Nunn and Lumb's Applied Respiratory Physiology

Front Cover
Inside Front Cover
Fronit matter
	Nunn and lumb’s applied respiratory physiology
Copyright
Dedication
Foreword
Preface to the ninth edition
Table of Contents
Videos table of contents
Part I Basic Principles
	1 Functional anatomy of the respiratory tract
		Keywords:
		Key points
		Mouth, nose and pharynx
		The larynx
			Speech
			Effort closure
		The tracheobronchial tree
			Trachea (generation 0)
			Main, lobar and segmental bronchi (generations 1–4)
			Small bronchi (generations 5–11)
			Bronchioles (generations 12–14)
			Respiratory bronchioles (generations 15–18)
			Alveolar ducts (generations 19–22)
			Alveolar sacs (generation 23)
			Pulmonary acinus
			Respiratory epithelium
				Ciliated epithelial cells5
				Goblet cells
				Airway glands⁶
				Basal cells
				Mast cells
				Club cells (formerly clara cells)
				Neuroepithelial cells
		The alveoli
			The alveolar septa
				The fibre scaffold¹¹
		Alveolar cell types
			Capillary endothelial cells
			Alveolar epithelial cells: Type I¹⁵
			Alveolar epithelial cells: Type II
			Alveolar macrophages
		The pulmonary vasculature
			Pulmonary arteries
			Pulmonary arterioles
			Pulmonary capillaries
			Pulmonary venules and veins
			Bronchial circulation²²
			Pulmonary lymphatics
		References
	2 Elastic forces and lung volumes
		Keywords:
		Key points
		Elastic recoil of the lungs¹
			The nature of the forces causing recoil of the lung
			The alveolar surfactant
				Synthesis of surfactant
				Action of surfactant
				Other effects of surfactant
			Alternative models to explain lung recoil
			Transmural pressure gradient and intrathoracic pressure
			Time dependence of pulmonary elastic behaviour
				Hysteresis
			Causes of time dependence of pulmonary elastic behaviour
			Factors affecting lung compliance
		Elastic recoil of the thoracic cage
			Factors influencing compliance of the thoracic cage
		Pressure–volume relationships of the lung plus thoracic cage
			Relationship between alveolar, intrathoracic and ambient pressures
		Static lung volumes
			Factors affecting static lung volumes
			Functional residual capacity in relation to closing capacity
		Principles of measurement of compliance
			Static compliance
			Dynamic compliance
			Automated measurement of compliance
		Principles of measurement of static lung volumes
			Measurement of functional residual capacity
		References
	3 Respiratory system resistance
		Keywords:
		Key points
		Physical principles of gas flow and resistance
			Laminar flow
				Quantitative relationships
			Turbulent flow
				Quantitative relationships
			Reynolds number
		Respiratory system resistance
			Airway resistance
			Tissue resistance
			Inertance as a component of respiratory system resistance
		Factors affecting respiratory resistance
			Volume-related airway collapse
				Effect of lung volume on resistance to breathing
				Gas trapping
				Closing capacity⁴’⁵
			Flow-related airway collapse
		Muscular control of airway diameter
			Neural pathways⁷
				Parasympathetic system⁸
				Sympathetic system
				Noncholinergic parasympathetic nerves⁷
			Humoral control
			Physical and chemical effects
			Local cellular mechanisms
		Drug effects on airway smooth muscle
			β₂-agonists
				The β₂-receptor
			Phosphodiesterase inhibitors¹⁶’¹⁷
			Anticholinergic drugs
				Acetylcholine receptor
			Leukotriene antagonists¹⁸
		Compensation for increased resistance to breathing
			Inspiratory resistance
			Expiratory resistance
		Principles of measurement of respiratory resistance and closing capacity
			Respiratory system resistance
				Pressure–flow technique
				Oscillating air flow
				Body plethysmograph
				Interrupter technique
				End-inspiratory interruption
			Measurement of closing capacity⁴’²¹
		References
	4 Control of breathing
		Keywords:
		Key points
		The origin of the respiratory rhythm¹
			Anatomical location of the ‘respiratory centre’
			Central pattern generator¹
				Cellular mechanisms of central pattern generation
			Neurotransmitters involved in central pattern generator and respiratory control³
			Efferent pathways from the respiratory centre
		Central nervous system connections to the respiratory centre
			The pons
			Cerebral cortex⁴
			Ondine’s curse (primary alveolar hypoventilation syndrome)
		Peripheral input to the respiratory centre and nonchemical reflexes
			Reflexes arising from the upper respiratory tract¹³
				Nose
				Pharynx
				Larynx
				Cough reflex¹⁴’¹⁵
				Expiration reflex¹⁴’¹⁶
			Reflexes arising in the lung
				Pulmonary stretch receptors and their associated reflexes¹⁶
				Head’s paradoxical reflex
			Other pulmonary afferents
			Reflexes arising from outside the airway and lungs
				Phrenic nerve afferents
				Baroreceptor reflexes²⁷
				Afferents from the musculoskeletal system
		The influence of carbon dioxide on respiratory control
			Localization of the central chemoreceptors
			Mechanism of action
				Compensatory bicarbonate shift in the csf
			The Pco₂/ventilation response curve
				Time course of Pco₂/ventilation response
		The influence of oxygen on respiratory control
			Peripheral chemoreceptors³⁶
