1

CHAPTER
Homeostasis:
A Framework for Human Physiology

1.1 The Scope of Human Physiology

1.2 How Is the Body Organized?
1.3 Body Fluid Compartments
1.4 Homeostasis: A Defining Feature
of Physiology
1.5 General Characteristics of
Homeostatic Control Systems
1.6 Components of Homeostatic Control
Systems
1.7 The Role of Intercellular Chemical
Messengers in Homeostasis
1.8 Processes Related to Homeostasis
1.9 General Principles of Physiology
Chapter 1 Clinical Case Study
Coping with changes in external temperature and oxygen levels even in extreme
conditions are examples of homeostasis. Andre Schoenherr/Stone/Getty Images

T
he purpose of this chapter is to provide an orientation to the
subject of human physiology and the central role of homeostasis—
the maintenance of a stable internal environment—in the study
of this science. The mountain climbers shown here are experiencing
numerous challenges that must be met by their hearts, lungs, and other
organs. For example, their hearts need to work harder to pump more
blood each minute to their muscles, their lungs must maximize the
amount of oxygen brought into the blood, and they must maintain their
body temperature in the cold environment. An understanding of these
processes requires knowledge of the structures and relationships of the
body parts. For this reason, this chapter also introduces the way the
body is organized into cells, tissues, organs, organ systems, and fluid
compartments. Lastly, several “General Principles of Physiology” are
introduced. These serve as unifying themes throughout the textbook,
and the reader is encouraged to return to them often to see how they
apply to the material covered in subsequent chapters. ■

1
1.1 The Scope of Human Fertilized egg

Physiology Cell
Physiology is the study of how living organisms function. At division
and
one end of the spectrum, it includes the study of individual growth
molecules—for example, how a particular protein’s shape and
electrical charge, if any, allow it to function as a channel for ions
Cell
to move into or out of a cell. At the other end, it is concerned with differentiation
complex processes that depend on the integrated functions of
many organs in the body—for example, how the heart, kidneys, Specialized
and several glands all function together to cause the excretion of cell types
more sodium ions in the urine when a person has eaten salty food.
Epithelial Connective- Neuron Muscle
Physiologists are interested in function and integration— cell tissue cell cell
how parts of the body work together at various levels of organi-
zation and, most importantly, in the entire organism. Even when
physiologists study parts of organisms, all the way down to indi-
Tissues
vidual molecules, the intention is ultimately to apply the informa-
tion they gain to understanding the function of the whole body. As
the nineteenth-century physiologist Claude Bernard put it, “After
carrying out an analysis of phenomena, we must . . . always recon-
struct our physiological synthesis, so as to see the joint action of Epithelial Connective Nervous Muscle
tissue tissue tissue tissue
all the parts we have isolated.”
In many areas of this text, we will relate physiology to human
health. Some disease states can be viewed as physiology “gone
wrong,” or pathophysiology, which makes an understanding of
physiology essential for the study and practice of medicine. Indeed,
many physiologists are actively engaged in research on the physi-
ological bases of a wide range of diseases. In this text, we will give
many examples of the pathophysiology that underlies disease. A Organ
handy index of all the diseases and medical conditions discussed in (kidney) Functional
this text, and their causes and treatments, appears in Appendix B. unit
A related field of science is anatomy, which is the study of (nephron)
the structures of body parts. Throughout this text, we will typically
provide an overview of the anatomy of body parts, such as the
lungs, kidneys, brain, and others. Without a basic understanding of
structures, it would be difficult to understand physiology because,
as we will see, the structures of objects determine their functions.
For this reason, we turn first to an overview of the anatomical
Kidney
organization of the human body, including the ways in which the
cells of the body are organized into higher levels of structure.
Ureter

Stu d y a n d Revi ew 1.1

■ Physiology: study of the functions of the body parts Bladder

■ Pathophysiology: study of disease states (physiological Urethra

dysfunction)
Organ system
Review Question: Distinguish between anatomy, physiology,
(Urinary system)
and pathophysiology. How are they related? (Answer found in
Appendix A.) Figure 1.1 Levels of cellular organization. The nephron is not drawn
to scale.

begins as a single cell, a fertilized egg, which divides to create

1.2 How Is the Body Organized? two cells, each of which divides in turn to result in four cells,
and so on.
The simplest structural units into which a complex multicellular If cell multiplication were the only event occurring, the end
organism can be divided and still retain the functions charac- result would be a spherical mass of identical cells. During develop-
teristic of life are called cells (Figure 1.1). Each human being ment, however, each cell becomes specialized for the performance
2 Chapter 1
of a particular function, such as producing force and movement or of the gastrointestinal tract—and their contraction decreases the
generating electrical signals. The process of transforming an unspe- diameter or shortens the length of these tubes. For example, con-
cialized cell into a specialized cell is known as cell differentiation, traction of smooth muscle cells along the esophagus—the tube
one of the most exciting areas of study in biology today. leading from the pharynx to the stomach—helps “squeeze” swal-
About 200 distinct kinds of cells can be identified in the lowed food down to the stomach.
body in terms of differences in structure and function. When cells Cardiac and smooth muscle tissues are said to be “involun-
are classified according to the broad types of function they per- tary” muscle, because you cannot consciously alter the activity
form, however, four major categories emerge: of these types of muscle. You will learn about the structure and
function of each of the three types of muscle cells in Chapters 9
■■ muscle cells
and 12.
■■ neurons
■■ epithelial cells
■■ connective-tissue cells Neurons and Nervous Tissue
A neuron is a cell of the nervous system that is specialized
In each of these functional categories, several cell types perform
to initiate, integrate, and conduct electrical signals to other
variations of the specialized function. For example, there are
cells, sometimes over long distances. A signal may initiate new
three types of muscle cells—skeletal, cardiac, and smooth. These
electrical signals in other neurons, or it may stimulate a gland
cells differ from each other in shape, in the mechanisms control-
cell to secrete substances or a muscle cell to contract. Thus,
ling their contractile activity, and in their location in the various
neurons provide a major means of controlling the activities of
organs of the body, but each of them is a muscle cell.
other cells.
In addition to differentiating, cells migrate to new locations
The incredible complexity of connections between neu-
during development and form selective adhesions with other cells
rons underlies such phenomena as consciousness and perception.
to produce multicellular structures. In this manner, the cells of the
A collection of neurons forms nervous tissue, such as that of the
body arrange themselves in various combinations to form a hierarchy
brain or spinal cord. In some parts of the body, cellular extensions
of organized structures. Differentiated cells with similar properties
from many neurons are packaged together along with connective
aggregate to form tissues. Corresponding to the four general catego-
tissue (described shortly); these neuron extensions form a nerve,
ries of differentiated cells, there are four general types of tissues:
which carries the signals from many neurons between the nervous
■■ muscle tissue system and other parts of the body. Neurons, nervous tissue, and
■■ nervous tissue the nervous system will be covered in Chapter 6.
■■ epithelial tissue
■■ connective tissue Epithelial Cells and Epithelial Tissue
The term tissue is used in different ways. It is formally defined Epithelial cells are specialized for the selective secretion and
as an aggregate of a single type of specialized cell. However, it is absorption of ions and organic molecules, and for protection.
also commonly used to denote the general cellular fabric of any These cells are characterized and named according to their unique
organ or structure—for example, kidney tissue or lung tissue, each shapes, including cuboidal (cube-shaped), columnar (elongated),
of which in fact usually contains all four types of tissue. squamous (flattened), and ciliated. Epithelial tissue (known as an
As you will see shortly, one type of tissue combines with epithelium) may form from any type of epithelial cell.
other types of tissues to form organs, such as the heart, lungs, and Epithelia may be arranged in single-cell-thick tissue, called
kidneys. Organs, in turn, work together as organ systems, such as a simple epithelium, or a thicker tissue consisting of numerous
the urinary system (see Figure 1.1). We turn now to a brief discus- layers of cells, called a stratified epithelium. The type of epithe-
sion of each of the four general types of cells and tissues that make lium that forms in a given region of the body reflects the function
up the organs of the human body. of that particular epithelium. For example, the epithelium that
lines the inner surface of the main airway, the trachea, consists of
ciliated epithelial cells (see Chapter 13). The beating of these cilia
Muscle Cells and Tissue helps propel mucus up the trachea and into the mouth, which aids
As noted, there are three types of muscle cells. These cells form in preventing airborne particles and pollutants from reaching the
skeletal, cardiac, or smooth muscle tissue. All muscle cells are sensitive lung tissue.
specialized to generate mechanical force. Epithelia are located at the surfaces that cover the body or
Skeletal muscle cells are attached through other structures individual organs, and they line the inner surfaces of the tubular
to bones and produce movements of the limbs or trunk. They are and hollow structures within the body, such as the trachea (just
also attached to skin, such as the muscles producing facial expres- mentioned). Epithelial cells rest on an extracellular protein layer called
sions. Contraction of skeletal muscle is under voluntary control, the basement membrane, which (among other functions) anchors
which means that you can choose to contract a skeletal muscle the tissue (Figure 1.2). The side of the cell anchored to the basement
whenever you wish. membrane is called the basolateral side; the opposite side, which typi-
Cardiac muscle cells are found only in the heart. When car- cally faces the interior (called the lumen) of a structure such as the
diac muscle cells generate force, the heart contracts and conse- trachea or the tubules of the kidneys, is called the apical side.
quently pumps blood into the circulation. A defining feature of many epithelia is that the two sides
Smooth muscle cells make up part of the walls of many of of all the epithelial cells in the tissue may perform different
the tubes in the body—blood vessels, for example, or the tubes physiological functions. In addition, the cells are held together
Homeostasis: A Framework for Human Physiology 3
 of a mixture of proteins; polysaccharides (chains of sugar mol-
ecules); and, in some cases, minerals, specific for any given tissue.
The ECM serves two general functions:
Blood vessel
Epithelial cell
■■ provides a scaffold for cellular attachments
Glucose
molecule ■■ transmits information in the form of chemical messengers
to the cells to help regulate their activity, migration,
Basolateral growth, and differentiation
membranes
(transport glucose
out of cell) Some of the proteins of the ECM are known as fibers, insolu-
ble proteins including ropelike collagen fibers and ­rubberband-like
Tight junction
elastin fibers. Others are a mixture of nonfibrous proteins that
Tubular contain carbohydrate. In some ways, the ECM is analogous
lumen Apical
membrane to reinforced concrete. The fibers of the matrix, particularly
(transports glucose collagen, which constitutes as much as one-third of all bodily
into cell) proteins, are like the reinforcing iron mesh or rods in the concrete.
The carbohydrate-­containing protein molecules are analogous to
Basement the surrounding cement. However, these latter molecules are not
membrane merely inert packing material, as in concrete, but function as adhe-
sion or recognition molecules between cells. Thus, they are links
in the communication between extracellular messenger molecules
Figure 1.2 Epithelial tissue lining the inside of a structure such as a and cells.
kidney tubule. The basolateral side of the cell is attached to a basement
membrane. Each side of the cell can perform different functions, as in
this example in which glucose is transported across the epithelium, first
directed into the cell, and then directed out of the cell.
Organs and Organ Systems
Organs are composed of two or more of the four kinds of tissues
arranged in various proportions and patterns, such as sheets,
along their lateral surfaces between the apical and basolateral tubes, layers, bundles, and strips. For example, the kidneys
membranes by extracellular barriers called tight junctions (look consist of:
ahead to Figure 3.9, b and c, for a depiction of tight junctions). ■■ a series of small tubes, each composed of a simple
Tight junctions function as selective barriers regulating the epithelium
exchange of molecules. For example, as shown in Figure 1.2 for ■■ blood vessels, whose walls contain varying quantities of
a kidney tubule, the apical membranes transport useful solutes smooth muscle and connective tissue
such as the sugar glucose from the tubule lumen into the epithe- ■■ extensions from neurons that end near the muscle and
lial cell; the basolateral sides of the cells transport glucose out epithelial cells
of the cell and into the surrounding fluid where it can reach the ■■ a loose network of connective-tissue elements that are
bloodstream. The tight junctions prevent glucose from leaking interspersed throughout the kidneys and include the
“backward.” protective capsule that surrounds the organ
Many organs are comprised of small, similar subunits
often referred to as functional units, each performing the func-
Connective-Tissue Cells and Connective Tissue tion of the organ. For example, the functional unit of the kidney,
Connective-tissue cells, as their name implies, connect, anchor, the nephron, contains the small tubes mentioned in the previous
and support the structures of the body. Some connective- paragraph. The total production of urine by the kidneys is the
tissue cells are found in the loose meshwork of cells and sum of the amounts produced by the 2 million or so individual
fibers underlying most epithelial layers; this is called loose nephrons.
connective tissue. Another type called dense connective tis- Finally, we have the organ system, a collection of organs
sue includes the tough, rigid tissue that makes up tendons that together perform an overall function (see Figure 1.1). For
and ligaments. Other types of connective tissue include bone, example, the urinary system consists of the kidneys; the uri-
cartilage, and adipose (fat-storing) tissue. Finally, blood is nary bladder; the ureters, the tubes leading from the kidneys
a type of fluid connective tissue. This is because the cells to the bladder; and the urethra, the tube leading from the
in the blood have the same embryonic origin as other connec- bladder to the exterior. Table 1.1 lists the components and
tive tissue, and because the blood connects the various organs functions of the organ systems in the body. It is critical to
and tissues of the body through the delivery of nutrients, recognize, however, that organ systems do not function “in a
removal of wastes, and transport of chemical signals from one vacuum.” That is, they function together to maintain a healthy
part of the body to another. body. As just one example, blood pressure is controlled by the
An important function of some connective tissue is to form circulatory, urinary, nervous, and endocrine systems working
the extracellular matrix (ECM) around cells. The ECM consists together.
4 Chapter 1
TABLE 1.1 Organ Systems of the Body
System Major Organs or Tissues Primary Functions
Circulatory Heart, blood vessels, blood Transport of blood throughout the body

