ACID-BASE BALANCE;

EFFECT OF FLUID AND NUTRITION

“A Stewart Approach”

Yohanes WH George
 Peter A.
Stewart.
• This approach is … more
HOW TO UNDERSTAND fundamentally correct
ACID-BASE than the conventional …
A quantitative Acid-Base Primer and it provides insight
For Biology and Medicine
into biological
Peter A. Stewart mechanisms.’
• ‘Anyone who studies acid-
Edward Arnold, London 1981 base physiology should
become familiar with this
approach’.
TRADITIONAL APPROACH

Hendersen-Hasselbalch (H-H)

pH = pK x Log [HCO3-/(0.03 x pCO2)]

RELATIONS
QUANTITATIVE METHOD OF STEWART

CAUSAL -
MECHANISM
The impact of Stewart analysis has been slow in
coming but there has been a recent resurgence
in interest, particularly as this approach
provides explanations for several areas which
are otherwise difficult to understand

– Dilutional acidosis
– Acid-base disorders related to changes
in plasma albumin concentration
 TERM AND CONCEPTS

Solutions as a system :

“….it is a general property of system that

the quantitative results of several
interacting but independent mechanisms
cannot be explained or understood solely in
terms of the action of any single one of
these mechanisms”.

(Stewart 1983, p144-

5)
 GENERAL PRICIPLES

Electrical neutrality:
All the solutions are electrically neutral, that
is, the total concentration of cations equals
the total concentration of anions
Conservation of mass:
The amounts of the major components (water,
electrolytes, metabolites, etc) remain
constant unless these are added or removed
from outside or created or destroyed by
chemical reaction
 Biochemistry of Aqueous
Solutions

• All solutions in human biology contain

water and aqueous solution. Provide a
virtually inexhaustible source of [H+]

• [H+] is determined by the dissociation of

water (Kw) into H+ and OH- ions.
 H2O ⇔ H+ + OH-

Changes in H+ occur not as a result of how

much H+ is added or removed, but as a
consequence of water dissociation….
Stewart: A formula for the calculation of the
equilibrium value of a [H+]
is
complex
BUT

easy and quick using

computer
 DETERMINANTS OF [H+] IN
BIOLOGICAL SOLUTION

Two types of variables

Dependent Independent
variables variables
Dependent variables
have values which are determined internally by the
system. They are determined by the equations
which determine the system and can be altered only
by changes in the values of the independent
variables.

Independent variables
have values which are determined by processes or
conditions which are external to the system; they
are imposed on the system rather than being
determined by it.
INDEPENDENT VARIABLES DEPENDENT VARIABLES

Strong Ions
Difference
H+
PHYSICOCHEMICAL HCO3-
Rx OH-
pCO2 tCO2
CONSERVATION of
MASS A-
ELECTRONEUTRALITY
CO3=

Protein
Concentration
DETERMINANTS OF BLOOD
pH

ISF,RBC &
PLASMA

Liver
 Why is this concept of dependent
and independent variables so
important?
• The reason is that the values of all dependent
variables are determined by and can be calculated
from the values of independent variables.

• In body fluids, [H+] is a dependent variables,

therefore can be calculated if the values of the
independent variables are known.
BASIC IDEA…
 PHYSIOLOGY…..

Two substances A and B reversibly combining to

form substance C, and when the reaction is at
equilibrium the equation governing the
equilibrium is:

[A] x [B] = K x [C]

K is the rate constant for reaction

Neutral, acidic and basic solutions are
defined with refference to the value of
square root of Kw
– Neutral : [H+] = sq rt Kw = [OH-]
– Acidic : [H+] > sq rt Kw > [OH-]
– Basic : [H+] < sq rt Kw < [OH-]
• Acid:
any substance which, when added to an
aqueous sol, will cause increase in [H+]

• Base:
any substance which, when added to an
aqueous sol, will cause decrease in [H+]
• Strong ions/electrolyte:
substance that exist as essentially
completely dissociated in aqueous
solution,

 KA > 10–4 Eq/L

- Na+, Cl-, K+, Ca+2, SO4-2 (Inorganik)

- Lactate – (Organik),
 CHEMICAL EQUILIBRIUM

100
80
70
% Ionized

-
3
O
60

in
tat

HC

um
50 Lac pK

Alb
⇔
40

2
CO
30
20
10

2 3 4 5 6 7 8 9

pH
Whether an ion is “strong” or “weak” depends on its pK (i.e., the pH at which half of
the substance is ionized, the other half not). The pK of Lactate is 3.9 (i.e, more than
99% of it is ionized at pH greater than 6). Carbonic acid and albumin are weak acids
because substantial portions of them are neutral in the physiologic range, requiring
that their ionized concentrations be computed.
• Weak ions/electrolyte:
substance that are only partially
dissociated in aqueous solution,

