Chapter 1 Conspectus of Disease 1
Concept of Disease 1
Etiology of Disease 1
Pathogenesis of Disease 3
Outcome of Disease 4
Chapter 2 Water and Electrolytes Balance and Imbalance 6
Water and Sodiun Balance and Imbalance 6
Water and Sodium Balance 6
Total Fluid Volume and Distribution 6
Body Fluid Composition 7
Osmolality of the Body Fluids 8
Water Balance 8
Mechanisms for Regulation of Body Fluid and Electrolyte Balance 9
Disorders of Sodium and Water Metabolism 11
Hyponatremia 11
Hypernatremia 13
Isotonic Dehydration 14
Edema 15
Disorder of Potassium Metabolism 16
Normal Potassium Metabolism 16
Internal Potassium Distribution 16
Regulation of Potassium Homeostasis 17
Physiological Function of Potassium 19
Disorders of Potassium Metabolism 20
Hypokalemia and Potassium Deficiency 20
Hyperkalemia 24
Disturbances of Magnesium Metabolism 26
Normal Metabolism and Function of Mag-nesium 26
Intake and Excretion 26
Regulation of Magnesium Balance 27
Distribution and Content of Magnesium 27
Function of Magnesium 27
Hypomagnesemia 27
Definition 27
Etiology and Pathogenesis 27
Alterations of Metabolism and Function 28
Pathophysiology Basis of Prevention and Treatment 29
Hypermagnesemia 29
Definition 29
Etiology and Pathogenesis 29
AIterations of Metabolism and Function 29
Pathophysiology Basis of Prevention and Treatment 30
Disorders of Calcium and Phosphorus Meta-bolism 30
Calcium and Phosphorus Homeostasis 30
Calcium and Phosphorus Intake and Excre-tion 30
Content and Distribution of Calcium and Phosphorus within the Body 31
Regulation of Internal Calcium and Pho-sphorus Balance 31
Regulation of Intracellular Calcium and Phosphorus Balance 33
Function of Calcium and Phosphorus 34
Hypocalcemia 34
Definition 34
Etiology and Pathogenesis 35
Alteration of Metabolism and Function 35
Pathophysiological Basis of Prevention and Treatment 36
Hypercalcemia 36
Definition 36
Etiology and Pathogenesis 36
Alteration of Metabolism and Function 37
Pathophysiological Basis of Prevention and Treatment 37
Hypophosphaternia 37
Definition 37
Etiology and Pathogenesis 37
Alteration of Metabolism and Function 38
Pathophysiological Basis of Prevention and Treatment 38
Hyperphosphatemia 38
Definition 38
Etiology and Pathogenesis 38
Alteration of Metabolism and Function 38
Pathophysiological Basis of Prevention and Treatment 38
Case Presentation 38
Chapter 3 Acid-Base Balance and Imba-lance 40
Normal Acid-Base Balance 40
Concepts of Acid and Base 40
Sources of Acids and Bases 40
Sources of Acids 40
Sources of Bases 41
Regulation of Acid-Base Balance 42
Buffer Systems 42
Respiratory Regulation of Acid-Base Bala-nce 43
Reral Regulation of Acid-Base Palance 43
Parameters of Acid-Base Balance 45
pH 45
PaCO2 45
Standard Bicarbonate and Actual Bicarbo-nate 46
Buffer Base 46
Base Excess 46
Anion Gap 46
Simple Acid-Base Disturbance 46
Metabolic Acidosis 47
Etiology 47
Classification 47
Compensation 48
Changes of Acid-Base Parameters and Electrolytes 48
Alterations of Metabolism and Function 48
Principles of Prevention and Treatment 49
Respiratory Acidosis 49
Etiology 49
Compensation 49
Changes of Acid-Base Parameters and Electrolytes 50
Alterations of Metabolism and Function 50
Principles of Prevention and Treatment 50
Metabolic Alkalsosis 50
Etiology 50
Classification 51
Compensation 51
Changes of Acid-Base Parameters and Electrolytes 51
A1terations of Metabolism and Function 51
Principles of Prevention and Treatment 51
Respiratory Alkalosis 52
Etiology 52
Classification and Compensation 52
Changes of Acid-Base Parameters 52
Alterations of Metabolism and Function 52
