Elsevier’s Integrated Physiology: With Student Consult Online Access

236 Pages·2006·14.193 MB·English

by  Robert G. Carroll

Elsevier’s Integrated
Physiology
Robert G. Carroll
PhD
Professor of Physiology
Brody School of Medicine
East Carolina University
Greenville, North Carolina
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ELSEVIER’S INTEGRATED PHYSIOLOGY ISBN-13: 978-0-323-04318-2
ISBN-10: 0-323-04318-6
Copyright © 2007 by Mosby, Inc., an affiliate of Elsevier Inc.
All rights reserved.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.Permissions may be sought
directly from Elsevier’s Health Sciences Rights Department in Philadelphia,PA,USA: phone: (+1) 215
239 3804,fax: [phone],e-mail: [email protected] may also complete
your request on-line via the Elsevier homepage (http://www.elsevier.com),by selecting ‘Customer
Support’ and then ‘Obtaining Permissions’.
Notice
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Knowledge and best practice in this field are constantly changing.As neVw research and
experience broaden our knowledge,changes in practice,treatment an d drug therapy may
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administered,to verify the recommended dose or formulhai,trhe method& and durantison of
administration,and contraindications.It is the responsiability of the practitionear,relying on
their own experience and knowledge of the patient,tto make diagnoses,tos idetermine dosages
and the best treatment for each individual patient,and to take all approrpriate safety
e
precautions.To the fullest extent of the law,neither the Publisher npor the Author assumes any
liability for any injury and/or damage to persons or property arpis.ing out or related to any use
of the material contained in this book. vi
The Publisher
Library of Congress Cataloging-in-Publication Data
Elsevier’s integrated physiology.
p.cm.
ISBN 0-323-04318-6
1.Human physiology.
QP34.5.E47 2007
612—dc22
2006043013
Acquisitions Editor: Alex Stibbe
Developmental Editor: Andrew Hall
Printed in China
Last digit is the print number: 9 8 7 6 5 4 3 2 1
In memory of my friend and mentor,
the late Dr. David F. Opdyke,
and with many thanks to my teachers
at the University of Medicine and Dentistry of New Jersey–Newark.
vii
Preface
At a conference, I was asked to summarize physiology in Function does indeed follow form,and the structure provides
twenty-five words or less. Here is my response: “The body limitations on physiology of a system.Physiology,however,is
consists of barriers and compartments.Life exists because the the study of anatomy in action.If anatomy is the study of the
body creates and maintains gradients.Physiology is the study body in three dimensions, physiologic function and
of movement across the barriers.” Twenty-five words exactly. regulation extend the study of the body into the fourth
This book is organized along those lines. Most chapters dimension,time.
begin with an anatomic/histologic presentation of the system. Robert G.Carroll,PhD
viii
Editorial Review Board
Chief Series Advisor James L.Hiatt,PhD
J.Hurley Myers,PhD Professor Emeritus
Professor Emeritus of Physiology and Medicine Department of Biomedical Sciences
Southern Illinois University School of Medicine Baltimore College of Dental Surgery
and Dental School
President and CEO University of Maryland at Baltimore
DxR Development Group,Inc. Baltimore,Maryland
Carbondale,Illinois
Immunology
Anatomy and Embryology Darren G.Woodside,PhD
Thomas R.Gest,PhD Principal Scientist
University of Michigan Medical School Drug Discovery
Division of Anatomical Sciences Encysive Pharmaceuticals Inc.