Digestive Mouth, salivary glands, pharynx, esophagus, stomach, small Digestion and absorption of nutrients and water;
and large intestines, anus, pancreas, liver, gallbladder elimination of wastes

Endocrine All glands or organs secreting hormones: pancreas, testes, Regulation and coordination of many activities in the
ovaries, hypothalamus, kidneys, pituitary, thyroid, parathyroids, body, including growth, metabolism, reproduction, blood
adrenals, stomach, small intestine, liver, adipose tissue, heart, pressure, water and electrolyte balance, and others
and pineal gland; and endocrine cells in other organs

Immune White blood cells and their organs of production Defense against pathogens

Integumentary Skin Protection against injury and dehydration; defense

against pathogens; regulation of body temperature

Lymphatic Lymph vessels, lymph nodes Collection of extracellular fluid for return to blood;
participation in immune defenses; absorption of fats from
digestive system

Musculoskeletal Cartilage, bone, ligaments, tendons, joints, skeletal muscle Support, protection, and movement of the body;
production of blood cells

Nervous Brain, spinal cord, peripheral nerves and ganglia, sense organs Regulation and coordination of many activities in
the body, including most of those regulated by the
endocrine system; detection of and response to changes
in the internal and external environments; states of
consciousness; learning; memory; emotion; others

Reproductive Male: testes, penis, and associated ducts and glands Male: production of sperm; transfer of sperm to female
Female: ovaries, fallopian tubes, uterus, vagina, mammary Female: production of eggs; provision of a nutritive
glands environment for the developing embryo and fetus;
nutrition of the infant

Respiratory Nose, pharynx, larynx, trachea, bronchi, lungs Exchange of carbon dioxide and oxygen; regulation of
hydrogen ion concentration in the body fluids

Urinary Kidneys, ureters, bladder, urethra Regulation of plasma composition through controlled
excretion of ions, water, and organic wastes

St u d y an d Review 1.2 St udy and Review 1 . 2 —c o ntinue d

■ Cells: simplest structural units into which a complex ■ Tissues: aggregates of differentiated cells with similar
multicellular organism can be divided and still retain the properties; correspond to the four general types of specialized
functions characteristic of life cells
■ Cell differentiation: formation of four general types of ■ Organs: composed of two or more of the four kinds of tissues
specialized cells ∙∙ Many organs contain multiple, small, similar functional units.
∙∙ Muscle cells: generate the mechanical activities that produce ■ Organ system: group of organs that perform an overall function
force and movement; 3 types include skeletal, cardiac, and
smooth muscle cells Review Question: It is a simplification to refer to organ systems
∙∙ Neurons: initiate and conduct electrical signals as if they function independently from each other. Why? Refer to
Table 1.1 and give two or three examples of how the functions of
∙∙ Epithelial cells: form barriers and selectively secrete and
different organ systems overlap. (Answer found in Appendix A.)
absorb ions and organic molecules; basolateral surface rests
on a basement membrane
∙∙ Connective-tissue cells: connect, anchor, and support
the structures of the body; form the extracellular 1.3 Body Fluid Compartments
matrix, which consists of fibers such as collagen and
Another useful way to think about how the body is organized
elastin
is to consider body fluid compartments. When we refer to
“body fluid,” we are referring to a watery solution of dissolved
Homeostasis: A Framework for Human Physiology 5
substances such as oxygen, nutrients, and wastes. This solution solute composition. In contrast, the composition of the extra-
is present within and around all cells of the body, and within cellular fluid is very different from that of the intracellular
blood vessels, and is known as the internal environment. Body fluid.
fluids exist in three compartments: Maintaining differences in fluid composition between
intracellular and extracellular fluid compartments is an impor-
■■ Intracellular fluid is the fluid contained within all the
tant way in which cells regulate their own activity. For example,
cells of the body and accounts for about 67% of all the
intracellular fluid contains many different proteins that are
water in the body.
important in regulating cellular events such as growth and
■■ Plasma is the fluid portion of blood in which blood cells
metabolism. These proteins must be retained within the intracel-
are suspended, and accounts for about 7% of total-body
lular fluid and are not required in the extracellular fluid.
water.
Compartmentalization is an important feature of physi-
■■ Interstitial fluid is the fluid that lies around and between
ology and is achieved by barriers between the compartments.
cells (in the space known as the interstitium) and makes
The properties of the barriers determine which substances
up about 26% of total-body water.
can move between compartments. These movements, in turn,
Together, the plasma and interstitial fluid comprise the extracell­ account for the differences in composition of the different com-
ular fluid of the body. Therefore, the total volume of extracel- partments. In the case of the body fluid compartments, plasma
lular fluid is the sum of the plasma and interstitial fluid volumes. membranes that surround each cell separate the intracellular
Figure 1.3 summarizes the relative volumes of water in the dif- fluid from the extracellular fluid. Chapters 3 and 4 describe the
ferent fluid compartments of the body. Water accounts for about properties of plasma membranes and how they account for the
55%–60% of body weight in an adult. profound differences between intracellular and extracellular
As the blood flows through the smallest of blood ves- fluid. In contrast, the two components of extracellular fluid—
sels in all parts of the body, the plasma exchanges oxygen, the interstitial fluid and the plasma—are separated from each
nutrients, wastes, and other substances with the interstitial other by the walls of the blood vessels. Chapter 12 discusses
fluid. Because of these exchanges, concentrations of dissolved how this barrier normally keeps most of the extracellular fluid
substances are virtually identical in the plasma and intersti- in the interstitial compartment and restricts proteins mainly to
tial fluid, except for protein concentration (which, as you will the plasma.
learn in Chapter 12, remains higher in plasma than in intersti- With this understanding of the structural organization of the
tial fluid). With this major exception, the entire extracellular body, we turn to a description of how balance is maintained in the
fluid may be considered to have an essentially homogeneous internal environment of the body.

70 (67%)
Percentage of total-body water

Intracellular fluid 60
28 L
50
Red blood
40
cell
Plasma 3 L
Capillary 30 (26%)

20

10 (7%)
Interstitial fluid
11 L
Plasma Interstitial Intracellular
fluid fluid
(a) Movements of water between body fluid (b) Relative amounts of water in body fluid
compartments compartments

Figure 1.3 Fluid compartments of the body. Volumes are for a typical 70-kilogram (kg) (154-pound) person. (a) The bidirectional arrows indicate
that fluid can move between any two adjacent compartments. Total-body water is about 42 liters (L), which makes up about 55%–60% of body
weight. (b) The approximate percentage of total-body water normally found in each compartment.