			Mechanism of action of peripheral chemoreceptors³⁶’³⁹
				Other effects of stimulation
			Time course of the ventilatory response to hypoxia⁴⁷
				Acute hypoxic ventilatory response
				Hypoxic ventilatory decline
				Response to sustained hypoxia
			Ventilatory response to progressive hypoxia
			Iatrogenic loss of peripheral chemoreceptor sensitivity⁵²
			Central hypoxic depression of breathing
				Integration of the chemical control of breathing
			Effects of Pco₂ and ph on the hypoxic ventilatory response
			Effects of Po₂ and ph on central chemoreceptor response³³’⁵⁸
		Periodic breathing
		Breath holding
			Influence of Pco₂ and Po₂
			Effect of lung volume
		Drug effects on the control of breathing
			Respiratory depressants
				Opioids64
				Benzodiazepines
			Respiratory stimulants⁷⁰
		Methods for assessment of breathing control
			Sensitivity to carbon dioxide
				Steady-state method
				Rebreathing method
			Sensitivity to hypoxia⁷⁴
				Steady-state method
				Rebreathing method
				Intermittent inhalation of high oxygen concentration
		References
	5 Pulmonary ventilation
		Keywords:
		Key points
		Upper airway muscles
			Laryngeal control of airway resistance
		Respiratory muscles of the trunk
			Diaphragm
				Mechanics of diaphragmatic function
			Rib cage muscles¹⁰
			Accessory muscles
			Abdominal muscles
		Integration of respiratory muscle activity
			Breathing
			Separation of volume contribution of rib cage and abdomen
			Effect of posture on respiratory muscles
				Supine position
				Lateral position
			Chemoreceptor activation
		Neuronal control of respiratory muscles
			Muscle fibre subtypes¹⁹
		Respiratory muscle fatigue and disuse¹⁹
			Effect of disuse²³
		The work of breathing
			Units of measurement of work
			Dissipation of the work of breathing
				Work against elastic recoil
				Work against resistance to gas flow
			The minimal work of breathing
		Measurement of ventilation
			Direct measurement of respired volumes²⁷
				Impellers and turbines
				Noninvasive measurement of ventilation
			Measurement of ventilatory volumes by integration of instantaneous gas flow rate
		Measurement of ventilatory capacity²⁷’³⁰
			Maximal voluntary ventilation
			Forced expiration
			Peak expiratory flow rate
		Assessment of the respiratory muscles
		References
	6 The pulmonary circulation
		Keywords:
		Key points
		Pulmonary blood flow
		Pulmonary blood volume
			Factors influencing pulmonary blood volume
				Posture
				Systemic vascular tone
		Pulmonary vascular pressures
			Effect of intraalveolar pressure
		Pulmonary vascular resistance
			Vascular resistance in the lung
			Localization of the pulmonary vascular resistance
		Passive changes in pulmonary vascular resistance
			Effect of pulmonary blood flow (cardiac output)
			Effect of lung inflation
			Effect of gravity on alveolar and vascular pressures
				Vascular weir
		Active control of pulmonary vascular resistance
			Cellular mechanisms controlling pulmonary vascular tone⁶
				Receptors
				Second messengers
				Role of the endothelium and nitric oxide
			Hypoxic pulmonary vasoconstriction⁶’⁸’⁹
			Mechanism of hypoxic pulmonary vasoconstriction⁶’⁹’¹⁵’¹⁶
				Oxygen sensing in pulmonary artery smooth muscle cells
				Modulation by the endothelial cell of the pulmonary artery smooth muscle cells¹⁷
				Iron and hypoxic pulmonary vasoconstriction²⁰’²²
			Effects of Pco₂ and pH on pulmonary vascular resistance
			Neural control
			Humoral control
		Drug effects on the pulmonary circulation
			Inhaled drugs
				Nitric oxide
				Prostacyclin (pgi²)²⁷
			Systemic drugs²⁸
		Principles of measurement of the pulmonary circulation
			Pulmonary vascular pressures
			Pulmonary blood flow
				Dye or thermal dilution
		References
	7 Distribution of pulmonary ventilation and perfusion
		Keywords:
		Key points
		Distribution of ventilation
			Spatial and anatomical distribution of inspired gas
			Distribution of inspired gas in relation to the rate of alveolar filling
			Effect of maldistribution on the alveolar ‘plateau’
		Distribution of perfusion
			Distribution between the two lungs
			Gravitational effects on regional pulmonary blood flow
			Gravity-independent regional blood flow⁵
		Ventilation in relation to perfusion
			Body position and ventilation and perfusion ratios
			Multiple inert gas elimination technique¹⁸
			Quantification of spread of v˙/q˙ ratios using three-compartment model
		Dead space
			Components of dead space
			Anatomical dead space
			Factors influencing the anatomical dead space
			Alveolar dead space
			Physiological dead space
			The bohr equation
			Factors influencing physiological dead space
			Effects of an increased physiological dead space
		Venous admixture or shunt
			Nomenclature of venous admixture
			Forms of venous admixture
			Effect of venous admixture on arterial pco2 and po2
			Effect of cardiac output on shunt
			The iso-shunt diagram
		The effect of scatter of v˙/q˙ ratios on arterial po2
			Modification of the iso-shunt diagram to include v˙/q˙ scatter
		Principles of assessment of distribution of ventilation and pulmonary blood flow
			Regional distribution of ventilation and perfusion
