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Chapter 1 Conspectus of Disease1

Concept of Disease1

Etiology of Disease1

Pathogenesis of Disease3

Outcome of Disease4

Chapter 2 Water and Electrolytes Balance and Imbalance6

Water and Sodiun Balance and Imbalance6

Water and Sodium Balance6

Total Fluid Volume and Distribution6

Body Fluid Composition7

Osmolality of the Body Fluids8

Water Balance8

Mechanisms for Regulation of Body Fluid and Electrolyte Balance9

Disorders of Sodium and Water Metabolism11

Hyponatremia11

Hypernatremia13

Isotonic Dehydration14

Edema15

Disorder of Potassium Metabolism16

Normal Potassium Metabolism16

Internal Potassium Distribution16

Regulation of Potassium Homeostasis17

Physiological Function of Potassium19

Disorders of Potassium Metabolism20

Hypokalemia and Potassium Deficiency20

Hyperkalemia24

Disturbances of Magnesium Metabolism26

Normal Metabolism and Function of Mag-nesium26

Intake and Excretion26

Regulation of Magnesium Balance27

Distribution and Content of Magnesium27

Function of Magnesium27

Hypomagnesemia27

Definition27

Etiology and Pathogenesis27

Alterations of Metabolism and Function28

Pathophysiology Basis of Prevention and Treatment29

Hypermagnesemia29

Definition29

Etiology and Pathogenesis29

AIterations of Metabolism and Function29

Pathophysiology Basis of Prevention and Treatment30

Disorders of Calcium and Phosphorus Meta-bolism30

Calcium and Phosphorus Homeostasis30

Calcium and Phosphorus Intake and Excre-tion30

Content and Distribution of Calcium and Phosphorus within the Body31

Regulation of Internal Calcium and Pho-sphorus Balance31

Regulation of Intracellular Calcium and Phosphorus Balance33

Function of Calcium and Phosphorus34

Hypocalcemia34

Definition34

Etiology and Pathogenesis35

Alteration of Metabolism and Function35

Pathophysiological Basis of Prevention and Treatment36

Hypercalcemia36

Definition36

Etiology and Pathogenesis36

Alteration of Metabolism and Function37

Pathophysiological Basis of Prevention and Treatment37

Hypophosphaternia37

Definition37

Etiology and Pathogenesis37

Alteration of Metabolism and Function38

Pathophysiological Basis of Prevention and Treatment38

Hyperphosphatemia38

Definition38

Etiology and Pathogenesis38

Alteration of Metabolism and Function38

Pathophysiological Basis of Prevention and Treatment38

Case Presentation38

Chapter 3 Acid-Base Balance and Imba-lance40

Normal Acid-Base Balance40

Concepts of Acid and Base40

Sources of Acids and Bases40

Sources of Acids40

Sources of Bases41

Regulation of Acid-Base Balance42

Buffer Systems42

Respiratory Regulation of Acid-Base Bala-nce43

Reral Regulation of Acid-Base Palance43

Parameters of Acid-Base Balance45

pH45

PaCO245

Standard Bicarbonate and Actual Bicarbo-nate46

Buffer Base46

Base Excess46

Anion Gap46

Simple Acid-Base Disturbance46

Metabolic Acidosis47

Etiology47

Classification47

Compensation48

Changes of Acid-Base Parameters and Electrolytes48

Alterations of Metabolism and Function48

Principles of Prevention and Treatment49

Respiratory Acidosis49

Etiology49

Compensation49

Changes of Acid-Base Parameters and Electrolytes50

Alterations of Metabolism and Function50

Principles of Prevention and Treatment50

Metabolic Alkalsosis50

Etiology50

Classification51

Compensation51

Changes of Acid-Base Parameters and Electrolytes51

A1terations of Metabolism and Function51

Principles of Prevention and Treatment51

Respiratory Alkalosis52

Etiology52

Classification and Compensation52

Changes of Acid-Base Parameters52

Alterations of Metabolism and Function52

Principles of Prevention and Treatment52

Mixed Acid-Base Disturbances52

Double Acid-Base Disturbances53

Respiratory Acidosis and Metabolic Aci-dosis53

Respiratory Alkalosis and Metabolic Alka-losis53

Respiratory Acidosis and Metabolic Alka-losis53

Metabolic Acidosis and Respiratory Alka-losis53

High AG Metabolic Acidosis and Meta-bolic Alkalosis53

Triple Acid-Base Disturbances53

Respiratory Acidosis and High AG Meta-bolic Acidosis and Metabolic Alkalosis53

Respiratory Alkalosis and High AG Meta-bolic Acidosis and Metabolic Alkalosis54

Guidelines for the Diagnosis of Acid-Base Disturbances54

Diagnosis of Simple Acid-Base Disturbances54

Diagnosis of Mixed Acid-Base Disturbances54

Differentiate Between Simple and Mixed Acid-base Disturbance According to Compensatory Formulas54

Changes of PaCO2 and HCO3￣in Opposite Directions55

Calculation of AG value is important for the difierentiation of the classes of simple metabolic acidosis and the diagnosis of mixed acid-base disorders55