Office of Medical Education Houston,Texas
Ann Arbor,Michigan
Microbiology
Biochemistry Richard C.Hunt,MA,PhD
John W.Baynes,MS,PhD ProfeGssor of Pathology,Microbiology,and Immunology
Graduate Science Research Center DRirector of the Biomedical Sciences Graduate Program
University of South Carolina V Department of Pathology and Microbiology

Columbia,South Carolina 9 9 - UConliuvemrbsiitays, .oSifo ruStohu tCha Croalrinoalina School of Medicine
MClainreicka lD Boimocinhiecmzaiskt,ryM SDe,rPvihcDe,FRCPath,FRCP(Glas) hir & n s
a Neauroscience
NHS Greater Glasgow and Clyde t Csiristian Stefan,MD
Gartnavel General Hospital er
Glasgow,United Kingdom p Associate Professor
p. Department of Cell Biology
vi University of Massachusetts Medical School
Clinical Medicine
Worcester,Massachusetts
Ted O’Connell,MD
Clinical Instructor
Pharmacology
David Geffen School of Medicine
Michael M.White,PhD
UCLA
Professor
Program Director
Department of Pharmacology and Physiology
Woodland Hills Family Medicine Residency Program
Drexel University College of Medicine
Woodland Hills,California
Philadelphia,Pennsylvania
Genetics
Physiology
Neil E.Lamb,PhD
Joel Michael,PhD
Director of Educational Outreach
Department of Molecular Biophysics and Physiology
Hudson Alpha Institute for Biotechnology
Rush Medical College
Huntsville,Alabama
Chicago,Illinois
Adjunct Professor
Department of Human Genetics
Pathology
Emory University
Peter G.Anderson,DVM,PhD
Atlanta,Georgia
Professor and Director of Pathology Undergraduate Education
Department of Pathology
Histology
University of Alabama at Birmingham
Leslie P.Gartner,PhD
Birmingham,Alabama
Professor of Anatomy
Department of Biomedical Sciences
Baltimore College of Dental Surgery
Dental School
University of Maryland at Baltimore
Baltimore,Maryland
tahir99-VRG & vip.persianss.ir
x
Series Preface
How to Use This Book confident in the subject matter of many of the integration
The idea for Elsevier’s Integrated Series came about at a boxes,so they will serve as helpful reminders.
seminar on the USMLE Step 1 exam at an American Medical At the back of the book we have included case study
Student Association (AMSA) meeting.We noticed that the questions relating to each chapter so that you can test
discussion between faculty and students focused on how the yourself as you work your way through the book.
exams were becoming increasingly integrated—with case
scenarios and questions often combining two or three science Online Version
disciplines.The students were clearly concerned about how An online version of the book is available on our Student
they could best integrate their basic science knowledge. Consult site.Use of this site is free to anyone who has bought
One faculty member gave some interesting advice: “read the printed book. Please see the inside front cover for full
through your textbook in, say, biochemistry, and every time details on the Student Consult and how to access the
you come across a section that mentions a concept or piece electronic version of this book.
of information relating to another basic science—for example, In addition to containing USMLE test questions, fully
immunology—highlight that section in the book.Then go to searchable text,and an image bank,the Student Consult site
your immunology textbook and look up this information,and offers additional integration links,both to the other books in
make sure you have a good understanding of it.When you Elsevier’s Integrated Series and to other key Elsevier
have, go back to your biochemistry textbook and carry on textbooks.
reading.”
This was a great suggestion—if only students had the time, Books in Elsevier’s Integrated Series
and all of the books necessary at hand,to do it! At Elsevier The nine books in the series cover all of the basic sciences.
we thought long and hard about a way of simplifying this The more books you buy in the series, the more links are
process, and eventually the idea for Elsevier’s Integrated made accessible across the series,both in print and online.
Series was born.
The series centers on the concept of the integration box. Anatomy and Embryology
These boxes occur throughout the text whenever a link to
another basic science is relevant.They’re easy to spot in the
text—with their color-coded headings and logos. Each box
Histology
contains a title for the integration topic and then a brief
summary of the topic.The information is complete in itself—
you probably won’t have to go to any other sources—and you
Neuroscience
have the basic knowledge to use as a foundation if you want
to expand your knowledge of the topic.
You can use this book in two ways. First, as a review book . . .
Biochemistry
When you are using the book for review, the integration
boxes will jog your memory on topics you have already
covered. You’ll be able to reassure yourself that you can
Physiology
identify the link, and you can quickly compare your
knowledge of the topic with the summary in the box.The
integration boxes might highlight gaps in your knowledge,
and then you can use them to determine what topics you Pathology
need to cover in more detail.
Second, the book can be used as a short text to have at hand
Immunology and Microbiology
while you are taking your course . . .
You may come across an integration box that deals with a
topic you haven’t covered yet,and this will ensure that you’re
one step ahead in identifying the links to other subjects Pharmacology
(especially useful if you’re working on a PBL exercise).On a
simpler level,the links in the boxes to other sciences and to
clinical medicine will help you see clearly the relevance of the Genetics
basic science topic you are studying. You may already be
SERIES PREFACE xi
Integration boxes:
Whenever the subject matter can be related to another
science discipline, we’ve put in an Integration Box.