DIG DEEPER
■ What fraction of total-body water is extracellular? Assume that water constitutes 60% of a person’s body weight. What fraction of a person’s
body weight is due to extracellular body water?
Answer found in Appendix A.

6 Chapter 1
 St u d y an d Review 1.3 Consider swings in the concentration of glucose in the blood
over the course of a day (Figure 1.4). After a typical meal, car-
■ Extracellular fluid: composed of the interstitial fluid (the fluid bohydrates in food are broken down in the intestines into glucose
between cells [within the space called the interstitium]) and molecules, which are then absorbed across the intestinal epithe-
the plasma (noncellular portion of blood) lium and released into the blood. As a consequence, the blood
∙∙ Interstititial fluid: ~75%–80% of the extracellular fluid ­glucose concentration increases considerably within a short time
∙∙ Plasma: ~20%–25% of the extracellular fluid after eating. Clearly, such a large change in the blood concentration
of glucose is not consistent with the idea of a stable or static inter-
■ Interstitial fluid and plasma have similar composition except
nal environment. What is important is that once the concentra-
plasma contains a much greater concentration of protein.
tion of glucose in the blood increases, compensatory ­mechanisms
■ Intracellular fluid: the fluid inside cells restore it toward the concentration it was before the meal.
■ Internal environment: total-body fluid, made up of 2/3 These homeostatic compensatory mechanisms do not, how-
intracellular fluid and 1/3 extracellular fluid ever, overshoot to any significant degree in the opposite direction.
That is, the blood glucose usually does not decrease below the pre-
■ Different compositions of the compartments reflect the
meal concentration, or does so only slightly. In the case of glucose,
activities of the barriers separating them.
the endocrine system is primarily responsible for this adjustment, by
Review Question: If a person were to receive a wound that resulted regulating the uptake of glucose from the blood into organs such as
in significant loss of blood, which body fluid compartment would muscles. However, a wide variety of control systems may be initiated
be immediately affected? How might a health care professional to regulate other homeostatic processes. In later chapters, we will
restore fluid to that compartment? (Answer found in Appendix A.)
see how every organ of the human body contributes to homeostasis,
sometimes in multiple ways, and usually in concert with each other.
Homeostasis, therefore, does not imply that a given physiologi-
1.4 Homeostasis: A Defining cal function or variable is rigidly constant with respect to time but
Feature of Physiology that it fluctuates within a predictable and often narrow range. When
disturbed above or below the normal range, it is restored to normal.
From the earliest days of physiology—at least as early as the time What do we mean when we say that something varies within
of Aristotle—physicians recognized that good health was some- a normal range? This depends on just what we are monitoring. If the
how associated with a balance among the multiple life-sustaining oxygen and carbon dioxide levels in the arterial blood of a healthy
forces (“humours”) in the body. It would take millennia, however, person are measured, they barely change over the course of time,
for scientists to determine what it was that was being balanced even if the person exercises. Such a system is said to be tightly con-
and how this balance was achieved. The advent of modern tools trolled and to demonstrate very little variability or scatter around an
of science, including the ordinary microscope, led to the discov- average value. Blood glucose concentrations, as we have seen, may
ery that the human body is composed of trillions of cells, each vary considerably over the course of a day. Yet, if the daily average
of which can permit movement of certain substances—but not glucose concentration was determined in the same person on many
others—across the plasma membrane. Over the course of the consecutive days, it would be much more predictable over days or
nineteenth and twentieth centuries, it became clear that most cells even years than random, individual measurements of glucose over
are in contact with the interstitial fluid. The interstitial fluid, in the course of a single day. In other words, there may be considerable
turn, was found to be in a state of flux, with water and solutes such variation in glucose values over short time periods, but less when
as ions and gases moving back and forth through it between the they are averaged over long periods of time. This has led to the con-
cell interiors and the blood in nearby capillaries (see Figure 1.3a). cept that homeostasis is a state of dynamic constancy. In such a
It was further determined by careful observation that most state, a given variable like blood glucose may vary in the short term
of the common physiological variables found in healthy organ- but is stable and predictable when averaged over the long term.
isms such as humans—blood pressure; body temperature; and
blood-borne factors such as oxygen, glucose, and sodium ions, 160
concentration (mg/dL)

for example—are maintained within a predictable range. This 140

Blood glucose

is true despite external environmental conditions that may be far Breakfast Lunch Dinner
from constant. Thus was born the idea, first put forth by Claude 120
Bernard, of a constant internal environment that is a prerequisite 100
for good health, a concept later refined by the American physiolo-
80
gist Walter Cannon, who coined the term homeostasis.
Originally, homeostasis was defined as a state of reason- 60
12:00 A.M. 6:00 A.M. 12:00 P.M. 6:00 P.M. 12:00 A.M.
ably stable balance between physiological variables such as those
Time of day
just described. However, this simple definition does not provide a
full appreciation of what homeostasis entails. There probably is
Figure 1.4 Changes in blood glucose concentration during a
no such thing as a physiological variable that is constant over long typical 24 h period. Note that glucose concentration increases after
periods of time. In fact, some variables undergo fairly dramatic each meal, more so after larger meals, and then returns to the premeal
swings around an average value during the course of a day, yet are concentration in a short while. The profile shown here is that of a person
still considered to be in balance. That is because homeostasis is a who is homeostatic for blood glucose, even though concentrations of
dynamic, not a static, process. this sugar vary considerably throughout the day.
Homeostasis: A Framework for Human Physiology 7
 It is also important to realize that a person may be homeo- remains more or less constant. The system is in a steady state, defined
static for one variable but not homeostatic for another. Homeosta- as a system in which a particular variable—temperature, in this
sis must be described differently, therefore, for each variable. For case—is not changing but in which energy—in this case, heat—must
example, as long as the concentration of sodium ions (Na+) in the be added continuously to maintain a stable, homeostatic condition.
blood remains within its normal range, Na+ homeostasis exists. (Steady state differs from equilibrium, in which a particular ­variable
However, a person whose Na+ concentration is homeostatic may is not changing but no input of energy is required to maintain the
suffer from other disturbances, such as an abnormally low pH in constancy.) The steady-state temperature in our example is known as
the blood resulting from kidney disease, a condition that could be the set point of the thermoregulatory system.
fatal. Just one nonhomeostatic variable, among the many that can All homeostatic control systems operate around a set point.
be described, can have life-threatening consequences. There are set points for blood pressure, plasma ion concentrations,
Often, when one variable becomes significantly out of bal- total-body water, and so on. Stability of an internal environmental
ance, other variables in the body become nonhomeostatic as a variable is achieved by the balancing of inputs and outputs. In the
consequence. For example, when you exercise strenuously and previous example, the variable (body temperature) remains constant
begin to get warm, you perspire, which helps maintain body because metabolic heat production (input) equals heat loss from the
temperature homeostasis. This is important, because many cells body (output).
(notably neurons) malfunction at elevated temperatures. However, Now imagine that we rapidly decrease the temperature of the
the water that is lost in perspiration creates a situation in which room, say to 5°C, and keep it there. This immediately increases
total-body water is no longer in balance. the loss of heat from our subject’s warm skin, upsetting the bal-
In general, if all the major organ systems are operating in a ance between heat gain and loss. The body temperature therefore
homeostatic manner, a person is in good health. Certain kinds of starts to decrease. Very rapidly, however, a variety of homeostatic
disease, in fact, can be defined as the loss of homeostasis in one or responses occur to limit the decrease. Figure 1.5 summarizes these
more systems in the body. To elaborate on our earlier definition of responses. The reader is urged to study Figure 1.5 and its legend
physiology, therefore, when homeostasis is maintained, we refer carefully because the figure is typical of those used throughout the
to physiology; when it is not, we refer to pathophysiology (from remainder of the book to illustrate homeostatic systems, and the
the Greek pathos, meaning “suffering” or “disease”). legend emphasizes several conventions common to such figures.

Begin
Stu d y a n d Revi ew 1.4
Room temperature
■ Internal environment: the extracellular fluid
■ Homeostasis: the process of maintaining a stable internal Heat loss from body
environment
∙∙ When homeostasis is disturbed for one variable, other
Body temperature
variables will compensate.
■ Dynamic constancy: a given variable may fluctuate in the body (Body’s responses)
in the short term, but is stable and predictable in the long term
Review Question: What is meant by “dynamic constancy”?
Constriction of skin
How does it relate to homeostasis, and what is one physiological Curling up Shivering
blood vessels
variable described in this section that illustrates this concept?
(Answer found in Appendix A.)
Heat loss from body Heat production

