2011 advanced respiratory critical care (oxford specialist handbooks in critical care) 1st edition 2011

Nik Hirani Senior Lecturer and Honorary Consultant in Respiratory Medicine Royal Infi rmary, Edinburgh, UK Consultant in Respiratory Medicine Scottish Pulmonary Vascular Unit, Golden

ADVANCED RESPIRATORY CRITICAL CARE

Advanced Respiratory Critical Care

General Oxford Specialist

Regional Anaesthesia, Stimulation

and Ultrasound Techniques

Thoracic Anaesthesia

Oxford Specialist Handbooks in

Cardiology

Adult Congenital Heart Disease

Cardiac Catheterization and

Pacemakers and ICDs

Oxford Specialist Handbooks in

Critical Care

Advanced Respiratory Critical Care

Oxford Specialist Handbooks in

End of Life Care

End of Life Care in Cardiology

End of Life Care in Dementia

End of Life Care in Nephrology

End of Life Care in Respiratory

Oxford Specialist Handbooks in Paediatrics

Paediatric Endocrinology and Diabetes

Paediatric DermatologyPaediatric Gastroenterology, Hepatology, and NutritionPaediatric Haematology and Oncology

Paediatric NephrologyPaediatric NeurologyPaediatric RadiologyPaediatric Respiratory Medicine

Oxford Specialist Handbooks in Psychiatry

Child and Adolescent PsychiatryOld Age Psychiatry

Oxford Specialist Handbooks in Radiology

Interventional RadiologyMusculoskeletal Imaging

Oxford Specialist Handbooks in Surgery

Cardiothoracic SurgeryHand SurgeryHepato-pancreatobiliary SurgeryOral Maxillo Facial SurgeryNeurosurgery

Operative Surgery, Second EditionOtolaryngology and Head and Neck Surgery

Plastic and Reconstructive SurgerySurgical Oncology

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Oxford Specialist Handbooks published and forthcoming

Handbooks in Critical Care

Advanced Respiratory Critical Care

1

1

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drug dosages in this book are correct Readers must therefore always check the

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Preface

Respiratory disease is the most common reason for admission to intensive

care, and advanced respiratory support is one of the most frequently used

interventions in critically ill patients A clear understanding of respiratory

disease is the cornerstone of high quality intensive care

Although a plethora of literature is available, both in print and online,

fi nding the necessary relevant information can be diffi cult and time

con-suming This handbook provides comprehensive clinical detail in an easily

readable format It is written by practising clinicians and has both in-depth

theoretical discussion and practical management advice

The book is divided into sections

Section 1 deals with the approach to the patient with respiratory

•

failure – including pathophysiology, investigation, and diagnosis

Section 2 covers non-invasive treatment modalities

•

Sections 3 and 4 examine invasive ventilation in detail Section 3

•

considers the principles of mechanical ventilation while section 4 deals

with individual ventilator modes

Section 5 discusses the management of the ventilated patient including

•

sedation, monitoring, asynchrony, heart – lung interaction, hypercapnia

and hypoxia, complications, weaning and extubation It also has

chapters on areas less frequently covered such as humidifi cation,

suction, tracheal tubes and principles of physiotherapy

Section 6 is a comprehensive breakdown of each respiratory condition

•

seen in ICU

This book is designed to bridge the gap between Intensive Care starter

texts and all-encompassing reference textbooks It is aimed at consultants

and senior trainees in Intensive Care Medicine, senior ICU nursing staff,

consultants in other specialties and allied healthcare professionals who

have an interest in advanced respiratory critical care

The editors would like to acknowledge Dr Rajkumar Rajendram,

Departments of General Medicine and Intensive Care, John Radcliffe

Hospital, Oxford, UK, as a reviewer

Acknowledgements

Contributors xi Symbols and abbreviations xvii

1 Approach to the patient with respiratory failure 1

2 Non-invasive treatment modalities 73

3 Invasive ventilation basics 101

4 Invasive ventilation modes 129

5 The ventilated patient 209

6 Treatment of specifi c diseases 369

Index 573

Contents

Consultant in Intensive Care and

Long Term Ventilation

Western General Hospital,

Southern General Hospital, Glasgow, UK

Luigi Camporota

Department of Adult Critical Care Medicine Guy’s and St Thomas’ NHS Foundation Trust, London, UK

Golden Jubilee National Hospital, Clydebank, UK

Julius Cranshaw

Consultant in Intensive Care Medicine and Anaesthesia Royal Bournemouth Hospital, Bournemouth, UK

Contributors

Brian Cuthbertson

Professor and Chief of

Depart-ment of Critical Care Medicine

Sunnybrook Health Sciences

Centre, Toronto, UK

James Dale

Clinical Research Fellow

Institute of Infection, Infl ammation

and Immunity, University of

Glasgow, UK

Dr Jonathan Dalzell

Clinical Research Fellow

British Heart Foundation

Cardiovascular Research Centre,

Consultant in Intensive Care

Medicine and Anaesthesia

Royal Alexandria Hospital, Paisley,

Institute of Infection, Infl ammation

and Immunity, University of

University of Manchester, UK

Andrew Foo

Registrar in Anaesthesia North Bristol NHS Trust, Bristol,

UK

Dimitris Georgopoulos

Professor of Medicine Intensive Care Medicine Department, University Hospital

of Heraklion, Crete, Greece

Dr Tim Gould

Consultant in Intensive Care Medicine and Anaesthesia Royal Infi rmary, Bristol, UK

Dr Duncan Gowans

Department of Haematology, Ninewells Hospital, Dundee, UK

Ian Grant

Consultant in Intensive Care Medicine and Long Term Ventilation

Western General Hospital, Edinburgh, UK

Dr David Halpin

Consultant in Respiratory Medicine

Royal Devon and Exeter Hospital, Exeter, UK

Nik Hirani

Senior Lecturer and Honorary

Consultant in Respiratory Medicine

Royal Infi rmary, Edinburgh, UK

Consultant in Respiratory Medicine

Scottish Pulmonary Vascular Unit,

Golden Jubilee National Hospital,

Clydebank, UK

Zuhal Karakurt

Sureyyepas‚a Chest Disease and

Thoracic Surgery Training and

Research Hospital, Istanbul, Turkey

William Kinnear

Consultant in Respiratory Medicine

Nottingham University Hospitals

NHS Trust, Nottingham, UK

John Kinsella

Professor of Critical Care,

Anaesthesia and Pain Medicine

Royal Infi rmary, Glasgow, UK

Pulmonary Vascular Fellow

Scottish Pulmonary Vascular Unit,

Golden Jubilee National Hospital,

Peter MacNaughton

Consultant in Intensive Care Derriford Hospital, Plymouth, UK

Institute of Infection, Infl ammation and Immunity, University of Glasgow, UK

Elizabeth McGrady

Consultant in Anaesthesia Royal Infi rmary, Glasgow, UK

Professor John McMurray

Professor of Medical Cardiology British Heart Foundation Cardiovascular Research Centre, University of Glasgow, UK

