Stewart Approach of Acid Base

Balance Interpretation
Erwin Pradian
Apa yang dimaksud
dengan pH?
• pH = derajat keasaman yg digunakan untuk
menyatakan tingkat keasaman atau
kebasaan yg dimiliki suatu larutan.
• pH  “potenz of Hydrogen”, merupakan
logaritme negatif dari jumlah ion hidrogen
(kologaritme aktivitas ion hidrogen terlarut)
• Tubuh selalu memelihara [H+] sekitar 36-
44 nM/l.
Mengapa pH secara ketat
diatur oleh tubuh?
• Reaksi biokimia seperti mekanisme obat,
hormon, ikatan reseptor sangat
dipengaruhi pH.
• Perubahan pada [H+] intrasel mempunyai
pengaruh yang besar pada performance sel
(reaksi enzimatik, protein charge).
 Bagaimana mempelajari
keseimbangan asam-basa?
Traditional Approach

Hendersen-Hasselbalch

The disadvantage of men not knowing

the past is that they do not know the
present.
G. K. Chesterton
Persamaan H-H:
CO2 + H2O H2CO3 H+ + HCO3-

 karena H2CO3 sangat tidak stabil

CO2 + H2O H+ + HCO3-

 PRINSIP DASAR
• Keberadaan ion H+ ditentukan oleh :
1. CO2 : diatur oleh sistem pernafasan.
2. Ion HCO3- : diatur oleh ginjal.
• Hubungan parameter tsb.(H+, CO2 dan HCO3-)
sebagai berikut:

[HCO3-]
Basa
pH = pK + log  pCO2
Asam
 Tidak puas???

HOW TO UNDERSTAND ACID-BASE

A quantitative Acid-Base Primer
For Biology and Medicine
Peter A. Stewart
Edward Arnold, London 1981

“The universe stands continually open to our gaze, but it cannot be understood unless
one first learns to comprehend the language……. It is written in the language of
mathematics.” (Galileo Galilei, 1623)
 Prinsip Dasar persamaan Stewart’s

• Hukum kekekalan massa:

– Massa suatu zat tidak akan berubah apabila tidak
ditambah, diproduksi, diambil atau dihancurkan.
• Electroneutrality:
 ion (+) =  ion (-)

Stewart PA. Modern quantitative acid-base chemistry. Can J Physiol Pharmacol 61:1444-1461, 1983.
 FAKTOR2 YANG MEMPENGARUHI KESEIMBANGAN ASAM
BASA
(menurut Stewart)
1. PCO2

2. SID (strong ion difference)

SID = {[Na+] + [K+] + [Ca+] + [Mg++]} – {[Cl-] + [strong
anion lainnya ]}.

3. Konsentrasi total asam lemah ( Atot).

mis : Hb, albumin, phosphat inorganik.

12
 SID (Strong Ion Difference)

• SID = (Jumlah seluruh kation kuat) - (Jumlah seluruh anion

kuat).

• SID = { [Na+] + [K+] + [Ca++] + [Mg++] }

- { [Cl-] + [lactate-] }
• Normal = 40 - 42 mEq/l.
 Total Asam lemah: [ATot]

• Merupakan total konsentrasi asam lemah

dalam larutan (albumin, fosfat)

[ATot] = [HA] + [A]

 Konsep larutan encer (Aqueous
solution)

• Semua cairan dalam tubuh manusia mengandung air,

dan air merupakan sumber [H+] yang tidak habis-
habisnya
• [H+] ditentukan oleh disosiasi air (Kw), dimana
molekul H2O akan berdisosiasi menjadi ion-ion H+
dan OH-

H2O  H+ + OH-
• [H2O] sangat besar (55.5M at 37oC), dapat dianggap
[H2O] konstan, sehingga Kw dan [H2O] dapat
dikombinasikan menjadi konstanta baru: K’w yang
disebut sebagai ion product for water.

• K’w = [H+] x [OH-]

• [H+] = [OH-]  law of electroneutrality.

