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14TH EDITION
Guyton and Hall

Textbook of Medical Physiology
John E. Hall, PhD

Arthur C. Guyton Professor and Chair
Department of Physiology and Biophysics
Director, Mississippi Center for Obesity Research
University of Mississippi Medical Center
Jackson, Mississippi
Michael E. Hall, MD, MS

Associate Professor
Department of Medicine, Division of
Cardiovascular Diseases
Associate Vice Chair for Research
Department of Physiology and Biophysics
University of Mississippi Medical Center
Jackson, Mississippi
Elsevier
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GUYTON AND HALL TEXTBOOK OF MEDICAL PHYSIOLOGY,

FOURTEENTH EDITION ISBN: 978-0-323-59712-8
INTERNATIONAL EDITION ISBN: 978-0-323-67280-1
Copyright © 2021 by Elsevier, Inc. All rights reserved.
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To
Our Families
For their abundant support, for their patience and
understanding, and for their love
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
Functional Organization of the Human Body
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
Figure 1-2. Diffusion of fluid and dissolved constituents through the

capillary walls and interstitial spaces.
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.
Regulation ORIGIN OF NUTRIENTS IN THE

of Excretion
electrolytes EXTRACELLULAR FLUID
Respiratory System. Figure 1-1 shows that each time
blood passes through the body, it also flows through the
Venous end Arterial end lungs. The blood picks up oxygen in alveoli, thus acquiring
the oxygen needed by cells. The membrane between the
alveoli and the lumen of the pulmonary capillaries, the
alveolar membrane, is only 0.4 to 2.0 micrometers thick,
and oxygen rapidly diffuses by molecular motion through
Capillaries this membrane into the blood.
Figure 1-1. General organization of the circulatory system.
Gastrointestinal Tract. A large portion of the blood pumped
by the heart also passes through the walls of the gastrointes-
of once each minute when the body is at rest and as many tinal tract. Here different dissolved nutrients, including car-
as six times each minute when a person is extremely active. bohydrates, fatty acids, and amino acids, are absorbed from
As blood passes through blood capillaries, continual ingested food into the extracellular fluid of the blood.
exchange of extracellular fluid occurs between the plasma
portion of the blood and the interstitial fluid that fills the Liver and Other Organs That Perform Primarily Meta-
intercellular spaces. This process is shown in Figure 1-2. bolic Functions. Not all substances absorbed from the
The capillary walls are permeable to most molecules in gastrointestinal tract can be used in their absorbed form
the blood plasma, with the exception of plasma proteins, by the cells. The liver changes the chemical compositions
which are too large to pass through capillaries readily. of many of these substances to more usable forms, and
Therefore, large amounts of fluid and its dissolved con- other tissues of the body—fat cells, gastrointestinal mu-
stituents diffuse back and forth between the blood and the cosa, kidneys, and endocrine glands—help modify the
tissue spaces, as shown by the arrows in Figure 1-2. absorbed substances or store them until they are needed.
This process of diffusion is caused by kinetic motion The liver also eliminates certain waste products produced
of the molecules in the plasma and the interstitial fluid. in the body and toxic substances that are ingested.
5
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 distances 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
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
Table 1-1 Important Constituents and Physical Characteristics of Extracellular Fluid

Constituent Normal Value Normal Range Approximate Short-Term Nonlethal Limit Unit
Oxygen (venous) 40 25–40 10–1000 mm Hg
Carbon dioxide (venous) 45 41–51 5–80 mm Hg
Sodium ion 142 135–145 115–175 mmol/L
Potassium ion 4.2 3.5–5.3 1.5–9.0 mmol/L
Calcium ion 1.2 1.0–1.4 0.5–2.0 mmol/L
Chloride ion 106 98–108 70–130 mmol/L
Bicarbonate ion 24 22–29 8–45 mmol/L
Glucose 90 70–115 20–1500 mg/dl
Body temperature 98.4 (37.0) 98–98.8 (37.0) 65–110 (18.3–43.3) °F (°C)
Acid–base (venous) 7.4 7.3–7.5 6.9–8.0 pH
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
5 overcome by the negative feedback control mechanisms

of the body, and the vicious cycle then fails to develop.
Pumping effectiveness of heart
Return to For example, if the person in the aforementioned example
(Liters pumped per minute)
4 normal
bleeds only 1 liter instead of 2 liters, the normal negative
Bled 1 liter
feedback mechanisms for controlling cardiac output and
3 arterial pressure can counterbalance the positive feedback
UNIT I
and the person can recover, as shown by the dashed curve
Bled 2 liters of Figure 1-4.
2
Positive Feedback Can Sometimes Be Useful. The body

1 sometimes uses positive feedback to its advantage. Blood
clotting is an example of a valuable use of positive feed-
Death back. When a blood vessel is ruptured, and a clot begins to
0
form, multiple enzymes called clotting factors are activated
1 2 3
within the clot. Some of these enzymes act on other inac-
Hours
tivated enzymes of the immediately adjacent blood, thus
Figure 1-4. Recovery of heart pumping caused by negative feedback
causing more blood clotting. This process continues until
after 1 liter of blood is removed from the circulation. Death is caused
by positive feedback when 2 liters or more blood is removed. the hole in the vessel is plugged and bleeding no longer
occurs. On occasion, this mechanism can get out of hand
for control of arterial pressure is −50 divided by +25, or and cause formation of unwanted clots. In fact, this is what
−2. That is, a disturbance that increases or decreases the initiates most acute heart attacks, which can be caused by
arterial pressure does so only one-third as much as would a clot beginning on the inside surface of an atherosclerotic
occur if this control system were not present. plaque in a coronary artery and then growing until the ar-
The gains of some other physiological control systems tery is blocked.
are much greater than that of the baroreceptor system. Childbirth is another situation in which positive feed-
For example, the gain of the system controlling internal back is valuable. When uterine contractions become
body temperature when a person is exposed to moder- strong enough for the baby’s head to begin pushing
ately cold weather is about −33. Therefore, one can see through the cervix, stretching of the cervix sends signals
that the temperature control system is much more effec- through the uterine muscle back to the body of the uterus,
tive than the baroreceptor pressure control system. causing even more powerful contractions. Thus, the uter-
ine contractions stretch the cervix, and cervical stretch
Positive Feedback May Cause Vicious causes stronger contractions. When this process becomes
Cycles and Death powerful enough, the baby is born. If they are not pow-
Why do most control systems of the body operate by erful enough, the contractions usually die out, and a few
negative feedback rather than by positive feedback? If days pass before they begin again.
one considers the nature of positive feedback, it is obvi- Another important use of positive feedback is for the
ous that positive feedback leads to instability rather than generation of nerve signals. Stimulation of the mem-
stability and, in some cases, can cause death. brane of a nerve fiber causes slight leakage of sodium ions
Figure 1-4 shows an example in which death can ensue through sodium channels in the nerve membrane to the
from positive feedback. This figure depicts the pumping fiber’s interior. The sodium ions entering the fiber then
effectiveness of the heart, showing the heart of a healthy change the membrane potential, which, in turn, causes
human pumping about 5 liters of blood per minute. If the more opening of channels, more change of potential, still
person suddenly bleeds a total of 2 liters, the amount of more opening of channels, and so forth. Thus, a slight leak
blood in the body is decreased to such a low level that becomes an explosion of sodium entering the interior of
not enough blood is available for the heart to pump effec- the nerve fiber, which creates the nerve action potential.
tively. As a result, the arterial pressure falls, and the flow This action potential, in turn, causes electrical current to
of blood to the heart muscle through the coronary ves- flow along the outside and inside of the fiber and initiates
sels diminishes. This scenario results in weakening of the additional action potentials. This process continues until
heart, further diminished pumping, a further decrease the nerve signal goes all the way to the end of the fiber.
in coronary blood flow, and still more weakness of the In each case in which positive feedback is useful, the
heart; the cycle repeats itself again and again until death positive feedback is part of an overall negative feedback
occurs. Note that each cycle in the feedback results in process. For example, in the case of blood clotting, the
further weakening of the heart. In other words, the initi- positive feedback clotting process is a negative feedback
ating stimulus causes more of the same, which is positive process for the maintenance of normal blood volume.
feedback. Also, the positive feedback that causes nerve signals
Positive feedback is sometimes known as a “vicious allows the nerves to participate in thousands of negative
cycle,” but a mild degree of positive feedback can be feedback nervous control systems.
9
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
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.
Proteins. After water, the most abundant substances in