David Mucuha Muigai

Assistant Professor, Department

Critical Care Medicine, University

of Pittsburgh; Medical Director,

Magee Womens Hospital of

UPMC, Adult ICU, Pittsburgh PA,

Director of Respiratory and

Critical Care Unit

Sant'Orsola Malpighi University

Hospital, Bologna, Italy

Graham Nimmo

Consultant Physician in Intensive

Care Medicine and Clinical

Golden Jubilee National Hospital, Clydebank, UK

Mr Giles Peek

Consultant in Cardiothoracic Surgery and ECMO, Glenfi eld Hospital, Leicester, UK

Michael Pinsky

Vice Chair, Academic Affairs Professor of Critical Care Medicine, Bioengineering, Cardiovascular Disease and Anesthesiology

University of Pittsburgh, PA, USA

Giles Roditi

Consultant in Radiology Royal Infi rmary, Glasgow, UK

Dr Lucy Smyth

Consultant in Renal Medicine Royal Devon and Exeter Hospital, Exeter, UK

Rosemary Snaith

Registrar in Anaesthesia Royal Infi rmary, Glasgow, UK

Dr Mike Spivey

Registrar in Anaesthesia Royal Devon and Exeter Hospital, Exeter, UK

Honorary Professor, Edinburgh

University and Consultant in

AAA abdominal aortic aneurysm

AAFB alcohol–acid fast bacilli

A-aO 2

gradient alveolar-arterial oxygen gradient

ABG arterial blood gas

ACBT active cycle of breathing technique

ACE angiotensin converting enzyme

ACh acetylcholine

ACT activated clotting time

ACV assist control ventilation

AF atrial fi brillation

AIDS acquired immunodefi ciency syndrome

AIP acute interstitial pneumonia

AKI acute kidney injury

ALI acute lung injury

ANA antinuclear antibody

ANCA anti-neutrophil cytoplasmic antibody

AP antero-posterior

APACHE acute physiology and chronic health evaluation

APF alveolo-pleural fi stulae

APRV airway pressure release ventilation

ARDS acute respiratory distress syndrome

ARF acute respiratory failure

AST aspartamine transaminase

ASV adaptive support ventilation

ATC automatic tube compensation

ATLS advanced trauma life support

AVCO 2 R artero-venous carbon dioxide removal

AVM arteriovenous malformations

BAL bronchoalveolar lavage

BCG bacille Calmette-Guerin

BHL bilateral hilar lymphadenopathy

BiPAP bi-level positive airway pressure

BIPAP biphasic positive airways pressure

BIS bispectral index

Symbols and abbreviations

xviii SYMBOLS AND ABBREVIATIONS

BLS basic life support

BMI body mass index

BNP brain natriuretic peptide

BOOP bronchiolitis obliterans organizing pneumonia

BOS bronchiolitis obliterans syndrome

BPF broncho-pleural fi stula

bpm beats per minute

BTS British Thoracic Society

BYCER buffered yeast extract charcoal agar

CABG coronary artery bypass graft

CAM-ICU confusion assessment method for ICU

c-ANCA antineutrophilic cytoplasmic antibody

CAP community-acquired pneumonia

CAPS COPD and asthma physiology score

CC closing capacity

CCF congestive cardiac failure

CDM clinical decision making

CF cystic fi brosis

CFA cryptogenic fi brosing alveolitis

CHF chronic heart failure

CI cardiac index

CIM critical illness myopathy

CIP critical illness polyneuropathy

CIPM critical illness polyneuromyopathy

COP cryptogenic organizing pneumonia

COPD chronic obstructive pulmonary disease

CPAP continuous positive airway pressure

CPB cardiopulmonary bypass

CPG central pattern generator

CPIS clinical pulmonary infection score

CPO cardiogenic pulmonary oedema

CPR cardiopulmonary resuscitation

CROP compliance respiratory rate oxygenation and pressure

CRP C-reactive protein

CSF cerebrospinal fl uid

CSHT context sensitive half times

CT computerized tomography

CTPA CT pulmonary angiography

CUS compression ultrasonography

CVA cerebrovascular accident

CVP central venous pressure

CVS cardiovascular system

CVVH continuous veno-venous haemofi ltration

CXR chest X-ray

DAD diffuse alveolar damage

DBP diastolic blood pressure

DILD drug-induced lung disease

DIP desquamative interstitial pneumonia

DLCO diffusing capacity of the lung for carbon monoxide

DMARD disease-modifying antirheumatic drug

DMD Duchenne muscular dystrophy

DTPA diethylenetriaminepentaacetic acid

DVT deep vein thrombosis

EAA extrinsic allergic alveolitis

EAdi electrical activity of the diaphragm

EBUS endobronchial ultrasound

ECCO 2 R extra-corporeal CO 2 removal

ECG electrocardiogram

ECMO extracorporeal membrane oxygenation

ED emergency department

EELV end expiratory lung volume

EIT electrical impedance tomography

ELISA enzyme-linked immunosorbent assay

ELSO extracorporeal life support registry

EMG electromyogram

ENT ear, nose and throat

EPAP expiratory positive airways pressure

ESR erythrocyte sedimentation rate

ET endo-tracheal

ETT endotracheal tube

ETS expiratory trigger sensor

EVLW extravascular lung water

FA fl ow assist

FBC full blood count

FEV forced expiratory volume

xx SYMBOLS AND ABBREVIATIONS

FFP fresh frozen plasma

FOB fi breoptic bronchoscope

FRC functional residual capacity

FSH facioscapulohumeral

FVC forced vital capacity

GABA G -amino butyrate

GBM glomerular basement membrane

GCS Glasgow Coma Score

GCSF granulocyte macrophage colony-stimulating factor

GFR glomerular fi ltration rate

GGO ground glass opacity

GM-CSF granulocyte-macrophage colony-stimulating factor

GTN glyceryl trinitrate

HAART highly active antiretroviral therapy

HAFOE high air fl ow oxygen enrichment

HAP hospital-acquired pneumonia

Hb haemoglobin

HbA haemoglobin A

HbF foetal haemoglobin

HbO 2 oxyhaemoglobin

HbS sickle cell haemoglobin

HDU high-dependency unit

HELLP syndrome of haemolysis, elevated liver enzymes, low

platelets HFOV high frequency oscillatory ventilation

HH heated humidifi ers

HHb deoxyhaemoglobin

HHT hereditary haemorrhagic telangiectasia

HIV human immunodefi ciency virus

HME heat and moisture exchanger

HPV hypoxic pulmonary vasoconstriction

HR heart rate

HRCT high-resolution CT

HRQL health-related quality of life

HRT hormone replacement therapy

HSV herpes simplex virus

HWH heated water humidifi er

IABP intra-aortic balloon pumps

IBW ideal body weight

ICMs intercostal muscles

ICP intracranial pressure

ICU intensive care unit

I:E inspiratory:expiratory

ILD interstitial lung disease

IMV intermittent mandatory ventilation

INR international normalized ratio

IPAP inspiratory positive airway pressure

IPF idiopathic pulmonary fi brosis

IPPV intermittent positive pressure ventilation

IRV inverse ratio ventilation

ITP intrathoracic pressure

IVC inferior vena cava

IVIG intravenous immunoglobulin

JVP jugular venous pressure

KCO transfer coeffi cient for carbon monoxide

LDH lactate dehydrogenase

LFT liver function tests

LMWH low molecular weight heparin

