Chapter 1 Concept of Disease 1
A Historical Perspective on Disease 1
A General Introduction to Disease 3
Health 3
Disease as States of Adaptation 3
Disease Etiology,Pathogenesis and Outcome 4
Etiology 4
Causative Factors 4
Predisposing Factors 5
Precipitating Factors 6
Pathogenesis 6
General Rule for Pathogenesis of Diseases 6
Fundamental Mechanisms for Diseases 7
Outcome 8
Complete Recovery 8
Incomplete Recovery 8
Death 8
Prevention of Diseases 9
Evidence-based Practice and Practice Guidelines of Disease 10
Chapter 2 Fluid and Electrolyte Balance and Imbalance 11
Body Fluid and Electrolyte Balance 11
Volume,Distribution and Composition of Body Fluids 11
Total Fluid Volume 11
Body Fluid Distribution 12
Body Fluid Composition 12
Osmolality of the Body Fluids 13
Mechanisms for Regulating Body Fluid and Electrolyte Balance 15
Thirst 15
Antidiuretic Hormone(ADH) 15
The Renin-Angiotensin-Aldosterone System 17
The Natriuretic Peptide Family 17
The Guanylin Family 18
Disorders of Water and Sodium Metabolism 19
Hyponatremia 20
Hypovolemic Hyponatremia 20
Hypervolemic Hyponatremia 21
Normovolemic Hyponatremia 22
Hypernatremia 23
Hypovolemic Hypernatremia 23
Hypervolemic Hypernatremia 24
Normovolemic Hypernatremia 25
Disorders of Water and Sodium Metabolism with A Normal Serum Sodium Concentration 25
Isotonic Dehydration 25
Edema 25
Disorders of Potassium Metabolism 28
Potassium Homeostasis 28
Potassium Content and Distribution 28
Maintenance of Potassium Balance 28
Potassium Function 30
Hypokalemia 32
Etiology and Pathogenesis 32
Alterations of Metabolism and Function 34
Hyperkalemia 36
Etiology and Pathogenesis 36
Alterations of Metabolism and Function 37
Pathophysiological Basis of Prevention and Treatment 38
Disorders of Magnesium Metabolism 38
Magnesium Homeostasis 38
Hypomagnesemia 40
Etiology and Pathogenesis 40
Alterations of Metabolism and Function 40
Principles of Treatment 41
Hypermagnesemia 41
Etiology and Pathogenesis 41
Alterations of Metabolism and Function 41
Pathophysiological Basis of Prevention and Treatment 42
Disorders of Calcium and Phosphorus Metabolism 42
Calcium and Phosphorus Homeostasis 42
Function of Calcium and Phosphorus 43
Hypocalcemia 43
Etiology and Pathogenesis 43
Alterations of Metabolism and Function 44
Pathophysiological Basis of Prevention and Treatment 45
Hypercalcemia 45
Etiology and Pathogenesis 45
Alterations of Metabolism and Function 45
Pathophysiological Basis of Prevention and Treatment 46
Hypophosphatemia 46
Etiology and Pathogenesis 46
Alterations of Metabolism and Function 46
Principles of Treatment 47
Hyperphosphatemia 47
Etiology and Pathogenesis 47
Alterations of Metabolism and Function 47
Principles of Treatment 47
Case Presentation 47
Chapter 3 Acid-Base Balance and Disturbances 52
Acid-Base Chemistry 52
Generation of Acids and Bases 52
Henderson-Hasselbalch Equation 53
Regulation of pH 53
Buffer Systems 53
Bicarbonate Buffer System 54
Protein Buffer System 54
Respiratory Regulatory Mechanisms 54
Renal Regulatory Mechanisms 55
Bicarbonate Conservation 55
Bicarbonate Reclamation by Proximal Tubule 55
Bicarbonate Regeneration by Distal Tubule and Collecting Duct 56
Hydrogen Ion Elimination(Acid Excretion） 56
Impact Factors for H+ Elimination 57
Laboratory Tests 58
pH 59
PaCO2 59
[HCO- 3] 59
Anion Gap(AG) 60
Simple Acid-Base Disorders 60
Concept of Simple Acid-base Disorders 60
Compensation for Simple Acid-base Disorders 61
