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NINTH EDITION
Andrew Lumb MB BS FRCA
Consultant Anaesthetist,
St James’s University Hospital,
Leeds, UK
Honorary Clinical Associate Professor,
University of Leeds,
Leeds, UK
The right of Andrew Lumb and Caroline Thomas to be identified as authors of this work has been asserted by
them in accordance with the Copyright, Designs and Patents Act 1988.
No part of this publication may be reproduced or transmitted in any form or by any means, electronic or
mechanical, including photocopying, recording or any information storage and retrieval system, without
permission in writing from the publisher. Details on how to seek permission, further information about the
Publisher’s permissions policies and our arrangements with organizations such as the Copyright Clearance
Center and the Copyright Licensing Agency, can be found at our website: www.elsevier.com/permissions.
This book and the individual contributions contained in it are protected under copyright by the Publisher
(other than as may be noted herein).
Notices
Practitioners and researchers must always rely on their own experience and knowledge in evaluating and
using any information, methods, compounds or experiments described herein. Because of rapid advances
in the medical sciences, in particular, independent verification of diagnoses and drug dosages should
be made. To the fullest extent of the law, no responsibility is assumed by Elsevier, authors, editors or
contributors for any injury and/or damage to persons or property as a matter of products liability,
negligence or otherwise, or from any use or operation of any methods, products, instructions or ideas
contained in the material herein.
ISBN: 978-0-7020-7908-5
Ink ISBN: 978-0-7020-7934-4
eBook ISBN: 978-0-7020-7933-7
Printed in China
It is truly an honor to be asked to write the Foreword to explains respiration starting with the relevant anatomy and
this newest edition of the landmark text in Respiratory progressing through lung mechanics, pulmonary circulation
Physiology. For 50 years this has been the acknowledged and gas exchange to cellular respiration. The final chapter
source for education and reference for physicians, scientists deals with the non-respiratory functions of the lungs. Part 2
and students whose clinical practice and curiosity involve then discusses several specific clinical conditions such as
the respiratory system. The first edition of the pioneering pregnancy, paediatrics, sleep, extremes of barometric pres-
text Nunn’s Applied Respiratory Physiology was published sure, anaesthesia and air pollution. A very well written and
in 1969 with Dr. John Nunn as the Editor. After the useful addition to the is 9th edition is Chapter 15 on Obesity.
4th edition, the torch was passed to Dr. Andrew Lumb who Obesity has become an epidemic in the developed world and
maintained the excellent standards and expanded the focus the ventilatory management of obese patients during mini-
through the 5th to 8th editions. Now with this 9th edition, mally invasive surgery is currently a significant clinical issue.
the text has become Nunn and Lumb’s Applied Physiology Part 3 on the Physiology of Pulmonary Disease presents
and Dr. Lumb has shared the authorship with Dr. Caroline chapters on a range of very important clinical topics from
Thomas. ventilatory failure to pulmonary surgery. Of particular note
I have been told that an efficient method of teaching is are the up-to-date chapters on acute lung injury and respira-
to: “Say what you’re going to say, say it, and then repeat tory support. This is a rapidly evolving area and recent devel-
what you said”. The Authors follow this scheme using Key opments are presented clearly and concisely.
Points at the beginning of each chapter then following at the I find Respiratory Physiology a difficult topic. I tell
end with an online Summary to reinforce the educational students that if the answer is simple, you don’t understand
material. Also, they have maintained the use of a large num- the question. Yet in the practice of Anaesthesia we are forced
ber of clear and memorable figures and diagrams. I believe to make important decisions on how to manage the airway,
their frequent use of electrical or hydrostatic models to ex- gas exchange and respiratory mechanics of diverse individu-
plain the underlying physiology is one of the elements that al patients on a daily basis. This text helps walk us through
makes this text so useful to learners. many of these complex clinical decisions. I would like to
The Editors have continued the logical progression of thank and congratulate Drs. Lumb and Thomas for their
this text, refined in previous editions, beginning with Part 1 excellent work.
on Basic Principles and then building on this foundation to
develop Part 2 on Applied Physiology and finally to extend Peter Slinger
to Part 3 on The Physiology of Pulmonary Disease. Part 1 Professor of Anesthesia , University of Toronto
vi
Preface to the Ninth Edition
Over the past five decades Nunn’s Applied Respiratory Physi- artificial ventilation in healthy lungs, for example, during
ology has developed into a renowned textbook on respira- anaesthesia, remains disputed; the section in Chapter 21 has
tion, providing both physiologists and clinicians with a been updated to reflect the physiological effects of these
unique fusion of underlying principles and their applica- strategies, for example, the recent focus on driving pressure
tions. After writing four editions, Dr John Nunn retired as the potentially damaging component. The role of intra-
in 1991, and a new author was required. As Dr Nunn’s operative ventilation strategy in the prevention of postop-
final research fellow in the Clinical Research Centre in erative pulmonary complications is becoming more clear.
Harrow, AL was honoured to be chosen as his successor. AL In keeping with its increasing worldwide prevalence,
has now also completed four editions and has chosen a suc- the effects of severe obesity on the respiratory system are
cessor to lead the project into the future whilst maintaining now brought together into a new chapter for this edition.
the fundamental ethos of the book. As practising clinicians Chapter 15 covers the predictable aspects of obesity on res-
with a fascination for physiology, the authors of the ninth piration, such as the effect of the mass of the chest wall and
edition have again focussed on combining a clear, logical abdomen on lung mechanics and lung volumes. Less pre-
and comprehensive account of basic respiratory physiology dictable topics include the effects of obesity hormones on
with a wide range of applications, both physiological and respiratory control. The chapter also covers the impact of
clinical. This approach acknowledges the popularity of childhood obesity on lung development, which may lead to
the book amongst doctors from many medical specialities, lung dysanapsis in which airway and gas exchange tissues
but also provides greater insight into the applications grow disproportionately.
of respiratory physiology to readers with a scientific back- For this edition the book is printed with a larger page
ground. The clinical chapters of Part 3 are not intended format to improve the clarity of the figures and tables, and
to be comprehensive reviews of the pulmonary diseases remains available in both print and electronic format. This
considered, but rather to provide a detailed description allows readers wishing to dip into the book access to chapter
of physiological changes, accompanied by a brief account summaries or individual chapters. For those who own a
of the clinical features and treatment of the disease. print copy, online access is automatically available. This
In this edition, the number of references provided has content includes additional chapters and self-assessment
been reduced by around a third in recognition of the ease material, useful for students approaching exams and, new
with which online searches may now be performed. Refer- for this edition, a series of 24 mini-lectures by AL to en-
ences retained are either historical or seminal papers, or re- hance the information provided in print.
cent high-quality publications. Key references are identified We wish to thank the many people who have helped with
by bold type in the reference list following each chapter. the preparation of the book at Elsevier and our colleagues
These highlighted references either provide outstanding re- who have assisted our acquisition of knowledge in subjects
cent reviews of their subject or describe research that has not so close to our own areas of expertise. We are indebted
made a significant impact on the topic under consideration. to Professor Peter Slinger for his kind words in the Foreword
Advances in respiratory physiology since the last edition and would like to thank Drs B. Oliver, J. Black, K. McKay
are too numerous to mention individually. Appreciation of and P. Johnson for permission to use the images in Figure
the impact of air quality on the lungs continues to develop, 28.3. Last, but by no means least, we thank our families for
and there is increasing awareness of the global health burden their continuing encouragement and for tolerating preoc-
of pollution. Chapter 20 has been updated in recognition cupied and reclusive parents/spouses for so long. AL’s
of this and the publication of new worldwide guidelines daughter Jenny, when aged 5, often enquired about his ac-
on pollution levels. The harmful effects of hyperoxia are be- tivities in the study, until one evening she nicely summa-
coming more accepted in clinical practice, and the physio- rized the years of work by confidently stating that ‘if you
logical mechanisms of these are described in Chapter 25. don’t breathe, you die’. So what were the other 423 pages
There is much recent literature on this topic, exemplified about?
by the U-shaped curve of oxygen levels and mortality in Andrew Lumb and Caroline Thomas
critical care patients (see Fig. 25.6). The optimal strategy for Leeds 2019
vii
Contents
viii
Videos Table of Contents
ix
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PART I
Basic Principles
1
1
Functional Anatomy
of the Respiratory Tract
K E Y P O I N TS
• In addition to conducting air to and from the lungs, the • The alveolar wall is ideally designed to provide the minimal
nose, mouth and pharynx have other important functions physical barrier to gas transfer, whilst also being structurally
including speech, swallowing and airway protection. strong enough to resist the large mechanical forces applied
• Starting at the trachea, the airway divides about 23 times, to the lung.
terminating in an estimated 30 000 pulmonary acini, each
containing more than 10 000 alveoli.
T
his chapter is not a comprehensive account of respi- tongue is lying against the hard palate. The soft palate is
ratory anatomy but concentrates on those aspects clear of the posterior pharyngeal wall. Figure 1.1, B, shows
that are most relevant to an understanding of func- forced mouth breathing, for instance when blowing through
tion. The respiratory muscles are covered in Chapter 5. the mouth without pinching the nose. The soft palate be-
comes rigid and is arched upwards and backwards by con-
Mouth, Nose and Pharynx traction of tensor and levator palati to lie against a band of
the superior constrictor of the pharynx known as Passavant’s
Breathing is normally possible through either the nose or ridge, which, together with the soft palate, forms the
the mouth, the two alternative air passages converging in palatopharyngeal sphincter. Note also that the orifices of
the oropharynx. Nasal breathing is the norm and has two the pharyngotympanic (Eustachian) tubes lie above the pal-
major advantages over mouth breathing: filtration of par- atopharyngeal sphincter and can be inflated by the subject
ticulate matter by the vibrissae hairs and better humidifica- only when the nose is pinched. As the mouth pressure is
tion of inspired gas. Humidification by the nose is highly raised, this tends to force the soft palate against the posterior
efficient because the nasal septum and turbinates increase pharyngeal wall to act as a valve. The combined palatopha-
the surface area of mucosa available for evaporation and ryngeal sphincter and valvular action of the soft palate is
produce turbulent flow, increasing contact between the very strong and can easily withstand mouth pressures in
mucosa and air. However, the nose may offer more resis- excess of 10 kPa (100 cmH2O).
tance to airflow than the mouth, particularly when ob- Figure 1.1, C, shows the occlusion of the respiratory tract
structed by polyps, adenoids or congestion of the nasal during a Valsalva manoeuvre. The airway is occluded at
mucosa. Nasal resistance may make oral breathing obliga- many sites: the lips are closed, the tongue is in contact with
tory, and many children and adults breathe only or partly the hard palate anteriorly, the palatopharyngeal sphincter is
through their mouths at rest. With increasing levels of exer- tightly closed, the epiglottis is in contact with the posterior
cise in normal adults, the respiratory minute volume in- pharyngeal wall, and the vocal folds are closed, becoming
creases, and at a level of around 35 L.min21 the oral airway visible in the midline in the figure.
comes into play. Deflection of gas into either the nasal or During swallowing the nasopharynx is occluded by con-
the oral route is under voluntary control and accomplished traction of both tensor and levator palati. The larynx is ele-
with the soft palate, tongue and lips. These functions vated 2 to 3 cm by contraction of the infrahyoid muscles,
are best considered in relation to a midline sagittal section stylopharyngeus and palatopharyngeus, coming to lie under
(Fig. 1.1). the epiglottis. In addition, the aryepiglottic folds are ap-
Figure 1.1, A, shows the normal position for nose breath- proximated, causing total occlusion of the entrance to the
ing: the mouth is closed by occlusion of the lips, and the larynx. This extremely effective protection of the larynx is
2
CHAPTER 1 Functional Anatomy of the Respiratory Tract 3
10
Oral cavity
Oropharynx
T 6 Bronchi
Incisors
L
Glottis
E 4
SP Trachea
0
0 5 10 15 20 25 30 35
Distance along airway (cm)
The Larynx
The larynx evolved in the lungfish for the protection of the
airway during such activities as feeding and perfusion of the
VF
gills with water. Although protection of the airway remains
important, the larynx now has many other functions, all
involving some degree of laryngeal occlusion.