[H+] = (K’w)1/2
Perubahan yang terjadi pada pH atau [H+] bukan
sebagai akibat dari penambahan atau
pengurangan H+, namun semata-mata akibat dari
disosiasi air…

Prinsip Dasar I (Perbedaan dengan H-H)

 Elektrolit = Ion-ion
Ion-ion kuat
(Strong ions) :
Substansi yang terdisosiasi
sempurna di dalam suatu larutan :
Kation; Na+,K+,Mg+,Ca++
Anion; Cl-,SO4-,PO4=,
laktat-, keto-.
Ion-ion lemah
(Weak ions) :
Substansi yang hanya
sebagian terdisosiasi dalam
suatu larutan :
 Albumin-, Posfat-, H2CO3
 MENGAPA DISEBUT ION KUAT DAN LEMAH ?

100
80
70
60
50 pK
40
30
20
10

2 3 4 5 6 7 8 9
pH
Suatu ion dikatakan kuat atau lemah tergantung dari pKnya (pH, dimana 50%
dari substansi tsb terdisosiasi). Mis; pK Lactate 3.9 (berarti, pada pH normal,
hampir 100% laktat terdisosiasi ). H2CO3 dan Alb disebut asam lemah karena
pada pH normal hanya 50% substansinya terdisosiasi.
 Strong Ions and Water
Jika larutan mengandung Cl-(anion) >>  (SID)  H3O+ >>

Jika larutan mengandung Na+ (kation) >>  (SID )  OH- >>

Water

O- H OH- +

H+
Strong ions dissosociate in water
Base
Acid
Na+ Cl- SID  “Proton Jumping”
SID 
SID n H3O+
Salt Na
H+ Na
Cl
- Cl
O
PlasmaH +

WORKSHOP ACIDBASE
STEWART PERDICI 2006
 Bagaimana menghitung pH dari larutan NaCl?

• Water Dissociation Equilibrium:

K’w = [H+] x [OH-]
• Electrical Neutrality:
[Na+] + [H+] = [Cl-] + [OH-]
Solving for [H+]:
• [Na+] - [Cl-] = [OH-] - [H+]
• [OH-] = K’w / [H+]
• Combining these:
[H+]2 + [H+] ([Na+] - [Cl-]) - K’w = 0
• Now ([Na+] - [Cl-]) = SID for the solution in
this example, so:
[H+]2 + ( SID . [H+] ) - K’w = 0
• Solving this quadratic equation:
[H+] = K’w + SID2/4 - SID/2
For solutions containing Na+ and Cl- in water, the [H+] is
determined by the SID alone !!
BLOOD PLASMA

H+

HCO3- SID
Na+ OH- CO32-
ATot
Alb -
Posfat - Unmeasured Anion
XA -
K+
Mg++
Ca++

Cl-

CATION ANION
 THE SIX SIMULTANEOUS EQUATIONS
USED BY STEWART
Water Dissociation Equlibrium

[H+] x [OH-] = Kw’

Electrical Neutrality Equation

[SID] + [H+] = [HCO3-] + [A-] + [CO3 –2] + [OH-]

Weak acid Dissociation Equilibrium Conservation of Mass for “A”
[H+] x [A-] = KA x [HA] [ATot] = [HA] + [A-]
Bicarbonate Ion Formation Equilibrium

[H+] x [HCO3] = Kc x pCO2

Carbonat Ion Formation Equilibrium

[H+] x [CO3–2] = K3 x [HCO3-]

WORKSHOP ACIDBASE
STEWART PERDICI 2006
A 4th polynomial order

ax4 + bx3 + cx2 + dx + e = 0

Substitute;

a.[H+]4 + b.[H+]3 + c.[H+]2 + d.[H+] + e = 0

Where,

a = 1
b = [SID] + KA
c = { KA ([SID] – [ATot]) – Kw’ – Kc.pCO2}
d = - {KA (Kw’ + Kc.pCO2) – K3.Kc.CO2}
e = - (KA.K3.Kc.pCO2)

WORKSHOP ACIDBASE
STEWART PERDICI 2006
[SID]+[H+]-KC.pCO2/[H+]-KA.[ATot]/(KA+[H+])-K3.KC.pCO2/[H+]2-Kw’/[H+]=0

[H+] dan [HCO3-] = ([SID], pCO2, [ATot])

In these solution it is clear that if the hydrogen or

bicarbonate ion concentration changes
Prinsip perbedaan II

the SID,ATot and pCO2 must have changed

The Earth was the center of the Universe? (Copernicus)

WORKSHOP ACIDBASE
STEWART PERDICI 2006
Menurut Stewart

pH atau [H+] DALAM PLASMA

DITENTUKAN OLEH

DUA VARIABEL

VARIABEL Variabel
INDEPENDEN Dependen

Stewart PA. Can J Physiol Pharmacol 61:1444-1461, 1983.

