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This page intentionally left blank
Core Topics in Mechanical Ventilation

i
Iain Mackenzie in zero-gravity training for Professor Hawking’s flight, April 26, 2007.
Core Topics in Mechanical Ventilation

Edited by

IAIN MACKENZIE
Consultant in Intensive Care Medicine
and Anaesthesia
CAMBRIDGE UNIVERSITY PRESS
Cambridge, New York, Melbourne, Madrid, Cape Town, Singapore, São Paulo

Cambridge University Press

The Edinburgh Building, Cambridge CB2 8RU, UK
Published in the United States of America by Cambridge University Press, New York

www.cambridge.org
Information on this title: www.cambridge.org/9780521867818
© Cambridge University Press 2008

This publication is in copyright. Subject to statutory exception and to the

provision of relevant collective licensing agreements, no reproduction of any part
may take place without the written permission of Cambridge University Press.
First published in print format 2008

ISBN-13 978-0-511-45164-5 eBook (Adobe Reader)

ISBN-13 978-0-521-86781-8 hardback

Cambridge University Press has no responsibility for the persistence or accuracy

of urls for external or third-party internet websites referred to in this publication,
and does not guarantee that any content on such websites is, or will remain,
accurate or appropriate.
Every effort has been made in preparing this book to provide accurate and up-to-
date information which is in accord with
accepted standards and practice at the time of publication. Although case histories
are drawn from actual cases, every effort
has been made to disguise the identities of the individuals involved. Never theless,
the authors, editors and publishers can
make no warranties that the information contained herein is totally free from
error, not least because clinical standards are
constantly changing through research and regulation. The authors, editors and
publishers therefore disclaim all liability for
direct or consequential damages resulting from the use of material contained in
this book. Readers are strongly advised to pay
careful attention to information provided by the manufacturer of any drugs or
equipment that they plan to use.
Contents

Contributors page vii

Foreword by Timothy W. Evans ix
Preface xi
Introductory Notes xiii

1. Physiology of ventilation and gas exchange 1

HUGH MONTGOMERY

2. Assessing the need for ventilatory support 21

MICK NIELSEN AND IAIN MACKENZIE

3. Oxygen therapy, continuous positive airway pressure and non-invasive ventilation 32

IAN CLEMENT, LEIGH MANSFIELD AND SIMON BAUDOUIN

4. Management of the artificial airway 54

PETER YOUNG AND IAIN MACKENZIE

5. Modes of mechanical ventilation 88

PETER MACNAUGHTON AND IAIN MACKENZIE

6. Oxygenation 115
BILL TUNNICLIFFE AND SANJOY SHAH

7. Carbon dioxide balance 142

BRIAN KEOGH AND SIMON FINNEY

8. Sedation, paralysis and analgesia 160

RUSSELL R . MILLER III AND E . WESLEY ELY

9. Nutrition in the mechanically ventilated patient 184

CLARE REID

10. Mechanical ventilation in asthma and chronic obstructive pulmonary disease 196
DAVID TUXEN AND MATTHEW T. NAUGHTON

v
Contents

11. Mechanical ventilation in patients with blast, burn and chest trauma injuries 210
WILLIAM T. MCBRIDE AND BARRY MCGRATTAN

12. Ventilatory support: extreme solutions 222

ALAIN VUYLSTEKE

13. Heliox in airway obstruction and mechanical ventilation 230

HUBERT TRÜBEL

14. Adverse effects and complications of mechanical ventilation 239

IAIN MACKENZIE AND PETER YOUNG

15. Mechanical ventilation for transport 284

TERRY MARTIN

16. Special considerations in infants and children 296

ROB ROSS RUSSELL AND NATALIE YEANEY

17. Tracheostomy 310

ABHIRAM MALLICK , ANDREW BODENHAM AND IAIN MACKENZIE

18. Weaning, extubation and de-cannulation 331

IAIN MACKENZIE

19. Long-term ventilatory support 372

CRAIG DAVIDSON

20. The history of mechanical ventilation 388

IAIN MACKENZIE

Glossary 404
Index 411

vi
Contributors

Simon Baudouin, FRCP Simon Finney, PhD MRCP FRCA

Senior Lecturer Consultant in Intensive Care Medicine and
Department of Anaesthesia and Critical Care Anaesthesia
Medicine Royal Brompton and Harefield NHS Trust
Royal Victoria Infirmary London, UK
Newcastle-upon-Tyne, UK
Brian Keogh, FRCA
Consultant in Intensive Care Medicine and
Andrew Bodenham, FRCA Anaesthesia
Consultant in Anaesthesia and Intensive Care Royal Brompton and Harefield NHS Trust
Medicine London, UK
Leeds General Infirmary
Leeds, UK Iain Mackenzie, DM MRCP FRCA
Consultant in Intensive Care Medicine and
Ian Clement, PhD MRCP FRCA Anaesthesia
Consultant in Anaesthesia and Intensive John Farman Intensive Care Unit
Medicine Addenbrooke’s Hospital
Department of Anaesthesia and Critical Care Cambridge, UK
Medicine Peter Macnaughton, MD MRCP FRCA
Royal Victoria Infirmary Consultant in Intensive Care Medicine and
Newcastle-upon-Tyne, UK Anaesthesia
Plymouth Hospitals NHS Trust
Craig Davidson, FRCP Derriford
Director, Lane Fox Respiratory Unit Plymouth, UK
Guy’s and St. Thomas’ NHS Foundation Trust
London, UK
Abhiram Mallick, FRCA
Consultant in Anaesthesia and Intensive Care
Medicine
E. Wesley Ely, MD MPH Leeds General Infirmary
Professor and Associate Director of Aging Leeds, UK
Research
Division of Allergy, Pulmonary, and Critical Care Leigh Mansfield
Medicine Senior Physiotherapist
Vanderbilt University School of Medicine Department of Anaesthesia and Critical Care
Veterans Affairs, Tennessee Valley Geriatric Research, Medicine
Education, and Clinical Center Royal Victoria Infirmary
Nashville, Tennessee, USA Newcastle-upon-Tyne, UK

vii
List of contributors

Terry Martin, MSc FRCS FRCA Rob Ross Russell, MD FRCPCH

Consultant in Anaesthesia and Intensive Care Consultant in Paediatric Intensive Care Medicine
The Royal Hampshire County Hospital Addenbrooke’s Hospital
Winchester, UK Cambridge, UK

William T. McBride, BSc MD FRCA FFARCS(I) Sanjoy Shah, MD MRCP EDIC

Consultant Cardiac Anaesthetist Consultant in Intensive Care Medicine
Royal Victoria Hospital University Hospital Wales
Belfast, UK Cardiff, UK

Barry McGrattan, FFARCS(I)

