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Seldin and Giebisch's The Kidney
Physiology and Pathophysiology
- 5th Edition - December 31, 2012
- Editors: Robert J. Alpern, Michael J. Caplan, Orson W. Moe
- Language: English
- eBook ISBN:9 7 8 - 0 - 1 2 - 3 8 1 4 6 3 - 0
A classic nephrology reference for over 25years, Seldin and Giebisch’s The Kidney, is the acknowledged authority on renal physiology and pathophysiology. In this 5th edition… Read more
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Request a sales quoteA classic nephrology reference for over 25years, Seldin and Giebisch’s The Kidney, is the acknowledged authority on renal physiology and pathophysiology. In this 5th edition, such new and powerful disciplines as genetics and cell biology have been deployed to deepen and widen further the explanatory framework. Not only have previous chapters been extensively updated, but new chapters have been added to incorporate additional disciplines. Individual chapters, for example, now provide detailed treatment of the significance of cilia; the role of stem cells is now given special consideration. Finally, there has been a significant expansion of the section of pathophysiology, incorporating the newer findings of cell biology and genetics. If you research the development of normal renal function or the mechanisms underlying renal disease, Seldin and Giebisch’s The Kidney is your number one source for information.
- Offers the most comprehensive coverage on the market of fluid and electrolyte regulation and dysregulation in 85 completely revised chapters and 10 new chapters
- Includes 4sections, 62 chapters, devoted to regulation and disorders of acid-base homeostasis, and epithelial and nonepithelial transport regulation
- Includes foreword by Donald Seldin and Gerhard Giebisch, world renowned names in nephrology and editors of the previous three editions
Academic and medical librarians in kidney physiology, nephrology and renal medicine. This will also serve as an excellent reference for clinical nephrologists and trainees, graduate students, researchers, academic clinicians and any pharmaceutical company working on renal medications
Dedication
Foreword
Preface
List of Contributors
List of Contributors
Volume 1
I: Epithelial and Nonepithelial Transport and Regulation
Chapter 1. Epithelial Cell Structure and Polarity
Introduction
Epithelial Cell Structure: Morphology and Physiology
Biogenesis of Epithelial Polarity
Acknowledgments
References
Chapter 2. Mechanisms of Ion Transport across Cell Membranes
Introduction
Mechanisms of ion TRANSPORT
Ion Transport PROTEINS
References
Chapter 3. Renal Ion-Translocating ATPases
P-ATPases
Structure and Function of Ca2+-ATPases (SERCA and PMCA)
Structure of Na,K-ATPase and H,K-ATPase
Properties of Na,K-ATPase and H,K-ATPase
Regulation of Na,K-ATPase
New Physiological Functions of Na,k-ATPase
Na,K-ATPase in the Kidney
H,K-ATPases in Kidney
Structure and Mechanism of Action of V-ATPases
References
Chapter 4. Mechanisms of Water Transport Across Cell Membranes and Epithelia
Introduction
Basic Principles
Water Transport Across the Cell Membrane
Water Transport in Epithelia
References
Chapter 5. Cell Volume Control
Cell Volume Regulatory Mechanisms
Challenges and Functions Affecting Cell Volume
References
Chapter 6. Solute Transport, Energy Consumption, and Production in the Kidney
Introduction
Energy Consumption
Metabolic Basis in the Kidney
Coupling of Transport and Metabolism in the Kidney
NA+,K+-ATPase
Pathophysiological States in Energy Production in the Kidney
Conclusions
References
Chapter 7. Electrophysiological Analysis of Transepithelial Transport
Introduction
Transepithelial Measurements
Conclusions
Intracellular Measurements
Conclusions
Parameters Measured on Single Channels
Number of Channels
Open and Closed Times
Application to Epithelia
Noise Analysis
Conclusions
Appendix 1 The Basic Equations for the General Equivalent Circuit
Relation Between the Real Change in EMF and the Measured Change in Potential
Equations for Partial Ionic Conductance
Contribution of the Electrogenic Na-K Pump to the Membrane Potential
References
Chapter 8. Renal Ion Channels, Electrophysiology of Transport, and Channelopathies
Structure–Function of Tubule Epithelium
Ion Channels: Biophysical Properties
Function of Renal Ion Channels
Ion Channel Structure
Tubulopathies Resulting from Changes in Channel Biophysical Properties
Acknowledgments
References
Chapter 9. Microvascular Permeability and the Exchange of Water and Solutes Across Microvascular Walls
Introduction
Microvascular Permeability
The Exchange of Fluid and Solutes by Convection and Diffusion through Microvascular Walls
References
Chapter 10. External Balance of Electrolytes and Acids and Alkali
Principles of Electrolyte Balance
Why is Balance Always Restored?
Is the Capacity of any System Always Limited?
