Textbook of medical physiology

Cell and General Physiology C H A P T E R 1 Functional Organization of the Human Body and Control of the “Internal Environment” 3 Cells as the Living Units of the Body 3 Extracellular Fluid—The “Internal Environment” 3 “Homeostatic” Mechanisms of the Major Functional Systems 4 Homeostasis 4 Extracellular Fluid Transport and Mixing System—The Blood Circulatory System 4 Origin of Nutrients in the Extracellular Fluid 5 Removal of Metabolic End Products 5 Regulation of Body Functions 5 Reproduction 6 Control Systems of the Body 6 Examples of Control Mechanisms 6 Characteristics of Control Systems 7 Summary—Automaticity of the Body 9 C H A P T E R 2 The Cell and Its Functions 11 Organization of the Cell 11 Physical Structure of the Cell 12 Membranous Structures of the Cell 12 Cytoplasm and Its Organelles 14 Nucleus 17 Nuclear Membrane 17 Nucleoli and Formation of Ribosomes 18 Comparison of the Animal Cell with Precellular Forms of Life 18 Functional Systems of the Cell 19 Ingestion by the Cell—Endocytosis 19 Digestion of Pinocytotic and Phagocytic Foreign Substances Inside the Cell— Function of the Lysosomes 20 Synthesis and Formation of Cellular Structures by Endoplasmic Reticulum and Golgi Apparatus 20 Extraction of Energy from Nutrients— Function of the Mitochondria 22 Locomotion of Cells 24 Ameboid Movement 24 Cilia and Ciliary Movement 24 C H A P T E R 3 Genetic Control of Protein Synthesis, Cell Function, and Cell Reproduction 27 Genes in the Cell Nucleus 27 Genetic Code 29 xiii The DNA Code in the Cell Nucleus Is Transferred to an RNA Code in the Cell Cytoplasm—The Process of Transcription 30 Synthesis of RNA 30 Assembly of the RNA Chain from Activated Nucleotides Using the DNA Strand as a Template—The Process of “Transcription” 31 Messenger RNA—The Codons 31 Transfer RNA—The Anticodons 32 Ribosomal RNA 33 Formation of Proteins on the Ribosomes— The Process of “Translation” 33 Synthesis of Other Substances in the Cell 35 Control of Gene Function and Biochemical Activity in Cells 35 Genetic Regulation 35 Control of Intracellular Function by Enzyme Regulation 36 The DNA-Genetic System Also Controls Cell Reproduction 37 Cell Reproduction Begins with Replication of DNA 37 Chromosomes and Their Replication 38 Cell Mitosis 38 Control of Cell Growth and Cell Reproduction 39 Cell Differentiation 40 Apoptosis—Programmed Cell Death 40 Cancer 40 U N I T I I Membrane Physiology, Nerve, and Muscle C H A P T E R 4 Transport of Substances Through the Cell Membrane 45 The Lipid Barrier of the Cell Membrane, and Cell Membrane Transport Proteins 45 Diffusion 46 Diffusion Through the Cell Membrane 46 Diffusion Through Protein Channels, and “Gating” of These Channels 47 Facilitated Diffusion 49 Factors That Affect Net Rate of Diffusion 50 Osmosis Across Selectively Permeable Membranes—“Net Diffusion” of Water 51 “Active Transport” of Substances Through Membranes 52 Primary Active Transport 53 Secondary Active Transport—Co-Transport and Counter-Transport 54 Active Transport Through Cellular Sheets 55 xiv Table of Contents C H A P T E R 5 Membrane Potentials and Action Potentials 57 Basic Physics of Membrane Potentials 57 Membrane Potentials Caused by Diffusion 57 Measuring the Membrane Potential 58 Resting Membrane Potential of Nerves 59 Origin of the Normal Resting Membrane Potential 60 Nerve Action Potential 61 Voltage-Gated Sodium and Potassium Channels 62 Summary of the Events That Cause the Action Potential 64 Roles of Other Ions During the Action Potential 64 Initiation of the Action Potential 65 Propagation of the Action Potential 65 Re-establishing Sodium and Potassium Ionic Gradients After Action Potentials Are Completed—Importance of Energy Metabolism 66 Plateau in Some Action Potentials 66 Rhythmicity of Some Excitable Tissues— Repetitive Discharge 67 Special Characteristics of Signal Transmission in Nerve Trunks 68 Excitation—The Process of Eliciting the Action Potential 