Table Of ContentControl of
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Edited by D.J. Palot
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CROOM HELM
London & Canberra
© 1983 David J. Pallot
Softcover reprint of the hardcover 1st edition 1983
Croom Helm Ltd, Provident House, Burrell Row,
Beckenham, Kent BR3 lAT
British Library Cataloguing in Publication Data
Control of respiration.
Respiration-Regulation
I. Pallot, David J.
612'.2 Q123
ISBN-13: 978-1-4684-1489-9 e-ISBN-13: 978-1-4684-1487-5
DOl: 10.1007/978-1-4684-1487-5
Typeset by Elephant Productions, London
CONTENTS
Contributors
Preface
1. Peripheral Arterial Chemoreceptors D. S. McQueen and
D.J. Pallot
2. Central Chemoreceptors Hans H. Loeschcke 41
3. Lung and Airway Receptors A.S. Paintal 78
4. Respiratory Reflexes Andrzej Trzebski 108
5. Tissue Oxygen Transport in Health and Disease H. Acker 157
6. Studies of Respiratory Control in Man J.M Patrick 203
7. Respiratory Oscillations in Health and Disease
Christopher B. Wolff 222
8. Control of Respiration in the Fetus and Newborn
Peter J. Fleming and Jose Ponte 276
9. Initiation and Control of Ventilatory Adaptation to Chronic
Hypoxia of High Altitude Sukhamay Lahiri, P. Barnard
and R. Zhang 298
Index 326
CONTRIBUTORS
H. Acker: Max-Planck-Institut fUr Systemphysiologie, Rheinlandamm
201, D-4600 Dortmund 1, Federal Republic of Germany
P.A. Barnard, PhD: Institute for Environmental Medicine and University
of Pennsylvania School of Medicine, Philadelphia PA 19104, USA
Peter J. Fleming, MB, ChB, MRCP, FRCP(C): Consultant in Neonatal
Paediatrics, Bristol Maternity Hospital, Southwell Street, Bristol 2,
England
Sukhamay lahiri, DPhil: Professor of Physiology, University of Penn
sylvania School of Medicine, Philadelphia PA 19104, USA
Hans H. Loeschcke: Institut fur Physiologie, Ruhr - Universitat Bochum,
Lehrstuhl 1, 4630 Bochum - Queremburg, Postfach 2148, Federal
Republic of Germany
D.S. McQueen, BPharm, PhD: Reader in Pharmacology, University of
Edinburgh, 1 George Square, Edinburgh EH8 9JZ, Scotland
A.S. Paintal: ICMR Centre for Respiratory Physiology and Department
of Physiology, Vallabhai Patel Chest Institute, University of Delhi,
Delhi - 11 0007, India
David J. Pallot, BSc, PhD: Senior Lecturer in Anatomy, Medical Sciences
Building, University of Leicester, University Road, Leicester LEI 7RH,
England
J .M. Patrick, MA, DPhil, BM, BCh: Senior Lecturer in Physiology,
University of Nottingham Medical School, Queens Medical Centre,
Clifton Boulevard, Nottingham NG7 2UH, England
Jose Ponte, MD, PhD, FFARCS: Senior Lecturer in Anaesthetics,
King's College Hospital Medical School, Denmark Hill, London SE5 9RS,
England
Andrzej Trzebski: Department of Physiology, Institute of Physiological
Sciences, Medical Academy, Warsaw 00-927, Poland
Christopher B. Wolff, MB, ChB, MRCP: Senior Lecturer in PhYSiology,
Guy's Hospital Medical School, London SEI 9RT, England
R. Zhang, MD: Institute of Biophysics, Chinese Academy of Sciences,
Beijing, People's Republic of China
PREFACE
The scientific literature has expanded dramatically in recent years,
making entry into the structure of any given area extremely difficult;
concurrent with this explosion more people are required to become
acquainted with information outside their main line of expertise.
For this reason there is a need for review articles which give an overall
review of circumscribed areas. This volume reviews the subject of
respiratory control mechanisms; the authors of each chapter are active
research workers engaged in the area covered by their chapter.
