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QUANTITATIVE HUMAN
PHYSIOLOGY

QUANTITATIVE
HUMAN PHYSIOLOGY

AN INTRODUCTION
Joseph Feher
Department of Physiology and Biophysics
Virginia Commonwealth University School of Medicine

AMSTERDAM • BOSTON • HEIDELBERG • LONDON • NEW YORK • OXFORD • PARIS
SAN DIEGO • SAN FRANCISCO • SINGAPORE • SYDNEY • TOKYO
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Notices
Knowledge and best practice in this field are constantly changing. As new research and experience
broaden our understanding, changes in research methods, professional practices, or medical
treatment may become necessary.
Practitioners and researchers must always rely on their own experience and knowledge in
evaluating and using any information, methods, compounds, or experiments described
herein. In using such information or methods they should be mindful of their own
safety and the safety of others, including parties for whom they have a professional responsibility.
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or editors, assume any liability for any injury and/or damage to persons or property
as a matter of products liability, negligence or otherwise, or from any use or
operation of any methods, products, instructions, or ideas contained in the material herein.
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11 12 13

10 9 8 7 6 5 4 3 2 1

Preface
THIS TEXT IS A PHYSIOLOGY TEXT
FIRST, AND A QUANTITATIVE
TEXT SECOND
First and foremost, this text is a physiology text,
designed for students who have never been exposed to
it and who know neither the language nor the concepts
of the subject. The text contains all elements of physiology in nine units: physical and chemical foundations;
cell physiology; excitable tissue physiology; neurophysiology; cardiovascular physiology; respiratory physiology; renal physiology; gastrointestinal physiology; and
endocrinology. The course was designed for a survey
course in quantitative physiology to undergraduate students majoring in Biomedical Engineering at Virginia
Commonwealth University in a two-semester sequence,
roughly in the order in the text.
Secondly, this text aims to be quantitative. Human physiology is all about everything that happens in the body
during its normal operation that makes that operation stable, smooth, and coordinated. Those things that happen
have flows and forces associated with them. In some cases
the flows are rates of secretion or absorption, or movement of dissolved solutes, fluid, or ions from one place to
another. How fast these movements occur is crucial, and
their function cannot be understood fully without a quantitative approach. For some aspects of physiology, there
currently is not enough information to make a detailed
quantitative analysis; or an in-depth analysis is beyond
the scope of this text. In these cases, this text is not very
different from more traditional texts. Where possible, the
text takes an analytical and quantitative approach.

THE TEXT USES MATHEMATICS
EXTENSIVELY
Carl Frederick Gauss famously said, “Mathematics is the
queen of sciences.” The quantitative approach in this text
is not just about assigning values to the controlled parameters, or rate constants to reactions or values of forces
and flows that normally occur; it is about discovering the
relationships between the forces and flows and the reason
controlled parameters are what they are. These relationships cannot be fully understood with words alone. They
require the language of mathematics. Students should be

able to articulate these relationships with words, but this
text demands more. Mathematical statements—equations—are simply logical sentences. You can read an
equation in words. But the mathematical statement uses
an economy of words, and extra words either make it false
or add no new information, like adding zero to both sides
of an equation. Mathematics also has specific rules for the
manipulation of the logical parts of the sentences, so that
rearrangement or combination of equations leads to new
insight. This text uses lots of mathematics at the level of
calculus and elementary differential equations. It is possible to understand the text by using only the final resulting
equations that describe physiologically relevant phenomena, but students want to know where things come from,
not just accept them from some higher authority. The text
aims to convince them that these equations are right and
applicable. Once convinced, application of the equations
follows.
The text does not say what I tell my students about the
applicability of equations in general. I tell my students
in lecture that all of these equations are wrong. They are
wrong in something of the same sense that Newtonian
mechanics is wrong. Relativity and quantum mechanics
supplant Newtonian mechanics (even in the macroscopic world), but Newtonian mechanics will still get
the rocket ship to the moon. So I tell them that these
equations are theoretically wrong but they give satisfactorily correct answers, in much the same way that
Newtonian mechanics still does, even though theoretically incomplete. Fick’s Law of Diffusion depends on
continuum mathematics for an inherently discrete process. But the discreteness is so finely divided that the
distinction is unimportant.