Speech
Phonation, the laryngeal component of speech, requires a
combination of changes in position, tension and mass of
C
the vocal folds (cords). Rotation of the arytenoid cartilages
by the posterior cricoarytenoid muscles opens the vocal
folds, while contraction of the lateral cricoarytenoid and
• Fig. 1.1 Magnetic resonance imaging scans showing median sagittal
sections of the pharynx in a normal subject. (A) Normal nasal breathing oblique arytenoid muscles opposes this. With the vocal
with the oral airway occluded by lips and tongue. (B) Deliberate oral folds almost closed, the respiratory muscles generate a posi-
breathing with the nasal airway occluded by elevation and backwards tive pressure of 5 to 35 cmH2O, which may then be re-
movement of the soft palate. (C) A Valsalva manoeuvre in which the leased by slight opening of the vocal folds to produce sound
subject deliberately tries to exhale against a closed airway. Data acqui-
waves. The cricothyroid muscle tilts the cricoid and aryte-
sition for scans (A) and (B) took 45 s, so anatomical differences
between inspiration and expiration will not be visible. I am indebted noid cartilages backwards and also moves them posteriorly
to Professor M. Bellamy for being the subject. E, Epiglottis; L, larynx; in relation to the thyroid cartilage. This produces up to
NC, nasal cavity; SP, soft palate; T, tongue; VF, vocal fold. 50% elongation and therefore tensioning of the vocal
4 PA RT I Basic Principles
folds, an action opposed by the thyroarytenoid muscles, Work using computed tomography to reconstruct, in
which draw the arytenoid cartilages forwards towards the three dimensions, the branching pattern of the airways has
thyroid, shortening and relaxing the vocal folds. Tension- shown that a regular dichotomy system does occur for at
ing of the folds results in both transverse and longitudinal least the first six generations.3 Beyond this point, the same
resonance of the vocal fold, allowing the formation of com- study demonstrated trifurcation of some bronchi and air-
plex sound waves. The deeper fibres of the thyroarytenoids ways that terminated at generation 8. Table 1.1 traces the
comprise the vocales muscles, which exert fine control characteristics of progressive generations of airways in the
over the pitch of the voice by creating slight variations in respiratory tract.
both the tension and mass of the vocal folds. A more dra-
matic example of the effect of vocal fold mass on voice Trachea (Generation 0)
production occurs with inflammation of the laryngeal
mucosa and the resulting hoarse voice or complete inability The adult trachea has a mean diameter of 1.8 cm and length
to phonate. of 11 cm. Anteriorly it comprises a row of U-shaped carti-
lages which are joined posteriorly by a fibrous membrane
Effort Closure incorporating the trachealis muscle (Fig. 1.3). The part of
the trachea in the neck is not subjected to intrathoracic
Tighter occlusion of the larynx, known as effort closure, is pressure changes, but it is very vulnerable to pressures aris-
required for making expulsive efforts. It is also needed to ing in the neck due, for example, to tumours or haematoma
lock the thoracic cage, securing the origin of the muscles of formation. An external pressure of the order of 4 kPa
the upper arm arising from the rib cage, thus increasing the (40 cmH2O) is sufficient to occlude the trachea. Within the
power which can be transmitted to the arm. In addition to chest, the trachea can be compressed by raised intrathoracic
simple apposition of the vocal folds described previously, pressure during, for example, a cough, when the decreased
the aryepiglottic muscles and their continuation, the diameter increases the linear velocity of gas flow, and there-
oblique and transverse arytenoids, act as a powerful sphinc- fore the efficiency of removal of secretions (page 47).
ter capable of closing the inlet of the larynx by bringing the
aryepiglottic folds tightly together. The full process enables Main, Lobar and Segmental Bronchi
the larynx to withstand the highest pressures which can (Generations 1–4)
be generated in the thorax, usually at least 12 kPa
(120 cmH2O) and often more. Sudden release of the The trachea bifurcates asymmetrically, and the right bron-
obstruction is essential for effective coughing (page 46), chus is wider and makes a smaller angle with the long axis
when the linear velocity of air through the larynx is said of the trachea. Foreign bodies therefore tend to enter the
to approach the speed of sound. right bronchus in preference to the left. Main, lobar and
Laryngeal muscles are involved in controlling airway re- segmental bronchi have firm cartilaginous support in their
sistance, particularly during expiration, and this aspect of walls that is U-shaped in the main bronchi, but in the form
vocal fold function is described in Chapter 5. of irregularly shaped and helical plates lower down, with
bronchial muscle between. Bronchi in this group (down to
The Tracheobronchial Tree generation 4) are sufficiently regular to be individually
named (Fig. 1.4). The total cross-sectional area of the respi-
An accurate and complete model of the branching pattern ratory tract is minimal at the third generation (Fig. 1.5).
of the human bronchial tree remains elusive, although sev- These bronchi are subjected to the full effect of changes
eral different models have been described. The most useful in intrathoracic pressure and will collapse when the intra-
and widely accepted approach remains that of Weibel,2 who thoracic pressure exceeds the intraluminar pressure by
numbered successive generations of air passages from the around 5 kPa (50 cmH2O). This occurs in the larger bron-
trachea (generation 0) down to alveolar sacs (generation 23). chi during a forced expiration, limiting peak expiratory flow
This ‘regular dichotomy’ model assumes that each bronchus rate (see Fig. 3.7).
regularly divides into two approximately equal size daugh-
ter bronchi. As a rough approximation it may therefore be Small Bronchi (Generations 5–11)
assumed that the number of passages in each generation is
double that in the previous generation, and the number of The small bronchi extend through about seven generations,
air passages in each generation is approximately indicated with their diameter progressively falling from 3.5 to 1 mm.
by the number 2 raised to the power of the generation num- Down to the level of the smallest true bronchi, air passages
ber. This formula indicates one trachea, two main bronchi, lie in close proximity to branches of the pulmonary artery in
four lobar bronchi, 16 segmental bronchi and so on. a sheath containing pulmonary lymphatics, which can be
However, this mathematical relationship is unlikely to be distended with oedema fluid, giving rise to the characteristic
true in practice, where bronchus length is variable, pairs ‘cuffing’ responsible for the earliest radiographic changes in
of daughter bronchi are often unequal in size, and trifurca- pulmonary oedema. Because these air passages are not di-
tions may occur. rectly attached to the lung parenchyma, they are not subject
TABLE
1.1 Structural Characteristics of the Air Passages
Mean
Diameter Area
Generation Number (mm) Supplied Cartilage Muscle Nutrition Emplacement Epithelium
5
6 PA RT I Basic Principles
Right Left
UPPER UPPER
Apical Apical
Posterior Posterior
Anterior Anterior
MIDDLE Lingula
Lateral Superior
Medial Inferior
LOWER
Lateral basal
Anterior basal LOWER
Posterior basal Lateral basal
Medial basal Posterior basal
Apical Anterior basal
Apical
• Fig. 1.4 Lobes and bronchopulmonary segments of the lungs. Red, upper lobes; blue, lower lobes;
green, right middle lobe. The 19 major lung segments are labelled.
CHAPTER 1 Functional Anatomy of the Respiratory Tract 7
Terminal bronchiole
1000
Respiratory bronchioles
100
10
Alveolar ducts
0
0 5 10 15 20 23
Airway generation
• Fig. 1.5 The total cross-sectional area of the air passages at different
generations of the airways. Note that the minimum cross-sectional
area is at generation 3 (lobar to segmental bronchi). The total cross-
sectional area becomes very large in the smaller air passages, ap- Alveolar sacs
proaching a square metre in the alveolar ducts.
Pulmonary Acinus
This is defined as the region of lung supplied by a first-order
respiratory bronchiole, and includes the respiratory bron-
chioles, alveolar ducts and alveolar sacs distal to a single
terminal bronchiole (Fig. 1.6). This represents the afore-
mentioned generations 15 to 23, but in practice the num-
ber of generations within a single acinus is quite variable,
being between six and 12 divisions beyond the terminal
bronchiole. A human lung contains about 30 000 acini, B
each with a diameter of around 3.5 mm and containing in
excess of 10 000 alveoli. A single pulmonary acinus is prob- • Fig. 1.6 (A) Schematic diagram of a single pulmonary acinus show-
ably the equivalent of the alveolus when it is considered ing four generations between the terminal bronchiole and the alveolar
from a functional standpoint, as gas movement within the sacs. The average number of generations in the human lung is eight,
but may be as many as 12. (B) Section of rabbit lung showing respira-
acinus when breathing at rest is by diffusion rather than tory bronchioles leading to alveolar ducts and sacs. Human alveoli
tidal ventilation. Acinar morphometry therefore becomes would be considerably larger. Scale bar 5 0.5 mm. (Photograph kindly
crucial,4 in particular the path length between the start of supplied by Professor E. R. Weibel.)
8 PA RT I Basic Principles
the acinus and the most distal alveolus, which in humans is Club Cells (Formerly Clara Cells)
between 5 and 12 mm. These nonciliated bronchiolar epithelial cells are found in
the mucosa of the terminal bronchioles, where they may be
Respiratory Epithelium the precursor of epithelial cells in the absence of basal cells.
They are metabolically active, secreting a club cell secretory
Before inspired air reaches the alveoli it must be ‘conditioned’, protein which has antioxidant and immune-modulatory
that is, warmed and humidified, and airborne particles, patho- functions.7
gens and irritant chemicals removed. These tasks are under-
taken by the respiratory epithelium and its overlying layer Neuroepithelial Cells
of airway lining fluid, and are described in Chapter 11. To These cells are found throughout the bronchial tree but oc-
facilitate these functions the respiratory epithelium contains cur in larger numbers in the terminal bronchioles. They
numerous cell types. may be found individually or in clusters as neuroepithelial
bodies, and are of uncertain function in the adult lung.
Ciliated Epithelial Cells5 Present in foetal lung tissue in a greater number, they may
These are the most abundant cell type in the respiratory have a role in controlling lung development. Similar cells
epithelium. In the nose, pharynx and larger airways the elsewhere in the body secrete a variety of amines and pep-
epithelial cells are pseudostratified, gradually changing to a tides such as calcitonin, gastrin-releasing peptide, calcitonin
single layer of columnar cells in bronchi, cuboidal cells in gene-related peptide and serotonin.
bronchioles and finally thinning further to merge with the
type I alveolar epithelial cells (see later). They are differenti- The Alveoli
ated from either basal or secretory cells (see later) and
are characterized by the presence of around 300 cilia per The mean total number of alveoli has been estimated as
cell (page 165). The ratio of secretory to ciliated cells in 400 million, but ranges from about 270 to 790 million,
the airway decreases in more distal airways from about correlating with the height of the subject and total lung
equal in the trachea to almost three-quarters ciliated in the volume.8 The size of the alveoli is dependent on lung
bronchioles. volume, but at functional residual capacity (FRC) they
are larger in the upper part of the lung because of gravity.