Case Presentation55

Chapter 4 Fever57

Etiology58

Exogenous Pyrogens58

Non-microbial Pyretic Substances58

Pathogenesis58

Endogenous Pyrogens58

EP and the Thermoregulatory Center59

Central Mediators of Fever60

Stages and Manifestations62

The Fervescence Stage62

The Persistent Febrile Stage62

The Defervescence Stage62

Alterations of Metabolism and Function62

Metabolism63

Central nervous System63

Cardiovascular System64

Respiratory System64

Digestive System64

Self-defense64

Pathophysiological Bosis of Prevention and Treatment64

Case Presentation65

Chapter 5 Stress66

Etiology and Pathogenesis66

Stressor66

The Stress Response67

Alterations of Metabolism and Function71

Stress and Disease72

General Adaptation Syndrome(GAS)73

Stress Ulcer73

Cardiovascular Diseases73

Immune Dysfunctions74

Posttraumatic Stress Disorder74

Basic Principle of Prevention and Treatment for Stress Disorders75

Case Presentation75

Chapter 6 Hypoxia76

Parameters of Blood Oxygen76

Partial Pressure of Oxygen76

Oxygen Binding Capacity of Haemoglobin76

Oxygen Content in Blood76

Oxygen Saturation of Haemoglobin76

Classification,Etiology and Mechanisms of Hypoxia77

Hypotonic Hypoxia77

Etiology and Mechanisms of Hypotonic Hypoxia77

Characteristics of Blood O277

Hemic Hypoxia77

Etiology and Mechanisms of Hemic Hypoxia77

Characteristics of Blood O278

Circulatory Hypoxia78

Etiology and Mechanisms of Circulatory Hypoxia78

Characteristic of Blood Oxygen78

Histogenous Hypoxia78

Etiology and Mechanisms of Histogenous Hypoxia79

Characteristics of Blood O279

Alterations of Metabolism and Function in the Body79

Alterations of Respiratory System79

Compensatory Response79

Injury Manifestation80

Alterations of Circulatory System80

Compensatory Response80

lnjury Manifestation81

Alterations of Hematologic System81

Compensatory Response81

Injury Manifestation81

Alterations of Central Nerve System81

Alterations of Tissues and Cells82

Compensatory Response82

Injured Manifestation82

Pathophysiological Basis of Prevention and Treatment83

Case Presentation83

Chapter 7 Shock84

Etiology and Classification of Shock84

Classification According to Causes84

Classification According to the Pathogene-sis of Shock Development84

Pathogenesis of Shock84

Microcirculatory Mechanisms85

Ischemic Hypoxia Stage(Compensatory Stage)85

Stagnant Hypoxia Stage(Reversible Decompensated Stage)87

Refractory Stage(Microcirculatory Fai-lure Stage)89

Cellular and Molecular Mechanisms90

Alterations of Cellular Metabolism90

Cell Injury and Apoptosis91

Humoral Factors91

Inflammatory Mediator and Inappropriate Inflammatory Response92

Alterations of Metabolism and Function93

Metabolic Derangement93

Water,Electrolytes and Acid-Base Distur-bance93

Organ Dysfunction93

Features of Several Common Types of Shock94

Hypovolemic Shock94

Septic Shock94

Anaphylactic Shock94

Neurogenic Shock94

Cardiogenic Shock95

Pathophysiologic Basis of Prevention and Treatment95

Improve Microcirculation95

Blockage of Humoral Factors95

Cell Protection96

Organ Protection96

Case Presentation96

Chapter 8 Disturbances of Hemostasis97

Coagulation Cascade and its Regulation97

Coagulation System and its Functions97

Extrinsic Coagulation Pathway98

Intrinsic Coagulation Pathway98

Roles of Platelet in Coagulation99

Adhesion and Conformational Change of Platelets99

Release Reaction of Platelets99

Platelet Aggregation Follows Adhesion and Secretion101

Anticoagulant Systems101

Actions of Serine Protease Inhibitors and Heparin101

Thrombomodulin-protein C System101

Tissue Factor Pathway Inhibitor102

Fibrinolytic System and its Function102

Endothelial Cells Modulate Several Aspects of Normal Hemostasis102

Coagulation and Anti-coagulation Disorders104

Bleeding Caused by Coagulation Factor Disorders104

Hereditary Coagulation Factor Disorders104

Acquired Coagulation Factor Disorders106

Hypercoagulable Status106

Hereditary Risk Factors For Thrombosis(Hereditary Thrombosis-Related Coagulation Factor Disorders)106

Acquired Risk Factors for Thrombosis-Secondary Hypercoagulable Status109

Atrophy110

P1asma Fibrinolysis Abnormalities110

Bleeding-related Fibrinolysis Abnorma-lities—α2-Antiplasmin Deficiency110

Thrombosis-related Fibrinolysis Abnor-malities110

Platelet Disorders110

Thrombocytopenia110

Thrombocytosis111

Qualitative Platelet Disorders111

Vessel Wall Disorders112

Disseminated Intravascular Coagulation(DIC)112

Etiologies and Mechanisms of DIC113

Extensive Tissue Injuries113

Damage of Vascular Endothelial Cells113

Destruction of Blood Cells and Activa-tion of Platelets115

Pro-coagulants Entering Circulation115

Factors Influencing the Formation and Development of DIC116

Inappropriately Conditioned Monocytes-Macrophages117

Impairment of Liver and Spleen Functions117

Hypercoagulable Status117

Dysfunction of Microcirculation118

Clinical Classifications118

Classification According to The Clinical Course118

Classification According to the Compensatory Level119

Alterations of Metabolism and Function119

Bleeding120

Organ Dysfunctions121

Shock122

Microangiopathic Hemolytic Anemia122

Pathophysiological Basis of Prevention and Treatment of DIC123

Reversing the Underlying Disorders Initiating DIC123

Improving the Microcirculation123

Reconstructing the Balance Among Coagulation,Anti-coagulation and Fibrinolysis123

