Advanced Physiology and Pathophysiology: Essentials for Clinical Practice

Title Page
Copyright
Dedication
Contents
Case Studies
Foreword
Acknowledgments
Contributors
Case Study Contributors
Reviewers
How to use this Book
Instructor Resources
List of Disorders
1. The Foundational Concepts of Clinical Practice
	PATHOPHYSIOLOGY AND THE PROCESS OF CLINICAL DECISION-MAKING
	BUILDING FROM A BASIC SCIENCE FOUNDATION: CHAPTERS 2 TO 4
		Chemistry (Chapter 2)
		Biochemistry (Chapter 2)
		Molecular Biology and Genetics (Chapter 3)
		Cell Biology (Chapter 4)
	ADVANCED PHYSIOLOGY AND PATHOPHYSIOLOGY: CHAPTERS 5 to 17
		Infectious Disease (Chapter 5)
		The Immune System and Leukocyte Function (Chapter 6)
		Neoplasia (Chapter 7)
		Blood and Clotting (Chapter 8)
		Circulation (Chapter 9)
		Heart (Chapter 10)
		Lungs (Chapter 11)
		Kidneys (Chapter 12)
		Gastrointestinal Tract (Chapter 13)
		Liver (Chapter 14)
		Nervous System (Chapter 15)
		Musculoskeletal System (Chapter 16)
		Endocrine System (Chapter 17)
	CONNECTING THE DOTS
	PATHOPHYSIOLOGY AND THE INDEPENDENT CLINICIAN
		References
2. Chemical and Biochemical Foundations
	THE CLINICAL CONTEXT
	CHEMICAL FOUNDATIONS OF LIFE
		Atomic Structure
		The Periodic Table and Families of Elements
		Electron Shells and Chemical Reactivity
		Thought Questions 1–3
		Ion Formation and Roles in the Body
	ACIDS AND BASES
	COVALENT BOND STRUCTURE AND FORMATION
		Thought Questions 4 and 5
	CHEMICAL PATTERNS IN PHYSIOLOGY AND PATHOPHYSIOLOGY
		Nonpolar versus Polar Covalent Bonds
		Molecular Geometry
		Molecular Properties of Water
		Hydrogen Bonding and Aqueous Solutions of Polar Molecules and Ions
		Hydrophobicity and Hydrophilicity
		Thought Questions 6 and 7
	ORGANIC CHEMISTRY FOUNDATIONS
		Carbon-Based Molecules
		Major Organic Functional Groups
		Major Biochemical Reaction Types
	BIOMOLECULES BUILD FROM SMALL TO LARGE
		Carbohydrates
		Thought Questions 8 and 9
		Lipids
		Thought Questions 10–12
		Amino Acids and Proteins
		Thought Questions 13–16
		Nucleotides and Nucleic Acids
		Thought Questions 17 and 18
	CONCLUSION: PHENYLKETONURIA REVISITED
	KEY POINTS
		References
		Suggested Resource
3. Molecular Biology, Genetics, and Genetic Diseases
	THE CLINICAL CONTEXT
	INFORMATION TRANSMISSION WITHIN CELLS AND BETWEEN CELL AND HUMAN GENERATIONS
		DNA Structure
		Molecular Biology of the Cell and DNA Replication
		RNA Function and Protein Synthesis
		Thought Questions 1 and 2
	CONCEPTS IN GENETICS AND GENOMICS
		Chromosome Terminology
		Gene Terminology
		Gene Variations
		Inheritance: Mendelian and Non-Mendelian
		Phenotypic Variability in Genetic Disorders: Penetrance and Expressivity
		Thought Questions 3–5
	TECHNICAL APPROACHES IN GENETICS AND GENOMICS
		Family History and Pedigree Analysis
		Karyotyping
		Hybridization Arrays and Gene Chips
		Whole Genome Sequencing
		Research Approaches
		Direct-to-Consumer Testing
	EPIGENETICS
		Thought Questions 6 and 7
	PEDIATRIC CONSIDERATIONS
		Prenatal Identification of Genetic Disorders
		Genetic Disorders Identified After Birth
	KEY POINTS
		References
		Suggested Resources
4. Cell Physiology and Pathophysiology
	THE CLINICAL CONTEXT
	OVERVIEW
	CELL COMPONENTS
		Cell Membrane
		Cytoplasm