69 “Refractory Period” After an Action Potential 70 Recording Membrane Potentials and Action Potentials 70 Inhibition of Excitability—“Stabilizers” and Local Anesthetics 70 C H A P T E R 6 Contraction of Skeletal Muscle 72 Physiologic Anatomy of Skeletal Muscle 72 Skeletal Muscle Fiber 72 General Mechanism of Muscle Contraction 74 Molecular Mechanism of Muscle Contraction 74 Molecular Characteristics of the Contractile Filaments 75 Effect of Amount of Actin and Myosin Filament Overlap on Tension Developed by the Contracting Muscle 77 Relation of Velocity of Contraction to Load 78 Energetics of Muscle Contraction 78 Work Output During Muscle Contraction 78 Sources of Energy for Muscle Contraction 79 Characteristics of Whole Muscle Contraction 80 Mechanics of Skeletal Muscle Contraction 81 Remodeling of Muscle to Match Function 82 Rigor Mortis 83 C H A P T E R 7 Excitation of Skeletal Muscle: Neuromuscular Transmission and Excitation-Contraction Coupling 85 Transmission of Impulses from Nerve Endings to Skeletal Muscle Fibers: The Neuromuscular Junction 85 Secretion of Acetylcholine by the Nerve Terminals 85 Molecular Biology of Acetyline Formation and Release 88 Drugs That Enhance or Block Transmission at the Neuromuscular Junction 88 Myasthenia Gravis 89 Muscle Action Potential 89 Spread of the Action Potential to the Interior of the Muscle Fiber by Way of “Transverse Tubules” 89 Excitation-Contraction Coupling 89 Transverse Tubule–Sarcoplasmic Reticulum System 89 Release of Calcium Ions by the Sarcoplasmic Reticulum 90 C H A P T E R 8 Contraction and Excitation of Smooth Muscle 92 Contraction of Smooth Muscle 92 Types of Smooth Muscle 92 Contractile Mechanism in Smooth Muscle 93 Regulation of Contraction by Calcium Ions 95 Nervous and Hormonal Control of Smooth Muscle Contraction 95 Neuromuscular Junctions of Smooth Muscle 95 Membrane Potentials and Action Potentials in Smooth Muscle 96 Effect of Local Tissue Factors and Hormones to Cause Smooth Muscle Contraction Without Action Potentials 98 Source of Calcium Ions That Cause Contraction (1) Through the Cell Membrane and (2) from the Sarcoplasmic Reticulum 99 U N I T I I I The Heart C H A P T E R 9 Heart Muscle; The Heart as a Pump and Function of the Heart Valves 103 Physiology of Cardiac Muscle 103 Physiologic Anatomy of Cardiac Muscle 103 Action Potentials in Cardiac Muscle 104 The Cardiac Cycle 106 Diastole and Systole 106 Relationship of the Electrocardiogram to the Cardiac Cycle 107 Function of the Atria as Primer Pumps 107 Function of the Ventricles as Pumps 108 Table of Contents xv Function of the Valves 109 Aortic Pressure Curve 109 Relationship of the Heart Sounds to Heart Pumping 109 Work Output of the Heart 110 Graphical Analysis of Ventricular Pumping 110 Chemical Energy Required for Cardiac Contraction: Oxygen Utilization by the Heart 111 Regulation of Heart Pumping 111 Intrinsic Regulation of Heart Pumping— The Frank-Starling Mechanism 111 Effect of Potassium and Calcium Ions on Heart Function 113 Effect of Temperature on Heart Function 114 Increasing the Arterial Pressure Load (up to a Limit) Does Not Decrease the Cardiac Output 114 C H A P T E R 1 0 Rhythmical Excitation of the Heart 116 Specialized Excitatory and Conductive System of the Heart 116 Sinus (Sinoatrial) Node 116 Internodal Pathways and Transmission of the Cardiac Impulse Through the Atria 118 Atrioventricular Node, and Delay of Impulse Conduction from the Atria to the Ventricles 118 Rapid Transmission in the Ventricular Purkinje System 119 Transmission of the Cardiac Impulse in the Ventricular Muscle 119 Summary of the Spread of the Cardiac Impulse Through the Heart 120 Control of Excitation and Conduction in the Heart 120 The Sinus Node as the Pacemaker of the Heart 120 Role of the Purkinje System in Causing Synchronous Contraction of the Ventricular Muscle 121 Control of Heart Rhythmicity and Impulse Conduction by the Cardiac Nerves: The Sympathetic and Parasympathetic