 VARIABEL INDEPENDEN

CO2 STRONG ION DIFFERENCE WEAK ACID

pCO2
SID Atot
Controlled by the
The protein
respiratory system
The electrolyte concentration
composition of the (controlled by the liver
blood and metabolic state)
(controlled by the
kidney)
 DEPENDENT VARIABLES

H+ HCO3-

OH- AH
CO3- A-
 Determinants of [H+]
• pCO2
 pCO2 + H2O  H2CO3  H+ + HCO3-
• SID (strong ion difference)
 Na+ + K+ + Ca++ + Mg++ - Cl- - L-
• ATOT
 ATOT  A- + AH
 Albumin (78%), phosphate (20%), other
(2%)
 Hubungan SID dgn pH/H+

Konsentrasi H+ [H+] ↑↑ [OH-] ↑↑

SID↓ SID
SID↑
Na Na Na
Cl Asidosis Cl Alkalosis Cl

(–) SID (+)

Dalam cairan biologis (plasma) dgn suhu 370C, SID selalu positif,
nilainya berkisar 30-40 mEq/Liter
WATER EXCESS

Plasma

1 Litre 140/2 = 70 mEq/L

Na+ = 140 mEq/L H2O 102/2 = 51 mEq/L
Cl- = 102 mEq/L SID = 19 mEq/L
SID = 38 mEq/L 1 litre 2 litre

SID : 38  19 = Acidosis
Dilutional acidosis
WATER DEFICIT

Diuretic
Diabetes Insipidus
Evaporasi

Plasma Plasma

Na+ = 140 mEq/L

Cl- = 102 mEq/L
SID = 38 mEq/L 140/1/2 = 280 mEq/L
102/1/2 = 204 mEq/L
1 litre SID = 76 mEq/L ½ litre

SID : 38  76 = alkalosis
CONTRACTION ALKALOSIS
SID Didorders
Cl- loss

Plasma

Na+ = 140 mEq/L

Cl- = 95 mEq/L
SID = 45 mEq/L
2 litre

SID  ALKALOSIS
HYPOCHLOREMIC ALKALOSIS
SID DISORDERS:
Cl- accumulation

Plasma

Na+ = 140 mEq/L

Cl- = 120 mEq/L
SID = 20 mEq/L 2 litre

SID  ACIDOSIS
HYPERCHLOREMIC ACIDOSIS
PLASMA + 0.9% NaCl

Plasma 0.9% NaCl

Na+ = 140 mEq/L Na+ = 154 mEq/L

Cl- = 102 mEq/L Cl- = 154 mEq/L
SID = 38 mEq/L 1 litre SID = 0 mEq/L 1 litre

SID : 38 
HYPERCHLOREMIC ACIDOSIS CAUSE by
0.9% NaCl

Plasma

= Na+ = (140+154)/2 mEq/L= 147 mEq/L

Cl- = (102+ 154)/2 mEq/L= 128 mEq/L

SID = 19 mEq/L 2 litre

SID : 19  Acidosis
PLASMA + LACTATE RINGER

Plasma lactate Ringer

Lactate
metabolisms

Cation+ = 137 mEq/L

Na+ = 140 mEq/L Cl- = 109 mEq/L
Cl- = 102 mEq/L Laktat- = 28 mEq/L
SID= 38 mEq/L 1 litre SID = 0 mEq/L 1 litre

SID : 38
 Plasma

= Na+ = (140+137)/2 mEq/L= 139 mEq/L

Cl- = (102+ 109)/2 mEq/L = 105 mEq/L
Laktat- (termetabolisme) = 0 mEq/L
2 litre
SID = 34 mEq/L