Clearly labeled and color-coded, these boxes include
nuggets of information on topics that require an inte-
Artwork: grated knowledge of the sciences to be fully under-
The books are packed with 4-color illustrations stood. The material in these boxes is complete in itself,
and photographs. When a concept can be and you can use them as a way of reminding yourself
better explained with a picture, we’ve drawn of information you already know and reinforcing key
one.Where possible,the pictures tell a dynamic links between the sciences. Or the boxes may contain
story that will help you remember the informa- information you have not come across before,in which
tion far more effectively than a paragraph of text. case you can use them a springboard for further
research or simply to appreciate the relevance of the
subject matter of the book to the study of medicine.
Text:
Succinct, clearly written text, focusing on
the core information you need to know and
no more. It’s the same level as a carefully
prepared course syllabus or lecture notes.
Physiology: The Regulation 1
of Normal Body Function
Life is not always about homeostasis and balance.The body
CONTENTS
must also adapt to changing requirements, such as during
PHYSIOLOGY exercise. Now the normal resting values are physiologically
LEVELS OF ORGANIZATION inappropriate,since an increase in muscle blood flow,cardiac
COMMON THEMES output, and respiratory rate are necessary to support the
Common Theme 1: Movement Across Barriers increased metabolic demands associated with physical
Common Theme 2: Indicator Dilution activity. Physiology is the study of adaptive adjustments to
Common Theme 3: Feedback Control new challenges.
Common Theme 4: Redundant Control Life is a state of constant change.The physiology of the
Common Theme 5: Integration body alters as we age.An infant is not a small adult, and
Common Theme 6: Graphs, Figures, and Equations
the physiology of an octogenarian is different from that of an
Common Theme 7: Autonomic Nervous System
adolescent. Chapter 16 provides a concise summary of
Common Theme 8: Physiologic Research
physiologic changes in each sex across the life span.
APPLICATION OF COMMON THEMES: PHYSIOLOGY OF
Finally,physiology makes sense.As a student,you need to
THERMOREGULATION
look for the organizing principles in your study of the body.
TOP 5 TAKE-HOME POINTS There are more details and variations than can be memor-
ized. However, if you focus on the organizing principles,
the details fall into a logical sequence. Look for the big
picture first—it is always correct.The details and complex
interactions all support the big picture.
●●● PHYSIOLOGY ●●● LEVELS OF ORGANIZATION
Body function requires a stable internal environment, Medical physiology applies basic principles from chemistry,
described by Claude Bernard as the “milieu intérieur,”in spite physics, and biology to the study of human life.Atoms are
of a changing outside world.Homeostasis,a state of balance, safely in the realm of chemistry. Physiologic study begins
is made possible by negative feedback control systems. with molecules and continues through the interaction of the
Complex neural and hormonal regulatory systems provide organism with its environment (Fig.1-1).
control and integration of body functions. Physicians Physiology is the study of normal body function.Physiol-
describe “normal” values for vital signs—blood pressure of ogy extends to the molecular level, the study of the regu-
120/80mm Hg,pulse of 72 beats/min,respiration rate of 14 lation of the synthesis of biomolecules,and to the subcellular
breaths/min.These “normal” vital sign values reflect a body level, details of the provision of nutrients to support mito-
in homeostatic balance. chondrial metabolism.Physiology includes cellular function,
A stable milieu interior also requires a balance between the study of the role of membrane transport, and describes
intake and output. Intake and production will increase organ function, including the mechanics of pressure genera-
the amount of a compound in the body. Excretion and tion by the heart. Integrative physiology is the study of the
consumption will decrease the amount of a compound in the function of the organism,including the coordinated response
body. Body fluid and electrolyte composition is regulated to digestion and absorption of the nutrients in a meal.
about a set point, which involves both control of ingestion The components of physiology are best approached as organ
and control of excretion.Any changes in ingestion must be systems.This approach allows all aspects of one system,e.g.,
compensated by changes in excretion, or the body is out of the circulatory system, to be discussed, emphasizing their
balance. commonalities and coordinated function.
2 PHYSIOLOGY: THE REGULATION OF NORMAL BODY FUNCTION
Ecology
Physiology
Cell biology
Molecular biology
Chemistry
Ecosystems
Atoms Molecules Cells Tissues Organs Organ Organisms Populations of of different Biosphere
systems one species species
Figure 1-1. Physiology bridges the gap between chemistry and ecology. Physiology incorporates the investigational techniques
from cell biology and molecular biology as well as ecology in order to better understand the function of the human body.