				Radioactive tracers
				Scanning techniques
				Noninvasive techniques
			Measurement of ventilation and perfusion as a function of v˙/q˙ ratios
			Measurement of venous admixture
			Alveolar air equation
			Distinction between shunt and the effect of v˙/q˙ scatter
			Measurement of dead space
		References
	8 Diffusion of respiratory gases
		Keywords:
		Key points
		Fundamentals of the diffusion process
			Quantification of resistance to diffusion
			Diffusion of gases in solution
				Partial pressure versus concentration gradients
		Diffusion of oxygen in the lungs
			Components of the alveolar/capillary diffusion pathway
				Gas space within the alveolus
				Alveolar lining fluid
				Tissue barrier
				Plasma layer
				Diffusion into and within the red blood cell⁵
				Uptake of oxygen by haemoglobin
			Quantification of the diffusing capacity for oxygen
				Forward integration¹⁰
			Capillary transit time
		Diffusion of carbon dioxide in the lungs
		Diffusion of carbon monoxide in the lungs
			Diffusion path for carbon monoxide
				Diffusion of co in plasma
			Uptake of co by haemoglobin
			Quantification of the components of the resistance to diffusion of co
		Factors affecting diffusing capacity
			Factors affecting the membrane surface area
				Body size
				Lung volume
				Ventilation/perfusion mismatch
				Posture
				Pathology
			Factors affecting the membrane diffusion barrier
			Factors affecting uptake of gases by haemoglobin
			Other determinants of diffusing capacity
		Diffusion of oxygen in the tissues¹³’¹⁴
		Principles of measurement of diffusing capacity¹⁸
			Steady-state method
			Single-breath method1
			Rebreathing method
		References
	9 Carbon dioxide
		Keywords:
		Key points
		Carriage of carbon dioxide in blood
			In physical solution
			As carbonic acid
				Carbonic anhydrase¹
			As bicarbonate ion
			As carbamino compounds
				Carbamino carriage and haemoglobin
				Haldane effect⁴
			Effect of buffering power of proteins on carbon dioxide carriage
			Distribution of carbon dioxide within the blood
				Haemoglobin buffering
				Hamburger shift
			Dissociation curves of carbon dioxide
		Factors influencing the pco2 in the steady state
			Alveolar Pco₂ (paco2)
			End-expiratory Pco₂ (pe’co2)
			Alveolar/arterial Pco₂ gradient
			Arterial Pco₂ (paco2)
		Carbon dioxide stores and the unsteady state
		Apnoea
		Carbon dioxide carriage during hypothermia
		Outline of methods of measurement of carbon dioxide
			Blood partial pressure
			Fractional concentration in gas mixtures¹⁷
				Infrared analysis
			Capnography¹⁷’¹⁸
				Arterial to end-expiratory pco2 gradient
		References
	10 Oxygen
		Keywords:
		Key points
		Oxygen cascade
			Dilution of inspired oxygen by water vapour
			Primary factors influencing alveolar oxygen partial pressure
				Dry barometric pressure
				Inspired oxygen concentration
				Oxygen consumption
				Alveolar ventilation
			Secondary factors influencing alveolar oxygen partial pressure
				Cardiac output
				‘concentration’, third gas or fink effect
			Alveolar/arterial po2 difference
			Factors influencing the magnitude of the alveolar/arterial po2 difference
			Compensation for increased alveolar/arterial po2 difference by raising the inspired oxygen concentration
		Carriage of oxygen in the blood
			Physical solution of oxygen in blood
			Haemoglobin
			Molecular mechanisms of oxygen binding²
				Oxygen-binding capacity of haemoglobin (bo2) or hüfner constant
			Kinetics of the reaction of oxygen with haemoglobin
			Oxyhaemoglobin dissociation curve
			Factors causing displacement of the dissociation curve
				Quantifying displacement of the haemoglobin dissociation curve
				Clinical significance of displacement of the haemoglobin dissociation curve
			2,3-diphosphoglycerate
			Normal arterial po2
			Nitric oxide and haemoglobin¹⁵
			Abnormal forms of haemoglobin
			Abnormal ligands
				Carboxyhaemoglobin
			Blood substitutes
				Perfluorocarbons²⁷
				Haemoglobin-based oxygen carriers³⁰’³¹
		Role of oxygen in the cell
			Energy production
			Glycolysis and anaerobic energy production
			Aerobic energy production
				Significance of aerobic metabolism
				Critical oxygen partial pressure for aerobic metabolism
			Tissue po2
		Transport of oxygen from the lungs to the cell
			The concept of oxygen delivery
			Quantification of oxygen delivery
			Interaction of the factors governing oxygen delivery
			Relationship between oxygen delivery and consumption
		Oxygen stores
		Cyanosis
			Central and peripheral cyanosis
			Sensitivity of cyanosis as an indication of hypoxaemia
		Principles of measurement of oxygen levels
			Oxygen concentration in gas samples
			Blood po2
				Errors in measuring oxygen levels
				Transcutaneous po2
			Oxygen saturation³’⁴⁸
				Pulse oximetry
			Tissue po2
				Tissue surface electrodes
				Near-infrared spectroscopy⁵⁶
				Indirect assessment of tissue oxygenation
		Measurement of oxygen consumption and delivery
			Oxygen consumption
				Oxygen loss from a closed breathing system
				Subtraction of expired from inspired volume of oxygen
				Multiplication of cardiac output by arterial/mixed venous oxygen content difference
