G ABOUT FLUID

EASY WAY

STEWART
TO UNDERSTAND
STEWART’S
ACID-BASE

APPROAC
OUT FLUID IN
TEWART’S
FROM “SALINE” TO MORE
“PHYSIOLOGIC” FLUID

Yohanes WH George, MD

PPROACH
THINKING A
G ABOUT FLUID
EASY WAY TO UNDERSTAND
STEWART’S ACID-BASE

Yohanes WH George, MD
EASY WAY TO UNDERSTAND STEWART’S ACID-BASE

NOTICE
Medicine is an everchanging field. Because of new research and clinical experience

broaden our knowledge, changes in treatment and drug therapy may become necessary

or appropriate, Readers are advised to check the most current product information

provided by the manufacturer of each drug to be administered to verify the recommended

standard of administration. It is the responsibility of the licensed prescriber, relying on

experience and knowledge of the patient, to determine the best treatment of each

individual patient. Neither the publisher nor the author assume any liability for any injury

and/or damage to persons or property arising from this publication.

All right reserved. No part of this publication may be reproduced or transmitted in any form or

by any means, electronic or mechanical; without permission in writing to the author or publisher.

Copyright © 2015 Centra Communciations

i
 Contents
Dedication .......................................................................................... iv
Foreword ............................................................................................ vi
Preface ............................................................................................... x

Stewart’s Approach in Brief ................................................................. 2

Strong Ion Difference ........................................................................... 3

Classification of Primary Acid Base Disturbances ................................ 9

The Effect of Saline and Balanced Fluid from Stewart’s Perspective .... 12
Designing Balanced Crystalloids ......................................................... 15

Body pH Regulation: Interaction Between Membranes ........................ 17

Strong Ion Difference in Kidney ............................................................ 20

Compensation ..................................................................................... 21

Clinical application ............................................................................... 23

Conclusions ........................................................................................ 31

References .......................................................................................... 32

ii
EASY WAY TO UNDERSTAND STEWART’S ACID-BASE

iii
Dedication

To my great teacher and mentor;

In memoriam

DR. Iqbal Mustafa, MD. FCCM

The pioneer of the modern critical care medicine in Indonesia,
Head of Intensive Care Unit Harapan Kita Hospital (1992-2004),
Jakarta- Indonesia

iv
EASY WAY TO UNDERSTAND STEWART’S ACID-BASE

To my parents: Rijklof George and Yuliana Bororing, and

my brother and sister: Ivan and Rina,
for teaching me through unforgettable life experiences

To my wife; Sari Mumpuni,

for always being there for me, supporting me through ups and downs

To my team in Emergency and Intensive Care Unit Pondok Indah Hospital and to
my colleagues and fellows in Jakarta Critical Care Alumni,
for providing me great suggestions and support to finish this handbook

To my great team, Staff Department of Anesthesiology and Intensive Therapy:

for giving me spirit and tremendous support

v
Foreword
The title of this monograph tells us everything!
Sometimes physiology (better, physiopathology) is thought to be very difficult.
Sometimes Physicians prefer to treat patients without understanding what is going
on. Sometimes Physicians realize that patientsneed fluids (which is good!) but the
quality of fluids administered is felt not so relevant (which is bad!). Fluids must be
regarded as a drug and, like every drug, can have positive or harmful effects. Dr
George wrote this book with the aim of making clear part of the human physiology
that is considered difficult to understand – the Stewart’s approach to acid-base
disorders; and what this approach teaches us in using the correct quality of fluids.
Iwill always remember the beautiful days spent in Indonesia with great friends
talking about the clinical role played by the hypercloremic acidosis, one of the most
relevant side effects of fluids therapy based on normal saline administration. I hope
that this fantastic book is born in one of the very hot evening (at least for me) when
we shared our ideas on the role played by fluids therapy. I will never forget that time
of my life and the enthusiasm creates by those meeting. Looking back to those days
I realize that this book isvery special for me.
I hope that it will guide the future generations in the difficult field of fluids therapy.
I always asked me if medicine is an art or science. Probably medicine is both;
but let me guess that books like this can help in making medicine an art based on
science.

Prof . Carlo Alberto Volta

Section of Anaesthesia and Intensive Care Medicine
University of Ferrara
S. Anna Hospital
Ferrara, Italy

vi
EASY WAY TO UNDERSTAND STEWART’S ACID-BASE

Foreword
Although often strangely neglected, Acid-Base equilibrium constitutes most
of the background of organ physiology and cellular biology of human beings.
Nonetheless, it’s complex. Many are the aspects we still need to elucidate and to
unveil. As such, in contrast to other parts of human physiology, we usually apply
interpretational models to describe how Acid-Base equilibrium is preserved. The
1912 Nobel Medicine Prize recipient Alexis Carrel, in his Reflections on Life (1952,
London: Hamish Hamilton) states that “a few observations and much reasoning
lead to error; many observations and a little reasoning to truth”, highlighting the
primacy of “reality and facts” over our pre-defined interpretations. I believe that such
statement may well describe the interpretational model to Acid-Base that Peter
Stewart has defined in the late ‘70s, starting from a quantitative chemical approach,
and taking into account two aspects intrinsically related to this topic (although
frequently omitted), i.e., electrolytes and plasma proteins. The remarkable results
of his approach are before our eyes. As very elegantly highlighted by Dr. George
in his Handbook, one of the most relevant example for our daily-life of physicians,
especially dealing with critically ill patients, is the understanding of the effects of fluid
therapy on Acid-Base. It is not a matter of “being right or wrong”, but rather of fully
elucidating what we are facing every days with our patients.
Dr. George has the great merit of having brought at bedside, in our clinical daily
practice, Stewart’s theories on Acid-Base equilibrium in a more comprehensible and
easy way, so to open wide our mind to its real comprehension. Let us hope to stick
on reality, rather than on our preconceptions.