Nerves 121 C H A P T E R 1 1 The Normal Electrocardiogram 123 Characteristics of the Normal Electrocardiogram 123 Depolarization Waves Versus Repolarization Waves 123 Relationship of Atrial and Ventricular Contraction to the Waves of the Electrocardiogram 125 Voltage and Time Calibration of the Electrocardiogram 125 Methods for Recording Electrocardiograms 126 Pen Recorder 126 Flow of Current Around the Heart During the Cardiac Cycle 126 Recording Electrical Potentials from a Partially Depolarized Mass of Syncytial Cardiac Muscle 126 Flow of Electrical Currents in the Chest Around the Heart 126 Electrocardiographic Leads 127 Three Bipolar Limb Leads 127 Chest Leads (Precordial Leads) 129 Augmented Unipolar Limb Leads 129 C H A P T E R 1 2 Electrocardiographic Interpretation of Cardiac Muscle and Coronary Blood Flow Abnormalities: Vectorial Analysis 131 Principles of Vectorial Analysis of Electrocardiograms 131 Use of Vectors to Represent Electrical Potentials 131 Direction of a Vector Is Denoted in Terms of Degrees 131 Axis for Each Standard Bipolar Lead and Each Unipolar Limb Lead 132 Vectorial Analysis of Potentials Recorded in Different Leads 133 Vectorial Analysis of the Normal Electrocardiogram 134 Vectors That Occur at Successive Intervals During Depolarization of the Ventricles— The QRS Complex 134 Electrocardiogram During Repolarization— The T Wave 134 Depolarization of the Atria—The P Wave 136 Vectorcardiogram 136 Mean Electrical Axis of the Ventricular QRS—And Its Significance 137 Determining the Electrical Axis from Standard Lead Electrocardiograms 137 Abnormal Ventricular Conditions That Cause Axis Deviation 138 Conditions That Cause Abnormal Voltages of the QRS Complex 140 Increased Voltage in the Standard Bipolar Limb Leads 140 Decreased Voltage of the Electrocardiogram 140 Prolonged and Bizarre Patterns of the QRS Complex 141 Prolonged QRS Complex as a Result of Cardiac Hypertrophy or Dilatation 141 Prolonged QRS Complex Resulting from Purkinje System Blocks 141 Conditions That Cause Bizarre QRS Complexes 141 Current of Injury 141 Effect of Current of Injury on the QRS Complex 141 The J Point—The Zero Reference Potential for Analyzing Current of Injury 142 Coronary Ischemia as a Cause of Injury Potential 143 Abnormalities in the T Wave 145 Effect of Slow Conduction of the Depolarization Wave on the Characteristics of the T Wave 145 Shortened Depolarization in Portions of the Ventricular Muscle as a Cause of T Wave Abnormalities 145 xvi Table of Contents C H A P T E R 1 3 Cardiac Arrhythmias and Their Electrocardiographic Interpretation 147 Abnormal Sinus Rhythms 147 Tachycardia 147 Bradycardia 147 Sinus Arrhythmia 148 Abnormal Rhythms That Result from Block of Heart Signals Within the Intracardiac Conduction Pathways 148 Sinoatrial Block 148 Atrioventricular Block 148 Incomplete Atrioventricular Heart Block 149 Incomplete Intraventricular Block— Electrical Alternans 150 Premature Contractions 150 Premature Atrial Contractions 150 A-V Nodal or A-V Bundle Premature Contractions 150 Premature Ventricular Contractions 151 Paroxysmal Tachycardia 151 Atrial Paroxysmal Tachycardia 152 Ventricular Paroxysmal Tachycardia 152 Ventricular Fibrillation 152 Phenomenon of Re-entry—“Circus Movements” as the Basis for Ventricular Fibrillation 153 Chain Reaction Mechanism of Fibrillation 153 Electrocardiogram in Ventricular Fibrillation 154 Electroshock Defibrillation of the Ventricle 154 Hand Pumping of the Heart (Cardiopulmonary Resuscitation) as an Aid to Defibrillation 155 Atrial Fibrillation 155 Atrial Flutter 156 Cardiac Arrest 156 U N I T I V The Circulation C H A P T E R 1 4 Overview of the Circulation; Medical Physics of Pressure, Flow, and Resistance 161 Physical Characteristics of the Circulation 161 Basic Theory of Circulatory Function 163 Interrelationships Among Pressure, Flow, and Resistance 164 Blood Flow 164 Blood Pressure 166 Resistance to Blood Flow 167 Effects of Pressure