			Oxygen delivery
		References
	11 Nonrespiratory functions of the lung
		Keywords:
		Key points
		Filtration
		Defence against inhaled substances
			Airway lining fluid
				Mucous layer⁵
				Ciliary function⁷’⁸
				Periciliary layer
				Humidification
			Inhaled particles
			Defence against inhaled pathogens¹⁵
				Direct removal of pathogens
				Chemical inactivation of pathogens
				Protease–antiprotease system
				Immune systems
		Chemical hazards
		Processing of endogenous compounds by the pulmonary vasculature
			Catecholamines and acetylcholine
				Noradrenaline (norepinephrine)
			Peptides
				Angiotensin
				Bradykinin
				Atrial natriuretic peptide
				Endothelins
			Arachidonic acid derivatives
			Purine derivatives
		Pharmacokinetics and the lung
			Drug delivery²⁶’²⁷
			Drug elimination
				Pulmonary circulation²⁹
				Pulmonary toxicity of drugs
		The endocrine lung
		References
Part II Applied Physiology
	12 Pregnancy, neonates and children
		Keywords:
		Key points
		Respiratory function in pregnancy
		The lungs before birth
			Embryology
			Lung liquid
			Lung development and lung function later in life
			Fetal circulation
		Events at birth
			Factors in the initiation of breathing
				Fate of the fetal lung liquid
			Changes in the circulation
			Mechanism of reduced pulmonary vascular resistance at birth
		Neonatal lung function
			Mechanics of breathing
			Ventilation and gas exchange
			Control of breathing
			Haemoglobin
		Premature birth and the lungs
			Respiratory distress syndrome
			Bronchopulmonary dysplasia²¹
		Sudden infant death syndrome²³
		Development of lung function during childhood
		References
	13 Exercise
		Keywords:
		Key points
		Oxygen consumption during exercise
			Time course of the increase in oxygen consumption
			Maximal oxygen uptake
			Response of the oxygen delivery system
				Oxygen delivery
				Oxygen extraction
		Anaerobic metabolism
			Oxygen debt
				Excess post-exercise oxygen consumption
		Ventilatory response to exercise
			Time course⁷
			Ventilation equivalent for oxygen
			Minute volume and dyspnoea
			Control of ventilation
				Neural factors
				Arterial blood gas partial pressures and the chemoreceptors
				Humoral mechanisms
		Fitness and training
			Minute volume of ventilation
			Ventilation equivalent for oxygen
			Exercise-induced arterial hypoxaemia
			Cardiorespiratory disease
				Exercise testing
		References
	14 Sleep
		Keywords:
		Key points
		Normal sleep
			Respiratory changes
				Ventilation¹
				Chemosensitivity
				Effect of age
				Pharyngeal airway resistance
			Snoring
		Sleep-disordered breathing
			The mechanism of airway obstruction⁹
				Anatomically narrow airway
				Inadequate control of respiratory muscles
				Arousal
				Respiratory instability
				Drug effects in sleep apnoea/hypopnoea syndrome
			Effects of sleep apnoea/hypopnoea syndrome
			Principles of therapy¹²’³⁸’³⁹
				Conservative treatment
				Surgical relief of obstruction
				Upper airway stimulation
		References
	15 Obesity
		Keywords:
		Key points
		Respiratory physiology of obesity
			Lung volumes and respiratory mechanics
				Static lung volumes
				Dynamic lung volumes
			Respiratory muscles
			Ventilation perfusion relationships
			Respiratory control
		Impact of obesity on lung disease
			Lung development in childhood
				Dysanapsis
			Asthma obesity phenotype
			Chronic obstructive pulmonary disease
				The obesity paradox
		Obesity hypoventilation syndrome
		References
	16 High altitude and flying
		Keywords:
		Key points
		Equivalent oxygen concentration
		Respiratory system responses to altitude
			Physiological effects of exposure to altitude
				Ventilatory changes
				Signs and symptoms
				Acclimatization to altitude
					Ventilatory control
					Blood gases
					Haemoglobin concentration and oxygen affinity
				Adaptation to altitude¹⁴
					Physiological adaptations
					Epigenetic adaptations
					Genetic adaptations
					Chronic mountain sickness (monge disease)¹
				Exercise at high altitude²²
					Capacity for work performed
					Ventilation equivalent of oxygen consumption
					Pco2 and po2
		Altitude illness²⁵’²⁶
			Acute mountain sickness
			High-altitude pulmonary oedema²⁸
			Other medical problems at altitude
			Therapy for altitude-induced illness²⁵
		Flying
			Altitude exposure
				Depressurization
			Air travel in patients with respiratory disease⁴⁶
			Cabin air quality
		References
	17 High pressure and diving
		Keywords:
		Key points
		Exchange of oxygen and carbon dioxide
			Effect of pressure on alveolar pco2 and po2
			Effect on mechanics of breathing¹­­¯³
			Effect on gas exchange¹’²’⁴
			Oxygen consumption
				Exercise
		Effects attributable to the composition of the inspired gas
			Air
				Oxygen
				Nitrogen
			Helium/oxygen mixtures
			Helium/oxygen/nitrogen mixtures
		Types of diving activity and their respiratory effects
			Breath-hold diving6
				Lung volume
				Alveolar po2
				Alveolar pco2
			Limited duration dives
			Saturation dives
		Respiratory aspects of decompression illness¹²’¹³
			Barotrauma
			Decompression sickness
			Altitude decompression sickness¹⁹’²⁰
		References