Pietro Caironi, MD
Associate Professor, Faculty of Medicine
Department of Pathophysiology and Transplantation
Fondazione IRCCS Ca’ Granda – Ospedale Maggiore Policlinico
Milan, Italy

vii
Foreword
Stewart is easy! However, this continues to be challenged by many. Especially
by those that have been trained according to the legacy approaches, including
bicarbonate based and base excess methods. In order to truly appreciate the
potential of quantitative acid base analysis, one needs to temporarily forget the
other approaches. This requires courage.
Therefore, I applaud the effort of dr. Yohannes, who has produced an excellent
introductory handbook to the Stewart approach. This will be of great help to those
wanting to explore the secrets of acid base medicine!

Paul WG Elbers, MD, PhD

Intensivist
VU University Medical Center
Amsterdam, The Netherlands

viii
EASY WAY TO UNDERSTAND STEWART’S ACID-BASE

Foreword
In critical care and anesthesia medicine, fluid administration is a key element
of resuscitation. Currently, there are still controversies regarding fluid resuscitation
strategies, both on ‘balanced fluid’ strategy, known as ‘goal-directed therapy’, and
from ‘fluid option’ point of view, which is about fluid type selection. In terms of
‘fluid option’, controversial debate about crystalloid and colloid has lasted for a
long time and is no more a special concern. Selection of resuscitation fluids based
on their effects on acid-base balance of the body is currently a particular concern.
Evidences suggest that saline use in fluid resuscitation causes hyperchloremic
acidosis, therefore nonsaline-based fluid, also known as ‘balanced fluid’, is currently
invented to avoid acidosis effect.
The mechanism of acidosis following saline administration is based on acid-
base balance method by Stewart, that is also called quantitative method or
physicochemical approach. Unfortunately, this theory is not widely understood
despite the fact that it has been known for quite some time (since 1978) and is being
accepted slowly in critical care and anesthesia medicine, which is partly caused by
its complexity and being not easily understood.
The Department of Anesthesia of RSCM - FKUI finds that this handbook of
“EASY WAY TO UNDERSTAND STEWART’S ACID-BASE” is very useful and it will
hopefully simplify the understanding of acid-base balance disturbance mechanism
based on Stewart’s method for doctors, especially anesthesiologists and doctors
who work in emergency departments and critical care units, which will eventually
improve the safety and quality of resuscitation fluids selection. We send our special
thanks to dr. Yohanes WH George who made this handbook schematic, practical
and easy to understand.

Aries Perdana, MD.

Head of Department of Anesthesiology and Intensive Care Unit 
Cipto Mangunkusumo Hospital, Medical Faculty, University of Indonesia

ix
Preface

Understanding the chemistry of water and hydrogen ions is an important part

of understanding the living system because hydrogen ions participate in so many
reactions. One interesting facet of human homeostasis is the tight control of hydrogen
ion concentration, [H+]. As metabolism creates about 300 liters of carbon dioxide
each day, and as we also consume about several hundred mEq of strong acids
and bases in the same period, it is remarkable that the biochemical and feedback
mechanism can maintain [H+] between 30 and 150 nanoEq/liter.
Appreciation of the physics and chemistry involved in the regulatory process is
essential for all life scientists, especially physiologists. Many physiology textbooks
start the discussion of acid-base equilibrium by defining pH , which immediately
followed by the Henderson-Hasselbalch equation.
Attention has recently shifted to a quantitative physicochemical approach to acid-
base physiology. Many of the generally accepted concepts of hydrogen ion behaviour
are viewed differently. This analysis, introduced by Peter Stewart in 1978, provides a
chemical insight into the complex chemical equilibrium system known as acid-base
balance.
The impact of Stewart’s analysis has been slow, but there has been a recent
resurgence in interest, particularly as this approach provides explanations for several
areas which are otherwise difficult to understand (e.g. dilutional acidosis, acid-base
disorders related to changes in plasma albumin concentration).
Undoubtedly, the physicochemical approach will become more important in the
future and this brief review provides an introduction to this method.

