Fundamental concepts in physiology: an illustrative study

214 Pages·2016·43.241 MB·English

by  Hai, Chi-Ming

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T I PHYSIOLOGY I FUNDAMENTAL CONCEPTS IN
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AN ILLUSTRATIVE STUDY
Fundamental Concepts in Physiology: An Illustrative Study is designed for
undergraduates interested in the functions of the human body as
preparation for medical school, or for graduate programs in health-related
disciplines. The book covers the basics of physiology while avoiding
excessive overlap with introductory biology or neuroscience.
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Students will learn fundamental concepts of physiology, cell membrane H
transport, and signaling, membrane potentials, synapses, and the
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autonomic nervous system before exploring the physiology of specific
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organ systems in the body. I
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Organ systems covered in the text include the physiology of muscles, the L
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endocrine system, the cardiovascular system, the respiratory and renal
systems, and the gastrointestinal system. Students will also learn about G
regulation of the substrate metabolism and reproductive physiology.
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The highly illustrative text covers basic principles without overloading A
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the reader with excessive detail suitable for more advanced study.
Fundamental Concepts in Physiology is ideal for introductory courses in ILL
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the discipline, as well as courses on human biology. S
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Chi-Ming Hai joined the faculty of Brown University as a professor of TIV
medical science after completion of his Ph.D. in physiology at the E

School of Medicine, Johns Hopkins University. Dr. Hai's research efforts ST
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focus on airway and vascular smooth muscle, asthma, nicotine, and D
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cytoskeleton remodeling. He is the recipient of grants from the National
Institute of Health, the American Heart Association, and the National
Science Foundation. Dr. Hai's written work has been published in
American Journal of Respiratory Cell and Molecular Biology, Circulation
Research, European Journal of Cell Biology, and Journal of Applied
Physiology. He is a member of the American Society for Cell Biology, the
Biophysical Society, and the Invadosome Consortium.
EEddiittiioonn CHI-MING HAI
SKU 80541-1A BY
FUNDAMENTAL CONCEPTS IN
PHYSIOLOGY
AN ILLUSTRATIVE STUDY
FIRST EDITION
CHI-MING HAI
BY
BROWN UNIVERSITY
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Printed in the United States of America
ISBN: 978-1-63487-412-0 (pbk) / 978-1-63487-413-7 (br)
CONTENTS
INTRODUCTION V
CHAPTER 1
Fundamental Concepts of Physiology 1
CHAPTER 2
Cell Membrane Transport and Signaling 5
CHAPTER 3
Cell Membrane Potentials, Synapses, and Autonomic Nervous System 17
CHAPTER 4
Muscle Physiology 33
CHAPTER 5
Endocrine Physiology 55
CHAPTER 6
Cardiovascular Physiology 65
CHAPTER 7
Respiratory Physiology 105
CHAPTER 8
Renal Physiology 129
CHAPTER 9
Gastrointestinal Physiology and Regulation of Substrate Metabolism 155
CHAPTER 10
Reproductive Physiology 179
INDEX 203
Introduction
Human physiology is the study of how organ systems function interactively to support life. As a biological
discipline, physiology is unique in having a focus on multiple layers of organization—organ systems, tis-
sues, cells, and molecules. For example, cardiovascular physiology studies the function of the whole heart,
cardiac muscle cells, ion channels, contractile proteins, neurotransmitters, and hormones. Physiology is
the foundation of medicine. For example, cardiovascular physiology provides the foundation for under-
standing the causes of hypertension and heart failure. Respiratory physiology provides the foundation for
understanding the causes of breathing diffi culties in premature babies and asthmatic patients.
Physiology has been my intellectual home since my undergraduate years. I have three degrees in
physiology, did my postdoctoral training in physiology, and have been teaching physiology at Brown
University for more than twenty-six years. I did my undergraduate degree work in physiology at the
University of Toronto, where I gained my fi rst research experience in physiology as a summer research
intern. I moved a bit north for work on my master’s degree in physiology at the University of Ottawa,
where I published my fi rst paper in a physiology journal. I then turned south for my doctorate in the
Department of Physiology at Johns Hopkins Medical School, where I began my long and continuing
journey in smooth muscle research. After Hopkins, I did my postdoctoral research training in Dr. Richard
Murphy’s laboratory in the Department of Physiology at the University of Virginia. Dr. Murphy and I
developed the four-state crossbridge model for explaining the regulation of smooth muscle contraction
by myosin light chain phosphorylation. Th is model has had some infl uence in smooth muscle research.
