Human Physiology: The Mechanism of Body Function - part 10 ppsx

Vander et al.: Human
Physiology: The
Mechanism of Body
Function, Eighth Edition
III. Coordinated Body
Functions
20. Defense Mechanisms of
the Body
© The McGraw−Hill
Companies, 2001
The Fetus as a Graft During pregnancy the fetal tro-
phoblast cells of the placenta (Chapter 19) lie in direct
contact with maternal immune cells. Since half of the
fetal genes are paternal, all proteins coded for by these
genes are foreign to the mother. Why does the mother’s
immune system not attack the trophoblast cells, which
express such proteins, and reject the placenta? This
problem is far from solved, but one critical mechanism
(there are certainly others) is as follows: Trophoblast
cells, unlike virtually all other nucleated cells, do not
express the usual MHC class I proteins; instead they
express a unique MHC class I protein that maternal
immune cells do not recognize as foreign.
Transfusion Reactions
Transfusion reactions, the illness caused when eryth-
rocytes are destroyed during blood transfusion, are a
special example of tissue rejection, one that illustrates
the fact that antibodies rather than cytotoxic T cells can
sometimes be the major factor in rejection. Erythro-
cytes do not have MHC proteins, but they do have

plasma-membrane proteins and carbohydrates (the
latter linked to the membrane by lipids) that can func-
tion as antigens when exposed to another person’s
blood. There are more than 400 erythrocyte antigens,
but the ABO system of carbohydrates is the most im-
portant for transfusion reactions.
Some people have the gene that results in synthe-
sis of the A antigen, some have the gene for the B anti-
gen, some have both genes, and some have neither
gene. (Genes cannot code for the carbohydrates that
function as antigens; rather they code for the particu-
lar enzymes that catalyze formation of the carbohy-
drates.) The erythrocytes of those with neither gene are
said to have O-type erythrocytes. Accordingly, the pos-
sible blood types are A, B, AB, and O (Table 20–8).
Type A individuals always have anti-B antibodies
in their plasma. Similarly, type B individuals have
plasma anti-A antibodies. Type AB individuals have
neither anti-A nor anti-B antibody, and type O indi-
viduals have both. These antierythrocyte antibodies
are called natural antibodies. How they arise “natu-
rally”—that is, without exposure to the appropriate
antigen-bearing erythrocytes—is not presently clear.
With this information as background, we can pre-
dict what happens if a type A person were given type
B blood. There are two incompatibilities: (1) The re-
cipient’s anti-B antibodies cause the transfused cells to
be attacked, and (2) the anti-A antibodies in the trans-
fused plasma cause the recipient’s cells to be attacked.
The latter is generally of little consequence, however,

because the transfused antibodies become so diluted
in the recipient’s plasma that they are ineffective in in-
ducing a response. It is the destruction of the trans-
fused cells by the recipient’s antibodies that produces
the problems.
Similar analyses show that the following situations
would result in an attack on the transfused erythro-
cytes: a type B person given either A or AB blood; a
type A person given either type B or AB blood; a type
O person given A, B, or AB blood. Type O people are,
therefore, sometimes called universal donors, whereas
type AB people are universal recipients. These terms
are misleading, however, since besides antigens of the
ABO system, there are a host of other erythrocyte anti-
gens and plasma antibodies against them. Therefore,
except in a dire emergency, the blood of donor and re-
cipient must be tested for incompatibilities directly by
the procedure called cross-matching. The recipient’s
serum is combined on a glass slide with the prospec-
tive donor’s erythrocytes (a “major” cross-match), and
the mixture is observed for rupture (hemolysis) or
clumping (agglutination) of the erythrocytes; this in-
dicates a mismatch. In addition, the recipient’s eryth-
rocytes can be combined with the prospective donor’s
serum (a “minor” cross-match), looking again for
mismatches.
Another group of erythrocyte membrane antigens
of medical importance is the Rh system of proteins.
There are more than 40 such antigens, but the one most
likely to cause a problem is termed Rh