Yohanes WH George, MD
Anesthesiology Intensivist
Head of Emergency & Intensive Care Unit, Pondok Indah Hospital – Jakarta Indonesia
Lecturer, Department of Anesthesiology and Intensive Therapy – Faculty of Medicine,
University of Indonesia.
Email [email protected]
Pages https://www.facebook.com/critcaremedcom

x
EASY WAY TO UNDERSTAND STEWART’S ACID-BASE
INTRODUCTION

1
EASY WAY TO UNDERSTAND STEWART’S ACID-BASE

STEWART’S APPROACH IN BRIEF

• GENERAL PRINCIPLES OF STEWART’S APPROACH
 Electroneutrality. In aqueous solutions in any compartment, the sum
of all the positively charged ions must equal to the sum of all the
negatively charged ions.
 The dissociation equilibria of all incompletely dissociated substances,
as derived from the law of mass action, must be satisfied at all times.
 Conservation of mass, the amount of a substance remains constant
unless it is added, removed, generated or destroyed. The relevance is
that the total concentration of an incompletely dissociated substance
is the sum of concentrations of its dissociated and undissociated
forms.

MATHEMATICAL ANALYSIS

The physicochemical acid-base approach (Stewart’s approach) is different

from the conventional approach based on the Henderson-Hasselbalch
equation, and requires a new way of approaching acid-base problems.
In Stewart’s approach, the [H+] is determined by the composition of
electrolytes and PCO2 of the solution.
Mathematical analysis shows that it is not absolute concentrations of almost
totally dissociated (“strong”) ions that influence hydrogen ion concentration,
but the difference between the activities of these strong ions (this “strong ion
difference” is commonly abbreviated ”[SID]”).

Stewart’s Textbook of acid-base. Edited by; John Kellum, Paul Elbers. Copyright © 2009 by AcidBase.
org/Paul Elbers, Amsterdam, The Netherlands [email protected]

2
STRONG ION DIFFERENCE
• DEFINITION:
 The strong ion difference is the charge imbalance of the strong
ions. In detail, the strong ion difference is the sum of the
concentration of the strong base cations, less the sum of the
concentrations of the strong acid anions.
 Strong electrolytes are those which are fully dissociated in
aqueous solution, such as the cation sodium (Na +), or the
anion chloride (Cl -). BECAUSE STRONG IONS ARE ALWAYS
DISSOCIATED, THEY DO NOT PARTICIPATE IN CHEMICAL
REACTIONS (UNMETABOLIZABLE IONS). Their only role in
acid-base chemistry is through the ELECTRONEUTRALITY
relationship

THE GAMBLEGRAM

STRONG ION DIFFERENCE IN WATER

Water dissociation into [H+] and [OH-]
determined by change in [SID]

K+ 4

The [H+] 4.0x10-8 OH- [SID]

Eq/L (very small)

Na+ [Na+] + [K+] - [Cl-] = [SID]

140 Cl- 140 + 4 – 102 = 34 mEq/L
102

CATION ANION
Stewart Textbook of acid-base. Edited by; John Kellum, Paul Elbers. Copyright 2009 by AcidBase.org/
Paul Elbers, Amsterdam, The Netherlands [email protected]

3
EASY WAY TO UNDERSTAND STEWART’S ACID-BASE

STRONG ION DIFFERENCE IN WATER

[H+] [H+] ↑↑ [OH-] ↑↑

Acidosis Alkalosis

OH-
OH-
OH-

Na Cl Na Na
Cl Cl

(–) [SID] (+)

THE RELATIONSHIP BETWEEN [SID] AND pH/[H+]

4
 STRONG ION DIFFERENCE IN PLASMA
BIOCHEMISTRY OF AQUEOUS SOLUTIONS

1. Virtually all solutions in human biology contain water and aqueous

solutions provide a virtually inexhaustible source of [H+]
2. In these solutions, [H+] concentration is determined by the

dissociation of water into H+ and OH- ions

3. Changes in [H+] concentration or pH occur NOT as a result of how

much [H+] is added or removed BUT as a consequence of water

dissociation in response to change in [SID], PCO2 and weak acid

STRONG ION DIFFERENCE IN PLASMA

ELECTRONEUTRALITY

H+ OH- CO 32-

[SID]a
HCO3 -

CHANGE IN pH OR [H+] AS A Weak acid

CONSEQUENCE OF WATER Na+ Alb -

Posfat -
DISSOCIATION IN RESPONSE UA = UNMEASURED ANION
TO CHANGE IN [SID], PCO2 UA - Mostly lactate and ketones
AND WEAK ACID

K+
Mg ++
Ca++
Cl -

CATION ANION
George 2015

5
EASY WAY TO UNDERSTAND STEWART’S ACID-BASE

pH or [H+] DETERMINED BY

TWO VARIABLES

Determine
INDEPENDENT DEPENDENT
VARIABLE VARIABLE

Primary (cause) Secondary (effect)

INDEPENDENT VARIABLES

CO2 STRONG ION WEAK ACID

DIFFERENCE

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

EVERY CHANGE OF THESE VARIABLE

WILL CHANGE THE pH

Stewart’s Textbook of acid-base. Edited by; John Kellum, Paul Elbers. Copyright © 2009 by AcidBase.
org/Paul Elbers, Amsterdam, The Netherlands [email protected]

6
 DEPENDENT VARIABLES

H+ HCO3-

OH- AH

CO3= A-

IF THESE VARIABLE CHANGE,

THE INDEPENDENT VARIABLES MUST HAVE
CHANGED
Stewart’s Textbook of acid-base. Edited by; John Kellum, Paul Elbers. Copyright © 2009 by AcidBase.
org/Paul Elbers, Amsterdam, The Netherlands [email protected]