Hubert Trübel, MD
Specialist Registrar in Anaesthesia
Consultant in Paediatrics
Royal Victoria Hospital
Department of Paediatrics
Belfast, UK
HELIOS Kilinikum Wuppertal
University of Wittenburg/Herdeche
Russell R. Miller III, MD MPH
Wuppertal, Germany
Assistant Professor
Division of Critical Care and Pulmonary Medicine
LDS and IMC Hospitals Bill Tunnicliffe, FRCA
University of Utah School of Medicine Consultant in Intensive Care Medicine and
Salt Lake City, Utah, USA Anaesthesia
Queen Elizabeth Hospital
Hugh Montgomery, MD FRCP Birmingham, UK
Director, Institute for Human Health and
Performance and Consultant Intensivist David Tuxen, MBBS FRACP MD Dip DHM FJFICM
UCL Hospitals Associate Professor of Critical Care
London, UK The Alfred Hospital
Prahran
Matthew T. Naughton, MD FRACP Melbourne, Australia
Associate Professor of Head, General Respiratory
and Sleep Medicine Alain Vuylsteke, MD FRCA
The Alfred Hospital Director of Critical Care
Prahran Papworth Hospital NHS Trust
Melbourne, Australia Papworth Everard
Cambridgeshire, UK
Mick Nielsen, FRCA
Consultant in Anaesthesia and Intensive Care
Southampton University Hospitals NHS Trust Natalie Yeaney, MD FAAP
Southampton, UK Consultant Neonatal Intensivist
Addenbrooke’s Hospital
Clare Reid, PhD SRD Cambridge, UK
Research Dietician
Division of Anaesthesia Peter Young, MD FRCA
University of Cambridge Consultant in Intensive Care and Anaesthesia
Addenbrooke’s Hospital The Queen Elizabeth Hospital
Cambridge, UK King’s Lynn, UK

viii
Foreword

Bjorn Ibsen, an anaesthetist and intensivist who expertise of those driving the change. In the United
practiced for most of his career in Copenhagen, States, physicians trained in pulmonary medicine
Denmark, died on 7 August 2007. Ibsen is widely have traditionally also provided critical care. In the
regarded as the father of Intensive Care Medicine, United Kingdom, the base specialty of anaesthesia
the nativity of which occurred in his home city in has borne the brunt of intensive care provision over
1952 during a polio epidemic. Ibsen had trained many decades. Only in recent years has the value
in radiology, surgery, pathology and gynaecology of bringing varying expertise to intensive care man-
before travelling to Massachusetts General Hospital agement (ICM) from different clinical base special-
in 1949 to gain specialist experience in anaesthesia. ties been recognized more formally. Thus in Aus-
He returned to Copenhagen in 1950 and assumed tralia a joint intercollegiate faculty of ICM has been
a leading role in managing one of the world’s worst developed, a model that was to an extent copied
polio epidemics that started only two years later. in the UK. Formal training programmes have been
Some 2899 cases developed among the population developed, culminating in the UK in ICM being rec-
of two million. Too weak to cough, many patients ognized as a specialty in the year 2000. The emer-
succumbed to secretion retention with associated gence of diploma and other examinations designed
carbon dioxide retention. Negative pressure ventila- to test competencies in intensive care has been rapid.
tion was effectively the only form of support then The strength of national and international special-
available, but Ibsen found that tracheostomy, or ist societies has grown, with associated academic
endotracheal intubation combined with the careful advancement publicized through congresses and
application of intermittent positive pressure venti- increasingly in highly cited journals.
lation administered by relays of doctors, medical Against this background, it has given me great
students and others, was an effective means of over- pleasure to write the foreword for this exciting vol-
coming the devastating effects of the disease. In ume, expertly conceived and edited by Dr Iain
the end, over 1500 practitioners aspirated secretions Mackenzie. The contributors to this book come
and performed manual ventilation in shifts. Mortal- from a wide range of clinical and national back-
ity fell markedly. As a result, the idea that critically grounds, thereby reflecting the heterogeneity that is
ill patients should be supported in centralized facil- in many senses the strength of the specialty. More-
ities by individuals experienced in their care was over, the content reflects the staggering advances
adopted worldwide. that have been made during the past 50 years
The new specialty emerged in varying phenotypes in the delivery of mechanical ventilatory support.
according to the history, individual preferences and Even those phenomena which would have been

ix
Foreword

easily recognizable to Ibsen, such as the deliv- tise into the wards in pursuit of the ‘intensive
ery of oxygen therapy, have been subjected to sci- care without walls’ has been greatly facilitated by
entific evaluation and technological development. the advent of non-invasive mechanical ventilatory
Tracheostomy, used widely in the 1950s polio support.
epidemic, is now performed at the bedside, an Finally, the scientific advances in our evaluation
innovation of which I suspect Ibsen would have of the effects of mechanical ventilation, the recogni-
approved. The content of chapters dealing with tion that it can do harm if applied inappropriately
sedation, paralysis and analgesia might have been and the evidence base concerning its use in patients
more familiar to him, but the agents now employed, with a wide variety of primary and secondary lung
the increased understanding of their properties and pathologies is a truly outstanding achievement that
the clinical benefits attributable to their avoidance, intensive care medicine can be proud of. I suspect
where possible, are evidence of the advances made that Bjorn Ibsen, were he privileged to read this vol-
in this area of pharmacology. The outreach of exper- ume, would feel the same.

Timothy W. Evans, BSC DSC FRCP FRCA FMedSci

Professor of Intensive Care Medicine
Imperial College
London

Consultant in Intensive Care Medicine

Royal Brompton Hospital
London

x
Preface

Respiratory support is recognized to be a key com- and teaching of, the art and science of mechanical
ponent in the resuscitation of acutely ill patients ventilation. In addition, since many of those who
and, as such, the basics are taught to all those who work with patients who require respiratory support
seek to acquire life support skills. Following sta- do not have an anaesthetic background, knowledge
bilization, the continued provision of respiratory particular to this specialty has not been assumed.
support, be it in the emergency department, respi- I would welcome any feedback so that future edi-
ratory ward or intensive care unit, is largely taken tions of this book can better meet the needs of its
for granted. However, as the ARDSnet study has readers.
recently reminded us, the way we manage mechan- My colleagues in Cambridge, both nursing and
ical ventilation in the medium and long term actu- medical, must be credited with persuading me of
ally has a significant impact on patient outcome. the need for a book such as this, and for that I am
Although the literature is full of the evidence nec- grateful. I am also indebted to the contributors from
essary to provide optimal respiratory support, syn- around the world who responded so favourably
thesizing this evidence into a cohesive and logi- to my request that they contribute, and then fol-
cal approach would be an enormous task for one lowed through with their chapters. Frank McGinn
individual. On the other hand, excellent sections (GE Healthcare Technologies), Dan Gleeson (Cape
on respiratory support can be found in the major Engineering) and John Wines (Cape Engineering)
textbooks on critical care and indeed the ‘princi- kindly supplied me with information about the his-
ples and practice of mechanical ventilation’ is the tories of their respective companies. I have received
sole subject of Martin Tobin’s authoritative tome of assistance in sourcing some of the images from Mr
that name. However, these large reference books are Pyush Jani and Dr Helen Smith. I am very grate-
expensive and less than suitable for those who need ful to David Miller for checking the correctness of
a more concise and practical overview of the subject. the English, but must accept any blame for any
This book therefore seeks to fill the gap between errors that have crept through. Finally, I would like
the journals and the major textbooks by bringing to thank Diane, my wife, and Katherine, Rebecca,
together clear, concise and evidence-based accounts Charlotte and Amy, my daughters, for their unfail-
of important topics in respiratory support, together ing support over the last two years while this book
with, where necessary, explanations of its physiol- was in production.
ogy and pathology. It is hoped, therefore, that this
book will appeal to a very wide audience, and will Iain Mackenzie
make a substantial contribution to the interest in,

