Renal Pathophysiology

390 Pages·2013·36.646 MB·English

by  Helmut Rennke MD, Bradley M. Denker MD

HELMUT G. RENNKE, M.D.
Professor of Pathology
Harvard Medical School and
Harvard–MIT Division of Health Sciences and Technology
Department of Pathology
Brigham & Women’s Hospital
Boston, Massachusetts
BRADLEY M. DENKER, M.D.
Associate Professor of Medicine
Harvard Medical School
Renal Division, Department of Medicine
Beth Israel Deaconess Medical Center
Chief of Nephrology
Harvard–Vanguard Medical Associates
Boston, Massachusetts
Acquisitions Editor: Crystal Taylor
Product Managers: Stacey Sebring, Angela Collins
Vendor Manager: Bridgett Dougherty
Manufacturing Coordinator: Margie Orzech
Marketing Manager: Joy Fisher-Williams
Graphic Designer: Stephen Druding
Compositor: Integra Software Services Pvt. Ltd.
Fourth Edition
Copyright © 2014 (2010, 2007, 1994) Lippincott Williams & Wilkins, a Wolters Kluwer business
351, West Camden Street Two Commerce Square; 2001 Market Street
Baltimore, MD 21201 Philadelphia, PA 19103
Printed in China
All rights reserved. This book is protected by copyright. No part of this book may be reproduced or
transmitted in any form or by any means, including as photocopies or scanned-in or other electronic copies,
or utilized by any information storage and retrieval system without written permission from the copyright
owner, except for brief quotations embodied in critical articles and reviews. Materials appearing in this book
prepared by individuals as part of their official duties as U.S. government employees are not covered by the
above-mentioned copyright. To request permission, please contact Lippincott Williams & Wilkins at Two
Commerce Square, 2001 Market Street, Philadelphia, PA 19103, via email at [email protected], or via
website at lww.com (products and services).
9 8 7 6 5 4 3 2 1
Library of Congress Cataloging-in-Publication Data
Rennke, Helmut G.
Renal pathophysiology : the essentials / Helmut G. Rennke, M.D., professor of pathology, Harvard Medical
School and Harvard-MIT Division of Health Sciences and Technology, Department of Pathology, Brigham &
Women’s Hospital, Boston, Massachusetts, Bradley M. Denker, M.D., associate professor of medicine, Harvard
Medical School, Renal Division, Department of Medicine, Beth Israel Deaconess Medical Center, chief of
nephrology, Harvard-Vanguard Medical Associates, Boston, Massachusetts. — Fourth edition.
pages cm
Includes bibliographical references and index.
ISBN 978-1-4511-7338-3
1. Kidneys--Pathophysiology. I. Denker, Bradley M. II. Title.
RC903.9.R672 2014
616.6'1—dc23
2013008378
DISCLAIMER
Care has been taken to confirm the accuracy of the information presented and to describe generally
accepted practices. However, the authors, editors, and publisher are not responsible for errors or omissions
or for any consequences from application of the information in this book and make no warranty, expressed
or implied, with respect to the currency, completeness, or accuracy of the contents of the publication.
Application of this information in a particular situation remains the professional responsibility of the
practitioner; the clinical treatments described and recommended may not be considered absolute and
universal recommendations.
The authors, editors, and publisher have exerted every effort to ensure that drug selection and dosage
set forth in this text are in accordance with the current recommendations and practice at the time of
publication. However, in view of ongoing research, changes in government regulations, and the constant
flow of information relating to drug therapy and drug reactions, the reader is urged to check the package
insert for each drug for any change in indications and dosage and for added warnings and precautions. This
is particularly important when the recommended agent is a new or infrequently employed drug.
Some drugs and medical devices presented in this publication have Food and Drug Administration
(FDA) clearance for limited use in restricted research settings. It is the responsibility of the health care
provider to ascertain the FDA status of each drug or device planned for use in their clinical practice.
The publishers have made every effort to trace the copyright holders for borrowed material. If they
have inadvertently overlooked any, they will be pleased to make the necessary arrangements at the first
opportunity.
To purchase additional copies of this book, call our customer service department at [phone] or fax
orders to [phone]. International customers should call [phone].
Visit Lippincott Williams & Wilkins on the Internet: http://www.lww.com. Lippincott Williams & Wilkins
customer service representatives are available from 8:30 am to 6:00 pm, EST.
To our families,
Stephanie and Christianne
Mary, Brendan, Jennifer, and Mackenzie
PREFACE
In this fourth edition of Renal Pathophysiology: The Essentials, we have main-
tained the general principles that guided us in the design and approach of
the last three versions of the book. Over these last years, we have received
many comments and suggestions not only from our second-year medical stu-
dents but also from house staff, nephrology fellows, and colleagues; we are
most grateful for their feedback and encouraging words. As a consequence
of these suggestions, we have expanded the sections on molecular aspects
of the mechanisms that result in kidney dysfunction and the morphologic
expression of the major diseases that affect the kidney; the illustrations are
now in full color and inserted into the text. The list of suggested readings has
been updated and summaries are included at the end of physiology chapters.
The core and the principal aim of this book remain unchanged: to provide
the student with a solid understanding of the mechanisms that result in kid-
ney dysfunction and disease and to serve as the basic reading material and
text for a course in kidney pathophysiology.
HGR and BMD
iv
CONTENTS
Preface iv
CHAPTER 1 Review of Renal Physiology 1
CHAPTER 2 Regulation of Salt and Water Balance 31
CHAPTER 3 Disorders of Water Balance: Hyponatremia,
Hypernatremia, and Polyuria 67
CHAPTER 4 Edematous States and the Use of Diuretics 97
CHAPTER 5 Acid–Base Physiology and Metabolic Alkalosis 124
CHAPTER 6 Metabolic Acidosis 153
CHAPTER 7 Disorders of Potassium Balance 174
CHAPTER 8 Urinalysis and Approach to the Patient with
Renal Disease 197
CHAPTER 9 Pathogenesis of Major Glomerular and Vascular
Diseases 217
CHAPTER 10 Tubulointerstitial Diseases 268
CHAPTER 11 Acute Renal Failure 295
CHAPTER 12 Progression of Chronic Renal Failure 315
CHAPTER 13 Signs and Symptoms of Chronic Renal Failure 339
Figure Credits 365
Index 369
v