1.5 General Characteristics of
Return of body temperature toward original value
Homeostatic Control Systems
The activities of cells, tissues, and organs must be regulated and Figure 1.5 A homeostatic control system maintains body temperature
integrated with each other so that any change in the internal envi- when room temperature decreases. This flow diagram is typical of those
ronment initiates a reaction to correct the change. The compen- used throughout this book to illustrate homeostatic systems, and several
sating mechanisms that mediate such responses are performed by conventions should be noted. The “Begin” sign indicates where to start. The
homeostatic control systems. arrows next to each term within the boxes denote increases or decreases. The
Consider again an example of the regulation of body tempera- arrows connecting any two boxes in the figure denote cause and effect—that
is, an arrow can be read as “causes” or “leads to.” (For example, decreased
ture. This time, our subject is a resting, lightly clad man in a room
room temperature “leads to” increased heat loss from the body.) In general,
at a temperature of 20°C and moderate humidity. His internal body you should add the words “tends to” in thinking about these cause-and-
temperature is 37°C, and he is losing heat to the external environment effect relationships. For example, decreased room temperature tends to
because the room is at a lower temperature. However, the chemical cause an increase in heat loss from the body, and curling up tends to cause a
reactions occurring within the cells of his body are producing heat decrease in heat loss from the body. Qualifying the relationship in this way is
at a rate equal to the rate of heat loss. Under these conditions, the necessary because variables like heat production and heat loss are under the
body undergoes no net gain or loss of heat, and the body temperature influence of many factors, some of which oppose each other.
8 Chapter 1
 The first homeostatic response is that blood vessels to the SUBSTRATE
skin become constricted (narrowed), reducing the amount of blood
flowing through the skin. This decreases heat loss from the warm Enzyme A
blood across the skin and out to the environment and helps slow the
loss of heat from the body. At a room temperature of 5°C, however, Inactive intermediate 1
blood vessel constriction cannot by itself eliminate the extra heat
loss from the body. Our subject hunches his shoulders and folds his Enzyme B
arms in order to reduce the surface area of the skin available for heat
loss. This helps somewhat, but heat loss still continues, and body Inactive intermediate 2
temperature keeps decreasing, although at a slower rate. Clearly,
Enzyme C
then, if excessive heat loss (output) cannot be prevented, the only
way of restoring the balance between heat input and output is to Active product
increase input, and this is precisely what occurs. Our subject begins
to shiver, and the chemical reactions responsible for the skeletal mus-
cle contractions that constitute shivering produce large quantities of Figure 1.6 Hypothetical example of negative feedback (as denoted
by the circled minus sign and dashed feedback line) occurring within
heat, thereby restoring body temperature homeostasis.
a set of sequential chemical reactions. By inhibiting the activity of the
Feedback Systems first enzyme involved in the formation of a product, the product can
regulate the rate of its own formation.
The thermoregulatory system just described is an example of a
negative feedback system, in which an increase or decrease in the
variable being regulated brings about responses that tend to move DIG DEEPER
the variable in the direction opposite (“negative” to) the direction ■ What would be the effect on this pathway if negative feedback
of the original change. Thus, in our example, a decrease in body was removed?
temperature led to responses that tended to increase the body Answer found in Appendix A.
temperature—that is, move it toward its original value.
Without negative feedback, oscillations like some of those
described in this chapter would be much greater and, therefore, the
variability in a given system would increase. Negative feedback also This is counter to homeostasis, because positive feedback has no
prevents the compensatory responses to a loss of homeostasis from obvious means of stopping. Not surprisingly, therefore, positive
continuing unabated. Details of the mechanisms and characteristics of feedback is much less common in nature than negative feedback.
negative feedback in different systems will be addressed in later chap- Nonetheless, there are examples in physiology in which positive
ters. For now, it is important to recognize that negative feedback has a feedback is very important. One well-described example, which
vital part in the checks and balances on most physiological variables. you will learn about in detail in Chapter 12, is the process of blood
Negative feedback may occur at the organ, cellular, or clotting (Figure 1.7). When a blood vessel is ruptured, damaged
molecular level. For instance, negative feedback regulates many cells in the vessel wall release chemicals into the blood that attract
enzymatic processes, as shown in schematic form in Figure 1.6. platelets to the injury site and activate them. Platelets are frag-
(An enzyme is a protein that catalyzes chemical reactions.) ments of cells that stick together and form clots that seal a wound.
In this example, the product formed from a substrate by an enzyme Once activated, platelets themselves then release additional acti-
negatively feeds back to inhibit further action of the enzyme. This vating chemicals, which activate more platelets, and so on. The
may occur by several processes, such as chemical modification cycle finally stops once the wound is fully sealed with a clot.
of the enzyme by the product of the reaction. The production of
adenosine triphosphate (ATP) within cells is a good example of a Resetting of Set Points
chemical process regulated by feedback. Normally, glucose mol- As we have seen, changes in the external environment can displace a
ecules are enzymatically broken down inside cells to release some variable from its set point. In addition, the set points for many regu-
of the chemical energy that was contained in the bonds of the mol- lated variables can be reset to a new value. A common example is
ecule. This energy is then stored in the bonds of ATP. The energy fever, the increase in body temperature that occurs in response to
from ATP can later be tapped by cells to power such functions infection and that is somewhat analogous to raising the setting of a
as muscle contraction, cellular secretions, and transport of mol- thermostat in a room. The homeostatic control systems regulating
ecules across cell membranes. As ATP accumulates in the cell, body temperature are still functioning during a fever, but they main-
however, it inhibits the activity of some of the enzymes involved tain the temperature at an increased value. This regulated increase
in the breakdown of glucose. Therefore, as ATP concentrations in body temperature is adaptive for fighting the infection, because
increase within a cell, further production of ATP slows down due elevated temperature inhibits proliferation of some pathogens. In
to negative feedback. Conversely, if ATP concentrations decrease fact, this is why a fever is often preceded by chills and shivering. The
within a cell, negative feedback is removed and more glucose is set point for body temperature has been reset to a higher value, and
broken down so that more ATP can be produced. the body responds by shivering to generate heat.
Not all forms of feedback are negative. In some cases, The example of fever may have left the impression that set
positive feedback accelerates a process, leading to an “explosive” points are reset only in response to external stimuli, such as the
system. In other words, an initial change in a particular variable presence of pathogens, but this is not the case. Indeed, the set points
subsequently leads to an even greater change in that variable. for many regulated variables change on a rhythmic basis every day.
Homeostasis: A Framework for Human Physiology 9
 Damaged Chemical
endothelial cell signals

1 Wounded cells secrete

chemical signals that
attract and activate
platelets.

Erythrocyte Platelets

2 Clotting begins as
activated platelets
adhere to the wound
site. Activated platelets
3 These signals then secrete more
attract and activate chemical signals.
yet more platelets.
Positive
feedback

4 Cycle ends once the

wound is fully sealed.

Figure 1.7 Positive feedback as illustrated by the clotting process in blood. Damaged endothelial cells (a type of epithelial cells) in the lining of a blood
vessel secrete chemical signals that attract and activate platelets, tiny cell fragments that form clots. As clotting begins, the activated platelets produce
chemical signals of their own, attracting and activating more platelets to the wound site, which then produce yet more chemical signals, and so on. The
cycle ends when the wound is fully sealed. (Most details of the clotting process are omitted for clarity; you can look ahead to Figure 12.71 for details.)

For example, the set point for body temperature is higher during phenomenon mentioned earlier about the interplay between body
the day, when we are active, than at night. temperature and water balance during exercise.
Although the resetting of a set point is adaptive in some The generalizations we have given about homeostatic con-
cases, in others it simply reflects the clashing demands of differ- trol systems are summarized in Table 1.2. One additional point is
ent regulatory systems. This brings us to one more generalization: that, as is illustrated by the regulation of body temperature, multi-
It is not possible for everything to be held constant by homeo- ple systems usually control a single parameter. The adaptive value
static control systems. In our earlier example, body temperature of such redundancy is that it provides much greater fine-tuning
was maintained despite large swings in ambient temperature, but and also permits regulation to occur even when one of the systems
only because the homeostatic control system brought about large is not functioning properly because of disease.
changes in skin blood flow and skeletal muscle contraction. More-
over, because so many properties of the internal environment are Feedforward Regulation
closely interrelated, it is often possible to keep one property rela- Another type of regulatory process is feedforward regulation, in
tively stable only by moving others away from their usual set point. which changes in regulated variables are anticipated and prepared
This is what we mean by “clashing demands,” which explains the for before they actually occur. Control of body temperature is a

TABLE 1.2 Some Important Generalizations About Homeostatic Control Systems

Stability of an internal environmental variable is achieved by balancing inputs and outputs. It is not the absolute magnitudes of the inputs and
outputs that matter but the balance between them.

In negative feedback, a change in the variable being regulated brings about responses that tend to move the variable in the direction opposite the
original change—that is, back toward the initial value (set point).

Homeostatic control systems cannot maintain complete constancy of any given feature of the internal environment. Therefore, any regulated
variable will have a more or less narrow range of normal values depending on the external environmental conditions.

The set point of some variables regulated by homeostatic control systems can be reset—that is, physiologically raised or lowered.

It is not always possible for homeostatic control systems to maintain every variable within a narrow normal range in response to an environmental
challenge. There is a hierarchy of importance, so that certain variables may be altered markedly to maintain others within their normal range.

10 Chapter 1
good example of a feedforward process. The temperature-sensitive
neurons that trigger negative feedback regulation of body tempera-
1.6 Components of Homeostatic
ture when it begins to decrease are located inside the body. In addi- Control Systems
tion, there are ­temperature-sensitive neurons in the skin; these cells,
in effect, monitor outside temperature. When outside temperature Reflexes
decreases, as in our example, these neurons immediately detect the The thermoregulatory system we used as an example in the previ-
change and relay this information to the brain. The brain then sends ous section and many of the other homeostatic control systems
out signals to the blood vessels and muscles, resulting in heat conser- belong to the general category of stimulus–response sequences
vation and increased heat production. In this manner, compensatory known as reflexes. In the narrowest sense of the word, a reflex is
thermoregulatory responses are activated before the colder outside a specific, involuntary, “built-in” response to a particular stimu-
temperature can cause the internal body temperature to decrease. lus. Some reflexes involve muscular activity, such as the famil-
In another familiar example, the smell of food triggers nerve iar knee-jerk reflex, or the startle reflex that follows when we are
responses from odor receptors in the nose to the cells of the diges- surprised by a loud noise. Other reflexes occur without our con-
tive system. The effect is to prepare the digestive system for the scious awareness and involve internal homeostatic responses such
arrival of food before we even consume it—for example, by induc- as those described in this chapter. For example, you are generally
ing saliva to be secreted in the mouth and causing the stomach to not aware of reflexive changes in blood pressure.
churn and produce acid. Thus, feedforward regulation improves Many responses appear automatic and stereotyped but are
the speed of the body’s homeostatic responses and minimizes actually the result of learning and practice. For example, an expe-
fluctuations in the level of the variable being regulated—that is, it rienced driver performs many complicated acts in operating a car.
reduces the amount of deviation from the set point. To the driver, these motions are, in large part, automatic, stereo-
In our examples, feedforward regulation utilizes a set of typed, and unpremeditated, but they occur only because a great
external or internal environmental detectors. It is likely, however, deal of conscious effort was spent learning them. We term such
that many examples of feedforward regulation are the result of a reflexes learned or acquired reflexes. In general, most reflexes,
different phenomenon—learning. The first times they occur, early no matter how simple they may appear to be, are subject to altera-
in life, perturbations in the external environment probably cause tion by learning.
relatively large changes in regulated internal environmental fac- The pathway mediating a reflex is known as the reflex arc,
tors, and in responding to these changes the central nervous sys- and its components are shown in Figure 1.8. A stimulus is defined
tem learns to anticipate them and resist them more effectively. A as a detectable change in the internal or external environment,
familiar form of this is the increased heart rate that occurs in an such as a change in temperature, plasma potassium concentration,
athlete just before a competition begins. or blood pressure. A receptor detects the environmental change. A
stimulus acts upon a receptor to produce a signal that is relayed to
an integrating center. The signal travels between the receptor and
St ud y an d Review 1.5 the integrating center along the afferent pathway (the general term
afferent means “to carry to,” in this case, to the integrating center).
■ Homeostasis results from the operation of compensatory An integrating center often receives signals from many
control systems. receptors, some of which may respond to quite different types of
∙∙ Homeostasis is a steady state in which a variable is stimuli. Thus, the output of an integrating center reflects the net
unchanging but only as long as energy is provided effect of the total afferent input—that is, it represents an integra-
(equilibrium does not require input of energy). tion of numerous bits of information.
■ Negative feedback control system: minimizes changes from
the set point of a system, leading to stability
∙∙ A change in a regulated variable brings about responses that
Integrating center
move the variable in the direction opposite to the original (Compare to set point)
change.
■ Positive feedback: accelerates a process by moving a variable Afferent Efferent
further from a set point pathway pathway

