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

ADVANCED
RESPIRATORY
CRITICAL CARE


OXFORD MEDICAL PUBLICATIONS

Advanced
Respiratory Critical
Care


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Oxford Specialist
Handbooks in
Critical Care

Advanced
Respiratory
Critical Care
Edited by

Martin Hughes
Consultant in Intensive Care Medicine
Royal Infirmary, Glasgow, UK

Roland Black
Consultant in Intensive Care Medicine
Royal Devon and Exeter Hospital
Exeter, UK

1


1
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and recommendations are for the non-pregnant adult who is not breast-feeding.


v

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,
finding the necessary relevant information can be difficult and time consuming. 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 humidification,
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.


vii

Acknowledgements
The editors would like to acknowledge Dr Rajkumar Rajendram,
Departments of General Medicine and Intensive Care, John Radcliffe
Hospital, Oxford, UK, as a reviewer


ix

Contents
Contributors xi
Symbols and abbreviations xvii
1
2
3
4
5
6

Approach to the patient with respiratory failure
Non-invasive treatment modalities
Invasive ventilation basics
Invasive ventilation modes
The ventilated patient
Treatment of specific diseases
Index 573

1
73
101
129
209
369


xi

Contributors
Rebecca Appelboam

Kevin Blyth

Consultant in Intensive Care
Medicine
Derriford Hospital, Plymouth, UK

Consultant in Respiratory
Medicine
Southern General Hospital,
Glasgow, UK

Hugh Bakere
Consultant in Respiratory
Medicine
Royal Devon and Exeter Hospital,
Exeter, UK

Malcolm Booth

Steve Banham

Chris Cairns

Consultant in Respiratory
Medicine
Gartnavel General Hospital,
Glasgow, UK

Consultant in Intensive Care
Medicine
Royal Infirmary, Stirling, UK

Anthony Bateman

Registrar in Anaesthesia
Royal Infirmary, Glasgow, UK

Consultant in Intensive Care and
Long Term Ventilation
Western General Hospital,
Edinburgh, UK

Catherine Bateman
Consultant Physician
United Bristol Hospitals NHS
Trust, Bristol, UK

Geoff Bellingan
Medical Director, Surgery and
Cancer Board
University College Hospital,
London, UK

Consultant in Intensive Care
Medicine
Royal Infirmary, Glasgow, UK

Alyson Calder

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

Colin Church
Research fellow in Respiratory
Medicine
Gartnavel General Hospital,
Glasgow, UK

Ian Colquhoun

Consultant in Intensive Care
Medicine
Western Infirmary, Glasgow, UK

Consultant Cardiothoracic
Surgeon
Golden Jubilee
National Hospital,
Clydebank, UK

Roland Black

Julius Cranshaw

Consultant in Intensive Care
Medicine
Royal Devon and Exeter Hospital,
Exeter, UK

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

Alexander Binning


xii

CONTRIBUTORS

Brian Cuthbertson

Timothy Felton

Professor and Chief of Department of Critical Care Medicine
Sunnybrook Health Sciences
Centre, Toronto, UK

Clinical Research Training Fellow,
Respiratory and Intensive Care
Medicine
University of Manchester, UK

James Dale

Andrew Foo

Clinical Research Fellow
Institute of Infection, Inflammation
and Immunity, University of
Glasgow, UK

Registrar in Anaesthesia
North Bristol NHS Trust, Bristol,
UK

Dr Jonathan Dalzell

Professor of Medicine
Intensive Care Medicine
Department, University Hospital
of Heraklion, Crete, Greece

Clinical Research Fellow
British Heart Foundation
Cardiovascular Research Centre,
University of Glasgow, UK

Christopher Day
Consultant in Intensive Care
Medicine,
Royal Devon and Exeter Hospital,
Exeter, UK

Brian Digby
Consultant in Intensive Care
Medicine and Anaesthesia
Royal Alexandria Hospital, Paisley,
UK