1
Review of Renal
Physiology
Objectives
By the end of this chapter, you should have an understanding of each
of the following issues:
⬒ The general mechanisms by which solute reabsorption and secretion
occur in the different nephron segments.
⬒ The factors regulating the glomerular filtration rate.
⬒ The mechanisms by which the glomerular filtration rate is measured
in patients.
Introduction
Although readers of this book should have already completed a course on
normal renal physiology, a brief review of the basic principles involved is
helpful in understanding the mechanisms by which disease might occur.
Tubular functions will be discussed with a major emphasis on sodium
and water reabsorption. The glomerular filtration rate (GFR) including
its regulation and how it is estimated in the clinical setting will also be
reviewed.
1
2 Renal Pathophysiology: The essentials
The kidney performs two major functions:
■ It participates in the maintenance of a relatively constant extracellular
environment that is necessary for the cells (and organism) to function nor-
mally. This is achieved by excretion of some waste products of metabolism
(such as urea, creatinine, and uric acid) and of water and electrolytes that
are derived primarily from dietary intake. Balance or steady state is a key
principle in understanding renal functions. Balance is maintained by keep-
ing the rate of excretion equal to the sum of net intake plus endogenous
production:
Excretion = Net Intake + Endogenous production
As will be seen, the kidney is able to individually regulate the excretion
of water and solutes (such as sodium, potassium, and hydrogen) largely
by changes in tubular reabsorption or secretion. If, for example, sodium
intake is increased, the excess sodium can be excreted without requiring
alterations in the excretion of water or other electrolytes.
■ It secretes hormones that participate in the regulation of systemic and
renal hemodynamics (renin, angiotensin II, and prostaglandins), red cell
production (erythropoietin), and mineral metabolism [calcitriol, (1,25-OH
dihydroxy vitamin D), the major active metabolite of vitamin D].
The kidney also performs a number of miscellaneous functions such as
the catabolism of peptide hormones and the synthesis of glucose (gluconeo-
genesis) under fasting conditions.
Relationship between Filtration
and Excretion
The normal GFR ranges from 130 to 145 L/day (90 to 100 mL/min) in women
and from 165 to 180 L/day (115 to 125 mL/min) in men. This represents a vol-
ume that is more than 10 times that of extracellular fluid and approximately
60 times that of plasma (see Fig. 2.5 for estimation of these volumes); as a
result, survival requires that virtually all of the filtered solutes and water be
returned to the systemic circulation by tubular reabsorption.
Preventing excessive urinary sodium loss is essential to maintenance
of the extracellular and plasma volumes (see Chapter 2). Figure 1.1 shows
the organization of the nephron, and Table 1.1 lists the relative contri-
bution of the different nephron segments to the reabsorption of filtered
sodium and the neurohumoral factors involved in regulating transport
at that site. The bulk of the filtered sodium is reabsorbed in the proxi-
mal tubule and loop of Henle; however, day-to-day regulation primarily
occurs in the collecting ducts, where the final composition of the urine is
determined.