for lmpendlng u1s
Case 3
1he pauenL ls LreaLed wlLh lv lorazepam and #-
blockers. 8ecause of worsenlng aglLauon hls
lorazepam ls uLraLed up by Lhe nurses. Pe ls afebrlle
wlLh normal vlLal slgns. Cn day 4 hls labs reveal:
na 133 k 4.0 Cl 100 PCC3 13 8un 8 mg/dl
Clucose 90 mg/dl
pP 7.29 CC2 30 PCC3 14
Serum osmolallLy 320 mosm/kg
Case 3
WhaL ls Lhe llkely cause of hls meLabollc acldosls?
A. uellrlum Lremens
8. Lorazepam drlp
C. unrecognlzed sepsls
u. Llver dlsease
L. ancreauus
Case 4
A 20 year old college sLudenL wlLh a hlsLory of
depresslon ls found crylng ln her dorm room aer
havlng a ghL wlLh her boyfrlend. She sLaLes she Look
some pllls several hours prevlously. LMS ls called
and LransporLs her Lo Lhe emergency room. hyslcal
exam ls unremarkable excepL for Lachypnea.
na 139 k 4.6 Cl 100 PCC3 18
A8C: p 7.30 pCC2 24 PCC3 18
Case 4
WhaL ls (are) Lhe acld-base dlsLurbance(s)?
A. MeLabollc acldosls
8. MeLabollc alkalosls
C. MeLabollc acldosls wlLh compensaLory resplraLory
alkalosls
u. Mlxed MeLabollc Acldosls/ 8esplraLory Alkalosls
L. Can noL lnLerpreL due Lo lab error

Case S
?ou are asked Lo evaluaLe a 64 y/o male wlLh a h/o
CCu who presenLed 4 days ago wlLh resplraLory
dlsLress. Pe was lnLubaLed and admlued Lo Lhe lCu. PL
has been LreaLed wlLh solumedrol, nebullzed albuLerol/
lpraLroplum, anubloucs and lnLravenous furosemlde.
na 144 k 3.2 Cl 102 PCC3 38
A8C pP 7.38 CC2 42
Case S
WhaL ls (are) Lhe acld-base dlsorder(s)
A. 8esplraLory acldosls
8. Mlxed meLabollc alkalosls and resplraLory acldosls
C. Mlxed meLabollc alkalosls and resplraLory alkalosls
u. Mlxed meLabollc alkalosls. MeLabollc acldosls and
resplraLory alkalosls
L. Can noL lnLerpreL due Lo lab error
Case 6
A 24 y/o woman wlLh asLhma presenLs Lo Lhe Lu wlLh
wheezlng and SC8. Cn exam her 8 ls 136/88 mm Pg,
110 bpm, 88 26 mln
A8C: pP 7. 36 C2 70 CC2 30 PCC3 24
na 138 Cl 104 k 3.6 PCC3 24
Case 6
WhaL ls Lhe acld -base dlsLurbance
A. 8esplraLory acldosls
8. 8esplraLory alkalosls
C. Mlxed resplraLory alkalosls and meLabollc acldosls
u. Mlxed resplraLory alkalosls, meLabollc acldosls and
meLabollc alkalosls
L. Can noL lnLerpreL due Lo lab error
Case 6
[P] = 24
[P] = 24 = 30 = pP = 7.3 = 7.36
CC2
PCC3
30
24
Summary of key o|nts
Lvaluauon of Acld-8ase dlsLurbances
1horough P&
MeasuremenL pP, CC2, PCC3
Calculauon correcLed Anlon Cap
Calculauon delLa/delLa
undersLandlng compensauon rules
kecommended kead|ng and Add|nona|
kesources
1) MehLa An and Lmmeu M. Approach Lo acld-base
dlsorders. ln rlmer on kldney ulseases. (3
Lh
edluon)
Creenberg A ( Ld). Saunders Llsevler, hlladelphla pp
98-107, 2009
2) Androgue P!, eL. al. Assesslng acld-base dlsorders.
kldney lnLernauonal 76:1239, 2009
3) 8ose 8. Slmple and mlxed acld-base dlsorder. ln
up1ouaLe
Cuesuons?