	18 Respiration in closed environments and space
		Keywords:
		Key points
		Closed-system anaesthesia
			Accumulation of other gases in closed circuits
		Submarines
			Physiological effects of prolonged hypercapnia⁴
				Respiratory changes⁷
				Calcium metabolism⁸
		Space⁹
			Atmosphere composition
			Oxygen supply
			Carbon dioxide removal
			Atmospheric contamination
			Long-term space travel
		Microgravity¹⁵
		Biospheres⁹
			Small-scale biological atmospheric regeneration
			Biosphere 29
				Outcome from the 2-year closure
		References
	19 Drowning
		Keywords:
		Key points
		Physiology of immersion²
		Physiological mechanisms of drowning
			Drowning without aspiration of water
			Drowning with aspiration of water
				Freshwater
				Seawater
		The role of hypothermia²
		Principles of therapy for near-drowning
			Immediate treatment
			Hospital treatment
		References
	20 Smoking and air pollution
		Keywords:
		Key points
		Tobacco smoke
			Constituents of tobacco smoke
				Gaseous phase
				Particulate phase
			Individual smoke exposure
				Quantifying cigarettes smoked
				Pattern of inhalation
				Respiratory effects of smoking
				Airway mucosa
				Airway diameter
				Ventilatory capacity
			Passive smoking
				Maternal smoking
			Smoking and perioperative complications
			Smoking cessation
				E-cigarettes
		Mechanisms of smoking-related lung damage
			Oxidative injury
				Direct oxidative damage
				Cell-mediated oxidative damage
			Carcinogenesis
			Immunological activation
		Air pollution²²
			Sources of pollutants
				Primary pollutants
				Secondary pollutants
				Meteorological conditions
			Respiratory effects of pollutants
			Indoor air pollution⁴⁴
				Allergens
				Carbon monoxide
				Nitrogen dioxide
		References
	21 Anaesthesia
		Keywords:
		Key points
		Control of breathing
			Unstimulated ventilation
			Effect on pco2/ventilation response curve
			Effect on po2/ventilation response curve³’⁴
			Implications of the depression of acute hypoxic ventilatory response by anaesthetic agents
		Pattern of contraction of respiratory muscles
			Pharynx
				Maintenance of pharyngeal airway patency
			Inspiratory muscles
			Expiratory muscles¹³
		Change in functional residual capacity
			Cause of the reduction in frc¹⁸
		Atelectasis during anaesthesia¹⁸
			Causes of atelectasis
			Prevention of atelectasis³⁰
				Inspired oxygen concentration
				Nitrous oxide
				Positive airway pressures
			Reexpansion of atelectasis
				Continuous positive airway pressure manoeuvres
				Positive end-expiratory pressure
		Respiratory mechanics⁴⁷
			Calibre of the lower airways
				Effect of reduced functional residual capacity
				Inhalational anaesthetics
			Other sites of increased airway resistance
			Compliance
		Gas exchange
			Dead space
			Shunt
				Magnitude of the change during anaesthesia
				Cause of venous admixture during anaesthesia
			Ventilation/perfusion relationships
				Effect of age on v˙/q˙ ratios during anaesthesia
				Effect of positive end-expiratory pressure
				Other factors affecting ventilation/perfusion relationships during anaesthesia
			Summary
		Other effects of general anaesthesia on the respiratory system
			Response to added resistance
			Hypoxic pulmonary vasoconstriction⁶²
		Anaesthesia in specific patient groups
			Paediatrics⁶³
			Obesity⁶⁶
		Special circumstances relevant during anaesthesia
			Patient position
				Lateral
				Prone
			Laparoscopic surgery
				Respiratory mechanics
				Carbon dioxide absorption⁷⁷
		Regional anaesthesia
			Control of breathing
		Respiratory function in the postoperative period
			Reversal of intraoperative physiological changes
			Postoperative pulmonary complications
				Preoperative interventions to avoid postoperative pulmonary complications
				Intraoperative considerations
				Postoperative considerations
		References
	22 Changes in the carbon dioxide partial pressure
		Keywords:
		Key points
		Causes of hypocapnia¹
		Causes of hypercapnia
		Effects of carbon dioxide on the nervous system
			Effects on consciousness
			Cerebral blood flow²
				Mechanisms
				Anaesthesia
			Effects on the autonomic and endocrine systems
		Effects on other body systems
			Respiratory system
				Pulmonary circulation
				Oxygenation of the blood
			Cardiovascular system
				Myocardial contractility and heart rate
				Arrhythmias
				Blood pressure
			Effect on the kidney
			Effect on blood electrolyte levels
		Hypercapnia in clinical practice
			Clinical signs
				Severe hypercapnia
		References
	23 Hypoxia
		Keywords:
		Key points
		Biochemical changes in hypoxia
			Depletion of high-energy compounds
			End products of metabolism
			Initiation of glycolysis
		Mechanisms of hypoxic cell damage
			Immediate cellular responses to hypoxia³
				Potassium and sodium flux
				Calcium
				Glutamate release
				Nonglutamate mechanisms
			Delayed cellular responses to hypoxia
				Hypoxia-inducible factor ¹⁷’⁸
			Ischaemic preconditioning¹¹
				Early protection
				Late protection
				Remote ischaemic preconditioning¹²’¹³
				Agents used for preconditioning
		Po2 level at which hypoxia occurs
			Critical arterial po2 for tissue function