LVAD left ventricular assist device

LVEDP left ventricular end diastolic pressure

LVF left ventricular failure

LVH left ventricular hypertrophy

MAP mean arterial pressure

MIGET multiple inert gas elimination technique

MIP maximal inspiratory pressure

MMF mycophenolate mofetil

MND motor neurone disease

MOF multi organ failure

xxii SYMBOLS AND ABBREVIATIONS

MPO myeloperoxidase

MRC medical research council

MRI magnetic resonance imaging

MRSA meticillin-resistant Staphylococcus aureus

MSSA meticillin-sensitive Staphylococcus aureus

MV minute volume

NAC N -acetyl cysteine

NAECC North American-European Consensus Conference

NAVA neurally adjusted ventilatory assist

NGT nasogastric tube

NICE National Institute for Health and Clinical Excellence

NIV non-invasive ventilation

NK natural killer

NMBA neuromuscular blockade agent

NNT number needed to treat

NPV negative pressure ventilation

NSAID non-steroidal anti-infl ammatory drug

NSIP non-specifi c interstitial pneumonia

NSTEMI non-ST-elevation myocardial infarction

nTe neural expiratory time

NT-proBNP N-terminal pro B type natriuretic peptide

NYHA New York Heart Association

OHS obesity hypoventilation syndrome

OLB open-lung biopsy

OSA obstructive sleep apnoea

PA postero-anterior

PACS picture archiving and communication systems

PaCO 2 arterial partial pressure of carbon dioxide

PAH pulmonary artery hypertension

p-ANCA antineutrophilic perinuclear antibody

PaO 2 arterial partial pressure of oxygen

PAO 2 alveolar partial pressure of oxygen

PAOP pulmonary artery occlusion pressure

PAS periodic acid-Schiff

PAV proportional assist ventilation

PAVM pulmonary arteriovenous malformations

PCI percutaneous coronary intervention

PCP Pneumocystis jirovecii pneumonia

PCR polymerase chain reaction

PCV pressure-controlled ventilation

PDE phosphodiesterase

PDT percutaneous dilational tracheostomy

PE pulmonary thromboembolism

PEEP positive end expiratory pressure

PEEP e extrinsic PEEP

PEEP i intrinsic PEEP

PEF peak expiratory fl ow

PEFR peak expiratory fl ow rate

P ES oesophageal pressure

PFT pulmonary function tests

PGE1 prostaglandin E1

PH pulmonary hypertension

PIFR peak inspiratory fl ow rate

PIP peak inspiratory pressure

pMDI pressurized metered dose inhaler

PMP polymethylpentene

PND paroxysmal nocturnal dyspnoea

PO 2 partial pressure of oxygen

PS pressure support

PSB protected specimen brush

PSG polysomnogram

PSI Pneumonia Severity Index

PSV pressure support ventilation

PTE pulmonary thromboembolism

PTI pressure time index

PTSD post-traumatic stress disorder

PVL Panton Valentine leukocidin

PVR pulmonary vascular resistance

RA right atrium

RACE repetitive alveolar collapse expansion

RBC red blood cell

RBILD respiratory bronchiolitis-associated interstitial lung

disease RCT randomized controlled trial

REM rapid eye movement

xxiv SYMBOLS AND ABBREVIATIONS

RR relative risk

RSBI rapid shallow breathing index

RSV respiratory syncytial virus

rv right ventricle

SAPS simplifi ed acute physiology score

SBD sleep-disordered breathing

SBP systolic blood pressure

SBT spontaneous breathing trial

SDD selective decontamination of the digestive tract

SIADH syndrome of inappropriate anti-diuretic hormone

SIMV synchronized intermittent mandatory ventilation

SIRS systemic infl ammatory response syndrome

SLB surgical lung biopsy

SLE systemic lupus erythematosis

SNIP sniff nasal inspiratory pressure

SOD selective oral decontamination

TBLB transbronchial lung biopsy

THAM tris-hydroxymethyl aminomethane

TLC total lung capacity

TPMT thiopurine methyltransferase

TSST toxic shock syndrome toxin

TTE trans-thoracic echocardiography

TV tidal volume

U+E urea and electrolytes

UIP usual interstitial pneumonia

VA volume assist

VALI ventilator associated lung injury

VAP ventilator-associated pneumonia

VAS visual analogue scale

VAT ventilator-associated tracheobronchitis

VATS video-assisted thoracic surgery

VC vital capacity

VCV volume controlled ventilation

VIDD ventilator-induced diaphragmatic dysfunction

VILI ventilator-induced lung injury

vTi ventilator inspiratory time

VTE venous thromboembolism

VZV Varicella zoster virus

WCC white cell count

WOB work of breathing

ZA zone of apposition

ZEEP zero PEEP

1.1 Respiratory physiology and pathophysiology 2

Dawn Fabbroni and Andrew Lamb1.2 Diagnosis of respiratory failure 22

Colin Church, Giles Roditi, and Steve Banham1.3 The microbiology laboratory 49

Marina Morgan1.4 Clinical decision making 64

Martin Hughes and Graham Nimmo1.5 Indications for ventilatory support 69

Rebecca Appelboam

Approach to the patient with respiratory failure

Section 1

1.1 Respiratory physiology and

pathophysiology

Control of breathing

Respiratory centre

The respiratory centre is located in the medulla It generates the

respi-ratory rhythm and co-ordinates voluntary and involuntary aspects of

breathing Functionally important components include the following

Central pattern generator

The central pattern generator (CPG) is where the respiratory rhythm

originates, with repetitive waves of activity in about six groups of

intercon-nected neurones, thus allowing multiple patterns of respiratory activity to

occur A system which involves groups of neurones, rather than a single

pacemaker cell, provides substantial physiological redundancy such that

respiration in some form is preserved even under extreme physiological

challenge Unfortunately the large number of neurotransmitters involved

in rhythm generation and modulation of the CPG also means that a wide

variety of pathological situations and pharmacological agents will affect

respiration

Afferent inputs to the respiratory centre

Central:

• Pontine respiratory group—not essential for ventilation but infl uences

fi ne control of respiration and co-ordinates the other central nervous

system (CNS) connections to the CPG

• Cerebral cortex—infl uences voluntary interruption in breathing

required for speech, singing, sniffi ng, coughing etc

Peripheral from the upper respiratory tract:

• Nasopharynx—water and irritants can cause apnoea, sneezing etc

Mechanoreceptors responding to negative pressure activate

pharyngeal dilator muscles; abnormalities of this refl ex are crucial

in sleep-disordered breathing

• Larynx—the supraglottic area receives sensory innervation from three

groups: mechanoreceptors (as for the pharynx), cold receptors on the

vocal folds that depress ventilation, and irritant receptors that cause

cough, laryngeal closure, and bronchoconstriction

From the lung:

• Slowly adapting stretch receptors are found in the airways and respond

to sustained lung infl ation

• Rapidly adapting stretch receptors occur in the superfi cial mucosal

layer and are stimulated by changes in tidal volume, respiratory rate, or

lung compliance

• C fi bre endings are closely related to capillaries in the bronchial

circulation and pulmonary microcirculation (J receptors) Stimulated by

pathological conditions and by noxious substances, tissue damage, and

accumulation of interstitial fl uid, they may be responsible for dyspnoea

associated with pulmonary vascular congestion or embolism

31.1 RESPIRATORY PHYSIOLOGY AND PATHOPHYSIOLOGY

Efferent output

Efferent pathways from the CPG go to separate inspiratory and expiratory

motor neurone pools located in the brainstem Arising from these are the

motor nerves for the pharyngeal dilator muscles, intercostals, diaphragm,

and expiratory muscles

Infl uence of CO 2

Central chemoreceptors are located in the anterior medulla, separate

from the respiratory centre Carbon dioxide, but not H + ions, pass across

the blood–brain barrier where carbonic anhydrase catalyses its hydration

into H + and HCO 3 – Central chemoreceptor neurones respond to a fall in

pH with a linear increase in minute ventilation

A compensatory shift in cerebrospinal fl uid (CSF) bicarbonate

con-centration occurs with chronic hyper- and hypocapnia, and is seen in

artifi cially ventilated patients The speed of pH compensation by the

bicarbonate shift depends on the extent of the arterial partial pressure

(PaCO 2 ) change and can take hours Artifi cially ventilated patients

that have been hyperventilated may continue to hyperventilate after

resuming spontaneous breathing because of this resetting of CSF pH by

a compensatory decrease in CSF bicarbonate Pathological states that

directly lower the CSF bicarbonate concentration and pH can result in

hyperventilation, for example following intracranial haemorrhage

Infl uence of O 2 and peripheral chemoreceptors

Peripheral chemoreceptors are located close to the bifurcation of the

common carotid artery and in the aortic bodies They have a high

per-fusion rate, much greater than their metabolic rate, and a small

arterio-venous PO 2 difference The glomus cell is the site of oxygen sensing, a

poorly understood process involving oxygen-sensitive voltage-gated

potassium channels and a variety of neurotransmitters and modulators

Features of the hypoxic ventilatory response include stimulation by:

• Decreased PaO 2 , not oxygen content, therefore there is no response

to anaemia, carboxyhaemoglobin or methaemoglobin

• Decreased pH or increased PaCO 2 —this response is only one-sixth of

the central chemoreceptor response but occurs very rapidly; may also

respond to cyclical oscillations in arterial PaCO 2 seen, for example, in

time with respiration during the hyperventilation of exercise or altitude

exposure

• Hypoperfusion (stagnant hypoxia) or raised temperature

Stimulation results in an increase in depth and rate of breathing,

brady-cardia, hypertension, increased bronchiolar tone, and adrenal stimulation

In response to sustained hypoxia, a series of ventilatory responses

occur:

• Acute hypoxia produces a rapid increase in the ventilatory rate within

a few seconds; with progressively severe hypoxia the increase in

ventilation is not linear, and forms a rectangular hyperbola

• The response curve is displaced upwards by hypercapnia and exercise,

and displaced downwards by hypocapnia

• After 5–10min of sustained hypoxia, hypoxic ventilatory decline occurs;

there is a reduction in ventilation until a plateau is reached, which is

still greater than the resting rate

• Both the acute response and hypoxic ventilatory decline are

less in poikilocapnic conditions when the hypocapnia induced by

hyperventilation partly counteracts the ventilatory effects of hypoxia

• With prolonged hypoxia there is a second slower rise in ventilation

rate for about 8h

Ventilation

Respiratory muscles

Numerous muscle groups are involved in changing lung volume Their

co-ordination by the medullary respiratory neurones and interaction with

each other are complex

• Upper airway muscles—pharyngeal dilator muscles contract both

tonically and phasically (with respiration) to prevent upper airway

collapse Minor abnormalities of this system result in airway collapse

by seemingly minor physiological challenges such as sleep or sedative

drugs Abduction and adduction of the posterior arytenoid muscles

control vocal fold position to retard expiration and reduce lower

airway collapse, in effect providing positive end expiratory pressure

(PEEP)

• Diaphragm—the most important respiratory muscle Contraction

of the diaphragm causes reduction in the zone of apposition (the

area around the outside of the diaphragm, which has direct contact

with the inside of the ribcage), thus increasing lung volume by a

‘piston-like’ action This is the most energy effi cient way of converting

diaphragm contraction into lung expansion, and is impaired either

by hyperexpanded lung or by raised intra-abdominal pressure

Contraction of the diaphragm also increases thoracic volume by

fl attening of the diaphragm dome and expansion of the lower ribcage

(Fig 1.1 )

• Ribcage muscles—three layers of intercostal muscles (ICMs) exist:

external, internal, and intercostalis intima Anteriorly the internal

ICMs become thicker to form the parasternal ICMs External ICMs

are primarily inspiratory and internal ICMs are mainly expiratory,

although these functions vary with posture Elevation of the ribs by the

ICMs results in a ‘bucket handle’ action to expand the chest wall while

elevation of the sternum by the sternomastoid and scalene muscles

results in a ‘pump handle’ action and opposes the upper ribs being

pulled inward during inspiration In vivo , these actions all occur together

in a co-ordinated fashion and are signifi cantly altered by posture

(see below) and respiratory pattern

51.1 RESPIRATORY PHYSIOLOGY AND PATHOPHYSIOLOGY

• Abdominal muscles—rectus abdominis, external oblique, internal

oblique, and transversalis muscle are mainly used in expiration

Contraction of these muscles increases intra-abdominal pressure,

resulting in cephalad displacement of the diaphragm Active

expiration occurs during stimulated breathing if the minute volume is

approximately >35L/min, or in the spontaneously breathing patient

under general anaesthetic

• Accessory muscles include the sternomastoids, pectoralis minor,

trapezius, extensors of the spine, and serrati muscles Inactive during

normal ventilation, these are employed with increasing respiratory rate

and tidal volume

Effect of posture

• Upright—associated with greater expansion of the ribcage Increased

activity in scalene muscles, and parasternal and external ICMs

• Supine—abdominal contents push the diaphragm cephalad, thus

reducing functional residual capacity (FRC) The diaphragmatic zone

of apposition (Fig 1.1 ) is increased in this position so the diaphragm

works effi ciently

• Lateral—the lower dome of the diaphragm is displaced cephalad so is

more effective than the upper dome Ventilation of the lower lung is

twice that of the upper, which matches the preferential perfusion to

the lower lung

Fig 1.1 Mechanisms of the respiratory actions of the diaphragm using a ‘piston

in a cylinder’ analogy (a) Resting end-expiratory position (b) Inspiration

showing ‘piston-like’ behaviour with shortening of the zone of apposition (ZA)