xi
Introductory notes

Physiological notation Table 1 In-text notation for commonly used

Those with a dislike of mathematics will be pleased physiological quantities
to know that none of the equations in this book
Correct In-text
need to be memorized. Having said that, though, Quantity notation notation
understanding the concepts that are encapsulated Fractional inspired oxygen FIO2 FIO2
by the equations presented will help the reader concentration
enormously in achieving a significantly deeper level Partial pressure of carbon PACO2 PACO2
of understanding. As many of the terms in the dioxide in alveolar gas
Partial pressure of carbon P aCO2 PaCO2
equations refer to physiological quantities, physi-
dioxide in arterial blood
ological notation is used, and therefore being able Partial pressure of oxygen in PAO2 PAO2
to decipher physiological notation will be helpful alveolar gas
Partial pressure of oxygen in P aO2 PaO2
. per unit time arterial blood
_ mean or mixed Partial pressure of carbon PCO2 PCO2
dioxide
Partial pressure of oxygen PO2 PO2

PV O2
Haemoglobin oxygen saturation
in arterial blood
SaO2 SaO2

C Content (mL. dL−1) A Alveolar O2 Oxygen

Fraction a Arterial CO2 Carbon dioxide (Figure 1). The reader may be relieved to hear that
P Pressure (kPa or mm Hg) b Barometric
Q Volume of blood (mL or L) c Capillary formal physiological notation has been completely
S Saturation (%) c’End-capillary
D Dead space
avoided in the text because it can sometimes extend
V Volume of gas (mL or L)
E Expired gas significantly below the text baseline, as in, for exam-
I Inspired gas
s Shunt ple, the notation representing the partial pressure of
t Total
Tidal oxygen in arterial blood:
v Venous
Pa O2 .
Figure 1 Key to physiological notation.
In the example illustrated, the physiological quantity being However, some quantities are mentioned so often
referred to is the mixed venous partial pressure of oxygen. in the text that to refer to these in words would hin-
Note also that when blood or gas volume, V and Q
der, rather than help, the flow of the text. There-
respectively, are expressed ‘per minute’ by placing a dot above
the letter, they then refer to volume/time, or flow. Thus Q, fore, for the most common of these quantities,
blood volume, can be converted to Q̇, blood flow. non-physiological notation has been used for

xiii
Introductory notes

Table 2 Pressure conversion Table 3 Convention for the use of compound

multiply units
−→
divide
←− Common Correct
mm Hg 1.3595 cm H2 O clinical scientific
kPa 10.197 cm H2 O Quantity notation notation
kPa 7.5 mm Hg Millilitres per kilogram mL/kg mL.kg−1
Atm 101.325 kPa Microgram per kilogram µg/kg/hr µg.kg−1 .hr−1
Bar 100 kPa per hour
Millilitres per minute mL/min mL.min−1
in-text references, as it is in many other publications Litres per minute L/min L.min−1
Milliequivalents per litre mEq/L mEq.L−1
(Table 1).
Millimoles per litre mmol/L mmol.L−1
Units Kilocalorie per milliliter kcal/mL kcal.mL−1
Millilitres per hour mL/hr mL.hr−1
The European convention on units has been main-
Milligrams per kilogram mg/kg mg.kg−1
tained throughout, using kilopascals (kPa) for Kilocalories per kilogram kcal/kg kcal.kg−1
gas pressures rather than millimetres of mercury Grams per kilogram g/kg g.kg−1
(mm Hg), but the conversion factors can be found Grams per deciliter g/dL g.dL−1
in Table 2. However, for clarity the symbol for the Micrograms per minute µg/min µg.min−1
litre, which is usually abbreviated to the lower case Millilitres per kilogram mL/kg mL.kg−1
Millilitres per day mL/d mL.d−1
letter ‘l’, has been substituted by the North Amer-
ican convention of using the capital letter ‘L’; thus
‘ml’ becomes ‘mL’ and ‘dl’ becomes ‘dL’. more than two components, the use of the for-
Compound units in clinical practice commonly ward slash is potentially confusing and should be
use the forward slash ‘/’ as the delimiter to denote avoided. The convention in this book, therefore,
a denominator unit. For example, ‘millilitres per is to use the more correct scientific notation. In
kilogram’ would be written ‘mL/kg’. In compound this form, the relationship between units is indi-
units with only two components, this usage is not cated by the superscript power notation, as shown in
subject to misunderstanding, but in those with Table 3.

xiv
 Chapter 1
Physiology of ventilation and gas exchange
HUGH MONTGOMERY

Among its many functions, the lung has two major the work of breathing becomes high and the fall
ones: it must harvest oxygen to fuel aerobic respira- in pharyngeal pressure too great for the adequate
tion and it must vent acid-forming carbon dioxide. intake of air: the mouth then becomes the preferred
This chapter will offer a brief overview of how the route for breathing.
lung fulfills these functions. It will also discuss some The larynx remains a protector of the airway, with
of the mechanisms through which adequate oxy- aryepiglottic and arytenoid muscles able to draw
genation can fail. A secure understanding of these the laryngeal entrance closed like a purse-string and
principles allows an insight into the way in which the epiglottis pulled down from above like a trap
mechanical ventilation strategies can be altered in door. In addition, the arytenoid cartilages can swing
order to enhance oxygenation and carbon dioxide inwards to appose the vocal cords themselves, thus
clearance. offering an effective seal to the entry of particles or
gases to the airway beneath. Meanwhile, tight occlu-
sion can be achieved during swallowing or to ‘fix’
Functional anatomy of the lung
the thorax during heavy lifting, allowing the larynx
The airways to resist internal pressures of some 120 cm H2 O.
During inspiration, air is drawn into the orophar- Laryngeal sensitivity to irritation, causing a cough,
ynx through either the mouth or the nasal air- makes the larynx effective at limiting entry of nox-
way. Nasal breathing is preferred, as it is associated ious gases or larger particles, while more intense
with enhanced particle removal (by nasal hairs and chemoreceptor stimulation can cause severe laryn-
mucus-laden turbinates) and humidification. How- geal spasm, preventing any meaningful gas flow. In
ever, this route is associated with a fall in pharyngeal the anaesthetic room, this can be life-threatening.
pressure. Just as Ohm’s law dictates that voltage is When air enters the trachea, it is supported
the product of current and resistance, so pharyngeal by anterior horse-shoes of cartilage (Figure 1.1).
pressure is the product of gas flow and pharyngeal However, these are compliant, and tracheal col-
resistance. A ‘fat apron’around the pharynx because lapse occurs with extrinsic pressures of only 40 cm
of obesity may lead to increased pharyngeal com- H2 O. Ciliated columnar epithelium yields an
pliance, and thus increase the risk of dynamic pha- upward-moving mucus ‘escalator’. The trachea then
ryngeal collapse in such patients. In adults, when divides into the right and left main bronchi
pharyngeal flows exceed 30 to 40 litres per minute, (generation 1 airways), and then into lobar and
Core Topics in Mechanical Ventilation, ed. Iain Mackenzie. Published by Cambridge University Press.