■ Homeostatic control systems minimize changes but cannot

maintain complete constancy of a regulated variable. Receptor Effector

■ Feedforward regulation:
Begin
∙∙ anticipates changes in a regulated variable
Stimulus Response
∙∙ fine-tunes homeostatic responses
∙∙ minimizes fluctuations in the regulated variable
Negative
Review Question: Distinguish between negative feedback,
feedback
positive feedback, and feedforward regulation. Which of the three
is least likely to contribute to homeostasis, and why? (Answer
Figure 1.8 General components of a reflex arc that functions as a
found in Appendix A.)
negative feedback control system. The response of the system has the
effect of counteracting or eliminating the stimulus.
Homeostasis: A Framework for Human Physiology 11
 The output of an integrating center is sent to the last compo- along neurons in other nerves that cause skeletal muscles and
nent of the system, known as an effector. The actions of the effector the muscles in skin blood vessels to contract. The nerves to the
constitute the overall response of the system. The information going muscles are the efferent pathway, and the muscles are the effec-
from an integrating center to an effector is like a command direct- tors. The dashed arrow and the negative sign indicate the nega-
ing the effector to alter its activity. This information travels along the tive feedback nature of the reflex.
efferent pathway (the general term efferent means “to carry away Almost all body cells can act as effectors in homeostatic
from,” in this case, away from the integrating center). reflexes. Muscles and glands, however, are the major effectors of
Thus far, we have described the reflex arc as the sequence biological control systems. In the case of glands, for example, the
of events linking a stimulus to a response. If the response pro- effector may be a hormone secreted into the blood. As will be
duced by the effector causes a decrease in the magnitude of the described in detail in Chapter 11, a hormone is a type of chemical
stimulus that triggered the sequence of events, then the reflex messenger secreted into the blood by cells of the endocrine system
leads to negative feedback and we have a typical homeostatic (see Table 1.1). Hormones may act on many different cells simulta-
control system. Not all reflexes are associated with such feed- neously because they circulate throughout the body.
back. For example, the smell of food stimulates the stomach to Traditionally, the term reflex was restricted to situations in
secrete molecules that are important for digestion, but these mol- which the receptors, afferent pathway, integrating center, and effer-
ecules do not eliminate our perception of the smell of food (the ent pathway were all parts of the nervous system, as in the thermo-
stimulus). regulatory reflex. However, the principles are essentially the same
Figure 1.9 demonstrates the components of a negative when a blood-borne chemical messenger, rather than a nerve, serves
feedback homeostatic reflex arc in the process of thermoregu- as the efferent pathway, or when a hormone-secreting gland serves
lation. The temperature receptors are the endings of certain as the integrating center.
neurons in various parts of the body. These receptors gener- In our use of the term reflex, therefore, we include hor-
ate electrical signals in the neurons at a rate determined by the mones as reflex components. Moreover, depending on the specific
temperature. These electrical signals are conducted by nerves nature of the reflex, the integrating center may reside either in the
containing processes from the neurons—the afferent pathway— nervous system or in a gland. In addition, a gland may act in more
to the brain, where the integrating center for temperature regula- than one way in a reflex. For example, when the glucose concen-
tion is located. The integrating center, in turn, sends signals out tration in the blood is increased, this is detected by gland cells

INTEGRATING CENTER

Specific neurons in brain

Compare to set point; alter rates of firing

AFFERENT PATHWAY
(Nerves) EFFERENT PATHWAY
(Nerves)
Temperature-sensitive Smooth muscle in Skeletal muscle
RECEPTORS neurons skin blood vessels EFFECTORS
Contraction
Signaling rate Contraction (Shivering)
(Decreases blood flow)

Begin
Decreased body
STIMULUS temperature

Heat loss Heat RESPONSES

production

Figure 1.9 Reflex for minimizing the decrease in body temperature that occurs on exposure to a reduced external environmental temperature. This
figure provides the internal components for the reflex shown in Figure 1.5. The dashed arrow and the ⊝ indicate the negative feedback nature of the
reflex, denoting that the reflex responses cause the decreased body temperature to return toward normal. An additional flow-diagram convention is shown
in this figure: Blue boxes always denote events that are occurring in anatomical structures (labeled in blue italic type in the upper portion of the boxes).

DIG DEEPER
■ What might happen to the efferent pathway in this control system if body temperature increased above normal?
Answer found in Appendix A.

12 Chapter 1
in the pancreas (receptor). These same cells then release the hor- Hormone-secreting Neuron
gland cell
mone insulin (effector) into the blood, which decreases the blood
glucose concentration.

Local Homeostatic Responses Electrical

Hormone signal
In addition to reflexes, another group of biological responses,
called local homeostatic responses, is of great importance for
homeostasis. These responses are initiated by a change in the
external or internal environment (that is, a stimulus), and they Blood Neurotransmitter
induce an alteration of cell activity with the net effect of coun- vessel
teracting the stimulus. Like a reflex, therefore, a local response
is the result of a sequence of events proceeding from a stimulus.
Unlike a reflex, however, the entire sequence occurs only in
the area of the stimulus. For example, when cells of a tissue Target cells in Neuron or effector
one or more cell in close proximity
become very metabolically active, they secrete substances into distant places in to site of neuro-
the interstitial fluid that dilate (widen) local blood vessels. the body transmitter release
The resulting increased blood flow increases the rate at which
nutrients and oxygen are delivered to that area, and the rate at Local cell Local cell
which wastes are removed. The significance of local responses
is that they provide individual areas of the body with mecha-
nisms for local self-regulation.
Paracrine substance Autocrine substance

