Human Acid-Base Physiology Human Acid-Base Physiology A student text Oliver Holmes DSc, MSc, MB, BS, MRCS, LRCP, BA Senior Lecturer in Physiology University of Glasgow Scotland Springer-Science+Business Media, B.V. ISBN 978-0-412-47610-5 ISBN 978-1-4899-7200-2 (eBook) DOI 10.1007/978-1-4899-7200-2 First edition 1993 © Oliver Holmes 1993 Originally published by Chapman & Hall 1993 Apart from any fair dealing for the purposes uf research or private study, or criticism or review, as permitted under the UK Copyright Designs and Patents Act, 1988, this publication may not be reproduced, stored, or transmitted, in any form or by any means, without the prior permission in writing of the publishers, or in the case of repro graphic reproduction only in accordance with the terms of the licences issued by the Copyright Licensing Agency in the UK, or in accordance with the terms oflicences issued by the appropriate Reproduction Rights Organization outside the UK. Enquiries concerning reproduction outside the terms stated here should be sent to the publishers at the London address printed on this page. The publisher makes no representation, express or implied, with regard to the accuracy of the information contained in this book and cannot accept any legal responsibility or liability for any errors or omissions that may be made. A catalogue record for this book is available from the British Library Library of Congress Cataloguing-in-Publication data Holmes Oliver Human acid-Base physiology a student text j Oliver Holmes. p. cm. Includes bibliographical references and index. ISBN 978-0-412-47610-5 1. Acid-Base equilibrium. 2. Acid-Base imbalances. I. Title. QP90.7.H65 1993 612'.0 22- dc20 92-41400 CIP § Printed on permanent acid-free text paper, manufactured in accordance with the proposed ANSljNISO Z 39.48-199X and ANSI Z 39.48-1984 Contents Preface xi Units of measurement xiii 1 FUNDAMENTALS 1 Acid-Base physiology 1 Water, the substrate of life 1 Water in the body 1 The dissociation of water in relation to acids and bases 2 Strong acids and weak acids 3 The law of mass action and the concentration of hydrogen and hydroxide ions 3 Dissociation of water 4 Measurement of pH 7 Titration curves and buffers 7 Making a buffer solution 8 The Henderson-Hasselbalch equation 9 The chemical reactions accompanying buffering 10 The pK of a buffer pair and buffering efficacy 11 Buffer value 12 The importance of the C0 -bicarbonate system 14 2 Kidney 16 Properties of gases: 17 Partial pressure 17 Avogadro's law 17 Dalton's law of partial pressures 17 The concentration of a constituent of a gas mixture 17 Henry's law 18 Appendix 1 18 A.1 Ionic product of water 18 A.2 Definition and measurement of pH 18 A.3 Buffer value 19 I l vi CONTENTS 2 INTRODUCTION TO ACID-BASE PHYSIOLOGY 21 The range of plasma pH in health and disease 21 Variations in ionic composition of the extracellular fluid compatible with life 22 Comparison of hydrogen ions with other electrolytes 22 Enzymes and hydrogen ion concentration 22 Effects of disturbances of hydrogen ion concentration 23 Defence of hydrogen ion concentration 23 Buffering action of the body 24 Graphic representation of acid-base status 24 A graphic representation 25 Graphs for real fluids 27 Distilled water 27 Sodium bicarbonate solution 29 Perfect buffer 30 Real buffer solutions 30 Blood plasma 31 Blood 31 Appendix 2 32 A.l The chemistry of carbon dioxide 32 A.2 Carbonate 32 3 DISORDERS OF ACID-BASE PHYSIOLOGY 33 3.1 Respiratory disorders 33 Respiratory acidosis (acute hypoventilation) 33 Compensation 36 Degrees of compensation 36 The time scale of compensation 37 The new blood line 37 Definition of acidaemia, acidosis etc. 38 Reinstatement of normal ventilation 40 Respiratory alkalosis 40 3.2 Metabolic disorders 41. Blood buffers 41 Metabolic acidosis 42 Infusion of hydrochloric acid 43 The role of bone in longer-term buffering 44 Compensation 44 Degree of compensation 45 Time scale 45 An advantage of acidaemia 46 Renal compensation 46 The final status 46 CONTENTS I I Vll Cell membranes are permeable to blood gases but relatively impermeable to ions 47 Treatment 47 Metabolic alkalosis 47 Potassium and acid-base physiology 48 The renal handling of electrolytes 49 Overview of hydrogen ion-potassium ion inter-relationships 51 Adverse effects of changes in extracellular potassium concentration 51 3.3 Gastric function 52 The composition of gastric juice 52 Interactions between responses to disturbances of acid-base physiology and of fluid volume such as vomiting 53 Vomiting of gastric contents 54 Outline of treatment 57 Appendix 3 57 A.l Renal compensation for respiratory acidosis 57 A.2 Causes of metabolic acidosis 58 A.3 Renal handling of potassium 58 4 ASSESSMENT OF ACID-BASE STATUS 59 4.1 Standard bicarbonate, base excess and buffer base 59 Measurement of acid-base status 59 Indicators of the metabolic component 60 The standard bicarbonate 60 Base excess 62 Buffer base or total buffer base 63 The effect of changes in Pco concentration on blood chemistry 65 2 Why are base excess and buffer base both used? 65 Specification of acid-base status 67 4.2 The Siggaard-Andersen nomogram for the parameters of acid-base status 70 The effect of haemoglobin