Speed of Balance Restoration
Mechanism of Balance Restoration
Models of External Balance
Infinite Gain Control Mechanism
Common Misconceptions and New Insights
Clinical Application of External Balance
External Balance of Protons
Measurement of Net Acid Excretion
Sources of Acid
Gi Absorption of Acids and Alkali
Bone Buffering in Metabolic Acidosis
References
Chapter 11. Renal Cilia Structure, Function, and Physiology
Introduction
Cilia Ultrastructure and Components
Cilia Transport and Trafficking
Ciliogenesis
Cilia Signaling in the Nephron
Model Systems for the Study of Ciliogenesis and Cilia Disease
The Human Renal Ciliopathies
Concluding Remarks
References
Chapter 12. Intercellular Junctions
Tight Junctions
Gap Junctions and Connexin Hemichannels
Adherens Junctions and Desmosomes
References
Chapter 13. Principles of Cell Signaling
Introduction
Cell Surface Receptors
Intracellular Signaling Pathways
Examples of Signaling Effectors in the Kidney
References
Chapter 14. Scaffolding Proteins in Transport Regulation
PDZ-Proteins
Classes of PDZ Domains
Structural Basis for PDZ Interaction
Regulation of PDZ Binding
Polarized Expression of PDZ Proteins in Epithelial Cells
MAGUKs, the Archetypal PDZ Scaffolds
Form and Function of PDZ Protein Families in the kidney
Basolateral Membrane PDZ Protein Complexes
Common Properties of AKAP Proteins
Conclusion
References
Chapter 15. The Renin–Angiotensin System
The Components of the renin–angiotensin System
Regulation of Renin
Renal Epithelial Actions of the RAS
References
Chapter 16. Neural Control of Renal Function
Renal Sympathetic Nerves
Neuroanatomy, Pharmacology, and Physiology
Physiology
Control of the Renal Circulation
Control of Renal Tubular Solute and Water Transport
Neural Control of Renin Release
Integration of Renal Nerve Activity and Function
Afferent Renal Sensory Nerves
Neuroanatomy
Renorenal Reflexes
Summary
Acknowledgments
References
Chapter 17. Eicosanoids and Renal Function
Cellular Origin of Eicosanoids
Cyclooxygenase Derived Prostanoids
Lipoxygenase Derived Eicosanoids: 5-, 12-, and 15-HETEs and Leukotrienes
Cytochrome P450 Monooxygenase-Derived Eicosanoids: 20-HETE and EETs
Summary
References
Chapter 18. Extracellular Nucleotides and Renal Function
P2 Receptors
P2 Receptors and Renal Function
Concluding Remarks
Acknowledgments
References
Chapter 19. Paracrine Regulation of Renal Function by Dopamine
II: Structural and Functional Organization of the Kidney
Chapter 20. Structural Organization of the Mammalian Kidney
Kidney types and Renal Pelvis
Renal Vasculature
Nephrons and Collecting Duct System
Interstitium
Periarterial Connective Tissue and Lymphatics
Nerves
Topographical Relationships
Glomerulus (Renal Corpuscle)
Structural Organization of Renal Electrolyte Transporting Epithelia
Proximal Tubule
Thin Limbs of Henle’s Loop (Intermediate Tubule)
Thick Ascending Limb of Henle’s Loop
Segments Downstream of the Tal: Distal Convoluted Tubule, Connecting Tubule, and Collecting Duct
Architectural–Functional Relationships
The Renal Medulla
Conclusion
References
Chapter 21. Biophysical Basis of Glomerular Filtration
Introduction
The Magnitude of Renal Blood Flow and Glomerular Filtration
Glomerular Hemodynamics by Inference
Glomerular Hemodynamics and Micropuncture
The Filtration Barrier and Filtration of Macromolecules
Summary
Acknowledgment
References
Chapter 22. Glomerular Cell Biology
Cell Biology of the Glomerulus
Glomerular Endothelial Cells
Mesangial Cells
The Glomerular Basement Membrane
Podocytes
Glomerular Parietal Epithelium
The Glomerular Filtration Barrier
References
Chapter 23. Function of the Juxtaglomerular Apparatus: Control of Glomerular Hemodynamics and Renin Secretion
Cellular Elements of the Juxtaglomerular Apparatus (JGA)
Macula Densa Control of Vascular Tone
Macula Densa Control of Renin Secretion
Acknowledgment
References
Chapter 24. Renal Cortical and Medullary Microcirculations: Structure and Function
Anatomy of the Renal Circulation
Transport Functions and Properties
Intrarenal Hematocrit
Methods for Measurement of Regional Blood flow to the Cortex and Medulla
Methods for Direct Measurements of Microvessel Reactivity
Vasoactivity of the Renal Microcirculation: Ion Channel Architecture
Regulation of Blood flow and Microvessel Contraction
Acknowledgments
References
Chapter 25. Molecular and Cellular Mechanisms of Kidney Development
Overview
Development of the Metanephros
Experimental Approaches to Kidney Development
Molecular Approaches to Kidney Development
Transcription Factors in Metanephrogenesis
Ureteric Bud Outgrowth from the Wolffian Duct
Ureteric Bud Branching Morphogenesis
