Renal Physiology

E. Koushanpour W. Kriz

Renal Physiology Principles, Structure, and Function

Second Edition

With 190 Illustrations and 3 Color Plates

Springer Science+Business Media, LLC

ESMAIL KOUSHANPOUR, PH.D.

Associate Professor of Physiology and Anesthesia, Northwestem University Medical School, Chicago, Illinois, USA

WILHELM KRIz, M.D.

Professor of Anatomy, University of Heidelberg, 6900 Heidelberg, Federal Republic of Germany

On the front cover: FIGURE 4.3. Organization of the intrarenal vasculature of the human kidney, p. xi.

Library of Congress Cataloging in Publication Data Koushanpour, Esmail.

Renal physiology. Inc1udes bibliographies and index. 1. Kidneys. 1. Kriz, Wilhelm, 1936-

IL Title. [DNLM: l. Body F1uids-physiology. 2. Kidney-physiology. WJ 300 K867r] QP249.K68 1986 612' .463 86-15431 The first edition was published by W.B. Saunders Company © 1976.

© 1986 by Springer Science+Business Media New York Originally puhlished by Springer-Verlag New York, Inc. in 1986 Softcover reprint ofthe hardcover 2nd edition 1986 All rights reserved. No part of this book may be translated or reproduced in any form without written permission from Springer Science+Business Media, u.e. The use of general descriptive names, trade names, trademarks, etc. in this publication, even if the former are not especially identified, is not to be taken as a sign that such names, as understood by the Trade Marks and Merchandise Marks Act, may accordingly be used freely by anyone. While the advice and information of this book is believed to be true and accurate at the date of going to press, neither the authors nor the editors nor the publisher can accept any legal responsibility for any errors or omissions that may be made. The publisher makes no warranty, express or implied, with respect to material contained herein.

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987 6 5 4 3 2 l

ISBN 978-1-4757-1914-7 ISBN 978-1-4757-1912-3 (eBook) DOI 10.1007/978-1-4757-1912-3

Preface to the Second Edition

The first edition of this book was well received by medical students, graduate students, and clinicians interested in furthering their understanding of basic principles of renal physiology. Most of the reviews of the first edition and comments from the various instructors who used the book were very positive and complimentary with regard to the presentation of the physiological information and the use of the system analysis approach to describe renal function. These positive and encouraging comments over the past nine years, since the publication of the first edition, gave us the impetus to consider the prepa­ration of a second edition. The explosive expansion of our knowledge of renal function, particularly the correlation of function with structure of the kidney, necessitated the complete reorganization of the book and substantial revision of its content. With this in mind, we undertook a comprehensive revision of the book integrating the structure of the mammalian kid­ney with renal function.

The major planning for revising this book was carried out in 1983-84, while Esmail Koushanpour was on an eight-month sabbatical as a Senior Ful­bright Professor, doing collaborative research on the effect of some diuretics on the structure and function of the kidney with Professor Wilhlem Kriz, Anatomy Department, University of Heidelberg, Federal Re­public of Germany.

As was mentioned in the preface to the first edition of this textbook, insofar as possible, an attempt was made to integrate the anatomical information with the functional description of the kidney. This ap­proach represents a marked departure from similar textbooks, in which the anatomical information is usually treated separately. In this second edition, the anatomical sections have been greatly enhanced and

updated. The two of us have made further collab­orative efforts to present a better understanding of the function of the kidney in conjunction with the most recent anatomical findings.

The second edition consists of 13 Chapters and 3 Appendices. As in the first edition, the anatomical description of the kidney is incorporated into the various chapters dealing with kidney functions. Most of the anatomical information was written by Wil­helm Kriz. The physiological information was writ­ten by Esmail Koushanpour, except for Chapter 12 which was jointly written. Chapters 1 through 3 were partly revised for clarity and to include new infor­mation about capillary permeability and a more de­tailed treatment of the application of the Darrow­Yannet diagram. Chapters 4, 5, and 6 are completely new. Chapters 7 and 8 were partly revised to include new information. Chapter 9 was completely revised to reflect the current understanding of tubular pro­cessing of filtrate along the nephron. Chapters 10, 11, and 13 were also partly revised to include new information. Appendices A and B are the same as in the first edition. Appendix C is new. It provides a summary of nomenclature used to describe the structure of the kidney.