THE PRACTICAL POINT

INDEPENDENT VARIABLES DEPENDENT VARIABLES

STRONG IONS
DIFFERENCE

WATER
DISSOCIATION
pCO2 H2O
OH-

Na+
PROTEIN Cl-
CONCENTRATION

7
EASY WAY TO UNDERSTAND STEWART’S ACID-BASE

THE DIFFERENCE
Henderson-Hasselbalch Stewart’s Approach
pH pH

Respiratory Metabolic Respiratory Metabolic

PCO2 Base Excess-HCO3

PCO2 [SID] A tot

[SID]
Cation; [SID] Cation;
Atot

Na+, K+, Cl-, Cl-,

Na+, K+,
Mg++, SO4-, SO4-,
Mg++,
Ca++ Lact, Lact,
Ca++
Keto Keto

Determinants of plasma pH, as assessed

Determinants of plasma pH, at 370C, as
by the H-H. Base excess and standard assessed by the Strong Ion Difference [SID]
HCO3- determine the metabolic model of Stewart. [SID+] and [Atot] determine
component of plasma pH the metabolic component of plasma pH
George 2015

• The Stewart’s approach emphasizes mathematically independent

and dependent variables.
• Actually, HCO3- and H+ ions represent the effects rather than the
causes of acid-base derangements.

8
CLASSIFICATION OF PRIMARY ACID BASE DISTURBANCE
Fencl V, Jabor A, Kazda A, Figge J. Diagnosis of metabolic acid-base disturbances in critically ill patients. Am J
Respir Crit Care Med 2000 Dec;162(6):2246-51

RESPIRATORY METABOLIC
pH
Abnormal Abnormal Strong Ion Di erence Abnormal Weak acid
pCO2

Water Abnormal Strong Anion Alb Po4-

Chloride Unmeasured
Anion

Hypoalbuminemia
Hypocarbia ALKALOSIS De cit Hypochloremia Hyposphatemia
Respiratory Hypernatremia/co a
Hypochloremic Hypoalbuminemic/posphate
alkalosis ntrac on alkalosis alkalosis mic alkalosis

Hypercarbia ACIDOSIS Excess Hyperchloremia Positive Hyperproteinemia

Respiratory Hyponatremia/ Hyperchloremic Lac c / keto Hyperposphatemia
acidosis Dilu onal acidosis acidosis acidosis Hyperalbuminemic/pospha
temic acidosis

LUNG BALANCE LIVER AND KIDNEY

Modified George 2015

9
EASY WAY TO UNDERSTAND STEWART’S ACID-BASE

simple analogy
WATER DEFICIT
Diuretic
Diabetes Insipidus
Evaporation

Plasma Plasma

Na+ = 140 mEq/L 1

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

[SID] : 38 76 = alkalosis
CONTRACTION ALKALOSIS

WATER EXCESS

Plasma

140/2 = 70 mEq/L
Na+ = 140 mEq/L 1 Liter 102/2 = 51 mEq/L
water [SID] = 19 mEq/L
Cl- = 102 mEq/L
[SID] = 38 mEq/L

1 liter 2 liter

[SID] : 38 19 = Acidosis

DILUTIONAL ACIDOSIS
10
ABNORMAL IN SID AND WEAK ACID
K
Mg [SID] ↓↓
[SID] ↓↓ [SID] ↓↓
Ca [SID]=34
[SID]↑↑
Alb Laktat/keto [SID]↑↑
PO4 Alb/
Alb Alb
PO4
PO4
PO4
Alb
Na PO4

140

Cl Cl ↑ CL ↓ Cl Cl Cl
102 115 95 102 102 102

Normal Hyperchlor Hypochlor Keto/lactate Hypoalb/ Hyperalb/

acidosis fosfat fosfat
alkalosis acidosis
alkalosis acidosis

George 2015

11
EASY WAY TO UNDERSTAND STEWART’S ACID-BASE

THE EFFECT OF SALINE AND BALANCED FLUID

FROM THE STEWART’S PERSPECTIVE
Stewart’s approach not only explains fluid induced acid–base phenomena but also
provides a framework for the design of fluids for specific acid–base effects

QUESTION:
How does saline infusion cause hyperchloremic acidosis?
ANSWER:
Saline infusion will Increase plasma Chloride more than Sodium leading to a
decrease in plasma SID (acidosis)

simple analogy
Hyperchloremia
Plasma + Saline 0.9%
Decrease [SID]

Plasma NaCl 0.9%

Na+=(140+154)/2L= 148 mEq/L
Cl-=(102+ 154)/2L= 128.5 mEq/L
Na+ = 140 mEq/L
Cl- = 102 mEq/L
[SID]= 38 mEq/L 1 liter
Na+ = 154 mEq/L
Cl- = 154 mEq/L
[SID]= 0 mEq/L
=
1 liter
[SID] = 19.5 mEq/L 2 liter