(c) Inspiration with fl attening of the diaphragm dome (d) Combination of

shortening of ZA, fl attening of the dome, and expansion of the ribcage, which

equates most closely with inspiration in vivo

Abdomen

• Prone—as in the supine position the diaphragm moves cephalad into

the chest In anaesthetized patients movement of non-dependent areas

of the diaphragm dominates Upper chest and pelvis need support to

allow free movement of the abdomen and chest

Pathophysiology of ventilatory failure

Ventilatory failure occurs when a patient cannot achieve the required

minute volume of alveolar ventilation There are many causes, conveniently

classifi ed as shown in Fig 1.2

• Respiratory centre neurones: stimulated by hypoxia or high PaCO 2

The response to PaCO 2 is blunted by anaesthesia and some drugs

Apnoea occurs if PaCO 2 falls below the apnoeic threshold in an

unconscious patient Chronic respiratory diseases may lead to a

reduction in the normal physiological response to hypercapnia Drugs,

particularly opioids and anaesthetic agents, may cause central apnoea

Neurological conditions, e.g cerebrovascular events, raised intracranial

pressure (ICP), or trauma may directly depress respiration

• Upper motor neurones: cervical spine trauma may affect nerves

supplying the respiratory muscles Demyelination, tumours, and

syringomyelia can involve upper motor neurones

• Anterior horn cells: may be affected by various diseases,

e.g poliomyelitis

• Lower motor neurones: may be affected by trauma and conditions such

as advanced motor neurone disease or Guillain–Barré syndrome

• Neuromuscular junction: routinely affected by neuromuscular blocking

agents in anaesthesia or pathologically by botulism, organophosphate

poisoning, nerve gas poisoning, or myasthenia gravis

• Respiratory muscle pathology: may develop fatigue through increased

work of breathing (WOB) Critical care patients commonly develop

polyneuropathy and myopathy of respiratory muscles as a result of

sepsis or prolonged disuse atrophy following a period of artifi cial

ventilation There is in vitro evidence indicating muscle fi bre atrophy

after only 18h of mechanical ventilation, and within days diaphragm

strength is substantially reduced

• Loss of lungs or chest wall elasticity: may occur within the lungs

(pulmonary fi brosis or lung injury), the pleura (empyema), chest wall

(kyphoscoliosis), or skin (contracted scars from burns)

• Loss of structural integrity of chest wall or pleural cavity: results

from multiple fractured ribs producing a fl ail segment, or from a

pneumothorax or pleural effusion

• Small airway resistance: the most common cause of ventilatory failure,

including asthma, chronic obstructive pulmonary disease (COPD), and

cystic fi brosis

• Upper airway obstruction: for example with airway and pharyngeal

tumours, infections, inhaled foreign bodies, and tumour or bleeding in

the neck

• Increased dead space: caused by ventilation of large areas of

unperfused lung, e.g pulmonary embolism or pulmonary hypotension

71.1 RESPIRATORY PHYSIOLOGY AND PATHOPHYSIOLOGY

Respiratory system mechanics

Lung movements depend on external forces, caused either by the

respira-tory muscles in spontaneous breathing or a pressure gradient produced

in artifi cial ventilation The response of the lung to these forces is

deter-mined by the impedence of the respiratory system, which comprises:

• Elastic resistance of the lung tissue and chest wall, and resistance from

the surface forces of the alveolar gas–liquid interface, which together

are referred to as compliance

• Non-elastic resistance, which includes frictional resistance to gas

fl ow through airways, deformation of thoracic tissue, and a negligible

component from inertia associated with movement of gas and tissue

Together these are referred to as respiratory system resistance

Fig 1.2 Sites at which lesions, drug action, or malfunction may result in ventilatory

failure (a) Respiratory centre (b) Upper motor neuron (c) Anterior horn cell

(d) Lower motor neuron (e) Neuromuscular junction (f) Respiratory muscles

(g) Altered elasticity of lungs or chest wall (h) Loss of structural integrity of chest

wall or pleura (i) Increased resistance of small airways (j) Upper airway

obstruc-tion Reproduced from Nunn’s Applied Respiratory Physiology by permission of the

author and publishers

a

b

cd

g

hij

Compliance

• Defi nition: change in lung volume per unit change in transmural

pressure gradient

• Includes components from the lung and thoracic cage

• Normal value for the whole respiratory system is 0.85L/kPa, for the

lungs only the value is 1.5L/kPa

• Elastance is the reciprocal of compliance

Lung recoil

The tendency of the lung to collapse is balanced against the outward recoil

of the thoracic cage In expiration, when no air is fl owing, the balance

between these forces determines the FRC

Recoil of the lung results from its inherent elasticity and surface

tension (ST) ST, not inherent elasticity, accounts for most of the lung

compliance The ST of alveolar lining fl uid is lower than that of water and

changes according to the size of the alveolus because of the presence of

surfactant

Alveolar surfactant

• Structure—composed of 90% lipids, mostly dipalmitoyl phosphatidyl

choline, and 10% proteins In the alveolus hydrophobic fatty acids lie in

parallel, projecting into the gas phase, with an opposite hydrophilic end

extending into alveolar lining fl uid

• Synthesised in type II alveolar epithelial cells Stored in lamellar bodies

and released by exocytosis in response to high-volume infl ation,

increased ventilation rate, or endocrine stimulation

• Alters the ST of alveoli as their size varies with inspiration and

expiration During expiration alveolar size decreases and surfactant

molecules become more closely packed together, possibly forming

multi-layered ‘rafts’, and exert a greater effect on ST This action is

controlled by the surfactant proteins, without which surfactant function

is poor

• Since the pulmonary capillary pressure in most of the lung is greater

than alveolar pressure it encourages transudation, which is opposed

by the oncotic pressure of plasma proteins By decreasing the ST,

surfactant reduces transudation

• Immunological—surfactant proteins have a variety of roles in the

defence of the lung from inhaled pathogens

Altered surfactant function contributes to pathological states, e.g acute

lung injury (ALI) Surfactant is diluted by alveolar oedema and inactivated

by infl ammatory proteins, and cyclical closure of airways during

expira-tion draws surfactant from the alveoli into small airways, contributing to

atelectrauma

Time dependence of pulmonary elasticity

If a lung is rapidly infl ated and then held at that volume for a few seconds

the infl ation pressure quickly falls to a lower level The extent to which

this occurs affects measurements of lung compliance and can vary in

dif-ferent regions of lung, resulting in ‘fast’ and ‘slow’ alveoli and less than

ideal V·/Q· ratios (see below)

91.1 RESPIRATORY PHYSIOLOGY AND PATHOPHYSIOLOGY

Causes of time dependency include:

• Changes in surfactant activity—the ST in alveoli is greater at larger lung

volumes

• Stress relaxation—if any elastic material is stretched to a fi xed length

it produces maximal tension and then declines exponentially to a

constant value

• Redistribution of gas—different parts of the lung have different time

constants

• Recruitment of alveoli—some alveoli close at low lung volume; this is

rare during normal breathing but occurs more easily in injured lungs

A much higher transmural pressure is needed to reopen them

This time dependence may be assessed by the difference between static

and dynamic compliance

Static compliance is measured by inhalation of a range of known volumes

of air from FRC and then allowing the patient to relax against a closed

airway for a few seconds before the airway pressure is measured (relative

to atmospheric) The volumes and pressures obtained are used to derive a

compliance curve for the respiratory system (including lungs and thoracic

cage)

Dynamic compliance is measured during rhythmical breathing, but

calculated from measurements of pressure and volume made when

there is no gas fl owing, i.e at end-inspiration and end-expiration Many

ventilators are able to produce pressure–volume loops and dynamic

compliance can be displayed with each breath

Factors affecting lung compliance:

• Lung volume: larger alveoli have higher compliance

• Posture: lung volume and therefore compliance changes with posture

• Pulmonary blood fl ow: venous congestion will decrease compliance

• Recent ventilation: hypoventilation may cause reduced compliance due

to formation of atelectasis

• Bronchial smooth muscle tone: bronchoconstriction may enhance time

dependence

• Disease: almost any lung disease will reduce lung compliance, either by

affecting the elasticity of lung tissue or by impairing surfactant function

Thoracic cage compliance

This includes compliance of the ribcage and diaphragm

• Defi ned as change in lung volume per unit change in the pressure

gradient between atmosphere and intrapleural space

• Measured as described above but using intrapleural pressure (from an

oesophageal balloon) rather than airway pressure

• The diaphragm maintains some tone at end-expiration to prevent the

abdominal contents pushing up into the thoracic cavity, which makes

measurement diffi cult in a conscious patient

• May be increased due to increased abdominal pressure, obesity, or

from ossifi cation of costal cartilages or chest wall scarring

A reciprocal relationship exists between respiratory system compliance

and its components:

Respiratory system resistance

Respiratory system resistance has two components

Tissue resistance

This is resistance caused by the deformation of lung and chest wall tissue

during breathing It includes the time-dependent element of elastance

(see above): when the volume is changed there is initial resistance as

tissue deformation occurs, but if infl ation is held for a few seconds the

elastance is reduced

Airway resistance

This is the most important cause of respiratory system resistance in

clin-ical practice and results from frictional resistance to gas fl ow within the

airways In healthy lungs the small airways contribute very little to total

airway resistance because of their large combined cross-sectional area, so

resistance is predominantly from larger airways Gas fl ow within the lungs

is a complex mixture of laminar and turbulent fl ow

Turbulent fl ow occurs in conducting airways where gas velocity is high:

• Flow is therefore signifi cantly infl uenced by the airway lining, e.g mucus

consistency

• The turbulent fl ow increases the effi ciency of humidifi cation by mixing

the inspired gas with the water vapour from the airway lining fl uid

• Helium gas mixtures (low Reynolds number, low viscosity) are of more

benefi t in overcoming resistance in large airways than small airways

Heliox has been used to treat acute asthmatic patients, perhaps

because fl ow within narrowed, infl amed airways becomes turbulent

Laminar fl ow normally occurs at around the 11th airway generation

because:

• The velocity of gas fl ow decreases with successive airway generations

• In small airways the entrance length (distance required for laminar fl ow

to become established) becomes short enough for laminar fl ow to

develop before the next airway division

Factors affecting respiratory resistance

Lung volume infl uences airway resistance As lung volume is reduced all

air containing components, including conducting airways, reduce in size

and therefore resistance increases At low lung volumes or during a rapid

expiration airway collapse occurs and may result in gas becoming trapped

distally This causes an increase in FRC and residual volume Use of

con-tinuous positive airway pressure (CPAP) or PEEP helps to prevent this

by increasing the transmural pressure gradient, reducing airway resistance

and preventing airway collapse and gas trapping

total compliance=lung compliance=thoracic cage complian

cecc

111.1 RESPIRATORY PHYSIOLOGY AND PATHOPHYSIOLOGY

Active physiological control of airway resistance occurs in the small

airways where bronchial smooth muscle is under the infl uence of several

systems:

• Neural:

• Parasympathetic system via the vagus nerve—important in control

of bronchomotor tone in humans Afferent nerves respond

to noxious stimuli or cytokines, and efferent nerves release acetylcholine (ACh) which acts on M3 muscarinic receptors to cause bronchoconstriction

• Sympathetic—minimal role in humans

• Non-adrenergic non-cholinergic system Nerve fi bres also in the vagus nerve Neurotransmitter is vasoactive intestinal peptide that produces smooth muscle relaxation by production of NO

• Humoral:

• β2-adrenergic receptors responsive to circulating adrenaline

• Local:

• Mechanical stimulation by laryngoscopy, foreign bodies, or aerosols

can cause bronchoconstriction

• Airway irritants, including air pollutants such as nitrogen dioxide and

ozone, can produce bronchoconstriction

• Infl ammatory mediators produce bronchoconstriction directly or by

amplifying the physiological systems above

Physiological response to increased resistance

• Inspiratory resistance: There is an immediate response detected by

understretched muscle spindles, resulting in enhanced inspiratory

muscle effort and little change in FRC With prolonged and severe

increased resistance a second compensation occurs over a few

minutes, resulting from hypercapnia

• Expiratory resistance: Expiration against a positive airway pressure of

up to 10 cm H2O does not cause any extra activation of expiratory

muscles Instead an increased respiratory force is produced to achieve

a larger FRC with suffi cient elastic recoil to overcome the expiratory

resistance

Intrinsic PEEP

If expiration is terminated early, before the lung volume has reached FRC,

there will be residual alveolar pressure, termed intrinsic PEEP (PEEPi)

or auto-PEEP This is most commonly seen with artifi cial ventilation,

increased expiratory fl ow resistance, or mucus retention Alveolar

pres-sures will rise with increased lung volumes and reduced lung compliance

Detrimental haemodynamic effects may also occur as a result of high

alveolar pressure

Pathophysiology of lung mechanics

Restrictive disease

These conditions result in reduced lung volumes (total lung capacity and

vital capacity) because of either:

• Disease of lung parenchyma characterized by infl ammation, scarring,

and exudate-fi lled alveoli (e.g pulmonary fi brosis)

• Disease of the chest wall or pleura, resulting in lung restriction,

impaired ventilatory function, and respiratory failure (e.g kyphoscoliosis)

by reduction in the total compliance of the respiratory system

Compensatory mechanisms include hyperventilation to maintain minute

ventilation with smaller lung volumes

Obstructive disease

In pathological states small airways obstruction is most important In

asthma, the increase in resistance is mostly due to airway mucosal infl

am-mation and contraction of airway smooth muscle due to an exaggerated

physiological response, both of which are quickly reversible In COPD,

damage to lung parenchyma, usually from smoking and repeated

infec-tions, causes a loss of lung elastin, so reducing the diameter of small

airways that lack the intrinsic structural strength seen in larger airways

In either asthma or COPD long-term airway disease leads to remodelling

of the airway smooth muscle and mucosal cells, resulting in a thickened

mucosa and dense, incompliant musculature, giving rise to irreversible loss

of lung function

Pulmonary circulation

The lungs receive the entire blood volume but unlike the systemic

circula-tion the pulmonary circulacircula-tion is a low-pressure system because:

• Pulmonary arteries and arterioles contain only a small amount of

smooth muscle compared with systemic vessels

• Pulmonary capillary networks surround alveoli to produce sheet-like

blood fl ow to maximize the surface area for gas exchange

• With resting cardiac output pulmonary capillaries in non-dependent

areas of the lung have little or no blood fl ow and can be ‘recruited’ if

cardiac output increases

• Pulmonary capillaries are distensible vessels, easily doubling in diameter

to accommodate large increases in fl ow with little change in driving

pressure

Pulmonary vascular resistance

pulmonary vascular resistance = pulmonary driving pressure/cardiac output

• The relationship is not linear due to fl ow being a mixture of laminar

and turbulent forms

• Increased blood fl ow only results in small increases in pulmonary

arterial pressure due to the mechanisms described above

• Changes in lung volume affect pulmonary vascular resistance, which is

minimal at FRC Alveolar capillaries lie between adjacent alveoli and

so are compressed when lung volume increases At low lung volumes

capillaries may lose support from septal tissue and collapse

Extra-alveolar vessels may be compressed in dependent lung areas at low

volumes

131.1 RESPIRATORY PHYSIOLOGY AND PATHOPHYSIOLOGY

Pulmonary blood fl ow

This is affected by:

• Posture—in the upright position pulmonary blood volume decreases

by a third as a result of blood pooling in dependent regions of the

systemic circulation In the upright position hydrostatic pressure

signifi cantly affects blood fl ow as there may be a 20mmHg difference in

vascular pressure between apex and lung bases

• Alveolar pressure—pulmonary capillary blood fl ow and vessel

patency depend on both vascular and alveolar pressures, and lungs are

traditionally divided into three zones:

• Zone 1—P alveolus > P artery > P venous : no blood fl ow and therefore alveolar dead space

• Zone 2—P artery > P alveolus > P venous : blood fl ow depends on the difference between arterial and alveolar pressure; venous pressure has no infl uence

• Zone 3—P artery > P venous > P alveolus : blood fl ow depends only on arterio-venous pressure difference

• Systemic vascular tone—the systemic vascular system has greater

vasomotor activity so blood is diverted into the pulmonary circulation

when vasoconstriction occurs and vice versa

• Left heart failure—pulmonary venous hypertension is likely to increase

pulmonary blood volume and reduce fl ow in all three zones

• Positive pressure ventilation increases alveolar pressure, changing

zone 3 areas into zone 2, and also reduces venous return, reducing

global cardiac output

Hypoxic pulmonary vasoconstriction

This refl ex occurs in response to regional hypoxia in the lung, and is

believed to optimize V·/Q· matching by diverting pulmonary blood fl ow

away from areas of low oxygen tension Alveolar PO 2 has a greater infl

u-ence than mixed venous (pulmonary arterial) PO 2 , although both

con-tribute The refl ex occurs within a few seconds of the onset of hypoxia,

with constriction of small arterioles With prolonged hypoxia the refl ex

is biphasic, with the initial rapid response being maximal after 5–10min

and followed by a second phase of vasoconstriction, occurring gradually

and reaching a plateau after 40min Hypoxic pulmonary vasoconstriction

is patchy in its onset even in healthy individuals exposed to global alveolar

hypoxia At high altitude the response also may be highly variable between

individuals, explaining why some patients develop pulmonary

hyperten-sion with respiratory disease and some do not

Mechanism of hypoxic pulmonary vasoconstriction

This is not fully elucidated There is likely to be a direct action on smooth

muscle and an indirect effect on endothelium-dependent systems

Proposed components include the following:

• Hypoxia may have a direct effect on pulmonary vascular smooth

muscle by altering the membrane potential, affecting potassium

channels, which in turn activate voltage-gated calcium channels to

produce contraction

• Inhibition of endothelial nitric oxide (NO) by hypoxia to produce

vasoconstriction, although NO is more likely to modulate the response

rather than initiate it

• Cyclooxygenase activity is inhibited by hypoxia and promotes

vasodilatory action by, for example, prostacyclin; this may also be a

modulatory effect

• Hypoxia promotes production of endothelin, a vasoconstrictor

peptide, and this is accepted as being responsible for the second,

slower phase of the response

Pulmonary hypertension

This can be both primary and secondary Secondary is more common

This is also discussed in b Pulmonary vascular disease, p 541

Primary pulmonary hypertension

This condition occurs in the absence of hypoxia and has a strong familial

association and a poor prognosis It is characterized by remodelling of the

pulmonary arterioles (proliferation of endothelial cells and smooth muscle

hypertrophy) and pulmonary vessel thrombosis Treatments include

pul-monary vasodilator drugs (oral or intravenous prostacyclin analogues or

oral endothelin antagonists) and ultimately lung transplantation

Secondary pulmonary hypertension

Chronic or intermittent hypoxic pulmonary vasoconstriction can lead to

pulmonary hypertension by remodelling of the pulmonary vascular smooth

muscle, producing irreversible increases in vascular resistance The

condi-tion may occur with any disease that results in long-term hypoxia It is also

caused by several other conditions

V·/Q· relationships

Ventilation and perfusion are both preferentially distributed to dependent

areas of the lung, partly as a result of gravity, and are therefore affected

by posture

Distribution of ventilation

The right lung is slightly larger so usually has 60% of total ventilation in

either upright or supine positions When lateral, the lower lung is always

better ventilated but perfusion also preferentially goes to the lower lung

and V·/Q· matching is maintained

Within each lung, regional ventilation is affected by gravity—lung

tissue has weight, so alveoli in dependent areas become compressed In

the upright position alveoli at the lung apices will be almost fully infl ated

while those at the bases will be small On inspiration the capacity of

alveoli in non-dependent regions to expand is therefore limited, and

regional ventilation increases with vertical distance down the lung This

variation in alveolar size causes regional differences in lung compliance

In a microgravity environment, where the lung has no weight, regional

variation in ventilation disappears almost completely

The ability of a lung region to ventilate may be quantifi ed by considering

its time constant This is the product of compliance and airway resistance,

151.1 RESPIRATORY PHYSIOLOGY AND PATHOPHYSIOLOGY

and is a measure of the time that would be required for infl ation of the

lung region if the initial fl ow rate of gas were maintained throughout

infl ation

Within the lung there are ‘fast alveoli’ with short time constants and

‘slow alveoli’ with long time constants If the time constants are identical

as the lung is infl ated the pressure and volume changes will be identical so

if inspiration stops there will be no redistribution of gas The distribution

is also independent of the rate, duration, or frequency of inspiration

However, if there are regions with different time constants within an

area of the lung, gas distribution will be affected by the rate, duration,

and frequency of inspiration At the termination of gas fl ow there will

be redistribution of gas because pressure and volume changes will be

different between lung regions

Distribution of perfusion

The pulmonary circulation is a lowpressure system and posture signifi

-cantly alters blood distribution

• Blood fl ow increases on descending down the lung, with minimal

perfusion in non-dependent areas, particularly in the upright position

• Lung perfusion per alveolus is reasonably uniform at normal tidal

volumes The dependent parts of the lung contain larger numbers of

smaller alveoli than the apices at FRC, therefore perfusion per unit of

lung volume is increased at the bases

• When supine or prone the same perfusion differences occur between

the anterior and posterior regions of the lung Blood fl ow per unit lung

volume increases by about 11% per centimetre of descent Ventilation

increases less so, resulting in a smaller V·/Q· ratio in dependent areas

It is now accepted that gravity is not the only factor affecting regional

blood fl ow and may only account for 10–40% of regional blood fl ow

vari-ability Pulmonary blood fl ow also varies in a radial fashion, with greater

fl ow to central than peripheral lung regions in each horizontal slice This

results simply from the branching pattern of the pulmonary vasculature

V·/Q· ratios

For both lungs considered together V·/Q· ratio = 0.8 (4L/min alveolar

ven-tilation, 5L/min pulmonary blood fl ow) As already described, ventilation

and perfusion are not uniform throughout the lung and within different

lung regions there is a spectrum of V·/Q· ratios from unventilated alveoli

(V·/Q· = 0) to unperfused alveoli (V·/Q· = ∞) and all ratios in between

The simplest way of understanding V·/Q· ratios is the Riley

three-compartment model, which considers the lungs as only having three

regions (Fig 1.3 ):