After Virginia, I joined the Department of Physiology and Biophysics at Brown University in 1988. After
two promotions and twenty-six years, I am still conducting research on smooth muscle and teaching
physiology at Brown. Th is book is a summary of the lectures I teach in a one-semester, intermediate-level
undergraduate course in physiology, designed to prepare students for careers in a host of health-related
disciplines, including medicine, physician assistant graduate programs, and biomedical engineering.
We live in a world of the Internet, where information is shared by people of the world. Many
high-quality diagrams of physiology and medicine are now available online through both Wikimedia
Commons and scientifi c journals. Authors of these diagrams are typically established scientists in their
fi eld of expertise. In the spirit of resource sharing, I have decided to use many diagrams from Wikimedia
Commons and scientifi c journals, with permission from the publishers. And when not able to fi nd the
necessary diagrams on these resources, I created some diagrams myself.
I sincerely thank Dr. George Biro at the University of Toronto, Dr. Th omas Eddinger at Marquette
University, and Dr. Hae Won Kim, Dr. John Stein, and Mrs. Andrea Sobieraj at Brown University for
reviewing some chapters of this book. Dr. Biro was a faculty member on my MS thesis committee at the
University of Ottawa. Dr. Eddinger and I both did our postdoctoral training in Dr. Richard Murphy’s
lab at the University of Virginia. Drs. Kim and Stein are my colleagues at Brown. Mrs. Sobieraj has been
my senior teaching associate at Brown for longer than I can remember.
1
Fundamental Concepts in Physiology
kkeeyy tteerrmmss
internal environment homeostasis
W hat is Human Physiology? Physiology is about life—the function of living
organisms. Human physiology is the study of how multiple organ systems enable a
human being to live a healthy life. Diagnosis and treatment of diseases of our organ systems
have been developed based on a clear understanding of physiology of organ systems at
multiple layers of organization—molecules, cells, organ systems, and whole organism. Th is
multilayer approach to physiology is emphasized in this book. Physiology is a quantitative
biomedical science. Many major physiological concepts include quantitative analysis of vital
variables, such as blood pressure, blood oxygen tension, blood glucose concentration, pH,
etc. Multiple organ systems are often involved in the regulation of a single variable. Within
limits, moderate dysfunction in one organ system can be compensated by adjustment in
another organ system. For example, the lungs and kidneys together regulate plasma pH. In
uncontrolled diabetes, the detrimental eff ect of excess acid production from dysfunctional
fat metabolism on plasma pH can be minimized by increasing excretion of carbon dioxide
by the lungs. An integrative understanding of the function of multiple organ systems is
important for learning physiology.
1
2 Fundamental Concepts in Physiology: An Illustrative Study
Fundamental Concepts in Physiology: Internal Environment and Homeostasis. Claude
Bernard, a French physiologist, recognized the importance of a physiological “internal environment”
for supporting the survival and function of all cells within the human body. Internal environment
refers to the physical and chemical states of the extracellular fl uid surrounding cells—temperature,
oxygen tension, pH, etc. For example, the core temperature in a healthy individual is regulated at
37oC, with relatively small fl uctuations during a day and menstrual cycle. Similarly, plasma pH in a
healthy person is normally regulated at 7.4 by the coordinated action of the respiratory and kidney
systems. Th erefore, from a physiologist’s point of view, the primary function of organ systems is
to maintain a normal composition of the internal environment—oxygen, carbon dioxide, glucose,
pH, etc.
Walter Cannon, an American physiologist, introduced the concept of homeostasis to describe
the dynamic but stable steady states (blood pressure, oxygen, glucose, etc.) of a living human body
that are maintained by a system of complex and coordinated physiological reactions. Th e term
homeostasis is still being used to describe the normal steady states of physiological variables that are
dynamically regulated by multiple and sometimes antagonistic regulatory mechanisms. For example,
blood pressure homeostasis is regulated by the coordinated regulation of two branches of the
autonomic nervous system—parasympathetic and sympathetic nervous systems. Similarly, plasma
glucose homeostasis is regulated by insulin, glucagon, cortisol, and other hormones. Homeostasis is
a useful concept for thinking about the healthy human body as integrated homeostasis of all physi-
ological variables, when all physiological systems are operating optimally.
Physiological Systems. Prior to the creation of neuroscience as a scientifi c discipline, physiology
covered all organs of the human body, including the nervous system as neurophysiology. Neuroscience
is now typically taught as an independent course in most colleges and universities. To avoid duplica-
tion, I cover mostly non-neural organ systems in this book. Exceptions include neural control of
muscle contraction and the autonomic nervous system. Th e autonomic nervous system regulates
almost all organ systems. Th e following summarizes the topics covered by the chapters in this book.