o
, known com-
monly as the Rh factor because it was first studied in
717
Defense Mechanisms of the Body CHAPTER TWENTY
TABLE 20–8
Human ABO Blood Groups
Genetic Possibilities
Blood Group Percent* Antigen on RBC Homozygous Heterozygous Antibody in Blood
A 42 A AA AO Anti-B
B 10 B BB BO Anti-A
AB 3 A and B — AB Neither anti-A nor anti-B
O 45 Neither A nor B OO — Both anti-A and anti-B
*In the United States.
Vander et al.: Human
Physiology: The
Mechanism of Body
Function, Eighth Edition
III. Coordinated Body
Functions
20. Defense Mechanisms of
the Body
© The McGraw−Hill
Companies, 2001
rhesus monkeys. Human erythrocytes either have the
antigen (Rh-positive) or lack it (Rh-negative). About 85
percent of the U.S. population is Rh-positive.
Antibodies in the Rh system, unlike the “natural
antibodies” of the ABO system, follow the classical im-
munity pattern in that no one has anti-Rh antibodies

unless exposed to Rh-positive cells from another per-
son. This can occur if an Rh-negative person is sub-
jected to multiple transfusions with Rh-positive blood,
but its major occurrence involves the mother-fetus re-
lationship. When an Rh-negative mother carries an Rh-
positive fetus, some of the fetal erythrocytes may cross
the placental barriers into the maternal circulation, in-
ducing her to synthesize anti-Rh antibodies. Because
this occurs mainly during separation of the placenta at
delivery, a first Rh-positive pregnancy rarely offers any
danger to the fetus since delivery occurs before the
antibodies are made by the mother. In future preg-
nancies, however, these antibodies will already be
present in the mother and can cross the placenta to at-
tack and hemolyze the erythrocytes of an Rh-positive
fetus. This condition, which can cause an anemia se-
vere enough to result in death of the fetus in utero
or of the newborn, is called hemolytic disease of the
newborn. The risk increases with each Rh-positive
pregnancy as the mother becomes more and more
sensitized.
Fortunately, this disease can be prevented by giv-
ing an Rh-negative mother human gamma globulin
against Rh-positive erythrocytes within 72 h after she
has delivered an Rh-positive infant. These antibodies
bind to the antigenic sites on any Rh-positive erythro-
cytes that might have entered the mother’s blood dur-
ing delivery and prevent them from inducing antibody
synthesis by the mother. The administered antibodies
are eventually catabolized.

You may be wondering whether ABO incompati-
bilities are also a cause of hemolytic disease of the new-
born. For example, a woman with type O blood has
antibodies to both the A and B antigens. If her fetus is
type A or B, this theoretically should cause a problem.
Fortunately, it usually does not, partly because the A
and B antigens are not strongly expressed in fetal eryth-
rocytes and partly because the antibodies, unlike the
anti-Rh antibodies, are of the IgM type, which do not
readily cross the placenta.
Allergy (Hypersensitivity)
Allergy or hypersensitivity refers to diseases in which
immune responses to environmental antigens cause in-
flammation and damage to the body itself. Antigens
that cause allergy are termed allergens, common ex-
amples of which include those in ragweed pollen and
poison ivy. Most allergens themselves are relatively or
completely harmless, and it is the immune responses
to them that cause the damage. In essence, then, al-
lergy is immunity gone wrong, for the response is in-
appropriate to the stimulus.
A word about terminology is useful here: As we
shall see, there are three major types of hypersensitiv-
ity, as categorized by the different immunologic effec-
tor pathways involved in the inflammatory response.
The term “allergy” is sometimes used popularly to de-
note only one of these types, that mediated by IgE an-
tibodies. We shall follow common practice, however,
of using the term “allergy” in its broader sense as syn-
onymous with “hypersensitivity.”

