The Kidney and Body Fluids in Health and Disease

Transcription

1 The Kidney and Body Fluids in Health and Disease

2 The Kidney and Body Fluids in Health and Disease Edited by SAULO KLAHR, M.D. Washington University School of Medicine St. Louis, Missouri SPRINGER SCIENCE+BUSINESS MEDIA, LLC

3 Main entry under title: Library of Congress Cataloging in Publication Data The Kidney and body fluids in health and disease. Includes bibliographies and index. 1.Kidneys-Diseases. 2. Body fluid disorders. 3. Kidneys. I. Klahr, Saulo. [DNLM: 1. Body fluids. 2. Kidney-Physiology. 3. Kidney diseases - Physiopathology. 4. Water-electrolyte balance. 5. Water-electrolyte imbalance - Physiopathology. W] 300 K 455] RC903.K ' ISBN ISBN (ebook) DOI / Springer Science+Business Media New York Originally published by Plenum Publishing Corporation in 1983 Softcover reprint of the hardcover 1st edition 1983 All rights reserved No part of this book may be reproduced, stored in a retrieval system, or transmitted in any form or by any means, electronic, mechanical, photocopying, microfilming, recording, or otherwise, without written permission from the Publisher

4 This book is dedicated to the memory of Dr. Carl V. Moore Chairman, Department of Internal Medicine Washington University School of Medicine St. Louis, Missouri

5 Contributors Elsa Bello-Reuss, M.D., Assistant Professor of Medicine, Departments of Medicine, and Physiology and Biophysics, Washington University School of Medicine and The Jewish Hospital of St. Louis, St. Louis, Missouri John Buerkert, M.D., Associate Professor of Medicine, Department of Medicine, Washington University School of Medicine and The Jewish Hospital of St. Louis, St. Louis, Missouri Barbara R. Cole, M.D., Associate Professor of Pediatrics, Department of Pediatrics, Washingtor. University School of Medicine, St. Louis, Missouri James A. Delmez, M.D., Assistant Professor of Medicine, Department of Medicine, Washington University School of Medicine, St. Louis, Missouri Jeffrey Freitag, M.D., Chief Medical Resident, Department of Medicine, Washington University School of Medicine, St. Louis, Missouri Present address: Saginaw General Hospital, Saginaw, Michigan Herschel R. Harter, M.D., Associate Professor of Medicine, Department of Medicine, Washington University School of Medicine, St. Louis, Missouri Phillip Hoffsten, M.D., Assistant Professor of Medicine, Department of Medicine, Washington University School of Medicine, St. Louis, Missouri 6311 O. Present address: Medical Associates Clinic, Pierre, South Dakota Keith Hruska, M.D., Associate Professor of Medicine, Department of Medicine, Washington University School of Medicine and The Jewish Hospital of St. Louis, St. Louis, Missouri Saulo Klahr, M.D., Professor of Medicine, Department of Medicine, Washington University School of Medicine, St. Louis, Missouri vii

6 viii Contributors Kevin Martin, M.D., Assistant Professor of Medicine, Department of Medicine, Washington University School of Medicine, St. Louis, Missouri Aubrey R. Morrison, M.D., Assistant Professor of Medicine and Pharmacology, Departments of Medicine and Pharmacology, Washington University School of Medicine, St. Louis, Missouri Luis Reuss, M.D., Professor of Physiology and Biophysics, Department of Physiology and Biophysics, Washington University School of Medicine, St. Louis, Missouri Alan M. Robson, M.D., Professor of Pediatrics, Department of Pediatrics, Washington University School of Medicine, St. Louis, Missouri Hector J. Rodriguez, M.D., Ph.D., Assistant Professor of Medicine, Department of Medicine, Washington University School of Medicine, St. Louis, Missouri Present address: 9400 Brighton Way, Beverly Hills, California Eduardo Slatopolsky, M.D., Professor of Medicine, Department of Medicine, Washington University School of Medicine, St. Louis, Missouri Andres J. Valdes, M.D., Clinical Assistant Professor of Pathology and Associate Pathologist and Director of Clinical Immunology, Department of Pathology, Washington University School of Medicine and St. John's Mercy Medical Center, St. Louis, Missouri 63110