Principles of Prevention and Treatment 52
Mixed Acid-Base Disturbances 52
Double Acid-Base Disturbances 53
Respiratory Acidosis and Metabolic Aci-dosis 53
Respiratory Alkalosis and Metabolic Alka-losis 53
Respiratory Acidosis and Metabolic Alka-losis 53
Metabolic Acidosis and Respiratory Alka-losis 53
High AG Metabolic Acidosis and Meta-bolic Alkalosis 53
Triple Acid-Base Disturbances 53
Respiratory Acidosis and High AG Meta-bolic Acidosis and Metabolic Alkalosis 53
Respiratory Alkalosis and High AG Meta-bolic Acidosis and Metabolic Alkalosis 54
Guidelines for the Diagnosis of Acid-Base Disturbances 54
Diagnosis of Simple Acid-Base Disturbances 54
Diagnosis of Mixed Acid-Base Disturbances 54
Differentiate Between Simple and Mixed Acid-base Disturbance According to Compensatory Formulas 54
Changes of PaCO2 and HCO3￣in Opposite Directions 55
Calculation of AG value is important for the difierentiation of the classes of simple metabolic acidosis and the diagnosis of mixed acid-base disorders 55
Case Presentation 55
Chapter 4 Fever 57
Etiology 58
Exogenous Pyrogens 58
Non-microbial Pyretic Substances 58
Pathogenesis 58
Endogenous Pyrogens 58
EP and the Thermoregulatory Center 59
Central Mediators of Fever 60
Stages and Manifestations 62
The Fervescence Stage 62
The Persistent Febrile Stage 62
The Defervescence Stage 62
Alterations of Metabolism and Function 62
Metabolism 63
Central nervous System 63
Cardiovascular System 64
Respiratory System 64
Digestive System 64
Self-defense 64
Pathophysiological Bosis of Prevention and Treatment 64
Case Presentation 65
Chapter 5 Stress 66
Etiology and Pathogenesis 66
Stressor 66
The Stress Response 67
Alterations of Metabolism and Function 71
Stress and Disease 72
General Adaptation Syndrome(GAS) 73
Stress Ulcer 73
Cardiovascular Diseases 73
Immune Dysfunctions 74
Posttraumatic Stress Disorder 74
Basic Principle of Prevention and Treatment for Stress Disorders 75
Case Presentation 75
Chapter 6 Hypoxia 76
Parameters of Blood Oxygen 76
Partial Pressure of Oxygen 76
Oxygen Binding Capacity of Haemoglobin 76
Oxygen Content in Blood 76
Oxygen Saturation of Haemoglobin 76
Classification,Etiology and Mechanisms of Hypoxia 77
Hypotonic Hypoxia 77
Etiology and Mechanisms of Hypotonic Hypoxia 77
Characteristics of Blood O2 77
Hemic Hypoxia 77
Etiology and Mechanisms of Hemic Hypoxia 77
Characteristics of Blood O2 78
Circulatory Hypoxia 78
Etiology and Mechanisms of Circulatory Hypoxia 78
Characteristic of Blood Oxygen 78
Histogenous Hypoxia 78
Etiology and Mechanisms of Histogenous Hypoxia 79
Characteristics of Blood O2 79
Alterations of Metabolism and Function in the Body 79
Alterations of Respiratory System 79
Compensatory Response 79
Injury Manifestation 80
Alterations of Circulatory System 80
Compensatory Response 80
lnjury Manifestation 81
Alterations of Hematologic System 81
Compensatory Response 81
Injury Manifestation 81
Alterations of Central Nerve System 81
Alterations of Tissues and Cells 82
Compensatory Response 82
Injured Manifestation 82
Pathophysiological Basis of Prevention and Treatment 83
Case Presentation 83
Chapter 7 Shock 84
Etiology and Classification of Shock 84
Classification According to Causes 84
Classification According to the Pathogene-sis of Shock Development 84
Pathogenesis of Shock 84
Microcirculatory Mechanisms 85
Ischemic Hypoxia Stage(Compensatory Stage) 85
Stagnant Hypoxia Stage(Reversible Decompensated Stage) 87
Refractory Stage(Microcirculatory Fai-lure Stage) 89
Cellular and Molecular Mechanisms 90
Alterations of Cellular Metabolism 90