1 ‘Ideal’ alveoli with a V·/Q· ratio of 1—blood leaving these regions has

PO 2 and PCO 2 values the same as for alveolar gas

2 Alveoli with no ventilation (V·/Q· ratio of 0), which constitutes an

intrapulmonary shunt PO 2 and PCO 2 values leaving these regions are

the same as for mixed venous blood

3 Alveoli with no perfusion (V·/Q· ratio of ∞), which constitutes alveolar

dead space Gas leaving these alveoli has the same composition as

inspired gas

There are of course infi nitely more compartments than this, but the

three-compartment model is useful for understanding the clinically relevant

con-cepts of shunt and dead space

middle alveolus (1 in the text) has the ‘ideal’ ventilaton and perfusion (V·/Q· = 1);

the upper alveolus (3) is ventilated but not perfused (V·/Q· = ∞) so forms alveolar

dead space; the lower alveolus (2) is perfused but not ventilated (V·/Q· = 0) and is an

intrapulmonary shunt In reality a wide range of V·/Q· ratios exist

Mixedvenous

Although not used in clinical practice, the multiple inert gas elimination

technique (MIGET) allows assessment of the wide range of V·/Q· ratios

seen in the lungs Several compounds of widely different solubility are

administered intravenously and their elimination in exhaled air measured

This allows a graph to be drawn showing the distribution of V·/Q· not

by anatomical location but by a large number of compartments of

different V·/Q· ratio (Fig 1.4 ), which gives a more realistic picture of V·/Q·

ratios in vivo

171.1 RESPIRATORY PHYSIOLOGY AND PATHOPHYSIOLOGY

Effect of V · /Q · ratios on gas exchange

Areas of lung with high V·/Q· ratios (between 1 and ∞) have more

ven-tilation than is required for gas exchange with the blood perfusing that

region Gas in these alveoli will therefore have lower PCO 2 and higher

PO 2 values than ideal alveolar gas, and these values will trend towards

those of inspired gas as the V·/Q· ratio increases These regions contribute

to alveolar dead space CO 2 transfer from blood to alveolus will be

increased because of the lower alveolar PCO 2 , and the blood will be fully

oxygenated

Areas of lung with low V·/Q· ratios (between 1 and 0) have less ventilation

than is required for the blood fl ow In these alveoli the PCO 2 will be

higher and the PO 2 lower than in ideal alveolar gas, and these values will

trend towards those of mixed venous blood with decreasing V·/Q· ratio

CO 2 transfer between blood and alveolus will be reduced Blood passing

through these lung regions will not become fully oxygenated and when

this mixes with blood from the rest of the lung arterial hypoxaemia occurs

with an increase in the alveolar–arterial PO 2 gradient In contrast to the

compensation that occurs with increased CO 2 elimination elsewhere

in the lung when dead space exists, there is no such mechanism for

oxygenation as the lung regions with normal or high V·/Q· ratios cannot

carry extra oxygen because the haemoglobin is already fully saturated

Shunt

Admixture of arterial blood with poorly oxygenated or mixed venous

blood is the most important cause of arterial hypoxaemia

elimi-nation technique (a) Normal pattern from a healthy 22-year-old subject, with all

lung regions having V·/Q· ratios in the range 0.3–3.0 (b) Increased scatter of V·/Q·

ratios such as may occur in older subjects or in younger patients during general

anaesthesia Note that the overall V·/Q· ratio remains normal at 0.8, but the areas of

low and high V·/Q· ratio will impair gas exchange (c) patient with COPD with areas

of low V·/Q· ratio that will cause venous admixture and hypoxaemia

Ventilation/perfusion ratio

Ventilation Blood flow

10.0 3.0 1.0 0.3 0.1 0.03 0.01 0

(a)

Blood flow

10.0 3.0 1.0 0.3 0.1 0.03 0.01 0

(b)

Ventilation

Blood flow

10.0 3.0 1.0 0.3 0.1 0.03 0.01 0 (c)

Types of true shunt include:

• Intrapulmonary shunt: perfusion through lung regions with V·/Q· ratio

of 0, i.e lung regions with non-ventilated alveoli such as atelectasis,

pneumonia, or pulmonary oedema

• Anatomical (extrapulmonary) shunt: blood that passes from the right

side of the circulation to the left without traversing the lung May be

physiological, including bronchial veins, Thebesian veins (small veins

of the left side of the heart), or pathological, usually from cyanotic

congenital heart disease

Venous admixture, often loosely termed shunt, is the degree of admixture

of mixed venous blood with pulmonary end-capillary blood that would

be required to produce the observed difference between the arterial and

pulmonary end-capillary PO 2 It is the calculated percentage of cardiac

output required to result in the observed blood gases, and includes the

effects of true shunt as described above along with a contribution from

perfusion of lung regions with V·/Q· ratio less than 1 but greater than 0 (see

above) The amount of venous admixture seen in lung disease is variable

and depends on the balance between hypoxic pulmonary vasoconstriction

(HPV) and pathological pulmonary vasodilatation

Effect of cardiac output on shunt

Within a few minutes a reduced cardiac output leads to a decrease in

mixed venous oxygen content, so even if the shunt fraction remains

unaltered there will be a greater reduction in arterial PO 2 However, a

reduction in cardiac output is also believed to reduce the shunt fraction,

possibly by activation of HPV due to the reduced mixed venous PO 2 As

a result arterial PO 2 may be unaffected by reduced cardiac output In an

extrapulmonary shunt, such as seen in cyanotic congenital heart disease,

this latter effect reduces shunt fraction, and arterial PO 2 becomes highly

dependent on adequate cardiac output

Dead space

This is the part of tidal volume that does not take part in gas exchange and

is therefore exhaled unchanged The part of the tidal volume involved in

ventilation is the alveolar ventilation:

alveolar ventilation = respiratory frequency × (tidal volume – dead

It is alveolar ventilation that determines the arterial PCO 2 , so in a

hyper-capnic patient all three terms on the right of this equation must be

consid-ered: dead space is often overlooked in the clinical setting

Components of dead space include:

• Apparatus dead space, including face mask, breathing circuit connectors

etc

• Anatomical—the volume of air contained in the conducting airways

(150mL approximately in normal subjects) Anatomical dead space

is affected by subject size, age, posture, neck and jaw position,

lung volume, presence of airway devices, endotracheal tubes or

tracheostomy, bronchodilators, tidal volume, and respiratory rate

• Alveolar—this is the part of tidal volume that passes through

the anatomical dead space to lung regions with V·/Q· ratios greater