Tubulogenesis after Induction of the Metanephric Mesenchyme
Vascular and Glomerular Development
Termination of Kidney Development
Acknowledgments
References
Chapter 26. Molecular and Cellular Mechanisms of Glomerular Capillary Development
Glomerular Morphogenesis
Origin of the Glomerular Endothelium
Endothelial Cell Recruitment and Differentiation
Development of the Mesangium
Factors Regulating Podocyte Differentiation
Formation of the Slit Diaphragm Complex
Developmental-Organizational Role of the Glomerular Basement Membrane
Receptors and Receptor-Associated Proteins Mediating Glomerular cell Interactions with The GBM
Concluding Remarks
Acknowledgments
References
Chapter 27. Postnatal Renal Development
Renal Blood Flow and Glomerular Filtration Rate
Sodium Chloride Transport
Regulation of Sodium Transport
Renal Acidification
Induction of Nephron Maturation
Phosphate Transport
Potassium Transport
Urinary Concentrating and Diluting Ability
References
Chapter 28. Renal Hyperplasia and Hypertrophy
Introduction
Measurement of Cell Growth
Cell Cycle and Cell Cycle Regulatory Proteins
Hyperplasia: An Increase in Cell Number Due to Proliferation
Hypertrophy
Tubular Hypertrophy
Conclusions
References
Chapter 29. Stem Cells and Generation of New Cells in the Adult Kidney
III: Fluid and Electrolyte Regulation and Dysregulation
Chapter 30. Epithelial Na+ Channels
Introduction
ENaC Structure and Function
ENaC Regulation
ENaC and Human Disorders
References
Chapter 31. Anion Channels
Introduction
Major Classes of Identified Anion Channels
Anion Channelopathies of the Kidney
Summary
References
Chapter 32. Physiology and Pathophysiology of the NaCl Co-Transporters in the Kidney
Introduction
The Physiology of NaCl Co-Transporters in the Kidney
Molecular Biology of the Sodium-Dependent Chloride Co-Transporters
Functional Properties
Structure–Function Relationships
Regulation of Sodium Cation-Coupled Co-Transporters
The Role of the Sodium-Coupled Cation Chloride Co-Transporters in Inherited Disease
Potential Role in Polygenic Diseases
Acknowledgments
References
Chapter 33. Sodium and Chloride Transport: Proximal Nephron
Introduction
Epithelial Function
The Transcellular Pathway
The Paracellular Pathway
Regulation of Proximal NaCl Transport
Perspective
Acknowledgment
References
Chapter 34. Sodium Chloride Transport in the Loop of Henle, Distal Convoluted Tubule, and Collecting Duct
Introduction
Anatomic Considerations
Na+ Transport in the Loop of Henle
Na+ Transport in Distal Convoluted Tubule
Na+ Transport in the Connecting Tubule and Collecting Duct
References
Chapter 35. Mineralocorticoid Action in the Aldosterone Sensitive Distal Nephron
Introduction
Sodium Transport Regulation by Aldosterone: Physiological and Biophysical Mechanisms
Sodium Transport Regulation by Aldosterone: Cellular and Molecular Mechanisms
Conclusion
Acknowledgment
References
Chapter 36. Inherited Disorders of Renal Salt Homeostasis: Insights from Molecular Genetics Studies
Introduction
Genetic Disorders Causing Hypertension
Genetic Disorders Causing Renal Salt Loss
Genetic Studies of Essential Hypertension in the General Population
New Insights into Basic Physiology, Prevention, and Therapeutics from Genetic Studies
References
Chapter 37. Natriuretic Hormones
Introduction
History of Atrial (Cardiac) Natriuretic Peptide Hormones
Family of Cardiac Natriuretic Hormones: Synthesis of Three Prohormones
Cardiac Peptide Hormones Originating from Atrial Natriuretic Peptide Prohormone
Origination of Peptide Hormones from Prohormones
Molecular Biology of the Cardiac Natriuretic Hormonal System
Processing of Atrial Natriuretic Peptide Prohormone in Kidney
Regulation of Atrial Natriuretic Peptide Prohormone Gene
Transgenic Knockout and/or Mice Overexpressing Atrial Natriuretic Peptide Prohormone Gene
Human Diseases with Upregulation of Atrial Natriuretic Peptide Prohormone Gene
Localization of Atrial Natriuretic Peptide Prohormone Gene on Chromosomes
Brain Natriuretic Peptide Prohormone Gene
Secretion of Cardiac Natriuretic Peptides
Biologic Effects of the Cardiac Natriuretic Hormones and Their Mechanisms of Action
Natriuretic Peptide Receptors A, B, and C
Degradation of Natriuretic Peptides by Kidney
Influence of Acute Renal Failure on Circulating Concentration of Cardiac Hormones
Hemodialysis
Renal Transplantation
Atrial Natriuretic Peptide Prohormone Gene Expression in Invertebrates and Plants
Protective and Therapeutic Effects of Cardiac and Renal Hormones in Acute Renal Failure
Treatment of other Diseases with Abnormal Blood Volume
Antiproliferative and Anti-Cancer Properties of Cardiac Natriuretic Hormones