most cells are proteins, which normally constitute 10% to Figure 2-1. Illustration of cell structures visible with a light microscope.
13
Chromosomes and DNA
Centrioles
Secretory
granule
Golgi
apparatus
Microtubules
Nuclear
membrane Cell
membrane
Nucleolus
Glycogen
Ribosomes
Lysosome
Mitochondrion Rough (granular) Smooth (agranular) Microfilaments

endoplasmic endoplasmic
reticulum reticulum
Figure 2-2. Reconstruction of a typical cell, showing the internal organelles in the cytoplasm and nucleus.
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
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
Ribosome Golgi vesicles
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.
vesicles are transported from the endoplasmic reticulum

reticulum and the multiple enzyme systems attached to to the Golgi apparatus. The transported substances are
its membranes provide the mechanisms for a major share then processed in the Golgi apparatus to form lysosomes,
of the cell’s metabolic functions. secretory vesicles, and other cytoplasmic components
(discussed later in this chapter).
Ribosomes and the Rough (Granular) Endoplasmic
Reticulum. Attached to the outer surfaces of many parts Lysosomes
of the endoplasmic reticulum are large numbers of minute Lysosomes, shown in Figure 2-2, are vesicular organ-
granular particles called ribosomes. Where these particles elles that form by breaking off from the Golgi appara-
are present, the reticulum is called the rough (granular) tus; they then disperse throughout the cytoplasm. The
endoplasmic reticulum. The ribosomes are composed of a lysosomes provide an intracellular digestive system that
mixture of RNA and proteins; they function to synthesize allows the cell to digest the following: (1) damaged cellu-
new protein molecules in the cell, as discussed later in this lar structures; (2) food particles that have been ingested
chapter and in Chapter 3. by the cell; and (3) unwanted matter such as bacteria.
Lysosome are different in various cell types but are usu-
Smooth (Agranular) Endoplasmic Reticulum. Part of ally 250 to 750 nanometers in diameter. They are sur-
the endoplasmic reticulum has no attached ribosomes. rounded by typical lipid bilayer membranes and are filled
This part is called the smooth, or agranular, endoplasmic with large numbers of small granules, 5 to 8 nanometers
reticulum. The smooth reticulum functions for the syn- in diameter, which are protein aggregates of as many as
thesis of lipid substances and for other processes of the 40 different hydrolase (digestive) enzymes. A hydrolytic
cells promoted by intrareticular enzymes. enzyme is capable of splitting an organic compound into
two or more parts by combining hydrogen from a water
Golgi Apparatus molecule with one part of the compound and combin-
The Golgi apparatus, shown in Figure 2-5, is closely ing the hydroxyl portion of the water molecule with the
related to the endoplasmic reticulum. It has membranes other part of the compound. For example, protein is
similar to those of the smooth endoplasmic reticulum. hydrolyzed to form amino acids, glycogen is hydrolyzed
The Golgi apparatus is usually composed of four or more to form glucose, and lipids are hydrolyzed to form fatty
stacked layers of thin, flat, enclosed vesicles lying near one acids and glycerol.
side of the nucleus. This apparatus is prominent in secre- Hydrolytic enzymes are highly concentrated in lyso-
tory cells, where it is located on the side of the cell from somes. Ordinarily, the membrane surrounding the lyso-
which secretory substances are extruded. some prevents the enclosed hydrolytic enzymes from
The Golgi apparatus functions in association with the coming into contact with other substances in the cell and
endoplasmic reticulum. As shown in Figure 2-5, small therefore prevents their digestive actions. However, some
transport vesicles (also called endoplasmic reticulum conditions of the cell break the membranes of lysosomes,
vesicles [ER vesicles]) continually pinch off from the endo- allowing release of the digestive enzymes. These enzymes
plasmic reticulum and shortly thereafter fuse with the then split the organic substances with which they come
Golgi apparatus. In this way, substances entrapped in ER in contact into small, highly diffusible substances such as
17
Secretory Outer membrane

granules Inner membrane
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
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)
Mitochondrion Two intertwined

F-actin chains
G-actin
monomer
Intermediate filament
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
Pores 15 nm: Small virus

Endoplasmic 150 nm: Large virus
reticulum
Nucleoplasm 350 nm: Rickettsia
Nucleolus
1 µm Bacterium
Nuclear envelope:
outer and inner
membranes Cell
Chromatin material (DNA)
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
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
Lysosomes proteins, carbohydrates, lipids, and other substances in the

vesicle. The products of digestion are small molecules of
substances such as amino acids, glucose, and phosphates
that can diffuse through the membrane of the vesicle into
the cytoplasm. What is left of the digestive vesicle, called
Pinocytotic or the residual body, represents indigestible substances. In
phagocytic most cases, the residual body is finally excreted through
vesicle the cell membrane by a process called exocytosis, which is
Digestive vesicle essentially the opposite of endocytosis. Thus, the pinocy-
totic and phagocytic vesicles containing lysosomes can be
called the digestive organs of the cells.
Residual body
Lysosomes and Regression of Tissues and Autolysis
of Damaged Cells. Tissues of the body often regress to
Excretion a smaller size. For example, this regression occurs in the
uterus after pregnancy, in muscles during long periods of
Figure 2-12. Digestion of substances in pinocytotic or phagocytic
vesicles by enzymes derived from lysosomes. inactivity, and in mammary glands at the end of lactation.
Lysosomes are responsible for much of this regression.
Another special role of the lysosomes is the removal
Phagocytosis is initiated when a particle such as a bac- of damaged cells or damaged portions of cells from tis-
terium, dead cell, or tissue debris binds with receptors sues. Damage to the cell—caused by heat, cold, trauma,
on the surface of the phagocyte. In the case of bacteria, chemicals, or any other factor—induces lysosomes to
each bacterium is usually already attached to a specific rupture. The released hydrolases immediately begin to
antibody; it is the antibody that attaches to the phago- digest the surrounding organic substances. If the damage
cyte receptors, dragging the bacterium along with it. This is slight, only a portion of the cell is removed, and the cell
intermediation of antibodies is called opsonization, which is then repaired. If the damage is severe, the entire cell is
is discussed in Chapters 34 and 35. digested, a process called autolysis. In this way, the cell is
Phagocytosis occurs in the following steps: completely removed, and a new cell of the same type is
1. The cell membrane receptors attach to the surface formed, ordinarily by mitotic reproduction of an adjacent
ligands of the particle. cell to take the place of the old one.
2. The edges of the membrane around the points of The lysosomes also contain bactericidal agents that can
attachment evaginate outward within a fraction of kill phagocytized bacteria before they cause cellular dam-
a second to surround the entire particle; then, pro- age. These agents include the following: (1) lysozyme, which
gressively more and more membrane receptors at- dissolves the bacterial cell wall; (2) lysoferrin, which binds
tach to the particle ligands. All this occurs suddenly iron and other substances before they can promote bacterial
in a zipper-like manner to form a closed phagocytic growth; and (3) acid at a pH of about 5.0, which activates the
vesicle. hydrolases and inactivates bacterial metabolic systems.
3. Actin and other contractile fibrils in the cytoplasm
surround the phagocytic vesicle and contract Autophagy and Recycling of Cell Organelles.
around its outer edge, pushing the vesicle to the in- Lysosomes play a key role in the process of autophagy,
terior. which literally means “to eat oneself.” Autophagy is
4. The contractile proteins then pinch the stem of the a housekeeping process whereby obsolete organelles
vesicle so completely that the vesicle separates from and large protein aggregates are degraded and re-
the cell membrane, leaving the vesicle in the cell in- cycled (Figure 2-13). Worn-o ut cell organelles are
terior in the same way that pinocytotic vesicles are transferred to lysosomes by double-m embrane struc-
formed. tures called autophagosomes, which are formed in the
cytosol. Invagination of the lysosomal membrane and
the formation of vesicles provides another pathway for
LYSOSOMES DIGEST PINOCYTOTIC AND
cytosolic structures to be transported into the lumen
PHAGOCYTIC FOREIGN SUBSTANCES
of lysosomes. Once inside the lysosomes, the orga-
INSIDE THE CELL
nelles are digested, and the nutrients are reused by the
Almost immediately after a pinocytotic or phagocytic ves- cell. Autophagy contributes to the routine turnover of
icle appears inside a cell, one or more lysosomes become cytoplasmic components; it is a key mechanism for
attached to the vesicle and empty their acid hydrolases to tissue development, cell survival when nutrients are
the inside of the vesicle, as shown in Figure 2-12. Thus, scarce, and maintenance of homeostasis. In liver cells,
a digestive vesicle is formed inside the cell cytoplasm in for example, the average mitochondrion normally has
which the vesicular hydrolases begin hydrolyzing the a life span of only about 10 days before it is destroyed.
22
Proteins Synthesis by the Rough Endoplasmic Reticu-

