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(Download PDF) Guyton and Hall Textbook of Medical Physiology 14Th Edition John E Hall Ebook Online Full Chapter
(Download PDF) Guyton and Hall Textbook of Medical Physiology 14Th Edition John E Hall Ebook Online Full Chapter
(Download PDF) Guyton and Hall Textbook of Medical Physiology 14Th Edition John E Hall Ebook Online Full Chapter
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14TH EDITION
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Previous editions copyrighted 2016, 2011, 2006, 2000, 1996, 1991, 1986, 1981, 1976, 1971, 1966, 1961, and 1956.
Printed in Canada
To
Arthur C. Guyton
For his imaginative and innovative research
For his dedication to education
For showing us the excitement and joy of physiology
And for serving as an inspirational role model
Preface
The first edition of the Textbook of Medical Physiology was review the basic principles needed for understanding the
written by Arthur C. Guyton almost 65 years ago. Unlike pathophysiology of human disease. We have attempted to
most major medical textbooks, which often have 20 or maintain the same unified organization of the text that
more authors, the first eight editions of the Textbook of has been useful to students in the past and to ensure that
Medical Physiology were written entirely by Dr. Guyton. the book is comprehensive enough that students will con-
He had a gift for communicating complex ideas in a clear tinue to use it during their professional careers.
and interesting manner that made studying physiology Our hope is that the Textbook of Medical Physiology
fun. He wrote the book to help students learn physiology, conveys the majesty of the human body and its many
not to impress his professional colleagues. functions and that it stimulates students to study physiol-
Dr. John Hall worked closely with Dr. Guyton for ogy throughout their careers. Physiology links the basic
almost 30 years and had the privilege of writing parts of sciences and medicine. The great beauty of physiology is
the 9th and 10th editions and of assuming sole responsi- that it integrates the individual functions of all the body’s
bility for completing the subsequent editions. different cells, tissues, and organs into a functional whole,
Dr. Michael Hall has joined in the preparation of the the human body. Indeed, the human body is much more
14th edition of the Textbook of Medical Physiology. He is than the sum of its parts, and life relies upon this total
a physician trained in internal medicine, cardiology, and function, not just on the function of individual body parts
physiology and has brought new insights that have helped in isolation from the others.
greatly to achieve the same goal as for previous editions— This brings us to an important question: How are the
to explain, in language easily understood by students, how separate organs and systems coordinated to maintain
the different cells, tissues, and organs of the human body proper function of the entire body? Fortunately, our bod-
work together to maintain life. ies are endowed with a vast network of feedback controls
This task has been challenging and fun because that achieve the necessary balances without which we
researchers continue to unravel new mysteries of body would be unable to live. Physiologists call this high level
functions. Advances in molecular and cellular physiology of internal bodily control homeostasis. In disease states,
have made it possible to explain some physiology princi- functional balances are often seriously disturbed, and
ples in the terminology of molecular and physical sciences homeostasis is impaired. When even a single disturbance
rather than in merely a series of separate and unexplained reaches a limit, the whole body can no longer live. One of
biological phenomena. However, the molecular events the goals of this text is to emphasize the effectiveness and
that underpin the functions of the body’s cells provide beauty of the body’s homeostasis mechanisms as well as
only a partial explanation of human physiology. The total to present their abnormal functions in disease.
function of the human body requires complex control Another objective is to be as accurate as possible. Sug-
systems that communicate with each other and coordi- gestions and critiques from many students, physiologists,
nate the molecular functions of the body’s cells, tissues, and clinicians throughout the world have checked factual
and organs in health and disease. accuracy as well as balance in the text. Even so, because
The Textbook of Medical Physiology is not a reference of the likelihood of error in sorting through many thou-
book that attempts to provide a compendium of the most sands of bits of information, we issue a further request
recent advances in physiology. It is a book that contin- for all readers to send notations of error or inaccuracy to
ues the tradition of being written for students. It focuses us. Physiologists understand the importance of feedback
on the basic principles of physiology needed to begin a for proper function of the human body; feedback is also
career in the health care professions, such as medicine, important for progressive improvement of a textbook of
dentistry, and nursing, as well as graduate studies in the physiology. To the many persons who have already helped,
biological and health sciences. It should also be useful we express sincere thanks. Your feedback has helped to
to physicians and health care professionals who wish to improve the text.
vii
Preface
A brief explanation is needed about several features most students will learn in more detail in other courses;
of the 14th edition. Although many of the chapters have (2) physiological information of special importance to
been revised to include new principles of physiology and certain fields of clinical medicine; and (3) information
new figures to illustrate these principles, the text length that will be of value to those students who wish to study
has been closely monitored to limit the book’s size so specific physiological mechanisms more deeply.
that it can be used effectively in physiology courses for The ebook version provides links to additional content
medical students and health care professionals. New including video animations and self-assessment questions
references have been chosen primarily for their pre- that can be accessed with computers, smart phones, and
sentation of physiological principles, for the quality of electronic tablets. For additional self-assessment beyond
their own references, and for their easy accessibility. these textbook supplements, the reader may consider
The selected bibliography at the end of the chapters lists using a copy of Guyton and Hall Physiology Review, which
mainly review papers from recently published scientific includes more than 1000 practice questions referenced to
journals that can be freely accessed from the PubMed site the textbook. We hope that these ancillary materials will
at https://www.ncbi.nlm.nih.gov/pubmed/. Use of these assist readers in testing their understanding of basic prin-
references, as well as cross-references from them, pro- ciples of physiology.
vides much more extensive coverage of the entire field of We express sincere thanks to many persons who have
physiology. helped to prepare this book, including our colleagues in
Our effort to be as concise as possible has, unfortu- the Department of Physiology and Biophysics at the Uni-
nately, necessitated a more simplified and dogmatic versity of Mississippi Medical Center who provided valu-
presentation of many physiological principles than we able suggestions. The members of our faculty and a brief
normally would have desired. However, the bibliogra- description of the research and educational activities of the
phy can be used to learn more about the controversies department can be found at http://physiology.umc.edu/.
and unanswered questions that remain in understanding We are especially grateful to Stephanie Lucas for excellent
the complex functions of the human body in health and assistance and to James Perkins for excellent illustrations.
disease. We also thank Elyse O’Grady, Jennifer Shreiner, Grace
Another feature of the book is that the print is set Onderlinde, Rebecca Gruliow, and the entire Elsevier
in two sizes. The material in large print constitutes the team for continued editorial and production excellence.
fundamental physiological information that students Finally, we thank the many readers who continue to
will require in virtually all of their medical studies. The help us improve the Textbook of Medical Physiology. We
material in small print and highlighted with a pale lav- hope that you enjoy the current edition and find it even
ender background (or identified by beginning and ending more useful than previous editions.
double gray arrowheads in the ebook version) is of several
different kinds: (1) anatomic, chemical, and other infor- John E. Hall
mation that is needed for immediate discussion but that Michael E. Hall
viii
CHAPTER 1
UNIT I
and Control of the “Internal Environment”
Physiology is the science that seeks to explain the physi- Each type of cell is specially adapted to perform one
cal and chemical mechanisms that are responsible for the or a few particular functions. For example, the red blood
origin, development, and progression of life. Each type cells, numbering about 25 trillion in each person, trans-
of life, from the simplest virus to the largest tree or the port oxygen from the lungs to the tissues. Although the
complicated human being, has its own functional char- red blood cells are the most abundant of any single type of
acteristics. Therefore, the vast field of physiology can be cell in the body, there are also trillions of additional cells
divided into viral physiology, bacterial physiology, cellular of other types that perform functions different from those
physiology, plant physiology, invertebrate physiology, ver- of the red blood cell. The entire body, then, contains about
tebrate physiology, mammalian physiology, human physi- 35 to 40 trillion human cells.
ology, and many more subdivisions. The many cells of the body often differ markedly from
one another but all have certain basic characteristics that
Human Physiology. The science of human physiology are alike. For example, oxygen reacts with carbohydrate,
attempts to explain the specific characteristics and mech- fat, and protein to release the energy required for all cells
anisms of the human body that make it a living being. The to function. Furthermore, the general chemical mecha-
fact that we remain alive is the result of complex control nisms for changing nutrients into energy are basically
systems. Hunger makes us seek food, and fear makes us the same in all cells, and all cells deliver products of their
seek refuge. Sensations of cold make us look for warmth. chemical reactions into the surrounding fluids.
Other forces cause us to seek fellowship and to reproduce. Almost all cells also have the ability to reproduce addi-
The fact that we are sensing, feeling, and knowledgeable tional cells of their own type. Fortunately, when cells of a
beings is part of this automatic sequence of life; these spe- particular type are destroyed, the remaining cells of this type
cial attributes allow us to exist under widely varying con- usually generate new cells until the supply is replenished.
ditions that otherwise would make life impossible.
Human physiology links the basic sciences with medicine Microorganisms Living in the Body Outnumber Hu-
and integrates multiple functions of the cells, tissues, and man Cells. In addition to human cells, trillions of microbes
organs into the functions of the living human being. This inte- inhabit the body, living on the skin and in the mouth, gut,
gration requires communication and coordination by a vast and nose. The gastrointestinal tract, for example, normally
array of control systems that operate at every level—from the contains a complex and dynamic population of 400 to 1000
genes that program synthesis of molecules to the complex species of microorganisms that outnumber our human
nervous and hormonal systems that coordinate functions of cells. Communities of microorganisms that inhabit the
cells, tissues, and organs throughout the body. Thus, the coor- body, often called microbiota, can cause diseases, but most
dinated functions of the human body are much more than the of the time they live in harmony with their human hosts
sum of its parts, and life in health, as well as in disease states, and provide vital functions that are essential for survival of
relies on this total function. Although the main focus of this their hosts. Although the importance of gut microbiota in
book is on normal human physiology, we will also discuss, the digestion of foodstuffs is widely recognized, additional
to some extent, pathophysiology, which is the study of disor- roles for the body’s microbes in nutrition, immunity, and
dered body function and the basis for clinical medicine. other functions are just beginning to be appreciated and
represent an intensive area of biomedical research.
CELLS ARE THE LIVING UNITS OF THE
BODY EXTRACELLULAR FLUID—THE
“INTERNAL ENVIRONMENT”
The basic living unit of the body is the cell. Each tissue or
organ is an aggregate of many different cells held together About 50% to 70% of the adult human body is fluid, mainly
by intercellular supporting structures. a water solution of ions and other substances. Although
3
UNIT I Introduction to Physiology: The Cell and General Physiology
most of this fluid is inside the cells and is called intracellu- regulated, normally varying only a few millimoles per liter,
lar fluid, about one-third is in the spaces outside the cells even with large changes in sodium intake, but these varia-
and is called extracellular fluid. This extracellular fluid is tions of sodium concentration are at least 1 million times
in constant motion throughout the body. It is transported greater than for hydrogen ions.
rapidly in the circulating blood and then mixed between Powerful control systems exist for maintaining concen-
the blood and tissue fluids by diffusion through the capil- trations of sodium and hydrogen ions, as well as for most
lary walls. of the other ions, nutrients, and substances in the body at
In the extracellular fluid are the ions and nutrients levels that permit the cells, tissues, and organs to perform
needed by the cells to maintain life. Thus, all cells live in their normal functions, despite wide environmental varia-
essentially the same environment—the extracellular fluid. tions and challenges from injury and diseases.