Brain Natriuretic Peptide and C-Natriuretic have Less Significant Anti-Cancer Effects
The Kidney Hormone Urodilatin also has Anti-Cancer Effects
Cardiac Natriuretic Hormones Eliminate up to 80% of Human Pancreatic Adenocarcinomas in Vivo
Cardiac Hormones Eliminate Two-Thirds of Human Breast Cancers in Vivo without any Surgery
Cardiac and Kidney Hormones Eliminate up to 86% of Human Small-Cell Lung Cancers in Mice in Vivo
Anti-Cancer Mechanism Within Cancer Cells of the Cardiac Hormones
Cardiac Hormones’ Mechanism of Action: Inhibition of DNA Synthesis
Localization of Cardiac Hormones to the Nucleus of Pancreatic Adenocarcinomas
Summary and Future Directions
References
Chapter 38. Pathophysiology of Sodium Retention and Wastage
Introduction
Sodium Intake and Sodium Balance
Primary and Secondary Edema
Concept of Effective Arterial Blood volume
Congestive Heart Failure
Cirrhosis
Nephrotic Syndrome
Sodium-Wastage
References
Chapter 39. Physiology and Pathophysiology of Hypertension
Introduction
Blood Pressure Classification for Hypertension Treatment
Basic Physiology of Blood Pressure Regulation
Renal Mechanisms of Hypertension
Neural and Hormonal Mechanisms of Hypertension
Primary Essential Hypertension
Genetic Causes of Hypertension
Secondary Causes of Hypertension
Acknowledgments
References
Chapter 40. Physiology and Pathophysiology of Diuretic Action
Introduction
Osmotic Diuretics
Proximal Tubule Diuretics
Loop Diuretics
Renal Hemodynamics and Oxygenation
Distal Convoluted Tubule Diuretics
Potassium-Sparing Diuretics
Aquaretics (Vasopressin Receptor Antagonists)
General Principles of Diuretic Action
Diuretic Adaptations anD diuretic Resistance
Acknowledgments
References
Chapter 41. Aquaporin Water Channels in Mammalian Kidney
Introduction
Discovery of Aquaporin-1 (AQP1)
Structure and Function of Aquaporins
Distribution of AQP1 in Kidney and Other Tissues
AQP1 Deficiency
Additional Functions of AQP1
Aquaporins in Kidney
Aquaglyceroporins
Vasopressin Regulation of Kidney Aquaporins
Dysregulation of Renal Aquaporins in Water Balance Disorders
Urinary Concentrating Defects
Water Retention
Acknowledgments
References
Chapter 42. Thirst and Vasopressin
Introduction
Vasopressin and Related Peptides
Anatomy
Biosynthesis
Secretion
Assay
Regulation
Non-Osmotic
Other Influences
Distribution and Clearance
Actions
Renal Actions
Extrarenal Actions
Thirst
Anatomy
Regulation
Other Influences
Effects
Vasopressin and Thirst in Osmoregulation
References
Chapter 43. The Urine Concentrating Mechanism and Urea Transporters
Kidney Structure
Transport Properties of Individual Nephron Segments
Thin Descending Limb
GeneRal Features of Urinary Concentration and Dilution
Urine Concentrating Mechanism: History and Theory
Osmoprotective Osmolytes
Role of Urea
Long-Term Regulation of Urea Transporters
Urea Recycling
Development of Urine Concentrating Ability
Summary
Acknowledgments
References
Chapter 44. Hyponatremia
The Plasma Sodium Concentration and Body Fluid Tonicity
Physiologic Control of Water Excretion
Hypotonic Hyponatremia: Classification and Pathogenesis
Water Intoxication with Maximally Dilute Urine
Vasopressin-Independent Defects in Water Excretion
Vasopressin-Dependent Defects in water Excretion
Hemodynamic Causes of Vasopressin-Mediated Hyponatremia
Inappropriate Vasopressin Secretion (SIADH)
Adaptations to Hypotonic Hyponatremia
Rapid Correction of Hyponatremia and Osmotic Demyelination
Bone Disease in Hyponatremia
Treatment of Hypotonic Hyponatremia
Non-Hypotonic Hyponatremia
References
Chapter 45. Hypernatremic States
Regulation of Water Homeostasis
Defense Mechanisms Against Water Depletion
Cellular Response to Hypernatremia
Etiology of Hypernatremic States
Classification of Hypernatremia Based on Total Body Sodium
Clinical Features in Hypernatremia
Therapy for Hypernatremia
Clinical Studies and Outcome
References
Chapter 46. Polyuria and Diabetes Insipidus
Arginine Vasopressin
The Brattleboro Rat with Autosomal Recessive Neurogenic Diabetes Insipidus
Knockout Mice with Urinary Concentration Defects
Quantitating Renal Water Excretion
Clinical Characteristics of Diabetes Insipidus Disorders
Loss-of-Function Mutations of AVPR2
Loss-of-Function Mutations of Aqp2 (Omim 222000, 125800, 107777)
Complex Polyuropolydipsic Syndrome
Acquired Nephrogenic Diabetes Insipidus
Investigation of a Patient with Polyuria
Radioimmunoassay of AVP and other Laboratory Determinations
Magnetic Resonance Imaging in Patients with diabetes Insipidus
Treatment
Acknowledgments
References
Chapter 47. The Molecular Biology of Renal K+ Channels
Introduction
The Molecular Biology of ROMK, a Distal K+ Secretory Channel
Other Renal Potassium Channels
Summary and Conclusions