SID : 34
 NA-BICARBONATE in ACIDOSIS

Plasma;
Plasma + NaHCO3
hyperchloremic
acidosis

25 mEq
NaHCO3 HCO3
Na+ = 140 mEq/L Na+ = 165 mEq/L metabolisms
Cl- = 130 mEq/L Cl-= 130 mEq/L
SID =10 mEq/L 1.025 SID = 35 mEq/L
1 litre
litre

SID  : 10  35 :  Alkalosis, pH normal

[Atot] disorders:
Hypo/Hyperalbumin- atau P-

K K HCO3 SID K
HCO3 SID HCO3 SID

Alb
Alb Alb 

Na Na Acidosis Na Alkalosis
hyperprotein/ hypoalbumin/
Cl Cl
hyperposphate Clhypoposphate
mi mi

Normal Acidosis Alkalosis

UA = unmeasured Anion :
Laktate, acetoacetate

K K HCO3- SID 
HCO3- SID
Keto-

A- A-

Na+ Na+

Cl- Cl-
Lactic/Keto asidosis

Normal Ketosis
UA = unmeasured Anion :
SO4, PO4

K K HCO3- SID 
HCO3- SID
SO4--

A- A-

Na+ Na+

Cl- Cl-

Normal ESRD
 Clasification (Fencl et al)

ACIDOSIS ALKALOSIS

I. Respiratory  PCO2  PCO2

II. Nonrespiratory (metabolic)

1. Abnormal SID

a. Water excess/deficit  SID,  [Na+]  SID,  [Na+]

b. Imbalance of strong anions

i. Chloride excess/deficit  SID,  [Cl-]  SID,  [Cl-]

ii. Unidentified anion excess  SID,  [XA-]

2. Non-volatile acids

i. Serum albumin  [Alb]  [Alb]

ii. Inorganic phosphate  [Pi]  [Pi]

SID Physiology in
human body intravascular

SID gastric fluid

negative () ; acid H+ Na+ Na+
Cl SID plasma 
Cl- Cl- Cl- Na+
Alkalosis
Na Cl-

Cl-
Cl- Na+ Na+ Na+
Cl-
Pancreas
Bile
Na+ Na+ SID plasma -
Na+
Cl- Acidosis
Cl-
SID intestine fluid Na+
normal Cl- Jejunum
Cl- Cl- Cl-

Na+

Na+
Na+ SID plasma
Na+
normal
 Renal & Liver
Interaction on
pH Regulation
Boron & Boulpaep, Medical Physiology,ch 38, 2003.

NH4CL
 How the body regulated pH?

Anaerobic met SID /Atot

(shock, MODS), DM PCO2
pH 
Laktat- / keto- Acute
compensation
Chronic
compensation hyperventilation
SID CO2
SO4,PO4= retention

Amoniagenesis 
Renal failure NH4
Sintesis Alb <<
Cl

Hypochloremia
NH4Cl
Hypoalbuminemia

pH n
Kompensasi terhadap kronik hiperkarbi (PPOK)

pH normal
pH PCO2
Kompensasi kronik

SID
PPOK

NH4
Absorpsi Cl  
Cl

NH4Cl 
Hipokloremi
Hipoprotein
George, 2003
 REVIEW
PERBEDAAN HH dengan Stewart
• Air merupakan sumber [H+] yang jumlahnya
ditentukan oleh disosiasi dari air (Kw).
• Dikenal variabel dependent dan independent.
• Determinant pH: pCO2, SID, Atot.
• Perbedaan terutama pada gangguan
metabolik (asidosis hiperkloremik, asidosis
dilutional, alkalosis kontraksi, alkalosis
hipoalbuminemi).
REVIEW
PRINSIP DASAR
• Keberadaan ion H+ ditentukan oleh :
1. CO2 : diatur oleh sistem pernafasan.
2. Ion HCO3- : diatur oleh ginjal.
• Hubungan parameter tsb.(H+, CO2 dan HCO3-)
sebagai berikut:

[HCO3-]
Basa
pH = pK + log  pCO2
Asam
 Anion Gap
(Emmett & Narins)

Law of Electro-neutrality

UA
AG = [Na+K] – [Cl+ HCO3]
= A- + UA
A-

Measured
Cations Measured
Anions A- = weak acid (albumin, fosfat)
UA = unmeasured anion (unmeasured
Na strong anion seperti laktat, keton
HCO3-
K dan unmeasured non strong anion)
Cl
 Tapi:
Jika [A-] menurun  hipoalbumin, hipofosfatemia, AG bisa
normal pada lactic/ketoacidosis.