For this reason, the extracellular fluid is also called the Much of this text is concerned with how each organ or
internal environment of the body, or the milieu intérieur, a tissue contributes to homeostasis. Normal body functions
term introduced by the great 19th-century French physi- require integrated actions of cells, tissues, organs, and
ologist Claude Bernard (1813–1878). multiple nervous, hormonal, and local control systems
Cells are capable of living and performing their spe- that together contribute to homeostasis and good health.
cial functions as long as the proper concentrations of
oxygen, glucose, different ions, amino acids, fatty sub- Homeostatic Compensations in Diseases. Disease is
stances, and other constituents are available in this inter- often considered to be a state of disrupted homeostasis.
nal environment. However, even in the presence of disease, homeostatic
mechanisms continue to operate and maintain vital func-
Differences in Extracellular and Intracellular Fluids. tions through multiple compensations. In some cases,
The extracellular fluid contains large amounts of sodium, these compensations may lead to major deviations of the
chloride, and bicarbonate ions plus nutrients for the cells, body’s functions from the normal range, making it diffi-
such as oxygen, glucose, fatty acids, and amino acids. It cult to distinguish the primary cause of the disease from
also contains carbon dioxide that is being transported the compensatory responses. For example, diseases that
from the cells to the lungs to be excreted, plus other cel- impair the kidneys’ ability to excrete salt and water may
lular waste products that are being transported to the kid- lead to high blood pressure, which initially helps return
neys for excretion. excretion to normal so that a balance between intake and
The intracellular fluid contains large amounts of potas- renal excretion can be maintained. This balance is needed
sium, magnesium, and phosphate ions instead of the to maintain life, but, over long periods of time, the high
sodium and chloride ions found in the extracellular fluid. blood pressure can damage various organs, including the
Special mechanisms for transporting ions through the cell kidneys, causing even greater increases in blood pressure
membranes maintain the ion concentration differences and more renal damage. Thus, homeostatic compensa-
between the extracellular and intracellular fluids. These tions that ensue after injury, disease, or major environ-
transport processes are discussed in Chapter 4. mental challenges to the body may represent trade-offs
that are necessary to maintain vital body functions but,
in the long term, contribute to additional abnormalities
HOMEOSTASIS—MAINTENANCE OF
of body function. The discipline of pathophysiology seeks
A NEARLY CONSTANT INTERNAL
to explain how the various physiological processes are al-
ENVIRONMENT
tered in diseases or injury.
In 1929, the American physiologist Walter Cannon This chapter outlines the different functional systems
(1871–1945) coined the term homeostasis to describe the of the body and their contributions to homeostasis. We
maintenance of nearly constant conditions in the internal then briefly discuss the basic theory of the body’s control
environment. Essentially, all organs and tissues of the body systems that allow the functional systems to operate in
perform functions that help maintain these relatively con- support of one another.
stant conditions. For example, the lungs provide oxygen
to the extracellular fluid to replenish the oxygen used by
EXTRACELLULAR FLUID TRANSPORT
the cells, the kidneys maintain constant ion concentra-
AND MIXING SYSTEM—THE BLOOD
tions, and the gastrointestinal system provides nutrients
CIRCULATORY SYSTEM
while eliminating waste from the body.
The various ions, nutrients, waste products, and other Extracellular fluid is transported through the body in two
constituents of the body are normally regulated within a stages. The first stage is movement of blood through the
range of values, rather than at fixed values. For some of the body in the blood vessels. The second is movement of
body’s constituents, this range is extremely small. Varia- fluid between the blood capillaries and the intercellular
tions in the blood hydrogen ion concentration, for exam- spaces between the tissue cells.
ple, are normally less than 5 nanomoles/L (0.000000005 Figure 1-1 shows the overall circulation of blood. All the
moles/L). The blood sodium concentration is also tightly blood in the circulation traverses the entire circuit an average
4
Chapter 1 Functional Organization of the Human Body and Control of the “Internal Environment”
Lungs Arteriole
UNIT I
CO2 O2
Right Left
heart heart
pump pump
Venule
Gut
Nutrition That is, the fluid and dissolved molecules are continually
and moving and bouncing in all directions in the plasma and
excretion
fluid in the intercellular spaces, as well as through capil-
lary pores. Few cells are located more than 50 microm-
eters from a capillary, which ensures diffusion of almost
any substance from the capillary to the cell within a few
Kidneys
seconds. Thus, the extracellular fluid everywhere in the
body—both that of the plasma and that of the interstitial
fluid—is continually being mixed, thereby maintaining
homogeneity of extracellular fluid throughout the body.
5
UNIT I Introduction to Physiology: The Cell and General Physiology
Musculoskeletal System. How does the musculoskeletal performs in response to the sensations. Appropriate sig-
system contribute to homeostasis? The answer is obvious nals are then transmitted through the motor output por-
and simple. Were it not for the muscles, the body could tion of the nervous system to carry out one’s desires.
not move to obtain the foods required for nutrition. The An important segment of the nervous system is called
musculoskeletal system also provides motility for protec- the autonomic system. It operates at a subconscious level
tion against adverse surroundings, without which the en- and controls many functions of internal organs, including
tire body, along with its homeostatic mechanisms, could the level of pumping activity by the heart, movements of
be destroyed. the gastrointestinal tract, and secretion by many of the
body’s glands.
REMOVAL OF METABOLIC END PRODUCTS
Hormone Systems. Located in the body are endocrine
Removal of Carbon Dioxide by the Lungs. At the same glands, organs and tissues that secrete chemical sub-
time that blood picks up oxygen in the lungs, carbon di- stances called hormones. Hormones are transported in
oxide is released from the blood into lung alveoli; the res- the extracellular fluid to other parts of the body to help
piratory movement of air into and out of the lungs carries regulate cellular function. For example, thyroid hormone
carbon dioxide to the atmosphere. Carbon dioxide is the increases the rates of most chemical reactions in all cells,
most abundant of all the metabolism products. thus helping set the tempo of bodily activity. Insulin con-
trols glucose metabolism, adrenocortical hormones con-
Kidneys. Passage of blood through the kidneys removes trol sodium and potassium ions and protein metabolism,
most of the other substances from the plasma besides car- and parathyroid hormone controls bone calcium and
bon dioxide that are not needed by cells. These substanc- phosphate. Thus, the hormones provide a regulatory sys-
es include different end products of cellular metabolism, tem that complements the nervous system. The nervous
such as urea and uric acid; they also include excesses of system controls many muscular and secretory activities
ions and water from the food that accumulate in the ex- of the body, whereas the hormonal system regulates many
tracellular fluid. metabolic functions. The nervous and hormonal systems
The kidneys perform their function first by filtering normally work together in a coordinated manner to con-
large quantities of plasma through the glomerular capil- trol essentially all the organ systems of the body.
laries into the tubules and then reabsorbing into the blood
substances needed by the body, such as glucose, amino
PROTECTION OF THE BODY
acids, appropriate amounts of water, and many of the
ions. Most of the other substances that are not needed Immune System. The immune system includes white
by the body, especially metabolic waste products such blood cells, tissue cells derived from white blood cells, the
as urea and creatinine, are reabsorbed poorly and pass thymus, lymph nodes, and lymph vessels that protect the
through the renal tubules into the urine. body from pathogens such as bacteria, viruses, parasites,
and fungi. The immune system provides a mechanism for
Gastrointestinal Tract. Undigested material that enters the body to carry out the following: (1) distinguish its own
the gastrointestinal tract and some waste products of me- cells from harmful foreign cells and substances; and (2)
tabolism are eliminated in the feces. destroy the invader by phagocytosis or by producing sensi-
tized lymphocytes or specialized proteins (e.g., antibodies)
Liver. Among the many functions of the liver is detoxifi- that destroy or neutralize the invader.
cation or removal of ingested drugs and chemicals. The
liver secretes many of these wastes into the bile to be Integumentary System. The skin and its various ap-
eventually eliminated in the feces. pendages (including the hair, nails, glands, and other
structures) cover, cushion, and protect the deeper tissues
and organs of the body and generally provide a bound-
REGULATION OF BODY FUNCTIONS
ary between the body’s internal environment and the out-
Nervous System. The nervous system is composed of side world. The integumentary system is also important
three major parts—the sensory input portion, the central for temperature regulation and excretion of wastes, and
nervous system (or integrative portion), and the motor out- it provides a sensory interface between the body and the
put portion. Sensory receptors detect the state of the body external environment. The skin generally comprises about
and its surroundings. For example, receptors in the skin 12% to 15% of body weight.
alert us whenever an object touches the skin. The eyes
are sensory organs that give us a visual image of the sur-
REPRODUCTION
rounding area. The ears are also sensory organs. The cen-
tral nervous system is composed of the brain and spinal Although reproduction is sometimes not considered a
cord. The brain stores information, generates thoughts, homeostatic function, it helps maintain homeostasis by
creates ambition, and determines reactions that the body generating new beings to take the place of those that are
6
Chapter 1 Functional Organization of the Human Body and Control of the “Internal Environment”
dying. This may sound like a permissive usage of the term Reference
homeostasis, but it illustrates that in the final analysis, set point
essentially all body structures are organized to help main- Error signal Effectors
tain the automaticity and continuity of life. Brain medulla
Sympathetic Blood vessels
Vasomotor
nervous system Heart
centers
CONTROL SYSTEMS OF THE BODY
UNIT I
The human body has thousands of control systems. Some Feedback signal
of the most intricate of these systems are genetic control
systems that operate in all cells to help regulate intracel- Baroreceptors Arterial
lular and extracellular functions. This subject is discussed pressure
in Chapter 3. Sensor Controlled variable
Many other control systems operate within the organs Figure 1-3. Negative feedback control of arterial pressure by the ar-
to regulate functions of the individual parts of the organs; terial baroreceptors. Signals from the sensor (baroreceptors) are sent
others operate throughout the entire body to control the to the medulla of the brain, where they are compared with a refer-
interrelationships between the organs. For example, the ence set point. When arterial pressure increases above normal, this
abnormal pressure increases nerve impulses from the baroreceptors
respiratory system, operating in association with the
to the medulla of the brain, where the input signals are compared
nervous system, regulates the concentration of carbon with the set point, generating an error signal that leads to decreased
dioxide in the extracellular fluid. The liver and pancreas sympathetic nervous system activity. Decreased sympathetic activity
control glucose concentration in the extracellular fluid, causes dilation of blood vessels and reduced pumping activity of the
and the kidneys regulate concentrations of hydrogen, heart, which return arterial pressure toward normal.