[SID] : 38 normal pH [SID] : 19.5↓ Acidosis

George 2015

Lactate Ringer infusion will not cause acidosis because it replaces

28 mEq/L of Cl- with lactate which can undergo rapid metabolism

simple analogy
Lactate (organic strong
anion) undergo rapid
Plasma + Lactate Ringer metabolism a er infusion

Lactate
Plasma ringer Na+ = (140+137)/2 L = 139 mEq/L
Cl- = (102+ 109)/2 L = 105 mEq/L
Na+ = 140 mEq/L
Cl- = 102 mEq/L
1 liter
Cation + = 137 mEq/L
Cl- = 109 mEq/L
Lactate- = 28 mEq/L
=
1 liter
Lactate- (metabolized) = 0 mEq/L
[SID] = 34 mEq/L 2 liter
[SID]= 38 mEq/L [SID]= 0 mEq/L

[SID] : 38 normal pH [SID] : 34 plasma pH

become more alkalosis than
plasma pH a er Saline infusion

12
 SALINE INFUSION CAUSE MORE
ACIDOSIS THAN LACTATE RINGER

Systemic [SID] (30+2L)=

[Na+] = 4508/32 = 140.8
BW 50 kg. 2 Liters [Cl-] = 3308/32 = 103.3
TBW 60% = 0.6.50 kg = 30L [SID] = 37.0 (more acidosis)
[Na+] = 140 = 30.140 = 4200 Give 2 liters of 0.9%
[Cl-] = 100 = 30.100 = 3000 Sodium Chloride:
[Na+] = 154 x 2 L = 308
[Cl-] = 154 x 2 L = 308
Normal plasma [SID] 40

Systemic [SID] (30+2L)=

TBW 30 Liters [Na+] = 4474/32 = 139.8
[Cl-] = 3218/32 = 100.5
2 Liters [SID] = 39.3 (more alkalosis)
Give 2 liters of LR :
[Na+] = 137 x 2 L = 274
[Cl-] = 109 x 2 L = 218
George 2015

LARGE INFUSION SALINE CAUSE MORE ACIDOSIS

Give 10 liters of 0.9%
Sodium Chloride:
[Na+] = 154 x 10L = 1540
[Cl-] = 154 x 10L = 1540
Dilutional [SID] (30+10L)=
BW 50 kg. [Na+] = 5740/40 = 143.5
TBW 60% = 0.6.50 kg = 30L [Cl-] = 4540/40 = 113.5
[Na+] = 140 = 30.140 = 4200 [SID] = 30.0 (dilutional acidosis)
[Cl-] = 100 = 30.100 = 3000
10 Liters of saline

Normal plasma
[SID] 40

TBW 30 Liters Dilutional [SID] (30+2L)=

2 Liters of saline [Na+] = 4508/32 = 140.8
[Cl-] = 3308/32 = 103.3
Give 2 liters of 0.9% [SID] = 37.0 (more alkalosis)
Sodium Chloride:
[Na+] = 154 x 2 L = 308
[Cl-] = 154 x 2 L = 308
George 2015

13
EASY WAY TO UNDERSTAND STEWART’S ACID-BASE

RAPID SALINE INFUSION PRODUCES HYPERCHLOREMIC ACIDOSIS

1. Saline 4. [SID] fall because Saline produce

produce more Increase in [Cl-] more than [Na]
acidosis than in
LR group

2. BE more
negative in
Saline group

3. [SID] in Saline grup fall

more than in LR group
Lactate Ringer * P< 5 in ragroup
Saline 0.9% # P< 5 in ergroup

simple analogy

How does bicarbonate increase the pH?

Plasma;
hyperchloremic Plasma + NaHCO3
acidosis

25 mEq
NaHCO3 HCO3 undergo
Na+ = 140 mEq/L Na+ = 165 mEq/L rapid metabolism
Cl- = 130 mEq/L Cl- = 130 mEq/L
1.025 [SID] = 35 mEq/L
[SID] =10 mEq/L 1 liter
liter

[SID]↑: from 10 to 35 → alkalosis, pH back to normal → the increase in

pH is not caused by bicarbonate itself, it is actually caused by sodium
without a strong anion (i.e Chloride)

14
DESIGNING ‘BALANCED’ CRYSTALLOIDS
The principles laid down by the late Peter Stewart have transformed
our ability to understand and predict the acid–base effects of fluids for

infusion. Now, designing fluids for specific acid–base outcomes is more

science than an art

Large volumes of intravenous saline tend to cause a metabolic acidosis,

to counteract this side effect, a number of commercial crystalloids have

been designed to be more ‘physiologic’ or ‘balanced’

They contain stable organic anions such as lactate, gluconate, malate

and acetate (metabolizable anion)

BALANCED CRYSTALLOIDS

Balanced crystalloid is a solu on who have zero [SID] before

infusion and have an e ec ve [SID] a er the metabolizable anion
was metabolized

15
EASY WAY TO UNDERSTAND STEWART’S ACID-BASE

• Balanced crystalloids thus must have [SID] lower than

plasma [SID] but higher than zero (about 24mEq/) to
counteract the progressive ATOT dilutional alkalosis during
rapid infusion
• In other words, Saline can be ‘balanced’ by replacing 24mEq/l
of Cl– with various organic metabolizable anions such as
Lactate, Malate, Acetate, Gluconate and Citrate as weak ion
surrogates
• These metabolizable anions undergo rapid metabolism in the
plasma after infusion, resulting only small increase in plasma
Cl- and then small change in plasma [SID]