Cell Membrane Transport and Signaling (Chapter 2). Cell membrane is the interface between
the inside and outside of a cell. Th e cell membrane regulates the transport between intracellular
and extracellular fl uids, a fundamental process for the function of all organ systems—for example,
transport of oxygen and carbon dioxide in the respiratory system and transport of ions and water in
the renal system. In addition, specialized protein molecules (receptors) located in the cell membrane
can respond to specifi c extracellular signal molecules (hormones and neurotransmitters) by activat-
ing intracellular processes, leading to specifi c cell functions, such as secretion and contraction.
Cell Membrane Potentials, Synapses, and Autonomic Nervous System (Chapter 3). Selective
transport of electrically charged ions across the cell membrane results in an electrical potential across
the cell membrane, which is the fundamental mechanism underlying the excitability of nerve and
muscle cells. Th e coupling between receptor signaling and ion transport is the fundamental mecha-
nism underlying synapses at neuron-neuron and neuromuscular junctions. Th e autonomic nervous
system, consisting of parasympathetic and sympathetic branches, regulates the activity of almost all
organ systems in response to whether a person is in the resting or fi ght-or fl ight state.
Fundamental Concepts in Physiology 3
Muscle Physiology (Chapter 4). Muscle contraction is perhaps the most explicit sign of life.
Th e musculoskeletal system under the control of the somatic nervous system supports the posture
and movement of the human body. Motor neurons from the somatic nervous system form junctions
with skeletal muscle cells, where a neurotransmitter released by motor neurons activates receptors
on skeletal muscle cells to initiate a cascade of intracellular signaling processes that lead to muscle
contraction. Finally, biochemical and biophysical interactions between two proteins inside a muscle
cell, actin and myosin, enable the conversion of biochemical energy from breaking a chemical bond
to the production of mechanical energy in the form of molecular motion.
Endocrine Physiology (Chapter 5). Hormones are powerful molecules. At extremely low
concentrations in the plasma, hormones regulate the function of multiple organ systems, such as the
basal metabolic rate, plasma glucose metabolism, cardiac output, and menstrual cycle. Hormones
have unique chemical structures that enable them to activate only specifi c receptors in specifi c target
organs. Th e hypothalamus and pituitary gland in the brain contain seven major hormonal systems
that regulate peripheral endocrine glands and other organ systems, including the thyroid gland,
liver, kidney, and uterus. Insuffi cient or excessive secretion of a hormone can lead to diseases. For
example, insuffi cient secretion of thyroid hormone in newborns can lead to irreversible retardation
in brain development; therefore, newborns are routinely screened for thyroid insuffi ciency and, if
necessary, treated with a thyroid hormone. In contrast, an excessive thyroid hormone secretion can
lead to uncontrolled increases in heart rate and body metabolism. Some hormones—e.g., insulin
and cortisol—are absolutely essential for survival. Th e availability of insulin now allows a person
with type 1 diabetes mellitus to live a reasonably normal life. Type 2 diabetes mellitus, however, is
increasingly becoming a major public health problem in affl uent societies.
Cardiovascular Physiology (Chapter 6). Blood oxygen transport by the cardiovascular system
is a major determinant of the level of physical activity that a person can achieve. Oxygen transport
is a product of cardiac output (the rate of blood fl ow pumped by the heart through the circulatory
system) multiplied by the blood oxygen content, which is determined by hemoglobin concentration
and its oxygenation. Th erefore, dysfunction of the cardiovascular system such as cardiac failure can
lead to abrupt termination of physical activity, and even death. Recognizing the critical role of the car-
diovascular system in determining performance in endurance exercise, some endurance athletes have
illegally boosted blood oxygen transport by blood transfusion (blood doping) prior to a competition.
Respiratory Physiology (Chapter 7). Breathing is a telling sign of life. Th e American Lung
Association used the following slogan some years ago: “When you can’t breathe, nothing else
matters.” Breathing is a major challenge to asthmatic patients because their hyperactive airways can
easily close. A limited list of medicine is available to dilate airways in asthmatic patients. Premature
babies have breathing diffi culties because immature lungs are stiff due to insuffi cient production of
the biological molecule, surfactant, in the lungs. Synthetic surfactant is now available for improving
the lung function of premature babies. High altitude is a challenging environment for the human
body because the low atmospheric pressure results in a low partial pressure of oxygen for blood
oxygenation. Adaptation to high altitude illustrates the important role of the respiratory system in
regulating both blood oxygen content and pH.