C Cambridge University Press 2008.

1
 Nasopharynx

Oropharynx

Epiglottis

Laryngopharynx i
Trachea
Vocal cords

iii
a
b c

iv ii a
b
b ba a a
c b b
a

vi

a
b x
ab b
c b a
vii viii c
c

d
c
a ix
b
 chapter 1: physiology of ventilation and g as exchange

segmental bronchi (generations 2–4). The right sufficient gas flow to maintain intra-bronchial pres-
main bronchus is wider and more vertical than the sures to a level above intrathoracic pressures.
left, and is thus the ‘preferred’ path for inhaled Bronchioles (generations 12–16) lack cartilagi-
foreign bodies. Cartilaginous horse-shoe supports nous support, but are held open by the elastic
in the upper airways give way to plates of cartilage recoil of the attached lung parenchyma, making
lower down, but all will collapse when exposed to airway collapse more likely at lower lung volumes.
intrathoracic pressures of >50 cm H2 O (or less in The cross-sectional area of these very small distal
situations in which the walls are diseased, such as airways, and their very thin walls, makes airway
in chronic obstructive pulmonary disease or bron- resistance at this level almost nil in the absence
chomalacia). of contraction (bronchoconstriction) of the wall’s
Successive division of bronchi (generations 5–11) smooth muscle cells. Subsequent respiratory bron-
yield ever-smaller airways (to about 1 mm diam- chioles (generations 17–19) have increasing num-
eter), all of which are surrounded by lymphatic bers of gas-exchanging alveolar sacs in their walls;
and pulmonary arterial branch vessels. They are these bronchioles are anchored open under tension
supported by their cartilaginous plates and rarely from surrounding parenchyma. Each of 150 000 or
collapse because intra-bronchial pressure is nearly so ‘primary lobules’represents the distal airway sub-
always positive. So long as there is patency between tended by a respiratory bronchiole. Distally (gener-
alveoli and bronchi, even forced expiration allows ation 20–22), alveolar duct walls give rise to some

Figure 1.1 Gross and microscopic anatomy of the respiratory tract.

Inset i: Conventional microscopy view of the surface of the ciliated epithelium of the trachea showing cells bearing cilia adjacent to
cells which appear flat, but which in fact bear microvilli. Photomicrograph courtesy of the Ernest Orlando Lawrence Berkeley
National Laboratory, California.
Inset ii: Transmission electron microscope image of a thin section cut through the bronchiolar epithelium of the lung showing
ciliated columnar cells (a) interspersed by non-ciliated mucous-secreting (goblet) cells (b). Slide courtesy of Dr Susan Wilson,
Histochemistry Research Unit, University of Southampton.
Inset iii: Section of bronchus lined with pseudo-stratified columnar epithelium (a), and surrounded by a ring of hyaline cartilage (b).
The presence of sero-mucous glands (c) differentiates this from a bronchiole. This section also contains an arteriole (d). Bar = 250
microns. Slide reproduced with permission. Copyright
C Department of Anatomy and Cell Biology, University of Kansas.

Inset iv: Tiny islands of hyaline cartilage (a) confirm that this is bronchus rather than bronchiole, and adjacent is a pulmonary vein
(b). Bar = 250 microns. Slide reproduced with permission. Copyright
C Department of Anatomy and Cell Biology, University of

Kansas.
Inset v: The absence of cartilage and sero-mucous glands means that this is a bronchiole, with a surrounding cuff of smooth muscle
(a). Bar = 25 microns. Slide courtesy of Dr Susan Wilson, Histochemistry Research Unit, University of Southampton.
Inset vi: A small bronchiole (a) surrounded by smooth muscle (b). Bar = 25 microns. Slide courtesy of Dr Susan Wilson,
Histochemistry Research Unit, University of Southampton.
Inset vii: An alveolus lined by thin flat type I pneumocytes (a) and cuboidal, surfactant-secreting type II pneumocytes (b), with an
integral network of fine capillaries (c) embedded within the alveolar walls. The lumen of the alveolus contains a large alveolar
macrophage (d). Bar = 25 microns. Slide courtesy of Dr Susan Wilson, Histochemistry Research Unit, University of Southampton.
Inset viii: Scanning electron microscope image of the alveolar honeycomb. Photomicrograph courtesy of the Ernest Orlando
Lawrence Berkeley National Laboratory, California.
Inset ix: This photomicrograph shows the fine network of capillaries that enmesh the alveoli.
Inset x: Transmission electron microscopic image of alveolar cells, showing large cuboidal type II pneumocytes (a) packed with
vesicles containing surfactant (b). Nearby alveolar capillaries containing red blood cells can be seen (c). Photomicrograph courtesy
of the Rippel Electron Microscope Facility, Dartmouth College, New Hampshire.

