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Daniel Pedro Cardinali Autonomic Nervous System Basic and Clinical Aspects 123 Autonomic Nervous System Daniel Pedro Cardinali Autonomic Nervous System Basic and Clinical Aspects Daniel Pedro Cardinali Facultad de Ciencias Médicas Pontificia Universidad Católica Argentina Buenos Aires, Capital Federal Argentina ISBN 978-3-319-57570-4 ISBN 978-3-319-57571-1 (eBook) DOI 10.1007/978-3-319-57571-1 Library of Congress Control Number: 2017949889 © Springer International Publishing AG 2018 This work is subject to copyright. All rights are reserved by the Publisher, whether the whole or part of the material is concerned, specifically the rights of translation, reprinting, reuse of illustrations, recita- tion, broadcasting, reproduction on microfilms or in any other physical way, and transmission or infor- mation storage and retrieval, electronic adaptation, computer software, or by similar or dissimilar methodology now known or hereafter developed. The use of general descriptive names, registered names, trademarks, service marks, etc. in this publica- tion does not imply, even in the absence of a specific statement, that such names are exempt from the relevant protective laws and regulations and therefore free for general use. The publisher, the authors and the editors are safe to assume that the advice and information in this book are believed to be true and accurate at the date of publication. Neither the publisher nor the authors or the editors give a warranty, express or implied, with respect to the material contained herein or for any errors or omissions that may have been made. The publisher remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. Printed on acid-free paper This Springer imprint is published by Springer Nature The registered company is Springer International Publishing AG The registered company address is: Gewerbestrasse 11, 6330 Cham, Switzerland Prologue The autonomic nervous system (ANS) is an important component of the nervous system consisting of a complex set of neurons and neural pathways that control the function of the various visceral organ systems. The overall function of the ANS is to maintain the body homeostasis and to react adaptively to changes in the external and internal milieu. The ANS innervates the heart, the smooth muscle in all the organs, the abdomi- nal viscera, the exocrine and endocrine glands, and the immune system. Thus, the ANS participates in the regulation of breathing, circulation, digestion, metabolism, and the internal milieu, exocrine and endocrine gland secretion, immune responses, body temperature, and reproduction [1, 2]. Unfortunately, such medical importance tends to be underscored in many books on physiology or neural sciences in which the subject takes up much less space than that accorded, for example, to somatosen- sory or cognitive functions. The basic structure and operation of the ANS were defined at the beginning of the last century, primarily by Gaskell and Langley, who recognized its two main divisions: the sympathetic and the parasympathetic [3]. Furthermore, Langley des- ignated the enteric nervous system as a third division based on the submucous plexus of Meissner and the myenteric plexus of Auerbach located in the wall of the gastrointestinal tract, albeit controlled by the sympathetic and parasympathetic divi- sions. Overcoming the classical concept of a purely efferent system, it is presently accepted that the ANS is composed of visceral afferents, integration centers, par- ticularly in the brainstem, hypothalamus, and limbic cortex, and visceral sympa- thetic and parasympathetic efferents; thus, the ANS extends both into the central nervous system (CNS) and to the periphery. Conceptually, the bio-psycho-social-ecological nature of the individual is truly expressed by the function of his or her ANS. Its name is misleading because none of the components shows “autonomy” in an integrated body. Nor are they solely “pas- sive” or generated “without elaboration by mind.” All body systems are dependent and affected by the action of others in a multicellular organization. These dynamic relationships are the core of homeostasis, a key concept in physiol- ogy. “Homeostasis” is used today to define not only the strategies that allow the body’s proper response to changes in the environment (reactive homeostasis), but also the remarkably developed, temporal mechanisms that allow the body to predict the timing of environmental stimuli (predictive homeostasis based on biological rhythms). v vi Prologue Autonomic reflexes are mediated by neural pathways in the brainstem and spinal cord and generally regulate organ and system performance very rapidly (in millisec- onds). Autonomic control is also mediated by specific brain regions, such as the hypothalamus, which is responsible for medium-term (minutes) and long-term (hours/days) regulation of internal organ systems. Importantly, autonomic reflexes are dynamic, where adaptations can alter rapid homeostatic control over longer time scales [4]. This book discusses the ANS from both an enlarged and a timed perspective. First, it presents how the organization of the ANS is built in four different hierarchi- cal levels. Next, it discusses how the ANS function changes in the three body con- figurations (wakefulness, slow- wave sleep, and rapid eye movement, REM, sleep) found