Graham Douglas
Consultant Physician
Chest Clinic, Royal Infirmary,
Aberdeen, UK

Dr Alasdair Dow

Dimitris Georgopoulos

Dr Tim Gould
Consultant in Intensive Care
Medicine and Anaesthesia
Royal Infirmary, 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

John Griffiths

Consultant in Intensive Care
Medicine
Royal Devon and Exeter Hospital,
Exeter, UK

Consultant and Honorary Senior
Lecturer
Nuffield Department of
Anaesthetics, John Radcliffe
Hospital, Oxford, UK

Tom Evans

Dr David Halpin

Professor of Molecular
Microbiology
Institute of Infection, Inflammation
and Immunity, University of
Glasgow, UK

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

Dawn Fabbroni

Consultant in Intensive Care
Medicine
Royal Infirmary, Stirling, UK

Consultant in Anaesthesia
Bradford Royal Infirmary,
Bradford, UK

Martyn Hawkins


CONTRIBUTORS

Nik Hirani

Andrew Lockwood

Senior Lecturer and Honorary
Consultant in Respiratory Medicine
Royal Infirmary, Edinburgh, UK

Team Leader in Critical Care
Physiotherapy
Royal Devon and Exeter Hospital,
Exeter, UK

Martin Hughes
Consultant in Intensive Care
Medicine
Royal Infirmary, Glasgow, UK

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

Martin Johnson
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

Andrew Lumb
Consultant in Anaesthesia
St James's University Hospital,
Leeds, UK

Andrew MacDuff
Registrar in Respiratory and
Critical Care Medicine
Western General Hospital,
Edinburgh, UK

Peter MacNaughton
Consultant in Intensive Care
Derriford Hospital,
Plymouth, UK

Paul McConnell
Consultant in Intensive Care
Medicine
Crosshouse Hospital, Kilmarnock,
UK

Iain McInnes

Professor of Critical Care,
Anaesthesia and Pain Medicine
Royal Infirmary, Glasgow, UK

Director and Professor of
Experimental Medicine and
Rheumatology
Institute of Infection, Inflammation
and Immunity, University of
Glasgow, UK

Maria Klimathianaki

Elizabeth McGrady

Department of Intensive Care
Medicine
University Hospital of Heraklion,
Crete, Greece

Consultant in Anaesthesia
Royal Infirmary, Glasgow, UK

John Kinsella

Eumorfia Kondili
Department of Intensive Care
Medicine
University Hospital of Heraklion,
Crete, Greece

Nicola Lee
Pulmonary Vascular Fellow
Scottish Pulmonary Vascular Unit,
Golden Jubilee National Hospital,
Clydebank, UK

Stuart McLellan
Consultant in Intensive Care
Medicine
Western General Hospital,
Edinburgh, UK

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

xiii


xiv

CONTRIBUTORS

Dr Nick Maskell

Derek Paul

Senior Lecturer and Honorary
Consultant in Respiratory
Medicine
University of Bristol, UK

Consultant in Cardiothoracic
Anaesthesia
Golden Jubilee National Hospital,
Clydebank, UK

Dr Marina Morgan

Mr Giles Peek

Consultant in Medical
Microbiology
Royal Devon and Exeter Hospital,
Exeter, UK

Consultant in Cardiothoracic
Surgery and ECMO,
Glenfield Hospital, Leicester, UK

David Mucuha Muigai

Vice Chair, Academic Affairs
Professor of Critical Care
Medicine, Bioengineering,
Cardiovascular Disease and
Anesthesiology
University of Pittsburgh, PA, USA

Assistant Professor, Department
Critical Care Medicine, University
of Pittsburgh; Medical Director,
Magee Womens Hospital of
UPMC, Adult ICU, Pittsburgh PA,
USA

Dr Julia Munn
Consultant in Intensive Care
Medicine
Royal Devon and Exeter Hospital,
Exeter, UK

Stephano Nava
Director of Respiratory and
Critical Care Unit
Sant'Orsola Malpighi University
Hospital, Bologna, Italy