lum. The rough endoplasmic reticulum is characterized by
large numbers of ribosomes attached to the outer surfaces
of the endoplasmic reticulum membrane. As discussed in
Chapter 3, protein molecules are synthesized within the
Isolation membrane structures of the ribosomes. The ribosomes extrude some
VESICLE
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.
Lipid Synthesis by the Smooth Endoplasmic Reticu-

lum. The endoplasmic reticulum also synthesizes lipids,
AUTOSOME
FORMATION
especially phospholipids and cholesterol. These lipids are
rapidly incorporated into the lipid bilayer of the endoplas-
mic reticulum, thus causing the endoplasmic reticulum to
Autophagosome grow more extensive. This process occurs mainly in the
smooth portion of the endoplasmic reticulum.
To keep the endoplasmic reticulum from growing
Lysosome beyond the needs of the cell, small vesicles called ER
vesicles or transport vesicles continually break away from
the smooth reticulum; most of these vesicles then migrate
rapidly to the Golgi apparatus.
Other Functions of the Endoplasmic Reticulum.

Other significant functions of the endoplasmic reticu-
DOCKING AND lum, especially the smooth reticulum, include the fol-
FUSION WITH Autolysosome
LYSOSOME lowing:
1. It provides the enzymes that control glycogen
breakdown when glycogen is to be used for energy.
Lysosomal 2. It provides a vast number of enzymes that are ca-
hydrolase pable of detoxifying substances, such as drugs, that
might damage the cell. It achieves detoxification by
processes such as coagulation, oxidation, hydroly-
sis, and conjugation with glycuronic acid.
VESICLE BREAKDOWN AND DEGRADATION

Golgi Apparatus Functions
Synthetic Functions of the Golgi Apparatus. Although
Figure 2-13. Schematic diagram of autophagy steps.
a major function of the Golgi apparatus is to provide ad-
ditional processing of substances already formed in the
SYNTHESIS OF CELLULAR STRUCTURES BY endoplasmic reticulum, it can also synthesize certain
ENDOPLASMIC RETICULUM AND GOLGI carbohydrates that cannot be formed in the endoplas-
APPARATUS mic reticulum. This is especially true for the formation of
large saccharide polymers bound with small amounts of
Endoplasmic Reticulum Functions protein; important examples include hyaluronic acid and
The extensiveness of the endoplasmic reticulum and Golgi chondroitin sulfate.
apparatus in secretory cells has already been emphasized. A few of the many functions of hyaluronic acid and
These structures are formed primarily of lipid bilayer chondroitin sulfate in the body are as follows: (1) they
membranes, similar to the cell membrane, and their walls are the major components of proteoglycans secreted in
are loaded with protein enzymes that catalyze the synthe- mucus and other glandular secretions; (2) they are the
sis of many substances required by the cell. major components of the ground substance, or nonfibrous
Most synthesis begins in the endoplasmic reticulum. components of the extracellular matrix, outside the cells
The products formed there are then passed on to the Golgi in the interstitial spaces, which act as fillers between col-
apparatus, where they are further processed before being lagen fibers and cells; (3) they are principal components of
released into the cytoplasm. First, however, let us note the the organic matrix in both cartilage and bone; and (4) they
specific products that are synthesized in specific portions are important in many cell activities, including migration
of the endoplasmic reticulum and Golgi apparatus. and proliferation.
23
Protein Lipid Secretory Types of Vesicles Formed by the Golgi Apparatus—

Ribosomes formation formation Lysosomes vesicles Secretory Vesicles and Lysosomes. In a highly secre-
tory cell, the vesicles formed by the Golgi apparatus are
mainly secretory vesicles containing proteins that are se-
creted through the surface of the cell membrane. These
secretory vesicles first diffuse to the cell membrane and
then fuse with it and empty their substances to the exte-
rior by the mechanism called exocytosis. Exocytosis, in
most cases, is stimulated by entry of calcium ions into
the cell. Calcium ions interact with the vesicular mem-
brane and cause its fusion with the cell membrane, fol-
lowed by exocytosis—opening of the membrane’s outer
surface and extrusion of its contents outside the cell.
Some vesicles, however, are destined for intracellular
Transport use.
Glycosylation vesicles
Rough Smooth Golgi Use of Intracellular Vesicles to Replenish Cellular
endoplasmic endoplasmic apparatus Membranes. Some intracellular vesicles formed by the
reticulum reticulum
Golgi apparatus fuse with the cell membrane or with the
Figure 2-14. Formation of proteins, lipids, and cellular vesicles by the
membranes of intracellular structures such as the mito-
endoplasmic reticulum and Golgi apparatus.
chondria and even the endoplasmic reticulum. This fusion
increases the expanse of these membranes and replenish-
Processing of Endoplasmic Secretions by the Golgi es the membranes as they are used up. For example, the
Apparatus—Formation of Vesicles. Figure 2-14 sum- cell membrane loses much of its substance every time it
marizes the major functions of the endoplasmic reticu- forms a phagocytic or pinocytotic vesicle, and the vesicu-
lum and Golgi apparatus. As substances are formed in lar membranes of the Golgi apparatus continually replen-
the endoplasmic reticulum, especially proteins, they are ish the cell membrane.
transported through the tubules toward portions of the In summary, the membranous system of the endo-
smooth endoplasmic reticulum that lie nearest to the plasmic reticulum and Golgi apparatus are highly
Golgi apparatus. At this point, transport vesicles com- metabolic and capable of forming new intracellular
posed of small envelopes of smooth endoplasmic retic- structures and secretory substances to be extruded
ulum continually break away and diffuse to the deepest from the cell.
layer of the Golgi apparatus. Inside these vesicles are
synthesized proteins and other products from the endo-
THE MITOCHONDRIA EXTRACT ENERGY
plasmic reticulum.
FROM NUTRIENTS
The transport vesicles instantly fuse with the Golgi
apparatus and empty their contained substances into The principal substances from which cells extract energy
the vesicular spaces of the Golgi apparatus. Here, are foods that react chemically with oxygen—carbo-
additional carbohydrate moieties are added to the hydrates, fats, and proteins. In the human body, essen-
secretions. Also, an important function of the Golgi tially all carbohydrates are converted into glucose by the
apparatus is to compact the endoplasmic reticular digestive tract and liver before they reach the other cells
secretions into highly concentrated packets. As the of the body. Similarly, proteins are converted into amino
secretions pass toward the outermost layers of the acids, and fats are converted into fatty acids. Figure 2-15
Golgi apparatus, the compaction and processing pro- shows oxygen and the foodstuffs—glucose, fatty acids,
ceed. Finally, both small and large vesicles continually and amino acids—all entering the cell. Inside the cell,
break away from the Golgi apparatus, carrying with they react chemically with oxygen under the influence
them the compacted secretory substances and diffus- of enzymes that control the reactions and channel the
ing throughout the cell. energy released in the proper direction. The details of all
The following example provides an idea of the tim- these digestive and metabolic functions are provided in
ing of these processes. When a glandular cell is bathed Chapters 63 through 73.
in amino acids, newly formed protein molecules can be Briefly, almost all these oxidative reactions occur
detected in the granular endoplasmic reticulum within 3 inside the mitochondria, and the energy that is released
to 5 minutes. Within 20 minutes, newly formed proteins is used to form the high-energy compound ATP. Then,
are already present in the Golgi apparatus and, within 1 ATP, not the original food, is used throughout the cell to
to 2 hours, the proteins are secreted from the surface of energize almost all the subsequent intracellular metabolic
the cell. reactions.
24
the cell’s other functions, such as syntheses of substances