 KA between 10–4 and 10-12 Eq/L

Carbon dioxide (volatile)  bicarb

system
Weak acids  Albumin & Pi (non-
volatile)
Strong and weak
ions
gamblegram for plasma

HCO3-
100% Alb-
Ca++
80% Mg+
UA-
60% H+
lactate-
40%
K+
Cl-
20%
Na+
0%
cations anions
DETERMINED [H+] IN A SPECIFIC SITUATIONS
 1. PURE WATER

Characteristic of water;
• Strongly ionic substances dissociate when placed
in water
• Water it self dissociates, but only a little
• Water containts a lot of water
Molecular weight are small (18) but…
Molar concentration is >> (55.3 mol/l at 370C)
Water dissociates as follow;

H2O  H+ + OH-
Very rapid reaction, equilibrium is reached instantaneously in
biological solution

At equilibrium

[H+].[OH-] = Kw.[H2O]
Kw is very small, 4.3 x 10-16 Eq/l at 370C and temperature
dependent, e.g at 250C is 1.8 x 10-16Eq/l
A new constant

Kw’ = Kw x [H2O]

Kw’ is product of the two constant;

- Kw and
- The molar concentration of water

Let’s find the pH of pure water…

 [H+] x [OH-] = Kw’
If we know the Kw’, we still need to find one of the other
variables, [OH-]

Electroneutrality;
[H+] – [OH-] = 0
[H+] = [OH-]
 [H+] = √ Kw’
if [H+] = √ Kw’ (neutral)
if [H+] > √ Kw’ (acidic)
if [H+] < √ Kw’ (basic)
2. STRONG ELECTROLYTES IN PURE
WATER
Water dissociation;
[H+] x [OH-] = Kw’ …equation 0
SID = STRONG IONS DIFFERENCE

Electroneutrality;
[H+] - [OH-] + [Na+] - [Cl-] = 0 …equation #1
Substitute Kw’/[H+] for [OH-]
[H+] – Kw’/[H+] + [Na+] – [Cl-] = 0
[H+]2 + [H+]([Na+] – [Cl-]) – Kw’ = 0
Quadratic equation a.x2 + b.x + c = 0
[H+] = - ([Na+] – [Cl-])/2 + {([Na+] – [Cl-])2/4 + Kw’}
• And solving for [H+]

[H+] = √ Kw’ + SID2/4 – SID/2 …equation #2

[OH-] = √ Kw’ + SID2/4 + SID/2 …equation #3

In these solution it is clear that if the hydrogen ion

concentration changes 
the SID must have changed
• If SID is positive and bigger than 10–6 Eq/l
we can see that Kw becomes insignificant,
and equation #3 becomes very nearly the
same as:
[OH-] = [SID]

• We can use this equation and equation #0

to derive the hydrogen ion concentration:

[H+] = Kw’/[SID]
• If the SID is negative and bigger
than about 10–6 Eq/liter then equation
#2 simplifies out to:

[H+] = - [SID]

But such solutions are not commonly

encountered in biological systems
SKETCH; RELATIONSHIP BETWEEN SID,H+
AND OH-

[H+] [OH+]

(–) SI (+)
D
In biological solutions at 370C, the SID nearly
always positive, usually around 40 mEq/Liter
 3. ADDING A WEAK
ELECTROLYTE

• A more complex setup – Adding a weak

electrolyte
• A weak electrolyte, [Atot ]:
– One that partially dissociated in the pH range
– The most important in plasma is albumin
– Represents the total amount of weak
electrolytes produced by biochemical reactions
within the body, or represents the total
amount of available “buffer” in body.
• Weak Acids:
– HA (such as albumin) dissociates to form H+
and A-, as follow:
HA  H+ + A-
Combined with two equation and the term of
electroneutrality
[H+] x [OH-] = Kw’ … eq#0
[H+] + [OH-] + [SID] + [A-] = 0 … eq#1A
Dissociation of acids and conservation of
mass;
[H+] x [A-] = KA x [HA] …eq #4
[HA] + [A-] = [ATot ] …eq #5
• Identify the independent variables (Kw’,[SID],[ATot ]
and KA) and dependent one ([H+],[OH-],[HA] and [A-]

• Eliminate all dependent variables apart from [H+]

from the equation by substitution:

[OH-] = Kw’/[H+] …from eq #0

[HA] = [ATot ] – [A-] …from eq #5

And substituting eq#5 into eq#4

[A-] = Ka x [ATot ] /([H+] + KA)

Substitute these values into equation #1A, and get;

[SID]+[H+]-Kw’/[H+]–KA[ATot ]/(KA+[H+]) =0… eq #6

Use a computer programe to find the [H+]

IT’S EASY AND QUICK !!!