sodium, potassium, phosphate, and other ions in the
extracellular fluid. Regulation of Arterial Blood Pressure. Several systems
contribute to arterial blood pressure regulation. One of
these, the baroreceptor system, is an excellent example of
EXAMPLES OF CONTROL MECHANISMS
a rapidly acting control mechanism (Figure 1-3). In the
Regulation of Oxygen and Carbon Dioxide Concen- walls of the bifurcation region of the carotid arteries in
trations in the Extracellular Fluid. Because oxygen is the neck, and also in the arch of the aorta in the thorax,
one of the major substances required for chemical reac- are many nerve receptors called baroreceptors that are
tions in cells, the body has a special control mechanism to stimulated by stretch of the arterial wall. When arterial
maintain an almost exact and constant oxygen concentra- pressure rises too high, the baroreceptors send barrages
tion in the extracellular fluid. This mechanism depends of nerve impulses to the medulla of the brain. Here, these
principally on the chemical characteristics of hemoglobin, impulses inhibit the vasomotor center, which in turn de-
which is present in red blood cells. Hemoglobin com- creases the number of impulses transmitted from the
bines with oxygen as the blood passes through the lungs. vasomotor center through the sympathetic nervous sys-
Then, as the blood passes through the tissue capillaries, tem to the heart and blood vessels. Lack of these impulses
hemoglobin, because of its own strong chemical affinity causes diminished pumping activity by the heart and dila-
for oxygen, does not release oxygen into the tissue fluid tion of peripheral blood vessels, allowing increased blood
if too much oxygen is already there. However, if oxygen flow through the vessels. Both these effects decrease the
concentration in the tissue fluid is too low, sufficient oxy- arterial pressure, moving it back toward normal.
gen is released to re-establish an adequate concentration. Conversely, a decrease in arterial pressure below nor-
Thus, regulation of oxygen concentration in the tissues mal relaxes the stretch receptors, allowing the vasomotor
relies to a great extent on the chemical characteristics of center to become more active than usual, thereby causing
hemoglobin. This regulation is called the oxygen-buffering vasoconstriction and increased heart pumping. The initial
function of hemoglobin. decrease in arterial pressure thus initiates negative feed-
Carbon dioxide concentration in the extracellular fluid back mechanisms that raise arterial pressure back toward
is regulated in a much different way. Carbon dioxide is a normal.
major end product of oxidative reactions in cells. If all the
carbon dioxide formed in the cells continued to accumu- Normal Ranges and Physical
late in the tissue fluids, all energy-giving reactions of the Characteristics of Important Extracellular
cells would cease. Fortunately, a higher than normal car- Fluid Constituents
bon dioxide concentration in the blood excites the respira- Table 1-1 lists some important constituents and physical
tory center, causing a person to breathe rapidly and deeply. characteristics of extracellular fluid, along with their nor-
This deep rapid breathing increases expiration of carbon mal values, normal ranges, and maximum limits without
dioxide and, therefore, removes excess carbon dioxide causing death. Note the narrowness of the normal range
from the blood and tissue fluids. This process continues for each one. Values outside these ranges are often caused
until the concentration returns to normal. by illness, injury, or major environmental challenges.
7
UNIT I Introduction to Physiology: The Cell and General Physiology
Most important are the limits beyond which abnor- the extracellular fluid carbon dioxide concentration
malities can cause death. For example, an increase in the because the lungs expire greater amounts of carbon diox-
body temperature of only 11°F (7°C) above normal can ide from the body. Thus, the high concentration of carbon
lead to a vicious cycle of increasing cellular metabolism dioxide initiates events that decrease the concentration
that destroys the cells. Note also the narrow range for toward normal, which is negative to the initiating stimu-
acid–base balance in the body, with a normal pH value lus. Conversely, a carbon dioxide concentration that falls
of 7.4 and lethal values only about 0.5 on either side of too low results in feedback to increase the concentration.
normal. Whenever the potassium ion concentration This response is also negative to the initiating stimulus.
decreases to less than one-third normal, paralysis may In the arterial pressure–regulating mechanisms, a high
result from the inability of the nerves to carry signals. pressure causes a series of reactions that promote reduced
Alternatively, if potassium ion concentration increases pressure, or a low pressure causes a series of reactions that
to two or more times normal, the heart muscle is likely promote increased pressure. In both cases, these effects
to be severely depressed. Also, when the calcium ion are negative with respect to the initiating stimulus.
concentration falls below about one-half normal, a per- Therefore, in general, if some factor becomes exces-
son is likely to experience tetanic contraction of muscles sive or deficient, a control system initiates negative feed-
throughout the body because of the spontaneous genera- back, which consists of a series of changes that return
tion of excess nerve impulses in peripheral nerves. When the factor toward a certain mean value, thus maintaining
the glucose concentration falls below one-half normal, a homeostasis.
person frequently exhibits extreme mental irritability and
sometimes even has convulsions. Gain of a Control System. The degree of effectiveness
These examples should give one an appreciation for with which a control system maintains constant condi-
the necessity of the vast numbers of control systems that tions is determined by the gain of negative feedback.
keep the body operating in health. In the absence of any For example, let us assume that a large volume of blood
one of these controls, serious body malfunction or death is transfused into a person whose baroreceptor pressure
can result. control system is not functioning, and the arterial pres-
sure rises from the normal level of 100 mm Hg up to 175
mm Hg. Then, let us assume that the same volume of
CHARACTERISTICS OF CONTROL SYSTEMS
blood is injected into the same person when the barore-
The aforementioned examples of homeostatic control ceptor system is functioning, and this time the pressure
mechanisms are only a few of the many thousands in the increases by only 25 mm Hg. Thus, the feedback control
body, all of which have some common characteristics, as system has caused a “correction” of −50 mm Hg, from
explained in this section. 175 mm Hg to 125 mm Hg. There remains an increase in
pressure of +25 mm Hg, called the “error,” which means
Negative Feedback Nature of Most that the control system is not 100% effective in preventing
Control Systems change. The gain of the system is then calculated by using
Most control systems of the body act by negative feed- the following formula:
back, which can be explained by reviewing some of the Correction
Gain =
homeostatic control systems mentioned previously. In Error
the regulation of carbon dioxide concentration, a high Thus, in the baroreceptor system example, the correc-
concentration of carbon dioxide in the extracellular fluid tion is −50 mm Hg, and the error persisting is +25 mm Hg.
increases pulmonary ventilation. This, in turn, decreases Therefore, the gain of the person’s baroreceptor system
8
Chapter 1 Functional Organization of the Human Body and Control of the “Internal Environment”
UNIT I
and the person can recover, as shown by the dashed curve
Bled 2 liters of Figure 1-4.
2
9
UNIT I Introduction to Physiology: The Cell and General Physiology
More Complex Types of Control for understanding normal physiology as well as for treat-
Systems—Feed-Forward and Adaptive ment of diseases.
Control Age-related and ethnic or racial differences in physiol-
Later in this text, when we study the nervous system, we ogy also have important influences on body composition,
shall see that this system contains great numbers of inter- physiological control systems, and pathophysiology of
connected control mechanisms. Some are simple feedback diseases. For example, in a lean young male the total body
systems similar to those already discussed. Many are not. water is about 60% of body weight. As a person grows and
For example, some movements of the body occur so rap- ages, this percentage gradually decreases, partly because
idly that there is not enough time for nerve signals to travel aging is usually associated with declining skeletal muscle
from the peripheral parts of the body all the way to the mass and increasing fat mass. Aging may also cause a
brain and then back to the periphery again to control the decline in the function and effectiveness of some organs
movement. Therefore, the brain uses a mechanism called and physiological control systems.
feed-forward control to cause required muscle contrac- These sources of physiological variability—sex differ-
tions. Sensory nerve signals from the moving parts apprise ences, aging, ethnic, and racial—are complex but impor-
the brain about whether the movement is performed cor- tant considerations when discussing normal physiology
rectly. If not, the brain corrects the feed-forward signals and the pathophysiology of diseases.
that it sends to the muscles the next time the movement
is required. Then, if still further correction is necessary,
SUMMARY—AUTOMATICITY OF THE
this process will be performed again for subsequent move-
BODY
ments. This process is called adaptive control. Adaptive
control, in a sense, is delayed negative feedback. The main purpose of this chapter has been to discuss
Thus, one can see how complex the feedback control briefly the overall organization of the body and the means
systems of the body can be. A person’s life depends on all whereby the different parts of the body operate in har-
of them. Therefore, much of this text is devoted to dis- mony. To summarize, the body is actually a social order of
cussing these life-giving mechanisms. about 35 to 40 trillion cells organized into different func-
tional structures, some of which are called organs. Each
functional structure contributes its share to the mainte-
PHYSIOLOGICAL VARIABILITY
nance of homeostasis in the extracellular fluid, which is
Although some physiological variables, such as plasma called the internal environment. As long as normal con-
concentrations of potassium, calcium, and hydrogen ditions are maintained in this internal environment, the
ions, are tightly regulated, others, such as body weight cells of the body continue to live and function properly.
and adiposity, show wide variation among different indi- Each cell benefits from homeostasis and, in turn, each
viduals and even in the same individual at different stages cell contributes its share toward the maintenance of
of life. Blood pressure, cardiac pumping, metabolic rate, homeostasis. This reciprocal interplay provides continu-
nervous system activity, hormones, and other physi- ous automaticity of the body until one or more functional
ological variables change throughout the day as we move systems lose their ability to contribute their share of func-
about and engage in normal daily activities. Therefore, tion. When this happens, all the cells of the body suffer.
when we discuss “normal” values, it is with the under- Extreme dysfunction leads to death; moderate dysfunc-
standing that many of the body’s control systems are con- tion leads to sickness.
stantly reacting to perturbations, and that variability may
exist among different individuals, depending on body
weight and height, diet, age, sex, environment, genetics, Bibliography
and other factors. Adolph EF: Physiological adaptations: hypertrophies and superfunc-
For simplicity, discussion of physiological functions tions. Am Sci 60:608, 1972.
often focuses on the “average” 70-kg young, lean male. Bentsen MA, Mirzadeh Z, Schwartz MW: Revisiting how the brain
senses glucose-and why. Cell Metab 29:11, 2019.
However, the American male no longer weighs an aver-
Bernard C: Lectures on the Phenomena of Life Common to Animals
age of 70 kg; he now weighs over 88 kg, and the average and Plants. Springfield, IL: Charles C Thomas, 1974.
American female weighs over 76 kg, more than the aver- Cannon WB: Organization for physiological homeostasis. Physiol Rev
age man in the 1960s. Body weight has also increased sub- 9:399, 1929.
stantially in most other industrialized countries during Chien S: Mechanotransduction and endothelial cell homeostasis: the
wisdom of the cell. Am J Physiol Heart Circ Physiol 292:H1209, 2007.
the past 40 to 50 years.
DiBona GF: Physiology in perspective: the wisdom of the body. Neu-
Except for reproductive and hormonal functions, ral control of the kidney. Am J Physiol Regul Integr Comp Physiol
many other physiological functions and normal values 289:R633, 2005.
are often discussed in terms of male physiology. However, Dickinson MH, Farley CT, Full RJ, et al: How animals move: an integra-
there are clearly differences in male and female physiology tive view. Science 288:100, 2000.
Eckel-Mahan K, Sassone-Corsi P: Metabolism and the circadian clock
beyond the obvious differences that relate to reproduc-
converge. Physiol Rev 93:107, 2013.
tion. These differences can have important consequences
10
Chapter 1 Functional Organization of the Human Body and Control of the “Internal Environment”
Guyton AC: Arterial Pressure and Hypertension. Philadelphia: WB Nishida AH, Ochman H: A great-ape view of the gut microbiome. Nat
Saunders, 1980. Rev Genet 20:185, 2019.
Herman MA, Kahn BB: Glucose transport and sensing in the mainte- Orgel LE: The origin of life on the earth. Sci Am 271:76,1994.
nance of glucose homeostasis and metabolic harmony. J Clin Invest Reardon C, Murray K, Lomax AE: Neuroimmune communication in
116:1767, 2006. health and disease. Physiol Rev 98:2287-2316, 2018.
