Ventilation, Blood Flow, and Diffusion

342 Pages·1980·5.095 MB·English

by  John West (Eds.)

PULMONARY
GAS EXCHANGE
Volume I
Ventilation, Blood Flow, and Diffusion
Edited by
John B. West
Department of Medicine
School of Medicine
University of California, San Diego
La Jolla, California
ACADEMIC PRESS 1980
A Subsidiary of Harcourt Brace Jovanovich, Publishers
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United Kingdom Edition published by
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Library of Congress Cataloging in Publication Data
Main entry under title:
Pulmonary gas exchange.
Includes bibliographies and index.
CONTENTS: v. 1. Ventilation, blood flow and
diffusion.
1. Respiration. 2. Blood gases. 3. Respiratory
insufficiency. I. West, John Burnard.
QP121.P78 612\22 80-12857
ISBN 0-12-744501-3
PRINTED IN THE UNITED STATES OF AMERICA
80 81 82 83 9 8 7 6 5 4 3 2 1
List of Contributors
Numbers in parentheses indicate the pages on which the authors' contributions begin.
John W. Evans (307), Department of Mathematics, University of Cali­
fornia, San Diego, La Jolla, California 92093
Robert A. Klocke (173), Department of Medicine, State University of New
York at Buffalo, Buffalo, New York 14214
Albert J. Olszowka (263), Department of Physiology, State University of
New York at Buffalo, Buffalo, New York 14214
Arthur B. Otis (33), Department of Physiology, University of Florida
College of Medicine, Gainesville, Florida 32610
Johannes Piiper (87, 131), Abteilung Physiologie, Max-Planck-Institut fur
experimentelle Medizin, D-3400 Gottingen, Federal Republic of
Germany
Hermann Rahn (33), Department of Physiology, State University of New
York at Buffalo, Buffalo, New York 14214
Richard L. Riley (67), Departments of Environmental Health Sciences and
Medicine, The Johns Hopkins Medical Institutions, Baltimore, Mary­
land 21205
Peter Scheid (87, 131), Abteilung Physiologie, Max-Planck-Institut fur
experimentelle Medizin, D-3400 Gottingen, Federal Republic of
Germany
Peter D. Wagner (219, 263), Department of Medicine, School of Medicine,
University of California, San Diego, La Jolla, California 92093
John B. West (1, 219), Department of Medicine, School of Medicine, Uni­
versity of California, San Diego, La Jolla, California 92093
ix
Preface
The purpose of this two-volume treatise is to provide an up-to-date
comprehensive account of pulmonary gas exchange, particularly in rela­
tion to the human lung. Interest in the lung has burgeoned over the last
few years and dramatic advances have been made in the area of gas ex­
change. This is the cardinal function of the lung and is of interest and
importance not only to physiologists but also to chest physicians, an­
esthesiologists, and cardiologists who are frequently confronted with
problems of disordered gas exchange.
This first volume is devoted to the mechanisms of gas exchange in the
lung, particularly the roles of ventilation, blood flow, and diffusion. The
opening chapter briefly traces the emergence of our knowledge from
ancient times; this is of interest because in the seventeenth and eighteenth
centuries pulmonary gas exchange was the central preoccupation of some
of the best scientists, and the history of pulmonary gas exchange is largely
the history of chemistry and physics. The next two chapters are devoted
to the momentous developments which took place near the end of the
Second World War, advances which established the modern basis of gas
exchange. We are fortunate that Dr. Richard Riley and Drs. Arthur Otis
and Hermann Rahn were persuaded to contribute first-hand accounts of
those pivotal times. Most of the remainder of the book is devoted to how
gas gets to the alveoli, how it crosses the blood-gas barrier, and the way
in which ventilation-perfusion relationships determine the efficiency of
exchange.
The second volume deals with how gas exchange is altered in a variety
of circumstances including exercise, high altitude, anesthesia, and lung
disease. Two chapters are concerned with highly contentious areas —
possible facilitated diffusion across the blood-gas barrier and the alleged
reversed arterial-alveolar difference for carbon dioxide.
I am indebted to the contributors, who are all authoritative (and cor­
respondingly busy), for keeping to the deadlines so effectively. It is a
pleasure to thank the staff of Academic Press for their help.
