High Altitude: Human Adaptation to Hypoxia

495 Pages·2014·10.55 MB·English

by  Paul T. Schumacker Ph.D. (auth.)

Erik R. Swenson
Peter Bärtsch
Editors
High Altitude
Human Adaptation
to Hypoxia
123
High Altitude

Erik R. Swenson (cid:129) Peter Bärtsch
Editors
High Altitude
Human Adaptation to Hypoxia
Editors
Erik R. Swenson Peter Bärtsch
VA Puget Sound Health Care System Medical University Clinic
University of Washington Heidelberg , Germany
Seattle , WA , USA
ISBN 978-1-4614-8771-5 ISBN 978-1-4614-8772-2 (eBook)
DOI 10.1007/978-1-4614-8772-2
Springer New York Heidelberg Dordrecht London
Library of Congress Control Number: 2013953322
© Springer Science+Business Media New York 2014
This work is subject to copyright. All rights are reserved by the Publisher, whether the whole or
part of the material is concerned, specifi cally the rights of translation, reprinting, reuse of
illustrations, recitation, broadcasting, reproduction on microfi lms or in any other physical way,
and transmission or information storage and retrieval, electronic adaptation, computer software,
or by similar or dissimilar methodology now known or hereafter developed. Exempted from this
legal reservation are brief excerpts in connection with reviews or scholarly analysis or material
supplied specifi cally for the purpose of being entered and executed on a computer system, for
exclusive use by the purchaser of the work. Duplication of this publication or parts thereof is
permitted only under the provisions of the Copyright Law of the Publisher’s location, in its
current version, and permission for use must always be obtained from Springer. Permissions for
use may be obtained through RightsLink at the Copyright Clearance Center. Violations are liable
to prosecution under the respective Copyright Law.
The use of general descriptive names, registered names, trademarks, service marks, etc. in this
publication does not imply, even in the absence of a specifi c statement, that such names are
exempt from the relevant protective laws and regulations and therefore free for general use.
While the advice and information in this book are believed to be true and accurate at the date of
publication, neither the authors nor the editors nor the publisher can accept any legal responsibility
for any errors or omissions that may be made. The publisher makes no warranty, express or
implied, with respect to the material contained herein.
Printed on acid-free paper
Springer is part of Springer Science+Business Media (www.springer.com)
Pref ace
Mountains stir our imagination and not solely for their beauty and
magnifi cence. Perhaps also because they tax our physical limits as individu-
als and as a population. As scientists and nonscientists we fi nd this an irresist-
ible subject. The rarifi ed air of the highest terrestrial altitudes poses one of the
greatest biological challenges to functioning and survival that our species has
faced in its radiation “out of Africa” over the globe. In moving into highlands
above 2,500 m whether transiently or permanently, humans have relied upon
an array of successful responses to hypoxia that range across the physiologi-
cal continuum from organs to cells and genome. Unraveling what transpires
with successful and unsuccessful adaptation to acute and chronic high altitude
is inextricably linked to better understanding and care of clinical conditions
involving ischemia, hypoxemia, and cellular hypoxia.
In this effort, which owes its lineage and draws great inspiration from its
predecessor “High Altitude: An Exploration of Human Adaptation” edited by
Thomas F. Hornbein and Robert B. Schoene and published in 2001, we have
reassembled many of the same authors and brought on a number of new
active younger researchers to update the fi eld. Many of our contributors are
mountaineers, who have taken the “bench to mountainside” and back
approach in impressive transnational collaborations. Over the past decade
there has been substantial work in better understanding the classic “oxygen
cascade” of O transport from inhaled air to the mitochondria. Equally excit-
2
ing has been the extent to which genetics and molecular biology have now
been brought to bear on hypoxia adaptation and maladaptation.
The 23 chapters comprising this book can be divided into several sections.
The fi rst chapters focus on how oxygen is sensed at the cellular level and how
changes in O tension evoke signaling cascades that mediate rapid non-
2
genomic responses and set the stage for more sustained tolerance by altering
gene expression. Particularly in this latter aspect, there has been a virtual
explosion in our understanding of how hypoxia-inducible factors (HIFs) are
regulated and how up- or down-regulation of many hundreds of genes accom-
plish tolerance for hypoxia. It is a very complicated story that only promises
to become more interesting and relevant to high-altitude physiology and clin-
ical medicine, since HIFs may be more than just gene transcription factors
responsive to hypoxia. The next section takes up the role of many organ sys-
tems involved in oxygen delivery to the tissues, and the costs and limits of
their compensatory capacity to contribute to adequate tissue oxygenation.
v
vi Preface
Of no less critical importance are other organs whose functioning in overall
homeostasis and population survival (nutrition, infection control, waste elim-
ination, and reproduction) succeed or fail in the face of hypoxia. The unique
and differing patterns of hypoxic tolerance in highly adapted populations liv-
ing at high altitude for many millennia are explored at the genetic and physi-
ological levels. Evolution over many generations involves strategies entirely