Kabashima K, Honda T, Ginhoux F, Egawa G: The immunological Sender R, Fuchs S, Milo R: Revised estimates for the number of human
anatomy of the skin. Nat Rev Immunol 19:19, 2019. and bacteria cells in the body. PLoS Biol 14(8):e1002533, 2016.
UNIT I
Khramtsova EA, Davis LK, Stranger BE: The role of sex in the genom- Smith HW: From Fish to Philosopher. New York: Doubleday, 1961.
ics of human complex traits. Nat Rev Genet 20: 173, 2019.
Kim KS, Seeley RJ, Sandoval DA: Signalling from the periphery to the
brain that regulates energy homeostasis. Nat Rev Neurosci 19:185,
2018.
11
CHAPTER 2
UNIT I
The Cell and Its Functions
Each of the trillions of cells in a human being is a living 20% of the cell mass. These proteins can be divided into
structure that can survive for months or years, provided two types, structural proteins and functional proteins.
its surrounding fluids contain appropriate nutrients. Cells Structural proteins are present in the cell mainly in the
are the building blocks of the body, providing structure form of long filaments that are polymers of many indi-
for the body’s tissues and organs, ingesting nutrients and vidual protein molecules. A prominent use of such intra-
converting them to energy, and performing specialized cellular filaments is to form microtubules, which provide
functions. Cells also contain the body’s hereditary code, the cytoskeletons of cellular organelles such as cilia, nerve
which controls the substances synthesized by the cells axons, the mitotic spindles of cells undergoing mitosis,
and permits them to make copies of themselves. and a tangled mass of thin filamentous tubules that hold
the parts of the cytoplasm and nucleoplasm together in
their respective compartments. Fibrillar proteins are
ORGANIZATION OF THE CELL
found outside the cell, especially in the collagen and elas-
A schematic drawing of a typical cell, as seen by the light tin fibers of connective tissue, and elsewhere, such as in
microscope, is shown in Figure 2-1. Its two major parts blood vessel walls, tendons, and ligaments.
are the nucleus and the cytoplasm. The nucleus is sepa- The functional proteins are usually composed of com-
rated from the cytoplasm by a nuclear membrane, and the binations of a few molecules in tubular-globular form.
cytoplasm is separated from the surrounding fluids by a These proteins are mainly the enzymes of the cell and, in
cell membrane, also called the plasma membrane. contrast to the fibrillar proteins, are often mobile in the
The different substances that make up the cell are cell fluid. Also, many of them are adherent to membra-
collectively called protoplasm. Protoplasm is composed nous structures inside the cell and catalyze specific intra-
mainly of five basic substances—water, electrolytes, pro- cellular chemical reactions. For example, the chemical
teins, lipids, and carbohydrates. reactions that split glucose into its component parts and
then combine these with oxygen to form carbon diox-
Water. Most cells, except for fat cells, are comprised ide and water while simultaneously providing energy for
mainly of water in a concentration of 70% to 85%. Many cellular function are all catalyzed by a series of protein
cellular chemicals are dissolved in the water. Others are enzymes.
suspended in the water as solid particulates. Chemical re-
actions take place among the dissolved chemicals or at the Lipids. Lipids are several types of substances that are
surfaces of the suspended particles or membranes. grouped together because of their common property of
being soluble in fat solvents. Especially important lipids
Ions. Important ions in the cell include potassium, magne-
sium, phosphate, sulfate, bicarbonate, and smaller quanti-
ties of sodium, chloride, and calcium. These ions are all Cell
discussed in Chapter 4, which considers the interrelations membrane
between the intracellular and extracellular fluids.
The ions provide inorganic chemicals for cellular reac- Cytoplasm
tions and are necessary for the operation of some cellular Nucleolus
control mechanisms. For example, ions acting at the cell Nucleoplasm
Nuclear
membrane are required for the transmission of electro- membrane Nucleus
chemical impulses in nerve and muscle fibers.
13
UNIT I Introduction to Physiology: The Cell and General Physiology
Centrioles
Secretory
granule
Golgi
apparatus
Microtubules
Nuclear
membrane Cell
membrane
Nucleolus
Glycogen
Ribosomes
Lysosome
are phospholipids and cholesterol, which together consti- that it is readily available to the cell. Also, a small amount
tute only about 2% of the total cell mass. Phospholipids of carbohydrate is stored in cells as glycogen, an insoluble
and cholesterol are mainly insoluble in water and there- polymer of glucose that can be depolymerized and used
fore are used to form the cell membrane and intracellular rapidly to supply the cell’s energy needs.
membrane barriers that separate the different cell com-
partments.
CELL STRUCTURE
In addition to phospholipids and cholesterol, some
cells contain large quantities of triglycerides, also called The cell contains highly organized physical structures
neutral fats. In fat cells (adipocytes), triglycerides often called intracellular organelles, which are critical for cell
account for as much as 95% of the cell mass. The fat stored function. For example, without one of the organelles, the
in these cells represents the body’s main storehouse of mitochondria, more than 95% of the cell’s energy release
energy-giving nutrients that can later be used to provide from nutrients would cease immediately. The most
energy wherever it is needed in the body. important organelles and other structures of the cell are
shown in Figure 2-2.
Carbohydrates. Carbohydrates play a major role in cell
nutrition and, as parts of glycoprotein molecules, have
MEMBRANOUS STRUCTURES OF THE CELL
structural functions. Most human cells do not maintain
large stores of carbohydrates; the amount usually averages Most organelles of the cell are covered by membranes
only about 1% of their total mass but increases to as much composed primarily of lipids and proteins. These mem-
as 3% in muscle cells and, occasionally, to 6% in liver cells. branes include the cell membrane, nuclear membrane,
However, carbohydrate in the form of dissolved glucose membrane of the endoplasmic reticulum, and membranes
is always present in the surrounding extracellular fluid so of the mitochondria, lysosomes, and Golgi apparatus.
14
Chapter 2 The Cell and Its Functions
Carbohydrate
Extracellular
fluid
UNIT I
Integral protein
Lipid
bilayer
Peripheral
protein
Intracellular
fluid
Cytoplasm
Integral protein
Figure 2-3. Structure of the cell membrane showing that it is composed mainly of a lipid bilayer of phospholipid molecules, but with large
numbers of protein molecules protruding through the layer. Also, carbohydrate moieties are attached to the protein molecules on the outside
of the membrane and to additional protein molecules on the inside.
The lipids in membranes provide a barrier that continuous over the entire cell surface. Interspersed in
impedes movement of water and water- soluble sub- this lipid film are large globular proteins.
stances from one cell compartment to another because The basic lipid bilayer is composed of three main types
water is not soluble in lipids. However, protein mole- of lipids—phospholipids, sphingolipids, and cholesterol.
cules often penetrate all the way through membranes, Phospholipids are the most abundant cell membrane
thus providing specialized pathways, often organized lipids. One end of each phospholipid molecule is hydro-
into actual pores, for passage of specific substances philic and soluble in water. The other end is hydropho-
through membranes. Also, many other membrane bic and soluble only in fats. The phosphate end of the
proteins are enzymes, which catalyze a multitude of phospholipid is hydrophilic, and the fatty acid portion is
different chemical reactions, discussed here and in sub- hydrophobic.
sequent chapters. Because the hydrophobic portions of the phospholipid
molecules are repelled by water but are mutually attracted
Cell Membrane to one another, they have a natural tendency to attach to
The cell membrane (also called the plasma membrane) one another in the middle of the membrane, as shown in
envelops the cell and is a thin, pliable, elastic structure Figure 2-3. The hydrophilic phosphate portions then con-
only 7.5 to 10 nanometers thick. It is composed almost stitute the two surfaces of the complete cell membrane, in
entirely of proteins and lipids. The approximate composi- contact with intracellular water on the inside of the mem-
tion is 55% proteins, 25% phospholipids, 13% cholesterol, brane and extracellular water on the outside surface.
4% other lipids, and 3% carbohydrates. The lipid layer in the middle of the membrane is
impermeable to the usual water-soluble substances, such
The Cell Membrane Lipid Barrier Impedes Penetra- as ions, glucose, and urea. Conversely, fat-soluble sub-
tion by Water-Soluble Substances. Figure 2-3 shows stances, such as oxygen, carbon dioxide, and alcohol, can
the structure of the cell membrane. Its basic structure penetrate this portion of the membrane with ease.
is a lipid bilayer, which is a thin, double-layered film Sphingolipids, derived from the amino alcohol sphin-
of lipids—each layer only one molecule thick—that is gosine, also have hydrophobic and hydrophilic groups and
15
UNIT I Introduction to Physiology: The Cell and General Physiology
are present in small amounts in the cell membranes, espe- these molecules almost invariably protrude to the outside
cially nerve cells. Complex sphingolipids in cell mem- of the cell, dangling outward from the cell surface. Many
branes are thought to serve several functions, including other carbohydrate compounds, called proteoglycans—
protection from harmful environmental factors, signal which are mainly carbohydrates bound to small protein
transmission, and adhesion sites for extracellular proteins. cores—are loosely attached to the outer surface of the cell
Cholesterol molecules in membranes are also lipids as well. Thus, the entire outside surface of the cell often
because their steroid nuclei are highly fat-soluble. These has a loose carbohydrate coat called the glycocalyx.
molecules, in a sense, are dissolved in the bilayer of the The carbohydrate moieties attached to the outer sur-
membrane. They mainly help determine the degree of face of the cell have several important functions:
permeability (or impermeability) of the bilayer to water- 1. Many of them have a negative electrical charge,
soluble constituents of body fluids. Cholesterol controls which gives most cells an overall negative surface
much of the fluidity of the membrane as well. charge that repels other negatively charged objects.
2. The glycocalyx of some cells attaches to the glycoca-
Integral and Peripheral Cell Membrane Proteins. lyx of other cells, thus attaching cells to one another.
Figure 2-3 also shows globular masses floating in the 3. Many of the carbohydrates act as receptors for bind-
lipid bilayer. These membrane proteins are mainly glyco- ing hormones, such as insulin. When bound, this
proteins. There are two types of cell membrane proteins, combination activates attached internal proteins that
integral proteins, which protrude all the way through in turn activate a cascade of intracellular enzymes.
the membrane, and peripheral proteins, which are 4. Some carbohydrate moieties enter into immune re-
attached only to one surface of the membrane and do actions, as discussed in Chapter 35.
not penetrate all the way through.
Many of the integral proteins provide structural chan-
CYTOPLASM AND ITS ORGANELLES
nels (or pores) through which water molecules and water-
soluble substances, especially ions, can diffuse between The cytoplasm is filled with minute and large dispersed
extracellular and intracellular fluids. These protein chan- particles and organelles. The jelly-like fluid portion of the
nels also have selective properties that allow preferential cytoplasm in which the particles are dispersed is called
diffusion of some substances over others. cytosol and contains mainly dissolved proteins, electro-
Other integral proteins act as carrier proteins for trans- lytes, and glucose.
porting substances that otherwise could not penetrate Dispersed in the cytoplasm are neutral fat globules,
the lipid bilayer. Sometimes, these carrier proteins even glycogen granules, ribosomes, secretory vesicles, and five
transport substances in the direction opposite to their especially important organelles—the endoplasmic reticu-
electrochemical gradients for diffusion, which is called lum, the Golgi apparatus, mitochondria, lysosomes, and
active transport. Still others act as enzymes. peroxisomes.