Case Presentation123

Chapter 9 Ischemia-Reperfusion Injury126

Etiology126

Duration of Ischemia126

Collateral Circulation126

Dependency on Oxygen Supply126

Condition of Reperfusion126

Pathogenesis126

Free Radicals127

Calcium Overload128

Neutrophils Activation128

Alterations of Metabolism and Function129

Myocardial Ischemia-repeffusion Injury129

Cerebral Ischemia-repeffusion Injury130

Ischemia-reperfusion Injury in Other Organs130

Pathophysiological Basis of Prevention and Treatment130

Control the Reperfusion Conditions130

Scavenge the Free Radicals131

Relieve Calcium Overload131

Improve the Metabolism131

Case Presentation131

Chapter 10 Signal Transduction and the Related Disorders133

General Concept133

Signal Transduction133

Transmembrane Signal Transduction133

Key Elements of Signal Transduction133

Relationship Between Stimulants and Pa-thological Effects133

Major Pathways for Cell Signaling134

G-Protein-Mediated Cell Signaling134

Tyrosine Protein Kinase Mediated Signa-ling134

Intracellular Receptor Signaling135

Dysfunction of Cell Signaling in Diseases135

Aberrant Receptors in Diseases136

Aberrant G-Proteins in Diseases137

Aberrant Intracellular Signal Molecules in Diseases137

Multiple Signaling Aberrations in Diseases139

Pathophysiologic Basis of Prevention and Treatment of Diseases141

To Regulate the Level of Extracellular Molecules141

To Regulate the Structure and the Func-tion of Receptors141

To Regulate the Level and Modifications of Intracellular Messenger Molecules and Transducers142