NOT ALL THINGS WORTH KNOWING
ARE WORTH KNOWING WELL
Derivations themselves often bore and lose students. In
many cases, the derivations in this text are placed in separate appendices, at the end of the chapter instead of the
end of the book. Students are encouraged to look at
these, but in my view the derivations are not the point.
Important derivations are in the text, but not all things
worth knowing are worth knowing well, and some are
placed in the appendices. The point is the final equation ix

x

PREFACE

and its application to real-world problems. The derivations develop understanding of how these equations
came to be, and what assumptions were made in their
construction, and what the variables in the equation
mean. These are useful in understanding the limits of
applicability of the final results.

EXAMPLES AND PROBLEM SETS AID IN
QUANTITATIVE UNDERSTANDING
There are several aids in the text to foster a quantitative
and analytical understanding. First, there are some
worked calculations in the text that are set apart in text
boxes as Examples. These aim to show the students how
to apply some of the ideas presented in the text. Second,
there are a total of 17 problem sets scattered throughout
the text. All units have at least one, most have two, and
the cardiovascular section has three. These are meant to
cover about three chapters each, so that a problems set
can be assigned approximately once a week, for three lectures per week. Students have told me that they want a
solution set to the problems to see how they can do
them, but this makes them useless as a graded assignment. There is something to be said for wrestling with
problems and thereby learning how to tackle a difficult
problem.
The problems themselves are generally meant to cover
some new idea or concept that could not be, or was not,
effectively covered in the text itself, and to expand on the
student’s understanding of the material. They are not
merely busy work or “plug and chug” exercises. The alert
student should not merely do the problem, but think
about what the result means. In many cases the problems
are written as a sequence of questions, each of which sets
up the student for further questions or insights. These
illustrate the process necessary for answering a larger question, breaking it up into parts of the answer that must
come first. This method aids the students in thinking
about larger problems: break it down into its simpler components. Some subject matter unfortunately does not lend
itself easily to such problems, but I have attempted to find
problems that students can do. The students in my classes
find the problems challenging. I allow them to work on
them collaboratively because they are meant to be part of
the instruction and less of the evaluation, but the problem
sets are graded and contribute significantly to the final
grades. Such policies are, of course, set at the discretion of
the instructor.

LEARNING OBJECTIVES, SUMMARIES,
AND REVIEW QUESTIONS GUIDE
STUDENT LEARNING
The Learning Objectives are meant as a guide to the
construction of examination questions, either directly or
indirectly. These learning objectives are fairly broad and

together they cover the breadth of physiology. The
chapter summaries review the most important concepts
in one page or less. These devices aid in understanding
by repetition in different words. Instructors, of course,
are free to add or subtract from the list of learning
objectives.

CLINICAL APPLICATIONS PIQUE
INTEREST
Pathological situations often illuminate normal physiology. Clinical Applications are scattered throughout
the text. Because it takes a lot of background material
to understand these clinical applications, Clinical
Applications are less prevalent in the early parts of the
text, which are foundational, than in the latter parts of
the text. There are 50 such Clinical Applications. The
students like them because these Clinical Applications
tell them that there is a reason for learning what might
otherwise appear arcane.

HOW INSTRUCTORS CAN USE
THIS TEXT
This text is meant for anyone with a fairly modest level
of mathematical skill, at the level of the calculus with
elementary differential equations. Students without this
level of training will find this book too difficult. I have
developed this book specifically with undergraduate
Biomedical Engineering students in mind and have
taught this material for 12 years. It is most useful in a
two-semester sequence, and I cover all chapters and all
problem sets in that time. The text would also be useful
for instructors with less time. UNIT 1, for example, covers physical and chemical foundations of physiology
that some instructors assume their students already
know well enough and will not cover. Some of my students take University Physics of Organic Chemistry concurrently, and they find this review helpful. It was not
originally constructed this way: student feedback caused
me to rework the sequence.
Each chapter is intended to be a single lecture, and the
length of the chapter is meant to be readable in a single sitting. There are 77 chapters, so this would be
impossible to cover in a single semester. However,
the depth and breadth of coverage are variables that
can be adjusted. Chapter summaries give the broad
picture of what is happening with fewer of the details.
It is entirely possible to cover the breadth of physiology if the depth is reduced. This can be done by focusing on the chapter summaries and combining lectures,
and possibly omitting some topics. In this regard, the
text is useful similarly to a cafeteria: the instructor is
free to choose those sections of most interest, and to
downplay those of lesser interest. Some instructors
may feel that knowing how to think about problems is
the most important thing, and that the details of the

PR E FACE

physiology are secondary. Such an instructor may want
to focus more on the appendices than on the chapter
matter themselves, and more on the problems and
how to solve them.