Metabolic Acidosis 61
Concept 61
Etiology and Pathogenesis 61
Compensation 63
Alteration of Metabolism and Function 63
Respiratory Acidosis 64
Concept 64
Etiology and Pathogenesis 64
Compensation 65
Alteration of Metabolism and Function 65
Metabolic Alkalosis 66
Concept 66
Etiology and Pathogenesis 66
Compensation 67
Alteration of Metabolism and Function 67
Respiratory Alkalosis 68
Concept 68
Etiology and Pathogenesis 68
Compensation 68
Alteration of Metabolism and Function 68
Mixed Acid-Base Disorders 69
Metabolic Alkalosis and Metabolic Acidosis 69
Metabolic Acidosis and Respiratory Alkalosis 69
Metabolic Acidosis+Respiratory Acidosis 70
Metabolic Alkalosis+Respiratory Alkalosis 70
Metabolic Alkalosis+Respiratory Acidosis 70
Triple Acid-base Disorders 70
Diagnosis of Acid-base Disorders 70
Case Presentation 72
Chapter 4 Hypoxia 74
Parameters of Blood Oxygen 74
Partial Pressure of Oxygen(PO2) 74
Oxygen Capacity(CO2max) 74
Oxygen Content(CO2) 74
Oxygen Saturation(SO2) 75
P50 76
Classification,Etiology and Pathogenesis of Hypoxia 76
Hypotonic Hypoxia 76
Causes 76
Alterations of Blood Oxygen Parameters and the Mechanism of Tissue Hypoxia 77
Cyanosis 78
Hemic Hypoxia 78
Causes 78
Alterations of Blood Oxygen Parameters and Mechanism of Tissue Hypoxia 79
Circulatory Hypoxia 79
Causes 79
Alterations of Blood Oxygen Parameters and Mechanism of Tissue Hypoxia 79
Histogenous Hypoxia 79
Causes 79
Alterations of Blood Oxygen Parameters 80
Alterations of Function and Metabolism 80
Respiratory System 80
Hyperventilation 80
High Altitude Pulmonary Edema 81
Respiratory Depression 81
Circulatory System 81
Increase of Cardiac Output 81
Blood Flow Redistribution 81
Pulmonary Vasoconstriction 81
Capillary Proliferation 82
Circulatory Failure 82
Hemic System 82
Increase of Erythrocytes 82
Decrease of the Affinity of Hb for Oxygen 82
Central Nervous System 82
Cellular Alterations 83
Cellular Adaptation 83
Hypoxic Cell Damage 83
Factors Affecting the Tolerance to Hypoxia 83
Oxygen Consumption Rate 83
Compensatory Ability of the Body 84
Oxygen Therapy and Oxygen Intoxication 84
Pulmonary Oxygen Intoxication 84
Cerebral Oxygen Intoxication 84
Case Presentation 85
Chapter 5 Fever 87
Regulation of Normal Body Temperature 87
Etiology 88
The Infectious Factors 88
The Non-infectious Factors 89
Pathogenesis 89
Endogenous Pyrogens 89
IL-1 Family 89
IL-6 90
Tumor Necrosis Factor 90
Interferons(IFNs) 91
Macrophage Inflammatory Protein-1(MIP-1) 91
Thermoregulation of Fever 91
Thermoregulating Center 91
The Routes of Peripheral Pyrogenic Signals into Thermoregulation Center 92
Central Mediators of Fever 93
Alterations of Metabolism and Function 97
Pathophysiological Basis of Prevention and Treatment 99
Case Presentation 100
Chapter 6 Cell Signaling in Diseases 102
Major Pathways for Cell Signaling 103
G-Protein-Mediated Cell Signaling 103
AC Pathway 104
PLC β Pathway 104
Tyrosine Kinase Mediated Signaling 105
Receptor Tyrosine Protein Kinase(RTPK)Pathway 105
Non RTPK Pathway 106
Guanylyl Cyclase(GC)Mediated Signaling 106
Dysfunction of Cell Signaling in Diseases 106
Aberrant Signal Molecules in Diseases 107
Aberrant Receptors in Diseases 107
Aberrant G-proteins in Diseases 108
Cholera 109
Pertussis 109
Pseudohypoparathyroidism(PHP) 109
Acromegaly and Gigantism 109
Aberrant Intracellular Signaling in Diseases 109
Multiple Signaling Aberrations in Diseases 110
Type 2 Diabetes Mellitus 110