To Regulate the Level of Nuclear Trans-cription Factors142

Case Presentation142

Chapter 11 Abnormal Cell Proliferation,Differenfiation and Related Diseases144

Deregulated Cell Proliferation and Diseases144

Concept and Phases of the Cell Cycle144

Regulation of the Cell Cycle145

Regulation of the Cell Cycle by Intracell-ular Signals146

Regulation of the Cell Cycle by Extracell-ular Signals147

Role of Abnormal Cell Cycle in the Path-ogenesis of Disease148

Overexpression of Cyclins148

Increased Activation of Cdks and Muta-tion of their Substrates148

Deficient Expression and Mutation of Ckis149

The Impairment of Checkpoint System149

Deregulated Cell Differentiation and Diseases149

Regulation of Cell Differentiation150

The Regulation on the Genomic Level150

Regulation on Transcription and Post-transcription Levels150

Extracellular Factors that Control Diif-erentiation151

The Role of Abnormal Cell Differentiationin the Pathogenesis of Diseases151

Chapter 12 Apoptosis and Related Dis-eases154

Introduction154

Features of Apoptotic Cells154

Phases of Apoptosis155

Influence Factors of Apoptosis155

Biochemical Mechanism of Apoptosis156

A Central Role for Caspases in Apoptosis156

Apoptosis Pathways157

Regulated Mechanism of Apoptosis159

Regulation of the Extrinsic Pathway159

Bcl-2 Family Proteins and Regulation of Apoptosis160

Regulation of Apoptosis by IAP Family Members161

p53161

Apoptosis and Diseases161

Regulation of Apoptosis in Treatment of Disease165

Chapter 13 Heart Failure166

Fundamental Knowledge166

Histology of Myocardium166

Physiology of the Whole Heart167

Cellular Physiology of Ventricular and Atrial Myocytes168

Biochemical Metabolic Particularity of Myocardium169

Etiology169

Classification170

Right-Side Versus left-side Heart Failure170

Acute Versus Chronic Heart Failure170

Low-output Versus High-Output Heart Failure171

Compensatory Responses171

Cardiac Compensation171

Systemic Compensation172

Pathogenesis173

Decreased Myocardial Contractility174

Diastolic Dvsfunction176

Altered Signal Transduction176

Excessive Cardiac Hypertrophy176

Clinical Manifestations177

Left Heart Failure177

Right Ventricular Failure179

Pathophysiologic Basis of Prevention and Treatment179

Etiologic Therapy179

Avoiding Precipitating Factors179

Improving Cardiac Functions180

Reducing Afterload and Preload180

Controlling Edema180

Case Presentation180

Chapter 14 Respiratory Failure182

Etiology and Classification182

Etiology182

Classification182

Pathogenesis183

Ventilation Disorder183

Gas-exchanging Dysfunction186

Alterations of Metabolism and Function190

Acid-Base Imbalance and Electrolyte Dis-turbance190

Changes of Respiratory System191

Changes of Circulatory System191

Changes of Central Nervous System192

Changes of Urinary System193

Changes of Digestive System193

Pathophvsiological Basis of Prevention and Treatment193

Prevent and Remove of Reasons193

Raise PaO2193

Degrade PaCO2193

Improve Internal Environment and Function of Critical Organ193

Case Presentation193

Chapter 15 Hepatic Failure195

Etiology195

Hepatic Insufficiency195

Metabolic Disorders195