3
chapter 1: physiology of ventilation and g as exchange

20 alveolar sacs, containing one third of all alveolar lung tissue during the thoracic expansion of inspi-
gas. The terminal alveolar sacs (generation 23) are ration. A small quantity of energy is also dissipated
blind-ending. in overcoming lung inertia and by the friction of
lung deformation.
The Alveoli and Their Blood Supply
Each lung may contain up to half a billion alve-
Elasticity and the lung
The lung’s elasticity derives from elastin fibres of
oli, which are compressed by the weight of over-
the lung parenchyma, which accounts for perhaps
lying lung and are thus progressively smaller in
one third of elastic recoil, and from the surface ten-
a vertical gradient. Alveolar gas can pass between
sion of the fluid film lining the alveoli. When fully
adjacent alveoli through small holes called ‘the
collapsed,2 the resting volume of the lung is con-
pores of Kohn’. The pulmonary capillaries form a
siderably smaller than the volume it occupies when
rich network enveloping the alveoli, with the alve-
fully expanded in the chest cavity. Fully expanded,
olar epithelium closely apposed to the capillary
the elasticity of the lungs generates a subatmo-
endothelium. The other surface of the capillary is
spheric pressure in the pleural space of about
embedded in the septal matrix.
−5.5 cm H2 O (Figure 1.2). At peak inspiration,
Blood delivered into the pulmonary arteries from
when the thoracic cage is maximally expanded, this
the right ventricle flows at a pressure less than 20%
pressure may fall to nearly −30 cm H2 O.
of that of the systemic circulation. With near identi-
It is worth giving some thought to the issue of
cal blood flows, one can infer that pulmonary vas-
surface tension forces within the lung. The pressure
cular resistance is correspondingly five- to sixfold
within a truly spherical alveolus (Pa) would nor-
lower than systemic. Working at lower pressure, the
mally be calculated as twice the surface tension (Ts )
pulmonary arterial wall is correspondingly thinner,
divided by the alveolar radius (r):
while the pulmonary arteriolar wall contains vir-
tually no smooth muscle cells at all. Capillaries in 2 × Ts
PA = . (1.1)
dependent areas of the lung tend to be better filled r
than areas higher up (due again to gravitational This equation tells us that if surface tension were
effects), while lung inflation compresses the capil- constant, the alveolar pressure would be inversely
lary bed and increases effective resistance to blood proportional to the alveolar radius. In other words,
flow. Blood flows across several alveolar units before alveolar pressure would be higher in alveoli with
passing into pulmonary venules and thence to the a smaller radius (Figure 1.3). If this were the case,
pulmonary veins. it would mean that smaller alveoli would rapidly
empty their gaseous content into larger adjacent
Pulmonary mechanics alveoli and collapse. Taken to its logical conclusion,
Air enters the lung in response to the generation of all of the alveoli in a lung would empty into one
a negative1 intrathoracic pressure (in normal venti- huge alveolus.
lation, or in negative pressure and cuirass mechan- Fortunately, surface tension is not constant
ical ventilation), or to the application of a positive because of the presence of a mixture of phospho-
airway pressure (in positive pressure ventilation lipids3 and proteins4 that floats on the surface of
modes). Work is thus performed in overcoming
both resistance to gas flow and elastic tension in the
2
For example, when removed from the chest at autopsy.
3
Mainly phosphatidylcholine, commonly referred to as lecithin.
1 4
Also referred to as subatmospheric. Surfactant proteins A to D, often referred to as SP-A, SP-B, etc.

4
 chapter 1: physiology of ventilation and g as exchange

Figure 1.2 Negative pleural pressure.

A: The respiratory system can be compared to a rubber balloon (the lungs) placed inside a glass jar (the chest cavity) with the
space between the outside of the balloon and the inside of the jar representing the pleural space.
B: The opening of the glass jar is sealed over by the rubber balloon, sealing the space between the outside of the balloon and the
inside of the jar from the atmosphere.
C: As residual gas in this space is evacuated the pressure in the ‘pleural space’ drops below atmospheric and the balloon expands.
D: Once all the gas in the ‘pleural space’ is evacuated the ‘lung’ is completely expanded to fill the ‘chest cavity’. The pressure inside
the ‘lung’ remains atmospheric while the pressure in the pleural space is subatmospheric (negative).

tends to flow from larger to smaller alveoli, produc-

ing homogeneity of alveolar volume and stabilizing
the lung. One other major advantage of this effect
r
2r on fluid surface tension is that the lung’s compli-
ance is significantly increased, reducing the negative
pressure generated by the lung in the pleural space.
A B This consequently reduces the hydrostatic pressure
Figure 1.3 Alveolar instability with constant surface tension. gradient between the inside of the pulmonary capil-
A: With constant surface tension (Ts ), the alveolar pressure in laries and the pulmonary interstitium, minimizing
the smaller alveolus is 2×T
r
s
and the pressure in the larger the rate at which intravascular fluid is drawn from
alveolus is 2×T
2r
s
, which means that whatever the values of Ts the capillaries. Lack of surfactant, for instance in
and r, the pressure is only half that in the larger alveolus.
intensive care patients with acute lung injury, thus
B: Under these circumstances, gas flows from the smaller
alveolus (higher pressure) to the larger alveolus (lower
tends to cause alveolar collapse and reduce lung
pressure). compliance, which substantially increases the work
of breathing.
As the chest expands during inspiration, intra-
the fluid lining the alveoli (the surfactant; see alveolar pressure falls to little more than −1 cm
Figure 1.4), which reduces the surface tension in pro- H2 O, causing the air to flow down a pressure gra-
portion to the change in the surface area: the smaller the dient from the nose and mouth to the alveoli.
surface area of the alveolus, the greater the reduc- It is notable just how modest the intra-alveolar
tion in surface tension. This means that gas in fact pressures have to be to cause gas to flow in and

5
 Lipid tails (hydrophobic)

Glycerol-based ‘torso’
Phosphoric acid ‘neck’
A Hydrophilic ‘head’

Air

Surfactant phospholipids

Surface-associated phase

Hypophase

Alveolar epithelium
B

Air

Surfactant phospholipids

Surface-associated phase

Hypophase

Alveolar epithelium
C
Figure 1.4 Surfactant.
A: Surfactant phospholipids are composed of two hydrophobic fatty acid tails joined to a hydrophilic head via glycerol and
phosphoric acid. The most common phospholipid in surfactant is phosphatidylcholine, while the hydrophilic head is choline. Fatty
acids in which all the bonds between adjacent carbon atoms are single are said to be ‘saturated’, and are physically flexible,
allowing the molecule to pack in closely to its neighbour. Fatty acids in which one or more of the carbon–carbon bonds are double
are said to be ‘unsaturated’. These double bonds impart an inflexible angulation to the molecule, which prevents it from packing
closely. The most effective phosphatidylcholine molecules are ones in which both fatty acid tails are saturated (‘di-saturated’), such
as dipalmitoyl-phosphatidylcholine.
B: The surfactant phospholipids float on the surface of the fluid lining the alveoli, with their hydrophilic heads in contact with the
aqueous phase and their hydrophobic tails sticking in the air.
C: Expiration reduces the surface area of the alveolus, squeezing the bulkier and less effective phospholipids into the
surface-associated phase. The remaining phospholipids, being predominantly disaturated, are more effective at reducing the
surface tension and, as their concentration is increased, the surface tension is reduced further.
 chapter 1: physiology of ventilation and g as exchange

Proximal airway

Pleural cavity
Interstitium
Alveolus
Pressure

Atmospheric pressure
Transmural pressure

Inspiration
Expiration
Figure 1.5 Absolute pressures along the airway during inspiration (blue) and expiration (green). During inspiration (blue) there is a
pressure gradient between the proximal airway that is at atmospheric pressure at the mouth and the pleural space that is reversed
during expiration.