Graham Nimmo

Michael Pinsky

Giles Roditi
Consultant in Radiology
Royal Infirmary, Glasgow, UK

Malcolm Sim
Consultant in Intensive Care
Medicine
Western Infirmary, Glasgow, UK

Christer Sinderby
Assistant Professor
Department of Medicine,
University of Toronto, Canada

Consultant Physician in Intensive
Care Medicine and Clinical
Education,
Western General Hospital,
Edinburgh, UK

Dr Lucy Smyth

Dr Bipen Patel

Registrar in Anaesthesia
Royal Infirmary, Glasgow, UK

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

Ross Paterson
Consultant in Intensive Care
Medicine
Western General Hospital,
Edinburgh, UK

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

Rosemary Snaith

Dr Mike Spivey
Registrar in Anaesthesia
Royal Devon and Exeter Hospital,
Exeter, UK

David Swann
Consultant in Intensive Care
Medicine
Royal Infirmary, Edinburgh, UK


CONTRIBUTORS

Anthony Todd

Louise Watson

Consultant in Haematology
Royal Devon and Exeter Hospital,
Exeter, UK

Clinical Lead in Critical Care
Physiotherapy
Royal Devon and Exeter Hospital,
Exeter, UK

Tim Walsh
Honorary Professor, Edinburgh
University and Consultant in
Critical Care
Royal Infirmary, Edinburgh, UK

xv


xvii

Symbols and abbreviations
AAA
AAFB
A-aO2
gradient
ABG
ACBT
ACE
ACh
ACT
ACV
AF
AIDS
AIP
AKI
ALI
ANA
ANCA
AP
APACHE
APF
APRV
ARDS
ARF
AST
ASV
ATC
ATLS
AVCO2R
AVM
BAL
BCG
BHL
BiPAP
BIPAP
BIS

abdominal aortic aneurysm
alcohol–acid fast bacilli
alveolar-arterial oxygen gradient
arterial blood gas
active cycle of breathing technique
angiotensin converting enzyme
acetylcholine
activated clotting time
assist control ventilation
atrial fibrillation
acquired immunodeficiency syndrome
acute interstitial pneumonia
acute kidney injury
acute lung injury
antinuclear antibody
anti-neutrophil cytoplasmic antibody
antero-posterior
acute physiology and chronic health evaluation
alveolo-pleural fistulae
airway pressure release ventilation
acute respiratory distress syndrome
acute respiratory failure
aspartamine transaminase
adaptive support ventilation
automatic tube compensation
advanced trauma life support
artero-venous carbon dioxide removal
arteriovenous malformations
bronchoalveolar lavage
bacille Calmette-Guerin
bilateral hilar lymphadenopathy
bi-level positive airway pressure
biphasic positive airways pressure
bispectral index


xviii

SYMBOLS AND ABBREVIATIONS

BLS
BMI
BNP
BOOP
BOS
BPF
bpm
BTS
BYCER
CABG
CAM-ICU
c-ANCA
CAP
CAPS
CC
CCF
CDM
CF
CFA
CHF
CI
CIM
CIP
CIPM
CK
CLED
CMV
CNS
CO
COP
COPD
CPAP
CPB
CPG
CPIS
CPO
CPR
CROP
CRP
CSF

basic life support
body mass index
brain natriuretic peptide
bronchiolitis obliterans organizing pneumonia
bronchiolitis obliterans syndrome
broncho-pleural fistula
beats per minute
British Thoracic Society
buffered yeast extract charcoal agar
coronary artery bypass graft
confusion assessment method for ICU
antineutrophilic cytoplasmic antibody
community-acquired pneumonia
COPD and asthma physiology score
closing capacity
congestive cardiac failure
clinical decision making
cystic fibrosis
cryptogenic fibrosing alveolitis
chronic heart failure
cardiac index
critical illness myopathy
critical illness polyneuropathy
critical illness polyneuromyopathy
creatine kinase
cystine–lactose–electrolyte deficient
cytomegalovirus
central nervous system
cardiac output
cryptogenic organizing pneumonia
chronic obstructive pulmonary disease
continuous positive airway pressure
cardiopulmonary bypass
central pattern generator
clinical pulmonary infection score
cardiogenic pulmonary oedema
cardiopulmonary resuscitation
compliance respiratory rate oxygenation and pressure
C-reactive protein
cerebrospinal fluid