Integral membrane proteins can also serve as receptors
for water-soluble chemicals, such as peptide hormones, Endoplasmic Reticulum
that do not easily penetrate the cell membrane. Interac- Figure 2-2 shows the endoplasmic reticulum, a network
tion of cell membrane receptors with specific ligands that of tubular structures called cisternae and flat vesicular
bind to the receptor causes conformational changes in structures in the cytoplasm. This organelle helps pro-
the receptor protein. This process, in turn, enzymatically cess molecules made by the cell and transports them to
activates the intracellular part of the protein or induces their specific destinations inside or outside the cell. The
interactions between the receptor and proteins in the tubules and vesicles interconnect. Also, their walls are
cytoplasm that act as second messengers, relaying the sig- constructed of lipid bilayer membranes that contain large
nal from the extracellular part of the receptor to the inte- amounts of proteins, similar to the cell membrane. The
rior of the cell. In this way, integral proteins spanning the total surface area of this structure in some cells—the liver
cell membrane provide a means of conveying information cells, for example—can be as much as 30 to 40 times the
about the environment to the cell interior. cell membrane area.
Peripheral protein molecules are often attached to The detailed structure of a small portion of endoplas-
integral proteins. These peripheral proteins function mic reticulum is shown in Figure 2-4. The space inside
almost entirely as enzymes or as controllers of transport the tubules and vesicles is filled with endoplasmic matrix,
of substances through cell membrane pores. a watery medium that is different from fluid in the cytosol
outside the endoplasmic reticulum. Electron micrographs
Membrane Carbohydrates—The Cell “Glycocalyx.” show that the space inside the endoplasmic reticulum is
Membrane carbohydrates occur almost invariably in com- connected with the space between the two membrane
bination with proteins or lipids in the form of glycopro- surfaces of the nuclear membrane.
teins or glycolipids. In fact, most of the integral proteins Substances formed in some parts of the cell enter the
are glycoproteins, and about one-tenth of the membrane space of the endoplasmic reticulum and are then directed
lipid molecules are glycolipids. The glyco- portions of to other parts of the cell. Also, the vast surface area of this
16
Chapter 2 The Cell and Its Functions
Matrix
Golgi
UNIT I
apparatus
ER vesicles
Endoplasmic
reticulum
Rough (granular)
endoplasmic
reticulum Smooth (agranular)
endoplasmic Figure 2-5. A typical Golgi apparatus and its relationship to the
reticulum endoplasmic reticulum (ER) and the nucleus.
Figure 2-4. Structure of the endoplasmic reticulum.
17
UNIT I Introduction to Physiology: The Cell and General Physiology
Cristae Matrix
Oxidative
phosphorylation
Outer chamber enzymes
Figure 2-6. Secretory granules (secretory vesicles) in acinar cells of
the pancreas. Figure 2-7. Structure of a mitochondrion.
amino acids and glucose. Some of the specific functions of Mitochondria are present in all areas of each cell’s
lysosomes are discussed later in this chapter. cytoplasm, but the total number per cell varies from less
than 100 up to several thousand, depending on the energy
Peroxisomes requirements of the cell. Cardiac muscle cells (cardiomyo-
Peroxisomes are physically similar to lysosomes, but cytes), for example, use large amounts of energy and have
they are different in two important ways. First, they are far more mitochondria than fat cells (adipocytes), which
believed to be formed by self-replication (or perhaps by are much less active and use less energy. Furthermore,
budding off from the smooth endoplasmic reticulum) the mitochondria are concentrated in those portions
rather than from the Golgi apparatus. Second, they con- of the cell responsible for the major share of its energy
tain oxidases rather than hydrolases. Several of the oxi- metabolism. They are also variable in size and shape.
dases are capable of combining oxygen with hydrogen Some mitochondria are only a few hundred nanometers
ions derived from different intracellular chemicals to in diameter and are globular in shape, whereas others are
form hydrogen peroxide (H2O2). Hydrogen peroxide is a elongated and are as large as 1 micrometer in diameter
highly oxidizing substance and is used in association with and 7 micrometers long. Still others are branching and
catalase, another oxidase enzyme present in large quan- filamentous.
tities in peroxisomes, to oxidize many substances that The basic structure of the mitochondrion, shown
might otherwise be poisonous to the cell. For example, in Figure 2-7, is composed mainly of two lipid bilayer-
about half the alcohol that a person drinks is detoxified protein membranes, an outer membrane and an inner
into acetaldehyde by the peroxisomes of the liver cells in membrane. Many infoldings of the inner membrane form
this manner. A major function of peroxisomes is to catab- shelves or tubules called cristae onto which oxidative
olize long-chain fatty acids. enzymes are attached. The cristae provide a large surface
area for chemical reactions to occur. In addition, the inner
Secretory Vesicles cavity of the mitochondrion is filled with a matrix that
One of the important functions of many cells is secretion contains large quantities of dissolved enzymes necessary
of special chemical substances. Almost all such secretory for extracting energy from nutrients. These enzymes oper-
substances are formed by the endoplasmic reticulum– ate in association with oxidative enzymes on the cristae
Golgi apparatus system and are then released from the to cause oxidation of nutrients, thereby forming carbon
Golgi apparatus into the cytoplasm in the form of stor- dioxide and water and, at the same time, releasing energy.
age vesicles called secretory vesicles or secretory granules. The liberated energy is used to synthesize a high-energy
Figure 2-6 shows typical secretory vesicles inside pancre- substance called adenosine triphosphate (ATP). ATP is
atic acinar cells; these vesicles store protein proenzymes then transported out of the mitochondrion and diffuses
(enzymes that are not yet activated). The proenzymes are throughout the cell to release its own energy wherever it
secreted later through the outer cell membrane into the is needed for performing cellular functions. The chemical
pancreatic duct and then into the duodenum, where they details of ATP formation by the mitochondrion are pro-
become activated and perform digestive functions on the vided in Chapter 68, but some basic functions of ATP in
food in the intestinal tract. the cell are introduced later in this chapter.
Mitochondria are self-replicative, which means that
Mitochondria one mitochondrion can form a second one, a third one,
The mitochondria, shown in Figure 2-2 and Figure 2-7, and so on whenever the cell needs increased amounts
are called the powerhouses of the cell. Without them, cells of ATP. Indeed, the mitochondria contain DNA similar
would be unable to extract enough energy from the nutri- to that found in the cell nucleus. In Chapter 3, we will
ents, and essentially all cellular functions would cease. see that DNA is the basic constituent of the nucleus that
18
Chapter 2 The Cell and Its Functions
α-Tubulin β-Tubulin
monomer monomer
Endoplasmic Ribosome Cell membrane Microfilaments
reticulum
Microtubule
(25 nm)
UNIT I
Fibrous protein
dimer
Intermediate
filament
(8-12 nm)
Microtubule Microfilament
(7 nm)
Figure 2-8. Cell cytoskeleton composed of protein fibers called microfilaments, intermediate filaments, and microtubules.
controls replication of the cell. The DNA of the mitochon- All cells have intermediate filaments, although the pro-
drion plays a similar role, controlling replication of the tein subunits of these structures vary, depending on the
mitochondrion. Cells that are faced with increased energy cell type. Specific intermediate filaments found in various
demands—for example, in skeletal muscles subjected to cells include desmin filaments in muscle cells, neurofila-
chronic exercise training—may increase the density of ments in neurons, and keratins in epithelial cells.
mitochondria to supply the additional energy required. A special type of stiff filament composed of polym-
erized tubulin molecules is used in all cells to construct
Cell Cytoskeleton—Filament and Tubular strong tubular structures, the microtubules. Figure 2-8
Structures shows typical microtubules of a cell.
The cell cytoskeleton is a network of fibrillar proteins Another example of microtubules is the tubular skeletal
organized into filaments or tubules. These originate as structure in the center of each cilium that radiates upward
precursor proteins synthesized by ribosomes in the cyto- from the cell cytoplasm to the tip of the cilium. This struc-
plasm. The precursor molecules then polymerize to form ture is discussed later in the chapter (see Figure 2-18). Also,
filaments (Figure 2-8). As an example, large numbers of both the centrioles and mitotic spindles of cells undergoing
actin microfilaments frequently occur in the outer zone mitosis are composed of stiff microtubules.
of the cytoplasm, called the ectoplasm, to form an elas- A major function of microtubules is to act as a cyto-
tic support for the cell membrane. Also, in muscle cells, skeleton, providing rigid physical structures for certain
actin and myosin filaments are organized into a special parts of cells. The cell cytoskeleton not only determines
contractile machine that is the basis for muscle contrac- cell shape but also participates in cell division, allows cells
tion, as discussed in Chapter 6. to move, and provides a tracklike system that directs the
Intermediate filaments are generally strong ropelike movement of organelles in the cells. Microtubules serve
filaments that often work together with microtubules, as the conveyor belts for the intracellular transport of
providing strength and support for the fragile tubulin vesicles, granules, and organelles such as mitochondria.
structures. They are called intermediate because their
average diameter is between that of narrower actin micro- Nucleus
filaments and wider myosin filaments found in muscle The nucleus is the control center of the cell and sends
cells. Their functions are mainly mechanical, and they are messages to the cell to grow and mature, replicate, or
less dynamic than actin microfilaments or microtubules. die. Briefly, the nucleus contains large quantities of DNA,
19
UNIT I Introduction to Physiology: The Cell and General Physiology
Nucleolus
1 µm Bacterium
Nuclear envelope:
outer and inner
membranes Cell
Cytoplasm
5-10 µm+
Figure 2-9. Structure of the nucleus.
Figure 2-10. Comparison of sizes of precellular organisms with that
of the average cell in the human body.
which comprise the genes. The genes determine the char-
acteristics of the cell’s proteins, including the structural RNA and proteins of the types found in ribosomes. The
proteins, as well as the intracellular enzymes that control nucleolus enlarges considerably when the cell is actively
cytoplasmic and nuclear activities. synthesizing proteins.
The genes also control and promote cell reproduction. Formation of the nucleoli (and of the ribosomes in
The genes first reproduce to create two identical sets of the cytoplasm outside the nucleus) begins in the nucleus.
genes; then the cell splits by a special process called mito- First, specific DNA genes in the chromosomes cause
sis to form two daughter cells, each of which receives one RNA to be synthesized. Some of this synthesized RNA is
of the two sets of DNA genes. All these activities of the stored in the nucleoli, but most of it is transported out-
nucleus are discussed in Chapter 3. ward through the nuclear pores into the cytoplasm. Here
Unfortunately, the appearance of the nucleus under the it is used in conjunction with specific proteins to assemble
microscope does not provide many clues to the mecha- “mature” ribosomes that play an essential role in forming
nisms whereby the nucleus performs its control activities. cytoplasmic proteins, as discussed in Chapter 3.
Figure 2-9 shows the light microscopic appearance of the
interphase nucleus (during the period between mitoses),
COMPARISON OF THE ANIMAL CELL
revealing darkly staining chromatin material throughout
WITH PRECELLULAR FORMS OF LIFE
the nucleoplasm. During mitosis, the chromatin material
organizes in the form of highly structured chromosomes, The cell is a complicated organism that required many
which can then be easily identified using the light micro- hundreds of millions of years to develop after the earli-
scope, as illustrated in Chapter 3. est forms of life, microorganisms that may have been
similar to present-day viruses, first appeared on earth.