7 Preface This volume was designed as a text for medical students, house officers, and even clinicians. It deals with the most common problems in nephrology, providing new insight into how to improve clinical skills. A comprehensive overview of renal physiology and electrolyte disorders lays the groundwork for a clear presentation of the pathophysiological principles that underlie these disorders and a step-by-step presentation of the mechanisms behind the signs and symptoms of kidney failure. The origins of this book can be traced to the teaching of a Renal Pathophysiology course at the Washington University School of Medicine, beginning in the mid-1960s. When changes in the medical school curriculum took place in the early 1970s, an effort was made to synthesize the minimum core curriculum for sophomore medical students, and the distillation of "essential material" to be covered in the area of renal pathophysiology led to the development of the first edition of a renal syllabus. This syllabus has been used in our department since 1974, and, following some of the recommendations and critiques of students and faculty, it has been entirely reworked many times to improve its effectiveness and value. This book is a direct extension of that syllabus, integrated with contributions from faculty members in our Renal Division, and expanded to include a section on therapy in most chapters. It is our hope that this format will serve the needs of not only sophomore and senior medical students, but also house officers, nephrology fellows, and clinicians. The book is divided into seven sections. Section I describes the basic concepts of fluid, electrolyte, and renal physiology and comprises three chapters entitled "Introduction to the Physiology of Body Fluids," "Homeostatic and Excretory Functions of the Kidney," and "Nonexcretory Functions of the Kidney." The second section discusses the pathophysiology of fluid and electrolyte disorders, including the regulation of volume sodium metabolis!ll, the development of edema and edema-forming states, the pathophysiological basis for alterations in water balance, the pathophysiology of potassium metabolism, the pathophysiology of acid-base metabolism, and ix

8 x Preface the pathophysiology of calcium, magnesium, and phosphorus metabolism. Section III comprises a single chapter devoted to the pathophysiology of hypertension. Section IV, "Pathophysiology of Proteinuric Renal Disease," is divided into two chapters, "Proteinuria and the Nephrotic Syndrome" and "Pathology and Pathophysiology of Proteinuric Glomerular Disease." Section V, "Renal Failure," contains chapters on the pathophysiology of acute renal failure, the pathophysiology of chronic renal failure, and the pathophysiological principles underlying the treatment of patients with renal failure. Section VI contains a single chapter, "Pathophysiology of Nephrolithiasis," and Section VII discusses renal pharmacology. Every attempt has been made to make the chapters uniform. No attempt has been made to be comprehensive and exhaustive, but we believe that most of the fundamental developments in each field have been included. All the authors of this book are or have been affiliated with the Washington University School of Medicine; most of them have been long-standing members of the Division of Pediatric or Renal Medicine at Washington University, a fact that greatly facilitated the writing and editing of this book. We hope that our readers will find this volume useful, and look forward to their constructive criticism for use in future editions. Saulo Klahr, M.D.

9 Contents I. Basic Concepts of Fluid, Electrolyte, and Renal Physiology 1. Introduction to the Physiology of Body Fluids Luis Reuss and Elsa Bello-Reuss I. Homeostasis of Water and Electrolytes: An Overview II. Body Water: Volume and Distribution... 4 III. Ionic Composition of Body Fluids... 6 A. Ionic Composition of the Main Two Subcompartments of the Extracellular Fluid... 7 B. Ionic Composition of the Intracellular Fluid C. Osmolality of Body Fluids... 8 IV. Balance of Water and Electrolytes... 9 A. Concept of Balance... 9 B. Pathways of Gains and Losses... 9 C. Overview of the Mechanisms of Regulation of Salt and Water Balance V. Barriers for Water and Ion Distribution A. Properties of the Cell Membrane as Related to Water and Electrolyte Metabolism B. Properties of the Capillary Endothelium as Related to Water and Electrolyte Metabolism C. Properties of Epithelia as Related to Water and Electrolyte Metabolism Appendix: Membrane Transport Processes (Luis Reuss) A. Introduction B. Downhill Transport C. Uphill Transport D. Effects of Concentration Differences across Biological Membranes: Gibbs-Donnan Equilibrium and Membrane Potentials Suggested Readings xi