ANCILLARY MATERIALS FOR
INSTRUCTORS
For instructors adopting this text for use in a course the
following ancillaries are available: PowerPoint lecture
slides, electronic images from the text, solutions manual
for the problem sets, and additional test questions. Please
visit http://booksite.academicpress.com/9780123821638
and click on the ‘instructor’ tab to register for access.

HOW STUDENTS CAN USE THIS TEXT
A student’s goal ought to be to learn as much physiology as possible within the constraints of available
time. This text is written with considerable detail. The
Learning Objectives and Review Questions set the stage
for the kinds of things you should be able to do, and
the kinds of questions you should be able to answer.
The chapter summaries encapsulate each chapter in an
economy of words and detail. Start with the Learning
Objectives, read the Summary, and then look at the
Review Questions. Then read the chapter and repeat
Learning Objectives, Summary, and Review Questions.
What you cannot answer at that point requires you to
reread the pertinent sections a second time.
The approach to the problem sets is different. The first
job is: find a bright fellow student to work with.
Second, read the question for understanding of what it
is asking. Then ask yourself, what is needed to answer

this question? How can you find out what is needed? If
it is a physical constant, where can you find it? Do you
know a relationship or equation that relates what is
being asked to what is given? Write it down and rearrange it to give the desired answer. Plug and chug what
is given and what else you have looked up to get a
numerical answer. It is very simple in principle but
sometimes very difficult in execution.

ANCILLARY MATERIALS FOR
STUDENTS
Student resources available with this text include a set
of online flashcards, a selection of animations based on
figures in the text, and online quizzes for self-study. Please
visit http://booksite.academicpress.com/9780123821638
and click on the ‘student’ tab for access.

STUDENT FEEDBACK
Students who have completed the course regularly tell
me that it is both one of the most challenging and one of
the most rewarding courses of their undergraduate
career. This is generally the case: what you get out of an
educational enterprise is proportionate to what you put
in. Physiology is an integrative science. There is great satisfaction in understanding how a system works from the
cellular and subcellular level all the way up to the organism level. Human beings do not come with an owner’s
manual. The idea that this text is a first approximation to
an owner’s manual resonates with the students.
Joseph Feher

xi

Acknowledgments
I would like to thank all the reviewers of the proposal
and drafts of this project. Their feedback was very helpful in improving the final version:
Vadim Backman
Trevor Cardinal
Lianne Cartee
Ronald Cechner
Jingjiao Guan
John K. Li
Donald McEachron
Tom Milner
Horst von Recum
Scott Seidman
George Shoane
Brad Sutton

Northwestern University
California Polytechnic State University,
San Luis Obispo
North Carolina State University
Case Western Reserve University
FAMU-FSU
Rutgers University
Drexel University
University of Texas at Austin
Case Western Reserve University
University of Rochester
Rutgers University
University of Illinois at Urbana-Champaign

I would also like to acknowledge the help and support of
my colleagues at the VCU School of Medicine, especially
Clive Baumgarten and Ray Witorsch, for their criticism of
early drafts, and Margaret Biber, who expressed the confidence in publishing this text that kept me going. I would
like to thank George Ford, VCU School of Medicine, who
helped develop the early outlines of the cardiovascular section; Scott Walsh, who provided the basis for some of the
endocrine chapters; and Andy Anderson, who helped critique multiple teaching efforts of mine. I especially
acknowledge the feedback from many years of sophomore
and junior BME students who pointed out errors and difficulties in the material and suggested improvements to
help their learning experience, which is really what this
text is all about. Special thanks go to students Woon
Chow, Yasha Mohajer, Matthew Caldwell, Matthew
Painter, Mary Beth Bird, Richard Boe, Linda Scheider,
William Eggleston, Alex Sherwood, Ross Pollansch, Kate
Proffitt, and Roshan George. Teaching these students and
many more like them, and getting to know them, has
been tremendously rewarding.
I would like to thank the publishing team at Elsevier
including Joe Hayton, Publisher; Steve Merken, Associate