different (and likely more successful and economical) when compared to how
lowlanders “partially adapt” over much shorter time durations. The last chap-
ters are devoted to the unique acute diseases of sojourners at high altitude,
chronic hypoxic maladaptation of high-altitude residents, and problems in
people with preexisting medical conditions who wish to work or take enjoy-
ment in the mountains.
We are grateful to many colleagues and friends over the years who have
contributed to this volume. It is our hope that our combined work will stimu-
late more questions and research, ultimately to yield better care of hypoxic
patients and safer sojourning and residence to those seeking the pleasure and
excitement of life and livelihood at high altitudes.
Seattle , WA , USA Erik R. Swenson
Heidelberg , Germany Peter Bärtsch
Contents
1 Cellular and Molecular Mechanisms of O Sensing ................... 1
2
Paul T. Schumacker
2 Cellular and Molecular Defenses Against Hypoxia ................... 23
Stilla Frede and Joachim Fandrey
3 Control of Breathing ..................................................................... 37
Luc J. Teppema and Remco R. Berendsen
4 Lung Function and Gas Exchange .............................................. 57
Andrew M. Luks and Susan R. Hopkins
5 Pulmonary Circulation ................................................................. 85
Marco Maggiorini, Peter Bärtsch, and Erik R. Swenson
6 Cardiovascular System ................................................................. 103
Aaron L. Baggish, Eugene E. Wolfel,
and Benjamin D. Levine
7 Cerebral Circulation and Brain ................................................... 141
Philip N. Ainslie, Mark H. Wilson,
and Christopher H.E. Imray
8 Autonomic Nervous System ......................................................... 171
Mark J. Drinkhill, Roger Hainsworth,
and Victoria E. Claydon
9 Skeletal Muscle Tissue Changes with Hypoxia .......................... 191
Hans Hoppeler, Matthias Mueller, and Michael Vogt
10 Blood and Haemostasis ................................................................. 203
James S. Milledge and Peter Bärtsch
11 Renal Function and Fluid Homeostasis ...................................... 217
Erik R. Swenson and Niels V. Olsen
12 Endocrine Function ...................................................................... 237
Jean-Paul Richalet
13 Gastrointestinal Function ............................................................. 253
Noor Hamad and Simon Travis
vii
viii Contents
14 Immune System ............................................................................. 271
Robert S. Mazzeo and Erik R. Swenson
15 Nutrition and Metabolism ............................................................ 285
George A. Brooks
16 Exercise .......................................................................................... 301
Carsten Lundby
17 Sleep ............................................................................................... 325
Yvonne Nussbaumer-Ochsner and Konrad E. Bloch
18 Reproduction and Growth ........................................................... 341
Susan Niermeyer
19 Human Evolution at High Altitude ............................................. 357
Cynthia M. Beall
20 Acute Mountain Sickness and High Altitude
Cerebral Oedema .......................................................................... 379
Peter Bärtsch and Damian Miles Bailey
21 High-Altitude Pulmonary Edema (HAPE) ................................. 405
Robert B. Schoene and Erik R. Swenson
22 Chronic Mountain Sickness ......................................................... 429
Fabiola León-Velarde, María Rivera-Ch,
Luis Huicho, and Francisco C. Villafuerte
23 High Altitude and Common Medical Conditions ....................... 449
Andrew M. Luks and Peter H. Hackett
Index ....................................................................................................... 479
Contributors
Philip N. Ainslie, Ph.D. Centre for Heart, Lung and Vascular Health, School
of Health and Exercise Sciences , University of British Columbia , Kelowna ,
BC , Canada
Aaron L. Baggish, M.D. Division of Cardiology , Massachusetts General
Hospital , Boston , MA , USA
Damian Miles Bailey, Ph.D. Neurovascular Research Laboratory, Faculty of
Life Sciences and Education , University of South Wales , Mid-Glamorgan , UK
Peter Bärtsch, M.D. Division of Sports Medicine, Department of Internal
Medicine, Medical University Clinic, University of Heidelberg , Heidelberg ,
Germany
Cynthia M. Beall, Ph.D. Department of Anthropology , Case Western
Reserve University , Cleveland , OH , USA
Remco R. Berendsen, M.D. Department of Anesthesiology , Leiden
University Medical Center , Leiden , The Netherlands
Konrad E. Bloch, M.D. Pulmonary Division, Sleep Disorders Center ,
University Hospital of Zürich , Zürich , Switzerland
George A. Brooks, Ph.D. Department of Integrative Biology , University of
California , Berkeley , CA , USA
Victoria E. Claydon, Ph.D. Department of Biomedical Physiology and
Kinesiology , Faculty of Science, Simon Fraser University , Burnaby , BC , C anada
Mark J. Drinkhill, Ph.D. Division of Cardiovascular and Neuronal
Remodelling, Faculty of Medicine , University of Leeds , Leeds , UK
Joachim Fandrey, M.D. Institut für Physiologie , Universität Duisburg-Essen ,
Essen , Germany
Stilla Frede, Ph.D. Institut für Physiologie , Universität Duisburg-Essen ,
Essen , Germany
Peter H. Hackett, M.D. Clinical Professor of Surgery, Division of
Emergency Medicine , Department of Surgery, Altitude Research Center,
University of Colorado Denver School of Medicine , Denver , CO , USA
Institute for Altitude Medicine, Telluride, CO, USA
ix