10 xii Contents 2. Homeostatic and Excretory Functions of the Kidney Elsa Bello-Reuss and Luis Reuss I. Introduction A. Renal Homeostatic Function B. Renal Excretory Function C. Overview of Glomerular Filtration and Tubular Transport. 36 II. Quantitative Analysis of Renal Function A. Clearance B. VIP Concentration Ratio C. Osmolar Clearance D. Kinetics of Transport by the Renal Tubule: T m and Gradient-Time Limited Transport III. Renal Hemodynamics A. Magnitude and Measurement of Renal Blood Flow B. Autoregulation of Renal Blood Flow C. Neurogenic Control of Renal Blood Flow IV. Glomerular Filtration A. Mechanism of Glomerular Filtration B. Measurement of Glomerular Filtration Rate C. Perm selectivity of the Glomerular Capillary Wall D. Structural Basis of Glomerular Filtration V. Tubular Transport A. Introduction B. Proximal Tubule C. Loop of Henle D. Distal Nephron (Distal Convoluted Tubule, Cortical Collecting Tubule, and Medullary Collecting Duct) E. Summary of Renal Tubule Transport Mechanisms Suggested Readings Nonexcretory Functions of the Kidney Saulo Klahr I. Introduction II. Substrate Utilization by the Kidney III. Carbohydrate Metabolism A. Glucose: Oxidative and Anaerobic Glycolysis B. Hexose-Monophosphate Shunt C. Glucose-Xylulose Pathway D. Renal Gluconeogenesis E. Control of Renal Gluconeogenesis in Vivo F. The Role of the Kidney in the Maintenance of Glucose Homeostasis IV. Lipid Metabolism... 69

11 Contents xiii V. Renal Metabolism of Plasma Protein and Peptide Hormones 70 A. Renal Handling of Intermediate and High-Molecular- Weight Proteins B. Products of Renal Protein Catabolism C. Peritubular Uptake of Plasma Proteins D. Kidney Metabolism of Peptide Hormones VI. Role of the Kidney in the Regulation of Vitamin D Metabolism 74 A. The 1,25-Dihydroxy Vitamin D B. The 24-Hydroxylated D Vitamins C. Alterations of Vitamin D Levels in Disease States VII. Role of the Kidney in the Regulation of Red Blood Cell Mass: Erythropoietin VIII. The Hormonal Role of the Kidney in the Regulation of Extracellular Fluid Volume and Blood Pressure A. The Renin-Angiotensin-Aldosterone System B. Factors Affecting Renin Release C. Pathophysiology of the Renin-Angiotensin System D. The Kallikrein-Bradykinin System E. Renal Prostaglandins F. Neutral Lipids G. Pathophysiology IX. Summary Suggested Readings II. Pathophysiology of Fluid and Electrolyte Disorders 4. Pathophysiology of Volume Regulation and Sodium Metabolism Elsa Bello-Reuss I. Sodium Balance and Extracellular Fluid Volume II. Renal Regulation of Sodium Balance A. General Considerations B. Control of Glomerular Filtration Rate C. Control of Tubular Sodium Reabsorption III. Sodium Depletion and ECF Volume Contraction A. Mechanisms of Production of Negative Sodium Balance B. Pathophysiological Consequences of Negative Sodium Balance (Sodium Depletion) IV. Positive Na Balance and ECF Volume Expansion A. Mechanisms of Production of Positive Sodium Balance B. Pathophysiological Consequences of Positive Sodium Balance Suggested Readings