St u d y an d Review 1.6 Target cells in close

proximity to site of Autocrine substance
release of paracrine acts on same cell
■ Reflex: specific, involuntary, unpremeditated response to a substance that secreted the
stimulus substance
∙∙ typically innate but some can be learned or acquired
■ Reflex arc: stimulus → receptor → afferent pathway → Figure 1.10 Categories of chemical messengers. With the exception
integrating center → efferent pathway → effector → response of autocrine messengers, all messengers act between cells—that is,
intercellularly.
■ Local homeostatic responses:
∙∙ involve stimulus–response sequences
∙∙ occur only in the area of the stimulus (no nerves or hormones with the blood acting as the delivery system. The cells on which hor-
directly involved) mones act are called the hormone’s target cells. Hormones are pro-
duced in and secreted from endocrine glands—such as the gonads,
Review Question: What might happen to a reflex arc in an
individual in whom the effectors for that reflex were not
pancreas, and thyroid gland—or in scattered cells that are distributed
functional? (Answer found in Appendix A.) throughout an organ. They have important functions in essentially all
physiological processes, including growth, reproduction, metabolism,
mineral balance, and blood pressure, and several of them are pro-
duced whenever homeostasis is threatened.
In contrast to hormones, neurotransmitters are chemical mes-
1.7 The Role of Intercellular sengers that are released from the endings of neurons onto other neu-
rons, muscle cells, or gland cells. A neurotransmitter diffuses through
Chemical Messengers in the extracellular fluid separating the neuron and its target cell; it is not
Homeostasis released into the blood like a hormone. Neurotransmitters and their
functions in neuronal signaling and brain function will be covered
Essential to reflexes and local homeostatic responses—and there- in Chapter 6. In the context of homeostasis, they form the signaling
fore to homeostasis—is the ability of cells to communicate with basis of many reflexes, as well as having a vital role in the compensa-
one another. In this way, cells in the brain, for example, can be tory responses to a wide variety of challenges, such as the require-
made aware of the status of activities of structures outside the ment for increased heart and lung function during exercise.
brain, such as the heart, and help regulate those activities to meet Chemical messengers participate not only in reflexes but
new homeostatic challenges. In the majority of cases, intercellular also in local responses. Chemical messengers involved in local
communication is performed by chemical messengers. There are communication between cells are known as paracrine substances
four categories of such messengers: hormones, neurotransmitters, (or agents). Paracrine substances are synthesized by cells and
paracrine substances, and autocrine substances (Figure 1.10). released, once given the appropriate stimulus, into the extracell­
As noted earlier, a hormone is a chemical messenger that ular fluid. They then diffuse to neighboring cells, some of which
enables the hormone-secreting cell to communicate with other cells, are their target cells. Given this broad definition, neurotransmitters
Homeostasis: A Framework for Human Physiology 13
could be classified as a subgroup of paracrine substances, but by
convention they are not. Once they have performed their func-
1.8 Processes Related to
tions, paracrine substances are generally inactivated by locally Homeostasis
existing enzymes and therefore they do not enter the bloodstream
in large quantities. Paracrine substances are produced throughout Adaptation and Acclimatization
the body; an example of their key role in homeostasis that you will The term adaptation denotes a characteristic that favors survival
learn about in Chapter 15 is their ability to fine-tune the amount of in specific environments. Common examples in humans include
acid produced by cells of the stomach in response to eating food. the ability of certain individuals to digest lactose in milk, and the
There is one category of local chemical messengers that protection against the dangerous effects of ultraviolet light con-
are not intercellular messengers—that is, they do not communi- ferred by dark skin. Homeostatic control systems are also inher-
cate between cells. Rather, the chemical is secreted by a cell into ited biological adaptations and allow an individual to adapt to
the extracellular fluid and then acts upon the very cell that secreted encountered environmental changes. In addition, in some cases
it. Such messengers are called autocrine substances (or agents) (see the effectiveness of such systems can be enhanced by prolonged
Figure 1.10). Frequently, a messenger may serve both paracrine and exposure to an environmental change. This type of adaptation—
autocrine functions simultaneously—that is, molecules of the mes- the improved functioning of an already existing homeostatic
senger released by a cell may act locally on adjacent cells as well as system—is known as acclimatization.
on the same cell that released the messenger. This type of signaling Let us take sweating in response to heat exposure as an
is commonly found in cells of the immune system (Chapter 18). example of an adaptation and perform a simple experiment. On
A point of great importance must be emphasized here to avoid day 1, we expose a person for 30 minutes (min) to an elevated
later confusion. A neuron, endocrine gland cell, and other cell types temperature and ask her to do a standardized exercise test. Body
may all secrete the same chemical messenger. In some cases, a par- temperature increases, and sweating begins after a certain period
ticular messenger may sometimes function as a neurotransmitter, of time. The sweating provides a mechanism for increasing heat
a hormone, or a paracrine or autocrine substance. Norepinephrine, loss from the body and therefore tends to minimize the increase
for example, is not only a neurotransmitter in the brain; it is also in body temperature in a hot environment. The volume of sweat
produced as a hormone by cells of the adrenal glands. produced under these conditions is measured. Then, for a week,
All types of intercellular communication described thus our subject enters the heat chamber for 1 or 2 hours (h) per day and
far in this section involve secretion of a chemical messenger into exercises. On day 8, her body temperature and sweating rate are
the extracellular fluid. However, there are two important types of again measured during the same exercise test performed on day 1.
chemical communication between cells that do not require such The striking finding is that the subject begins to sweat sooner and
secretion. The first type occurs via gap junctions, which are physical much more profusely than she did on day 1. As a consequence, her
linkages connecting the cytosol between two cells (see Chapter 3). body temperature does not increase to nearly the same degree. The
Molecules can move directly from one cell to an adjacent cell subject has become acclimatized to the heat. She has undergone a
through gap junctions without entering the extracellular fluid. In the beneficial change induced by repeated exposure to the heat and is
second type, the chemical messenger is not actually released from now better able to respond to heat exposure.
the cell producing it but rather is located in the plasma membrane Acclimatizations are usually reversible. If, in the example
of that cell. For example, the messenger may be a plasma mem- just described, the daily exposures to heat are discontinued, our
brane protein with part of its structure extending into the extracel- subject’s sweating rate will revert to the preacclimatized value
lular space. When the cell encounters another cell type capable of within a relatively short time.
responding to the message, the two cells link up via the membrane- The precise anatomical and physiological changes that
bound protein. This type of signaling, sometimes termed juxtacrine, bring about increased capacity to withstand change during accli-
is of particular importance in the growth and differentiation of matization are highly varied. Typically, they involve an increase
tissues as well as in the functioning of cells that protect the body in the number, size, or sensitivity of one or more of the cell
against pathogens (Chapter 18). It is one way in which similar types types in the homeostatic control system that mediates the basic
of cells “recognize” each other and form tissues. response.

Stu d y a n d Revi ew 1.7 Biological Rhythms

■ Intercellular communication: cell-to-cell communication
As noted, a striking characteristic of many body functions is the
facilitates homeostasis rhythmic changes they manifest. The most common type is the
circadian rhythm, which cycles approximately once every 24 h.
∙∙ essential to reflexes and local responses
Waking and sleeping, body temperature, hormone concentrations
∙∙ achieved by neurotransmitters, hormones (many of which
in the blood, the excretion of ions into the urine, and many other
are secreted from endocrine glands), paracrine substances,
or autocrine substances
functions undergo circadian variation; an example of one type of
rhythm is shown in Figure 1.11.
∙∙ also occurs to a lesser extent through gap junctions or cell-
bound messengers
What do biological rhythms have to do with homeosta-
sis? They add an anticipatory component to homeostatic control
Review Question: Explain how intercellular communication facilitates systems—in effect, a feedforward system operating without detec-
the maintenance of homeostasis. (Answer found in Appendix A.)
tors. The negative feedback homeostatic responses we described ear-
lier in this chapter are corrective responses. They are initiated after
14 Chapter 1
 exerted by the external environment. In turn, the pacemaker sends

temperature (°C)
Lights on Lights off
38
out neural signals to other parts of the brain, which then influence
the various body systems, activating some and inhibiting others. One