SYMBOLS AND ABBREVIATIONS

CSHT
CT
CTPA
CUS
CVA
CVP
CVS
CVVH
CXR
DAD
DBP
DILD
DIP
DLCO
DMARD
DMD
DTPA
DVT
EAA
EAdi
EBUS
ECCO2R
ECG
ECMO
ED
EELV
EIT
ELISA
ELSO
EMG
ENT
EPAP
ESR
ET
ETT
ETS
EVLW
FA
FBC
FEV

context sensitive half times
computerized tomography
CT pulmonary angiography
compression ultrasonography
cerebrovascular accident
central venous pressure
cardiovascular system
continuous veno-venous haemofiltration
chest X-ray
diffuse alveolar damage
diastolic blood pressure
drug-induced lung disease
desquamative interstitial pneumonia
diffusing capacity of the lung for carbon monoxide
disease-modifying antirheumatic drug
Duchenne muscular dystrophy
diethylenetriaminepentaacetic acid
deep vein thrombosis
extrinsic allergic alveolitis
electrical activity of the diaphragm
endobronchial ultrasound
extra-corporeal CO2 removal
electrocardiogram
extracorporeal membrane oxygenation
emergency department
end expiratory lung volume
electrical impedance tomography
enzyme-linked immunosorbent assay
extracorporeal life support registry
electromyogram
ear, nose and throat
expiratory positive airways pressure
erythrocyte sedimentation rate
endo-tracheal
endotracheal tube
expiratory trigger sensor
extravascular lung water
flow assist
full blood count
forced expiratory volume

xix


xx

SYMBOLS AND ABBREVIATIONS

FFP
FOB
FRC
FSH
FVC
GABA
GBM
GCS
GCSF
GFR
GGO
GM-CSF
GTN
HAART
HAFOE
HAP
Hb
HbA
HbF
HbO2
HbS
HDU
HELLP
HFOV
HH
HHb
HHT
HIV
HME
HPV
HR
HRCT
HRQL
HRT
HSV
HWH
IABP
IBW
ICMs

fresh frozen plasma
fibreoptic bronchoscope
functional residual capacity
facioscapulohumeral
forced vital capacity
G-amino butyrate
glomerular basement membrane
Glasgow Coma Score
granulocyte macrophage colony-stimulating factor
glomerular filtration rate
ground glass opacity
granulocyte-macrophage colony-stimulating factor
glyceryl trinitrate
highly active antiretroviral therapy
high air flow oxygen enrichment
hospital-acquired pneumonia
haemoglobin
haemoglobin A
foetal haemoglobin
oxyhaemoglobin
sickle cell haemoglobin
high-dependency unit
syndrome of haemolysis, elevated liver enzymes, low
platelets
high frequency oscillatory ventilation
heated humidifiers
deoxyhaemoglobin
hereditary haemorrhagic telangiectasia
human immunodeficiency virus
heat and moisture exchanger
hypoxic pulmonary vasoconstriction
heart rate
high-resolution CT
health-related quality of life
hormone replacement therapy
herpes simplex virus
heated water humidifier
intra-aortic balloon pumps
ideal body weight
intercostal muscles


SYMBOLS AND ABBREVIATIONS

ICP
ICU
I:E
ILD
IMV
INR
IPAP
IPF
IPPV
IRV
ITP
IVC
IVIG
JVP
KCO
LDH
LFT
LMWH
LPS
LPV
LR
LTV
LV
LVAD
LVEDP
LVF
LVH
MAP
MDR
MDT
MIC
met Hb
MH
MHI
MI
MIGET
MIP
MMF
MND
MOF