12 xiv Contents 5. Edema and Edema-Forming States Alan M. Robson I. Introduction II. Normal Physiology A. Regulation of Body Fluid Spaces B. Characteristics of Peripheral Capillaries C. Interstitial Fluid Sodium III. Edema Formation A. General Considerations B. Causes of Edema IV. Treatment of Edema A. General Approach B. Increasing Urinary Salt and Water Losses C. Restriction of Sodium and Water Intakes D. Special Therapeutic Approaches to Specific Disease States Suggested Readings The Pathophysiologic Bases for Alterations in Water Balance John Buerkert I. Physiologic Considerations A. Mechanisms Involved in the Control of Thirst B. Mechanisms Which Control Antidiuretic Hormone Release. 153 C. Renal Regulation of Water Excretion II. Pathophysiologic Considerations A. Hyponatremia B. Hypernatremia Suggested Readings Pathophysiology of Potassium Metabolism Hector J. Rodriguez and Saulo Klahr I. Introduction II. Regulation of ECF Potassium Concentration A. ECF ph B. Renal Tubular Function III. Hypokalemia A. Clinical Manifestation of Hypokalemia B. Differential Diagnosis of Hypokalemia C. Management of Hypokalemia IV. Hyperkalemia A. Differential Diagnosis of Hyperkalemia B. Management of Hyperkalemia Suggested Readings

13 Contentll xv 8. Pathophysiology of Acid-Base Metabolism Keith Hruska I. Introduction II. Chemistry of Acids and Bases III. Extracellular Buffers and Function of the Bicarbonate-C0 2 System as a Physiologic Buffer IV. Intracellular Buffering A. Bone as a Buffer Source V. Physiology of Acid-Base Regulation A. Renal Excretion of Hydrogen B. Regulation of Renal Hydrogen Ion Excretion VI. Control of Ventilation VII. Characteristics of Acid-Base Disorders A. Metabolic Acidosis B. Metabolic Alkalosis C. Respiratory Acidosis D. Respiratory Alkalosis E. Mixed Acid-Base Disorders VIII. Metabolic Acidosis A. Extracellular Buffering B. Intracellular Buffering and the Plasma Potassium Concentration C. Respiratory Compensation D. Renal Hydrogen Excretion E. Causes of Metabolic Acidosis F. Acidosis of Chronic Renal Failure G. Renal Tubular Acidosis H. Principles of Treatment for Metabolic Acidosis IX. Metabolic Alkalosis A. Respiratory Compensation to Metabolic Alkalosis B. Etiology of Metabolic Alkalosis X. Respiratory Acidosis A. Acute Respiratory Acidosis B. Chronic Respiratory Acidosis XI. Respiratory Alkalosis A. Chronic Respiratory Alkalosis Suggested Readings Pathophysiology of Calcium, Magnesium, and Phosphorus Metabolism Eduardo Slatopolsky I. Calcium A. Introduction B. Hypercalcemia C. Hypocalcemia

14 XVI Contents II. Magnesium A. Introduction B. Hypomagnesemia C. Hypermagnesemia III. Phosphate A. Introduction B. Hyperphosphatemia C. Hypophosphatemia IV. Treatment of Disorders of Calcium, Phosphate, and Magnesium Metabolism A. Treatment of Disorders of Calcium Metabolism B. Treatment of Disorders of Phosphate Metabolism C. Treatment of Alterations in Magnesium Metabolism Suggested Readings III. Pathophysiology of Hypertension 10. Pathophysiology of Hypertension Herschel R. Harter I. Introduction II. Essential Hypertension A. Alterations in Plasma Volume B. Alterations in Cardiac Output C. Alterations in Renal Function in Essential Hypertension D. Neurogenic Factors E. Increased Vascular Resistance F. Other Factors... '.' III. Secondary Causes of Hypertension A. Hypertension Associated with Renal Insufficiency B. Hypertension Associated with Endocrine Abnormalities IV. Low-Renin Hypertension V. High-Renin Hypertension VI. Mechanisms of Vascular Damage Secondary to Hypertension VII. Therapeutic Considerations in the Hypertensive Patient A. Diuretics B. Drugs Affecting the Sympathetic Nervous System Suggested Readings IV. Pathophysiology of Proteinuric Renal Disease 11. Proteinuria and the Nephrotic Syndrome Alan M. Robson I. Introduction II. Physiology of Renal Protein Handling