4 Fundamental Concepts in Physiology: An Illustrative Study
Renal Physiology (Chapter 8). Kidneys are essential for removal of waste products from the
body, activation of vitamin D, and production of erythropoietin. Patients with kidney failure need
dialysis regularly to remove waste products from the body, and often erythropoietin and activated
vitamin D supplementation for survival. Th e kidneys—by controlling the output from the body—
and the gastrointestinal system—by controlling the input to the body—together regulate the chemi-
cal composition of the extracellular fl uid. Th e kidneys consist of blood vessels and urinary tubules,
where waste products are transported from the blood to the urine. Th erefore, renal physiology is
concerned with understanding the basic mechanisms for water and solute transport, as well as their
regulation by several hormonal systems. Discovery of the transport mechanisms in the kidneys has
led to the development of drugs for treating hypertension by controlling extracellular fl uid volume.
Gastrointestinal Physiology and Regulation of Substrate Metabolism (Chapter 9). Th e
ingestion, digestion, and absorption of food by the gastrointestinal system are essential for survival of
the human body. Excessive intake of food, however, can result in obesity and associated diseases such
as diabetes, atherosclerosis, and cancer. Th e gastrointestinal system is essentially a tube that begins
in the mouth and ends in the anus. Movement of food along the gastrointestinal tract is powered
mostly by smooth muscle cells and regulated by multiple sphincters. To extract nutrients from food,
secretory cells lining the gastrointestinal system produce digestive enzymes and other factors for
breaking down food into small molecules, which are then transported by absorptive cells to the blood
and lymphatic circulation. Multiple hormones regulate the function of the gastrointestinal tract.
Hormones and the autonomic nervous system regulate gastrointestinal motility and secretion. In
addition, multiple hormones are involved in the control of appetite.
Reproductive Physiology (Chapter 10). Th anks to reproductive physiology, we have all
arrived safely in this world. I fi nd reproductive physiology a particularly fascinating subject because
it not only regulates the health of the individual, but also enables the production of new human
beings. Both male and female reproductive systems consist of reproductive organs for producing
sperms or eggs, and endocrine organs for regulating the function of reproductive organs. Th ere are
major similarities and diff erences between the male and female reproductive systems. For example,
testosterone is the major male reproductive hormone produced by the testis, whereas estrogen
and progesterone are the major female reproductive hormones produced by the ovaries; however,
both male and female endocrine systems utilize the same hypothalamic and pituitary hormones to
regulate reproductive function. Furthermore, the female reproductive hormones oscillate during
menstrual cycles, whereas the male reproductive hormones are relatively stable. Meiosis is the basic
process for production of both sperms and oocytes; however, the progression of fi rst and second
meiosis in the male reproductive system is continuous, whereas the progression of second meiosis
in the female reproductive system requires fertilization of the oocyte. Understanding reproductive
physiology has led to the development of contraceptives and i n vitro fertilization, which have had
a dramatic eff ect on human population.
2
Cell Membrane Transport and Signaling
kkeeyy tteerrmmss
diff usion ion channels
osmosis facilitated diff usion
osmolarity coupled carrier transport
osmotic pressure primary active transport
exocytosis epithelial transport
T he c ell membrane is a selective and regulated barrier between intracellular and e xtra-
cellular fl uids. As shown in Fig. 2.1, a phospholipid bilayer forms the basic backbone
of the cell membrane. Small and lipid-soluble molecules (e.g., oxygen and carbon dioxide)
can cross the phospholipid bilayer by simple diff usion, whereas large and charged molecules
require transport proteins in the cell membrane for crossing the cell membrane.
Diff usion is a process by which molecules move from a region of higher concentration to
a region of lower concentration, as shown in Fig. 2.2. Random motion of molecules is the
fundamental mechanism of d iff usion. Molecules in the region of higher concentration have
a higher probability of molecular collisions, which can result in movement to the region of
lower concentration. In comparison, molecules in the region of lower concentration have
a lower probability of molecular collisions. Concentration diff erence is the fundamental
driving force for diff usional transport. For diff usion of a molecule across the cell membrane,
the permeability of the cell membrane for the molecule and the total surface area available
for diff usion are additional determinants of diff usional transport. Th e following equation
summarizes the contributions of these variables to the net fl ux of diff usion in moles/time:
Net Flux = Permeability × Surface Area × (Concentration – Concentration )
1 2
5