Nuclear Membrane. The nuclear membrane, also called Figure 2-10 shows the relative sizes of the following: (1)
the nuclear envelope, is actually two separate bilayer the smallest known virus; (2) a large virus; (3) a Rickett-
membranes, one inside the other. The outer membrane sia; (4) a bacterium; and (5) a nucleated cell, This dem-
is continuous with the endoplasmic reticulum of the cell onstrates that the cell has a diameter about 1000 times
cytoplasm, and the space between the two nuclear mem- that of the smallest virus and therefore a volume about 1
branes is also continuous with the space inside the endo- billion times that of the smallest virus. Correspondingly,
plasmic reticulum, as shown in Figure 2-9. the functions and anatomical organization of the cell are
The nuclear membrane is penetrated by several thou- also far more complex than those of the virus.
sand nuclear pores. Large complexes of proteins are The essential life-giving constituent of the small virus is
attached at the edges of the pores so that the central area a nucleic acid embedded in a coat of protein. This nucleic
of each pore is only about 9 nanometers in diameter. acid is composed of the same basic nucleic acid constit-
Even this size is large enough to allow molecules up to a uents (DNA or RNA) found in mammalian cells and is
molecular weight of 44,000 to pass through with reason- capable of reproducing itself under appropriate condi-
able ease. tions. Thus, the virus propagates its lineage from genera-
tion to generation and is therefore a living structure in the
Nucleoli and Formation of Ribosomes. The nuclei of same way that cells and humans are living structures.
most cells contain one or more highly staining structures As life evolved, other chemicals in addition to nucleic
called nucleoli. The nucleolus, unlike most other orga- acid and simple proteins became integral parts of the
nelles discussed here, does not have a limiting membrane. organism, and specialized functions began to develop
Instead, it is simply an accumulation of large amounts of in different parts of the virus. A membrane formed
20
Chapter 2 The Cell and Its Functions
around the virus and, inside the membrane, a fluid matrix Proteins Receptors
appeared. Specialized chemicals then developed inside Coated pit
Clathrin
the fluid to perform special functions; many protein
enzymes appeared that were capable of catalyzing chemi-
cal reactions, thus determining the organism’s activities.
In still later stages of life, particularly in the rickett-
UNIT I
sial and bacterial stages, organelles developed inside the A B
organism. These represent physical structures of chemi-
cal aggregates that perform functions in a more efficient Actin and myosin Dissolving clathrin
manner than what can be achieved by dispersed chemi-
cals throughout the fluid matrix.
Finally, in the nucleated cell, still more complex organ-
elles developed, the most important of which is the
nucleus. The nucleus distinguishes this type of cell from
all lower forms of life; it provides a control center for all C D
cellular activities and for reproduction of new cells gen- Figure 2-11. Mechanism of pinocytosis.
eration after generation, with each new cell having almost
exactly the same structure as its progenitor. Pinocytosis is the only means whereby most large
macromolecules, such as most proteins, can enter cells.
In fact, the rate at which pinocytotic vesicles form is usu-
FUNCTIONAL SYSTEMS OF THE CELL
ally enhanced when such macromolecules attach to the
In the remainder of this chapter, we discuss some func- cell membrane.
tional systems of the cell that make it a living organism. Figure 2-11 demonstrates the successive steps of
pinocytosis (A–D), showing three molecules of protein
attaching to the membrane. These molecules usually
ENDOCYTOSIS—INGESTION BY THE CELL
attach to specialized protein receptors on the surface of
If a cell is to live and grow and reproduce, it must obtain the membrane that are specific for the type of protein
nutrients and other substances from the surrounding flu- that is to be absorbed. The receptors generally are con-
ids. Most substances pass through the cell membrane by centrated in small pits on the outer surface of the cell
the processes of diffusion and active transport. membrane, called coated pits. On the inside of the cell
Diffusion involves simple movement through the mem- membrane beneath these pits is a latticework of fibrillar
brane caused by the random motion of the molecules of protein called clathrin, as well as other proteins, perhaps
the substance. Substances move through cell membrane including contractile filaments of actin and myosin. Once
pores or, in the case of lipid-soluble substances, through the protein molecules have bound with the receptors, the
the lipid matrix of the membrane. surface properties of the local membrane change in such
Active transport involves actually carrying a substance a way that the entire pit invaginates inward, and fibrillar
through the membrane by a physical protein structure proteins surrounding the invaginating pit cause its bor-
that penetrates all the way through the membrane. These ders to close over the attached proteins, as well as over a
active transport mechanisms are so important to cell small amount of extracellular fluid. Immediately thereaf-
function that they are presented in detail in Chapter 4. ter, the invaginated portion of the membrane breaks away
Large particles enter the cell by a specialized func- from the surface of the cell, forming a pinocytotic vesicle
tion of the cell membrane called endocytosis (Video 2-1). inside the cytoplasm of the cell.
The principal forms of endocytosis are pinocytosis and What causes the cell membrane to go through the
phagocytosis. Pinocytosis means the ingestion of minute necessary contortions to form pinocytotic vesicles is still
particles that form vesicles of extracellular fluid and par- unclear. This process requires energy from within the cell,
ticulate constituents inside the cell cytoplasm. Phagocyto- which is supplied by ATP, a high-energy substance dis-
sis means the ingestion of large particles, such as bacteria, cussed later in this chapter. This process also requires the
whole cells, or portions of degenerating tissue. presence of calcium ions in the extracellular fluid, which
probably react with contractile protein filaments beneath
Pinocytosis. Pinocytosis occurs continually in the cell the coated pits to provide the force for pinching the vesi-
membranes of most cells, but is especially rapid in some cles away from the cell membrane.
cells. For example, it occurs so rapidly in macrophages
that about 3% of the total macrophage membrane is en- Phagocytosis. Phagocytosis occurs in much the same
gulfed in the form of vesicles each minute. Even so, the way as pinocytosis, except that it involves large particles
pinocytotic vesicles are so small—usually only 100 to 200 rather than molecules. Only certain cells have the capa-
nanometers in diameter—that most of them can be seen bility of phagocytosis—notably, tissue macrophages and
only with an electron microscope. some white blood cells.
21
UNIT I Introduction to Physiology: The Cell and General Physiology
22
Chapter 2 The Cell and Its Functions
UNIT I
NUCLEATION
of the synthesized protein molecules directly into the cy-
tosol, but they also extrude many more through the wall
of the endoplasmic reticulum to the interior of the endo-
plasmic vesicles and tubules into the endoplasmic matrix.
23
UNIT I Introduction to Physiology: The Cell and General Physiology
24
Chapter 2 The Cell and Its Functions
UNIT I
Acetoacetic has been called the energy currency of the cell because it
acid can be spent and reformed continually, having a turnover
Acetyl-CoA time of only a few minutes.
O2 O2 O2 ADP
CO2 CO2 CO2 + H2O ATP Chemical Processes in the Formation of ATP—Role
of the Mitochondria. On entry into the cells, glucose is
converted by enzymes in the cytoplasm into pyruvic acid
H2O H2O 36 ATP (a process called glycolysis). A small amount of ADP is
changed into ATP by the energy released during this con-
Mitochondrion
version, but this amount accounts for less than 5% of the
Cell membrane Cytoplasm overall energy metabolism of the cell.
About 95% of the cell’s ATP formation occurs in the
Figure 2-15. Formation of adenosine triphosphate (ATP) in the cell mitochondria. The pyruvic acid derived from carbo-
showing that most of the ATP is formed in the mitochondria. (ADP,
Adenosine diphosphate; CoA, coenzyme A.)
hydrates, fatty acids from lipids, and amino acids from
proteins is eventually converted into the compound
acetyl-coenzyme A (CoA) in the matrix of mitochondria.
Functional Characteristics of Adenosine This substance, in turn, is further dissolved (for the pur-
Triphosphate pose of extracting its energy) by another series of enzymes
NH2 in the mitochondrion matrix, undergoing dissolution in a
sequence of chemical reactions called the citric acid cycle,
N C or Krebs cycle. These chemical reactions are so important
C N
HC Adenine that they are explained in detail in Chapter 68.
C CH In this citric acid cycle, acetyl-CoA is split into its
N N O O O
component parts, hydrogen atoms and carbon dioxide.
O CH2 O P O~P O~P O– The carbon dioxide diffuses out of the mitochondria and
eventually out of the cell; finally, it is excreted from the
C H H C O– O– O–
body through the lungs.
Phosphate
H C C H The hydrogen atoms, conversely, are highly reactive;
they combine with oxygen that has also diffused into
OH OH
the mitochondria. This combination releases a tremen-
Ribose dous amount of energy, which is used by mitochondria
Adenosine triphosphate to convert large amounts of ADP to ATP. The processes
of these reactions are complex, requiring the participa-
ATP is a nucleotide composed of the following: (1) the tion of many protein enzymes that are integral parts of
nitrogenous base adenine; (2) the pentose sugar ribose; mitochondrial membranous shelves that protrude into the
and (3) three phosphate radicals. The last two phosphate mitochondrial matrix. The initial event is the removal of
radicals are connected with the remainder of the mol- an electron from the hydrogen atom, thus converting it to
ecule by high-energy phosphate bonds, which are rep- a hydrogen ion. The terminal event is the combination of
resented in the formula shown by the symbol ∼. Under hydrogen ions with oxygen to form water and the release
the physical and chemical conditions of the body, each of of large amounts of energy to globular proteins that pro-
these high-energy bonds contains about 12,000 calories trude like knobs from the membranes of the mitochon-
of energy per mole of ATP, which is many times greater drial shelves; these proteins are called ATP synthetase.
than the energy stored in the average chemical bond, thus Finally, the enzyme ATP synthetase uses the energy from
giving rise to the term high-energy bond. Furthermore, the the hydrogen ions to convert ADP to ATP. The newly
high-energy phosphate bond is very labile, so that it can formed ATP is transported out of the mitochondria into
be split instantly on demand whenever energy is required all parts of the cell cytoplasm and nucleoplasm, where it
to promote other intracellular reactions. energizes multiple cell functions.
When ATP releases its energy, a phosphoric acid This overall process for formation of ATP is called the
radical is split away, and adenosine diphosphate (ADP) is chemiosmotic mechanism of ATP formation. The chemi-
formed. This released energy is used to energize many of cal and physical details of this mechanism are presented
25
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quarter, days. A day is one revolution of Terra. From Mars, say, a
Terran year is something else entirely. Mars, of course, is not too
good an example for its sidereal day is very close to Terra's. But your
Venus, with its eighteen hour day—eighteen Terran hours—sees
Terra's year as four hundred eighty-six, plus, days. On Ertene, we
have no year. We had one, once. It was composed of four hundred
twelve point seven zero four two two nine three one days, sidereal.
Now, our day is different, since the length of the solar day depends
upon the progression of the planet about its luminary. Our luminary
behaves as a moon with a high ecliptic-angle as I have explained.
No, Guy, I have been mentally converting my year to your year, by
crude approximation."
The next panel was an ornate painting of the Ertinian system,
showing—out of scale for artistic purpose—the planets and sun, with
Ertene drawing away in a long spiral.