15 Contents xvii A. Glomerular Filtration of Proteins B. Tubular Reabsorption of Proteins.... C. Tubular Secretion of Proteins.... III. Normal Proteinuria.... A. Quantitative Aspects.... B. Qualitative Aspects.... IV. Pathologic Proteinuria.... A. Intermittent Proteinuria.... B. Postural Proteinuria.... C. Persistent Proteinuria.... D. Consequences of Proteinuria.... E. Clinical Evaluation of Proteinuria.... V. Treatment.... A. Treatment of Primary Disease.... B. Symptomatic Treatment.... Suggested Readings Pathology and Pathophysiology of Proteinuric Glomerular Disease Barbara R. Cole and Andres J. Valdes I. Introduction II. Immunofluorescence Techniques III. Characteristic Glomerular Alterations Demonstrable by Electron Microscopy IV. Pathogenesis of Glomerular Diseases V. Experimental Glomerular Injury Mediated by Soluble Immune Complexes A. Exogenous Antigen B. Autologous Antigen VI. Experimental Glomerular Injury Mediated by in Situ Immune Complex Formation VII. Experimental Glomerular Injury Mediated by Antibodies to Glomerular Basement Membrane A. Nephrotoxic Nephritis (Masugi Nephritis) B. Autoimmune Anti-Glomerular Basement Membrane Nephritis (Steblay Nephritis) VIII. Pathogenesis of Human Glomerulonephritis IX. Human Glomerular Injury Mediated by Immune Complexes X. Human Glomerular Injury Mediated by Antibodies to Glomerular Basement Membrane XI. Pathogenesis of Human Glomerular Diseases Other Than Glomerulonephritis XII. Pathogenesis of Interstitial Nephritis XIII. Morphologic Patterns of Glomerular Injury A. Diffuse Proliferative B. Focal Proliferative C. Mesangiopathic

16 xviii Contents D. Focal Sclerosis E. Membranous.... F. Membranoproliferative.... G. Crescentic.... H. Subendothelial Fibrin Deposition.... I. End Stage.... J. Miscellaneous Alterations.... XIV. Pathophysiology of Glomerular Disease.... A. Asymptomatic Hematuria and/or Proteinuria.... B. The Symptom Complex of Acute Glomerulonephritis.... C. The Symptom Complex of Chronic Glomerulonephritis.... D. Nephrotic Syndrome.... XV. Clinicopathologic Correlations.... A. Diffuse Proliferative Glomerulonephritis.... B. Focal Proliferative Glomerulonephritis.... C. Membranoproliferative Glomerulonephritis-Types I, II, and III.... D. Crescentic Glomerulonephritis.... E. Membranous Glomerulonephritis.... F. Minimal-Change Nephrotic Syndrome.... G. Focal Sclerosing Glomerulopathy.... H. Glomerulopathy of Systemic Disease.... I. Glomerulopathy of Congenital and Hereditary Disease.... J. Glomerulopathy of Renal Transplantation.... K. Interstitial Nephritis.... L. Treatment of Glomerular Disease.... Sugge~ed Readings V. Renal Failure 13. Pathophysiology of Acute Renal Failure Kevin Martin I. Introduction II. Causes of Acute Renal Failure III. Pathophysiology A. Ischemic, Nephrotoxic, and Pigment Release Acute Renal Failure B. Integration of Experimental Data C. Inflammatory Acute Renal Failure D. Acute Renal Failure Related to Pregnancy E. Hepatorenal Syndrome F. Major Renovascular Disease G. Acute Uric Acid Nephropathy