2ADP 2ATP and muscular contraction.
To reconstitute the cellular ATP as it is used up, energy
Glucose Gl
36 ADP derived from the cellular nutrients causes ADP and phos-
Fatty acids FA
phoric acid to recombine to form new ATP, and the entire
Amino acids AA Pyruvic acid process is repeated over and over. For these reasons, ATP
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
Ribosomes Movement of cell
Membrane
transport Endoplasmic Endocytosis
reticulum
Pseudopodium
Protein synthesis
Na+ Na+ ATP ADP
Exocytosis
ADP
Mitochondrion
ATP ATP ADP

Surrounding tissue Receptor binding
Figure 2-17. Ameboid motion by a cell.
ATP ADP
simply to synthesize new chemical compounds, especially
protein molecules; this is particularly true during the
growth phase of cells.
Muscle contraction Another use of ATP is to supply energy for special
Figure 2-16. Use of adenosine triphosphate (ATP; formed in the mi- cells to perform mechanical work. We discuss in Chap-
tochondrion) to provide energy for three major cellular functions— ter 6 that each contraction of a muscle fiber requires the
membrane transport, protein synthesis, and muscle contraction. expenditure of large quantities of ATP energy. Other cells
(ADP, Adenosine diphosphate.)
perform mechanical work in other ways, especially by cili-
ary and ameboid motion, described later in this chapter.
in Chapter 68, and many of the detailed metabolic func- The source of energy for all these types of mechanical
tions of ATP in the body are discussed in Chapters 68 work is ATP.
through 72. In summary, ATP is readily available to release its
energy rapidly wherever it is needed in the cell. To replace
Uses of ATP for Cellular Function. Energy from ATP ATP used by the cell, much slower chemical reactions
is used to promote three major categories of cellular break down carbohydrates, fats, and proteins and use the
functions: (1) transport of substances through multiple energy derived from these processes to form new ATP.
cell membranes; (2) synthesis of chemical compounds More than 95% of this ATP is formed in the mitochon-
throughout the cell; and (3) mechanical work. These uses dria, which is why the mitochondria are called the power-
of ATP are illustrated by the examples in Figure 2-16: houses of the cell.
(1) to supply energy for the transport of sodium through
the cell membrane; (2) to promote protein synthesis by
LOCOMOTION OF CELLS
the ribosomes; and (3) to supply the energy needed dur-
ing muscle contraction. The most obvious type of movement in the body is that
In addition to the membrane transport of sodium, which occurs in skeletal, cardiac, and smooth muscle cells,
energy from ATP is required for the membrane transport which constitute almost 50% of the entire body mass. The
of potassium, calcium, magnesium, phosphate, chloride, specialized functions of these cells are discussed in Chapters
urate, and hydrogen ions and many other ions, as well 6 through 9. Two other types of movement—ameboid loco-
as various organic substances. Membrane transport is motion and ciliary movement—occur in other cells.
so important to cell function that some cells—the renal
tubular cells, for example—use as much as 80% of the
AMEBOID MOVEMENT
ATP that they form for this purpose alone.
In addition to synthesizing proteins, cells make phos- Ameboid movement is a crawling-like movement of an
pholipids, cholesterol, purines, pyrimidines, and many entire cell in relation to its surroundings, such as move-
other substances. Synthesis of almost any chemical com- ment of white blood cells through tissues. This type of
pound requires energy. For example, a single protein mol- movement gets its name from the fact that amebae move
ecule might be composed of as many as several thousand in this manner, and amebae have provided an excellent
amino acids attached to one another by peptide linkages. tool for studying the phenomenon.
The formation of each of these linkages requires energy Typically, ameboid locomotion begins with the protru-
derived from the breakdown of four high-energy bonds; sion of a pseudopodium from one end of the cell. The pseu-
thus, many thousand ATP molecules must release their dopodium projects away from the cell body and partially
energy as each protein molecule is formed. Indeed, some secures itself in a new tissue area; then the remainder of
cells use as much as 75% of all the ATP formed in the cell the cell is pulled toward the pseudopodium. Figure 2-17
26
demonstrates this process, showing an elongated cell, the Some types of cancer cells, such as sarcomas, which
right-hand end of which is a protruding pseudopodium. arise from connective tissue cells, are especially proficient
The membrane of this end of the cell is continually mov- at ameboid movement. This partially accounts for their
ing forward, and the membrane at the left-hand end of the relatively rapid spreading from one part of the body to
cell is continually following along as the cell moves. another, known as metastasis.
UNIT I
Mechanism of Ameboid Locomotion. Figure 2-17 Control of Ameboid Locomotion—Chemotaxis. An
shows the general principle of ameboid motion. Basical- important initiator of ameboid locomotion is the process
ly, this results from the continual formation of new cell called chemotaxis, which results from the appearance of
membrane at the leading edge of the pseudopodium and certain chemical substances in the tissues. Any chemi-
continual absorption of the membrane in the mid and rear cal substance that causes chemotaxis to occur is called
portions of the cell. Two other effects are also essential for a chemotactic substance. Most cells that exhibit ameboid
forward movement of the cell. The first is attachment of locomotion move toward the source of a chemotactic
the pseudopodium to surrounding tissues so that it be- substance—that is, from an area of lower concentration
comes fixed in its leading position while the remainder toward an area of higher concentration. This is called pos-
of the cell body is being pulled forward toward the point itive chemotaxis. Some cells move away from the source,
of attachment. This attachment is caused by receptor pro- which is called negative chemotaxis.
teins that line the insides of exocytotic vesicles. When the How does chemotaxis control the direction of ame-
vesicles become part of the pseudopodial membrane, they boid locomotion? Although the answer is not certain,
open so that their insides evert to the outside, and the re- it is known that the side of the cell most exposed to the
ceptors now protrude to the outside and attach to ligands chemotactic substance develops membrane changes that
in the surrounding tissues. cause pseudopodial protrusion.
At the opposite end of the cell, the receptors pull away
from their ligands and form new endocytotic vesicles.
CILIA AND CILIARY MOVEMENTS
Then, inside the cell, these vesicles stream toward the
pseudopodial end of the cell, where they are used to form There are two types of cilia, motile and nonmotile, or pri-
new membrane for the pseudopodium. mary, cilia. Motile cilia can undergo a whiplike movement
The second essential effect for locomotion is to provide on the surfaces of cells. This movement occurs mainly
the energy required to pull the cell body in the direction in two places in the human body, on the surfaces of the
of the pseudopodium. A moderate to large amount of the respiratory airways and on the inside surfaces of the uter-
protein actin is in the cytoplasm of all cells. Much of the ine tubes (fallopian tubes) of the reproductive tract. In the
actin is in the form of single molecules that do not provide nasal cavity and lower respiratory airways, the whiplike
any motive power; however, these molecules polymerize motion of motile cilia causes a layer of mucus to move at
to form a filamentous network, and the network contracts a rate of about 1 cm/min toward the pharynx, in this way
when it binds with an actin-binding protein such as myosin. continually clearing these passageways of mucus and parti-
The entire process is energized by the high-energy com- cles that have become trapped in the mucus. In the uterine
pound ATP. This is what occurs in the pseudopodium of a tubes, cilia cause slow movement of fluid from the ostium
moving cell, where such a network of actin filaments forms of the uterine tube toward the uterus cavity; this movement
anew inside the enlarging pseudopodium. Contraction also of fluid transports the ovum from the ovary to the uterus.
occurs in the ectoplasm of the cell body, where a preexisting As shown in Figure 2-18, a cilium has the appearance
actin network is already present beneath the cell membrane. of a sharp-pointed straight or curved hair that projects
2 to 4 micrometers from the surface of the cell. Often,
Types of Cells That Exhibit Ameboid Locomotion. many motile cilia project from a single cell—for example,
The most common cells to exhibit ameboid locomotion as many as 200 cilia on the surface of each epithelial cell
in the human body are the white blood cells when they inside the respiratory passageways. The cilium is covered
move out of the blood into the tissues to form tissue mac- by an outcropping of the cell membrane, and it is sup-
rophages. Other types of cells can also move by ameboid ported by 11 microtubules—nine double tubules located
locomotion under certain circumstances. For example, around the periphery of the cilium and two single tubules
fibroblasts move into a damaged area to help repair the down the center, as demonstrated in the cross section
damage, and even the germinal cells of the skin, although shown in Figure 2-18. Each cilium is an outgrowth of
ordinarily completely sessile cells, move toward a cut area a structure that lies immediately beneath the cell mem-
to repair the opening. Cell locomotion is also especially brane, called the basal body of the cilium.
important in the development of the embryo and fetus The flagellum of a sperm is similar to a motile cilium;
after fertilization of an ovum. For example, embryonic in fact, it has much the same type of structure and same
cells often must migrate long distances from their sites type of contractile mechanism. The flagellum, however, is
of origin to new areas during the development of special much longer and moves in quasisinusoidal waves instead
structures. of whiplike movements.
27
the cilium can still beat under appropriate conditions.