Acknowledgments
References
Chapter 48. Extrarenal Potassium Metabolism
Potassium Depletion and Repletion
Insulin
Glucagon
Catecholamines
Thyroid
Acid–Base
Aldosterone
Renal Failure
Magnesium
Drugs
Other Factors
References
Chapter 49. Regulation of K+ Excretion
Overview of K+ Distribution and Excretion–Internal and External Balance
Internal K+ Balance
External K+ Balance: The Role of the Kidney
Distal Convoluted Tubule Cell: Direction, Magnitude, and Mechanism of Transport
K+ Reabsorption
Control of Renal K+ Transport
Acknowledgments
References
Chapter 50. Physiopathology of Potassium Deficiency
Volume 2
Chapter 51. Clinical Disorders of Hyperkalemia
Introduction
Regulation of K+ Homeostasis
Long-Term Regulation of K+ Homeostasis
Clinical Tools to Assess the Control of the Renal Excretion of K+
Clinical Approach to the Patient with Hyperkalemia
specific Causes of Hyperkalemia
Therapy of Hyperkalemia
References
Chapter 52. Control of Intracellular pH
Methods for Measuring pHi
Forces Affecting the Passive Movement of H+ and Other Charged Acids and Bases
Effects of Weak Acids and Bases on pHi
Intracellular Buffering
Acid–Base Transport Systems
Factors Influencing pHi
References
Chapter 53. SLC4 Sodium-Driven Bicarbonate Transporters
Functional Categorization of the SLC4 Family
Sodium Bicarbonate Cotransporters (Electrogenic)
Systemic Factors Affecting NBCe-1 Function in the Kidney
Sodium Bicarbonate Cotransporters (Electroneutral)
Na+-Driven Exchanger
SLC4 Transporters whose Function is Controversial
References
Chapter 54. The SLC4 Anion Exchanger Gene Family
Introduction
AE Domain Structure and Alternative Transcripts
Localization and Function of Anion Exchangers in Tissues
AE1 N-Terminal Cytoplasmic Domain Structure and Binding Proteins
AE1 C-Terminal Transmembrane Domain Structure and Binding Proteins
Mechanisms of SLC4/AE Anion Transport
Pharmacology of SLC4/AE Anion Exchangers
The Anion Translocation Pathway of AE1
Anion Conductance Associated with AE1
The AE1 C-Terminal Cytoplasmic Tail: Carbonic Anhydrase Binding, Anion Selectivity, and Other Functions
Acute Regulation of Anion Exchangers
Developmental and Chronic Regulation of Anion Exchangers
AE1 Deficiency Diseases of Erythrocytes
Benign Erythroid Phenotypes of AE1 Polypeptide Variants
AE1 and Distal Renal Tubular Acidosis (dRTA)
Knockout Mouse Models of Deficiency of AE2/SLC4A2 and AE3/SLC4A3
Conclusion
References
Chapter 55. Cellular Mechanisms of Renal Tubular Acidification
Proximal Tubule
Loop of Henle and Thick Ascending Limb
Distal Nephron
References
Chapter 56. Chemoreceptors, Breathing and pH
Introduction
CO2
Peripheral Chemoreceptors
Central Chemoreceptors
Paradox: Central Chemoreceptors Located in an Environment with Tight pH Regulation
Summary
Breathing and pH Regulation
Summary
Acknowledgments
References
Chapter 57. Renal Ammonium Ion Production and Excretion
Introduction
Role of Renal Ammonium Ion Production and Excretion in the Maintenance of Acid–Base Balance
Pathways of Renal Ammoniagenesis
Acute Regulation of Renal Ammoniagenesis
Chronic Adaptations to Metabolic Acidosis
Signal Trandsduction Pathways that Mediate the Adaptive Responses to Acidosis
Countercurrent Transport of Ammonium Ions
Excretion of Ammonium Ions
Pathophysiology
Future Directions
References
Chapter 58. Clinical Syndromes of Metabolic Alkalosis
Introduction
Defense Against Excess Extracellular Fluid (ECF) HCO3
Mechanisms of Metabolic Alkalosis
Clinical Syndromes of Metabolic Alkalosis
Concluding Remarks
References
Chapter 59. Clinical Syndromes of Metabolic Acidosis
Introduction
Definition of Metabolic Acidosis
Systemic and Renal Acid–Base Homeostasis
Clinical Consequences
Clinical Disorders
Poison-Associated Anion Gap Acidosis
Acknowledgments
References
Chapter 60. Respiratory Acid–Base Disorders
Respiratory Acidosis
Pathophysiology
Cerebrospinal Fluid Composition during Respiratory Acidosis
Pathophysiologic Effects and Clinical Manifestations of Respiratory Acidosis
Diagnosis of Respiratory Acidosis
Management of Respiratory Acidosis
Mixed Acid–Base Disorders Associated with Respiratory Acidosis
Respiratory Alkalosis
Pathophysiology
Pathophysiologic Effects and Clinical Manifestations of Respiratory Alkalosis
Diagnosis of Respiratory Alkalosis
Management of Respiratory Alkalosis
Mixed Acid–Base Disorders Associated with Respiratory Alkalosis
References
Chapter 61. Mechanisms and Disorders of Magnesium Metabolism
Introduction
Physiology of Renal Magnesium Handling
Pathophysiology of Renal Magnesium Handling
References
Chapter 62. Calcium Channels
CA2+ Channels in the KIDNEY
Epithelial CA2+ Channels: TRPV5 and TRPV6