out of the lung during normal breathing, a fac- the alveoli, but the lower down in the lung the alve-
tor to be considered when comparison is made oli are, the more the distending transmural pressure
with mechanical modes of ventilation. Of course, gradient is counteracted by the weight of lung tissue
much higher pressures can be achieved. Strain- compressing the alveolus from above. For this rea-
ing against a closed glottis, for example, can raise son, dependent alveoli tend to have a smaller radius
alveolar pressure to 190 cm H2 O, while maximal and are more likely to collapse.
inspiratory effort can reduce pressure to as low as The ‘expandability’ of the lung is known as its
−140 cm H2 O. compliance. A high compliance means that the lung
Transmural pressure is defined as the difference expands easily. The compliance of the normal res-
between the pressure in the pleural cavity and that in piratory system (lungs and thoracic cage) in upright
the alveolus (Figure 1.5). To remain open, alveolar humans is about 130 mL.cm H2 O−1 , while that of
pressure must be greater than that of the surround- the lungs alone is roughly twice that value, demon-
ing tissue. During inspiration, intra-pleural pres- strating that half of the work of breathing during
sure falls to a greater degree than alveolar pressure, health simply goes into expanding the rib cage.
and the transmural pressure gradient thus increases. When a positive pressure is applied to the respira-
Over the range of a normal breath, the relationship tory system, such as during positive pressure venti-
between transmural pressure gradient and lung vol- lation, gas immediately starts to flow into the lungs,
ume is almost linear. This relationship holds true for which then expand. However, while gas is flowing,

7
chapter 1: physiology of ventilation and g as exchange

Pressure, P0 Low compliance proximal airways

A
High compliance alveoli
Resistance

Pressure, P1

B
Volume delivered, V

Pressure, P2

C
Volume delivered, V

‘Lungs’

Figure 1.6 Two-compartment model of static and dynamic compliance.

A: In this model the ventilator is represented by the syringe, which is attached to the two-compartment lung model that consists of
a low-compliance proximal chamber (the proximal airways) separated from a high-compliance distal chamber (the alveoli) by a
fixed resistance. Prior to the onset of gas delivery (inspiration), the whole system is at the same pressure: P0 .
B: Gas is delivered to the lung model with a moderate increase in gas pressure in the syringe (the ventilator) and proximal
chamber (the large airways) but with only a small increase in pressure in the distal chamber (the alveoli) as gas seeps through the
resistance. Compliance measured just prior to the end of inspiration would be given by V/P1 .
C: Without the delivery of any further gas from the ventilator, the volume of the distal chamber continues to increase until the
pressure in both chambers becomes the same. As gas redistributes from the high-pressure proximal chamber to the low-pressure
distal chamber, the gas also expands slightly. At equilibrium, the compliance is given by V/P2 , which is larger than that calculated
in B because P2 < P1 .

the proximal airway pressure must be higher than to gas flow (Figure 1.6). At the end of inspiration,
alveolar pressure,5 and the steepness of this pres- the proximal airway pressure immediately falls as
sure gradient will depend on the resistance to gas gas delivery ceases (and with it, the resistive con-
flow. Therefore, during inflation the ratio of vol- tribution to airway pressure) and then falls a little
ume change to inflating pressure (known as dynamic further as gas is redistributed from low-compliance
compliance) is lowered by the effect of resistance proximal airways to high-compliance alveoli. There
is also an associated small increase in total lung vol-
5
Otherwise gas would not flow. ume. The percentage of total change in lung volume

8
 chapter 1: physiology of ventilation and g as exchange

I EIP

End-inspiratory lung volume

Inspiration
Peak inspiratory pressure, Ppeak Expiration

Initial plateau pressure, Pplat-i

Pressure

Volume (ml)
Hysteresis
Plateau pressure, Pplat

End-expiratory lung volume

Pressure (cm water)

Time Figure 1.8 Inspiratory and expiratory volume/pressure loop

during positive pressure inflation showing the phenomenon of
Figure 1.7 A pressure and time profile during volume-targeted
hysteresis.
constant flow mechanical ventilation.
During inspiration (blue) of the lung, both pressure (x-axis)
For a delivered tidal volume of V mL, dynamic compliance is
and volume (y-axis) increase, but this is non-linear. During
given by V/Ppeak and static compliance is given by V/Pplat . The
expiration, the volume/pressure curve traces a different path.
difference between Ppeak and Pplat-i is due to airways
The area subtended by the inspiratory and expiratory paths
resistance, while the difference between Pplat-i and Pplat is due
represents the energy consumed by hysteresis.
to inter-alveolar gas redistribution (pendelluft) and hysteresis.

when held at a set pressure is known as the lung’s LUNG VOLUMES

static compliance. Put another way, if a set volume Total lung capacity (TLC) is the volume of intrapul-
of air is used to inflate a lung, pressure will rise monary gas at the end of a maximal inspiration.
accordingly, but (with lung volume held) will then Functional residual capacity (FRC) is the volume
gradually fall by some 25% or so (Figure 1.7). This remaining in the lungs at the end of normal expi-
effect is one of the contributing factors to a phe- ration that rises with body size (as determined by
nomenon known as hysteresis in which the lung height) and on assumption of the upright pos-
traces a different path on an expiratory plot of lung ture. In mechanically ventilated subjects, FRC is
pressure (x-axis) against volume (y-axis) than it also known as the end-expiratory lung volume
does during inflation (Figure 1.8). Other contrib- (EELV). FRC is reduced when the lung is extrinsically
utors to hysteresis include the opening of previ- compressed (from pleural fluid or abdominal dis-
ously collapsed alveoli during inflation,6 displace- tension), when lung elastic recoil is increased, or
ment of lung blood at higher lung volumes, ‘stress when the lungs are fibrosed.
relaxation’ of lung elastic fibres, and perhaps most
importantly, the surface-area-dependent effect of Gas exchange
surfactant in reducing surface tension. In practice, OXYGEN UPTAKE
what this means is that at any given inflation pres- Oxygenation is accomplished through the diffu-
sure, lung volume will be greater during expiration sion of oxygen down its partial pressure gradient
than inspiration because the lungs are resistant to (Box 1.1) from the alveolus, across the alveolar
accepting a new higher volume, and then resistant epithelium, and thence across the closely apposed
to giving it up again. capillary endothelium to the capillary blood, a
distance of <0.3 µm. The capacity to transfer oxygen
from alveolus to red blood cell is determined by
6
Commonly referred to as alveolar ‘recruitment’. (1) the surface area for diffusion and (2) the ratio