Goblet Cells At total lung capacity this situation reverses, and there
These are present at a density of approximately 6000 per are estimated to be 32 alveoli per mm3 at the lung apices
mm2 (in the trachea) and are responsible for producing compared with 21 at the lung bases.9 At FRC the mean
the thick layer of mucus that lines all but the smallest diameter of a single alveolus is 0.2 mm, and the total
conducting airways (page 165). surface area of the alveoli is around 130 m2.
Airway Glands6
The Alveolar Septa
Submucosal glands occur predominantly in the trachea and
larger bronchi, diminishing in both size and numbers in The septa are under tension generated partly by collagen
more distal airways. The glands consist of a series of branch- and elastin fibres, but more by surface tension at the
ing ducts, ending with a single terminal duct opening into air–fluid interface (page 14). They are therefore generally
the airway and contain both serous cells and mucous cells, flat, making the alveoli polyhedral rather than spherical.
with serous cells occurring in the gland acinus, whereas The septa are perforated by small fenestrations known as the
mucous cells are found closer to the collecting duct. The pores of Kohn (Fig. 1.7), which provide collateral ventila-
serous cells have the highest levels of membrane-bound tion between alveoli. Collateral ventilation also occurs be-
cystic fibrosis transmembrane conductance regulator in the tween small bronchioles and neighbouring alveoli (Lambert
lung (Chapter 28). channels) and through interbronchiolar pathways of
Martin, and is more pronounced in patients with emphy-
Basal Cells sema (page 332) and in some other species of mammal
These cells lie underneath the columnar cells, giving rise to (page 310).
the pseudostratified appearance, and are absent in the bron- On one side of the alveolar wall the capillary endotheli-
chioles and beyond. They are the stem cells responsible for um and the alveolar epithelium are closely apposed, with
producing new epithelial and goblet cells. almost no interstitial space, such that the total thickness
from gas to blood is around 0.3 mm (Figs 1.8 and 1.9).10
Mast Cells This may be considered the ‘active’ side of the capillary, and
The lungs contain numerous mast cells which are located gas exchange must be more efficient on this side. The other
underneath the epithelial cells of the airways and in the al- side of the capillary, which may be considered the ‘service’
veolar septa. Some also lie free in the lumen of the airways side, is usually more than 1- to 2-mm thick, and contains
and may be recovered by bronchial lavage. Their important a recognizable interstitial space containing elastin and
role in bronchoconstriction is described in Chapter 28. collagen fibres, nerve endings and occasional migrant
CHAPTER 1 Functional Anatomy of the Respiratory Tract 9
5 µm
2 µm
BM
FB Ep 0.5 µm
B
AE
AE
AE
AE
AE
A B
• Fig. 1.10 Electron micrographs of the collagen fibre network of rat lung at low lung volume (A) and when
fully inflated (B).12 Note the folded, zigzag shape of the collagen at low lung volume in (A). (Photograph
from Professor Ohtani. Reproduced by permission of Archives of Histology and Cytology.)
How the shape of this complex structure changes with endothelium and/or epithelium, whereas the basement
breathing remains uncertain.13 Increasing lung volume may membrane tends to remain intact, sometimes as the only re-
be achieved by increasing the size of alveolar ducts, expand- maining separation between blood and gas.
ing alveoli or recruiting previously collapsed alveoli. All
three undoubtedly contribute, as lung volume increases
approximately fivefold from residual volume to total lung Alveolar Cell Types
capacity (page 22). Recent work using a new imaging tech- Capillary Endothelial Cells
nique demonstrated only small changes in alveolar size at
different lung volumes, but a large change in alveolar num- These cells are continuous with the endothelium of the
bers, indicating recruitment as the main mechanism for in- general circulation and, in the pulmonary capillary bed,
creasing lung volume.8,13 Change in alveolar size is have a thickness of only 0.1 mm, except where expanded to
facilitated by the molecular structures of both the elastin contain nuclei (Fig. 1.8). Electron microscopy shows the
and collagen that make up the fibre scaffold, with the flat parts of the cytoplasm are devoid of all organelles except
collagen forming helices or zigzags at lower lung volumes for small vacuoles (caveolae or plasmalemmal vesicles)
(Fig. 1.10).12 which may open onto the basement membrane or the lu-
At the cellular level, the scaffolding for the alveolar septa men of the capillary or be entirely contained within the
is provided by the basement membrane, which provides cytoplasm (Fig. 1.9). The endothelial cells abut one another
the blood–gas barrier with enough strength to withstand the at fairly loose junctions of the order of 5 nm wide. These
enormous forces applied to lung tissue.14 At the centre of the junctions permit the passage of quite large molecules, and
basement membrane is a layer of type IV collagen, the lami- the pulmonary lymph contains albumin at about half the
na densa, which is around 50 nm thick and made up of concentration as that found in plasma. Macrophages pass
many layers of a diamond-shaped matrix of collagen mole- freely through these junctions under normal conditions,
cules. On each side of the lamina densa the collagen layer is and polymorphs can also pass in response to chemotaxis
attached to the alveolar or endothelial cells by a series of pro- (page 353).
teins collectively known as laminins, of which seven subtypes
are now known. The laminins are more than simple struc- Alveolar Epithelial Cells: Type I15
tural molecules, having complex interactions with mem-
brane proteins and the intracellular cytoskeleton to help These cells line the alveoli and exist as a thin sheet of around
regulate cell shape, permeability and so on. These aspects of 0.1 mm in thickness, except where expanded to contain
the function of the basement membrane are important. In- nuclei. Like the endothelium, the flat part of the cytoplasm
creases in the capillary transmural pressure gradient greater is devoid of organelles, except for small vacuoles. Epithelial
than around 3 kPa (30 cmH2O) may cause disruption of cells each cover several capillaries and are joined into a
CHAPTER 1 Functional Anatomy of the Respiratory Tract 11
Alv
Pulmonary Arterioles
The transition to arterioles occurs at an internal diameter of
100 mm. These vessels differ radically from their counter-
parts in the systemic circulation and are virtually devoid of
• Fig. 1.11 Electron micrograph of a type II alveolar epithelial cell of a
muscular tissue. There is a thin media of elastic tissue sepa-
dog. Note the large nucleus, the microvilli and the osmiophilic lamellar
bodies thought to release surfactant. Alv, alveolus; C, capillary; LB, rated from the blood by endothelium. Structurally there
lamellar bodies; N, nucleus. (From reference 17 by permission of Pro- is no real difference between pulmonary arterioles and
fessor E. R. Weibel and the editors of Physiological Reviews.) venules.
12 PA RT I Basic Principles
TABLE Dimensions of the Branches of the Human from one alveolus to another, and blood traverses a number
1.2 Pulmonary Artery of alveolar septa before reaching a venule. This clearly has a
bearing on the efficiency of gas exchange. From the func-
Mean
tional standpoint it is often more convenient to consider
Diameter Cumulative
the pulmonary microcirculation rather than just the capil-
Orders Numbers (mm) Volume (mL)
laries. The microcirculation is defined as the vessels that are
17 1 30 64 devoid of a muscular layer, and it commences with arteri-
16 3 15 81 oles with a diameter of 75 mm and continues through the
capillary bed as far as venules with a diameter of 200 mm.
15 8 8.1 85
Special roles of the microcirculation are considered in
14 20 5.8 96 Chapters 11 and 29.
13 66 3.7 108
12 203 2.1 116 Pulmonary Venules and Veins
11 675 1.3 122 Pulmonary capillary blood is collected into venules that are
10 2300 0.85 128 structurally almost identical to the arterioles. In fact, Duke21
obtained satisfactory gas exchange when an isolated cat lung
9 5900 0.53 132
was perfused in reverse. The pulmonary veins do not run
8 18 000 0.35 136 alongside the pulmonary arteries, but lie some distance
7 53 000 0.22 138 away, close to the septa which separate the segments of
the lung.
6 160 000 0.14 141
5 470 000 0.086 142
Bronchial Circulation22
4 1 400 000 0.054 144
The conducting airways (from trachea to the terminal bron-
3 4 200 000 0.034 145
chioles) and the accompanying blood vessels receive their
2 13 000 000 0.021 146 nutrition from the bronchial circulation, which arises from
1 300 000 000 0.013 151 the systemic circulation. The bronchial circulation therefore
provides the heat required for warming and humidification
In contrast to the airways (Table 1.1), the branching is asymmetric and not
of inspired air, and cooling of the respiratory epithelium
dichotomous, and so the vessels are grouped according to orders and
not generations as in Table 1.1. (Modified from Singhal S, Henderson R, causes vasodilation and an increase in the bronchial artery
Horsfield K, et al. Morphometry of the human pulmonary arterial tree. Circ blood flow. About one-third of the bronchial circulation
Res. 1973;33:190-197.)
returns to the systemic venous system, with the remainder
draining into the pulmonary veins, constituting a form of
venous admixture (page 100). The bronchial circulation
also differs from the pulmonary circulation in its capacity
The normal human pulmonary circulation also contains for angiogenesis.23 Pulmonary vessels have very limited abil-
intrapulmonary arteriovenous anastomoses involving pul- ity to remodel themselves in response to pathological
monary arterioles of 25 to 50 mm diameter. These pathways changes, whereas bronchial vessels, like other systemic arter-
are normally closed, and open only when cardiac output ies, can undergo prolific angiogenesis. As a result, the blood
increases, for example during exercise (page 185)19 or in re- supply to most lung cancers (Chapter 30) is derived from
sponse to hypoxia.20 Their presence has clinical implications the bronchial circulation.
for the lung as a filtration system within the circulation
(page 164). Pulmonary Lymphatics
Pulmonary Capillaries There are no lymphatics visible in the interalveolar septa,
but small lymph vessels commence at the junction between
Pulmonary capillaries tend to arise abruptly from much alveolar and extraalveolar spaces. There is a well-developed
larger vessels, the pulmonary metarterioles. The capillaries lymphatic system around the bronchi and pulmonary ves-
form a dense network over the walls of one or more alveoli, sels, capable of containing up to 500 mL of lymph, and
and the spaces between the capillaries are similar in size to draining towards the hilum. Down to airway generation 11
the capillaries themselves (Fig. 1.7). In the resting state, the lymphatics lay in a potential space around the air
around 75% of the capillary bed is filled but the percentage passages and vessels, separating them from the lung paren-
is higher in the dependent parts of the lungs. Inflation of chyma. This space becomes distended with lymph in pul-
the alveoli reduces the cross-sectional area of the capillary monary oedema and accounts for the characteristic butter-
bed and increases resistance to blood flow (Chapter 6). One fly shadow of the chest radiograph. In the hilum of the
capillary network is not confined to one alveolus, but passes lung, the lymphatic drainage passes through several groups
CHAPTER 1 Functional Anatomy of the Respiratory Tract 13
of tracheobronchial lymph glands, where they receive tribu- 9. McDonough JE, Knudsen L, Wright AC. Regional differences
taries from the superficial subpleural plexus. Most of the in alveolar density in the human lung are related to lung height.