Cell Injury and Apoptosis 91
Humoral Factors 91
Inflammatory Mediator and Inappropriate Inflammatory Response 92
Alterations of Metabolism and Function 93
Metabolic Derangement 93
Water,Electrolytes and Acid-Base Distur-bance 93
Organ Dysfunction 93
Features of Several Common Types of Shock 94
Hypovolemic Shock 94
Septic Shock 94
Anaphylactic Shock 94
Neurogenic Shock 94
Cardiogenic Shock 95
Pathophysiologic Basis of Prevention and Treatment 95
Improve Microcirculation 95
Blockage of Humoral Factors 95
Cell Protection 96
Organ Protection 96
Case Presentation 96
Chapter 8 Disturbances of Hemostasis 97
Coagulation Cascade and its Regulation 97
Coagulation System and its Functions 97
Extrinsic Coagulation Pathway 98
Intrinsic Coagulation Pathway 98
Roles of Platelet in Coagulation 99
Adhesion and Conformational Change of Platelets 99
Release Reaction of Platelets 99
Platelet Aggregation Follows Adhesion and Secretion 101
Anticoagulant Systems 101
Actions of Serine Protease Inhibitors and Heparin 101
Thrombomodulin-protein C System 101
Tissue Factor Pathway Inhibitor 102
Fibrinolytic System and its Function 102
Endothelial Cells Modulate Several Aspects of Normal Hemostasis 102
Coagulation and Anti-coagulation Disorders 104
Bleeding Caused by Coagulation Factor Disorders 104
Hereditary Coagulation Factor Disorders 104
Acquired Coagulation Factor Disorders 106
Hypercoagulable Status 106
Hereditary Risk Factors For Thrombosis(Hereditary Thrombosis-Related Coagulation Factor Disorders) 106
Acquired Risk Factors for Thrombosis-Secondary Hypercoagulable Status 109
Atrophy 110
P1asma Fibrinolysis Abnormalities 110
Bleeding-related Fibrinolysis Abnorma-lities—α2-Antiplasmin Deficiency 110
Thrombosis-related Fibrinolysis Abnor-malities 110
Platelet Disorders 110
Thrombocytopenia 110
Thrombocytosis 111
Qualitative Platelet Disorders 111
Vessel Wall Disorders 112
Disseminated Intravascular Coagulation(DIC) 112
Etiologies and Mechanisms of DIC 113
Extensive Tissue Injuries 113
Damage of Vascular Endothelial Cells 113
Destruction of Blood Cells and Activa-tion of Platelets 115
Pro-coagulants Entering Circulation 115
Factors Influencing the Formation and Development of DIC 116
Inappropriately Conditioned Monocytes-Macrophages 117
Impairment of Liver and Spleen Functions 117
Hypercoagulable Status 117
Dysfunction of Microcirculation 118
Clinical Classifications 118
Classification According to The Clinical Course 118
Classification According to the Compensatory Level 119
Alterations of Metabolism and Function 119
Bleeding 120
Organ Dysfunctions 121
Shock 122
Microangiopathic Hemolytic Anemia 122
Pathophysiological Basis of Prevention and Treatment of DIC 123
Reversing the Underlying Disorders Initiating DIC 123
Improving the Microcirculation 123
Reconstructing the Balance Among Coagulation,Anti-coagulation and Fibrinolysis 123
Case Presentation 123
Chapter 9 Ischemia-Reperfusion Injury 126
Etiology 126
Duration of Ischemia 126
Collateral Circulation 126
Dependency on Oxygen Supply 126
Condition of Reperfusion 126
Pathogenesis 126
Free Radicals 127
Calcium Overload 128
Neutrophils Activation 128
Alterations of Metabolism and Function 129
Myocardial Ischemia-repeffusion Injury 129
Cerebral Ischemia-repeffusion Injury 130
Ischemia-reperfusion Injury in Other Organs 130
Pathophysiological Basis of Prevention and Treatment 130
Control the Reperfusion Conditions 130
Scavenge the Free Radicals 131
Relieve Calcium Overload 131
Improve the Metabolism 131
Case Presentation 131
Chapter 10 Signal Transduction and the Related Disorders 133