Regulation of the Epithelial Ca2+ CHANNELS
Acknowledgements
References
Chapter 63. The Calcium-Sensing Receptor
Ligand Binding: the CaSR is a Ca2+/Mg2+ and an “Extracellular Environment” Sensor
Binding Partners of the CaSR
Regulation of CaSR Gene Expression
Overview of the CaSR’s Role in Ca2+ Homeostasis
CaSR Function in Parathyroid
CaSR and C-Cell Function
CaSR and Kidney Function
CaSR and the Skeleton
The CaSR and the Gastrointestinal Tract
Modulation of the CaSR in 2° HPT
Other Applications of Calcimimetics in CKD
Other Applications of Calcimimetics
Summary and Perspectives
Conflict of Interest
References
Chapter 64. Renal Calcium Metabolism
Introduction
Calcium Chemistry
Calcium Transport Along the Nephron
Regulation of Renal Calcium Transport
Acknowledgements
References
Chapter 65. The Hormonal Regulation of Calcium Metabolism
Introduction
Calcium Balance
Vitamin D Endocrine System
Parathyroid Hormone
Calcitonin
Conclusion
References
Chapter 66. Disorders of Calcium Metabolism
Introduction
Regulators of Calcium Homeostasis
Calcitonin
Integrated Regulation of Calcium Metabolism
Hypercalcemia
Parathyroid-Independent Hypercalcemia
Hypocalcemia
References
Chapter 67. Pathogenesis and Treatment of Nephrolithiasis
Stones, Clinical Presentation, and Natural History
Natural History
Primary Process of Crystallization
Control of Supersaturation
Inhibitors of Crystallization and Cell Crystal Interactions
Disorders of Calcium Stone Formation
Idiopathic Calcium Stones: Pathology
Calcium Stones Arising from Systemic Diseases
Uric Acid (And Other Purines) in Stones
Cystinuria and Cystine Stones
Plaque and Deposits in all Forms of Stone Disease: An Integration
Infection (Struvite) Stones
Final Thoughts
Acknowledgment
References
Chapter 68. Proximal Tubular Handling of Phosphate
Introduction
Proximal Tubular Reabsorption of Phosphate
Gene Products Involved in Proximal Tubular Phosphate Reabsorption
Protein-Protein Interactions of Type II Na/Pi-co-Transporters
Regulation of Proximal Tubular Reabsorption of Pi
Genetic Alterations Leading to Imbalance of Pi Homeostasis
Acknowledgments
References
Chapter 69. Clinical Disturbances of Phosphate Homeostasis
The Importance of Phosphorus in Biological Systems
The Regulation of Phosphate Balance
The Physiology of Phosphate in the Kidney
Factors Regulating Renal Phosphate Excretion
Acute and Chronic Hypophosphatemia
Acute and Chronic Hyperphosphatemia
References
Chapter 70. Glucose Reabsorption in The Kidney
Overview of Glucose Homeostasis
Glucose Transporters in glucose Homeostasis
Cellular and Molecular Physiology of SGLTs
SGLTs and Renal Glucose Reabsorption
Genetic Ablation of SGLTs
Genetics of Renal Glycosuria
Diabetes Mellitus: A Disease of Hyperglycemia
Blocking Renal Glucose Reabsorption as a Treatment for Diabetes
Conclusions
Acknowledgments
References
Chapter 71. Kidney Transport of Amino Acids and Oligopeptides, and Aminoacidurias
Filtration and Reabsorption of Amino Acids and Oligopeptides
From “Transport Systems” to Transporters
Functional Schema of Amino Acid Reabsorption by Proximal Tubule Epithelial Cells
Transporters Involved in the Luminal Uptake of Amino Acids and Oligopeptides
Transporters Involved in Basolateral Efflux of Amino Acids
Aminoacidurias
Perspectives
Acknowledgments
References
Chapter 72. Organic Anion and Cation Transporters in Renal Elimination of Drugs
Introduction
Organic Anion Transport Systems
Drug Transporters in the Basolateral Membrane of Proximal Tubule Cells
The Organic Anion Transporter 3 (OAT3/Oat3; SLC22A8/Slc22a8)
Drug Transporters in the Apical Membrane of Proximal Tubule Cells
Overview of Transporters Involved in Transport of Selected Anionic Drugs
Organic Cation Transport Systems
Outlook
References
Chapter 73. Renal Filtration, Transport, and Metabolism of Albumin and Albuminuria
Introduction
Albumin
Glomerular Filtration
Renal Tubular Albumin Metabolism
Mechanisms of Albuminuria in Disease
References
IV: Pathophysiology of Renal Disease
Chapter 74. Physiologic Principles in the Clinical Evaluation of Electrolyte, Water, and Acid–Base Disorders
Concept of External Balance and Steady-State
Urinary Constituents as Clinical Indices: General Considerations
Evaluation of Disorders of Water Excretion
Evaluation of Potassium Disorders
Evaluation of Metabolic Acidosis
References
Chapter 75. Biomarkers for Assessment of Renal Function During Acute Kidney Injury
Biomarkers of Acute Kidney Injury—an Un-Met Need
Desirable Characteristics of aki Biomarkers
Neutrophil Gelatinase-Associated Lipocalin (NGAL) as an AKI Biomarker
Kidney Injury Molecule-1 (KIM-1) as an AKI Biomarker
Liver-Type Fatty Acid Binding Protein (L-FABP) as an AKI Biomarker