17 Contents xix H. Hypercalcemic Nephropathy I. Ureteral Obstruction IV. Differential Diagnosis of Acute Renal Failure V. Clinical Consequences of Acute Renal Failure VI. Clinical Course of Acute Intrinsic Renal Failure VII. Management VIII. Prognosis IX. Summary Suggested Readings Pathophysiology of Chronic Renal Failure Phillip HoJJsten and Saulo Klahr I. Introduction A. Incidence and Prevalence of Renal Disease B. Nature of the Kidney Adaptations in Chronic Renal Disease 465 C. Limitations in Renal Function in Chronic Kidney Disease II. Consequences of Chronic Renal Failure A. Water Excretion B. Sodium Excretion C. Potassium Excretion D. Acid-Base Balance E. Magnesium F. Phosphate and Calcium III. Systemic Involvement in Chronic Renal Disease A. Hematological Disorders B. Cardiopulmonary Complications C. Hypertension... ; D. Neurological-Muscular Abnormalities E. Gastrointestinal Disturbances F. Immunologic and Infectious Complications G. Renal Osteodystrophy H. Nutritional and Metabolic Alterations I. Endocrine Alterations IV. The Uremic Syndrome: Description of Pathogenesis A.Uremic Toxins B. Accumulation of Peptide Hormones C. Deficiency of Essential Compounds V. Rate of Progression of Chronic Renal Failure and Consideration of Reversible Factors Which May Accelerate the Progression of Chronic Renal Failure VI. Causes of Acute Deterioration in Renal Function A. Inadequate Renal Blood Flow B. Urinary Tract Obstruction C. Infection D. Hypercalcemia

18 xx Contents E. Hyperuricemia Suggested Readings Pathophysiological Principles in the Treatment of Patients with Renal Failure James A. Delmez I. Introduction II. Principles of Conservative Therapy, Dialysis, and Transplantation A. Description of Hemodialysis and Determinants of Mass Transport B: Description of Peritoneal Dialysis and Mass Transport Characteristics C. Description of Renal Transplantation III. Effects of Treatment on Specific Pathophysiological Alterations in Renal Failure A. Treatment of Pathophysiological Alterations of Sodium and Water in Renal Failure B. Effects of Treatment on the Pathophysiology of Potassium in Renal Failure C. Effects of Treatment on Acid-Base Pathophysiology in Renal Failure D. Effects of Treatment on the Anemia of Renal Failure E. Effects of Treatments on the Hypertension of Renal Failure 509 F. Effects of Treatment on the Renal Osteodystrophy of Renal Failure G. Effects of Treatment on the Lipoprotein Abnormalities of Renal Failure H. Effects of Dialysis on the Carbohydrate Abnormalities of Renal Failure I. Effects of Dialysis on the Alterations of Protein Metabolism in Renal Failure J. Summary Suggested Readings VI. Pathophysiology of Nephrolithiasis 16. Pathophysiology of Nephrolithiasis Jeffrey Freitag and Keith Hruska I. Introduction II. Description of Terms... ; A. Crystals (Crystalluria) B. Stones

19 Contents xxi III. Physical Chemistry of Stone Formation A. Supersaturation of Urine B. Inhibitors of Supersaturation in Urine C. Promoters of Crystallization and Crystal Growth IV. Types of Urolithiasis A. Calcium Urolithiasis B. Oxalate Urolithiasis C. Uric Acid Urolithiasis D. Magnesium Ammonium Phosphate Urolithiasis E. Cystine Urolithiasis V. Treatment of Urolithiasis A. General Principles B. Specific Modalities of Therapy VI. Conclusion: Summary of Pathogenesis Suggested Readings VII. Renal Pharmacology 17. Renal Pharmacology Aubrey R. Morrison I. The Kidney and Pharmacokinetics A. Bioavailability B. Route of Administration C. Distribution D. Protein Binding E. Drug Elimination by the Kidney F. Clearance G. Tubular Secretion H. Clearance by Dialysis I. Drug Metabolism J. Drug Regimen in Renal Disease II. Drug Nephrotoxicity A. Direct Toxicities B. Immunological III. Diuretics A. Possible Renal Mechanisms of Action of Diuretics IV. Miscellaneous Drugs with Renal Action A. Probenecid B. Drugs Affecting Uric Acid Handling C. Drugs Affecting Prostaglandin Biosynthesis Sugge~ed Readings Index