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 any form or by any means, electronic or mechanical, including photocopying, record- ing, or any information storage and retrieval system, without permission in writing from the publisher. Permissions may be sought directly from Elsevier’s Rights Depart- ment: phone: (+1) 215 239 3804 (US) or (+44) 1865 843830 (UK); fax: (+44) 1865 853333, e-mail: [email protected]. You may also complete your request on-line via the Elsevier website at http://www.elsevier.com/permissions. 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.
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