General Concept 133
Signal Transduction 133
Transmembrane Signal Transduction 133
Key Elements of Signal Transduction 133
Relationship Between Stimulants and Pa-thological Effects 133
Major Pathways for Cell Signaling 134
G-Protein-Mediated Cell Signaling 134
Tyrosine Protein Kinase Mediated Signa-ling 134
Intracellular Receptor Signaling 135
Dysfunction of Cell Signaling in Diseases 135
Aberrant Receptors in Diseases 136
Aberrant G-Proteins in Diseases 137
Aberrant Intracellular Signal Molecules in Diseases 137
Multiple Signaling Aberrations in Diseases 139
Pathophysiologic Basis of Prevention and Treatment of Diseases 141
To Regulate the Level of Extracellular Molecules 141
To Regulate the Structure and the Func-tion of Receptors 141
To Regulate the Level and Modifications of Intracellular Messenger Molecules and Transducers 142
To Regulate the Level of Nuclear Trans-cription Factors 142
Case Presentation 142
Chapter 11 Abnormal Cell Proliferation,Differenfiation and Related Diseases 144
Deregulated Cell Proliferation and Diseases 144
Concept and Phases of the Cell Cycle 144
Regulation of the Cell Cycle 145
Regulation of the Cell Cycle by Intracell-ular Signals 146
Regulation of the Cell Cycle by Extracell-ular Signals 147
Role of Abnormal Cell Cycle in the Path-ogenesis of Disease 148
Overexpression of Cyclins 148
Increased Activation of Cdks and Muta-tion of their Substrates 148
Deficient Expression and Mutation of Ckis 149
The Impairment of Checkpoint System 149
Deregulated Cell Differentiation and Diseases 149
Regulation of Cell Differentiation 150
The Regulation on the Genomic Level 150
Regulation on Transcription and Post-transcription Levels 150
Extracellular Factors that Control Diif-erentiation 151
The Role of Abnormal Cell Differentiationin the Pathogenesis of Diseases 151
Chapter 12 Apoptosis and Related Dis-eases 154
Introduction 154
Features of Apoptotic Cells 154
Phases of Apoptosis 155
Influence Factors of Apoptosis 155
Biochemical Mechanism of Apoptosis 156
A Central Role for Caspases in Apoptosis 156
Apoptosis Pathways 157
Regulated Mechanism of Apoptosis 159
Regulation of the Extrinsic Pathway 159
Bcl-2 Family Proteins and Regulation of Apoptosis 160
Regulation of Apoptosis by IAP Family Members 161
p53 161
Apoptosis and Diseases 161
Regulation of Apoptosis in Treatment of Disease 165
Chapter 13 Heart Failure 166
Fundamental Knowledge 166
Histology of Myocardium 166
Physiology of the Whole Heart 167
Cellular Physiology of Ventricular and Atrial Myocytes 168
Biochemical Metabolic Particularity of Myocardium 169
Etiology 169
Classification 170
Right-Side Versus left-side Heart Failure 170
Acute Versus Chronic Heart Failure 170
Low-output Versus High-Output Heart Failure 171
Compensatory Responses 171
Cardiac Compensation 171
Systemic Compensation 172
Pathogenesis 173
Decreased Myocardial Contractility 174
Diastolic Dvsfunction 176
Altered Signal Transduction 176
Excessive Cardiac Hypertrophy 176
Clinical Manifestations 177
Left Heart Failure 177
Right Ventricular Failure 179
Pathophysiologic Basis of Prevention and Treatment 179
Etiologic Therapy 179
Avoiding Precipitating Factors 179
Improving Cardiac Functions 180
Reducing Afterload and Preload 180
Controlling Edema 180
Case Presentation 180
Chapter 14 Respiratory Failure 182
Etiology and Classification 182
Etiology 182
Classification 182
Pathogenesis 183
Ventilation Disorder 183
Gas-exchanging Dysfunction 186
Alterations of Metabolism and Function 190
Acid-Base Imbalance and Electrolyte Dis-turbance 190
Changes of Respiratory System 191