Acquisition Editor; Fiona Geraghty, Editorial Project
Manager; Eric DeCicco, Designer; and especially Renata
Corbani, Senior Project Manager.
Much more indirectly, I wish to thank a long line of scientific mentors who instilled in me the academic integrity
and the desire to be thorough and correct. Included in
this list are Lemuel Wright, and Donald B. McCormick, of
Cornell University, who advised me on my master’s thesis;
Robert Hall of Upstate Medical Center, with whom I
worked for a short but meaningful time and who provided the epiphany for my pursuit of an academic career;
Robert Wasserman, of Cornell University, who first
inspired me to apply mathematics to transport processes;
Norm Briggs, of VCU School of Medicine, who first
thought I would be a good bet for a tenure track position;
Don Mikulecky, who introduced me to many ideas of theoretical biology; and Margaret Biber, who first presented
me with the daunting task of developing a year-long physiology sequence for BME students, with laboratories, that
formed the text.
Although I desire to be thorough and correct, often I
am mistaken. I acknowledge the help of all those listed
above, but reserve to myself the blame for any errors in
the text. If the reader finds any errors of fact or analysis,
I would appreciate them letting me know so that I can
evaluate and correct it.
Lastly, I express my deep appreciation for my wife, Lee,
who put up with innumerable late nights and weekends
with a husband glued to the chair in front of the computer screen. Her support and encouragement made the
work possible. During the writing of the manuscript, the
author’s family suffered the loss of Karen Esterline Feher,
who died in a tragic climbing accident in the New River
Gorge of West Virginia. She left behind a husband and
two young children. The text is dedicated to the memory
of Karen and to the future of her beautiful children.

xiii

The Core Principles of Physiology

Learning Objectives
G
G
G
G
G
G
G
G
G
G
G

Define the discipline of physiology
Describe in general terms how each organ system contributes to homeostasis
Define reductionism and compare it to holism
Describe what is meant by emergent properties
Define homeostasis
List the four Aristotelian causes and define teleology
Define mechanism
Describe how evolution is a cause of human form and
function
Write equations for the conservation of mass and energy
for the body
Give an example of signaling at the organ or cellular level
of organization
List the core principles of physiology

HUMAN PHYSIOLOGY IS THE
INTEGRATED STUDY OF THE NORMAL
FUNCTION OF THE HUMAN BODY
ORGAN SYSTEMS WORK TOGETHER TO
PRODUCE OVERALL BODY BEHAVIOR

1.1

REDUCTIONISM EXPLAINS SOMETHING
ON THE BASIS OF ITS PARTS
The process of explaining something on the basis of its
parts is called reductionism. Thus, the behavior of the
body can be explained by the coordinated behavior of its
component organ systems. In turn, each organ system
can be explained in terms of the behavior of the component organs. In this reduction recursion, the behavior of
the component organs can be explained by their components, the individual cells that make up the organ. These
cells, in turn, can be explained by the behavior of their
component subcellular organelles; the subcellular organelles can be explained by the macrochemicals and
biochemicals that make up these organelles; the biochemicals can be explained by their component atoms; the
atoms can be explained by their component subatomic
particles; the subatomic particles can be explained by fundamental particles. According to this reductionist recursion, we might anticipate that the final explanation of our
own bodies lies in the physics of the fundamental particles. Beyond being impractical, there is a growing realization that it is theoretically impossible to describe complex
and complicated living beings solely on this basis of fundamental physics, because at each step in the process
some information is lost.

PHYSIOLOGICAL SYSTEMS ARE PART OF
A HIERARCHY OF LEVELS OF ORGANIZATION

The human body consists of parts. We consider an
assortment of parts that usually relate to each other in
defined ways to be a system. In physiology a system is
usually considered to be a group of organs that serve
some well-defined function of the body. The parts of
these systems can be described separately, but they work
together to produce the overall system behavior. That is,
the individual behavior of the parts is integrated to
produce overall behavior. The various organ systems
and their functions in the body are summarized in
Table 1.1.1.

The recursion of explanation described above for reductionism involves various levels of complexity in a hierarchical description of living beings, as shown in
Figure 1.1.1 Understanding any particular level entails
relating that level to the one immediately above it and the
one immediately below it. For example, scientists studying
a particular subcellular organelle can be said to have mastered it when they can explain how the function of the
organelle derives from the activities of its parts, the molecules that make it up, and how the organelle’s function is
regulated by and contributes to the function of the cell.

Each of these organ systems is essential to the survival
of the organism, the living human being. It is possible
to survive with a single compromised system—such as
persons with failed kidneys or failed immunological
systems—but these persons could not survive in natural
ecosystems.