John B. West
xi
Contents of Volume II
1 Inert Gas Exchange
Leon E. Farhi and John L. Plewes
2 Dynamics of Pulmonary Gas Exchange during Exercise
Brian J. Whipp and Michael Mahler
3 Gas Exchange at High Altitude
Paolo Cerretelli
4 Gas Exchange during Anesthesia
Kai Rehder and H. Michael Marsh
5 Gas Exchange during Liquid Breathing
Johannes A. Kylstra
6 Evidence for Facilitated Transport of Oxygen and
Carbon Monoxide
Gail H. Gurtner
7 Evidence for Active Elimination of Carbon Dioxide
from the Lung
Michael P. Hlastala and H. Thomas Robertson
8 Gas Transfer in Diseased Lungs
William A. Briscoe
Index
xiii
1
Historical Development
John B. West
I. Introduction 1
II. Knowledge prior to the Seventeenth Century 3
A. Greeks and Romans 3
B. The Dark Ages and Renaissance 5
III. Seventeenth and Eighteenth Centuries 6
A. Harvey and the Microscopists 6
B. Oxford School 7
C. Phlogiston Theory 8
D. Carbon Dioxide and Oxygen 9
E. Lavoisier 11
IV. Nineteenth Century 12
A. Site of Respiration 12
B. Energy Production 14
V. Alveolar Gas and Dead Space 15
A. Size of Dead Space 15
B. Inhomogeneity of Alveolar Gas 18
VI. Secretion versus Diffusion 19
VII. Blood Gases 22
A. Carriage of Oxygen 22
B. Carriage of Carbon Dioxide 25
C. Measurement of Blood Gases 26
References 29
I. INTRODUCTION
In a book devoted to pulmonary gas exchange, it is worth tracing the
historical development of the topic for at least two reasons. First, there is
the intrinsic interest of the subject. For example, the evolution of ideas on
respiration in the seventeenth and eighteenth centuries is one of the scien­
tific sagas of civilized man. Indeed, the development of chemistry and
physics during that time was largely the history of pulmonary gas ex­
change.
PULMONARY GAS EXCHANGE, VOL. I J
Copyright © 1980 by Academic Press, Inc.
All rights of reproduction in any form reserved.
ISBN 0-12-744501-3
2 John B. West
But perhaps a more compelling reason is that our modern understanding
of any subject must reflect to some extent the way knowledge has devel­
oped, and it is important to be aware of this. In the future, historians will
no doubt recognize where some of our current misconceptions had their
origin, and a sense of history should help to keep us alert for change.
It is easy to forget how recently prejudices have been corrected. For
example, only 80 years ago Bohr (1909) vehemently argued in one of his
best-known papers that up to 60% of the oxygen consumption of an an­
imal occurs in the tissue cells of the lung. If this were true it would mean
that the Fick principle for measuring pulmonary blood flow from the
arterial-venous oxygen difference and oxygen uptake would be invalid.
Indeed, Bohr staunchly took this position. This seems a very bizarre at­
titude for one of the most distinguished physiologists of his time/until we
realize that in the eighteenth century all oxygen consumption and heat
production was thought to take place in lung tissue (an idea that is trace­
able to the early Greek philosophers) and that the site of oxygen usage in
the body remained a contentious issue right through the nineteenth cen­
tury (see Section IV,A).
Another notion that took an "unconscionable time adying" was active
secretion of oxygen by the lungs against a partial pressure gradient. Only
50 or so years ago, Haldane and Priestley (1935) devoted a whole chapter
in their book "Respiration" to the evidence for this long after the Kroghs
and Barcroft had apparently clinched the issue in favor of passive diffu­
sion. Was this a dying gasp of the vitalism that had had so enormous an
influence on the whole history of respiration from the time of Aristotle,
and that was thought to have received a mortal blow from Claude Bernard
in the 1880s?
Of course, it is easy to be wise after the event and no doubt historians in
the future will be able to point a finger at some of our modern prejudices.
In any event a sense of history can be very humbling and smooths the way
to accepting changes, even when these are in conflict with prevailing
opinion.
In this chapter, the history of pulmonary gas exchange is briefly traced
from ancient times. There is, however, no attempt at a comprehensive ac­
count; the ideas followed are those most relevant to the subject as we see
it today. Most of the material is necessarily derivative, the chief sources
being Clendening (1960), Foster (1901), Fulton (1930), Goodfield (1960),
Perkins (1964), Singer (1957, 1959), and Stirling (1902).
1. Historical Development 3
II. KNOWLEDGE PRIOR TO THE SEVENTEENTH CENTURY
A. Greeks and Romans
A central notion of many of the Greek philosophers as early as the sixth
century B.C. was that the essence of all things is "pneuma," which can be
translated as air, breath, or spirit. This was seen to be essential for life.