J Appl Physiol. 2015;118:1429-1434.
lymph from the left lung usually enters the thoracic duct, 10. Gil J, Bachofen H, Gehr P, et al. Alveolar volume-surface area
whereas the right side drains into the right lymphatic duct. relation in air and saline filled lungs fixed by vascular perfusion.
However, the pulmonary lymphatics often cross the mid- J Appl Physiol. 1979;47:990-995.
line and pass independently into the junction of the inter- 11. Weibel ER. It takes more than cells to make a good lung. Am J
nal jugular and subclavian veins on the corresponding sides Respir Crit Care Med. 2013;187:342-346.
12. Toshima M, Ohtani Y, Ohtani O. Three-dimensional architec-
of the body. ture of elastin and collagen fiber networks in the human and rat
lung. Arch Histol Cytol. 2004;67:31-40.
13. Nieman G. Amelia Earhart, alveolar mechanics, and other great
mysteries. J Appl Physiol. 2012;112:935-936.
References 14. Maina JN, West JB. Thin and strong! The bioengineering
dilemma in the structural and functional design of the blood-
1. Patel SR, Frame JM, Larkin EK, et al. Heritability of upper gas barrier. Physiol Rev. 2005;85:811-844.
airway dimensions derived using acoustic pharyngometry. Eur *15. Weibel ER. On the tricks alveolar epithelial cells play to make
Respir J. 2008;32:1304-1308. a good lung. Am J Respir Crit Care Med. 2015;191:504-513.
2. Weibel ER. Why measure lung structure? Am J Respir Crit Care 16. Hogan B. Stemming lung disease? N Engl J Med. 2018;378:
Med. 2001;163:314-315. 2439-2440.
17. Weibel ER. Morphological basis of alveolar-capillary gas exchange.
3. Sauret V, Halson PM, Brown IW, et al. Study of the three-dimen-
Physiol Rev. 1973;53:419-495.
sional geometry of the central conducting airways in man using 18. Staples KJ. Lung macrophages: old hands required rather than
computed tomographic (CT) images. J Anat. 2002;200:123-134. new blood? Thorax. 2016;71:973-974.
4. Sapoval B, Filoche M, Weibel ER. Smaller is better—but not too 19. Kennedy JM, Foster GE, Koehle MS, et al. Exercise-induced
small: a physical scale for the design of the mammalian pulmonary intrapulmonary arteriovenous shunt in healthy women. Respir
acinus. Proc Natl Acad Sci USA. 2002;99:10411-10416. Physiol Neurobiol. 2012;181:8-13.
5. Tilley AE, Walters MS, Shaykhiev R, et al. Cilia dysfunction in 20. Duke JW, Davis JT, Ryan BJ, et al. Decreased arterial PO2, not
lung disease. Annu Rev Physiol. 2015;77:379-406. O2 content, increases blood flow through intrapulmonary arte-
6. Widdicombe JH, Wine JJ. Airway gland structure and function. riovenous anastomoses at rest. J Physiol. 2016;594:4981-4996.
Physiol Rev. 2015;95:1241-1319. 21. Duke HN. The site of action of anoxia on the pulmonary blood
vessels of the cat. J Physiol. 1954;125:373.
7. Barnes PJ. Club cells, their secretory protein, and COPD. Chest.
22. Paredi P, Barnes PJ. The airway vasculature: recent advances and
2015;147:1447-1448. clinical implications. Thorax. 2009;64:444-450.
8. Hajari AJ, Yablonskiy DA, Sukstanskii AL, et al. Morphometric 23. Mitzner W, Wagner EM. Vascular remodeling in the circulations
changes in the human pulmonary acinus during inflation. J Appl of the lung. J Appl Physiol. 2004;97:1999-2004.
Physiol. 2012;112:937-943.
e1
Chapter 1 Summary—Functional Anatomy throughout the airway, producing mucus. Other cells in
of the Respiratory Tract the epithelium are basal cells (the stem cells for other
cell types), mast cells and nonciliated epithelial cells
• The upper airway describes the mouth, nose and phar- (club cells) of uncertain function.
ynx, and is responsible for conducting air into the lar- • A pulmonary acinus is the region of lung in which gas
ynx. Mouth breathing and nasal breathing are controlled exchange occurs. The term ‘acinar airways’ therefore
by pharyngeal muscles, particularly those of the tongue includes all airways that have alveoli in their walls, in-
and soft palate. Mouth breathing becomes obligatory cluding respiratory bronchioles, alveolar ducts and
with nasal obstruction from common diseases and is the alveolar sacs in which each airway terminates. The
required when hyperventilating, for example during epithelial cells lining acinar airways gradually thin from
exercise, to reduce respiratory resistance to high gas cuboidal in the terminal bronchioles to become con-
flows. tinuous with the alveolar epithelial cells.
• Filtration of large inhaled particles and humidification • A fibre scaffold of collagen and elastin maintains the
of inspired gas are important roles for the upper structure of the acinus, with interconnected axial fibres
airway and are more efficiently performed when nose running along the airways, peripheral fibres extending
breathing. from the visceral pleura into the lung tissue and septal
• The larynx has many physiological roles, including con- fibres forming the alveolar structure itself. This basket-
trolling the rate of expiratory airflow by partial closure like structure of fibres includes many components under
of the vocal folds or effort closure in which the vocal tension, so that when a small area is damaged large holes
folds close completely to allow intrathoracic pressure to can occur, as seen, for example, in emphysema.
be raised, for example during a cough. Fine control of • An adult lung contains around 400 million alveoli with
vocal fold position and tension is also achieved by the an average diameter at resting lung volume of 0.2 mm
larynx to facilitate phonation, the laryngeal compo- and a total surface area of 130 m2. Alveoli contain type 1
nent of speech. This requires excellent coordination be- epithelial cells over the gas exchange area, type 2 epithe-
tween the respiratory and laryngeal muscles to achieve lial cells in the corners of the alveoli which produce
the correct, and highly variable, airflows through the surfactant and are the stem cells for type 1 cells and
vocal folds. alveolar macrophages responsible for removal of in-
• The term conducting airways describes all the air passages haled particles in the alveolus. The alveolar epithelial
from the trachea to the terminal bronchioles, which is and pulmonary capillary endothelial cells are both
about 14 airway generations. Airway diameter reduces extremely thin in the area of the alveoli where gas ex-
with each division from around 18 mm in the trachea to change occurs, referred to as the ‘active side’ of the alveo-
1 mm in the bronchioles, and as the number of airways lar capillary barrier. The cell organelles and much of the
increases so the cross-sectional area increases and gas interstitial space are located on the ‘service side’ of the
velocity decreases. Airway integrity is maintained by the alveolus where significant gas exchange does not occur.
presence of cartilage in the airway walls down to about • Pulmonary blood vessels branch in a similar pattern to
the 11th generation (small airways with a diameter of ,1 their corresponding airways, and, unlike their systemic
mm), but beyond this airway patency is dependent on counterparts, are virtually devoid of muscular tissue.
the elasticity of the surrounding lung tissue in which Pulmonary capillaries form a dense network around
the airway is embedded. the walls of alveoli, weaving across the septa and bulging
• Conducting airways are lined with respiratory epithe- into the alveoli with their active sides exposed to the
lium, which is responsible for further humidification alveolar gas.
of inspired gases and removal and disposal of inhaled • The bronchial circulation is separate from the pulmo-
particles and chemicals. The epithelium is mostly nary circulation, arising from the systemic circulation
made up of ciliated cells: pseudostratified in the upper and supplying the conducting airways, with some of its
airway, columnar in large airways and cuboidal in venous drainage returning to the right side of the sys-
bronchioles. In larger airways submucosal glands exist, temic circulation and some draining directly into the
containing secretory cells, and goblet cells are present pulmonary veins.
2
Elastic Forces and Lung Volumes
K E Y P O I N TS
• Inward elastic recoil of the lung opposes outward elastic • Compliance is defined as the change in lung volume per
recoil of the chest wall, and the balance of these forces unit change in pressure gradient, and may be measured
determines static lung volumes. for the lung, the thoracic cage or both.
• Surface tension within the alveoli contributes significantly • Various static lung volumes may be measured, and the
to lung recoil and is reduced by the presence of surfactant, volumes obtained are affected by a variety of physiological
although the mechanism by which this occurs is poorly and pathological factors.
understood.
A
n isolated lung will tend to contract until eventually energy for expiration during both spontaneous and artifi-
all the contained air is expelled. In contrast, when cial breathing.
the thoracic cage is opened it tends to expand to a This chapter is concerned with the elastic resistance
volume about 1 L greater than functional residual capacity afforded by the lungs and chest wall, which will be consid-
(FRC). Thus in a relaxed subject with an open airway and ered separately and then together. When the respiratory
no air flowing, for example, at the end of expiration or in- muscles are totally relaxed, these factors govern the resting
spiration, the inward elastic recoil of the lungs is exactly end-expiratory lung volume or FRC; therefore lung volumes
balanced by the outward recoil of the thoracic cage. will also be considered in this chapter.
The movements of the lungs are entirely passive and re-
sult from forces external to the lungs. With spontaneous Elastic Recoil of the Lungs1
breathing, the external forces are the respiratory muscles,
whereas artificial ventilation is usually in response to a pres- Lung compliance is defined as the change in lung volume
sure gradient developed between the airway and the envi- per unit change in transmural pressure gradient (i.e., be-
ronment. In each case, the pattern of response by the lung tween the alveolus and pleural space). Compliance is usu-
is governed by the physical impedance of the respiratory ally expressed in litres (or millilitres) per kilopascal (or
system. This impedance, or hindrance, has numerous ori- centimetres of water), with a normal value of 1.5 L.kPa21
gins, the most important of which are the following: (150 mL.cmH2O21). Stiff lungs have a low compliance.
• Elastic resistance of lung tissue and chest wall Compliance may be described as static or dynamic, de-
• Resistance from surface forces at the alveolar gas–liquid pending on the method of measurement (page 23). Static
interface compliance is measured after the lungs have been held at a
• Frictional resistance to gas flow through the airways fixed volume for as long as is practicable, whereas dynamic
• Frictional resistance from deformation of thoracic tissues compliance is usually measured in the course of normal
(viscoelastic tissue resistance) rhythmic breathing. Elastance is the reciprocal of compli-
• Inertia associated with movement of gas and tissue. ance and is expressed in kilopascals per litre. Stiff lungs have
The last three may be grouped together as nonelastic a high elastance.
resistance or respiratory system resistance; they are discussed
in Chapter 3. They occur while gas is flowing within the The Nature of the Forces Causing Recoil
airways, and work performed in overcoming this ‘frictional’ of the Lung
resistance is dissipated as heat and lost.