Cancers 110
Relationship between Stimulants and Pathological Effects 112
Pathophysiological Basis of Prevention and Treatment 112
To Regulate the Level of Extracellular Molecules 113
To Regulate the Structure and the Function of Receptors 113
To Regulate the Level and Modifications of Intracellular Messenger Molecules and Transducers 113
To Regulate the Level of Nuclear Transcription Factors 113
Case Presentation 114
Chapter 7 Cell Proliferation,Differentiation,Apoptosis and the Related Diseases 116
Cell Proliferation and Diseases 116
Cell Cycle and its Control 117
Cell Cycle 117
Cell Cycle Control System 117
Specific Checkpoints in the Cell Cycle 118
Control of Cell Proliferation by Extracellular Signals 119
Control of Cell Proliferation by Gene Expression 119
Deregulation of Cell Proliferation and Diseases 119
Tumor 120
Cardiac Hypertrophy 121
Cell Differentiation and Diseases 121
Control of Cell Differentiation 121
Intracellular Regulators 122
Extracellular Factors That Control Differentiation 123
Differentiation Abnormalities 124
Abnormal Differentiation in Embryonic Development 124
Abnormal Differentiation in Tumors 124
Cell Apoptosis and Diseases 124
Inducers of Apoptosis 125
Effectors and Regulators of Apoptosis 125
Effectors of Apoptosis 125
Regulators of Apoptosis 125
The Biochemical Pathways in Apoptosis 126
Abnormal Cell Apoptosis in Diseases 127
Chapter 8 Stress and Stress-related Diseases 131
Terminology of Stress 131
Stress Responses 133
Neuroendocrine Responses 133
Locus Ceruleus(LC)-norepinephrine Neurons(NE)-sympathetic/Adrenal Medulla Axis 133
Hypothalamus-pituitary-adrenal Cortex Axis(HPA) 134
Other Hormones in Stress 136
Molecular,Cellular and Humoral Stress Responses 136
Stress-activated Protein Kinases(SAPKs) 137
Acute Phase Proteins 137
Heat Shock Proteins(HSP) 139
Functional and Metabolic Responses 141
Central Nervous System 141
Immune System 142
Cardiovascular System 143
Digestive System 143
Genito-urinary System 144
Metabolism 144
Stress-related Disease 144
Stress Ulcer 145
Pathogenesis 145
Stress and Cardiovascular Diseases 146
Stress and Endocrinous Disorders 146
Stress-induced Disturbance in Growth-thyroid Function 147
Stress-induced Disturbance in Gonadal Axis 147
Stress and Psychosocial Disturbance-the PTSD 147
Pathophysiological Basis of Prevention and Treatment for Stress Disorders 148
Case Presentation 148
Chapter 9 Coagulation-anticoagulation Balance and Disorders of Hemostatic System 151
Overview of Hemostatic System 151
Vasospasm 151
Blood Coagulation 151
Formation of the Platelet Plug 152
Platelet Activation 152
Platelet Adhesion 152
Platelet Aggregation 153
P1atelet Secretion 153
Clot Dissolution(Fibrinolysis) 154
Anticoagulation System 154
Thrombomodulin(TM)-Protein C(PC)System 154
Antithrombin Ⅲ(AT Ⅲ) 155
Tissue Factor Pathway Inhibitor(TFPI) 155
Roles of Endothelial Cells 155
Disseminated Intravascular Coagulation 156
Etiology 157
Pathogenesis 157
Tissue Factor and Systemic Activation of Coagulation 157
Endothelial Lesion and Unbalance of Procoagulation and Anticoagulation 158
Entrance of Procoagulant Substances to Blood 158
B1ood Cells Damage 158
Factors Influencing the Development of DIC 159
Mononuclear Phagocyte System Dysfunction 159
Liver Dysfunction 159
Hypercoagulable State 159
Microcirculation Dysfunction 160
Clinical Classificayion of DIC 160
Acute DIC 160
Subacute DIC 160
Chronic DIC 160