Interleukin-18 (IL-18) as an AKI Biomarker
AKI Biomarker Combinations
Limitations of Existing Studies Examining AKI Biomarkers
References
Chapter 76. Pathophysiology of Acute Kidney Injury
Clinical Overview
Models of Acute Kidney Injury
Pathophysiology of Acute Kidney Injury
Microvascular Insult in AKI—Functional Basis and Morphological Changes
Role of Endothelin
Endothelial Cell Injury in AKI
Endothelium and Coagulation Abnormalities In AKI
Inflammation in Acute Kidney Injury
AKI in Sepsis
Cellular Repair, Regeneration and Recovery
Clinical Course & Diagnostic Tests in AKI
Pathophysiologic Basis of Therapy of AKI
Conclusion
References
Chapter 77. Ischemic Renal Disease
Atherosclerotic Renal Artery Stenosis: A Common Disorder With Increasing Clinical Recognition and Public Health Importance
Clinical Presentations of Ischemic Nephropathy
Diagnosis of Ischemic Nephropathy
Clinical Significance of Atherosclerotic Renal Artery Stenosis
Pathophysiology of Renal Underperfusion and Ischemic Nephropathy
Adaptive Responses to Renal Underperfusion
Pathology of the Kidney in Ischemic Nephropathy
Natural History of Ischemic Nephropathy
Medical Management
Summary
References
Chapter 78. Pathophysiology and Pathogenesis of Diabetic Nephropathy
Epidemiology
Clinical Course of Diabetic Nephropathy in Type 1 and Type 2 Diabetes
Pathology of Kidney Disease in Diabetes Mellitus
The Central Role of Podocytes in the Pathophysiology of Diabetic Proteinuria
Cellular and Molecular Mechanisms in the Pathophysiology of Diabetic Nephropathy
Role of Amadori-Glycated Albumin
Role of Advanced Glycation End Products
Metabolic Syndrome/Obesity and Renal Disease
Regression
Summary and Outlook
References
Chapter 79. Renal Failure in Cirrhosis
Definition
Management
Liver Transplantation
Prevention
Reference
Chapter 80. Autosomal Dominant Polycystic Kidney Disease
Clinical Features of Autosomal Dominant Polycystic Kidney Disease
Cilia and the Spectrum of Inherited Cystic Disease
Genetics of ADPKD
The PKD Genes and Their Protein Products
Cellular Pathways Affected by Polycystins
Prospects for Therapy in ADPKD
References
Chapter 81. Renal Physiology and Disease in Pregnancy
Anatomical Changes
Renal Hemodynamics
Renal Tubular Function
Osmoregulation and Renal Water Handling
Volume Homeostasis
Renal Disorders and Gestation
Chronic Parenchymal Renal Disease
Hypertension
Cardiovascular Changes in Normal Pregnancy
References
Chapter 82. Immune and Inflammatory Glomerular Diseases
Glomerulonephritis
Primary Renal Diseases Causing Nephrotic Syndrome
Infectious Causes of the Nephrotic Syndrome
Malignancy-Associated Glomerular Diseases
Drug-Induced Glomerular Diseases
References
Chapter 83. Immunologic Mechanisms of Vasculitis
Immunopatholgic Categories of Vasculitis
Basic Pathogenic Events in Small-Vessel Vasculitis
Adhesion Strengthening
Immune Complex–Mediated Vasculitis
Pauci-Immune Antineutrophil Cytoplasmic Autoantibody Vasculitis
References
Chapter 84. Genetic Abnormalities in Glomerular Function
Introduction
Disorders of Extracellular Matrix
Storage Disorders
Other Storage Disorders Associated with Glomerular Dysfunction
Disorders of the Podocyte Slit Diaphragm
Disorders of the Podocyte Cytoskeleton
Disorders of Podocyte Gene Regulation
References
Chapter 85. Cellular Mechanisms of Drug Nephrotoxicity
Introduction
Localization of Injury
Cellular Targets
Cell Injury Pathways
Biomarkers of Nephrotoxic Injury
Cyclosporin A
Cisplatin
Acetaminophen Nephrotoxicity
Aminoglycosides
Lithium
References
Chapter 86. Role of Glomerular Mechanical Stress in the Pathogenesis of Chronic Kidney Disease
Determinants of Glomerular Ultrafiltration and How They are Influenced by the Glomerular Arterioles
The “Hyperfiltration Hypothesis” and the Progressive Nature of Chronic Kidney Disease
The Importance of Glomerular Hypertrophy and the Concept of Mechanical Aggression
The Immense Pathogenic Importance of Angiotensin II in CKD
The Role of Other Vasoactive Compounds in Glomerular Mechanical Strain
Genetic and Environmental Factors Causing Glomerular Injury Through Mechanical Strain
Preventing the Progression of CKD by Treatment of the Glomerular Hemodynamic Derangement
Mechanical Stretch in the Pathogenesis of Immune-Mediated Glomerulonephritis
Glomerular Hemodynamics and the Clinical Translation of Experimental Data: A Word of Caution
Summary and Conclusions
References
Chapter 87. Role of Proteinuria in the Progression of Renal Disease
Introduction
Summary
Acknowledgment
References
Chapter 88. The Inflammatory Response to Ischemic Acute Renal Injury
Introduction
Leukocytes in Injured, Ischemic Tissues: Friend, and Foe.