Tip Third, two conditions are necessary for continued beating
of the axoneme after removal of the other structures of
the cilium: (1) the availability of ATP; and (2) appropriate
ionic conditions, especially appropriate concentrations of
magnesium and calcium. Fourth, during forward motion
Membrane
of the cilium, the double tubules on the front edge of the
cilium slide outward toward the tip of the cilium, whereas
Cross section those on the back edge remain in place. Fifth, multiple
Ciliary stalk
protein arms composed of the protein dynein, which has

adenosine triphosphatase (ATPase) enzymatic activity,
Filament project from each double tubule toward an adjacent dou-
ble tubule.
Given this basic information, it has been determined
that the release of energy from ATP in contact with the
ATPase dynein arms causes the heads of these arms to
Forward stroke
“crawl” rapidly along the surface of the adjacent double
tubule. If the front tubules crawl outward while the back
tubules remain stationary, bending occurs.
Basal plate The way in which cilia contraction is controlled is not
well understood. The cilia of some genetically abnormal
Cell
membrane cells do not have the two central single tubules, and these
Backward stroke cilia fail to beat. Therefore, it is presumed that some signal,
Basal body perhaps an electrochemical signal, is transmitted along
these two central tubules to activate the dynein arms.
Rootlet
Nonmotile Primary Cilia Serve as Cell Sensory “An-
tennae.” Primary cilia are nonmotile and generally
occur only as a single cilium on each cell. Although the
physiological functions of primary cilia are not fully un-
Figure 2-18. Structure and function of the cilium. (Modified from derstood, current evidence indicates that they function
Satir P: Cilia. Sci Am 204:108, 1961.) as cellular ‘’sensory antennae,” which coordinate cellular
signaling pathways involved in chemical and mechani-
In the inset of Figure 2-18, movement of the motile cal sensation, signal transduction, and cell growth. In the
cilium is shown. The cilium moves forward with a sudden, kidneys, for example, primary cilia are found in most epi-
rapid whiplike stroke 10 to 20 times per second, bending thelial cells of the tubules, projecting into the tubule lu-
sharply where it projects from the surface of the cell. Then men and acting as a flow sensor. In response to fluid flow
it moves backward slowly to its initial position. The rapid, over the tubular epithelial cells, the primary cilia bend and
forward-thrusting, whiplike movement pushes the fluid cause flow-induced changes in intracellular calcium sign-
lying adjacent to the cell in the direction that the cilium aling. These signals, in turn, initiate multiple effects on
moves; the slow dragging movement in the backward the cells. Defects in signaling by primary cilia in renal tu-
direction has almost no effect on fluid movement. As a bular epithelial cells are thought to contribute to various
result, the fluid is continually propelled in the direction of disorders, including the development of large fluid-filled
the fast-forward stroke. Because most motile ciliated cells cysts, a condition called polycystic kidney disease.
have large numbers of cilia on their surfaces, and because
all the cilia are oriented in the same direction, this is an
effective means for moving fluids from one part of the Bibliography
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membrane traffic control. Nat Rev Mol Cell Biol 14:382, 2013.
aspects of ciliary movement are known, we are aware
Dikic I, Elazar Z. Mechanism and medical implications of mammalian
of the following elements. First, the nine double tubules autophagy. Nat Rev Mol Cell Biol 19:349, 2018.
and two single tubules are all linked to one another by a Eisner V, Picard M, Hajnóczky G. Mitochondrial dynamics in adap-
complex of protein cross-linkages; this total complex of tive and maladaptive cellular stress responses. Nat Cell Biol 20:755,
tubules and cross-linkages is called the axoneme. Second, 2018.
Galluzzi L, Yamazaki T, Kroemer G. Linking cellular stress responses
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other elements of the cilium in addition to the axoneme,
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Guerriero CJ, Brodsky JL: The delicate balance between secreted pro- Palikaras K, Lionaki E, Tavernarakis N. Mechanisms of mitophagy
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Insall R: The interaction between pseudopods and extracellular signal- Rev Mol Cell Biol 18:361, 2017.
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UNIT I
25:526, 2013. dria to cellular metabolism. Nat Cell Biol. 20:745, 2018.
Kaksonen M, Roux A. Mechanisms of clathrin-mediated endocytosis. Walker CL, Pomatto LCD, Tripathi DN, Davies KJA. Redox regulation
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Lawrence RE, Zoncu R. The lysosome as a cellular centre for signalling, 2018.
metabolism and quality control. Nat Cell Biol 21: 133, 2019. Zhou K, Gaullier G, Luger K. Nucleosome structure and dynamics are
Nakamura N, Wei JH, Seemann J: Modular organization of the mam- coming of age. Nat Struct Mol Biol 26:3, 2019.
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29
CHAPTER 3
Genetic Control of Protein Synthesis, Cell
UNIT I
Function, and Cell Reproduction
Genes, which are located in the nuclei of all cells of the Building Blocks of DNA
body, control heredity from parents to children, as well Figure 3-3 shows the basic chemical compounds involved
as the daily functioning of all the body’s cells. The genes in the formation of DNA. These compounds include the
control cell function by determining which structures, following: (1) phosphoric acid; (2) a sugar called deoxyri-
enzymes, and chemicals are synthesized within the cell. bose; and (3) four nitrogenous bases (two purines, adenine
Figure 3-1 shows the general schema of genetic con- and guanine, and two pyrimidines, thymine and cytosine).
trol. Each gene, which is composed of deoxyribonucleic The phosphoric acid and deoxyribose form the two heli-
acid (DNA), controls the formation of another nucleic cal strands that are the backbone of the DNA molecule,
acid, ribonucleic acid (RNA); this RNA then spreads and the nitrogenous bases lie between the two strands
throughout the cell to control formation of a specific pro- and connect them, as illustrated in Figure 3-2.
tein. The entire process, from transcription of the genetic
code in the nucleus to translation of the RNA code and Nucleotides
the formation of proteins in the cell cytoplasm, is often The first stage of DNA formation is to combine one mol-
referred to as gene expression. ecule of phosphoric acid, one molecule of deoxyribose, and
Because the human body has approximately 20,000 one of the four bases to form an acidic nucleotide. Four
to 25,000 different genes that code for proteins in each separate nucleotides are thus formed, one for each of the
cell, it is possible to form a large number of different cel- four bases: deoxyadenylic, deoxythymidylic, deoxyguanylic,
lular proteins. In fact, RNA molecules transcribed from and deoxycytidylic acids. Figure 3-4 shows the chemical
the same segment of DNA—the same gene—can be pro-
cessed in more than one way by the cell, giving rise to
alternate versions of the protein. The total number of
Plasma Nuclear
different proteins produced by the various cell types in membrane envelope
humans is estimated to be at least 100,000.
Some of the cellular proteins are structural proteins,
which, in association with various lipids and carbohy- Nucleus
drates, form structures of the various intracellular organ- DNA Gene (DNA)
elles discussed in Chapter 2. However, most of the proteins DNA Transcription
transcription
are enzymes that catalyze different chemical reactions in
the cells. For example, enzymes promote all the oxidative RNA RNA formation
reactions that supply energy to the cell, along with synthe-
sis of all the cell chemicals, such as lipids, glycogen, and RNA
splicing
adenosine triphosphate (ATP). mRNA Translation
Ribosomes RNA transport