The first four chapters are concerned with the basic physiological
mechanisms which sense changes in the respiratory system, in the
standard physiology textbook parlance chemical and neural sensory
receptors. The peripheral arterial chemoreceptors sense changes in
arterial oxygen tension, carbon dioxide and pH. The first chapter
describes the basic responses in the organ produced by changes in blood
chemistry. Later chapters discuss changes in activity produced by
exercise, chronic hypoxia and the possible role of the chemoreceptors
in initiation of respiration in the new-born. In Chapter 1, a section
considers the action of drugs on the peripheral chemoreceptors, and
finally there is a discussion of the possible mechanisms whereby the
organs sense changes in blood chemistry. This pattern is followed in
subsequent chapters wherever possible; first a discussion of the basic
physiological properties, followed by any clinical application and dis
cussion of the mechanism whereby the receptor might operate.
The remaining chapters are of a more applied nature. In Chapter 5
Acker discusses a most important field, often neglected in textbooks,
that of the mechanisms controlling the distribution of oxygen to the
tissues at the level of the microcirculation. Included in this chapter is
a discussion of oxygen and blood supply to tumours, a topic of con
siderable clinical importance. In Chapter 7 there is a discussion of the
periodic nature of O2 , CO2 and pH changes during the respiratory cycle,
and of the use such information is put to in controlling respiration and
the changes in respiratory oscillations produced by some disease states.
Other chapters are concerned more directly with the clinical situa
tion and adaptations of the respiratory system. Chapter 6 on respiratory
control in man discusses the method and problems of collecting data in
human subjects, the respiratory control system in disease and drugs
Preface
affecting the respiratory control system. Chapter 8 discusses the onset
of respiration in the new-born whilst the final chapter is concerned with
adaptation to high altitude.
The volume, in setting out reviews of these areas, will be of use to
those requiring either an up-to-date view of respiratory control mechan
isms or to people requiring an entree to a massive literature. Clinicians,
in particular those with an interest in chest medicine and anaesthesia,
will be able to update their knowledge, while advanced students of
biology can obtain an introduction to respiratory mechanisms.
1 PERIPHERAL ARTERIAL CHEMORECEPTORS
0.5. McQueen and D.J. Pallot
This chapter describes the influence of the peripheral arterial chemo
receptors on respiration and also examines the transduction mechanism
of these receptors. It is our intention to concentrate mainly on the
recent literature; readers requiring information about historical aspects,
or more detailed evidence than it is possible to give in this chapter, are
referred to reviews on chemoreceptors (e.g. Schmidt & Comroe, 1940;
Heymans & Neil, 1958; Dejours, 1962; Anichkov & Belen'kii, 1963;
Torrance, 1968; Biscoe, 1971; Eyzaguirre & Fidone, 1980) and the
proceedings of recent international meetings on arterial chemoreceptors
(Purves, 1975; Paintal, 1976; Acker et al., 1977; Belmonte et al., 1981).
The peripheral arterial chemoreceptors are sensory receptors which
monitor the oxygen and carbon dioxide tensions and pH of arterial
blood, and form part of the integrated system that controls respiration.
A fall in the partial pressure of oxygen in arterial blood (Pa02), a rise
in PaC02 or a fall in pH, increases the activity of these receptors,
increases discharge frequency in their sensory (afferent) nerves, which
terminate centrally mainly in the nucleus tractus solitarius, and
ultimately may stimulate respiration. Two main groups of arterial
chemoreceptors exist in mammals, namely the aortic and carotid
bodies located, respectively, near the arch of the aorta and in the
bifurcation of the common carotid arteries. The carotid body is very
vascular and is supplied with arterial blood by one or more arteries
originating from the bifurcation or the external carotid artery; venous
blood drains into the internal jugular vein. The aortic bodies are supplied
with blood from small branches of the aortic arch. In addition, pul
monary chemoreceptors have been described (Coleridge, Coleridge &
Howe, 1967) and tissue similar in structure to that of chemoreceptors
is found along the course of the abdominal aorta (abdominal para
ganglia, Abbot & Howe, 1972). This review will only be concerned
with chemoreceptors of the aortic and carotid bodies because it is
these which have been most extensively studied and they appear to
be of greatest importance.