Empodocles (ca. 495-435 B.C.) taught that all matter was composed of
four elements: earth, air, fire, and water. The purpose of respiration was
to cool the heart and blood, and the blood was then responsible for distrib­
uting "innate heat" from the heart to the various parts of the body. The
ideas of Empodocles are important because he greatly influenced Aris­
totle (384-322 B.C.), many of whose views held sway until the eighteenth
century. In addition, Aristotle was a vitalist who believed that the pres­
ence of a peculiar spirit, which he called "psyche," was responsible for
the different functioning of animate and inanimate things. This view was
opposed by Democritus (470-400 B.C.), an atomist, who favored mechan­
istic, deterministic causes. Aristotle was a keen observer of many species
of animals, but he was not an experimentalist. For example, he taught that
the arteries normally contain air.
Galen (130-199 A.D.) was born in Asia Minor and became a physician
to the emperor Marcus Aurelius. Through his writings he exerted an enor­
mous influence on the way men thought for 1500 years, his teachings
being embellished by Arabic and medieval commentators. Many of his
views can be traced to Erasistratus (born ca. 304 B.C.), who is credited
with originating the "pneumatic" theory of respiration. Galen believed
that blood was formed in the liver from food absorbed in the gut (Fig. 1).
In the liver, it was imbued with "natural spirit." The blood then flowed to
the right ventricle, where some of it went through the pulmonary artery to
nourish the lungs, while a portion passed through "invisible pores" in the
interventricular septum into the left ventricle. Here it was mixed with
"pneuma" from the inspired air, and the resulting "vital spirit" was dis­
tributed throughout the body by the arterial blood. Blood that reached the
brain received "animal spirit" and was distributed from there through the
nerves, which were thought to be hollow. Galen also believed that fu­
liginous (sooty) waste products were eliminated from the blood by the
lungs, though the route was a strange one in that the blood was thought to
travel back through the pulmonary vein.
Although much of what Galen taught now seems quaint, it can be
argued that the elements of pulmonary gas exchange had been estab­
lished. Blood was enriched with a vital element from the inspired air and
distributed by means of the arteries throughout the body. Waste materials
Fig. 1. Galen's cardiopulmonary system, which held sway for 1300 years. During inspi­
ration, pneuma entered the lung through the trachea and reached the left ventricle via the
pulmonary vein (arteria venalis). Blood was formed in the liver, and imbued there with natu­
ral spirit. A portion passed through minute channels in the interventricular septum to the left
ventricle, where vital spirit was formed and distributed through arteries to the rest of the
body. The blood that reached the brain was charged with animal spirit, which was distrib­
uted through the hollow nerves. (From Singer, 1957, reproduced by permission.)
1. Historical Development 5
in the blood were eliminated via the lungs. Unfortunately, the anatomical
basis for these functions was in a very confused state, chiefly because the
circulation of the blood was unsuspected.
B. The Dark Ages and Renaissance
For 1300 years, from the third to the sixteenth century, very little
progress in physiology was made. The teachings of Galen and Aristotle
were preserved chiefly in Arabic writings and were forgotten in much of
Europe when the Roman civilization was destroyed. When the univer­
sities began to form in the twelfth century, medieval scholars started to
discuss and embellish the knowledge inherited from the Arabs but little
direct observation or experiment accompanied their theoretical studies.
A few events toward the end of this dismal period presaged the reawak­
ening of science and the consequent rapid expansion of knowledge,
which continues to the present day. Several of these advances were in the
area of the pulmonary circulation, where the erroneous ideas of Galen and
Aristotle so effectively stifled progress. For example, Ibn An-Nafis (ca.
1210-1288), a physician in Damascus, argued that blood did not go
through the septum between right and left ventricles as Galen had taught,
but through the lung. Because he could not see direct communications
between the pulmonary artery and vein, he supposed that there must be
invisible pores linking the two. Presumably this notion was not difficult to
accept because the existence of invisible pores in the demonstrably solid
interventricular septum was a central tenet in Galen's scheme (Fig. 1). In­
deed, the possibility of pores between systemic arteries and veins had
been suggested by Erasistratus in the fourth century B.C.
The manuscript of Ibn An-Nafis was not known to the medieval schol­
ars and therefore Servetus (1511-1533) can be credited with indepen­
dently discovering the pulmonary circulation (or more strictly the transit of
blood through the lung), when he stated the blood passed from the right
venticle to the left, not through the interventricular septum "as is com­
monly believed" but through the lungs from pulmonary artery to vein. He
also wrote that the blood became reddish yellow in the process. However,
his book "Christianismi Restitutio" was considered heretical by both
Catholics and Calvinists, and Servetus and his books were burned at the
stake in Geneva by the latter. Six years later Realdus Columbus
(1516-1559) also clearly described the pulmonary transit, though it should
be emphasized that the notion of the continuous circulation of blood
through the lungs had not emerged at this time.
One of the most significant scientific events in the sixteenth century
was the resurgence of anatomy, especially in the work of Vesalius