CORRECTED ANION GAP

Figge and Colleague

Calculated AG + 0,25 (42 – Albumin)

Kita masih menggunakan faktor dependen HCO3 dalam perhitungan, sehingga

pendekatan AG tetap akan underestimated pada keadaan gangguan
metabolik !!
 Hubungan antara SID, AG dan SIG
• Law of electro‐neutrality:

• (Na+ + K+ + Ca2+ + Mg2+) – (Cl− + lactate + other strong anions) – (HCO3− + A−) = 0
SIDa SIDe

• AG = Semua kation – Cl- - HCO3-

• SIG = SIDa – SIDe (normal = 0).
 Normal
 
AG AG = 10-15

Na HCO-3 25

145
K Cl 105

Metabolic acidosis
HCO3- 
Normal anion gap acidosis Increased anion gap acidosis
AG = 15 (normal) AG/
HCO-3 15 Other = 25 
Na Na anion
HCO-3 15
145 145
K Cl K
115  105
Cl (normal)

HCO3- decreases and replaced by Cl- so HCO3- decreases and replaced by anions
there is a Cl- shift :Eg. Diarrhea or simple other than Cl- so no Cl- shift: Eg.renal failure
gain of H+ and diabetic keto-acidosis
 STRONG ION GAP
Kellum JA, Kramer DJ, Pinsky MR: Strong ion gap: A methodology for exploring
unexplained anions. J Crit Care 1995,10:51--55.
SIG
Mg++
Ca++

K+ 4
SIDa HCO3-
A-
SIDe
Lactate

= [Na+] + [K+] + [Mg++] + [Ca++] - [Cl-] – [Lactate-]

+ Cl-
Na
= 12.2×pCO2/(10-pH )+10×[alb]×(0.123×pH–0.631) +[PO4–]×(0.309×pH–0.

SIG = SIDa – SIDe  Normal value = zero

Jika SIG >  terdapat UA
KATION ANION
Perbedaan dgn AG  pd SIG, nilai albumin ikut dalam kalkulasi
 Modified Fencl-Stewart
(menilai asam basa bed-side)

UA = BE – SID effect – Albumin effect

– SID effect = [Na-Cl]-38

– Albumin effect = 0,25 X (42-albumin)
– If UA (+)  Kation excess
– If (-)  Anion excess
Membaca Hasil AGD II

Erwin Pradian
Strong ions, weak acids and base excess:
a simplified Fencl–Stewart approach to
clinical acid–base disorders
Story, Morimatsu, Bellomo (2004), British Journal of Anaesthesia. Vol. 92,

• SBE = from a blood gas machine =…

• Na–Cl effect = [Na+]–[Cl–]–38 =...
• Albumin effect = 0.25 x [42–Alb(g/l)] =…
• UA = SBE –(Na–Cl)effect – Albumin effect =…
 Kasus 1
• Seorang pria 54 th, post operasi Craniotomi
tumor selama 8 jam. Op selesai jam 11 pm.
• Kesadaran: GCS 10 BP 135/60 HR 84 RR 18
dengan T-piece 5 L/mnt SpO2 99% .
Pasien kemudian disedasi dan masuk ICU.
 Kasus 1:

7.25 / 30 / -10 / 14
Na 140; Cl 112; Alb 4.0

• SBE = from a blood gas machine =…

• Na–Cl effect = [Na+]–[Cl–]–38 =...
• Albumin effect = 0.25 x [42–Alb(g/l)] =…
• UA = SBE –(Na–Cl)effect – Albumin effect =…

• SBE = -10
• Na–Cl effect = [Na+]–[Cl–]–38 = 140–112–38 = -10
• Albumin effect = 0.25 x [42–40(g/l)] = 0.5
• UA = -10 – (-10) – 0.5 = -0.5
BASE EXCESS DAN STEWART