intracranial pressure
intensive care unit
inspiratory:expiratory
interstitial lung disease
intermittent mandatory ventilation
international normalized ratio
inspiratory positive airway pressure
idiopathic pulmonary fibrosis
intermittent positive pressure ventilation
inverse ratio ventilation
intrathoracic pressure
inferior vena cava
intravenous immunoglobulin
jugular venous pressure
transfer coefficient for carbon monoxide
lactate dehydrogenase
liver function tests
low molecular weight heparin
lipopolysaccharide
lung protective ventilation
likelihood ratio
long-term ventilation
left ventricle
left ventricular assist device
left ventricular end diastolic pressure
left ventricular failure
left ventricular hypertrophy
mean arterial pressure
multi-drug resistant
multidisciplinary team
minimum inhibitory concentration
methaemoglobin
malignant hyperpyrexia
manual hyperinflation
myocardial infarction
multiple inert gas elimination technique
maximal inspiratory pressure
mycophenolate mofetil
motor neurone disease
multi organ failure

xxi


xxii

SYMBOLS AND ABBREVIATIONS

MPO
MRC
MRI
MRSA
MSSA
MV
NAC
NAECC
NAVA
NGT
NICE
NIV
NK
NMBA
NNT
NPV
NSAID
NSIP
NSTEMI
nTe
NT-proBNP
NYHA
OHS
OLB
OSA
PA
PACS
PaCO2
PAH
p-ANCA
PaO2
PAO2
PAOP
PAS
PAV
PAVM
PCI
PCP
PCR
PCV

myeloperoxidase
medical research council
magnetic resonance imaging
meticillin-resistant Staphylococcus aureus
meticillin-sensitive Staphylococcus aureus
minute volume
N-acetyl cysteine
North American-European Consensus Conference
neurally adjusted ventilatory assist
nasogastric tube
National Institute for Health and Clinical Excellence
non-invasive ventilation
natural killer
neuromuscular blockade agent
number needed to treat
negative pressure ventilation
non-steroidal anti-inflammatory drug
non-specific interstitial pneumonia
non-ST-elevation myocardial infarction
neural expiratory time
N-terminal pro B type natriuretic peptide
New York Heart Association
obesity hypoventilation syndrome
open-lung biopsy
obstructive sleep apnoea
postero-anterior
picture archiving and communication systems
arterial partial pressure of carbon dioxide
pulmonary artery hypertension
antineutrophilic perinuclear antibody
arterial partial pressure of oxygen
alveolar partial pressure of oxygen
pulmonary artery occlusion pressure
periodic acid-Schiff
proportional assist ventilation
pulmonary arteriovenous malformations
percutaneous coronary intervention
Pneumocystis jirovecii pneumonia
polymerase chain reaction
pressure-controlled ventilation


SYMBOLS AND ABBREVIATIONS

PDE
PDT
PE
PEEP
PEEPe
PEEPi
PEF
PEFR
PES
PFT
PGE1
PH
PIFR
PIP
pMDI
PMP
PND
PO2
PS
PSB
PSG
PSI
PSV
PTE
PTI
PTSD
PVL
PVR
RA
RACE
RBC
RBILD
RCT
REM
RhF
RIP
RM
ROS
RQ

phosphodiesterase
percutaneous dilational tracheostomy
pulmonary thromboembolism
positive end expiratory pressure
extrinsic PEEP
intrinsic PEEP
peak expiratory flow
peak expiratory flow rate
oesophageal pressure
pulmonary function tests
prostaglandin E1
pulmonary hypertension
peak inspiratory flow rate
peak inspiratory pressure
pressurized metered dose inhaler
polymethylpentene
paroxysmal nocturnal dyspnoea
partial pressure of oxygen
pressure support
protected specimen brush
polysomnogram
Pneumonia Severity Index
pressure support ventilation
pulmonary thromboembolism
pressure time index
post-traumatic stress disorder
Panton Valentine leukocidin
pulmonary vascular resistance
right atrium
repetitive alveolar collapse expansion
red blood cell
respiratory bronchiolitis-associated interstitial lung
disease
randomized controlled trial
rapid eye movement
rheumatoid factor
respiratory inductance plethysmography
recruitment manoeuvres
reactive oxygen species
respiratory quotient