 4. STRONG IONS WITH CO2

• Take a mixture of strong ions and water, and

expose it to CO2

• What happen to CO2 gas when exposed to water

– Dissolved
– React with water to form carbonic acid
– Bicarbonate or
– Carbonate ions
a. CO2 can dissolved:

CO2(gas) ⇔ CO2(dissolved)

Equilibrium:

[CO2dissolved ] = SCO x PCO

2 2 …equation #7A

SCO 2 = Solubility of CO2, 3.0 x 10–5 Eq/l/mmHg at 370C

b. Can react with water;

CO2 + H2O ⇔ H2CO3

Equilibrium;
[CO2 dissolved] x [H2O] = K x [H2CO3]…equation #7B
If [H2O] constant;

[H2CO3] = KH x PCO2
KH at 370C is 9 x 10–8 Eq/l
c. H2CO3 dissociate;
H2CO3 ⇔ H+ + HCO3-

• Equilibrium;

[H+] x [HCO3-] = K x [H2CO3]

[H+] x [HCO3-] = KC x PCO2 …equation #8

KC is 2.6 x 10–11 Eq/l2/mmHg

d. HCO3- rapidly dissociate:
HCO3- ⇔ H+ + CO3–2

• Equilibrium;

[H+] x [CO3–2] = K3 x [HCO3-] …equation #9

K3 is 6 x 10–11 Eq/l

K3 is 6 x 10 –11 Eq/l
 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-]

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

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

In these solution it is clear that if the hydrogen or

bicarbonate ion concentration changes

the SID,ATot and pCO2 must have changed

 The practical significance of all this
maths
If we want to calculate the pH, we must:
1. Know the concentrations of the
strong ions, and
2. Plug these value into equations;

Note:
If you add basic or acidic substance, you cannot just
say” We added so much hydroxide so the pH will
change by so much.”

You have to work things out using the equations.

BLOOD PLASMA

H+

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

Mg++
Ca++

Cl-

CATION ANION
USING STEWART FOR
CLINICAL GAIN
 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]

 RESPIRATORY
SIMILAR WITH H-H…

PCO2  Ph

PCO2  Ph
METABOLIC

• SID
• WEAK ACID
 SID
• CHANGING THE WATER CONTENT OF PLASMA
(CONTRACTION ALKALOSIS AND DILUTIONAL
ACIDOSIS

• CHANGING THE Cl- (HYPERCHLOREMIC

ACIDOSIS AND HYPOCHLOREMIC ALKALOSIS)

• INCREASING THE CONCENTRATION OF

UNIDENTIFIED ANIONS (ORGANIC ACIDOSIS)
 DILUTIONAL ACIDOSIS
NaCl + H2O  Na+ + Cl- + H+ + OH- + H2O

H2O

Na+ = 70 mEq/L
2 liter
1 liter Cl- = 55 mEq/L
Na+ = 140 mEq/L
Cl- = 110 mEq/L SID = 15 mEq/L
SID = 30 mEq/L OH- = 15 mEq/L
OH- = 30 mEq/L
 PLASMA PLUS NORMAL SALINE

Na+ = 154 mEq/L

2 liter
Na+ = 140 mEq/L Cl- = 154 mEq/L
Cl- = 110 mEq/L SID = 0 mEq/L
SID = 30 mEq/L OH- = 0 mEq/L
OH- = 30 mEq/L
1 liter
HYPERCHLOREMIC ACIDOSIS RESULTING FROM
NORMAL SALINE

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

Cl- = (110+ 154)/2 mEq/L= 132 mEq/L 2 liter
SID = 15 mEq/L
OH- = 15 mEq/L
PLASMA PLUS RINGER’S LACTATE SOLUTION

Cation+ = 137 mEq/L 2 liter

Cl- = 109 mEq/L
Na+ = 140 mEq/L Lactate = 28 mEq/L
Cl- = 110 mEq/L SID = 0 mEq/L
SID = 30 mEq/L OH- = 0 mEq/L
OH- = 30 mEq/L
1 liter
NORMAL ACID-BASE STATE FOLLOWING
RINGER’S LACTATE