CELL NUCLEUS GENES CONTROL
PROTEIN SYNTHESIS mRNA Protein formation
In the cell nucleus, large numbers of genes are attached end Translation of
mRNA Cell Cell
on end in extremely long, double-stranded helical molecules
structure enzymes
of DNA having molecular weights measured in the billions.
A very short segment of such a molecule is shown in Figure Protein
Cytosol
3-2. This molecule is composed of several simple chemical Cell function
compounds bound together in a regular pattern, the details Figure 3-1 The general schema whereby genes control cell function.
of which are explained in the next few paragraphs. mRNA, Messenger RNA.
31
Adenine NH2 O Thymine Guanine O H2N Cytosine
P A N H T P G H N C
Sugar P Sugar P
Sugar NH2 O Sugar
Sugar-phosphate Sugar-phosphate
backbone backbone
5’
5’
C T
G T G C A T
C
3’ G C A C G T
A G A
Base pairs Base pairs

3’
Figure 3-2 The helical double-stranded structure of the gene. The outside strands are composed of phosphoric acid and the sugar deoxyribose.
The internal molecules connecting the two strands of the helix are purine and pyrimidine bases, which determine the “code” of the gene.
Phosphoric acid O
H O P O H
H
Deoxyribose H
H H
O C O H
H O C C
C H
C
H
H
H
O
H
Bases H H
N H O
N C N C H
C N
H C O C C C H
C C H
N N N C H
H H H
Adenine Thymine
H
O
N H
N C N C
C N H
H C H O C C H
C C N
N N H N C
H H H
Guanine Cytosine
Purines Pyrimidines
Figure 3-3 The basic building blocks of DNA.
32
Chapter 3 Genetic Control of Protein Synthesis, Cell Function, and Cell Reproduction
structure of deoxyadenylic acid, and Figure 3-5 shows lines) between the purine and pyrimidine bases, the two
simple symbols for the four nucleotides that form DNA. respective DNA strands are held together. Note the fol-
lowing caveats, however:
Nucleotides Are Organized to Form Two 1. Each purine base adenine of one strand always bonds
Strands of DNA Loosely Bound to Each with a pyrimidine base thymine of the other strand.
Other 2. Each purine base guanine always bonds with a py-
UNIT I
Figure 3-2 shows the manner in which multiple nucleo- rimidine base cytosine.
tides are bound together to form two strands of DNA. The Thus, in Figure 3-6, the sequence of complementary
two strands are, in turn, loosely bonded with each other pairs of bases is CG, CG, GC, TA, CG, TA, GC, AT, and
by weak cross-linkages, as illustrated in Figure 3-6 by the AT. Because of the looseness of the hydrogen bonds, the
central dashed lines. Note that the backbone of each DNA two strands can pull apart with ease, and they do so many
strand is composed of alternating phosphoric acid and times during the course of their function in the cell.
deoxyribose molecules. In turn, purine and pyrimidine To put the DNA of Figure 3-6 into its proper physical
bases are attached to the sides of the deoxyribose mol- perspective, one could merely pick up the two ends and
ecules. Then, by means of loose hydrogen bonds (dashed twist them into a helix. Ten pairs of nucleotides are pres-
ent in each full turn of the helix in the DNA molecule.
H H
N
Adenine
N C GENETIC CODE
C N
H C The importance of DNA lies in its ability to control the
Phosphate C C H formation of proteins in the cell, which it achieves by
N N
O H H
O
means of a genetic code. That is, when the two strands of
C H Deoxyribose
a DNA molecule are split apart, the purine and pyrimi-
H O P O C C
C H dine bases projecting to the side of each DNA strand are
C
O H exposed, as shown by the top strand in Figure 3-7. It is
H O H
H
these projecting bases that form the genetic code.
H The genetic code consists of successive “triplets” of
bases—that is, each three successive bases is a code word.
Figure 3-4. Deoxyadenylic acid, one of the nucleotides that make
up DNA. The successive triplets eventually control the sequence of
amino acids in a protein molecule that is to be synthe-
sized in the cell. Note in Figure 3-6 that the top strand
of DNA, reading from left to right, has the genetic code
GGC, AGA, CTT, with the triplets being separated from
A T one another by the arrows. As we follow this genetic code
through Figure 3-7 and Figure 3-8, we see that these
P D P D
Deoxyadenylic acid Deoxythymidylic acid three respective triplets are responsible for successive
placement of the three amino acids, proline, serine, and
glutamic acid, in a newly formed molecule of protein.
TRANSCRIPTION—TRANSFER OF CELL
G C
NUCLEUS DNA CODE TO CYTOPLASM
P D P D RNA CODE
Deoxyguanylic acid Deoxycytidylic acid
Because DNA is located in the cell nucleus, yet most of
Figure 3-5. Symbols for the four nucleotides that combine to form
DNA. Each nucleotide contains phosphoric acid (P), deoxyribose (D),
the cell functions are carried out in the cytoplasm, there
and one of the four nucleotide bases: adenine (A); thymine (T); gua- must be some means for DNA genes of the nucleus to
nine (G); or cytosine (C). control chemical reactions of the cytoplasm. This control
P D P D P D P D P D P D P D P D P D P
G G C A G A C T T
C C G T C T G A A
P D P D P D P D P D P D P D P D P D
Figure 3-6. Arrangement of deoxyribose nucleotides
in a double strand of DNA.
33
DNA strand
D P D P D P D P D P D P D P D P D P
G G C A G A C T T
C C G U C U G A
Figure 3-7. Combination of ribose nucleotides R

