Fluid, Electrolyte and Acid-Base Physiology: A Problem-Based Approach, Fourth Edition

615 Pages·2010·21.45 MB·English

by  Mitchell L. Halperin MD FRCPC

F o u r t h E d i t i o n
Fluid, Electrolyte, and
Acid-Base Physiology
A Problem-Based Approach
Mitchell L. Halperin, ,
md frcpc
St. Michael’s Hospital
University of Toronto
Toronto, Canada
Kamel S. Kamel, ,
md frcpc
St. Michael’s Hospital
University of Toronto
Toronto, Canada
Marc B. Goldstein, ,
md frcpc
St. Michael’s Hospital
University of Toronto
Toronto, Canada
1600 John F. Kennedy Boulevard
Suite 1800
Philadelphia, PA 19103-2899
FLUID, ELECTROLYTE, AND ACID-BASE PHYSIOLOGY:  
A PROBLEM-BASED APPROACH  ISBN: 978-1-4160-2442-2
Copyright © 2010, 1999, 1994, 1988 by Saunders, an imprint of Elsevier Inc.
All rights reserved. No part of this publication may be reproduced or transmitted in 
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Notice
Knowledge and best practice in this field are constantly changing. As new research 
and experience broaden our knowledge, changes in practice, treatment, and drug 
therapy may become necessary or appropriate. Readers are advised to check the 
most current information provided (i) on procedures featured or (ii) by the man-
ufacturer of each product to be administered, to verify the recommended dose 
or formula, the method and duration of administration, and contraindications. 
It is the responsibility of the practitioners, relying on their own experience and 
knowledge of the patient, to make diagnoses, to determine dosages and the best 
treatment for each individual patient, and to take all appropriate safety precau-
tions. To the fullest extent of the law, neither the Publisher nor the Authors assume 
any liability for any injury and/or damage to persons or property arising out of or 
related to any use of the material contained in this book.
The Publisher
Library of Congress Cataloging-in-Publication Data
Halperin, M. L. (Mitchell L.)
Fluid, electrolyte, and acid-base physiology : a problem-based
approach / Mitchell L. Halperin, Kamel S. Kamel, Marc B. Goldstein. —4th ed.
p. ; cm.
Includes bibliographical references and index.
ISBN 978-1-4160-2442-2
1. Water-electrolyte imbalances. 2. Acid-base imbalances.  
3. Water-electrolyte imbalances—Case studies. 4.  Acid-base
imbalances—Case studies. I. Kamel, Kamel S. II. Goldstein, Marc B.
III. Title. 
[DNLM: 1. Acid-Base Imbalance—physiopathology. 2.  Water-Electrolyte
Imbalance—physiopathology. 3. Acid-Base Imbalance—diagnosis. 
4. Potassium—metabolism. 5. Water-Electrolyte Imbalance—diagnosis.  WD
220 H195f 2009]
RC630.H34 2009
616.3´992—dc22
2008020019
Acquisitions Editor: Adrianne Brigido
Developmental Editor: Angela Norton
Project Manager: Bryan Hayward
Design Direction: Steven Stave
Printed in the United States of America  
Last digit is the print number:  9  8  7  6  5  4  3  2  1
To Brenda, Marylin, and Ellen: 
We are indeed extremely  
grateful for your patience;
your strong,  
unwavering support;
and your understanding.