9
chapter 1: physiology of ventilation and g as exchange

Box 1.1 Diffusion and partial

PO2
pressures Final

Diffusion describes the passive movement of a

PO2
substance from an area of high concentration to Initial
one of low concentration. Diffusion also applies to
Thickness
gases, but in this case the motive force is the
differential partial pressure of the gas. Partial
pressure simply refers to the proportion of the total
gas pressure that is attributable to the gas in
question. As an example, if you have a 1-litre flask
containing 800 mL of helium and 200 mL of oxygen Alveolar gas Capillary blood
at atmospheric pressure (101 kPa), the partial

Alveolar epithelium
Capillary endothelium
pressure of oxygen in the flask will be Surface area

200
× 101 = 20.2 kPa.
800 + 200

between the speed of diffusion and the alveolar con-

Figure 1.9 Factors that determine the capacity to transfer
tact time, which is the length of time the red cell oxygen from alveolar gas to capillary blood. Oxygen diffusion
remains in contact with the alveolus (Figure 1.9). (blue arrow) proceeds from alveolar gas (shown on the left) to
The speed of diffusion is determined by the par- capillary blood (shown on the right) across the intervening
barrier of the alveolar epithelium and capillary endothelium,
tial pressure gradient of oxygen between alveolar
with capillary blood shown flowing away from the observer
gas and capillary blood, the thickness of the bar- (red arrow). The capacity to transfer oxygen to red blood cells
rier between alveolus and capillary, and the sol- depends on the surface area for diffusion, and the ratio
between the speed of diffusion and the length of time that the
ubility of oxygen in this barrier. Because there
red cells spend in contact with the alveolus (referred to as the
are no factors that influence oxygen’s solubility ‘contact time’).
under physiological conditions, the only sources The speed of diffusion is determined by the (1) initial partial
of variation in the speed of diffusion are the par- pressure gradient of oxygen between alveolar gas and
tial pressure gradient of oxygen and the barrier capillary blood; (2) the thickness of the barrier constituted by
the alveolar epithelium, capillary endothelium and any other
thickness.
intervening tissue; and (3) the solubility of oxygen in this
The partial pressure of oxygen in alveolar gas barrier.
is not the same as the partial pressure of oxy- The contact time is inversely proportional to the cardiac output
gen in inspired gas because alveolar gas contains and at rest is normally 0.75 seconds. Breathing air at sea level,
two other constituents: carbon dioxide and water red cells passing the alveolus are normally fully saturated after
only 0.25 seconds, leaving a ‘reserve’ of 0.5 seconds. Diffusion
vapour. Therefore, breathing air at sea level, the
limitation to oxygen transfer is therefore only seen with
alveolus contains four gases: nitrogen, oxygen, car- conditions that reduce the speed of diffusion (low alveolar
bon dioxide and water vapour. The total pressure partial pressure of oxygen or increased barrier thickness),
reduce the contact time, or both. In trained athletes at
of these gases must equal atmospheric pressure
maximum exertion the contact time falls to just over 0.25
(101 kPa): seconds.

P A N2 + P A O2 + P AC O2 + P A H2 O = 101 kPa. (1.2)

10
 chapter 1: physiology of ventilation and g as exchange

The saturated vapour pressure of water at body The thickness of the diffusion barrier between
temperature is 6.3 kPa, leaving 94.7 kPa of pressure the alveolus and the capillary is largely determined
for nitrogen, oxygen and carbon dioxide. Because by the combined thickness of the alveolar epithe-
nitrogen is not exchanged in the alveoli, it continues lium and capillary endothelium, which is usually
to occupy 79% of the remaining gas mixture, and less than 0.3 µm. Increases in barrier thickness can
so has an alveolar partial pressure of 74.8 kPa. This be caused by the accumulation of fluid in the space
leaves the remaining 19.9 kPa for oxygen and carbon between these two layers of cells, or by the accumu-
dioxide: lation of other material such as collagen (lung fibro-
sis) or malignant cells (carcinomatosis). Increased
P A O2 + P AC O2 = 94.7 − 74.8 = 19.9 kPa. (1.3)
barrier thickness can also be caused by the accu-
Alveolar carbon dioxide diffuses from mixed mulation of material on the alveolar surface itself,
venous blood into the alveolus until the partial pres- including fluid (pulmonary oedema), blood, pus or
sures in the two compartments are the same. The protein.
partial pressure of carbon dioxide in arterial blood, As the blood transits the capillary, it absorbs
about 4.5 kPa, therefore serves as a good estimate increasing amounts of oxygen, and the gradient-
of the partial pressure of alveolar carbon dioxide. driving diffusion falls. However, haemoglobin’s
However, because the metabolism of fats produces affinity for oxygen has unique characteristics
less carbon dioxide than the metabolism of carbo- (Figure 1.10), and blood oxygen tension nearly
hydrate per unit volume of oxygen consumed, the matches alveolar by the time that only a third
alveolar partial pressure of carbon dioxide must be of the capillary has been transited, which occurs
corrected for the respiratory quotient (RQ) when in about 0.25 seconds at rest. The alveolar con-
substituted into Equation 1.3: tact time is inversely proportional to cardiac out-
put, and in trained athletes can fall to as lit-
P AC O2
P A O2 + = 19.9 kPa tle as 0.25 seconds, the time normally required
RQ
4.5 for full saturation. Under these conditions, small
⇒ P A O2 + = 19.9 kPa decreases in the speed of diffusion, such as by exer-
0.8
⇒ P A O2 = 19.9 − 5.625 = 14.275 kPa cising at altitude, can result in significant arterial
desaturation.
In general, therefore, the partial pressure of alveolar
Even when all the blood leaving the alveoli has
oxygen is given by the equation:
an oxygen partial pressure that is the same as the

 P aCO2 alveolar partial pressure, the partial pressure of
P AO2 = F I O2 ×(Pb − 6.3) − . (1.4)
0.8 oxygen in arterial blood leaving the left ventricle is
When FiO2 is the fractional concentration of oxy- slightly lower because of the presence of an anatom-
gen in the inspired air, Pb is the barometric (atmo- ical shunt. This shunt is caused by the dilution of
spheric) pressure, and PaCO2 is the arterial partial arterialized blood that has come from the alveoli by
pressure of carbon dioxide, all measured in kPa. true venous blood that drains into the pulmonary
Oxygen partial pressure in mixed venous blood veins from the bronchial circulation (supplying the
is roughly 5.3 kPa and, as calculated above, in airways rather than alveoli) or from the left ven-
alveolar gas is about 14.3 kPa. A diffusion gradi- tricular endocardium via the tiny thebesian veins.
ent of about 8 kPa thus drives oxygen across the Such effects are normally only minor, causing a fall
alveolar surface and into the blood under normal in anticipated arterial partial pressure of oxygen of
conditions. just 0.5 to 0.8 kPa.