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

Cl- = (110+ 109)/2 mEq/L= 110 mEq/L
2 liter
SID = 29 mEq/L
OH- = 29 mEq/L
 CONTRACTION ALKALOSIS

Na+ = 140 mEq/L

Cl- = 110 mEq/L 1 liter Na+ = 280 mEq/L ½ liter
SID = 30 mEq/L Cl- = 220 mEq/L
OH- = 30 mEq/L SID = 60 mEq/L
OH- = 60 mEq/L
HYPOCHLOREMIC ALKALOSIS

Na+ = 140 mEq/L 2 liter

Cl- = 95 mEq/L
SID = 45 mEq/L
OH- = 45 mEq/L
HYPERCHLOREMIC ACIDOSIS

Na+ = 140 mEq/L 2 liter

Cl- = 120 mEq/L
SID = 20 mEq/L
OH- = 20 mEq/L
CLINICAL STUDIES
 Hyperchloremic Acidosis

Kellum JA, Bellomo R, Kramer DJ, Pinsky MR: Etiology

of Metabolic Acidosis During Saline Resuscitation
in Endotoxemia. Shock 1998, 9: 364--368.

Experimental evidence of the effect of saline

resuscitation on acid-base parameters in an endotoxic
animal model.
Scheingraber S, Rehm M, Sehmisch C, Finsterer U:
Rapid saline infusion produces hyperchloremic
acidosis in patients undergoing gynecologic
surgery. Anesthesiology 1999, 90:1265--1270.

Waters JH, Miller LR, Clack S, Kim JV. Cause of

metabolic acidosis in prolonged surgery. Crit Care
Med. 1999; 27:2142-6.

A clinical study detailing the acidosis associated with

saline vs. no change in pH with lactated Ringer’s
solution in patient undergoing major abdominal/pelvic
surgery.
Liskaser FJ, Bellomo R, Hayhoe M, et al: Role of Pump
Prime in the Etiology and Pathogenesis of
Cardiopulmonary Bypass-associated Acidosis.
Anesthesiology 2000; 93:1170-1173

Rehm M, Orth V, Scheingraber S, et al: Acid-Base

Changes Caused by 5% Albumin versus 6%
Hydroxyethyl Starch Solution in Patients Undergoing
Acute Normovolemic Hemodilution: A Randomized
Prospective Study. Anesthesiology 2000; 93:1174-1183

Waters JH, Bernstein CA: Dilutional Acidosis following

Hetastarch or Albumin in Healthy Volunteers.
Anesthesiology 2000; 93:1184-1187
These three studies published in the November, 2000 issue of the
journal Anesthesiology provide conclusive evidence that the Chloride
content of volume expanding solutions determines the degree of
acidosis.

In the study by Lisaker, two types of pump-priming solutions for

cardiopulmonary bypass are compared. A hyperchloremic solution and
a solution with acetate and gluconate as metabolizable anions are
used. As predicted, both cause an acute acidosis but with the
acetate/gluconate solution, it resolves quickly while the
hyperchloremic solution causes a persistent hyperchloremic
acidosis.

The next two studies found that normovolumic hemodilution with HES
or Albumin in saline (Rhem et al.) produced similar amounts of acidosis
while Albumin in a normo-chloremic solution (Waters et al.)
produced no acidosis at all.
 Weak Acids (ATOT )

Jabor A. Kazda A: Modeling of acid-base

equilibria. Acta Anaesth Scand 1995, 39: Suppl
107:119--122.

Classification of acid-base disorders remains

controversial. These authors argue for the use of
three types of disorders based on the three
independent variables identified by Stewart.
However, there is little evidence that this approach to
classification is logical or helpful.
Figge J, Jabor A, Kazda A, Fencl V: Anion gap and
hypoalbuminemia. Crit Care Med. 1998, 26:1807--10.

These authors demonstrate how the anion gap must

be corrected for changes in albumin concentration.
Patients with severe disorders of phosphate will
require additional correction not detailed by the
authors but available in this review.
Wilkes P: Hypoproteinemia, strong ion difference,
and acid-base status in critically ill patients. J Appl
Physiol 1998, 84:1740--1748.