Question: NOTE: One might think that 0.9%

Why is Saline so acidic? saline solu on have a neutral pH
of 7. In fact it is acidic: the pH
Answer: actually as low as 4.6
Because it has no Strong Ion Difference [SID] (Story DA, Anaesth Intensive Care. 2000)

STRONG CATIONS

STRONG ANIONS
‘Unmetabolizable’

STRONG ION
DIFFERENCE [SID]

Lactate
Acetate HCO 3 -
Acetate Malate lactate

[SID] of “BALANCED SOLUTION” Plasma Saline

replaced by metabolizable has a has no
anions [SID] [SID]

George 2015

16
 BODY pH REGULATION:
Interaction Between Membranes

SERIES OF EVENT OF ELECTROLYTE

AND ACID-BASE REGULATION IN THE
GI TRACT

• GI tract is important in acid-base balance because it deals

directly with strong ions. It does so differently in different

regions along its length, so its useful to consider four separate

parts that are quantitatively important in their effects on plasma

[SID]

• There are four important parts (region);

• Stomach (Event 1)

• Pancreas (Event 2)

• Duodenum (small intestine) (event 3)

• Colon (large intestine) (event 4)

17
EASY WAY TO UNDERSTAND STEWART’S ACID-BASE

1. Physiologically, Cl- (not H+) is

secreted into the lumen as a gastric
acid. It leaves the plasma temporary
GI site Plasma site Na
normal
plasma [SID]
Cl
and will return to plasma when it
absorbed in the small intestine

Na+ plasma [SID]

2. Increasing Cl- more than H+ Cl- Cl- Na+
Na
Alkalosis
cation (Na+) make the [SID] of Cl
Na+ Cl-
gastric acid become very Cl-
negative (acidosis) Na Cl
Cl- Na+ Cl-

3. As a consequence; the plasma site [SID]

will increase plasma alkalosis

4. There is Cl- loss in cases such as

Notes: The mechanism of antacid 2 prolonged vomiting or enterocutaneous
lowering the pH of gastric acid is not stula, and it will cause persistent
because we add the CO3-2, OH- or HCO3- hypochloremia and increase the plasma
, but because we add the strong ca on [SID], causing metabolic alkalosis
like Na+, Al2+, Ca2+ or Mg2+ which will
increase the [SID] of gastric uids

5. Fluid therapy using Saline is more

appropiate in those cases to replace the
plasma Cl- and normalize the pH

EVENT 1 George, 2003

normal
plasma [SID]
GI site Plasma site Na
Cl
1. C - wi continue p ssing
to duodenum
2. L rge mount of sodium Na+
(c tions) secreted by the bi e nd
Na+ plasma [SID]
p ncre s to neutr ize the C - in
Alkalosis
duodenum to prevent the Na+ Cl- Na
Cl- cidifying process Na+ Cl-
Cl

Cl- Cl-

Na+ Pancreas
Na+
Na+

Cl-
Na+ H+ plasma [SID]-
Cl-
Cl- Cl
Cl- Na+ Acidosis
Na+ Cl- Cl- Na+ Cl- Na
Na+
Na+ Cl-

3. The [SID] of the ti

uids become norm 4. In the jejunum, C - is 5. As consequence; the
re bsorbed into the p sm p sm [SID] decre ses or
site becomes very neg tive, e ding
to decre se in p sm pH
( cidosis)

EVENT 2 & 3 George, 2003

18
 GI site Plasma site

Cl-

Cl-
1.Cations and Na+ return to Cl-
plasma together with water
absorption in the large Cl-
intestine (colon)

Na+
2. Plasma [SID] back to
Notes: During diarrhea, normal
intestinal uids passes through
Na+
the colon too fast to be properly
processed, therefore water and
cations have lost from the body
metabolic acidosis
Na+

Na+

Na+ normal
Notes: Balanced uids or plasma [SID]
Na+
Lactate Ringer is more Na+
Na+ Na+ Na
appropiate for uid therapy Na+ Cl- Cl
in metabolic acidosis during
Na+ Cl-
diarrhea

EVENT 4 Diarrhea George, 2003

19
EASY WAY TO UNDERSTAND STEWART’S ACID-BASE

STRONG ION DIFFERENCE IN KIDNEY

THE KIDNEYS ARE THE MOST IMPORTANT REGULATOR
OF [SID] FOR ACID-BASE PURPOSE
TUBULAR FLUID CELL INTERSTITIAL PLASMA

George, 2015

EFFECT OF DIURETICS IN URINE COMPOSITION

Volume pH Sodium Potassium Chloride SID
(ml/min) (mEq/l) (mEq/l) (mEq/l) (mEq/l)
No drug 1 6.4 50 15 60 1