Body
37 output of the pacemaker goes to the pineal gland, a gland within
the brain, which secretes the hormone melatonin. These neural sig-
36 nals from the pacemaker cause the pineal gland to secrete melatonin
6:00 2:00 10:00 6:00 2:00 10:00 during darkness but not during daylight. It has been hypothesized,
A.M. P.M. P.M. A.M. P.M. P.M. therefore, that melatonin may act as an important mediator to influ-
Time of day ence other organs either directly or by altering the activity of the
parts of the brain that control these organs.
Figure 1.11 Circadian rhythm of body temperature in a human
subject with room lights on (open bars at top) for 16 h, and off (blue
bars at top) for 8 h. Note the increase in body temperature that occurs
Balance of Chemical Substances in the Body
just prior to lights on, in anticipation of the increased activity and Many homeostatic systems regulate the balance between addition
metabolism that occur during waking hours. Source: Moore-Ede, Martin C., and removal of a chemical substance from the body. Figure 1.12
Sulzman, Frank M., and Fuller, Charles A., The Clocks that Time Us. Harvard University Press, 1982. is a generalized schema of the possible pathways involved in
maintaining such balance. The pool occupies a position of central
importance in the balance sheet. It is the body’s readily available
the steady state of the individual has been perturbed. In contrast,
quantity of the substance and is often identical to the amount pres-
biological rhythms enable homeostatic mechanisms to be utilized
ent in the extracellular fluid. The pool receives substances and
immediately and automatically by activating them at times when
redistributes them to all the pathways.
a challenge is likely to occur but before it actually does occur—for
The pathways on the left of Figure 1.12 are sources of net
example, body temperature increases prior to waking in a person on
gain to the body. A substance may enter the body through the gas-
a typical sleep–wake cycle. This allows the metabolic machinery
trointestinal (GI) tract or the lungs. Alternatively, a substance may
of the body to operate most efficiently immediately upon waking,
be synthesized within the body from other materials.
because metabolism (chemical reactions) is to some extent temper-
The pathways on the right of the figure are causes of net loss
ature dependent. During sleep, metabolism is slower than during
from the body. A substance may be lost in the urine, feces, expired
the active hours, and therefore body temperature decreases at that
air, or menstrual fluid, as well as from the surface of the body as
time. A crucial point concerning most body rhythms is that they are
skin, hair, nails, sweat, or tears. The substance may also be chemi-
internally driven. Environmental factors do not drive the rhythm
cally altered by enzymes and thus removed by metabolism.
but rather provide the timing cues important for entrainment, or
The central portion of Figure 1.12 illustrates the distribu-
setting of the actual hours of the rhythm. A classic experiment will
tion of the substance within the body. The substance may be
clarify this distinction.
taken from the pool and accumulated in storage depots—such
Subjects were put in experimental chambers that completely
as the accumulation of fat in adipose tissue. Conversely, it may
isolated them from their usual external environment, including
leave the storage depots to reenter the pool. Finally, the substance
knowledge of the time of day. For the first few days, they were
may be incorporated reversibly into some other molecular struc-
exposed to a 24 h rest–activity cycle in which the room lights
ture, such as fatty acids into plasma membranes. Incorporation
were turned on and off at the same times each day. Under these
is reversible because the substance is liberated again whenever the
conditions, their sleep–wake cycles were 24 h long. Then, all
more complex structure is broken down. This pathway is distin-
environmental time cues were eliminated, and the subjects were
guished from storage in that the incorporation of the substance into
allowed to control the lights themselves. Immediately, their sleep–
other molecules produces new molecules with specific functions.
wake patterns began to change. On average, bedtime began about
Substances do not necessarily follow all pathways of this
30 min later each day, and so did wake-up time. Thus, a sleep–
generalized schema. For example, minerals such as Na+ cannot be
wake cycle persisted in the complete absence of environmental
synthesized, do not normally enter through the lungs, and cannot
cues. Such a rhythm is called a free-running rhythm. In this
be removed by metabolism.
case, it was approximately 24.5 h rather than 24. This indicates
that cues are required to entrain or set a circa-
NET GAIN TO BODY DISTRIBUTION WITHIN NET LOSS FROM
dian rhythm to 24 h. BODY BODY
What is the neural basis of body rhythms?
In the part of the brain called the hypothalamus a Food GI tract Storage depots Metabolism
specific collection of neurons (the suprachiasmatic
nucleus) functions as the principal pacemaker, or
time clock, for circadian rhythms. How it keeps Air Lungs POOL
time independent of any external environmen-
tal cues is not fully understood, but it appears to Excretion from body
Reversible via lungs, GI tract,
involve the rhythmic turning on and off of critical Synthesis in body kidneys, skin,
incorporation
genes in the pacemaker cells. into other menstrual flow
The pacemaker receives input from the molecules
eyes and many other parts of the nervous system,
and these inputs mediate the entrainment effects Figure 1.12 Balance diagram for a chemical substance.
Homeostasis: A Framework for Human Physiology 15
 The orientation of Figure 1.12 illustrates two important gen-
St udy and Review 1.8 — co ntinue d
eralizations concerning the balance concept: (1) During any period
of time, total-body balance depends upon the relative rates of net ■ Circadian rhythms: biological functions with a cycle of
gain and net loss to the body; and (2) the pool concentration depends approximately 24 h
not only upon the total amount of the substance in the body but also ∙∙ feedforward component to homeostatic control systems
upon exchanges of the substance within the body.
∙∙ internally driven by pacemakers
For any substance, three states of total-body balance
∙∙ entrained by light
are possible:
∙∙ free run without entrainment
■■ Loss exceeds gain, so that the total amount of the substance
■ Total-body (mass) balance: matching inputs and outputs of a
in the body is decreasing, and the person is in negative substance in the body
balance.
∙∙ can be negative (net loss), positive (net gain), or stable (loss = gain)
■■ Gain exceeds loss, so that the total amount of the substance
in the body is increasing, and the person is in ­positive Review Question: Distinguish between acclimatization and
balance. adaptation. Considering organ systems and referring back to
■■ Gain equals loss, and the person is in stable balance. Table 1.1 if necessary, what are one or two general adaptations
that are important for our ability to survive in a terrestrial
Clearly, a stable balance can be upset by a change in the environment? (Answer found in Appendix A.)
amount being gained or lost in any single pathway in the schema.
For example, increased sweating can cause severe negative water
balance. Conversely, stable balance can be restored by homeo-
static control of water intake and output.
1.9 General Principles
Let us take the balance of calcium ions (Ca2+) as another of Physiology
example. The concentration of Ca2+ in the extracellular fluid is crit- This chapter has highlighted several fundamental and recurring
ical for normal cellular functioning, notably muscle cells and neu- themes or principles in physiology. Recognizing these principles
rons, but also for the formation and maintenance of the skeleton. and how they manifest in the different organ systems can provide
The vast majority of the body’s Ca2+ is present in bone. The control a deeper understanding of the integrated function of the human
systems for Ca2+ balance target the intestines and kidneys such that body. To help you gain this insight, beginning with Chapter 2, the
the amount of Ca2+ absorbed from the diet is balanced with the introduction to each chapter will highlight the general principles
amount excreted in the urine. During infancy and childhood, how- demonstrated in that chapter. Your understanding of how to apply
ever, the net balance of Ca2+ is positive, and Ca2+ is deposited in the following general principles of physiology to a given chapter’s
growing bone. In later life, especially in women after menopause content will then be assessed at the end of the chapter and in Dig
(see Chapter 17), Ca2+ is released from bones faster than it can Deeper questions associated with certain figures.
be deposited, and that extra Ca2+ is lost in the urine. Consequently,
the bone pool of Ca2+ becomes smaller, the rate of Ca2+ loss from 1. Homeostasis is essential for health and survival. The
the body exceeds the rate of intake, and Ca2+ balance is negative. ability to maintain physiological variables such as body
In summary, homeostasis is a complex, dynamic process temperature and blood sugar concentrations within
that regulates the adaptive responses of the body to changes in the normal ranges is the underlying principle upon which all
external and internal environments. To work properly, homeostatic physiology is based. Keys to this principle are the processes
systems require a sensor to detect the environmental change as well of feedback and feedforward. Challenges to homeostasis
as a means to produce a compensatory response. Because compen- may result from disease or from environmental factors such
satory responses require muscle activity, behavioral changes, or as famine or exposure to extremes of temperature.
synthesis of chemical messengers such as hormones, homeostasis 2. The functions of organ systems are coordinated with
is achieved by the expenditure of energy. The nutrients that provide each other. Physiological mechanisms operate and
this energy, as well as the cellular structures and chemical reactions interact at the levels of cells, tissues, organs, and organ
that release the energy stored in the chemical bonds of the nutrients, systems. Furthermore, the different organ systems in
are described in the following two chapters. the human body do not function independently of each
other. Each system typically interacts with one or more
Stu d y a n d Revi ew 1.8 others to control a homeostatic variable. A good example
that you will learn about in Chapters 12 and 14 is the
■ Adaptation: any characteristic that favors survival in a specific coordinated activity of the circulatory and urinary systems
environment; many are inheritable, such as homeostatic control in regulating blood pressure. This type of coordination is
systems often referred to as “integration” in physiological contexts.
3. Most physiological functions are controlled by multiple
■ Acclimatization: improved functioning of an already existing
homeostatic system regulatory systems, often working in opposition. Typically,
control systems in the human body operate such that a given
∙∙ induced by prolonged exposure to a stress with no change in
variable, such as heart rate, receives both stimulatory and
genetic endowment
inhibitory signals. As you will learn in detail in Chapter 6,
∙∙ typically reversible
for example, the nervous system sends both types of signals
to the heart; adjusting the ratio of stimulatory to inhibitory
16 Chapter 1
 signals allows for fine-tuning of the heart rate under homeostasis require regulation of the movement and
changing conditions such as rest or exercise. transformation of energy-yielding nutrients and molecular
4. Information flow between cells, tissues, and organs is an building blocks between the body and the environment and
essential feature of homeostasis and allows for integration between different regions of the body. Nutrients are ingested
of physiological processes. Cells can communicate with (Chapter 15), stored in various forms (Chapter 16), and
nearby cells via locally secreted chemical signals; a good ultimately metabolized to provide energy that can be stored
example of this is the signaling between cells of the stomach in the bonds of ATP (Chapters 3 and 16). The concentrations
that results in acid production, a key feature of the digestion of many inorganic molecules must also be regulated to
of proteins (see Chapter 15). Cells in one structure can maintain body structure and function—for example, the
also communicate long distances using electrical signals Ca2+ found in bones (Chapter 11). One of the most important
or chemical messengers such as hormones. Electrical functions of the body is to respond to changing demands,
and hormonal signaling will be discussed throughout the such as the increased requirement for nutrients and oxygen
textbook and particularly in Chapters 6, 7, and 11. in exercising muscle. This requires a coordinated allocation
5. Controlled exchange of materials occurs between of resources to regions that most require them at a particular
compartments and across cellular membranes. The time. The mechanisms by which the organ systems of the
movement of water and solutes—such as ions, sugars, and body recognize and respond to changing demands is a theme
other molecules—between the extracellular and intracellular you will encounter repeatedly in Chapters 6 through 19.
fluid is critical for the survival of all cells, tissues, and organs. 8. Structure is a determinant of—and has coevolved
In this way, important biological molecules are delivered to with—function. The form and composition of cells,
cells and wastes are removed and eliminated from the body. tissues, organs, and organ systems determine how they
In addition, regulation of ion movements creates the electrical interact with each other and with the physical world.
properties that are crucial to the function of many cell types. Throughout the text, you will see examples of how different
These exchanges occur via several different mechanisms, body parts converge in their structure to accomplish similar
which are introduced in Chapter 4 and are reinforced where functions. For example, enormous elaborations of surface
appropriate for each organ system throughout the book. areas to facilitate membrane transport and diffusion can
6. Physiological processes are dictated by the laws of be observed in the circulatory (Chapter 12), respiratory
chemistry and physics. Throughout this textbook, you (Chapter 13), urinary (Chapter 14), digestive (Chapter 15),
will encounter some simple chemical reactions, such as and reproductive (Chapter 17) systems.
the reversible binding of oxygen to the protein hemoglobin
in red blood cells (Chapter 13). The basic mechanisms St udy and Review 1 . 9
that regulate such reactions are reviewed in Chapter 3.
Physical laws, too, such as gravity, electromagnetism, and ■ General principles of physiology: include homeostasis;
the relation between the diameter of a tube and the flow of information flow; coordination between the functions of
liquid through the tube, help explain things like why we may different organ systems; transfer of matter and energy; structure
feel light-headed upon standing too suddenly (Chapter 12, determines function; physiological processes follow the laws of
but also see the Clinical Case Study that follows in this chemistry and physics
chapter), how our eyes detect light (Chapter 7), and how we Review Question: Refer back to Figure 1.9. Which general
inflate our lungs with air (Chapter 13). principles of physiology are depicted by the reflexes that control
7. Physiological processes require the transfer and balance body temperature homeostasis? (Answer found in Appendix A.)
of matter and energy. Growth and the maintenance of

CHAPTER 1 Clinical Case Study: L oss of Consciousness in a 64-Year-Old Man

While Gardening on a Hot Day
Throughout this text, you will find a fea- previous chapters. In this first clinical case study, we examine a seri-
ture at the end of each chapter called ous and potentially life-threatening condition that can occur in individ-
the “Clinical Case Study.” These seg- uals in whom body temperature homeostasis is disrupted. All of the
ments reinforce what you have learned material presented in this clinical case study will be explored in depth
in that chapter by applying it to real-life in subsequent chapters, as you learn the mechanisms that underlie
examples of different medical condi- the pathologies and compensatory responses illustrated here in brief.
tions. The clinical case studies will Notice as you read that the first two general principles of physiology
increase in complexity as you progress described earlier are particularly relevant to this case. It is highly rec-
through the text and will enable you to ommended that you return to this case study as a benchmark at the
integrate recent material from a given end of your semester; we are certain that you will be amazed at how
Comstock Images/Getty Images chapter with information learned in your understanding of physiology has grown in that time.
—Continued next page