REDUCTIONISM IS AN EXPERIMENTAL
PROCEDURE; RECONSTITUTION IS A
THEORETICAL PROCEDURE
The processes used in going “down” or “up” in this
hierarchy are not the same. We use reductionism to

3
© 2012 Elsevier Inc. All rights reserved.

4

QUANTITATIVE HUMAN PHYSIOLOGY

TABLE 1.1.1 Organ Systems of the Body
Organ System

Function

Nervous system/endocrine
system

Sensory input and integration;
command and control

Musculoskeletal system

Support and movement

Cardiovascular system

Transportation between tissues
and environmental interfaces

Gastrointestinal system

Digestion of food and absorption
of nutrients

Respiratory system

Regulation of blood gases and
exchange of gas with the air

Renal system

Regulation of volume and
composition of body fluids

Integumentary system (skin)

Protection from microbial
invasion and water vapor barrier

Reproductive system

Pass life on to the next
generation

Immune system

Removal of microbes and other
foreign materials

Level

Discipline

Universe

Cosmology

Society

Sociology

Body
Explanation
Physiological systems

Function

Physiology

Organs
Cells and cell products

Cell physiology

Subcellular organelles
Biochemistry
Molecules
Chemistry
Atoms
Subatomic particles

High-energy physics

FIGURE 1.1.1 Hierarchical description of physical reality as applied to
physiological systems. We attempt to “explain” something in terms of its
component parts and describe a function for a part in terms of its role
in the “higher” organizational entity.

explain the function of the whole in terms of its parts,
by going “down” in the levels of organization. We
describe the function of the parts at one level by showing how they contribute to the behavior of the larger
level of organization, going “up” in Figure 1.1.1. These
processes are fundamentally different. Reductionism
involves actually breaking the system into its parts and
studying the parts’ behavior in isolation under controlled conditions. For example, we can take a sample
of tissue and disrupt its cells so that the cell membranes
are ruptured. We can then isolate various subcellular
organelles and study their behavior. This procedure
characterizes the behavior of the subcellular organelle.

Knowing the behavior of the individual parts and paying close attention to how these parts are connected, it
is possible to predict system behavior from the parts’
behavior using simulation or other techniques. Because
it is impossible, except in rare and limited cases, to reassemble broken systems (we cannot unscramble the
egg!), we must test our ideas of subcellular function
theoretically.

HOLISM PROPOSES THAT THE BEHAVIOR OF
THE PARTS IS ALTERED BY THEIR CONTEXT IN
THE WHOLE
Holism conveys the idea that the parts of an organism
are interconnected and that each part affects others. The
parts cannot be studied in isolation because important
aspects of their behavior depend solely on their interaction with other parts. Reductionism seems to imply that
the whole is the sum of the parts, whereas holism suggests that the whole is greater than the sum of the parts.
Emergent properties of systems arise from complex
interactions among the parts. Examples of emergent
properties include self-replication. The ability of cells
to form daughter cells is a system property that does
not belong to any one part, but belongs to the entire
system. Consciousness is also an emergent property that
arises from neuronal function, but at a much higher
level of organization.

PHYSIOLOGICAL SYSTEMS OPERATE AT
MULTIPLE LEVELS OF ORGANIZATION
SIMULTANEOUSLY
It should be clear from Figure 1.1.1 that all the levels
of organization simultaneously operate in the living
human being. Processes occur at the molecular, subcellular, cellular, organ and system level simultaneously
and dynamically.

CELLS ARE THE ORGANIZATIONAL
UNIT OF LIFE
THE CELL THEORY IS A UNIFYING PRINCIPLE
OF BIOLOGY
The cell theory states that all biological organisms are
composed of cells; cells are the unit of life and all life
comes from preexisting life. The cell theory is so established today that it forms one of the unifying principles
of biology.
The word cell was first used by Robert Hooke
(1635 1703) when he looked at cork with a simple
microscope and found what appeared to be blocks of
material making up the cork. The term today describes a
microscopic unit of life that separates itself from its surroundings by a thin partition, the cell membrane.
The statement “all life comes from preexisting life” means
that there is no spontaneous generation of life from inanimate materials. Most biologists believe that life did arise
spontaneously, but over a very long period of time. This
statement was made by Virchow (1821 1902) when
he wrote “omnis cellula e cellula”—all cells come from


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