Thiazide diuretics 13 7.4 150 25 150 25

Loop diuretics 8 6.0 140 25 155 1

Osmotic diuretics 10 6.5 90 15 110 4

Potassium-sparing 3 7.2 130 10 120 15

diurtics
Carbonic anhydrase 3 8.2 70 60 15 120
inhibitors

Loop Diuretics (Furosemide) increase the excretion of Cl- via urine

reducing urine [SID] and increasing the plasma [SID] alkalosis

Tonnesen AS, Clincal pharmacology and use of diuretics. In: Hershey SG,
Bamforth BJ, Zauder H, eds, Review courses in anesthesiology. Philadelphia: Lippincott, 1983; 217-226

20
COMPENSATION

21
EASY WAY TO UNDERSTAND STEWART’S ACID-BASE

Renal Compensation for

Chronic Respiratory Acidosis

1. Increase CO
2 2
4. Hypochloremia increase
increase the [H+] [SID] decrease [H+]

COPD
H+
HCO3 HCO3 [SID]↑
30
Na pH ↓ Na
140 Cl 140 Cl ↓
100 90

CO2↑
2. ↑NH4Cl
urine
3. Hypochloremia

George 2015

RENAL & RESPIRATORY COMPENSATION

FOR NON RENAL METABOLIC ACIDOSIS (UA) IN STEWART’S TERM
Non Renal
Met Acidosis (UA); Shock, MODS
Hyperven la on
Plasma UA decrease the decrease [H+]
[SID] increase the [H+]

H+ 1. Early Removal CO2 HCO3 -

[SID]
HCO3 - [SID] 22
compensation UA
UA

Na+ hyperventilation Na+

Brain 140 Cl-
140 Cl- pH ↓ Hours
Stem 100
100

NH3 Sintesis ↑
↑NH4Cl urine HCO3 -
(Ammoniagenesis) [SID]
30
2. Late
UA
compensation Days ↑NH 4 Hypochloremia Na+
140
Cl- ↓
Liver
Kidney 90

Removal Chlor-
George 2015 Hypochloremia will increase [SID]
decrease [H+]

22
 Clinical Application

EASY WAY TO UNDERSTAND BLOOD GAS

ANALYSIS USING STEWART ‘S FORMULA

THE PRACTICAL POINT; IF WE WANT TO CALCULATE

THE pH, WE MUST KNOW THE CONCENTRATIONS OF
THE STRONG IONS, AND PLUG THESE VALUE INTO
EQUATIONS

23
EASY WAY TO UNDERSTAND STEWART’S ACID-BASE

REUNIFICATION OF ACIDBASE:
SID & BUFFER BASE
BBe = Buffer Baseexpected = SID = HCO3- + A-
(expected if pH = 7.4 and pCO2 = 40)

Mg++
Ca++
K+ 4
HCO3 +
HCO3 + BBactual
A- BBe A-
BECl (-)
Hyperchloremia case
Base De cit due to increase Cl =
Na+ BBa – BBe
Cl- Cl-
140
102 112
Any deviation in [Na+], [Cl-] or
[Alb-] from normal values will
produce either a positive or
negative base excess

A SIMPLIFIED
FENCL-STEWART-STORY FORMULA

BE from blood gas

machine The [SID] e ect
SBE = …
Weak acid e ect
Na–Cl e ect = [Na+]–[Cl–]–38 =...
Albumin e ect = 0.25 x [42–Alb(g/l)] =… Unmeasured anion

UA = SBE – (Na–Cl)e ect – Albumin e ect =…

Story, Morimatsu, Bellomo (2004), Bri sh Journal of Anaesthesia. Vol. 92,

24
 CASE EXAMPLES
Case 1;
pH 7.25 / PaCO2 30 / BE -10 / HCO3 14
Na 140; Cl 112; Alb 4.0
SBE = …
Na–Cl e ect = [Na+]–[Cl–]–38 =... Base De cit – 10
(metabolic acidosis
Albumin e ect = 0.25 x [42–Alb(g/l)] =… due to
UA = SBE – (Na–Cl)e ect – Albumin e ect =… hyperchloremia)

• 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

No unmeasured No alkalinizing e ect

anion was found of albumin

The gamblegram
150
pH 7.25 / PCO2 30 / BE -10 / HCO3 14
140
HCO3-
Alb 112
Base De cit due to ↑ Cl- -10
Alb
102

WD/: Metabolic acidosis due to

hyperchloremia
Etiology: Large saline
administration, Acute Kidney Injury
Th/: Saline restriction
RRT

Na+ Cl-
25
EASY WAY TO UNDERSTAND STEWART’S ACID-BASE

Case 2:
pH 7.48 / PaCO2 50 / BE + 9 / HCO3 34
Na 140; Cl 93; Alb 4.2
SBE = …
Na–Cl effect = [Na+]–[Cl–]–38 =...
Base Excess +9
Albumin effect = 0.25 x [42–Alb(g/l)] =… (metabolic
alkalosis due to
UA = SBE – (Na–Cl)effect – Albumin effect =… hypochloremia)

• 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

No unmeasured No alkalinizing e ect

anion was found of albumin

The gamblegram
pH 7.48 / PaCO2 45 / BE + 9 / HCO3 34
140

HCO3-
Alb
BE due to ↓ Cl- +9 Alb

WD/: Metabolic alkalosis due to

hypochloremia
ETIOLOGY: Loop diuretic, Vomiting,
enterocutaneous stula
Th/: Saline administration, limit the use
of diuretic