"For many years we pursued that spiral, withdrawing from the sun by
slow degrees. Then we broke free." Charalas indicated the panel
which showed Ertene in the foreground while the clustered system
was far behind.
They passed from panel to panel, all of which were interesting to Guy
Maynard. There was a series of the first star contacted by Ertene. It
was a small system, cold and forbidding, or hot and equally
forbidding. The outer planets were in the grip of frozen air, and the
inner planets bubbled in moltenness "This system was too far out of
line to turn. It was our first star, and we might have stayed in
youthfulness. Now, we know better."
The next panel showed a dimly-lighted landscape; a portrayal of
Ertene without its synthetic sun. The luminous sky was beautiful in a
nocturnal sort of way; to Guy it was slightly nostalgic for some
unknown reason, at any rate it was the soul of sadness, that
landscape.
Charalas shook his head and then smiled. He led Guy to the next
panel, and there was a portrait of an elderly man, quite a bit older
than Charalas though the neuro-surgeon was no young man.
"Timalas," said Charalas proudly. "He gave us the next panel."
The following panel was a similar scene to the dismal one, but now
the same trees and buildings and hills and sky were illuminated by a
sun. It was a cheerful, uplifting scene compared to the soul-clouding
darkness.
Maynard turned to Charalas and saw that the elderly doctor had been
watching him intently. Before he could speak, the Ertinian said: "It is a
hard nut to crack, lad. Many have tried but none have succeeded.
Like most things that are best for people, they are the least exciting
and the most formal, and people do not react cheerfully to a formal
diet."
Maynard shook his head. "But unlike a man with ulcers, I cannot
prescribe a diet of milk lest he die. Ertene will go on living no matter
whether I speak and sway them or whether I never say another word.
I am asked to convince an entire world against their will. I can not tell
them that it is the slightest bit dangerous to go on as they have. In
fact, it may be dangerous for them to remain. In all honesty, I must
admit that Terra is not without her battle scars."
Charalas said, thoughtfully: "Who knows what is best for civilization?
We do not, for we are civilization. We do as we think best, and if it is
not best, we die and another civilization replaces us in Nature's long-
time program to find the real survivor."
He faced the panel and said, partly to himself and partly to Guy:
"Is it best for Ertene to go on through time experimenting? Gathering
the fruits of a million civilizations bound forever to their stellar homes
because of the awful abyss between the stars? For the planets all to
become wanderers would be chaos.
"Therefore is it Nature's plan that Ertene be the one planet to gather
unto herself the fruit of all knowledge and ultimately lie barren
because of the sterility of her culture? Are we to be the sponge for all
thought? If so, where must it end? What good is it? Is this some great
master plan? Will we, after a million galactic years, reach a state
where we may disseminate the knowledge we have gained, or are we
merely greedy, taking all and giving nothing?
"What are we learning? And, above all, are we certain that Ertene's
culture is best for civilization? How may we tell? The strong and best
adapted survive, and since we are no longer striving against the
lesser forces of Nature on our planet, and indeed, are no longer
striving against those of antisocial thought among our own people—
against whom or what do we fight?
"Guy Maynard, you are young and intelligent. Perhaps by some
whimsy of fate you may be the deciding factor in Ertene's
aimlessness. We are here, Guy. We are at the gates to the future. My
real reason for bringing you to the Center of Ertene is to have you
present your case to the Council."
He took Guy's arm and led him through the door at the end of the
corridor. They went into the gilt-and-ivory room with the vast
hemispherical dome and as the door slowly closed behind them, Guy
Maynard, Terran, and Charalas, Ertinian, stood facing a quarter-circle
of ornate desks behind which sat the Council.
Obviously, they had been waiting.
IV.
Guy Maynard looked reproachfully at Charalas. He felt that he had
been tricked, that Charalas had kicked the bottom out of his argument
and then had forced him into the debate with but an impromptu
defense. He wondered how this discussion was to be conducted, and
while he was striving to collect a lucid story, part of his mind heard
Charalas going through the usual procedure for recording purposes.
"Who is this man?"
"He is Junior Executive Guy Maynard of the Terran Space Patrol."
"Explain his title."
"It is a rank of official service. It denotes certain abilities and
responsibilities."
"Can you explain the position of his rank with respect to other ratings
of more or less responsibility?"
Charalas counted off on his fingers. "From the lowest rank upward,
the following titles are used: Junior Aide, Senior Aide, Junior
Executive, Senior Executive, Sector Commander, Patrol Marshal,
Sector Marshal, and Space Marshal."
"These are the commissioned officers? Are there other ratings?"
"Yes, shall I name them?"
"Prepare them for the record. There is no need of recounting the
noncommissioned officials."
"I understand."
"How did Guy Maynard come to Ertene?"
"Maynard was rescued from a derelict spaceship."
"By whom?"
"Thomakein."
"Am I to assume that Thomakein brought him to Ertene for study?"
"That assumption is correct."
"The knowledge of the system of Sol is complete?"
"Between the information furnished by Guy Maynard and the
observations made by Thomakein, the knowledge of Sol's planets is
sufficient. More may be learned before Ertene loses contact, but for
the time, it is adequate."
"And Guy Maynard is present for the purpose of explaining the Terran
wishes in the question of whether Ertene is to remain here?"
"Correct."
The councilor who sat in the center of the group smiled at Guy and
said: "Guy Maynard, this is an informal meeting. You are to rest
assured we will not attempt to goad you into saying something you do
not mean. If you are unprepared to answer a given question, ask for
time to think. We will understand. However, we ask that you do not try
to shade your answers in such a manner as to convey erring
impressions. This is not a court of law; procedure is not important.
Speak when and as you desire and understand that you will not be
called to account for slight breaches of etiquette, since we all know
that formality is a deterrent to the real point in argument."
Charalas added: "Absolute formality in argument usually ends in the
decision going to the best orator. This is not desirable, since some of
the more learned men are poor orators, while some of the best
orators must rely upon the information furnished them by the
learned."
The center councilor arose and called the other six councilors by
name in introduction. This was slightly redundant since their names
were all present in little bronze signs on the desks. It was a
pleasantry aimed at putting the Terran at ease and offering him the
right to call them by name.
"Now," said Terokar, the center one, "we shall begin. Everything we
have said has been recorded for the records. But, Guy, we will
remove anything from the record that would be detrimental to the
integrity of any of us. We will play it back before you leave and you
may censor it."
"Thank you," said Guy. "Knowing that records are to be kept as
spoken will often deter honest expression."
"Quite true. That is why we permit censoring. Now, Guy, your wishes
concerning Ertene's alliance with Sol."
"I invite Ertene to join the Solar System."
"Your invitation is appreciated. Please understand that the
acceptance of such an invitation will change Ertene's social structure
forever, and that it is not to be taken lightly."
"I realize that the invitation is not one to accept lightly. It is a large
decision."
"Then what has Sol to offer?"
"A stable existence. The commerce of an entire system and the
friendship of another world of similar type in almost every respect.
The opportunity to partake in a veritable twinship between Ertene and
Sol, with all the ramifications that such a brotherhood would offer."
"Ertene's existence is stable, Guy. Let us consider that point first."
"How can any wandering program be considered stable?"
"We are born, we live, and we die. Whether we are fated to spend our
lives on a nomad planet or ultimately become the very center of the
universe about which everything revolves, making Ertene the most
stable planet of them all, Ertinians will continue living. When
nomadism includes the entire resources of a planet, it can not be
instable."
"Granted. But do you hope to go on forever?"
"How old is your history, Guy?"
"From the earliest of established dates, taken from the stones of
Assyria and the artifacts of Maya, some seven thousand years."
Charalas added a lengthy discussion setting the length of a Terran
year.
"Ertinian history is perhaps a bit longer," said Terokar. "And so who
can say 'forever'?"
"No comment," said Guy with a slight laugh. "But my statements
concerning stability are not to be construed as the same type of
instability suffered by an itinerant human. He has no roots, and few
friends, and he gains nothing nor does he offer anything to society.
No, I am wrong. It is the same thing. Ertene goes on through the eons
of wandering. She has no friends and no roots and while she may
gain experience and knowledge of the universe just as the tramp will,
her ultimate gain is poor and her offering to civilization is zero."
"I dispute that. Ertene's life has become better for the experience she
has gained and the knowledge, too."
"Perhaps. But her offering to civilization?"
"We are not a dead world. Perhaps some day we may be able to offer
the storehouses of our knowledge to some system that will need it.
Perhaps we are destined to become the nucleus of a great, galactic
civilization."
"Such a civilization will never work as long as men are restrained as
to speed of transportation. Could any pact be sustained between
planets a hundred light-years apart? Indeed, could any pact be
agreed upon?"
"I cannot answer that save to agree. However, somewhere there may
be some means of faster-than-light travel and communication. If this
is found, galactic-wide civilization will not only be possible but a
definite expectation."
"You realize that you are asking for Ertene a destiny that sounds
definitely egotistic?"
"And why not? Are you not sold on the fact that Terra is the best
planet in the Solar System?"
"Naturally."
"Also," smiled Charalas, "the Martians admit that Mars is the best
planet."
"Granted then that Ertene is stable. Even granting for the moment
that Ertene is someday to become the nucleus of the galaxy. I still
claim that Ertene is missing one item." Guy waited for a moment and
then added: "Ertene is missing the contact and commerce with other
races. Ertene is self-sufficient and as such is stagnant as far as new
life goes. Life on Ertene has reached the ultimate—for Ertene.
Similarly, life on Terra had reached that point prior to the opening of
space. Life must struggle against something, and when the struggle
is no longer possible—when all possible obstruction has been
circumvented—then life decays."
"You see us as decadent?"
"Not yet. The visiting of system after system has kept you from total
decadence. It is but a stasis, however. Unless one has the samples of
right and wrong from which to choose, how may he know his own
course?"
"Of what difference is it?" asked the councilor named Baranon. "If
there is no dissenting voice, if life thrives, if knowledge and science
advance, what difference does it make whether we live under one
social order or any other? If thievery and wrongdoing, for instance,
could support a system of social importance, and the entire
population lives under that code and thrives, of what necessity is it to
change?"
"Any social order will pyramid," said Guy. "Either up or down."
"Granted. But if all are prepared to withstand the ravages of their
neighbors, and are eternally prepared to live under constant strife, no
man will have his rights trod upon."
"But what good is this eternal wandering? This everlasting eye upon
the constantly receding horizon? This never ending search for the
proper place to stop in order that this theoretical galactic civilization
may start? At Ertene's state of progress, one place will be as good as
any other," said Guy.
"Precisely, except that some places are definitely less desirable.
Recall, Guy, that Ertene needs nothing."
"I dispute that. Ertene needs the contact with the outside worlds."
"No."
"You are in the position of a recluse who loves his seclusion."
"Certainly."
"Then you are in no position to appreciate any other form of social
order."
"We care for no other social order."
"I mentioned to Charalas that in my eyes, you are wrong. That I am
being asked to prescribe for a patient who will not die for lack of my
prescription. I can not even say that the patient will benefit directly.
My belief is as good as yours. I believe that Ertene is suffering
because of her seclusion and that her peoples will advance more
swiftly with commerce between the planets—and once again in
interstellar space, Ertene will have no planets with which to conduct
trade."