Preface
T
here has been a long interval between this, the fourth edition 
of Fluid, Electrolyte, and Acid-Base Physiology, and the third 
edition of the book. This delay was caused, in part, by our 
decision to virtually rewrite the text, which resulted from our collabo-
ration with Professor Kamel S. Kamel, whose input has had a major 
impact on the content of the current edition. A creative and critical 
individual who is highly motivated to understand “why things hap-
pen in biology,” Dr. Kamel encouraged us to intensify our tradition-
ally bold challenge of some of the classical thinking on physiologic 
processes. This iconoclastic emphasis we applied, for example, to our 
clinical approach to disorders that include abnormalities in acid-base, 
salt and water, and/or potassium homeostasis. 
In each section of the book, we begin with a chapter in which we 
highlight principles of physiology and biochemistry. The greater part 
of each chapter describes more classical aspects, but with a focus that 
is often distinct from that of other textbooks. In the last part of each 
chapter, we turn our attention to integrative physiology, providing 
new insights that rely on a deductive analysis rather than on available 
experimental evidence (which has been known to impose certain 
constraints). Our goals here are to raise questions and to reject mere 
repetition of currently accepted dogma in favor of demonstrating a 
different way of thinking. Thus, although not every reader will agree 
with our explanations, they serve the essential function of indicating 
where controversies and uncertainties exist. 
In Chapter 1, Principles of Acid-Base Physiology, for example, we 
encourage the reader to take a critical look at how we describe “good” 
and “bad” buffering of hydrogen ions. Because base balance is largely 
ignored in classical descriptions of acid-base balance in favor of a pri-
mary focus on acid balance, we have included a strong emphasis on 
base balance. We also stress that the renal contribution to acid-base 
balance must occur without sacrificing the need to minimize the risk 
of forming kidney stones (i.e., it is essential to maintain a urine pH 
close to 6 and to have a concentration of citrate that is close to that 
of calcium in the urine). In the final part of Chapter 1, we encourage 
the reader to think broadly by asking a question with far-reaching 
implications: Why is the normal blood pH 7.40? The analysis begins 
with issues that concern survival; moves to respiratory physiology, 
mitochondrial metabolism, and bone physiology that helps maintain 
vii
viii PREFACE
an “ideal” concentration of ionized calcium in plasma; and then 
returns to the acid-base physiology during a sprint. 
In the section on integrative physiology in Chapter 9, Sodium and 
Water Physiology, we emphasize regulation and also question many 
of the accepted dogmas about the urine concentrating mechanisms. 
We begin with a function/control analysis of regulation, aided by a 
new discovery of great importance: the absence of aquaporin 1 water 
channels in the thin descending limbs of the loop of Henle. The focus 
of regulation is on inhibitory control mechanisms that act on the 
medullary thick ascending limb of the loop of Henle, which leads 
us to propose a system of regulation that begins paradoxically with 
dilution of the medullary interstitial compartment (rather than with 
the so-called single effect in the loop of Henle). In this way, not only 
is the reader spared the discomfort of wrestling with the elusive (and 
incomplete or incorrect) countercurrent multiplier hypothesis. We 
present an alternative way to examine events that is consistent with 
the facts and allows for the regulation of the reabsorption of Na+ and 
Cl– in the medullary thick ascending limbs of the loop of Henle.
An emphasis on biochemistry contributes to the most important 
feature of this book: improvement of the reader’s understanding by 
providing the rationale for the regulation of each major component 
of physiology. In Chapter 5, Ketoacidosis, we highlight principles of 
metabolic regulation. In this context, we look at the possible role for 
the uncoupling of oxidative phosphorylation in diabetic ketoacido-
sis, a discussion that leads us to consider the generation of reactive 
oxygen species and how the body reacts to this threat. Similarly, 
Chapter  6,  Metabolic  Acidosis,  contains  a  strong  biochemical 
component in its discussion of lactic acidosis and pyroglutamic 
acidosis. 
By providing increased detail about regulation, we provide the 
background for the reader to deduce how a metabolic process is likely 
to be controlled, by asking the question What is the primary function
of this process? An examination of the principal types of regulation, 
control by the quantity of enzyme, the concentration of substrate, 
and/or the concentration of its key product follows. Because chang-
ing the quantity of enzyme usually occurs after a considerable delay 
and because controls exerted by the concentration of substrate are 
designed primarily to remove a dangerous substrate, acute control is 
most often initiated by inhibitory influences, which commence when 
the concentration of the key product rises or falls sufficiently (see, 
e.g., the discussion of concentration of the urine in Chapter 9). 
The final emphasis in this area is the examination of control mech-
anisms from a Paleolithic perspective, since control mechanisms to 
ensure survival were most likely to have developed during this period. 
Parenthetically, the pressures of modern times are unlikely to have a 
sufficiently large control strength to overcome these primitive inhibi-
tory control mechanisms. In this regard, it is tempting to speculate, 
for example, that genes for obesity were “good” in Paleolithic times, 
when food could not be stored for prolonged periods. In contrast, 
because these genes decrease the human lifespan by predisposing 
individuals to disorders such as diabetes mellitus and cardiovascular 
disease, they are considered “bad” today. Admittedly, in various parts 
of the book, we allowed our excitement with respect to interesting 
ideas in biology to take us beyond a basic description of the topics. 
Also featured prominently throughout the book is integrative 
physiology, and we encourage readers to take the time to examine 
the pathophysiology far beyond the area of discussion. For example, 
in the management of diabetic ketoacidosis, readers are challenged to
PREFACE ix
think deeply about cerebral edema and to consider how the incidence 
of this serious complication can be minimized. Similarly, in the course 
of discussing the renal role in maintaining acid-base homeostasis, we 
integrate into the physiology the importance of minimizing the likeli-
hood of renal stone formation (i.e., the importance of maintaining a 
urine pH close to 6 and a concentration of citrate that is close to that 
of calcium in the urine).
The clinical areas in the chapters also have a unique focus. We 
begin consistently with emergencies on first contact, with “Patient, 
please do not die!” as our theme. The anticipation of dangers that 
might be induced by our therapy and the strategies needed to pre-
vent them from occurring ensue, followed by a diagnostic workup in 
which principles of physiology are applied to the bedside.