		Effects of hypoxia
		References
	24 Anaemia
		Keywords:
		Key points
		Pulmonary function
			Gas exchange
			Haemoglobin dissociation curve
			Arterial oxygen content
		Oxygen delivery
			Effect of anaemia on cardiac output
				Acute anaemia
				Chronic anaemia
			The influence of cardiac output on oxygen delivery
				Relationship between oxygen delivery and consumption
		Anaemia and exercise
		Anaemia in the clinical setting?⁵
		References
	25 Oxygen toxicity and hyperoxia
		Keywords:
		Key points
		Hyperoxia
		Oxygen toxicity
			The oxygen molecule and reactive derivatives²
				Singlet oxygen
				Superoxide anion
				Hydroperoxyl radical
				Hydrogen peroxide
				Three-stage reduction of oxygen
			Secondary derivatives of the products of dioxygen reduction
			Sources of electrons for the reduction of oxygen to superoxide anion
				Mitochondrial enzymes
				Nadph oxidase system
				Xanthine oxidoreductase and reperfusion injury⁶
				Ferrous iron
				High po2
				Exogenous compounds
			Biological effects of reactive oxygen species
		Defences against reactive oxygen species
			Antioxidant enzymes
				Superoxide dismutase¹¹
			Endogenous antioxidants
			Exogenous antioxidants
		Normobaric hyperoxia
			Increasing the inspired oxygen concentration¹⁶
				Fixed performance devices
				Variable performance devices
				High-flow nasal therapy
		Clinical effects of normobaric hyperoxia
			Retinopathy of prematurity²⁷
			Pulmonary oxygen toxicity
				Symptoms³⁰
				Cellular changes³¹
				Limits of survival
				Pulmonary absorption collapse
				Bleomycin lung toxicity
			Hyperoxia in the perioperative period
			Hyperoxia in acute medicine
			Hyperoxia in critical care
		Hyperbaric hyperoxia
			Oxygen convulsions (the paul bert effect)
				Incidence
			Therapeutic effects of hyperbaric oxygen
			Clinical applications of hyperbaric oxygenation therapy
		References
	26 Comparative respiratory physiology
		Keywords:
		Key points
		Designs of respiratory system
			Structural designs for gas-exchange apparatus
			Factors affecting respiratory system design
				Respiratory medium for breathing
				Body temperature
				Metabolic rate
		Respiratory systems of major phyla
			Aquatic respiration
				Diffusion respiration in small species
				Echinodermata
				Mollusca
				Crustacea
				Fish
				Amphibia
			Air respiration
				Annelida
				Arthropoda
				Reptilia
				Mammalia
				Aves (birds)¹⁰’¹¹
		Carriage of gases in blood
			Circulation configurations
				Fish
				Amphibians
				Reptiles
				Birds and mammals
			Oxygen-carrying molecules
				Haemerythrin
				Haemocyanin
				Haemoglobin
		Animals at physiological extremes
			Mammals at altitude
				Oxygen carriage¹⁶’¹⁷
				Pulmonary vasculature
				Collateral ventilation
			Exercising horses²⁰
			Diving mammals
		Pathophysiology of animal respiratory diseases in veterinary practice
			Ruminants
				Bovine respiratory disease²⁷
				Acute interstitial pneumonia
				Vena caval thrombosis
				Parasitic bronchitis (lungworm or husk)
			Equine respiratory disease
		References
Part III Physiology of Pulmonary Disease
	27 Ventilatory failure
		Keywords:
		Key points
		Definitions
		Pattern of changes in arterial blood gases
			Time course of changes in blood gases in acute ventilatory failure
		Causes of ventilatory failure¹
			Increased dead space
		Relationship between ventilatory capacity and ventilatory failure
			Metabolic demand and ventilatory failure
		Breathlessness⁵
			The origin of the sensation
				Treatment of breathlessness
		Principles of therapy for ventilatory failure
			Treatment of hypoxaemia caused by hypoventilation by administration of oxygen
			Improvement of alveolar ventilation
		References
	28 Airways disease
		Keywords:
		Key points
		Asthma
			Clinical features
			Asthma phenotypes⁹
			Cellular mechanisms of asthma¹⁰
			Causes of airway obstruction in asthma
				Airway smooth muscle
				Inflammation
				Airway remodelling¹⁹
			Aetiology of asthma²³
				Genetics
				Allergy
				Infection
				Hygiene hypothesis
				Smoking and air pollution
				Obesity
				Paracetamol (acetaminophen)
			Aspirin and asthma³⁵
				Mechanism of aspirin sensitivity
			Principles of therapy¹
		Chronic obstructive pulmonary disease
			Aetiology of chronic obstructive pulmonary disease
				Emphysema
				Airway obstruction
				Hyperinflation
				Respiratory muscles in chronic obstructive pulmonary disease
			Principles of therapy⁴⁴
				Smoking cessation (page 239)
				Medical treatment⁶⁸
				Long-term supplemental oxygen⁷¹
				Pulmonary rehabilitation⁷²
			Oxygen therapy in chronic obstructive pulmonary disease⁷⁵
		Cystic fibrosis⁷⁹
			Aetiology of cystic fibrosis
				Biochemical abnormality
				Causes of lung disease
			Principles of therapy⁹⁰
				Correcting the abnormal cystic fibrosis transmembrane conductance regulator
		References
	29 Pulmonary vascular disease
		Keywords:
		Key points
		Pulmonary oedema
			Anatomical factors
			Pulmonary fluid dynamics
				Fluid exchange across the endothelium⁴
				Fluid dynamics within the interstitial space
				Fluid exchange across the alveolar epithelium⁶
			Stages of pulmonary oedema
				Stage I: Interstitial pulmonary oedema