P R P R P R P R P R P R P R P
with a strand of DNA to form a molecule of RNA Triphosphate
RNA molecule
that carries the genetic code from the gene to the P P
cytoplasm. The RNA polymerase enzyme moves P P
along the DNA strand and builds the RNA mol-
ecule. RNA polymerase
C C G U C U G A A
Figure 3-8. A portion of an RNA molecule showing three
RNA codons—CCG, UCU, and GAA—that control attachment P R P R P R P R P R P R P R P R P R
of the three amino acids, proline, serine, and glutamic acid,
respectively, to the growing RNA chain. Proline Serine Glutamic acid
is achieved through the intermediary of another type of triphosphates (shown in Figure 3-7 by the two RNA nucleo-
nucleic acid, RNA, the formation of which is controlled tides to the far right during RNA chain formation). These
by DNA of the nucleus. Thus, as shown in Figure 3-7, the last two phosphates are combined with the nucleotide by
code is transferred to RNA in a process called transcrip- high-energy phosphate bonds derived from ATP in the cell.
tion. The RNA, in turn, diffuses from the nucleus through The result of this activation process is that large quan-
nuclear pores into the cytoplasmic compartment, where tities of ATP energy are made available to each of the
it controls protein synthesis. nucleotides. This energy is used to promote chemical
reactions that add each new RNA nucleotide at the end of
RNA IS SYNTHESIZED IN THE NUCLEUS the developing RNA chain.
FROM A DNA TEMPLATE
During RNA synthesis, the two strands of DNA separate RNA CHAIN ASSEMBLY FROM ACTIVATED
temporarily; one of these strands is used as a template for NUCLEOTIDES USING THE DNA STRAND
synthesis of an RNA molecule. The code triplets in the AS A TEMPLATE
DNA result in the formation of complementary code trip-
As shown in Figure 3-7, assembly of RNA is accomplished
lets (called codons) in the RNA. These codons, in turn,
under the influence of an enzyme, RNA polymerase. This
will control the sequence of amino acids in a protein to be
large protein enzyme has many functional properties nec-
synthesized in the cell cytoplasm.
essary for formation of RNA, as follows:
Building Blocks of RNA. The basic building blocks of 1. In the DNA strand immediately ahead of the gene
RNA are almost the same as those of DNA, except for to be transcribed is a sequence of nucleotides called
two differences. First, the sugar deoxyribose is not used the promoter. The RNA polymerase has an appro-
in RNA formation. In its place is another sugar of slightly priate complementary structure that recognizes this
different composition, ribose, which contains an extra hy- promoter and becomes attached to it, which is the
droxyl ion appended to the ribose ring structure. Second, essential step for initiating the formation of RNA.
thymine is replaced by another pyrimidine, uracil. 2. After the RNA polymerase attaches to the promot-
er, the polymerase causes unwinding of about two
Formation of RNA Nucleotides. The basic building
turns of the DNA helix and separation of the un-
blocks of RNA form RNA nucleotides, exactly as described
wound portions of the two strands.
previously for DNA synthesis. Here again, four separate
3. The polymerase then moves along the DNA strand,
nucleotides are used to form RNA. These nucleotides
temporarily unwinding and separating the two
contain the bases adenine, guanine, cytosine, and uracil.
DNA strands at each stage of its movement. As it
Note that these bases are the same as in DNA, except that
moves along, at each stage it adds a new activated
uracil in RNA replaces thymine in DNA.
RNA nucleotide to the end of the newly forming
“Activation” of RNA Nucleotides. The next step in the RNA chain through the following steps:
synthesis of RNA is “activation” of RNA nucleotides by an a. First, it causes a hydrogen bond to form between
enzyme, RNA polymerase. This activation occurs by add- the end base of the DNA strand and the base of
ing two extra phosphate radicals to each nucleotide to form an RNA nucleotide in the nucleoplasm.
34
b. Then, one at a time, the RNA polymerase breaks structures on which protein molecules are actually
two of the three phosphate radicals away from each assembled.
of these RNA nucleotides, liberating large amounts 6. MicroRNAs (miRNAs) are single- stranded RNA
of energy from the broken high-energy phosphate molecules of 21 to 23 nucleotides that can regulate
bonds. This energy is used to cause covalent linkage gene transcription and translation.
of the remaining phosphate on the nucleotide with
MESSENGER RNA—THE CODONS
UNIT I
the ribose on the end of the growing RNA chain.
c. When the RNA polymerase reaches the end of Messenger RNA molecules are long single RNA strands
the DNA gene, it encounters a new sequence of that are suspended in the cytoplasm. These molecules are
DNA nucleotides called the chain-terminating composed of several hundred to several thousand RNA
sequence, which causes the polymerase and the nucleotides in unpaired strands, and they contain codons
newly formed RNA chain to break away from the that are exactly complementary to the code triplets of the
DNA strand. The polymerase then can be used DNA genes. Figure 3-8 shows a small segment of mRNA.
again and again to form more new RNA chains. Its codons are CCG, UCU, and GAA, which are the
d. As the new RNA strand is formed, its weak hy- codons for the amino acids proline, serine, and glutamic
drogen bonds with the DNA template break acid. The transcription of these codons from the DNA
away because the DNA has a high affinity for molecule to the RNA molecule is shown in Figure 3-7.
rebonding with its own complementary DNA
strand. Thus, the RNA chain is forced away from RNA Codons for the Different Amino Acids. Table 3-1
the DNA and is released into the nucleoplasm. lists the RNA codons for the 20 common amino acids
Therefore, the code that is present in the DNA strand found in protein molecules. Note that most of the amino
is eventually transmitted in complementary form to the acids are represented by more than one codon; also, one
RNA chain. The ribose nucleotide bases always combine codon represents the signal “start manufacturing the pro-
with the deoxyribose bases in the following combinations: tein molecule,” and three codons represent “stop manu-
facturing the protein molecule.” In Table 3-1, these two
DNA Base RNA Base
guanine Cytosine
cytosine Guanine Table 3-1 RNA Codons for Amino Acids and for Start
and Stop
adenine Uracil
thymine adenine Amino Acid RNA Codons
Alanine GCU GCC GCA GCG
There Are Several Different Types of RNA. As research
Arginine CGU CGC CGA CGG AGA AGG
on RNA has continued to advance, many different types
of RNA have been discovered. Some types of RNA are in- Asparagine AAU AAC
volved in protein synthesis, whereas other types serve gene Aspartic acid GAU GAC
regulatory functions or are involved in posttranscription- Cysteine UGU UGC
al modification of RNA. The functions of some types of Glutamic acid GAA GAG
RNA, especially those that do not appear to code for pro-
Glutamine CAA CAG
teins, are still mysterious. The following six types of RNA
Glycine GGU GGC GGA GGG
play independent and different roles in protein synthesis:
1. Precursor messenger RNA (pre-mRNA) is a large, Histidine CAU CAC
immature, single strand of RNA that is processed Isoleucine AUU AUC AUA
in the nucleus to form mature messenger RNA Leucine CUU CUC CUA CUG UUA UUG
(mRNA). The pre-RNA includes two different types Lysine AAA AAG
of segments, called introns, which are removed by
Methionine AUG
a process called splicing, and exons, which are re-
Phenylalanine UUU UUC
tained in the final mRNA.
2. Small nuclear RNA (snRNA) directs the splicing of Proline CCU CCC CCA CCG
pre-mRNA to form mRNA. Serine UCU UCC UCA UCG AGC AGU
3. Messenger RNA (mRNA) carries the genetic code Threonine ACU ACC ACA ACG
to the cytoplasm for controlling the type of protein Tryptophan UGG
formed. Tyrosine UAU UAC
4. Transfer RNA (tRNA) transports activated amino
Valine GUU GUC GUA GUG
acids to the ribosomes to be used in assembling the
protein molecule. Start (CI) AUG
5. Ribosomal RNA, along with about 75 different pro- Stop (CT) UAA UAG UGA
teins, forms ribosomes, the physical and chemical CI, Chain-initiating; CT, chain-terminating.
35
types of codons are designated CI for “chain-initiating” appropriate sequence of amino acids in the newly form-
or “start” codon and CT for “chain-terminating” or “stop” ing protein molecule.
codon.
RIBOSOMAL RNA
TRANSFER RNA—THE ANTICODONS
The third type of RNA in the cell is ribosomal RNA,
Another type of RNA that is essential for protein synthesis which constitutes about 60% of the ribosome. The remain-
is called transfer RNA (tRNA) because it transfers amino der of the ribosome is protein, including about 75 types
acids to protein molecules as the protein is being syn- of proteins that are both structural proteins and enzymes
thesized. Each type of tRNA combines specifically with needed to manufacture proteins.
1 of the 20 amino acids that are to be incorporated into The ribosome is the physical structure in the cytoplasm
proteins. The tRNA then acts as a carrier to transport its on which proteins are actually synthesized. However, it
specific type of amino acid to the ribosomes, where pro- always functions in association with the other two types
tein molecules are forming. In the ribosomes, each spe- of RNA; tRNA transports amino acids to the ribosome
cific type of tRNA recognizes a particular codon on the for incorporation into the developing protein, whereas
mRNA (described later) and thereby delivers the appro- mRNA provides the information necessary for sequenc-
priate amino acid to the appropriate place in the chain of ing the amino acids in proper order for each specific type
the newly forming protein molecule. of protein to be manufactured. Thus, the ribosome acts
Transfer RNA, which contains only about 80 nucleo- as a manufacturing plant in which the protein molecules
tides, is a relatively small molecule in comparison with are formed.
mRNA. It is a folded chain of nucleotides with a cloverleaf
appearance similar to that shown in Figure 3-9. At one Formation of Ribosomes in the Nucleolus. The DNA
end of the molecule there is always an adenylic acid to genes for the formation of ribosomal RNA are located in
which the transported amino acid attaches at a hydroxyl five pairs of chromosomes in the nucleus. Each of these
group of the ribose in the adenylic acid. chromosomes contains many duplicates of these particu-
Because the function of tRNA is to cause attachment lar genes because of the large amounts of ribosomal RNA
of a specific amino acid to a forming protein chain, it is required for cellular function.
essential that each type of tRNA also have specificity for As the ribosomal RNA forms, it collects in the nucleo-
a particular codon in the mRNA. The specific code in the lus, a specialized structure lying adjacent to the chromo-
tRNA that allows it to recognize a specific codon is again somes. When large amounts of ribosomal RNA are being
a triplet of nucleotide bases and is called an anticodon. synthesized, as occurs in cells that manufacture large
This anticodon is located approximately in the middle of amounts of protein, the nucleolus is a large structure,
the tRNA molecule (at the bottom of the cloverleaf con- whereas in cells that synthesize little protein, the nucle-
figuration shown in Figure 3-9). During formation of the olus may not even be seen. Ribosomal RNA is specially
protein molecule, the anticodon bases combine loosely by processed in the nucleolus, where it binds with ribosomal
hydrogen bonding with the codon bases of the mRNA. In proteins to form granular condensation products that
this way, the respective amino acids are lined up one after are primordial subunits of ribosomes. These subunits are
another along the mRNA chain, thus establishing the then released from the nucleolus and transported through
the large pores of the nuclear envelope to almost all parts
Alanine
of the cytoplasm. After the subunits enter the cytoplasm,
Cysteine they are assembled to form mature functional ribosomes.
Forming protein Therefore, proteins are formed in the cytoplasm of the
Histidine
Alanine cell, but not in the cell nucleus, because the nucleus does
Phenylalanine not contain mature ribosomes.
Serine
Transfer RNA Proline
Start codon
miRNA AND SMALL INTERFERING RNA
Anticodon A fourth type of RNA in the cell is microRNA (miRNA);
Codon miRNA are short (21 to 23 nucleotides) single-stranded
GGG
AUG GCC UGU CAU GCC UUU UCC CCC AAA CAG GAC UAU
RNA fragments that regulate gene expression (Figure
3-10). The miRNAs are encoded from the transcribed
Ribosome Ribosome DNA of genes, but they are not translated into pro-
Messenger teins and are therefore often called noncoding RNA. The
RNA movement
miRNAs are processed by the cell into molecules that
Figure 3-9. A messenger RNA strand is moving through two ribo- are complementary to mRNA and act to decrease gene
somes. As each codon passes through, an amino acid is added to the
growing protein chain, which is shown in the right-hand ribosome.
expression. The generation of miRNAs involves special
The transfer RNA molecule transports each specific amino acid to the processing of longer primary precursor RNAs called pri-
newly forming protein. miRNAs, which are the primary transcripts of the gene.
36
Another type of miRNA is small interfering RNA