Metabolic Disorders of Water and Electro-lytes196

Disorders in Production of Bile Salts and Elimination of Bilirubin197

Impaired Kupffer Cells Function197

Hepatic Encephalopathy197

Etiology and Classification197

Pathaogenesis198

Precipitating Factors of Hepatic Encepha-lopathy202

Principles of Treatment203

Hepatorenal Syndrome203

Principles of Treatment and Prevention205

Case Presentation205

Chapter 16 Renal Failure207

Acute Renal Failure207

Etiology and Classification207

Prerenal Acute Renal Failure208

Intrarenal Acute Renal Failure208

Posuenal Acute Renal Failure208

Pathogenesis209

Alterations of Metabolism and Function210

Urinary Abnormalities210

Hyperkalemia210

Other Abnormalities210

Pathophysiological Basis of Prevention and Treatment210

Chronic Renal Failure211

Etiology211

Clinical Course of Chronic Renal Failure211

Stage of Decreased Renal Reserve211

Stage of Renal Insufficiency211

Stage of Renal Failure211

Stage of Uremia211

Pathogenesis212

Intact Nephron Hypothesis212

Trade-Off Hypothesis212

Glomerular Hyperfiltration Hypothesis213

Alterations of Metabolism and Function213

Disorders of Urine213

Disorders of Water and Sodium Balance213

Disorders of Potassium Balance213

Metabolic Acidosis214

Renal Azotemia214

Renal Hypertension214

Calcium,Phosphate and Bone Metabolism214

Renal Anemia and Bleeding Tendency214

Uremia215

Etiology and Pathogenesis215

Urea and Other Small Molecular Weight Molecules215

Middle Molecules216

Polypeptide Hormones216

Alterations of Metabolism and Function216

Neuromuscular Abnormalities216

Cardiovascular and Pulmonary Abnorma-lities216

Hematological Abnormalities217

Gastrointestinal Abnormalities217

Endocrine and Metabolic Abnormalities217

Dermatologic Abnormalities217

Inmunologic Abnormalities217

Pathophysiological Basis of Prevention and Treatment217

Case Presentation218

Chapter 17 Brain Dysfunction219

Cell Biology of the Brain219

Neurons219

Astrocytes221

Oligodendrocytes221

Microglia221

Basic Knowledge on Consciousness221

Anatomy221

Physiology222

Pathophysiology of Selected Brain Disorders225

Parkinson's Disease225

Epilepsy226

Alzheimer's Disease228

Stroke231

Case Presentation234

Chapter 18 Multiple Organ Dysfunction Syndrome236

Overview236

Systemic Inflarmmatory Response Syndrome(SIRS)237

Etiology237

Diagnostic Criteria of SIRS238

Stages of SIRS238

Pathogenesis of SIRS239

Multiple Organ Dysfunction245

Types of MODS245

Alterations of Metabolism and Function During MODS246

Pathophysiological Basis of Prevention and Treatment248

Case Presentation249

Chapter 19 Metabolic Syndrome253

Etiology and Pathogenesis253

Obesity and Abnormal Body Fat Distri-bution253

Insulin Resistance254

Independent Factors that Mediate Specific Components of the Metabolic Syndrome254

Other Contributing Factors255

Alterations of Metabolism and Function255

Hyperglycemia255

Obesity256

Hypertension257

Hypertriglyceridemia257

Principles of Prevention and Treatment258

Life-style Modification258

Pharmacological Therapy258

Other Managements258

Case Presentation259

English-Chinese Comparison260