150 7.25 / 30 / -10 / 14

140
HCO3-
Alb
112
BE akibat pe Cl-  -10
Alb
102

WD/: Asidosis metabolik karena hiperkloremia

Causal: - Pemberian Lar NaCl berlebihan
- Th/: Batasi NaCl
- Terapi diuretik
Na+ Cl-
 Kasus 2
Seorang wanita G1P0A0 30 th kehamilan 12 minggu
mengeluh muntah-muntah sejak 3 hari yang lalu.
KU = CM, lemah BP 90/50 HR 104 RR 10 S= normal
Datang ke IGD dan kemudian dirawat di ruang
OBGYN.
 Kasus 2:

7.48 / 50 / + 9 / 34
Na 140; Cl 93; Alb 4.2

• SBE = from a blood gas machine =…

• Na–Cl effect = [Na+]–[Cl–]–38 =...
• Albumin effect = 0.25 x [42–Alb(g/l)] =…
• UA = SBE –(Na–Cl)effect – Albumin effect =…

• SBE = +9
• Na–Cl effect = [Na+]–[Cl–]–38 = 140–93–38 = 9
• Albumin effect = 0.25 x [42–42(g/l)] = 0
• UA = 9 – 9 – 0 = 0
BASE EXCESS DAN STEWART
7.48 / 45 / + 9 / 34

140

HCO3-
BE akibat  Cl-  +9 Alb

Alb

WD/: Alkalosis metabolik karena hipokloremia

Causal:
- Muntah
Th: NaCl 0.9%

Na+ Cl-
 Kasus 3
Seorang pria 62 tahun post operasi TURP.
Pasien mengalami keluhan sakit kepala, nafas agak
berat.
Kesadaran CM, lemah BP 180/100 HR 100 RR 32
SpO2 99% dengan simple mask 6 L/mnt
 Kasus 3:

7.30 / 27 / -7 / 18
Na 128; Cl 100; Alb 3.0

• SBE = from a blood gas machine =…

• Na–Cl effect = [Na+]–[Cl–]–38 =...
• Albumin effect = 0.25 x [42–Alb(g/l)] =…
• UA = SBE –(Na–Cl)effect – Albumin effect =…

• SBE = -7
• Na–Cl effect = [Na+]–[Cl–]–38 = 128–100–38 = -10
• Albumin effect = 0.25 x [42–30(g/l)] = 3
• UA = -7 + 10 – 3 = 0
BASE EXCESS DAN STEWART
7.30 / 27 / -7 / 18

140

128
Alb

BE akibat  Na  -7

WD/: Acidosis metabolik karena hiponatremia

Causal:
- hemodilusi

Na+ Cl-
 Kasus 4
Seorang wanita 45 tahun dengan tumor ganas
ovarium. Post operatif debulking. Perdarahan 3L
Kesadaran= Somnolent BP 90/45 HR 112 RR 30 S
36,5
SpO2 96% dengan simple mask 6 L/mnt
 Kasus 4 :

7.42 / 35 / 100 / -2 / 21 ;

Na 140; Cl 102; Alb 1.8

• SBE = from a blood gas machine =…

• Na–Cl effect = [Na+]–[Cl–]–38 =...
• Albumin effect = 0.25 x [42–Alb(g/l)] =…
• UA = SBE –(Na–Cl)effect – Albumin effect =…

• SBE = -2
• Na–Cl effect = [Na+]–[Cl–]–38 = 140–102–38 = 0
• Albumin effect = 0.25 x [42–18(g/l)] = 6
• UA = -2 – 0 – 6 = -8
BASE EXCESS DAN STEWART
7.42 / 35 / 100 / -2 / 21

140 -
HCO
HCO3-
3
SID  normal
24 22 -
BE astrup = - 8 + 6 = - 2 HCO3
30.7
UA = - 8 BE akibat lact  - 8
BE akibat hipoalb  + 6 Alb
hipoalbumin
102

Lactic Asidosis metabolik “masking” oleh hipoalbumin

Na+ Cl-