		Nucleus
		Ribosomes and Rough Endoplasmic Reticulum
		Smooth Endoplasmic Reticulum
		Golgi Apparatus
		Mitochondria
		Lysosomes
		Peroxisomes
		Cytoskeleton
	MECHANISMS OF MEMBRANE TRANSPORT
		Diffusion
		Endocytosis and Exocytosis
		Facilitated Diffusion
		Active Transport
		Aquaporins
		Ion Channels
		Thought Questions 1–3
	MECHANISMS OF CELL SIGNALING
		Overview of Signal Transduction
		Autonomic Nervous System and Signaling by G Protein–Coupled Receptors
		Cell Signaling by Cyclic Guanosine Monophosphate
		Cell Signaling by Enzyme-Linked Receptors
		Cell Signaling by Cytoplasmic and Nuclear Receptors
		Summary of Cell Signaling
		Thought Questions 4–6
	MECHANISMS OF CONTRACTILE CELLS
		Overview of Contractile Cell Structure and Function
		The Sarcomere of Skeletal and Cardiac Muscle
		Mechanism of Myofibril Crossbridge Formation and Contraction
		Comparison of Skeletal Muscle Fibers and Cardiac Muscle Cells
		Mechanisms of Smooth Muscle Contraction
		Summary of Muscle Cell Function
		Thought Questions 7 and 8
	CELL RENEWAL, STRESS, AND CELL DEATH
		Overview of Cell Renewal, Maintenance, and Adaptation
		Overview of Cell Injury and Death
		Thought Questions 9 and 10
	GERONTOLOGICAL CONSIDERATIONS
		Cellular Theories of Aging
		Nine Hallmarks of Aging
		Frailty
		Thought Questions 11 and 12
	KEY POINTS
		References
		Suggested Resources
5. Infectious Disease
	THE CLINICAL CONTEXT
	OVERVIEW OF INFECTIOUS DISEASE PATHOPHYSIOLOGY
		Human–Microbe Interactions
		Mechanisms of Protection from Pathogens
		Portals of Pathogen Entry and Targets of Colonization
		Pathogen Virulence Factors
		Host Response Factors
		Thought Questions 1–3
	MICROBIAL PATHOGENICITY
		Overview
		Characteristics of Pathogen Classes
		Thought Questions 4 and 5
	CLINICAL CONCEPTS IN INFECTIOUS DISEASE
		Methods of Pathogen Identification
		Drug-Resistant Pathogens
		Antimicrobial Stewardship
		Thought Question 6
	PATHOGENESIS OF SELECTED MICROBES
		Streptococcus pyogenes
		Methicillin-Resistant Staphylococcus aureus
		Mycobacterium tuberculosis
		Chlamydia trachomatis
		Neisseria gonorrhoeae
		Clostridioides difficile
		Borrelia burgdorferi
		Influenza Virus
		Human Immunodeficiency Virus
		Plasmodium Species
		Thought Question 7
	PEDIATRIC CONSIDERATIONS
		Norovirus
		Measles, Mumps, and Rubella
	GERONTOLOGICAL CONSIDERATIONS
		Community-Acquired Pneumonia
		Varicella-Zoster Virus
		HIV
	CASE STUDY 5.1 A Patient With Acute HIV Infection
	CASE STUDY 5.2 A Child With Hand, Foot, and Mouth Disease
	BRIDGE TO CLINICAL PRACTICE
	KEY POINTS
		References
		Suggested Resources
6. The Immune System and Leukocyte Function
	THE CLINICAL CONTEXT
	ROLE OF THE IMMUNE SYSTEM
	INTRODUCTION TO HOST DEFENSESS
		Overview of Physical and Chemical Barriers
		Overview of the Innate Immune Response
		Overview of the Adaptive Immune Response
		Thought Questions 1 and 2
	FUNCTIONAL ANATOMY OF THE IMMUNE SYSTEM
		Hematopoiesis
		Cells and Tissues of the Immune System
		Thought Questions 3 and 4
	INNATE IMMUNITY
		Acute Inflammation
		Innate Immune Cells
		Innate Lymphoid Cells
		Activation of the Innate Inflammatory Response
		The Complement Pathway
		Innate Responses to Viral Infection
		Chronic Inflammation
		Trained Innate Immunity
		Transition from Innate to Adaptive Immunity: Antigen Presentation and the Major Histocompatibility Complex
		Thought Questions 5–9
	ADAPTIVE IMMUNITY
		B Cells are Responsible for Humoral Immunity
		Thought Questions 10 and 11
		T-Cell Functions
		Pathogen–Host Immune Evasion Mechanisms
		Vaccination
		Hypersensitivity
		Autoimmunity
		Immunodeficiency
		Thought Questions 12–14
	IMMUNE RESPONSES ACROSS THE LIFE SPAN
	PEDIATRIC CONSIDERATIONS
		Type 1 Hypersensitivity in Children and Adolescents
		Atopic Dermatitis
		Food Allergies
	GERONTOLOGICAL CONSIDERATIONS
		Immune Cellular Senescence and Disease
		Inflammaging
	CASE STUDY 6.1 A Patient With Allergic Rhinitis
	BRIDGE TO CLINICAL PRACTICE
	KEY POINTS
		References
		Suggested Resources
7. Neoplasia
	THE CLINICAL CONTEXT
	OVERVIEW OF CANCER PATHOPHYSIOLOGY
	THE CELL CYCLE
		Interphase
		M-Phase (Mitotic Phase)
		Exit and Reentry of the Cell Cycle
		Control of the Cell Cycle
		Checkpoints
		Thought Questions 1 and 2
	PROPERTIES OF NEOPLASMS
		Tumor Terminology
		Thought Questions 3 and 4
		Characteristics of a Cancer Cell
		Recently Identified Cancer Cell Characteristics
		Thought Questions 5–7
	CLINICAL ASPECTS OF NEOPLASIA
		Pathophysiology of Cancer Manifestations and Treatment Sequelae
		Biological Aspects of Gene Mutations and Cancer Risk Factors
		Viral Causes of Cancer
		Thought Questions 8–10
	GENOTYPING IN CANCER DIAGNOSIS AND TREATMENT
		Thought Questions 11 and 12
	PEDIATRIC CONSIDERATIONS
		Overview of Pediatric Cancer
		Leukemias
		Bone Tumors
		Nervous System Tumors
	GERONTOLOGICAL CONSIDERATIONS
		Physiological Processes of Aging that May Promote Cancer Development
		Aging and Cancer: Practice Implications
	CASE STUDY 7.1 A Patient With Breast Cancer
	BRIDGE TO CLINICAL PRACTICE
	KEY POINTS
		References
		Suggested Resources
8. Blood and Clotting
	THE CLINICAL CONTEXT
	OVERVIEW OF BLOOD AND CLOTTING
	RED BLOOD CELLS
		Erythropoiesis
		Thought Questions 1 and 2
		Hemoglobin
		Iron
		Vitamin B12 and Folate
		Thought Questions 3 and 4
	GENERAL CONCEPTS IN ANEMIA
		Iron-Deficiency Anemia (Microcytic Anemia)
		Vitamin B12 Deficiency Anemia (Macrocytic Anemia)
		Anemia of Chronic Inflammation
		Anemia in Chronic Kidney Disease
		Hemolytic Anemia
		Thought Questions 5 and 6
	HEMOSTASIS
		Platelet Structure and Function
		Modulation of Clotting and Anticlotting by Products of Arachidonic Acid Metabolism
		Thought Questions 7 and 8
	COAGULATION CASCADE
		Laboratory Assessment of Clotting
		Control of the Clotting Process
		Thought Questions 9 and 10
	THROMBOEMBOLIC STATES
		Specific Disorders of Hypercoagulation
	STATES OF EXCESS BLEEDING
		Thrombocytopenia
		von Willebrand Disease
		Coagulation Cascade–Associated Disorders
		Thought Questions 11 and 12
	PEDIATRIC CONSIDERATIONS
		Developmental Changes in Red Blood Cell Measures
		Iron-Deficiency Anemia
		Hyperbilirubinemia
		Sickle Cell Disease
		Von Willebrand Disease
	GERONTOLOGICAL CONSIDERATIONS
		Anemia
		Changes in Bone Marrow
		Hypercoagulability
		Medication Effects on Blood and Clotting
	CASE STUDY 8.1 A Patient With Pernicious Anemia
	CASE STUDY 8.2 A Patient With Deep Venous Thrombosis
	BRIDGE TO CLINICAL PRACTICE
	KEY POINTS
		References
		Suggested Resources
9. Circulation
	THE CLINICAL CONTEXT
	OVERVIEW OF CIRCULATORY STRUCTURE AND FUNCTION
		Homeostatic Functions of the Circulatory System
		Organizing Principles of the Circulatory System
		Structure and Properties of Blood Vessels
	PROPERTIES AND DISORDERS OF LARGE ARTERIES
		Overview of Large Artery Structure and Function
		Atherosclerosis: The Most Common Disease of Large Arteries
		Thought Questions 1–3
	PROPERTIES AND DISORDERS OF ARTERIOLES
		Overview of Arteriole Structure and Function
		Thought Questions 4 and 5
		Regulation of Blood Pressure
		Thought Questions 6–8
		Pathophysiology of Elevated Vascular Resistance: Hypertension
		Pathophysiology of Decreased Blood Pressure and Peripheral Resistance: Shock
		Thought Questions 9–11
	PROPERTIES AND DISORDERS OF CAPILLARIES
		Overview of Capillary Structure and Function
		Thought Question 12
	PROPERTIES AND DISORDERS OF VEINS
		Overview of Venous Structure and Function, and Vulnerability to Pressure Elevations
		Venous Disorders
		Thought Questions 13 and 14
	PEDIATRIC CONSIDERATIONS
		Embryological Development of the Circulatory System
		Blood Pressure and Pediatric Hypertension
	GERONTOLOGICAL CONSIDERATIONS
		Vascular Changes with Aging
		Aging-Associated Vascular Disorders
	CASE STUDY 9.1 A Patient With Hypertension
	CASE STUDY 9.2 A Patient With Edema
	BRIDGE TO CLINICAL PRACTICE
	KEY POINTS
		References
		Suggested Resources
10. Heart
	THE CLINICAL CONTEXT
	OVERVIEW OF CARDIOVASCULAR STRUCTURE AND FUNCTION
		Homeostatic Functions of the Heart
		Structural Organization of the Heart
		Overview of Myocardial Cell Structure
		Myocardial Oxygen Supply and Demand
	CARDIAC ELECTROPHYSIOLOGY AND PATHOPHYSIOLOGY
		Myocardial Cell Ion Channels and Transporters
		Structure of the Cardiac Conduction System
		Cardiac Cell Action Potentials
		Thought Questions 1 and 2
		Functional Aspects of Cardiac Action Potentials
		Thought Question 3
		Disorders of Cardiac Electrical Activity (Arrhythmias or Dysrhythmias)
		Thought Questions 4 and 5
	CARDIAC PERFORMANCE PHYSIOLOGY
		Cardiac Muscle
		Thought Questions 6-8
		Cardiac Cycle
		Thought Question 9
	CORONARY BLOOD FLOW ANDISCHEMIC HEART DISEASE
		Cardiac Vasculature
		Cardiac Oxygen Supply and Demand
		Coronary Artery Disease
		Acute Coronary Syndromes
		Thought Questions 10 and 11
	HEART FAILURE
		Left-Sided Heart Failure
		Right-Sided Heart Failure
		Management of Heart Failure
		Thought Questions 12 and 13
	STRUCTURAL CARDIAC DISORDERS
		Normal Structure of the Heart and Cardiac Valves
		Valve Diseases
		Cardiomyopathies
	PEDIATRIC CONSIDERATIONS
		Normal Cardiac Development
		Principles of Developmental Cardiac Anomalies
	GERONTOLOGICAL CONSIDERATIONS
		Age-Related Changes in Cardiac Structure
		Age-Related Changes in Cardiac Function
		Summary of Age-Related Cardiac Changes
	CASE STUDY 10.1 A Patient With Heart Failure Symptoms
	CASE STUDY 10.2 A Patient With Angina
	CASE STUDY 10.3 A Patient With Atrial Fibrillation
	BRIDGE TO CLINICAL PRACTICE
	KEY POINTS
		References
		Suggested Resources
11. Lungs
	THE CLINICAL CONTEXT
	OVERVIEW OF LUNG STRUCTURE AND FUNCTION
		Structures of the Respiratory System
		Mechanisms of Respiration
		Anatomy and Histology of Airways and Alveoli
		Mechanisms of Lung Protection
		Lung Volumes and Capacities
		Lung–Chest Wall Interactions
		Thought Questions 1–3
	COMPLIANCE OF THE LUNGS AND CHEST WALL IN HEALTH AND DISEASE
		Surfactant and Lung Compliance
		Diseases of Decreased Lung Compliance
		Chest Wall Compliance
		Thought Question 4
	AIRWAY RESISTANCE
		Overview of Airway Resistance
		Forced Expiratory Maneuvers are Used to Assess Airway Resistance
		Concepts in Obstructive Lung Disease
		Thought Questions 5–7
	GAS EXCHANGE IN THE LUNGS
		Overview of Gas Exchange
		Oxygen–Hemoglobin Dissociation Curve
		Hypoxia and Hypoxemia
		Thought Questions 8 and 9
	LUNG VASCULAR CONSIDERATIONS
		Cardiac Consequences of Pulmonary Disease
		Pulmonary Embolism
		Pulmonary Edema
		Pulmonary Hypertension
		Thought Questions 10 and 11
	PEDIATRIC CONSIDERATIONS
		Lung Development
		Respiratory Problems Associated with Preterm Birth
		Lung Concerns in Infancy
		Childhood Asthma
	GERONTOLOGICAL CONSIDERATIONS
		Pneumonia
		Chronic Obstructive Pulmonary Disease (Chronic Bronchitis and Emphysema)
	CASE STUDY 11.1 A Child With Asthma
	CASE STUDY 11.2 A Patient With Chronic Bronchitis
	BRIDGE TO CLINICAL PRACTICE
	KEY POINTS
		References
		Suggested Resources
12. Kidneys
	THE CLINICAL CONTEXT
	OVERVIEW OF KIDNEY STRUCTURE AND FUNCTION
		The Kidney and Homeostasis
		Overview of Body Fluid Compartments
		Kidney Structure
		Nephron Structure
		Glomerular Function
		Thought Questions 1 and 2
	GLOMERULAR INJURIES
		Glomerular Injury by Immune Mechanisms
		Diabetic Nephropathy
		Hypertensive Nephropathy
		Thought Questions 3 and 4
	REGULATION OF RENAL BLOOD FLOW AND GLOMERULAR FILTRATION RATE
		Autoregulation of Renal Blood Flow
		Extrinsic Regulation of RBF and GFR
		Importance of eGFR as the Indicator of Renal Function
		Factors Reducing RBF and GFR in Disease States
		Thought Questions 5 and 6
	STRUCTURE AND FUNCTION OF THE RENAL TUBULE
		Tubular Transport Overview
		Segmental Tubular Processing
		Thought Questions 7 and 8
	REGIONAL KIDNEY FUNCTION
		Corticomedullary Osmolarity Gradient
		Production of Concentrated Urine and Homeostatic Regulation of Urine Composition and Osmolarity
	CONCEPTS IN FLUID, ELECTROLYTE, AND ACID–BASE BALANCE
		Renal Compensation in States of Hypovolemia and Hypotension
		Renal Compensation in States of Hypervolemia and Hypertension
		Thought Question 9
	ACUTE KIDNEY INJURY–CHRONIC KIDNEY DISEASE CONTINUUM
		Assessment of Kidney Function
		Mechanisms and Manifestations of Acute Kidney Injury
		Thought Question 10
		Mechanisms and Manifestations of Chronic Kidney Disease
		End-Stage Renal Disease
		Thought Questions 11–13
		APOL1 and CKD Progression
	PEDIATRIC CONSIDERATIONS
		Urinary System Development
		Pediatric Disorders of Urinary Tract and Kidneys
	GERONTOLOGICAL CONSIDERATIONS
		Age-Related Changes in the Kidney
		Clinical Considerations in Older Adults
		Summary of Age-Related Concerns
	CASE STUDY 12.1 A Patient With Chronic Kidney Disease
	CASE STUDY 12.2 A Patient With a Kidney Stone
	BRIDGE TO CLINICAL PRACTICE
	KEY POINTS
		References
		Suggested Resources
13. Gastrointestinal Tract
	THE CLINICAL CONTEXT
	OVERVIEW OF GASTROINTESTINAL STRUCTURE AND FUNCTION
		Alimentary Canal Structure and Motor Activity
		Neural, Humoral, and Immune Regulation of Gastrointestinal Function
		Thought Questions 1–3
	PROPERTIES AND DISORDERS OF DIGESTIVE TRACT ORGANS
		Mouth
		Salivary Glands
		Esophagus
		Stomach
		Thought Questions 4 and 5
		Small and Large Intestines
		Pancreas
	DIGESTION AND ABSORPTION
		Overview of Macronutrient Digestion and Absorption
		Thought Questions 6 and 7
		Principles of Micronutrient Absorption
		Principles of Fluid and Electrolyte Absorption
	IMMUNE-RELATED GASTROINTESTINAL DISORDERS
		Celiac Disease
		Inflammatory Bowel Disease
	ABDOMINAL PAIN PATTERNS
		Irritable Bowel Syndrome
		Hemorrhoids
	INTESTINAL FAILURE AND SHORT BOWEL SYNDROME
		Thought Questions 8 and 9
	MALNUTRITION AND OBESITY
	Lynch Syndrome
	PEDIATRIC CONSIDERATIONS
		Gastrointestinal Development and Function in Childhood
		Gastroenteritis
		Gastroesophageal Reflux
		Hypertrophic Pyloric Stenosis
		Intussusception
		Hirschsprung Disease
	GERONTOLOGICAL CONSIDERATIONS
		Age-Related Changes of the Gastrointestinal Tract
		Age-Associated Alterations in Mastication
		Dysphagia
		Gastroesophageal Reflux Disease in Older Adults
		Altered Digestion
		Peptic Ulcer Disease
		Constipation
		Diverticular Disease
	CASE STUDY 13.1 A Patient With Peptic Ulcer Disease
	CASE STUDY 13.2 A Teenage Boy With Celiac Disease
	BRIDGE TO CLINICAL PRACTICE
	KEY POINTS
		References
		Suggested Resources
14. Liver
	THE CLINICAL CONTEXT
	OVERVIEW OF LIVER STRUCTURE AND FUNCTION
		Liver Structure
		Thought Questions 1 and 2
		Liver Function
		Thought Questions 3 and 4
		Thought Question 5
	LIVER DISORDERS
		Measures of Liver Function and Dysfunction
		Acute Liver Disorders
		Thought Questions 6 and 7
		Chronic Liver Disorders
		Thought Questions 8 and 9
		Hereditary Hemochromatosis
	PEDIATRIC CONSIDERATIONS
		Fetal and Childhood Liver Development
		Hyperbilirubinemia
		Other Liver Disorders Presenting in Children
		Nonalcoholic Fatty Liver Disease
	GERONTOLOGICAL CONSIDERATIONS
		Aging and Hepatitis C
		Alcoholic Liver Disease
		Nonalcoholic Fatty Liver Disease
		Drug-Induced Liver Injury
		Autoimmune Hepatitis
		Primary Biliary Cholangitis (Primary Biliary Cirrhosis)
		Hepatocellular Carcinoma
	CASE STUDY 14.1 A Patient With Hepatitis A Virus Infection
	CASE STUDY 14.2 A Patient With Nonalcoholic Fatty Liver Disease
	BRIDGE TO CLINICAL PRACTICE
	KEY POINTS
		References
		Suggested Resources
15. Nervous System
	THE CLINICAL CONTEXT
	OVERVIEW OF NERVOUS SYSTEM FUNCTION AND NEUROANATOMY
		Nervous System Function
		Anatomy of the Nervous System
		Neurons
		Thought Questions 1–3
		Synaptic Transmission
		Thought Questions 4–7
	NEUROTRANSMITTERS
		Two Main Transmitter Families
		Thought Questions 8 and 9
		Neuromodulatory Transmitters: Amines
		Neuromodulatory Transmitters: Peptides
		Application of Neurotransmitter Concepts
		Summary of Neurotransmitter Concepts
		Thought Questions 10–12
	SENSORY NEUROPHYSIOLOGY
		Overview of Spinal Cord Anatomy
		Somatic Sensory Function
		Thought Questions 13 and 14
	PAIN
		Neurophysiology of Pain
		Pharmacological Modulation of Pain
		Nonpharmacological Modulation of Pain
		Thought Questions 15–17
	SPECIAL SENSES: VISION AND HEARING
		Visual System
		Auditory System
	MOTOR ACTIVITY AND MOVEMENT DISORDERS
		Motor Neurons and the Neuromuscular Junction
		Lower Motor Neuron Lesions
		Spinal Cord Reflex Circuits
		Motor Pathways from the Pons and Medulla
		Motor Pathways from the Cortex and Midbrain
		Accessory Systems in Motor Control
		Summary of Motor Disorders
		Thought Questions 18–20
	HIGHER FUNCTIONS OF THE NERVOUS SYSTEM
		Functional Anatomy of Cognition and Behavior
		Brain Mechanisms of Stress
		Neurobiology of Depression, Anxiety, and Substance Use Disorders
		Thought Questions 21–24
	PEDIATRIC CONSIDERATIONS
		Overview of Brain Development
		Spinal Muscular Atrophy
		Pediatric Seizures and Epilepsies
		Developmental Delay
		Headaches
		Concussion
	GERONTOLOGICAL CONSIDERATIONS
		Aging and Structural Changes in Cerebral Cortex
		Cognitive Dysfunction
		Neurodegenerative Disorders
		Vascular Disease
		Gait Dysfunction
		Aging and Sense Organs
	CASE STUDY 15.1 A Teenage Girl With Migraine
	CASE STUDY 15.2 A Child With a Seizure Disorder
	CASE STUDY 15.3 A Patient With Depression
	BRIDGE TO CLINICAL PRACTICE
	KEY POINTS
		References
		Suggested Resources
16. Musculoskeletal System
	THE CLINICAL CONTEXT
	OVERVIEW OF BONES AND SKELETAL PHYSIOLOGY
		Bone Histology
		Osteogenesis and Bone Remodeling
		Thought Questions 1 and 2
	BONE FRACTURES
		Types of Fractures
		Fracture Healing
		Recovery from Fracture
		Thought Questions 3 and 4
	JOINTS
		Functional Classification
		Structural Classification
		Thought Questions 5 and 6
	STRAINS AND SPRAINS
		Ankle Sprains
		Structure and Conditions of the Knee
		Thought Questions 7 and 8
	HERNIATED DISC DISEASE
		Pathophysiology of Disc Herniation
		Anatomical Correlations
		Clinical Presentation and Management
	CUMULATIVE TRAUMA DISORDERS
		Causes of Cumulative Stress Injury
		Clinical Syndromes
		Thought Questions 9 and 10
	PEDIATRIC CONSIDERATIONS
		Musculoskeletal Development
		Youth Sports and Musculoskeletal Injuries
		Genetic Musculoskletal Conditions
	GERONTOLOGICAL CONSIDERATIONS
		Aging and Muscle Integrity: Sarcopenia and Frailty
		Bone Density And Osteoporosis
		Joint Disorders In Older Adults
		Parkinson Disease and Pisa Syndrome
	CASE STUDY 16.1 A Patient With a Sprained Ankle
	CASE STUDY 16.2 A Patient With Acute Gouty Arthritis
	BRIDGE TO CLINICAL PRACTICE
	KEY POINTS
		References
		Suggested Resources
17. Endocrine System
	THE CLINICAL CONTEXT
	PRINCIPLES OF ENDOCRINE FUNCTION
		Hormone Structures
		Cell Signaling by Hormones
		Circulating Hormone Levels
		Hormone Control Axes
		Thought Questions 1 and 2
	HYPOTHALAMUS AND PITUITARY GLAND
	STRUCTURE OF THE HYPOTHALAMUS
	FUNCTIONS OF THE HYPOTHALAMUS
		Thirst and Fluid Balance Control
		Regulation of Uterine Contractility
		Regulation of Body Energy Balance and Weight
		Thought Questions 3–5
	DEVELOPMENT OF THE HYPOTHALAMUS AND RELATIONSHIP WITH THE PITUITARY GLAND
	ENDOCRINE CELLS OF THE ANTERIOR PITUITARY
		Corticotroph Cells: Adrenocorticotrophic Hormone
		Lactotroph Cells: Prolactin
		Somatotroph Cells: Growth Hormone
		Gonadotroph Cells: Luteinizing Hormone and Follicle-Stimulating Hormone
		Thyrotroph Cells: Thyroid-stimulating Hormone
	POSTERIOR PITUITARY HORMONES
		Vasopressin: Antidiuretic Hormone
		Oxytocin
		Thought Questions 6 and 7
	ADRENAL GLANDS
	DEVELOPMENT, STRUCTURE, AND FUNCTION OF THE ADRENAL GLANDS
	ADRENAL CORTEX ZONES AND HORMONES
		Zona Glomerulosa: Aldosterone
		Zona Fasciculata: Glucocorticoids and Cortisol Production
		Zona Reticularis: Androgens
	ADRENAL MEDULLA AND CATECHOLAMINES
		Adrenomedullary Dysfunction
		Thought Questions 8–10
	PEDIATRIC CONSIDERATIONS: HYPOTHALAMUS, PITUITARY, AND ADRENAL GLANDS
		Endocrine Control of Growth
		Genetic Disorder: Congenital Adrenal Hyperplasia
	GERONTOLOGICAL CONSIDERATIONS: HYPOTHALAMUS, PITUITARY, AND ADRENAL GLANDS
		Decline in Growth Hormone
		Adrenal Gland Changes
	KEY POINTS: ENDOCRINE CONCEPTS; HYPOTHALAMUS, PITUITARY, AND ADRENAL GLANDS
	THYROID GLAND
	STRUCTURE AND FUNCTION OF THE THYROID GLAND
	THYROID HORMONE SYNTHESIS
	THYROXINE METABOLISM
		Alterations of Serum Thyroid-Binding Globulin Concentrations
	THYROID HORMONE ACTIONS
		Screening for Serum Thyroid Dysfunction
		Thought Questions 11–13
	THYROID DISORDERS
		Hypothyroidism
		Hyperthyroidism
		Nonthyroidal Illness with Altered Thyroid Function Tests (Euthyroid Sick Syndrome)
		Thought Questions 14 and 15
	PEDIATRIC CONSIDERATIONS: THYROID GLAND
	GERONTOLOGICAL CONSIDERATIONS: Thyroid Gland
	CASE STUDY 17.1 A Patient With Graves Disease
	BRIDGE TO CLINICAL PRACTICE: THYROID
	KEY POINTS: THYROID GLAND
	THE GONADS
	OVERVIEW OF THE REPRODUCTIVE SYSTEM
	THE FEMALE REPRODUCTIVE SYSTEM
		Structure and Functions of the Female Reproductive System
		Female Hypothalamic-Pituitary-Gonadal Function
		Thought Questions 16 and 17
		Abnormalities of the Menstrual Cycle, Ovaries, and Endometrium
		Thought Question 18
		Breast Cancer
		Menopausal Transition and Aging
		Osteoporosis in Postmenopausal Women (and Older Men)
		Thought Question 19
	THE MALE REPRODUCTIVE SYSTEM
		Structures and Functions of the Male Reproductive System
		Regulation and Spermatogenesis of the Male Reproductive System
		Prostate Disorders
		Thought Questions 20 and 21
		CASE STUDY 17.2 A Patient With Hyperparathyroidism
	KEY POINTS: THE GONADS
	METABOLISM AND THE PANCREAS
	OVERVIEW
	REVIEW OF METABOLISM
		Metabolic Processes in the Fed State
		Metabolic Processes in the Fasting State
		Thought Questions 22 and 23
	HORMONAL REGULATION OF METABOLISM
		Insulin
		Additional Hormones Regulating Metabolic Homeostasis
		Thought Questions 24–26
	DIABETES MELLITUS
		Diagnostic Criteria
		Type 1 Diabetes Mellitus
		Type 2 Diabetes Mellitus
		Complications of Diabetes Mellitus
	OTHER FORMS OF DIABETES AND DIABETES-RELATED CONDITIONS
		Gestational Diabetes
		Latent Autoimmune Diabetes in Adults
		Polycystic Ovary Syndrome
		Obstructive Sleep Apnea
	SUMMARY
	PEDIATRIC CONSIDERATIONS: METABOLISM AND THE PANCREAS
		Type 1 Diabetes Mellitus
		Type 2 Diabetes Mellitus
	GERONTOLOGICAL CONSIDERATIONS: METABOLISM AND THE PANCREAS
		Type 2 Diabetes Mellitus
	CASE STUDY 17.3 A Patient With Gestational Diabetes
	BRIDGE TO CLINICAL PRACTICE: Diabetes
	KEY POINTS: METABOLISM AND THE PANCREAS
	SUMMARY: ENDOCRINE PHYSIOLOGY AND PATHOPHYSIOLOGY
		References
		Suggested Resources
List of Abbreviations
Index