The Proinflammatory Effects of Injury—Damps, Sterile Inflammation, and the “Danger/ Damage” Hypothesis
TLR4 and HMGB1
When Death is no Accident: Necrosis as a Programmed Event
After the Suicide, Disposal of the Corpse: Regulation of Inflammation by Macrophages after they Phagocytose Apoptotic Cells
Summary
References
Chapter 89. Catalytic (Labile) Iron in Kidney Disease
Introduction
Definition of Catalytic (Labile) Iron and Its Importance in Tissue Injury
Role of Catalytic Iron in Acute Kidney Injury
Catalytic Iron in Chronic Kidney Disease
Concluding Comments
References
Chapter 90. Chronic Kidney Disease: Pathophysiology and the Influence of Dietary Protein
Introduction
Measurement and Natural History of CKD
Serum Creatinine
Creatinine Clearance
Formulas for Estimatng GFR
Epidemiology of Chronic Kidney Disease
Pathophysiology of CKD
Influence of Dietary Therapy in Patients with Chronic Kidney Disease
Dietary Protein Restriction and Progression of Renal Insufficiency
Conclusions
References
Chapter 91. Management of Calcium and Bone Disease in Renal Patients
Introduction
References
Chapter 92. Hematopoiesis and the Kidney
Introduction
Erythropoiesis
Cellular Oxygen Sensing Regulating Erythropoietin Gene Transcription
Plasma Erythropoietin Concentration and Requirement for Erythropoiesis
Renal Anemia
Thrombocytopoiesis
Thrombopoietin
Future Aspects
References
Chapter 93. Individualizing the Dialysate to Address Electrolyte Disturbances in the Dialysis Patient
Introduction
Sodium
Potassium
Clinical Disorders of Potassium in the Dialysis Patient
Calcium
Magnesium
References
Chapter 94. Homeostasis of Solute and Water by the Transplanted Kidney
Introduction
Intrinsic Capacity of the Denervated Transplanted Isograft
Ischemia Attendant to Harvest, Preservation, and Engraftment
Allograft in the Azotemic Solute-Loaded Recipient
Solute Regulation During Rejection
Renal Tubular Acidosis Associated With Ischemia and Rejection
Syndromes of Potassium Handling
Mineral Metabolism States After Transplant
Handling of Urate After Transplant
Renal Transport and Immunosuppressive Drugs
References
Chapter 95. Renal Disposition of Drugs and Translation to Dosing Strategies
Introduction
Role of the Kidney in Drug Disposition
Influence of Drugs and Renal Disease on Drug Disposition and Response
Influence of Renal Disease on Drug Disposition and Response
Dosing Recommendations in Patients with Renal Insufficiency
References
Index
- No. of pages: 3290
- Language: English
- Edition: 5
- Published: December 31, 2012
- Imprint: Academic Press
- eBook ISBN: 9780123814630
RA
Robert J. Alpern
Dr. Alpern has performed research in the area of epithelial physiology, focusing on the mechanisms and regulation of acid transport. He received his MD degree from the University of Chicago and then trained in Internal Medicine at Columbia Presbyterian. Following postdoctoral training in the Cardiovascular Research Institute at the University of California, San Francisco, Alpern joined the faculty at UCSF, then moved to the University of Texas Southwestern Medical School as Chief of Nephrology and later Dean of the medical school. He is now Dean of Yale School of Medicine and Ensign Professor.
Affiliations and expertise
Dean and Ensign Professor of Medicine, Yale University School of Medicine, New Haven, Connecticut, USAMC
Michael J. Caplan
Dr. Caplan studies epithelial cell biology and physiology. His work focuses on the trafficking and regulation of renal ion transport proteins. His group also studies the signaling pathways involved in Autosomal Dominant Polycystic Kidney Disease. He received his MD and PhD degrees from Yale University, having pursued his dissertation work in the Department of Cell Biology under the guidance of Drs. James D. Jamieson and George E. Palade. Following postdoctoral work in the Department of Cellular and Molecular Physiology at Yale, Caplan joined that department as a faculty member. He is currently the C.N.H. Long Professor and Chair of Yale University School of Medicine’s Department of Cellular and Molecular Physiology.
Affiliations and expertise
C.N.H. Long Professor and Chair, Department of Cellular and Molecular Physiology, Yale University School of Medicine, New Haven, Connecticut, USAOM
Orson W. Moe
Dr. Moe received his medical degree from the University of Toronto where he also did his internal medicine residency and clinical nephrology fellowship. Orson Moe moved to the University of Texas Southwestern Medical Center for research training in renal physiology. He is currently Professor of Internal Medicine and Physiology and is a member of the Nephrology Division at the University of Texas Southwestern Medical Center in Dallas. He is also the Director of the Charles and Jane Pak Center of Mineral Metabolism and Clinical Research and holds the Charles and Jane Pak Chair in Mineral Metabolism Research and the Donald Seldin Professorship in Clinical Investigation. Orson Moe conducts both basic science and patient-oriented research on renal physiology and metabolism, and epithelial biology.
Affiliations and expertise
Professor of Internal Medicine and Physiology, University of Texas Southwestern Medical Center, Dallas, Texas, USARead Seldin and Giebisch's The Kidney on ScienceDirect