Changes of Circulatory System 191
Changes of Central Nervous System 192
Changes of Urinary System 193
Changes of Digestive System 193
Pathophvsiological Basis of Prevention and Treatment 193
Prevent and Remove of Reasons 193
Raise PaO2 193
Degrade PaCO2 193
Improve Internal Environment and Function of Critical Organ 193
Case Presentation 193
Chapter 15 Hepatic Failure 195
Etiology 195
Hepatic Insufficiency 195
Metabolic Disorders 195
Metabolic Disorders of Water and Electro-lytes 196
Disorders in Production of Bile Salts and Elimination of Bilirubin 197
Impaired Kupffer Cells Function 197
Hepatic Encephalopathy 197
Etiology and Classification 197
Pathaogenesis 198
Precipitating Factors of Hepatic Encepha-lopathy 202
Principles of Treatment 203
Hepatorenal Syndrome 203
Principles of Treatment and Prevention 205
Case Presentation 205
Chapter 16 Renal Failure 207
Acute Renal Failure 207
Etiology and Classification 207
Prerenal Acute Renal Failure 208
Intrarenal Acute Renal Failure 208
Posuenal Acute Renal Failure 208
Pathogenesis 209
Alterations of Metabolism and Function 210
Urinary Abnormalities 210
Hyperkalemia 210
Other Abnormalities 210
Pathophysiological Basis of Prevention and Treatment 210
Chronic Renal Failure 211
Etiology 211
Clinical Course of Chronic Renal Failure 211
Stage of Decreased Renal Reserve 211
Stage of Renal Insufficiency 211
Stage of Renal Failure 211
Stage of Uremia 211
Pathogenesis 212
Intact Nephron Hypothesis 212
Trade-Off Hypothesis 212
Glomerular Hyperfiltration Hypothesis 213
Alterations of Metabolism and Function 213
Disorders of Urine 213
Disorders of Water and Sodium Balance 213
Disorders of Potassium Balance 213
Metabolic Acidosis 214
Renal Azotemia 214
Renal Hypertension 214
Calcium,Phosphate and Bone Metabolism 214
Renal Anemia and Bleeding Tendency 214
Uremia 215
Etiology and Pathogenesis 215
Urea and Other Small Molecular Weight Molecules 215
Middle Molecules 216
Polypeptide Hormones 216
Alterations of Metabolism and Function 216
Neuromuscular Abnormalities 216
Cardiovascular and Pulmonary Abnorma-lities 216
Hematological Abnormalities 217
Gastrointestinal Abnormalities 217
Endocrine and Metabolic Abnormalities 217
Dermatologic Abnormalities 217
Inmunologic Abnormalities 217
Pathophysiological Basis of Prevention and Treatment 217
Case Presentation 218
Chapter 17 Brain Dysfunction 219
Cell Biology of the Brain 219
Neurons 219
Astrocytes 221
Oligodendrocytes 221
Microglia 221
Basic Knowledge on Consciousness 221
Anatomy 221
Physiology 222
Pathophysiology of Selected Brain Disorders 225
Parkinson's Disease 225
Epilepsy 226
Alzheimer's Disease 228
Stroke 231
Case Presentation 234
Chapter 18 Multiple Organ Dysfunction Syndrome 236
Overview 236
Systemic Inflarmmatory Response Syndrome(SIRS) 237
Etiology 237
Diagnostic Criteria of SIRS 238
Stages of SIRS 238
Pathogenesis of SIRS 239
Multiple Organ Dysfunction 245
Types of MODS 245
Alterations of Metabolism and Function During MODS 246
Pathophysiological Basis of Prevention and Treatment 248
Case Presentation 249
Chapter 19 Metabolic Syndrome 253
Etiology and Pathogenesis 253
Obesity and Abnormal Body Fat Distri-bution 253
Insulin Resistance 254
Independent Factors that Mediate Specific Components of the Metabolic Syndrome 254
Other Contributing Factors 255
Alterations of Metabolism and Function 255
Hyperglycemia 255
Obesity 256
Hypertension 257
Hypertriglyceridemia 257
Principles of Prevention and Treatment 258
Life-style Modification 258
Pharmacological Therapy 258
Other Managements 258
Case Presentation 259
English-Chinese Comparison 260