The first two forms of impedance may be grouped to- For many years it was thought that the recoil of the lung
gether as ‘elastic’ resistance. These are measured when gas is was caused entirely by stretching of the yellow elastin fibres
not flowing within the lung. Work performed in overcom- present in the lung parenchyma. In 1929 von Neergaard
ing elastic resistance is stored as potential energy, and elas- (see section on Lung Mechanics in Chapter 35) showed that
tic deformation during inspiration is the usual source of a lung completely filled with and immersed in water had an
14
CHAPTER 2 Elastic Forces and Lung Volumes 15
elastance that was much less than the normal value obtained Appendix A), the appropriate units would be pressure in
when the lung was filled with air. He correctly concluded pascals (Pa), surface tension in newtons/metre (N.m21) and
that much of the ‘elastic recoil’ was caused by surface ten- radius in metres (m).
sion acting throughout the vast air/water interface lining Figure 2.1, A, left, shows a typical alveolus with a radius
the alveoli. of 0.1 mm. Assuming that the alveolar lining fluid has a
Surface tension at an air/water interface produces forces normal surface tension of 20 mN.m21 (20 dyn.cm21), the
that tend to reduce the area of the interface. Thus the gas pressure within the alveolus will be 0.4 kPa (4 cmH2O),
pressure within a bubble is always higher than the surround- which is rather less than the normal transmural pressure at
ing gas pressure because the surface of the bubble is in a FRC. If the alveolar lining fluid had the same surface ten-
state of tension. Alveoli resemble bubbles in this respect, sion as water (72 mN.m21), the lungs would be very stiff.
although the alveolar gas is connected to the exterior by the The alveolus in Figure 2.1, A, right, has a radius of only
air passages. The pressure inside a bubble is higher than the 0.05 mm, and the Laplace equation indicates that, if the
surrounding pressure by an amount depending on the sur- surface tension of the alveolus is the same, its pressure
face tension of the liquid and the radius of curvature of the should be double the pressure in the left-hand alveolus.
bubble according to the Laplace equation: Thus gas would tend to flow from smaller alveoli into larger
2T alveoli and the lung would be unstable which, of course, is
P5 not true. Similarly, the retractive forces of the alveolar lining
R fluid would increase at low lung volumes and decrease at
where P is the pressure within the bubble (dyn.cm22), high lung volumes, which is exactly the reverse of what is
T is the surface tension of the liquid (dyn.cm21) and R is the observed. These paradoxes were clear to von Neergaard, and
radius of the bubble (cm). In coherent SI units (see he concluded that the surface tension of the alveolar lining
Pressure Pressure
2 x 20 Direction 2 x 20
= of gas flow =
0.1 0.05
= 400 Pa 0.1 mm 0.05 mm = 800 Pa
= 0.4 kPa 2T = 0.8 kPa
P=
= 4 cmH2O R = 8 cmH2O
B Device to measure
surface tension on
n)
platinum strip 40 tio
ira
Surface tension (mN.m–1)
p
(ins
n
Platinum strip sio
Floating bar 30 an n)
p tio
Ex ira
xp
20 (e
n
c tio
ntra
Co
10
0
0 50 100
Relative area of surface
Pressure Pressure
2 x 20 Direction 2x5
= of gas flow =
0.1 0.05
= 400 Pa 0.1 mm 0.05 mm = 200 Pa
= 0.4 kPa 2T = 0.2 kPa
P=
= 4 cmH2O R = 2 cmH2O
• Fig. 2.1Surface tension and alveolar transmural pressure. (A) Pressure relations in two alveoli of different
size but with the same surface tension of their lining fluids. (B) The changes in surface tension in relation
to the area of the alveolar lining film. (C) Pressure relations of two alveoli of different size when allowance
is made for the probable changes in surface tension induced by surfactant.
16 PA RT I Basic Principles
fluid must be considerably less than would be expected from After release, surfactant initially forms areas of a lattice
the properties of simple liquids and, furthermore, that its structure termed tubular myelin, which is then reorganized
value must be variable. Observations 30 years later con- into monolayered or multilayered surface films. This con-
firmed this when alveolar extracts were shown to have a sur- version into the functionally active form of surfactant is
face tension much lower than water and which varied in critically dependent on SP-B and SP-C (see later).3,4 The
proportion to the area of the interface. Figure 2.1, B, shows alveolar half-life of surfactant is 15 to 30 h, with most of its
an experiment in which a floating bar is moved in a trough components recycled by type II alveolar cells. SP-A is inti-
containing an alveolar extract. As the bar is moved to the mately involved in controlling the surfactant present in the
right, the surface film is concentrated and the surface ten- alveolus, with type II alveolar cells having SP-A surface re-
sion changes, as shown in the graph on the right of the fig- ceptors, the stimulation of which exerts negative feedback
ure. During expansion, the surface tension increases to on surfactant secretion and increases reuptake of surfactant
40 mN.m21, a value which is close to that of plasma but, components into the cell.
during contraction, the surface tension falls to 19 mN.m21,
a lower value than any other body fluid. The course of the Action of Surfactant
relationship between pressure and area is different during To maintain the stability of alveoli as shown in Figure 2.1,
expansion and contraction, and a loop is described. surfactant must alter the surface tension in the alveoli as
The consequences of these changes are important. In their size varies with inspiration and expiration. A simple
contrast to a bubble of soap solution, the pressure within explanation of how this occurs is that during expiration, as
an alveolus tends to decrease as the radius of curvature is the surface area of the alveolus diminishes, the surfactant
decreased. This is illustrated in Figure 2.1, C, in which molecules are packed more densely, and so exert a greater
the right-hand alveolus has a smaller diameter and a much effect on the surface tension, which then decreases as shown
lower surface tension than the left-hand alveolus. Gas tends in Figure 2.1, B. In reality, the situation is more complex,
to flow from the larger to the smaller alveolus, and stability and at present poorly elucidated.3 The classical explanation,
is maintained. referred to as the ‘squeeze out’ hypothesis, is that as a sur-
factant monolayer is compressed, the less stable phospholip-
The Alveolar Surfactant ids are squeezed out of the layer, increasing the amount of
stable DPPC molecules which have the greatest effect in
The low surface tension of the alveolar lining fluid and its reducing surface tension.6 Surfactant phospholipid is also
dependence on alveolar radius are because of the presence known to exist in vivo in both monolayer and multilayer
of a surface-active material known as surfactant. Approxi- forms,2 and it is possible that in some areas of the alveoli the
mately 90% of surfactant consists of lipids, and the remain- surfactant layer alternates between these two forms as alveo-
der is proteins and small amounts of carbohydrate. Most of lar size changes during the respiratory cycle. This aspect of
the lipid is phospholipid, of which 70% to 80% is dipalmi- surfactant function is entirely dependent on the presence of
toyl phosphatidyl choline (DPPC), the main constituent SP-B, a small hydrophobic protein that can be incorporated
responsible for the effect on surface tension. The fatty acids into a phospholipid monolayer, and SP-C, a larger protein
are hydrophobic and generally straight, lying parallel to with a hydrophobic central portion allowing it to span a
each other and projecting into the gas phase. The other end lipid bilayer.3 When alveolar size reduces and the surface
of the molecule is hydrophilic and lies within the alveolar film is compressed, SP-B molecules may be squeezed out of
lining fluid. The molecules are thus confined to the surface the lipid layer, changing its surface properties, whereas
where, being detergents, they lower surface tension in pro- SP-C may serve to stabilize bilayers of lipid to act as a res-
portion to the concentration at the interface. ervoir from which the surface film reforms when alveolar
Approximately 2% of surfactant by weight consists of size increases.
surfactant proteins (SPs), of which there are four types la-
belled A to D.2,3 SP-B and SP-C are small proteins vital to Other Effects of Surfactant
the stabilization of the surfactant monolayer (see later); a Pulmonary transudation is also affected by surface forces.
congenital lack of SP-B results in severe and progressive re- Surface tension causes the pressure within the alveolar lining
spiratory failure,3 and genetic abnormalities of SP-C lead to fluid to be less than the alveolar pressure. Because the pul-
pulmonary fibrosis in later life.4 SP-A, and to a lesser extent monary capillary pressure in most of the lung is greater than
SP-D, are involved in the control of surfactant release, and the alveolar pressure (page 340), both factors encourage
possibly the prevention of pulmonary infection (see later).5 transudation, a tendency checked by the oncotic pressure of
the plasma proteins. Thus the surfactant, by reducing surface
Synthesis of Surfactant forces, diminishes one component of the pressure gradient
Surfactant is both formed in and liberated from the alveolar and helps to prevent transudation.
epithelial type II cell (page 11). The lamellar bodies (see Surfactant also plays an important part in the immunol-
Fig. 1.11) contain stored surfactant that is released into the ogy of the lung.7 The lipid component of surfactant has
alveolus by exocytosis in response to high volume lung in- antioxidant activity and may attenuate lung damage from a
flation, increased ventilation rate or endocrine stimulation. variety of causes, suppressing some groups of lymphocytes,
CHAPTER 2 Elastic Forces and Lung Volumes 17
theoretically protecting the lungs from autoimmune dam- Two quite different alternative models have been proposed:
age. In vitro studies have shown that SP-A or SP-D can bind Morphological model. Hills’ model proposes that the surfac-
to a wide range of pulmonary pathogens, including viruses, tant lining alveoli results in a ‘discontinuous’ liquid lin-
bacteria, fungi, Pneumocystis jirovecii and Mycobacterium ing.10 Based on knowledge of the physical chemistry of
tuberculosis. Polymorphisms of the surfactant genes are as- surfactants, this model shows that surfactant phospholip-
sociated with the severity of some respiratory diseases; for ids are adsorbed directly onto the epithelial cell surface,
example, the likelihood of developing severe pulmonary forming multilayered rafts of surfactant (Fig. 2.2). These
manifestations of an influenza infection is influenced by a rafts cause patches of the surface to become less wettable,
single nucleotide polymorphism of the gene encoding and these areas are interspersed with fluid pools. Surface
SP-B.8 Acting via specific surface receptors, both SP-A and forces generated by the interaction between the ‘dry’ areas
SP-D activate alveolar neutrophils and macrophages and of surfactant and the areas of liquid are theoretically large
enhance the phagocytic actions of the latter during lung enough to maintain alveolar stability. The rafts of surfac-
inflammation.7 tant may be many layers thick, and are believed to form
and disperse with each breath; their function is almost
Alternative Models to Explain Lung Recoil certainly dependent on both SP-B and SP-C.
Foam model. Scarpelli developed different techniques for
Treating surfactant-lined alveoli as bubbles that obey preparing lung tissue for microscopy.11 By maintaining
Laplace’s law has aided the understanding of lung recoil in tissue in a more natural state than previous studies, in-
health and disease for many decades (see section on Lung cluding keeping lung volume close to normal, he sug-
Mechanics in online Chapter 35: The History of Respiratory gested that in vivo there are bubble films across alveolar
Physiology). This ‘bubble model’ of alveolar stability is not entrances, across alveolar ducts and within respiratory
universally accepted,9 and there is evidence that the real bronchioles. In this model, each acinus may be consid-
situation is more complex. Arguments against the bubble ered as a series of interconnected, but closed, bubbles
model include the following: forming a stable ‘foam’. The bubble films are estimated
• In theory, differing surface tensions in adjacent alveoli to be thin enough to offer minimal resistance to gas dif-
cannot occur if the liquid lining the alveoli is connected fusion, the normal mechanism by which gas movement
by a continuous liquid layer. occurs in a single pulmonary acinus (page 7).