Alterations of Metabolism and Function 160
Bleeding 160
Organ Dysfunction 161
Shock 162
Hemolytic Anemia 162
Pathophysiological Basis of Prevention and Treatment 162
Management of the Underlying Disorder 162
Improving the Microcirculation 162
Reconstructing the Balance of Coagulation and Fibrinolysis 162
Case Presentation 163
Chapter 10 Shock 165
Etiology and Classification 165
Hypovolemic Shock 165
Cardiogenic Shock 165
Infectious Shock 165
Anaphylactic Shock 166
Neurogenic Shock 166
Traumatic Shock 166
Pathogenesis 166
Stages of Shock and Their Pathological Changes 166
Ischemic Hypoxia Stage 166
Stagnant Hypoxia Stage 168
Organ Failure Stage 170
Roles of Humoral Factors in Pathogenesis of Shock 170
Catecholamine and Angiotensin 170
Cytokines 171
Adhesion Molecules 172
Endothelium-derived Vasoactive Mediators 172
Activation of Complement Cascade 172
Lysosomal Enzymes 172
Redox Imbalance 173
Alterations of Metabolism and Function 173
Neuroendocrine System 173
Cardiovascular System 174
Hematologic System 174
Immune System 174
Lung 175
Kidney 175
Gastrointestinal Tract 176
Liver 176
Metabolic Derangement 176
Cellular Responses 176
Pathophysiological Basis of Shock Prevention and Treatment 177
Volume Replacement 178
Application of Vasoactive Drugs 178
Treatment of Acidosis 178
Treatment of DIC or Organ Dysfunction(See Related Chapter) 178
Multiple Organ Dysfunction Syndrome(MODS) 178
Systemic Inflammatory Response Syndrome(SIRS) 178
Compensatory Anti-inflammatory Response Syndrome(CARS) 179
Mixed Antagonist Response Syndrome(MARS) 180
Case Presentation 181
Chapter 11 Ischemia-Reperfusion Injury 184
Etiology of Ischemia-Reperfusion Injury 184
Duration of Ischemia 184
Dependency on Oxygen Supply 184
Condition of Reperfusion 184
Pathogenesis of Ischemia-Reperfusion Injury 185
Injury of Free Radicals 185
Generation of Free Radical 185
Alterations Induced by Oxygen Free Radicals 187
Calcium Overload 188
Mechanism of Calcium Overload 188
Alterations Induced by Calcium Overload 189
Endothelial Injury and Neutrophil Activation 191
Alterations of Metabolism and Function During Ischemia-Reperfusion Injury 192
Myocardial Ischemia-Reperfusion Injury 192
Reperfusion Arrhythmias 192
Myocardial Stunning 192
Influence of Reperfusion on Myocardium Metabolism 193
Influence of Reperfusion on Ultrastructure of Myocardium 193
Cerebral Ischemia-Reperfusion Injury 194
Hepatic Ischemia-Reperfusion Injury 194
Renal Ischemia-Reperfusion Injury 195
Pathophysiological Basis of Prevention and Treatment for Ischemia-Reperfusion Injury 195
Controlling Reperfusion Conditions 195
Antioxidants and Free Radical Scavengers 196
Inhibitors of Neutrophils Activation 196
Calcium Antagonists or Calcium Channel Blocker 196
Case Presentation 197
Chapter 12 Heart Failure 200
Etiology 200
Causes 200
Precipitating Factors 201
Classification 201
By the Side of Heart Involved 201
By Degrees of Changes in Cardiac Output 201
By Acute or Chronic Onset 202
By Systolic or Diastolic Dysfunction 202
By Severity and Stages 202
Compensatory and Adaptive Response 203
Activation of Neurohumoral System 204
Activation of Sympathetic Nervous System 204
Activation of Renin-angiotensin-aldosterone System 204
Natriuretic Peptides 204
Cytokines 205
Functional Adjustment 205
Increasing Heart Rate and Cardiac Contractility 205
Increasing Cardiac Output by Frank-Starling Mechanism 205
Myocardial Remodeling 205
Extracardial Compensation 206
Redistribution of Blood Flow 206
Increase of Erythrocytes 207
Increased Ability of Tissues to Utilize Oxygen 207
Pathogenesis 207
Injury and Rearrangement of Myocardium 207
Disorders in Energy Metabolism 208
Disorders in Energy Production 208
Disorders in Energy Utilization 208
Dysfunction of Excitation-Contraction Coupling 208
Reduced Influx of Extracellular Ca2+ 208
Disorders of SR in Ca2+ Handling 209
Dysfunction of Ca2+ Binding to Troponin 209
Decreased Ventricular Compliance 209
Asynergic Myocardial Contraction and Dilation 210
Alterations of Metabolism and Function 210
Low Output Syndrome 210
Changes of Hemodynamic Parameters 210
Ischemia of Organs 211
Venous Congestion Syndrome 211
Congestion of Systemic Circulation 211
Congestion of Pulmonary Circulation 211
Pathophysiological Basis of Prevention and Treatment 212
Control and Removal of Causes and Precipitating Factors 212
Improvement of Cardiac Pump Function 213
Reducing Cardiac Preload and Afterload 213
Improving Cardiac Contractility and Diastolic Properties 213
Intervention of Myocardial Remodeling 213
Promotion of Myocardial Growth and Replacement of Failing Heart 213
Case Presentation 214
Chapter 13 Respiratory Failure 218
Etiology and Pathogenesis 218
Ventilatory Disorder 218
Restrictive Ventilatory Disorder 218
Obstructive Ventilatory Disorder 219
Diffusion Disorder 220
Ventilation and Perfusion Imbalance 221
Functional Shunt Caused by Local Hypoventilation 222
Dead Space Like Ventilation Caused by Local Hypoperfusion 222
Anatomic Shunt 222
Acute Respiratory Failure and Chronic Respiratory Failure 223
Pathogenesis of Acute RF in Acute Respiratory Distress Syndrome(ARDS) 223
Pathogenesis of Chronic RF in Chronic Obstructive Pulmonary Disease(COPD) 224
Alterations of Function and Metabolism 224
Acid-base Imbalance and Electrolyte Imbalance 224
Respiratory System 224
Cardiovascular System 225
Central Nervous System 225
Pathophysiological Basis of Treatment 226
Treating the Causes of Respiratory Failure 226
Increasing PaO2 226
Decreasing PaCO2 226
Case Presentation 227
Chapter 14 Hepatic Failure 230
Etiology 230
Hepatic Insufficiency 230
Metabolic Disorders 230
Carbohydrate Metabolic Disorders 230
Lipid Metabolic Disorders 231
Protein Metabolic Disorders 231
Metabolic Disorders of Water and Electrolytes 232
Hepatic Ascites 232
Electrolytic Metabolic Disorders 232
Disorders in Production of Bile Salts and Elimination of Bilirubin 232
Disorders in Biochemical Transformation 232
Impaired Kupffer Cells Function 232
Hepatic Encephalopathy 233
Etiology and Classification 233
Pathogenesis 234
Ammonia Intoxication 234
False Neurotransmitters and Amino Acid Imbalance 236
The Gamma-aminobutyric Acid Hypothesis 238
Precipitating Factors of HE 239
Gastrointestinal Bleeding 239
Abuse of Sedatives and Narcotics 240
Massive Paracentesis and Excessive Diuresis 240
Infections 240
Principles of Treatment 240
Hepatorenal Syndrome 241
Pathogenesis 241
Stimulated Sympathetic Nervous System 241
Activated Rennin-angiotensin-aldosterone System 241
Increased Vasopressin Release 241
Other Humoral Factors 241
Principles of Treatment and Prevention 243
Case Presentation 244
Chapter 15 Renal Insufficiency 247
Basic Tache of Pathogenesis for Renal Insufficiency 247
Dysfunction of Glomerular Filtration 248
Decrease of Renal Blood Flow 249
Decrease of Glomerular Effective Filtration Pressure 249
Decrease of Glomerular Capillary Surface Area 249
Alterations of Permeability of Glomerular Filtration Member 249
Renal Tubular Dysfunction 249
Dysfunction of Proximal Convoluted Tubules 250
Dysfunction of Henle's Loop 250
Dysfunction of the Distal Convoluted Tubules and Collecting Ducts 250
Renal Endocrine Dysfunction 250
Renin-angiotensin-aldosterone System(RAAS) 250
Erythropoietin(EPO) 250
1α,25-dihydroxyvitamin D3(1,25-[OH]2D3) 250
Kallikrein-kinin-prostaglandin-system(KKPGS) 251
Parathyroid Hormone(PTH) and Gastrin 251
Acute Renal Failure 251
Etiology and Classification of ARF 251
Prerenal ARF 252
Intrarenal ARF 252
Postrenal ARF 252
Pathogenesis of ARF 253
Glomerular Factors 253
Renal Tubular Factors 253
Renal Cellular Injury and Its Mechanisms 255
Alterations of Metabolism and Function During ARF 256
The Oliguric Stage 256
The Polyuric Stage 257
The Recovery Stage 258
Pathophysiological Basis of Prevention and Treatment for ARF 258
Chronic Renal Failure 258
Etiology of CRF 259
Progressive Stages of CRF 259
Pathogenesis of CRF 259
The Major Hypotheses on CRF 259
Mechanism Responsible for the Loss of Nephron Function 261
Alterations of Metabolism and Function During CRF 263
Alteration of Urine 263
Azotemia 263
Water,Electrolytes and Acid-base Imbalance 263
Renal Hypertension 264
Renal Osteodystrophy 265
Tendency to Hemorrhage 265
Renal Anemia 265
Uremia 266
Pathogenesis of Uremia 266
Retained Metabolic Products 266
Overproduction of Counter-regulatory Hormones 267
Underproduction of Renal Hormones 267
Functional and Metabolic Alterations During Uremia 267
Nervous System 267
Digestive System 267
Cardiovascular System 267
Respiratory System 268
Immune System 268
Skin Changes(Dermatologic Abnormalities) 268
Metabolic Disorders 268
Pathophysiological Basis of Prevention and Treatment for CRF and Uremia 269
Case Presentation 270
Chapter 16 Brain Dysfunction 277
Introduction 277
Characteristics of Brain Structure,Metabolism and Function 277
Characteristics of Brain Diseases 277
Cognitive Disorders 278
Structural Basis of Cognition 278
Physiology of Cognition 279
Major Manifestations of Cognitive Disorders 279
Learning and Memory Disorders 280
Aphasia 280
Agonosia 280
Apraxia 280
Dementia 280
Etiology and Pathogenesis of Cognitive Disorders 281
Chronic Brain Damage 281
Chronic Systemic Diseases 284
Mental and Psychic Disorders 285
Other Factors 285
Principles for Treatment of Cognitive Disorders 285
General Neuroprotective Treatments 285
Maintenance of Normal Neurotransmitter Level 286
Surgery 286
Consciousness Disorder 286
The Structural Basis of the Brain in Consciousness and Consciousness Disorders 286
Dysfunction of Brain Stem Reticular Formation 286
Dysfunction of Thalamus 287
Dysfunction of Cerebral Cortex 287
Major Manifestations in Consciousness Disorders 287
Delirium 287
Confusion 287
Stupor 287
Coma 288
The Etiology and Pathogenesis of Consciousness Disorder 288
Acute Brain Injury 288
Acute Brain Intoxication 288
Intracranial Extrusion and Destructive Lesion 289
Systemic Disturbance Caused by Consciousness Disorder 289
Respiratory Disorders 290
Disturbance of Fluid-electrolyte and Acid-base Balance 290
Circulation Dysfunction 291
Others 291
Principles of Prevention and Therapy 291
Urgent Management 291
Making A Definite Diagnosis as Soon as Possible 291
Monitoring Vital Signs and Consciousness State 291
Brain Protections 291
Case Presentation 292
Index 295