concentration 74 Review of methods of plotting acid-base status 77 Appendix 4 79 A.l Measurement of total buffer base 79 A.2 log [C0 as a function of pH for a constant value of 2] [HC03 -] 79 5 ACIDS AND BASES IN THE BODY 81 Sources of acid or alkali 81 Buffering of an acid load 82 I viii l._ ___________c _o_N_T_E_N_T_s_ _________ ____J Acid-base physiology in the context of body fluids 83 Composition of plasma 85 Total buffer base of plasma and of whole blood 86 The charge on one ion of protein buffer base 86 The blood as a buffer 87 The Henderson-Hasselbalch equation expressed in terms of carbonic acid 88 The complex nature of blood and its acid-base implications 90 The 'chloride shift' 91 Blood in the body 92 Treatment of acid-base disorders 94 Intracellular hydrogen ion concentration 96 Comparison of extra- and intracellular hydrogen ion concentration in disorders of acid-base physiology 96 Homeostasis 96 Appendix 5 99 A.1 Carbon dioxide and carbonic acid 99 6 OXYGEN CARRIAGE, RESPIRATION AND ACID-BASE PHYSIOLOGY 101 6.1 Carriage by the blood of oxygen and carbon dioxide 101 The oxygen dissociation curve of the blood 101 Typical values for Pco and oxygen content in arterial 2 and mixed venous blood 103 The Bohr effect 104 Acid-base balance and the carbon-dioxide dissociation curve of the blood 106 Uptake and release in capillaries of carbon dioxide 108 Comparison of the oxygen and carbon dioxide dissociation curves of blood 109 The respiratory quotient 110 The difference in pH of systemic arterial and venous blood 110 Erythrocytes swell as they traverse systemic capillaries 111 Carbon dioxide and respiratory acidosis 111 6.2 The respiratory system in acid-base physiology 114 The composition of atmospheric air 114 Inspired air and alveolar gas 114 The partial pressure of gases in alveolar gas and in systemic arterial blood 11 5 The body regulates the partial pressure of carbon dioxide in the systemic blood 11 5 CONTENTS ix I I So long as hypoxia is excluded, the body does not regulate the partial pressure of oxygen in the systemic blood 116 The partial pressure of nitrogen 116 The see-saw of carbon dioxide and oxygen 116 In hyperventilation, the body is depleted of carbon dioxide but is not loaded with extra oxygen 117 Blood oxygenation and disorders of acid-base physiology 119 The control of ventilation 120 Appendix 6 121 A.1 'Oxygen dissociation' curve of the blood 121 A.2 The pH of blood as it passes through a systemic capillary 121 7 RENAL ASPECTS OF ACID-BASE PHYSIOLOGY 123 The mechanism of the renal secretion of hydrogen ions 123 Hydrogen ion secretion along the nephron 128 Excretion of acid 128 Phosphate as a buffer of urine 129 Ammonia 129 Ammonia formation in the body 130 Ammonia and renal acid-base physiology 130 Titratable acid and total acid excretion 132 Renal failure 132 Diuretic therapy 132 Appendix 7 133 A.1 The bicarbonate-sodium co-transporter for movement from the renal tubular intracellular fluid to the renal interstitial fluid 133 A.2 The production of ammonia from glutamine 133 8 SELF-TEST QUESTIONS AND ANSWERS 135 LEARNING OBJECTIVES IN ACID-BASE PHYSIOLOGY 169 REFERENCES 177 GLOSSARY 179 UNITS AND ABBREVIATIONS 183 INDEX 185 Preface This textbook of human acid-base physiology is intended for pre-clinical medical students and other university students studying physiology courses of equivalent standard. This is a self-contained basic physiological text, in which the science emerges from a consideration of the physiological aspects of clinical acid-base disorders and is developed from basic principles. In writing the book, I have tried to produce a logical and sequential text in which the relevant physical chemistry is reviewed (Chapter 1), the essentials of acid-base physiology are established (Chapters 2 and 3), the assessment of acid-base status is described (Chapter 4) and the subject of acid-base physiology is put into perspective in the wider context of the physiology of the whole organism (Chapters 5 to 7). The main points developed in the text are gathered in tables. This provides the reader, as information is assimilated, with a precis which is subsequently useful for reviewing or revising. Key references are included, so that the inquisitive can read more widely, and there are frequent allusions to clinical relevance. Furthermore, the book has been kept to a size that can reasonably be read by a junior undergraduate student. The text is fully illustrated with original line diagrams. The final chapter is a substantial section of self-assessment material (including structured exercises and multiple choice questions), enabling readers to monitor their own progress. A glossary of terms is provided to help readers to understand the jargon of the subject and to check definitions etc. An informal style of writing has been adopted with the hope of conveying the enthusiasm that the lecturer can achieve in the lecture theatre. A draft of this book has been extensively used by university undergraduates studying acid-base physiology and its effectiveness as a teaching text has been established on the campus. ACKNOWLEDGEMENTS I wish to express my indebtedness to the following people who have helped me so much in writing this book: