Anatomy
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Anatomy & Physiology

Anatomy and Physiology

By: OpenStax College

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ISBN-10 1938168135/dd> ISBN-13 978-1-938168-13-0 Revision AP-1-000-DW

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Anatomy & Physiology

Table of Contents
  • Preface
    • 1. About OpenStax College
    • 2. About OpenStax College’s Resources
      • Customization
      • Curation
      • Cost
    • 3. About Human Anatomy and Physiology
      • Coverage and Scope
        • Unit 1: Levels of Organization
        • Unit 2: Support and Movement
        • Unit 3: Regulation, Integration, and Control
        • Unit 4: Fluids and Transport
        • Unit 5: Energy, Maintenance, and Environmental Exchange
        • Unit 6: Human Development and the Continuity of Life
      • Pedagogical Foundation and Features
      • Dynamic, Learner-Centered Art
        • Micrographs
        • Learning Resources
    • 4. About Our Team
      • Senior Contributors
      • Advisor
      • Other Contributors
    • 5. Special Thanks
  • I. Unit 1: Levels of Organization
    • Chapter 1. An Introduction to the Human Body
      • 1.1. Overview of Anatomy and Physiology
        • 1.2. Introduction to Anatomy Module 3: Structural Organization of the Human Body
          • The Levels of Organization
        • 1.3. Introduction to Anatomy Module 4: Functions of Human Life
          • Organization
          • Metabolism
          • Responsiveness
          • Movement
          • Development, growth and reproduction
        • 1.4. Requirements for Human Life
          • Oxygen
          • Nutrients
          • Narrow Range of Temperature
          • Narrow Range of Atmospheric Pressure
        • 1.5. Homeostasis
          • Negative Feedback
          • Positive Feedback
        • 1.6. Anatomical Terminology
          • Anatomical Position
          • Regional Terms
          • Directional Terms
          • Body Planes
          • Body Cavities and Serous Membranes
            • Subdivisions of the Posterior (Dorsal) and Anterior (Ventral) Cavities
            • Abdominal Regions and Quadrants
            • Membranes of the Anterior (Ventral) Body Cavity
        • 1.7. Medical Imaging
          • X-Rays
          • Modern Medical Imaging
            • Computed Tomography
            • Magnetic Resonance Imaging
            • Positron Emission Tomography
            • Ultrasonography
      • Chapter 2. The Chemical Level of Organization
        • 2.1. Elements and Atoms: The Building Blocks of Matter
          • Elements and Compounds
          • Atoms and Subatomic Particles
            • Atomic Structure and Energy
            • Atomic Number and Mass Number
            • Isotopes
          • The Behavior of Electrons
        • 2.2. Chemical Bonds
          • Ions and Ionic Bonds
          • Covalent Bonds
            • Nonpolar Covalent Bonds
            • Polar Covalent Bonds
          • Hydrogen Bonds
        • 2.3. Chemical Reactions
          • The Role of Energy in Chemical Reactions
          • Forms of Energy Important in Human Functioning
          • Characteristics of Chemical Reactions
          • Factors Influencing the Rate of Chemical Reactions
            • Properties of the Reactants
            • Temperature
            • Concentration and Pressure
            • Enzymes and Other Catalysts
        • 2.4. Inorganic Compounds Essential to Human Functioning
          • Water
            • Water as a Lubricant and Cushion
            • Water as a Heat Sink
            • Water as a Component of Liquid Mixtures
            • Concentrations of Solutes
            • The Role of Water in Chemical Reactions
          • Salts
          • Acids and Bases
            • Acids
            • Bases
            • The Concept of pH
            • Buffers
        • 2.5. Organic Compounds Essential to Human Functioning
          • The Chemistry of Carbon
          • Carbohydrates
            • Monosaccharides
            • Disaccharides
            • Polysaccharides
            • Functions of Carbohydrates
          • Lipids
            • Triglycerides
            • Phospholipids
            • Steroids
            • Prostaglandins
          • Proteins
            • Microstructure of Proteins
            • Shape of Proteins
            • Proteins Function as Enzymes
            • Other Functions of Proteins
          • Nucleotides
            • Nucleic Acids
            • Adenosine Triphosphate
      • Chapter 3. The Cellular Level of Organization
        • 3.1. The Cell Membrane
          • Structure and Composition of the Cell Membrane
          • Membrane Proteins
          • Transport across the Cell Membrane
            • Passive Transport
            • Active Transport
        • 3.2. The Cytoplasm and Cellular Organelles
          • Organelles of the Endomembrane System
            • Endoplasmic Reticulum
            • The Golgi Apparatus
            • Lysosomes
          • Organelles for Energy Production and Detoxification
            • Mitochondria
            • Peroxisomes
          • The Cytoskeleton
        • 3.3. The Nucleus and DNA Replication
          • Organization of the Nucleus and Its DNA
          • DNA Replication
        • 3.4. Protein Synthesis
          • From DNA to RNA: Transcription
          • From RNA to Protein: Translation
        • 3.5. Cell Growth and Division
          • The Cell Cycle
            • Interphase
            • The Structure of Chromosomes
            • Mitosis and Cytokinesis
          • Cell Cycle Control
            • Mechanisms of Cell Cycle Control
            • The Cell Cycle Out of Control: Implications
        • 3.6. Cellular Differentiation
          • Stem Cells
          • Differentiation
      • Chapter 4. The Tissue Level of Organization
        • 4.1. Types of Tissues
          • The Four Types of Tissues
          • Embryonic Origin of Tissues
          • Tissue Membranes
            • Connective Tissue Membranes
            • Epithelial Membranes
        • 4.2. Epithelial Tissue
          • Generalized Functions of Epithelial Tissue
          • The Epithelial Cell
          • Cell to Cell Junctions
          • Classification of Epithelial Tissues
            • Simple Epithelium
            • Stratified Epithelium
          • Glandular Epithelium
            • Endocrine Glands
            • Exocrine Glands
            • Glandular Structure
            • Methods and Types of Secretion
        • 4.3. Connective Tissue Supports and Protects
          • Functions of Connective Tissues
          • Embryonic Connective Tissue
          • Classification of Connective Tissues
          • Connective Tissue Proper
            • Cell Types
            • Connective Tissue Fibers and Ground Substance
            • Loose Connective Tissue
            • Dense Connective Tissue
          • Supportive Connective Tissues
            • Cartilage
            • Bone
          • Fluid Connective Tissue
        • 4.4. Muscle Tissue and Motion
          • 4.5. Nervous Tissue Mediates Perception and Response
            • 4.6. Tissue Injury and Aging
              • Tissue Injury and Repair
              • Tissue and Aging
        • II. Unit 2: Support and Movement
          • Chapter 5. The Integumentary System
            • 5.1. Layers of the Skin
              • The Epidermis
                • Stratum Basale
                • Stratum Spinosum
                • Stratum Granulosum
                • Stratum Lucidum
                • Stratum Corneum
              • Dermis
                • Papillary Layer
                • Reticular Layer
              • Hypodermis
              • Pigmentation
            • 5.2. Accessory Structures of the Skin
              • Hair
                • Hair Growth
                • Hair Color
              • Nails
              • Sweat Glands
              • Sebaceous Glands
            • 5.3. Functions of the Integumentary System
              • Protection
              • Sensory Function
              • Thermoregulation
              • Vitamin D Synthesis
            • 5.4. Diseases, Disorders, and Injuries of the Integumentary System
              • Diseases
                • Basal Cell Carcinoma
                • Squamous Cell Carcinoma
                • Melanoma
              • Skin Disorders
                • Eczema
                • Acne
              • Injuries
                • Burns
                • Scars and Keloids
                • Bedsores and Stretch Marks
                • Calluses
          • Chapter 6. Bone Tissue and the Skeletal System
            • 6.1. The Functions of the Skeletal System
              • Support, Movement, and Protection
              • Mineral Storage, Energy Storage, and Hematopoiesis
            • 6.2. Bone Classification
              • Long Bones
              • Short Bones
              • Flat Bones
              • Irregular Bones
              • Sesamoid Bones
            • 6.3. Bone Structure
              • Gross Anatomy of Bone
              • Bone Markings
              • Bone Cells and Tissue
              • Compact and Spongy Bone
                • Compact Bone
                • Spongy (Cancellous) Bone
              • Blood and Nerve Supply
            • 6.4. Bone Formation and Development
              • Cartilage Templates
              • Intramembranous Ossification
              • Endochondral Ossification
              • How Bones Grow in Length
              • How Bones Grow in Diameter
              • Bone Remodeling
            • 6.5. Fractures: Bone Repair
              • Types of Fractures
              • Bone Repair
            • 6.6. Exercise, Nutrition, Hormones, and Bone Tissue
              • Exercise and Bone Tissue
              • Nutrition and Bone Tissue
                • Calcium and Vitamin D
                • Other Nutrients
              • Hormones and Bone Tissue
                • Hormones That Influence Osteoblasts and/or Maintain the Matrix
                • Hormones That Influence Osteoclasts
            • 6.7. Calcium Homeostasis: Interactions of the Skeletal System and Other Organ Systems
            • Chapter 7. Axial Skeleton
              • 7.1. Divisions of the Skeletal System
                • The Axial Skeleton
                • The Appendicular Skeleton
              • 7.2. The Skull
                • Anterior View of Skull
                • Lateral View of Skull
                • Bones of the Brain Case
                  • Parietal Bone
                  • Temporal Bone
                  • Frontal Bone
                  • Occipital Bone
                  • Sphenoid Bone
                  • Ethmoid Bone
                • Sutures of the Skull
                • Facial Bones of the Skull
                  • Maxillary Bone
                  • Palatine Bone
                  • Zygomatic Bone
                  • Nasal Bone
                  • Lacrimal Bone
                  • Inferior Nasal Conchae
                  • Vomer Bone
                  • Mandible
                • The Orbit
                • The Nasal Septum and Nasal Conchae
                • Cranial Fossae
                  • Anterior Cranial Fossa
                  • Middle Cranial Fossa
                  • Posterior Cranial Fossa
                • Paranasal Sinuses
                • Hyoid Bone
              • 7.3. The Vertebral Column
                • Regions of the Vertebral Column
                • Curvatures of the Vertebral Column
                • General Structure of a Vertebra
                • Regional Modifications of Vertebrae
                  • Cervical Vertebrae
                  • Thoracic Vertebrae
                  • Lumbar Vertebrae
                  • Sacrum and Coccyx
                • Intervertebral Discs and Ligaments of the Vertebral Column
                  • Intervertebral Disc
                  • Ligaments of the Vertebral Column
              • 7.4. The Thoracic Cage
                • Sternum
                • Ribs
                  • Parts of a Typical Rib
                  • Rib Classifications
              • 7.5. Embryonic Development of the Axial Skeleton
                • Development of the Skull
                • Development of the Vertebral Column and Thoracic cage
            • Chapter 8. The Appendicular Skeleton
              • 8.1. The Pectoral Girdle
                • Clavicle
                • Scapula
              • 8.2. Bones of the Upper Limb
                • Humerus
                • Ulna
                • Radius
                • Carpal Bones
                • Metacarpal Bones
                • Phalanx Bones
              • 8.3. The Pelvic Girdle and Pelvis
                • Hip Bone
                  • Ilium
                  • Ischium
                  • Pubis
                • Pelvis
                  • Comparison of the Female and Male Pelvis
              • 8.4. Bones of the Lower Limb
                • Femur
                • Patella
                • Tibia
                • Fibula
                • Tarsal Bones
                • Metatarsal Bones
                • Phalanges
                • Arches of the Foot
              • 8.5. Development of the Appendicular Skeleton
                • Limb Growth
                • Ossification of Appendicular Bones
            • Chapter 9. Joints
              • 9.1. Classification of Joints
                • Structural Classification of Joints
                • Functional Classification of Joints
                  • Synarthrosis
                  • Amphiarthrosis
                  • Diarthrosis
              • 9.2. Fibrous Joints
                • Suture
                • Syndesmosis
                • Gomphosis
              • 9.3. Cartilaginous Joints
                • Synchondrosis
                • Symphysis
              • 9.4. Synovial Joints
                • Structural Features of Synovial Joints
                • Additional Structures Associated with Synovial Joints
                • Types of Synovial Joints
                  • Pivot Joint
                  • Hinge Joint
                  • Condyloid Joint
                  • Saddle Joint
                  • Plane Joint
                  • Ball-and-Socket Joint
              • 9.5. Types of Body Movements
                • Flexion and Extension
                • Abduction and Adduction
                • Circumduction
                • Rotation
                • Supination and Pronation
                • Dorsiflexion and Plantar Flexion
                • Inversion and Eversion
                • Protraction and Retraction
                • Depression and Elevation
                • Excursion
                • Superior Rotation and Inferior Rotation
                • Opposition and Reposition
              • 9.6. Anatomy of Selected Synovial Joints
                • Articulations of the Vertebral Column
                • Temporomandibular Joint
                • Shoulder Joint
                • Elbow Joint
                • Hip Joint
                • Knee Joint
                • Ankle and Foot Joints
              • 9.7. Development of Joints
              • Chapter 10. Muscle Tissue
                • 10.1. Overview of Muscle Tissues
                  • 10.2. Skeletal Muscle
                    • Skeletal Muscle Fibers
                    • The Sarcomere
                    • The Neuromuscular Junction
                    • Excitation-Contraction Coupling
                  • 10.3. Muscle Fiber Contraction and Relaxation
                    • The Sliding Filament Model of Contraction
                    • ATP and Muscle Contraction
                    • Sources of ATP
                    • Relaxation of a Skeletal Muscle
                    • Muscle Strength
                  • 10.4. Nervous System Control of Muscle Tension
                    • Motor Units
                    • The Length-Tension Range of a Sarcomere
                    • The Frequency of Motor Neuron Stimulation
                    • Treppe
                    • Muscle Tone
                  • 10.5. Types of Muscle Fibers
                    • 10.6. Exercise and Muscle Performance
                      • Endurance Exercise
                      • Resistance Exercise
                      • Performance-Enhancing Substances
                    • 10.7. Cardiac Muscle Tissue
                      • 10.8. Smooth Muscle
                        • Hyperplasia in Smooth Muscle
                      • 10.9. Development and Regeneration of Muscle Tissue
                      • Chapter 11. The Muscular System
                        • 11.1. Interactions of Skeletal Muscles, Their Fascicle Arrangement, and Their Lever Systems
                          • Interactions of Skeletal Muscles in the Body
                          • Patterns of Fascicle Organization
                          • The Lever System of Muscle and Bone Interactions
                        • 11.2. Naming Skeletal Muscles
                          • 11.3. Axial Muscles of the Head, Neck, and Back
                            • Muscles That Create Facial Expression
                            • Muscles That Move the Eyes
                            • Muscles That Move the Lower Jaw
                            • Muscles That Move the Tongue
                            • Muscles of the Anterior Neck
                            • Muscles That Move the Head
                            • Muscles of the Posterior Neck and the Back
                          • 11.4. Axial Muscles of the Abdominal Wall and Thorax
                            • Muscles of the Abdomen
                            • Muscles of the Thorax
                              • The Diaphragm
                              • The Intercostal Muscles
                            • Muscles of the Pelvic Floor and Perineum
                          • 11.5. Muscles of the Pectoral Girdle and Upper Limbs
                            • Muscles That Position the Pectoral Girdle
                            • Muscles That Move the Humerus
                            • Muscles That Move the Forearm
                            • Muscles That Move the Wrist, Hand, and Fingers
                              • Muscles of the Arm That Move the Wrists, Hands, and Fingers
                              • Intrinsic Muscles of the Hand
                          • 11.6. Appendicular Muscles of the Pelvic Girdle and Lower Limbs
                            • Muscles of the Thigh
                              • Gluteal Region Muscles That Move the Femur
                              • Thigh Muscles That Move the Femur, Tibia, and Fibula
                            • Muscles That Move the Feet and Toes
                      • III. Unit 3: Regulation, Integration, and Control
                        • Chapter 12. The Nervous System and Nervous Tissue
                          • 12.1. Basic Structure and Function of the Nervous System
                            • The Central and Peripheral Nervous Systems
                            • Functional Divisions of the Nervous System
                              • Basic Functions
                              • Controlling the Body
                          • 12.2. Nervous Tissue
                            • Neurons
                              • Parts of a Neuron
                              • Types of Neurons
                            • Glial Cells
                              • Glial Cells of the CNS
                              • Glial Cells of the PNS
                              • Myelin
                          • 12.3. The Function of Nervous Tissue
                            • 12.4. The Action Potential
                              • Electrically Active Cell Membranes
                              • The Membrane Potential
                                • The Action Potential
                                • Propagation of the Action Potential
                            • 12.5. Communication Between Neurons
                              • Graded Potentials
                                • Types of Graded Potentials
                                • Summation
                              • Synapses
                                • Neurotransmitter Release
                                • Neurotransmitter Systems
                          • Chapter 13. Anatomy of the Nervous System
                            • 13.1. The Embryologic Perspective
                              • The Neural Tube
                              • Primary Vesicles
                              • Secondary Vesicles
                              • Spinal Cord Development
                              • Relating Embryonic Development to the Adult Brain
                            • 13.2. The Central Nervous System
                              • The Cerebrum
                                • Cerebral Cortex
                                • Subcortical structures
                              • The Diencephalon
                                • Thalamus
                                • Hypothalamus
                              • Brain Stem
                                • Midbrain
                                • Pons
                                • Medulla
                              • The Cerebellum
                              • The Spinal Cord
                                • Gray Horns
                                • White Columns
                            • 13.3. Circulation and the Central Nervous System
                              • Blood Supply to the Brain
                                • Arterial Supply
                                • Venous Return
                              • Protective Coverings of the Brain and Spinal Cord
                                • Dura Mater
                                • Arachnoid Mater
                                • Pia Mater
                              • The Ventricular System
                                • The Ventricles
                                • Cerebrospinal Fluid Circulation
                            • 13.4. The Peripheral Nervous System
                              • Ganglia
                              • Nerves
                                • Cranial Nerves
                                • Spinal Nerves
                          • Chapter 14. The Brain and Cranial Nerves
                            • 14.1. Sensory Perception
                              • Sensory Receptors
                                • Structural Receptor Types
                                • Functional Receptor Types
                              • Sensory Modalities
                                • Gustation (Taste)
                                • Olfaction (Smell)
                                • Audition (Hearing)
                                • Equilibrium (Balance)
                                • Somatosensation (Touch)
                                • Vision
                              • Sensory Nerves
                                • Spinal Nerves
                                • Cranial Nerves
                            • 14.2. Central Processing
                              • Sensory Pathways
                                • Spinal Cord and Brain Stem
                                • Diencephalon
                              • Cortical Processing
                            • 14.3. Motor Responses
                              • Cortical Responses
                                • Secondary Motor Cortices
                                • Primary Motor Cortex
                              • Descending Pathways
                                • Appendicular Control
                                • Axial Control
                              • Extrapyramidal Controls
                              • Ventral Horn Output
                              • Reflexes
                          • Chapter 15. The Autonomic Nervous System
                            • 15.1. Divisions of the Autonomic Nervous System
                              • Sympathetic Division of the Autonomic Nervous System
                              • Parasympathetic Division of the Autonomic Nervous System
                              • Chemical Signaling in the Autonomic Nervous System
                            • 15.2. Autonomic Reflexes and Homeostasis
                              • The Structure of Reflexes
                                • Afferent Branch
                                • Efferent Branch
                                • Short and Long Reflexes
                              • Balance in Competing Autonomic Reflex Arcs
                                • Competing Neurotransmitters
                                • Autonomic Tone
                            • 15.3. Central Control
                              • Forebrain Structures
                                • The Hypothalamus
                                • The Amygdala
                              • The Medulla
                            • 15.4. Drugs that Affect the Autonomic System
                              • Broad Autonomic Effects
                              • Sympathetic Effect
                                • Sympathomimetic Drugs
                                • Sympatholytic Drugs
                              • Parasympathetic Effects
                          • Chapter 16. The Neurological Exam
                            • 16.1. Overview of the Neurological Exam
                              • Neuroanatomy and the Neurological Exam
                              • Causes of Neurological Deficits
                            • 16.2. The Mental Status Exam
                              • Functions of the Cerebral Cortex
                              • Cognitive Abilities
                                • Orientation and Memory
                                • Language and Speech
                                • Sensorium
                                • Judgment and Abstract Reasoning
                              • The Mental Status Exam
                            • 16.3. The Cranial Nerve Exam
                              • Sensory Nerves
                              • Gaze Control
                              • Nerves of the Face and Oral Cavity
                              • Motor Nerves of the Neck
                              • The Cranial Nerve Exam
                            • 16.4. The Sensory and Motor Exams
                              • Sensory Modalities and Location
                              • Muscle Strength and Voluntary Movement
                              • Reflexes
                              • Comparison of Upper and Lower Motor Neuron Damage
                            • 16.5. The Coordination and Gait Exams
                              • Location and Connections of the Cerebellum
                              • Coordination and Alternating Movement
                              • Posture and Gait
                              • Ataxia
                          • Chapter 17. The Endocrine System
                            • 17.1. An Overview of the Endocrine System
                              • Neural and Endocrine Signaling
                              • Structures of the Endocrine System
                              • Other Types of Chemical Signaling
                            • 17.2. Hormones
                              • Types of Hormones
                                • Amine Hormones
                                • Peptide and Protein Hormones
                                • Steroid Hormones
                              • Pathways of Hormone Action
                                • Pathways Involving Intracellular Hormone Receptors
                                • Pathways Involving Cell Membrane Hormone Receptors
                              • Factors Affecting Target Cell Response
                              • Regulation of Hormone Secretion
                                • Role of Feedback Loops
                                • Role of Endocrine Gland Stimuli
                            • 17.3. The Pituitary Gland and Hypothalamus
                              • Posterior Pituitary
                                • Oxytocin
                                • Antidiuretic Hormone (ADH)
                              • Anterior Pituitary
                                • Growth Hormone
                                • Thyroid-Stimulating Hormone
                                • Adrenocorticotropic Hormone
                                • Follicle-Stimulating Hormone and Luteinizing Hormone
                                • Prolactin
                              • Intermediate Pituitary: Melanocyte-Stimulating Hormone
                            • 17.4. The Thyroid Gland
                              • Synthesis and Release of Thyroid Hormones
                              • Regulation of TH Synthesis
                              • Functions of Thyroid Hormones
                              • Calcitonin
                            • 17.5. The Parathyroid Glands
                              • 17.6. The Adrenal Glands
                                • Adrenal Cortex
                                  • Hormones of the Zona Glomerulosa
                                  • Hormones of the Zona Fasciculata
                                  • Hormones of the Zona Reticularis
                                • Adrenal Medulla
                                • Disorders Involving the Adrenal Glands
                              • 17.7. The Pineal Gland
                                • 17.8. Gonadal and Placental Hormones
                                  • 17.9. The Endocrine Pancreas
                                    • Cells and Secretions of the Pancreatic Islets
                                    • Regulation of Blood Glucose Levels by Insulin and Glucagon
                                      • Glucagon
                                      • Insulin
                                  • 17.10. Organs with Secondary Endocrine Functions
                                    • Heart
                                    • Gastrointestinal Tract
                                    • Kidneys
                                    • Skeleton
                                    • Adipose Tissue
                                    • Skin
                                    • Thymus
                                    • Liver
                                  • 17.11. Development and Aging of the Endocrine System
                                • IV. Unit 4: Fluids and Transport
                                  • Chapter 18. The Cardiovascular System: Blood
                                    • 18.1. An Overview of Blood
                                      • Functions of Blood
                                        • Transportation
                                        • Defense
                                        • Maintenance of Homeostasis
                                      • Composition of Blood
                                      • Characteristics of Blood
                                      • Blood Plasma
                                        • Plasma Proteins
                                        • Other Plasma Solutes
                                    • 18.2. Production of the Formed Elements
                                      • Sites of Hemopoiesis
                                      • Differentiation of Formed Elements from Stem Cells
                                      • Hemopoietic Growth Factors
                                      • Bone Marrow Sampling and Transplants
                                    • 18.3. Erythrocytes
                                      • Shape and Structure of Erythrocytes
                                      • Hemoglobin
                                      • Lifecycle of Erythrocytes
                                      • Disorders of Erythrocytes
                                    • 18.4. Leukocytes and Platelets
                                      • Characteristics of Leukocytes
                                      • Classification of Leukocytes
                                        • Granular Leukocytes
                                        • Agranular Leukocytes
                                      • Lifecycle of Leukocytes
                                      • Disorders of Leukocytes
                                      • Platelets
                                      • Disorders of Platelets
                                    • 18.5. Hemostasis
                                      • Vascular Spasm
                                      • Formation of the Platelet Plug
                                      • Coagulation
                                        • Clotting Factors Involved in Coagulation
                                        • Extrinsic Pathway
                                        • Intrinsic Pathway
                                        • Common Pathway
                                      • Fibrinolysis
                                      • Plasma Anticoagulants
                                      • Disorders of Clotting
                                    • 18.6. Blood Typing
                                      • Antigens, Antibodies, and Transfusion Reactions
                                      • The ABO Blood Group
                                      • Rh Blood Groups
                                      • ABO Cross Matching
                                      • ABO Transfusion Protocols
                                  • Chapter 19. The Cardiovascular System: The Heart
                                    • 19.1. Heart Anatomy
                                      • Location of the Heart
                                      • Shape and Size of the Heart
                                      • Chambers and Circulation through the Heart
                                      • Membranes, Surface Features, and Layers
                                        • Membranes
                                        • Surface Features of the Heart
                                        • Layers
                                      • Internal Structure of the Heart
                                        • Septa of the Heart
                                        • Right Atrium
                                        • Right Ventricle
                                        • Left Atrium
                                        • Left Ventricle
                                        • Heart Valve Structure and Function
                                      • Coronary Circulation
                                        • Coronary Arteries
                                        • Coronary Veins
                                    • 19.2. Cardiac Muscle and Electrical Activity
                                      • Structure of Cardiac Muscle
                                      • Conduction System of the Heart
                                        • Sinoatrial (SA) Node
                                        • Atrioventricular (AV) Node
                                        • Atrioventricular Bundle (Bundle of His), Bundle Branches, and Purkinje Fibers
                                        • Membrane Potentials and Ion Movement in Cardiac Conductive Cells
                                        • Membrane Potentials and Ion Movement in Cardiac Contractile Cells
                                        • Calcium Ions
                                        • Comparative Rates of Conduction System Firing
                                      • Electrocardiogram
                                      • Cardiac Muscle Metabolism
                                    • 19.3. Cardiac Cycle
                                      • Pressures and Flow
                                      • Phases of the Cardiac Cycle
                                        • Atrial Systole and Diastole
                                        • Ventricular Systole
                                        • Ventricular Diastole
                                      • Heart Sounds
                                    • 19.4. Cardiac Physiology
                                      • Resting Cardiac Output
                                      • Exercise and Maximum Cardiac Output
                                      • Heart Rates
                                      • Correlation Between Heart Rates and Cardiac Output
                                      • Cardiovascular Centers
                                      • Input to the Cardiovascular Center
                                      • Other Factors Influencing Heart Rate
                                        • Epinephrine and Norepinephrine
                                        • Thyroid Hormones
                                        • Calcium
                                        • Caffeine and Nicotine
                                        • Factors Decreasing Heart Rate
                                      • Stroke Volume
                                        • Preload
                                        • Contractility
                                        • Afterload
                                    • 19.5. Development of the Heart
                                    • Chapter 20. The Cardiovascular System: Blood Vessels and Circulation
                                      • 20.1. Structure and Function of Blood Vessels
                                        • Shared Structures
                                          • Tunica Intima
                                          • Tunica Media
                                          • Tunica Externa
                                        • Arteries
                                        • Arterioles
                                        • Capillaries
                                          • Continuous Capillaries
                                          • Fenestrated Capillaries
                                          • Sinusoid Capillaries
                                        • Metarterioles and Capillary Beds
                                        • Venules
                                        • Veins
                                        • Veins as Blood Reservoirs
                                      • 20.2. Blood Flow, Blood Pressure, and Resistance
                                        • Components of Arterial Blood Pressure
                                          • Systolic and Diastolic Pressures
                                          • Pulse Pressure
                                          • Mean Arterial Pressure
                                        • Pulse
                                        • Measurement of Blood Pressure
                                        • Variables Affecting Blood Flow and Blood Pressure
                                          • Cardiac Output
                                          • Compliance
                                          • A Mathematical Approach to Factors Affecting Blood Flow
                                          • Blood Volume
                                          • Blood Viscosity
                                          • Vessel Length and Diameter
                                          • The Roles of Vessel Diameter and Total Area in Blood Flow and Blood Pressure
                                        • Venous System
                                          • Skeletal Muscle Pump
                                          • Respiratory Pump
                                          • Pressure Relationships in the Venous System
                                          • The Role of Venoconstriction in Resistance, Blood Pressure, and Flow
                                      • 20.3. Capillary Exchange
                                        • Bulk Flow
                                          • Hydrostatic Pressure
                                          • Osmotic Pressure
                                          • Interaction of Hydrostatic and Osmotic Pressures
                                        • The Role of Lymphatic Capillaries
                                      • 20.4. Homeostatic Regulation of the Vascular System
                                        • Neural Regulation
                                          • The Cardiovascular Centers in the Brain
                                          • Baroreceptor Reflexes
                                          • Chemoreceptor Reflexes
                                        • Endocrine Regulation
                                          • Epinephrine and Norepinephrine
                                          • Antidiuretic Hormone
                                          • Renin-Angiotensin-Aldosterone Mechanism
                                          • Erythropoietin
                                          • Atrial Natriuretic Hormone
                                        • Autoregulation of Perfusion
                                          • Chemical Signals Involved in Autoregulation
                                          • The Myogenic Response
                                        • Effect of Exercise on Vascular Homeostasis
                                        • Clinical Considerations in Vascular Homeostasis
                                          • Hypertension and Hypotension
                                          • Hemorrhage
                                          • Circulatory Shock
                                      • 20.5. Circulatory Pathways
                                        • Pulmonary Circulation
                                        • Overview of Systemic Arteries
                                        • The Aorta
                                          • Coronary Circulation
                                          • Aortic Arch Branches
                                          • Thoracic Aorta and Major Branches
                                          • Abdominal Aorta and Major Branches
                                        • Arteries Serving the Upper Limbs
                                        • Arteries Serving the Lower Limbs
                                        • Overview of Systemic Veins
                                          • The Superior Vena Cava
                                          • Veins of the Head and Neck
                                          • Venous Drainage of the Brain
                                          • Veins Draining the Upper Limbs
                                          • The Inferior Vena Cava
                                          • Veins Draining the Lower Limbs
                                        • Hepatic Portal System
                                      • 20.6. Development of Blood Vessels and Fetal Circulation
                                      • Chapter 21. The Lymphatic and Immune System
                                        • 21.1. Anatomy of the Lymphatic and Immune Systems
                                          • Functions of the Lymphatic System
                                          • Structure of the Lymphatic System
                                            • Lymphatic Capillaries
                                            • Larger Lymphatic Vessels, Trunks, and Ducts
                                          • The Organization of Immune Function
                                          • Lymphocytes: B Cells, T Cells, Plasma Cells, and Natural Killer Cells
                                            • B Cells
                                            • T Cells
                                            • Plasma Cells
                                            • Natural Killer Cells
                                          • Primary Lymphoid Organs and Lymphocyte Development
                                            • Bone Marrow
                                            • Thymus
                                          • Secondary Lymphoid Organs and their Roles in Active Immune Responses
                                            • Lymph Nodes
                                            • Spleen
                                            • Lymphoid Nodules
                                        • 21.2. Barrier Defenses and the Innate Immune Response
                                          • Cells of the Innate Immune Response
                                            • Phagocytes: Macrophages and Neutrophils
                                            • Natural Killer Cells
                                          • Recognition of Pathogens
                                          • Soluble Mediators of the Innate Immune Response
                                            • Cytokines and Chemokines
                                            • Early induced Proteins
                                            • Complement System
                                          • Inflammatory Response
                                        • 21.3. The Adaptive Immune Response: T lymphocytes and Their Functional Types
                                          • The Benefits of the Adaptive Immune Response
                                            • Primary Disease and Immunological Memory
                                            • Self Recognition
                                          • T Cell-Mediated Immune Responses
                                          • Antigens
                                            • Antigen Processing and Presentation
                                            • Professional Antigen-presenting Cells
                                          • T Cell Development and Differentiation
                                          • Mechanisms of T Cell-mediated Immune Responses
                                          • Clonal Selection and Expansion
                                          • The Cellular Basis of Immunological Memory
                                          • T Cell Types and their Functions
                                            • Helper T Cells and their Cytokines
                                            • Cytotoxic T cells
                                            • Regulatory T Cells
                                        • 21.4. The Adaptive Immune Response: B-lymphocytes and Antibodies
                                          • B Cell Differentiation and Activation
                                          • Antibody Structure
                                            • Four-chain Models of Antibody Structures
                                            • Five Classes of Antibodies and their Functions
                                            • Clonal Selection of B Cells
                                            • Primary versus Secondary B Cell Responses
                                          • Active versus Passive Immunity
                                          • T cell-dependent versus T cell-independent Antigens
                                        • 21.5. The Immune Response against Pathogens
                                          • The Mucosal Immune Response
                                          • Defenses against Bacteria and Fungi
                                          • Defenses against Parasites
                                          • Defenses against Viruses
                                          • Evasion of the Immune System by Pathogens
                                        • 21.6. Diseases Associated with Depressed or Overactive Immune Responses
                                          • Immunodeficiencies
                                            • Inherited Immunodeficiencies
                                            • Human Immunodeficiency Virus/AIDS
                                          • Hypersensitivities
                                            • Immediate (Type I) Hypersensitivity
                                            • Type II and Type III Hypersensitivities
                                            • Delayed (Type IV) Hypersensitivity
                                          • Autoimmune Responses
                                        • 21.7. Transplantation and Cancer Immunology
                                          • The Rh Factor
                                          • Tissue Transplantation
                                          • Immune Responses Against Cancer
                                    • V. Unit 5: Energy, Maintenance, and Environmental Exchange
                                      • Chapter 22. The Respiratory System
                                        • 22.1. Organs and Structures of the Respiratory System
                                          • Conducting Zone
                                            • The Nose and its Adjacent Structures
                                            • Pharynx
                                            • Larynx
                                            • Trachea
                                            • Bronchial Tree
                                          • Respiratory Zone
                                            • Alveoli
                                        • 22.2. The Lungs
                                          • Gross Anatomy of the Lungs
                                          • Blood Supply and Nervous Innervation of the Lungs
                                            • Blood Supply
                                            • Nervous Innervation
                                          • Pleura of the Lungs
                                        • 22.3. The Process of Breathing
                                          • Mechanisms of Breathing
                                            • Pressure Relationships
                                            • Physical Factors Affecting Ventilation
                                          • Pulmonary Ventilation
                                          • Respiratory Volumes and Capacities
                                          • Respiratory Rate and Control of Ventilation
                                            • Ventilation Control Centers
                                            • Factors That Affect the Rate and Depth of Respiration
                                        • 22.4. Gas Exchange
                                          • Gas Exchange
                                            • Gas Laws and Air Composition
                                            • Solubility of Gases in Liquids
                                            • Ventilation and Perfusion
                                          • Gas Exchange
                                            • External Respiration
                                            • Internal Respiration
                                        • 22.5. Transport of Gases
                                          • Oxygen Transport in the Blood
                                            • Function of Hemoglobin
                                            • Oxygen Dissociation from Hemoglobin
                                            • Hemoglobin of the Fetus
                                          • Carbon Dioxide Transport in the Blood
                                            • Dissolved Carbon Dioxide
                                            • Bicarbonate Buffer
                                            • Carbaminohemoglobin
                                        • 22.6. Modifications in Respiratory Functions
                                          • Hyperpnea
                                          • High Altitude Effects
                                            • Acclimatization
                                        • 22.7. Embryonic Development of the Respiratory System
                                          • Time Line
                                            • Weeks 4–7
                                            • Weeks 7–16
                                            • Weeks 16–24
                                            • Weeks 24–Term
                                          • Fetal “Breathing”
                                          • Birth
                                      • Chapter 23. The Digestive System
                                        • 23.1. Overview of the Digestive System
                                          • Digestive System Organs
                                            • Alimentary Canal Organs
                                            • Accessory Structures
                                          • Histology of the Alimentary Canal
                                          • Nerve Supply
                                          • Blood Supply
                                          • The Peritoneum
                                        • 23.2. Digestive System Processes and Regulation
                                          • Digestive Processes
                                          • Regulatory Mechanisms
                                            • Neural Controls
                                            • Hormonal Controls
                                        • 23.3. The Mouth, Pharynx, and Esophagus
                                          • The Mouth
                                          • The Tongue
                                          • The Salivary Glands
                                            • The Major Salivary Glands
                                            • Saliva
                                            • Regulation of Salivation
                                          • The Teeth
                                            • Types of Teeth
                                            • Anatomy of a Tooth
                                          • The Pharynx
                                          • The Esophagus
                                            • Passage of Food through the Esophagus
                                            • Histology of the Esophagus
                                          • Deglutition
                                            • The Voluntary Phase
                                            • The Pharyngeal Phase
                                            • The Esophageal Phase
                                        • 23.4. The Stomach
                                          • Structure
                                          • Histology
                                          • Gastric Secretion
                                          • The Mucosal Barrier
                                          • Digestive Functions of the Stomach
                                            • Mechanical Digestion
                                            • Chemical Digestion
                                        • 23.5. The Small and Large Intestines
                                          • The Small Intestine
                                            • Structure
                                            • Histology
                                              • Circular folds
                                              • Villi
                                              • Microvilli
                                              • Intestinal Glands
                                              • Intestinal MALT
                                            • Mechanical Digestion in the Small Intestine
                                            • Chemical Digestion in the Small Intestine
                                          • The Large Intestine
                                            • Structure
                                            • Subdivisions
                                              • Cecum
                                              • Colon
                                              • Rectum
                                              • Anal Canal
                                            • Histology
                                            • Anatomy
                                            • Bacterial Flora
                                            • Digestive Functions of the Large Intestine
                                              • Mechanical Digestion
                                              • Chemical Digestion
                                            • Absorption, Feces Formation, and Defecation
                                        • 23.6. Accessory Organs in Digestion: The Liver, Pancreas, and Gallbladder
                                          • The Liver
                                            • Histology
                                            • Bile
                                          • The Pancreas
                                            • Pancreatic Juice
                                            • Pancreatic Secretion
                                          • The Gallbladder
                                        • 23.7. Chemical Digestion and Absorption: A Closer Look
                                          • Chemical Digestion
                                            • Carbohydrate Digestion
                                            • Protein Digestion
                                            • Lipid Digestion
                                            • Nucleic Acid Digestion
                                          • Absorption
                                            • Carbohydrate Absorption
                                            • Protein Absorption
                                            • Lipid Absorption
                                            • Nucleic Acid Absorption
                                            • Mineral Absorption
                                            • Vitamin Absorption
                                            • Water Absorption
                                      • Chapter 24. Metabolism and Nutrition
                                        • 24.1. Overview of Metabolic Reactions
                                          • Catabolic Reactions
                                          • Anabolic Reactions
                                          • Hormonal Regulation of Metabolism
                                          • Oxidation-Reduction Reactions
                                        • 24.2. Carbohydrate Metabolism
                                          • Glycolysis
                                            • Anaerobic Respiration
                                            • Aerobic Respiration
                                          • Krebs Cycle/Citric Acid Cycle/Tricarboxylic Acid Cycle
                                          • Oxidative Phosphorylation and the Electron Transport Chain
                                          • Gluconeogenesis
                                        • 24.3. Lipid Metabolism
                                          • Lipolysis
                                          • Ketogenesis
                                          • Ketone Body Oxidation
                                          • Lipogenesis
                                        • 24.4. Protein Metabolism
                                          • Urea Cycle
                                        • 24.5. Metabolic States of the Body
                                          • The Absorptive State
                                          • The Postabsorptive State
                                          • Starvation
                                        • 24.6. Energy and Heat Balance
                                          • Mechanisms of Heat Exchange
                                          • Metabolic Rate
                                        • 24.7. Nutrition and Diet
                                          • Food and Metabolism
                                          • Vitamins
                                          • Minerals
                                      • Chapter 25. The Urinary System
                                        • 25.1. Physical Characteristics of Urine
                                          • 25.2. Gross Anatomy of Urine Transport
                                            • Urethra
                                              • Female Urethra
                                              • Male Urethra
                                            • Bladder
                                              • Micturition Reflex
                                            • Ureters
                                          • 25.3. Gross Anatomy of the Kidney
                                            • External Anatomy
                                            • Internal Anatomy
                                            • Renal Hilum
                                              • Nephrons and Vessels
                                              • Cortex
                                          • 25.4. Microscopic Anatomy of the Kidney
                                            • Nephrons: The Functional Unit
                                              • Renal Corpuscle
                                              • Proximal Convoluted Tubule (PCT)
                                              • Loop of Henle
                                              • Distal Convoluted Tubule (DCT)
                                              • Collecting Ducts
                                          • 25.5. Physiology of Urine Formation
                                            • Glomerular Filtration Rate (GFR)
                                            • Net Filtration Pressure (NFP)
                                          • 25.6. Tubular Reabsorption
                                            • Mechanisms of Recovery
                                            • Reabsorption and Secretion in the PCT
                                            • Reabsorption and Secretion in the Loop of Henle
                                              • Descending Loop
                                              • Ascending Loop
                                              • Countercurrent Multiplier System
                                            • Reabsorption and Secretion in the Distal Convoluted Tubule
                                            • Collecting Ducts and Recovery of Water
                                          • 25.7. Regulation of Renal Blood Flow
                                            • Sympathetic Nerves
                                            • Autoregulation
                                              • Arteriole Myogenic Mechanism
                                              • Tubuloglomerular Feedback
                                          • 25.8. Endocrine Regulation of Kidney Function
                                            • Renin–Angiotensin–Aldosterone
                                            • Antidiuretic Hormone (ADH)
                                            • Endothelin
                                            • Natriuretic Hormones
                                            • Parathyroid Hormone
                                          • 25.9. Regulation of Fluid Volume and Composition
                                            • Volume-sensing Mechanisms
                                            • Diuretics and Fluid Volume
                                            • Regulation of Extracellular Na+
                                            • Regulation of Extracellular K+
                                            • Regulation of Cl–
                                            • Regulation of Ca++ and Phosphate
                                            • Regulation of H+, Bicarbonate, and pH
                                            • Regulation of Nitrogen Wastes
                                            • Elimination of Drugs and Hormones
                                          • 25.10. The Urinary System and Homeostasis
                                            • Vitamin D Synthesis
                                            • Erythropoiesis
                                            • Blood Pressure Regulation
                                            • Regulation of Osmolarity
                                            • Recovery of Electrolytes
                                            • pH Regulation
                                        • Chapter 26. Fluid, Electrolyte, and Acid-Base Balance
                                          • 26.1. Body Fluids and Fluid Compartments
                                            • Body Water Content
                                            • Fluid Compartments
                                              • Intracellular Fluid
                                              • Extracellular Fluid
                                            • Composition of Body Fluids
                                            • Fluid Movement between Compartments
                                            • Solute Movement between Compartments
                                          • 26.2. Water Balance
                                            • Regulation of Water Intake
                                            • Regulation of Water Output
                                            • Role of ADH
                                          • 26.3. Electrolyte Balance
                                            • Roles of Electrolytes
                                              • Sodium
                                              • Potassium
                                              • Chloride
                                              • Bicarbonate
                                              • Calcium
                                              • Phosphate
                                            • Regulation of Sodium and Potassium
                                              • Aldosterone
                                              • Angiotensin II
                                            • Regulation of Calcium and Phosphate
                                          • 26.4. Acid-Base Balance
                                            • Buffer Systems in the Body
                                              • Protein Buffers in Blood Plasma and Cells
                                              • Hemoglobin as a Buffer
                                              • Phosphate Buffer
                                              • Bicarbonate-Carbonic Acid Buffer
                                            • Respiratory Regulation of Acid-Base Balance
                                            • Renal Regulation of Acid-Base Balance
                                          • 26.5. Disorders of Acid-Base Balance
                                            • Metabolic Acidosis: Primary Bicarbonate Deficiency
                                            • Metabolic Alkalosis: Primary Bicarbonate Excess
                                            • Respiratory Acidosis: Primary Carbonic Acid/CO2 Excess
                                            • Respiratory Alkalosis: Primary Carbonic Acid/CO2 Deficiency
                                            • Compensation Mechanisms
                                              • Respiratory Compensation
                                              • Metabolic Compensation
                                              • Diagnosing Acidosis and Alkalosis
                                      • VI. Unit 6: Human Development and the Continuity of Life
                                        • Chapter 27. The Reproductive System
                                          • 27.1. Anatomy and Physiology of the Male Reproductive System
                                            • Scrotum
                                            • Testes
                                              • Sertoli Cells
                                              • Germ Cells
                                              • Spermatogenesis
                                            • Structure of Formed Sperm
                                            • Sperm Transport
                                              • Role of the Epididymis
                                              • Duct System
                                              • Seminal Vesicles
                                              • Prostate Gland
                                              • Bulbourethral Glands
                                            • The Penis
                                            • Testosterone
                                              • Functions of Testosterone
                                              • Control of Testosterone
                                          • 27.2. Anatomy and Physiology of the Female Reproductive System
                                            • External Female Genitals
                                            • Vagina
                                            • Ovaries
                                            • The Ovarian Cycle
                                              • Oogenesis
                                              • Folliculogenesis
                                              • Hormonal Control of the Ovarian Cycle
                                            • The Uterine Tubes
                                            • The Uterus and Cervix
                                            • The Menstrual Cycle
                                              • Menses Phase
                                              • Proliferative Phase
                                              • Secretory Phase
                                            • The Breasts
                                            • Hormonal Birth Control
                                          • 27.3. Development of the Male and Female Reproductive Systems
                                            • Development of the Sexual Organs in the Embryo and Fetus
                                            • Further Sexual Development Occurs at Puberty
                                              • Signs of Puberty
                                        • Chapter 28. Development and Inheritance
                                          • 28.1. Fertilization
                                            • Transit of Sperm
                                            • Contact Between Sperm and Oocyte
                                            • The Zygote
                                          • 28.2. Embryonic Development
                                            • Pre-implantation Embryonic Development
                                            • Implantation
                                            • Embryonic Membranes
                                            • Embryogenesis
                                            • Development of the Placenta
                                            • Organogenesis
                                          • 28.3. Fetal Development
                                            • Sexual Differentiation
                                            • The Fetal Circulatory System
                                            • Other Organ Systems
                                          • 28.4. Maternal Changes During Pregnancy, Labor, and Birth
                                            • Effects of Hormones
                                            • Weight Gain
                                            • Changes in Organ Systems During Pregnancy
                                              • Digestive and Urinary System Changes
                                              • Circulatory System Changes
                                              • Respiratory System Changes
                                              • Integumentary System Changes
                                            • Physiology of Labor
                                            • Stages of Childbirth
                                              • Cervical Dilation
                                              • Expulsion Stage
                                              • Afterbirth
                                          • 28.5. Adjustments of the Infant at Birth and Postnatal Stages
                                            • Respiratory Adjustments
                                            • Circulatory Adjustments
                                            • Thermoregulatory Adjustments
                                            • Gastrointestinal and Urinary Adjustments
                                          • 28.6. Lactation
                                            • Structure of the Lactating Breast
                                            • The Process of Lactation
                                            • Changes in the Composition of Breast Milk
                                          • 28.7. Patterns of Inheritance
                                            • From Genotype to Phenotype
                                            • Mendel’s Theory of Inheritance
                                            • Autosomal Dominant Inheritance
                                            • Autosomal Recessive Inheritance
                                            • X-linked Dominant or Recessive Inheritance
                                            • Other Inheritance Patterns: Incomplete Dominance, Codominance, and Lethal Alleles
                                            • Mutations
                                            • Chromosomal Disorders
                                      • Index

                                      Preface

                                      Creative Commons Attribution License 4.0 http://creativecommons.org/licenses/by/4.0/

                                      2014/03/03 10:25:22 -0600

                                      Human Anatomy and Physiology is designed for the two-semester anatomy and physiology course taken by life science and allied health students. The textbook follows the scope and sequence of most Human Anatomy and Physiology courses, and its coverage and organization were informed by hundreds of instructors who teach the course. Instructors can customize the book, adapting it to the approach that works best in their classroom. The artwork for this textbook is aimed focusing student learning through a powerful blend of traditional depictions and instructional innovations. Color is used sparingly, to emphasize the most important aspects of any given illustration. Significant use of micrographs from the University of Michigan complement the illustrations, and provide the students with a meaningful alternate depiction of each concept. Finally, enrichment elements provide relevance and deeper context for students, particularly in the areas of health, disease, and information relevant to their intended careers.

                                      Welcome to Human Anatomy and Physiology, an OpenStax College resource. We created this textbook with several goals in mind: accessibility, customization, and student engagement—helping students reach high levels of academic scholarship. Instructors and students alike will find that this textbook offers a thorough introduction to the content in an accessible format.

                                      1About OpenStax College

                                      OpenStax College is a nonprofit organization committed to improving student access to quality learning materials. Our free textbooks are developed and peer-reviewed by educators to ensure that they are readable, accurate, and organized in accordance with the scope and sequence requirements of today’s college courses. Unlike traditional textbooks, OpenStax College resources live online and are owned by the community of educators using them. Through partnerships with companies and foundations committed to reducing costs for students, we are working to improve access to higher education for all. OpenStax College is an initiative of Rice University and is made possible through the generous support of several philanthropic foundations.

                                      2About OpenStax College’s Resources

                                      • Customization
                                      • Curation
                                      • Cost

                                      OpenStax College resources provide quality academic instruction. Three key features set our materials apart from others: 1) They can be easily customized by instructors for each class, 2) they are “living” resources that grow online through contributions from science educators, and 3) they are available for free or for a minimal cost.

                                      Customization

                                      OpenStax College learning resources are conceived and written with flexibility in mind so that they can be customized for each course. Our textbooks provide a solid foundation on which instructors can build their own texts. Instructors can select the sections that are most relevant to their curricula and create a textbook that speaks directly to the needs of their students. Instructors are encouraged to expand on existing examples in the text by adding unique context via geographically localized applications and topical connections.

                                      Human Anatomy and Physiology can be easily customized using our online platform (https://openstaxcollege.org/textbooks/anatomy-and-physiology/adapt). The text is arranged in a modular chapter format. Simply select the content most relevant to your syllabus and create a textbook that addresses the needs of your class. This customization feature will ensure that your textbook reflects the goals of your course.

                                      Curation

                                      To broaden access and encourage community curation, Human Anatomy and Physiology is “open source” under a Creative Commons Attribution (CC BY) license. Members of the scientific community are invited to submit examples, emerging research, and other feedback to enhance and strengthen the material, keeping it current and relevant for today’s students. Submit your suggestions to info@openstaxcollege.org, and check in on edition status, alternate versions, errata, and news on the StaxDash at http://openstaxcollege.org.

                                      Cost

                                      Our textbooks are available for free online, and in low-cost print and tablet editions.

                                      3About Human Anatomy and Physiology

                                      • Coverage and Scope
                                        • Unit 1: Levels of Organization
                                        • Unit 2: Support and Movement
                                        • Unit 3: Regulation, Integration, and Control
                                        • Unit 4: Fluids and Transport
                                        • Unit 5: Energy, Maintenance, and Environmental Exchange
                                        • Unit 6: Human Development and the Continuity of Life
                                      • Pedagogical Foundation and Features
                                      • Dynamic, Learner-Centered Art
                                        • Micrographs
                                        • Learning Resources

                                      Human Anatomy and Physiology is designed for the two-semester anatomy and physiology course taken by life science and allied health students. It supports effective teaching and learning, and prepares students for further learning and future careers. The text focuses on the most important concepts and aims to minimize distracting students with more minor details.

                                      The development choices for this textbook were made with the guidance of hundreds of faculty who are deeply involved in teaching this course. These choices led to innovations in art, terminology, career orientation, practical applications, and multimedia-based learning, all with a goal of increasing relevance to students. We strove to make the discipline meaningful and memorable to students, so that they can draw from it a working knowledge that will enrich their future studies.

                                      Coverage and Scope

                                      The units of our Human Anatomy and Physiology textbook adhere to the scope and sequence followed by most two-semester courses nationwide.

                                      Unit 1: Levels of Organization

                                      Chapters 1–4 provide students with a basic understanding of human anatomy and physiology, including its language, the levels of organization, and the basics of chemistry and cell biology. These chapters provide a foundation for the further study of the body. They also focus particularly on how the body’s regions, important chemicals, and cells maintain homeostasis.
                                      Chapter 1 An Introduction to the Human Body
                                      Chapter 2 The Chemical Level of Organization
                                      Chapter 3 The Cellular Level of Organization
                                      Chapter 4 The Tissue Level of Organization

                                      Unit 2: Support and Movement

                                      In Chapters 5–11, students explore the skin, the largest organ of the body, and examine the body’s skeletal and muscular systems, following a traditional sequence of topics. This unit is the first to walk students through specific systems of the body, and as it does so, it maintains a focus on homeostasis as well as those diseases and conditions that can disrupt it.
                                      Chapter 5 The Integumentary System
                                      Chapter 6 Bone and Skeletal Tissue
                                      Chapter 7 The Axial Skeleton
                                      Chapter 8 The Appendicular Skeleton
                                      Chapter 9 Joints
                                      Chapter 10 Muscle Tissue
                                      Chapter 11 The Muscular System

                                      Unit 3: Regulation, Integration, and Control

                                      Chapters 12–17 help students answer questions about nervous and endocrine system control and regulation. In a break with the traditional sequence of topics, the special senses are integrated into the chapter on the somatic nervous system. The chapter on the neurological examination offers students a unique approach to understanding nervous system function using five simple but powerful diagnostic tests.
                                      Chapter 12 Introduction to the Nervous System
                                      Chapter 13 The Anatomy of the Nervous System
                                      Chapter 14 The Somatic Nervous System
                                      Chapter 15 The Autonomic Nervous System
                                      Chapter 16 The Neurological Exam
                                      Chapter 17 The Endocrine System

                                      Unit 4: Fluids and Transport

                                      In Chapters 18–21, students examine the principal means of transport for materials needed to support the human body, regulate its internal environment, and provide protection.
                                      Chapter 18 Blood
                                      Chapter 19 The Cardiovascular System: The Heart
                                      Chapter 20 The Cardiovascular System: Blood Vessels and Circulation
                                      Chapter 21 The Lymphatic System and Immunity

                                      Unit 5: Energy, Maintenance, and Environmental Exchange

                                      In Chapters 22–26, students discover the interaction between body systems and the outside environment for the exchange of materials, the capture of energy, the release of waste, and the overall maintenance of the internal systems that regulate the exchange. The explanations and illustrations are particularly focused on how structure relates to function.
                                      Chapter 22 The Respiratory System
                                      Chapter 23 The Digestive System
                                      Chapter 24 Nutrition and Metabolism
                                      Chapter 25 The Urinary System
                                      Chapter 26 Fluid, Electrolyte, and Acid–Base Balance

                                      Unit 6: Human Development and the Continuity of Life

                                      The closing chapters examine the male and female reproductive systems, describe the process of human development and the different stages of pregnancy, and end with a review of the mechanisms of inheritance.
                                      Chapter 27 The Reproductive System
                                      Chapter 28 Development and Genetic Inheritance

                                      Pedagogical Foundation and Features

                                      Human Anatomy and Physiology is designed to promote scientific literacy. Throughout the text, you will find features that engage the students by taking selected topics a step further.

                                      • Homeostatic Imbalances discusses the effects and results of imbalances in the body.

                                      • Disorders showcases a disorder that is relevant to the body system at hand. This feature may focus on a specific disorder, or a set of related disorders.

                                      • Diseases showcases a disease that is relevant to the body system at hand.

                                      • Aging explores the effect aging has on a body’s system and specific disorders that manifest over time.

                                      • Career Connections presents information on the various careers often pursued by allied health students, such as medical technician, medical examiner, and neurophysiologist. Students are introduced to the educational requirements for and day-to-day responsibilities in these careers.

                                      • Everyday Connections tie anatomical and physiological concepts to emerging issues and discuss these in terms of everyday life. Topics include “Anabolic Steroids” and “The Effect of Second-Hand Tobacco Smoke.”

                                      • Interactive Links direct students to online exercises, simulations, animations, and videos to add a fuller context to core content and help improve understanding of the material. Many features include links to the University of Michigan’s interactive WebScopes, which allow students to zoom in on micrographs in the collection. These resources were vetted by reviewers and other subject matter experts to ensure that they are effective and accurate. We strongly urge students to explore these links, whether viewing a video or inputting data into a simulation, to gain the fullest experience and to learn how to search for information independently.

                                      Dynamic, Learner-Centered Art

                                      Our unique approach to visuals is designed to emphasize only the components most important in any given illustration. The art style is particularly aimed at focusing student learning through a powerful blend of traditional depictions and instructional innovations.

                                      Much of the art in this book consists of black line illustrations. The strongest line is used to highlight the most important structures, and shading is used to show dimension and shape. Color is used sparingly to highlight and clarify the primary anatomical or functional point of the illustration. This technique is intended to draw students’ attention to the critical learning point in the illustration, without distraction from excessive gradients, shadows, and highlights. Full color is used when the structure or process requires it (for example, muscle diagrams and cardiovascular system illustrations).

                                      A color illustration of the pharynx.
                                      Figure 1The Pharynx
                                      By highlighting the most important portions of the illustration, the artwork helps students focus on the most important points, without overwhelming them.

                                      Micrographs

                                      Micrograph magnifications have been calculated based on the objective provided with the image. If a micrograph was recorded at 40×, and the image was magnified an additional 2×, we calculated the final magnification of the micrograph to be 80×.

                                      Please note that, when viewing the textbook electronically, the micrograph magnification provided in the text does not take into account the size and magnification of the screen on your electronic device. There may be some variation.

                                      A color illustration of the pharynx.
                                      Figure 2Sebaceous Glands
                                      These glands secrete oils that lubricate and protect the skin. LM × 400. (Micrograph provided by the Regents of University of Michigan Medical School © 2012)

                                      Learning Resources

                                      The following resources are (or will be) available in addition to main text:

                                      • PowerPoint slides: For each chapter, the illustrations are presented, one per slide, with their respective captions.

                                      • Pronunciation guide: A subset of the text’s key terms are presented with easy-to-follow phonetic transcriptions. For example, blastocyst is rendered as “blas'to-sist”

                                      4About Our Team

                                      • Senior Contributors
                                      • Advisor
                                      • Other Contributors

                                      Senior Contributors

                                      Table 1.
                                      J. Gordon Betts Tyler Junior College
                                      Peter Desaix University of North Carolina at Chapel Hill
                                      Eddie Johnson Central Oregon Community College
                                      Jody E. Johnson Arapahoe Community College
                                      Oksana Korol Aims Community College
                                      Dean Kruse Portland Community College
                                      Brandon Poe Springfield Technical Community College
                                      James A. Wise Hampton University
                                      Mark Womble Youngstown State University
                                      Kelly A. Young California State University, Long Beach

                                      Advisor

                                      Robin J. Heyden

                                      Other Contributors

                                      Table 2.
                                      Kim Aaronson Aquarius Institute; Triton College
                                      Lopamudra Agarwal Augusta Technical College
                                      Gary Allen Dalhousie University
                                      Robert Allison McLennan Community College
                                      Heather Armbruster Southern Union State Community College
                                      Timothy Ballard University of North Carolina Wilmington
                                      Matthew Barlow Eastern New Mexico University
                                      William Blaker Furman University
                                      Julie Bowers East Tennessee State University
                                      Emily Bradshaw Florida Southern College
                                      Nishi Bryska University of North Carolina, Charlotte
                                      Susan Caley Opsal Illinois Valley Community College
                                      Boyd Campbell Southwest College of Naturopathic Medicine and Health Sciences
                                      Ann Caplea Walsh University
                                      Marnie Chapman University of Alaska, Sitka
                                      Barbara Christie-Pope Cornell College
                                      Kenneth Crane Texarkana College
                                      Maurice Culver Florida State College at Jacksonville
                                      Heather Cushman Tacoma Community College
                                      Noelle Cutter Molloy College
                                      Lynnette Danzl-Tauer Rock Valley College
                                      Jane Davis Aurora University
                                      AnnMarie DelliPizzi Dominican College
                                      Susan Dentel Washtenaw Community College
                                      Pamela Dobbins Shelton State Community College
                                      Patty Dolan Pacific Lutheran University
                                      Sondra Dubowsky McLennan Community College
                                      Peter Dukehart Three Rivers Community College
                                      Ellen DuPré Central College
                                      Elizabeth DuPriest Warner Pacific College
                                      Pam Elf University of Minnesota
                                      Sharon Ellerton Queensborough Community College
                                      Carla Endres Utah State University - College of Eastern Utah: San Juan Campus
                                      Myriam Feldman Lake Washington Institute of Technology; Cascadia Community College
                                      Greg Fitch Avila University
                                      Lynn Gargan Tarant County College
                                      Michael Giangrande Oakland Community College
                                      Chaya Gopalan St. Louis College of Pharmacy
                                      Victor Greco Chattahoochee Technical College
                                      Susanna Heinze Skagit Valley College
                                      Ann Henninger Wartburg College
                                      Dale Horeth Tidewater Community College
                                      Michael Hortsch University of Michigan
                                      Rosemary Hubbard Marymount University
                                      Mark Hubley Prince George's Community College
                                      Branko Jablanovic College of Lake County
                                      Norman Johnson University of Massachusetts Amherst
                                      Mark Jonasson North Arkansas College
                                      Jeff Keyte College of Saint Mary
                                      William Kleinelp Middlesex County College
                                      Leigh Kleinert Grand Rapids Community College
                                      Brenda Leady University of Toledo
                                      John Lepri University of North Carolina, Greensboro
                                      Sarah Leupen University of Maryland, Baltimore County
                                      Lihua Liang Johns Hopkins University
                                      Robert Mallet University of North Texas Health Science Center
                                      Bruce Maring Daytona State College
                                      Elisabeth Martin College of Lake County
                                      Natalie Maxwell Carl Albert State College, Sallisaw
                                      Julie May William Carey University
                                      Debra McLaughlin University of Maryland University College
                                      Nicholas Mitchell St. Bonaventure University
                                      Shobhana Natarajan Brookhaven College
                                      Phillip Nicotera St. Petersburg College
                                      Mary Jane Niles University of San Francisco
                                      Ikemefuna Nwosu Parkland College; Lake Land College
                                      Betsy Ott Tyler Junior College
                                      Ivan Paul John Wood Community College
                                      Aaron Payette College of Southern Nevada
                                      Scott Payne Kentucky Wesleyan College
                                      Cameron Perkins South Georgia College
                                      David Pfeiffer University of Alaska, Anchorage
                                      Thomas Pilat Illinois Central College
                                      Eileen Preston Tarrant County College
                                      Mike Pyle Olivet Nazarene University
                                      Robert Rawding Gannon University
                                      Jason Schreer State University of New York at Potsdam
                                      Laird Sheldahl Mt. Hood Community College
                                      Brian Shmaefsky Lone Star College System
                                      Douglas Sizemore Bevill State Community College
                                      Susan Spencer Mount Hood Community College
                                      Cynthia Standley University of Arizona
                                      Robert Sullivan Marist College
                                      Eric Sun Middle Georgia State College
                                      Tom Swenson Ithaca College
                                      Kathleen Tallman Azusa Pacific University
                                      Rohinton Tarapore University of Pennsylvania
                                      Elizabeth Tattersall Western Nevada College
                                      Mark Thomas University of Northern Colorado
                                      Janis Thompson Lorain County Community College
                                      Rita Thrasher Pensacola State College
                                      David Van Wylen St. Olaf College
                                      Lynn Wandrey Mott Community College
                                      Margaret Weck St. Louis College of Pharmacy
                                      Kathleen Weiss George Fox University
                                      Neil Westergaard Williston State College
                                      David Wortham West Georgia Technical College
                                      Umesh Yadav University of Texas Medical Branch
                                      Tony Yates Oklahoma Baptist University
                                      Justin York Glendale Community College
                                      Cheri Zao North Idaho College
                                      Elena Zoubina Bridgewater State University; Massasoit Community College
                                      Shobhana Natarajan Alcon Laboratories, Inc.

                                      5Special Thanks

                                      OpenStax College wishes to thank the Regents of University of Michigan Medical School for the use of their extensive micrograph collection. Many of the UM micrographs that appear in Human Anatomy and Physiology are interactive WebScopes, which students can explore by zooming in and out.

                                      We also wish to thank the Open Learning Initiative at Carnegie Mellon University, with whom we shared and exchanged resources during the development of Human Anatomy and Physiology.

                                      Chapter 22The Respiratory System

                                      This photo shows a group of people climbing a mountain.
                                      Figure 22.1Mountain Climbers
                                      The thin air at high elevations can strain the human respiratory system. (credit: “bortescristian”/flickr.com)

                                      Introduction*

                                      Chapter Objectives

                                      After studying this chapter, you will be able to:

                                      • List the structures of the respiratory system

                                      • List the major functions of the respiratory system

                                      • Outline the forces that allow for air movement into and out of the lungs

                                      • Outline the process of gas exchange

                                      • Summarize the process of oxygen and carbon dioxide transport within the respiratory system

                                      • Create a flow chart illustrating how respiration is controlled

                                      • Discuss how the respiratory system responds to exercise

                                      • Describe the development of the respiratory system in the embryo

                                      Hold your breath. Really! See how long you can hold your breath as you continue reading…How long can you do it? Chances are you are feeling uncomfortable already. A typical human cannot survive without breathing for more than 3 minutes, and even if you wanted to hold your breath longer, your autonomic nervous system would take control. This is because every cell in the body needs to run the oxidative stages of cellular respiration, the process by which energy is produced in the form of adenosine triphosphate (ATP). For oxidative phosphorylation to occur, oxygen is used as a reactant and carbon dioxide is released as a waste product. You may be surprised to learn that although oxygen is a critical need for cells, it is actually the accumulation of carbon dioxide that primarily drives your need to breathe. Carbon dioxide is exhaled and oxygen is inhaled through the respiratory system, which includes muscles to move air into and out of the lungs, passageways through which air moves, and microscopic gas exchange surfaces covered by capillaries. The circulatory system transports gases from the lungs to tissues throughout the body and vice versa. A variety of diseases can affect the respiratory system, such as asthma, emphysema, chronic obstruction pulmonary disorder (COPD), and lung cancer. All of these conditions affect the gas exchange process and result in labored breathing and other difficulties.

                                      22.1Organs and Structures of the Respiratory System*

                                      By the end of this section, you will be able to:

                                      • List the structures that make up the respiratory system

                                      • Describe how the respiratory system processes oxygen and CO2

                                      • Compare and contrast the functions of upper respiratory tract with the lower respiratory tract

                                      • Conducting Zone
                                        • The Nose and its Adjacent Structures
                                        • Pharynx
                                        • Larynx
                                        • Trachea
                                        • Bronchial Tree
                                      • Respiratory Zone
                                        • Alveoli

                                      The major organs of the respiratory system function primarily to provide oxygen to body tissues for cellular respiration, remove the waste product carbon dioxide, and help to maintain acid-base balance. Portions of the respiratory system are also used for non-vital functions, such as sensing odors, speech production, and for straining, such as during childbirth or coughing (Figure 22.2).

                                      This figure shows the upper half of the human body. The major organs in the respiratory system are labeled.
                                      Figure 22.2Major Respiratory Structures
                                      The major respiratory structures span the nasal cavity to the diaphragm.

                                      Functionally, the respiratory system can be divided into a conducting zone and a respiratory zone. The conducting zone of the respiratory system includes the organs and structures not directly involved in gas exchange. The gas exchange occurs in the respiratory zone.

                                      Conducting Zone

                                      The major functions of the conducting zone are to provide a route for incoming and outgoing air, remove debris and pathogens from the incoming air, and warm and humidify the incoming air. Several structures within the conducting zone perform other functions as well. The epithelium of the nasal passages, for example, is essential to sensing odors, and the bronchial epithelium that lines the lungs can metabolize some airborne carcinogens.

                                      The Nose and its Adjacent Structures

                                      The major entrance and exit for the respiratory system is through the nose. When discussing the nose, it is helpful to divide it into two major sections: the external nose, and the nasal cavity or internal nose.

                                      The external nose consists of the surface and skeletal structures that result in the outward appearance of the nose and contribute to its numerous functions (Figure 22.3). The root is the region of the nose located between the eyebrows. The bridge is the part of the nose that connects the root to the rest of the nose. The dorsum nasi is the length of the nose. The apex is the tip of the nose. On either side of the apex, the nostrils are formed by the alae (singular = ala). An ala is a cartilaginous structure that forms the lateral side of each naris (plural = nares), or nostril opening. The philtrum is the concave surface that connects the apex of the nose to the upper lip.

                                      This figure shows the human nose. The top left panel shows the front view, and the top right panel shows the side view. The bottom panel shows the cartilaginous components of the nose.
                                      Figure 22.3Nose
                                      This illustration shows features of the external nose (top) and skeletal features of the nose (bottom).

                                      Underneath the thin skin of the nose are its skeletal features (see Figure 22.3, lower illustration). While the root and bridge of the nose consist of bone, the protruding portion of the nose is composed of cartilage. As a result, when looking at a skull, the nose is missing. The nasal bone is one of a pair of bones that lies under the root and bridge of the nose. The nasal bone articulates superiorly with the frontal bone and laterally with the maxillary bones. Septal cartilage is flexible hyaline cartilage connected to the nasal bone, forming the dorsum nasi. The alar cartilage consists of the apex of the nose; it surrounds the naris.

                                      The nares open into the nasal cavity, which is separated into left and right sections by the nasal septum (Figure 22.4). The nasal septum is formed anteriorly by a portion of the septal cartilage (the flexible portion you can touch with your fingers) and posteriorly by the perpendicular plate of the ethmoid bone (a cranial bone located just posterior to the nasal bones) and the thin vomer bones (whose name refers to its plough shape). Each lateral wall of the nasal cavity has three bony projections, called the superior, middle, and inferior nasal conchae. The inferior conchae are separate bones, whereas the superior and middle conchae are portions of the ethmoid bone. Conchae serve to increase the surface area of the nasal cavity and to disrupt the flow of air as it enters the nose, causing air to bounce along the epithelium, where it is cleaned and warmed. The conchae and meatuses also conserve water and prevent dehydration of the nasal epithelium by trapping water during exhalation. The floor of the nasal cavity is composed of the palate. The hard palate at the anterior region of the nasal cavity is composed of bone. The soft palate at the posterior portion of the nasal cavity consists of muscle tissue. Air exits the nasal cavities via the internal nares and moves into the pharynx.

                                      This figure shows a cross section view of the nose and throat. The major parts are labeled.
                                      Figure 22.4Upper Airway

                                      Several bones that help form the walls of the nasal cavity have air-containing spaces called the paranasal sinuses, which serve to warm and humidify incoming air. Sinuses are lined with a mucosa. Each paranasal sinus is named for its associated bone: frontal sinus, maxillary sinus, sphenoidal sinus, and ethmoidal sinus. The sinuses produce mucus and lighten the weight of the skull.

                                      The nares and anterior portion of the nasal cavities are lined with mucous membranes, containing sebaceous glands and hair follicles that serve to prevent the passage of large debris, such as dirt, through the nasal cavity. An olfactory epithelium used to detect odors is found deeper in the nasal cavity.

                                      The conchae, meatuses, and paranasal sinuses are lined by respiratory epithelium composed of pseudostratified ciliated columnar epithelium (Figure 22.5). The epithelium contains goblet cells, one of the specialized, columnar epithelial cells that produce mucus to trap debris. The cilia of the respiratory epithelium help remove the mucus and debris from the nasal cavity with a constant beating motion, sweeping materials towards the throat to be swallowed. Interestingly, cold air slows the movement of the cilia, resulting in accumulation of mucus that may in turn lead to a runny nose during cold weather. This moist epithelium functions to warm and humidify incoming air. Capillaries located just beneath the nasal epithelium warm the air by convection. Serous and mucus-producing cells also secrete the lysozyme enzyme and proteins called defensins, which have antibacterial properties. Immune cells that patrol the connective tissue deep to the respiratory epithelium provide additional protection.

                                      This figure shows a micrograph of pseudostratified epithelium.
                                      Figure 22.5Pseudostratified Ciliated Columnar Epithelium
                                      Respiratory epithelium is pseudostratified ciliated columnar epithelium. Seromucous glands provide lubricating mucus. LM × 680. (Micrograph provided by the Regents of University of Michigan Medical School © 2012)
                                      QR Code representing a URL

                                      View the University of Michigan WebScope at http://141.214.65.171/Histology/Basic%20Tissues/Epithelium%20and%20CT/040_HISTO_40X.svs/view.apml? to explore the tissue sample in greater detail.

                                      Pharynx

                                      The pharynx is a tube formed by skeletal muscle and lined by mucous membrane that is continuous with that of the nasal cavities (see Figure 22.4). The pharynx is divided into three major regions: the nasopharynx, the oropharynx, and the laryngopharynx (Figure 22.6).

                                      This figure shows the side view of the face. The different parts of the pharynx are color-coded and labeled.
                                      Figure 22.6Divisions of the Pharynx
                                      The pharynx is divided into three regions: the nasopharynx, the oropharynx, and the laryngopharynx.

                                      The nasopharynx is flanked by the conchae of the nasal cavity, and it serves only as an airway. At the top of the nasopharynx are the pharyngeal tonsils. A pharyngeal tonsil, also called an adenoid, is an aggregate of lymphoid reticular tissue similar to a lymph node that lies at the superior portion of the nasopharynx. The function of the pharyngeal tonsil is not well understood, but it contains a rich supply of lymphocytes and is covered with ciliated epithelium that traps and destroys invading pathogens that enter during inhalation. The pharyngeal tonsils are large in children, but interestingly, tend to regress with age and may even disappear. The uvula is a small bulbous, teardrop-shaped structure located at the apex of the soft palate. Both the uvula and soft palate move like a pendulum during swallowing, swinging upward to close off the nasopharynx to prevent ingested materials from entering the nasal cavity. In addition, auditory (Eustachian) tubes that connect to each middle ear cavity open into the nasopharynx. This connection is why colds often lead to ear infections.

                                      The oropharynx is a passageway for both air and food. The oropharynx is bordered superiorly by the nasopharynx and anteriorly by the oral cavity. The fauces is the opening at the connection between the oral cavity and the oropharynx. As the nasopharynx becomes the oropharynx, the epithelium changes from pseudostratified ciliated columnar epithelium to stratified squamous epithelium. The oropharynx contains two distinct sets of tonsils, the palatine and lingual tonsils. A palatine tonsil is one of a pair of structures located laterally in the oropharynx in the area of the fauces. The lingual tonsil is located at the base of the tongue. Similar to the pharyngeal tonsil, the palatine and lingual tonsils are composed of lymphoid tissue, and trap and destroy pathogens entering the body through the oral or nasal cavities.

                                      The laryngopharynx is inferior to the oropharynx and posterior to the larynx. It continues the route for ingested material and air until its inferior end, where the digestive and respiratory systems diverge. The stratified squamous epithelium of the oropharynx is continuous with the laryngopharynx. Anteriorly, the laryngopharynx opens into the larynx, whereas posteriorly, it enters the esophagus.

                                      Larynx

                                      The larynx is a cartilaginous structure inferior to the laryngopharynx that connects the pharynx to the trachea and helps regulate the volume of air that enters and leaves the lungs (Figure 22.7). The structure of the larynx is formed by several pieces of cartilage. Three large cartilage pieces—the thyroid cartilage (anterior), epiglottis (superior), and cricoid cartilage (inferior)—form the major structure of the larynx. The thyroid cartilage is the largest piece of cartilage that makes up the larynx. The thyroid cartilage consists of the laryngeal prominence, or “Adam’s apple,” which tends to be more prominent in males. The thick cricoid cartilage forms a ring, with a wide posterior region and a thinner anterior region. Three smaller, paired cartilages—the arytenoids, corniculates, and cuneiforms—attach to the epiglottis and the vocal cords and muscle that help move the vocal cords to produce speech.

                                      The top panel of this figure shows the anterior view of the larynx, and the bottom panel shows the right lateral view of the larynx.
                                      Figure 22.7Larynx
                                      The larynx extends from the laryngopharynx and the hyoid bone to the trachea.

                                      The epiglottis, attached to the thyroid cartilage, is a very flexible piece of elastic cartilage that covers the opening of the trachea (see Figure 22.4). When in the “closed” position, the unattached end of the epiglottis rests on the glottis. The glottis is composed of the vestibular folds, the true vocal cords, and the space between these folds (Figure 22.8). A vestibular fold, or false vocal cord, is one of a pair of folded sections of mucous membrane. A true vocal cord is one of the white, membranous folds attached by muscle to the thyroid and arytenoid cartilages of the larynx on their outer edges. The inner edges of the true vocal cords are free, allowing oscillation to produce sound. The size of the membranous folds of the true vocal cords differs between individuals, producing voices with different pitch ranges. Folds in males tend to be larger than those in females, which create a deeper voice. The act of swallowing causes the pharynx and larynx to lift upward, allowing the pharynx to expand and the epiglottis of the larynx to swing downward, closing the opening to the trachea. These movements produce a larger area for food to pass through, while preventing food and beverages from entering the trachea.

                                      This diagram shows the cross section of the larynx. The different types of cartilages are labeled.
                                      Figure 22.8Vocal Cords
                                      The true vocal cords and vestibular folds of the larynx are viewed inferiorly from the laryngopharynx.

                                      Continuous with the laryngopharynx, the superior portion of the larynx is lined with stratified squamous epithelium, transitioning into pseudostratified ciliated columnar epithelium that contains goblet cells. Similar to the nasal cavity and nasopharynx, this specialized epithelium produces mucus to trap debris and pathogens as they enter the trachea. The cilia beat the mucus upward towards the laryngopharynx, where it can be swallowed down the esophagus.

                                      Trachea

                                      The trachea (windpipe) extends from the larynx toward the lungs (Figure 22.9a). The trachea is formed by 16 to 20 stacked, C-shaped pieces of hyaline cartilage that are connected by dense connective tissue. The trachealis muscle and elastic connective tissue together form the fibroelastic membrane, a flexible membrane that closes the posterior surface of the trachea, connecting the C-shaped cartilages. The fibroelastic membrane allows the trachea to stretch and expand slightly during inhalation and exhalation, whereas the rings of cartilage provide structural support and prevent the trachea from collapsing. In addition, the trachealis muscle can be contracted to force air through the trachea during exhalation. The trachea is lined with pseudostratified ciliated columnar epithelium, which is continuous with the larynx. The esophagus borders the trachea posteriorly.

                                      The top panel of this figure shows the trachea and its organs. The major parts including the larynx, trachea, bronchi, and lungs are labeled.
                                      Figure 22.9Trachea
                                      (a) The tracheal tube is formed by stacked, C-shaped pieces of hyaline cartilage. (b) The layer visible in this cross-section of tracheal wall tissue between the hyaline cartilage and the lumen of the trachea is the mucosa, which is composed of pseudostratified ciliated columnar epithelium that contains goblet cells. LM × 1220. (Micrograph provided by the Regents of University of Michigan Medical School © 2012)

                                      Bronchial Tree

                                      The trachea branches into the right and left primary bronchi at the carina. These bronchi are also lined by pseudostratified ciliated columnar epithelium containing mucus-producing goblet cells (Figure 22.9b). The carina is a raised structure that contains specialized nervous tissue that induces violent coughing if a foreign body, such as food, is present. Rings of cartilage, similar to those of the trachea, support the structure of the bronchi and prevent their collapse. The primary bronchi enter the lungs at the hilum, a concave region where blood vessels, lymphatic vessels, and nerves also enter the lungs. The bronchi continue to branch into bronchial a tree. A bronchial tree (or respiratory tree) is the collective term used for these multiple-branched bronchi. The main function of the bronchi, like other conducting zone structures, is to provide a passageway for air to move into and out of each lung. In addition, the mucous membrane traps debris and pathogens.

                                      A bronchiole branches from the tertiary bronchi. Bronchioles, which are about 1 mm in diameter, further branch until they become the tiny terminal bronchioles, which lead to the structures of gas exchange. There are more than 1000 terminal bronchioles in each lung. The muscular walls of the bronchioles do not contain cartilage like those of the bronchi. This muscular wall can change the size of the tubing to increase or decrease airflow through the tube.

                                      Respiratory Zone

                                      In contrast to the conducting zone, the respiratory zone includes structures that are directly involved in gas exchange. The respiratory zone begins where the terminal bronchioles join a respiratory bronchiole, the smallest type of bronchiole (Figure 22.10), which then leads to an alveolar duct, opening into a cluster of alveoli.

                                      This image shows the bronchioles and alveolar sacs in the lungs and depicts the exchange of oxygenated and deoxygenated blood in the pulmonary blood vessels.
                                      Figure 22.10Respiratory Zone
                                      Bronchioles lead to alveolar sacs in the respiratory zone, where gas exchange occurs.

                                      Alveoli

                                      An alveolar duct is a tube composed of smooth muscle and connective tissue, which opens into a cluster of alveoli. An alveolus is one of the many small, grape-like sacs that are attached to the alveolar ducts.

                                      An alveolar sac is a cluster of many individual alveoli that are responsible for gas exchange. An alveolus is approximately 200 mm in diameter with elastic walls that allow the alveolus to stretch during air intake, which greatly increases the surface area available for gas exchange. Alveoli are connected to their neighbors by alveolar pores, which help maintain equal air pressure throughout the alveoli and lung (Figure 22.11).

                                      This figure shows the detailed structure of the alveolus. The top panel shows the alveolar sacs and the bronchioles. The middle panel shows a magnified view of the alveolus, and the bottom panel shows a micrograph of the cross section of a bronchiole.
                                      Figure 22.11Structures of the Respiratory Zone
                                      (a) The alveolus is responsible for gas exchange. (b) A micrograph shows the alveolar structures within lung tissue. LM × 178. (Micrograph provided by the Regents of University of Michigan Medical School © 2012)

                                      The alveolar wall consists of three major cell types: type I alveolar cells, type II alveolar cells, and alveolar macrophages. A type I alveolar cell is a squamous epithelial cell of the alveoli, which constitute up to 97 percent of the alveolar surface area. These cells are about 25 nm thick and are highly permeable to gases. A type II alveolar cell is interspersed among the type I cells and secretes pulmonary surfactant, a substance composed of phospholipids and proteins that reduces the surface tension of the alveoli. Roaming around the alveolar wall is the alveolar macrophage, a phagocytic cell of the immune system that removes debris and pathogens that have reached the alveoli.

                                      The simple squamous epithelium formed by type I alveolar cells is attached to a thin, elastic basement membrane. This epithelium is extremely thin and borders the endothelial membrane of capillaries. Taken together, the alveoli and capillary membranes form a respiratory membrane that is approximately 0.5 mm thick. The respiratory membrane allows gases to cross by simple diffusion, allowing oxygen to be picked up by the blood for transport and CO2 to be released into the air of the alveoli.

                                      Diseases of the…

                                      Respiratory System: Asthma

                                      Asthma is common condition that affects the lungs in both adults and children. Approximately 8.2 percent of adults (18.7 million) and 9.4 percent of children (7 million) in the United States suffer from asthma. In addition, asthma is the most frequent cause of hospitalization in children.

                                      Asthma is a chronic disease characterized by inflammation and edema of the airway, and bronchospasms (that is, constriction of the bronchioles), which can inhibit air from entering the lungs. In addition, excessive mucus secretion can occur, which further contributes to airway occlusion (Figure 22.12). Cells of the immune system, such as eosinophils and mononuclear cells, may also be involved in infiltrating the walls of the bronchi and bronchioles.

                                      Bronchospasms occur periodically and lead to an “asthma attack.” An attack may be triggered by environmental factors such as dust, pollen, pet hair, or dander, changes in the weather, mold, tobacco smoke, and respiratory infections, or by exercise and stress.

                                      The top panel of this figure shows normal lung tissue, and the bottom panel shows lung tissue inflamed by asthma.
                                      Figure 22.12Normal and Bronchial Asthma Tissues
                                      (a) Normal lung tissue does not have the characteristics of lung tissue during (b) an asthma attack, which include thickened mucosa, increased mucus-producing goblet cells, and eosinophil infiltrates.

                                      Symptoms of an asthma attack involve coughing, shortness of breath, wheezing, and tightness of the chest. Symptoms of a severe asthma attack that requires immediate medical attention would include difficulty breathing that results in blue (cyanotic) lips or face, confusion, drowsiness, a rapid pulse, sweating, and severe anxiety. The severity of the condition, frequency of attacks, and identified triggers influence the type of medication that an individual may require. Longer-term treatments are used for those with more severe asthma. Short-term, fast-acting drugs that are used to treat an asthma attack are typically administered via an inhaler. For young children or individuals who have difficulty using an inhaler, asthma medications can be administered via a nebulizer.

                                      In many cases, the underlying cause of the condition is unknown. However, recent research has demonstrated that certain viruses, such as human rhinovirus C (HRVC), and the bacteria Mycoplasma pneumoniae and Chlamydia pneumoniae that are contracted in infancy or early childhood, may contribute to the development of many cases of asthma.

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                                      22.2The Lungs*

                                      By the end of this section, you will be able to:

                                      • Describe the overall function of the lung

                                      • Summarize the blood flow pattern associated with the lungs

                                      • Outline the anatomy of the blood supply to the lungs

                                      • Describe the pleura of the lungs and their function

                                      • Gross Anatomy of the Lungs
                                      • Blood Supply and Nervous Innervation of the Lungs
                                        • Blood Supply
                                        • Nervous Innervation
                                      • Pleura of the Lungs

                                      A major organ of the respiratory system, each lung houses structures of both the conducting and respiratory zones. The main function of the lungs is to perform the exchange of oxygen and carbon dioxide with air from the atmosphere. To this end, the lungs exchange respiratory gases across a very large epithelial surface area—about 70 square meters—that is highly permeable to gases.

                                      Gross Anatomy of the Lungs

                                      The lungs are pyramid-shaped, paired organs that are connected to the trachea by the right and left bronchi; on the inferior surface, the lungs are bordered by the diaphragm. The diaphragm is the flat, dome-shaped muscle located at the base of the lungs and thoracic cavity. The lungs are enclosed by the pleurae, which are attached to the mediastinum. The right lung is shorter and wider than the left lung, and the left lung occupies a smaller volume than the right. The cardiac notch is an indentation on the surface of the left lung, and it allows space for the heart (Figure 22.13). The apex of the lung is the superior region, whereas the base is the opposite region near the diaphragm. The costal surface of the lung borders the ribs. The mediastinal surface faces the midline.

                                      This figure shows the structure of the lungs with the major parts labeled.
                                      Figure 22.13Gross Anatomy of the Lungs

                                      Each lung is composed of smaller units called lobes. Fissures separate these lobes from each other. The right lung consists of three lobes: the superior, middle, and inferior lobes. The left lung consists of two lobes: the superior and inferior lobes. A bronchopulmonary segment is a division of a lobe, and each lobe houses multiple bronchopulmonary segments. Each segment receives air from its own tertiary bronchus and is supplied with blood by its own artery. Some diseases of the lungs typically affect one or more bronchopulmonary segments, and in some cases, the diseased segments can be surgically removed with little influence on neighboring segments. A pulmonary lobule is a subdivision formed as the bronchi branch into bronchioles. Each lobule receives its own large bronchiole that has multiple branches. An interlobular septum is a wall, composed of connective tissue, which separates lobules from one another.

                                      Blood Supply and Nervous Innervation of the Lungs

                                      The blood supply of the lungs plays an important role in gas exchange and serves as a transport system for gases throughout the body. In addition, innervation by the both the parasympathetic and sympathetic nervous systems provides an important level of control through dilation and constriction of the airway.

                                      Blood Supply

                                      The major function of the lungs is to perform gas exchange, which requires blood from the pulmonary circulation. This blood supply contains deoxygenated blood and travels to the lungs where erythrocytes, also known as red blood cells, pick up oxygen to be transported to tissues throughout the body. The pulmonary artery is an artery that arises from the pulmonary trunk and carries deoxygenated, arterial blood to the alveoli. The pulmonary artery branches multiple times as it follows the bronchi, and each branch becomes progressively smaller in diameter. One arteriole and an accompanying venule supply and drain one pulmonary lobule. As they near the alveoli, the pulmonary arteries become the pulmonary capillary network. The pulmonary capillary network consists of tiny vessels with very thin walls that lack smooth muscle fibers. The capillaries branch and follow the bronchioles and structure of the alveoli. It is at this point that the capillary wall meets the alveolar wall, creating the respiratory membrane. Once the blood is oxygenated, it drains from the alveoli by way of multiple pulmonary veins, which exit the lungs through the hilum.

                                      Nervous Innervation

                                      Dilation and constriction of the airway are achieved through nervous control by the parasympathetic and sympathetic nervous systems. The parasympathetic system causes bronchoconstriction, whereas the sympathetic nervous system stimulates bronchodilation. Reflexes such as coughing, and the ability of the lungs to regulate oxygen and carbon dioxide levels, also result from this autonomic nervous system control. Sensory nerve fibers arise from the vagus nerve, and from the second to fifth thoracic ganglia. The pulmonary plexus is a region on the lung root formed by the entrance of the nerves at the hilum. The nerves then follow the bronchi in the lungs and branch to innervate muscle fibers, glands, and blood vessels.

                                      Pleura of the Lungs

                                      Each lung is enclosed within a cavity that is surrounded by the pleura. The pleura (plural = pleurae) is a serous membrane that surrounds the lung. The right and left pleurae, which enclose the right and left lungs, respectively, are separated by the mediastinum. The pleurae consist of two layers. The visceral pleura is the layer that is superficial to the lungs, and extends into and lines the lung fissures (Figure 22.14). In contrast, the parietal pleura is the outer layer that connects to the thoracic wall, the mediastinum, and the diaphragm. The visceral and parietal pleurae connect to each other at the hilum. The pleural cavity is the space between the visceral and parietal layers.

                                      This figure shows the lungs and the chest wall, which protects the lungs, in the left panel. In the right panel, a magnified image shows the pleural cavity and a pleural sac.
                                      Figure 22.14Parietal and Visceral Pleurae of the Lungs

                                      The pleurae perform two major functions: They produce pleural fluid and create cavities that separate the major organs. Pleural fluid is secreted by mesothelial cells from both pleural layers and acts to lubricate their surfaces. This lubrication reduces friction between the two layers to prevent trauma during breathing, and creates surface tension that helps maintain the position of the lungs against the thoracic wall. This adhesive characteristic of the pleural fluid causes the lungs to enlarge when the thoracic wall expands during ventilation, allowing the lungs to fill with air. The pleurae also create a division between major organs that prevents interference due to the movement of the organs, while preventing the spread of infection.

                                      Everyday Connection

                                      The Effects of Second-Hand Tobacco Smoke

                                      The burning of a tobacco cigarette creates multiple chemical compounds that are released through mainstream smoke, which is inhaled by the smoker, and through sidestream smoke, which is the smoke that is given off by the burning cigarette. Second-hand smoke, which is a combination of sidestream smoke and the mainstream smoke that is exhaled by the smoker, has been demonstrated by numerous scientific studies to cause disease. At least 40 chemicals in sidestream smoke have been identified that negatively impact human health, leading to the development of cancer or other conditions, such as immune system dysfunction, liver toxicity, cardiac arrhythmias, pulmonary edema, and neurological dysfunction. Furthermore, second-hand smoke has been found to harbor at least 250 compounds that are known to be toxic, carcinogenic, or both. Some major classes of carcinogens in second-hand smoke are polyaromatic hydrocarbons (PAHs), N-nitrosamines, aromatic amines, formaldehyde, and acetaldehyde.

                                      Tobacco and second-hand smoke are considered to be carcinogenic. Exposure to second-hand smoke can cause lung cancer in individuals who are not tobacco users themselves. It is estimated that the risk of developing lung cancer is increased by up to 30 percent in nonsmokers who live with an individual who smokes in the house, as compared to nonsmokers who are not regularly exposed to second-hand smoke. Children are especially affected by second-hand smoke. Children who live with an individual who smokes inside the home have a larger number of lower respiratory infections, which are associated with hospitalizations, and higher risk of sudden infant death syndrome (SIDS). Second-hand smoke in the home has also been linked to a greater number of ear infections in children, as well as worsening symptoms of asthma.

                                      22.3The Process of Breathing*

                                      By the end of this section, you will be able to:

                                      • Describe the mechanisms that drive breathing

                                      • Discuss how pressure, volume, and resistance are related

                                      • List the steps involved in pulmonary ventilation

                                      • Discuss the physical factors related to breathing

                                      • Discuss the meaning of respiratory volume and capacities

                                      • Define respiratory rate

                                      • Outline the mechanisms behind the control of breathing

                                      • Describe the respiratory centers of the medulla oblongata

                                      • Describe the respiratory centers of the pons

                                      • Discuss factors that can influence the respiratory rate

                                      • Mechanisms of Breathing
                                        • Pressure Relationships
                                        • Physical Factors Affecting Ventilation
                                      • Pulmonary Ventilation
                                      • Respiratory Volumes and Capacities
                                      • Respiratory Rate and Control of Ventilation
                                        • Ventilation Control Centers
                                        • Factors That Affect the Rate and Depth of Respiration

                                      Pulmonary ventilation is the act of breathing, which can be described as the movement of air into and out of the lungs. The major mechanisms that drive pulmonary ventilation are atmospheric pressure (Patm); the air pressure within the alveoli, called alveolar pressure (Palv); and the pressure within the pleural cavity, called intrapleural pressure (Pip).

                                      Mechanisms of Breathing

                                      The alveolar and intrapleural pressures are dependent on certain physical features of the lung. However, the ability to breathe—to have air enter the lungs during inspiration and air leave the lungs during expiration—is dependent on the air pressure of the atmosphere and the air pressure within the lungs.

                                      Pressure Relationships

                                      Inspiration (or inhalation) and expiration (or exhalation) are dependent on the differences in pressure between the atmosphere and the lungs. In a gas, pressure is a force created by the movement of gas molecules that are confined. For example, a certain number of gas molecules in a two-liter container has more room than the same number of gas molecules in a one-liter container (Figure 22.15). In this case, the force exerted by the movement of the gas molecules against the walls of the two-liter container is lower than the force exerted by the gas molecules in the one-liter container. Therefore, the pressure is lower in the two-liter container and higher in the one-liter container. At a constant temperature, changing the volume occupied by the gas changes the pressure, as does changing the number of gas molecules. Boyle’s law describes the relationship between volume and pressure in a gas at a constant temperature. Boyle discovered that the pressure of a gas is inversely proportional to its volume: If volume increases, pressure decreases. Likewise, if volume decreases, pressure increases. Pressure and volume are inversely related (P = k/V). Therefore, the pressure in the one-liter container (one-half the volume of the two-liter container) would be twice the pressure in the two-liter container. Boyle’s law is expressed by the following formula:

                                      (22.1) P1 V1 =P2 V2

                                      In this formula, P1 represents the initial pressure and V1 represents the initial volume, whereas the final pressure and volume are represented by P2 and V2, respectively. If the two- and one-liter containers were connected by a tube and the volume of one of the containers were changed, then the gases would move from higher pressure (lower volume) to lower pressure (higher volume).

                                      This diagram shows two canisters containing a gas. The two canisters show how volume and pressure are inversely proportional, which illustrates Boyle’s law.
                                      Figure 22.15Boyle's Law
                                      In a gas, pressure increases as volume decreases.

                                      Pulmonary ventilation is dependent on three types of pressure: atmospheric, intra-alveolar, and interpleural. Atmospheric pressure is the amount of force that is exerted by gases in the air surrounding any given surface, such as the body. Atmospheric pressure can be expressed in terms of the unit atmosphere, abbreviated atm, or in millimeters of mercury (mm Hg). One atm is equal to 760 mm Hg, which is the atmospheric pressure at sea level. Typically, for respiration, other pressure values are discussed in relation to atmospheric pressure. Therefore, negative pressure is pressure lower than the atmospheric pressure, whereas positive pressure is pressure that it is greater than the atmospheric pressure. A pressure that is equal to the atmospheric pressure is expressed as zero.

                                      Intra-alveolar pressure is the pressure of the air within the alveoli, which changes during the different phases of breathing (Figure 22.16). Because the alveoli are connected to the atmosphere via the tubing of the airways (similar to the two- and one-liter containers in the example above), the interpulmonary pressure of the alveoli always equalizes with the atmospheric pressure.

                                      This diagram shows the lungs and the air pressure in different regions.
                                      Figure 22.16Intrapulmonary and Intrapleural Pressure Relationships
                                      Alveolar pressure changes during the different phases of the cycle. It equalizes at 760 mm Hg but does not remain at 760 mm Hg.

                                      Intrapleural pressure is the pressure of the air within the pleural cavity, between the visceral and parietal pleurae. Similar to intra-alveolar pressure, intrapleural pressure also changes during the different phases of breathing. However, due to certain characteristics of the lungs, the intrapleural pressure is always lower than, or negative to, the intra-alveolar pressure (and therefore also to atmospheric pressure). Although it fluctuates during inspiration and expiration, intrapleural pressure remains approximately –4 mm Hg throughout the breathing cycle.

                                      Competing forces within the thorax cause the formation of the negative intrapleural pressure. One of these forces relates to the elasticity of the lungs themselves—elastic tissue pulls the lungs inward, away from the thoracic wall. Surface tension of alveolar fluid, which is mostly water, also creates an inward pull of the lung tissue. This inward tension from the lungs is countered by opposing forces from the pleural fluid and thoracic wall. Surface tension within the pleural cavity pulls the lungs outward. Too much or too little pleural fluid would hinder the creation of the negative intrapleural pressure; therefore, the level must be closely monitored by the mesothelial cells and drained by the lymphatic system. Since the parietal pleura is attached to the thoracic wall, the natural elasticity of the chest wall opposes the inward pull of the lungs. Ultimately, the outward pull is slightly greater than the inward pull, creating the –4 mm Hg intrapleural pressure relative to the intra-alveolar pressure. Transpulmonary pressure is the difference between the intrapleural and intra-alveolar pressures, and it determines the size of the lungs. A higher transpulmonary pressure corresponds to a larger lung.

                                      Physical Factors Affecting Ventilation

                                      In addition to the differences in pressures, breathing is also dependent upon the contraction and relaxation of muscle fibers of both the diaphragm and thorax. The lungs themselves are passive during breathing, meaning they are not involved in creating the movement that helps inspiration and expiration. This is because of the adhesive nature of the pleural fluid, which allows the lungs to be pulled outward when the thoracic wall moves during inspiration. The recoil of the thoracic wall during expiration causes compression of the lungs. Contraction and relaxation of the diaphragm and intercostals muscles (found between the ribs) cause most of the pressure changes that result in inspiration and expiration. These muscle movements and subsequent pressure changes cause air to either rush in or be forced out of the lungs.

                                      Other characteristics of the lungs influence the effort that must be expended to ventilate. Resistance is a force that slows motion, in this case, the flow of gases. The size of the airway is the primary factor affecting resistance. A small tubular diameter forces air through a smaller space, causing more collisions of air molecules with the walls of the airways. The following formula helps to describe the relationship between airway resistance and pressure changes:

                                      (22.2) F = ∆ P / R

                                      As noted earlier, there is surface tension within the alveoli caused by water present in the lining of the alveoli. This surface tension tends to inhibit expansion of the alveoli. However, pulmonary surfactant secreted by type II alveolar cells mixes with that water and helps reduce this surface tension. Without pulmonary surfactant, the alveoli would collapse during expiration.

                                      Thoracic wall compliance is the ability of the thoracic wall to stretch while under pressure. This can also affect the effort expended in the process of breathing. In order for inspiration to occur, the thoracic cavity must expand. The expansion of the thoracic cavity directly influences the capacity of the lungs to expand. If the tissues of the thoracic wall are not very compliant, it will be difficult to expand the thorax to increase the size of the lungs.

                                      Pulmonary Ventilation

                                      The difference in pressures drives pulmonary ventilation because air flows down a pressure gradient, that is, air flows from an area of higher pressure to an area of lower pressure. Air flows into the lungs largely due to a difference in pressure; atmospheric pressure is greater than intra-alveolar pressure, and intra-alveolar pressure is greater than intrapleural pressure. Air flows out of the lungs during expiration based on the same principle; pressure within the lungs becomes greater than the atmospheric pressure.

                                      Pulmonary ventilation comprises two major steps: inspiration and expiration. Inspiration is the process that causes air to enter the lungs, and expiration is the process that causes air to leave the lungs (Figure 22.17). A respiratory cycle is one sequence of inspiration and expiration. In general, two muscle groups are used during normal inspiration: the diaphragm and the external intercostal muscles. Additional muscles can be used if a bigger breath is required. When the diaphragm contracts, it moves inferiorly toward the abdominal cavity, creating a larger thoracic cavity and more space for the lungs. Contraction of the external intercostal muscles moves the ribs upward and outward, causing the rib cage to expand, which increases the volume of the thoracic cavity. Due to the adhesive force of the pleural fluid, the expansion of the thoracic cavity forces the lungs to stretch and expand as well. This increase in volume leads to a decrease in intra-alveolar pressure, creating a pressure lower than atmospheric pressure. As a result, a pressure gradient is created that drives air into the lungs.

                                      The left panel of this image shows a person inhaling air and the location of the chest muscles. The right panel shows the person exhaling air and the contraction of the thoracic cavity.
                                      Figure 22.17Inspiration and Expiration
                                      Inspiration and expiration occur due to the expansion and contraction of the thoracic cavity, respectively.

                                      The process of normal expiration is passive, meaning that energy is not required to push air out of the lungs. Instead, the elasticity of the lung tissue causes the lung to recoil, as the diaphragm and intercostal muscles relax following inspiration. In turn, the thoracic cavity and lungs decrease in volume, causing an increase in interpulmonary pressure. The interpulmonary pressure rises above atmospheric pressure, creating a pressure gradient that causes air to leave the lungs.

                                      There are different types, or modes, of breathing that require a slightly different process to allow inspiration and expiration. Quiet breathing, also known as eupnea, is a mode of breathing that occurs at rest and does not require the cognitive thought of the individual. During quiet breathing, the diaphragm and external intercostals must contract.

                                      A deep breath, called diaphragmatic breathing, requires the diaphragm to contract. As the diaphragm relaxes, air passively leaves the lungs. A shallow breath, called costal breathing, requires contraction of the intercostal muscles. As the intercostal muscles relax, air passively leaves the lungs.

                                      In contrast, forced breathing, also known as hyperpnea, is a mode of breathing that can occur during exercise or actions that require the active manipulation of breathing, such as singing. During forced breathing, inspiration and expiration both occur due to muscle contractions. In addition to the contraction of the diaphragm and intercostal muscles, other accessory muscles must also contract. During forced inspiration, muscles of the neck, including the scalenes, contract and lift the thoracic wall, increasing lung volume. During forced expiration, accessory muscles of the abdomen, including the obliques, contract, forcing abdominal organs upward against the diaphragm. This helps to push the diaphragm further into the thorax, pushing more air out. In addition, accessory muscles (primarily the internal intercostals) help to compress the rib cage, which also reduces the volume of the thoracic cavity.

                                      Respiratory Volumes and Capacities

                                      Respiratory volume is the term used for various volumes of air moved by or associated with the lungs at a given point in the respiratory cycle. There are four major types of respiratory volumes: tidal, residual, inspiratory reserve, and expiratory reserve (Figure 22.18). Tidal volume (TV) is the amount of air that normally enters the lungs during quiet breathing, which is about 500 milliliters. Expiratory reserve volume (ERV) is the amount of air you can forcefully exhale past a normal tidal expiration, up to 1200 milliliters for men. Inspiratory reserve volume (IRV) is produced by a deep inhalation, past a tidal inspiration. This is the extra volume that can be brought into the lungs during a forced inspiration. Residual volume (RV) is the air left in the lungs if you exhale as much air as possible. The residual volume makes breathing easier by preventing the alveoli from collapsing. Respiratory volume is dependent on a variety of factors, and measuring the different types of respiratory volumes can provide important clues about a person’s respiratory health (Figure 22.19).

                                      The left panel shows a graph of different respiratory volumes. The right panel shows how the different respiratory volumes result in respiratory capacity.
                                      Figure 22.18Respiratory Volumes and Capacities
                                      These two graphs show (a) respiratory volumes and (b) the combination of volumes that results in respiratory capacity.
                                      This tables describes methods of pulmonary function testing. Spirometry tests require a spirometer. These tests can measure forced vital capacity (FVC), the volume of air that is exhaled after maximum inhalation; foreced expiratory volume (FEV), the volume of air exhaled in one breath; forced expiratory flow, 25 to 75 percent, the air flow in the middle of exhalation; peak expiratory flow (PEF), the rate of exhalation; maximum voluntary ventilation (MVV), the volume of air that can be inspired and expired in 1 minute; slow vital capacity (SVC), the volume of air that can be slowly exhaled after inhaling past the tidal volume; total lung capacity (TLC), the volume of air in the lungs after maximum inhalation; functional residual capacity (FRC), the volume of air left in the lungs after normal expiration; residual volume (RV), the volume of air in the lungs after maximum exhalation; total lung capacity (TLC), the maximum volume of air that the lungs can hold; and expiratory reserve volume (ERV), the volume of air that can be exhaled beyond normal exhalation. Gas diffusion tests require a blood gas analyzer. These tests can measure arterial blood gases, the concentration of oxygen and carbon dioxide in the blood.
                                      Figure 22.19Pulmonary Function Testing

                                      Respiratory capacity is the combination of two or more selected volumes, which further describes the amount of air in the lungs during a given time. For example, total lung capacity (TLC) is the sum of all of the lung volumes (TV, ERV, IRV, and RV), which represents the total amount of air a person can hold in the lungs after a forceful inhalation. TLC is about 6000 mL air for men, and about 4200 mL for women. Vital capacity (VC) is the amount of air a person can move into or out of his or her lungs, and is the sum of all of the volumes except residual volume (TV, ERV, and IRV), which is between 4000 and 5000 milliliters. Inspiratory capacity (IC) is the maximum amount of air that can be inhaled past a normal tidal expiration, is the sum of the tidal volume and inspiratory reserve volume. On the other hand, the functional residual capacity (FRC) is the amount of air that remains in the lung after a normal tidal expiration; it is the sum of expiratory reserve volume and residual volume (see Figure 22.18).

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                                      Watch this video to learn more about lung volumes and spirometers. Explain how spirometry test results can be used to diagnose respiratory diseases or determine the effectiveness of disease treatment.

                                      In addition to the air that creates respiratory volumes, the respiratory system also contains anatomical dead space, which is air that is present in the airway that never reaches the alveoli and therefore never participates in gas exchange. Alveolar dead space involves air found within alveoli that are unable to function, such as those affected by disease or abnormal blood flow. Total dead space is the anatomical dead space and alveolar dead space together, and represents all of the air in the respiratory system that is not being used in the gas exchange process.

                                      Respiratory Rate and Control of Ventilation

                                      Breathing usually occurs without thought, although at times you can consciously control it, such as when you swim under water, sing a song, or blow bubbles. The respiratory rate is the total number of breaths, or respiratory cycles, that occur each minute. Respiratory rate can be an important indicator of disease, as the rate may increase or decrease during an illness or in a disease condition. The respiratory rate is controlled by the respiratory center located within the medulla oblongata in the brain, which responds primarily to changes in carbon dioxide, oxygen, and pH levels in the blood.

                                      The normal respiratory rate of a child decreases from birth to adolescence. A child under 1 year of age has a normal respiratory rate between 30 and 60 breaths per minute, but by the time a child is about 10 years old, the normal rate is closer to 18 to 30. By adolescence, the normal respiratory rate is similar to that of adults, 12 to 18 breaths per minute.

                                      Ventilation Control Centers

                                      The control of ventilation is a complex interplay of multiple regions in the brain that signal the muscles used in pulmonary ventilation to contract (Table 22.1). The result is typically a rhythmic, consistent ventilation rate that provides the body with sufficient amounts of oxygen, while adequately removing carbon dioxide.

                                      Table 22.1.
                                      Summary of Ventilation Regulation
                                      System component Function
                                      Medullary respiratory renter Sets the basic rhythm of breathing
                                      Ventral respiratory group (VRG) Generates the breathing rhythm and integrates data coming into the medulla
                                      Dorsal respiratory group (DRG) Integrates input from the stretch receptors and the chemoreceptors in the periphery
                                      Pontine respiratory group (PRG) Influences and modifies the medulla oblongata’s functions
                                      Aortic body Monitors blood PCO2, PO2, and pH
                                      Carotid body Monitors blood PCO2, PO2, and pH
                                      Hypothalamus Monitors emotional state and body temperature
                                      Cortical areas of the brain Control voluntary breathing
                                      Proprioceptors Send impulses regarding joint and muscle movements
                                      Pulmonary irritant reflexes Protect the respiratory zones of the system from foreign material
                                      Inflation reflex Protects the lungs from over-inflating

                                      Neurons that innervate the muscles of the respiratory system are responsible for controlling and regulating pulmonary ventilation. The major brain centers involved in pulmonary ventilation are the medulla oblongata and the pontine respiratory group (Figure 22.20).

                                      The top panel of this image shows the regions of the brain that control respiration. The middle panel shows a magnified view of these regions and links the regions of the brain to the specific organs that they control.
                                      Figure 22.20Respiratory Centers of the Brain

                                      The medulla oblongata contains the dorsal respiratory group (DRG) and the ventral respiratory group (VRG). The DRG is involved in maintaining a constant breathing rhythm by stimulating the diaphragm and intercostal muscles to contract, resulting in inspiration. When activity in the DRG ceases, it no longer stimulates the diaphragm and intercostals to contract, allowing them to relax, resulting in expiration. The VRG is involved in forced breathing, as the neurons in the VRG stimulate the accessory muscles involved in forced breathing to contract, resulting in forced inspiration. The VRG also stimulates the accessory muscles involved in forced expiration to contract.

                                      The second respiratory center of the brain is located within the pons, called the pontine respiratory group, and consists of the apneustic and pneumotaxic centers. The apneustic center is a double cluster of neuronal cell bodies that stimulate neurons in the DRG, controlling the depth of inspiration, particularly for deep breathing. The pneumotaxic center is a network of neurons that inhibits the activity of neurons in the DRG, allowing relaxation after inspiration, and thus controlling the overall rate.

                                      Factors That Affect the Rate and Depth of Respiration

                                      The respiratory rate and the depth of inspiration are regulated by the medulla oblongata and pons; however, these regions of the brain do so in response to systemic stimuli. It is a dose-response, positive-feedback relationship in which the greater the stimulus, the greater the response. Thus, increasing stimuli results in forced breathing. Multiple systemic factors are involved in stimulating the brain to produce pulmonary ventilation.

                                      The major factor that stimulates the medulla oblongata and pons to produce respiration is surprisingly not oxygen concentration, but rather the concentration of carbon dioxide in the blood. As you recall, carbon dioxide is a waste product of cellular respiration and can be toxic. Concentrations of chemicals are sensed by chemoreceptors. A central chemoreceptor is one of the specialized receptors that are located in the brain and brainstem, whereas a peripheral chemoreceptor is one of the specialized receptors located in the carotid arteries and aortic arch. Concentration changes in certain substances, such as carbon dioxide or hydrogen ions, stimulate these receptors, which in turn signal the respiration centers of the brain. In the case of carbon dioxide, as the concentration of CO2 in the blood increases, it readily diffuses across the blood-brain barrier, where it collects in the extracellular fluid. As will be explained in more detail later, increased carbon dioxide levels lead to increased levels of hydrogen ions, decreasing pH. The increase in hydrogen ions in the brain triggers the central chemoreceptors to stimulate the respiratory centers to initiate contraction of the diaphragm and intercostal muscles. As a result, the rate and depth of respiration increase, allowing more carbon dioxide to be expelled, which brings more air into and out of the lungs promoting a reduction in the blood levels of carbon dioxide, and therefore hydrogen ions, in the blood. In contrast, low levels of carbon dioxide in the blood cause low levels of hydrogen ions in the brain, leading to a decrease in the rate and depth of pulmonary ventilation, producing shallow, slow breathing.

                                      Another factor involved in influencing the respiratory activity of the brain is systemic arterial concentrations of hydrogen ions. Increasing carbon dioxide levels can lead to increased H+ levels, as mentioned above, as well as other metabolic activities, such as lactic acid accumulation after strenuous exercise. Peripheral chemoreceptors of the aortic arch and carotid arteries sense arterial levels of hydrogen ions. When peripheral chemoreceptors sense decreasing, or more acidic, pH levels, they stimulate an increase in ventilation to remove carbon dioxide from the blood at a quicker rate. Removal of carbon dioxide from the blood helps to reduce hydrogen ions, thus increasing systemic pH.

                                      Blood levels of oxygen are also important in influencing respiratory rate. The peripheral chemoreceptors are responsible for sensing large changes in blood oxygen levels. If blood oxygen levels become quite low—about 60 mm Hg or less—then peripheral chemoreceptors stimulate an increase in respiratory activity. The chemoreceptors are only able to sense dissolved oxygen molecules, not the oxygen that is bound to hemoglobin. As you recall, the majority of oxygen is bound by hemoglobin; when dissolved levels of oxygen drop, hemoglobin releases oxygen. Therefore, a large drop in oxygen levels is required to stimulate the chemoreceptors of the aortic arch and carotid arteries.

                                      The hypothalamus and other brain regions associated with the limbic system also play roles in influencing the regulation of breathing by interacting with the respiratory centers. The hypothalamus and other regions associated with the limbic system are involved in regulating respiration in response to emotions, pain, and temperature. For example, an increase in body temperature causes an increase in respiratory rate. Feeling excited or the fight-or-flight response will also result in an increase in respiratory rate.

                                      Disorders of the…

                                      Respiratory System: Sleep Apnea

                                      Sleep apnea is a chronic disorder that can occur in children or adults, and is characterized by the cessation of breathing during sleep. These episodes may last for several seconds or several minutes, and may differ in the frequency with which they are experienced. Sleep apnea leads to poor sleep, which is reflected in the symptoms of fatigue, evening napping, irritability, memory problems, and morning headaches. In addition, many individuals with sleep apnea experience a dry throat in the morning after waking from sleep, which may be due to excessive snoring.

                                      There are two types of sleep apnea: obstructive sleep apnea and central sleep apnea. Obstructive sleep apnea is caused by an obstruction of the airway during sleep, which can occur at different points in the airway, depending on the underlying cause of the obstruction. For example, the tongue and throat muscles of some individuals with obstructive sleep apnea may relax excessively, causing the muscles to push into the airway. Another example is obesity, which is a known risk factor for sleep apnea, as excess adipose tissue in the neck region can push the soft tissues towards the lumen of the airway, causing the trachea to narrow.

                                      In central sleep apnea, the respiratory centers of the brain do not respond properly to rising carbon dioxide levels and therefore do not stimulate the contraction of the diaphragm and intercostal muscles regularly. As a result, inspiration does not occur and breathing stops for a short period. In some cases, the cause of central sleep apnea is unknown. However, some medical conditions, such as stroke and congestive heart failure, may cause damage to the pons or medulla oblongata. In addition, some pharmacologic agents, such as morphine, can affect the respiratory centers, causing a decrease in the respiratory rate. The symptoms of central sleep apnea are similar to those of obstructive sleep apnea.

                                      A diagnosis of sleep apnea is usually done during a sleep study, where the patient is monitored in a sleep laboratory for several nights. The patient’s blood oxygen levels, heart rate, respiratory rate, and blood pressure are monitored, as are brain activity and the volume of air that is inhaled and exhaled. Treatment of sleep apnea commonly includes the use of a device called a continuous positive airway pressure (CPAP) machine during sleep. The CPAP machine has a mask that covers the nose, or the nose and mouth, and forces air into the airway at regular intervals. This pressurized air can help to gently force the airway to remain open, allowing more normal ventilation to occur. Other treatments include lifestyle changes to decrease weight, eliminate alcohol and other sleep apnea–promoting drugs, and changes in sleep position. In addition to these treatments, patients with central sleep apnea may need supplemental oxygen during sleep.

                                      22.4Gas Exchange*

                                      By the end of this section, you will be able to:

                                      • Compare the composition of atmospheric air and alveolar air

                                      • Describe the mechanisms that drive gas exchange

                                      • Discuss the importance of sufficient ventilation and perfusion, and how the body adapts when they are insufficient

                                      • Discuss the process of external respiration

                                      • Describe the process of internal respiration

                                      • Gas Exchange
                                        • Gas Laws and Air Composition
                                        • Solubility of Gases in Liquids
                                        • Ventilation and Perfusion
                                      • Gas Exchange
                                        • External Respiration
                                        • Internal Respiration

                                      The purpose of the respiratory system is to perform gas exchange. Pulmonary ventilation provides air to the alveoli for this gas exchange process. At the respiratory membrane, where the alveolar and capillary walls meet, gases move across the membranes, with oxygen entering the bloodstream and carbon dioxide exiting. It is through this mechanism that blood is oxygenated and carbon dioxide, the waste product of cellular respiration, is removed from the body.

                                      Gas Exchange

                                      In order to understand the mechanisms of gas exchange in the lung, it is important to understand the underlying principles of gases and their behavior. In addition to Boyle’s law, several other gas laws help to describe the behavior of gases.

                                      Gas Laws and Air Composition

                                      Gas molecules exert force on the surfaces with which they are in contact; this force is called pressure. In natural systems, gases are normally present as a mixture of different types of molecules. For example, the atmosphere consists of oxygen, nitrogen, carbon dioxide, and other gaseous molecules, and this gaseous mixture exerts a certain pressure referred to as atmospheric pressure (Table 22.2). Partial pressure (Px) is the pressure of a single type of gas in a mixture of gases. For example, in the atmosphere, oxygen exerts a partial pressure, and nitrogen exerts another partial pressure, independent of the partial pressure of oxygen (Figure 22.21). Total pressure is the sum of all the partial pressures of a gaseous mixture. Dalton’s law describes the behavior of nonreactive gases in a gaseous mixture and states that a specific gas type in a mixture exerts its own pressure; thus, the total pressure exerted by a mixture of gases is the sum of the partial pressures of the gases in the mixture.

                                      Table 22.2.
                                      Partial Pressures of Atmospheric Gases
                                      Gas Percent of total composition Partial pressure
                                      (mm Hg)
                                      Nitrogen (N2) 78.6 597.4
                                      Oxygen (O2) 20.9 158.8
                                      Water (H2O) 0.04 3.0
                                      Carbon dioxide (CO2) 0.004 0.3
                                      Others 0.0006 0.5
                                      Total composition/total atmospheric pressure 100% 760.0
                                      The left panel of this figure shows a canister of oxygen. The middle panel shows a canister of nitrogen. The right panel shows a canister containing a mixture of oxygen and nitrogen. A pressure gauge on each container shows the pressure exerted by the gas in that container.
                                      Figure 22.21Partial and Total Pressures of a Gas
                                      Partial pressure is the force exerted by a gas. The sum of the partial pressures of all the gases in a mixture equals the total pressure.

                                      Partial pressure is extremely important in predicting the movement of gases. Recall that gases tend to equalize their pressure in two regions that are connected. A gas will move from an area where its partial pressure is higher to an area where its partial pressure is lower. In addition, the greater the partial pressure difference between the two areas, the more rapid is the movement of gases.

                                      Solubility of Gases in Liquids

                                      Henry’s law describes the behavior of gases when they come into contact with a liquid, such as blood. Henry’s law states that the concentration of gas in a liquid is directly proportional to the solubility and partial pressure of that gas. The greater the partial pressure of the gas, the greater the number of gas molecules that will dissolve in the liquid. The concentration of the gas in a liquid is also dependent on the solubility of the gas in the liquid. For example, although nitrogen is present in the atmosphere, very little nitrogen dissolves into the blood, because the solubility of nitrogen in blood is very low. The exception to this occurs in scuba divers; the composition of the compressed air that divers breathe causes nitrogen to have a higher partial pressure than normal, causing it to dissolve in the blood in greater amounts than normal. Too much nitrogen in the bloodstream results in a serious condition that can be fatal if not corrected. Gas molecules establish an equilibrium between those molecules dissolved in liquid and those in air.

                                      The composition of air in the atmosphere and in the alveoli differs. In both cases, the relative concentration of gases is nitrogen > oxygen > water vapor > carbon dioxide. The amount of water vapor present in alveolar air is greater than that in atmospheric air (Table 22.3). Recall that the respiratory system works to humidify incoming air, thereby causing the air present in the alveoli to have a greater amount of water vapor than atmospheric air. In addition, alveolar air contains a greater amount of carbon dioxide and less oxygen than atmospheric air. This is no surprise, as gas exchange removes oxygen from and adds carbon dioxide to alveolar air. Both deep and forced breathing cause the alveolar air composition to be changed more rapidly than during quiet breathing. As a result, the partial pressures of oxygen and carbon dioxide change, affecting the diffusion process that moves these materials across the membrane. This will cause oxygen to enter and carbon dioxide to leave the blood more quickly.

                                      Table 22.3.
                                      Composition and Partial Pressures of Alveolar Air
                                      Gas Percent of total composition Partial pressure
                                      (mm Hg)
                                      Nitrogen (N2) 74.9 569
                                      Oxygen (O2) 13.7 104
                                      Water (H2O) 6.2 40
                                      Carbon dioxide (CO2) 5.2 47
                                      Total composition/total alveolar pressure 100% 760.0

                                      Ventilation and Perfusion

                                      Two important aspects of gas exchange in the lung are ventilation and perfusion. Ventilation is the movement of air into and out of the lungs, and perfusion is the flow of blood in the pulmonary capillaries. For gas exchange to be efficient, the volumes involved in ventilation and perfusion should be compatible. However, factors such as regional gravity effects on blood, blocked alveolar ducts, or disease can cause ventilation and perfusion to be imbalanced.

                                      The partial pressure of oxygen in alveolar air is about 104 mm Hg, whereas the partial pressure of the oxygenated pulmonary venous blood is about 100 mm Hg. When ventilation is sufficient, oxygen enters the alveoli at a high rate, and the partial pressure of oxygen in the alveoli remains high. In contrast, when ventilation is insufficient, the partial pressure of oxygen in the alveoli drops. Without the large difference in partial pressure between the alveoli and the blood, oxygen does not diffuse efficiently across the respiratory membrane. The body has mechanisms that counteract this problem. In cases when ventilation is not sufficient for an alveolus, the body redirects blood flow to alveoli that are receiving sufficient ventilation. This is achieved by constricting the pulmonary arterioles that serves the dysfunctional alveolus, which redirects blood to other alveoli that have sufficient ventilation. At the same time, the pulmonary arterioles that serve alveoli receiving sufficient ventilation vasodilate, which brings in greater blood flow. Factors such as carbon dioxide, oxygen, and pH levels can all serve as stimuli for adjusting blood flow in the capillary networks associated with the alveoli.

                                      Ventilation is regulated by the diameter of the airways, whereas perfusion is regulated by the diameter of the blood vessels. The diameter of the bronchioles is sensitive to the partial pressure of carbon dioxide in the alveoli. A greater partial pressure of carbon dioxide in the alveoli causes the bronchioles to increase their diameter as will a decreased level of oxygen in the blood supply, allowing carbon dioxide to be exhaled from the body at a greater rate. As mentioned above, a greater partial pressure of oxygen in the alveoli causes the pulmonary arterioles to dilate, increasing blood flow.

                                      Gas Exchange

                                      Gas exchange occurs at two sites in the body: in the lungs, where oxygen is picked up and carbon dioxide is released at the respiratory membrane, and at the tissues, where oxygen is released and carbon dioxide is picked up. External respiration is the exchange of gases with the external environment, and occurs in the alveoli of the lungs. Internal respiration is the exchange of gases with the internal environment, and occurs in the tissues. The actual exchange of gases occurs due to simple diffusion. Energy is not required to move oxygen or carbon dioxide across membranes. Instead, these gases follow pressure gradients that allow them to diffuse. The anatomy of the lung maximizes the diffusion of gases: The respiratory membrane is highly permeable to gases; the respiratory and blood capillary membranes are very thin; and there is a large surface area throughout the lungs.

                                      External Respiration

                                      The pulmonary artery carries deoxygenated blood into the lungs from the heart, where it branches and eventually becomes the capillary network composed of pulmonary capillaries. These pulmonary capillaries create the respiratory membrane with the alveoli (Figure 22.22). As the blood is pumped through this capillary network, gas exchange occurs. Although a small amount of the oxygen is able to dissolve directly into plasma from the alveoli, most of the oxygen is picked up by erythrocytes (red blood cells) and binds to a protein called hemoglobin, a process described later in this chapter. Oxygenated hemoglobin is red, causing the overall appearance of bright red oxygenated blood, which returns to the heart through the pulmonary veins. Carbon dioxide is released in the opposite direction of oxygen, from the blood to the alveoli. Some of the carbon dioxide is returned on hemoglobin, but can also be dissolved in plasma or is present as a converted form, also explained in greater detail later in this chapter.

                                      External respiration occurs as a function of partial pressure differences in oxygen and carbon dioxide between the alveoli and the blood in the pulmonary capillaries.

                                      This figure shows the pathway in which external respiration takes place. The exchange of oxygen and carbon dioxide between the alveolus and blood plasma is detailed.
                                      Figure 22.22External Respiration
                                      In external respiration, oxygen diffuses across the respiratory membrane from the alveolus to the capillary, whereas carbon dioxide diffuses out of the capillary into the alveolus.

                                      Although the solubility of oxygen in blood is not high, there is a drastic difference in the partial pressure of oxygen in the alveoli versus in the blood of the pulmonary capillaries. This difference is about 64 mm Hg: The partial pressure of oxygen in the alveoli is about 104 mm Hg, whereas its partial pressure in the blood of the capillary is about 40 mm Hg. This large difference in partial pressure creates a very strong pressure gradient that causes oxygen to rapidly cross the respiratory membrane from the alveoli into the blood.

                                      The partial pressure of carbon dioxide is also different between the alveolar air and the blood of the capillary. However, the partial pressure difference is less than that of oxygen, about 5 mm Hg. The partial pressure of carbon dioxide in the blood of the capillary is about 45 mm Hg, whereas its partial pressure in the alveoli is about 40 mm Hg. However, the solubility of carbon dioxide is much greater than that of oxygen—by a factor of about 20—in both blood and alveolar fluids. As a result, the relative concentrations of oxygen and carbon dioxide that diffuse across the respiratory membrane are similar.

                                      Internal Respiration

                                      Internal respiration is gas exchange that occurs at the level of body tissues (Figure 22.23). Similar to external respiration, internal respiration also occurs as simple diffusion due to a partial pressure gradient. However, the partial pressure gradients are opposite of those present at the respiratory membrane. The partial pressure of oxygen in tissues is low, about 40 mm Hg, because oxygen is continuously used for cellular respiration. In contrast, the partial pressure of oxygen in the blood is about 100 mm Hg. This creates a pressure gradient that causes oxygen to dissociate from hemoglobin, diffuse out of the blood, cross the interstitial space, and enter the tissue. Hemoglobin that has little oxygen bound to it loses much of its brightness, so that blood returning to the heart is more burgundy in color.

                                      Considering that cellular respiration continuously produces carbon dioxide, the partial pressure of carbon dioxide is lower in the blood than it is in the tissue, causing carbon dioxide to diffuse out of the tissue, cross the interstitial fluid, and enter the blood. It is then carried back to the lungs either bound to hemoglobin, dissolved in plasma, or in a converted form. By the time blood returns to the heart, the partial pressure of oxygen has returned to about 40 mm Hg, and the partial pressure of carbon dioxide has returned to about 45 mm Hg. The blood is then pumped back to the lungs to be oxygenated once again during external respiration.

                                      This diagram details the pathway of internal respiration. The exchange of oxygen and carbon dioxide between a red blood cell and a tissue cell is shown.
                                      Figure 22.23Internal Respiration
                                      Oxygen diffuses out of the capillary and into cells, whereas carbon dioxide diffuses out of cells and into the capillary.
                                      Everyday Connection

                                      Hyperbaric Chamber Treatment

                                      A type of device used in some areas of medicine that exploits the behavior of gases is hyperbaric chamber treatment. A hyperbaric chamber is a unit that can be sealed and expose a patient to either 100 percent oxygen with increased pressure or a mixture of gases that includes a higher concentration of oxygen than normal atmospheric air, also at a higher partial pressure than the atmosphere. There are two major types of chambers: monoplace and multiplace. Monoplace chambers are typically for one patient, and the staff tending to the patient observes the patient from outside of the chamber (Figure 22.24). Some facilities have special monoplace hyperbaric chambers that allow multiple patients to be treated at once, usually in a sitting or reclining position, to help ease feelings of isolation or claustrophobia. Multiplace chambers are large enough for multiple patients to be treated at one time, and the staff attending these patients is present inside the chamber. In a multiplace chamber, patients are often treated with air via a mask or hood, and the chamber is pressurized.

                                      This photo shows two hyperbaric chambers.
                                      Figure 22.24Hyperbaric Chamber
                                      (credit: “komunews”/flickr.com)

                                      Hyperbaric chamber treatment is based on the behavior of gases. As you recall, gases move from a region of higher partial pressure to a region of lower partial pressure. In a hyperbaric chamber, the atmospheric pressure is increased, causing a greater amount of oxygen than normal to diffuse into the bloodstream of the patient. Hyperbaric chamber therapy is used to treat a variety of medical problems, such as wound and graft healing, anaerobic bacterial infections, and carbon monoxide poisoning. Exposure to and poisoning by carbon monoxide is difficult to reverse, because hemoglobin’s affinity for carbon monoxide is much stronger than its affinity for oxygen, causing carbon monoxide to replace oxygen in the blood. Hyperbaric chamber therapy can treat carbon monoxide poisoning, because the increased atmospheric pressure causes more oxygen to diffuse into the bloodstream. At this increased pressure and increased concentration of oxygen, carbon monoxide is displaced from hemoglobin. Another example is the treatment of anaerobic bacterial infections, which are created by bacteria that cannot or prefer not to live in the presence of oxygen. An increase in blood and tissue levels of oxygen helps to kill the anaerobic bacteria that are responsible for the infection, as oxygen is toxic to anaerobic bacteria. For wounds and grafts, the chamber stimulates the healing process by increasing energy production needed for repair. Increasing oxygen transport allows cells to ramp up cellular respiration and thus ATP production, the energy needed to build new structures.

                                      22.5Transport of Gases*

                                      By the end of this section, you will be able to:

                                      • Describe the principles of oxygen transport

                                      • Describe the structure of hemoglobin

                                      • Compare and contrast fetal and adult hemoglobin

                                      • Describe the principles of carbon dioxide transport

                                      • Oxygen Transport in the Blood
                                        • Function of Hemoglobin
                                        • Oxygen Dissociation from Hemoglobin
                                        • Hemoglobin of the Fetus
                                      • Carbon Dioxide Transport in the Blood
                                        • Dissolved Carbon Dioxide
                                        • Bicarbonate Buffer
                                        • Carbaminohemoglobin

                                      The other major activity in the lungs is the process of respiration, the process of gas exchange. The function of respiration is to provide oxygen for use by body cells during cellular respiration and to eliminate carbon dioxide, a waste product of cellular respiration, from the body. In order for the exchange of oxygen and carbon dioxide to occur, both gases must be transported between the external and internal respiration sites. Although carbon dioxide is more soluble than oxygen in blood, both gases require a specialized transport system for the majority of the gas molecules to be moved between the lungs and other tissues.

                                      Oxygen Transport in the Blood

                                      Even though oxygen is transported via the blood, you may recall that oxygen is not very soluble in liquids. A small amount of oxygen does dissolve in the blood and is transported in the bloodstream, but it is only about 1.5% of the total amount. The majority of oxygen molecules are carried from the lungs to the body’s tissues by a specialized transport system, which relies on the erythrocyte—the red blood cell. Erythrocytes contain a metalloprotein, hemoglobin, which serves to bind oxygen molecules to the erythrocyte (Figure 22.25). Heme is the portion of hemoglobin that contains iron, and it is heme that binds oxygen. One erythrocyte contains four iron ions, and because of this, each erythrocyte is capable of carrying up to four molecules of oxygen. As oxygen diffuses across the respiratory membrane from the alveolus to the capillary, it also diffuses into the red blood cell and is bound by hemoglobin. The following reversible chemical reaction describes the production of the final product, oxyhemoglobin (Hb–O2), which is formed when oxygen binds to hemoglobin. Oxyhemoglobin is a bright red-colored molecule that contributes to the bright red color of oxygenated blood.

                                      (22.3) Hb + O 2 ↔Hb −  O 2

                                      In this formula, Hb represents reduced hemoglobin, that is, hemoglobin that does not have oxygen bound to it. There are multiple factors involved in how readily heme binds to and dissociates from oxygen, which will be discussed in the subsequent sections.

                                      This diagram shows a red blood cell and the structure of a hemoglobin molecule.
                                      Figure 22.25Erythrocyte and Hemoglobin
                                      Hemoglobin consists of four subunits, each of which contains one molecule of iron.

                                      Function of Hemoglobin

                                      Hemoglobin is composed of subunits, a protein structure that is referred to as a quaternary structure. Each of the four subunits that make up hemoglobin is arranged in a ring-like fashion, with an iron atom covalently bound to the heme in the center of each subunit. Binding of the first oxygen molecule causes a conformational change in hemoglobin that allows the second molecule of oxygen to bind more readily. As each molecule of oxygen is bound, it further facilitates the binding of the next molecule, until all four heme sites are occupied by oxygen. The opposite occurs as well: After the first oxygen molecule dissociates and is “dropped off” at the tissues, the next oxygen molecule dissociates more readily. When all four heme sites are occupied, the hemoglobin is said to be saturated. When one to three heme sites are occupied, the hemoglobin is said to be partially saturated. Therefore, when considering the blood as a whole, the percent of the available heme units that are bound to oxygen at a given time is called hemoglobin saturation. Hemoglobin saturation of 100 percent means that every heme unit in all of the erythrocytes of the body is bound to oxygen. In a healthy individual with normal hemoglobin levels, hemoglobin saturation generally ranges from 95 percent to 99 percent.

                                      Oxygen Dissociation from Hemoglobin

                                      Partial pressure is an important aspect of the binding of oxygen to and disassociation from heme. An oxygen–hemoglobin dissociation curve is a graph that describes the relationship of partial pressure to the binding of oxygen to heme and its subsequent dissociation from heme (Figure 22.26). Remember that gases travel from an area of higher partial pressure to an area of lower partial pressure. In addition, the affinity of an oxygen molecule for heme increases as more oxygen molecules are bound. Therefore, in the oxygen–hemoglobin saturation curve, as the partial pressure of oxygen increases, a proportionately greater number of oxygen molecules are bound by heme. Not surprisingly, the oxygen–hemoglobin saturation/dissociation curve also shows that the lower the partial pressure of oxygen, the fewer oxygen molecules are bound to heme. As a result, the partial pressure of oxygen plays a major role in determining the degree of binding of oxygen to heme at the site of the respiratory membrane, as well as the degree of dissociation of oxygen from heme at the site of body tissues.

                                      The top panel of this figure shows a graph with oxygen saturation of the y-axis and partial pressure of oxygen on the x-axis.
                                      (a)
                                      The middle panel shows oxygen saturation versus partial pressure of oxygen as a function of pH.
                                      (b)
                                      The bottom panel shows the same relationship as a function of temperature.
                                      (c)
                                      Figure 22.26Oxygen-Hemoglobin Dissociation and Effects of pH and Temperature
                                      These three graphs show (a) the relationship between the partial pressure of oxygen and hemoglobin saturation, (b) the effect of pH on the oxygen–hemoglobin dissociation curve, and (c) the effect of temperature on the oxygen–hemoglobin dissociation curve.

                                      The mechanisms behind the oxygen–hemoglobin saturation/dissociation curve also serve as automatic control mechanisms that regulate how much oxygen is delivered to different tissues throughout the body. This is important because some tissues have a higher metabolic rate than others. Highly active tissues, such as muscle, rapidly use oxygen to produce ATP, lowering the partial pressure of oxygen in the tissue to about 20 mm Hg. The partial pressure of oxygen inside capillaries is about 100 mm Hg, so the difference between the two becomes quite high, about 80 mm Hg. As a result, a greater number of oxygen molecules dissociate from hemoglobin and enter the tissues. The reverse is true of tissues, such as adipose (body fat), which have lower metabolic rates. Because less oxygen is used by these cells, the partial pressure of oxygen within such tissues remains relatively high, resulting in fewer oxygen molecules dissociating from hemoglobin and entering the tissue interstitial fluid. Although venous blood is said to be deoxygenated, some oxygen is still bound to hemoglobin in its red blood cells. This provides an oxygen reserve that can be used when tissues suddenly demand more oxygen.

                                      Factors other than partial pressure also affect the oxygen–hemoglobin saturation/dissociation curve. For example, a higher temperature promotes hemoglobin and oxygen to dissociate faster, whereas a lower temperature inhibits dissociation (see Figure 22.26, middle). However, the human body tightly regulates temperature, so this factor may not affect gas exchange throughout the body. The exception to this is in highly active tissues, which may release a larger amount of energy than is given off as heat. As a result, oxygen readily dissociates from hemoglobin, which is a mechanism that helps to provide active tissues with more oxygen.

                                      Certain hormones, such as androgens, epinephrine, thyroid hormones, and growth hormone, can affect the oxygen–hemoglobin saturation/disassociation curve by stimulating the production of a compound called 2,3-bisphosphoglycerate (BPG) by erythrocytes. BPG is a byproduct of glycolysis. Because erythrocytes do not contain mitochondria, glycolysis is the sole method by which these cells produce ATP. BPG promotes the disassociation of oxygen from hemoglobin. Therefore, the greater the concentration of BPG, the more readily oxygen dissociates from hemoglobin, despite its partial pressure.

                                      The pH of the blood is another factor that influences the oxygen–hemoglobin saturation/dissociation curve (see Figure 22.26). The Bohr effect is a phenomenon that arises from the relationship between pH and oxygen’s affinity for hemoglobin: A lower, more acidic pH promotes oxygen dissociation from hemoglobin. In contrast, a higher, or more basic, pH inhibits oxygen dissociation from hemoglobin. The greater the amount of carbon dioxide in the blood, the more molecules that must be converted, which in turn generates hydrogen ions and thus lowers blood pH. Furthermore, blood pH may become more acidic when certain byproducts of cell metabolism, such as lactic acid, carbonic acid, and carbon dioxide, are released into the bloodstream.

                                      Hemoglobin of the Fetus

                                      The fetus has its own circulation with its own erythrocytes; however, it is dependent on the mother for oxygen. Blood is supplied to the fetus by way of the umbilical cord, which is connected to the placenta and separated from maternal blood by the chorion. The mechanism of gas exchange at the chorion is similar to gas exchange at the respiratory membrane. However, the partial pressure of oxygen is lower in the maternal blood in the placenta, at about 35 to 50 mm Hg, than it is in maternal arterial blood. The difference in partial pressures between maternal and fetal blood is not large, as the partial pressure of oxygen in fetal blood at the placenta is about 20 mm Hg. Therefore, there is not as much diffusion of oxygen into the fetal blood supply. The fetus’ hemoglobin overcomes this problem by having a greater affinity for oxygen than maternal hemoglobin (Figure 22.27). Both fetal and adult hemoglobin have four subunits, but two of the subunits of fetal hemoglobin have a different structure that causes fetal hemoglobin to have a greater affinity for oxygen than does adult hemoglobin.

                                      This graph shows the oxygen saturation versus the partial pressure of oxygen in fetal hemoglobin and adult hemoglobin.
                                      Figure 22.27Oxygen-Hemoglobin Dissociation Curves in Fetus and Adult
                                      Fetal hemoglobin has a greater affinity for oxygen than does adult hemoglobin.

                                      Carbon Dioxide Transport in the Blood

                                      Carbon dioxide is transported by three major mechanisms. The first mechanism of carbon dioxide transport is by blood plasma, as some carbon dioxide molecules dissolve in the blood. The second mechanism is transport in the form of bicarbonate (HCO3–), which also dissolves in plasma. The third mechanism of carbon dioxide transport is similar to the transport of oxygen by erythrocytes (Figure 22.28).

                                      This figure shows how carbon dioxide is transported from the tissue to the red blood cell.
                                      Figure 22.28Carbon Dioxide Transport
                                      Carbon dioxide is transported by three different methods: (a) in erythrocytes; (b) after forming carbonic acid (H2CO3 ), which is dissolved in plasma; (c) and in plasma.

                                      Dissolved Carbon Dioxide

                                      Although carbon dioxide is not considered to be highly soluble in blood, a small fraction—about 7 to 10 percent—of the carbon dioxide that diffuses into the blood from the tissues dissolves in plasma. The dissolved carbon dioxide then travels in the bloodstream and when the blood reaches the pulmonary capillaries, the dissolved carbon dioxide diffuses across the respiratory membrane into the alveoli, where it is then exhaled during pulmonary ventilation.

                                      Bicarbonate Buffer

                                      A large fraction—about 70 percent—of the carbon dioxide molecules that diffuse into the blood is transported to the lungs as bicarbonate. Most bicarbonate is produced in erythrocytes after carbon dioxide diffuses into the capillaries, and subsequently into red blood cells. Carbonic anhydrase (CA) causes carbon dioxide and water to form carbonic acid (H2CO3), which dissociates into two ions: bicarbonate (HCO3–) and hydrogen (H+). The following formula depicts this reaction:

                                      (22.4)

                                      Bicarbonate tends to build up in the erythrocytes, so that there is a greater concentration of bicarbonate in the erythrocytes than in the surrounding blood plasma. As a result, some of the bicarbonate will leave the erythrocytes and move down its concentration gradient into the plasma in exchange for chloride (Cl–) ions. This phenomenon is referred to as the chloride shift and occurs because by exchanging one negative ion for another negative ion, neither the electrical charge of the erythrocytes nor that of the blood is altered.

                                      At the pulmonary capillaries, the chemical reaction that produced bicarbonate (shown above) is reversed, and carbon dioxide and water are the products. Much of the bicarbonate in the plasma re-enters the erythrocytes in exchange for chloride ions. Hydrogen ions and bicarbonate ions join to form carbonic acid, which is converted into carbon dioxide and water by carbonic anhydrase. Carbon dioxide diffuses out of the erythrocytes and into the plasma, where it can further diffuse across the respiratory membrane into the alveoli to be exhaled during pulmonary ventilation.

                                      Carbaminohemoglobin

                                      About 20 percent of carbon dioxide is bound by hemoglobin and is transported to the lungs. Carbon dioxide does not bind to iron as oxygen does; instead, carbon dioxide binds amino acid moieties on the globin portions of hemoglobin to form carbaminohemoglobin, which forms when hemoglobin and carbon dioxide bind. When hemoglobin is not transporting oxygen, it tends to have a bluish-purple tone to it, creating the darker maroon color typical of deoxygenated blood. The following formula depicts this reversible reaction:

                                      (22.5) CO 2  + Hb↔ HbCO 2

                                      Similar to the transport of oxygen by heme, the binding and dissociation of carbon dioxide to and from hemoglobin is dependent on the partial pressure of carbon dioxide. Because carbon dioxide is released from the lungs, blood that leaves the lungs and reaches body tissues has a lower partial pressure of carbon dioxide than is found in the tissues. As a result, carbon dioxide leaves the tissues because of its higher partial pressure, enters the blood, and then moves into red blood cells, binding to hemoglobin. In contrast, in the pulmonary capillaries, the partial pressure of carbon dioxide is high compared to within the alveoli. As a result, carbon dioxide dissociates readily from hemoglobin and diffuses across the respiratory membrane into the air.

                                      In addition to the partial pressure of carbon dioxide, the oxygen saturation of hemoglobin and the partial pressure of oxygen in the blood also influence the affinity of hemoglobin for carbon dioxide. The Haldane effect is a phenomenon that arises from the relationship between the partial pressure of oxygen and the affinity of hemoglobin for carbon dioxide. Hemoglobin that is saturated with oxygen does not readily bind carbon dioxide. However, when oxygen is not bound to heme and the partial pressure of oxygen is low, hemoglobin readily binds to carbon dioxide.

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                                      Watch this video to see the transport of oxygen from the lungs to the tissues. Why is oxygenated blood bright red, whereas deoxygenated blood tends to be more of a purple color?

                                      22.6Modifications in Respiratory Functions*

                                      By the end of this section, you will be able to:

                                      • Define the terms hyperpnea and hyperventilation

                                      • Describe the effect of exercise on the respiratory system

                                      • Describe the effect of high altitude on the respiratory system

                                      • Discuss the process of acclimatization

                                      • Hyperpnea
                                      • High Altitude Effects
                                        • Acclimatization

                                      At rest, the respiratory system performs its functions at a constant, rhythmic pace, as regulated by the respiratory centers of the brain. At this pace, ventilation provides sufficient oxygen to all the tissues of the body. However, there are times that the respiratory system must alter the pace of its functions in order to accommodate the oxygen demands of the body.

                                      Hyperpnea

                                      Hyperpnea is an increased depth and rate of ventilation to meet an increase in oxygen demand as might be seen in exercise or disease, particularly diseases that target the respiratory or digestive tracts. This does not significantly alter blood oxygen or carbon dioxide levels, but merely increases the depth and rate of ventilation to meet the demand of the cells. In contrast, hyperventilation is an increased ventilation rate that is independent of the cellular oxygen needs and leads to abnormally low blood carbon dioxide levels and high (alkaline) blood pH.

                                      Interestingly, exercise does not cause hyperpnea as one might think. Muscles that perform work during exercise do increase their demand for oxygen, stimulating an increase in ventilation. However, hyperpnea during exercise appears to occur before a drop in oxygen levels within the muscles can occur. Therefore, hyperpnea must be driven by other mechanisms, either instead of or in addition to a drop in oxygen levels. The exact mechanisms behind exercise hyperpnea are not well understood, and some hypotheses are somewhat controversial. However, in addition to low oxygen, high carbon dioxide, and low pH levels, there appears to be a complex interplay of factors related to the nervous system and the respiratory centers of the brain.

                                      First, a conscious decision to partake in exercise, or another form of physical exertion, results in a psychological stimulus that may trigger the respiratory centers of the brain to increase ventilation. In addition, the respiratory centers of the brain may be stimulated through the activation of motor neurons that innervate muscle groups that are involved in the physical activity. Finally, physical exertion stimulates proprioceptors, which are receptors located within the muscles, joints, and tendons, which sense movement and stretching; proprioceptors thus create a stimulus that may also trigger the respiratory centers of the brain. These neural factors are consistent with the sudden increase in ventilation that is observed immediately as exercise begins. Because the respiratory centers are stimulated by psychological, motor neuron, and proprioceptor inputs throughout exercise, the fact that there is also a sudden decrease in ventilation immediately after the exercise ends when these neural stimuli cease, further supports the idea that they are involved in triggering the changes of ventilation.

                                      High Altitude Effects

                                      An increase in altitude results in a decrease in atmospheric pressure. Although the proportion of oxygen relative to gases in the atmosphere remains at 21 percent, its partial pressure decreases (Table 22.4). As a result, it is more difficult for a body to achieve the same level of oxygen saturation at high altitude than at low altitude, due to lower atmospheric pressure. In fact, hemoglobin saturation is lower at high altitudes compared to hemoglobin saturation at sea level. For example, hemoglobin saturation is about 67 percent at 19,000 feet above sea level, whereas it reaches about 98 percent at sea level.

                                      Table 22.4.
                                      Partial Pressure of Oxygen at Different Altitudes
                                      Example location Altitude (feet above sea level) Atmospheric pressure (mm Hg) Partial pressure of oxygen (mm Hg)
                                      New York City, New York 0 760 159
                                      Boulder, Colorado 5000 632 133
                                      Aspen, Colorado 8000 565 118
                                      Pike’s Peak, Colorado 14,000 447 94
                                      Denali (Mt. McKinley), Alaska 20,000 350 73
                                      Mt. Everest, Tibet 29,000 260 54

                                      As you recall, partial pressure is extremely important in determining how much gas can cross the respiratory membrane and enter the blood of the pulmonary capillaries. A lower partial pressure of oxygen means that there is a smaller difference in partial pressures between the alveoli and the blood, so less oxygen crosses the respiratory membrane. As a result, fewer oxygen molecules are bound by hemoglobin. Despite this, the tissues of the body still receive a sufficient amount of oxygen during rest at high altitudes. This is due to two major mechanisms. First, the number of oxygen molecules that enter the tissue from the blood is nearly equal between sea level and high altitudes. At sea level, hemoglobin saturation is higher, but only a quarter of the oxygen molecules are actually released into the tissue. At high altitudes, a greater proportion of molecules of oxygen are released into the tissues. Secondly, at high altitudes, a greater amount of BPG is produced by erythrocytes, which enhances the dissociation of oxygen from hemoglobin. Physical exertion, such as skiing or hiking, can lead to altitude sickness due to the low amount of oxygen reserves in the blood at high altitudes. At sea level, there is a large amount of oxygen reserve in venous blood (even though venous blood is thought of as “deoxygenated”) from which the muscles can draw during physical exertion. Because the oxygen saturation is much lower at higher altitudes, this venous reserve is small, resulting in pathological symptoms of low blood oxygen levels. You may have heard that it is important to drink more water when traveling at higher altitudes than you are accustomed to. This is because your body will increase micturition (urination) at high altitudes to counteract the effects of lower oxygen levels. By removing fluids, blood plasma levels drop but not the total number of erythrocytes. In this way, the overall concentration of erythrocytes in the blood increases, which helps tissues obtain the oxygen they need.

                                      Acute mountain sickness (AMS), or altitude sickness, is a condition that results from acute exposure to high altitudes due to a low partial pressure of oxygen at high altitudes. AMS typically can occur at 2400 meters (8000 feet) above sea level. AMS is a result of low blood oxygen levels, as the body has acute difficulty adjusting to the low partial pressure of oxygen. In serious cases, AMS can cause pulmonary or cerebral edema. Symptoms of AMS include nausea, vomiting, fatigue, lightheadedness, drowsiness, feeling disoriented, increased pulse, and nosebleeds. The only treatment for AMS is descending to a lower altitude; however, pharmacologic treatments and supplemental oxygen can improve symptoms. AMS can be prevented by slowly ascending to the desired altitude, allowing the body to acclimate, as well as maintaining proper hydration.

                                      Acclimatization

                                      Especially in situations where the ascent occurs too quickly, traveling to areas of high altitude can cause AMS. Acclimatization is the process of adjustment that the respiratory system makes due to chronic exposure to a high altitude. Over a period of time, the body adjusts to accommodate the lower partial pressure of oxygen. The low partial pressure of oxygen at high altitudes results in a lower oxygen saturation level of hemoglobin in the blood. In turn, the tissue levels of oxygen are also lower. As a result, the kidneys are stimulated to produce the hormone erythropoietin (EPO), which stimulates the production of erythrocytes, resulting in a greater number of circulating erythrocytes in an individual at a high altitude over a long period. With more red blood cells, there is more hemoglobin to help transport the available oxygen. Even though there is low saturation of each hemoglobin molecule, there will be more hemoglobin present, and therefore more oxygen in the blood. Over time, this allows the person to partake in physical exertion without developing AMS.

                                      22.7Embryonic Development of the Respiratory System*

                                      By the end of this section, you will be able to:

                                      • Create a timeline of the phases of respiratory development in the fetus

                                      • Propose reasons for fetal breathing movements

                                      • Explain how the lungs become inflated after birth

                                      • Time Line
                                        • Weeks 4–7
                                        • Weeks 7–16
                                        • Weeks 16–24
                                        • Weeks 24–Term
                                      • Fetal “Breathing”
                                      • Birth

                                      Development of the respiratory system begins early in the fetus. It is a complex process that includes many structures, most of which arise from the endoderm. Towards the end of development, the fetus can be observed making breathing movements. Until birth, however, the mother provides all of the oxygen to the fetus as well as removes all of the fetal carbon dioxide via the placenta.

                                      Time Line

                                      The development of the respiratory system begins at about week 4 of gestation. By week 28, enough alveoli have matured that a baby born prematurely at this time can usually breathe on its own. The respiratory system, however, is not fully developed until early childhood, when a full complement of mature alveoli is present.

                                      Weeks 4–7

                                      Respiratory development in the embryo begins around week 4. Ectodermal tissue from the anterior head region invaginates posteriorly to form olfactory pits, which fuse with endodermal tissue of the developing pharynx. An olfactory pit is one of a pair of structures that will enlarge to become the nasal cavity. At about this same time, the lung bud forms. The lung bud is a dome-shaped structure composed of tissue that bulges from the foregut. The foregut is endoderm just inferior to the pharyngeal pouches. The laryngotracheal bud is a structure that forms from the longitudinal extension of the lung bud as development progresses. The portion of this structure nearest the pharynx becomes the trachea, whereas the distal end becomes more bulbous, forming bronchial buds. A bronchial bud is one of a pair of structures that will eventually become the bronchi and all other lower respiratory structures (Figure 22.29).

                                      This flowchart shows the embryonic development of the respiratory system and correlates the gestational age to the appearance of new features.
                                      Figure 22.29Development of the Lower Respiratory System

                                      Weeks 7–16

                                      Bronchial buds continue to branch as development progresses until all of the segmental bronchi have been formed. Beginning around week 13, the lumens of the bronchi begin to expand in diameter. By week 16, respiratory bronchioles form. The fetus now has all major lung structures involved in the airway.

                                      Weeks 16–24

                                      Once the respiratory bronchioles form, further development includes extensive vascularization, or the development of the blood vessels, as well as the formation of alveolar ducts and alveolar precursors. At about week 19, the respiratory bronchioles have formed. In addition, cells lining the respiratory structures begin to differentiate to form type I and type II pneumocytes. Once type II cells have differentiated, they begin to secrete small amounts of pulmonary surfactant. Around week 20, fetal breathing movements may begin.

                                      Weeks 24–Term

                                      Major growth and maturation of the respiratory system occurs from week 24 until term. More alveolar precursors develop, and larger amounts of pulmonary surfactant are produced. Surfactant levels are not generally adequate to create effective lung compliance until about the eighth month of pregnancy. The respiratory system continues to expand, and the surfaces that will form the respiratory membrane develop further. At this point, pulmonary capillaries have formed and continue to expand, creating a large surface area for gas exchange. The major milestone of respiratory development occurs at around week 28, when sufficient alveolar precursors have matured so that a baby born prematurely at this time can usually breathe on its own. However, alveoli continue to develop and mature into childhood. A full complement of functional alveoli does not appear until around 8 years of age.

                                      Fetal “Breathing”

                                      Although the function of fetal breathing movements is not entirely clear, they can be observed starting at 20–21 weeks of development. Fetal breathing movements involve muscle contractions that cause the inhalation of amniotic fluid and exhalation of the same fluid, with pulmonary surfactant and mucus. Fetal breathing movements are not continuous and may include periods of frequent movements and periods of no movements. Maternal factors can influence the frequency of breathing movements. For example, high blood glucose levels, called hyperglycemia, can boost the number of breathing movements. Conversely, low blood glucose levels, called hypoglycemia, can reduce the number of fetal breathing movements. Tobacco use is also known to lower fetal breathing rates. Fetal breathing may help tone the muscles in preparation for breathing movements once the fetus is born. It may also help the alveoli to form and mature. Fetal breathing movements are considered a sign of robust health.

                                      Birth

                                      Prior to birth, the lungs are filled with amniotic fluid, mucus, and surfactant. As the fetus is squeezed through the birth canal, the fetal thoracic cavity is compressed, expelling much of this fluid. Some fluid remains, however, but is rapidly absorbed by the body shortly after birth. The first inhalation occurs within 10 seconds after birth and not only serves as the first inspiration, but also acts to inflate the lungs. Pulmonary surfactant is critical for inflation to occur, as it reduces the surface tension of the alveoli. Preterm birth around 26 weeks frequently results in severe respiratory distress, although with current medical advancements, some babies may survive. Prior to 26 weeks, sufficient pulmonary surfactant is not produced, and the surfaces for gas exchange have not formed adequately; therefore, survival is low.

                                      Disorders of the…

                                      Respiratory System: Respiratory Distress Syndrome

                                      Respiratory distress syndrome (RDS) primarily occurs in infants born prematurely. Up to 50 percent of infants born between 26 and 28 weeks and fewer than 30 percent of infants born between 30 and 31 weeks develop RDS. RDS results from insufficient production of pulmonary surfactant, thereby preventing the lungs from properly inflating at birth. A small amount of pulmonary surfactant is produced beginning at around 20 weeks; however, this is not sufficient for inflation of the lungs. As a result, dyspnea occurs and gas exchange cannot be performed properly. Blood oxygen levels are low, whereas blood carbon dioxide levels and pH are high.

                                      The primary cause of RDS is premature birth, which may be due to a variety of known or unknown causes. Other risk factors include gestational diabetes, cesarean delivery, second-born twins, and family history of RDS. The presence of RDS can lead to other serious disorders, such as septicemia (infection of the blood) or pulmonary hemorrhage. Therefore, it is important that RDS is immediately recognized and treated to prevent death and reduce the risk of developing other disorders.

                                      Medical advances have resulted in an improved ability to treat RDS and support the infant until proper lung development can occur. At the time of delivery, treatment may include resuscitation and intubation if the infant does not breathe on his or her own. These infants would need to be placed on a ventilator to mechanically assist with the breathing process. If spontaneous breathing occurs, application of nasal continuous positive airway pressure (CPAP) may be required. In addition, pulmonary surfactant is typically administered. Death due to RDS has been reduced by 50 percent due to the introduction of pulmonary surfactant therapy. Other therapies may include corticosteroids, supplemental oxygen, and assisted ventilation. Supportive therapies, such as temperature regulation, nutritional support, and antibiotics, may be administered to the premature infant as well.

                                      Glossary

                                      acclimatization

                                      process of adjustment that the respiratory system makes due to chronic exposure to high altitudes

                                      acute mountain sickness (AMS)

                                      condition that occurs a result of acute exposure to high altitude due to a low partial pressure of oxygen

                                      ala

                                      (plural = alae) small, flaring structure of a nostril that forms the lateral side of the nares

                                      alar cartilage

                                      cartilage that supports the apex of the nose and helps shape the nares; it is connected to the septal cartilage and connective tissue of the alae

                                      alveolar dead space

                                      air space within alveoli that are unable to participate in gas exchange

                                      alveolar duct

                                      small tube that leads from the terminal bronchiole to the respiratory bronchiole and is the point of attachment for alveoli

                                      alveolar macrophage

                                      immune system cell of the alveolus that removes debris and pathogens

                                      alveolar pore

                                      opening that allows airflow between neighboring alveoli

                                      alveolar sac

                                      cluster of alveoli

                                      alveolus

                                      small, grape-like sac that performs gas exchange in the lungs

                                      anatomical dead space

                                      air space present in the airway that never reaches the alveoli and therefore never participates in gas exchange

                                      apex

                                      tip of the external nose

                                      apneustic center

                                      network of neurons within the pons that stimulate the neurons in the dorsal respiratory group; controls the depth of inspiration

                                      atmospheric pressure

                                      amount of force that is exerted by gases in the air surrounding any given surface

                                      Bohr effect

                                      relationship between blood pH and oxygen dissociation from hemoglobin

                                      Boyle’s law

                                      relationship between volume and pressure as described by the formula: P1V1 = P2V2

                                      bridge

                                      portion of the external nose that lies in the area of the nasal bones

                                      bronchial bud

                                      structure in the developing embryo that forms when the laryngotracheal bud extends and branches to form two bulbous structures

                                      bronchial tree

                                      collective name for the multiple branches of the bronchi and bronchioles of the respiratory system

                                      bronchiole

                                      branch of bronchi that are 1 mm or less in diameter and terminate at alveolar sacs

                                      bronchoconstriction

                                      decrease in the size of the bronchiole due to contraction of the muscular wall

                                      bronchodilation

                                      increase in the size of the bronchiole due to contraction of the muscular wall

                                      bronchus

                                      tube connected to the trachea that branches into many subsidiaries and provides a passageway for air to enter and leave the lungs

                                      carbaminohemoglobin

                                      bound form of hemoglobin and carbon dioxide

                                      carbonic anhydrase (CA)

                                      enzyme that catalyzes the reaction that causes carbon dioxide and water to form carbonic acid

                                      cardiac notch

                                      indentation on the surface of the left lung that allows space for the heart

                                      central chemoreceptor

                                      one of the specialized receptors that are located in the brain that sense changes in hydrogen ion, oxygen, or carbon dioxide concentrations in the brain

                                      chloride shift

                                      facilitated diffusion that exchanges bicarbonate (HCO3–) with chloride (Cl–) ions

                                      conducting zone

                                      region of the respiratory system that includes the organs and structures that provide passageways for air and are not directly involved in gas exchange

                                      cricoid cartilage

                                      portion of the larynx composed of a ring of cartilage with a wide posterior region and a thinner anterior region; attached to the esophagus

                                      Dalton’s law

                                      statement of the principle that a specific gas type in a mixture exerts its own pressure, as if that specific gas type was not part of a mixture of gases

                                      dorsal respiratory group (DRG)

                                      region of the medulla oblongata that stimulates the contraction of the diaphragm and intercostal muscles to induce inspiration

                                      dorsum nasi

                                      intermediate portion of the external nose that connects the bridge to the apex and is supported by the nasal bone

                                      epiglottis

                                      leaf-shaped piece of elastic cartilage that is a portion of the larynx that swings to close the trachea during swallowing

                                      expiration

                                      (also, exhalation) process that causes the air to leave the lungs

                                      expiratory reserve volume (ERV)

                                      amount of air that can be forcefully exhaled after a normal tidal exhalation

                                      external nose

                                      region of the nose that is easily visible to others

                                      external respiration

                                      gas exchange that occurs in the alveoli

                                      fauces

                                      portion of the posterior oral cavity that connects the oral cavity to the oropharynx

                                      fibroelastic membrane

                                      specialized membrane that connects the ends of the C-shape cartilage in the trachea; contains smooth muscle fibers

                                      forced breathing

                                      (also, hyperpnea) mode of breathing that occurs during exercise or by active thought that requires muscle contraction for both inspiration and expiration

                                      foregut

                                      endoderm of the embryo towards the head region

                                      functional residual capacity (FRC)

                                      sum of ERV and RV, which is the amount of air that remains in the lungs after a tidal expiration

                                      glottis

                                      opening between the vocal folds through which air passes when producing speech

                                      Haldane effect

                                      relationship between the partial pressure of oxygen and the affinity of hemoglobin for carbon dioxide

                                      Henry’s law

                                      statement of the principle that the concentration of gas in a liquid is directly proportional to the solubility and partial pressure of that gas

                                      hilum

                                      concave structure on the mediastinal surface of the lungs where blood vessels, lymphatic vessels, nerves, and a bronchus enter the lung

                                      hyperpnea

                                      increased rate and depth of ventilation due to an increase in oxygen demand that does not significantly alter blood oxygen or carbon dioxide levels

                                      hyperventilation

                                      increased ventilation rate that leads to abnormally low blood carbon dioxide levels and high (alkaline) blood pH

                                      inspiration

                                      (also, inhalation) process that causes air to enter the lungs

                                      inspiratory capacity (IC)

                                      sum of the TV and IRV, which is the amount of air that can maximally be inhaled past a tidal expiration

                                      inspiratory reserve volume (IRV)

                                      amount of air that enters the lungs due to deep inhalation past the tidal volume

                                      internal respiration

                                      gas exchange that occurs at the level of body tissues

                                      intra-alveolar pressure

                                      (intrapulmonary pressure) pressure of the air within the alveoli

                                      intrapleural pressure

                                      pressure of the air within the pleural cavity

                                      laryngeal prominence

                                      region where the two lamina of the thyroid cartilage join, forming a protrusion known as “Adam’s apple”

                                      laryngopharynx

                                      portion of the pharynx bordered by the oropharynx superiorly and esophagus and trachea inferiorly; serves as a route for both air and food

                                      laryngotracheal

                                      bud forms from the lung bud, has a tracheal end and bulbous bronchial buds at the distal end

                                      larynx

                                      cartilaginous structure that produces the voice, prevents food and beverages from entering the trachea, and regulates the volume of air that enters and leaves the lungs

                                      lingual tonsil

                                      lymphoid tissue located at the base of the tongue

                                      lung bud

                                      median dome that forms from the endoderm of the foregut

                                      lung

                                      organ of the respiratory system that performs gas exchange

                                      meatus

                                      one of three recesses (superior, middle, and inferior) in the nasal cavity attached to the conchae that increase the surface area of the nasal cavity

                                      naris

                                      (plural = nares) opening of the nostrils

                                      nasal bone

                                      bone of the skull that lies under the root and bridge of the nose and is connected to the frontal and maxillary bones

                                      nasal septum

                                      wall composed of bone and cartilage that separates the left and right nasal cavities

                                      nasopharynx

                                      portion of the pharynx flanked by the conchae and oropharynx that serves as an airway

                                      olfactory pit

                                      invaginated ectodermal tissue in the anterior portion of the head region of an embryo that will form the nasal cavity

                                      oropharynx

                                      portion of the pharynx flanked by the nasopharynx, oral cavity, and laryngopharynx that is a passageway for both air and food

                                      oxygen–hemoglobin dissociation curve

                                      graph that describes the relationship of partial pressure to the binding and disassociation of oxygen to and from heme

                                      oxyhemoglobin

                                      (Hb–O2) bound form of hemoglobin and oxygen

                                      palatine tonsil

                                      one of the paired structures composed of lymphoid tissue located anterior to the uvula at the roof of isthmus of the fauces

                                      paranasal sinus

                                      one of the cavities within the skull that is connected to the conchae that serve to warm and humidify incoming air, produce mucus, and lighten the weight of the skull; consists of frontal, maxillary, sphenoidal, and ethmoidal sinuses

                                      parietal pleura

                                      outermost layer of the pleura that connects to the thoracic wall, mediastinum, and diaphragm

                                      partial pressure

                                      force exerted by each gas in a mixture of gases

                                      peripheral chemoreceptor

                                      one of the specialized receptors located in the aortic arch and carotid arteries that sense changes in pH, carbon dioxide, or oxygen blood levels

                                      pharyngeal tonsil

                                      structure composed of lymphoid tissue located in the nasopharynx

                                      pharynx

                                      region of the conducting zone that forms a tube of skeletal muscle lined with respiratory epithelium; located between the nasal conchae and the esophagus and trachea

                                      philtrum

                                      concave surface of the face that connects the apex of the nose to the top lip

                                      pleural cavity

                                      space between the visceral and parietal pleurae

                                      pleural fluid

                                      substance that acts as a lubricant for the visceral and parietal layers of the pleura during the movement of breathing

                                      pneumotaxic center

                                      network of neurons within the pons that inhibit the activity of the neurons in the dorsal respiratory group; controls rate of breathing

                                      pulmonary artery

                                      artery that arises from the pulmonary trunk and carries deoxygenated, arterial blood to the alveoli

                                      pulmonary plexus

                                      network of autonomic nervous system fibers found near the hilum of the lung

                                      pulmonary surfactant

                                      substance composed of phospholipids and proteins that reduces the surface tension of the alveoli; made by type II alveolar cells

                                      pulmonary ventilation

                                      exchange of gases between the lungs and the atmosphere; breathing

                                      quiet breathing

                                      (also, eupnea) mode of breathing that occurs at rest and does not require the cognitive thought of the individual

                                      residual volume (RV)

                                      amount of air that remains in the lungs after maximum exhalation

                                      respiratory bronchiole

                                      specific type of bronchiole that leads to alveolar sacs

                                      respiratory cycle

                                      one sequence of inspiration and expiration

                                      respiratory epithelium

                                      ciliated lining of much of the conducting zone that is specialized to remove debris and pathogens, and produce mucus

                                      respiratory membrane

                                      alveolar and capillary wall together, which form an air-blood barrier that facilitates the simple diffusion of gases

                                      respiratory rate

                                      total number of breaths taken each minute

                                      respiratory volume

                                      varying amounts of air within the lung at a given time

                                      respiratory zone

                                      includes structures of the respiratory system that are directly involved in gas exchange

                                      root

                                      region of the external nose between the eyebrows

                                      thoracic wall compliance

                                      ability of the thoracic wall to stretch while under pressure

                                      thyroid cartilage

                                      largest piece of cartilage that makes up the larynx and consists of two lamina

                                      tidal volume (TV)

                                      amount of air that normally enters the lungs during quiet breathing

                                      total dead space

                                      sum of the anatomical dead space and alveolar dead space

                                      total lung capacity (TLC)

                                      total amount of air that can be held in the lungs; sum of TV, ERV, IRV, and RV

                                      total pressure

                                      sum of all the partial pressures of a gaseous mixture

                                      trachealis muscle

                                      smooth muscle located in the fibroelastic membrane of the trachea

                                      trachea

                                      tube composed of cartilaginous rings and supporting tissue that connects the lung bronchi and the larynx; provides a route for air to enter and exit the lung

                                      transpulmonary pressure

                                      pressure difference between the intrapleural and intra-alveolar pressures

                                      true vocal cord

                                      one of the pair of folded, white membranes that have a free inner edge that oscillates as air passes through to produce sound

                                      type I alveolar cell

                                      squamous epithelial cells that are the major cell type in the alveolar wall; highly permeable to gases

                                      type II alveolar cell

                                      cuboidal epithelial cells that are the minor cell type in the alveolar wall; secrete pulmonary surfactant

                                      ventilation

                                      movement of air into and out of the lungs; consists of inspiration and expiration

                                      ventral respiratory group (VRG)

                                      region of the medulla oblongata that stimulates the contraction of the accessory muscles involved in respiration to induce forced inspiration and expiration

                                      vestibular fold

                                      part of the folded region of the glottis composed of mucous membrane; supports the epiglottis during swallowing

                                      visceral pleura

                                      innermost layer of the pleura that is superficial to the lungs and extends into the lung fissures

                                      vital capacity (VC)

                                      sum of TV, ERV, and IRV, which is all the volumes that participate in gas exchange

                                      Chapter Review
                                      22.. Introduction
                                      22.1. Organs and Structures of the Respiratory System

                                      The respiratory system is responsible for obtaining oxygen and getting rid of carbon dioxide, and aiding in speech production and in sensing odors. From a functional perspective, the respiratory system can be divided into two major areas: the conducting zone and the respiratory zone. The conducting zone consists of all of the structures that provide passageways for air to travel into and out of the lungs: the nasal cavity, pharynx, trachea, bronchi, and most bronchioles. The nasal passages contain the conchae and meatuses that expand the surface area of the cavity, which helps to warm and humidify incoming air, while removing debris and pathogens. The pharynx is composed of three major sections: the nasopharynx, which is continuous with the nasal cavity; the oropharynx, which borders the nasopharynx and the oral cavity; and the laryngopharynx, which borders the oropharynx, trachea, and esophagus. The respiratory zone includes the structures of the lung that are directly involved in gas exchange: the terminal bronchioles and alveoli.

                                      The lining of the conducting zone is composed mostly of pseudostratified ciliated columnar epithelium with goblet cells. The mucus traps pathogens and debris, whereas beating cilia move the mucus superiorly toward the throat, where it is swallowed. As the bronchioles become smaller and smaller, and nearer the alveoli, the epithelium thins and is simple squamous epithelium in the alveoli. The endothelium of the surrounding capillaries, together with the alveolar epithelium, forms the respiratory membrane. This is a blood-air barrier through which gas exchange occurs by simple diffusion.

                                      22.2. The Lungs

                                      The lungs are the major organs of the respiratory system and are responsible for performing gas exchange. The lungs are paired and separated into lobes; The left lung consists of two lobes, whereas the right lung consists of three lobes. Blood circulation is very important, as blood is required to transport oxygen from the lungs to other tissues throughout the body. The function of the pulmonary circulation is to aid in gas exchange. The pulmonary artery provides deoxygenated blood to the capillaries that form respiratory membranes with the alveoli, and the pulmonary veins return newly oxygenated blood to the heart for further transport throughout the body. The lungs are innervated by the parasympathetic and sympathetic nervous systems, which coordinate the bronchodilation and bronchoconstriction of the airways. The lungs are enclosed by the pleura, a membrane that is composed of visceral and parietal pleural layers. The space between these two layers is called the pleural cavity. The mesothelial cells of the pleural membrane create pleural fluid, which serves as both a lubricant (to reduce friction during breathing) and as an adhesive to adhere the lungs to the thoracic wall (to facilitate movement of the lungs during ventilation).

                                      22.3. The Process of Breathing

                                      Pulmonary ventilation is the process of breathing, which is driven by pressure differences between the lungs and the atmosphere. Atmospheric pressure is the force exerted by gases present in the atmosphere. The force exerted by gases within the alveoli is called intra-alveolar (intrapulmonary) pressure, whereas the force exerted by gases in the pleural cavity is called intrapleural pressure. Typically, intrapleural pressure is lower, or negative to, intra-alveolar pressure. The difference in pressure between intrapleural and intra-alveolar pressures is called transpulmonary pressure. In addition, intra-alveolar pressure will equalize with the atmospheric pressure. Pressure is determined by the volume of the space occupied by a gas and is influenced by resistance. Air flows when a pressure gradient is created, from a space of higher pressure to a space of lower pressure. Boyle’s law describes the relationship between volume and pressure. A gas is at lower pressure in a larger volume because the gas molecules have more space to in which to move. The same quantity of gas in a smaller volume results in gas molecules crowding together, producing increased pressure.

                                      Resistance is created by inelastic surfaces, as well as the diameter of the airways. Resistance reduces the flow of gases. The surface tension of the alveoli also influences pressure, as it opposes the expansion of the alveoli. However, pulmonary surfactant helps to reduce the surface tension so that the alveoli do not collapse during expiration. The ability of the lungs to stretch, called lung compliance, also plays a role in gas flow. The more the lungs can stretch, the greater the potential volume of the lungs. The greater the volume of the lungs, the lower the air pressure within the lungs.

                                      Pulmonary ventilation consists of the process of inspiration (or inhalation), where air enters the lungs, and expiration (or exhalation), where air leaves the lungs. During inspiration, the diaphragm and external intercostal muscles contract, causing the rib cage to expand and move outward, and expanding the thoracic cavity and lung volume. This creates a lower pressure within the lung than that of the atmosphere, causing air to be drawn into the lungs. During expiration, the diaphragm and intercostals relax, causing the thorax and lungs to recoil. The air pressure within the lungs increases to above the pressure of the atmosphere, causing air to be forced out of the lungs. However, during forced exhalation, the internal intercostals and abdominal muscles may be involved in forcing air out of the lungs.

                                      Respiratory volume describes the amount of air in a given space within the lungs, or which can be moved by the lung, and is dependent on a variety of factors. Tidal volume refers to the amount of air that enters the lungs during quiet breathing, whereas inspiratory reserve volume is the amount of air that enters the lungs when a person inhales past the tidal volume. Expiratory reserve volume is the extra amount of air that can leave with forceful expiration, following tidal expiration. Residual volume is the amount of air that is left in the lungs after expelling the expiratory reserve volume. Respiratory capacity is the combination of two or more volumes. Anatomical dead space refers to the air within the respiratory structures that never participates in gas exchange, because it does not reach functional alveoli. Respiratory rate is the number of breaths taken per minute, which may change during certain diseases or conditions.

                                      Both respiratory rate and depth are controlled by the respiratory centers of the brain, which are stimulated by factors such as chemical and pH changes in the blood. These changes are sensed by central chemoreceptors, which are located in the brain, and peripheral chemoreceptors, which are located in the aortic arch and carotid arteries. A rise in carbon dioxide or a decline in oxygen levels in the blood stimulates an increase in respiratory rate and depth.

                                      22.4. Gas Exchange

                                      The behavior of gases can be explained by the principles of Dalton’s law and Henry’s law, both of which describe aspects of gas exchange. Dalton’s law states that each specific gas in a mixture of gases exerts force (its partial pressure) independently of the other gases in the mixture. Henry’s law states that the amount of a specific gas that dissolves in a liquid is a function of its partial pressure. The greater the partial pressure of a gas, the more of that gas will dissolve in a liquid, as the gas moves toward equilibrium. Gas molecules move down a pressure gradient; in other words, gas moves from a region of high pressure to a region of low pressure. The partial pressure of oxygen is high in the alveoli and low in the blood of the pulmonary capillaries. As a result, oxygen diffuses across the respiratory membrane from the alveoli into the blood. In contrast, the partial pressure of carbon dioxide is high in the pulmonary capillaries and low in the alveoli. Therefore, carbon dioxide diffuses across the respiratory membrane from the blood into the alveoli. The amount of oxygen and carbon dioxide that diffuses across the respiratory membrane is similar.

                                      Ventilation is the process that moves air into and out of the alveoli, and perfusion affects the flow of blood in the capillaries. Both are important in gas exchange, as ventilation must be sufficient to create a high partial pressure of oxygen in the alveoli. If ventilation is insufficient and the partial pressure of oxygen drops in the alveolar air, the capillary is constricted and blood flow is redirected to alveoli with sufficient ventilation. External respiration refers to gas exchange that occurs in the alveoli, whereas internal respiration refers to gas exchange that occurs in the tissue. Both are driven by partial pressure differences.

                                      22.5. Transport of Gases

                                      Oxygen is primarily transported through the blood by erythrocytes. These cells contain a metalloprotein called hemoglobin, which is composed of four subunits with a ring-like structure. Each subunit contains one atom of iron bound to a molecule of heme. Heme binds oxygen so that each hemoglobin molecule can bind up to four oxygen molecules. When all of the heme units in the blood are bound to oxygen, hemoglobin is considered to be saturated. Hemoglobin is partially saturated when only some heme units are bound to oxygen. An oxygen–hemoglobin saturation/dissociation curve is a common way to depict the relationship of how easily oxygen binds to or dissociates from hemoglobin as a function of the partial pressure of oxygen. As the partial pressure of oxygen increases, the more readily hemoglobin binds to oxygen. At the same time, once one molecule of oxygen is bound by hemoglobin, additional oxygen molecules more readily bind to hemoglobin. Other factors such as temperature, pH, the partial pressure of carbon dioxide, and the concentration of 2,3-bisphosphoglycerate can enhance or inhibit the binding of hemoglobin and oxygen as well. Fetal hemoglobin has a different structure than adult hemoglobin, which results in fetal hemoglobin having a greater affinity for oxygen than adult hemoglobin.

                                      Carbon dioxide is transported in blood by three different mechanisms: as dissolved carbon dioxide, as bicarbonate, or as carbaminohemoglobin. A small portion of carbon dioxide remains. The largest amount of transported carbon dioxide is as bicarbonate, formed in erythrocytes. For this conversion, carbon dioxide is combined with water with the aid of an enzyme called carbonic anhydrase. This combination forms carbonic acid, which spontaneously dissociates into bicarbonate and hydrogen ions. As bicarbonate builds up in erythrocytes, it is moved across the membrane into the plasma in exchange for chloride ions by a mechanism called the chloride shift. At the pulmonary capillaries, bicarbonate re-enters erythrocytes in exchange for chloride ions, and the reaction with carbonic anhydrase is reversed, recreating carbon dioxide and water. Carbon dioxide then diffuses out of the erythrocyte and across the respiratory membrane into the air. An intermediate amount of carbon dioxide binds directly to hemoglobin to form carbaminohemoglobin. The partial pressures of carbon dioxide and oxygen, as well as the oxygen saturation of hemoglobin, influence how readily hemoglobin binds carbon dioxide. The less saturated hemoglobin is and the lower the partial pressure of oxygen in the blood is, the more readily hemoglobin binds to carbon dioxide. This is an example of the Haldane effect.

                                      22.6. Modifications in Respiratory Functions

                                      Normally, the respiratory centers of the brain maintain a consistent, rhythmic breathing cycle. However, in certain cases, the respiratory system must adjust to situational changes in order to supply the body with sufficient oxygen. For example, exercise results in increased ventilation, and chronic exposure to a high altitude results in a greater number of circulating erythrocytes. Hyperpnea, an increase in the rate and depth of ventilation, appears to be a function of three neural mechanisms that include a psychological stimulus, motor neuron activation of skeletal muscles, and the activation of proprioceptors in the muscles, joints, and tendons. As a result, hyperpnea related to exercise is initiated when exercise begins, as opposed to when tissue oxygen demand actually increases.

                                      In contrast, acute exposure to a high altitude, particularly during times of physical exertion, does result in low blood and tissue levels of oxygen. This change is caused by a low partial pressure of oxygen in the air, because the atmospheric pressure at high altitudes is lower than the atmospheric pressure at sea level. This can lead to a condition called acute mountain sickness (AMS) with symptoms that include headaches, disorientation, fatigue, nausea, and lightheadedness. Over a long period of time, a person’s body will adjust to the high altitude, a process called acclimatization. During acclimatization, the low tissue levels of oxygen will cause the kidneys to produce greater amounts of the hormone erythropoietin, which stimulates the production of erythrocytes. Increased levels of circulating erythrocytes provide an increased amount of hemoglobin that helps supply an individual with more oxygen, preventing the symptoms of AMS.

                                      22.7. Embryonic Development of the Respiratory System

                                      The development of the respiratory system in the fetus begins at about 4 weeks and continues into childhood. Ectodermal tissue in the anterior portion of the head region invaginates posteriorly, forming olfactory pits, which ultimately fuse with endodermal tissue of the early pharynx. At about this same time, an protrusion of endodermal tissue extends anteriorly from the foregut, producing a lung bud, which continues to elongate until it forms the laryngotracheal bud. The proximal portion of this structure will mature into the trachea, whereas the bulbous end will branch to form two bronchial buds. These buds then branch repeatedly, so that at about week 16, all major airway structures are present. Development progresses after week 16 as respiratory bronchioles and alveolar ducts form, and extensive vascularization occurs. Alveolar type I cells also begin to take shape. Type II pulmonary cells develop and begin to produce small amounts of surfactant. As the fetus grows, the respiratory system continues to expand as more alveoli develop and more surfactant is produced. Beginning at about week 36 and lasting into childhood, alveolar precursors mature to become fully functional alveoli. At birth, compression of the thoracic cavity forces much of the fluid in the lungs to be expelled. The first inhalation inflates the lungs. Fetal breathing movements begin around week 20 or 21, and occur when contractions of the respiratory muscles cause the fetus to inhale and exhale amniotic fluid. These movements continue until birth and may help to tone the muscles in preparation for breathing after birth and are a sign of good health.

                                      Interactive Link Questions
                                      22.. Introduction
                                      22.1. Organs and Structures of the Respiratory System
                                      Exercise 1.

                                      Visit this site to learn more about what happens during an asthma attack. What are the three changes that occur inside the airways during an asthma attack?

                                      (Return to Exercise)

                                      Inflammation and the production of a thick mucus; constriction of the airway muscles, or bronchospasm; and an increased sensitivity to allergens.

                                      22.2. The Lungs
                                      22.3. The Process of Breathing
                                      Exercise 17.

                                      Watch this video to learn more about lung volumes and spirometers. Explain how spirometry test results can be used to diagnose respiratory diseases or determine the effectiveness of disease treatment.

                                      (Return to Exercise)

                                      Patients with respiratory ailments (such as asthma, emphysema, COPD, etc.) have issues with airway resistance and/or lung compliance. Both of these factors can interfere with the patient’s ability to move air effectively. A spirometry test can determine how much air the patient can move into and out of the lungs. If the air volumes are low, this can indicate that the patient has a respiratory disease or that the treatment regimen may need to be adjusted. If the numbers are normal, the patient does not have a significant respiratory disease or the treatment regimen is working as expected.

                                      22.4. Gas Exchange
                                      22.5. Transport of Gases
                                      Exercise 33.

                                      Watch this video to see the transport of oxygen from the lungs to the tissues. Why is oxygenated blood bright red, whereas deoxygenated blood tends to be more of a purple color?

                                      (Return to Exercise)

                                      When oxygen binds to the hemoglobin molecule, oxyhemoglobin is created, which has a red color to it. Hemoglobin that is not bound to oxygen tends to be more of a blue–purple color. Oxygenated blood traveling through the systemic arteries has large amounts of oxyhemoglobin. As blood passes through the tissues, much of the oxygen is released into systemic capillaries. The deoxygenated blood returning through the systemic veins, therefore, contains much smaller amounts of oxyhemoglobin. The more oxyhemoglobin that is present in the blood, the redder the fluid will be. As a result, oxygenated blood will be much redder in color than deoxygenated blood.

                                      22.6. Modifications in Respiratory Functions
                                      22.7. Embryonic Development of the Respiratory System
                                      Review Questions
                                      22.. Introduction
                                      22.1. Organs and Structures of the Respiratory System
                                      Exercise 2.

                                      Which of the following anatomical structures is not part of the conducting zone?

                                      1. pharynx

                                      2. nasal cavity

                                      3. alveoli

                                      4. bronchi

                                      (Return to Exercise)

                                      C

                                      Exercise 3.

                                      What is the function of the conchae in the nasal cavity?

                                      1. increase surface area

                                      2. exchange gases

                                      3. maintain surface tension

                                      4. maintain air pressure

                                      (Return to Exercise)

                                      A

                                      Exercise 4.

                                      The fauces connects which of the following structures to the oropharynx?

                                      1. nasopharynx

                                      2. laryngopharynx

                                      3. nasal cavity

                                      4. oral cavity

                                      (Return to Exercise)

                                      D

                                      Exercise 5.

                                      Which of the following are structural features of the trachea?

                                      1. C-shaped cartilage

                                      2. smooth muscle fibers

                                      3. cilia

                                      4. all of the above

                                      (Return to Exercise)

                                      A

                                      Exercise 6.

                                      Which of the following structures is not part of the bronchial tree?

                                      1. alveoli

                                      2. bronchi

                                      3. terminal bronchioles

                                      4. respiratory bronchioles

                                      (Return to Exercise)

                                      C

                                      Exercise 7.

                                      What is the role of alveolar macrophages?

                                      1. to secrete pulmonary surfactant

                                      2. to secrete antimicrobial proteins

                                      3. to remove pathogens and debris

                                      4. to facilitate gas exchange

                                      (Return to Exercise)

                                      C

                                      22.2. The Lungs
                                      Exercise 11.

                                      Which of the following structures separates the lung into lobes?

                                      1. mediastinum

                                      2. fissure

                                      3. root

                                      4. pleura

                                      (Return to Exercise)

                                      B

                                      Exercise 12.

                                      A section of the lung that receives its own tertiary bronchus is called the ________.

                                      1. bronchopulmonary segment

                                      2. pulmonary lobule

                                      3. interpulmonary segment

                                      4. respiratory segment

                                      (Return to Exercise)

                                      A

                                      Exercise 13.

                                      The ________ circulation picks up oxygen for cellular use and drops off carbon dioxide for removal from the body.

                                      1. pulmonary

                                      2. interlobular

                                      3. respiratory

                                      4. bronchial

                                      (Return to Exercise)

                                      C

                                      Exercise 14.

                                      The pleura that surrounds the lungs consists of two layers, the ________.

                                      1. visceral and parietal pleurae.

                                      2. mediastinum and parietal pleurae.

                                      3. visceral and mediastinum pleurae.

                                      4. none of the above

                                      (Return to Exercise)

                                      A

                                      22.3. The Process of Breathing
                                      Exercise 18.

                                      Which of the following processes does atmospheric pressure play a role in?

                                      1. pulmonary ventilation

                                      2. production of pulmonary surfactant

                                      3. resistance

                                      4. surface tension

                                      (Return to Exercise)

                                      A

                                      Exercise 19.

                                      A decrease in volume leads to a(n) ________ pressure.

                                      1. decrease in

                                      2. equalization of

                                      3. increase in

                                      4. zero

                                      (Return to Exercise)

                                      C

                                      Exercise 20.

                                      The pressure difference between the intra-alveolar and intrapleural pressures is called ________.

                                      1. atmospheric pressure

                                      2. pulmonary pressure

                                      3. negative pressure

                                      4. transpulmonary pressure

                                      (Return to Exercise)

                                      D

                                      Exercise 21.

                                      Gas flow decreases as ________ increases.

                                      1. resistance

                                      2. pressure

                                      3. airway diameter

                                      4. friction

                                      (Return to Exercise)

                                      A

                                      Exercise 22.

                                      Contraction of the external intercostal muscles causes which of the following to occur?

                                      1. The diaphragm moves downward.

                                      2. The rib cage is compressed.

                                      3. The thoracic cavity volume decreases.

                                      4. The ribs and sternum move upward.

                                      (Return to Exercise)

                                      D

                                      Exercise 23.

                                      Which of the following prevents the alveoli from collapsing?

                                      1. residual volume

                                      2. tidal volume

                                      3. expiratory reserve volume

                                      4. inspiratory reserve volume

                                      (Return to Exercise)

                                      A

                                      22.4. Gas Exchange
                                      Exercise 27.

                                      Gas moves from an area of ________ partial pressure to an area of ________ partial pressure.

                                      1. low; high

                                      2. low; low

                                      3. high; high

                                      4. high; low

                                      (Return to Exercise)

                                      D

                                      Exercise 28.

                                      When ventilation is not sufficient, which of the following occurs?

                                      1. The capillary constricts.

                                      2. The capillary dilates.

                                      3. The partial pressure of oxygen in the affected alveolus increases.

                                      4. The bronchioles dilate.

                                      (Return to Exercise)

                                      A

                                      Exercise 29.

                                      Gas exchange that occurs at the level of the tissues is called ________.

                                      1. external respiration

                                      2. interpulmonary respiration

                                      3. internal respiration

                                      4. pulmonary ventilation

                                      (Return to Exercise)

                                      C

                                      Exercise 30.

                                      The partial pressure of carbon dioxide is 45 mm Hg in the blood and 40 mm Hg in the alveoli. What happens to the carbon dioxide?

                                      1. It diffuses into the blood.

                                      2. It diffuses into the alveoli.

                                      3. The gradient is too small for carbon dioxide to diffuse.

                                      4. It decomposes into carbon and oxygen.

                                      (Return to Exercise)

                                      B

                                      22.5. Transport of Gases
                                      Exercise 34.

                                      Oxyhemoglobin forms by a chemical reaction between which of the following?

                                      1. hemoglobin and carbon dioxide

                                      2. carbonic anhydrase and carbon dioxide

                                      3. hemoglobin and oxygen

                                      4. carbonic anhydrase and oxygen

                                      (Return to Exercise)

                                      C

                                      Exercise 35.

                                      Which of the following factors play a role in the oxygen–hemoglobin saturation/dissociation curve?

                                      1. temperature

                                      2. pH

                                      3. BPG

                                      4. all of the above

                                      (Return to Exercise)

                                      D

                                      Exercise 36.

                                      Which of the following occurs during the chloride shift?

                                      1. Chloride is removed from the erythrocyte.

                                      2. Chloride is exchanged for bicarbonate.

                                      3. Bicarbonate is removed from the erythrocyte.

                                      4. Bicarbonate is removed from the blood.

                                      (Return to Exercise)

                                      B

                                      Exercise 37.

                                      A low partial pressure of oxygen promotes hemoglobin binding to carbon dioxide. This is an example of the ________.

                                      1. Haldane effect

                                      2. Bohr effect

                                      3. Dalton’s law

                                      4. Henry’s law

                                      (Return to Exercise)

                                      A

                                      22.6. Modifications in Respiratory Functions
                                      Exercise 41.

                                      Increased ventilation that results in an increase in blood pH is called ________.

                                      1. hyperventilation

                                      2. hyperpnea

                                      3. acclimatization

                                      4. apnea

                                      (Return to Exercise)

                                      A

                                      Exercise 42.

                                      Exercise can trigger symptoms of AMS due to which of the following?

                                      1. low partial pressure of oxygen

                                      2. low atmospheric pressure

                                      3. abnormal neural signals

                                      4. small venous reserve of oxygen

                                      (Return to Exercise)

                                      D

                                      Exercise 43.

                                      Which of the following stimulates the production of erythrocytes?

                                      1. AMS

                                      2. high blood levels of carbon dioxide

                                      3. low atmospheric pressure

                                      4. erythropoietin

                                      (Return to Exercise)

                                      D

                                      22.7. Embryonic Development of the Respiratory System
                                      Exercise 46.

                                      The olfactory pits form from which of the following?

                                      1. mesoderm

                                      2. cartilage

                                      3. ectoderm

                                      4. endoderm

                                      (Return to Exercise)

                                      C

                                      Exercise 47.

                                      A full complement of mature alveoli are present by ________.

                                      1. early childhood, around 8 years of age

                                      2. birth

                                      3. 37 weeks

                                      4. 16 weeks

                                      (Return to Exercise)

                                      A

                                      Exercise 48.

                                      If a baby is born prematurely before type II cells produce sufficient pulmonary surfactant, which of the following might you expect?

                                      1. difficulty expressing fluid

                                      2. difficulty inflating the lungs

                                      3. difficulty with pulmonary capillary flow

                                      4. no difficulty as type I cells can provide enough surfactant for normal breathing

                                      (Return to Exercise)

                                      B

                                      Exercise 49.

                                      When do fetal breathing movements begin?

                                      1. around week 20

                                      2. around week 37

                                      3. around week 16

                                      4. after birth

                                      (Return to Exercise)

                                      A

                                      Exercise 50.

                                      What happens to the fluid that remains in the lungs after birth?

                                      1. It reduces the surface tension of the alveoli.

                                      2. It is expelled shortly after birth.

                                      3. It is absorbed shortly after birth.

                                      4. It lubricates the pleurae.

                                      (Return to Exercise)

                                      C

                                      Critical Thinking Questions
                                      22.. Introduction
                                      22.1. Organs and Structures of the Respiratory System
                                      Exercise 8.

                                      Describe the three regions of the pharynx and their functions.

                                      (Return to Exercise)

                                      The pharynx has three major regions. The first region is the nasopharynx, which is connected to the posterior nasal cavity and functions as an airway. The second region is the oropharynx, which is continuous with the nasopharynx and is connected to the oral cavity at the fauces. The laryngopharynx is connected to the oropharynx and the esophagus and trachea. Both the oropharynx and laryngopharynx are passageways for air and food and drink.

                                      Exercise 9.

                                      If a person sustains an injury to the epiglottis, what would be the physiological result?

                                      (Return to Exercise)

                                      The epiglottis is a region of the larynx that is important during the swallowing of food or drink. As a person swallows, the pharynx moves upward and the epiglottis closes over the trachea, preventing food or drink from entering the trachea. If a person’s epiglottis were injured, this mechanism would be impaired. As a result, the person may have problems with food or drink entering the trachea, and possibly, the lungs. Over time, this may cause infections such as pneumonia to set in.

                                      Exercise 10.

                                      Compare and contrast the conducting and respiratory zones.

                                      (Return to Exercise)

                                      The conducting zone of the respiratory system includes the organs and structures that are not directly involved in gas exchange, but perform other duties such as providing a passageway for air, trapping and removing debris and pathogens, and warming and humidifying incoming air. Such structures include the nasal cavity, pharynx, larynx, trachea, and most of the bronchial tree. The respiratory zone includes all the organs and structures that are directly involved in gas exchange, including the respiratory bronchioles, alveolar ducts, and alveoli.

                                      22.2. The Lungs
                                      Exercise 15.

                                      Compare and contrast the right and left lungs.

                                      (Return to Exercise)

                                      The right and left lungs differ in size and shape to accommodate other organs that encroach on the thoracic region. The right lung consists of three lobes and is shorter than the left lung, due to the position of the liver underneath it. The left lung consist of two lobes and is longer and narrower than the right lung. The left lung has a concave region on the mediastinal surface called the cardiac notch that allows space for the heart.

                                      Exercise 16.

                                      Why are the pleurae not damaged during normal breathing?

                                      (Return to Exercise)

                                      There is a cavity, called the pleural cavity, between the parietal and visceral layers of the pleura. Mesothelial cells produce and secrete pleural fluid into the pleural cavity that acts as a lubricant. Therefore, as you breathe, the pleural fluid prevents the two layers of the pleura from rubbing against each other and causing damage due to friction.

                                      22.3. The Process of Breathing
                                      Exercise 24.

                                      Describe what is meant by the term “lung compliance.”

                                      (Return to Exercise)

                                      Lung compliance refers to the ability of lung tissue to stretch under pressure, which is determined in part by the surface tension of the alveoli and the ability of the connective tissue to stretch. Lung compliance plays a role in determining how much the lungs can change in volume, which in turn helps to determine pressure and air movement.

                                      Exercise 25.

                                      Outline the steps involved in quiet breathing.

                                      (Return to Exercise)

                                      Quiet breathing occurs at rest and without active thought. During quiet breathing, the diaphragm and external intercostal muscles work at different extents, depending on the situation. For inspiration, the diaphragm contracts, causing the diaphragm to flatten and drop towards the abdominal cavity, helping to expand the thoracic cavity. The external intercostal muscles contract as well, causing the rib cage to expand, and the rib cage and sternum to move outward, also expanding the thoracic cavity. Expansion of the thoracic cavity also causes the lungs to expand, due to the adhesiveness of the pleural fluid. As a result, the pressure within the lungs drops below that of the atmosphere, causing air to rush into the lungs. In contrast, expiration is a passive process. As the diaphragm and intercostal muscles relax, the lungs and thoracic tissues recoil, and the volume of the lungs decreases. This causes the pressure within the lungs to increase above that of the atmosphere, causing air to leave the lungs.

                                      Exercise 26.

                                      What is respiratory rate and how is it controlled?

                                      (Return to Exercise)

                                      Respiratory rate is defined as the number of breaths taken per minute. Respiratory rate is controlled by the respiratory center, located in the medulla oblongata. Conscious thought can alter the normal respiratory rate through control by skeletal muscle, although one cannot consciously stop the rate altogether. A typical resting respiratory rate is about 14 breaths per minute.

                                      22.4. Gas Exchange
                                      Exercise 31.

                                      Compare and contrast Dalton’s law and Henry’s law.

                                      (Return to Exercise)

                                      Both Dalton’s and Henry’s laws describe the behavior of gases. Dalton’s law states that any gas in a mixture of gases exerts force as if it were not in a mixture. Henry’s law states that gas molecules dissolve in a liquid proportional to their partial pressure.

                                      Exercise 32.

                                      A smoker develops damage to several alveoli that then can no longer function. How does this affect gas exchange?

                                      (Return to Exercise)

                                      The damaged alveoli will have insufficient ventilation, causing the partial pressure of oxygen in the alveoli to decrease. As a result, the pulmonary capillaries serving these alveoli will constrict, redirecting blood flow to other alveoli that are receiving sufficient ventilation.

                                      22.5. Transport of Gases
                                      Exercise 38.

                                      Compare and contrast adult hemoglobin and fetal hemoglobin.

                                      (Return to Exercise)

                                      Both adult and fetal hemoglobin transport oxygen via iron molecules. However, fetal hemoglobin has about a 20-fold greater affinity for oxygen than does adult hemoglobin. This is due to a difference in structure; fetal hemoglobin has two subunits that have a slightly different structure than the subunits of adult hemoglobin.

                                      Exercise 39.

                                      Describe the relationship between the partial pressure of oxygen and the binding of oxygen to hemoglobin.

                                      (Return to Exercise)

                                      The relationship between the partial pressure of oxygen and the binding of hemoglobin to oxygen is described by the oxygen–hemoglobin saturation/dissociation curve. As the partial pressure of oxygen increases, the number of oxygen molecules bound by hemoglobin increases, thereby increasing the saturation of hemoglobin.

                                      Exercise 40.

                                      Describe three ways in which carbon dioxide can be transported.

                                      (Return to Exercise)

                                      Carbon dioxide can be transported by three mechanisms: dissolved in plasma, as bicarbonate, or as carbaminohemoglobin. Dissolved in plasma, carbon dioxide molecules simply diffuse into the blood from the tissues. Bicarbonate is created by a chemical reaction that occurs mostly in erythrocytes, joining carbon dioxide and water by carbonic anhydrase, producing carbonic acid, which breaks down into bicarbonate and hydrogen ions. Carbaminohemoglobin is the bound form of hemoglobin and carbon dioxide.

                                      22.6. Modifications in Respiratory Functions
                                      Exercise 44.

                                      Describe the neural factors involved in increasing ventilation during exercise.

                                      (Return to Exercise)

                                      There are three neural factors that play a role in the increased ventilation observed during exercise. Because this increased ventilation occurs at the beginning of exercise, it is unlikely that only blood oxygen and carbon dioxide levels are involved. The first neural factor is the psychological stimulus of making a conscious decision to exercise. The second neural factor is the stimulus of motor neuron activation by the skeletal muscles, which are involved in exercise. The third neural factor is activation of the proprioceptors located in the muscles, joints, and tendons that stimulate activity in the respiratory centers.

                                      Exercise 45.

                                      What is the major mechanism that results in acclimatization?

                                      (Return to Exercise)

                                      A major mechanism involved in acclimatization is the increased production of erythrocytes. A drop in tissue levels of oxygen stimulates the kidneys to produce the hormone erythropoietin, which signals the bone marrow to produce erythrocytes. As a result, individuals exposed to a high altitude for long periods of time have a greater number of circulating erythrocytes than do individuals at lower altitudes.

                                      22.7. Embryonic Development of the Respiratory System
                                      Exercise 51.

                                      During what timeframe does a fetus have enough mature structures to breathe on its own if born prematurely? Describe the other structures that develop during this phase.

                                      (Return to Exercise)

                                      At about week 28, enough alveolar precursors have matured so that a baby born prematurely at this time can usually breathe on its own. Other structures that develop about this time are pulmonary capillaries, expanding to create a large surface area for gas exchange. Alveolar ducts and alveolar precursors have also developed.

                                      Exercise 52.

                                      Describe fetal breathing movements and their purpose.

                                      (Return to Exercise)

                                      Fetal breathing movements occur due to the contraction of respiratory muscles, causing the fetus to inhale and exhale amniotic fluid. It is thought that these movements are a way to “practice” breathing, which results in toning the muscles in preparation for breathing after birth. In addition, fetal breathing movements may help alveoli to form and mature.

                                      Solutions
                                      (Return to Exercise)

                                      Inflammation and the production of a thick mucus; constriction of the airway muscles, or bronchospasm; and an increased sensitivity to allergens.

                                      (Return to Exercise)

                                      Patients with respiratory ailments (such as asthma, emphysema, COPD, etc.) have issues with airway resistance and/or lung compliance. Both of these factors can interfere with the patient’s ability to move air effectively. A spirometry test can determine how much air the patient can move into and out of the lungs. If the air volumes are low, this can indicate that the patient has a respiratory disease or that the treatment regimen may need to be adjusted. If the numbers are normal, the patient does not have a significant respiratory disease or the treatment regimen is working as expected.

                                      (Return to Exercise)

                                      When oxygen binds to the hemoglobin molecule, oxyhemoglobin is created, which has a red color to it. Hemoglobin that is not bound to oxygen tends to be more of a blue–purple color. Oxygenated blood traveling through the systemic arteries has large amounts of oxyhemoglobin. As blood passes through the tissues, much of the oxygen is released into systemic capillaries. The deoxygenated blood returning through the systemic veins, therefore, contains much smaller amounts of oxyhemoglobin. The more oxyhemoglobin that is present in the blood, the redder the fluid will be. As a result, oxygenated blood will be much redder in color than deoxygenated blood.

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                                      The pharynx has three major regions. The first region is the nasopharynx, which is connected to the posterior nasal cavity and functions as an airway. The second region is the oropharynx, which is continuous with the nasopharynx and is connected to the oral cavity at the fauces. The laryngopharynx is connected to the oropharynx and the esophagus and trachea. Both the oropharynx and laryngopharynx are passageways for air and food and drink.

                                      (Return to Exercise)

                                      The epiglottis is a region of the larynx that is important during the swallowing of food or drink. As a person swallows, the pharynx moves upward and the epiglottis closes over the trachea, preventing food or drink from entering the trachea. If a person’s epiglottis were injured, this mechanism would be impaired. As a result, the person may have problems with food or drink entering the trachea, and possibly, the lungs. Over time, this may cause infections such as pneumonia to set in.

                                      (Return to Exercise)

                                      The conducting zone of the respiratory system includes the organs and structures that are not directly involved in gas exchange, but perform other duties such as providing a passageway for air, trapping and removing debris and pathogens, and warming and humidifying incoming air. Such structures include the nasal cavity, pharynx, larynx, trachea, and most of the bronchial tree. The respiratory zone includes all the organs and structures that are directly involved in gas exchange, including the respiratory bronchioles, alveolar ducts, and alveoli.

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                                      The right and left lungs differ in size and shape to accommodate other organs that encroach on the thoracic region. The right lung consists of three lobes and is shorter than the left lung, due to the position of the liver underneath it. The left lung consist of two lobes and is longer and narrower than the right lung. The left lung has a concave region on the mediastinal surface called the cardiac notch that allows space for the heart.

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                                      There is a cavity, called the pleural cavity, between the parietal and visceral layers of the pleura. Mesothelial cells produce and secrete pleural fluid into the pleural cavity that acts as a lubricant. Therefore, as you breathe, the pleural fluid prevents the two layers of the pleura from rubbing against each other and causing damage due to friction.

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                                      Lung compliance refers to the ability of lung tissue to stretch under pressure, which is determined in part by the surface tension of the alveoli and the ability of the connective tissue to stretch. Lung compliance plays a role in determining how much the lungs can change in volume, which in turn helps to determine pressure and air movement.

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                                      Quiet breathing occurs at rest and without active thought. During quiet breathing, the diaphragm and external intercostal muscles work at different extents, depending on the situation. For inspiration, the diaphragm contracts, causing the diaphragm to flatten and drop towards the abdominal cavity, helping to expand the thoracic cavity. The external intercostal muscles contract as well, causing the rib cage to expand, and the rib cage and sternum to move outward, also expanding the thoracic cavity. Expansion of the thoracic cavity also causes the lungs to expand, due to the adhesiveness of the pleural fluid. As a result, the pressure within the lungs drops below that of the atmosphere, causing air to rush into the lungs. In contrast, expiration is a passive process. As the diaphragm and intercostal muscles relax, the lungs and thoracic tissues recoil, and the volume of the lungs decreases. This causes the pressure within the lungs to increase above that of the atmosphere, causing air to leave the lungs.

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                                      Respiratory rate is defined as the number of breaths taken per minute. Respiratory rate is controlled by the respiratory center, located in the medulla oblongata. Conscious thought can alter the normal respiratory rate through control by skeletal muscle, although one cannot consciously stop the rate altogether. A typical resting respiratory rate is about 14 breaths per minute.

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                                      Both Dalton’s and Henry’s laws describe the behavior of gases. Dalton’s law states that any gas in a mixture of gases exerts force as if it were not in a mixture. Henry’s law states that gas molecules dissolve in a liquid proportional to their partial pressure.

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                                      The damaged alveoli will have insufficient ventilation, causing the partial pressure of oxygen in the alveoli to decrease. As a result, the pulmonary capillaries serving these alveoli will constrict, redirecting blood flow to other alveoli that are receiving sufficient ventilation.

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                                      Both adult and fetal hemoglobin transport oxygen via iron molecules. However, fetal hemoglobin has about a 20-fold greater affinity for oxygen than does adult hemoglobin. This is due to a difference in structure; fetal hemoglobin has two subunits that have a slightly different structure than the subunits of adult hemoglobin.

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                                      The relationship between the partial pressure of oxygen and the binding of hemoglobin to oxygen is described by the oxygen–hemoglobin saturation/dissociation curve. As the partial pressure of oxygen increases, the number of oxygen molecules bound by hemoglobin increases, thereby increasing the saturation of hemoglobin.

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                                      Carbon dioxide can be transported by three mechanisms: dissolved in plasma, as bicarbonate, or as carbaminohemoglobin. Dissolved in plasma, carbon dioxide molecules simply diffuse into the blood from the tissues. Bicarbonate is created by a chemical reaction that occurs mostly in erythrocytes, joining carbon dioxide and water by carbonic anhydrase, producing carbonic acid, which breaks down into bicarbonate and hydrogen ions. Carbaminohemoglobin is the bound form of hemoglobin and carbon dioxide.

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                                      There are three neural factors that play a role in the increased ventilation observed during exercise. Because this increased ventilation occurs at the beginning of exercise, it is unlikely that only blood oxygen and carbon dioxide levels are involved. The first neural factor is the psychological stimulus of making a conscious decision to exercise. The second neural factor is the stimulus of motor neuron activation by the skeletal muscles, which are involved in exercise. The third neural factor is activation of the proprioceptors located in the muscles, joints, and tendons that stimulate activity in the respiratory centers.

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                                      A major mechanism involved in acclimatization is the increased production of erythrocytes. A drop in tissue levels of oxygen stimulates the kidneys to produce the hormone erythropoietin, which signals the bone marrow to produce erythrocytes. As a result, individuals exposed to a high altitude for long periods of time have a greater number of circulating erythrocytes than do individuals at lower altitudes.

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                                      At about week 28, enough alveolar precursors have matured so that a baby born prematurely at this time can usually breathe on its own. Other structures that develop about this time are pulmonary capillaries, expanding to create a large surface area for gas exchange. Alveolar ducts and alveolar precursors have also developed.

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                                      Fetal breathing movements occur due to the contraction of respiratory muscles, causing the fetus to inhale and exhale amniotic fluid. It is thought that these movements are a way to “practice” breathing, which results in toning the muscles in preparation for breathing after birth. In addition, fetal breathing movements may help alveoli to form and mature.

                                      Chapter 2The Chemical Level of Organization

                                      This figure shows a double helix.
                                      Figure 2.1Human DNA
                                      Human DNA is described as a double helix that resembles a molecular spiral staircase. In humans the DNA is organized into 46 chromosomes.

                                      Introduction*

                                      Chapter Objectives

                                      After studying this chapter, you will be able to:

                                      • Describe the fundamental composition of matter

                                      • Identify the three subatomic particles

                                      • Identify the four most abundant elements in the body

                                      • Explain the relationship between an atom’s number of electrons and its relative stability

                                      • Distinguish between ionic bonds, covalent bonds, and hydrogen bonds

                                      • Explain how energy is invested, stored, and released via chemical reactions, particularly those reactions that are critical to life

                                      • Explain the importance of the inorganic compounds that contribute to life, such as water, salts, acids, and bases

                                      • Compare and contrast the four important classes of organic (carbon-based) compounds—proteins, carbohydrates, lipids and nucleic acids—according to their composition and functional importance to human life

                                      The smallest, most fundamental material components of the human body are basic chemical elements. In fact, chemicals called nucleotide bases are the foundation of the genetic code with the instructions on how to build and maintain the human body from conception through old age. There are about three billion of these base pairs in human DNA.

                                      Human chemistry includes organic molecules (carbon-based) and biochemicals (those produced by the body). Human chemistry also includes elements. In fact, life cannot exist without many of the elements that are part of the earth. All of the elements that contribute to chemical reactions, to the transformation of energy, and to electrical activity and muscle contraction—elements that include phosphorus, carbon, sodium, and calcium, to name a few—originated in stars.

                                      These elements, in turn, can form both the inorganic and organic chemical compounds important to life, including, for example, water, glucose, and proteins. This chapter begins by examining elements and how the structures of atoms, the basic units of matter, determine the characteristics of elements by the number of protons, neutrons, and electrons in the atoms. The chapter then builds the framework of life from there.

                                      2.1Elements and Atoms: The Building Blocks of Matter*

                                      By the end of this section, you will be able to:

                                      • Discuss the relationships between matter, mass, elements, compounds, atoms, and subatomic particles

                                      • Distinguish between atomic number and mass number

                                      • Identify the key distinction between isotopes of the same element

                                      • Explain how electrons occupy electron shells and their contribution to an atom’s relative stability

                                      • Elements and Compounds
                                      • Atoms and Subatomic Particles
                                        • Atomic Structure and Energy
                                        • Atomic Number and Mass Number
                                        • Isotopes
                                      • The Behavior of Electrons

                                      The substance of the universe—from a grain of sand to a star—is called matter. Scientists define matter as anything that occupies space and has mass. An object’s mass and its weight are related concepts, but not quite the same. An object’s mass is the amount of matter contained in the object, and the object’s mass is the same whether that object is on Earth or in the zero-gravity environment of outer space. An object’s weight, on the other hand, is its mass as affected by the pull of gravity. Where gravity strongly pulls on an object’s mass its weight is greater than it is where gravity is less strong. An object of a certain mass weighs less on the moon, for example, than it does on Earth because the gravity of the moon is less than that of Earth. In other words, weight is variable, and is influenced by gravity. A piece of cheese that weighs a pound on Earth weighs only a few ounces on the moon.

                                      Elements and Compounds

                                      All matter in the natural world is composed of one or more of the 92 fundamental substances called elements. An element is a pure substance that is distinguished from all other matter by the fact that it cannot be created or broken down by ordinary chemical means. While your body can assemble many of the chemical compounds needed for life from their constituent elements, it cannot make elements. They must come from the environment. A familiar example of an element that you must take in is calcium (Ca++). Calcium is essential to the human body; it is absorbed and used for a number of processes, including strengthening bones. When you consume dairy products your digestive system breaks down the food into components small enough to cross into the bloodstream. Among these is calcium, which, because it is an element, cannot be broken down further. The elemental calcium in cheese, therefore, is the same as the calcium that forms your bones. Some other elements you might be familiar with are oxygen, sodium, and iron. The elements in the human body are shown in Figure 2.2, beginning with the most abundant: oxygen (O), carbon (C), hydrogen (H), and nitrogen (N). Each element’s name can be replaced by a one- or two-letter symbol; you will become familiar with some of these during this course. All the elements in your body are derived from the foods you eat and the air you breathe.

                                      This figure shows a human body with the percentage of the main elements in the body, in the left panel. In the right panel, a table lists the elements and the percentages in the body.
                                      Figure 2.2Elements of the Human Body
                                      The main elements that compose the human body are shown from most abundant to least abundant.

                                      In nature, elements rarely occur alone. Instead, they combine to form compounds. A compound is a substance composed of two or more elements joined by chemical bonds. For example, the compound glucose is an important body fuel. It is always composed of the same three elements: carbon, hydrogen, and oxygen. Moreover, the elements that make up any given compound always occur in the same relative amounts. In glucose, there are always six carbon and six oxygen units for every twelve hydrogen units. But what, exactly, are these “units” of elements?

                                      Atoms and Subatomic Particles

                                      An atom is the smallest quantity of an element that retains the unique properties of that element. In other words, an atom of hydrogen is a unit of hydrogen—the smallest amount of hydrogen that can exist. As you might guess, atoms are almost unfathomably small. The period at the end of this sentence is millions of atoms wide.

                                      Atomic Structure and Energy

                                      Atoms are made up of even smaller subatomic particles, three types of which are important: the proton, neutron, and electron. The number of positively-charged protons and non-charged (“neutral”) neutrons, gives mass to the atom, and the number of each in the nucleus of the atom determine the element. The number of negatively-charged electrons that “spin” around the nucleus at close to the speed of light equals the number of protons. An electron has about 1/2000th the mass of a proton or neutron.

                                      Figure 2.3 shows two models that can help you imagine the structure of an atom—in this case, helium (He). In the planetary model, helium’s two electrons are shown circling the nucleus in a fixed orbit depicted as a ring. Although this model is helpful in visualizing atomic structure, in reality, electrons do not travel in fixed orbits, but whiz around the nucleus erratically in a so-called electron cloud.

                                      The top panel of this figure shows two electrons orbiting around the nucleus of a Helium atom. The bottom panel of this figure shows a cloud of electrons surrounding the nucleus of a Helium atom.
                                      Figure 2.3Two Models of Atomic Structure
                                      (a) In the planetary model, the electrons of helium are shown in fixed orbits, depicted as rings, at a precise distance from the nucleus, somewhat like planets orbiting the sun. (b) In the electron cloud model, the electrons of carbon are shown in the variety of locations they would have at different distances from the nucleus over time.

                                      An atom’s protons and electrons carry electrical charges. Protons, with their positive charge, are designated p+. Electrons, which have a negative charge, are designated e–. An atom’s neutrons have no charge: they are electrically neutral. Just as a magnet sticks to a steel refrigerator because their opposite charges attract, the positively charged protons attract the negatively charged electrons. This mutual attraction gives the atom some structural stability. The attraction by the positively charged nucleus helps keep electrons from straying far. The number of protons and electrons within a neutral atom are equal, thus, the atom’s overall charge is balanced.

                                      Atomic Number and Mass Number

                                      An atom of carbon is unique to carbon, but a proton of carbon is not. One proton is the same as another, whether it is found in an atom of carbon, sodium (Na), or iron (Fe). The same is true for neutrons and electrons. So, what gives an element its distinctive properties—what makes carbon so different from sodium or iron? The answer is the unique quantity of protons each contains. Carbon by definition is an element whose atoms contain six protons. No other element has exactly six protons in its atoms. Moreover, all atoms of carbon, whether found in your liver or in a lump of coal, contain six protons. Thus, the atomic number, which is the number of protons in the nucleus of the atom, identifies the element. Because an atom usually has the same number of electrons as protons, the atomic number identifies the usual number of electrons as well.

                                      In their most common form, many elements also contain the same number of neutrons as protons. The most common form of carbon, for example, has six neutrons as well as six protons, for a total of 12 subatomic particles in its nucleus. An element’s mass number is the sum of the number of protons and neutrons in its nucleus. So the most common form of carbon’s mass number is 12. (Electrons have so little mass that they do not appreciably contribute to the mass of an atom.) Carbon is a relatively light element. Uranium (U), in contrast, has a mass number of 238 and is referred to as a heavy metal. Its atomic number is 92 (it has 92 protons) but it contains 146 neutrons; it has the most mass of all the naturally occurring elements.

                                      The periodic table of the elements, shown in Figure 2.4, is a chart identifying the 92 elements found in nature, as well as several larger, unstable elements discovered experimentally. The elements are arranged in order of their atomic number, with hydrogen and helium at the top of the table, and the more massive elements below. The periodic table is a useful device because for each element, it identifies the chemical symbol, the atomic number, and the mass number, while organizing elements according to their propensity to react with other elements. The number of protons and electrons in an element are equal. The number of protons and neutrons may be equal for some elements, but are not equal for all.

                                      This figure shows the periodic table.
                                      Figure 2.4The Periodic Table of the Elements
                                      (credit: R.A. Dragoset, A. Musgrove, C.W. Clark, W.C. Martin)
                                      QR Code representing a URL

                                      Visit this website to view the periodic table. In the periodic table of the elements, elements in a single column have the same number of electrons that can participate in a chemical reaction. These electrons are known as “valence electrons.” For example, the elements in the first column all have a single valence electron, an electron that can be “donated” in a chemical reaction with another atom. What is the meaning of a mass number shown in parentheses?

                                      Isotopes

                                      Although each element has a unique number of protons, it can exist as different isotopes. An isotope is one of the different forms of an element, distinguished from one another by different numbers of neutrons. The standard isotope of carbon is 12C, commonly called carbon twelve. 12C has six protons and six neutrons, for a mass number of twelve. All of the isotopes of carbon have the same number of protons; therefore, 13C has seven neutrons, and 14C has eight neutrons. The different isotopes of an element can also be indicated with the mass number hyphenated (for example, C-12 instead of 12C). Hydrogen has three common isotopes, shown in Figure 2.5.

                                      This figure shows the three isotopes of hydrogen: hydrogen, deuterium, and tritium.
                                      Figure 2.5Isotopes of Hydrogen
                                      Protium, designated 1H, has one proton and no neutrons. It is by far the most abundant isotope of hydrogen in nature. Deuterium, designated 2H, has one proton and one neutron. Tritium, designated 3H, has two neutrons.

                                      An isotope that contains more than the usual number of neutrons is referred to as a heavy isotope. An example is 14C. Heavy isotopes tend to be unstable, and unstable isotopes are radioactive. A radioactive isotope is an isotope whose nucleus readily decays, giving off subatomic particles and electromagnetic energy. Different radioactive isotopes (also called radioisotopes) differ in their half-life, the time it takes for half of any size sample of an isotope to decay. For example, the half-life of tritium—a radioisotope of hydrogen—is about 12 years, indicating it takes 12 years for half of the tritium nuclei in a sample to decay. Excessive exposure to radioactive isotopes can damage human cells and even cause cancer and birth defects, but when exposure is controlled, some radioactive isotopes can be useful in medicine. For more information, see the Career Connections.

                                      Career Connection

                                      Interventional Radiologist

                                      The controlled use of radioisotopes has advanced medical diagnosis and treatment of disease. Interventional radiologists are physicians who treat disease by using minimally invasive techniques involving radiation. Many conditions that could once only be treated with a lengthy and traumatic operation can now be treated non-surgically, reducing the cost, pain, length of hospital stay, and recovery time for patients. For example, in the past, the only options for a patient with one or more tumors in the liver were surgery and chemotherapy (the administration of drugs to treat cancer). Some liver tumors, however, are difficult to access surgically, and others could require the surgeon to remove too much of the liver. Moreover, chemotherapy is highly toxic to the liver, and certain tumors do not respond well to it anyway. In some such cases, an interventional radiologist can treat the tumors by disrupting their blood supply, which they need if they are to continue to grow. In this procedure, called radioembolization, the radiologist accesses the liver with a fine needle, threaded through one of the patient’s blood vessels. The radiologist then inserts tiny radioactive “seeds” into the blood vessels that supply the tumors. In the days and weeks following the procedure, the radiation emitted from the seeds destroys the vessels and directly kills the tumor cells in the vicinity of the treatment.

                                      Radioisotopes emit subatomic particles that can be detected and tracked by imaging technologies. One of the most advanced uses of radioisotopes in medicine is the positron emission tomography (PET) scanner, which detects the activity in the body of a very small injection of radioactive glucose, the simple sugar that cells use for energy. The PET camera reveals to the medical team which of the patient’s tissues are taking up the most glucose. Thus, the most metabolically active tissues show up as bright “hot spots” on the images (Figure 2.6). PET can reveal some cancerous masses because cancer cells consume glucose at a high rate to fuel their rapid reproduction.

                                      This figure shows multiple images from a PET scan.
                                      Figure 2.6PET Scan
                                      PET highlights areas in the body where there is relatively high glucose use, which is characteristic of cancerous tissue. This PET scan shows sites of the spread of a large primary tumor to other sites.

                                      The Behavior of Electrons

                                      In the human body, atoms do not exist as independent entities. Rather, they are constantly reacting with other atoms to form and to break down more complex substances. To fully understand anatomy and physiology you must grasp how atoms participate in such reactions. The key is understanding the behavior of electrons.

                                      Although electrons do not follow rigid orbits a set distance away from the atom’s nucleus, they do tend to stay within certain regions of space called electron shells. An electron shell is a layer of electrons that encircle the nucleus at a distinct energy level.

                                      The atoms of the elements found in the human body have from one to five electron shells, and all electron shells hold eight electrons except the first shell, which can only hold two. This configuration of electron shells is the same for all atoms. The precise number of shells depends on the number of electrons in the atom. Hydrogen and helium have just one and two electrons, respectively. If you take a look at the periodic table of the elements, you will notice that hydrogen and helium are placed alone on either sides of the top row; they are the only elements that have just one electron shell (Figure 2.7). A second shell is necessary to hold the electrons in all elements larger than hydrogen and helium.

                                      Lithium (Li), whose atomic number is 3, has three electrons. Two of these fill the first electron shell, and the third spills over into a second shell. The second electron shell can accommodate as many as eight electrons. Carbon, with its six electrons, entirely fills its first shell, and half-fills its second. With ten electrons, neon (Ne) entirely fills its two electron shells. Again, a look at the periodic table reveals that all of the elements in the second row, from lithium to neon, have just two electron shells. Atoms with more than ten electrons require more than two shells. These elements occupy the third and subsequent rows of the periodic table.

                                      This four panel figure shows four different atoms with the electrons in orbit around the nucleus.
                                      Figure 2.7Electron Shells
                                      Electrons orbit the atomic nucleus at distinct levels of energy called electron shells. (a) With one electron, hydrogen only half-fills its electron shell. Helium also has a single shell, but its two electrons completely fill it. (b) The electrons of carbon completely fill its first electron shell, but only half-fills its second. (c) Neon, an element that does not occur in the body, has 10 electrons, filling both of its electron shells.

                                      The factor that most strongly governs the tendency of an atom to participate in chemical reactions is the number of electrons in its valence shell. A valence shell is an atom’s outermost electron shell. If the valence shell is full, the atom is stable; meaning its electrons are unlikely to be pulled away from the nucleus by the electrical charge of other atoms. If the valence shell is not full, the atom is reactive; meaning it will tend to react with other atoms in ways that make the valence shell full. Consider hydrogen, with its one electron only half-filling its valence shell. This single electron is likely to be drawn into relationships with the atoms of other elements, so that hydrogen’s single valence shell can be stabilized.

                                      All atoms (except hydrogen and helium with their single electron shells) are most stable when there are exactly eight electrons in their valence shell. This principle is referred to as the octet rule, and it states that an atom will give up, gain, or share electrons with another atom so that it ends up with eight electrons in its own valence shell. For example, oxygen, with six electrons in its valence shell, is likely to react with other atoms in a way that results in the addition of two electrons to oxygen’s valence shell, bringing the number to eight. When two hydrogen atoms each share their single electron with oxygen, covalent bonds are formed, resulting in a molecule of water, H2O.

                                      In nature, atoms of one element tend to join with atoms of other elements in characteristic ways. For example, carbon commonly fills its valence shell by linking up with four atoms of hydrogen. In so doing, the two elements form the simplest of organic molecules, methane, which also is one of the most abundant and stable carbon-containing compounds on Earth. As stated above, another example is water; oxygen needs two electrons to fill its valence shell. It commonly interacts with two atoms of hydrogen, forming H2O. Incidentally, the name “hydrogen” reflects its contribution to water (hydro- = “water”; -gen = “maker”). Thus, hydrogen is the “water maker.”

                                      2.2Chemical Bonds*

                                      By the end of this section, you will be able to:

                                      • Explain the relationship between molecules and compounds

                                      • Distinguish between ions, cations, and anions

                                      • Identify the key difference between ionic and covalent bonds

                                      • Distinguish between nonpolar and polar covalent bonds

                                      • Explain how water molecules link via hydrogen bonds

                                      • Ions and Ionic Bonds
                                      • Covalent Bonds
                                        • Nonpolar Covalent Bonds
                                        • Polar Covalent Bonds
                                      • Hydrogen Bonds

                                      Atoms separated by a great distance cannot link; rather, they must come close enough for the electrons in their valence shells to interact. But do atoms ever actually touch one another? Most physicists would say no, because the negatively charged electrons in their valence shells repel one another. No force within the human body—or anywhere in the natural world—is strong enough to overcome this electrical repulsion. So when you read about atoms linking together or colliding, bear in mind that the atoms are not merging in a physical sense.

                                      Instead, atoms link by forming a chemical bond. A bond is a weak or strong electrical attraction that holds atoms in the same vicinity. The new grouping is typically more stable—less likely to react again—than its component atoms were when they were separate. A more or less stable grouping of two or more atoms held together by chemical bonds is called a molecule. The bonded atoms may be of the same element, as in the case of H2, which is called molecular hydrogen or hydrogen gas. When a molecule is made up of two or more atoms of different elements, it is called a chemical compound. Thus, a unit of water, or H2O, is a compound, as is a single molecule of the gas methane, or CH4.

                                      Three types of chemical bonds are important in human physiology, because they hold together substances that are used by the body for critical aspects of homeostasis, signaling, and energy production, to name just a few important processes. These are ionic bonds, covalent bonds, and hydrogen bonds.

                                      Ions and Ionic Bonds

                                      Recall that an atom typically has the same number of positively charged protons and negatively charged electrons. As long as this situation remains, the atom is electrically neutral. But when an atom participates in a chemical reaction that results in the donation or acceptance of one or more electrons, the atom will then become positively or negatively charged. This happens frequently for most atoms in order to have a full valence shell, as described previously. This can happen either by gaining electrons to fill a shell that is more than half-full, or by giving away electrons to empty a shell than is less than half-full, thereby leaving the next smaller electron shell as the new, full, valence shell. An atom that has an electrical charge—whether positive or negative—is an ion.

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                                      Visit this website to learn about electrical energy and the attraction/repulsion of charges. What happens to the charged electroscope when a conductor is moved between its plastic sheets, and why?

                                      Potassium (K), for instance, is an important element in all body cells. Its atomic number is 19. It has just one electron in its valence shell. This characteristic makes potassium highly likely to participate in chemical reactions in which it donates one electron. (It is easier for potassium to donate one electron than to gain seven electrons.) The loss will cause the positive charge of potassium’s protons to be more influential than the negative charge of potassium’s electrons. In other words, the resulting potassium ion will be slightly positive. A potassium ion is written K+, indicating that it has lost a single electron. A positively charged ion is known as a cation.

                                      Now consider fluorine (F), a component of bones and teeth. Its atomic number is nine, and it has seven electrons in its valence shell. Thus, it is highly likely to bond with other atoms in such a way that fluorine accepts one electron (it is easier for fluorine to gain one electron than to donate seven electrons). When it does, its electrons will outnumber its protons by one, and it will have an overall negative charge. The ionized form of fluorine is called fluoride, and is written as F–. A negatively charged ion is known as an anion.

                                      Atoms that have more than one electron to donate or accept will end up with stronger positive or negative charges. A cation that has donated two electrons has a net charge of +2. Using magnesium (Mg) as an example, this can be written Mg++ or Mg2+. An anion that has accepted two electrons has a net charge of –2. The ionic form of selenium (Se), for example, is typically written Se2–.

                                      The opposite charges of cations and anions exert a moderately strong mutual attraction that keeps the atoms in close proximity forming an ionic bond. An ionic bond is an ongoing, close association between ions of opposite charge. The table salt you sprinkle on your food owes its existence to ionic bonding. As shown in Figure 2.8, sodium commonly donates an electron to chlorine, becoming the cation Na+. When chlorine accepts the electron, it becomes the chloride anion, Cl–. With their opposing charges, these two ions strongly attract each other.

                                      The top panel of this figure shows the orbit model of a sodium atom and a chlorine atom and arrows pointing towards the transfer of electrons from sodium to chlorine to form sodium and chlorine ions. The bottom panel shows sodium and chloride ions in a crystal structure.
                                      Figure 2.8Ionic Bonding
                                      (a) Sodium readily donates the solitary electron in its valence shell to chlorine, which needs only one electron to have a full valence shell. (b) The opposite electrical charges of the resulting sodium cation and chloride anion result in the formation of a bond of attraction called an ionic bond. (c) The attraction of many sodium and chloride ions results in the formation of large groupings called crystals.

                                      Water is an essential component of life because it is able to break the ionic bonds in salts to free the ions. In fact, in biological fluids, most individual atoms exist as ions. These dissolved ions produce electrical charges within the body. The behavior of these ions produces the tracings of heart and brain function observed as waves on an electrocardiogram (EKG or ECG) or an electroencephalogram (EEG). The electrical activity that derives from the interactions of the charged ions is why they are also called electrolytes.

                                      Covalent Bonds

                                      Unlike ionic bonds formed by the attraction between a cation’s positive charge and an anion’s negative charge, molecules formed by a covalent bond share electrons in a mutually stabilizing relationship. Like next-door neighbors whose kids hang out first at one home and then at the other, the atoms do not lose or gain electrons permanently. Instead, the electrons move back and forth between the elements. Because of the close sharing of pairs of electrons (one electron from each of two atoms), covalent bonds are stronger than ionic bonds.

                                      Nonpolar Covalent Bonds

                                      Figure 2.9 shows several common types of covalent bonds. Notice that the two covalently bonded atoms typically share just one or two electron pairs, though larger sharings are possible. The important concept to take from this is that in covalent bonds, electrons in the outermost valence shell are shared to fill the valence shells of both atoms, ultimately stabilizing both of the atoms involved. In a single covalent bond, a single electron is shared between two atoms, while in a double covalent bond, two pairs of electrons are shared between two atoms. There even are triple covalent bonds, where three atoms are shared.

                                      The top panel in this figure shows two hydrogen atoms sharing two electrons. The middle panel shows two oxygen atoms sharing four electrons, and the bottom panel shows two oxygen atoms and one carbon atom sharing 2 pairs of electrons each.
                                      Figure 2.9Covalent Bonding

                                      You can see that the covalent bonds shown in Figure 2.9 are balanced. The sharing of the negative electrons is relatively equal, as is the electrical pull of the positive protons in the nucleus of the atoms involved. This is why covalently bonded molecules that are electrically balanced in this way are described as nonpolar; that is, no region of the molecule is either more positive or more negative than any other.

                                      Polar Covalent Bonds

                                      Groups of legislators with completely opposite views on a particular issue are often described as “polarized” by news writers. In chemistry, a polar molecule is a molecule that contains regions that have opposite electrical charges. Polar molecules occur when atoms share electrons unequally, in polar covalent bonds.

                                      The most familiar example of a polar molecule is water (Figure 2.10). The molecule has three parts: one atom of oxygen, the nucleus of which contains eight protons, and two hydrogen atoms, whose nuclei each contain only one proton. Because every proton exerts an identical positive charge, a nucleus that contains eight protons exerts a charge eight times greater than a nucleus that contains one proton. This means that the negatively charged electrons present in the water molecule are more strongly attracted to the oxygen nucleus than to the hydrogen nuclei. Each hydrogen atom’s single negative electron therefore migrates toward the oxygen atom, making the oxygen end of their bond slightly more negative than the hydrogen end of their bond.

                                      This figure shows the structure of a water molecule. The top panel shows two oxygen atoms and one hydrogen atom with electrons in orbit and the shared electrons. The middle panel shows a three-dimensional model of a water molecule and the bottom panel shows the structural formula for water.
                                      Figure 2.10Polar Covalent Bonds in a Water Molecule

                                      What is true for the bonds is true for the water molecule as a whole; that is, the oxygen region has a slightly negative charge and the regions of the hydrogen atoms have a slightly positive charge. These charges are often referred to as “partial charges” because the strength of the charge is less than one full electron, as would occur in an ionic bond. As shown in Figure 2.10, regions of weak polarity are indicated with the Greek letter delta (∂) and a plus (+) or minus (–) sign.

                                      Even though a single water molecule is unimaginably tiny, it has mass, and the opposing electrical charges on the molecule pull that mass in such a way that it creates a shape somewhat like a triangular tent (see Figure 2.10b). This dipole, with the positive charges at one end formed by the hydrogen atoms at the “bottom” of the tent and the negative charge at the opposite end (the oxygen atom at the “top” of the tent) makes the charged regions highly likely to interact with charged regions of other polar molecules. For human physiology, the resulting bond is one of the most important formed by water—the hydrogen bond.

                                      Hydrogen Bonds

                                      A hydrogen bond is formed when a weakly positive hydrogen atom already bonded to one electronegative atom (for example, the oxygen in the water molecule) is attracted to another electronegative atom from another molecule. In other words, hydrogen bonds always include hydrogen that is already part of a polar molecule.

                                      The most common example of hydrogen bonding in the natural world occurs between molecules of water. It happens before your eyes whenever two raindrops merge into a larger bead, or a creek spills into a river. Hydrogen bonding occurs because the weakly negative oxygen atom in one water molecule is attracted to the weakly positive hydrogen atoms of two other water molecules (Figure 2.11).

                                      This figure shows three water molecules and the hydrogen bonds between them.
                                      Figure 2.11Hydrogen Bonds between Water Molecules
                                      Notice that the bonds occur between the weakly positive charge on the hydrogen atoms and the weakly negative charge on the oxygen atoms. Hydrogen bonds are relatively weak, and therefore are indicated with a dotted (rather than a solid) line.

                                      Water molecules also strongly attract other types of charged molecules as well as ions. This explains why “table salt,” for example, actually is a molecule called a “salt” in chemistry, which consists of equal numbers of positively-charged sodium (Na+) and negatively-charged chloride (Cl–), dissolves so readily in water, in this case forming dipole-ion bonds between the water and the electrically-charged ions (electrolytes). Water molecules also repel molecules with nonpolar covalent bonds, like fats, lipids, and oils. You can demonstrate this with a simple kitchen experiment: pour a teaspoon of vegetable oil, a compound formed by nonpolar covalent bonds, into a glass of water. Instead of instantly dissolving in the water, the oil forms a distinct bead because the polar water molecules repel the nonpolar oil.

                                      2.3Chemical Reactions*

                                      By the end of this section, you will be able to:

                                      • Distinguish between kinetic and potential energy, and between exergonic and endergonic chemical reactions

                                      • Identify four forms of energy important in human functioning

                                      • Describe the three basic types of chemical reactions

                                      • Identify several factors influencing the rate of chemical reactions

                                      • The Role of Energy in Chemical Reactions
                                      • Forms of Energy Important in Human Functioning
                                      • Characteristics of Chemical Reactions
                                      • Factors Influencing the Rate of Chemical Reactions
                                        • Properties of the Reactants
                                        • Temperature
                                        • Concentration and Pressure
                                        • Enzymes and Other Catalysts

                                      One characteristic of a living organism is metabolism, which is the sum total of all of the chemical reactions that go on to maintain that organism’s health and life. The bonding processes you have learned thus far are anabolic chemical reactions; that is, they form larger molecules from smaller molecules or atoms. But recall that metabolism can proceed in another direction: in catabolic chemical reactions, bonds between components of larger molecules break, releasing smaller molecules or atoms. Both types of reaction involve exchanges not only of matter, but of energy.

                                      The Role of Energy in Chemical Reactions

                                      Chemical reactions require a sufficient amount of energy to cause the matter to collide with enough precision and force that old chemical bonds can be broken and new ones formed. In general, kinetic energy is the form of energy powering any type of matter in motion. Imagine you are building a brick wall. The energy it takes to lift and place one brick atop another is kinetic energy—the energy matter possesses because of its motion. Once the wall is in place, it stores potential energy. Potential energy is the energy of position, or the energy matter possesses because of the positioning or structure of its components. If the brick wall collapses, the stored potential energy is released as kinetic energy as the bricks fall.

                                      In the human body, potential energy is stored in the bonds between atoms and molecules. Chemical energy is the form of potential energy in which energy is stored in chemical bonds. When those bonds are formed, chemical energy is invested, and when they break, chemical energy is released. Notice that chemical energy, like all energy, is neither created nor destroyed; rather, it is converted from one form to another. When you eat an energy bar before heading out the door for a hike, the honey, nuts, and other foods the bar contains are broken down and rearranged by your body into molecules that your muscle cells convert to kinetic energy.

                                      Chemical reactions that release more energy than they absorb are characterized as exergonic. The catabolism of the foods in your energy bar is an example. Some of the chemical energy stored in the bar is absorbed into molecules your body uses for fuel, but some of it is released—for example, as heat. In contrast, chemical reactions that absorb more energy than they release are endergonic. These reactions require energy input, and the resulting molecule stores not only the chemical energy in the original components, but also the energy that fueled the reaction. Because energy is neither created nor destroyed, where does the energy needed for endergonic reactions come from? In many cases, it comes from exergonic reactions.

                                      Forms of Energy Important in Human Functioning

                                      You have already learned that chemical energy is absorbed, stored, and released by chemical bonds. In addition to chemical energy, mechanical, radiant, and electrical energy are important in human functioning.

                                      • Mechanical energy, which is stored in physical systems such as machines, engines, or the human body, directly powers the movement of matter. When you lift a brick into place on a wall, your muscles provide the mechanical energy that moves the brick.

                                      • Radiant energy is energy emitted and transmitted as waves rather than matter. These waves vary in length from long radio waves and microwaves to short gamma waves emitted from decaying atomic nuclei. The full spectrum of radiant energy is referred to as the electromagnetic spectrum. The body uses the ultraviolet energy of sunlight to convert a compound in skin cells to vitamin D, which is essential to human functioning. The human eye evolved to see the wavelengths that comprise the colors of the rainbow, from red to violet, so that range in the spectrum is called “visible light.”

                                      • Electrical energy, supplied by electrolytes in cells and body fluids, contributes to the voltage changes that help transmit impulses in nerve and muscle cells.

                                      Characteristics of Chemical Reactions

                                      All chemical reactions begin with a reactant, the general term for the one or more substances that enter into the reaction. Sodium and chloride ions, for example, are the reactants in the production of table salt. The one or more substances produced by a chemical reaction are called the product.

                                      In chemical reactions, the components of the reactants—the elements involved and the number of atoms of each—are all present in the product(s). Similarly, there is nothing present in the products that are not present in the reactants. This is because chemical reactions are governed by the law of conservation of mass, which states that matter cannot be created or destroyed in a chemical reaction.

                                      Just as you can express mathematical calculations in equations such as 2 + 7 = 9, you can use chemical equations to show how reactants become products. As in math, chemical equations proceed from left to right, but instead of an equal sign, they employ an arrow or arrows indicating the direction in which the chemical reaction proceeds. For example, the chemical reaction in which one atom of nitrogen and three atoms of hydrogen produce ammonia would be written as N + 3H→ NH 3 . Correspondingly, the breakdown of ammonia into its components would be written as NH 3 →N + 3H.

                                      Notice that, in the first example, a nitrogen (N) atom and three hydrogen (H) atoms bond to form a compound. This anabolic reaction requires energy, which is then stored within the compound’s bonds. Such reactions are referred to as synthesis reactions. A synthesis reaction is a chemical reaction that results in the synthesis (joining) of components that were formerly separate (Figure 2.12a). Again, nitrogen and hydrogen are reactants in a synthesis reaction that yields ammonia as the product. The general equation for a synthesis reaction is A + B→AB.

                                      This figure shows three chemical reactions.
                                      Figure 2.12The Three Fundamental Chemical Reactions
                                      The atoms and molecules involved in the three fundamental chemical reactions can be imagined as words.

                                      In the second example, ammonia is catabolized into its smaller components, and the potential energy that had been stored in its bonds is released. Such reactions are referred to as decomposition reactions. A decomposition reaction is a chemical reaction that breaks down or “de-composes” something larger into its constituent parts (see Figure 2.12b). The general equation for a decomposition reaction is: AB→A+B .

                                      An exchange reaction is a chemical reaction in which both synthesis and decomposition occur, chemical bonds are both formed and broken, and chemical energy is absorbed, stored, and released (see Figure 2.12c). The simplest form of an exchange reaction might be: A+BC→AB+C . Notice that, to produce these products, B and C had to break apart in a decomposition reaction, whereas A and B had to bond in a synthesis reaction. A more complex exchange reaction might be: AB+CD→AC+BD . Another example might be: AB+CD→AD+BC .

                                      In theory, any chemical reaction can proceed in either direction under the right conditions. Reactants may synthesize into a product that is later decomposed. Reversibility is also a quality of exchange reactions. For instance, A+BC→AB+C could then reverse to AB+C→A+BC . This reversibility of a chemical reaction is indicated with a double arrow: A+BC⇄AB+C . Still, in the human body, many chemical reactions do proceed in a predictable direction, either one way or the other. You can think of this more predictable path as the path of least resistance because, typically, the alternate direction requires more energy.

                                      Factors Influencing the Rate of Chemical Reactions

                                      If you pour vinegar into baking soda, the reaction is instantaneous; the concoction will bubble and fizz. But many chemical reactions take time. A variety of factors influence the rate of chemical reactions. This section, however, will consider only the most important in human functioning.

                                      Properties of the Reactants

                                      If chemical reactions are to occur quickly, the atoms in the reactants have to have easy access to one another. Thus, the greater the surface area of the reactants, the more readily they will interact. When you pop a cube of cheese into your mouth, you chew it before you swallow it. Among other things, chewing increases the surface area of the food so that digestive chemicals can more easily get at it. As a general rule, gases tend to react faster than liquids or solids, again because it takes energy to separate particles of a substance, and gases by definition already have space between their particles. Similarly, the larger the molecule, the greater the number of total bonds, so reactions involving smaller molecules, with fewer total bonds, would be expected to proceed faster.

                                      In addition, recall that some elements are more reactive than others. Reactions that involve highly reactive elements like hydrogen proceed more quickly than reactions that involve less reactive elements. Reactions involving stable elements like helium are not likely to happen at all.

                                      Temperature

                                      Nearly all chemical reactions occur at a faster rate at higher temperatures. Recall that kinetic energy is the energy of matter in motion. The kinetic energy of subatomic particles increases in response to increases in thermal energy. The higher the temperature, the faster the particles move, and the more likely they are to come in contact and react.

                                      Concentration and Pressure

                                      If just a few people are dancing at a club, they are unlikely to step on each other’s toes. But as more and more people get up to dance—especially if the music is fast—collisions are likely to occur. It is the same with chemical reactions: the more particles present within a given space, the more likely those particles are to bump into one another. This means that chemists can speed up chemical reactions not only by increasing the concentration of particles—the number of particles in the space—but also by decreasing the volume of the space, which would correspondingly increase the pressure. If there were 100 dancers in that club, and the manager abruptly moved the party to a room half the size, the concentration of the dancers would double in the new space, and the likelihood of collisions would increase accordingly.

                                      Enzymes and Other Catalysts

                                      For two chemicals in nature to react with each other they first have to come into contact, and this occurs through random collisions. Because heat helps increase the kinetic energy of atoms, ions, and molecules, it promotes their collision. But in the body, extremely high heat—such as a very high fever—can damage body cells and be life-threatening. On the other hand, normal body temperature is not high enough to promote the chemical reactions that sustain life. That is where catalysts come in.

                                      In chemistry, a catalyst is a substance that increases the rate of a chemical reaction without itself undergoing any change. You can think of a catalyst as a chemical change agent. They help increase the rate and force at which atoms, ions, and molecules collide, thereby increasing the probability that their valence shell electrons will interact.

                                      The most important catalysts in the human body are enzymes. An enzyme is a catalyst composed of protein or ribonucleic acid (RNA), both of which will be discussed later in this chapter. Like all catalysts, enzymes work by lowering the level of energy that needs to be invested in a chemical reaction. A chemical reaction’s activation energy is the “threshold” level of energy needed to break the bonds in the reactants. Once those bonds are broken, new arrangements can form. Without an enzyme to act as a catalyst, a much larger investment of energy is needed to ignite a chemical reaction (Figure 2.13).

                                      The left panel shows a graph of energy versus progress of reaction in the absence of enzymes. The right panel shows the graph in the presence of enzymes.
                                      Figure 2.13Enzymes
                                      Enzymes decrease the activation energy required for a given chemical reaction to occur. (a) Without an enzyme, the energy input needed for a reaction to begin is high. (b) With the help of an enzyme, less energy is needed for a reaction to begin.

                                      Enzymes are critical to the body’s healthy functioning. They assist, for example, with the breakdown of food and its conversion to energy. In fact, most of the chemical reactions in the body are facilitated by enzymes.

                                      2.4Inorganic Compounds Essential to Human Functioning*

                                      By the end of this section, you will be able to:

                                      • Compare and contrast inorganic and organic compounds

                                      • Identify the properties of water that make it essential to life

                                      • Explain the role of salts in body functioning

                                      • Distinguish between acids and bases, and explain their role in pH

                                      • Discuss the role of buffers in helping the body maintain pH homeostasis

                                      • Water
                                        • Water as a Lubricant and Cushion
                                        • Water as a Heat Sink
                                        • Water as a Component of Liquid Mixtures
                                        • Concentrations of Solutes
                                        • The Role of Water in Chemical Reactions
                                      • Salts
                                      • Acids and Bases
                                        • Acids
                                        • Bases
                                        • The Concept of pH
                                        • Buffers

                                      The concepts you have learned so far in this chapter govern all forms of matter, and would work as a foundation for geology as well as biology. This section of the chapter narrows the focus to the chemistry of human life; that is, the compounds important for the body’s structure and function. In general, these compounds are either inorganic or organic.

                                      • An inorganic compound is a substance that does not contain both carbon and hydrogen. A great many inorganic compounds do contain hydrogen atoms, such as water (H2O) and the hydrochloric acid (HCl) produced by your stomach. In contrast, only a handful of inorganic compounds contain carbon atoms. Carbon dioxide (CO2) is one of the few examples.

                                      • An organic compound, then, is a substance that contains both carbon and hydrogen. Organic compounds are synthesized via covalent bonds within living organisms, including the human body. Recall that carbon and hydrogen are the second and third most abundant elements in your body. You will soon discover how these two elements combine in the foods you eat, in the compounds that make up your body structure, and in the chemicals that fuel your functioning.

                                      The following section examines the three groups of inorganic compounds essential to life: water, salts, acids, and bases. Organic compounds are covered later in the chapter.

                                      Water

                                      As much as 70 percent of an adult’s body weight is water. This water is contained both within the cells and between the cells that make up tissues and organs. Its several roles make water indispensable to human functioning.

                                      Water as a Lubricant and Cushion

                                      Water is a major component of many of the body’s lubricating fluids. Just as oil lubricates the hinge on a door, water in synovial fluid lubricates the actions of body joints, and water in pleural fluid helps the lungs expand and recoil with breathing. Watery fluids help keep food flowing through the digestive tract, and ensure that the movement of adjacent abdominal organs is friction free.

                                      Water also protects cells and organs from physical trauma, cushioning the brain within the skull, for example, and protecting the delicate nerve tissue of the eyes. Water cushions a developing fetus in the mother’s womb as well.

                                      Water as a Heat Sink

                                      A heat sink is a substance or object that absorbs and dissipates heat but does not experience a corresponding increase in temperature. In the body, water absorbs the heat generated by chemical reactions without greatly increasing in temperature. Moreover, when the environmental temperature soars, the water stored in the body helps keep the body cool. This cooling effect happens as warm blood from the body’s core flows to the blood vessels just under the skin and is transferred to the environment. At the same time, sweat glands release warm water in sweat. As the water evaporates into the air, it carries away heat, and then the cooler blood from the periphery circulates back to the body core.

                                      Water as a Component of Liquid Mixtures

                                      A mixture is a combination of two or more substances, each of which maintains its own chemical identity. In other words, the constituent substances are not chemically bonded into a new, larger chemical compound. The concept is easy to imagine if you think of powdery substances such as flour and sugar; when you stir them together in a bowl, they obviously do not bond to form a new compound. The room air you breathe is a gaseous mixture, containing three discrete elements—nitrogen, oxygen, and argon—and one compound, carbon dioxide. There are three types of liquid mixtures, all of which contain water as a key component. These are solutions, colloids, and suspensions.

                                      For cells in the body to survive, they must be kept moist in a water-based liquid called a solution. In chemistry, a liquid solution consists of a solvent that dissolves a substance called a solute. An important characteristic of solutions is that they are homogeneous; that is, the solute molecules are distributed evenly throughout the solution. If you were to stir a teaspoon of sugar into a glass of water, the sugar would dissolve into sugar molecules separated by water molecules. The ratio of sugar to water in the left side of the glass would be the same as the ratio of sugar to water in the right side of the glass. If you were to add more sugar, the ratio of sugar to water would change, but the distribution—provided you had stirred well—would still be even.

                                      Water is considered the “universal solvent” and it is believed that life cannot exist without water because of this. Water is certainly the most abundant solvent in the body; essentially all of the body’s chemical reactions occur among compounds dissolved in water. Because water molecules are polar, with regions of positive and negative electrical charge, water readily dissolves ionic compounds and polar covalent compounds. Such compounds are referred to as hydrophilic, or “water-loving.” As mentioned above, sugar dissolves well in water. This is because sugar molecules contain regions of hydrogen-oxygen polar bonds, making it hydrophilic. Nonpolar molecules, which do not readily dissolve in water, are called hydrophobic, or “water-fearing.”

                                      Concentrations of Solutes

                                      Various mixtures of solutes and water are described in chemistry. The concentration of a given solute is the number of particles of that solute in a given space (oxygen makes up about 21 percent of atmospheric air). In the bloodstream of humans, glucose concentration is usually measured in milligram (mg) per deciliter (dL), and in a healthy adult averages about 100 mg/dL. Another method of measuring the concentration of a solute is by its molarilty—which is moles (M) of the molecules per liter (L). The mole of an element is its atomic weight, while a mole of a compound is the sum of the atomic weights of its components, called the molecular weight. An often-used example is calculating a mole of glucose, with the chemical formula C6H12O6. Using the periodic table, the atomic weight of carbon (C) is 12.011 grams (g), and there are six carbons in glucose, for a total atomic weight of 72.066 g. Doing the same calculations for hydrogen (H) and oxygen (O), the molecular weight equals 180.156g (the “gram molecular weight” of glucose). When water is added to make one liter of solution, you have one mole (1M) of glucose. This is particularly useful in chemistry because of the relationship of moles to “Avogadro’s number.” A mole of any solution has the same number of particles in it: 6.02 × 1023. Many substances in the bloodstream and other tissue of the body are measured in thousandths of a mole, or millimoles (mM).

                                      A colloid is a mixture that is somewhat like a heavy solution. The solute particles consist of tiny clumps of molecules large enough to make the liquid mixture opaque (because the particles are large enough to scatter light). Familiar examples of colloids are milk and cream. In the thyroid glands, the thyroid hormone is stored as a thick protein mixture also called a colloid.

                                      A suspension is a liquid mixture in which a heavier substance is suspended temporarily in a liquid, but over time, settles out. This separation of particles from a suspension is called sedimentation. An example of sedimentation occurs in the blood test that establishes sedimentation rate, or sed rate. The test measures how quickly red blood cells in a test tube settle out of the watery portion of blood (known as plasma) over a set period of time. Rapid sedimentation of blood cells does not normally happen in the healthy body, but aspects of certain diseases can cause blood cells to clump together, and these heavy clumps of blood cells settle to the bottom of the test tube more quickly than do normal blood cells.

                                      The Role of Water in Chemical Reactions

                                      Two types of chemical reactions involve the creation or the consumption of water: dehydration synthesis and hydrolysis.

                                      • In dehydration synthesis, one reactant gives up an atom of hydrogen and another reactant gives up a hydroxyl group (OH) in the synthesis of a new product. In the formation of their covalent bond, a molecule of water is released as a byproduct (Figure 2.14). This is also sometimes referred to as a condensation reaction.

                                      • In hydrolysis, a molecule of water disrupts a compound, breaking its bonds. The water is itself split into H and OH. One portion of the severed compound then bonds with the hydrogen atom, and the other portion bonds with the hydroxyl group.

                                      These reactions are reversible, and play an important role in the chemistry of organic compounds (which will be discussed shortly).

                                      The top panel in this figure shows a dehydration-synthesis reaction, and the bottom panel shows a hydrolysis reaction.
                                      Figure 2.14Dehydration Synthesis and Hydrolysis
                                      Monomers, the basic units for building larger molecules, form polymers (two or more chemically-bonded monomers). (a) In dehydration synthesis, two monomers are covalently bonded in a reaction in which one gives up a hydroxyl group and the other a hydrogen atom. A molecule of water is released as a byproduct during dehydration reactions. (b) In hydrolysis, the covalent bond between two monomers is split by the addition of a hydrogen atom to one and a hydroxyl group to the other, which requires the contribution of one molecule of water.

                                      Salts

                                      Recall that salts are formed when ions form ionic bonds. In these reactions, one atom gives up one or more electrons, and thus becomes positively charged, whereas the other accepts one or more electrons and becomes negatively charged. You can now define a salt as a substance that, when dissolved in water, dissociates into ions other than H+ or OH–. This fact is important in distinguishing salts from acids and bases, discussed next.

                                      A typical salt, NaCl, dissociates completely in water (Figure 2.15). The positive and negative regions on the water molecule (the hydrogen and oxygen ends respectively) attract the negative chloride and positive sodium ions, pulling them away from each other. Again, whereas nonpolar and polar covalently bonded compounds break apart into molecules in solution, salts dissociate into ions. These ions are electrolytes; they are capable of conducting an electrical current in solution. This property is critical to the function of ions in transmitting nerve impulses and prompting muscle contraction.

                                      This figure shows a crystal lattice of sodium chloride interacting with water to form a hydrated sodium ion and a hydrated chloride ion.
                                      Figure 2.15Dissociation of Sodium Chloride in Water
                                      Notice that the crystals of sodium chloride dissociate not into molecules of NaCl, but into Na+ cations and Cl– anions, each completely surrounded by water molecules.

                                      Many other salts are important in the body. For example, bile salts produced by the liver help break apart dietary fats, and calcium phosphate salts form the mineral portion of teeth and bones.

                                      Acids and Bases

                                      Acids and bases, like salts, dissociate in water into electrolytes. Acids and bases can very much change the properties of the solutions in which they are dissolved.

                                      Acids

                                      An acid is a substance that releases hydrogen ions (H+) in solution (Figure 2.16a). Because an atom of hydrogen has just one proton and one electron, a positively charged hydrogen ion is simply a proton. This solitary proton is highly likely to participate in chemical reactions. Strong acids are compounds that release all of their H+ in solution; that is, they ionize completely. Hydrochloric acid (HCl), which is released from cells in the lining of the stomach, is a strong acid because it releases all of its H+ in the stomach’s watery environment. This strong acid aids in digestion and kills ingested microbes. Weak acids do not ionize completely; that is, some of their hydrogen ions remain bonded within a compound in solution. An example of a weak acid is vinegar, or acetic acid; it is called acetate after it gives up a proton.

                                      This figure shows four beakers containing different liquids.
                                      Figure 2.16Acids and Bases
                                      (a) In aqueous solution, an acid dissociates into hydrogen ions (H+) and anions. Nearly every molecule of a strong acid dissociates, producing a high concentration of H+. (b) In aqueous solution, a base dissociates into hydroxyl ions (OH–) and cations. Nearly every molecule of a strong base dissociates, producing a high concentration of OH–.

                                      Bases

                                      A base is a substance that releases hydroxyl ions (OH–) in solution, or one that accepts H+ already present in solution (see Figure 2.16b). The hydroxyl ions or other base combine with H+ present to form a water molecule, thereby removing H+ and reducing the solution’s acidity. Strong bases release most or all of their hydroxyl ions; weak bases release only some hydroxyl ions or absorb only a few H+. Food mixed with hydrochloric acid from the stomach would burn the small intestine, the next portion of the digestive tract after the stomach, if it were not for the release of bicarbonate (HCO3–), a weak base that attracts H+. Bicarbonate accepts some of the H+ protons, thereby reducing the acidity of the solution.

                                      The Concept of pH

                                      The relative acidity or alkalinity of a solution can be indicated by its pH. A solution’s pH is the negative, base-10 logarithm of the hydrogen ion (H+) concentration of the solution. As an example, a pH 4 solution has an H+ concentration that is ten times greater than that of a pH 5 solution. That is, a solution with a pH of 4 is ten times more acidic than a solution with a pH of 5. The concept of pH will begin to make more sense when you study the pH scale, like that shown in Figure 2.17. The scale consists of a series of increments ranging from 0 to 14. A solution with a pH of 7 is considered neutral—neither acidic nor basic. Pure water has a pH of 7. The lower the number below 7, the more acidic the solution, or the greater the concentration of H+. The concentration of hydrogen ions at each pH value is 10 times different than the next pH. For instance, a pH value of 4 corresponds to a proton concentration of 10–4 M, or 0.0001M, while a pH value of 5 corresponds to a proton concentration of 10–5 M, or 0.00001M. The higher the number above 7, the more basic (alkaline) the solution, or the lower the concentration of H+. Human urine, for example, is ten times more acidic than pure water, and HCl is 10,000,000 times more acidic than water.

                                      This figure shows a vertical arrow with the top half showing the basic scale and the bottom half showing the acidic scale. Different chemicals and their pH are also shown.
                                      Figure 2.17The pH Scale

                                      Buffers

                                      The pH of human blood normally ranges from 7.35 to 7.45, although it is typically identified as pH 7.4. At this slightly basic pH, blood can reduce the acidity resulting from the carbon dioxide (CO2) constantly being released into the bloodstream by the trillions of cells in the body. Homeostatic mechanisms (along with exhaling CO2 while breathing) normally keep the pH of blood within this narrow range. This is critical, because fluctuations—either too acidic or too alkaline—can lead to life-threatening disorders.

                                      All cells of the body depend on homeostatic regulation of acid–base balance at a pH of approximately 7.4. The body therefore has several mechanisms for this regulation, involving breathing, the excretion of chemicals in urine, and the internal release of chemicals collectively called buffers into body fluids. A buffer is a solution of a weak acid and its conjugate base. A buffer can neutralize small amounts of acids or bases in body fluids. For example, if there is even a slight decrease below 7.35 in the pH of a bodily fluid, the buffer in the fluid—in this case, acting as a weak base—will bind the excess hydrogen ions. In contrast, if pH rises above 7.45, the buffer will act as a weak acid and contribute hydrogen ions.

                                      Homeostatic Imbalances

                                      Acids and Bases

                                      Excessive acidity of the blood and other body fluids is known as acidosis. Common causes of acidosis are situations and disorders that reduce the effectiveness of breathing, especially the person’s ability to exhale fully, which causes a buildup of CO2 (and H+) in the bloodstream. Acidosis can also be caused by metabolic problems that reduce the level or function of buffers that act as bases, or that promote the production of acids. For instance, with severe diarrhea, too much bicarbonate can be lost from the body, allowing acids to build up in body fluids. In people with poorly managed diabetes (ineffective regulation of blood sugar), acids called ketones are produced as a form of body fuel. These can build up in the blood, causing a serious condition called diabetic ketoacidosis. Kidney failure, liver failure, heart failure, cancer, and other disorders also can prompt metabolic acidosis.

                                      In contrast, alkalosis is a condition in which the blood and other body fluids are too alkaline (basic). As with acidosis, respiratory disorders are a major cause; however, in respiratory alkalosis, carbon dioxide levels fall too low. Lung disease, aspirin overdose, shock, and ordinary anxiety can cause respiratory alkalosis, which reduces the normal concentration of H+.

                                      Metabolic alkalosis often results from prolonged, severe vomiting, which causes a loss of hydrogen and chloride ions (as components of HCl). Medications also can prompt alkalosis. These include diuretics that cause the body to lose potassium ions, as well as antacids when taken in excessive amounts, for instance by someone with persistent heartburn or an ulcer.

                                      2.5Organic Compounds Essential to Human Functioning*

                                      By the end of this section, you will be able to:

                                      • Identify four types of organic molecules essential to human functioning

                                      • Explain the chemistry behind carbon’s affinity for covalently bonding in organic compounds

                                      • Provide examples of three types of carbohydrates, and identify the primary functions of carbohydrates in the body

                                      • Discuss four types of lipids important in human functioning

                                      • Describe the structure of proteins, and discuss their importance to human functioning

                                      • Identify the building blocks of nucleic acids, and the roles of DNA, RNA, and ATP in human functioning

                                      • The Chemistry of Carbon
                                      • Carbohydrates
                                        • Monosaccharides
                                        • Disaccharides
                                        • Polysaccharides
                                        • Functions of Carbohydrates
                                      • Lipids
                                        • Triglycerides
                                        • Phospholipids
                                        • Steroids
                                        • Prostaglandins
                                      • Proteins
                                        • Microstructure of Proteins
                                        • Shape of Proteins
                                        • Proteins Function as Enzymes
                                        • Other Functions of Proteins
                                      • Nucleotides
                                        • Nucleic Acids
                                        • Adenosine Triphosphate

                                      Organic compounds typically consist of groups of carbon atoms covalently bonded to hydrogen, usually oxygen, and often other elements as well. Created by living things, they are found throughout the world, in soils and seas, commercial products, and every cell of the human body. The four types most important to human structure and function are carbohydrates, lipids, proteins, and nucleotides. Before exploring these compounds, you need to first understand the chemistry of carbon.

                                      The Chemistry of Carbon

                                      What makes organic compounds ubiquitous is the chemistry of their carbon core. Recall that carbon atoms have four electrons in their valence shell, and that the octet rule dictates that atoms tend to react in such a way as to complete their valence shell with eight electrons. Carbon atoms do not complete their valence shells by donating or accepting four electrons. Instead, they readily share electrons via covalent bonds.

                                      Commonly, carbon atoms share with other carbon atoms, often forming a long carbon chain referred to as a carbon skeleton. When they do share, however, they do not share all their electrons exclusively with each other. Rather, carbon atoms tend to share electrons with a variety of other elements, one of which is always hydrogen. Carbon and hydrogen groupings are called hydrocarbons. If you study the figures of organic compounds in the remainder of this chapter, you will see several with chains of hydrocarbons in one region of the compound.

                                      Many combinations are possible to fill carbon’s four “vacancies.” Carbon may share electrons with oxygen or nitrogen or other atoms in a particular region of an organic compound. Moreover, the atoms to which carbon atoms bond may also be part of a functional group. A functional group is a group of atoms linked by strong covalent bonds and tending to function in chemical reactions as a single unit. You can think of functional groups as tightly knit “cliques” whose members are unlikely to be parted. Five functional groups are important in human physiology; these are the hydroxyl, carboxyl, amino, methyl and phosphate groups (Table 2.1).

                                      Table 2.1.
                                      Functional Groups Important in Human Physiology
                                      Functional group Structural formula Importance
                                      Hydroxyl —O—H Hydroxyl groups are polar. They are components of all four types of organic compounds discussed in this chapter. They are involved in dehydration synthesis and hydrolysis reactions.
                                      Carboxyl O—C—OH Carboxyl groups are found within fatty acids, amino acids, and many other acids.
                                      Amino —N—H2 Amino groups are found within amino acids, the building blocks of proteins.
                                      Methyl —C—H3 Methyl groups are found within amino acids.
                                      Phosphate —P—O42– Phosphate groups are found within phospholipids and nucleotides.

                                      Carbon’s affinity for covalent bonding means that many distinct and relatively stable organic molecules nevertheless readily form larger, more complex molecules. Any large molecule is referred to as macromolecule (macro- = “large”), and the organic compounds in this section all fit this description. However, some macromolecules are made up of several “copies” of single units called monomer (mono- = “one”; -mer = “part”). Like beads in a long necklace, these monomers link by covalent bonds to form long polymers (poly- = “many”). There are many examples of monomers and polymers among the organic compounds.

                                      Monomers form polymers by engaging in dehydration synthesis (see Figure 2.14). As was noted earlier, this reaction results in the release of a molecule of water. Each monomer contributes: One gives up a hydrogen atom and the other gives up a hydroxyl group. Polymers are split into monomers by hydrolysis (-lysis = “rupture”). The bonds between their monomers are broken, via the donation of a molecule of water, which contributes a hydrogen atom to one monomer and a hydroxyl group to the other.

                                      Carbohydrates

                                      The term carbohydrate means “hydrated carbon.” Recall that the root hydro- indicates water. A carbohydrate is a molecule composed of carbon, hydrogen, and oxygen; in most carbohydrates, hydrogen and oxygen are found in the same two-to-one relative proportions they have in water. In fact, the chemical formula for a “generic” molecule of carbohydrate is (CH2O)n.

                                      Carbohydrates are referred to as saccharides, a word meaning “sugars.” Three forms are important in the body. Monosaccharides are the monomers of carbohydrates. Disaccharides (di- = “two”) are made up of two monomers. Polysaccharides are the polymers, and can consist of hundreds to thousands of monomers.

                                      Monosaccharides

                                      A monosaccharide is a monomer of carbohydrates. Five monosaccharides are important in the body. Three of these are the hexose sugars, so called because they each contain six atoms of carbon. These are glucose, fructose, and galactose, shown in Figure 2.18a. The remaining monosaccharides are the two pentose sugars, each of which contains five atoms of carbon. They are ribose and deoxyribose, shown in Figure 2.18b.

                                      This figure shows the structure of glucose, fructose, galactose, deoxyribose, and ribose.
                                      Figure 2.18Five Important Monosaccharides

                                      Disaccharides

                                      A disaccharide is a pair of monosaccharides. Disaccharides are formed via dehydration synthesis, and the bond linking them is referred to as a glycosidic bond (glyco- = “sugar”). Three disaccharides (shown in Figure 2.19) are important to humans. These are sucrose, commonly referred to as table sugar; lactose, or milk sugar; and maltose, or malt sugar. As you can tell from their common names, you consume these in your diet; however, your body cannot use them directly. Instead, in the digestive tract, they are split into their component monosaccharides via hydrolysis.

                                      This figure shows the structure of sucrose, lactose, and maltose.
                                      Figure 2.19Three Important Disaccharides
                                      All three important disaccharides form by dehydration synthesis.
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                                      Watch this video to observe the formation of a disaccharide. What happens when water encounters a glycosidic bond?

                                      Polysaccharides

                                      Polysaccharides can contain a few to a thousand or more monosaccharides. Three are important to the body (Figure 2.20):

                                      • Starches are polymers of glucose. They occur in long chains called amylose or branched chains called amylopectin, both of which are stored in plant-based foods and are relatively easy to digest.

                                      • Glycogen is also a polymer of glucose, but it is stored in the tissues of animals, especially in the muscles and liver. It is not considered a dietary carbohydrate because very little glycogen remains in animal tissues after slaughter; however, the human body stores excess glucose as glycogen, again, in the muscles and liver.

                                      • Cellulose, a polysaccharide that is the primary component of the cell wall of green plants, is the component of plant food referred to as “fiber”. In humans, cellulose/fiber is not digestible; however, dietary fiber has many health benefits. It helps you feel full so you eat less, it promotes a healthy digestive tract, and a diet high in fiber is thought to reduce the risk of heart disease and possibly some forms of cancer.

                                      This figure shows the structure of starch, glycogen, and cellulose.
                                      Figure 2.20Three Important Polysaccharides
                                      Three important polysaccharides are starches, glycogen, and fiber.

                                      Functions of Carbohydrates

                                      The body obtains carbohydrates from plant-based foods. Grains, fruits, and legumes and other vegetables provide most of the carbohydrate in the human diet, although lactose is found in dairy products.

                                      Although most body cells can break down other organic compounds for fuel, all body cells can use glucose. Moreover, nerve cells (neurons) in the brain, spinal cord, and through the peripheral nervous system, as well as red blood cells, can use only glucose for fuel. In the breakdown of glucose for energy, molecules of adenosine triphosphate, better known as ATP, are produced. Adenosine triphosphate (ATP) is composed of a ribose sugar, an adenine base, and three phosphate groups. ATP releases free energy when its phosphate bonds are broken, and thus supplies ready energy to the cell. More ATP is produced in the presence of oxygen (O2) than in pathways that do not use oxygen. The overall reaction for the conversion of the energy in glucose to energy stored in ATP can be written:

                                      (2.1) C6 H 12 O6  + 6 O 2  →  6 CO 2  + 6 H 2 O + ATP

                                      In addition to being a critical fuel source, carbohydrates are present in very small amounts in cells’ structure. For instance, some carbohydrate molecules bind with proteins to produce glycoproteins, and others combine with lipids to produce glycolipids, both of which are found in the membrane that encloses the contents of body cells.

                                      Lipids

                                      A lipid is one of a highly diverse group of compounds made up mostly of hydrocarbons. The few oxygen atoms they contain are often at the periphery of the molecule. Their nonpolar hydrocarbons make all lipids hydrophobic. In water, lipids do not form a true solution, but they may form an emulsion, which is the term for a mixture of solutions that do not mix well.

                                      Triglycerides

                                      A triglyceride is one of the most common dietary lipid groups, and the type found most abundantly in body tissues. This compound, which is commonly referred to as a fat, is formed from the synthesis of two types of molecules (Figure 2.21):

                                      • A glycerol backbone at the core of triglycerides, consists of three carbon atoms.

                                      • Three fatty acids, long chains of hydrocarbons with a carboxyl group and a methyl group at opposite ends, extend from each of the carbons of the glycerol.

                                      This image shows the reaction for the formation of triglycerides.
                                      Figure 2.21Triglycerides
                                      Triglycerides are composed of glycerol attached to three fatty acids via dehydration synthesis. Notice that glycerol gives up a hydrogen atom, and the carboxyl groups on the fatty acids each give up a hydroxyl group.

                                      Triglycerides form via dehydration synthesis. Glycerol gives up hydrogen atoms from its hydroxyl groups at each bond, and the carboxyl group on each fatty acid chain gives up a hydroxyl group. A total of three water molecules are thereby released.

                                      Fatty acid chains that have no double carbon bonds anywhere along their length and therefore contain the maximum number of hydrogen atoms are called saturated fatty acids. These straight, rigid chains pack tightly together and are solid or semi-solid at room temperature (Figure 2.22a). Butter and lard are examples, as is the fat found on a steak or in your own body. In contrast, fatty acids with one double carbon bond are kinked at that bond (Figure 2.22b). These monounsaturated fatty acids are therefore unable to pack together tightly, and are liquid at room temperature. Polyunsaturated fatty acids contain two or more double carbon bonds, and are also liquid at room temperature. Plant oils such as olive oil typically contain both mono- and polyunsaturated fatty acids.

                                      This diagram shows the chain structures of a saturated and an unsaturated fatty acid.
                                      Figure 2.22Fatty Acid Shapes
                                      The level of saturation of a fatty acid affects its shape. (a) Saturated fatty acid chains are straight. (b) Unsaturated fatty acid chains are kinked.

                                      Whereas a diet high in saturated fatty acids increases the risk of heart disease, a diet high in unsaturated fatty acids is thought to reduce the risk. This is especially true for the omega-3 unsaturated fatty acids found in cold-water fish such as salmon. These fatty acids have their first double carbon bond at the third hydrocarbon from the methyl group (referred to as the omega end of the molecule).

                                      Finally, trans fatty acids found in some processed foods, including some stick and tub margarines, are thought to be even more harmful to the heart and blood vessels than saturated fatty acids. Trans fats are created from unsaturated fatty acids (such as corn oil) when chemically treated to produce partially hydrogenated fats.

                                      As a group, triglycerides are a major fuel source for the body. When you are resting or asleep, a majority of the energy used to keep you alive is derived from triglycerides stored in your fat (adipose) tissues. Triglycerides also fuel long, slow physical activity such as gardening or hiking, and contribute a modest percentage of energy for vigorous physical activity. Dietary fat also assists the absorption and transport of the nonpolar fat-soluble vitamins A, D, E, and K. Additionally, stored body fat protects and cushions the body’s bones and internal organs, and acts as insulation to retain body heat.

                                      Fatty acids are also components of glycolipids, which are sugar-fat compounds found in the cell membrane. Lipoproteins are compounds in which the hydrophobic triglycerides are packaged in protein envelopes for transport in body fluids.

                                      Phospholipids

                                      As its name suggests, a phospholipid is a bond between the glycerol component of a lipid and a phosphorous molecule. In fact, phospholipids are similar in structure to triglycerides. However, instead of having three fatty acids, a phospholipid is generated from a diglyceride, a glycerol with just two fatty acid chains (Figure 2.23). The third binding site on the glycerol is taken up by the phosphate group, which in turn is attached to a polar “head” region of the molecule. Recall that triglycerides are nonpolar and hydrophobic. This still holds for the fatty acid portion of a phospholipid compound. However, the phosphate-containing group at the head of the compound is polar and thereby hydrophilic. In other words, one end of the molecule can interact with oil, and the other end with water. This makes phospholipids ideal emulsifiers, compounds that help disperse fats in aqueous liquids, and enables them to interact with both the watery interior of cells and the watery solution outside of cells as components of the cell membrane.

                                      This figure shows the chemical structure of different lipids.
                                      Figure 2.23Other Important Lipids
                                      (a) Phospholipids are composed of two fatty acids, glycerol, and a phosphate group. (b) Sterols are ring-shaped lipids. Shown here is cholesterol. (c) Prostaglandins are derived from unsaturated fatty acids. Prostaglandin E2 (PGE2) includes hydroxyl and carboxyl groups.

                                      Steroids

                                      A steroid compound (referred to as a sterol) has as its foundation a set of four hydrocarbon rings bonded to a variety of other atoms and molecules (see Figure 2.23b). Although both plants and animals synthesize sterols, the type that makes the most important contribution to human structure and function is cholesterol, which is synthesized by the liver in humans and animals and is also present in most animal-based foods. Like other lipids, cholesterol’s hydrocarbons make it hydrophobic; however, it has a polar hydroxyl head that is hydrophilic. Cholesterol is an important component of bile acids, compounds that help emulsify dietary fats. In fact, the word root chole- refers to bile. Cholesterol is also a building block of many hormones, signaling molecules that the body releases to regulate processes at distant sites. Finally, like phospholipids, cholesterol molecules are found in the cell membrane, where their hydrophobic and hydrophilic regions help regulate the flow of substances into and out of the cell.

                                      Prostaglandins

                                      Like a hormone, a prostaglandin is one of a group of signaling molecules, but prostaglandins are derived from unsaturated fatty acids (see Figure 2.23c). One reason that the omega-3 fatty acids found in fish are beneficial is that they stimulate the production of certain prostaglandins that help regulate aspects of blood pressure and inflammation, and thereby reduce the risk for heart disease. Prostaglandins also sensitize nerves to pain. One class of pain-relieving medications called nonsteroidal anti-inflammatory drugs (NSAIDs) works by reducing the effects of prostaglandins.

                                      Proteins

                                      You might associate proteins with muscle tissue, but in fact, proteins are critical components of all tissues and organs. A protein is an organic molecule composed of amino acids linked by peptide bonds. Proteins include the keratin in the epidermis of skin that protects underlying tissues, the collagen found in the dermis of skin, in bones, and in the meninges that cover the brain and spinal cord. Proteins are also components of many of the body’s functional chemicals, including digestive enzymes in the digestive tract, antibodies, the neurotransmitters that neurons use to communicate with other cells, and the peptide-based hormones that regulate certain body functions (for instance, growth hormone). While carbohydrates and lipids are composed of hydrocarbons and oxygen, all proteins also contain nitrogen (N), and many contain sulfur (S), in addition to carbon, hydrogen, and oxygen.

                                      Microstructure of Proteins

                                      Proteins are polymers made up of nitrogen-containing monomers called amino acids. An amino acid is a molecule composed of an amino group and a carboxyl group, together with a variable side chain. Just 20 different amino acids contribute to nearly all of the thousands of different proteins important in human structure and function. Body proteins contain a unique combination of a few dozen to a few hundred of these 20 amino acid monomers. All 20 of these amino acids share a similar structure (Figure 2.24). All consist of a central carbon atom to which the following are bonded:

                                      • a hydrogen atom

                                      • an alkaline (basic) amino group NH2 (see Table 2.1)

                                      • an acidic carboxyl group COOH (see Table 2.1)

                                      • a variable group

                                      This figure shows the structure of an amino acid.
                                      Figure 2.24Structure of an Amino Acid

                                      Notice that all amino acids contain both an acid (the carboxyl group) and a base (the amino group) (amine = “nitrogen-containing”). For this reason, they make excellent buffers, helping the body regulate acid–base balance. What distinguishes the 20 amino acids from one another is their variable group, which is referred to as a side chain or an R-group. This group can vary in size and can be polar or nonpolar, giving each amino acid its unique characteristics. For example, the side chains of two amino acids—cysteine and methionine—contain sulfur. Sulfur does not readily participate in hydrogen bonds, whereas all other amino acids do. This variation influences the way that proteins containing cysteine and methionine are assembled.

                                      Amino acids join via dehydration synthesis to form protein polymers (Figure 2.25). The unique bond holding amino acids together is called a peptide bond. A peptide bond is a covalent bond between two amino acids that forms by dehydration synthesis. A peptide, in fact, is a very short chain of amino acids. Strands containing fewer than about 100 amino acids are generally referred to as polypeptides rather than proteins.

                                      This figure shows the formation of a peptide bond, highlighted in blue.
                                      Figure 2.25Peptide Bond
                                      Different amino acids join together to form peptides, polypeptides, or proteins via dehydration synthesis. The bonds between the amino acids are peptide bonds.

                                      The body is able to synthesize most of the amino acids from components of other molecules; however, nine cannot be synthesized and have to be consumed in the diet. These are known as the essential amino acids.

                                      Free amino acids available for protein construction are said to reside in the amino acid pool within cells. Structures within cells use these amino acids when assembling proteins. If a particular essential amino acid is not available in sufficient quantities in the amino acid pool, however, synthesis of proteins containing it can slow or even cease.

                                      Shape of Proteins

                                      Just as a fork cannot be used to eat soup and a spoon cannot be used to spear meat, a protein’s shape is essential to its function. A protein’s shape is determined, most fundamentally, by the sequence of amino acids of which it is made (Figure 2.26a). The sequence is called the primary structure of the protein.

                                      This figure shows the secondary structure of peptides. The top panel shows a straight chain, the middle panel shows an alpha-helix and a beta sheet. The bottom panel shows the tertiary structure and fully folded protein.
                                      Figure 2.26The Shape of Proteins
                                      (a) The primary structure is the sequence of amino acids that make up the polypeptide chain. (b) The secondary structure, which can take the form of an alpha-helix or a beta-pleated sheet, is maintained by hydrogen bonds between amino acids in different regions of the original polypeptide strand. (c) The tertiary structure occurs as a result of further folding and bonding of the secondary structure. (d) The quaternary structure occurs as a result of interactions between two or more tertiary subunits. The example shown here is hemoglobin, a protein in red blood cells which transports oxygen to body tissues.

                                      Although some polypeptides exist as linear chains, most are twisted or folded into more complex secondary structures that form when bonding occurs between amino acids with different properties at different regions of the polypeptide. The most common secondary structure is a spiral called an alpha-helix. If you were to take a length of string and simply twist it into a spiral, it would not hold the shape. Similarly, a strand of amino acids could not maintain a stable spiral shape without the help of hydrogen bonds, which create bridges between different regions of the same strand (see Figure 2.26b). Less commonly, a polypeptide chain can form a beta-pleated sheet, in which hydrogen bonds form bridges between different regions of a single polypeptide that has folded back upon itself, or between two or more adjacent polypeptide chains.

                                      The secondary structure of proteins further folds into a compact three-dimensional shape, referred to as the protein’s tertiary structure (see Figure 2.26c). In this configuration, amino acids that had been very distant in the primary chain can be brought quite close via hydrogen bonds or, in proteins containing cysteine, via disulfide bonds. A disulfide bond is a covalent bond between sulfur atoms in a polypeptide. Often, two or more separate polypeptides bond to form an even larger protein with a quaternary structure (see Figure 2.26d). The polypeptide subunits forming a quaternary structure can be identical or different. For instance, hemoglobin, the protein found in red blood cells is composed of four tertiary polypeptides, two of which are called alpha chains and two of which are called beta chains.

                                      When they are exposed to extreme heat, acids, bases, and certain other substances, proteins will denature. Denaturation is a change in the structure of a molecule through physical or chemical means. Denatured proteins lose their functional shape and are no longer able to carry out their jobs. An everyday example of protein denaturation is the curdling of milk when acidic lemon juice is added.

                                      The contribution of the shape of a protein to its function can hardly be exaggerated. For example, the long, slender shape of protein strands that make up muscle tissue is essential to their ability to contract (shorten) and relax (lengthen). As another example, bones contain long threads of a protein called collagen that acts as scaffolding upon which bone minerals are deposited. These elongated proteins, called fibrous proteins, are strong and durable and typically hydrophobic.

                                      In contrast, globular proteins are globes or spheres that tend to be highly reactive and are hydrophilic. The hemoglobin proteins packed into red blood cells are an example (see Figure 2.26d); however, globular proteins are abundant throughout the body, playing critical roles in most body functions. Enzymes, introduced earlier as protein catalysts, are examples of this. The next section takes a closer look at the action of enzymes.

                                      Proteins Function as Enzymes

                                      If you were trying to type a paper, and every time you hit a key on your laptop there was a delay of six or seven minutes before you got a response, you would probably get a new laptop. In a similar way, without enzymes to catalyze chemical reactions, the human body would be nonfunctional. It functions only because enzymes function.

                                      Enzymatic reactions—chemical reactions catalyzed by enzymes—begin when substrates bind to the enzyme. A substrate is a reactant in an enzymatic reaction. This occurs on regions of the enzyme known as active sites (Figure 2.27). Any given enzyme catalyzes just one type of chemical reaction. This characteristic, called specificity, is due to the fact that a substrate with a particular shape and electrical charge can bind only to an active site corresponding to that substrate.

                                      This image shows the steps in which an enzyme can act. The substrate is shown binding to the enzyme, forming a product, and the detachment of the product.
                                      Figure 2.27Steps in an Enzymatic Reaction
                                      (a) Substrates approach active sites on enzyme. (b) Substrates bind to active sites, producing an enzyme–substrate complex. (c) Changes internal to the enzyme–substrate complex facilitate interaction of the substrates. (d) Products are released and the enzyme returns to its original form, ready to facilitate another enzymatic reaction.

                                      Binding of a substrate produces an enzyme–substrate complex. It is likely that enzymes speed up chemical reactions in part because the enzyme–substrate complex undergoes a set of temporary and reversible changes that cause the substrates to be oriented toward each other in an optimal position to facilitate their interaction. This promotes increased reaction speed. The enzyme then releases the product(s), and resumes its original shape. The enzyme is then free to engage in the process again, and will do so as long as substrate remains.

                                      Other Functions of Proteins

                                      Advertisements for protein bars, powders, and shakes all say that protein is important in building, repairing, and maintaining muscle tissue, but the truth is that proteins contribute to all body tissues, from the skin to the brain cells. Also, certain proteins act as hormones, chemical messengers that help regulate body functions, For example, growth hormone is important for skeletal growth, among other roles.

                                      As was noted earlier, the basic and acidic components enable proteins to function as buffers in maintaining acid–base balance, but they also help regulate fluid–electrolyte balance. Proteins attract fluid, and a healthy concentration of proteins in the blood, the cells, and the spaces between cells helps ensure a balance of fluids in these various “compartments.” Moreover, proteins in the cell membrane help to transport electrolytes in and out of the cell, keeping these ions in a healthy balance. Like lipids, proteins can bind with carbohydrates. They can thereby produce glycoproteins or proteoglycans, both of which have many functions in the body.

                                      The body can use proteins for energy when carbohydrate and fat intake is inadequate, and stores of glycogen and adipose tissue become depleted. However, since there is no storage site for protein except functional tissues, using protein for energy causes tissue breakdown, and results in body wasting.

                                      Nucleotides

                                      The fourth type of organic compound important to human structure and function are the nucleotides (Figure 2.28). A nucleotide is one of a class of organic compounds composed of three subunits:

                                      • one or more phosphate groups

                                      • a pentose sugar: either deoxyribose or ribose

                                      • a nitrogen-containing base: adenine, cytosine, guanine, thymine, or uracil

                                      Nucleotides can be assembled into nucleic acids (DNA or RNA) or the energy compound adenosine triphosphate.

                                      This figure shows the structure of nucleotides.
                                      Figure 2.28Nucleotides
                                      (a) The building blocks of all nucleotides are one or more phosphate groups, a pentose sugar, and a nitrogen-containing base. (b) The nitrogen-containing bases of nucleotides. (c) The two pentose sugars of DNA and RNA.

                                      Nucleic Acids

                                      The nucleic acids differ in their type of pentose sugar. Deoxyribonucleic acid (DNA) is nucleotide that stores genetic information. DNA contains deoxyribose (so-called because it has one less atom of oxygen than ribose) plus one phosphate group and one nitrogen-containing base. The “choices” of base for DNA are adenine, cytosine, guanine, and thymine. Ribonucleic acid (RNA) is a ribose-containing nucleotide that helps manifest the genetic code as protein. RNA contains ribose, one phosphate group, and one nitrogen-containing base, but the “choices” of base for RNA are adenine, cytosine, guanine, and uracil.

                                      The nitrogen-containing bases adenine and guanine are classified as purines. A purine is a nitrogen-containing molecule with a double ring structure, which accommodates several nitrogen atoms. The bases cytosine, thymine (found in DNA only) and uracil (found in RNA only) are pyramidines. A pyramidine is a nitrogen-containing base with a single ring structure

                                      Bonds formed by dehydration synthesis between the pentose sugar of one nucleic acid monomer and the phosphate group of another form a “backbone,” from which the components’ nitrogen-containing bases protrude. In DNA, two such backbones attach at their protruding bases via hydrogen bonds. These twist to form a shape known as a double helix (Figure 2.29). The sequence of nitrogen-containing bases within a strand of DNA form the genes that act as a molecular code instructing cells in the assembly of amino acids into proteins. Humans have almost 22,000 genes in their DNA, locked up in the 46 chromosomes inside the nucleus of each cell (except red blood cells which lose their nuclei during development). These genes carry the genetic code to build one’s body, and are unique for each individual except identical twins.

                                      This figure shows a double helix.
                                      Figure 2.29DNA
                                      In the DNA double helix, two strands attach via hydrogen bonds between the bases of the component nucleotides.

                                      In contrast, RNA consists of a single strand of sugar-phosphate backbone studded with bases. Messenger RNA (mRNA) is created during protein synthesis to carry the genetic instructions from the DNA to the cell’s protein manufacturing plants in the cytoplasm, the ribosomes.

                                      Adenosine Triphosphate

                                      The nucleotide adenosine triphosphate (ATP), is composed of a ribose sugar, an adenine base, and three phosphate groups (Figure 2.30). ATP is classified as a high energy compound because the two covalent bonds linking its three phosphates store a significant amount of potential energy. In the body, the energy released from these high energy bonds helps fuel the body’s activities, from muscle contraction to the transport of substances in and out of cells to anabolic chemical reactions.

                                      This figure shows the structure of ATP.
                                      Figure 2.30Structure of Adenosine Triphosphate (ATP)

                                      When a phosphate group is cleaved from ATP, the products are adenosine diphosphate (ADP) and inorganic phosphate (Pi). This hydrolysis reaction can be written:

                                      (2.2) ATP + H 2 O →  ADP + P i  + energy

                                      Removal of a second phosphate leaves adenosine monophosphate (AMP) and two phosphate groups. Again, these reactions also liberate the energy that had been stored in the phosphate-phosphate bonds. They are reversible, too, as when ADP undergoes phosphorylation. Phosphorylation is the addition of a phosphate group to an organic compound, in this case, resulting in ATP. In such cases, the same level of energy that had been released during hydrolysis must be reinvested to power dehydration synthesis.

                                      Cells can also transfer a phosphate group from ATP to another organic compound. For example, when glucose first enters a cell, a phosphate group is transferred from ATP, forming glucose phosphate (C6H12O6—P) and ADP. Once glucose is phosphorylated in this way, it can be stored as glycogen or metabolized for immediate energy.

                                      Glossary

                                      acid

                                      compound that releases hydrogen ions (H+) in solution

                                      activation energy

                                      amount of energy greater than the energy contained in the reactants, which must be overcome for a reaction to proceed

                                      adenosine triphosphate (ATP)

                                      nucleotide containing ribose and an adenine base that is essential in energy transfer

                                      amino acid

                                      building block of proteins; characterized by an amino and carboxyl functional groups and a variable side-chain

                                      anion

                                      atom with a negative charge

                                      atom

                                      smallest unit of an element that retains the unique properties of that element

                                      atomic number

                                      number of protons in the nucleus of an atom

                                      base

                                      compound that accepts hydrogen ions (H+) in solution

                                      bond

                                      electrical force linking atoms

                                      buffer

                                      solution containing a weak acid or a weak base that opposes wide fluctuations in the pH of body fluids

                                      carbohydrate

                                      class of organic compounds built from sugars, molecules containing carbon, hydrogen, and oxygen in a 1-2-1 ratio

                                      catalyst

                                      substance that increases the rate of a chemical reaction without itself being changed in the process

                                      cation

                                      atom with a positive charge

                                      chemical energy

                                      form of energy that is absorbed as chemical bonds form, stored as they are maintained, and released as they are broken

                                      colloid

                                      liquid mixture in which the solute particles consist of clumps of molecules large enough to scatter light

                                      compound

                                      substance composed of two or more different elements joined by chemical bonds

                                      concentration

                                      number of particles within a given space

                                      covalent bond

                                      chemical bond in which two atoms share electrons, thereby completing their valence shells

                                      decomposition reaction

                                      type of catabolic reaction in which one or more bonds within a larger molecule are broken, resulting in the release of smaller molecules or atoms

                                      denaturation

                                      change in the structure of a molecule through physical or chemical means

                                      deoxyribonucleic acid (DNA)

                                      deoxyribose-containing nucleotide that stores genetic information

                                      disaccharide

                                      pair of carbohydrate monomers bonded by dehydration synthesis via a glycosidic bond

                                      disulfide bond

                                      covalent bond formed within a polypeptide between sulfide groups of sulfur-containing amino acids, for example, cysteine

                                      electron shell

                                      area of space a given distance from an atom’s nucleus in which electrons are grouped

                                      electron

                                      subatomic particle having a negative charge and nearly no mass; found orbiting the atom’s nucleus

                                      element

                                      substance that cannot be created or broken down by ordinary chemical means

                                      enzyme

                                      protein or RNA that catalyzes chemical reactions

                                      exchange reaction

                                      type of chemical reaction in which bonds are both formed and broken, resulting in the transfer of components

                                      functional group

                                      group of atoms linked by strong covalent bonds that tends to behave as a distinct unit in chemical reactions with other atoms

                                      hydrogen bond

                                      dipole-dipole bond in which a hydrogen atom covalently bonded to an electronegative atom is weakly attracted to a second electronegative atom

                                      inorganic compound

                                      substance that does not contain both carbon and hydrogen

                                      ionic bond

                                      attraction between an anion and a cation

                                      ion

                                      atom with an overall positive or negative charge

                                      isotope

                                      one of the variations of an element in which the number of neutrons differ from each other

                                      kinetic energy

                                      energy that matter possesses because of its motion

                                      lipid

                                      class of nonpolar organic compounds built from hydrocarbons and distinguished by the fact that they are not soluble in water

                                      macromolecule

                                      large molecule formed by covalent bonding

                                      mass number

                                      sum of the number of protons and neutrons in the nucleus of an atom

                                      matter

                                      physical substance; that which occupies space and has mass

                                      molecule

                                      two or more atoms covalently bonded together

                                      monosaccharide

                                      monomer of carbohydrate; also known as a simple sugar

                                      neutron

                                      heavy subatomic particle having no electrical charge and found in the atom’s nucleus

                                      nucleotide

                                      class of organic compounds composed of one or more phosphate groups, a pentose sugar, and a base

                                      organic compound

                                      substance that contains both carbon and hydrogen

                                      pH

                                      negative logarithm of the hydrogen ion (H+) concentration of a solution

                                      peptide bond

                                      covalent bond formed by dehydration synthesis between two amino acids

                                      periodic table of the elements

                                      arrangement of the elements in a table according to their atomic number; elements having similar properties because of their electron arrangements compose columns in the table, while elements having the same number of valence shells compose rows in the table

                                      phospholipid

                                      a lipid compound in which a phosphate group is combined with a diglyceride

                                      phosphorylation

                                      addition of one or more phosphate groups to an organic compound

                                      polar molecule

                                      molecule with regions that have opposite charges resulting from uneven numbers of electrons in the nuclei of the atoms participating in the covalent bond

                                      polysaccharide

                                      compound consisting of more than two carbohydrate monomers bonded by dehydration synthesis via glycosidic bonds

                                      potential energy

                                      stored energy matter possesses because of the positioning or structure of its components

                                      product

                                      one or more substances produced by a chemical reaction

                                      prostaglandin

                                      lipid compound derived from fatty acid chains and important in regulating several body processes

                                      protein

                                      class of organic compounds that are composed of many amino acids linked together by peptide bonds

                                      proton

                                      heavy subatomic particle having a positive charge and found in the atom’s nucleus

                                      purine

                                      nitrogen-containing base with a double ring structure; adenine and guanine

                                      pyrimidine

                                      nitrogen-containing base with a single ring structure; cytosine, thiamine, and uracil

                                      radioactive isotope

                                      unstable, heavy isotope that gives off subatomic particles, or electromagnetic energy, as it decays; also called radioisotopes

                                      reactant

                                      one or more substances that enter into the reaction

                                      ribonucleic acid (RNA)

                                      ribose-containing nucleotide that helps manifest the genetic code as protein

                                      solution

                                      homogeneous liquid mixture in which a solute is dissolved into molecules within a solvent

                                      steroid

                                      (also, sterol) lipid compound composed of four hydrocarbon rings bonded to a variety of other atoms and molecules

                                      substrate

                                      reactant in an enzymatic reaction

                                      suspension

                                      liquid mixture in which particles distributed in the liquid settle out over time

                                      synthesis reaction

                                      type of anabolic reaction in which two or more atoms or molecules bond, resulting in the formation of a larger molecule

                                      triglyceride

                                      lipid compound composed of a glycerol molecule bonded with three fatty acid chains

                                      valence shell

                                      outermost electron shell of an atom

                                      Chapter Review
                                      2.. Introduction
                                      2.1. Elements and Atoms: The Building Blocks of Matter

                                      The human body is composed of elements, the most abundant of which are oxygen (O), carbon (C), hydrogen (H) and nitrogen (N). You obtain these elements from the foods you eat and the air you breathe. The smallest unit of an element that retains all of the properties of that element is an atom. But, atoms themselves contain many subatomic particles, the three most important of which are protons, neutrons, and electrons. These particles do not vary in quality from one element to another; rather, what gives an element its distinctive identification is the quantity of its protons, called its atomic number. Protons and neutrons contribute nearly all of an atom’s mass; the number of protons and neutrons is an element’s mass number. Heavier and lighter versions of the same element can occur in nature because these versions have different numbers of neutrons. Different versions of an element are called isotopes.

                                      The tendency of an atom to be stable or to react readily with other atoms is largely due to the behavior of the electrons within the atom’s outermost electron shell, called its valence shell. Helium, as well as larger atoms with eight electrons in their valence shell, is unlikely to participate in chemical reactions because they are stable. All other atoms tend to accept, donate, or share electrons in a process that brings the electrons in their valence shell to eight (or in the case of hydrogen, to two).

                                      2.2. Chemical Bonds

                                      Each moment of life, atoms of oxygen, carbon, hydrogen, and the other elements of the human body are making and breaking chemical bonds. Ions are charged atoms that form when an atom donates or accepts one or more negatively charged electrons. Cations (ions with a positive charge) are attracted to anions (ions with a negative charge). This attraction is called an ionic bond. In covalent bonds, the participating atoms do not lose or gain electrons, but rather share them. Molecules with nonpolar covalent bonds are electrically balanced, and have a linear three-dimensional shape. Molecules with polar covalent bonds have “poles”—regions of weakly positive and negative charge—and have a triangular three-dimensional shape. An atom of oxygen and two atoms of hydrogen form water molecules by means of polar covalent bonds. Hydrogen bonds link hydrogen atoms already participating in polar covalent bonds to anions or electronegative regions of other polar molecules. Hydrogen bonds link water molecules, resulting in the properties of water that are important to living things.

                                      2.3. Chemical Reactions

                                      Chemical reactions, in which chemical bonds are broken and formed, require an initial investment of energy. Kinetic energy, the energy of matter in motion, fuels the collisions of atoms, ions, and molecules that are necessary if their old bonds are to break and new ones to form. All molecules store potential energy, which is released when their bonds are broken.

                                      Four forms of energy essential to human functioning are: chemical energy, which is stored and released as chemical bonds are formed and broken; mechanical energy, which directly powers physical activity; radiant energy, emitted as waves such as in sunlight; and electrical energy, the power of moving electrons.

                                      Chemical reactions begin with reactants and end with products. Synthesis reactions bond reactants together, a process that requires energy, whereas decomposition reactions break the bonds within a reactant and thereby release energy. In exchange reactions, bonds are both broken and formed, and energy is exchanged.

                                      The rate at which chemical reactions occur is influenced by several properties of the reactants: temperature, concentration and pressure, and the presence or absence of a catalyst. An enzyme is a catalytic protein that speeds up chemical reactions in the human body.

                                      2.4. Inorganic Compounds Essential to Human Functioning

                                      Inorganic compounds essential to human functioning include water, salts, acids, and bases. These compounds are inorganic; that is, they do not contain both hydrogen and carbon. Water is a lubricant and cushion, a heat sink, a component of liquid mixtures, a byproduct of dehydration synthesis reactions, and a reactant in hydrolysis reactions. Salts are compounds that, when dissolved in water, dissociate into ions other than H+ or OH–. In contrast, acids release H+ in solution, making it more acidic. Bases accept H+, thereby making the solution more alkaline (caustic).

                                      The pH of any solution is its relative concentration of H+. A solution with pH 7 is neutral. Solutions with pH below 7 are acids, and solutions with pH above 7 are bases. A change in a single digit on the pH scale (e.g., from 7 to 8) represents a ten-fold increase or decrease in the concentration of H+. In a healthy adult, the pH of blood ranges from 7.35 to 7.45. Homeostatic control mechanisms important for keeping blood in a healthy pH range include chemicals called buffers, weak acids and weak bases released when the pH of blood or other body fluids fluctuates in either direction outside of this normal range.

                                      2.5. Organic Compounds Essential to Human Functioning

                                      Organic compounds essential to human functioning include carbohydrates, lipids, proteins, and nucleotides. These compounds are said to be organic because they contain both carbon and hydrogen. Carbon atoms in organic compounds readily share electrons with hydrogen and other atoms, usually oxygen, and sometimes nitrogen. Carbon atoms also may bond with one or more functional groups such as carboxyls, hydroxyls, aminos, or phosphates. Monomers are single units of organic compounds. They bond by dehydration synthesis to form polymers, which can in turn be broken by hydrolysis.

                                      Carbohydrate compounds provide essential body fuel. Their structural forms include monosaccharides such as glucose, disaccharides such as lactose, and polysaccharides, including starches (polymers of glucose), glycogen (the storage form of glucose), and fiber. All body cells can use glucose for fuel. It is converted via an oxidation-reduction reaction to ATP.

                                      Lipids are hydrophobic compounds that provide body fuel and are important components of many biological compounds. Triglycerides are the most abundant lipid in the body, and are composed of a glycerol backbone attached to three fatty acid chains. Phospholipids are compounds composed of a diglyceride with a phosphate group attached at the molecule’s head. The result is a molecule with polar and nonpolar regions. Steroids are lipids formed of four hydrocarbon rings. The most important is cholesterol. Prostaglandins are signaling molecules derived from unsaturated fatty acids.

                                      Proteins are critical components of all body tissues. They are made up of monomers called amino acids, which contain nitrogen, joined by peptide bonds. Protein shape is critical to its function. Most body proteins are globular. An example is enzymes, which catalyze chemical reactions.

                                      Nucleotides are compounds with three building blocks: one or more phosphate groups, a pentose sugar, and a nitrogen-containing base. DNA and RNA are nucleic acids that function in protein synthesis. ATP is the body’s fundamental molecule of energy transfer. Removal or addition of phosphates releases or invests energy.

                                      Interactive Link Questions
                                      2.. Introduction
                                      2.1. Elements and Atoms: The Building Blocks of Matter
                                      Exercise 1.

                                      Visit this website to view the periodic table. In the periodic table of the elements, elements in a single column have the same number of electrons that can participate in a chemical reaction. These electrons are known as “valence electrons.” For example, the elements in the first column all have a single valence electron—an electron that can be “donated” in a chemical reaction with another atom. What is the meaning of a mass number shown in parentheses?

                                      (Return to Exercise)

                                      The mass number is the total number of protons and neutrons in the nucleus of an atom.

                                      2.2. Chemical Bonds
                                      Exercise 10.

                                      Visit this website to learn about electrical energy and the attraction/repulsion of charges. What happens to the charged electroscope when a conductor is moved between its plastic sheets, and why?

                                      (Return to Exercise)

                                      The plastic sheets jump to the nail (the conductor), because the conductor takes on electrons from the electroscope, reducing the repellant force of the two sheets.

                                      2.3. Chemical Reactions
                                      2.4. Inorganic Compounds Essential to Human Functioning
                                      2.5. Organic Compounds Essential to Human Functioning
                                      Exercise 34.

                                      Watch this video to observe the formation of a disaccharide. What happens when water encounters a glycosidic bond?

                                      (Return to Exercise)

                                      The water hydrolyses, or breaks, the glycosidic bond, forming two monosaccharides.

                                      Review Questions
                                      2.. Introduction
                                      2.1. Elements and Atoms: The Building Blocks of Matter
                                      Exercise 2.

                                      Together, just four elements make up more than 95 percent of the body’s mass. These include ________.

                                      1. calcium, magnesium, iron, and carbon

                                      2. oxygen, calcium, iron, and nitrogen

                                      3. sodium, chlorine, carbon, and hydrogen

                                      4. oxygen, carbon, hydrogen, and nitrogen

                                      (Return to Exercise)

                                      D

                                      Exercise 3.

                                      The smallest unit of an element that still retains the distinctive behavior of that element is an ________.

                                      1. electron

                                      2. atom

                                      3. elemental particle

                                      4. isotope

                                      (Return to Exercise)

                                      B

                                      Exercise 4.

                                      The characteristic that gives an element its distinctive properties is its number of ________.

                                      1. protons

                                      2. neutrons

                                      3. electrons

                                      4. atoms

                                      (Return to Exercise)

                                      A

                                      Exercise 5.

                                      On the periodic table of the elements, mercury (Hg) has an atomic number of 80 and a mass number of 200.59. It has seven stable isotopes. The most abundant of these probably have ________.

                                      1. about 80 neutrons each

                                      2. fewer than 80 neutrons each

                                      3. more than 80 neutrons each

                                      4. more electrons than neutrons

                                      (Return to Exercise)

                                      C

                                      Exercise 6.

                                      Nitrogen has an atomic number of seven. How many electron shells does it likely have?

                                      1. one

                                      2. two

                                      3. three

                                      4. four

                                      (Return to Exercise)

                                      B

                                      2.2. Chemical Bonds
                                      Exercise 11.

                                      Which of the following is a molecule, but not a compound?

                                      1. H2O

                                      2. 2H

                                      3. H2

                                      4. H+

                                      (Return to Exercise)

                                      C

                                      Exercise 12.

                                      A molecule of ammonia contains one atom of nitrogen and three atoms of hydrogen. These are linked with ________.

                                      1. ionic bonds

                                      2. nonpolar covalent bonds

                                      3. polar covalent bonds

                                      4. hydrogen bonds

                                      (Return to Exercise)

                                      C

                                      Exercise 13.

                                      When an atom donates an electron to another atom, it becomes

                                      1. an ion

                                      2. an anion

                                      3. nonpolar

                                      4. all of the above

                                      (Return to Exercise)

                                      A

                                      Exercise 14.

                                      A substance formed of crystals of equal numbers of cations and anions held together by ionic bonds is called a(n) ________.

                                      1. noble gas

                                      2. salt

                                      3. electrolyte

                                      4. dipole

                                      (Return to Exercise)

                                      B

                                      Exercise 15.

                                      Which of the following statements about chemical bonds is true?

                                      1. Covalent bonds are stronger than ionic bonds.

                                      2. Hydrogen bonds occur between two atoms of hydrogen.

                                      3. Bonding readily occurs between nonpolar and polar molecules.

                                      4. A molecule of water is unlikely to bond with an ion.

                                      (Return to Exercise)

                                      A

                                      2.3. Chemical Reactions
                                      Exercise 19.

                                      The energy stored in a foot of snow on a steep roof is ________.

                                      1. potential energy

                                      2. kinetic energy

                                      3. radiant energy

                                      4. activation energy

                                      (Return to Exercise)

                                      A

                                      Exercise 20.

                                      The bonding of calcium, phosphorus, and other elements produces mineral crystals that are found in bone. This is an example of a(n) ________ reaction.

                                      1. catabolic

                                      2. synthesis

                                      3. decomposition

                                      4. exchange

                                      (Return to Exercise)

                                      B

                                      Exercise 21.

                                      AB→A+B is a general notation for a(n) ________ reaction.

                                      1. anabolic

                                      2. endergonic

                                      3. decomposition

                                      4. exchange

                                      (Return to Exercise)

                                      C

                                      Exercise 22.

                                      ________ reactions release energy.

                                      1. Catabolic

                                      2. Exergonic

                                      3. Decomposition

                                      4. Catabolic, exergonic, and decomposition

                                      (Return to Exercise)

                                      D

                                      Exercise 23.

                                      Which of the following combinations of atoms is most likely to result in a chemical reaction?

                                      1. hydrogen and hydrogen

                                      2. hydrogen and helium

                                      3. helium and helium

                                      4. neon and helium

                                      (Return to Exercise)

                                      A

                                      Exercise 24.

                                      Chewing a bite of bread mixes it with saliva and facilitates its chemical breakdown. This is most likely due to the fact that ________.

                                      1. the inside of the mouth maintains a very high temperature

                                      2. chewing stores potential energy

                                      3. chewing facilitates synthesis reactions

                                      4. saliva contains enzymes

                                      (Return to Exercise)

                                      D

                                      2.4. Inorganic Compounds Essential to Human Functioning
                                      Exercise 27.

                                      CH4 is methane. This compound is ________.

                                      1. inorganic

                                      2. organic

                                      3. reactive

                                      4. a crystal

                                      (Return to Exercise)

                                      B

                                      Exercise 28.

                                      Which of the following is most likely to be found evenly distributed in water in a homogeneous solution?

                                      1. sodium ions and chloride ions

                                      2. NaCl molecules

                                      3. salt crystals

                                      4. red blood cells

                                      (Return to Exercise)

                                      A

                                      Exercise 29.

                                      Jenny mixes up a batch of pancake batter, then stirs in some chocolate chips. As she is waiting for the first few pancakes to cook, she notices the chocolate chips sinking to the bottom of the clear glass mixing bowl. The chocolate-chip batter is an example of a ________.

                                      1. solvent

                                      2. solute

                                      3. solution

                                      4. suspension

                                      (Return to Exercise)

                                      D

                                      Exercise 30.

                                      A substance dissociates into K+ and Cl– in solution. The substance is a(n) ________.

                                      1. acid

                                      2. base

                                      3. salt

                                      4. buffer

                                      (Return to Exercise)

                                      C

                                      Exercise 31.

                                      Ty is three years old and as a result of a “stomach bug” has been vomiting for about 24 hours. His blood pH is 7.48. What does this mean?

                                      1. Ty’s blood is slightly acidic.

                                      2. Ty’s blood is slightly alkaline.

                                      3. Ty’s blood is highly acidic.

                                      4. Ty’s blood is within the normal range

                                      (Return to Exercise)

                                      B

                                      2.5. Organic Compounds Essential to Human Functioning
                                      Exercise 35.

                                      C6H12O6 is the chemical formula for a ________.

                                      1. polymer of carbohydrate

                                      2. pentose monosaccharide

                                      3. hexose monosaccharide

                                      4. all of the above

                                      (Return to Exercise)

                                      C

                                      Exercise 36.

                                      What organic compound do brain cells primarily rely on for fuel?

                                      1. glucose

                                      2. glycogen

                                      3. galactose

                                      4. glycerol

                                      (Return to Exercise)

                                      A

                                      Exercise 37.

                                      Which of the following is a functional group that is part of a building block of proteins?

                                      1. phosphate

                                      2. adenine

                                      3. amino

                                      4. ribose

                                      (Return to Exercise)

                                      C

                                      Exercise 38.

                                      A pentose sugar is a part of the monomer used to build which type of macromolecule?

                                      1. polysaccharides

                                      2. nucleic acids

                                      3. phosphorylated glucose

                                      4. glycogen

                                      (Return to Exercise)

                                      B

                                      Exercise 39.

                                      A phospholipid ________.

                                      1. has both polar and nonpolar regions

                                      2. is made up of a triglyceride bonded to a phosphate group

                                      3. is a building block of ATP

                                      4. can donate both cations and anions in solution

                                      (Return to Exercise)

                                      A

                                      Exercise 40.

                                      In DNA, nucleotide bonding forms a compound with a characteristic shape known as a(n) ________.

                                      1. beta chain

                                      2. pleated sheet

                                      3. alpha helix

                                      4. double helix

                                      (Return to Exercise)

                                      D

                                      Exercise 41.

                                      Uracil ________.

                                      1. contains nitrogen

                                      2. is a pyrimidine

                                      3. is found in RNA

                                      4. all of the above

                                      (Return to Exercise)

                                      D

                                      Exercise 42.

                                      The ability of an enzyme’s active sites to bind only substrates of compatible shape and charge is known as ________.

                                      1. selectivity

                                      2. specificity

                                      3. subjectivity

                                      4. specialty

                                      (Return to Exercise)

                                      B

                                      Critical Thinking Questions
                                      2.. Introduction
                                      2.1. Elements and Atoms: The Building Blocks of Matter
                                      Exercise 7.

                                      The most abundant elements in the foods and beverages you consume are oxygen, carbon, hydrogen, and nitrogen. Why might having these elements in consumables be useful?

                                      (Return to Exercise)

                                      These four elements—oxygen, carbon, hydrogen, and nitrogen—together make up more than 95 percent of the mass of the human body, and the body cannot make elements, so it is helpful to have them in consumables.

                                      Exercise 8.

                                      Oxygen, whose atomic number is eight, has three stable isotopes: 16O, 17O, and 18O. Explain what this means in terms of the number of protons and neutrons.

                                      (Return to Exercise)

                                      Oxygen has eight protons. In its most abundant stable form, it has eight neutrons, too, for a mass number of 16. In contrast, 17O has nine neutrons, and 18O has 10 neutrons.

                                      Exercise 9.

                                      Magnesium is an important element in the human body, especially in bones. Magnesium’s atomic number is 12. Is it stable or reactive? Why? If it were to react with another atom, would it be more likely to accept or to donate one or more electrons?

                                      (Return to Exercise)

                                      Magnesium’s 12 electrons are distributed as follows: two in the first shell, eight in the second shell, and two in its valence shell. According to the octet rule, magnesium is unstable (reactive) because its valence shell has just two electrons. It is therefore likely to participate in chemical reactions in which it donates two electrons.

                                      2.2. Chemical Bonds
                                      Exercise 16.

                                      Explain why CH4 is one of the most common molecules found in nature. Are the bonds between the atoms ionic or covalent?

                                      (Return to Exercise)

                                      A carbon atom has four electrons in its valence shell. According to the octet rule, it will readily participate in chemical reactions that result in its valence shell having eight electrons. Hydrogen, with one electron, will complete its valence shell with two. Electron sharing between an atom of carbon and four atoms of hydrogen meets the requirements of all atoms. The bonds are covalent because the electrons are shared: although hydrogen often participates in ionic bonds, carbon does not because it is highly unlikely to donate or accept four electrons.

                                      Exercise 17.

                                      In a hurry one day, you merely rinse your lunch dishes with water. As you are drying your salad bowl, you notice that it still has an oily film. Why was the water alone not effective in cleaning the bowl?

                                      (Return to Exercise)

                                      Water is a polar molecule. It has a region of weakly positive charge and a region of weakly negative charge. These regions are attracted to ions as well as to other polar molecules. Oils are nonpolar, and are repelled by water.

                                      Exercise 18.

                                      Could two atoms of oxygen engage in ionic bonding? Why or why not?

                                      (Return to Exercise)

                                      Identical atoms have identical electronegativity and cannot form ionic bonds. Oxygen, for example, has six electrons in its valence shell. Neither donating nor accepting the valence shell electrons of the other will result in the oxygen atoms completing their valence shells. Two atoms of the same element always form covalent bonds.

                                      2.3. Chemical Reactions
                                      Exercise 25.

                                      AB+CD→AD+BE Is this a legitimate example of an exchange reaction? Why or why not?

                                      (Return to Exercise)

                                      It is not. An exchange reaction might be AB+CD→AC+BD or AB+CD→AD+BC . In all chemical reactions, including exchange reactions, the components of the reactants are identical to the components of the products. A component present among the reactants cannot disappear, nor can a component not present in the reactants suddenly appear in the products.

                                      Exercise 26.

                                      When you do a load of laundry, why do you not just drop a bar of soap into the washing machine? In other words, why is laundry detergent sold as a liquid or powder?

                                      (Return to Exercise)

                                      Recall that the greater the surface area of the reactants, the more quickly and easily they will interact. It takes energy to separate particles of a substance. Powder and liquid laundry detergents, with relatively more surface area per unit, can quickly dissolve into their reactive components when added to the water.

                                      2.4. Inorganic Compounds Essential to Human Functioning
                                      Exercise 32.

                                      The pH of lemon juice is 2, and the pH of orange juice is 4. Which of these is more acidic, and by how much? What does this mean?

                                      (Return to Exercise)

                                      Lemon juice is one hundred times more acidic than orange juice. This means that lemon juice has a one hundred-fold greater concentration of hydrogen ions.

                                      Exercise 33.

                                      During a party, Eli loses a bet and is forced to drink a bottle of lemon juice. Not long thereafter, he begins complaining of having difficulty breathing, and his friends take him to the local emergency room. There, he is given an intravenous solution of bicarbonate. Why?

                                      (Return to Exercise)

                                      Lemon juice, like any acid, releases hydrogen ions in solution. As excessive H+ enters the digestive tract and is absorbed into blood, Eli’s blood pH falls below 7.35. Recall that bicarbonate is a buffer, a weak base that accepts hydrogen ions. By administering bicarbonate intravenously, the emergency department physician helps raise Eli’s blood pH back toward neutral.

                                      2.5. Organic Compounds Essential to Human Functioning
                                      Exercise 43.

                                      If the disaccharide maltose is formed from two glucose monosaccharides, which are hexose sugars, how many atoms of carbon, hydrogen, and oxygen does maltose contain and why?

                                      (Return to Exercise)

                                      Maltose contains 12 atoms of carbon, but only 22 atoms of hydrogen and 11 atoms of oxygen, because a molecule of water is removed during its formation via dehydration synthesis.

                                      Exercise 44.

                                      Once dietary fats are digested and absorbed, why can they not be released directly into the bloodstream?

                                      (Return to Exercise)

                                      All lipids are hydrophobic and unable to dissolve in the watery environment of blood. They are packaged into lipoproteins, whose outer protein envelope enables them to transport fats in the bloodstream.

                                      Solutions
                                      (Return to Exercise)

                                      The mass number is the total number of protons and neutrons in the nucleus of an atom.

                                      (Return to Exercise)

                                      The plastic sheets jump to the nail (the conductor), because the conductor takes on electrons from the electroscope, reducing the repellant force of the two sheets.

                                      (Return to Exercise)

                                      The water hydrolyses, or breaks, the glycosidic bond, forming two monosaccharides.

                                      (Return to Exercise)

                                      D

                                      (Return to Exercise)

                                      B

                                      (Return to Exercise)

                                      A

                                      (Return to Exercise)

                                      C

                                      (Return to Exercise)

                                      B

                                      (Return to Exercise)

                                      C

                                      (Return to Exercise)

                                      C

                                      (Return to Exercise)

                                      A

                                      (Return to Exercise)

                                      B

                                      (Return to Exercise)

                                      A

                                      (Return to Exercise)

                                      A

                                      (Return to Exercise)

                                      B

                                      (Return to Exercise)

                                      C

                                      (Return to Exercise)

                                      D

                                      (Return to Exercise)

                                      A

                                      (Return to Exercise)

                                      D

                                      (Return to Exercise)

                                      B

                                      (Return to Exercise)

                                      A

                                      (Return to Exercise)

                                      D

                                      (Return to Exercise)

                                      C

                                      (Return to Exercise)

                                      B

                                      (Return to Exercise)

                                      C

                                      (Return to Exercise)

                                      A

                                      (Return to Exercise)

                                      C

                                      (Return to Exercise)

                                      B

                                      (Return to Exercise)

                                      A

                                      (Return to Exercise)

                                      D

                                      (Return to Exercise)

                                      D

                                      (Return to Exercise)

                                      B

                                      (Return to Exercise)

                                      These four elements—oxygen, carbon, hydrogen, and nitrogen—together make up more than 95 percent of the mass of the human body, and the body cannot make elements, so it is helpful to have them in consumables.

                                      (Return to Exercise)

                                      Oxygen has eight protons. In its most abundant stable form, it has eight neutrons, too, for a mass number of 16. In contrast, 17O has nine neutrons, and 18O has 10 neutrons.

                                      (Return to Exercise)

                                      Magnesium’s 12 electrons are distributed as follows: two in the first shell, eight in the second shell, and two in its valence shell. According to the octet rule, magnesium is unstable (reactive) because its valence shell has just two electrons. It is therefore likely to participate in chemical reactions in which it donates two electrons.

                                      (Return to Exercise)

                                      A carbon atom has four electrons in its valence shell. According to the octet rule, it will readily participate in chemical reactions that result in its valence shell having eight electrons. Hydrogen, with one electron, will complete its valence shell with two. Electron sharing between an atom of carbon and four atoms of hydrogen meets the requirements of all atoms. The bonds are covalent because the electrons are shared: although hydrogen often participates in ionic bonds, carbon does not because it is highly unlikely to donate or accept four electrons.

                                      (Return to Exercise)

                                      Water is a polar molecule. It has a region of weakly positive charge and a region of weakly negative charge. These regions are attracted to ions as well as to other polar molecules. Oils are nonpolar, and are repelled by water.

                                      (Return to Exercise)

                                      Identical atoms have identical electronegativity and cannot form ionic bonds. Oxygen, for example, has six electrons in its valence shell. Neither donating nor accepting the valence shell electrons of the other will result in the oxygen atoms completing their valence shells. Two atoms of the same element always form covalent bonds.

                                      (Return to Exercise)

                                      It is not. An exchange reaction might be AB+CD→AC+BD or AB+CD→AD+BC . In all chemical reactions, including exchange reactions, the components of the reactants are identical to the components of the products. A component present among the reactants cannot disappear, nor can a component not present in the reactants suddenly appear in the products.

                                      (Return to Exercise)

                                      Recall that the greater the surface area of the reactants, the more quickly and easily they will interact. It takes energy to separate particles of a substance. Powder and liquid laundry detergents, with relatively more surface area per unit, can quickly dissolve into their reactive components when added to the water.

                                      (Return to Exercise)

                                      Lemon juice is one hundred times more acidic than orange juice. This means that lemon juice has a one hundred-fold greater concentration of hydrogen ions.

                                      (Return to Exercise)

                                      Lemon juice, like any acid, releases hydrogen ions in solution. As excessive H+ enters the digestive tract and is absorbed into blood, Eli’s blood pH falls below 7.35. Recall that bicarbonate is a buffer, a weak base that accepts hydrogen ions. By administering bicarbonate intravenously, the emergency department physician helps raise Eli’s blood pH back toward neutral.

                                      (Return to Exercise)

                                      Maltose contains 12 atoms of carbon, but only 22 atoms of hydrogen and 11 atoms of oxygen, because a molecule of water is removed during its formation via dehydration synthesis.

                                      (Return to Exercise)

                                      All lipids are hydrophobic and unable to dissolve in the watery environment of blood. They are packaged into lipoproteins, whose outer protein envelope enables them to transport fats in the bloodstream.

                                      Chapter 20The Cardiovascular System: Blood Vessels and Circulation

                                      This photo shows a forearm with the veins bulging.
                                      Figure 20.1Blood Vessels
                                      While most blood vessels are located deep from the surface and are not visible, the superficial veins of the upper limb provide an indication of the extent, prominence, and importance of these structures to the body. (credit: Colin Davis)

                                      Introduction*

                                      Chapter Objectives

                                      After studying this chapter, you will be able to:

                                      • Compare and contrast the anatomical structure of arteries, arterioles, capillaries, venules, and veins

                                      • Accurately describe the forces that account for capillary exchange

                                      • List the major factors affecting blood flow, blood pressure, and resistance

                                      • Describe how blood flow, blood pressure, and resistance interrelate

                                      • Discuss how the neural and endocrine mechanisms maintain homeostasis within the blood vessels

                                      • Describe the interaction of the cardiovascular system with other body systems

                                      • Label the major blood vessels of the pulmonary and systemic circulations

                                      • Identify and describe the hepatic portal system

                                      • Describe the development of blood vessels and fetal circulation

                                      • Compare fetal circulation to that of an individual after birth

                                      In this chapter, you will learn about the vascular part of the cardiovascular system, that is, the vessels that transport blood throughout the body and provide the physical site where gases, nutrients, and other substances are exchanged with body cells. When vessel functioning is reduced, blood-borne substances do not circulate effectively throughout the body. As a result, tissue injury occurs, metabolism is impaired, and the functions of every bodily system are threatened.

                                      20.1Structure and Function of Blood Vessels*

                                      By the end of this section, you will be able to:

                                      • Compare and contrast the three tunics that make up the walls of most blood vessels

                                      • Distinguish between elastic arteries, muscular arteries, and arterioles on the basis of structure, location, and function

                                      • Describe the basic structure of a capillary bed, from the supplying metarteriole to the venule into which it drains

                                      • Explain the structure and function of venous valves in the large veins of the extremities

                                      • Shared Structures
                                        • Tunica Intima
                                        • Tunica Media
                                        • Tunica Externa
                                      • Arteries
                                      • Arterioles
                                      • Capillaries
                                        • Continuous Capillaries
                                        • Fenestrated Capillaries
                                        • Sinusoid Capillaries
                                      • Metarterioles and Capillary Beds
                                      • Venules
                                      • Veins
                                      • Veins as Blood Reservoirs

                                      Blood is carried through the body via blood vessels. An artery is a blood vessel that carries blood away from the heart, where it branches into ever-smaller vessels. Eventually, the smallest arteries, vessels called arterioles, further branch into tiny capillaries, where nutrients and wastes are exchanged, and then combine with other vessels that exit capillaries to form venules, small blood vessels that carry blood to a vein, a larger blood vessel that returns blood to the heart.

                                      Arteries and veins transport blood in two distinct circuits: the systemic circuit and the pulmonary circuit (Figure 20.2). Systemic arteries provide blood rich in oxygen to the body’s tissues. The blood returned to the heart through systemic veins has less oxygen, since much of the oxygen carried by the arteries has been delivered to the cells. In contrast, in the pulmonary circuit, arteries carry blood low in oxygen exclusively to the lungs for gas exchange. Pulmonary veins then return freshly oxygenated blood from the lungs to the heart to be pumped back out into systemic circulation. Although arteries and veins differ structurally and functionally, they share certain features.

                                      This diagram shows how oxygenated and deoxygenated blood flow through the major organs in the body.
                                      Figure 20.2Cardiovascular Circulation
                                      The pulmonary circuit moves blood from the right side of the heart to the lungs and back to the heart. The systemic circuit moves blood from the left side of the heart to the head and body and returns it to the right side of the heart to repeat the cycle. The arrows indicate the direction of blood flow, and the colors show the relative levels of oxygen concentration.

                                      Shared Structures

                                      Different types of blood vessels vary slightly in their structures, but they share the same general features. Arteries and arterioles have thicker walls than veins and venules because they are closer to the heart and receive blood that is surging at a far greater pressure (Figure 20.3). Each type of vessel has a lumen—a hollow passageway through which blood flows. Arteries have smaller lumens than veins, a characteristic that helps to maintain the pressure of blood moving through the system. Together, their thicker walls and smaller diameters give arterial lumens a more rounded appearance in cross section than the lumens of veins.

                                      The top left panel of this figure shows the ultrastructure of an artery, and the top right panel shows the ultrastructure of a vein. The bottom panel shows a micrograph with the cross sections of an artery and a vein.
                                      Figure 20.3Structure of Blood Vessels
                                      (a) Arteries and (b) veins share the same general features, but the walls of arteries are much thicker because of the higher pressure of the blood that flows through them. (c) A micrograph shows the relative differences in thickness. LM × 160. (Micrograph provided by the Regents of the University of Michigan Medical School © 2012)

                                      By the time blood has passed through capillaries and entered venules, the pressure initially exerted upon it by heart contractions has diminished. In other words, in comparison to arteries, venules and veins withstand a much lower pressure from the blood that flows through them. Their walls are considerably thinner and their lumens are correspondingly larger in diameter, allowing more blood to flow with less vessel resistance. In addition, many veins of the body, particularly those of the limbs, contain valves that assist the unidirectional flow of blood toward the heart. This is critical because blood flow becomes sluggish in the extremities, as a result of the lower pressure and the effects of gravity.

                                      The walls of arteries and veins are largely composed of living cells and their products (including collagenous and elastic fibers); the cells require nourishment and produce waste. Since blood passes through the larger vessels relatively quickly, there is limited opportunity for blood in the lumen of the vessel to provide nourishment to or remove waste from the vessel’s cells. Further, the walls of the larger vessels are too thick for nutrients to diffuse through to all of the cells. Larger arteries and veins contain small blood vessels within their walls known as the vasa vasorum—literally “vessels of the vessel”—to provide them with this critical exchange. Since the pressure within arteries is relatively high, the vasa vasorum must function in the outer layers of the vessel (see Figure 20.3) or the pressure exerted by the blood passing through the vessel would collapse it, preventing any exchange from occurring. The lower pressure within veins allows the vasa vasorum to be located closer to the lumen. The restriction of the vasa vasorum to the outer layers of arteries is thought to be one reason that arterial diseases are more common than venous diseases, since its location makes it more difficult to nourish the cells of the arteries and remove waste products. There are also minute nerves within the walls of both types of vessels that control the contraction and dilation of smooth muscle. These minute nerves are known as the nervi vasorum.

                                      Both arteries and veins have the same three distinct tissue layers, called tunics (from the Latin term tunica), for the garments first worn by ancient Romans; the term tunic is also used for some modern garments. From the most interior layer to the outer, these tunics are the tunica intima, the tunica media, and the tunica externa (see Figure 20.3). Table 20.1 compares and contrasts the tunics of the arteries and veins.

                                      Table 20.1.
                                      Comparison of Tunics in Arteries and Veins
                                        Arteries Veins
                                      General appearance Thick walls with small lumens
                                      Generally appear rounded
                                      Thin walls with large lumens
                                      Generally appear flattened
                                      Tunica intima Endothelium usually appears wavy due to constriction of smooth muscle
                                      Internal elastic membrane present in larger vessels
                                      Endothelium appears smooth
                                      Internal elastic membrane absent
                                      Tunica media Normally the thickest layer in arteries
                                      Smooth muscle cells and elastic fibers predominate (the proportions of these vary with distance from the heart)
                                      External elastic membrane present in larger vessels
                                      Normally thinner than the tunica externa
                                      Smooth muscle cells and collagenous fibers predominate
                                      Nervi vasorum and vasa vasorum present
                                      External elastic membrane absent
                                      Tunica externa Normally thinner than the tunica media in all but the largest arteries
                                      Collagenous and elastic fibers
                                      Nervi vasorum and vasa vasorum present
                                      Normally the thickest layer in veins
                                      Collagenous and smooth fibers predominate
                                      Some smooth muscle fibers
                                      Nervi vasorum and vasa vasorum present

                                      Tunica Intima

                                      The tunica intima (also called the tunica interna) is composed of epithelial and connective tissue layers. Lining the tunica intima is the specialized simple squamous epithelium called the endothelium, which is continuous throughout the entire vascular system, including the lining of the chambers of the heart. Damage to this endothelial lining and exposure of blood to the collagenous fibers beneath is one of the primary causes of clot formation. Until recently, the endothelium was viewed simply as the boundary between the blood in the lumen and the walls of the vessels. Recent studies, however, have shown that it is physiologically critical to such activities as helping to regulate capillary exchange and altering blood flow. The endothelium releases local chemicals called endothelins that can constrict the smooth muscle within the walls of the vessel to increase blood pressure. Uncompensated overproduction of endothelins may contribute to hypertension (high blood pressure) and cardiovascular disease.

                                      Next to the endothelium is the basement membrane, or basal lamina, that effectively binds the endothelium to the connective tissue. The basement membrane provides strength while maintaining flexibility, and it is permeable, allowing materials to pass through it. The thin outer layer of the tunica intima contains a small amount of areolar connective tissue that consists primarily of elastic fibers to provide the vessel with additional flexibility; it also contains some collagenous fibers to provide additional strength.

                                      In larger arteries, there is also a thick, distinct layer of elastic fibers known as the internal elastic membrane (also called the internal elastic lamina) at the boundary with the tunica media. Like the other components of the tunica intima, the internal elastic membrane provides structure while allowing the vessel to stretch. It is permeated with small openings that allow exchange of materials between the tunics. The internal elastic membrane is not apparent in veins. In addition, many veins, particularly in the lower limbs, contain valves formed by sections of thickened endothelium that are reinforced with connective tissue, extending into the lumen.

                                      Under the microscope, the lumen and the entire tunica intima of a vein will appear smooth, whereas those of an artery will normally appear wavy because of the partial constriction of the smooth muscle in the tunica media, the next layer of blood vessel walls.

                                      Tunica Media

                                      The tunica media is the substantial middle layer of the vessel wall (see Figure 20.3). It is generally the thickest layer in arteries, and it is much thicker in arteries than it is in veins. The tunica media consists of layers of smooth muscle supported by connective tissue that is primarily made up of elastic fibers, most of which are arranged in circular sheets. Toward the outer portion of the tunic, there are also layers of longitudinal muscle. Contraction and relaxation of the circular muscles decrease and increase the diameter of the vessel lumen, respectively. Specifically in arteries, vasoconstriction decreases blood flow as the smooth muscle in the walls of the tunica media contracts, making the lumen narrower and increasing blood pressure. Similarly, vasodilation increases blood flow as the smooth muscle relaxes, allowing the lumen to widen and blood pressure to drop. Both vasoconstriction and vasodilation are regulated in part by small vascular nerves, known as nervi vasorum, or “nerves of the vessel,” that run within the walls of blood vessels. These are generally all sympathetic fibers, although some trigger vasodilation and others induce vasoconstriction, depending upon the nature of the neurotransmitter and receptors located on the target cell. Parasympathetic stimulation does trigger vasodilation as well as erection during sexual arousal in the external genitalia of both sexes. Nervous control over vessels tends to be more generalized than the specific targeting of individual blood vessels. Local controls, discussed later, account for this phenomenon. (Seek additional content for more information on these dynamic aspects of the autonomic nervous system.) Hormones and local chemicals also control blood vessels. Together, these neural and chemical mechanisms reduce or increase blood flow in response to changing body conditions, from exercise to hydration. Regulation of both blood flow and blood pressure is discussed in detail later in this chapter.

                                      The smooth muscle layers of the tunica media are supported by a framework of collagenous fibers that also binds the tunica media to the inner and outer tunics. Along with the collagenous fibers are large numbers of elastic fibers that appear as wavy lines in prepared slides. Separating the tunica media from the outer tunica externa in larger arteries is the external elastic membrane (also called the external elastic lamina), which also appears wavy in slides. This structure is not usually seen in smaller arteries, nor is it seen in veins.

                                      Tunica Externa

                                      The outer tunic, the tunica externa (also called the tunica adventitia), is a substantial sheath of connective tissue composed primarily of collagenous fibers. Some bands of elastic fibers are found here as well. The tunica externa in veins also contains groups of smooth muscle fibers. This is normally the thickest tunic in veins and may be thicker than the tunica media in some larger arteries. The outer layers of the tunica externa are not distinct but rather blend with the surrounding connective tissue outside the vessel, helping to hold the vessel in relative position. If you are able to palpate some of the superficial veins on your upper limbs and try to move them, you will find that the tunica externa prevents this. If the tunica externa did not hold the vessel in place, any movement would likely result in disruption of blood flow.

                                      Arteries

                                      An artery is a blood vessel that conducts blood away from the heart. All arteries have relatively thick walls that can withstand the high pressure of blood ejected from the heart. However, those close to the heart have the thickest walls, containing a high percentage of elastic fibers in all three of their tunics. This type of artery is known as an elastic artery (Figure 20.4). Vessels larger than 10 mm in diameter are typically elastic. Their abundant elastic fibers allow them to expand, as blood pumped from the ventricles passes through them, and then to recoil after the surge has passed. If artery walls were rigid and unable to expand and recoil, their resistance to blood flow would greatly increase and blood pressure would rise to even higher levels, which would in turn require the heart to pump harder to increase the volume of blood expelled by each pump (the stroke volume) and maintain adequate pressure and flow. Artery walls would have to become even thicker in response to this increased pressure. The elastic recoil of the vascular wall helps to maintain the pressure gradient that drives the blood through the arterial system. An elastic artery is also known as a conducting artery, because the large diameter of the lumen enables it to accept a large volume of blood from the heart and conduct it to smaller branches.

                                      The left panel shows the cross-section of an elastic artery, the middle panel shows the cross section of a muscular artery, and the right panel shows the cross-section of an arteriole.
                                      Figure 20.4Types of Arteries and Arterioles
                                      Comparison of the walls of an elastic artery, a muscular artery, and an arteriole is shown. In terms of scale, the diameter of an arteriole is measured in micrometers compared to millimeters for elastic and muscular arteries.

                                      Farther from the heart, where the surge of blood has dampened, the percentage of elastic fibers in an artery’s tunica intima decreases and the amount of smooth muscle in its tunica media increases. The artery at this point is described as a muscular artery. The diameter of muscular arteries typically ranges from 0.1 mm to 10 mm. Their thick tunica media allows muscular arteries to play a leading role in vasoconstriction. In contrast, their decreased quantity of elastic fibers limits their ability to expand. Fortunately, because the blood pressure has eased by the time it reaches these more distant vessels, elasticity has become less important.

                                      Notice that although the distinctions between elastic and muscular arteries are important, there is no “line of demarcation” where an elastic artery suddenly becomes muscular. Rather, there is a gradual transition as the vascular tree repeatedly branches. In turn, muscular arteries branch to distribute blood to the vast network of arterioles. For this reason, a muscular artery is also known as a distributing artery.

                                      Arterioles

                                      An arteriole is a very small artery that leads to a capillary. Arterioles have the same three tunics as the larger vessels, but the thickness of each is greatly diminished. The critical endothelial lining of the tunica intima is intact. The tunica media is restricted to one or two smooth muscle cell layers in thickness. The tunica externa remains but is very thin (see Figure 20.4).

                                      With a lumen averaging 30 micrometers or less in diameter, arterioles are critical in slowing down—or resisting—blood flow and, thus, causing a substantial drop in blood pressure. Because of this, you may see them referred to as resistance vessels. The muscle fibers in arterioles are normally slightly contracted, causing arterioles to maintain a consistent muscle tone—in this case referred to as vascular tone—in a similar manner to the muscular tone of skeletal muscle. In reality, all blood vessels exhibit vascular tone due to the partial contraction of smooth muscle. The importance of the arterioles is that they will be the primary site of both resistance and regulation of blood pressure. The precise diameter of the lumen of an arteriole at any given moment is determined by neural and chemical controls, and vasoconstriction and vasodilation in the arterioles are the primary mechanisms for distribution of blood flow.

                                      Capillaries

                                      A capillary is a microscopic channel that supplies blood to the tissues themselves, a process called perfusion. Exchange of gases and other substances occurs in the capillaries between the blood and the surrounding cells and their tissue fluid (interstitial fluid). The diameter of a capillary lumen ranges from 5–10 micrometers; the smallest are just barely wide enough for an erythrocyte to squeeze through. Flow through capillaries is often described as microcirculation.

                                      The wall of a capillary consists of the endothelial layer surrounded by a basement membrane with occasional smooth muscle fibers. There is some variation in wall structure: In a large capillary, several endothelial cells bordering each other may line the lumen; in a small capillary, there may be only a single cell layer that wraps around to contact itself.

                                      For capillaries to function, their walls must be leaky, allowing substances to pass through. There are three major types of capillaries, which differ according to their degree of “leakiness:” continuous, fenestrated, and sinusoid capillaries (Figure 20.5).

                                      Continuous Capillaries

                                      The most common type of capillary, the continuous capillary, is found in almost all vascularized tissues. Continuous capillaries are characterized by a complete endothelial lining with tight junctions between endothelial cells. Although a tight junction is usually impermeable and only allows for the passage of water and ions, they are often incomplete in capillaries, leaving intercellular clefts that allow for exchange of water and other very small molecules between the blood plasma and the interstitial fluid. Substances that can pass between cells include metabolic products, such as glucose, water, and small hydrophobic molecules like gases and hormones, as well as various leukocytes. Continuous capillaries not associated with the brain are rich in transport vesicles, contributing to either endocytosis or exocytosis. Those in the brain are part of the blood-brain barrier. Here, there are tight junctions and no intercellular clefts, plus a thick basement membrane and astrocyte extensions called end feet; these structures combine to prevent the movement of nearly all substances.

                                      The left panel shows the structure of a continuous capillary, the middle panel shows a fenestrated capillary, and the right panel shows a sinusoid capillary.
                                      Figure 20.5Types of Capillaries
                                      The three major types of capillaries: continuous, fenestrated, and sinusoid.

                                      Fenestrated Capillaries

                                      A fenestrated capillary is one that has pores (or fenestrations) in addition to tight junctions in the endothelial lining. These make the capillary permeable to larger molecules. The number of fenestrations and their degree of permeability vary, however, according to their location. Fenestrated capillaries are common in the small intestine, which is the primary site of nutrient absorption, as well as in the kidneys, which filter the blood. They are also found in the choroid plexus of the brain and many endocrine structures, including the hypothalamus, pituitary, pineal, and thyroid glands.

                                      Sinusoid Capillaries

                                      A sinusoid capillary (or sinusoid) is the least common type of capillary. Sinusoid capillaries are flattened, and they have extensive intercellular gaps and incomplete basement membranes, in addition to intercellular clefts and fenestrations. This gives them an appearance not unlike Swiss cheese. These very large openings allow for the passage of the largest molecules, including plasma proteins and even cells. Blood flow through sinusoids is very slow, allowing more time for exchange of gases, nutrients, and wastes. Sinusoids are found in the liver and spleen, bone marrow, lymph nodes (where they carry lymph, not blood), and many endocrine glands including the pituitary and adrenal glands. Without these specialized capillaries, these organs would not be able to provide their myriad of functions. For example, when bone marrow forms new blood cells, the cells must enter the blood supply and can only do so through the large openings of a sinusoid capillary; they cannot pass through the small openings of continuous or fenestrated capillaries. The liver also requires extensive specialized sinusoid capillaries in order to process the materials brought to it by the hepatic portal vein from both the digestive tract and spleen, and to release plasma proteins into circulation.

                                      Metarterioles and Capillary Beds

                                      A metarteriole is a type of vessel that has structural characteristics of both an arteriole and a capillary. Slightly larger than the typical capillary, the smooth muscle of the tunica media of the metarteriole is not continuous but forms rings of smooth muscle (sphincters) prior to the entrance to the capillaries. Each metarteriole arises from a terminal arteriole and branches to supply blood to a capillary bed that may consist of 10–100 capillaries.

                                      The precapillary sphincters, circular smooth muscle cells that surround the capillary at its origin with the metarteriole, tightly regulate the flow of blood from a metarteriole to the capillaries it supplies. Their function is critical: If all of the capillary beds in the body were to open simultaneously, they would collectively hold every drop of blood in the body and there would be none in the arteries, arterioles, venules, veins, or the heart itself. Normally, the precapillary sphincters are closed. When the surrounding tissues need oxygen and have excess waste products, the precapillary sphincters open, allowing blood to flow through and exchange to occur before closing once more (Figure 20.6). If all of the precapillary sphincters in a capillary bed are closed, blood will flow from the metarteriole directly into a thoroughfare channel and then into the venous circulation, bypassing the capillary bed entirely. This creates what is known as a vascular shunt. In addition, an arteriovenous anastomosis may bypass the capillary bed and lead directly to the venous system.

                                      Although you might expect blood flow through a capillary bed to be smooth, in reality, it moves with an irregular, pulsating flow. This pattern is called vasomotion and is regulated by chemical signals that are triggered in response to changes in internal conditions, such as oxygen, carbon dioxide, hydrogen ion, and lactic acid levels. For example, during strenuous exercise when oxygen levels decrease and carbon dioxide, hydrogen ion, and lactic acid levels all increase, the capillary beds in skeletal muscle are open, as they would be in the digestive system when nutrients are present in the digestive tract. During sleep or rest periods, vessels in both areas are largely closed; they open only occasionally to allow oxygen and nutrient supplies to travel to the tissues to maintain basic life processes.

                                      This diagram shows a capillary bed connecting an arteriole and a venule.
                                      Figure 20.6Capillary Bed
                                      In a capillary bed, arterioles give rise to metarterioles. Precapillary sphincters located at the junction of a metarteriole with a capillary regulate blood flow. A thoroughfare channel connects the metarteriole to a venule. An arteriovenous anastomosis, which directly connects the arteriole with the venule, is shown at the bottom.

                                      Venules

                                      A venule is an extremely small vein, generally 8–100 micrometers in diameter. Postcapillary venules join multiple capillaries exiting from a capillary bed. Multiple venules join to form veins. The walls of venules consist of endothelium, a thin middle layer with a few muscle cells and elastic fibers, plus an outer layer of connective tissue fibers that constitute a very thin tunica externa (Figure 20.7). Venules as well as capillaries are the primary sites of emigration or diapedesis, in which the white blood cells adhere to the endothelial lining of the vessels and then squeeze through adjacent cells to enter the tissue fluid.

                                      Veins

                                      A vein is a blood vessel that conducts blood toward the heart. Compared to arteries, veins are thin-walled vessels with large and irregular lumens (see Figure 20.7). Because they are low-pressure vessels, larger veins are commonly equipped with valves that promote the unidirectional flow of blood toward the heart and prevent backflow toward the capillaries caused by the inherent low blood pressure in veins as well as the pull of gravity. Table 20.2 compares the features of arteries and veins.

                                      The top panel shows the cross-section of a large vein, the middle panel shows the cross-section of a medium sized vein, and the bottom panel shows the cross-section of a venule.
                                      Figure 20.7Comparison of Veins and Venules
                                      Many veins have valves to prevent back flow of blood, whereas venules do not. In terms of scale, the diameter of a venule is measured in micrometers compared to millimeters for veins.
                                      Table 20.2.
                                      Comparison of Arteries and Veins
                                        Arteries Veins
                                      Direction of blood flow Conducts blood away from the heart Conducts blood toward the heart
                                      General appearance Rounded Irregular, often collapsed
                                      Pressure High Low
                                      Wall thickness Thick Thin
                                      Relative oxygen concentration Higher in systemic arteries
                                      Lower in pulmonary arteries
                                      Lower in systemic veins
                                      Higher in pulmonary veins
                                      Valves Not present Present most commonly in limbs and in veins inferior to the heart
                                      Disorders of the…

                                      Cardiovascular System: Edema and Varicose Veins

                                      Despite the presence of valves and the contributions of other anatomical and physiological adaptations we will cover shortly, over the course of a day, some blood will inevitably pool, especially in the lower limbs, due to the pull of gravity. Any blood that accumulates in a vein will increase the pressure within it, which can then be reflected back into the smaller veins, venules, and eventually even the capillaries. Increased pressure will promote the flow of fluids out of the capillaries and into the interstitial fluid. The presence of excess tissue fluid around the cells leads to a condition called edema.

                                      Most people experience a daily accumulation of tissue fluid, especially if they spend much of their work life on their feet (like most health professionals). However, clinical edema goes beyond normal swelling and requires medical treatment. Edema has many potential causes, including hypertension and heart failure, severe protein deficiency, renal failure, and many others. In order to treat edema, which is a sign rather than a discrete disorder, the underlying cause must be diagnosed and alleviated.

                                      This photo shows a person’s leg.
                                      Figure 20.8Varicose Veins
                                      Varicose veins are commonly found in the lower limbs. (credit: Thomas Kriese)

                                      Edema may be accompanied by varicose veins, especially in the superficial veins of the legs (Figure 20.8). This disorder arises when defective valves allow blood to accumulate within the veins, causing them to distend, twist, and become visible on the surface of the integument. Varicose veins may occur in both sexes, but are more common in women and are often related to pregnancy. More than simple cosmetic blemishes, varicose veins are often painful and sometimes itchy or throbbing. Without treatment, they tend to grow worse over time. The use of support hose, as well as elevating the feet and legs whenever possible, may be helpful in alleviating this condition. Laser surgery and interventional radiologic procedures can reduce the size and severity of varicose veins. Severe cases may require conventional surgery to remove the damaged vessels. As there are typically redundant circulation patterns, that is, anastomoses, for the smaller and more superficial veins, removal does not typically impair the circulation. There is evidence that patients with varicose veins suffer a greater risk of developing a thrombus or clot.

                                      Veins as Blood Reservoirs

                                      In addition to their primary function of returning blood to the heart, veins may be considered blood reservoirs, since systemic veins contain approximately 64 percent of the blood volume at any given time (Figure 20.9). Their ability to hold this much blood is due to their high capacitance, that is, their capacity to distend (expand) readily to store a high volume of blood, even at a low pressure. The large lumens and relatively thin walls of veins make them far more distensible than arteries; thus, they are said to be capacitance vessels.

                                      This table describes the distribution of blood flow. 84 percent of blood flow is systemic circulation, of which 64 percent happens in systemic veins (18 percent in large veins, 21 percent in large venous networks such as liver, bone marrow, and integument, and 25 percent in venules and medium-sized veins); 13 percent happens in systemic arteries (2 percent in arterioles, 5 percent in muscular arteries, 4 percent in elastic arteries, and 2 percent in the aorta); and 7 percent happens in systemic capillaries. 9 percent of blood flow is pulmonary circulation, of which 4 percent happens in pulmonary veins, 2 percent happens in pulmonary capillaries, and 3 percent happens in pulmonary arteries. The remaining 7 percent of blood flow is in the heart.
                                      Figure 20.9Distribution of Blood Flow

                                      When blood flow needs to be redistributed to other portions of the body, the vasomotor center located in the medulla oblongata sends sympathetic stimulation to the smooth muscles in the walls of the veins, causing constriction—or in this case, venoconstriction. Less dramatic than the vasoconstriction seen in smaller arteries and arterioles, venoconstriction may be likened to a “stiffening” of the vessel wall. This increases pressure on the blood within the veins, speeding its return to the heart. As you will note in Figure 20.9, approximately 21 percent of the venous blood is located in venous networks within the liver, bone marrow, and integument. This volume of blood is referred to as venous reserve. Through venoconstriction, this “reserve” volume of blood can get back to the heart more quickly for redistribution to other parts of the circulation.

                                      Career Connection

                                      Vascular Surgeons and Technicians

                                      Vascular surgery is a specialty in which the physician deals primarily with diseases of the vascular portion of the cardiovascular system. This includes repair and replacement of diseased or damaged vessels, removal of plaque from vessels, minimally invasive procedures including the insertion of venous catheters, and traditional surgery. Following completion of medical school, the physician generally completes a 5-year surgical residency followed by an additional 1 to 2 years of vascular specialty training. In the United States, most vascular surgeons are members of the Society of Vascular Surgery.

                                      Vascular technicians are specialists in imaging technologies that provide information on the health of the vascular system. They may also assist physicians in treating disorders involving the arteries and veins. This profession often overlaps with cardiovascular technology, which would also include treatments involving the heart. Although recognized by the American Medical Association, there are currently no licensing requirements for vascular technicians, and licensing is voluntary. Vascular technicians typically have an Associate’s degree or certificate, involving 18 months to 2 years of training. The United States Bureau of Labor projects this profession to grow by 29 percent from 2010 to 2020.

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                                      Visit this site to learn more about vascular technicians.

                                      20.2Blood Flow, Blood Pressure, and Resistance*

                                      By the end of this section, you will be able to:

                                      • Distinguish between systolic pressure, diastolic pressure, pulse pressure, and mean arterial pressure

                                      • Describe the clinical measurement of pulse and blood pressure

                                      • Identify and discuss five variables affecting arterial blood flow and blood pressure

                                      • Discuss several factors affecting blood flow in the venous system

                                      • Components of Arterial Blood Pressure
                                        • Systolic and Diastolic Pressures
                                        • Pulse Pressure
                                        • Mean Arterial Pressure
                                      • Pulse
                                      • Measurement of Blood Pressure
                                      • Variables Affecting Blood Flow and Blood Pressure
                                        • Cardiac Output
                                        • Compliance
                                        • A Mathematical Approach to Factors Affecting Blood Flow
                                        • Blood Volume
                                        • Blood Viscosity
                                        • Vessel Length and Diameter
                                        • The Roles of Vessel Diameter and Total Area in Blood Flow and Blood Pressure
                                      • Venous System
                                        • Skeletal Muscle Pump
                                        • Respiratory Pump
                                        • Pressure Relationships in the Venous System
                                        • The Role of Venoconstriction in Resistance, Blood Pressure, and Flow

                                      Blood flow refers to the movement of blood through a vessel, tissue, or organ, and is usually expressed in terms of volume of blood per unit of time. It is initiated by the contraction of the ventricles of the heart. Ventricular contraction ejects blood into the major arteries, resulting in flow from regions of higher pressure to regions of lower pressure, as blood encounters smaller arteries and arterioles, then capillaries, then the venules and veins of the venous system. This section discusses a number of critical variables that contribute to blood flow throughout the body. It also discusses the factors that impede or slow blood flow, a phenomenon known as resistance.

                                      As noted earlier, hydrostatic pressure is the force exerted by a fluid due to gravitational pull, usually against the wall of the container in which it is located. One form of hydrostatic pressure is blood pressure, the force exerted by blood upon the walls of the blood vessels or the chambers of the heart. Blood pressure may be measured in capillaries and veins, as well as the vessels of the pulmonary circulation; however, the term blood pressure without any specific descriptors typically refers to systemic arterial blood pressure—that is, the pressure of blood flowing in the arteries of the systemic circulation. In clinical practice, this pressure is measured in mm Hg and is usually obtained using the brachial artery of the arm.

                                      Components of Arterial Blood Pressure

                                      Arterial blood pressure in the larger vessels consists of several distinct components (Figure 20.10): systolic and diastolic pressures, pulse pressure, and mean arterial pressure.

                                      Systolic and Diastolic Pressures

                                      When systemic arterial blood pressure is measured, it is recorded as a ratio of two numbers (e.g., 120/80 is a normal adult blood pressure), expressed as systolic pressure over diastolic pressure. The systolic pressure is the higher value (typically around 120 mm Hg) and reflects the arterial pressure resulting from the ejection of blood during ventricular contraction, or systole. The diastolic pressure is the lower value (usually about 80 mm Hg) and represents the arterial pressure of blood during ventricular relaxation, or diastole.

                                      This graph shows the value of pulse pressure in different types of blood vessels.
                                      Figure 20.10Systemic Blood Pressure
                                      The graph shows the components of blood pressure throughout the blood vessels, including systolic, diastolic, mean arterial, and pulse pressures.

                                      Pulse Pressure

                                      As shown in Figure 20.10, the difference between the systolic pressure and the diastolic pressure is the pulse pressure. For example, an individual with a systolic pressure of 120 mm Hg and a diastolic pressure of 80 mm Hg would have a pulse pressure of 40 mmHg.

                                      Generally, a pulse pressure should be at least 25 percent of the systolic pressure. A pulse pressure below this level is described as low or narrow. This may occur, for example, in patients with a low stroke volume, which may be seen in congestive heart failure, stenosis of the aortic valve, or significant blood loss following trauma. In contrast, a high or wide pulse pressure is common in healthy people following strenuous exercise, when their resting pulse pressure of 30–40 mm Hg may increase temporarily to 100 mm Hg as stroke volume increases. A persistently high pulse pressure at or above 100 mm Hg may indicate excessive resistance in the arteries and can be caused by a variety of disorders. Chronic high resting pulse pressures can degrade the heart, brain, and kidneys, and warrant medical treatment.

                                      Mean Arterial Pressure

                                      Mean arterial pressure (MAP) represents the “average” pressure of blood in the arteries, that is, the average force driving blood into vessels that serve the tissues. Mean is a statistical concept and is calculated by taking the sum of the values divided by the number of values. Although complicated to measure directly and complicated to calculate, MAP can be approximated by adding the diastolic pressure to one-third of the pulse pressure or systolic pressure minus the diastolic pressure:

                                      In Figure 20.10, this value is approximately 80 + (120 − 80) / 3, or 93.33. Normally, the MAP falls within the range of 70–110 mm Hg. If the value falls below 60 mm Hg for an extended time, blood pressure will not be high enough to ensure circulation to and through the tissues, which results in ischemia, or insufficient blood flow. A condition called hypoxia, inadequate oxygenation of tissues, commonly accompanies ischemia. The term hypoxemia refers to low levels of oxygen in systemic arterial blood. Neurons are especially sensitive to hypoxia and may die or be damaged if blood flow and oxygen supplies are not quickly restored.

                                      Pulse

                                      After blood is ejected from the heart, elastic fibers in the arteries help maintain a high-pressure gradient as they expand to accommodate the blood, then recoil. This expansion and recoiling effect, known as the pulse, can be palpated manually or measured electronically. Although the effect diminishes over distance from the heart, elements of the systolic and diastolic components of the pulse are still evident down to the level of the arterioles.

                                      Because pulse indicates heart rate, it is measured clinically to provide clues to a patient’s state of health. It is recorded as beats per minute. Both the rate and the strength of the pulse are important clinically. A high or irregular pulse rate can be caused by physical activity or other temporary factors, but it may also indicate a heart condition. The pulse strength indicates the strength of ventricular contraction and cardiac output. If the pulse is strong, then systolic pressure is high. If it is weak, systolic pressure has fallen, and medical intervention may be warranted.

                                      Pulse can be palpated manually by placing the tips of the fingers across an artery that runs close to the body surface and pressing lightly. While this procedure is normally performed using the radial artery in the wrist or the common carotid artery in the neck, any superficial artery that can be palpated may be used (Figure 20.11). Common sites to find a pulse include temporal and facial arteries in the head, brachial arteries in the upper arm, femoral arteries in the thigh, popliteal arteries behind the knees, posterior tibial arteries near the medial tarsal regions, and dorsalis pedis arteries in the feet. A variety of commercial electronic devices are also available to measure pulse.

                                      This image shows the pulse points in a woman’s body.
                                      Figure 20.11Pulse Sites
                                      The pulse is most readily measured at the radial artery, but can be measured at any of the pulse points shown.

                                      Measurement of Blood Pressure

                                      Blood pressure is one of the critical parameters measured on virtually every patient in every healthcare setting. The technique used today was developed more than 100 years ago by a pioneering Russian physician, Dr. Nikolai Korotkoff. Turbulent blood flow through the vessels can be heard as a soft ticking while measuring blood pressure; these sounds are known as Korotkoff sounds. The technique of measuring blood pressure requires the use of a sphygmomanometer (a blood pressure cuff attached to a measuring device) and a stethoscope. The technique is as follows:

                                      • The clinician wraps an inflatable cuff tightly around the patient’s arm at about the level of the heart.

                                      • The clinician squeezes a rubber pump to inject air into the cuff, raising pressure around the artery and temporarily cutting off blood flow into the patient’s arm.

                                      • The clinician places the stethoscope on the patient’s antecubital region and, while gradually allowing air within the cuff to escape, listens for the Korotkoff sounds.

                                      Although there are five recognized Korotkoff sounds, only two are normally recorded. Initially, no sounds are heard since there is no blood flow through the vessels, but as air pressure drops, the cuff relaxes, and blood flow returns to the arm. As shown in Figure 20.12, the first sound heard through the stethoscope—the first Korotkoff sound—indicates systolic pressure. As more air is released from the cuff, blood is able to flow freely through the brachial artery and all sounds disappear. The point at which the last sound is heard is recorded as the patient’s diastolic pressure.

                                      This image shows blood pressure as a function of time.
                                      Figure 20.12Blood Pressure Measurement
                                      When pressure in a sphygmomanometer cuff is released, a clinician can hear the Korotkoff sounds. In this graph, a blood pressure tracing is aligned to a measurement of systolic and diastolic pressures.

                                      The majority of hospitals and clinics have automated equipment for measuring blood pressure that work on the same principles. An even more recent innovation is a small instrument that wraps around a patient’s wrist. The patient then holds the wrist over the heart while the device measures blood flow and records pressure.

                                      Variables Affecting Blood Flow and Blood Pressure

                                      Five variables influence blood flow and blood pressure:

                                      • Cardiac output

                                      • Compliance

                                      • Volume of the blood

                                      • Viscosity of the blood

                                      • Blood vessel length and diameter

                                      Recall that blood moves from higher pressure to lower pressure. It is pumped from the heart into the arteries at high pressure. If you increase pressure in the arteries (afterload), and cardiac function does not compensate, blood flow will actually decrease. In the venous system, the opposite relationship is true. Increased pressure in the veins does not decrease flow as it does in arteries, but actually increases flow. Since pressure in the veins is normally relatively low, for blood to flow back into the heart, the pressure in the atria during atrial diastole must be even lower. It normally approaches zero, except when the atria contract (see Figure 20.10).

                                      Cardiac Output

                                      Cardiac output is the measurement of blood flow from the heart through the ventricles, and is usually measured in liters per minute. Any factor that causes cardiac output to increase, by elevating heart rate or stroke volume or both, will elevate blood pressure and promote blood flow. These factors include sympathetic stimulation, the catecholamines epinephrine and norepinephrine, thyroid hormones, and increased calcium ion levels. Conversely, any factor that decreases cardiac output, by decreasing heart rate or stroke volume or both, will decrease arterial pressure and blood flow. These factors include parasympathetic stimulation, elevated or decreased potassium ion levels, decreased calcium levels, anoxia, and acidosis.

                                      Compliance

                                      Compliance is the ability of any compartment to expand to accommodate increased content. A metal pipe, for example, is not compliant, whereas a balloon is. The greater the compliance of an artery, the more effectively it is able to expand to accommodate surges in blood flow without increased resistance or blood pressure. Veins are more compliant than arteries and can expand to hold more blood. When vascular disease causes stiffening of arteries, compliance is reduced and resistance to blood flow is increased. The result is more turbulence, higher pressure within the vessel, and reduced blood flow. This increases the work of the heart.

                                      A Mathematical Approach to Factors Affecting Blood Flow

                                      Jean Louis Marie Poiseuille was a French physician and physiologist who devised a mathematical equation describing blood flow and its relationship to known parameters. The same equation also applies to engineering studies of the flow of fluids. Although understanding the math behind the relationships among the factors affecting blood flow is not necessary to understand blood flow, it can help solidify an understanding of their relationships. Please note that even if the equation looks intimidating, breaking it down into its components and following the relationships will make these relationships clearer, even if you are weak in math. Focus on the three critical variables: radius (r), vessel length (λ), and viscosity (η).

                                      Poiseuille’s equation:

                                      (20.1)
                                      • π is the Greek letter pi, used to represent the mathematical constant that is the ratio of a circle’s circumference to its diameter. It may commonly be represented as 3.14, although the actual number extends to infinity.

                                      • ΔP represents the difference in pressure.

                                      • r4 is the radius (one-half of the diameter) of the vessel to the fourth power.

                                      • η is the Greek letter eta and represents the viscosity of the blood.

                                      • λ is the Greek letter lambda and represents the length of a blood vessel.

                                      One of several things this equation allows us to do is calculate the resistance in the vascular system. Normally this value is extremely difficult to measure, but it can be calculated from this known relationship:

                                      (20.2)

                                      If we rearrange this slightly,

                                      (20.3)

                                      Then by substituting Pouseille’s equation for blood flow:

                                      (20.4)

                                      By examining this equation, you can see that there are only three variables: viscosity, vessel length, and radius, since 8 and π are both constants. The important thing to remember is this: Two of these variables, viscosity and vessel length, will change slowly in the body. Only one of these factors, the radius, can be changed rapidly by vasoconstriction and vasodilation, thus dramatically impacting resistance and flow. Further, small changes in the radius will greatly affect flow, since it is raised to the fourth power in the equation.

                                      We have briefly considered how cardiac output and blood volume impact blood flow and pressure; the next step is to see how the other variables (contraction, vessel length, and viscosity) articulate with Pouseille’s equation and what they can teach us about the impact on blood flow.

                                      Blood Volume

                                      The relationship between blood volume, blood pressure, and blood flow is intuitively obvious. Water may merely trickle along a creek bed in a dry season, but rush quickly and under great pressure after a heavy rain. Similarly, as blood volume decreases, pressure and flow decrease. As blood volume increases, pressure and flow increase.

                                      Under normal circumstances, blood volume varies little. Low blood volume, called hypovolemia, may be caused by bleeding, dehydration, vomiting, severe burns, or some medications used to treat hypertension. It is important to recognize that other regulatory mechanisms in the body are so effective at maintaining blood pressure that an individual may be asymptomatic until 10–20 percent of the blood volume has been lost. Treatment typically includes intravenous fluid replacement.

                                      Hypervolemia, excessive fluid volume, may be caused by retention of water and sodium, as seen in patients with heart failure, liver cirrhosis, some forms of kidney disease, hyperaldosteronism, and some glucocorticoid steroid treatments. Restoring homeostasis in these patients depends upon reversing the condition that triggered the hypervolemia.

                                      Blood Viscosity

                                      Viscosity is the thickness of fluids that affects their ability to flow. Clean water, for example, is less viscous than mud. The viscosity of blood is directly proportional to resistance and inversely proportional to flow; therefore, any condition that causes viscosity to increase will also increase resistance and decrease flow. For example, imagine sipping milk, then a milkshake, through the same size straw. You experience more resistance and therefore less flow from the milkshake. Conversely, any condition that causes viscosity to decrease (such as when the milkshake melts) will decrease resistance and increase flow.

                                      Normally the viscosity of blood does not change over short periods of time. The two primary determinants of blood viscosity are the formed elements and plasma proteins. Since the vast majority of formed elements are erythrocytes, any condition affecting erythropoiesis, such as polycythemia or anemia, can alter viscosity. Since most plasma proteins are produced by the liver, any condition affecting liver function can also change the viscosity slightly and therefore decrease blood flow. Liver abnormalities include hepatitis, cirrhosis, alcohol damage, and drug toxicities. While leukocytes and platelets are normally a small component of the formed elements, there are some rare conditions in which severe overproduction can impact viscosity as well.

                                      Vessel Length and Diameter

                                      The length of a vessel is directly proportional to its resistance: the longer the vessel, the greater the resistance and the lower the flow. As with blood volume, this makes intuitive sense, since the increased surface area of the vessel will impede the flow of blood. Likewise, if the vessel is shortened, the resistance will decrease and flow will increase.

                                      The length of our blood vessels increases throughout childhood as we grow, of course, but is unchanging in adults under normal physiological circumstances. Further, the distribution of vessels is not the same in all tissues. Adipose tissue does not have an extensive vascular supply. One pound of adipose tissue contains approximately 200 miles of vessels, whereas skeletal muscle contains more than twice that. Overall, vessels decrease in length only during loss of mass or amputation. An individual weighing 150 pounds has approximately 60,000 miles of vessels in the body. Gaining about 10 pounds adds from 2000 to 4000 miles of vessels, depending upon the nature of the gained tissue. One of the great benefits of weight reduction is the reduced stress to the heart, which does not have to overcome the resistance of as many miles of vessels.

                                      In contrast to length, the diameter of blood vessels changes throughout the body, according to the type of vessel, as we discussed earlier. The diameter of any given vessel may also change frequently throughout the day in response to neural and chemical signals that trigger vasodilation and vasoconstriction. The vascular tone of the vessel is the contractile state of the smooth muscle and the primary determinant of diameter, and thus of resistance and flow. The effect of vessel diameter on resistance is inverse: Given the same volume of blood, an increased diameter means there is less blood contacting the vessel wall, thus lower friction and lower resistance, subsequently increasing flow. A decreased diameter means more of the blood contacts the vessel wall, and resistance increases, subsequently decreasing flow.

                                      The influence of lumen diameter on resistance is dramatic: A slight increase or decrease in diameter causes a huge decrease or increase in resistance. This is because resistance is inversely proportional to the radius of the blood vessel (one-half of the vessel’s diameter) raised to the fourth power (R = 1/r4). This means, for example, that if an artery or arteriole constricts to one-half of its original radius, the resistance to flow will increase 16 times. And if an artery or arteriole dilates to twice its initial radius, then resistance in the vessel will decrease to 1/16 of its original value and flow will increase 16 times.

                                      The Roles of Vessel Diameter and Total Area in Blood Flow and Blood Pressure

                                      Recall that we classified arterioles as resistance vessels, because given their small lumen, they dramatically slow the flow of blood from arteries. In fact, arterioles are the site of greatest resistance in the entire vascular network. This may seem surprising, given that capillaries have a smaller size. How can this phenomenon be explained?

                                      Figure 20.13 compares vessel diameter, total cross-sectional area, average blood pressure, and blood velocity through the systemic vessels. Notice in parts (a) and (b) that the total cross-sectional area of the body’s capillary beds is far greater than any other type of vessel. Although the diameter of an individual capillary is significantly smaller than the diameter of an arteriole, there are vastly more capillaries in the body than there are other types of blood vessels. Part (c) shows that blood pressure drops unevenly as blood travels from arteries to arterioles, capillaries, venules, and veins, and encounters greater resistance. However, the site of the most precipitous drop, and the site of greatest resistance, is the arterioles. This explains why vasodilation and vasoconstriction of arterioles play more significant roles in regulating blood pressure than do the vasodilation and vasoconstriction of other vessels.

                                      Part (d) shows that the velocity (speed) of blood flow decreases dramatically as the blood moves from arteries to arterioles to capillaries. This slow flow rate allows more time for exchange processes to occur. As blood flows through the veins, the rate of velocity increases, as blood is returned to the heart.

                                      This figure shows four graphs. The top left graph shows the vessel diameter for different types of blood vessels. The top right panel shows cross-sectional area for different blood vessels. The bottom left panel shows the average blood pressure for different blood vessels, and the bottom right panel shows the velocity of blood flow in different blood vessels.
                                      Figure 20.13Relationships among Vessels in the Systemic Circuit
                                      The relationships among blood vessels that can be compared include (a) vessel diameter, (b) total cross-sectional area, (c) average blood pressure, and (d) velocity of blood flow.
                                      Disorders of the…

                                      Cardiovascular System: Arteriosclerosis

                                      Compliance allows an artery to expand when blood is pumped through it from the heart, and then to recoil after the surge has passed. This helps promote blood flow. In arteriosclerosis, compliance is reduced, and pressure and resistance within the vessel increase. This is a leading cause of hypertension and coronary heart disease, as it causes the heart to work harder to generate a pressure great enough to overcome the resistance.

                                      Arteriosclerosis begins with injury to the endothelium of an artery, which may be caused by irritation from high blood glucose, infection, tobacco use, excessive blood lipids, and other factors. Artery walls that are constantly stressed by blood flowing at high pressure are also more likely to be injured—which means that hypertension can promote arteriosclerosis, as well as result from it.

                                      Recall that tissue injury causes inflammation. As inflammation spreads into the artery wall, it weakens and scars it, leaving it stiff (sclerotic). As a result, compliance is reduced. Moreover, circulating triglycerides and cholesterol can seep between the damaged lining cells and become trapped within the artery wall, where they are frequently joined by leukocytes, calcium, and cellular debris. Eventually, this buildup, called plaque, can narrow arteries enough to impair blood flow. The term for this condition, atherosclerosis (athero- = “porridge”) describes the mealy deposits (Figure 20.14).

                                      The left panel shows the cross-section of a normal and a narrowed artery. The right panel shows a micrograph of an artery with plaque in it.
                                      Figure 20.14Atherosclerosis
                                      (a) Atherosclerosis can result from plaques formed by the buildup of fatty, calcified deposits in an artery. (b) Plaques can also take other forms, as shown in this micrograph of a coronary artery that has a buildup of connective tissue within the artery wall. LM × 40. (Micrograph provided by the Regents of University of Michigan Medical School © 2012)

                                      Sometimes a plaque can rupture, causing microscopic tears in the artery wall that allow blood to leak into the tissue on the other side. When this happens, platelets rush to the site to clot the blood. This clot can further obstruct the artery and—if it occurs in a coronary or cerebral artery—cause a sudden heart attack or stroke. Alternatively, plaque can break off and travel through the bloodstream as an embolus until it blocks a more distant, smaller artery.

                                      Even without total blockage, vessel narrowing leads to ischemia—reduced blood flow—to the tissue region “downstream” of the narrowed vessel. Ischemia in turn leads to hypoxia—decreased supply of oxygen to the tissues. Hypoxia involving cardiac muscle or brain tissue can lead to cell death and severe impairment of brain or heart function.

                                      A major risk factor for both arteriosclerosis and atherosclerosis is advanced age, as the conditions tend to progress over time. Arteriosclerosis is normally defined as the more generalized loss of compliance, “hardening of the arteries,” whereas atherosclerosis is a more specific term for the build-up of plaque in the walls of the vessel and is a specific type of arteriosclerosis. There is also a distinct genetic component, and pre-existing hypertension and/or diabetes also greatly increase the risk. However, obesity, poor nutrition, lack of physical activity, and tobacco use all are major risk factors.

                                      Treatment includes lifestyle changes, such as weight loss, smoking cessation, regular exercise, and adoption of a diet low in sodium and saturated fats. Medications to reduce cholesterol and blood pressure may be prescribed. For blocked coronary arteries, surgery is warranted. In angioplasty, a catheter is inserted into the vessel at the point of narrowing, and a second catheter with a balloon-like tip is inflated to widen the opening. To prevent subsequent collapse of the vessel, a small mesh tube called a stent is often inserted. In an endarterectomy, plaque is surgically removed from the walls of a vessel. This operation is typically performed on the carotid arteries of the neck, which are a prime source of oxygenated blood for the brain. In a coronary bypass procedure, a non-vital superficial vessel from another part of the body (often the great saphenous vein) or a synthetic vessel is inserted to create a path around the blocked area of a coronary artery.

                                      Venous System

                                      The pumping action of the heart propels the blood into the arteries, from an area of higher pressure toward an area of lower pressure. If blood is to flow from the veins back into the heart, the pressure in the veins must be greater than the pressure in the atria of the heart. Two factors help maintain this pressure gradient between the veins and the heart. First, the pressure in the atria during diastole is very low, often approaching zero when the atria are relaxed (atrial diastole). Second, two physiologic “pumps” increase pressure in the venous system. The use of the term “pump” implies a physical device that speeds flow. These physiological pumps are less obvious.

                                      Skeletal Muscle Pump

                                      In many body regions, the pressure within the veins can be increased by the contraction of the surrounding skeletal muscle. This mechanism, known as the skeletal muscle pump (Figure 20.15), helps the lower-pressure veins counteract the force of gravity, increasing pressure to move blood back to the heart. As leg muscles contract, for example during walking or running, they exert pressure on nearby veins with their numerous one-way valves. This increased pressure causes blood to flow upward, opening valves superior to the contracting muscles so blood flows through. Simultaneously, valves inferior to the contracting muscles close; thus, blood should not seep back downward toward the feet. Military recruits are trained to flex their legs slightly while standing at attention for prolonged periods. Failure to do so may allow blood to pool in the lower limbs rather than returning to the heart. Consequently, the brain will not receive enough oxygenated blood, and the individual may lose consciousness.

                                      The left panel shows the structure of a skeletal muscle vein pump when the muscle is relaxed, and the right panel shows the structure of a skeletal muscle vein pump when the muscle is contracted.
                                      Figure 20.15Skeletal Muscle Pump
                                      The contraction of skeletal muscles surrounding a vein compresses the blood and increases the pressure in that area. This action forces blood closer to the heart where venous pressure is lower. Note the importance of the one-way valves to assure that blood flows only in the proper direction.

                                      Respiratory Pump

                                      The respiratory pump aids blood flow through the veins of the thorax and abdomen. During inhalation, the volume of the thorax increases, largely through the contraction of the diaphragm, which moves downward and compresses the abdominal cavity. The elevation of the chest caused by the contraction of the external intercostal muscles also contributes to the increased volume of the thorax. The volume increase causes air pressure within the thorax to decrease, allowing us to inhale. Additionally, as air pressure within the thorax drops, blood pressure in the thoracic veins also decreases, falling below the pressure in the abdominal veins. This causes blood to flow along its pressure gradient from veins outside the thorax, where pressure is higher, into the thoracic region, where pressure is now lower. This in turn promotes the return of blood from the thoracic veins to the atria. During exhalation, when air pressure increases within the thoracic cavity, pressure in the thoracic veins increases, speeding blood flow into the heart while valves in the veins prevent blood from flowing backward from the thoracic and abdominal veins.

                                      Pressure Relationships in the Venous System

                                      Although vessel diameter increases from the smaller venules to the larger veins and eventually to the venae cavae (singular = vena cava), the total cross-sectional area actually decreases (see Figure 20.15a and b). The individual veins are larger in diameter than the venules, but their total number is much lower, so their total cross-sectional area is also lower.

                                      Also notice that, as blood moves from venules to veins, the average blood pressure drops (see Figure 20.15c), but the blood velocity actually increases (see Figure 20.15). This pressure gradient drives blood back toward the heart. Again, the presence of one-way valves and the skeletal muscle and respiratory pumps contribute to this increased flow. Since approximately 64 percent of the total blood volume resides in systemic veins, any action that increases the flow of blood through the veins will increase venous return to the heart. Maintaining vascular tone within the veins prevents the veins from merely distending, dampening the flow of blood, and as you will see, vasoconstriction actually enhances the flow.

                                      The Role of Venoconstriction in Resistance, Blood Pressure, and Flow

                                      As previously discussed, vasoconstriction of an artery or arteriole decreases the radius, increasing resistance and pressure, but decreasing flow. Venoconstriction, on the other hand, has a very different outcome. The walls of veins are thin but irregular; thus, when the smooth muscle in those walls constricts, the lumen becomes more rounded. The more rounded the lumen, the less surface area the blood encounters, and the less resistance the vessel offers. Vasoconstriction increases pressure within a vein as it does in an artery, but in veins, the increased pressure increases flow. Recall that the pressure in the atria, into which the venous blood will flow, is very low, approaching zero for at least part of the relaxation phase of the cardiac cycle. Thus, venoconstriction increases the return of blood to the heart. Another way of stating this is that venoconstriction increases the preload or stretch of the cardiac muscle and increases contraction.

                                      20.3Capillary Exchange*

                                      By the end of this section, you will be able to:

                                      • Identify the primary mechanisms of capillary exchange

                                      • Distinguish between capillary hydrostatic pressure and blood colloid osmotic pressure, explaining the contribution of each to net filtration pressure

                                      • Compare filtration and reabsorption

                                      • Explain the fate of fluid that is not reabsorbed from the tissues into the vascular capillaries

                                      • Bulk Flow
                                        • Hydrostatic Pressure
                                        • Osmotic Pressure
                                        • Interaction of Hydrostatic and Osmotic Pressures
                                      • The Role of Lymphatic Capillaries

                                      The primary purpose of the cardiovascular system is to circulate gases, nutrients, wastes, and other substances to and from the cells of the body. Small molecules, such as gases, lipids, and lipid-soluble molecules, can diffuse directly through the membranes of the endothelial cells of the capillary wall. Glucose, amino acids, and ions—including sodium, potassium, calcium, and chloride—use transporters to move through specific channels in the membrane by facilitated diffusion. Glucose, ions, and larger molecules may also leave the blood through intercellular clefts. Larger molecules can pass through the pores of fenestrated capillaries, and even large plasma proteins can pass through the great gaps in the sinusoids. Some large proteins in blood plasma can move into and out of the endothelial cells packaged within vesicles by endocytosis and exocytosis. Water moves by osmosis.

                                      Bulk Flow

                                      The mass movement of fluids into and out of capillary beds requires a transport mechanism far more efficient than mere diffusion. This movement, often referred to as bulk flow, involves two pressure-driven mechanisms: Volumes of fluid move from an area of higher pressure in a capillary bed to an area of lower pressure in the tissues via filtration. In contrast, the movement of fluid from an area of higher pressure in the tissues into an area of lower pressure in the capillaries is reabsorption. Two types of pressure interact to drive each of these movements: hydrostatic pressure and osmotic pressure.

                                      Hydrostatic Pressure

                                      The primary force driving fluid transport between the capillaries and tissues is hydrostatic pressure, which can be defined as the pressure of any fluid enclosed in a space. Blood hydrostatic pressure is the force exerted by the blood confined within blood vessels or heart chambers. Even more specifically, the pressure exerted by blood against the wall of a capillary is called capillary hydrostatic pressure (CHP), and is the same as capillary blood pressure. CHP is the force that drives fluid out of capillaries and into the tissues.

                                      As fluid exits a capillary and moves into tissues, the hydrostatic pressure in the interstitial fluid correspondingly rises. This opposing hydrostatic pressure is called the interstitial fluid hydrostatic pressure (IFHP). Generally, the CHP originating from the arterial pathways is considerably higher than the IFHP, because lymphatic vessels are continually absorbing excess fluid from the tissues. Thus, fluid generally moves out of the capillary and into the interstitial fluid. This process is called filtration.

                                      Osmotic Pressure

                                      The net pressure that drives reabsorption—the movement of fluid from the interstitial fluid back into the capillaries—is called osmotic pressure (sometimes referred to as oncotic pressure). Whereas hydrostatic pressure forces fluid out of the capillary, osmotic pressure draws fluid back in. Osmotic pressure is determined by osmotic concentration gradients, that is, the difference in the solute-to-water concentrations in the blood and tissue fluid. A region higher in solute concentration (and lower in water concentration) draws water across a semipermeable membrane from a region higher in water concentration (and lower in solute concentration).

                                      As we discuss osmotic pressure in blood and tissue fluid, it is important to recognize that the formed elements of blood do not contribute to osmotic concentration gradients. Rather, it is the plasma proteins that play the key role. Solutes also move across the capillary wall according to their concentration gradient, but overall, the concentrations should be similar and not have a significant impact on osmosis. Because of their large size and chemical structure, plasma proteins are not truly solutes, that is, they do not dissolve but are dispersed or suspended in their fluid medium, forming a colloid rather than a solution.

                                      The pressure created by the concentration of colloidal proteins in the blood is called the blood colloidal osmotic pressure (BCOP). Its effect on capillary exchange accounts for the reabsorption of water. The plasma proteins suspended in blood cannot move across the semipermeable capillary cell membrane, and so they remain in the plasma. As a result, blood has a higher colloidal concentration and lower water concentration than tissue fluid. It therefore attracts water. We can also say that the BCOP is higher than the interstitial fluid colloidal osmotic pressure (IFCOP), which is always very low because interstitial fluid contains few proteins. Thus, water is drawn from the tissue fluid back into the capillary, carrying dissolved molecules with it. This difference in colloidal osmotic pressure accounts for reabsorption.

                                      Interaction of Hydrostatic and Osmotic Pressures

                                      The normal unit used to express pressures within the cardiovascular system is millimeters of mercury (mm Hg). When blood leaving an arteriole first enters a capillary bed, the CHP is quite high—about 35 mm Hg. Gradually, this initial CHP declines as the blood moves through the capillary so that by the time the blood has reached the venous end, the CHP has dropped to approximately 18 mm Hg. In comparison, the plasma proteins remain suspended in the blood, so the BCOP remains fairly constant at about 25 mm Hg throughout the length of the capillary and considerably below the osmotic pressure in the interstitial fluid.

                                      The net filtration pressure (NFP) represents the interaction of the hydrostatic and osmotic pressures, driving fluid out of the capillary. It is equal to the difference between the CHP and the BCOP. Since filtration is, by definition, the movement of fluid out of the capillary, when reabsorption is occurring, the NFP is a negative number.

                                      NFP changes at different points in a capillary bed (Figure 20.16). Close to the arterial end of the capillary, it is approximately 10 mm Hg, because the CHP of 35 mm Hg minus the BCOP of 25 mm Hg equals 10 mm Hg. Recall that the hydrostatic and osmotic pressures of the interstitial fluid are essentially negligible. Thus, the NFP of 10 mm Hg drives a net movement of fluid out of the capillary at the arterial end. At approximately the middle of the capillary, the CHP is about the same as the BCOP of 25 mm Hg, so the NFP drops to zero. At this point, there is no net change of volume: Fluid moves out of the capillary at the same rate as it moves into the capillary. Near the venous end of the capillary, the CHP has dwindled to about 18 mm Hg due to loss of fluid. Because the BCOP remains steady at 25 mm Hg, water is drawn into the capillary, that is, reabsorption occurs. Another way of expressing this is to say that at the venous end of the capillary, there is an NFP of −7 mm Hg.

                                      This diagram shows the process of fluid exchange in a capillary from the arterial end to the venous end.
                                      Figure 20.16Capillary Exchange
                                      Net filtration occurs near the arterial end of the capillary since capillary hydrostatic pressure (CHP) is greater than blood colloidal osmotic pressure (BCOP). There is no net movement of fluid near the midpoint since CHP = BCOP. Net reabsorption occurs near the venous end since BCOP is greater than CHP.

                                      The Role of Lymphatic Capillaries

                                      Since overall CHP is higher than BCOP, it is inevitable that more net fluid will exit the capillary through filtration at the arterial end than enters through reabsorption at the venous end. Considering all capillaries over the course of a day, this can be quite a substantial amount of fluid: Approximately 24 liters per day are filtered, whereas 20.4 liters are reabsorbed. This excess fluid is picked up by capillaries of the lymphatic system. These extremely thin-walled vessels have copious numbers of valves that ensure unidirectional flow through ever-larger lymphatic vessels that eventually drain into the subclavian veins in the neck. An important function of the lymphatic system is to return the fluid (lymph) to the blood. Lymph may be thought of as recycled blood plasma. (Seek additional content for more detail on the lymphatic system.)

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                                      Watch this video to explore capillaries and how they function in the body. Capillaries are never more than 100 micrometers away. What is the main component of interstitial fluid?

                                      20.4Homeostatic Regulation of the Vascular System*

                                      By the end of this section, you will be able to:

                                      • Discuss the mechanisms involved in the neural regulation of vascular homeostasis

                                      • Describe the contribution of a variety of hormones to the renal regulation of blood pressure

                                      • Identify the effects of exercise on vascular homeostasis

                                      • Discuss how hypertension, hemorrhage, and circulatory shock affect vascular health

                                      • Neural Regulation
                                        • The Cardiovascular Centers in the Brain
                                        • Baroreceptor Reflexes
                                        • Chemoreceptor Reflexes
                                      • Endocrine Regulation
                                        • Epinephrine and Norepinephrine
                                        • Antidiuretic Hormone
                                        • Renin-Angiotensin-Aldosterone Mechanism
                                        • Erythropoietin
                                        • Atrial Natriuretic Hormone
                                      • Autoregulation of Perfusion
                                        • Chemical Signals Involved in Autoregulation
                                        • The Myogenic Response
                                      • Effect of Exercise on Vascular Homeostasis
                                      • Clinical Considerations in Vascular Homeostasis
                                        • Hypertension and Hypotension
                                        • Hemorrhage
                                        • Circulatory Shock

                                      In order to maintain homeostasis in the cardiovascular system and provide adequate blood to the tissues, blood flow must be redirected continually to the tissues as they become more active. In a very real sense, the cardiovascular system engages in resource allocation, because there is not enough blood flow to distribute blood equally to all tissues simultaneously. For example, when an individual is exercising, more blood will be directed to skeletal muscles, the heart, and the lungs. Following a meal, more blood is directed to the digestive system. Only the brain receives a more or less constant supply of blood whether you are active, resting, thinking, or engaged in any other activity.

                                      Table 20.3 provides the distribution of systemic blood at rest and during exercise. Although most of the data appears logical, the values for the distribution of blood to the integument may seem surprising. During exercise, the body distributes more blood to the body surface where it can dissipate the excess heat generated by increased activity into the environment.

                                      Table 20.3.
                                      Systemic Blood Flow During Rest, Mild Exercise, and Maximal Exercise in a Healthy Young Individual
                                      Organ Resting
                                      (mL/min)
                                      Mild exercise
                                      (mL/min)
                                      Maximal exercise
                                      (mL/min)
                                      Skeletal muscle 1200 4500 12,500
                                      Heart 250 350 750
                                      Brain 750 750 750
                                      Integument 500 1500 1900
                                      Kidney 1100 900 600
                                      Gastrointestinal 1400 1100 600
                                      Others
                                      (i.e., liver, spleen)
                                      600 400 400
                                      Total 5800 9500 17,500

                                      Three homeostatic mechanisms ensure adequate blood flow, blood pressure, distribution, and ultimately perfusion: neural, endocrine, and autoregulatory mechanisms. They are summarized in Figure 20.17.

                                      This flowchart shows the various factors that control the flow of blood. The top panel focuses on autoregulation, and the bottom panel focuses on neural and endocrine mechanisms.
                                      Figure 20.17Summary of Factors Maintaining Vascular Homeostasis
                                      Adequate blood flow, blood pressure, distribution, and perfusion involve autoregulatory, neural, and endocrine mechanisms.

                                      Neural Regulation

                                      The nervous system plays a critical role in the regulation of vascular homeostasis. The primary regulatory sites include the cardiovascular centers in the brain that control both cardiac and vascular functions. In addition, more generalized neural responses from the limbic system and the autonomic nervous system are factors.

                                      The Cardiovascular Centers in the Brain

                                      Neurological regulation of blood pressure and flow depends on the cardiovascular centers located in the medulla oblongata. This cluster of neurons responds to changes in blood pressure as well as blood concentrations of oxygen, carbon dioxide, and hydrogen ions. The cardiovascular center contains three distinct paired components:

                                      • The cardioaccelerator centers stimulate cardiac function by regulating heart rate and stroke volume via sympathetic stimulation from the cardiac accelerator nerve.

                                      • The cardioinhibitor centers slow cardiac function by decreasing heart rate and stroke volume via parasympathetic stimulation from the vagus nerve.

                                      • The vasomotor centers control vessel tone or contraction of the smooth muscle in the tunica media. Changes in diameter affect peripheral resistance, pressure, and flow, which affect cardiac output. The majority of these neurons act via the release of the neurotransmitter norepinephrine from sympathetic neurons.

                                      Although each center functions independently, they are not anatomically distinct.

                                      There is also a small population of neurons that control vasodilation in the vessels of the brain and skeletal muscles by relaxing the smooth muscle fibers in the vessel tunics. Many of these are cholinergic neurons, that is, they release acetylcholine, which in turn stimulates the vessels’ endothelial cells to release nitric oxide (NO), which causes vasodilation. Others release norepinephrine that binds to β2 receptors. A few neurons release NO directly as a neurotransmitter.

                                      Recall that mild stimulation of the skeletal muscles maintains muscle tone. A similar phenomenon occurs with vascular tone in vessels. As noted earlier, arterioles are normally partially constricted: With maximal stimulation, their radius may be reduced to one-half of the resting state. Full dilation of most arterioles requires that this sympathetic stimulation be suppressed. When it is, an arteriole can expand by as much as 150 percent. Such a significant increase can dramatically affect resistance, pressure, and flow.

                                      Baroreceptor Reflexes

                                      Baroreceptors are specialized stretch receptors located within thin areas of blood vessels and heart chambers that respond to the degree of stretch caused by the presence of blood. They send impulses to the cardiovascular center to regulate blood pressure. Vascular baroreceptors are found primarily in sinuses (small cavities) within the aorta and carotid arteries: The aortic sinuses are found in the walls of the ascending aorta just superior to the aortic valve, whereas the carotid sinuses are in the base of the internal carotid arteries. There are also low-pressure baroreceptors located in the walls of the venae cavae and right atrium.

                                      When blood pressure increases, the baroreceptors are stretched more tightly and initiate action potentials at a higher rate. At lower blood pressures, the degree of stretch is lower and the rate of firing is slower. When the cardiovascular center in the medulla oblongata receives this input, it triggers a reflex that maintains homeostasis (Figure 20.18):

                                      • When blood pressure rises too high, the baroreceptors fire at a higher rate and trigger parasympathetic stimulation of the heart. As a result, cardiac output falls. Sympathetic stimulation of the peripheral arterioles will also decrease, resulting in vasodilation. Combined, these activities cause blood pressure to fall.

                                      • When blood pressure drops too low, the rate of baroreceptor firing decreases. This will trigger an increase in sympathetic stimulation of the heart, causing cardiac output to increase. It will also trigger sympathetic stimulation of the peripheral vessels, resulting in vasoconstriction. Combined, these activities cause blood pressure to rise.

                                      This flow chart shows what happens when blood pressure is increased or decreased. The top panel shows the events that take place when blood pressure is increased, and the bottom panel shows the events that take place when blood pressure is decreased.
                                      Figure 20.18Baroreceptor Reflexes for Maintaining Vascular Homeostasis
                                      Increased blood pressure results in increased rates of baroreceptor firing, whereas decreased blood pressure results in slower rates of fire, both initiating the homeostatic mechanism to restore blood pressure.

                                      The baroreceptors in the venae cavae and right atrium monitor blood pressure as the blood returns to the heart from the systemic circulation. Normally, blood flow into the aorta is the same as blood flow back into the right atrium. If blood is returning to the right atrium more rapidly than it is being ejected from the left ventricle, the atrial receptors will stimulate the cardiovascular centers to increase sympathetic firing and increase cardiac output until homeostasis is achieved. The opposite is also true. This mechanism is referred to as the atrial reflex.

                                      Chemoreceptor Reflexes

                                      In addition to the baroreceptors are chemoreceptors that monitor levels of oxygen, carbon dioxide, and hydrogen ions (pH), and thereby contribute to vascular homeostasis. Chemoreceptors monitoring the blood are located in close proximity to the baroreceptors in the aortic and carotid sinuses. They signal the cardiovascular center as well as the respiratory centers in the medulla oblongata.

                                      Since tissues consume oxygen and produce carbon dioxide and acids as waste products, when the body is more active, oxygen levels fall and carbon dioxide levels rise as cells undergo cellular respiration to meet the energy needs of activities. This causes more hydrogen ions to be produced, causing the blood pH to drop. When the body is resting, oxygen levels are higher, carbon dioxide levels are lower, more hydrogen is bound, and pH rises. (Seek additional content for more detail about pH.)

                                      The chemoreceptors respond to increasing carbon dioxide and hydrogen ion levels (falling pH) by stimulating the cardioaccelerator and vasomotor centers, increasing cardiac output and constricting peripheral vessels. The cardioinhibitor centers are suppressed. With falling carbon dioxide and hydrogen ion levels (increasing pH), the cardioinhibitor centers are stimulated, and the cardioaccelerator and vasomotor centers are suppressed, decreasing cardiac output and causing peripheral vasodilation. In order to maintain adequate supplies of oxygen to the cells and remove waste products such as carbon dioxide, it is essential that the respiratory system respond to changing metabolic demands. In turn, the cardiovascular system will transport these gases to the lungs for exchange, again in accordance with metabolic demands. This interrelationship of cardiovascular and respiratory control cannot be overemphasized.

                                      Other neural mechanisms can also have a significant impact on cardiovascular function. These include the limbic system that links physiological responses to psychological stimuli, as well as generalized sympathetic and parasympathetic stimulation.

                                      Endocrine Regulation

                                      Endocrine control over the cardiovascular system involves the catecholamines, epinephrine and norepinephrine, as well as several hormones that interact with the kidneys in the regulation of blood volume.

                                      Epinephrine and Norepinephrine

                                      The catecholamines epinephrine and norepinephrine are released by the adrenal medulla, and enhance and extend the body’s sympathetic or “fight-or-flight” response (see Figure 20.17). They increase heart rate and force of contraction, while temporarily constricting blood vessels to organs not essential for flight-or-fight responses and redirecting blood flow to the liver, muscles, and heart.

                                      Antidiuretic Hormone

                                      Antidiuretic hormone (ADH), also known as vasopressin, is secreted by the cells in the hypothalamus and transported via the hypothalamic-hypophyseal tracts to the posterior pituitary where it is stored until released upon nervous stimulation. The primary trigger prompting the hypothalamus to release ADH is increasing osmolarity of tissue fluid, usually in response to significant loss of blood volume. ADH signals its target cells in the kidneys to reabsorb more water, thus preventing the loss of additional fluid in the urine. This will increase overall fluid levels and help restore blood volume and pressure. In addition, ADH constricts peripheral vessels.

                                      Renin-Angiotensin-Aldosterone Mechanism

                                      The renin-angiotensin-aldosterone mechanism has a major effect upon the cardiovascular system (Figure 20.19). Renin is an enzyme, although because of its importance in the renin-angiotensin-aldosterone pathway, some sources identify it as a hormone. Specialized cells in the kidneys found in the juxtaglomerular apparatus respond to decreased blood flow by secreting renin into the blood. Renin converts the plasma protein angiotensinogen, which is produced by the liver, into its active form—angiotensin I. Angiotensin I circulates in the blood and is then converted into angiotensin II in the lungs. This reaction is catalyzed by the enzyme angiotensin-converting enzyme (ACE).

                                      Angiotensin II is a powerful vasoconstrictor, greatly increasing blood pressure. It also stimulates the release of ADH and aldosterone, a hormone produced by the adrenal cortex. Aldosterone increases the reabsorption of sodium into the blood by the kidneys. Since water follows sodium, this increases the reabsorption of water. This in turn increases blood volume, raising blood pressure. Angiotensin II also stimulates the thirst center in the hypothalamus, so an individual will likely consume more fluids, again increasing blood volume and pressure.

                                      This flow chart shows the action of decreased blood pressure in the short and long term.
                                      Figure 20.19Hormones Involved in Renal Control of Blood Pressure
                                      In the renin-angiotensin-aldosterone mechanism, increasing angiotensin II will stimulate the production of antidiuretic hormone and aldosterone. In addition to renin, the kidneys produce erythropoietin, which stimulates the production of red blood cells, further increasing blood volume.

                                      Erythropoietin

                                      Erythropoietin (EPO) is released by the kidneys when blood flow and/or oxygen levels decrease. EPO stimulates the production of erythrocytes within the bone marrow. Erythrocytes are the major formed element of the blood and may contribute 40 percent or more to blood volume, a significant factor of viscosity, resistance, pressure, and flow. In addition, EPO is a vasoconstrictor. Overproduction of EPO or excessive intake of synthetic EPO, often to enhance athletic performance, will increase viscosity, resistance, and pressure, and decrease flow in addition to its contribution as a vasoconstrictor.

                                      Atrial Natriuretic Hormone

                                      Secreted by cells in the atria of the heart, atrial natriuretic hormone (ANH) (also known as atrial natriuretic peptide) is secreted when blood volume is high enough to cause extreme stretching of the cardiac cells. Cells in the ventricle produce a hormone with similar effects, called B-type natriuretic hormone. Natriuretic hormones are antagonists to angiotensin II. They promote loss of sodium and water from the kidneys, and suppress renin, aldosterone, and ADH production and release. All of these actions promote loss of fluid from the body, so blood volume and blood pressure drop.

                                      Autoregulation of Perfusion

                                      As the name would suggest, autoregulation mechanisms require neither specialized nervous stimulation nor endocrine control. Rather, these are local, self-regulatory mechanisms that allow each region of tissue to adjust its blood flow—and thus its perfusion. These local mechanisms include chemical signals and myogenic controls.

                                      Chemical Signals Involved in Autoregulation

                                      Chemical signals work at the level of the precapillary sphincters to trigger either constriction or relaxation. As you know, opening a precapillary sphincter allows blood to flow into that particular capillary, whereas constricting a precapillary sphincter temporarily shuts off blood flow to that region. The factors involved in regulating the precapillary sphincters include the following:

                                      • Opening of the sphincter is triggered in response to decreased oxygen concentrations; increased carbon dioxide concentrations; increasing levels of lactic acid or other byproducts of cellular metabolism; increasing concentrations of potassium ions or hydrogen ions (falling pH); inflammatory chemicals such as histamines; and increased body temperature. These conditions in turn stimulate the release of NO, a powerful vasodilator, from endothelial cells (see Figure 20.17).

                                      • Contraction of the precapillary sphincter is triggered by the opposite levels of the regulators, which prompt the release of endothelins, powerful vasoconstricting peptides secreted by endothelial cells. Platelet secretions and certain prostaglandins may also trigger constriction.

                                      Again, these factors alter tissue perfusion via their effects on the precapillary sphincter mechanism, which regulates blood flow to capillaries. Since the amount of blood is limited, not all capillaries can fill at once, so blood flow is allocated based upon the needs and metabolic state of the tissues as reflected in these parameters. Bear in mind, however, that dilation and constriction of the arterioles feeding the capillary beds is the primary control mechanism.

                                      The Myogenic Response

                                      The myogenic response is a reaction to the stretching of the smooth muscle in the walls of arterioles as changes in blood flow occur through the vessel. This may be viewed as a largely protective function against dramatic fluctuations in blood pressure and blood flow to maintain homeostasis. If perfusion of an organ is too low (ischemia), the tissue will experience low levels of oxygen (hypoxia). In contrast, excessive perfusion could damage the organ’s smaller and more fragile vessels. The myogenic response is a localized process that serves to stabilize blood flow in the capillary network that follows that arteriole.

                                      When blood flow is low, the vessel’s smooth muscle will be only minimally stretched. In response, it relaxes, allowing the vessel to dilate and thereby increase the movement of blood into the tissue. When blood flow is too high, the smooth muscle will contract in response to the increased stretch, prompting vasoconstriction that reduces blood flow.

                                      Figure 20.20 summarizes the effects of nervous, endocrine, and local controls on arterioles.

                                      This table summarizes mechanisms that regulate arteriole smooth muscle and veins. Neural controls are regulated by sympathetic stimulation and parasympathetic. Endocrine controls are regulated by epinephrine, norepinephrine, angiotensin II, ANH (peptide), and ADH. Other factors include decreasing levels of oxygen, decreasing pH, increasing levels of carbon dioxide, increasing levels of potassium ion, increasing levels of prostaglandins, increasing levels of andenosine, increasing levels of NO, increasing levels of lactic acid and other metabolites, increasing levels of endothelins, increasing levels of platelet secretions, increasing hyperhtermia, stretching of vascular wall (myogenic), and increasing levels of histamines from basophils and mast cells.
                                      Figure 20.20Summary of Mechanisms Regulating Arteriole Smooth Muscle and Veins

                                      Effect of Exercise on Vascular Homeostasis

                                      The heart is a muscle and, like any muscle, it responds dramatically to exercise. For a healthy young adult, cardiac output (heart rate × stroke volume) increases in the nonathlete from approximately 5.0 liters (5.25 quarts) per minute to a maximum of about 20 liters (21 quarts) per minute. Accompanying this will be an increase in blood pressure from about 120/80 to 185/75. However, well-trained aerobic athletes can increase these values substantially. For these individuals, cardiac output soars from approximately 5.3 liters (5.57 quarts) per minute resting to more than 30 liters (31.5 quarts) per minute during maximal exercise. Along with this increase in cardiac output, blood pressure increases from 120/80 at rest to 200/90 at maximum values.

                                      In addition to improved cardiac function, exercise increases the size and mass of the heart. The average weight of the heart for the nonathlete is about 300 g, whereas in an athlete it will increase to 500 g. This increase in size generally makes the heart stronger and more efficient at pumping blood, increasing both stroke volume and cardiac output.

                                      Tissue perfusion also increases as the body transitions from a resting state to light exercise and eventually to heavy exercise (see Figure 20.20). These changes result in selective vasodilation in the skeletal muscles, heart, lungs, liver, and integument. Simultaneously, vasoconstriction occurs in the vessels leading to the kidneys and most of the digestive and reproductive organs. The flow of blood to the brain remains largely unchanged whether at rest or exercising, since the vessels in the brain largely do not respond to regulatory stimuli, in most cases, because they lack the appropriate receptors.

                                      As vasodilation occurs in selected vessels, resistance drops and more blood rushes into the organs they supply. This blood eventually returns to the venous system. Venous return is further enhanced by both the skeletal muscle and respiratory pumps. As blood returns to the heart more quickly, preload rises and the Frank-Starling principle tells us that contraction of the cardiac muscle in the atria and ventricles will be more forceful. Eventually, even the best-trained athletes will fatigue and must undergo a period of rest following exercise. Cardiac output and distribution of blood then return to normal.

                                      Regular exercise promotes cardiovascular health in a variety of ways. Because an athlete’s heart is larger than a nonathlete’s, stroke volume increases, so the athletic heart can deliver the same amount of blood as the nonathletic heart but with a lower heart rate. This increased efficiency allows the athlete to exercise for longer periods of time before muscles fatigue and places less stress on the heart. Exercise also lowers overall cholesterol levels by removing from the circulation a complex form of cholesterol, triglycerides, and proteins known as low-density lipoproteins (LDLs), which are widely associated with increased risk of cardiovascular disease. Although there is no way to remove deposits of plaque from the walls of arteries other than specialized surgery, exercise does promote the health of vessels by decreasing the rate of plaque formation and reducing blood pressure, so the heart does not have to generate as much force to overcome resistance.

                                      Generally as little as 30 minutes of noncontinuous exercise over the course of each day has beneficial effects and has been shown to lower the rate of heart attack by nearly 50 percent. While it is always advisable to follow a healthy diet, stop smoking, and lose weight, studies have clearly shown that fit, overweight people may actually be healthier overall than sedentary slender people. Thus, the benefits of moderate exercise are undeniable.

                                      Clinical Considerations in Vascular Homeostasis

                                      Any disorder that affects blood volume, vascular tone, or any other aspect of vascular functioning is likely to affect vascular homeostasis as well. That includes hypertension, hemorrhage, and shock.

                                      Hypertension and Hypotension

                                      Chronically elevated blood pressure is known clinically as hypertension. It is defined as chronic and persistent blood pressure measurements of 140/90 mm Hg or above. Pressures between 120/80 and 140/90 mm Hg are defined as prehypertension. About 68 million Americans currently suffer from hypertension. Unfortunately, hypertension is typically a silent disorder; therefore, hypertensive patients may fail to recognize the seriousness of their condition and fail to follow their treatment plan. The result is often a heart attack or stroke. Hypertension may also lead to an aneurism (ballooning of a blood vessel caused by a weakening of the wall), peripheral arterial disease (obstruction of vessels in peripheral regions of the body), chronic kidney disease, or heart failure.

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                                      Hemorrhage

                                      Minor blood loss is managed by hemostasis and repair. Hemorrhage is a loss of blood that cannot be controlled by hemostatic mechanisms. Initially, the body responds to hemorrhage by initiating mechanisms aimed at increasing blood pressure and maintaining blood flow. Ultimately, however, blood volume will need to be restored, either through physiological processes or through medical intervention.

                                      In response to blood loss, stimuli from the baroreceptors trigger the cardiovascular centers to stimulate sympathetic responses to increase cardiac output and vasoconstriction. This typically prompts the heart rate to increase to about 180–200 contractions per minute, restoring cardiac output to normal levels. Vasoconstriction of the arterioles increases vascular resistance, whereas constriction of the veins increases venous return to the heart. Both of these steps will help increase blood pressure. Sympathetic stimulation also triggers the release of epinephrine and norepinephrine, which enhance both cardiac output and vasoconstriction. If blood loss were less than 20 percent of total blood volume, these responses together would usually return blood pressure to normal and redirect the remaining blood to the tissues.

                                      Additional endocrine involvement is necessary, however, to restore the lost blood volume. The angiotensin-renin-aldosterone mechanism stimulates the thirst center in the hypothalamus, which increases fluid consumption to help restore the lost blood. More importantly, it increases renal reabsorption of sodium and water, reducing water loss in urine output. The kidneys also increase the production of EPO, stimulating the formation of erythrocytes that not only deliver oxygen to the tissues but also increase overall blood volume. Figure 20.21 summarizes the responses to loss of blood volume.

                                      This flowchart shows the action of decreased blood pressure and volume in the neural and endocrine mechanisms.
                                      Figure 20.21Homeostatic Responses to Loss of Blood Volume

                                      Circulatory Shock

                                      The loss of too much blood may lead to circulatory shock, a life-threatening condition in which the circulatory system is unable to maintain blood flow to adequately supply sufficient oxygen and other nutrients to the tissues to maintain cellular metabolism. It should not be confused with emotional or psychological shock. Typically, the patient in circulatory shock will demonstrate an increased heart rate but decreased blood pressure, but there are cases in which blood pressure will remain normal. Urine output will fall dramatically, and the patient may appear confused or lose consciousness. Urine output less than 1 mL/kg body weight/hour is cause for concern. Unfortunately, shock is an example of a positive-feedback loop that, if uncorrected, may lead to the death of the patient.

                                      There are several recognized forms of shock:

                                      • Hypovolemic shock in adults is typically caused by hemorrhage, although in children it may be caused by fluid losses related to severe vomiting or diarrhea. Other causes for hypovolemic shock include extensive burns, exposure to some toxins, and excessive urine loss related to diabetes insipidus or ketoacidosis. Typically, patients present with a rapid, almost tachycardic heart rate; a weak pulse often described as “thread;” cool, clammy skin, particularly in the extremities, due to restricted peripheral blood flow; rapid, shallow breathing; hypothermia; thirst; and dry mouth. Treatments generally involve providing intravenous fluids to restore the patient to normal function and various drugs such as dopamine, epinephrine, and norepinephrine to raise blood pressure.

                                      • Cardiogenic shock results from the inability of the heart to maintain cardiac output. Most often, it results from a myocardial infarction (heart attack), but it may also be caused by arrhythmias, valve disorders, cardiomyopathies, cardiac failure, or simply insufficient flow of blood through the cardiac vessels. Treatment involves repairing the damage to the heart or its vessels to resolve the underlying cause, rather than treating cardiogenic shock directly.

                                      • Vascular shock occurs when arterioles lose their normal muscular tone and dilate dramatically. It may arise from a variety of causes, and treatments almost always involve fluid replacement and medications, called inotropic or pressor agents, which restore tone to the muscles of the vessels. In addition, eliminating or at least alleviating the underlying cause of the condition is required. This might include antibiotics and antihistamines, or select steroids, which may aid in the repair of nerve damage. A common cause is sepsis (or septicemia), also called “blood poisoning,” which is a widespread bacterial infection that results in an organismal-level inflammatory response known as septic shock. Neurogenic shock is a form of vascular shock that occurs with cranial or spinal injuries that damage the cardiovascular centers in the medulla oblongata or the nervous fibers originating from this region. Anaphylactic shock is a severe allergic response that causes the widespread release of histamines, triggering vasodilation throughout the body.

                                      • Obstructive shock, as the name would suggest, occurs when a significant portion of the vascular system is blocked. It is not always recognized as a distinct condition and may be grouped with cardiogenic shock, including pulmonary embolism and cardiac tamponade. Treatments depend upon the underlying cause and, in addition to administering fluids intravenously, often include the administration of anticoagulants, removal of fluid from the pericardial cavity, or air from the thoracic cavity, and surgery as required. The most common cause is a pulmonary embolism, a clot that lodges in the pulmonary vessels and interrupts blood flow. Other causes include stenosis of the aortic valve; cardiac tamponade, in which excess fluid in the pericardial cavity interferes with the ability of the heart to fully relax and fill with blood (resulting in decreased preload); and a pneumothorax, in which an excessive amount of air is present in the thoracic cavity, outside of the lungs, which interferes with venous return, pulmonary function, and delivery of oxygen to the tissues.

                                      20.5Circulatory Pathways*

                                      By the end of this section, you will be able to:

                                      • Identify the vessels through which blood travels within the pulmonary circuit, beginning from the right ventricle of the heart and ending at the left atrium

                                      • Create a flow chart showing the major systemic arteries through which blood travels from the aorta and its major branches, to the most significant arteries feeding into the right and left upper and lower limbs

                                      • Create a flow chart showing the major systemic veins through which blood travels from the feet to the right atrium of the heart

                                      • Pulmonary Circulation
                                      • Overview of Systemic Arteries
                                      • The Aorta
                                        • Coronary Circulation
                                        • Aortic Arch Branches
                                        • Thoracic Aorta and Major Branches
                                        • Abdominal Aorta and Major Branches
                                      • Arteries Serving the Upper Limbs
                                      • Arteries Serving the Lower Limbs
                                      • Overview of Systemic Veins
                                        • The Superior Vena Cava
                                        • Veins of the Head and Neck
                                        • Venous Drainage of the Brain
                                        • Veins Draining the Upper Limbs
                                        • The Inferior Vena Cava
                                        • Veins Draining the Lower Limbs
                                      • Hepatic Portal System

                                      Virtually every cell, tissue, organ, and system in the body is impacted by the circulatory system. This includes the generalized and more specialized functions of transport of materials, capillary exchange, maintaining health by transporting white blood cells and various immunoglobulins (antibodies), hemostasis, regulation of body temperature, and helping to maintain acid-base balance. In addition to these shared functions, many systems enjoy a unique relationship with the circulatory system. Figure 20.22 summarizes these relationships.

                                      This table outlines the role of the circulatory system in the other organ systems in the body.
                                      Figure 20.22Interaction of the Circulatory System with Other Body Systems

                                      As you learn about the vessels of the systemic and pulmonary circuits, notice that many arteries and veins share the same names, parallel one another throughout the body, and are very similar on the right and left sides of the body. These pairs of vessels will be traced through only one side of the body. Where differences occur in branching patterns or when vessels are singular, this will be indicated. For example, you will find a pair of femoral arteries and a pair of femoral veins, with one vessel on each side of the body. In contrast, some vessels closer to the midline of the body, such as the aorta, are unique. Moreover, some superficial veins, such as the great saphenous vein in the femoral region, have no arterial counterpart. Another phenomenon that can make the study of vessels challenging is that names of vessels can change with location. Like a street that changes name as it passes through an intersection, an artery or vein can change names as it passes an anatomical landmark. For example, the left subclavian artery becomes the axillary artery as it passes through the body wall and into the axillary region, and then becomes the brachial artery as it flows from the axillary region into the upper arm (or brachium). You will also find examples of anastomoses where two blood vessels that previously branched reconnect. Anastomoses are especially common in veins, where they help maintain blood flow even when one vessel is blocked or narrowed, although there are some important ones in the arteries supplying the brain.

                                      As you read about circular pathways, notice that there is an occasional, very large artery referred to as a trunk, a term indicating that the vessel gives rise to several smaller arteries. For example, the celiac trunk gives rise to the left gastric, common hepatic, and splenic arteries.

                                      As you study this section, imagine you are on a “Voyage of Discovery” similar to Lewis and Clark’s expedition in 1804–1806, which followed rivers and streams through unfamiliar territory, seeking a water route from the Atlantic to the Pacific Ocean. You might envision being inside a miniature boat, exploring the various branches of the circulatory system. This simple approach has proven effective for many students in mastering these major circulatory patterns. Another approach that works well for many students is to create simple line drawings similar to the ones provided, labeling each of the major vessels. It is beyond the scope of this text to name every vessel in the body. However, we will attempt to discuss the major pathways for blood and acquaint you with the major named arteries and veins in the body. Also, please keep in mind that individual variations in circulation patterns are not uncommon.

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                                      Pulmonary Circulation

                                      Recall that blood returning from the systemic circuit enters the right atrium (Figure 20.23) via the superior and inferior venae cavae and the coronary sinus, which drains the blood supply of the heart muscle. These vessels will be described more fully later in this section. This blood is relatively low in oxygen and relatively high in carbon dioxide, since much of the oxygen has been extracted for use by the tissues and the waste gas carbon dioxide was picked up to be transported to the lungs for elimination. From the right atrium, blood moves into the right ventricle, which pumps it to the lungs for gas exchange. This system of vessels is referred to as the pulmonary circuit.

                                      The single vessel exiting the right ventricle is the pulmonary trunk. At the base of the pulmonary trunk is the pulmonary semilunar valve, which prevents backflow of blood into the right ventricle during ventricular diastole. As the pulmonary trunk reaches the superior surface of the heart, it curves posteriorly and rapidly bifurcates (divides) into two branches, a left and a right pulmonary artery. To prevent confusion between these vessels, it is important to refer to the vessel exiting the heart as the pulmonary trunk, rather than also calling it a pulmonary artery. The pulmonary arteries in turn branch many times within the lung, forming a series of smaller arteries and arterioles that eventually lead to the pulmonary capillaries. The pulmonary capillaries surround lung structures known as alveoli that are the sites of oxygen and carbon dioxide exchange.

                                      Once gas exchange is completed, oxygenated blood flows from the pulmonary capillaries into a series of pulmonary venules that eventually lead to a series of larger pulmonary veins. Four pulmonary veins, two on the left and two on the right, return blood to the left atrium. At this point, the pulmonary circuit is complete. Table 20.4 defines the major arteries and veins of the pulmonary circuit discussed in the text.

                                      This diagram shows the network of blood vessels in the lungs.
                                      Figure 20.23Pulmonary Circuit
                                      Blood exiting from the right ventricle flows into the pulmonary trunk, which bifurcates into the two pulmonary arteries. These vessels branch to supply blood to the pulmonary capillaries, where gas exchange occurs within the lung alveoli. Blood returns via the pulmonary veins to the left atrium.
                                      Table 20.4.
                                      Pulmonary Arteries and Veins
                                      Vessel Description
                                      Pulmonary trunk Single large vessel exiting the right ventricle that divides to form the right and left pulmonary arteries
                                      Pulmonary arteries Left and right vessels that form from the pulmonary trunk and lead to smaller arterioles and eventually to the pulmonary capillaries
                                      Pulmonary veins Two sets of paired vessels—one pair on each side—that are formed from the small venules, leading away from the pulmonary capillaries to flow into the left atrium

                                      Overview of Systemic Arteries

                                      Blood relatively high in oxygen concentration is returned from the pulmonary circuit to the left atrium via the four pulmonary veins. From the left atrium, blood moves into the left ventricle, which pumps blood into the aorta. The aorta and its branches—the systemic arteries—send blood to virtually every organ of the body (Figure 20.24).

                                      This diagrams shows the major arteries in the human body.
                                      Figure 20.24Systemic Arteries
                                      The major systemic arteries shown here deliver oxygenated blood throughout the body.

                                      The Aorta

                                      The aorta is the largest artery in the body (Figure 20.25). It arises from the left ventricle and eventually descends to the abdominal region, where it bifurcates at the level of the fourth lumbar vertebra into the two common iliac arteries. The aorta consists of the ascending aorta, the aortic arch, and the descending aorta, which passes through the diaphragm and a landmark that divides into the superior thoracic and inferior abdominal components. Arteries originating from the aorta ultimately distribute blood to virtually all tissues of the body. At the base of the aorta is the aortic semilunar valve that prevents backflow of blood into the left ventricle while the heart is relaxing. After exiting the heart, the ascending aorta moves in a superior direction for approximately 5 cm and ends at the sternal angle. Following this ascent, it reverses direction, forming a graceful arc to the left, called the aortic arch. The aortic arch descends toward the inferior portions of the body and ends at the level of the intervertebral disk between the fourth and fifth thoracic vertebrae. Beyond this point, the descending aorta continues close to the bodies of the vertebrae and passes through an opening in the diaphragm known as the aortic hiatus. Superior to the diaphragm, the aorta is called the thoracic aorta, and inferior to the diaphragm, it is called the abdominal aorta. The abdominal aorta terminates when it bifurcates into the two common iliac arteries at the level of the fourth lumbar vertebra. See Figure 20.25 for an illustration of the ascending aorta, the aortic arch, and the initial segment of the descending aorta plus major branches; Table 20.5 summarizes the structures of the aorta.

                                      This diagram shows the aorta and the major parts are labeled.
                                      Figure 20.25Aorta
                                      The aorta has distinct regions, including the ascending aorta, aortic arch, and the descending aorta, which includes the thoracic and abdominal regions.
                                      Table 20.5.
                                      Components of the Aorta
                                      Vessel Description
                                      Aorta Largest artery in the body, originating from the left ventricle and descending to the abdominal region, where it bifurcates into the common iliac arteries at the level of the fourth lumbar vertebra; arteries originating from the aorta distribute blood to virtually all tissues of the body
                                      Ascending aorta Initial portion of the aorta, rising superiorly from the left ventricle for a distance of approximately 5 cm
                                      Aortic arch Graceful arc to the left that connects the ascending aorta to the descending aorta; ends at the intervertebral disk between the fourth and fifth thoracic vertebrae
                                      Descending aorta Portion of the aorta that continues inferiorly past the end of the aortic arch; subdivided into the thoracic aorta and the abdominal aorta
                                      Thoracic aorta Portion of the descending aorta superior to the aortic hiatus
                                      Abdominal aorta Portion of the aorta inferior to the aortic hiatus and superior to the common iliac arteries

                                      Coronary Circulation

                                      The first vessels that branch from the ascending aorta are the paired coronary arteries (see Figure 20.25), which arise from two of the three sinuses in the ascending aorta just superior to the aortic semilunar valve. These sinuses contain the aortic baroreceptors and chemoreceptors critical to maintain cardiac function. The left coronary artery arises from the left posterior aortic sinus. The right coronary artery arises from the anterior aortic sinus. Normally, the right posterior aortic sinus does not give rise to a vessel.

                                      The coronary arteries encircle the heart, forming a ring-like structure that divides into the next level of branches that supplies blood to the heart tissues. (Seek additional content for more detail on cardiac circulation.)

                                      Aortic Arch Branches

                                      There are three major branches of the aortic arch: the brachiocephalic artery, the left common carotid artery, and the left subclavian (literally “under the clavicle”) artery. As you would expect based upon proximity to the heart, each of these vessels is classified as an elastic artery.

                                      The brachiocephalic artery is located only on the right side of the body; there is no corresponding artery on the left. The brachiocephalic artery branches into the right subclavian artery and the right common carotid artery. The left subclavian and left common carotid arteries arise independently from the aortic arch but otherwise follow a similar pattern and distribution to the corresponding arteries on the right side (see Figure 20.23).

                                      Each subclavian artery supplies blood to the arms, chest, shoulders, back, and central nervous system. It then gives rise to three major branches: the internal thoracic artery, the vertebral artery, and the thyrocervical artery. The internal thoracic artery, or mammary artery, supplies blood to the thymus, the pericardium of the heart, and the anterior chest wall. The vertebral artery passes through the vertebral foramen in the cervical vertebrae and then through the foramen magnum into the cranial cavity to supply blood to the brain and spinal cord. The paired vertebral arteries join together to form the large basilar artery at the base of the medulla oblongata. This is an example of an anastomosis. The subclavian artery also gives rise to the thyrocervical artery that provides blood to the thyroid, the cervical region of the neck, and the upper back and shoulder.

                                      The common carotid artery divides into internal and external carotid arteries. The right common carotid artery arises from the brachiocephalic artery and the left common carotid artery arises directly from the aortic arch. The external carotid artery supplies blood to numerous structures within the face, lower jaw, neck, esophagus, and larynx. These branches include the lingual, facial, occipital, maxillary, and superficial temporal arteries. The internal carotid artery initially forms an expansion known as the carotid sinus, containing the carotid baroreceptors and chemoreceptors. Like their counterparts in the aortic sinuses, the information provided by these receptors is critical to maintaining cardiovascular homeostasis (see Figure 20.23).

                                      The internal carotid arteries along with the vertebral arteries are the two primary suppliers of blood to the human brain. Given the central role and vital importance of the brain to life, it is critical that blood supply to this organ remains uninterrupted. Recall that blood flow to the brain is remarkably constant, with approximately 20 percent of blood flow directed to this organ at any given time. When blood flow is interrupted, even for just a few seconds, a transient ischemic attack (TIA), or mini-stroke, may occur, resulting in loss of consciousness or temporary loss of neurological function. In some cases, the damage may be permanent. Loss of blood flow for longer periods, typically between 3 and 4 minutes, will likely produce irreversible brain damage or a stroke, also called a cerebrovascular accident (CVA). The locations of the arteries in the brain not only provide blood flow to the brain tissue but also prevent interruption in the flow of blood. Both the carotid and vertebral arteries branch once they enter the cranial cavity, and some of these branches form a structure known as the arterial circle (or circle of Willis), an anastomosis that is remarkably like a traffic circle that sends off branches (in this case, arterial branches to the brain). As a rule, branches to the anterior portion of the cerebrum are normally fed by the internal carotid arteries; the remainder of the brain receives blood flow from branches associated with the vertebral arteries.

                                      The internal carotid artery continues through the carotid canal of the temporal bone and enters the base of the brain through the carotid foramen where it gives rise to several branches (Figure 20.26 and Figure 20.27). One of these branches is the anterior cerebral artery that supplies blood to the frontal lobe of the cerebrum. Another branch, the middle cerebral artery, supplies blood to the temporal and parietal lobes, which are the most common sites of CVAs. The ophthalmic artery, the third major branch, provides blood to the eyes.

                                      The right and left anterior cerebral arteries join together to form an anastomosis called the anterior communicating artery. The initial segments of the anterior cerebral arteries and the anterior communicating artery form the anterior portion of the arterial circle. The posterior portion of the arterial circle is formed by a left and a right posterior communicating artery that branches from the posterior cerebral artery, which arises from the basilar artery. It provides blood to the posterior portion of the cerebrum and brain stem. The basilar artery is an anastomosis that begins at the junction of the two vertebral arteries and sends branches to the cerebellum and brain stem. It flows into the posterior cerebral arteries. Table 20.6 summarizes the aortic arch branches, including the major branches supplying the brain.

                                      This diagram shows the blood vessels in the head and brain.
                                      Figure 20.26Arteries Supplying the Head and Neck
                                      The common carotid artery gives rise to the external and internal carotid arteries. The external carotid artery remains superficial and gives rise to many arteries of the head. The internal carotid artery first forms the carotid sinus and then reaches the brain via the carotid canal and carotid foramen, emerging into the cranium via the foramen lacerum. The vertebral artery branches from the subclavian artery and passes through the transverse foramen in the cervical vertebrae, entering the base of the skull at the vertebral foramen. The subclavian artery continues toward the arm as the axillary artery.
                                      This diagram shows the arteries of the brain.
                                      Figure 20.27Arteries Serving the Brain
                                      This inferior view shows the network of arteries serving the brain. The structure is referred to as the arterial circle or circle of Willis.
                                      Table 20.6.
                                      Aortic Arch Branches and Brain Circulation
                                      Vessel Description
                                      Brachiocephalic artery Single vessel located on the right side of the body; the first vessel branching from the aortic arch; gives rise to the right subclavian artery and the right common carotid artery; supplies blood to the head, neck, upper limb, and wall of the thoracic region
                                      Subclavian artery The right subclavian artery arises from the brachiocephalic artery while the left subclavian artery arises from the aortic arch; gives rise to the internal thoracic, vertebral, and thyrocervical arteries; supplies blood to the arms, chest, shoulders, back, and central nervous system
                                      Internal thoracic artery Also called the mammary artery; arises from the subclavian artery; supplies blood to the thymus, pericardium of the heart, and anterior chest wall
                                      Vertebral artery Arises from the subclavian artery and passes through the vertebral foramen through the foramen magnum to the brain; joins with the internal carotid artery to form the arterial circle; supplies blood to the brain and spinal cord
                                      Thyrocervical artery Arises from the subclavian artery; supplies blood to the thyroid, the cervical region, the upper back, and shoulder
                                      Common carotid artery The right common carotid artery arises from the brachiocephalic artery and the left common carotid artery arises from the aortic arch; each gives rise to the external and internal carotid arteries; supplies the respective sides of the head and neck
                                      External carotid artery Arises from the common carotid artery; supplies blood to numerous structures within the face, lower jaw, neck, esophagus, and larynx
                                      Internal carotid artery Arises from the common carotid artery and begins with the carotid sinus; goes through the carotid canal of the temporal bone to the base of the brain; combines with the branches of the vertebral artery, forming the arterial circle; supplies blood to the brain
                                      Arterial circle or circle of Willis An anastomosis located at the base of the brain that ensures continual blood supply; formed from the branches of the internal carotid and vertebral arteries; supplies blood to the brain
                                      Anterior cerebral artery Arises from the internal carotid artery; supplies blood to the frontal lobe of the cerebrum
                                      Middle cerebral artery Another branch of the internal carotid artery; supplies blood to the temporal and parietal lobes of the cerebrum
                                      Ophthalmic artery Branch of the internal carotid artery; supplies blood to the eyes
                                      Anterior communicating artery An anastomosis of the right and left internal carotid arteries; supplies blood to the brain
                                      Posterior communicating artery Branches of the posterior cerebral artery that form part of the posterior portion of the arterial circle; supplies blood to the brain
                                      Posterior cerebral artery Branch of the basilar artery that forms a portion of the posterior segment of the arterial circle of Willis; supplies blood to the posterior portion of the cerebrum and brain stem
                                      Basilar artery Formed from the fusion of the two vertebral arteries; sends branches to the cerebellum, brain stem, and the posterior cerebral arteries; the main blood supply to the brain stem

                                      Thoracic Aorta and Major Branches

                                      The thoracic aorta begins at the level of vertebra T5 and continues through to the diaphragm at the level of T12, initially traveling within the mediastinum to the left of the vertebral column. As it passes through the thoracic region, the thoracic aorta gives rise to several branches, which are collectively referred to as visceral branches and parietal branches (Figure 20.28). Those branches that supply blood primarily to visceral organs are known as the visceral branches and include the bronchial arteries, pericardial arteries, esophageal arteries, and the mediastinal arteries, each named after the tissues it supplies. Each bronchial artery (typically two on the left and one on the right) supplies systemic blood to the lungs and visceral pleura, in addition to the blood pumped to the lungs for oxygenation via the pulmonary circuit. The bronchial arteries follow the same path as the respiratory branches, beginning with the bronchi and ending with the bronchioles. There is considerable, but not total, intermingling of the systemic and pulmonary blood at anastomoses in the smaller branches of the lungs. This may sound incongruous—that is, the mixing of systemic arterial blood high in oxygen with the pulmonary arterial blood lower in oxygen—but the systemic vessels also deliver nutrients to the lung tissue just as they do elsewhere in the body. The mixed blood drains into typical pulmonary veins, whereas the bronchial artery branches remain separate and drain into bronchial veins described later. Each pericardial artery supplies blood to the pericardium, the esophageal artery provides blood to the esophagus, and the mediastinal artery provides blood to the mediastinum. The remaining thoracic aorta branches are collectively referred to as parietal branches or somatic branches, and include the intercostal and superior phrenic arteries. Each intercostal artery provides blood to the muscles of the thoracic cavity and vertebral column. The superior phrenic artery provides blood to the superior surface of the diaphragm. Table 20.7 lists the arteries of the thoracic region.

                                      This diagram shows the arteries in the thoracic and abdominal cavity.
                                      Figure 20.28Arteries of the Thoracic and Abdominal Regions
                                      The thoracic aorta gives rise to the arteries of the visceral and parietal branches.
                                      Table 20.7.
                                      Arteries of the Thoracic Region
                                      Vessel Description
                                      Visceral branches A group of arterial branches of the thoracic aorta; supplies blood to the viscera (i.e., organs) of the thorax
                                      Bronchial artery Systemic branch from the aorta that provides oxygenated blood to the lungs; this blood supply is in addition to the pulmonary circuit that brings blood for oxygenation
                                      Pericardial artery Branch of the thoracic aorta; supplies blood to the pericardium
                                      Esophageal artery Branch of the thoracic aorta; supplies blood to the esophagus
                                      Mediastinal artery Branch of the thoracic aorta; supplies blood to the mediastinum
                                      Parietal branches Also called somatic branches, a group of arterial branches of the thoracic aorta; include those that supply blood to the thoracic wall, vertebral column, and the superior surface of the diaphragm
                                      Intercostal artery Branch of the thoracic aorta; supplies blood to the muscles of the thoracic cavity and vertebral column
                                      Superior phrenic artery Branch of the thoracic aorta; supplies blood to the superior surface of the diaphragm

                                      Abdominal Aorta and Major Branches

                                      After crossing through the diaphragm at the aortic hiatus, the thoracic aorta is called the abdominal aorta (see Figure 20.28). This vessel remains to the left of the vertebral column and is embedded in adipose tissue behind the peritoneal cavity. It formally ends at approximately the level of vertebra L4, where it bifurcates to form the common iliac arteries. Before this division, the abdominal aorta gives rise to several important branches. A single celiac trunk (artery) emerges and divides into the left gastric artery to supply blood to the stomach and esophagus, the splenic artery to supply blood to the spleen, and the common hepatic artery, which in turn gives rise to the hepatic artery proper to supply blood to the liver, the right gastric artery to supply blood to the stomach, the cystic artery to supply blood to the gall bladder, and several branches, one to supply blood to the duodenum and another to supply blood to the pancreas. Two additional single vessels arise from the abdominal aorta. These are the superior and inferior mesenteric arteries. The superior mesenteric artery arises approximately 2.5 cm after the celiac trunk and branches into several major vessels that supply blood to the small intestine (duodenum, jejunum, and ileum), the pancreas, and a majority of the large intestine. The inferior mesenteric artery supplies blood to the distal segment of the large intestine, including the rectum. It arises approximately 5 cm superior to the common iliac arteries.

                                      In addition to these single branches, the abdominal aorta gives rise to several significant paired arteries along the way. These include the inferior phrenic arteries, the adrenal arteries, the renal arteries, the gonadal arteries, and the lumbar arteries. Each inferior phrenic artery is a counterpart of a superior phrenic artery and supplies blood to the inferior surface of the diaphragm. The adrenal artery supplies blood to the adrenal (suprarenal) glands and arises near the superior mesenteric artery. Each renal artery branches approximately 2.5 cm inferior to the superior mesenteric arteries and supplies a kidney. The right renal artery is longer than the left since the aorta lies to the left of the vertebral column and the vessel must travel a greater distance to reach its target. Renal arteries branch repeatedly to supply blood to the kidneys. Each gonadal artery supplies blood to the gonads, or reproductive organs, and is also described as either an ovarian artery or a testicular artery (internal spermatic), depending upon the sex of the individual. An ovarian artery supplies blood to an ovary, uterine (Fallopian) tube, and the uterus, and is located within the suspensory ligament of the uterus. It is considerably shorter than a testicular artery, which ultimately travels outside the body cavity to the testes, forming one component of the spermatic cord. The gonadal arteries arise inferior to the renal arteries and are generally retroperitoneal. The ovarian artery continues to the uterus where it forms an anastomosis with the uterine artery that supplies blood to the uterus. Both the uterine arteries and vaginal arteries, which distribute blood to the vagina, are branches of the internal iliac artery. The four paired lumbar arteries are the counterparts of the intercostal arteries and supply blood to the lumbar region, the abdominal wall, and the spinal cord. In some instances, a fifth pair of lumbar arteries emerges from the median sacral artery.

                                      The aorta divides at approximately the level of vertebra L4 into a left and a right common iliac artery but continues as a small vessel, the median sacral artery, into the sacrum. The common iliac arteries provide blood to the pelvic region and ultimately to the lower limbs. They split into external and internal iliac arteries approximately at the level of the lumbar-sacral articulation. Each internal iliac artery sends branches to the urinary bladder, the walls of the pelvis, the external genitalia, and the medial portion of the femoral region. In females, they also provide blood to the uterus and vagina. The much larger external iliac artery supplies blood to each of the lower limbs. Figure 20.29 shows the distribution of the major branches of the aorta into the thoracic and abdominal regions. Figure 20.30 shows the distribution of the major branches of the common iliac arteries. Table 20.8 summarizes the major branches of the abdominal aorta.

                                      This table shows the different arteries in the thoracic and abdominal cavity. The list on the left shows unpaired arteries, and the list on the right shows paired cavities.
                                      Figure 20.29Major Branches of the Aorta
                                      The flow chart summarizes the distribution of the major branches of the aorta into the thoracic and abdominal regions.
                                      This flowchart shows the different branches into which that the abdominal aorta is divided.
                                      Figure 20.30Major Branches of the Iliac Arteries
                                      The flow chart summarizes the distribution of the major branches of the common iliac arteries into the pelvis and lower limbs. The left side follows a similar pattern to the right.
                                      Table 20.8.
                                      Vessels of the Abdominal Aorta
                                      Vessel Description
                                      Celiac trunk Also called the celiac artery; a major branch of the abdominal aorta; gives rise to the left gastric artery, the splenic artery, and the common hepatic artery that forms the hepatic artery to the liver, the right gastric artery to the stomach, and the cystic artery to the gall bladder
                                      Left gastric artery Branch of the celiac trunk; supplies blood to the stomach
                                      Splenic artery Branch of the celiac trunk; supplies blood to the spleen
                                      Common hepatic artery Branch of the celiac trunk that forms the hepatic artery, the right gastric artery, and the cystic artery
                                      Hepatic artery proper Branch of the common hepatic artery; supplies systemic blood to the liver
                                      Right gastric artery Branch of the common hepatic artery; supplies blood to the stomach
                                      Cystic artery Branch of the common hepatic artery; supplies blood to the gall bladder
                                      Superior mesenteric artery Branch of the abdominal aorta; supplies blood to the small intestine (duodenum, jejunum, and ileum), the pancreas, and a majority of the large intestine
                                      Inferior mesenteric artery Branch of the abdominal aorta; supplies blood to the distal segment of the large intestine and rectum
                                      Inferior phrenic arteries Branches of the abdominal aorta; supply blood to the inferior surface of the diaphragm
                                      Adrenal artery Branch of the abdominal aorta; supplies blood to the adrenal (suprarenal) glands
                                      Renal artery Branch of the abdominal aorta; supplies each kidney
                                      Gonadal artery Branch of the abdominal aorta; supplies blood to the gonads or reproductive organs; also described as ovarian arteries or testicular arteries, depending upon the sex of the individual
                                      Ovarian artery Branch of the abdominal aorta; supplies blood to ovary, uterine (Fallopian) tube, and uterus
                                      Testicular artery Branch of the abdominal aorta; ultimately travels outside the body cavity to the testes and forms one component of the spermatic cord
                                      Lumbar arteries Branches of the abdominal aorta; supply blood to the lumbar region, the abdominal wall, and spinal cord
                                      Common iliac artery Branch of the aorta that leads to the internal and external iliac arteries
                                      Median sacral artery Continuation of the aorta into the sacrum
                                      Internal iliac artery Branch from the common iliac arteries; supplies blood to the urinary bladder, walls of the pelvis, external genitalia, and the medial portion of the femoral region; in females, also provides blood to the uterus and vagina
                                      External iliac artery Branch of the common iliac artery that leaves the body cavity and becomes a femoral artery; supplies blood to the lower limbs

                                      Arteries Serving the Upper Limbs

                                      As the subclavian artery exits the thorax into the axillary region, it is renamed the axillary artery. Although it does branch and supply blood to the region near the head of the humerus (via the humeral circumflex arteries), the majority of the vessel continues into the upper arm, or brachium, and becomes the brachial artery (Figure 20.31). The brachial artery supplies blood to much of the brachial region and divides at the elbow into several smaller branches, including the deep brachial arteries, which provide blood to the posterior surface of the arm, and the ulnar collateral arteries, which supply blood to the region of the elbow. As the brachial artery approaches the coronoid fossa, it bifurcates into the radial and ulnar arteries, which continue into the forearm, or antebrachium. The radial artery and ulnar artery parallel their namesake bones, giving off smaller branches until they reach the wrist, or carpal region. At this level, they fuse to form the superficial and deep palmar arches that supply blood to the hand, as well as the digital arteries that supply blood to the digits. Figure 20.32 shows the distribution of systemic arteries from the heart into the upper limb. Table 20.9 summarizes the arteries serving the upper limbs.

                                      This diagram shows the arteries in the arm.
                                      Figure 20.31Major Arteries Serving the Thorax and Upper Limb
                                      The arteries that supply blood to the arms and hands are extensions of the subclavian arteries.
                                      This chart shows the arteries present in the thoracic upper limb.
                                      Figure 20.32Major Arteries of the Upper Limb
                                      The flow chart summarizes the distribution of the major arteries from the heart into the upper limb.
                                      Table 20.9.
                                      Arteries Serving the Upper Limbs
                                      Vessel Description
                                      Axillary artery Continuation of the subclavian artery as it penetrates the body wall and enters the axillary region; supplies blood to the region near the head of the humerus (humeral circumflex arteries); the majority of the vessel continues into the brachium and becomes the brachial artery
                                      Brachial artery Continuation of the axillary artery in the brachium; supplies blood to much of the brachial region; gives off several smaller branches that provide blood to the posterior surface of the arm in the region of the elbow; bifurcates into the radial and ulnar arteries at the coronoid fossa
                                      Radial artery Formed at the bifurcation of the brachial artery; parallels the radius; gives off smaller branches until it reaches the carpal region where it fuses with the ulnar artery to form the superficial and deep palmar arches; supplies blood to the lower arm and carpal region
                                      Ulnar artery Formed at the bifurcation of the brachial artery; parallels the ulna; gives off smaller branches until it reaches the carpal region where it fuses with the radial artery to form the superficial and deep palmar arches; supplies blood to the lower arm and carpal region
                                      Palmar arches (superficial and deep) Formed from anastomosis of the radial and ulnar arteries; supply blood to the hand and digital arteries
                                      Digital arteries Formed from the superficial and deep palmar arches; supply blood to the digits

                                      Arteries Serving the Lower Limbs

                                      The external iliac artery exits the body cavity and enters the femoral region of the lower leg (Figure 20.33). As it passes through the body wall, it is renamed the femoral artery. It gives off several smaller branches as well as the lateral deep femoral artery that in turn gives rise to a lateral circumflex artery. These arteries supply blood to the deep muscles of the thigh as well as ventral and lateral regions of the integument. The femoral artery also gives rise to the genicular artery, which provides blood to the region of the knee. As the femoral artery passes posterior to the knee near the popliteal fossa, it is called the popliteal artery. The popliteal artery branches into the anterior and posterior tibial arteries.

                                      The anterior tibial artery is located between the tibia and fibula, and supplies blood to the muscles and integument of the anterior tibial region. Upon reaching the tarsal region, it becomes the dorsalis pedis artery, which branches repeatedly and provides blood to the tarsal and dorsal regions of the foot. The posterior tibial artery provides blood to the muscles and integument on the posterior surface of the tibial region. The fibular or peroneal artery branches from the posterior tibial artery. It bifurcates and becomes the medial plantar artery and lateral plantar artery, providing blood to the plantar surfaces. There is an anastomosis with the dorsalis pedis artery, and the medial and lateral plantar arteries form two arches called the dorsal arch (also called the arcuate arch) and the plantar arch, which provide blood to the remainder of the foot and toes. Figure 20.34 shows the distribution of the major systemic arteries in the lower limb. Table 20.10 summarizes the major systemic arteries discussed in the text.

                                      The left panel shows the anterior view of arteries in the legs, and the right panel shows the posterior view.
                                      Figure 20.33Major Arteries Serving the Lower Limb
                                      Major arteries serving the lower limb are shown in anterior and posterior views.
                                      This chart shows the major arteries present in the lower limbs.
                                      Figure 20.34Systemic Arteries of the Lower Limb
                                      The flow chart summarizes the distribution of the systemic arteries from the external iliac artery into the lower limb.
                                      Table 20.10.
                                      Arteries Serving the Lower Limbs
                                      Vessel Description
                                      Femoral artery Continuation of the external iliac artery after it passes through the body cavity; divides into several smaller branches, the lateral deep femoral artery, and the genicular artery; becomes the popliteal artery as it passes posterior to the knee
                                      Deep femoral artery Branch of the femoral artery; gives rise to the lateral circumflex arteries
                                      Lateral circumflex artery Branch of the deep femoral artery; supplies blood to the deep muscles of the thigh and the ventral and lateral regions of the integument
                                      Genicular artery Branch of the femoral artery; supplies blood to the region of the knee
                                      Popliteal artery Continuation of the femoral artery posterior to the knee; branches into the anterior and posterior tibial arteries
                                      Anterior tibial artery Branches from the popliteal artery; supplies blood to the anterior tibial region; becomes the dorsalis pedis artery
                                      Dorsalis pedis artery Forms from the anterior tibial artery; branches repeatedly to supply blood to the tarsal and dorsal regions of the foot
                                      Posterior tibial artery Branches from the popliteal artery and gives rise to the fibular or peroneal artery; supplies blood to the posterior tibial region
                                      Medial plantar artery Arises from the bifurcation of the posterior tibial arteries; supplies blood to the medial plantar surfaces of the foot
                                      Lateral plantar artery Arises from the bifurcation of the posterior tibial arteries; supplies blood to the lateral plantar surfaces of the foot
                                      Dorsal or arcuate arch Formed from the anastomosis of the dorsalis pedis artery and the medial and plantar arteries; branches supply the distal portions of the foot and digits
                                      Plantar arch Formed from the anastomosis of the dorsalis pedis artery and the medial and plantar arteries; branches supply the distal portions of the foot and digits

                                      Overview of Systemic Veins

                                      Systemic veins return blood to the right atrium. Since the blood has already passed through the systemic capillaries, it will be relatively low in oxygen concentration. In many cases, there will be veins draining organs and regions of the body with the same name as the arteries that supplied these regions and the two often parallel one another. This is often described as a “complementary” pattern. However, there is a great deal more variability in the venous circulation than normally occurs in the arteries. For the sake of brevity and clarity, this text will discuss only the most commonly encountered patterns. However, keep this variation in mind when you move from the classroom to clinical practice.

                                      In both the neck and limb regions, there are often both superficial and deeper levels of veins. The deeper veins generally correspond to the complementary arteries. The superficial veins do not normally have direct arterial counterparts, but in addition to returning blood, they also make contributions to the maintenance of body temperature. When the ambient temperature is warm, more blood is diverted to the superficial veins where heat can be more easily dissipated to the environment. In colder weather, there is more constriction of the superficial veins and blood is diverted deeper where the body can retain more of the heat.

                                      The “Voyage of Discovery” analogy and stick drawings mentioned earlier remain valid techniques for the study of systemic veins, but veins present a more difficult challenge because there are numerous anastomoses and multiple branches. It is like following a river with many tributaries and channels, several of which interconnect. Tracing blood flow through arteries follows the current in the direction of blood flow, so that we move from the heart through the large arteries and into the smaller arteries to the capillaries. From the capillaries, we move into the smallest veins and follow the direction of blood flow into larger veins and back to the heart. Figure 20.35 outlines the path of the major systemic veins.

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                                      This diagram shows the major veins in the human body.
                                      Figure 20.35Major Systemic Veins of the Body
                                      The major systemic veins of the body are shown here in an anterior view.

                                      The right atrium receives all of the systemic venous return. Most of the blood flows into either the superior vena cava or inferior vena cava. If you draw an imaginary line at the level of the diaphragm, systemic venous circulation from above that line will generally flow into the superior vena cava; this includes blood from the head, neck, chest, shoulders, and upper limbs. The exception to this is that most venous blood flow from the coronary veins flows directly into the coronary sinus and from there directly into the right atrium. Beneath the diaphragm, systemic venous flow enters the inferior vena cava, that is, blood from the abdominal and pelvic regions and the lower limbs.

                                      The Superior Vena Cava

                                      The superior vena cava drains most of the body superior to the diaphragm (Figure 20.36). On both the left and right sides, the subclavian vein forms when the axillary vein passes through the body wall from the axillary region. It fuses with the external and internal jugular veins from the head and neck to form the brachiocephalic vein. Each vertebral vein also flows into the brachiocephalic vein close to this fusion. These veins arise from the base of the brain and the cervical region of the spinal cord, and flow largely through the intervertebral foramina in the cervical vertebrae. They are the counterparts of the vertebral arteries. Each internal thoracic vein, also known as an internal mammary vein, drains the anterior surface of the chest wall and flows into the brachiocephalic vein.

                                      The remainder of the blood supply from the thorax drains into the azygos vein. Each intercostal vein drains muscles of the thoracic wall, each esophageal vein delivers blood from the inferior portions of the esophagus, each bronchial vein drains the systemic circulation from the lungs, and several smaller veins drain the mediastinal region. Bronchial veins carry approximately 13 percent of the blood that flows into the bronchial arteries; the remainder intermingles with the pulmonary circulation and returns to the heart via the pulmonary veins. These veins flow into the azygos vein, and with the smaller hemiazygos vein (hemi- = “half”) on the left of the vertebral column, drain blood from the thoracic region. The hemiazygos vein does not drain directly into the superior vena cava but enters the brachiocephalic vein via the superior intercostal vein.

                                      The azygos vein passes through the diaphragm from the thoracic cavity on the right side of the vertebral column and begins in the lumbar region of the thoracic cavity. It flows into the superior vena cava at approximately the level of T2, making a significant contribution to the flow of blood. It combines with the two large left and right brachiocephalic veins to form the superior vena cava.

                                      Table 20.11 summarizes the veins of the thoracic region that flow into the superior vena cava.

                                      This diagram shows the veins present in the thoracic abdominal cavity.
                                      Figure 20.36Veins of the Thoracic and Abdominal Regions
                                      Veins of the thoracic and abdominal regions drain blood from the area above the diaphragm, returning it to the right atrium via the superior vena cava.
                                      Table 20.11.
                                      Veins of the Thoracic Region
                                      Vessel Description
                                      Superior vena cava Large systemic vein; drains blood from most areas superior to the diaphragm; empties into the right atrium
                                      Subclavian vein Located deep in the thoracic cavity; formed by the axillary vein as it enters the thoracic cavity from the axillary region; drains the axillary and smaller local veins near the scapular region and leads to the brachiocephalic vein
                                      Brachiocephalic veins Pair of veins that form from a fusion of the external and internal jugular veins and the subclavian vein; subclavian, external and internal jugulars, vertebral, and internal thoracic veins flow into it; drain the upper thoracic region and lead to the superior vena cava
                                      Vertebral vein Arises from the base of the brain and the cervical region of the spinal cord; passes through the intervertebral foramina in the cervical vertebrae; drains smaller veins from the cranium, spinal cord, and vertebrae, and leads to the brachiocephalic vein; counterpart of the vertebral artery
                                      Internal thoracic veins Also called internal mammary veins; drain the anterior surface of the chest wall and lead to the brachiocephalic vein
                                      Intercostal vein Drains the muscles of the thoracic wall and leads to the azygos vein
                                      Esophageal vein Drains the inferior portions of the esophagus and leads to the azygos vein
                                      Bronchial vein Drains the systemic circulation from the lungs and leads to the azygos vein
                                      Azygos vein Originates in the lumbar region and passes through the diaphragm into the thoracic cavity on the right side of the vertebral column; drains blood from the intercostal veins, esophageal veins, bronchial veins, and other veins draining the mediastinal region, and leads to the superior vena cava
                                      Hemiazygos vein Smaller vein complementary to the azygos vein; drains the esophageal veins from the esophagus and the left intercostal veins, and leads to the brachiocephalic vein via the superior intercostal vein

                                      Veins of the Head and Neck

                                      Blood from the brain and the superficial facial vein flow into each internal jugular vein (Figure 20.37). Blood from the more superficial portions of the head, scalp, and cranial regions, including the temporal vein and maxillary vein, flow into each external jugular vein. Although the external and internal jugular veins are separate vessels, there are anastomoses between them close to the thoracic region. Blood from the external jugular vein empties into the subclavian vein. Table 20.12 summarizes the major veins of the head and neck.

                                      Table 20.12.
                                      Major Veins of the Head and Neck
                                      Vessel Description
                                      Internal jugular vein Parallel to the common carotid artery, which is more or less its counterpart, and passes through the jugular foramen and canal; primarily drains blood from the brain, receives the superficial facial vein, and empties into the subclavian vein
                                      Temporal vein Drains blood from the temporal region and flows into the external jugular vein
                                      Maxillary vein Drains blood from the maxillary region and flows into the external jugular vein
                                      External jugular vein Drains blood from the more superficial portions of the head, scalp, and cranial regions, and leads to the subclavian vein

                                      Venous Drainage of the Brain

                                      Circulation to the brain is both critical and complex (see Figure 20.37). Many smaller veins of the brain stem and the superficial veins of the cerebrum lead to larger vessels referred to as intracranial sinuses. These include the superior and inferior sagittal sinuses, straight sinus, cavernous sinuses, left and right sinuses, the petrosal sinuses, and the occipital sinuses. Ultimately, sinuses will lead back to either the inferior jugular vein or vertebral vein.

                                      Most of the veins on the superior surface of the cerebrum flow into the largest of the sinuses, the superior sagittal sinus. It is located midsagittally between the meningeal and periosteal layers of the dura mater within the falx cerebri and, at first glance in images or models, can be mistaken for the subarachnoid space. Most reabsorption of cerebrospinal fluid occurs via the chorionic villi (arachnoid granulations) into the superior sagittal sinus. Blood from most of the smaller vessels originating from the inferior cerebral veins flows into the great cerebral vein and into the straight sinus. Other cerebral veins and those from the eye socket flow into the cavernous sinus, which flows into the petrosal sinus and then into the internal jugular vein. The occipital sinus, sagittal sinus, and straight sinuses all flow into the left and right transverse sinuses near the lambdoid suture. The transverse sinuses in turn flow into the sigmoid sinuses that pass through the jugular foramen and into the internal jugular vein. The internal jugular vein flows parallel to the common carotid artery and is more or less its counterpart. It empties into the brachiocephalic vein. The veins draining the cervical vertebrae and the posterior surface of the skull, including some blood from the occipital sinus, flow into the vertebral veins. These parallel the vertebral arteries and travel through the transverse foramina of the cervical vertebrae. The vertebral veins also flow into the brachiocephalic veins. Table 20.13 summarizes the major veins of the brain.

                                      This diagram shows the veins present in the head and neck.
                                      Figure 20.37Veins of the Head and Neck
                                      This left lateral view shows the veins of the head and neck, including the intercranial sinuses.
                                      Table 20.13.
                                      Major Veins of the Brain
                                      Vessel Description
                                      Superior sagittal sinus Enlarged vein located midsagittally between the meningeal and periosteal layers of the dura mater within the falx cerebri; receives most of the blood drained from the superior surface of the cerebrum and leads to the inferior jugular vein and the vertebral vein
                                      Great cerebral vein Receives most of the smaller vessels from the inferior cerebral veins and leads to the straight sinus
                                      Straight sinus Enlarged vein that drains blood from the brain; receives most of the blood from the great cerebral vein and leads to the left or right transverse sinus
                                      Cavernous sinus Enlarged vein that receives blood from most of the other cerebral veins and the eye socket, and leads to the petrosal sinus
                                      Petrosal sinus Enlarged vein that receives blood from the cavernous sinus and leads into the internal jugular veins
                                      Occipital sinus Enlarged vein that drains the occipital region near the falx cerebelli and leads to the left and right transverse sinuses, and also the vertebral veins
                                      Transverse sinuses Pair of enlarged veins near the lambdoid suture that drains the occipital, sagittal, and straight sinuses, and leads to the sigmoid sinuses
                                      Sigmoid sinuses Enlarged vein that receives blood from the transverse sinuses and leads through the jugular foramen to the internal jugular vein

                                      Veins Draining the Upper Limbs

                                      The digital veins in the fingers come together in the hand to form the palmar venous arches (Figure 20.38). From here, the veins come together to form the radial vein, the ulnar vein, and the median antebrachial vein. The radial vein and the ulnar vein parallel the bones of the forearm and join together at the antebrachium to form the brachial vein, a deep vein that flows into the axillary vein in the brachium.

                                      The median antebrachial vein parallels the ulnar vein, is more medial in location, and joins the basilic vein in the forearm. As the basilic vein reaches the antecubital region, it gives off a branch called the median cubital vein that crosses at an angle to join the cephalic vein. The median cubital vein is the most common site for drawing venous blood in humans. The basilic vein continues through the arm medially and superficially to the axillary vein.

                                      The cephalic vein begins in the antebrachium and drains blood from the superficial surface of the arm into the axillary vein. It is extremely superficial and easily seen along the surface of the biceps brachii muscle in individuals with good muscle tone and in those without excessive subcutaneous adipose tissue in the arms.

                                      The subscapular vein drains blood from the subscapular region and joins the cephalic vein to form the axillary vein. As it passes through the body wall and enters the thorax, the axillary vein becomes the subclavian vein.

                                      Many of the larger veins of the thoracic and abdominal region and upper limb are further represented in the flow chart in Figure 20.39. Table 20.14 summarizes the veins of the upper limbs.

                                      This diagram shows the veins present in the upper limb.
                                      Figure 20.38Veins of the Upper Limb
                                      This anterior view shows the veins that drain the upper limb.
                                      This flowchart shows the different veins in the body, and how they are connected to the superior vena cava.
                                      Figure 20.39Veins Flowing into the Superior Vena Cava
                                      The flow chart summarizes the distribution of the veins flowing into the superior vena cava.
                                      Table 20.14.
                                      Veins of the Upper Limbs
                                      Vessel Description
                                      Digital veins Drain the digits and lead to the palmar arches of the hand and dorsal venous arch of the foot
                                      Palmar venous arches Drain the hand and digits, and lead to the radial vein, ulnar veins, and the median antebrachial vein
                                      Radial vein Vein that parallels the radius and radial artery; arises from the palmar venous arches and leads to the brachial vein
                                      Ulnar vein Vein that parallels the ulna and ulnar artery; arises from the palmar venous arches and leads to the brachial vein
                                      Brachial vein Deeper vein of the arm that forms from the radial and ulnar veins in the lower arm; leads to the axillary vein
                                      Median antebrachial vein Vein that parallels the ulnar vein but is more medial in location; intertwines with the palmar venous arches; leads to the basilic vein
                                      Basilic vein Superficial vein of the arm that arises from the median antebrachial vein, intersects with the median cubital vein, parallels the ulnar vein, and continues into the upper arm; along with the brachial vein, it leads to the axillary vein
                                      Median cubital vein Superficial vessel located in the antecubital region that links the cephalic vein to the basilic vein in the form of a v; a frequent site from which to draw blood
                                      Cephalic vein Superficial vessel in the upper arm; leads to the axillary vein
                                      Subscapular vein Drains blood from the subscapular region and leads to the axillary vein
                                      Axillary vein The major vein in the axillary region; drains the upper limb and becomes the subclavian vein

                                      The Inferior Vena Cava

                                      Other than the small amount of blood drained by the azygos and hemiazygos veins, most of the blood inferior to the diaphragm drains into the inferior vena cava before it is returned to the heart (see Figure 20.36). Lying just beneath the parietal peritoneum in the abdominal cavity, the inferior vena cava parallels the abdominal aorta, where it can receive blood from abdominal veins. The lumbar portions of the abdominal wall and spinal cord are drained by a series of lumbar veins, usually four on each side. The ascending lumbar veins drain into either the azygos vein on the right or the hemiazygos vein on the left, and return to the superior vena cava. The remaining lumbar veins drain directly into the inferior vena cava.

                                      Blood supply from the kidneys flows into each renal vein, normally the largest veins entering the inferior vena cava. A number of other, smaller veins empty into the left renal vein. Each adrenal vein drains the adrenal or suprarenal glands located immediately superior to the kidneys. The right adrenal vein enters the inferior vena cava directly, whereas the left adrenal vein enters the left renal vein.

                                      From the male reproductive organs, each testicular vein flows from the scrotum, forming a portion of the spermatic cord. Each ovarian vein drains an ovary in females. Each of these veins is generically called a gonadal vein. The right gonadal vein empties directly into the inferior vena cava, and the left gonadal vein empties into the left renal vein.

                                      Each side of the diaphragm drains into a phrenic vein; the right phrenic vein empties directly into the inferior vena cava, whereas the left phrenic vein empties into the left renal vein. Blood supply from the liver drains into each hepatic vein and directly into the inferior vena cava. Since the inferior vena cava lies primarily to the right of the vertebral column and aorta, the left renal vein is longer, as are the left phrenic, adrenal, and gonadal veins. The longer length of the left renal vein makes the left kidney the primary target of surgeons removing this organ for donation. Figure 20.40 provides a flow chart of the veins flowing into the inferior vena cava. Table 20.15 summarizes the major veins of the abdominal region.

                                      This chart shows the connection between the different veins and the inferior vena cava.
                                      Figure 20.40Venous Flow into Inferior Vena Cava
                                      The flow chart summarizes veins that deliver blood to the inferior vena cava.
                                      Table 20.15.
                                      Major Veins of the Abdominal Region
                                      Vessel Description
                                      Inferior vena cava Large systemic vein that drains blood from areas largely inferior to the diaphragm; empties into the right atrium
                                      Lumbar veins Series of veins that drain the lumbar portion of the abdominal wall and spinal cord; the ascending lumbar veins drain into the azygos vein on the right or the hemiazygos vein on the left; the remaining lumbar veins drain directly into the inferior vena cava
                                      Renal vein Largest vein entering the inferior vena cava; drains the kidneys and flows into the inferior vena cava
                                      Adrenal vein Drains the adrenal or suprarenal; the right adrenal vein enters the inferior vena cava directly and the left adrenal vein enters the left renal vein
                                      Testicular vein Drains the testes and forms part of the spermatic cord; the right testicular vein empties directly into the inferior vena cava and the left testicular vein empties into the left renal vein
                                      Ovarian vein Drains the ovary; the right ovarian vein empties directly into the inferior vena cava and the left ovarian vein empties into the left renal vein
                                      Gonadal vein Generic term for a vein draining a reproductive organ; may be either an ovarian vein or a testicular vein, depending on the sex of the individual
                                      Phrenic vein Drains the diaphragm; the right phrenic vein flows into the inferior vena cava and the left phrenic vein empties into the left renal vein
                                      Hepatic vein Drains systemic blood from the liver and flows into the inferior vena cava

                                      Veins Draining the Lower Limbs

                                      The superior surface of the foot drains into the digital veins, and the inferior surface drains into the plantar veins, which flow into a complex series of anastomoses in the feet and ankles, including the dorsal venous arch and the plantar venous arch (Figure 20.41). From the dorsal venous arch, blood supply drains into the anterior and posterior tibial veins. The anterior tibial vein drains the area near the tibialis anterior muscle and combines with the posterior tibial vein and the fibular vein to form the popliteal vein. The posterior tibial vein drains the posterior surface of the tibia and joins the popliteal vein. The fibular vein drains the muscles and integument in proximity to the fibula and also joins the popliteal vein. The small saphenous vein located on the lateral surface of the leg drains blood from the superficial regions of the lower leg and foot, and flows into to the popliteal vein. As the popliteal vein passes behind the knee in the popliteal region, it becomes the femoral vein. It is palpable in patients without excessive adipose tissue.

                                      Close to the body wall, the great saphenous vein, the deep femoral vein, and the femoral circumflex vein drain into the femoral vein. The great saphenous vein is a prominent surface vessel located on the medial surface of the leg and thigh that collects blood from the superficial portions of these areas. The deep femoral vein, as the name suggests, drains blood from the deeper portions of the thigh. The femoral circumflex vein forms a loop around the femur just inferior to the trochanters and drains blood from the areas in proximity to the head and neck of the femur.

                                      As the femoral vein penetrates the body wall from the femoral portion of the upper limb, it becomes the external iliac vein, a large vein that drains blood from the leg to the common iliac vein. The pelvic organs and integument drain into the internal iliac vein, which forms from several smaller veins in the region, including the umbilical veins that run on either side of the bladder. The external and internal iliac veins combine near the inferior portion of the sacroiliac joint to form the common iliac vein. In addition to blood supply from the external and internal iliac veins, the middle sacral vein drains the sacral region into the common iliac vein. Similar to the common iliac arteries, the common iliac veins come together at the level of L5 to form the inferior vena cava.

                                      Figure 20.42 is a flow chart of veins flowing into the lower limb. Table 20.16 summarizes the major veins of the lower limbs.

                                      The left panel shows the anterior view of veins in the legs, and the right panel shows the posterior view.
                                      Figure 20.41Major Veins Serving the Lower Limbs
                                      Anterior and posterior views show the major veins that drain the lower limb into the inferior vena cava.
                                      This charts shows the veins in the lower limbs, and how they are connected.
                                      Figure 20.42Major Veins of the Lower Limb
                                      The flow chart summarizes venous flow from the lower limb.
                                      Table 20.16.
                                      Veins of the Lower Limbs
                                      Vessel Description
                                      Plantar veins Drain the foot and flow into the plantar venous arch
                                      Dorsal venous arch Drains blood from digital veins and vessels on the superior surface of the foot
                                      Plantar venous arch Formed from the plantar veins; flows into the anterior and posterior tibial veins through anastomoses
                                      Anterior tibial vein Formed from the dorsal venous arch; drains the area near the tibialis anterior muscle and flows into the popliteal vein
                                      Posterior tibial vein Formed from the dorsal venous arch; drains the area near the posterior surface of the tibia and flows into the popliteal vein
                                      Fibular vein Drains the muscles and integument near the fibula and flows into the popliteal vein
                                      Small saphenous vein Located on the lateral surface of the leg; drains blood from the superficial regions of the lower leg and foot, and flows into the popliteal vein
                                      Popliteal vein Drains the region behind the knee and forms from the fusion of the fibular, anterior, and posterior tibial veins; flows into the femoral vein
                                      Great saphenous vein Prominent surface vessel located on the medial surface of the leg and thigh; drains the superficial portions of these areas and flows into the femoral vein
                                      Deep femoral vein Drains blood from the deeper portions of the thigh and flows into the femoral vein
                                      Femoral circumflex vein Forms a loop around the femur just inferior to the trochanters; drains blood from the areas around the head and neck of the femur; flows into the femoral vein
                                      Femoral vein Drains the upper leg; receives blood from the great saphenous vein, the deep femoral vein, and the femoral circumflex vein; becomes the external iliac vein when it crosses the body wall
                                      External iliac vein Formed when the femoral vein passes into the body cavity; drains the legs and flows into the common iliac vein
                                      Internal iliac vein Drains the pelvic organs and integument; formed from several smaller veins in the region; flows into the common iliac vein
                                      Middle sacral vein Drains the sacral region and flows into the left common iliac vein
                                      Common iliac vein Flows into the inferior vena cava at the level of L5; the left common iliac vein drains the sacral region; formed from the union of the external and internal iliac veins near the inferior portion of the sacroiliac joint

                                      Hepatic Portal System

                                      The liver is a complex biochemical processing plant. It packages nutrients absorbed by the digestive system; produces plasma proteins, clotting factors, and bile; and disposes of worn-out cell components and waste products. Instead of entering the circulation directly, absorbed nutrients and certain wastes (for example, materials produced by the spleen) travel to the liver for processing. They do so via the hepatic portal system (Figure 20.43). Portal systems begin and end in capillaries. In this case, the initial capillaries from the stomach, small intestine, large intestine, and spleen lead to the hepatic portal vein and end in specialized capillaries within the liver, the hepatic sinusoids. You saw the only other portal system with the hypothalamic-hypophyseal portal vessel in the endocrine chapter.

                                      The hepatic portal system consists of the hepatic portal vein and the veins that drain into it. The hepatic portal vein itself is relatively short, beginning at the level of L2 with the confluence of the superior mesenteric and splenic veins. It also receives branches from the inferior mesenteric vein, plus the splenic veins and all their tributaries. The superior mesenteric vein receives blood from the small intestine, two-thirds of the large intestine, and the stomach. The inferior mesenteric vein drains the distal third of the large intestine, including the descending colon, the sigmoid colon, and the rectum. The splenic vein is formed from branches from the spleen, pancreas, and portions of the stomach, and the inferior mesenteric vein. After its formation, the hepatic portal vein also receives branches from the gastric veins of the stomach and cystic veins from the gall bladder. The hepatic portal vein delivers materials from these digestive and circulatory organs directly to the liver for processing.

                                      Because of the hepatic portal system, the liver receives its blood supply from two different sources: from normal systemic circulation via the hepatic artery and from the hepatic portal vein. The liver processes the blood from the portal system to remove certain wastes and excess nutrients, which are stored for later use. This processed blood, as well as the systemic blood that came from the hepatic artery, exits the liver via the right, left, and middle hepatic veins, and flows into the inferior vena cava. Overall systemic blood composition remains relatively stable, since the liver is able to metabolize the absorbed digestive components.

                                      This diagram shows the veins in the digestive system.
                                      Figure 20.43Hepatic Portal System
                                      The liver receives blood from the normal systemic circulation via the hepatic artery. It also receives and processes blood from other organs, delivered via the veins of the hepatic portal system. All blood exits the liver via the hepatic vein, which delivers the blood to the inferior vena cava. (Different colors are used to help distinguish among the different vessels in the system.)

                                      20.6Development of Blood Vessels and Fetal Circulation*

                                      By the end of this section, you will be able to:

                                      • Describe the development of blood vessels

                                      • Describe the fetal circulation

                                        In a developing embryo,the heart has developed enough by day 21 post-fertilization to begin beating. Circulation patterns are clearly established by the fourth week of embryonic life. It is critical to the survival of the developing human that the circulatory system forms early to supply the growing tissue with nutrients and gases, and to remove waste products. Blood cells and vessel production in structures outside the embryo proper called the yolk sac, chorion, and connecting stalk begin about 15 to 16 days following fertilization. Development of these circulatory elements within the embryo itself begins approximately 2 days later. You will learn more about the formation and function of these early structures when you study the chapter on development. During those first few weeks, blood vessels begin to form from the embryonic mesoderm. The precursor cells are known as hemangioblasts. These in turn differentiate into angioblasts, which give rise to the blood vessels and pluripotent stem cells, which differentiate into the formed elements of blood. (Seek additional content for more detail on fetal development and circulation.) Together, these cells form masses known as blood islands scattered throughout the embryonic disc. Spaces appear on the blood islands that develop into vessel lumens. The endothelial lining of the vessels arise from the angioblasts within these islands. Surrounding mesenchymal cells give rise to the smooth muscle and connective tissue layers of the vessels. While the vessels are developing, the pluripotent stem cells begin to form the blood.

                                        Vascular tubes also develop on the blood islands, and they eventually connect to one another as well as to the developing, tubular heart. Thus, the developmental pattern, rather than beginning from the formation of one central vessel and spreading outward, occurs in many regions simultaneously with vessels later joining together. This angiogenesis—the creation of new blood vessels from existing ones—continues as needed throughout life as we grow and develop.

                                        Blood vessel development often follows the same pattern as nerve development and travels to the same target tissues and organs. This occurs because the many factors directing growth of nerves also stimulate blood vessels to follow a similar pattern. Whether a given vessel develops into an artery or a vein is dependent upon local concentrations of signaling proteins.

                                        As the embryo grows within the mother’s uterus, its requirements for nutrients and gas exchange also grow. The placenta—a circulatory organ unique to pregnancy—develops jointly from the embryo and uterine wall structures to fill this need. Emerging from the placenta is the umbilical vein, which carries oxygen-rich blood from the mother to the fetal inferior vena cava via the ductus venosus to the heart that pumps it into fetal circulation. Two umbilical arteries carry oxygen-depleted fetal blood, including wastes and carbon dioxide, to the placenta. Remnants of the umbilical arteries remain in the adult. (Seek additional content for more information on the role of the placenta in fetal circulation.)

                                        There are three major shunts—alternate paths for blood flow—found in the circulatory system of the fetus. Two of these shunts divert blood from the pulmonary to the systemic circuit, whereas the third connects the umbilical vein to the inferior vena cava. The first two shunts are critical during fetal life, when the lungs are compressed, filled with amniotic fluid, and nonfunctional, and gas exchange is provided by the placenta. These shunts close shortly after birth, however, when the newborn begins to breathe. The third shunt persists a bit longer but becomes nonfunctional once the umbilical cord is severed. The three shunts are as follows (Figure 20.44):

                                        • The foramen ovale is an opening in the interatrial septum that allows blood to flow from the right atrium to the left atrium. A valve associated with this opening prevents backflow of blood during the fetal period. As the newborn begins to breathe and blood pressure in the atria increases, this shunt closes. The fossa ovalis remains in the interatrial septum after birth, marking the location of the former foramen ovale.

                                        • The ductus arteriosus is a short, muscular vessel that connects the pulmonary trunk to the aorta. Most of the blood pumped from the right ventricle into the pulmonary trunk is thereby diverted into the aorta. Only enough blood reaches the fetal lungs to maintain the developing lung tissue. When the newborn takes the first breath, pressure within the lungs drops dramatically, and both the lungs and the pulmonary vessels expand. As the amount of oxygen increases, the smooth muscles in the wall of the ductus arteriosus constrict, sealing off the passage. Eventually, the muscular and endothelial components of the ductus arteriosus degenerate, leaving only the connective tissue component of the ligamentum arteriosum.

                                        • The ductus venosus is a temporary blood vessel that branches from the umbilical vein, allowing much of the freshly oxygenated blood from the placenta—the organ of gas exchange between the mother and fetus—to bypass the fetal liver and go directly to the fetal heart. The ductus venosus closes slowly during the first weeks of infancy and degenerates to become the ligamentum venosum.

                                        This figure shows the blood vessels in a fetus.
                                        Figure 20.44Fetal Shunts
                                        The foramen ovale in the interatrial septum allows blood to flow from the right atrium to the left atrium. The ductus arteriosus is a temporary vessel, connecting the aorta to the pulmonary trunk. The ductus venosus links the umbilical vein to the inferior vena cava largely through the liver.

                                        Glossary

                                        abdominal aorta

                                        portion of the aorta inferior to the aortic hiatus and superior to the common iliac arteries

                                        adrenal artery

                                        branch of the abdominal aorta; supplies blood to the adrenal (suprarenal) glands

                                        adrenal vein

                                        drains the adrenal or suprarenal glands that are immediately superior to the kidneys; the right adrenal vein enters the inferior vena cava directly and the left adrenal vein enters the left renal vein

                                        anaphylactic shock

                                        type of shock that follows a severe allergic reaction and results from massive vasodilation

                                        angioblasts

                                        stem cells that give rise to blood vessels

                                        angiogenesis

                                        development of new blood vessels from existing vessels

                                        anterior cerebral artery

                                        arises from the internal carotid artery; supplies the frontal lobe of the cerebrum

                                        anterior communicating artery

                                        anastomosis of the right and left internal carotid arteries; supplies blood to the brain

                                        anterior tibial artery

                                        branches from the popliteal artery; supplies blood to the anterior tibial region; becomes the dorsalis pedis artery

                                        anterior tibial vein

                                        forms from the dorsal venous arch; drains the area near the tibialis anterior muscle and leads to the popliteal vein

                                        aorta

                                        largest artery in the body, originating from the left ventricle and descending to the abdominal region where it bifurcates into the common iliac arteries at the level of the fourth lumbar vertebra; arteries originating from the aorta distribute blood to virtually all tissues of the body

                                        aortic arch

                                        arc that connects the ascending aorta to the descending aorta; ends at the intervertebral disk between the fourth and fifth thoracic vertebrae

                                        aortic hiatus

                                        opening in the diaphragm that allows passage of the thoracic aorta into the abdominal region where it becomes the abdominal aorta

                                        aortic sinuses

                                        small pockets in the ascending aorta near the aortic valve that are the locations of the baroreceptors (stretch receptors) and chemoreceptors that trigger a reflex that aids in the regulation of vascular homeostasis

                                        arterial circle

                                        (also, circle of Willis) anastomosis located at the base of the brain that ensures continual blood supply; formed from branches of the internal carotid and vertebral arteries; supplies blood to the brain

                                        arteriole

                                        (also, resistance vessel) very small artery that leads to a capillary

                                        arteriovenous anastomosis

                                        short vessel connecting an arteriole directly to a venule and bypassing the capillary beds

                                        artery

                                        blood vessel that conducts blood away from the heart; may be a conducting or distributing vessel

                                        ascending aorta

                                        initial portion of the aorta, rising from the left ventricle for a distance of approximately 5 cm

                                        atrial reflex

                                        mechanism for maintaining vascular homeostasis involving atrial baroreceptors: if blood is returning to the right atrium more rapidly than it is being ejected from the left ventricle, the atrial receptors will stimulate the cardiovascular centers to increase sympathetic firing and increase cardiac output until the situation is reversed; the opposite is also true

                                        axillary artery

                                        continuation of the subclavian artery as it penetrates the body wall and enters the axillary region; supplies blood to the region near the head of the humerus (humeral circumflex arteries); the majority of the vessel continues into the brachium and becomes the brachial artery

                                        axillary vein

                                        major vein in the axillary region; drains the upper limb and becomes the subclavian vein

                                        azygos vein

                                        originates in the lumbar region and passes through the diaphragm into the thoracic cavity on the right side of the vertebral column; drains blood from the intercostal veins, esophageal veins, bronchial veins, and other veins draining the mediastinal region; leads to the superior vena cava

                                        basilar artery

                                        formed from the fusion of the two vertebral arteries; sends branches to the cerebellum, brain stem, and the posterior cerebral arteries; the main blood supply to the brain stem

                                        basilic vein

                                        superficial vein of the arm that arises from the palmar venous arches, intersects with the median cubital vein, parallels the ulnar vein, and continues into the upper arm; along with the brachial vein, it leads to the axillary vein

                                        blood colloidal osmotic pressure (BCOP)

                                        pressure exerted by colloids suspended in blood within a vessel; a primary determinant is the presence of plasma proteins

                                        blood flow

                                        movement of blood through a vessel, tissue, or organ that is usually expressed in terms of volume per unit of time

                                        blood hydrostatic pressure

                                        force blood exerts against the walls of a blood vessel or heart chamber

                                        blood islands

                                        masses of developing blood vessels and formed elements from mesodermal cells scattered throughout the embryonic disc

                                        blood pressure

                                        force exerted by the blood against the wall of a vessel or heart chamber; can be described with the more generic term hydrostatic pressure

                                        brachial artery

                                        continuation of the axillary artery in the brachium; supplies blood to much of the brachial region; gives off several smaller branches that provide blood to the posterior surface of the arm in the region of the elbow; bifurcates into the radial and ulnar arteries at the coronoid fossa

                                        brachial vein

                                        deeper vein of the arm that forms from the radial and ulnar veins in the lower arm; leads to the axillary vein

                                        brachiocephalic artery

                                        single vessel located on the right side of the body; the first vessel branching from the aortic arch; gives rise to the right subclavian artery and the right common carotid artery; supplies blood to the head, neck, upper limb, and wall of the thoracic region

                                        brachiocephalic vein

                                        one of a pair of veins that form from a fusion of the external and internal jugular veins and the subclavian vein; subclavian, external and internal jugulars, vertebral, and internal thoracic veins lead to it; drains the upper thoracic region and flows into the superior vena cava

                                        bronchial artery

                                        systemic branch from the aorta that provides oxygenated blood to the lungs in addition to the pulmonary circuit

                                        bronchial vein

                                        drains the systemic circulation from the lungs and leads to the azygos vein

                                        capacitance vessels

                                        veins

                                        capacitance

                                        ability of a vein to distend and store blood

                                        capillary bed

                                        network of 10–100 capillaries connecting arterioles to venules

                                        capillary hydrostatic pressure (CHP)

                                        force blood exerts against a capillary

                                        capillary

                                        smallest of blood vessels where physical exchange occurs between the blood and tissue cells surrounded by interstitial fluid

                                        cardiogenic shock

                                        type of shock that results from the inability of the heart to maintain cardiac output

                                        carotid sinuses

                                        small pockets near the base of the internal carotid arteries that are the locations of the baroreceptors and chemoreceptors that trigger a reflex that aids in the regulation of vascular homeostasis

                                        cavernous sinus

                                        enlarged vein that receives blood from most of the other cerebral veins and the eye socket, and leads to the petrosal sinus

                                        celiac trunk

                                        (also, celiac artery) major branch of the abdominal aorta; gives rise to the left gastric artery, the splenic artery, and the common hepatic artery that forms the hepatic artery to the liver, the right gastric artery to the stomach, and the cystic artery to the gall bladder

                                        cephalic vein

                                        superficial vessel in the upper arm; leads to the axillary vein

                                        cerebrovascular accident (CVA)

                                        blockage of blood flow to the brain; also called a stroke

                                        circle of Willis

                                        (also, arterial circle) anastomosis located at the base of the brain that ensures continual blood supply; formed from branches of the internal carotid and vertebral arteries; supplies blood to the brain

                                        circulatory shock

                                        also simply called shock; a life-threatening medical condition in which the circulatory system is unable to supply enough blood flow to provide adequate oxygen and other nutrients to the tissues to maintain cellular metabolism

                                        common carotid artery

                                        right common carotid artery arises from the brachiocephalic artery, and the left common carotid arises from the aortic arch; gives rise to the external and internal carotid arteries; supplies the respective sides of the head and neck

                                        common hepatic artery

                                        branch of the celiac trunk that forms the hepatic artery, the right gastric artery, and the cystic artery

                                        common iliac artery

                                        branch of the aorta that leads to the internal and external iliac arteries

                                        common iliac vein

                                        one of a pair of veins that flows into the inferior vena cava at the level of L5; the left common iliac vein drains the sacral region; divides into external and internal iliac veins near the inferior portion of the sacroiliac joint

                                        compliance

                                        degree to which a blood vessel can stretch as opposed to being rigid

                                        continuous capillary

                                        most common type of capillary, found in virtually all tissues except epithelia and cartilage; contains very small gaps in the endothelial lining that permit exchange

                                        cystic artery

                                        branch of the common hepatic artery; supplies blood to the gall bladder

                                        deep femoral artery

                                        branch of the femoral artery; gives rise to the lateral circumflex arteries

                                        deep femoral vein

                                        drains blood from the deeper portions of the thigh and leads to the femoral vein

                                        descending aorta

                                        portion of the aorta that continues downward past the end of the aortic arch; subdivided into the thoracic aorta and the abdominal aorta

                                        diastolic pressure

                                        lower number recorded when measuring arterial blood pressure; represents the minimal value corresponding to the pressure that remains during ventricular relaxation

                                        digital arteries

                                        formed from the superficial and deep palmar arches; supply blood to the digits

                                        digital veins

                                        drain the digits and feed into the palmar arches of the hand and dorsal venous arch of the foot

                                        dorsal arch

                                        (also, arcuate arch) formed from the anastomosis of the dorsalis pedis artery and medial and plantar arteries; branches supply the distal portions of the foot and digits

                                        dorsal venous arch

                                        drains blood from digital veins and vessels on the superior surface of the foot

                                        dorsalis pedis artery

                                        forms from the anterior tibial artery; branches repeatedly to supply blood to the tarsal and dorsal regions of the foot

                                        ductus arteriosus

                                        shunt in the fetal pulmonary trunk that diverts oxygenated blood back to the aorta

                                        ductus venosus

                                        shunt that causes oxygenated blood to bypass the fetal liver on its way to the inferior vena cava

                                        elastic artery

                                        (also, conducting artery) artery with abundant elastic fibers located closer to the heart, which maintains the pressure gradient and conducts blood to smaller branches

                                        esophageal artery

                                        branch of the thoracic aorta; supplies blood to the esophagus

                                        esophageal vein

                                        drains the inferior portions of the esophagus and leads to the azygos vein

                                        external carotid artery

                                        arises from the common carotid artery; supplies blood to numerous structures within the face, lower jaw, neck, esophagus, and larynx

                                        external elastic membrane

                                        membrane composed of elastic fibers that separates the tunica media from the tunica externa; seen in larger arteries

                                        external iliac artery

                                        branch of the common iliac artery that leaves the body cavity and becomes a femoral artery; supplies blood to the lower limbs

                                        external iliac vein

                                        formed when the femoral vein passes into the body cavity; drains the legs and leads to the common iliac vein

                                        external jugular vein

                                        one of a pair of major veins located in the superficial neck region that drains blood from the more superficial portions of the head, scalp, and cranial regions, and leads to the subclavian vein

                                        femoral artery

                                        continuation of the external iliac artery after it passes through the body cavity; divides into several smaller branches, the lateral deep femoral artery, and the genicular artery; becomes the popliteal artery as it passes posterior to the knee

                                        femoral circumflex vein

                                        forms a loop around the femur just inferior to the trochanters; drains blood from the areas around the head and neck of the femur; leads to the femoral vein

                                        femoral vein

                                        drains the upper leg; receives blood from the great saphenous vein, the deep femoral vein, and the femoral circumflex vein; becomes the external iliac vein when it crosses the body wall

                                        fenestrated capillary

                                        type of capillary with pores or fenestrations in the endothelium that allow for rapid passage of certain small materials

                                        fibular vein

                                        drains the muscles and integument near the fibula and leads to the popliteal vein

                                        filtration

                                        in the cardiovascular system, the movement of material from a capillary into the interstitial fluid, moving from an area of higher pressure to lower pressure

                                        foramen ovale

                                        shunt that directly connects the right and left atria and helps to divert oxygenated blood from the fetal pulmonary circuit

                                        genicular artery

                                        branch of the femoral artery; supplies blood to the region of the knee

                                        gonadal artery

                                        branch of the abdominal aorta; supplies blood to the gonads or reproductive organs; also described as ovarian arteries or testicular arteries, depending upon the sex of the individual

                                        gonadal vein

                                        generic term for a vein draining a reproductive organ; may be either an ovarian vein or a testicular vein, depending on the sex of the individual

                                        great cerebral vein

                                        receives most of the smaller vessels from the inferior cerebral veins and leads to the straight sinus

                                        great saphenous vein

                                        prominent surface vessel located on the medial surface of the leg and thigh; drains the superficial portions of these areas and leads to the femoral vein

                                        hemangioblasts

                                        embryonic stem cells that appear in the mesoderm and give rise to both angioblasts and pluripotent stem cells

                                        hemiazygos vein

                                        smaller vein complementary to the azygos vein; drains the esophageal veins from the esophagus and the left intercostal veins, and leads to the brachiocephalic vein via the superior intercostal vein

                                        hepatic artery proper

                                        branch of the common hepatic artery; supplies systemic blood to the liver

                                        hepatic portal system

                                        specialized circulatory pathway that carries blood from digestive organs to the liver for processing before being sent to the systemic circulation

                                        hepatic vein

                                        drains systemic blood from the liver and flows into the inferior vena cava

                                        hypertension

                                        chronic and persistent blood pressure measurements of 140/90 mm Hg or above

                                        hypervolemia

                                        abnormally high levels of fluid and blood within the body

                                        hypovolemia

                                        abnormally low levels of fluid and blood within the body

                                        hypovolemic shock

                                        type of circulatory shock caused by excessive loss of blood volume due to hemorrhage or possibly dehydration

                                        hypoxia

                                        lack of oxygen supply to the tissues

                                        inferior mesenteric artery

                                        branch of the abdominal aorta; supplies blood to the distal segment of the large intestine and rectum

                                        inferior phrenic artery

                                        branch of the abdominal aorta; supplies blood to the inferior surface of the diaphragm

                                        inferior vena cava

                                        large systemic vein that drains blood from areas largely inferior to the diaphragm; empties into the right atrium

                                        intercostal artery

                                        branch of the thoracic aorta; supplies blood to the muscles of the thoracic cavity and vertebral column

                                        intercostal vein

                                        drains the muscles of the thoracic wall and leads to the azygos vein

                                        internal carotid artery

                                        arises from the common carotid artery and begins with the carotid sinus; goes through the carotid canal of the temporal bone to the base of the brain; combines with branches of the vertebral artery forming the arterial circle; supplies blood to the brain

                                        internal elastic membrane

                                        membrane composed of elastic fibers that separates the tunica intima from the tunica media; seen in larger arteries

                                        internal iliac artery

                                        branch from the common iliac arteries; supplies blood to the urinary bladder, walls of the pelvis, external genitalia, and the medial portion of the femoral region; in females, also provide blood to the uterus and vagina

                                        internal iliac vein

                                        drains the pelvic organs and integument; formed from several smaller veins in the region; leads to the common iliac vein

                                        internal jugular vein

                                        one of a pair of major veins located in the neck region that passes through the jugular foramen and canal, flows parallel to the common carotid artery that is more or less its counterpart; primarily drains blood from the brain, receives the superficial facial vein, and empties into the subclavian vein

                                        internal thoracic artery

                                        (also, mammary artery) arises from the subclavian artery; supplies blood to the thymus, pericardium of the heart, and the anterior chest wall

                                        internal thoracic vein

                                        (also, internal mammary vein) drains the anterior surface of the chest wall and leads to the brachiocephalic vein

                                        interstitial fluid colloidal osmotic pressure (IFCOP)

                                        pressure exerted by the colloids within the interstitial fluid

                                        interstitial fluid hydrostatic pressure (IFHP)

                                        force exerted by the fluid in the tissue spaces

                                        ischemia

                                        insufficient blood flow to the tissues

                                        Korotkoff sounds

                                        noises created by turbulent blood flow through the vessels

                                        lateral circumflex artery

                                        branch of the deep femoral artery; supplies blood to the deep muscles of the thigh and the ventral and lateral regions of the integument

                                        lateral plantar artery

                                        arises from the bifurcation of the posterior tibial arteries; supplies blood to the lateral plantar surfaces of the foot

                                        left gastric artery

                                        branch of the celiac trunk; supplies blood to the stomach

                                        lumbar arteries

                                        branches of the abdominal aorta; supply blood to the lumbar region, the abdominal wall, and spinal cord

                                        lumbar veins

                                        drain the lumbar portion of the abdominal wall and spinal cord; the superior lumbar veins drain into the azygos vein on the right or the hemiazygos vein on the left; blood from these vessels is returned to the superior vena cava rather than the inferior vena cava

                                        lumen

                                        interior of a tubular structure such as a blood vessel or a portion of the alimentary canal through which blood, chyme, or other substances travel

                                        maxillary vein

                                        drains blood from the maxillary region and leads to the external jugular vein

                                        mean arterial pressure (MAP)

                                        average driving force of blood to the tissues; approximated by taking diastolic pressure and adding 1/3 of pulse pressure

                                        medial plantar artery

                                        arises from the bifurcation of the posterior tibial arteries; supplies blood to the medial plantar surfaces of the foot

                                        median antebrachial vein

                                        vein that parallels the ulnar vein but is more medial in location; intertwines with the palmar venous arches

                                        median cubital vein

                                        superficial vessel located in the antecubital region that links the cephalic vein to the basilic vein in the form of a v; a frequent site for a blood draw

                                        median sacral artery

                                        continuation of the aorta into the sacrum

                                        mediastinal artery

                                        branch of the thoracic aorta; supplies blood to the mediastinum

                                        metarteriole

                                        short vessel arising from a terminal arteriole that branches to supply a capillary bed

                                        microcirculation

                                        blood flow through the capillaries

                                        middle cerebral artery

                                        another branch of the internal carotid artery; supplies blood to the temporal and parietal lobes of the cerebrum

                                        middle sacral vein

                                        drains the sacral region and leads to the left common iliac vein

                                        muscular artery

                                        (also, distributing artery) artery with abundant smooth muscle in the tunica media that branches to distribute blood to the arteriole network

                                        myogenic response

                                        constriction or dilation in the walls of arterioles in response to pressures related to blood flow; reduces high blood flow or increases low blood flow to help maintain consistent flow to the capillary network

                                        nervi vasorum

                                        small nerve fibers found in arteries and veins that trigger contraction of the smooth muscle in their walls

                                        net filtration pressure (NFP)

                                        force driving fluid out of the capillary and into the tissue spaces; equal to the difference of the capillary hydrostatic pressure and the blood colloidal osmotic pressure

                                        neurogenic shock

                                        type of shock that occurs with cranial or high spinal injuries that damage the cardiovascular centers in the medulla oblongata or the nervous fibers originating from this region

                                        obstructive shock

                                        type of shock that occurs when a significant portion of the vascular system is blocked

                                        occipital sinus

                                        enlarged vein that drains the occipital region near the falx cerebelli and flows into the left and right transverse sinuses, and also into the vertebral veins

                                        ophthalmic artery

                                        branch of the internal carotid artery; supplies blood to the eyes

                                        ovarian artery

                                        branch of the abdominal aorta; supplies blood to the ovary, uterine (Fallopian) tube, and uterus

                                        ovarian vein

                                        drains the ovary; the right ovarian vein leads to the inferior vena cava and the left ovarian vein leads to the left renal vein

                                        palmar arches

                                        superficial and deep arches formed from anastomoses of the radial and ulnar arteries; supply blood to the hand and digital arteries

                                        palmar venous arches

                                        drain the hand and digits, and feed into the radial and ulnar veins

                                        parietal branches

                                        (also, somatic branches) group of arterial branches of the thoracic aorta; includes those that supply blood to the thoracic cavity, vertebral column, and the superior surface of the diaphragm

                                        perfusion

                                        distribution of blood into the capillaries so the tissues can be supplied

                                        pericardial artery

                                        branch of the thoracic aorta; supplies blood to the pericardium

                                        petrosal sinus

                                        enlarged vein that receives blood from the cavernous sinus and flows into the internal jugular vein

                                        phrenic vein

                                        drains the diaphragm; the right phrenic vein flows into the inferior vena cava and the left phrenic vein leads to the left renal vein

                                        plantar arch

                                        formed from the anastomosis of the dorsalis pedis artery and medial and plantar arteries; branches supply the distal portions of the foot and digits

                                        plantar veins

                                        drain the foot and lead to the plantar venous arch

                                        plantar venous arch

                                        formed from the plantar veins; leads to the anterior and posterior tibial veins through anastomoses

                                        popliteal artery

                                        continuation of the femoral artery posterior to the knee; branches into the anterior and posterior tibial arteries

                                        popliteal vein

                                        continuation of the femoral vein behind the knee; drains the region behind the knee and forms from the fusion of the fibular and anterior and posterior tibial veins

                                        posterior cerebral artery

                                        branch of the basilar artery that forms a portion of the posterior segment of the arterial circle; supplies blood to the posterior portion of the cerebrum and brain stem

                                        posterior communicating artery

                                        branch of the posterior cerebral artery that forms part of the posterior portion of the arterial circle; supplies blood to the brain

                                        posterior tibial artery

                                        branch from the popliteal artery that gives rise to the fibular or peroneal artery; supplies blood to the posterior tibial region

                                        posterior tibial vein

                                        forms from the dorsal venous arch; drains the area near the posterior surface of the tibia and leads to the popliteal vein

                                        precapillary sphincters

                                        circular rings of smooth muscle that surround the entrance to a capillary and regulate blood flow into that capillary

                                        pulmonary artery

                                        one of two branches, left and right, that divides off from the pulmonary trunk and leads to smaller arterioles and eventually to the pulmonary capillaries

                                        pulmonary circuit

                                        system of blood vessels that provide gas exchange via a network of arteries, veins, and capillaries that run from the heart, through the body, and back to the lungs

                                        pulmonary trunk

                                        single large vessel exiting the right ventricle that divides to form the right and left pulmonary arteries

                                        pulmonary veins

                                        two sets of paired vessels, one pair on each side, that are formed from the small venules leading away from the pulmonary capillaries that flow into the left atrium

                                        pulse pressure

                                        difference between the systolic and diastolic pressures

                                        pulse

                                        alternating expansion and recoil of an artery as blood moves through the vessel; an indicator of heart rate

                                        radial artery

                                        formed at the bifurcation of the brachial artery; parallels the radius; gives off smaller branches until it reaches the carpal region where it fuses with the ulnar artery to form the superficial and deep palmar arches; supplies blood to the lower arm and carpal region

                                        radial vein

                                        parallels the radius and radial artery; arises from the palmar venous arches and leads to the brachial vein

                                        reabsorption

                                        in the cardiovascular system, the movement of material from the interstitial fluid into the capillaries

                                        renal artery

                                        branch of the abdominal aorta; supplies each kidney

                                        renal vein

                                        largest vein entering the inferior vena cava; drains the kidneys and leads to the inferior vena cava

                                        resistance

                                        any condition or parameter that slows or counteracts the flow of blood

                                        respiratory pump

                                        increase in the volume of the thorax during inhalation that decreases air pressure, enabling venous blood to flow into the thoracic region, then exhalation increases pressure, moving blood into the atria

                                        right gastric artery

                                        branch of the common hepatic artery; supplies blood to the stomach

                                        sepsis

                                        (also, septicemia) organismal-level inflammatory response to a massive infection

                                        septic shock

                                        (also, blood poisoning) type of shock that follows a massive infection resulting in organism-wide inflammation

                                        sigmoid sinuses

                                        enlarged veins that receive blood from the transverse sinuses; flow through the jugular foramen and into the internal jugular vein

                                        sinusoid capillary

                                        rarest type of capillary, which has extremely large intercellular gaps in the basement membrane in addition to clefts and fenestrations; found in areas such as the bone marrow and liver where passage of large molecules occurs

                                        skeletal muscle pump

                                        effect on increasing blood pressure within veins by compression of the vessel caused by the contraction of nearby skeletal muscle

                                        small saphenous vein

                                        located on the lateral surface of the leg; drains blood from the superficial regions of the lower leg and foot, and leads to the popliteal vein

                                        sphygmomanometer

                                        blood pressure cuff attached to a device that measures blood pressure

                                        splenic artery

                                        branch of the celiac trunk; supplies blood to the spleen

                                        straight sinus

                                        enlarged vein that drains blood from the brain; receives most of the blood from the great cerebral vein and flows into the left or right transverse sinus

                                        subclavian artery

                                        right subclavian arises from the brachiocephalic artery, whereas the left subclavian artery arises from the aortic arch; gives rise to the internal thoracic, vertebral, and thyrocervical arteries; supplies blood to the arms, chest, shoulders, back, and central nervous system

                                        subclavian vein

                                        located deep in the thoracic cavity; becomes the axillary vein as it enters the axillary region; drains the axillary and smaller local veins near the scapular region; leads to the brachiocephalic vein

                                        subscapular vein

                                        drains blood from the subscapular region and leads to the axillary vein

                                        superior mesenteric artery

                                        branch of the abdominal aorta; supplies blood to the small intestine (duodenum, jejunum, and ileum), the pancreas, and a majority of the large intestine

                                        superior phrenic artery

                                        branch of the thoracic aorta; supplies blood to the superior surface of the diaphragm

                                        superior sagittal sinus

                                        enlarged vein located midsagittally between the meningeal and periosteal layers of the dura mater within the falx cerebri; receives most of the blood drained from the superior surface of the cerebrum and leads to the inferior jugular vein and the vertebral vein

                                        superior vena cava

                                        large systemic vein; drains blood from most areas superior to the diaphragm; empties into the right atrium

                                        systolic pressure

                                        larger number recorded when measuring arterial blood pressure; represents the maximum value following ventricular contraction

                                        temporal vein

                                        drains blood from the temporal region and leads to the external jugular vein

                                        testicular artery

                                        branch of the abdominal aorta; will ultimately travel outside the body cavity to the testes and form one component of the spermatic cord

                                        testicular vein

                                        drains the testes and forms part of the spermatic cord; the right testicular vein empties directly into the inferior vena cava and the left testicular vein empties into the left renal vein

                                        thoracic aorta

                                        portion of the descending aorta superior to the aortic hiatus

                                        thoroughfare channel

                                        continuation of the metarteriole that enables blood to bypass a capillary bed and flow directly into a venule, creating a vascular shunt

                                        thyrocervical artery

                                        arises from the subclavian artery; supplies blood to the thyroid, the cervical region, the upper back, and shoulder

                                        transient ischemic attack (TIA)

                                        temporary loss of neurological function caused by a brief interruption in blood flow; also known as a mini-stroke

                                        transverse sinuses

                                        pair of enlarged veins near the lambdoid suture that drain the occipital, sagittal, and straight sinuses, and leads to the sigmoid sinuses

                                        trunk

                                        large vessel that gives rise to smaller vessels

                                        tunica externa

                                        (also, tunica adventitia) outermost layer or tunic of a vessel (except capillaries)

                                        tunica intima

                                        (also, tunica interna) innermost lining or tunic of a vessel

                                        tunica media

                                        middle layer or tunic of a vessel (except capillaries)

                                        ulnar artery

                                        formed at the bifurcation of the brachial artery; parallels the ulna; gives off smaller branches until it reaches the carpal region where it fuses with the radial artery to form the superficial and deep palmar arches; supplies blood to the lower arm and carpal region

                                        ulnar vein

                                        parallels the ulna and ulnar artery; arises from the palmar venous arches and leads to the brachial vein

                                        umbilical arteries

                                        pair of vessels that runs within the umbilical cord and carries fetal blood low in oxygen and high in waste to the placenta for exchange with maternal blood

                                        umbilical vein

                                        single vessel that originates in the placenta and runs within the umbilical cord, carrying oxygen- and nutrient-rich blood to the fetal heart

                                        vasa vasorum

                                        small blood vessels located within the walls or tunics of larger vessels that supply nourishment to and remove wastes from the cells of the vessels

                                        vascular shock

                                        type of shock that occurs when arterioles lose their normal muscular tone and dilate dramatically

                                        vascular shunt

                                        continuation of the metarteriole and thoroughfare channel that allows blood to bypass the capillary beds to flow directly from the arterial to the venous circulation

                                        vascular tone

                                        contractile state of smooth muscle in a blood vessel

                                        vascular tubes

                                        rudimentary blood vessels in a developing fetus

                                        vasoconstriction

                                        constriction of the smooth muscle of a blood vessel, resulting in a decreased vascular diameter

                                        vasodilation

                                        relaxation of the smooth muscle in the wall of a blood vessel, resulting in an increased vascular diameter

                                        vasomotion

                                        irregular, pulsating flow of blood through capillaries and related structures

                                        vein

                                        blood vessel that conducts blood toward the heart

                                        venous reserve

                                        volume of blood contained within systemic veins in the integument, bone marrow, and liver that can be returned to the heart for circulation, if needed

                                        venule

                                        small vessel leading from the capillaries to veins

                                        vertebral artery

                                        arises from the subclavian artery and passes through the vertebral foramen through the foramen magnum to the brain; joins with the internal carotid artery to form the arterial circle; supplies blood to the brain and spinal cord

                                        vertebral vein

                                        arises from the base of the brain and the cervical region of the spinal cord; passes through the intervertebral foramina in the cervical vertebrae; drains smaller veins from the cranium, spinal cord, and vertebrae, and leads to the brachiocephalic vein; counterpart of the vertebral artery

                                        visceral branches

                                        branches of the descending aorta that supply blood to the viscera

                                        Chapter Review
                                        20.. Introduction
                                        20.1. Structure and Function of Blood Vessels

                                        Blood pumped by the heart flows through a series of vessels known as arteries, arterioles, capillaries, venules, and veins before returning to the heart. Arteries transport blood away from the heart and branch into smaller vessels, forming arterioles. Arterioles distribute blood to capillary beds, the sites of exchange with the body tissues. Capillaries lead back to small vessels known as venules that flow into the larger veins and eventually back to the heart.

                                        The arterial system is a relatively high-pressure system, so arteries have thick walls that appear round in cross section. The venous system is a lower-pressure system, containing veins that have larger lumens and thinner walls. They often appear flattened. Arteries, arterioles, venules, and veins are composed of three tunics known as the tunica intima, tunica media, and tunica externa. Capillaries have only a tunica intima layer. The tunica intima is a thin layer composed of a simple squamous epithelium known as endothelium and a small amount of connective tissue. The tunica media is a thicker area composed of variable amounts of smooth muscle and connective tissue. It is the thickest layer in all but the largest arteries. The tunica externa is primarily a layer of connective tissue, although in veins, it also contains some smooth muscle. Blood flow through vessels can be dramatically influenced by vasoconstriction and vasodilation in their walls.

                                        20.2. Blood Flow, Blood Pressure, and Resistance

                                        Blood flow is the movement of blood through a vessel, tissue, or organ. The slowing or blocking of blood flow is called resistance. Blood pressure is the force that blood exerts upon the walls of the blood vessels or chambers of the heart. The components of blood pressure include systolic pressure, which results from ventricular contraction, and diastolic pressure, which results from ventricular relaxation. Pulse pressure is the difference between systolic and diastolic measures, and mean arterial pressure is the “average” pressure of blood in the arterial system, driving blood into the tissues. Pulse, the expansion and recoiling of an artery, reflects the heartbeat. The variables affecting blood flow and blood pressure in the systemic circulation are cardiac output, compliance, blood volume, blood viscosity, and the length and diameter of the blood vessels. In the arterial system, vasodilation and vasoconstriction of the arterioles is a significant factor in systemic blood pressure: Slight vasodilation greatly decreases resistance and increases flow, whereas slight vasoconstriction greatly increases resistance and decreases flow. In the arterial system, as resistance increases, blood pressure increases and flow decreases. In the venous system, constriction increases blood pressure as it does in arteries; the increasing pressure helps to return blood to the heart. In addition, constriction causes the vessel lumen to become more rounded, decreasing resistance and increasing blood flow. Venoconstriction, while less important than arterial vasoconstriction, works with the skeletal muscle pump, the respiratory pump, and their valves to promote venous return to the heart.

                                        20.3. Capillary Exchange

                                        Small molecules can cross into and out of capillaries via simple or facilitated diffusion. Some large molecules can cross in vesicles or through clefts, fenestrations, or gaps between cells in capillary walls. However, the bulk flow of capillary and tissue fluid occurs via filtration and reabsorption. Filtration, the movement of fluid out of the capillaries, is driven by the CHP. Reabsorption, the influx of tissue fluid into the capillaries, is driven by the BCOP. Filtration predominates in the arterial end of the capillary; in the middle section, the opposing pressures are virtually identical so there is no net exchange, whereas reabsorption predominates at the venule end of the capillary. The hydrostatic and colloid osmotic pressures in the interstitial fluid are negligible in healthy circumstances.

                                        20.4. Homeostatic Regulation of the Vascular System

                                        Neural, endocrine, and autoregulatory mechanisms affect blood flow, blood pressure, and eventually perfusion of blood to body tissues. Neural mechanisms include the cardiovascular centers in the medulla oblongata, baroreceptors in the aorta and carotid arteries and right atrium, and associated chemoreceptors that monitor blood levels of oxygen, carbon dioxide, and hydrogen ions. Endocrine controls include epinephrine and norepinephrine, as well as ADH, the renin-angiotensin-aldosterone mechanism, ANH, and EPO. Autoregulation is the local control of vasodilation and constriction by chemical signals and the myogenic response. Exercise greatly improves cardiovascular function and reduces the risk of cardiovascular diseases, including hypertension, a leading cause of heart attacks and strokes. Significant hemorrhage can lead to a form of circulatory shock known as hypovolemic shock. Sepsis, obstruction, and widespread inflammation can also cause circulatory shock.

                                        20.5. Circulatory Pathways

                                        The right ventricle pumps oxygen-depleted blood into the pulmonary trunk and right and left pulmonary arteries, which carry it to the right and left lungs for gas exchange. Oxygen-rich blood is transported by pulmonary veins to the left atrium. The left ventricle pumps this blood into the aorta. The main regions of the aorta are the ascending aorta, aortic arch, and descending aorta, which is further divided into the thoracic and abdominal aorta. The coronary arteries branch from the ascending aorta. After oxygenating tissues in the capillaries, systemic blood is returned to the right atrium from the venous system via the superior vena cava, which drains most of the veins superior to the diaphragm, the inferior vena cava, which drains most of the veins inferior to the diaphragm, and the coronary veins via the coronary sinus. The hepatic portal system carries blood to the liver for processing before it enters circulation. Review the figures provided in this section for circulation of blood through the blood vessels.

                                        20.6. Development of Blood Vessels and Fetal Circulation

                                        Blood vessels begin to form from the embryonic mesoderm. The precursor hemangioblasts differentiate into angioblasts, which give rise to the blood vessels and pluripotent stem cells that differentiate into the formed elements of the blood. Together, these cells form blood islands scattered throughout the embryo. Extensions known as vascular tubes eventually connect the vascular network. As the embryo grows within the mother’s womb, the placenta develops to supply blood rich in oxygen and nutrients via the umbilical vein and to remove wastes in oxygen-depleted blood via the umbilical arteries. Three major shunts found in the fetus are the foramen ovale and ductus arteriosus, which divert blood from the pulmonary to the systemic circuit, and the ductus venosus, which carries freshly oxygenated blood high in nutrients to the fetal heart.

                                        Interactive Link Questions
                                        20.. Introduction
                                        20.1. Structure and Function of Blood Vessels
                                        20.2. Blood Flow, Blood Pressure, and Resistance
                                        20.3. Capillary Exchange
                                        Exercise 16.

                                        Watch this video to explore capillaries and how they function in the body. Capillaries are never more than 100 micrometers away. What is the main component of interstitial fluid?

                                        (Return to Exercise)

                                        Water.

                                        20.4. Homeostatic Regulation of the Vascular System
                                        Exercise 22.

                                        Listen to this CDC podcast to learn about hypertension, often described as a “silent killer.” What steps can you take to reduce your risk of a heart attack or stroke?

                                        (Return to Exercise)

                                        Take medications as prescribed, eat a healthy diet, exercise, and don’t smoke.

                                        20.5. Circulatory Pathways
                                        20.6. Development of Blood Vessels and Fetal Circulation
                                        Review Questions
                                        20.. Introduction
                                        20.1. Structure and Function of Blood Vessels
                                        Exercise 1.

                                        The endothelium is found in the ________.

                                        1. tunica intima

                                        2. tunica media

                                        3. tunica externa

                                        4. lumen

                                        (Return to Exercise)

                                        A

                                        Exercise 2.

                                        Nervi vasorum control ________.

                                        1. vasoconstriction

                                        2. vasodilation

                                        3. capillary permeability

                                        4. both vasoconstriction and vasodilation

                                        (Return to Exercise)

                                        D

                                        Exercise 3.

                                        Closer to the heart, arteries would be expected to have a higher percentage of ________.

                                        1. endothelium

                                        2. smooth muscle fibers

                                        3. elastic fibers

                                        4. collagenous fibers

                                        (Return to Exercise)

                                        C

                                        Exercise 4.

                                        Which of the following best describes veins?

                                        1. thick walled, small lumens, low pressure, lack valves

                                        2. thin walled, large lumens, low pressure, have valves

                                        3. thin walled, small lumens, high pressure, have valves

                                        4. thick walled, large lumens, high pressure, lack valves

                                        (Return to Exercise)

                                        B

                                        Exercise 5.

                                        An especially leaky type of capillary found in the liver and certain other tissues is called a ________.

                                        1. capillary bed

                                        2. fenestrated capillary

                                        3. sinusoid capillary

                                        4. metarteriole

                                        (Return to Exercise)

                                        C

                                        20.2. Blood Flow, Blood Pressure, and Resistance
                                        Exercise 9.

                                        In a blood pressure measurement of 110/70, the number 70 is the ________.

                                        1. systolic pressure

                                        2. diastolic pressure

                                        3. pulse pressure

                                        4. mean arterial pressure

                                        (Return to Exercise)

                                        B

                                        Exercise 10.

                                        A healthy elastic artery ________.

                                        1. is compliant

                                        2. reduces blood flow

                                        3. is a resistance artery

                                        4. has a thin wall and irregular lumen

                                        (Return to Exercise)

                                        A

                                        Exercise 11.

                                        Which of the following statements is true?

                                        1. The longer the vessel, the lower the resistance and the greater the flow.

                                        2. As blood volume decreases, blood pressure and blood flow also decrease.

                                        3. Increased viscosity increases blood flow.

                                        4. All of the above are true.

                                        (Return to Exercise)

                                        B

                                        Exercise 12.

                                        Slight vasodilation in an arteriole prompts a ________.

                                        1. slight increase in resistance

                                        2. huge increase in resistance

                                        3. slight decrease in resistance

                                        4. huge decrease in resistance

                                        (Return to Exercise)

                                        D

                                        Exercise 13.

                                        Venoconstriction increases which of the following?

                                        1. blood pressure within the vein

                                        2. blood flow within the vein

                                        3. return of blood to the heart

                                        4. all of the above

                                        (Return to Exercise)

                                        D

                                        20.3. Capillary Exchange
                                        Exercise 17.

                                        Hydrostatic pressure is ________.

                                        1. greater than colloid osmotic pressure at the venous end of the capillary bed

                                        2. the pressure exerted by fluid in an enclosed space

                                        3. about zero at the midpoint of a capillary bed

                                        4. all of the above

                                        (Return to Exercise)

                                        B

                                        Exercise 18.

                                        Net filtration pressure is calculated by ________.

                                        1. adding the capillary hydrostatic pressure to the interstitial fluid hydrostatic pressure

                                        2. subtracting the fluid drained by the lymphatic vessels from the total fluid in the interstitial fluid

                                        3. adding the blood colloid osmotic pressure to the capillary hydrostatic pressure

                                        4. subtracting the blood colloid osmotic pressure from the capillary hydrostatic pressure

                                        (Return to Exercise)

                                        D

                                        Exercise 19.

                                        Which of the following statements is true?

                                        1. In one day, more fluid exits the capillary through filtration than enters through reabsorption.

                                        2. In one day, approximately 35 mm of blood are filtered and 7 mm are reabsorbed.

                                        3. In one day, the capillaries of the lymphatic system absorb about 20.4 liters of fluid.

                                        4. None of the above are true.

                                        (Return to Exercise)

                                        A

                                        20.4. Homeostatic Regulation of the Vascular System
                                        Exercise 23.

                                        Clusters of neurons in the medulla oblongata that regulate blood pressure are known collectively as ________.

                                        1. baroreceptors

                                        2. angioreceptors

                                        3. the cardiomotor mechanism

                                        4. the cardiovascular center

                                        (Return to Exercise)

                                        D

                                        Exercise 24.

                                        In the renin-angiotensin-aldosterone mechanism, ________.

                                        1. decreased blood pressure prompts the release of renin from the liver

                                        2. aldosterone prompts increased urine output

                                        3. aldosterone prompts the kidneys to reabsorb sodium

                                        4. all of the above

                                        (Return to Exercise)

                                        C

                                        Exercise 25.

                                        In the myogenic response, ________.

                                        1. muscle contraction promotes venous return to the heart

                                        2. ventricular contraction strength is decreased

                                        3. vascular smooth muscle responds to stretch

                                        4. endothelins dilate muscular arteries

                                        (Return to Exercise)

                                        C

                                        Exercise 26.

                                        A form of circulatory shock common in young children with severe diarrhea or vomiting is ________.

                                        1. hypovolemic shock

                                        2. anaphylactic shock

                                        3. obstructive shock

                                        4. hemorrhagic shock

                                        (Return to Exercise)

                                        A

                                        20.5. Circulatory Pathways
                                        Exercise 29.

                                        The coronary arteries branch off of the ________.

                                        1. aortic valve

                                        2. ascending aorta

                                        3. aortic arch

                                        4. thoracic aorta

                                        (Return to Exercise)

                                        B

                                        Exercise 30.

                                        Which of the following statements is true?

                                        1. The left and right common carotid arteries both branch off of the brachiocephalic trunk.

                                        2. The brachial artery is the distal branch of the axillary artery.

                                        3. The radial and ulnar arteries join to form the palmar arch.

                                        4. All of the above are true.

                                        (Return to Exercise)

                                        C

                                        Exercise 31.

                                        Arteries serving the stomach, pancreas, and liver all branch from the ________.

                                        1. superior mesenteric artery

                                        2. inferior mesenteric artery

                                        3. celiac trunk

                                        4. splenic artery

                                        (Return to Exercise)

                                        C

                                        Exercise 32.

                                        The right and left brachiocephalic veins ________.

                                        1. drain blood from the right and left internal jugular veins

                                        2. drain blood from the right and left subclavian veins

                                        3. drain into the superior vena cava

                                        4. all of the above are true

                                        (Return to Exercise)

                                        D

                                        Exercise 33.

                                        The hepatic portal system delivers blood from the digestive organs to the ________.

                                        1. liver

                                        2. hypothalamus

                                        3. spleen

                                        4. left atrium

                                        (Return to Exercise)

                                        A

                                        20.6. Development of Blood Vessels and Fetal Circulation
                                        Exercise 37.

                                        Blood islands are ________.

                                        1. clusters of blood-filtering cells in the placenta

                                        2. masses of pluripotent stem cells scattered throughout the fetal bone marrow

                                        3. vascular tubes that give rise to the embryonic tubular heart

                                        4. masses of developing blood vessels and formed elements scattered throughout the embryonic disc

                                        (Return to Exercise)

                                        D

                                        Exercise 38.

                                        Which of the following statements is true?

                                        1. Two umbilical veins carry oxygen-depleted blood from the fetal circulation to the placenta.

                                        2. One umbilical vein carries oxygen-rich blood from the placenta to the fetal heart.

                                        3. Two umbilical arteries carry oxygen-depleted blood to the fetal lungs.

                                        4. None of the above are true.

                                        (Return to Exercise)

                                        B

                                        Exercise 39.

                                        The ductus venosus is a shunt that allows ________.

                                        1. fetal blood to flow from the right atrium to the left atrium

                                        2. fetal blood to flow from the right ventricle to the left ventricle

                                        3. most freshly oxygenated blood to flow into the fetal heart

                                        4. most oxygen-depleted fetal blood to flow directly into the fetal pulmonary trunk

                                        (Return to Exercise)

                                        C

                                        Critical Thinking Questions
                                        20.. Introduction
                                        20.1. Structure and Function of Blood Vessels
                                        Exercise 6.

                                        Arterioles are often referred to as resistance vessels. Why?

                                        (Return to Exercise)

                                        Arterioles receive blood from arteries, which are vessels with a much larger lumen. As their own lumen averages just 30 micrometers or less, arterioles are critical in slowing down—or resisting—blood flow. The arterioles can also constrict or dilate, which varies their resistance, to help distribute blood flow to the tissues.

                                        Exercise 7.

                                        Cocaine use causes vasoconstriction. Is this likely to increase or decrease blood pressure, and why?

                                        (Return to Exercise)

                                        Vasoconstriction causes the lumens of blood vessels to narrow. This increases the pressure of the blood flowing within the vessel.

                                        Exercise 8.

                                        A blood vessel with a few smooth muscle fibers and connective tissue, and only a very thin tunica externa conducts blood toward the heart. What type of vessel is this?

                                        (Return to Exercise)

                                        This is a venule.

                                        20.2. Blood Flow, Blood Pressure, and Resistance
                                        Exercise 14.

                                        You measure a patient’s blood pressure at 130/85. Calculate the patient’s pulse pressure and mean arterial pressure. Determine whether each pressure is low, normal, or high.

                                        (Return to Exercise)

                                        The patient’s pulse pressure is 130 – 85 = 45 mm Hg. Generally, a pulse pressure should be at least 25 percent of the systolic pressure, but not more than 100 mm Hg. Since 25 percent of 130 = 32.5, the patient’s pulse pressure of 45 is normal. The patient’s mean arterial pressure is 85 + 1/3 (45) = 85 + 15 = 100. Normally, the mean arterial blood pressure falls within the range of 70 – 110 mmHg, so 100 is normal.

                                        Exercise 15.

                                        An obese patient comes to the clinic complaining of swollen feet and ankles, fatigue, shortness of breath, and often feeling “spaced out.” She is a cashier in a grocery store, a job that requires her to stand all day. Outside of work, she engages in no physical activity. She confesses that, because of her weight, she finds even walking uncomfortable. Explain how the skeletal muscle pump might play a role in this patient’s signs and symptoms.

                                        (Return to Exercise)

                                        People who stand upright all day and are inactive overall have very little skeletal muscle activity in the legs. Pooling of blood in the legs and feet is common. Venous return to the heart is reduced, a condition that in turn reduces cardiac output and therefore oxygenation of tissues throughout the body. This could at least partially account for the patient’s fatigue and shortness of breath, as well as her “spaced out” feeling, which commonly reflects reduced oxygen to the brain.

                                        20.3. Capillary Exchange
                                        Exercise 20.

                                        A patient arrives at the emergency department with dangerously low blood pressure. The patient’s blood colloid osmotic pressure is normal. How would you expect this situation to affect the patient’s net filtration pressure?

                                        (Return to Exercise)

                                        The patient’s blood would flow more sluggishly from the arteriole into the capillary bed. Thus, the patient’s capillary hydrostatic pressure would be below the normal 35 mm Hg at the arterial end. At the same time, the patient’s blood colloidal osmotic pressure is normal—about 25 mm Hg. Thus, even at the arterial end of the capillary bed, the net filtration pressure would be below 10 mm Hg, and an abnormally reduced level of filtration would occur. In fact, reabsorption might begin to occur by the midpoint of the capillary bed.

                                        Exercise 21.

                                        True or false? The plasma proteins suspended in blood cross the capillary cell membrane and enter the tissue fluid via facilitated diffusion. Explain your thinking.

                                        (Return to Exercise)

                                        False. The plasma proteins suspended in blood cannot cross the semipermeable capillary cell membrane, and so they remain in the plasma within the vessel, where they account for the blood colloid osmotic pressure.

                                        20.4. Homeostatic Regulation of the Vascular System
                                        Exercise 27.

                                        A patient arrives in the emergency department with a blood pressure of 70/45 confused and complaining of thirst. Why?

                                        (Return to Exercise)

                                        This blood pressure is insufficient to circulate blood throughout the patient’s body and maintain adequate perfusion of the patient’s tissues. Ischemia would prompt hypoxia, including to the brain, prompting confusion. The low blood pressure would also trigger the renin-angiotensin-aldosterone mechanism, and release of aldosterone would stimulate the thirst mechanism in the hypothalamus.

                                        Exercise 28.

                                        Nitric oxide is broken down very quickly after its release. Why?

                                        (Return to Exercise)

                                        Nitric oxide is a very powerful local vasodilator that is important in the autoregulation of tissue perfusion. If it were not broken down very quickly after its release, blood flow to the region could exceed metabolic needs.

                                        20.5. Circulatory Pathways
                                        Exercise 34.

                                        Identify the ventricle of the heart that pumps oxygen-depleted blood and the arteries of the body that carry oxygen-depleted blood.

                                        (Return to Exercise)

                                        The right ventricle of the heart pumps oxygen-depleted blood to the pulmonary arteries.

                                        Exercise 35.

                                        What organs do the gonadal veins drain?

                                        (Return to Exercise)

                                        The gonadal veins drain the testes in males and the ovaries in females.

                                        Exercise 36.

                                        What arteries play the leading roles in supplying blood to the brain?

                                        (Return to Exercise)

                                        The internal carotid arteries and the vertebral arteries provide most of the brain’s blood supply.

                                        20.6. Development of Blood Vessels and Fetal Circulation
                                        Exercise 40.

                                        All tissues, including malignant tumors, need a blood supply. Explain why drugs called angiogenesis inhibitors would be used in cancer treatment.

                                        (Return to Exercise)

                                        Angiogenesis inhibitors are drugs that inhibit the growth of new blood vessels. They can impede the growth of tumors by limiting their blood supply and therefore their access to gas and nutrient exchange.

                                        Exercise 41.

                                        Explain the location and importance of the ductus arteriosus in fetal circulation.

                                        (Return to Exercise)

                                        The ductus arteriosus is a blood vessel that provides a passageway between the pulmonary trunk and the aorta during fetal life. Most blood ejected from the fetus’ right ventricle and entering the pulmonary trunk is diverted through this structure into the fetal aorta, thus bypassing the fetal lungs.

                                        Solutions
                                        (Return to Exercise)

                                        Water.

                                        (Return to Exercise)

                                        Take medications as prescribed, eat a healthy diet, exercise, and don’t smoke.

                                        (Return to Exercise)

                                        A

                                        (Return to Exercise)

                                        D

                                        (Return to Exercise)

                                        C

                                        (Return to Exercise)

                                        B

                                        (Return to Exercise)

                                        C

                                        (Return to Exercise)

                                        B

                                        (Return to Exercise)

                                        A

                                        (Return to Exercise)

                                        B

                                        (Return to Exercise)

                                        D

                                        (Return to Exercise)

                                        D

                                        (Return to Exercise)

                                        B

                                        (Return to Exercise)

                                        D

                                        (Return to Exercise)

                                        A

                                        (Return to Exercise)

                                        D

                                        (Return to Exercise)

                                        C

                                        (Return to Exercise)

                                        C

                                        (Return to Exercise)

                                        A

                                        (Return to Exercise)

                                        B

                                        (Return to Exercise)

                                        C

                                        (Return to Exercise)

                                        C

                                        (Return to Exercise)

                                        D

                                        (Return to Exercise)

                                        A

                                        (Return to Exercise)

                                        D

                                        (Return to Exercise)

                                        B

                                        (Return to Exercise)

                                        C

                                        (Return to Exercise)

                                        Arterioles receive blood from arteries, which are vessels with a much larger lumen. As their own lumen averages just 30 micrometers or less, arterioles are critical in slowing down—or resisting—blood flow. The arterioles can also constrict or dilate, which varies their resistance, to help distribute blood flow to the tissues.

                                        (Return to Exercise)

                                        Vasoconstriction causes the lumens of blood vessels to narrow. This increases the pressure of the blood flowing within the vessel.

                                        (Return to Exercise)

                                        This is a venule.

                                        (Return to Exercise)

                                        The patient’s pulse pressure is 130 – 85 = 45 mm Hg. Generally, a pulse pressure should be at least 25 percent of the systolic pressure, but not more than 100 mm Hg. Since 25 percent of 130 = 32.5, the patient’s pulse pressure of 45 is normal. The patient’s mean arterial pressure is 85 + 1/3 (45) = 85 + 15 = 100. Normally, the mean arterial blood pressure falls within the range of 70 – 110 mmHg, so 100 is normal.

                                        (Return to Exercise)

                                        People who stand upright all day and are inactive overall have very little skeletal muscle activity in the legs. Pooling of blood in the legs and feet is common. Venous return to the heart is reduced, a condition that in turn reduces cardiac output and therefore oxygenation of tissues throughout the body. This could at least partially account for the patient’s fatigue and shortness of breath, as well as her “spaced out” feeling, which commonly reflects reduced oxygen to the brain.

                                        (Return to Exercise)

                                        The patient’s blood would flow more sluggishly from the arteriole into the capillary bed. Thus, the patient’s capillary hydrostatic pressure would be below the normal 35 mm Hg at the arterial end. At the same time, the patient’s blood colloidal osmotic pressure is normal—about 25 mm Hg. Thus, even at the arterial end of the capillary bed, the net filtration pressure would be below 10 mm Hg, and an abnormally reduced level of filtration would occur. In fact, reabsorption might begin to occur by the midpoint of the capillary bed.

                                        (Return to Exercise)

                                        False. The plasma proteins suspended in blood cannot cross the semipermeable capillary cell membrane, and so they remain in the plasma within the vessel, where they account for the blood colloid osmotic pressure.

                                        (Return to Exercise)

                                        This blood pressure is insufficient to circulate blood throughout the patient’s body and maintain adequate perfusion of the patient’s tissues. Ischemia would prompt hypoxia, including to the brain, prompting confusion. The low blood pressure would also trigger the renin-angiotensin-aldosterone mechanism, and release of aldosterone would stimulate the thirst mechanism in the hypothalamus.

                                        (Return to Exercise)

                                        Nitric oxide is a very powerful local vasodilator that is important in the autoregulation of tissue perfusion. If it were not broken down very quickly after its release, blood flow to the region could exceed metabolic needs.

                                        (Return to Exercise)

                                        The right ventricle of the heart pumps oxygen-depleted blood to the pulmonary arteries.

                                        (Return to Exercise)

                                        The gonadal veins drain the testes in males and the ovaries in females.

                                        (Return to Exercise)

                                        The internal carotid arteries and the vertebral arteries provide most of the brain’s blood supply.

                                        (Return to Exercise)

                                        Angiogenesis inhibitors are drugs that inhibit the growth of new blood vessels. They can impede the growth of tumors by limiting their blood supply and therefore their access to gas and nutrient exchange.

                                        (Return to Exercise)

                                        The ductus arteriosus is a blood vessel that provides a passageway between the pulmonary trunk and the aorta during fetal life. Most blood ejected from the fetus’ right ventricle and entering the pulmonary trunk is diverted through this structure into the fetal aorta, thus bypassing the fetal lungs.

                                        Chapter 9Joints

                                        This picture shows a girl kayaking in the ocean.
                                        Figure 9.1Girl Kayaking
                                        Without joints, body movements would be impossible. (credit: Graham Richardson/flickr.com)

                                        Introduction*

                                        Chapter Objectives

                                        After this chapter, you will be able to:

                                        • Discuss both functional and structural classifications for body joints

                                        • Describe the characteristic features for fibrous, cartilaginous, and synovial joints and give examples of each

                                        • Define and identify the different body movements

                                        • Discuss the structure of specific body joints and the movements allowed by each

                                        • Explain the development of body joints

                                        The adult human body has 206 bones, and with the exception of the hyoid bone in the neck, each bone is connected to at least one other bone. Joints are the location where bones come together. Many joints allow for movement between the bones. At these joints, the articulating surfaces of the adjacent bones can move smoothly against each other. However, the bones of other joints may be joined to each other by connective tissue or cartilage. These joints are designed for stability and provide for little or no movement. Importantly, joint stability and movement are related to each other. This means that stable joints allow for little or no mobility between the adjacent bones. Conversely, joints that provide the most movement between bones are the least stable. Understanding the relationship between joint structure and function will help to explain why particular types of joints are found in certain areas of the body.

                                        The articulating surfaces of bones at stable types of joints, with little or no mobility, are strongly united to each other. For example, most of the joints of the skull are held together by fibrous connective tissue and do not allow for movement between the adjacent bones. This lack of mobility is important, because the skull bones serve to protect the brain. Similarly, other joints united by fibrous connective tissue allow for very little movement, which provides stability and weight-bearing support for the body. For example, the tibia and fibula of the leg are tightly united to give stability to the body when standing. At other joints, the bones are held together by cartilage, which permits limited movements between the bones. Thus, the joints of the vertebral column only allow for small movements between adjacent vertebrae, but when added together, these movements provide the flexibility that allows your body to twist, or bend to the front, back, or side. In contrast, at joints that allow for wide ranges of motion, the articulating surfaces of the bones are not directly united to each other. Instead, these surfaces are enclosed within a space filled with lubricating fluid, which allows the bones to move smoothly against each other. These joints provide greater mobility, but since the bones are free to move in relation to each other, the joint is less stable. Most of the joints between the bones of the appendicular skeleton are this freely moveable type of joint. These joints allow the muscles of the body to pull on a bone and thereby produce movement of that body region. Your ability to kick a soccer ball, pick up a fork, and dance the tango depend on mobility at these types of joints.

                                        9.1Classification of Joints*

                                        By the end of this section, you will be able to:

                                        • Distinguish between the functional and structural classifications for joints

                                        • Describe the three functional types of joints and give an example of each

                                        • List the three types of diarthrodial joints

                                        • Structural Classification of Joints
                                        • Functional Classification of Joints
                                          • Synarthrosis
                                          • Amphiarthrosis
                                          • Diarthrosis

                                        A joint, also called an articulation, is any place where adjacent bones or bone and cartilage come together (articulate with each other) to form a connection. Joints are classified both structurally and functionally. Structural classifications of joints take into account whether the adjacent bones are strongly anchored to each other by fibrous connective tissue or cartilage, or whether the adjacent bones articulate with each other within a fluid-filled space called a joint cavity. Functional classifications describe the degree of movement available between the bones, ranging from immobile, to slightly mobile, to freely moveable joints. The amount of movement available at a particular joint of the body is related to the functional requirements for that joint. Thus immobile or slightly moveable joints serve to protect internal organs, give stability to the body, and allow for limited body movement. In contrast, freely moveable joints allow for much more extensive movements of the body and limbs.

                                        Structural Classification of Joints

                                        The structural classification of joints is based on whether the articulating surfaces of the adjacent bones are directly connected by fibrous connective tissue or cartilage, or whether the articulating surfaces contact each other within a fluid-filled joint cavity. These differences serve to divide the joints of the body into three structural classifications. A fibrous joint is where the adjacent bones are united by fibrous connective tissue. At a cartilaginous joint, the bones are joined by hyaline cartilage or fibrocartilage. At a synovial joint, the articulating surfaces of the bones are not directly connected, but instead come into contact with each other within a joint cavity that is filled with a lubricating fluid. Synovial joints allow for free movement between the bones and are the most common joints of the body.

                                        Functional Classification of Joints

                                        The functional classification of joints is determined by the amount of mobility found between the adjacent bones. Joints are thus functionally classified as a synarthrosis or immobile joint, an amphiarthrosis or slightly moveable joint, or as a diarthrosis, which is a freely moveable joint (arthroun = “to fasten by a joint”). Depending on their location, fibrous joints may be functionally classified as a synarthrosis (immobile joint) or an amphiarthrosis (slightly mobile joint). Cartilaginous joints are also functionally classified as either a synarthrosis or an amphiarthrosis joint. All synovial joints are functionally classified as a diarthrosis joint.

                                        Synarthrosis

                                        An immobile or nearly immobile joint is called a synarthrosis. The immobile nature of these joints provide for a strong union between the articulating bones. This is important at locations where the bones provide protection for internal organs. Examples include sutures, the fibrous joints between the bones of the skull that surround and protect the brain (Figure 9.2), and the manubriosternal joint, the cartilaginous joint that unites the manubrium and body of the sternum for protection of the heart.

                                        This image shows the lateral view of the human skeleton. The lambdoid, coronal, and squamous sutures are labeled.
                                        Figure 9.2Suture Joints of Skull
                                        The suture joints of the skull are an example of a synarthrosis, an immobile or essentially immobile joint.

                                        Amphiarthrosis

                                        An amphiarthrosis is a joint that has limited mobility. An example of this type of joint is the cartilaginous joint that unites the bodies of adjacent vertebrae. Filling the gap between the vertebrae is a thick pad of fibrocartilage called an intervertebral disc (Figure 9.3). Each intervertebral disc strongly unites the vertebrae but still allows for a limited amount of movement between them. However, the small movements available between adjacent vertebrae can sum together along the length of the vertebral column to provide for large ranges of body movements.

                                        Another example of an amphiarthrosis is the pubic symphysis of the pelvis. This is a cartilaginous joint in which the pubic regions of the right and left hip bones are strongly anchored to each other by fibrocartilage. This joint normally has very little mobility. The strength of the pubic symphysis is important in conferring weight-bearing stability to the pelvis.

                                        This image shows the lateral view of the intervertebral disc located between two vertebral discs.
                                        Figure 9.3Intervertebral Disc
                                        An intervertebral disc unites the bodies of adjacent vertebrae within the vertebral column. Each disc allows for limited movement between the vertebrae and thus functionally forms an amphiarthrosis type of joint. Intervertebral discs are made of fibrocartilage and thereby structurally form a symphysis type of cartilaginous joint.

                                        Diarthrosis

                                        A freely mobile joint is classified as a diarthrosis. These types of joints include all synovial joints of the body, which provide the majority of body movements. Most diarthrotic joints are found in the appendicular skeleton and thus give the limbs a wide range of motion. These joints are divided into three categories, based on the number of axes of motion provided by each. An axis in anatomy is described as the movements in reference to the three anatomical planes: transverse, frontal, and sagittal. Thus, diarthroses are classified as uniaxial (for movement in one plane), biaxial (for movement in two planes), or multiaxial joints (for movement in all three anatomical planes).

                                        A uniaxial joint only allows for a motion in a single plane (around a single axis). The elbow joint, which only allows for bending or straightening, is an example of a uniaxial joint. A biaxial joint allows for motions within two planes. An example of a biaxial joint is a metacarpophalangeal joint (knuckle joint) of the hand. The joint allows for movement along one axis to produce bending or straightening of the finger, and movement along a second axis, which allows for spreading of the fingers away from each other and bringing them together. A joint that allows for the several directions of movement is called a multiaxial joint (polyaxial or triaxial joint). This type of diarthrotic joint allows for movement along three axes (Figure 9.4). The shoulder and hip joints are multiaxial joints. They allow the upper or lower limb to move in an anterior-posterior direction and a medial-lateral direction. In addition, the limb can also be rotated around its long axis. This third movement results in rotation of the limb so that its anterior surface is moved either toward or away from the midline of the body.

                                        This image shows a multiaxial joint. The left panel shows the acetabulum of the hip bone and the head of the femur. The right panel shows a simplified ball-and-socket joint structure to illustrate the movement of the hip joint.
                                        Figure 9.4Multiaxial Joint
                                        A multiaxial joint, such as the hip joint, allows for three types of movement: anterior-posterior, medial-lateral, and rotational.

                                        9.2Fibrous Joints*

                                        By the end of this section, you will be able to:

                                        • Describe the structural features of fibrous joints

                                        • Distinguish between a suture, syndesmosis, and gomphosis

                                        • Give an example of each type of fibrous joint

                                        • Suture
                                        • Syndesmosis
                                        • Gomphosis

                                        At a fibrous joint, the adjacent bones are directly connected to each other by fibrous connective tissue, and thus the bones do not have a joint cavity between them (Figure 9.5). The gap between the bones may be narrow or wide. There are three types of fibrous joints. A suture is the narrow fibrous joint found between most bones of the skull. At a syndesmosis joint, the bones are more widely separated but are held together by a narrow band of fibrous connective tissue called a ligament or a wide sheet of connective tissue called an interosseous membrane. This type of fibrous joint is found between the shaft regions of the long bones in the forearm and in the leg. Lastly, a gomphosis is the narrow fibrous joint between the roots of a tooth and the bony socket in the jaw into which the tooth fits.

                                        This figure shows the different types of fibrous joints. The right panel shows sutures, the middle panel shows an interosseous membrane, and the left panel shows a gomphosis.
                                        Figure 9.5Fibrous Joints
                                        Fibrous joints form strong connections between bones. (a) Sutures join most bones of the skull. (b) An interosseous membrane forms a syndesmosis between the radius and ulna bones of the forearm. (c) A gomphosis is a specialized fibrous joint that anchors a tooth to its socket in the jaw.

                                        Suture

                                        All the bones of the skull, except for the mandible, are joined to each other by a fibrous joint called a suture. The fibrous connective tissue found at a suture (“to bind or sew”) strongly unites the adjacent skull bones and thus helps to protect the brain and form the face. In adults, the skull bones are closely opposed and fibrous connective tissue fills the narrow gap between the bones. The suture is frequently convoluted, forming a tight union that prevents most movement between the bones. (See Figure 9.5a.) Thus, skull sutures are functionally classified as a synarthrosis, although some sutures may allow for slight movements between the cranial bones.

                                        In newborns and infants, the areas of connective tissue between the bones are much wider, especially in those areas on the top and sides of the skull that will become the sagittal, coronal, squamous, and lambdoid sutures. These broad areas of connective tissue are called fontanelles (Figure 9.6). During birth, the fontanelles provide flexibility to the skull, allowing the bones to push closer together or to overlap slightly, thus aiding movement of the infant’s head through the birth canal. After birth, these expanded regions of connective tissue allow for rapid growth of the skull and enlargement of the brain. The fontanelles greatly decrease in width during the first year after birth as the skull bones enlarge. When the connective tissue between the adjacent bones is reduced to a narrow layer, these fibrous joints are now called sutures. At some sutures, the connective tissue will ossify and be converted into bone, causing the adjacent bones to fuse to each other. This fusion between bones is called a synostosis (“joined by bone”). Examples of synostosis fusions between cranial bones are found both early and late in life. At the time of birth, the frontal and maxillary bones consist of right and left halves joined together by sutures, which disappear by the eighth year as the halves fuse together to form a single bone. Late in life, the sagittal, coronal, and lambdoid sutures of the skull will begin to ossify and fuse, causing the suture line to gradually disappear.

                                        This figure shows the lateral view of the newborn skull with the major parts labeled.
                                        Figure 9.6The Newborn Skull
                                        The fontanelles of a newborn’s skull are broad areas of fibrous connective tissue that form fibrous joints between the bones of the skull.

                                        Syndesmosis

                                        A syndesmosis (“fastened with a band”) is a type of fibrous joint in which two parallel bones are united to each other by fibrous connective tissue. The gap between the bones may be narrow, with the bones joined by ligaments, or the gap may be wide and filled in by a broad sheet of connective tissue called an interosseous membrane.

                                        In the forearm, the wide gap between the shaft portions of the radius and ulna bones are strongly united by an interosseous membrane (see Figure 9.5b). Similarly, in the leg, the shafts of the tibia and fibula are also united by an interosseous membrane. In addition, at the distal tibiofibular joint, the articulating surfaces of the bones lack cartilage and the narrow gap between the bones is anchored by fibrous connective tissue and ligaments on both the anterior and posterior aspects of the joint. Together, the interosseous membrane and these ligaments form the tibiofibular syndesmosis.

                                        The syndesmoses found in the forearm and leg serve to unite parallel bones and prevent their separation. However, a syndesmosis does not prevent all movement between the bones, and thus this type of fibrous joint is functionally classified as an amphiarthrosis. In the leg, the syndesmosis between the tibia and fibula strongly unites the bones, allows for little movement, and firmly locks the talus bone in place between the tibia and fibula at the ankle joint. This provides strength and stability to the leg and ankle, which are important during weight bearing. In the forearm, the interosseous membrane is flexible enough to allow for rotation of the radius bone during forearm movements. Thus in contrast to the stability provided by the tibiofibular syndesmosis, the flexibility of the antebrachial interosseous membrane allows for the much greater mobility of the forearm.

                                        The interosseous membranes of the leg and forearm also provide areas for muscle attachment. Damage to a syndesmotic joint, which usually results from a fracture of the bone with an accompanying tear of the interosseous membrane, will produce pain, loss of stability of the bones, and may damage the muscles attached to the interosseous membrane. If the fracture site is not properly immobilized with a cast or splint, contractile activity by these muscles can cause improper alignment of the broken bones during healing.

                                        Gomphosis

                                        A gomphosis (“fastened with bolts”) is the specialized fibrous joint that anchors the root of a tooth into its bony socket within the maxillary bone (upper jaw) or mandible bone (lower jaw) of the skull. A gomphosis is also known as a peg-and-socket joint. Spanning between the bony walls of the socket and the root of the tooth are numerous short bands of dense connective tissue, each of which is called a periodontal ligament (see Figure 9.5c). Due to the immobility of a gomphosis, this type of joint is functionally classified as a synarthrosis.

                                        9.3Cartilaginous Joints*

                                        By the end of this section, you will be able to:

                                        • Describe the structural features of cartilaginous joints

                                        • Distinguish between a synchondrosis and symphysis

                                        • Give an example of each type of cartilaginous joint

                                        • Synchondrosis
                                        • Symphysis

                                        As the name indicates, at a cartilaginous joint, the adjacent bones are united by cartilage, a tough but flexible type of connective tissue. These types of joints lack a joint cavity and involve bones that are joined together by either hyaline cartilage or fibrocartilage (Figure 9.7). There are two types of cartilaginous joints. A synchondrosis is a cartilaginous joint where the bones are joined by hyaline cartilage. Also classified as a synchondrosis are places where bone is united to a cartilage structure, such as between the anterior end of a rib and the costal cartilage of the thoracic cage. The second type of cartilaginous joint is a symphysis, where the bones are joined by fibrocartilage.

                                        This figure shows the cartilaginous joints. The left panel shows a hyaline cartilage joint, and the right panel shows the fibrocartilaginous joint of the pubic symphisis.
                                        Figure 9.7Cartiliginous Joints
                                        At cartilaginous joints, bones are united by hyaline cartilage to form a synchondrosis or by fibrocartilage to form a symphysis. (a) The hyaline cartilage of the epiphyseal plate (growth plate) forms a synchondrosis that unites the shaft (diaphysis) and end (epiphysis) of a long bone and allows the bone to grow in length. (b) The pubic portions of the right and left hip bones of the pelvis are joined together by fibrocartilage, forming the pubic symphysis.

                                        Synchondrosis

                                        A synchondrosis (“joined by cartilage”) is a cartilaginous joint where bones are joined together by hyaline cartilage, or where bone is united to hyaline cartilage. A synchondrosis may be temporary or permanent. A temporary synchondrosis is the epiphyseal plate (growth plate) of a growing long bone. The epiphyseal plate is the region of growing hyaline cartilage that unites the diaphysis (shaft) of the bone to the epiphysis (end of the bone). Bone lengthening involves growth of the epiphyseal plate cartilage and its replacement by bone, which adds to the diaphysis. For many years during childhood growth, the rates of cartilage growth and bone formation are equal and thus the epiphyseal plate does not change in overall thickness as the bone lengthens. During the late teens and early 20s, growth of the cartilage slows and eventually stops. The epiphyseal plate is then completely replaced by bone, and the diaphysis and epiphysis portions of the bone fuse together to form a single adult bone. This fusion of the diaphysis and epiphysis is a synostosis. Once this occurs, bone lengthening ceases. For this reason, the epiphyseal plate is considered to be a temporary synchondrosis. Because cartilage is softer than bone tissue, injury to a growing long bone can damage the epiphyseal plate cartilage, thus stopping bone growth and preventing additional bone lengthening.

                                        Growing layers of cartilage also form synchondroses that join together the ilium, ischium, and pubic portions of the hip bone during childhood and adolescence. When body growth stops, the cartilage disappears and is replaced by bone, forming synostoses and fusing the bony components together into the single hip bone of the adult. Similarly, synostoses unite the sacral vertebrae that fuse together to form the adult sacrum.

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                                        Visit this website to view a radiograph (X-ray image) of a child’s hand and wrist. The growing bones of child have an epiphyseal plate that forms a synchondrosis between the shaft and end of a long bone. Being less dense than bone, the area of epiphyseal cartilage is seen on this radiograph as the dark epiphyseal gaps located near the ends of the long bones, including the radius, ulna, metacarpal, and phalanx bones. Which of the bones in this image do not show an epiphyseal plate (epiphyseal gap)?

                                        Examples of permanent synchondroses are found in the thoracic cage. One example is the first sternocostal joint, where the first rib is anchored to the manubrium by its costal cartilage. (The articulations of the remaining costal cartilages to the sternum are all synovial joints.) Additional synchondroses are formed where the anterior end of the other 11 ribs is joined to its costal cartilage. Unlike the temporary synchondroses of the epiphyseal plate, these permanent synchondroses retain their hyaline cartilage and thus do not ossify with age. Due to the lack of movement between the bone and cartilage, both temporary and permanent synchondroses are functionally classified as a synarthrosis.

                                        Symphysis

                                        A cartilaginous joint where the bones are joined by fibrocartilage is called a symphysis (“growing together”). Fibrocartilage is very strong because it contains numerous bundles of thick collagen fibers, thus giving it a much greater ability to resist pulling and bending forces when compared with hyaline cartilage. This gives symphyses the ability to strongly unite the adjacent bones, but can still allow for limited movement to occur. Thus, a symphysis is functionally classified as an amphiarthrosis.

                                        The gap separating the bones at a symphysis may be narrow or wide. Examples in which the gap between the bones is narrow include the pubic symphysis and the manubriosternal joint. At the pubic symphysis, the pubic portions of the right and left hip bones of the pelvis are joined together by fibrocartilage across a narrow gap. Similarly, at the manubriosternal joint, fibrocartilage unites the manubrium and body portions of the sternum.

                                        The intervertebral symphysis is a wide symphysis located between the bodies of adjacent vertebrae of the vertebral column. Here a thick pad of fibrocartilage called an intervertebral disc strongly unites the adjacent vertebrae by filling the gap between them. The width of the intervertebral symphysis is important because it allows for small movements between the adjacent vertebrae. In addition, the thick intervertebral disc provides cushioning between the vertebrae, which is important when carrying heavy objects or during high-impact activities such as running or jumping.

                                        9.4Synovial Joints*

                                        By the end of this section, you will be able to:

                                        • Describe the structural features of a synovial joint

                                        • Discuss the function of additional structures associated with synovial joints

                                        • List the six types of synovial joints and give an example of each

                                        • Structural Features of Synovial Joints
                                        • Additional Structures Associated with Synovial Joints
                                        • Types of Synovial Joints
                                          • Pivot Joint
                                          • Hinge Joint
                                          • Condyloid Joint
                                          • Saddle Joint
                                          • Plane Joint
                                          • Ball-and-Socket Joint

                                        Synovial joints are the most common type of joint in the body (Figure 9.8). A key structural characteristic for a synovial joint that is not seen at fibrous or cartilaginous joints is the presence of a joint cavity. This fluid-filled space is the site at which the articulating surfaces of the bones contact each other. Also unlike fibrous or cartilaginous joints, the articulating bone surfaces at a synovial joint are not directly connected to each other with fibrous connective tissue or cartilage. This gives the bones of a synovial joint the ability to move smoothly against each other, allowing for increased joint mobility.

                                        This figure shows a synovial joint. The cavity between two bones contains the synovial fluid which lubricates the two joints.
                                        Figure 9.8Synovial Joints
                                        Synovial joints allow for smooth movements between the adjacent bones. The joint is surrounded by an articular capsule that defines a joint cavity filled with synovial fluid. The articulating surfaces of the bones are covered by a thin layer of articular cartilage. Ligaments support the joint by holding the bones together and resisting excess or abnormal joint motions.

                                        Structural Features of Synovial Joints

                                        Synovial joints are characterized by the presence of a joint cavity. The walls of this space are formed by the articular capsule, a fibrous connective tissue structure that is attached to each bone just outside the area of the bone’s articulating surface. The bones of the joint articulate with each other within the joint cavity.

                                        Friction between the bones at a synovial joint is prevented by the presence of the articular cartilage, a thin layer of hyaline cartilage that covers the entire articulating surface of each bone. However, unlike at a cartilaginous joint, the articular cartilages of each bone are not continuous with each other. Instead, the articular cartilage acts like a Teflon® coating over the bone surface, allowing the articulating bones to move smoothly against each other without damaging the underlying bone tissue. Lining the inner surface of the articular capsule is a thin synovial membrane. The cells of this membrane secrete synovial fluid (synovia = “a thick fluid”), a thick, slimy fluid that provides lubrication to further reduce friction between the bones of the joint. This fluid also provides nourishment to the articular cartilage, which does not contain blood vessels. The ability of the bones to move smoothly against each other within the joint cavity, and the freedom of joint movement this provides, means that each synovial joint is functionally classified as a diarthrosis.

                                        Outside of their articulating surfaces, the bones are connected together by ligaments, which are strong bands of fibrous connective tissue. These strengthen and support the joint by anchoring the bones together and preventing their separation. Ligaments allow for normal movements at a joint, but limit the range of these motions, thus preventing excessive or abnormal joint movements. Ligaments are classified based on their relationship to the fibrous articular capsule. An extrinsic ligament is located outside of the articular capsule, an intrinsic ligament is fused to or incorporated into the wall of the articular capsule, and an intracapsular ligament is located inside of the articular capsule.

                                        At many synovial joints, additional support is provided by the muscles and their tendons that act across the joint. A tendon is the dense connective tissue structure that attaches a muscle to bone. As forces acting on a joint increase, the body will automatically increase the overall strength of contraction of the muscles crossing that joint, thus allowing the muscle and its tendon to serve as a “dynamic ligament” to resist forces and support the joint. This type of indirect support by muscles is very important at the shoulder joint, for example, where the ligaments are relatively weak.

                                        Additional Structures Associated with Synovial Joints

                                        A few synovial joints of the body have a fibrocartilage structure located between the articulating bones. This is called an articular disc, which is generally small and oval-shaped, or a meniscus, which is larger and C-shaped. These structures can serve several functions, depending on the specific joint. In some places, an articular disc may act to strongly unite the bones of the joint to each other. Examples of this include the articular discs found at the sternoclavicular joint or between the distal ends of the radius and ulna bones. At other synovial joints, the disc can provide shock absorption and cushioning between the bones, which is the function of each meniscus within the knee joint. Finally, an articular disc can serve to smooth the movements between the articulating bones, as seen at the temporomandibular joint. Some synovial joints also have a fat pad, which can serve as a cushion between the bones.

                                        Additional structures located outside of a synovial joint serve to prevent friction between the bones of the joint and the overlying muscle tendons or skin. A bursa (plural = bursae) is a thin connective tissue sac filled with lubricating liquid. They are located in regions where skin, ligaments, muscles, or muscle tendons can rub against each other, usually near a body joint (Figure 9.9). Bursae reduce friction by separating the adjacent structures, preventing them from rubbing directly against each other. Bursae are classified by their location. A subcutaneous bursa is located between the skin and an underlying bone. It allows skin to move smoothly over the bone. Examples include the prepatellar bursa located over the kneecap and the olecranon bursa at the tip of the elbow. A submuscular bursa is found between a muscle and an underlying bone, or between adjacent muscles. These prevent rubbing of the muscle during movements. A large submuscular bursa, the trochanteric bursa, is found at the lateral hip, between the greater trochanter of the femur and the overlying gluteus maximus muscle. A subtendinous bursa is found between a tendon and a bone. Examples include the subacromial bursa that protects the tendon of shoulder muscle as it passes under the acromion of the scapula, and the suprapatellar bursa that separates the tendon of the large anterior thigh muscle from the distal femur just above the knee.

                                        This diagram shows the location of the bursae which are fluid filled sacs in a bone joint. The major parts of the joint are labeled.
                                        Figure 9.9Bursae
                                        Bursae are fluid-filled sacs that serve to prevent friction between skin, muscle, or tendon and an underlying bone. Three major bursae and a fat pad are part of the complex joint that unites the femur and tibia of the leg.

                                        A tendon sheath is similar in structure to a bursa, but smaller. It is a connective tissue sac that surrounds a muscle tendon at places where the tendon crosses a joint. It contains a lubricating fluid that allows for smooth motions of the tendon during muscle contraction and joint movements.

                                        Homeostatic Imbalances

                                        Bursitis

                                        Bursitis is the inflammation of a bursa near a joint. This will cause pain, swelling, or tenderness of the bursa and surrounding area, and may also result in joint stiffness. Bursitis is most commonly associated with the bursae found at or near the shoulder, hip, knee, or elbow joints. At the shoulder, subacromial bursitis may occur in the bursa that separates the acromion of the scapula from the tendon of a shoulder muscle as it passes deep to the acromion. In the hip region, trochanteric bursitis can occur in the bursa that overlies the greater trochanter of the femur, just below the lateral side of the hip. Ischial bursitis occurs in the bursa that separates the skin from the ischial tuberosity of the pelvis, the bony structure that is weight bearing when sitting. At the knee, inflammation and swelling of the bursa located between the skin and patella bone is prepatellar bursitis (“housemaid’s knee”), a condition more commonly seen today in roofers or floor and carpet installers who do not use knee pads. At the elbow, olecranon bursitis is inflammation of the bursa between the skin and olecranon process of the ulna. The olecranon forms the bony tip of the elbow, and bursitis here is also known as “student’s elbow.”

                                        Bursitis can be either acute (lasting only a few days) or chronic. It can arise from muscle overuse, trauma, excessive or prolonged pressure on the skin, rheumatoid arthritis, gout, or infection of the joint. Repeated acute episodes of bursitis can result in a chronic condition. Treatments for the disorder include antibiotics if the bursitis is caused by an infection, or anti-inflammatory agents, such as nonsteroidal anti-inflammatory drugs (NSAIDs) or corticosteroids if the bursitis is due to trauma or overuse. Chronic bursitis may require that fluid be drained, but additional surgery is usually not required.

                                        Types of Synovial Joints

                                        Synovial joints are subdivided based on the shapes of the articulating surfaces of the bones that form each joint. The six types of synovial joints are pivot, hinge, condyloid, saddle, plane, and ball-and socket-joints (Figure 9.10).

                                        This composite image shows the different types of synovial joints in the body. In the center of the figure is a skeleton, and call outs from each joint show their names and locations.
                                        Figure 9.10Types of Synovial Joints
                                        The six types of synovial joints allow the body to move in a variety of ways. (a) Pivot joints allow for rotation around an axis, such as between the first and second cervical vertebrae, which allows for side-to-side rotation of the head. (b) The hinge joint of the elbow works like a door hinge. (c) The articulation between the trapezium carpal bone and the first metacarpal bone at the base of the thumb is a saddle joint. (d) Plane joints, such as those between the tarsal bones of the foot, allow for limited gliding movements between bones. (e) The radiocarpal joint of the wrist is a condyloid joint. (f) The hip and shoulder joints are the only ball-and-socket joints of the body.

                                        Pivot Joint

                                        At a pivot joint, a rounded portion of a bone is enclosed within a ring formed partially by the articulation with another bone and partially by a ligament (see Figure 9.10a). The bone rotates within this ring. Since the rotation is around a single axis, pivot joints are functionally classified as a uniaxial diarthrosis type of joint. An example of a pivot joint is the atlantoaxial joint, found between the C1 (atlas) and C2 (axis) vertebrae. Here, the upward projecting dens of the axis articulates with the inner aspect of the atlas, where it is held in place by a ligament. Rotation at this joint allows you to turn your head from side to side. A second pivot joint is found at the proximal radioulnar joint. Here, the head of the radius is largely encircled by a ligament that holds it in place as it articulates with the radial notch of the ulna. Rotation of the radius allows for forearm movements.

                                        Hinge Joint

                                        In a hinge joint, the convex end of one bone articulates with the concave end of the adjoining bone (see Figure 9.10b). This type of joint allows only for bending and straightening motions along a single axis, and thus hinge joints are functionally classified as uniaxial joints. A good example is the elbow joint, with the articulation between the trochlea of the humerus and the trochlear notch of the ulna. Other hinge joints of the body include the knee, ankle, and interphalangeal joints between the phalanx bones of the fingers and toes.

                                        Condyloid Joint

                                        At a condyloid joint (ellipsoid joint), the shallow depression at the end of one bone articulates with a rounded structure from an adjacent bone or bones (see Figure 9.10e). The knuckle (metacarpophalangeal) joints of the hand between the distal end of a metacarpal bone and the proximal phalanx bone are condyloid joints. Another example is the radiocarpal joint of the wrist, between the shallow depression at the distal end of the radius bone and the rounded scaphoid, lunate, and triquetrum carpal bones. In this case, the articulation area has a more oval (elliptical) shape. Functionally, condyloid joints are biaxial joints that allow for two planes of movement. One movement involves the bending and straightening of the fingers or the anterior-posterior movements of the hand. The second movement is a side-to-side movement, which allows you to spread your fingers apart and bring them together, or to move your hand in a medial-going or lateral-going direction.

                                        Saddle Joint

                                        At a saddle joint, both of the articulating surfaces for the bones have a saddle shape, which is concave in one direction and convex in the other (see Figure 9.10c). This allows the two bones to fit together like a rider sitting on a saddle. Saddle joints are functionally classified as biaxial joints. The primary example is the first carpometacarpal joint, between the trapezium (a carpal bone) and the first metacarpal bone at the base of the thumb. This joint provides the thumb the ability to move away from the palm of the hand along two planes. Thus, the thumb can move within the same plane as the palm of the hand, or it can jut out anteriorly, perpendicular to the palm. This movement of the first carpometacarpal joint is what gives humans their distinctive “opposable” thumbs. The sternoclavicular joint is also classified as a saddle joint.

                                        Plane Joint

                                        At a plane joint (gliding joint), the articulating surfaces of the bones are flat or slightly curved and of approximately the same size, which allows the bones to slide against each other (see Figure 9.10d). The motion at this type of joint is usually small and tightly constrained by surrounding ligaments. Based only on their shape, plane joints can allow multiple movements, including rotation. Thus plane joints can be functionally classified as a multiaxial joint. However, not all of these movements are available to every plane joint due to limitations placed on it by ligaments or neighboring bones. Thus, depending upon the specific joint of the body, a plane joint may exhibit only a single type of movement or several movements. Plane joints are found between the carpal bones (intercarpal joints) of the wrist or tarsal bones (intertarsal joints) of the foot, between the clavicle and acromion of the scapula (acromioclavicular joint), and between the superior and inferior articular processes of adjacent vertebrae (zygapophysial joints).

                                        Ball-and-Socket Joint

                                        The joint with the greatest range of motion is the ball-and-socket joint. At these joints, the rounded head of one bone (the ball) fits into the concave articulation (the socket) of the adjacent bone (see Figure 9.10f). The hip joint and the glenohumeral (shoulder) joint are the only ball-and-socket joints of the body. At the hip joint, the head of the femur articulates with the acetabulum of the hip bone, and at the shoulder joint, the head of the humerus articulates with the glenoid cavity of the scapula.

                                        Ball-and-socket joints are classified functionally as multiaxial joints. The femur and the humerus are able to move in both anterior-posterior and medial-lateral directions and they can also rotate around their long axis. The shallow socket formed by the glenoid cavity allows the shoulder joint an extensive range of motion. In contrast, the deep socket of the acetabulum and the strong supporting ligaments of the hip joint serve to constrain movements of the femur, reflecting the need for stability and weight-bearing ability at the hip.

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                                        Watch this video to see an animation of synovial joints in action. Synovial joints are places where bones articulate with each other inside of a joint cavity. The different types of synovial joints are the ball-and-socket joint (shoulder joint), hinge joint (knee), pivot joint (atlantoaxial joint, between C1 and C2 vertebrae of the neck), condyloid joint (radiocarpal joint of the wrist), saddle joint (first carpometacarpal joint, between the trapezium carpal bone and the first metacarpal bone, at the base of the thumb), and plane joint (facet joints of vertebral column, between superior and inferior articular processes). Which type of synovial joint allows for the widest range of motion?

                                        Aging and the…

                                        Joints

                                        Arthritis is a common disorder of synovial joints that involves inflammation of the joint. This often results in significant joint pain, along with swelling, stiffness, and reduced joint mobility. There are more than 100 different forms of arthritis. Arthritis may arise from aging, damage to the articular cartilage, autoimmune diseases, bacterial or viral infections, or unknown (probably genetic) causes.

                                        The most common type of arthritis is osteoarthritis, which is associated with aging and “wear and tear” of the articular cartilage (Figure 9.11). Risk factors that may lead to osteoarthritis later in life include injury to a joint; jobs that involve physical labor; sports with running, twisting, or throwing actions; and being overweight. These factors put stress on the articular cartilage that covers the surfaces of bones at synovial joints, causing the cartilage to gradually become thinner. As the articular cartilage layer wears down, more pressure is placed on the bones. The joint responds by increasing production of the lubricating synovial fluid, but this can lead to swelling of the joint cavity, causing pain and joint stiffness as the articular capsule is stretched. The bone tissue underlying the damaged articular cartilage also responds by thickening, producing irregularities and causing the articulating surface of the bone to become rough or bumpy. Joint movement then results in pain and inflammation. In its early stages, symptoms of osteoarthritis may be reduced by mild activity that “warms up” the joint, but the symptoms may worsen following exercise. In individuals with more advanced osteoarthritis, the affected joints can become more painful and therefore are difficult to use effectively, resulting in increased immobility. There is no cure for osteoarthritis, but several treatments can help alleviate the pain. Treatments may include lifestyle changes, such as weight loss and low-impact exercise, and over-the-counter or prescription medications that help to alleviate the pain and inflammation. For severe cases, joint replacement surgery (arthroplasty) may be required.

                                        Joint replacement is a very invasive procedure, so other treatments are always tried before surgery. However arthroplasty can provide relief from chronic pain and can enhance mobility within a few months following the surgery. This type of surgery involves replacing the articular surfaces of the bones with prosthesis (artificial components). For example, in hip arthroplasty, the worn or damaged parts of the hip joint, including the head and neck of the femur and the acetabulum of the pelvis, are removed and replaced with artificial joint components. The replacement head for the femur consists of a rounded ball attached to the end of a shaft that is inserted inside the diaphysis of the femur. The acetabulum of the pelvis is reshaped and a replacement socket is fitted into its place. The parts, which are always built in advance of the surgery, are sometimes custom made to produce the best possible fit for a patient.

                                        Gout is a form of arthritis that results from the deposition of uric acid crystals within a body joint. Usually only one or a few joints are affected, such as the big toe, knee, or ankle. The attack may only last a few days, but may return to the same or another joint. Gout occurs when the body makes too much uric acid or the kidneys do not properly excrete it. A diet with excessive fructose has been implicated in raising the chances of a susceptible individual developing gout.

                                        Other forms of arthritis are associated with various autoimmune diseases, bacterial infections of the joint, or unknown genetic causes. Autoimmune diseases, including rheumatoid arthritis, scleroderma, or systemic lupus erythematosus, produce arthritis because the immune system of the body attacks the body joints. In rheumatoid arthritis, the joint capsule and synovial membrane become inflamed. As the disease progresses, the articular cartilage is severely damaged or destroyed, resulting in joint deformation, loss of movement, and severe disability. The most commonly involved joints are the hands, feet, and cervical spine, with corresponding joints on both sides of the body usually affected, though not always to the same extent. Rheumatoid arthritis is also associated with lung fibrosis, vasculitis (inflammation of blood vessels), coronary heart disease, and premature mortality. With no known cure, treatments are aimed at alleviating symptoms. Exercise, anti-inflammatory and pain medications, various specific disease-modifying anti-rheumatic drugs, or surgery are used to treat rheumatoid arthritis.

                                        The top panel in this figure shows a normal hip joint, and the bottom panel shows a hip joint with osteoarthritis.
                                        Figure 9.11Osteoarthritis
                                        Osteoarthritis of a synovial joint results from aging or prolonged joint wear and tear. These cause erosion and loss of the articular cartilage covering the surfaces of the bones, resulting in inflammation that causes joint stiffness and pain.
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                                        Visit this website to learn about a patient who arrives at the hospital with joint pain and weakness in his legs. What caused this patient’s weakness?

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                                        Watch this animation to observe hip replacement surgery (total hip arthroplasty), which can be used to alleviate the pain and loss of joint mobility associated with osteoarthritis of the hip joint. What is the most common cause of hip disability?

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                                        Watch this video to learn about the symptoms and treatments for rheumatoid arthritis. Which system of the body malfunctions in rheumatoid arthritis and what does this cause?

                                        9.5Types of Body Movements*

                                        By the end of this section, you will be able to:

                                        • Define the different types of body movements

                                        • Identify the joints that allow for these motions

                                        • Flexion and Extension
                                        • Abduction and Adduction
                                        • Circumduction
                                        • Rotation
                                        • Supination and Pronation
                                        • Dorsiflexion and Plantar Flexion
                                        • Inversion and Eversion
                                        • Protraction and Retraction
                                        • Depression and Elevation
                                        • Excursion
                                        • Superior Rotation and Inferior Rotation
                                        • Opposition and Reposition

                                        Synovial joints allow the body a tremendous range of movements. Each movement at a synovial joint results from the contraction or relaxation of the muscles that are attached to the bones on either side of the articulation. The type of movement that can be produced at a synovial joint is determined by its structural type. While the ball-and-socket joint gives the greatest range of movement at an individual joint, in other regions of the body, several joints may work together to produce a particular movement. Overall, each type of synovial joint is necessary to provide the body with its great flexibility and mobility. There are many types of movement that can occur at synovial joints (Table 9.1). Movement types are generally paired, with one being the opposite of the other. Body movements are always described in relation to the anatomical position of the body: upright stance, with upper limbs to the side of body and palms facing forward. Refer to Figure 9.12 as you go through this section.

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                                        Watch this video to learn about anatomical motions. What motions involve increasing or decreasing the angle of the foot at the ankle?

                                        This multi-part image shows different types of movements that are possible by different joints in the body.
                                        Figure 9.12Movements of the Body, Part 1
                                        Synovial joints give the body many ways in which to move. (a)–(b) Flexion and extension motions are in the sagittal (anterior–posterior) plane of motion. These movements take place at the shoulder, hip, elbow, knee, wrist, metacarpophalangeal, metatarsophalangeal, and interphalangeal joints. (c)–(d) Anterior bending of the head or vertebral column is flexion, while any posterior-going movement is extension. (e) Abduction and adduction are motions of the limbs, hand, fingers, or toes in the coronal (medial–lateral) plane of movement. Moving the limb or hand laterally away from the body, or spreading the fingers or toes, is abduction. Adduction brings the limb or hand toward or across the midline of the body, or brings the fingers or toes together. Circumduction is the movement of the limb, hand, or fingers in a circular pattern, using the sequential combination of flexion, adduction, extension, and abduction motions. Adduction/abduction and circumduction take place at the shoulder, hip, wrist, metacarpophalangeal, and metatarsophalangeal joints. (f) Turning of the head side to side or twisting of the body is rotation. Medial and lateral rotation of the upper limb at the shoulder or lower limb at the hip involves turning the anterior surface of the limb toward the midline of the body (medial or internal rotation) or away from the midline (lateral or external rotation).
                                        This multi-part image shows different types of movements that are possible by different joints in the body.
                                        Figure 9.13Movements of the Body, Part 2
                                        (g) Supination of the forearm turns the hand to the palm forward position in which the radius and ulna are parallel, while forearm pronation turns the hand to the palm backward position in which the radius crosses over the ulna to form an "X." (h) Dorsiflexion of the foot at the ankle joint moves the top of the foot toward the leg, while plantar flexion lifts the heel and points the toes. (i) Eversion of the foot moves the bottom (sole) of the foot away from the midline of the body, while foot inversion faces the sole toward the midline. (j) Protraction of the mandible pushes the chin forward, and retraction pulls the chin back. (k) Depression of the mandible opens the mouth, while elevation closes it. (l) Opposition of the thumb brings the tip of the thumb into contact with the tip of the fingers of the same hand and reposition brings the thumb back next to the index finger.

                                        Flexion and Extension

                                        Flexion and extension are movements that take place within the sagittal plane and involve anterior or posterior movements of the body or limbs. For the vertebral column, flexion (anterior flexion) is an anterior (forward) bending of the neck or body, while extension involves a posterior-directed motion, such as straightening from a flexed position or bending backward. Lateral flexion is the bending of the neck or body toward the right or left side. These movements of the vertebral column involve both the symphysis joint formed by each intervertebral disc, as well as the plane type of synovial joint formed between the inferior articular processes of one vertebra and the superior articular processes of the next lower vertebra.

                                        In the limbs, flexion decreases the angle between the bones (bending of the joint), while extension increases the angle and straightens the joint. For the upper limb, all anterior-going motions are flexion and all posterior-going motions are extension. These include anterior-posterior movements of the arm at the shoulder, the forearm at the elbow, the hand at the wrist, and the fingers at the metacarpophalangeal and interphalangeal joints. For the thumb, extension moves the thumb away from the palm of the hand, within the same plane as the palm, while flexion brings the thumb back against the index finger or into the palm. These motions take place at the first carpometacarpal joint. In the lower limb, bringing the thigh forward and upward is flexion at the hip joint, while any posterior-going motion of the thigh is extension. Note that extension of the thigh beyond the anatomical (standing) position is greatly limited by the ligaments that support the hip joint. Knee flexion is the bending of the knee to bring the foot toward the posterior thigh, and extension is the straightening of the knee. Flexion and extension movements are seen at the hinge, condyloid, saddle, and ball-and-socket joints of the limbs (see Figure 9.12a-d).

                                        Hyperextension is the abnormal or excessive extension of a joint beyond its normal range of motion, thus resulting in injury. Similarly, hyperflexion is excessive flexion at a joint. Hyperextension injuries are common at hinge joints such as the knee or elbow. In cases of “whiplash” in which the head is suddenly moved backward and then forward, a patient may experience both hyperextension and hyperflexion of the cervical region.

                                        Abduction and Adduction

                                        Abduction and adduction motions occur within the coronal plane and involve medial-lateral motions of the limbs, fingers, toes, or thumb. Abduction moves the limb laterally away from the midline of the body, while adduction is the opposing movement that brings the limb toward the body or across the midline. For example, abduction is raising the arm at the shoulder joint, moving it laterally away from the body, while adduction brings the arm down to the side of the body. Similarly, abduction and adduction at the wrist moves the hand away from or toward the midline of the body. Spreading the fingers or toes apart is also abduction, while bringing the fingers or toes together is adduction. For the thumb, abduction is the anterior movement that brings the thumb to a 90° perpendicular position, pointing straight out from the palm. Adduction moves the thumb back to the anatomical position, next to the index finger. Abduction and adduction movements are seen at condyloid, saddle, and ball-and-socket joints (see Figure 9.12e).

                                        Circumduction

                                        Circumduction is the movement of a body region in a circular manner, in which one end of the body region being moved stays relatively stationary while the other end describes a circle. It involves the sequential combination of flexion, adduction, extension, and abduction at a joint. This type of motion is found at biaxial condyloid and saddle joints, and at multiaxial ball-and-sockets joints (see Figure 9.12e).

                                        Rotation

                                        Rotation can occur within the vertebral column, at a pivot joint, or at a ball-and-socket joint. Rotation of the neck or body is the twisting movement produced by the summation of the small rotational movements available between adjacent vertebrae. At a pivot joint, one bone rotates in relation to another bone. This is a uniaxial joint, and thus rotation is the only motion allowed at a pivot joint. For example, at the atlantoaxial joint, the first cervical (C1) vertebra (atlas) rotates around the dens, the upward projection from the second cervical (C2) vertebra (axis). This allows the head to rotate from side to side as when shaking the head “no.” The proximal radioulnar joint is a pivot joint formed by the head of the radius and its articulation with the ulna. This joint allows for the radius to rotate along its length during pronation and supination movements of the forearm.

                                        Rotation can also occur at the ball-and-socket joints of the shoulder and hip. Here, the humerus and femur rotate around their long axis, which moves the anterior surface of the arm or thigh either toward or away from the midline of the body. Movement that brings the anterior surface of the limb toward the midline of the body is called medial (internal) rotation. Conversely, rotation of the limb so that the anterior surface moves away from the midline is lateral (external) rotation (see Figure 9.12f). Be sure to distinguish medial and lateral rotation, which can only occur at the multiaxial shoulder and hip joints, from circumduction, which can occur at either biaxial or multiaxial joints.

                                        Supination and Pronation

                                        Supination and pronation are movements of the forearm. In the anatomical position, the upper limb is held next to the body with the palm facing forward. This is the supinated position of the forearm. In this position, the radius and ulna are parallel to each other. When the palm of the hand faces backward, the forearm is in the pronated position, and the radius and ulna form an X-shape.

                                        Supination and pronation are the movements of the forearm that go between these two positions. Pronation is the motion that moves the forearm from the supinated (anatomical) position to the pronated (palm backward) position. This motion is produced by rotation of the radius at the proximal radioulnar joint, accompanied by movement of the radius at the distal radioulnar joint. The proximal radioulnar joint is a pivot joint that allows for rotation of the head of the radius. Because of the slight curvature of the shaft of the radius, this rotation causes the distal end of the radius to cross over the distal ulna at the distal radioulnar joint. This crossing over brings the radius and ulna into an X-shape position. Supination is the opposite motion, in which rotation of the radius returns the bones to their parallel positions and moves the palm to the anterior facing (supinated) position. It helps to remember that supination is the motion you use when scooping up soup with a spoon (see Figure 9.13g).

                                        Dorsiflexion and Plantar Flexion

                                        Dorsiflexion and plantar flexion are movements at the ankle joint, which is a hinge joint. Lifting the front of the foot, so that the top of the foot moves toward the anterior leg is dorsiflexion, while lifting the heel of the foot from the ground or pointing the toes downward is plantar flexion. These are the only movements available at the ankle joint (see Figure 9.13h).

                                        Inversion and Eversion

                                        Inversion and eversion are complex movements that involve the multiple plane joints among the tarsal bones of the posterior foot (intertarsal joints) and thus are not motions that take place at the ankle joint. Inversion is the turning of the foot to angle the bottom of the foot toward the midline, while eversion turns the bottom of the foot away from the midline. The foot has a greater range of inversion than eversion motion. These are important motions that help to stabilize the foot when walking or running on an uneven surface and aid in the quick side-to-side changes in direction used during active sports such as basketball, racquetball, or soccer (see Figure 9.13i).

                                        Protraction and Retraction

                                        Protraction and retraction are anterior-posterior movements of the scapula or mandible. Protraction of the scapula occurs when the shoulder is moved forward, as when pushing against something or throwing a ball. Retraction is the opposite motion, with the scapula being pulled posteriorly and medially, toward the vertebral column. For the mandible, protraction occurs when the lower jaw is pushed forward, to stick out the chin, while retraction pulls the lower jaw backward. (See Figure 9.13j.)

                                        Depression and Elevation

                                        Depression and elevation are downward and upward movements of the scapula or mandible. The upward movement of the scapula and shoulder is elevation, while a downward movement is depression. These movements are used to shrug your shoulders. Similarly, elevation of the mandible is the upward movement of the lower jaw used to close the mouth or bite on something, and depression is the downward movement that produces opening of the mouth (see Figure 9.13k).

                                        Excursion

                                        Excursion is the side to side movement of the mandible. Lateral excursion moves the mandible away from the midline, toward either the right or left side. Medial excursion returns the mandible to its resting position at the midline.

                                        Superior Rotation and Inferior Rotation

                                        Superior and inferior rotation are movements of the scapula and are defined by the direction of movement of the glenoid cavity. These motions involve rotation of the scapula around a point inferior to the scapular spine and are produced by combinations of muscles acting on the scapula. During superior rotation, the glenoid cavity moves upward as the medial end of the scapular spine moves downward. This is a very important motion that contributes to upper limb abduction. Without superior rotation of the scapula, the greater tubercle of the humerus would hit the acromion of the scapula, thus preventing any abduction of the arm above shoulder height. Superior rotation of the scapula is thus required for full abduction of the upper limb. Superior rotation is also used without arm abduction when carrying a heavy load with your hand or on your shoulder. You can feel this rotation when you pick up a load, such as a heavy book bag and carry it on only one shoulder. To increase its weight-bearing support for the bag, the shoulder lifts as the scapula superiorly rotates. Inferior rotation occurs during limb adduction and involves the downward motion of the glenoid cavity with upward movement of the medial end of the scapular spine.

                                        Opposition and Reposition

                                        Opposition is the thumb movement that brings the tip of the thumb in contact with the tip of a finger. This movement is produced at the first carpometacarpal joint, which is a saddle joint formed between the trapezium carpal bone and the first metacarpal bone. Thumb opposition is produced by a combination of flexion and abduction of the thumb at this joint. Returning the thumb to its anatomical position next to the index finger is called reposition (see Figure 9.13l).

                                        Table 9.1.
                                        Movements of the Joints
                                        Type of Joint Movement Example
                                        Pivot Uniaxial joint; allows rotational movement Atlantoaxial joint (C1–C2 vertebrae articulation); proximal radioulnar joint
                                        Hinge Uniaxial joint; allows flexion/extension movements Knee; elbow; ankle; interphalangeal joints of fingers and toes
                                        Condyloid Biaxial joint; allows flexion/extension, abduction/adduction, and circumduction movements Metacarpophalangeal (knuckle) joints of fingers; radiocarpal joint of wrist; metatarsophalangeal joints for toes
                                        Saddle Biaxial joint; allows flexion/extension, abduction/adduction, and circumduction movements First carpometacarpal joint of the thumb; sternoclavicular joint
                                        Plane Multiaxial joint; allows inversion and eversion of foot, or flexion, extension, and lateral flexion of the vertebral column Intertarsal joints of foot; superior-inferior articular process articulations between vertebrae
                                        Ball-and-socket Multiaxial joint; allows flexion/extension, abduction/adduction, circumduction, and medial/lateral rotation movements Shoulder and hip joints</