xxiii


xxiv

SYMBOLS AND ABBREVIATIONS

RR
RSBI
RSV
rv
SAPS
SBD
SBP
SBT
SDD
SIADH
SIMV
SIRS
SLB
SLE
SNIP
SOD
ST
STEMI
SV
SVR
TB
TBLB
THAM
TLC
TPMT
TSST
TTE
TV
U+E
UIP
VA
VALI
VAP
VAS
VAT
VATS
VC
VCV
VIDD
VILI

relative risk
rapid shallow breathing index
respiratory syncytial virus
right ventricle
simplified acute physiology score
sleep-disordered breathing
systolic blood pressure
spontaneous breathing trial
selective decontamination of the digestive tract
syndrome of inappropriate anti-diuretic hormone
synchronized intermittent mandatory ventilation
systemic inflammatory response syndrome
surgical lung biopsy
systemic lupus erythematosis
sniff nasal inspiratory pressure
selective oral decontamination
surface tension
ST elevation myocardial infarction
stroke volume
systemic vascular resistance
tuberculosis
transbronchial lung biopsy
tris-hydroxymethyl aminomethane
total lung capacity
thiopurine methyltransferase
toxic shock syndrome toxin
trans-thoracic echocardiography
tidal volume
urea and electrolytes
usual interstitial pneumonia
volume assist
ventilator associated lung injury
ventilator-associated pneumonia
visual analogue scale
ventilator-associated tracheobronchitis
video-assisted thoracic surgery
vital capacity
volume controlled ventilation
ventilator-induced diaphragmatic dysfunction
ventilator-induced lung injury


SYMBOLS AND ABBREVIATIONS

vTi
VTE
VZV
WCC
WOB
ZA
ZEEP

ventilator inspiratory time
venous thromboembolism
Varicella zoster virus
white cell count
work of breathing
zone of apposition
zero PEEP

xxv


Section 1

Approach to the patient
with respiratory failure
1.1 Respiratory physiology and pathophysiology 2
Dawn Fabbroni and Andrew Lamb
1.2 Diagnosis of respiratory failure 22
Colin Church, Giles Roditi, and Steve Banham
1.3 The microbiology laboratory 49
Marina Morgan
1.4 Clinical decision making 64
Martin Hughes and Graham Nimmo
1.5 Indications for ventilatory support 69
Rebecca Appelboam

1


2

SECTION 1

The patient with respiratory failure

1.1 Respiratory physiology and
pathophysiology
Control of breathing
Respiratory centre
The respiratory centre is located in the medulla. It generates the respiratory 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 interconnected 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 influences
fine control of respiration and co-ordinates the other central nervous
system (CNS) connections to the CPG.
• Cerebral cortex—influences voluntary interruption in breathing
required for speech, singing, sniffing, 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 reflex 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 inflation.
• Rapidly adapting stretch receptors occur in the superficial mucosal
layer and are stimulated by changes in tidal volume, respiratory rate, or
lung compliance.
• C fibre 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 fluid, they may be responsible for dyspnoea
associated with pulmonary vascular congestion or embolism.


1.1 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.
Influence of CO2
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 HCO3–. Central chemoreceptor neurones respond to a fall in
pH with a linear increase in minute ventilation.
A compensatory shift in cerebrospinal fluid (CSF) bicarbonate concentration occurs with chronic hyper- and hypocapnia, and is seen in
artificially ventilated patients. The speed of pH compensation by the
bicarbonate shift depends on the extent of the arterial partial pressure
(PaCO2) change and can take hours. Artificially 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.
Influence of O2 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 perfusion rate, much greater than their metabolic rate, and a small arteriovenous PO2 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 PaO2, not oxygen content, therefore there is no response
to anaemia, carboxyhaemoglobin. or methaemoglobin
• Decreased pH or increased PaCO2—this response is only one-sixth of
the central chemoreceptor response but occurs very rapidly; may also
respond to cyclical oscillations in arterial PaCO2 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, bradycardia, hypertension, increased bronchiolar tone, and adrenal stimulation.

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