"And Sol, like complex society, will never miss the recluse. Let the
hermit live in his cave, he is neither hindering nor helping civilization."
"Indirectly, the hermit hinders. He excites curiosity and the wonder if a
hermit's existence might not be desirable and thus diverts other
thinkers to seclusion."
"But if the hermit withdraws alone and unnoticed, no one will know of
the hermitage, and then no one will wonder."
"But I know, and though no one else in the Solar System knows, I am
trying to bring you into our society. I have the desire of brotherhood,
the gregarious instinct that wants to be friend with all men. It annoys
me—as it annoys all men—to see one of us alone and unloved by his
fellows. I have a burning desire to have Ertene as a twin world with
Terra."
"But Ertene likes her itinerant existence. The fires that burn beyond
the horizon are interesting. Also," smiled Terokar, "the grass is
greener over there."
"One day you will come to the end of the block," said Guy, "and find
that the grass is no greener anywhere, with the exception that you
now have no more grass to look at, plus the sorry fact that you cannot
return. A million galactic years from now, Ertene will have passed
through the galaxy and will find herself looking at intergalactic space.
Then what?"
"Then our children will learn to live in a starless sky for a hundred
thousand generations. Solarians live in a sky of constant placement;
Ertene's sky is ever changing and all sky maps are obsolete in thirty
or forty years. You must remember that to us, wandering is the
normal way of life. Some of us believe that we may eventually return
to our parent sun. We may. But all of us believe that we would find
our parent sun no more interesting than others. No Guy, I doubt that
we will stop there either."
"You are assuming that you will not remain at Sol?"
"We are a shy planet. We do not like to change our way of life. You
are asking us to give up our life and to accept yours. It is similar to a
man asking a woman to marry. But a woman is not completely
reversed in her life when she marries. Here you are asking us to
cleave unto you forever—and there is no bond of love to soften the
hard spots."
"I did mention the bond of brotherhood," said Guy.
"Brotherhood with what?" asked Terokar. "You ask us to enter a bond
of twinship with a planet that is the center of strife. You ask us in the
name of similarity to join you—and help you gain mastery over the
Solar System."
"And why not?"
"Which of you is right? Is the Terran combine more righteous than the
Martian alliance?"
"Certainly."
"Why?"
Guy asked for a moment to think. The room was silent for a moment
and then he said, slowly and painfully: "I can think of no other reason
than the trite and no-answer reason: 'We're right because we're right!'
The Martian combine fights us to gain the land and the commerce
that we have taken because of superiority in space."
"A superiority given merely because of sheer size," said Baranon.
"The Martians, raised under a gravity of less than one third of Terra's
find it difficult to keep pace with the Terrans, who can live under three
times as much acceleration. Battle under such conditions is unfair,
and the fact that the Martians have been able to survive indicates that
their code is not entirely wrong."
Charalas nodded. "Any code that is entirely in error will not be able to
survive."
"So," said Terokar, "you ask us to join your belligerent system. You
ask us to emerge from our pleasure and join you in a struggle for
existence. You ask that we give up the peace that has survived for a
thousand years, and in doing so you ask that we come willingly and
permit our cities to be war-scarred and our men killed. You ask that
we join in battle against a smaller, less adapted race that still is able
to survive in spite of its ill-adaption to the rigors of space."
Guy was silent.
"Is that the way of life? Must we fight for our life? Strife is deplorable,
Guy Maynard, and I am saying that to you, who come of a planet
steeped in strife. You wear a uniform—or did—that is dedicated to the
job of doing a better job of fighting than the enemy. Continual warlike
activity has no place on Ertene.
"Plus one other thing, Guy Maynard. You are honorable and your
intent is clear. But your fellows are none too like you. Ertene would
become the playground of the Solar System. There would be
continual battles over Ertene, and Ertene with her inexperience in
warfare would be forced to accept the protection of Terra. That
protection would break down into the same sort of protection that is
offered the Plutonians by a handful of Terrans. In exchange for
'protection' against enemies that would possibly be no better or
worse, the Plutonians are stripped of their metal. They are not
accorded the privilege of schooling because they are too ignorant to
enter even the most elementary of schools. Besides, schooling would
make them aware of their position and they might rebel against the
system that robs them of their substance under the name of
'protection.' Protection? May the Highest Law protect me from my
protectors!" Terokar's lips curled slightly. "Am I not correct? Have not
the Plutonians the right to life, liberty, and the pursuit of happiness? It
would be a heavy blow to Terra if the third planet were forced to pay
value for the substance that comes from Pluto."
"After all," said Guy, "if Terra hadn't got there first, Mars would be
doing the same thing."
"Granted," said Baranon. "Absolutely correct. But two wrongs do not
make a right. Terra is no worse than Mars. But that does not excuse
either of them. They are both wrong!"
"Are you asking Terra to change its way of life?" demanded Guy.
"You are asking Ertene to change. We have the same privilege."
"Obviously in a system such as ours a completely altruistic society
would be wiped out."
"Obviously," said Baranon.
"Then—"
"Then Ertene will change its way of life—providing Terra changes
hers."
"Mars—"
"Mars will have to change hers, too. Can you not live in harmony?"
"Knowing what the Martians did to me—can you expect me to greet
one of them with open arms?"
"Knowing what you have done to them, I wouldn't expect either one of
you to change your greetings. No, Guy, I fear that Ertene will continue
on her path until such a time as we meet a system that is less
belligerent and more adapted to our way of life."
"Then I have failed?"
"Do not feel badly. You have failed, but you were fighting a huge,
overwhelming force. You fought the inheritance of a hundred
generations of wanderers. You fought the will of an integrated people
who deplore strife. You fought the desire of everyone on Ertene, and
since no Ertinian could change Solar society, we cannot expect a
Terran to change Ertinian ideals. You failed, but it is no disgrace to fail
against such an overwhelming defense."
Guy smiled weakly. "I presume that I was fighting against a
determined front?"
"You were trying to do the most difficult job of all. In order to have
succeeded, you would first have had to unsell us on our firm
convictions, and then sell us the desirability of yours. A double job,
both uphill."
"Then I am to consider the matter closed?"
"Yes. We have decided not to remain."
"You decided that before I came in," said Guy bitterly.
"We decided that a thousand years before you were born, so do not
feel bitter."
"I presume that a change in your plans is out of the question even
though further information on Sol's planets proves you wrong?"
"It will never be brought up again."
"I see," said Guy unhappily. "Part of my desire to convince you was
the hope of seeing my home again."
"Oh, but you will," said Charalas.
Guy was dumfounded. He could hardly believe his ears. He asked for
a repeat, and got it. It was still amazing. To Guy, it was outright
foolishness. He wouldn't have trusted anyone with such a secret. To
permit him to return to Terra with the knowledge he had—
"Charalas, what would prevent me from bringing my people to
Ertene? I could bring the forces of Terra down about your very ears."
"But you will not. We have a strict, value-even trade to offer you."
"But it would be so easy to keep me here."
"We could not restrain you without force. And if we must rely upon
your honor, we'd be equally reliant whether you be here or on Terra."
"Here," said Guy dryly, "I'd be away from temptation. If I were tempted
to tell, there'd be no one to tell it to."
"We must comply with an ancient rule," explained Terokar. "It says
specifically that no man without Ertinian blood may remain on Ertene.
It was made to keep the race pure when we were still about our
parent sun and has never been revoked. We wouldn't revoke it for
you alone."
"But permitting me to go free would be sheer madness."
"Not quite. We are mutually indebted to one another, Guy. There is
the matter of knowledge. You gave freely of yours, we gave you ours.
We have gained some points that were missing in our science, you
have a number of points that will make you rich, famous, and
remembered. Use them as your own, only do it logically in order that
they seem to be discoveries of your own. You admit the worth of
them?"
"Oh, but yes," said Guy eagerly. "Wonderful—"
"Then there is no debt for knowledge?"
"If any, I am in your debt."
"We'll call it even," said Baranon, dryly.
"Then there is the matter of life," said Terokar. "You know how you
were found?"
Guy shook his head in wonder. "I had been through the Martian idea
of how to get information out of a reluctant man," he said slowly. "I
know that their methods result in a terrible mindless state which to my
own belief is worse than death itself. I know that as I lost
consciousness, I prayed for death to come, even though I knew that
they would not permit it."
"We found you that way. You know. And we brought you back to life.
You owe us that."
"Indeed I do."
"Then for your life, we demand our life in return."
"I do not understand."
"Your life is yours. We ask that you say nothing of us—for we feel that
we will die if we are found. At least, the integrity of Ertene is at stake.
In any event, we will not be taken, you may as well know that. And
when I say die, I mean that Ertene will not go on living in the way we
want her to live. Therefore you will disclose nothing that will point our
way to anyone."
"And you are willing that I should return to Terra with such an oath?
What of my oath to Terra?"
"Do you feel that your presence on Ertene will benefit Terra in some
small way?" asked Charalas.
"Now that you have given me the things we spoke of before, I do."
"Then," said Charalas, "consider this point. You may not return unless
you swear to keep us secret. You may not give Terra the benefit of
your knowledge unless you deprive them of Ertene. Is that clear?"
"If I may not return to Terra, and may not remain on Ertene, I can
guess the other alternative and will admit that I do not like it. On the
returning angle, about all I can do is to justify myself in my own mind
that I have done all that I can by bringing these scientific items back
with me. Since doing the best I can for Terra includes keeping your
secret, I can do that also. But tell me, how do you hope to cover the
fact that I've been missing for almost a year? That will take more than
mere explanation."
"The process is easy," said Charalas. "We have one of the lifeships
from the derelict. It was slightly damaged in the blast. It is
maneuverable, but unwieldy. Evidence has been painstakingly
forged. Apparently you will have broken your straps under the shock
of the blast—and before the torture reached its height—and you
found yourself in a derelict with no one left alive but yourself. You
were hurt, mentally, and didn't grasp the situation clearly. There was
no way to signal your plight in secrecy, and open signaling would
have been dangerous since you were too close to Mars.
"You found the lifeship and waited until you could safely take off. The
derelict took a crazy course, according to the recorded log in your
own handwriting, and headed for interstellar space. You took off at
the safe time and have been floating free in the damaged lifeship.
You've been on a free orbit for the best part of a year."
"Sounds convincing enough."
"The evidence includes empty air cans, your own fingerprints on
everything imaginable, a dulled can opener and the remnants of can
labels that have fallen into nooks and crannies of the ship. The water-
recovery device has been under constant operation and examination
will show about a year's accumulation of residual matter. A scratch-
mark calendar has been kept on the wall of the lifeship, and daily it
has been added to. That is important since the wall will show more
oxidation in the scratches made a year ago than the ones made
recently. The accumulators of the ship have been run down as if in
service while you were forcing the little ship into its orbit, and the
demand recorder shows how the drain was used. The lights in the
ship have been burned, and the deposits of fluorescent material in
the tubes have been used about the calculated number of hours.
Books have been nearly worn out from re-reading and they were
used with fingerprint gloves though they were studied by us.
Instruments and gadgets are strewn about the ship in profusion,
indicating the attempts of an intelligent man trying to kill time. Also
you will find the initial findings on the energy collector we used in
conjunction with the light-shield.
"Now, yourself. Into your body we will inject the hormones that occur
with fear and worry. You will not enjoy a bit of atmosphobia, but