on Vascular Resistance and Tissue Blood Flow 170 C H A P T E R 1 5 Vascular Distensibility and Functions of the Arterial and Venous Systems 171 Vascular Distensibility 171 Vascular Compliance (or Vascular Capacitance) 171 Volume-Pressure Curves of the Arterial and Venous Circulations 172 Arterial Pressure Pulsations 173 Transmission of Pressure Pulses to the Peripheral Arteries 174 Clinical Methods for Measuring Systolic and Diastolic Pressures 175 Veins and Their Functions 176 Venous Pressures—Right Atrial Pressure (Central Venous Pressure) and Peripheral Venous Pressures 176 Blood Reservoir Function of the Veins 179 C H A P T E R 1 6 The Microcirculation and the Lymphatic System: Capillary Fluid Exchange, Interstitial Fluid, and Lymph Flow 181 Structure of the Microcirculation and Capillary System 181 Flow of Blood in the Capillaries— Vasomotion 182 Average Function of the Capillary System 183 Exchange of Water, Nutrients, and Other Substances Between the Blood and Interstitial Fluid 183 Diffusion Through the Capillary Membrane 183 The Interstitium and Interstitial Fluid 184 Fluid Filtration Across Capillaries Is Determined by Hydrostatic and Colloid Osmotic Pressures, and Capillary Filtration Coefficient 185 Capillary Hydrostatic Pressure 186 Interstitial Fluid Hydrostatic Pressure 187 Plasma Colloid Osmotic Pressure 188 Interstitial Fluid Colloid Osmotic Pressure 188 Exchange of Fluid Volume Through the Capillary Membrane 189 Starling Equilibrium for Capillary Exchange 189 Lymphatic System 190 Lymph Channels of the Body 190 Formation of Lymph 191 Rate of Lymph Flow 192 Role of the Lymphatic System in Controlling Interstitial Fluid Protein Concentration, Interstitial Fluid Volume, and Interstitial Fluid Pressure 193 C H A P T E R 1 7 Local and Humoral Control of Blood Flow by the Tissues 195 Local Control of Blood Flow in Response to Tissue Needs 195 Mechanisms of Blood Flow Control 196 Acute Control of Local Blood Flow 196 Long-Term Blood Flow Regulation 200 Development of Collateral Circulation—A Phenomenon of Long-Term Local Blood Flow Regulation 201 Humoral Control of the Circulation 201 Vasoconstrictor Agents 201 Vasodilator Agents 202 Vascular Control by Ions and Other Chemical Factors 202 Table of Contents xvii C H A P T E R 1 8 Nervous Regulation of the Circulation, and Rapid Control of Arterial Pressure 204 Nervous Regulation of the Circulation 204 Autonomic Nervous System 204 Role of the Nervous System in Rapid Control of Arterial Pressure 208 Increase in Arterial Pressure During Muscle Exercise and Other Types of Stress 208 Reflex Mechanisms for Maintaining Normal Arterial Pressure 209 Central Nervous System Ischemic Response—Control of Arterial Pressure by the Brain’s Vasomotor Center in Response to Diminished Brain Blood Flow 212 Special Features of Nervous Control of Arterial Pressure 213 Role of the Skeletal Nerves and Skeletal Muscles in Increasing Cardiac Output and Arterial Pressure 213 Respiratory Waves in the Arterial Pressure 214 Arterial Pressure “Vasomotor” Waves— Oscillation of Pressure Reflex Control Systems 214 C H A P T E R 1 9 Dominant Role of the Kidney in Long- Term Regulation of Arterial Pressure and in Hypertension: The Integrated System for Pressure Control 216 Renal–Body Fluid System for Arterial Pressure Control 216 Quantitation of Pressure Diuresis as a Basis for Arterial Pressure Control 217 Chronic Hypertension (High Blood Pressure) Is Caused by Impaired Renal Fluid Excretion 220 The Renin-Angiotensin System: Its Role in Pressure Control and in Hypertension 223 Components of the Renin-Angiotensin System 223 Types of Hypertension in Which Angiotensin Is Involved: Hypertension Caused by a Renin-Secreting Tumor or by Infusion of Angiotensin II 226 Other Types of Hypertension Caused by Combinations of Volume Loading and Vasoconstriction 227 “Primary (Essential) Hypertension” 228 Summary of the Integrated, Multifaceted System for Arterial Pressure Regulation 230 C H A P T E R 2 0 Cardiac Output, Venous Return, and Their Regulation 232 Normal Values for Cardiac Output at Rest and During Activity 232 Control of Cardiac Output by Venous Return—Role of the Frank-Starling Mechanism of the Heart 232 Cardiac Output Regulation Is the Sum of Blood Flow Regulation in All the Local Tissues of the Body—Tissue Metabolism Regulates Most Local Blood Flow 233 The Heart Has Limits for the Cardiac Output That It Can Achieve 234 What Is the Role of the Nervous System in Controlling Cardiac Output? 