				Stage II: Crescentic filling of the alveoli
				Stage III: Alveolar flooding
				Stage IV: Froth in the air passages
			Aetiology of pulmonary oedema
				Increased capillary pressure (haemodynamic pulmonary oedema)
				Increased permeability of the capillary/endothelial glycocalyx/alveolar barrier (permeability oedema)
				Decreased osmotic pressure of the plasma proteins
				Other causes of pulmonary oedema
			Principles of therapy
				Haemodynamic pulmonary oedema
				Permeability pulmonary oedema
				Artificial ventilation and positive end-expiratory pressure
			Measurement of extravascular lung water
		Pulmonary embolism
			Thromboembolism
				Diagnosis of pulmonary thromboembolus¹³
				Pathophysiology
				Principles of therapy¹³
			Air embolism
				Detection of air embolism
				Pathophysiology of air embolus
				Paradoxical air embolism
			Fat embolism
			Amniotic fluid embolism¹⁸’¹⁹
		Pulmonary hypertension
			Secondary pulmonary arterial hypertension
			Primary pulmonary arterial hypertension
				Pathophysiology of vascular remodelling
				Treatment²⁰’²¹
		Hepatopulmonary syndrome
		References
	30 Diseases of the lung parenchyma and pleura
		Keywords:
		Key points
		Pulmonary collapse
			Loss of forces opposing retraction of the lung
			Absorption of trapped gas
				The effect of respired gases
				Magnitude of the pressure gradients
				Effect of reduced ventilation/perfusion ratio
			Diagnosis of pulmonary collapse
			Principles of therapy
		Pulmonary consolidation (pneumonia)
			Pathophysiology⁸¯¹⁰
				Margination of neutrophils¹¹
		Interstitial lung disease and pulmonary fibrosis
			Causes of pulmonary fibrosis
			Cellular mechanisms of pulmonary fibrosis¹⁹¯²¹
			Principles of therapy¹⁸’²⁴’²⁵
		Lung cancer
			Epidemiology
				Tobacco
				Radon
			Carcinogenesis of lung cancer
				Radiation
				Tobacco smoke carcinogens
				Molecular mechanisms of carcinogenesis
				Target genes for pulmonary carcinogenesis
			Clinical aspects
				Pathology
				Clinical features³⁹
			Principles of therapy
		Pleural disease
			Physiology of the pleural space⁴³
			Pleural effusion
			Pneumothorax
				Tension pneumothorax
				Principles of therapy for spontaneous pneumothorax
				Absorption of air from the pleural space
			Empyema
		References
	31 Acute lung injury
		Keywords:
		Key points
		Clinical aspects of acute lung injury¹’²
			Definition
			Predisposing conditions and risk factors for acute lung injury
				Pulmonary and extrapulmonary acute lung injury
			Incidence and mortality
			Clinical course
			Pathophysiology²
				Alveolar/capillary permeability
				Maldistribution of ventilation and perfusion¹⁵
				Lung mechanics
		Mechanisms of acute lung injury
			Histopathology
				Acute stage
				Fibroproliferative stage
			Cellular mechanisms¹⁹
		Principles of therapy²’¹⁰’²³’²⁴
			Artificial ventilation in acute respiratory distress syndrome
				Tidal volume
				Ventilation mode
				Positive end-expiratory pressure³⁵
				Protective ventilation strategy
				Recruitment manouevres⁴⁶
				Prone positioning⁵⁰
				Alternative respiratory support strategies⁵³
			Other therapeutic options⁵⁸
			Future directions
		References
	32 Respiratory support and artificial ventilation
		Keywords:
		Key points
		Respiratory physiotherapy
			Physiology of respiratory interventions
				To increase lung volume
				To decrease the work of breathing
				To clear secretions
		Noninvasive ventilation
			Negative pressure ventilation
			Noninvasive positive pressure ventilation
				Clinical applications
		Intermittent positive pressure ventilation
			Phases of the respiratory cycle
				Inspiration
				Expiration
			Time course of inflation and deflation
			Effect of changes in inflation pressure, resistance and compliance
				Effect of changes in compliance and resistance
				Overpressure
				Deviations from true exponential character of expiration
			Alternative patterns of application of inflation pressure
			Control of duration of inspiration
			The inspiratory to expiratory ratio
		Clinical use of intermittent positive pressure ventilation
			Interactions between patient and ventilator
				Pressure sensing
				Flow sensing
				Neurally adjusted ventilatory assist
			Ventilatory modes in common use
				Mandatory minute volume
				Airway pressure release ventilation
				Synchronized intermittent mandatory ventilation
				Pressure support ventilation
			High-frequency ventilation
			Weaning²³
				Predicting successful weaning
				Techniques for weaning
		Positive end-expiratory pressure
			Intrinsic positive end-expiratory pressure
		Physiological effects of positive pressure ventilation
			Respiratory effects³³
				Distribution of ventilation
				Apparatus dead space
				Physiological dead space
				Lung volume
				Arterial po2
			Pulmonary neutrophil retention
			Valsalva effect
			Cardiovascular effects of positive pressure ventilation³⁵
				Cardiac output
				Oxygen delivery
				Arterial blood pressure
				Interpretation of vascular pressures
				Transmission of airway pressure to other intrathoracic structures
				Haemodynamic response in heart failure
			Renal effects⁴⁰
		Ventilator-induced lung injury⁴¹’⁴²