• When surfactant layers are compressed at 37°C, multi- More research is clearly needed to either confirm or refute
layered ‘rafts’ of dry surfactant form, although inclusion these models.
of surfactant proteins reduces this physicochemical
change. Transmural Pressure Gradient and
• Alveoli are not shaped like perfect spheres with a single Intrathoracic Pressure
entrance point; they are variable polyhedrons with con-
vex bulges in their walls where pulmonary capillaries The transmural pressure gradient is the difference between
bulge into them (see Fig. 1.7). intrathoracic (or ‘intrapleural’) and alveolar pressure. The
SP-B
SP-C
• Fig. 2.2Morphological model of alveolar surfactant. Multilayered, less wettable rafts of surfactant are inter-
spersed with fluid pools. Surfactant proteins lie within (SP-B) or across (SP-C) the lipid bilayers, facilitating
the formation and dispersion of the rafts with each breath to modify the surface forces within the alveolus.
(From Webster NR, Galley HF. Anaesthesia Science. Oxford: Blackwell Publishing; 2006. With permission.)
18 PA RT I Basic Principles
–2 kPa
0 (–20 cmH2O)
Slope = ∆V = lung compliance
0 ∆P
At residual volume
Total collapse
0 10 20
All pressures are Transmural pressure gradient (cmH2O)
indicated relative to
atmospheric pressure
• Fig. 2.3 Relationship between lung volume and the difference in pressure between the alveoli and the
intrathoracic space (transmural pressure gradient). The relationship is almost linear over the normal tidal
volume range. The calibre of small air passages decreases in parallel with alveolar volume. Airways begin
to close at the closing capacity, and there is widespread airway closure at residual volume. Values in
the diagram relate to the upright position and to decreasing pressure. The opening pressure of a closed
alveolus is not shown.
pressure within an alveolus is always greater than the pressure ratios, and therefore gas exchange. These matters are consid-
in the surrounding interstitial tissue, except when the volume ered in detail in Chapters 3 and 7.
has been reduced to zero. By increasing lung volume, the At first sight it might be thought that the subatmospher-
transmural pressure gradient steadily increases, as shown for ic intrapleural pressure would result in the accumulation of
the whole lung in Figure 2.3. If an appreciable pneumotho- gas evolved from solution in blood and tissues. In fact the
rax is present, the pressure gradient from alveolus to pleural total of the partial pressures of gases dissolved in blood, and
cavity provides a measure of the overall transmural pressure therefore tissues, is always less than 1 atm (see Table 25.2),
gradient. Otherwise, the oesophageal pressure may be used to and this factor keeps the pleural cavity free of gas.
indicate the pleural pressure, but there are conceptual and
technical difficulties. The technical difficulties are considered Time Dependence of Pulmonary
at the end of this chapter, whereas some of the conceptual Elastic Behaviour
difficulties are indicated in Figure 2.4.
The alveoli in the upper regions of the lung have a larger If an excised lung is rapidly inflated and then held at the
volume than those in the lower regions, except at total lung new volume, the inflation pressure falls exponentially from
capacity. The greater degree of expansion of the alveoli in the its initial value to reach a lower level attained after a few
upper part results in a greater transmural pressure gradient, seconds. This also occurs in the intact subject, and is readily
which decreases steadily down the lung at approximately observed during an inspiratory pause in a patient receiving
0.1 kPa (or 1 cmH2O) per 3 cm of vertical height; such a dif- artificial ventilation (page 25). It is broadly true to say that
ference is indicated in Figure 2.4, A. Because the pleural cav- the volume change divided by the initial change in trans-
ity is normally empty, it is not strictly correct to speak of an mural pressure gradient corresponds to the dynamic com-
intrapleural pressure; furthermore, it would not be constant pliance, whereas the volume change divided by the
throughout the pleural ‘cavity’. One should think rather of ultimate change in transmural pressure gradient (i.e., mea-
the relationship shown in Figure 2.3 as applying to various sured after it has become steady) corresponds to the static
horizontal strata of the lung, each with its own volume and compliance. Static compliance will thus be greater than
therefore its own transmural pressure gradient on which its the dynamic compliance by an amount determined by the
own intrapleural pressure would depend. The transmural degree of time dependence in the elastic behaviour of a
pressure gradient has an important influence on many as- particular lung. The respiratory frequency has been shown
pects of pulmonary function, so its horizontal stratification to influence dynamic lung compliance in the normal sub-
confers a regional difference on many features of pulmonary ject, but frequency dependence is much more pronounced
function, including airway closure and ventilation/perfusion in the presence of lung disease.
CHAPTER 2 Elastic Forces and Lung Volumes 19
A Upright position
Trachea Oesophagus
0 0
Supine position
B
Lungs
Heart and
great vessels
• Fig. 2.4 Intrathoracic pressures: static relationships in the resting end-expiratory position. The lung
volume corresponds to the functional residual capacity (FRC). (A) and (B) indicate the pressure relative to
ambient (atmospheric). Arrows show the direction of elastic forces. The heavy arrow in (B) indicates dis-
placement by the abdominal viscera. (C) The tension in the two springs is the same and will be indicated
on the spring balance. In the supine position: 1, the FRC is reduced; 2, the intrathoracic pressure is raised;
3, the weight of the heart raises the oesophageal pressure above the intrapleural pressure.
Hysteresis
Causes of Time Dependence of Pulmonary
If the lungs are slowly inflated and then slowly deflated, the
Elastic Behaviour
pressure/volume curve for static points during inflation dif-
fers from that obtained during deflation. The two curves There are many possible explanations of the time depen-
form a loop, which becomes progressively broader as the dence of pulmonary elastic behaviour, the relative impor-
tidal volume is increased (Fig. 2.5). Expressed in words, the tance of which may vary in different circumstances.
loop in Figure 2.5 means that rather more than the ex- Changes in surfactant activity. It has been explained previ-
pected pressure is required during inflation, and rather less ously that the surface tension of the alveolar lining fluid
than the expected recoil pressure is available during defla- is greater at larger lung volume and also during inspira-
tion. This resembles the behaviour of perished rubber or tion than at the same lung volume during expiration
polyvinyl chloride, both of which are reluctant to accept (Fig. 2.1, B). This is probably the most important cause
deformation under stress but, once deformed, are again re- of the observed hysteresis in the intact lung (Fig. 2.5).
luctant to assume their original shape. This phenomenon is Stress relaxation. If a spring is pulled out to a fixed increase
present to a greater or lesser extent in all elastic bodies, and in its length, the resultant tension is maximal at first and
is known as elastic hysteresis. then declines exponentially to a constant value. This is
20 PA RT I Basic Principles
1.5
Expiration
Low High
1.0 compliance
compliance
Inspiration (stiff)
0.5 B High
Low
resistance
resistance
High
compliance
0
0 –0.5 –1.0 –1.5 –2.0
Transmural pressure gradient (kPa) ‘Fast’ ‘Slow’
alveolus alveolus
Low
• Fig. 2.5 tatic plot of lung volume against transmural pressure gradi-
S compliance
ent (intraoesophageal pressure relative to atmospheric at zero air flow). (stiff)
Note that inspiratory and expiratory curves form a loop that gets wider
the greater the tidal volume. These loops are typical of elastic hyster- • Fig. 2.6 Schematic diagrams of alveoli to illustrate conditions under
esis. For a particular lung volume, the elastic recoil of the lung during which static and dynamic compliance may differ. (A) Represents a
expiration is always less than the distending transmural pressure gradi- theoretically ideal state in which there is a reciprocal relationship be-
ent required during inspiration at the same lung volume. tween resistance and compliance resulting in gas flow being preferen-
tially delivered to the most compliant regions, regardless of the state of
inflation. Static and dynamic compliance are equal. This situation is
an inherent property of elastic bodies, known as stress probably never realized even in the normal subject. (B) Illustrates a
state that is typical of many patients with respiratory disease. The al-
relaxation. Thoracic tissues display stress relaxation, and veoli can conveniently be divided into fast and slow groups. The direct
these ‘viscoelastic’ properties contribute significantly to relationship between compliance and resistance results in inspired gas
the difference between static and dynamic compliance, being preferentially delivered to the stiff alveoli if the rate of inflation is
as well as forming a component of pulmonary resistance rapid. An end-inspiratory pause then permits redistribution from the
(page 29). The crinkled structure of collagen in the lung fast alveoli to the slow alveoli.
(see Fig. 1.10) is likely to favour stress relaxation, and
excised strips of human lung show stress relaxation when
stretched. and is preferentially filled during a short inflation. This
Redistribution of gas. In a lung consisting of functional units preferential filling of alveoli with low compliance gives
with identical time constants* of inflation, the distribu- an overall higher pulmonary transmural pressure gradi-
tion of gas should be independent of the rate of infla- ent. A slow or sustained inflation permits increased dis-
tion, and there should be no redistribution when the tribution of gas to slow alveoli and tends to distribute gas
lungs are held inflated. However, if different parts of the in accord with the compliance of the different functional
lungs have different time constants, the distribution of units. There should then be a lower overall transmural
inspired gas will be dependent on the rate of inflation, pressure and no redistribution of gas when inflation is
and redistribution (pendelluft) will occur when inflation held. The extreme difference between fast and slow al-
is held. This problem is discussed in detail on page 90, veoli shown in Figure 2.6, B, applies to diseased lungs,
but for the time being we can distinguish ‘fast’ and ‘slow’ and no such difference exists in normal lungs. Gas redis-
alveoli (the term alveoli here refers to functional units tribution is therefore unlikely to be a major factor in
rather than the anatomical entity). The fast alveolus has healthy subjects, but it can be important in patients with
a low airway resistance and/or low compliance (or both), airways disease.
whereas the slow alveolus has a high airway resistance Recruitment of alveoli. Below a certain lung volume, some
and/or a high compliance (Fig. 2.6, B). These properties alveoli tend to close and only reopen at a greater lung
mean that the fast alveolus has a shorter time constant volume and in response to a higher transmural pressure
gradient than that at which they closed. Despite this
need for higher pressure to open lung units, recruitment
of alveoli is a plausible explanation for the time-
*Time constants are used to describe the exponential filling and emptying
of a lung unit. One time constant is the time taken to achieve 63%
dependent phenomena described earlier, and there is
of maximal inflation or deflation of the lung unit. See Appendix E for now some evidence that this does occur in healthy lungs
details. at FRC.
CHAPTER 2 Elastic Forces and Lung Volumes 21
Factors Affecting Lung Compliance Compliance of the thoracic cage is defined as change in
lung volume per unit change in the pressure gradient be-
Lung volume. It is important to remember that compliance tween atmosphere and the intrapleural space. The units are
is related to lung volume. This factor may be excluded by the same as for pulmonary compliance. The measurement
relating compliance to FRC to yield the specific compli- is seldom made but the value is of the order of 2 L.kPa21
ance (i.e., compliance/FRC), which in humans is almost (200 mL.cmH2O21).
constant for both sexes and all ages down to neonates.