during a 24-h cycle. Finally, the most important clinical implications for this enlarged and timed vision of the ANS are discussed. The Autonomic Nervous System – Basic and Clinical Aspects is designed as a comprehensive textbook for advanced medical students and health professionals. It primes for a detailed and complete understanding of the neuroscience behind the ANS and a proper clinical applicability of this knowledge. ANS dysfunction and clinical manifestations involve multiple variables, which are often undervalued in clinical practice. However, symptoms and signs of ANS disturbances should always be considered according to their diagnostic implication, their impact on the quality of life of patients, and their prognostic value for life expectancy. References 1. Saper CB. The central autonomic nervous system: conscious visceral perception and auto- nomic pattern generation. Annu Rev Neurosci. 2002;25:433–69. 2. Benarroch EE. The central autonomic network: functional organization, dysfunction, and per- spective. Mayo Clin Proc. 1993;68:988–1001. 3. Oakes PC, Fisahn C, Iwanaga J, DiLorenzo D, Oskouian RJ, Tubbs RS. A history of the auto- nomic nervous system: part II: from Reil to the modern era. Childs Nerv Syst. 2016;32:2309–15. 4. McDougall SJ, Munzberg H, Derbenev AV, Zsombok A. Central control of autonomic func- tions in health and disease. Front Neurosci. 2014;8:440. Contents 1 The Enlarged Autonomic Nervous System . . . . . . . . . . . . . . . . . . . . . . 1 The Control of Homeostasis Is the Most Important Function of the ANS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2 There Are Functional Similarities in the Hierarchical Organization of the Autonomic and Somatic Motor Pathways . . . . . . . . . . . . . . . . . . . 6 The Autonomic Posture . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10 Basic Neuronal Organization of ANS . . . . . . . . . . . . . . . . . . . . . . . . . . . . 14 References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 17 2 The Timed Autonomic Nervous System . . . . . . . . . . . . . . . . . . . . . . . . 19 Biological Rhythms Are the Basis of Predictive Homeostasis . . . . . . . . . 20 The Sleep/Wake Cycle as the Major 24-h Rhythm . . . . . . . . . . . . . . . . . . 31 Neurophysiology of Sleep . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 36 Three Different ANS Programs (“Body Configurations”) Occur in a 24-h Day/Night Cycle . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 45 The Meaning of Dreaming . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 51 The Glymphatic System and Sleep . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 52 References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 54 3 F irst Level: Peripheral Sympathetic and Parasympathetic Nervous System . . . . . . . . . . . . . . . . . . . . . . . . . 57 The Organization of the ANS at a Peripheral Level Comprises Two Neurons in a Series . . . . . . . . . . . . . . . . . . . . . . . . 58 Cholinergic and Adrenergic Neurotransmission and Peptidergic Co-transmission Are the Basis of the Peripheral Motor Constituents of the ANS . . . . . . . . . . . . . . . . . . . 63 Sensory Autonomic Neurons . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 79 Spinal Autonomic Reflexes Have Homologies and Differences with Spinal Motor Reflexes . . . . . . . . . . . . . . . . . . . . . . 87 Urination, Defecation, and Pupillary and Sexual Responses Are Examples of Spinal Autonomic Reflexes . . . . . . . . . . . . . . . . . . . . . . 89 The Enteric ANS as an Individual Entity . . . . . . . . . . . . . . . . . . . . . . . . . 95 vii viii Contents The Overlooked Role of the Local Autonomic Projections in Neuroendocrine Communication . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 102 The ANS Contributes to the Maintenance of Healthy Bone Tissue . . . . . 106 References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 109 4 Second Level: The Brainstem . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 113 At the Brainstem, Various Complex Autonomic Responses Are Coordinated . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 114 Monoaminergic Systems in the Brainstem Modulate 24-h Rhythms in Physiological Function . . . . . . . . . . . . . . . . . . . . . . . 120 24 -h Rhythms in Cardiovascular Control . . . . . . . . . . . . . . . . . . . . . . . . 125 24 -h Rhythms in Respiratory Control . . . . . . . . . . . . . . . . . . . . . . . . . . . 133 The Cerebellum and the Autonomic Posture . . . . . . . . . . . . . . . . . . . . . 138 24 -h Rhythms in the Immune Response . . . . . . . . . . . . . . . . . . . . . . . . . 144 24 -h Rhythms in Gastrointestinal Function . . . . . . . . . . . . . . . . . . . . . . 160 References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 171 5 Third Level: The Hypothalamus . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 175 Hypothalamic Behaviors Comprise Coordinated Mechanisms, Including Autonomic, Neuroendocrine, and Motivational Components . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 176 24 -h Rhythms in Neuroendocrine Function . . . . . . . . . . . . . . . . . . . . . . . 180 Defense Behavior as a Paradigm of Reactive Homeostasis . . . . . . . . . . . 190 24 -h Rhythms in Food Intake, Energy Storage, and Metabolism . . . . . . . 203 24 -h Rhythms in Plasma Osmolality and the Intravascular Volume . . . . . 