This excellent observational study details the changes

in strong ion difference as a function of changes in ATOT.
The study provides convincing evidence that the
normal physiologic response to hypoalbuminemia is to
reduce the strong ion difference, principally by
increasing the plasma chloride concentration.
Fencl V and Rossing TH.
Acid-base disorders in Critical Care Medicine

 ‘In critically ill patients, nonrespiratory (metabolic)

alkalosis is the most common acid-base disturbance:
it is caused by hypochloraemia and/ or by
hypoproteinaemia.
 Information on the concentration of plasma proteins
should be included when evaluating acid-base
status.’ Their in vitro experiments on effect of plasma
protein concentration on base excess or anion gap
summarised.
Fencl V and Leith DE
Stewart’s quantitative acid-base chemistry…

 Includes [Ca++] and [Mg++] as strong cations in the SID

formulae. Gives formulae for estimation of anionic
equivalence of albumin (Prx-) and inorganic
phosphates (Piy-) from their measured concentrations
and the pH of the sample.
 SID apparent = Na + K + Ca + Mg - Cl
 SID effective approx= Bicarbonate + Prx- + Piy-
 Unidentified anions [XA-] = SIDapp – SIDeff
Fencl V, Jobor A, Kazda A and Figge J.
Diagnosis of metabolic acid base disturbances in
critically-ill patients.

Compares anion gap and base excess approaches

with Fencl & Leith’s quantitative formulae. ‘The third
approach … allows one to detect and quantify even
the most complex acid-base disturbances seen in
critically-ill patients. All the calculations can be done
at the bedside with a simple hand-held calculator.’
Gilfix BM, Bique M and Magder S.
A physical chemical approach to the analysis of
acid base balance in the clinical setting.
 A different approach, examines the
contributions to net base excess status of
 Free water

0.3 x (Na-140)
 Chloride effect

102-(Cl x 140/Na)
 Albumin effect
 (0.148 x pH-0.818)(42-[alb])
 Other species (gap between net base excess and
sum of three above)
Balasubramanian N, Havens PL and Hoffman GM.
Unmeasured anions identified by the Fencl-Stewart method predict
mortality better than base excess, anion gap and lactate in patients in
the pediatric intensive care unit

Confusing because the formulae are essentially those

of Gilfix et al rather than those of Fencl and Leith.
- Base excess due to free water effect
- Base excess due to chloride
- Base Excess due to albumin
= (simplified to) 0.34 x (45-alb)
- Base Excess due to unmeasured anions
= BE - (BEfw + BECl + BEalb)
Story DA, Bellomo R. Hendersen-Hasselbach vs
Stewart: Another Acid-Base Controversy; Review
Article, Crit Care & Shock (2002)2:59-63
• Stewart and Base-excess
– BE from the Blood Gas Machine
– SID effect, mEq/l = A + B
• A. Free Water effect on Na+
= 0.3 x ([Na+] – 140)
• B. Corrected Cl- effect
= 102 – ([Cl-] x 140/[Na+])
– Total weak acids effect, mEq/l
= 0.123 x pH - 0.6310 x (42 - [Albumin])
– UA effect = BE ef – SID ef – ATot ef
 Case study
• pH 7.39 BE effects (mEq/l):
• CO2 (mmHg) 36 SBE -3.1
• Sodium (mEq/l) 139 Free Water ef -0.3
• Chloride (mEq/l) 105 Corrected Cl- ef -3.8
• Anion Gap (mEq/l) 17.0 Albumin ef 8.8
• Albumin (g/l) 18 Unmeasured Anion ef -7.9

1. H-H : Metabolic acidosis but normal anion gap  No important UA

2. Stewart: Profound alkalinizing effect of low plasma albumin  a
substantial effect of UA
⇒ This patient had an elevated Plasma Phosphate –5 mEq/l
SHOW

Inadequacy of the H-H approach

INTERACTION BETWEEN
MEMBRANE
Body fluids

other

RBC PROTEIN

Plasma Interstitial Intracellular

 ISF=13.5
L Na +

ICF Lymph
Cl-
CO2

Na+ CO2
Cl-
Blood dCO
2
Alb
pH
pCO ATot
Cl- 2

LIVER
Synthesis
 Lactic acidosis
DISTURBANCE
Vomiting Keto-acidosis
Diare
Renal Failure

SID
Heart Failure
Charge Balance
[H+]
Dissociation of:
PCO2 [HCO3-]
Water
Lung disease Etc.
Protein
Hyperventilation
Hypoventilation
Carbonic acid
Plasma
Protein

Nephrotic Syndrome
Dehydration
Malnutrition
THANK YOU