Each carotid and aortic body receives nerve fibres from two sources.
The glossopharyngeal (cranial IX) nerve supplies sensory fibres to the
2 Peripheral Arterial Chemoreceptors
carotid body (glomus caroticum) via a branch known variously as the
carotid nerve, the intercarotid nerve, the carotid sinus nerve, the sinus
nerve or Hering's nerve, and the cell bodies of these sensory fibres are
located in the sensory (petrosal) ganglion of the IXth nerve. In addition,
the carotid body is also innervated by sympathetic fibres (ganglio
glomerular nerves) from the superior cervical ganglion (see Figure 1.1).
Some sympathetic fibres also course down the sinus nerve. The aortic
bodies are innervated by the (aortic) vasodepressor nerve (a branch of
the vagus) which has its cell bodies in the nodose ganglion; they also
receive a sympathetic nerve supply from the stellate ganglion.
Figure 1.1: A Diagrammatic Representation of the Innervation of the
Cat Carotid Body. Note the dual innervation from the sinus nerve and
ganglioglomerular nerve. The aortic bodies also receive a dual innervation.
Petrosal & Erhrenritters
ganglia
, glossopharyngeal
/~r---sinus nerve
internal carotid artery
ganglioglomerular nerve
superior cervical ganglion
common
---f-:,l~
carotid artery
Peripheral Arterial Chemoreceptors 3
Histologically the carotid and aortic bodies consist of groups of cells
collected around numerous large capillaries. A connective tissue stroma
is found between groups of cells and contains numerous nerve fibres;
on closer examination each cell group is seen to contain two cell types
which have been given a variety of names (see Biscoe, 1971). We shall
apply the term Type I to the most common type of cell, and Type II
for the less frequently encountered cell which is often located at the
periphery of a cell group. The general histological features of the
carotid body are illustrated in Figure 1.2; and we shall make a more
detailed examination of the important structural features of peripheral
chemoreceptors in a later section.
The embryological origin of the carotid body has only recently
been established. Using a heterospecific grafting technique (i.e Dovarin,
i.e Lievre & Fontaine, referred to by Verna, 1979) which enabled
donor cells to be identified in the recipient, Pearse and his colleagues
(see Verna, 1979) established that in birds Type I cells were definitely
derived from neural crest tissue, and Type II cells may also originate
from the same source. A number of studies have described the develop
ment of the carotid body (see Verna, 1979); all of these demonstrate
that the carotid body is structurally mature well before birth, a some
what surprising finding in view of the physiological immaturity of the
organ prior to the onset of respiration (see Chapter 8).
Two particularly interesting features of the carotid chemoreceptors
emerged from studies performed on cats. They have a very high oxygen
consumption of"" 9ml (l00g-1 )min-1, indicative of intense metabolic
activity, together with a very substantial blood flow of 2litres (l00g-1)
min -1. The difference between arterial and venous blood oxygen
content is, however, fairly low (0.2 - 0.5 ml/100ml) and the venous
blood is quite red; this could result from low oxygen extraction from
the blood, or from direct passage of blood from arteries to veins via
extensive anastamoses in the carotid body.
Study of Peripheral Arterial Chemoreceptor Activity
Various techniques are employed for studying chemoreceptor activity,
including the classical approach of using reflexly induced respiratory
changes as an indicator of receptor activity (see Heymans & Neil,
1958). Electrophysiological techniques are now commonly used because
they avoid some of the complications associated with reflex studies,
such as the influence of the anaesthetic on the reflex pathway, or
4 Peripheral Arterial Chemoreceptors
Figure 1.2: The Histology of the Carotid Body. Note how the cells are
set in a connective tissue stroma (ct) amidst numerous blood vessels
(c). Some bundles of nerve fibres are also seen (small arrow head).
Even at this magnification two cell types are visible on the basis of
nuclear morphology (T1 and large arrow heads), and position in the
cell groups.