235 Pathologically High and Pathologically Low Cardiac Outputs 236 High Cardiac Output Caused by Reduced Total Peripheral Resistance 236 Low Cardiac Output 237 A More Quantitative Analysis of Cardiac Output Regulation 237 Cardiac Output Curves Used in the Quantitative Analysis 237 Venous Return Curves 238 Analysis of Cardiac Output and Right Atrial Pressure, Using Simultaneous Cardiac Output and Venous Return Curves 241 Methods for Measuring Cardiac Output 243 Pulsatile Output of the Heart as Measured by an Electromagnetic or Ultrasonic Flowmeter 243 Measurement of Cardiac Output Using the Oxygen Fick Principle 244 Indicator Dilution Method for Measuring Cardiac Output 244 C H A P T E R 2 1 Muscle Blood Flow and Cardiac Output During Exercise; the Coronary Circulation and Ischemic Heart Disease 246 Blood Flow in Skeletal Muscle and Blood Flow Regulation During Exercise 246 Rate of Blood Flow Through the Muscles 246 Control of Blood Flow Through the Skeletal Muscles 247 Total Body Circulatory Readjustments During Exercise 247 Coronary Circulation 249 Physiologic Anatomy of the Coronary Blood Supply 249 Normal Coronary Blood Flow 249 Control of Coronary Blood Flow 250 Special Features of Cardiac Muscle Metabolism 251 Ischemic Heart Disease 252 Causes of Death After Acute Coronary Occlusion 253 Stages of Recovery from Acute Myocardial Infarction 254 Function of the Heart After Recovery from Myocardial Infarction 255 Pain in Coronary Heart Disease 255 Surgical Treatment of Coronary Disease 256 C H A P T E R 2 2 Cardiac Failure 258 Dynamics of the Circulation in Cardiac Failure 258 xviii Table of Contents Acute Effects of Moderate Cardiac Failure 258 Chronic Stage of Failure—Fluid Retention Helps to Compensate Cardiac Output 259 Summary of the Changes That Occur After Acute Cardiac Failure—“Compensated Heart Failure” 260 Dynamics of Severe Cardiac Failure— Decompensated Heart Failure 260 Unilateral Left Heart Failure 262 Low-Output Cardiac Failure— Cardiogenic Shock 262 Edema in Patients with Cardiac Failure 263 Cardiac Reserve 264 Quantitative Graphical Method for Analysis of Cardiac Failure 265 C H A P T E R 2 3 Heart Valves and Heart Sounds; Dynamics of Valvular and Congenital Heart Defects 269 Heart Sounds 269 Normal Heart Sounds 269 Valvular Lesions 271 Abnormal Circulatory Dynamics in Valvular Heart Disease 272 Dynamics of the Circulation in Aortic Stenosis and Aortic Regurgitation 272 Dynamics of Mitral Stenosis and Mitral Regurgitation 273 Circulatory Dynamics During Exercise in Patients with Valvular Lesions 273 Abnormal Circulatory Dynamics in Congenital Heart Defects 274 Patent Ductus Arteriosus—A Left-to-Right Shunt 274 Tetralogy of Fallot—A Right-to-Left Shunt 274 Causes of Congenital Anomalies 276 Use of Extracorporeal Circulation During Cardiac Surgery 276 Hypertrophy of the Heart in Valvular and Congenital Heart Disease 276 C H A P T E R 2 4 Circulatory Shock and Physiology of Its Treatment 278 Physiologic Causes of Shock 278 Circulatory Shock Caused by Decreased Cardiac Output 278 Circulatory Shock That Occurs Without Diminished Cardiac Output 278 What Happens to the Arterial Pressure in Circulatory Shock? 