The relationship between compliance and lung volume is Factors Influencing Compliance
true not only within an individual lung, but also be- of the Thoracic Cage
tween species. Larger animal species have thicker alveolar
septa containing increased amounts of collagen and elas- Anatomical factors include the ribs and the state of ossifica-
tin, resulting in larger alveolar diameters, so reducing the tion of the costal cartilages, which explains the progressive
pressure needed to expand them. An elephant therefore reduction in chest wall compliance with increasing age.
has larger alveoli and higher compliance than a mouse. Obesity and even pathological skin conditions may also
Posture. Lung volume, and therefore compliance, changes have an appreciable effect. In particular, scarring of the skin
with posture (page 22). There are, however, problems in overlying the front of the chest, for example from burns,
the measurement of intrapleural pressure in the supine may impair breathing.
position, and when this is considered it seems unlikely In terms of compliance, a relaxed diaphragm simply
that changes of posture have any significant effect on the transmits pressure from the abdomen that may be increased
specific compliance. in obesity (Chapter 15) and abdominal distension. Posture
Pulmonary blood volume. The pulmonary blood vessels clearly has a major effect, and this is considered below in
probably make an appreciable contribution to the stiff- relation to FRC. Compared with the supine position, tho-
ness of the lung. Pulmonary venous congestion from racic cage compliance is 30% greater in the seated subject,
whatever cause is associated with reduced compliance. and the total static compliance of the respiratory system is
Age. There is a small increase in lung compliance with in- reduced by 60% in the prone position because of the dimin-
creasing age, believed to be caused by changes to the ished elasticity of the ribcage and diaphragm when prone.
structure,12 or microstructural distribution, of lung col-
lagen and elastin.13 Both of these changes will affect lung
tissue elasticity, but the latter also leads to the enlarge- Pressure–Volume Relationships of the
ment of lung airspaces13 and so reduces surface forces, Lung Plus Thoracic Cage
mitigating the gradual loss of tissue elasticity.
Bronchial smooth muscle tone. Animal studies14 have shown Compliance is analogous to electrical capacitance, and in
that an infusion of methacholine sufficient to result in a the respiratory system the compliance of lungs and thoracic
doubling of airway resistance decreases dynamic compli- cage are in series. Therefore the total compliance of the
ance by 50%. The airways might contribute to overall system obeys the same relationship as that for capacitances
compliance or, alternatively, bronchoconstriction could in series, in which reciprocals are added to obtain the recip-
enhance time dependence and reduce dynamic, but rocal of the total value, thus
perhaps not static, compliance (Fig. 2.6). This interde-
pendence between small airways and their surrounding 1
alveoli also affects airway resistance (page 29). total compliance
Disease. Important changes in lung pressure–volume rela-
1 1
tionships are found in some lung diseases, and these are
described in Part 3, Physiology of pulmonary disease. lung compliance thora cic cage compliance
Elastic Recoil of the Thoracic Cage typical static values (L.kPa21) for the supine paralysed
patient are
The thoracic cage comprises the ribcage and the diaphragm. 1 1 1
Each is a muscular structure and can be considered as an
0 . 85 1 . 5 2
elastic structure only when the muscles are relaxed, which is
not easy to achieve except under the conditions of paralysis. Instead of compliance, we may consider its reciprocal,
Relaxation curves have been prepared relating pressure and elastance. The relationship is then much simpler:
volumes in the supposedly relaxed subject, but it is now
Total elastance
doubted whether total relaxation was ever achieved. For
lung elastance thoracic cag e elastance
example, in the supine position the diaphragm is not fully
relaxed at the end of expiration but maintains a resting tone The corresponding values (kPa.L21) are then
to prevent the abdominal contents from pushing the dia-
phragm cephalad. 1 . 17 0 . 67 0 . 5
22 PA RT I Basic Principles
Intrathoracic
minus ambient volumes as shown in Figure 2.9. On average, FRC in-
+2
creases by around 16 mL per year.
Posture. Moving from the upright (seated) to the
Alveolar minus
supine position leads to a significantly reduced FRC (see
+1
ambient (relaxation
curve of total system)
Fig. 15.2). The changes are caused by the increased pres-
Alveolar minus
sure of the abdominal contents on the diaphragm in the
intrathoracic (transmural) supine position, displacing it in a cephalad direction
0 and reducing thoracic volume. This is demonstrated in
Functional residual capacity
Figure 2.10 and Table 2.1 showing the influence of dif-
–1
ferent degrees of body tilting and other body positions
–1 0 +1 +2 +3 on FRC. Values of FRC in these figures and Table 2.1 are
Pressure gradient (kPa) typical for a subject of 1.70 m height, and reported mean
differences between supine and upright positions rang-
• Fig. 2.7 Static pressure/volume relations for the intact thorax for the
conscious subject in the upright position. The transmural pressure
ing from 500 to 1000 mL.
gradient bears the same relationship to lung volume during both inter- Obesity. The effect of obesity on lung volumes is described
mittent positive pressure ventilation and spontaneous breathing. The on page 200.
intrathoracic-to-ambient pressure difference, however, differs in the Ethnic group. Values for lung volumes vary between the dif-
two types of ventilation because of muscle action during spontaneous ferent principal ethnic groups in the world, even after
respiration. At all times: alveolar/ambient pressure difference 5 alveo-
lar/intrathoracic pressure difference 1 intrathoracic/ambient pressure
age and stature have been taken into account. Causes of
difference (due attention being paid to the sign of the pressure differ- these differences include geographic location, diet and
ence). FRC, Functional residual capacity. levels of activity in childhood, all of which can influence
CHAPTER 2 Elastic Forces and Lung Volumes 23
5
Inspiratory
4 reserve Inspiratory Vital
3 Tidal Total
volume lung
capacity
2 Expiratory
Functional reserve
residual volume
1 capacity
Residual
volume
0
0 30 60
Time (seconds)
• Fig. 2.8 Static lung volumes of Dr. Nunn in 1990. The ‘spirometer curve’ indicates the lung volumes that
can be measured by simple spirometry. These are tidal volume, inspiratory reserve volume, inspiratory
capacity, expiratory reserve volume and vital capacity. The residual volume, total lung capacity and
functional residual capacity cannot be measured by observation of a spirometer without further elabora-
tion of methods. BTPS, Body temperature and pressure, saturated.
VC Ribcage Expiratory
4 y FRC (L) Breathinga Volume In
Functional residual capacit
ERV
Position (BTPS) (%) 1 s (L) (BTPS)
e Sitting 2.91 69.7 3.79
2 Residual volum
Supine 2.10 32.3 3.70
Supine 2.36 33.0 3.27
0 (arms up)
30 40 50 60 70
Age (years) Prone 2.45 32.6 3.49
• Fig. 2.9 Changes in static lung volumes with age. The largest Lateral 2.44 36.5 3.67
change is in residual volume, the increase in which reduces both
Data for 13 healthy males aged 24 to 64 years.
expiratory reserve volume and vital capacity whereas inspiratory a
Proportion of breathing accounted for by movement of the ribcage.
capacity remains mostly unchanged. (After Janssens JP, Pache JC, BTPS, Body temperature and pressure, saturated; FRC, functional
Nicod LD. Physiological changes in respiratory function associated residual capacity.
with ageing. Eur Respir J. 1999;13:197-205) (From Lumb AB, Nunn JF. Respiratory function and ribcage contribution
to ventilation in body positions commonly used during anesthesia.
Anesth Analg. 1991;73:422-426.)
Functional residual capacity (litres) (BTPS)
is usually some uncertainty about the pulmonary compli- where the trace is horizontal and the dynamic compliance
ance. For static compliance it is therefore easier to measure is the slope of the line joining these points.
lung compliance in the upright position and total compli-
ance in the anaesthetized paralysed patient, who will usually Automated Measurement of Compliance
be in the supine position.
In a spontaneously breathing awake patient, lung compli-
Dynamic Compliance ance measurement is difficult because of the requirement
to place an oesophageal balloon. However, in anaesthetized
These measurements are made during rhythmic breathing, patients or those patients receiving intermittent positive
but compliance is calculated from pressure and volume pressure ventilation (IPPV) in intensive care, the measure-
measurements made when no gas is flowing, usually at end- ment of compliance is considerably easier. Many ventila-
inspiratory and end-expiratory ‘no-flow’ points. The usual tors and anaesthetic monitoring systems now routinely
method involves creation of a pressure–volume loop by measure airway pressure and tidal volume. This enables a
displaying simultaneously as x- and y-coordinates the re- pressure–volume loop to be displayed (Fig. 2.12, A), from
quired pressure gradient and the respired volume. In the which the dynamic compliance of the respiratory system
resultant loop, as in Figure 2.12, A, the no-flow points are may be calculated on a continuous breath-by-breath basis.
When no gas is flowing during IPPV (at the end of inspira-
tion and expiration), the airway pressure equals alveolar
A pressure. At this point, the airway pressure recorded by the
1200 ventilator therefore equals the difference between alveolar
Slope = compliance
800
and atmospheric pressure, allowing derivation of the total
= 32 ml.cmH2O–1 compliance.
Tidal volume (ml)
25
800 Some ventilators will also measure static compliance. The
ventilator will inflate the lung with the patient’s usual tidal
volume and then pause at end-inspiration for between
400 0.5 and 2 s, until the airway pressure falls to a plateau lasting
300 ms (Fig. 2.12, B). Static compliance is then calculated
from the volume delivered and pressure recorded during
0 the plateau and may be easily compared with dynamic
0 20 40
Airway pressure (cmH2O)
compliance.
B
Inspiration Pause Expiration
Inspiratory flow
Principles of Measurement
Tidal
of Static Lung Volumes
volume
Vital capacity, tidal volume, inspiratory reserve and expira-
tory reserve can all be measured with a simple spirometer
0
(Fig. 2.8). Total lung capacity, FRC and RV all contain a
Pmax
Airway pressure
rapidly, or helium dissolving in the tissues and blood will 7. Janssen WJ, McPhillips KA, Dickinson MG, et al. Surfactant
introduce errors. proteins A and D suppress alveolar macrophage phagocytosis via
interaction with SIRPa. Am J Respir Crit Care Med. 2008;
The third method uses the body plethysmograph. The 178:158-167.
subject is totally contained within a gas-tight box and at- 8. To KKW, Zhou J, Song Y-Q, et al. Surfactant protein B gene
tempts to breathe against an occluded airway. Changes in polymorphism is associated with severe influenza. Chest. 2014;
alveolar pressure are recorded at the mouth and compared 145:1237-1243.
with the small changes in lung volume, derived from pres- *9. Scarpelli EM, Hills BA. Opposing views on the alveolar sur-
face, alveolar models, and the role of surfactant. J Appl
sure changes within the plethysmograph. Application of Physiol. 2000;89:408-412.
Boyle’s law then permits calculation of lung volume. 10. Hills BA. An alternative view of the role(s) of surfactant and the
The last method is the only technique for FRC measure- alveolar model. J Appl Physiol. 1999;87:1567-1583.
ment that includes gas trapped within the lung distal to 11. Scarpelli EM. The alveolar surface network: a new anatomy and
closed airways. its physiological significance. Anat Rec. 1998;251:491-527.
12. Janssens JP, Pache JC, Nicod LD. Physiological changes in
respiratory function associated with ageing. Eur Respir J. 1999;
References 13:197-205.