Homeostasis: A Framework for Human Physiology 17

—Continued ability of his heart to pump sufficient blood against gravity up to
A 64-year-old, fair-skinned man in good overall health spent his brain also decreased; when brain cells are deprived of blood
a very hot, humid summer day gardening in his backyard. After flow, they begin to malfunction. Suddenly standing only made mat-
several hours in the sun, he began to feel light-headed and con- ters worse. Perhaps you have occasionally experienced a little
fused as he knelt over his vegetable garden. Although earlier he of this light-headed feeling when you have jumped out of a chair
had been perspiring profusely and appeared flushed, his sweating or bed and stood up too quickly. Normally, your nervous system
had eventually stopped. Because he also felt confused and dis- quickly compensates for the effects of gravity on blood flowing up
oriented, he could not recall for how long he had not been per- to the brain, as will be described in Chapters 6 and 12. In a person
spiring, or even how long it had been since he had taken a drink with decreased blood volume and pressure, however, this com-
of water. He called to his wife, who was alarmed to see that his pensation may not happen and the person can lose conscious-
skin had since turned a pale-blue color. She asked her husband ness. After fainting and falling, the man’s head and heart were at
to come indoors, but he fainted as soon as he tried to stand. The the same horizontal level; consequently, blood could more easily
wife called for an ambulance, and the man was taken to a hospital reach his brain.
and diagnosed with a condition called heatstroke. What happened Another concern is that the salt (ion) concentrations in the
to this man that would explain his condition? How does it relate to body fluids changed. If you have ever tasted the sweat on your
homeostasis? upper lip on a hot day, you know that it is somewhat salty. That
is because sweat is derived from extracellular fluid, which as you
Reflect and Review #1 have learned is a watery solution of ions (derived from salts, such
■■ Review the homeostatic control of body temperature in as NaCl) and other substances. Sweat, however, is slightly more
Figure 1.5. Based on that, what would you expect to occur dilute than extracellular fluid because more water than ions is
to skin blood vessels when a person first starts feeling secreted from sweat glands. Consequently, the more heavily one
warm? perspires, the more concentrated the extracellular fluid becomes.
In other words, the total amount of water and ions in the extra-
As you learned in this chapter, body temperature is a physi- cellular fluid decreases with perspiration, but the remaining fluid
ological function that is under homeostatic control. If body tem- is “saltier.” Heavy perspiration, therefore, not only disrupts fluid
perature decreases, heat production increases and heat loss balance and blood pressure homeostasis but also has an impact
decreases, as illustrated in Figures 1.5 and 1.9. Conversely, as in on the balance of the ions in the body fluids, notably Na +, K+,
our example here, if body temperature increases, heat produc- and Cl −. A homeostatic balance of ion concentrations in the body
tion decreases and heat loss increases. When our patient began fluids is absolutely essential for normal heart and brain function,
gardening on a hot, humid day, his body temperature began to as you will learn in Chapters 4 and 6. As the man’s ion concentra-
increase. At first, the blood vessels in his skin dilated, making tions changed, therefore, the change affected the activity of the
him appear flushed and helping him dissipate heat across his cells of his brain.
skin. In addition, he perspired heavily. As you will learn in Chap-
ter 16, perspiration is an important mechanism by which the body
Reflect and Review #2
loses heat; it takes considerable heat to evaporate water from
■■ Refer to Figure 1.12. Was the man in a positive or negative
the surface of the skin, and the source of that heat is from the
balance for total-body Na+?
body. However, as you likely know from personal experience,
evaporation of water from the body is less effective in humid Why did the man stop perspiring, and why did his skin turn pale?
environments, which makes it more dangerous to exercise when To understand this, we must consider that several homeostatic vari-
it is not only hot but also humid. ables were disrupted by his activities. His body temperature increased,
The sources of perspiration are the sweat glands, which which initially resulted in heavy sweating. As the sweating continued,
are located beneath the skin and which secrete a salty solu- it resulted in decreased fluid levels and a negative balance of key ion
tion through ducts to the surface of the skin. The fluid in sweat concentrations in his body; this contributed to a decrease in mental
comes from the extracellular fluid compartment, which, as you function, and he became confused. As his body fluid levels continued
have learned, consists of the plasma and interstitial fluid compart- to decrease, his blood pressure also decreased, further endangering
ments (see Figure 1.3). Consequently, the profuse sweating that brain function. At this point, the homeostatic control systems were
initially occurred in this man caused his extracellular fluid levels to essentially in competition. Though it is potentially life threatening for
decrease. In fact, the fluid levels decreased so severely that the body temperature to increase too much, it is also life threatening for
amount of blood available to be pumped out of his heart with each blood pressure to decrease too much. Eventually, many of the blood
heartbeat also decreased. The relationship between fluid volume vessels in regions of the body that are not immediately required for
and blood pressure is an important one that you will learn about in survival—such as the skin—began to constrict, or close off. By doing
detail in Chapter 12. Generally speaking, if extracellular fluid lev- so, the more vital organs of the body—such as the brain—could receive
els decrease, blood pressure decreases as a consequence. This sufficient blood. This is why the man’s skin turned a pale blue, because
explains why our subject felt light-headed, particularly when he the amount of oxygen-rich blood flowing to the surface of his skin was
tried to stand up too quickly. As his blood pressure decreased, the decreased. Unfortunately, although this compensatory mechanism

18 Chapter 1
helped protect the man’s brain and other vital organs by providing the Begin
necessary blood flow to them, the reduction in blood flow to the skin
Body temperature
made it increasingly more difficult to dissipate heat from the body to
the environment. It also made it more difficult for sweat glands in the
skin to obtain the fluid required to produce sweat. The man gradually Sweat glands
decreased perspiring and eventually stopped sweating altogether. At
Heavy sweating
that point, his body temperature spiraled out of control and he was hos-
pitalized (Figure 1.13).
This case illustrates a critical feature of homeostasis that you Volume of body fluids
will encounter throughout this textbook and that was emphasized in
this chapter. Often, when one physiological variable—such as body
temperature—is disrupted, the compensatory responses initiated to Blood pressure
correct that disruption cause, in turn, imbalances in other variables.
These secondary imbalances must also be compensated for, and
the significance of each imbalance must be “weighed” against the Constriction of skin
blood vessels
others. In this example, the man was treated with intravenous fluids
made up of a salt solution to restore his fluid levels and concentra-
tions, and he was immersed in a cool bath and given cool compresses Heat loss and sweating
to help reduce his body temperature. Although he recovered, many
people do not survive heatstroke because of its profound impact on Rapid increase in
homeostasis. body temperature

Figure 1.13 Sequence of events that occurred in the man

described in this case study.

See Chapter 19 for complete, integrative case studies.

1.5 General Characteristics of Homeostatic Control Systems

K EY A N D CL INICA L T ER M S
equilibrium positive feedback
1.1 The Scope of Human Physiology feedforward regulation set point
homeostatic control systems steady state
pathophysiology physiology
negative feedback
1.2 How Is the Body Organized?
1.6 Components of Homeostatic Control Systems
basement membrane fibers
acquired reflexes learned reflexes
cell differentiation functional units
afferent pathway local homeostatic responses
cells muscle cells
effector receptor
collagen fibers muscle tissue
efferent pathway reflex
connective tissue nerve
hormone reflex arc
connective-tissue cells nervous tissue
integrating center stimulus
elastin fibers neuron
epithelial cells organs
epithelial tissue organ system 1.7 The Role of Intercellular Chemical Messengers
epithelium tissues in Homeostasis
extracellular matrix (ECM) autocrine substances neurotransmitters
endocrine glands paracrine substances
1.3 Body Fluid Compartments
extracellular fluid interstitium 1.8 Processes Related to Homeostasis
internal environment intracellular fluid acclimatization negative balance
interstitial fluid plasma adaptation pacemaker
circadian rhythm pineal gland
1.4 Homeostasis: A Defining Feature of Physiology entrainment pool
free-running rhythm positive balance
dynamic constancy homeostasis
melatonin stable balance

Homeostasis: A Framework for Human Physiology 19

 CHAPTER 1 TEST QU E ST ION S Recall and Comprehend Answers appear in Appendix A.

These questions test your recall of important details covered in this chapter. They also help prepare you for the type of questions
encountered in standardized exams. Many additional questions of this type are available on Connect and LearnSmart.

1. Which of the following is one of the four basic cell types in the body? d. Drinking an excess of water will create a negative balance of water in
a. respiratory the body.
b. epithelial e. Acclimatization requires a modification of a person’s genetic makeup.
c. endocrine 5. Most of the water in the human body is found in
d. integumentary a. the interstitial fluid compartment.
e. immune b. the intracellular fluid compartment.
2. Which of the following is incorrect? c. the plasma compartment.
a. Equilibrium requires a constant input of energy. d. the total extracellular fluid compartment.
b. Positive feedback is less common in nature than negative feedback. 6. The type of tissue involved in many types of transport processes, and
c. Homeostasis does not imply that a given variable is unchanging. which often lines the inner surfaces of tubular structures, is called    .
d. Fever is an example of resetting a set point.
7. All the fluid found outside cells is collectively called     fluid, and
e. Efferent pathways carry information away from the integrating center
consists of     and     fluid.
of a reflex arc.
8. Physiological changes that occur in anticipation of a future change to a
3. In a reflex arc initiated by touching a hand to a hot stove, the effector
homeostatic variable are called     processes.
belongs to which class of tissue?
a. nervous c. muscle 9. A     is a chemical factor released by cells that acts on neighboring
b. connective d. epithelial cells without having to first enter the blood.
4. Which is correct? 10. When loss of a substance from the body exceeds its gain, a person is said to
a. Circadian rhythms can only free-run; they cannot be fixed to some be in     balance for that substance.
environmental cue.
b. Being able to perceive color is an example of an acclimatization.
c. Eating a very salty meal will create a period of positive sodium balance
in the blood.

CHAPTER 1 TEST QU E ST ION S Apply, Analyze, and Evaluate Answers appear in Appendix A.

These questions, which are designed to be challenging, require you to integrate concepts covered in the chapter to draw your own
conclusions. See if you can first answer the questions without using the hints that are provided; then, if you are having difficulty, refer
back to the figures or sections indicated in the hints.

1. The Inuit of Alaska and Canada have a remarkable ability to work in the 2. Explain how an imbalance in any given physiological variable may produce
cold without gloves and not suffer decreased skin blood flow. Does this a change in one or more other variables. Hint: For help, see Section 1.4 and
prove that there is a genetic difference between the Inuit and other people Figure 1.13.
with regard to this characteristic? Hint: Refer back to “Adaptation and
Acclimatization” in Section 1.8.

20 Chapter 1