279 Tissue Deterioration Is the End Result of Circulatory Shock, Whatever the Cause 279 Stages of Shock 279 Shock Caused by Hypovolemia— Hemorrhagic Shock 279 Relationship of Bleeding Volume to Cardiac Output and Arterial Pressure 279 Progressive and Nonprogressive Hemorrhagic Shock 280 Irreversible Shock 284 Hypovolemic Shock Caused by Plasma Loss 284 Hypovolemic Shock Caused by Trauma 285 Neurogenic Shock—Increased Vascular Capacity 285 Anaphylactic Shock and Histamine Shock 285 Septic Shock 286 Physiology of Treatment in Shock 286 Replacement Therapy 286 Treatment of Shock with Sympathomimetic Drugs—Sometimes Useful, Sometimes Not 287 Other Therapy 287 Circulatory Arrest 287 Effect of Circulatory Arrest on the Brain 287 U N I T V The Body Fluids and Kidneys C H A P T E R 2 5 The Body Fluid Compartments: Extracellular and Intracellular Fluids; Interstitial Fluid and Edema 291 Fluid Intake and Output Are Balanced During Steady-State Conditions 291 Daily Intake of Water 291 Daily Loss of Body Water 291 Body Fluid Compartments 292 Intracellular Fluid Compartment 293 Extracellular Fluid Compartment 293 Blood Volume 293 Constituents of Extracellular and Intracellular Fluids 293 Ionic Composition of Plasma and Interstitial Fluid Is Similar 293 Important Constituents of the Intracellular Fluid 295 Measurement of Fluid Volumes in the Different Body Fluid Compartments— The Indicator-Dilution Principle 295 Determination of Volumes of Specific Body Fluid Compartments 295 Regulation of Fluid Exchange and Osmotic Equilibrium Between Intracellular and Extracellular Fluid 296 Basic Principles of Osmosis and Osmotic Pressure 296 Osmotic Equilibrium Is Maintained Between Intracellular and Extracellular Fluids 298 Volume and Osmolality of Extracellular and Intracellular Fluids in Abnormal States 299 Effect of Adding Saline Solution to the Extracellular Fluid 299 Glucose and Other Solutions Administered for Nutritive Purposes 301 Clinical Abnormalities of Fluid Volume Regulation: Hyponatremia and Hypernatremia 301 Causes of Hyponatremia: Excess Water or Loss of Sodium 301 Causes of Hypernatremia: Water Loss or Excess Sodium 302 Edema: Excess Fluid in the Tissues 302 Intracellular Edema 302 Extracellular Edema 302 Table of Contents xix Summary of Causes of Extracellular Edema 303 Safety Factors That Normally Prevent Edema 304 Fluids in the “Potential Spaces” of the Body 305 C H A P T E R 2 6 Urine Formation by the Kidneys: I. Glomerular Filtration, Renal Blood Flow, and Their Control 307 Multiple Functions of the Kidneys in Homeostasis 307 Physiologic Anatomy of the Kidneys 308 General Organization of the Kidneys and Urinary Tract 308 Renal Blood Supply 309 The Nephron Is the Functional Unit of the Kidney 310 Micturition 311 Physiologic Anatomy and Nervous Connections of the Bladder 311 Transport of Urine from the Kidney Through the Ureters and into the Bladder 312 Innervation of the Bladder 312 Filling of the Bladder and Bladder Wall Tone; the Cystometrogram 312 Micturition Reflex 313 Facilitation or Inhibition of Micturition by the Brain 313 Abnormalities of Micturition 313 Urine Formation Results from Glomerular Filtration, Tubular Reabsorption, and Tubular Secretion 314 Filtration, Reabsorption, and Secretion of Different Substances 315 Glomerular Filtration—The First Step in Urine Formation 316 Composition of the Glomerular Filtrate 316 GFR Is About 20 Per Cent of the Renal Plasma Flow 316 Glomerular Capillary Membrane 316 Determinants of the GFR 317 Increased Glomerular Capillary Filtration Coefficient Increases GFR 318 Increased Bowman’s Capsule Hydrostatic Pressure Decreases GFR 318 Increased Glomerular Capillary Colloid Osmotic Pressure Decreases GFR 318 Increased Glomerular Capillary Hydrostatic Pressure Increases GFR 319 Renal Blood Flow 320 Renal Blood Flow and Oxygen Consumption 320 Determinants of Renal Blood Flow 320 Blood Flow in the Vasa Recta of the Renal Medulla Is Very Low Compared with Flow in the Renal Cortex 321 Physiologic Control of Glomerular Filtration and Renal Blood Flow 321 Sympathetic Nervous System Activation Decreases GFR 321 Hormonal and Autacoid Control of Renal Circulation 322 Autoregulation of GFR and Renal Blood Flow 323 Importance of