Protein-coding gene miRNA (siRNA), also called silencing RNA or short interfering
RNA. The siRNAs are short, double-stranded RNA mol-
ecules, comprised of 20 to 25 nucleotides, that interfere
Transcription Transcription
with expression of specific genes. siRNAs generally refer
of mRNA of pri-miRNA to synthetic miRNAs and can be administered to silence
UNIT I
pri-miRNA expression of specific genes. They are designed to avoid
nuclear processing by the microprocessor complex and,
Microprocessor after the siRNA enters the cytoplasm, it activates the RISC
complex silencing complex, blocking the translation of mRNA.
Because siRNAs can be tailored for any specific sequence
Nucleus in the gene, they can be used to block translation of any
pre-miRNA mRNA and therefore expression by any gene for which
the nucleotide sequence is known. Researchers have pro-
Cytoplasm posed that siRNAs may become useful therapeutic tools
Transport of pre-miRNA
into cytoplasm to silence genes that contribute to the pathophysiology of
diseases.
Dicer TRANSLATION—FORMATION OF
PROTEINS ON THE RIBOSOMES
Processing of
pre-miRNA into small When a molecule of mRNA comes in contact with a
RNA duplexes ribosome, it travels through the ribosome, beginning at
a predetermined end of the RNA molecule specified by
an appropriate sequence of RNA bases called the chain-
RISC initiating codon. Then, as shown in Figure 3-9, while the
mRNA travels through the ribosome, a protein molecule
is formed, a process called translation. Thus, the ribo-
some reads the codons of the mRNA in much the same
mRNA way that a tape is read as it passes through the playback
RISC-miRNA
head of a tape recorder. Then, when a “stop” (or “chain-
complex terminating”) codon slips past the ribosome, the end of a
protein molecule is signaled, and the protein molecule is
freed into the cytoplasm.
mRNA degradation Translational repression
Polyribosomes. A single mRNA molecule can form
Figure 3-10. Regulation of gene expression by microRNA (miRNA). protein molecules in several ribosomes at the same time
Primary miRNA (pri-miRNA), the primary transcripts of a gene pro-
because the initial end of the RNA strand can pass to a
cessed in the cell nucleus by the microprocessor complex, are con-
verted to pre-miRNAs. These pre-miRNAs are then further processed successive ribosome as it leaves the first, as shown at the
in the cytoplasm by dicer, an enzyme that helps assemble an RNA- bottom left in Figure 3-9 and Figure 3-11. The protein
induced silencing complex (RISC) and generates miRNAs. The miRNAs molecules are in different stages of development in each
regulate gene expression by binding to the complementary region of ribosome. As a result, clusters of ribosomes frequently
the RNA and repressing translation or promoting degradation of the
occur, with 3 to 10 ribosomes being attached to a single
messenger RNA (mRNA) before it can be translated by the ribosome.
mRNA at the same time. These clusters are called polyri-
bosomes.
The pri-miRNAs are then processed in the cell nucleus
An mRNA can cause formation of a protein molecule
by the microprocessor complex to pre-miRNAs, which are
in any ribosome; there is no specificity of ribosomes for
70-nucleotide, stem loop structures. These pre-miRNAs
given types of protein. The ribosome is simply the physi-
are then further processed in the cytoplasm by a specific
cal manufacturing plant in which the chemical reactions
dicer enzyme that helps assemble an RNA-induced silenc-
take place.
ing complex (RISC) and generates miRNAs.
The miRNAs regulate gene expression by binding to the Many Ribosomes Attach to the Endoplasmic
complementary region of the RNA and promoting repres- Reticulum. In Chapter 2, we noted that many ribosomes
sion of translation or degradation of the mRNA before it become attached to the endoplasmic reticulum. This at-
can be translated by the ribosome. miRNAs are believed to tachment occurs because the initial ends of many forming
play an important role in normal regulation of cell function, protein molecules have amino acid sequences that imme-
and alterations in miRNA function have been associated diately attach to specific receptor sites on the endoplas-
with diseases such as cancer and heart disease. mic reticulum, causing these molecules to penetrate the
37
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Guyton & Hall Physiology Review (Guyton Physiology) 4th

Guyton & Hall. Tratado de fisiología médica 14th

Guyton E Hall Tratado De Fisiologia Médica John E. Hall

Tratado de fisiología médica. Guyton y Hall 14th

Guyton E Hall Tratado De Fisiologia Médica John E. Hall

Guyton and Hall

John E. Hall, PhD

Michael E. Hall, MD, MS

GUYTON AND HALL TEXTBOOK OF MEDICAL PHYSIOLOGY,

Copyright © 2021 by Elsevier, Inc. All rights reserved.

Library of Congress Control Number: 2020936245

Publisher: Elyse O’Grady

Last digit is the print number: 9 8 7 6 5 4 3 2 1

Functional Organization of the Human Body

Figure 1-2. Diffusion of fluid and dissolved constituents through the

Regulation ORIGIN OF NUTRIENTS IN THE

Table 1-1 Important Constituents and Physical Characteristics of Extracellular Fluid

5 overcome by the negative feedback control mechanisms

Positive Feedback Can Sometimes Be Useful. The body

Proteins. After water, the most abundant substances in

Chromosomes and DNA

Mitochondrion Rough (granular) Smooth (agranular) Microfilaments

Ribosome Golgi vesicles

vesicles are transported from the endoplasmic reticulum

Secretory Outer membrane

Mitochondrion Two intertwined

Pores 15 nm: Small virus

Chromatin material (DNA)

Lysosomes proteins, carbohydrates, lipids, and other substances in the

Proteins Synthesis by the Rough Endoplasmic Reticu-

Lipid Synthesis by the Smooth Endoplasmic Reticu-

Other Functions of the Endoplasmic Reticulum.

VESICLE BREAKDOWN AND DEGRADATION

Protein Lipid Secretory Types of Vesicles Formed by the Golgi Apparatus—

the cell’s other functions, such as syntheses of substances

Ribosomes Movement of cell

ATP ATP ADP

the cilium can still beat under appropriate conditions.

protein arms composed of the protein dynein, which has

Genetic Control of Protein Synthesis, Cell

Ribosomes RNA transport

Adenine NH2 O Thymine Guanine O H2N Cytosine

Base pairs Base pairs

Figure 3-3 The basic building blocks of DNA.

Figure 3-7. Combination of ribose nucleotides R

Another type of miRNA is small interfering RNA

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Table 1-1 Important Constituents and Physical Characteristics of Extracellular Fluid