TABLE 1-1. Specific Examples of the Movement Theme
Process Movement Driving Force Modulated by
Flow Flow Pressure gradient Resistance (–)
Diffusion Net flux Concentration gradient Permeability (+)
Surface area (+) Distance (–)
Osmosis Water Particle gradient Barrier particle permeability (–)
Barrier water permeability (+)
Electrochemical Current Ionic gradient Membrane permeability (+)
Capillary filtration Flow Combined pressure and Capillary surface area (+)
oncotic gradient
Transport Secondary active Ion gradient Concentration gradient (–)
+, Modulators enhance the movement; –, modulators impede the movement.
●●●
COMMON THEMES
If any two of the above are known, the third can be
Common Theme 1: Movement Across calculated.This approach is used to determine a physiologic
Barriers volume that cannot be directly measured. For example,
plasma volume can be estimated by adding a known amount
Life is characterized as a nonequilibrium steady state.The of the dye Evans blue, which binds tightly to albumin and
body achieves homeostatic balance—but only by expending remains mostly in the plasma space.After the dye distributes
energy derived from metabolism. Although the processes equally throughout the plasma volume,a plasma sample can
listed below appear different, they share common features. be taken.The observed concentration of the sample, together
Movement results from a driving force and is opposed by with the amount of dye added, allows calculation of the
some aspect of resistance (Table 1-1). plasma volume (Fig.1-2).
Movement against a gradient requires energy. ATP is There are some assumptions in this process that are rarely
ultimately the source of energy used to move compounds met, but the estimations are close enough to be clinically
against a gradient. This is important, because after the useful.The indicator should be distributed only in the volume
gradients are created,the concentration gradients can serve as of interest.There must be sufficient time for the indicator to
a source of energy for other movement (e.g.,secondary active equilibrate so that all areas of the volume have an identical
transport and osmosis). concentration. For estimation of plasma volume with Evans
blue, those assumptions are not met. Some albumin is lost
Common Theme 2: Indicator Dilution for the plasma volume over time, so an early sampling is
desirable.But some plasma spaces have slow exchange rates,
Amount/volume = concentration and Evans blue dye requires additional time to reach those
spaces. In practice, a plasma sample is drawn at 10 or 20
or,rearranged, minutes after indicator injection, and the plasma volume is
calculated with the knowledge that it is an estimate and with
Volume = concentration/amount awareness of the limitations of the technique.
COMMON THEMES 3
Figure 1-2. Indicator dilution allows
calculation of unknown volumes and
Unknown volume Calculate
flows. A, The indicator dilution technique
uses addition of a known quantity of a
marker, and the final concentration of
+ 1 mg dye 1 mg
Sample = 20 mL that marker, to calculate the volume in
concentration 0.05 mg/mL which it was distributed. B, The
0.05 mg/mL procedure is the same even if some of
the marker is already present in the
volume. The only alteration is that the
A final concentration is subtracted from the
starting concentration to determine the
change in concentration caused by
Starting concentration adding the marker. C, An equivalent
0.01 mg/mL Calculate procedure can be used to calculate
flows. If you know the amount of
1 mg O2absorbed across the lungs per
+ 1 mg dye = 20 mL minute, and the change in blood O
Sample final [0.06 - 0.01] concentration that resulted from tha2t
concentration mg/mL
absorption, you can calculate the blood
0.06 mg/mL
flow through the lungs, or the cardiac
output.
B
Lungs
Calculate
250 mL O /min
2
O2 consumed 250 mL O2/min
A-V O gradient 0.20 mL O /min - 0.15 mL O /min
2 2 2
0.15 mL O /min 0.20 mL O /min
2 2
250 mL O /min
2 = 5000 mL
0.05 mL O /min
2
C
TABLE 1-2. Application of Indicator Dilution
Volume or Flow Indicator (The Tracer) The Change
Total body water Iothalamate Iothalamate concentration
Extracellular fluid volume Inulin Inulin concentration
RBC volume 51Cr-labeled RBC 51Cr-labeled RBC concentration
Residual lung volume N N washout
2 2
Cardiac output Temperature (a volume of cold saline) Change in blood temperature over time
Cardiac output Rate of O uptake in the lungs Change in O content in blood flowing through the lungs
2 2
Glomerular filtration rate Inulin Inulin excretion rate
Renal blood flow Para-aminohippuric acid Para-aminohippuric acid excretion rate
In the best case,the only indicator in the system is the new A flow is actually a volume over time, so the indicator
indicator that was added.Alternatively, if the compound is dilution technique can also be used to estimate flows.Instead
already in the system, the term “change in amount” can be of amount, the indicator is expressed as amount per time
substituted for “amount” and “change in concentration” can (Table 1-2).
be substituted for “concentration.”
Flow = amount per time/change in concentration
Change in amount/volume = change in concentration
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