GFR Autoregulation in Preventing Extreme Changes in Renal Excretion 323 Role of Tubuloglomerular Feedback in Autoregulation of GFR 323 Myogenic Autoregulation of Renal Blood Flow and GFR 325 Other Factors That Increase Renal Blood Flow and GFR: High Protein Intake and Increased Blood Glucose 325 C H A P T E R 2 7 Urine Formation by the Kidneys: II. Tubular Processing of the Glomerular Filtrate 327 Reabsorption and Secretion by the Renal Tubules 327 Tubular Reabsorption Is Selective and Quantitatively Large 327 Tubular Reabsorption Includes Passive and Active Mechanisms 328 Active Transport 328 Passive Water Reabsorption by Osmosis Is Coupled Mainly to Sodium Reabsorption 332 Reabsorption of Chloride, Urea, and Other Solutes by Passive Diffusion 332 Reabsorption and Secretion Along Different Parts of the Nephron 333 Proximal Tubular Reabsorption 333 Solute and Water Transport in the Loop of Henle 334 Distal Tubule 336 Late Distal Tubule and Cortical Collecting Tubule 336 Medullary Collecting Duct 337 Summary of Concentrations of Different Solutes in the Different Tubular Segments 338 Regulation of Tubular Reabsorption 339 Glomerulotubular Balance—The Ability of the Tubules to Increase Reabsorption Rate in Response to Increased Tubular Load 339 Peritubular Capillary and Renal Interstitial Fluid Physical Forces 339 Effect of Arterial Pressure on Urine Output—The Pressure-Natriuresis and Pressure-Diuresis Mechanisms 341 Hormonal Control of Tubular Reabsorption 342 Sympathetic Nervous System Activation Increases Sodium Reabsorption 343 Use of Clearance Methods to Quantify Kidney Function 343 Inulin Clearance Can Be Used to Estimate GFR 344 Creatine Clearance and Plasma Creatinine Clearance Can Be Used to Estimate GFR 344 PAH Clearance Can Be Used to Estimate Renal Plasma Flow 345 Filtration Fraction Is Calculated from GFR Divided by Renal Plasma Flow 346 Calculation of Tubular Reabsorption or Secretion from Renal Clearance 346 xx Table of Contents C H A P T E R 2 8 Regulation of Extracellular Fluid Osmolarity and Sodium Concentration 348 The Kidneys Excrete Excess Water by Forming a Dilute Urine 348 Antidiuretic Hormone Controls Urine Concentration 348 Renal Mechanisms for Excreting a Dilute Urine 349 The Kidneys Conserve Water by Excreting a Concentrated Urine 350 Obligatory Urine Volume 350 Requirements for Excreting a Concentrated Urine—High ADH Levels and Hyperosmotic Renal Medulla 350 Countercurrent Mechanism Produces a Hyperosmotic Renal Medullary Interstitium 351 Role of Distal Tubule and Collecting Ducts in Excreting a Concentrated Urine 352 Urea Contributes to Hyperosmotic Renal Medullary Interstitium and to a Concentrated Urine 353 Countercurrent Exchange in the Vasa Recta Preserves Hyperosmolarity of the Renal Medulla 354 Summary of Urine Concentrating Mechanism and Changes in Osmolarity in Different Segments of the Tubules 355 Quantifying Renal Urine Concentration and Dilution: “Free Water” and Osmolar Clearances 357 Disorders of Urinary Concentrating Ability 357 Control of Extracellular Fluid Osmolarity and Sodium Concentration 358 Estimating Plasma Osmolarity from Plasma Sodium Concentration 358 Osmoreceptor-ADH Feedback System 358 ADH Synthesis in Supraoptic and Paraventricular Nuclei of the Hypothalamus and ADH Release from the Posterior Pituitary 359 Cardiovascular Reflex Stimulation of ADH Release by Decreased Arterial Pressure and/or Decreased Blood Volume 360 Quantitative Importance of Cardiovascular Reflexes and Osmolarity in Stimulating ADH Secretion 360 Other Stimuli for ADH Secretion 360 Role of Thirst in Controlling Extracellular Fluid Osmolarity and Sodium Concentration 361 Central Nervous System Centers for Thirst 361 Stimuli for Thirst 361 Threshold for Osmolar Stimulus of Drinking 362 Integrated Responses of Osmoreceptor-ADH and Thirst Mechanisms in Controlling Extracellular Fluid Osmolarity and Sodium Concentration 362 Role of Angiotensin II and Aldosterone in Controlling