We wish to thank many people who helped in the revision of this book. In particular, we wish to thank Ms. Ingrid Ertel (Heidelberg) and the staff of Kascot Media, Inc. (Chicago) for the photographic work. We wish to thank Mr. Rolf Nonnenmacher (Hei­delberg) and the staff of Kascot Media, Inc. '(Chi­cago) for much of the original color and black and white art work. We wish to thank Mrs. Jenny Lee Koushanpour (Chicago) and Mrs. Helene Dehoust (Heidelberg) for typing the manuscript, and Mrs. Jenny Lee Koushanpour for proofreading the manu-

vi Preface to the Second Edition

script. We wish to express our appreciation to all the authors and publishers who kindly permitted the reproduction of borrowed illustrations. Finally, we

ESMAIL KOUSHANPOUR

Chicago

wish to thank the staff of Springer-Verlag for their assistance in the production of this book.

WILHELM KRIZ

Heidelberg

Preface to the First Edition*

Physiologists and clinicians are keenly aware of the truth in the century-old statement by Claude Bernard that constancy of internal milieu is prerequisite to a normal life. The mechanisms by which this con­stancy of internal environment or "homeostasis" is maintained involve the dynamic interplay of several organ systems, of which the kidney is the most prom­inent. However, few textbooks on renal function have even attempted to, much less succeeded in, explaining this dynamic interaction to medical and allied health students.

This interdependence is well demonstrated by pa­tients with primary or secondary renal disease, who often exhibit a wide variety of clinical symptoms, seemingly unrelated to the failure of the kidney. Included in these symptoms are: hypertension, of both the arterial and the portal vein variety; fluid retention in dependent extremities, often accom­panied by acute renal failure; congestive heart failure; and liver cirrhosis; as well as acid-base disturbances associated with abnormal metabolism, such as dia­betes mellitus and gastrointestinal disorders. Al­though not readily apparent, a careful analysis of the patient's physical and laboratory findings, as well as of the physiology of renal function, would reveal that most, if not all, of these unrelated symptoms can be traced to some disturbance in normal renal regulatory functions. Therefore, to facilitate an in­telligent approach to the diagnosis of the underlying cause and the management of the clinical symptoms, it is necessary to acquire a thorough understanding of the renal function in relation to its dynamic in­teraction with other major organ systems involved in homeostatic regulation.

This book has developed from a 20-lecture course

*Amended

in renal physiology given for the past 12 years by the author to medical students at Northwestern Uni­versity Medical School. It is an attempt to present an integrated, quantitative analysis of renal function and its role in body fluid homeostasis. The book uses the systems analysis and synthesis approach, which represents a significant departure from the traditional and conventional presentation of the subject. The understanding that such an approach provides is not descriptive, but mechanistic; it imposes mathemat­ical rigor on conceptual processes. It facilitates the search for key factors, alternate possibilities, and missing links that guide experimentation in fruitful directions. At each stage of progress, it summarizes in unambiguous form the current state of understand­ing so that deficiencies are well exposed to prod further efforts. This approach does not replace ex­perimental ingenuity nor depth of knowledge of the subject, but facilitates and stimulates both. There­fore, application of systems analysis to the study of renal function developed in the present book rep­resents a new and novel approach to the description of this complex physiological system.

This book consists of 13 chapters and 2 append­ices. The first chapter presents an overview of the renal-body fluid regulating system. It not only in­troduces the reader to the author's approach to the subject, but also brings into focus the unique role the kidney plays in the regulation of body fluid ho­meostasis. Chapters 2 through 11 are devoted to a rigorous and mechanistic description of body fluids and renal function. Where appropriate, sufficient background materials are included in each chapter so as to minimize the need for review. For example, Chapter 7 gives a detailed analysis of the biochemical and quantitative concepts necessary to understand the mechanisms of renal transport and the concen-

viii Preface to the First Edition

tration and dilution of urine discussed in Chapters 8, 9, and 11. To better understand the role of the kidney in the regulation of acid-base balance, an extensive discussion of buffers and associated con­cepts as well as respiratory regulation of acid-base are included in Chapter 10. In this way, the materials in each chapter not only introduce and develop sys­tematically some aspects of renal function, but they also provide the necessary background for the ma­terials presented in the succeeding chapters. Fur­thermore, unlike other books on the subject, in which the anatomy of the kidney is treated separately, we have integrated the anatomical information with the discussion of kidney function. Also, at the end of each chapter, numerous problems are included, which are designed to further the students' understanding of the materials covered in the text.