Na+ Cl-
26
 Case 3:
pH 7.30 / PaCO2 27 /BE -7 / HCO3 18
Na 128; Cl 100; Alb 3.0

SBE = … Base De cit – 7

Na–Cl effect = [Na+]–[Cl–]–38 =... [metabolic acidosis
due to the e ect of
Albumin effect = 0.25 x [42–Alb(g/l)] =… hyponatremia (-10)]
with alkalinizing e ect
UA = SBE – (Na–Cl)effect – Albumin effect =… of albumin (+3)

• 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

No unmeasured Slight alkalinizing e ect

anion was found (+3) of hypoalbuminemia

The gamblegram
pH 7.30 / PaCO2 27 / BE -7 / HCO3 18
140
BE due to ↓ Na -7
128
BE due to ↓ alb +3 Alb

WD/: metabolic acidosis due to hyponatremia

masking by slight alkalinizing e ect of
hypoalbuminemia.
ETIOLOGY: Hemodilution, overload, early
phase of shock.
TH/: Diuretic, inotrope, RRT

Na+ Cl-
27
EASY WAY TO UNDERSTAND STEWART’S ACID-BASE

Case 4 :
pH 7.42 / PaCO2 35 / PaO2 81 / BE -2 / HCO3 21 ; it’s a normal blood
gas according to the
Na 140; Cl 102; Alb 1.8; lactate 8 traditional method

SBE = … it’s a metabolic/lactic

Na–Cl effect = [Na+]–[Cl–]–38 =... acidosis masking by
hypoalbuminemia
Albumin effect = 0.25 x [42–Alb(g/l)] =… according to Stewart’s
UA = SBE – (Na–Cl)effect – Albumin effect =… approach

No SID e ect was

found

• 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

Alkalinizing e ect of
Unmeasured anion of hypoalbuminemia (+6) masking
lactate (-8) unmeasured anion

The gamblegram
pH 7.42 / PaCO2 35 / PaO2 100 / BE -2 / HCO3 21
140
-
HCOHCO3-
3
BE = - 8 + 6 = - 2 SID normal
24 22
HCO3-
30.7
BE due to hypoalb + 6 UA = - 8 BE due to UA -8
Alb
masking the UA - 8
hipoalbumin
102

Lac c Acidosis “masking” by hypoalbuminemia

Na+ Cl-
28
EASY WAY TO INTERPRET BLOOD GAS ANALYSIS
USING STEWART CALCULATOR

29
EASY WAY TO UNDERSTAND STEWART’S ACID-BASE

Case 5;
pH 7.32 /PaCO2 30 /PaO2 100 / BE -1 / HCO3 21
Na 134; K 4.2; Cl 97; Alb 2.8

INTERPRETATION
INTERPRETATION

UA

3 Independent
variables Alkalinizing process
Acidifying process

30
 CONCLUSION
There are three mathematically independent determinants of blood pH:
 Strong ion Difference, the difference between the sum of the
concentrations of strong cations and the sum of the concentrations
of strong anions
 Weak acid, the total weak acid “buffers” concentration (ATOT), which
is mostly composed of albumin and phosphate
 PCO2
Stewart’s quantitative physical chemical approach enables us to
understand the acid–base properties of intravenous fluids
Lowering and raising plasma SID with constant ATOT cause
metabolic acidosis and alkalosis, respectively
Raising and lowering ATOT with constant SID can cause metabolic
acidosis and alkalosis, respectively
Zero SID crystalloids such as saline cause a ‘dilutional’ acidosis by
lowering extracellular SID
Plasma [SID] changes by plasma interaction with interstitial fluid through
tissue capillary membranes. Interstitial fluid in turn may interact with
intracellular fluid through cell membranes
If we want to calculate the pH, we must: know the concentrations of
the strong ions, and plug these value into equations

31
EASY WAY TO UNDERSTAND STEWART’S ACID-BASE

REFERENCES
Stewart’s Textbook of acid-base. Edited by; John Kellum, Paul Elbers. Copyright © 2009
by AcidBase.org/Paul Elbers, Amsterdam, The Netherlands [email protected]
Kellum JA. Determinants of blood pH in health and disease Crit Care 2000, 4:6–14
Fencl V, Jabor A, Kazda A, Figge J. Diagnosis of metabolic acid-base disturbances in

critically ill patients. Am J Respir Crit Care Med 2000 Dec;162(6):2246-51

Tonnesen AS, Clincal pharmacology and use of diuretics. In: Hershey SG, Bamforth BJ,
Zauder H, eds, Review courses in anesthesiology. Philadelphia: Lippincott, 1983; 217-226

Scheingraber S, Rehm M, Rapid Saline Infusion Produces Hyperchloremic Acidosis in

Patients Undergoing Gynecologic Surgery. Anesthesiology 1999; 90:1247–9
Story, Morimatsu, Bellomo (2004), British Journal of Anaesthesia. Vol. 92

Story DA, Anaesth Intensive Care. 2000

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EASY WAY TO UNDERSTAND STEWART’S ACID-BASE