			Barotrauma
			Volutrauma
			Atelectrauma
			Biotrauma
			Prevention of ventilator-induced lung injury⁴¹
		Artificial ventilation for resuscitation
			Expired air ventilation
		Extrapulmonary gas exchange
			Factors in design
				Factors favouring performance
				Unfavourable factors
				Bubble oxygenators
				Membrane oxygenators
			Damage to blood
			Systems for extrapulmonary gas exchange
				Extracorporeal membrane oxygenation⁵⁶
				Extracorporeal carbon dioxide removal⁵⁷
				Intravascular oxygenators
			Clinical applications⁵⁹
				Neonates and infants
				Adults
		References
	33 Pulmonary surgery
		Keywords:
		Key points
		Physiological aspects of common interventions
			Bronchoscopy
				Flexible bronchoscopy¹
				Rigid bronchoscopy
			Thoracoscopy
			Thoracotomy
			Lung resection
				Assessing patient fitness for lung resection⁹
				Partial lung resection
				Pneumonectomy
			Surgery for emphysema
			Pleurodesis
		One-lung ventilation
			Lung isolation techniques
			Physiology of one-lung ventilation
				Patient position
				Open chest
				Perfusion of the nonventilated lung
			Management of one-lung ventilation
				Ventilation
				Management of the nonventilated lung
			Summary of the clinical management of one-lung ventilation
				Lung injury following one-lung ventilation⁴⁰
		Lung transplantation
			Clinical aspects⁴²’⁴³
				Indications
				Types of transplant
				Outcome following transplant
				Rejection
			Physiological effects of lung transplant
				Denervated lung
				Ventilation/perfusion relationships
				Mucociliary clearance
		References
	34 The atmosphere
		Keywords:
		Key points
		Evolution of the atmosphere
			Formation of the earth and the prebiotic atmosphere
			Significance of the mass of earth and its distance from sun
			Origin of life and the development of photosynthesis
			The appearance of oxygen in the atmosphere
			Biological consequences of an oxidizing environment
			Changes in carbon dioxide levels
			Carbon dioxide and the ice ages
			Recent changes in carbon dioxide levels
		The greenhouse effect
			Other greenhouse gases
		Turnover rates of atmospheric gases
		Oxygen, ozone and ultraviolet screening
		Evolution and adaptation
		References
	35 The history of respiratory physiology
		Keywords:
		Key points
		Ancient civilizations
			Egyptian physiology⁷
				Medical papyri
			Ancient greece
			Roman medicine and galen (129–199 bce)
				Galen’s system of physiology and anatomy
				Experiments on respiration
				The functions of breathing
				Galen’s legacy
			After galen
		The renaissance
			Leonardo da vinci (1452–1519)⁴’¹⁴
				Da vinci and the bronchial circulation
			Anatomy in the renaissance
				Pulmonary circulation²¹
		Experimental physiology in the 17th century
			Discoveries to assist the respiratory physiologists
				Circulation
				Atmospheric pressure4
				The microscope
			The oxford physiologists and the ‘use of breathing’¹’⁵’⁶
				Robert boyle (1627–1691)³⁰
				Robert hooke (1635–1702)³¹
				Richard lower (1631–1691)
				John mayow (1641–1679)⁴
			Physiology hibernates
		Chemistry and respiration
			Different types of air
				Phlogiston⁶
				Fixed air and vitiated air
				Dephlogisticated air
				Fire air
			Oxygen
		Early development of current ideas of respiratory physiology
			Tissue respiration
			Blood gases⁴⁰’⁴¹
				Partial pressure
				Haemoglobin and its dissociation curve
				The oxygen secretion controversy¹’⁴¹’⁵⁰
			Lung mechanics⁵⁹
				Elasticity and surfactant
				Lung volumes
			Control of ventilation
				Chemical control of breathing⁶³
		References
	Appendix A Physical quantities and units of measurement
		International system of units
			Volume (dimensions: L³)
			Fluid flow rate (dimensions: L³/T, or L³.T¯¹)
			Force (dimensions: MLT¯²)
			Pressure (dimensions: MLT¯²/L², Or ML¯¹T¯²)
			Compliance (dimensions: M¯¹L⁴T²)
			Resistance to fluid flow (dimensions: ML¯⁴T¯¹)
			Work (Dimensions: ML²T¯², Derived from MLT¯² × L OR ML¯¹T¯² × L³)
			Power (dimensions: ML²T–²/T OR ML²T¯³)
	Appendix B The gas laws
	Appendix C Conversion factors for gas volumes
		Conversion of gas volume—atps to btps
			Derivation of conversion factors
		Conversion of gas volume—atps to stpd
	Appendix D Symbols and abbreviations
		Reference
	Appendix E Mathematical functions relevant to respiratory physiology
		Linear function
			Examples
				Mathematical statement
				Graphical representation
		The rectangular hyperbola or inverse function
			Examples
				Mathematical statement
				Graphical representation
		The parabola or squared function
			Example
				Mathematical statement
				Graphical representation
		Exponential functions
			General statement
			The tear-away exponential function
				Simple statement
				Examples
				Mathematical statement
				Graphical representation
			The wash-out or die-away exponential function
				Simple statement
				Examples
				Mathematical statement
				Half-life
				Graphical representation
			The wash-in exponential function
				Simple statement
				Examples
				Mathematical statement
				Graphical representation
Index
	A
	B
	C
	D
	E
	F
	G
	H
	I
	J
	K
	L
	M
	N
	O
	P
	R
	S
	T
	U
	V
	W
	X
	Z
Inside back cover