13. Subramaniam K, Kumar H, Tawhai MH. Evidence for age-de-
1. Faffe DS, Zin WA. Lung parenchymal mechanics in health and pendent air-space enlargement contributing to loss of lung tissue
disease. Physiol Rev. 2009;89:759-775. elastic recoil pressure and increased shear modulus in older age. J
*2. Whitsett JA, Weaver TE. Hydrophobic surfactant proteins in Appl Physiol. 2017;123:79-87.
lung function and disease. N Engl J Med. 2002;347:2141-2148. 14. Mitzner W, Blosser S, Yager D, et al. Effect of bronchial smooth
3. Weaver TE, Conkright JJ. Functions of surfactant proteins B and muscle contraction on lung compliance. J Appl Physiol. 1992;
C. Annu Rev Physiol. 2001;63:555-578. 72:158-167.
4. van Moorsel CHM, van Oosterhout MFM, Barlo NP, et al. Sur- 15. Galanter JM. Bringing lung function prediction equations to
factant protein C mutations are the basis of a significant portion diverse populations. Am J Respir Crit Care Med. 2017;196:
of adult familial pulmonary fibrosis in a Dutch cohort. Am J 942-944.
Respir Crit Care Med. 2010;182:1419-1425. 16. Ntima N, Lumb AB. Pulmonary function tests in anaesthetic
5. Hawgood S, Poulain FR. The pulmonary collectins and surfac- practice. Br J Anaesth Educ. 2019;19:206-211.
tant metabolism. Annu Rev Physiol. 2001;63:495-519. 17. Khelifa MB, Salem HB, Sfaxi R. “Spirometric” lung age refer-
*6. Zuo YY, Possmayer F. How does pulmonary surfactant reduce sur- ence equations: A narrative review. Respir Physiol Neurobiol.
face tension to very low values? J Appl Physiol. 2007;102:1733-1734. 2018;247:31-42.
e1
Chapter 2 Summary—Elastic Forces and time-dependency of the respiratory system. Factors af-
Lung Volumes fecting lung compliance include lung volume, posture,
age and disease.
• Both lung and chest wall have elastic properties such • Static lung volumes describe the amount of gas in the
that, when isolated from the chest, a lung will contract, lung at different points when no air is flowing. These
expelling the air from within, and the chest wall will include residual volume (RV, volume in the lung after a
expand by a similar amount. The balance of these two maximal exhalation), functional residual capacity
opposing forces determines the lung volume when no (FRC, volume in the lung after a normal tidal breath),
gas is flowing. Elastic recoil of the lungs results partly tidal volume (volume taken into the lung during a nor-
from the elastin molecules that form the lung paren- mal breath) and total lung capacity (TLC, volume in
chyma, and also from the surface forces at the air/water the lung after a maximal inhalation). Other terms used
interface within the alveoli. can be derived from these volumes, including vital ca-
• Surface tension in the lung would quickly cause total pacity (TLC-RV), expiratory reserve volume (FRC-
lung collapse were it not for the presence of surfactant RV) and inspiratory reserve capacity (TLC-FRC).
in the alveoli and small airways which reduces the sur- • Static lung volumes are affected by posture, for example
face forces by a variable amount depending on alveolar the FRC is reduced when supine compared with up-
volume. Surfactant is 90% phospholipid and 10% right, because of the pressure of the abdominal contents
protein, and is produced by type II alveolar epithelial displacing the diaphragm in a cephalad direction, re-
cells. Its mechanism of action is poorly understood. The ducing chest volume. Other factors affecting lung vol-
surfactant proteins are involved in organizing the umes include subject height, sex, age and ethnic group,
phospholipid molecules into layers, and also have other all of which must be considered when calculating ‘nor-
functions such as antioxidant effects and the binding mal’ predicted values for an individual. Obesity and
of inhaled pathogens. lung disease also affect lung volumes.
• Elastic properties of the respiratory system are time- • Measurement of compliance requires both lung volume
dependent, that is, the relationship changes from the and the required pressure to be recorded simultaneously
initial values if the pressure or volume is held constant. when no gas is flowing. For dynamic compliance this
This gives rise to hysteresis, in which the inflation and may be done by calculating the gradient between the no-
deflation curves of a pressure–volume plot are different, flow points on a pressure–volume loop, and this is done
forming a loop. Causes of time dependency include automatically on some ventilators. Static compliance
molecular changes in surfactant or lung elastin, and requires the lung to be inflated and held at different
redistribution of gas between areas of lung with differ- volumes, so it is much harder to perform, but again, may
ing compliances. be automated by some ventilators. Division of the mea-
• Compliance describes the change in lung volume per surements into compliance of lung and chest wall re-
unit change of pressure, and may be measured for the quires measurement of intrapleural pressure, which is
lungs, chest wall or both together. Lung compliance done using an oesophageal balloon, so this is an invasive
requires measurement of pressure between the alveolus procedure not routinely performed.
and pleural space (transmural pressure), chest wall • Some static lung volumes can be measured using a
compliance between the pleural space and atmosphere. spirometer or pneumotachograph which integrates the
Dynamic compliance is measured during a normal tidal flow readings, but those volumes involving the residual
breath, and static compliance measured after the lung volume require a tracer dilution or body plethysmo-
has been maintained at a constant pressure for a few graph technique to measure the volume of the gas that
seconds: the difference between the two reflects the cannot be exhaled.
3
Respiratory System Resistance
K E Y P O I N TS
• Gas flow in the airway is a mixture of laminar and turbulent • In smaller airways smooth muscle controls airway diameter
flow, becoming more laminar in smaller airways. under the influence of neural, humoral and cellular
• Respiratory system resistance is a combination of resistance mechanisms.
to gas flow in the airways and resistance to deformation of • The respiratory system can rapidly compensate for increases
tissues of both the lung and chest wall. in either inspiratory or expiratory resistance.
E
lastic resistance, which occurs when no gas is flowing, central cylinder moving fastest, the advancing cone forming
results from only two of the numerous causes of im- a parabola (Fig. 3.2, A).
pedance to inflation of the lung (listed in Chapter 2). The advancing cone front means that some fresh gas will
This chapter considers the remaining components, which reach the end of a tube, but the volume entering the tube is
together are referred to as nonelastic resistance or respiratory still less than the volume of the tube. In the context of the
system resistance. Most nonelastic resistance is provided by respiratory tract, there may be significant alveolar ventila-
frictional resistance to air flow and thoracic tissue deforma- tion when the tidal volume is less than the volume of the
tion (both lung and chest wall), with small contributions airways (the anatomical dead space), a fact that is very
from the inertia of gas and tissue and compression of intra- relevant to high-frequency ventilation (page 384). For the
thoracic gas. Unlike elastic resistance, work performed same reason, laminar flow is relatively inefficient for purging
against nonelastic resistance is not stored as potential energy the contents of a tube.
(and therefore recoverable), but is lost and dissipated as heat. In theory, gas adjacent to the tube wall is stationary, so fric-
tion between fluid and the tube wall is negligible. The physical
characteristics of the airway or vessel wall should therefore not
Physical Principles of Gas Flow and affect resistance to laminar flow. Similarly, the composition of
Resistance gas sampled from the periphery of a tube during laminar flow
may not be representative of the gas advancing down the
Gas flows from a region of high pressure to one of lower centre of the tube. To complicate matters further, laminar
pressure. The rate at which it does so is a function of the flow requires a critical length of tubing before the characteris-
pressure difference and the resistance to gas flow, analogous tic advancing cone pattern can be established. This is known as
to the flow of an electrical current (Fig. 3.1). The precise the entrance length and is related to the diameter of the tube
relationship between pressure difference and flow rate de- and the Reynolds number of the fluid (see later).
pends on the nature of the flow, which may be laminar,
turbulent or a mixture of the two. It is useful to consider Quantitative Relationships
laminar and turbulent flow as two separate entities, but With laminar flow, the gas flow rate is directly proportional
mixed patterns of flow usually occur in the respiratory tract. to the pressure gradient along the tube (Fig. 3.2, B); the
With a number of important caveats, similar basic consid- constant is thus defined as resistance to gas flow:
erations apply to the flow of liquids through tubes, which is
P flow rate resistance
considered in Chapter 6.
where DP 5 pressure gradient.
Laminar Flow In a straight unbranched tube, the Hagen–Poiseuille
equation allows gas flow to be quantified
With laminar flow, gas flows along a straight unbranched
P ( radius )
4
tube as a series of concentric cylinders that slide over one Flowrate
another, with the peripheral cylinder stationary and the 8 length viscosity
27
28 PA RT I Basic Principles
Current
flow rate Electrical
(amps) pressure In this equation, the fourth power of the radius of the tube
difference explains the critical importance of narrowing of air pas-
(volts) sages. With constant tube dimensions, viscosity is the only
Resistance
property of a gas relevant under conditions of laminar flow.
Gas flow Helium has a low density but a viscosity close to that of air;
rate
therefore it will not improve gas flow if the flow is laminar
(page 29).
In the Hagen–Poiseuille equation, the units must be
coherent. In CGS units (see Appendix A), dyn.cm22 (pres-
sure), mL.s21 (flow) and cm (length and radius) are compat-
Pressure ible with the unit of poise for viscosity (dyn.s.cm22). In
difference
SI units, with pressure in kilopascals, the unit of viscosity
is newton.s.m22. However, in practice it is still customary
Pressure difference
to express gas pressure in cmH2O and flow in L.s21. Resis-
Resistance = tance therefore continues to usually be expressed as
flow rate
cmH2O per litre per second (cmH2O.L21.s).
• Fig. 3.1 Electrical analogy of gas flow. Resistance is pressure differ-
ence per unit flow rate. Resistance to gas flow is analogous to electri-
cal resistance (provided that flow is laminar). Gas flow corresponds to Turbulent Flow
electrical current (amps), gas pressure to potential difference (volts),
gas flow resistance to electrical resistance (ohms), and Poiseuille’s law
High flow rates, particularly through branched or irregular
corresponds to Ohm’s law. tubes, result in a breakdown of the orderly flow of gas de-
scribed earlier. An irregular movement is superimposed on
the general progression along the tube (Fig. 3.3, A), with a
square front replacing the cone front of laminar flow.
Turbulent flow is almost invariably present when high resis-
A tance to gas flow is a problem.
The square front means that no fresh gas can reach the
end of a tube until the amount of gas entering the tube is
almost equal to the volume of the tube. Turbulent flow is
more effective than laminar flow in purging the contents of
a tube, and also provides the best conditions for drawing a
Pressure
B = Resistance x Flow rate representative sample of gas from the periphery of a tube.
gradient
40 0.4 Frictional forces between the tube wall and fluid become
more important in turbulent flow.
in
.m
Quantitative Relationships
Pressure gradient (Pa)
30 0.3
in
Pa
.L
Pa differs from the relationship described earlier for laminar
nce
20 1 0.2
= in flow in three important respects:
sta
e –1 .m
nc a.L 1. The driving pressure is proportional to the square of the
ta
si
is .5 P
Re
A (i) High flow rates (ii) Sharp angles TABLE Physical Properties of Clinically Used Gas
3.1 Mixtures Relating to Gas Flow
Viscosity Density
Relative Relative Density
(iii) Changes in diameter (iv) Branches to Air to Air Viscosity
Oxygen 1.11 1.11 1.00
70% N2O/30% O2 0.89 1.41 1.59
B 80% He/20% O2 1.08 0.33 0.31
2.5 25
0.05
(0.5)
Values for ‘resistance’
(= pressure gradient
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