Chapters 12 and 13 are devoted to a detailed and integrated analysis and synthesis of the renal-body fluid regulating system, in the light of what has been presented before, and from the standpoints of both normal and pathophysiological disturbances. In­cluded are a mechanistic description of renal function in disease and the extent of its involvement in con­ditions such as acute glomerulonephritis, pyelone­phritis, nephrotic syndrome, hypertension, liver cirrhosis, and congestive heart failure. It is hoped that these clinical examples will provide a clear dem­onstration to the reader of the utility and relevance of materials presented earlier and contribute to his understanding of the diverse processes which un­derlie a disease state.

Appendix A is an attempt to introduce the student to the principles of systems analysis and synthesis and its potential application to physiological systems. Appendix B presents a mathematical background for the principle of dilution used in this book. Finally, at the end of the book we have provided answers to some of the problems given at the end of each chap­ter, designed to increase the understanding of the student of the principles presented in the text.

As written, this book should fulfill the needs of all types of students, including those with little or no mathematical background. At first glance, the

quantitative and rigorous approach to the subject may be considered somewhat beyond the need of the med­ical students. Our experience at Northwestern Uni­versity Medical School has proved otherwise. The materials presented and the systems analysis ap­proach were received enthusiastically not only by the medical students, but also by the physical therapy and medical technology students. Of course, for the latter group we minimized the extent of mathematical notations, but we made no compromise in the flow and functional diagram approach.

Finally, although the author's primary goal has been to write a book which satisfies the needs of several groups of students, it could be of special interest to researchers in renal physiology as well as medical practioners. For the latter audience, it should provide a fresh approach to a complex field hitherto not within easy grasp.

It would be impossible to acknowledge and ade­quately thank everyone who has helped make this book possible. The author is indebted to Professor John S. Gray, who not only introduced him to sys­tems analysis and its application to physiological systems, but also helped with the development of some aspects of the book, especially the acid-base chapter. I wish to express my sincere appreciation to many former medical students, who made valuable contributions to the development of this book by their enthusiastic and critical feedback as well as their continuous encouragement. I can only say that they made the effort very much worthwhile. I wish to specially thank Miss Jenny L. Forman, who, as a devoted secretary, both encouraged me in the writing of the book and diligently undertook the typing of the manuscript, during all phases of its development. She also meticulously and patiently typed the final manuscript and assisted in proofreading. Special thanks are extended to Mr. Donald Z. Shutters, who skillfully rendered all the original illustrations. I also wish to express my appreciation to all the authors and publishers who kindly permitted the reproduction of the borrowed illustrations. I would like to thank the National Institutes of Health for their generous support of my research, mentioned in the book.

ESMAIL KOUSHANPOUR

Chicago

Contents

Preface to the Second Edition. . . . . . . . . . .. . . . . . . v

Preface to the First Edition .................... vii

Color Plates. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . xi

1 Introduction to the Renal-Body Fluid Regulating System ........................ .

2 Body Fluids: Normal Volumes and Compositions . . . . . . . . . . . . . . . . . . . . . . . . . . 8

3 Body Fluids: Turnover Rates and Dynamics of Fluid Shifts .............................. 21

4 An Overview of the Structural and Functional Organization of the Kidney. . . .. 41

5 Formation of Glomerular Ultrafiltrate . . . . .. 53

6 Regulation of Renal Blood Flow and Glomerular Filtration Rate ................. 73

7 Renal Clearance: Measurements of Glomerular Filtration Rate and Renal Blood Flow ....................................... 96

8 Structural and Biophysical Basis of Tubular Transport .......................... 112

9 Tubular Processing of Glomerular Ultrafiltrate: Mechanisms of Electrolyte and Water Transport ....................... 132

10 Tubular Reabsorption and Secretion: Classification Based on Overall Clearance Measurements ................... 214

11 Regulation of Acid-Base Balance .......... 240

12 Mechanism of Concentration and Dilution of Urine .................................... 270

13 Renal Regulation of Extracellular Volume and Osmolality ............................. 310

Appendices

A Introduction to Quantitative Description of Biological Control Systems ............. 353

B Mathematical Basis of Dilution Principle ... 367

C Anatomical Nomenclatures .................. 370

Answers to Problems ....................... 372

Index .......................................... 375

x Color Plates

FIGURE 4.2. Structural organization of the nephrons and collecting ducts of the human kidney. There are three nephron types depicted: short loop nephron (left), cortical nephron (middle), and long loop nephron (right). The renal parenchyma is divided into the cortex (C), outer stripe (OS), inner stripe (IS), and inner medulla (1M). The cortex consists of two parts: the cortical labyrinth (containing the vessels, the glomeruli, and the convoluted tubules), and the medullary rays (containing the straight tubules). Note that the outer stripe does not include the medullary rays of the cortex. Two interlobular arteries are drawn on either