221 24 -h Rhythms in Body Temperature Control . . . . . . . . . . . . . . . . . . . . . . 228 Sexual and Maternal Behavior . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 235 References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 239 6 F ourth Level: The Limbic System . . . . . . . . . . . . . . . . . . . . . . . . . . . 245 The Limbic System Is Essential in Emotionality, Motivation, Learning, and Memory . . . . . . . . . . . . . . . . . . . . . . . . . . . 246 The Amygdala Is the Main “Motor Nucleus” of the Limbic System . . 252 Emotions Comprise Feelings and Moods, and Their Expression in Somatic and Autonomic Behaviors . . . . . . . . . . . . . . . . . . . . . . . . . . 257 Limbic Components of the Basal Ganglia . . . . . . . . . . . . . . . . . . . . . . . 262 Functional Neuroimaging of ANS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 268 Chronotypes, 24-h Rhythms and Emotion . . . . . . . . . . . . . . . . . . . . . . . 271 24 -h Rhythms and Learning and Memory . . . . . . . . . . . . . . . . . . . . . . . 274 References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 283 7 C linical Implications of the Enlarged Autonomic Nervous System 287 Semiological Aspects of ANS Disorders . . . . . . . . . . . . . . . . . . . . . . . 288 Classification of ANS Disorders . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 292 Some Clinical Autonomic Entities . . . . . . . . . . . . . . . . . . . . . . . . . . . . 293 Peripheral Neuropathies with Dysautonomia . . . . . . . . . . . . . . . . . . 293 α-Synucleinopathies . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 296 Contents ix Diabetes Mellitus Autonomic Dysfunction . . . . . . . . . . . . . . . . . . . . 298 Autoimmune Autonomic Ganglionopathy . . . . . . . . . . . . . . . . . . . . . 299 Paraneoplastic Autonomic Dysfunction . . . . . . . . . . . . . . . . . . . . . . . 299 Amyloidotic Autonomic Failure . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 299 Autonomic Dysfunction in Primary Sleep Disorders . . . . . . . . . . . . . 300 Autonomic Dysfunction in Cardiovascular Disorders . . . . . . . . . . . . 303 Autonomic Dysfunction Associated with Aging . . . . . . . . . . . . . . . . 305 Guillain–Barré Syndrome . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 306 Hereditary Autonomic Neuropathies . . . . . . . . . . . . . . . . . . . . . . . . . 306 Autonomic Disturbances in Spinal Cord Injuries . . . . . . . . . . . . . . . . 307 Drug-Induced Autonomic Dysfunction . . . . . . . . . . . . . . . . . . . . . . . 307 Autonomic Disorder in Fibromyalgia, Chronic Fatigue Syndrome and Chronic Pain . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 307 Hyperthermia, Hypothermia . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 309 References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 310 8 Clinical Implications of the Timed Autonomic Nervous System . . 313 Due to the “24/7 Society,” the ANS Has Lost Adequate Experience of Day and Night . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 314 The Disruption of the Three ANS Physiological Programs (“Body Configurations”) Is a Major Consequence for the “24/7 Society” . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 316 Jet Lag, Shift Work, and Chronodisruption as Examples of a Desynchronized ANS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 319 Jet Lag . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 321 Shift-Work Disorder . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 324 Chronodisruption . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 327 Chronobiological Treatment of a Desynchronized ANS . . . . . . . . . . . . 328 Some Clinical Autonomic Entities Associated with a Desynchronized ANS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 332 Metabolic Syndrome . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 332 Mental Illnesses . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 339 Brain Aging . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 349 Cancer . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 361 References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 365 Epilogue . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 375 References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 376 Index . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 377 Abbreviations 3V Third ventricle 5-HT Serotonin ACh Acetylcholine ACTH Adrenocorticotropin AD Alzheimer’s disease AgRP Agouti protein-related peptide AMPK AMP-activated protein kinase AN Ambiguous nucleus ANP Atrial natriuretic peptide ANS Autonomic nervous system AP Area postrema APP Amyloid precursor protein ARC Arcuate nucleus AV3V Anterior ventral region of the third ventricle AVP Arginine vasopressin AVPV Anteroventral periventricular Aβ Amyloid β BAT Brown adipose tissue BCRs B cell receptors BF Basal forebrain BMD Bone mineral density BNP Brain natriuretic peptide BP Blood pressure BRAC Basic rest–activity cycle BZD Benzodiazepine CALB Calbindin CALR Calretinin CART Cocaine and amphetamine-regulated transcript CCG Controlled clock genes CCK Cholecystokinin CGRP Calcitonin gene-related peptide CNP C-type natriuretic peptide CNS Central nervous system CO Carbon monoxide xi

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Most books are stored in the elastic cloud where traffic is expensive. For this reason, we have a limit on daily download.