Extracellular Fluid Osmolarity and Sodium Concentration 362 Salt-Appetite Mechanism for Controlling Extracellular Fluid Sodium Concentration and Volume 363 C H A P T E R 2 9 Renal Regulation of Potassium, Calcium, Phosphate, and Magnesium; Integration of Renal Mechanisms for Control of Blood Volume and Extracellular Fluid Volume 365 Regulation of Potassium Excretion and Potassium Concentration in Extracellular Fluid 365 Regulation of Internal Potassium Distribution 366 Overview of Renal Potassium Excretion 367 Potassium Secretion by Principal Cells of Late Distal and Cortical Collecting Tubules 367 Summary of Factors That Regulate Potassium Secretion: Plasma Potassium Concentration, Aldosterone, Tubular Flow Rate, and Hydrogen Ion Concentration 368 Control of Renal Calcium Excretion and Extracellular Calcium Ion Concentration 371 Control of Calcium Excretion by the Kidneys 372 Regulation of Renal Phosphate Excretion 372 Control of Renal Magnesium Excretion and Extracellular Magnesium Ion Concentration 373 Integration of Renal Mechanisms for Control of Extracellular Fluid 373 Sodium Excretion Is Precisely Matched to Intake Under Steady-State Conditions 373 Sodium Excretion Is Controlled by Altering Glomerular Filtration or Tubular Sodium Reabsorption Rates 374 Importance of Pressure Natriuresis and Pressure Diuresis in Maintaining Body Sodium and Fluid Balance 374 Pressure Natriuresis and Diuresis Are Key Components of a Renal-Body Fluid Feedback for Regulating Body Fluid Volumes and Arterial Pressure 375 Precision of Blood Volume and Extracellular Fluid Volume Regulation 376 Distribution of Extracellular Fluid Between the Interstitial Spaces and Vascular System 376 Nervous and Hormonal Factors Increase the Effectiveness of Renal-Body Fluid Feedback Control 377 Sympathetic Nervous System Control of Renal Excretion: Arterial Baroreceptor and Low-Pressure Stretch Receptor Reflexes 377 Role of Angiotensin II In Controlling Renal Excretion 377 Role of Aldosterone in Controlling Renal Excretion 378 Role of ADH in Controlling Renal Water Excretion 379 Role of Atrial Natriuretic Peptide in Controlling Renal Excretion 378 Integrated Responses to Changes in Sodium Intake 380 Conditions That Cause Large Increases in Blood Volume and Extracellular Fluid Volume 380 Table of Contents xxi Increased Blood Volume and Extracellular Fluid Volume Caused by Heart Diseases 380 Increased Blood Volume Caused by Increased Capacity of Circulation 380 Conditions That Cause Large Increases in Extracellular Fluid Volume but with Normal Blood Volume 381 Nephrotic Syndrome—Loss of Plasma Proteins in Urine and Sodium Retention by the Kidneys 381 Liver Cirrhosis—Decreased Synthesis of Plasma Proteins by the Liver and Sodium Retention by the Kidneys 381 C H A P T E R 3 0 Regulation of Acid-Base Balance 383 Hydrogen Ion Concentration Is Precisely Regulated 383 Acids and Bases—Their Definitions and Meanings 383 Defenses Against Changes in Hydrogen Ion Concentration: Buffers, Lungs, and Kidneys 384 Buffering of Hydrogen Ions in the Body Fluids 385 Bicarbonate Buffer System 385 Quantitative Dynamics of the Bicarbonate Buffer System 385 Phosphate Buffer System 387 Proteins: Important Intracellular Buffers 387 Respiratory Regulation of Acid-Base Balance 388 Pulmonary Expiration of CO2 Balances Metabolic Formation of CO2 388 Increasing Alveolar Ventilation Decreases Extracellular Fluid Hydrogen Ion Concentration and Raises pH 388 Increased Hydrogen Ion Concentration Stimulates Alveolar Ventilation 389 Renal Control of Acid-Base Balance 390 Secretion of Hydrogen Ions and Reabsorption of Bicarbonate Ions by the Renal Tubules 390 Hydrogen Ions Are Secreted by Secondary Active Transport in the Early Tubular Segments 391 Filtered Bicarbonate Ions Are Reabsorbed by Interaction with Hydrogen Ions in the Tubules 391 Primary Active Secretion of Hydrogen Ions in the Intercalated Cells of Late Distal and Collecting Tubules 392 Combination of Excess