FIGURE 4.3. Organization of the intrarenal vasculature of the human kidney. The renal parenchyma is divided into the cortex (C), the outer stripe (OS), the inner stripe (IS), and the inner medulla (1M). At the corticomedullary bor­der, short segments of arcuate artery (shown in red) and vein (shown in blue) are depicted. The interlobular artery arises from the arcuate artery and ascends within the cor­tical labyrinth. The interlobular artery gives rise to three afferent arterioles which supply, respectively, a superficial glomerulus, a midcortical glomerulus, and a juxtamedul­lary glomerulus. The efferent arterioles of the superficial and midcortical glomeruli supply both capillary plexuses of the cortex, namely, the round-meshed capillaries of the cortical labyrinth and the long-meshed capillaries of the medullary ray. The cortex is drained by interlobular veins, some of them begin as stellate veins at the surface of the

site within the cortical labyrinth; together with their af- ~ ferent and efferent arterioles they are shown in red. The renal corpuscles and the proximal tubules (convoluted and straight parts) are shown in brown. The thin limbs are shown in pale brown. The thick ascending limb (straight part of the distal tubule including the macula densa, which is shown as a bulging portion of the tubule) and the distal convoluted tubule are shown in yellow. The connecting tubules are shown in light green. Note that the connecting tubule of the long loop nephron forms an arcade. Finally, the collecting duct system is shown in dark green.

kidney, as depicted in this figure. The efferent arterioles~ of the juxtamedullary glomeruli descend into the outer stripe and divide into the descending vasa recta, which descend within the vascular bundles. At successive levels within the medulla, descending vasa recta leave the bundles to supply the adjacent capillary plexus. In the inner stripe the capillary plexus is dense round-meshed, whereas in the inner medulla the capillary plexus is long-meshed. The drainage of the medulla is achieved by ascending vasa recta. Those originating in the inner medulla together with the descending vasa recta form the vascular bundles. Most of those originating from the inner stripe ascend indepen­dently from the vascular bundles. In the outer stripe, the ascending vasa recta form a dense pattern of vessels that supply the tubules. True capillaries are sparse within the outer stripe.

xi Color Plates

/ I I \ \ C \ \ \ \ \ I

I ./

OS

------\S

----

\N\

FtGURE 4 .3 FIGURE 4 .2

Xli Color Plates

a

Figure 12.6. Possible connections established by the med­ullary circulation. In each of the three panels a short loop (yellow), a long loop (green), and a collecting duct (brown­ish) are shown. Descending vasa recta (DVR) (derived from efferent arterioles of juxtamedullary glomeruli) and capillaries are shown in red; ascending vasa recta (A VR), drawn en bloc, are shown in blue. C = cortex , OS = outer stripe, IS = inner stripe, and 1M = inner medulla. The left panel (a) shows the simple type of medulla, where vascular bundles represent a countercurrent arrangement between D VR and A VR. Countercurrent exchange of some substance (e.g., urea) from ascending vasa recta to de­scending vasa recta (middle arrowhead) will trap the sub­stance in the inner medulla. As A VR from 1M are also arranged along DVR destined for IS, there is a possibility that some substance (e .g., urea, originating from 1M) will also be transferred to the IS capillary plexus (upper ar­rowhead). Entry into tubules ofIS (descending thin limbs of short loops!) will open a recycling possibility back to the inner medulla via the distal tubule/collecting duct route.

b c

Reentry into the ascending vasa recta within the inner medulla (lower arrowhead) will restart the process. The middle panel (b) shows the complex type of medulla, where in addition to DVR, descending thin limbs of short loops descend within bundles in a countercurrent arrangement with AVR from 1M. In addition to countercurrent trapping between AVR and DVR (middle arrowhead), a recycling route via short loops of Henle is seen. Countercurrent exchange from A VR to descending limbs of short loops (upper arrowhead) will return some substance to 1M via the normal nephron and the collecting duct route. The right panel (c) shows the relationships between A VR and tubules in OS (valid for both simple and complex type of medulla). The total venous blood from the medulla trav­erses the outer stripe in wide tortuous channels contacting tubules of OS like capillaries. Whether this arrangement serves as an ultimate trap for medullary solutes and/or is part of a recycling route for substances coming up from the medulla and secreted into the proximal tubules is un­known. (Modified from KriZ.47)