11
chapter 1: physiology of ventilation and g as exchange

100

Haemoglobin saturation (%)

75

50

25

0 5 10 15
Oxygen binding site
Partial pressure of oxygen (kPa)

Haemoglobin

Oxygen molecules
Figure 1.10 Intermolecular co-operation and the oxy-haemoglobin dissociation curve. A haemoglobin molecule consists of four
chains, each with one binding site for molecular oxygen (O2 ). When a molecule of oxygen occupies its binding site on any one of
the chains, it provokes a change in the shape of that chain which increases the affinity of its neighbouring chain for oxygen (shown
here in amber), making it easier for that chain to bind oxygen. This intermolecular co-operation accounts for the non-linear
relationship between haemoglobin oxygen saturation and oxygen partial pressure, often referred to as the ‘oxy-haemoglobin
dissociation curve’ (shown on the right). Haemoglobin’s affinity for oxygen can be either increased (blue interrupted line) or
decreased (pink interrupted line) by other factors, effects which are often referred to as ‘left-shift’ or ‘right-shift’, respectively.
Increased temperature and acidosis decrease haemoglobin’s affinity for oxygen (right-shift), while decreased temperature and
alkalosis do the reverse. Fetal variants of haemoglobin bind oxygen with greater affinity than do adult variants, making it possible
for oxygen to be transferred from maternal to fetal haemoglobin in the placenta.

Causes of low arterial partial pressure that is determined by the alveolar partial pressure of
of oxygen oxygen, as shown in Equation (1.4) above. This tells
As described previously, the arterial partial pressure us that under these conditions, the principal vari-
of oxygen is derived from the mixture in the left ables involved in determining PO2 are (1) the frac-
side of the heart of blood having a range of partial tional concentration of oxygen in the inspired gas
pressures of oxygen, depending on its source. Blood (FiO2 ), (2) the barometric pressure of the inspired
leaving normally ventilated alveoli with optimal oxy- gas and (3) the alveolar partial pressure of carbon
gen transfer will have a partial pressure of oxygen dioxide.

12
 chapter 1: physiology of ventilation and g as exchange

Altitude (feet)

100,000
10,000

20,000

30,000

40,000

50,000

60,000

70,000

80,000

90,000
120

100
Barometric pressure (kPa)

80 Denver, Colorado

Cuzco, Peru
60

40
Everest

20

SR-71
0
10,000

15,000

20,000

25,000

30,000
5,000
0

Altitude (metres)
Figure 1.11 A fall in barometric pressure with increasing altitude.
The barometric (atmospheric) pressure falls non-linearly with increasing altitude. The highest permanent human habitation is
believed to be La Rinconada, Peru, at 16 700 feet (5100 metres).

FiO2 . Low fractional concentration of inspired to be incapable of delivering hypoxic gas mixtures,
oxygen is not usually a problem in patients receiv- though old machines which can do so remain in
ing mechanical ventilation, though it did cause the use in many countries.
death of a child in the UK as recently as 2001 when Barometric pressure. Low barometric pressure is
they were ventilated with a hypoxic gas mixture from never a problem in Europe except during aerial
an old anaesthetic machine. Modern anaesthetic transport (see Chapter 16), but in other parts of the
machines and intensive care ventilators are designed world this may be a significant factor (Figure 1.11).

13
chapter 1: physiology of ventilation and g as exchange

Hypoventilation. If oxygen consumption in periph- pulmonary arterio-venous malformations. Intra-

eral tissues remains constant, so too must the quan- pulmonary shunts acquired in adulthood are also
tity of oxygen extracted from the alveolus. In pro- very uncommon, but can occur in patients with
found hypoventilation, the amount of oxygen being severe liver disease.
delivered to the alveolus will fall, as will the ratio Alveolar shunts. So far, the discussion has assumed
of delivery to extraction. As a result, alveolar (and that blood draining from the alveoli has come from
thus arterial) partial pressure of oxygen will fall. alveoli with completely normal ventilation and per-
This phenomenon will be compounded by a rise fusion, and is therefore optimally oxygenated. In
in alveolar carbon dioxide tension due to failure reality, both alveolar ventilation and perfusion can
of clearance, which will cause a further fall in range from normal to none (Figure 1.12). Thus at
alveolar PO2 . one end of the spectrum there are alveoli with nor-
Diffusion limitation. The three factors above have mal ventilation but no perfusion (so-called ‘dead
all assumed optimal oxygen transfer between alveo- space’), and at the other end there are alveoli with
lar gas and capillary blood, but as discussed above, normal perfusion but no ventilation (a so-called
this assumes a normal ratio between the speed of ‘true shunt’). With respect to oxygenation, it is the
diffusion and the alveolar contact time. A reduction perfused units with markedly reduced or absent venti-
of contact time (with an increase in cardiac output) lation which are important, as these act as ‘shunts’
or reduction in the speed of diffusion caused by an through which blood can travel from systemic veins
increased diffusion distance can also cause a low to systemic arteries without becoming oxygenated.
arterial partial pressure of oxygen. The impact of a shunt on arterial haemoglobin oxy-
Besides the normal ‘anatomical’ shunts that con- gen saturation is directly proportional to the size of
tribute venous blood to the arterial pool described the shunt in terms of blood flow. So, for example, if
above, two other sources of shunt can contribute 80% of pulmonary venous blood comes from ven-
to arterial hypoxaemia: pathological and alveolar tilated alveoli with an SaO2 of 98% and 20% comes
shunts. from non-ventilated alveoli with an SaO2 of 75%,
Pathological shunts. These are caused by abnor- the resulting SaO2 is calculated as
mal connections between the right and left sides
(0.8 × 98) + (0.2 × 75) = 93.4%. (1.5)
of the heart, allowing venous blood to join arterial
blood in the left ventricle without passing through This calculation allows the size of the shunt to
the lungs. When arising during fetal development, be estimated (Box 1.2). It is also worth noting that
these shunts are usually situated within the heart because the blood coming from ventilated alveoli
itself and are caused by failure in the development has almost the same PO2 as alveolar gas, there is
of midline structures such as the septa between the almost no capacity for these alveoli to absorb addi-
atria or ventricles. tional oxygen in order to compensate for blood
Similar defects can occasionally arise in adult- coming from alveoli that are poorly ventilated (low

hood following infarction of the septal tissue or as V̇ Q̇) or not ventilated at all (a true shunt). In con-
a consequence of cardiac trauma. Even less com- trast, venous blood only loses 10 to 15% of its car-
monly, a right-to-left shunt can arise in adult- bon dioxide content in passing through ventilated
hood when either surgery or pulmonary disease alveoli. In this case, failure to clear carbon dioxide
allows blood to pass through a patent foramen from blood passing through unventilated alveoli is
ovale. Congenital intra-pulmonary shunts are rare easily compensated by an increase in carbon dioxide
and are usually associated with massive intra- elimination from blood passing through ventilated

14
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