To develop a particular allergy, a genetically pre-
disposed person must first be exposed to the allergen.
This initial exposure causes “sensitization,” and it is
the subsequent exposures that elicit the damaging im-
mune responses we recognize as the disease. The di-
versity of allergic responses reflects the different im-
munological effector pathways elicited, and the
classification of allergic diseases is based on these
mechanisms (Table 20–9).
In one type of allergy, the inflammatory response
is independent of antibodies. It is due to marked se-
cretion of cytokines by helper T cells activated by anti-
gen in the area. These cytokines themselves act as in-
flammatory mediators and also activate macrophages
to secrete their potent mediators. Because it takes sev-
eral days to develop, this type of allergy is known as
delayed hypersensitivity. The skin rash that appears
after contact with poison ivy is an example.
In contrast to this are the various types of
antibody-mediated allergic responses. One important
type is termed immune-complex hypersensitivity. It
occurs when so many antibodies (of either the IgG or
IgM types) combine with free antigens that large num-
bers of antigen-antibody complexes precipitate out on
the surface of endothelial cells or are trapped in cap-
illary walls, particularly those of the renal corpuscles.
These immune complexes activate complement, which
then induces an inflammatory response that damages
the tissues immediately surrounding the complexes.
Allergy to penicillin is an example.

718
PART THREE Coordinated Body Functions
1. Delayed hypersensitivity—Mediated by helper T cells
and macrophages; independent of antibodies
2. Immune-complex hypersensitivity—Mediated by
antigen-antibody complexes deposited in tissue
3. Immediate hypersensitivity—Mediated by IgE
antibodies, mast cells, and eosinophils
TABLE 20–9
Major Types of Hypersensitivity
Vander et al.: Human
Physiology: The
Mechanism of Body
Function, Eighth Edition
III. Coordinated Body
Functions
20. Defense Mechanisms of
the Body
© The McGraw−Hill
Companies, 2001
The more common type of antibody-mediated al-
lergic responses, however, are those termed immedi-
ate hypersensitivity, because they are usually very
rapid in onset. They are also called IgE-mediated hy-
persensitivity because they involve IgE antibodies.
Immediate Hypersensitivity In immediate hypersensi-
tivity, initial exposure to the antigen leads to some an-
tibody synthesis and, more important, to the produc-
tion of memory B cells that mediate active immunity.
Upon reexposure, the antigen elicits a more powerful

antibody response. So far, none of this is unusual, but
the difference is that the particular antigens that elicit
immediate hypersensitivity reactions stimulate, in ge-
netically susceptible persons, the production of type
IgE antibodies. Production of IgE requires the partici-
pation of a particular subset of helper T cells that are
activated by the allergens presented by B cells. These
activated helper T cells then release cytokines that pref-
erentially stimulate differentiation of the B cells into
IgE-producing plasma cells.
Upon their release from plasma cells, IgE anti-
bodies circulate to various parts of the body and be-
come attached, via binding sites on their Fc portions,
to connective-tissue mast cells (Figure 20–20). When
subsequently the same antigen type enters the body
and combines with the IgE bound to the mast cell, this
triggers the mast cell to secrete many inflammatory
719
Defense Mechanisms of the Body CHAPTER TWENTY
Mediator release
Mediator release
Begin
Antigen
Mast cell
Mediator release
Early allergic reactions
(immediate hypersensitivity)
Late-phase reactions
Smooth muscle contraction (asthma)
Vascular leakage (swelling)

Hypotension (shock)
Mucus secretion
Itching
Onset in minutes Onset in 2–8 h
Persists for
1–2 days
Infiltration of local
area with eosinophils
Infiltration of local
area with macrophages
Tissue destruction
IgE
FIGURE 20–20
Sequence of events in an immediate hypersensitivity allergic response.
Vander et al.: Human
Physiology: The
Mechanism of Body
Function, Eighth Edition
III. Coordinated Body
Functions
20. Defense Mechanisms of
the Body
© The McGraw−Hill
Companies, 2001
mediators, including histamine, various eicosanoids,
and chemokines. All these mediators then initiate a lo-
cal inflammatory response. (The entire sequence of
events just described for mast cells can also occur with
basophils in the circulation.)
Thus, the symptoms of IgE-mediated allergy reflect

the various effects of these inflammatory mediators and
the body site in which the antigen-IgE-mast cell com-
bination occurs. For example, when a previously sen-
sitized person inhales ragweed pollen, the antigen com-
bines with IgE on mast cells in the respiratory passages.
The mediators released cause increased secretion of
mucus, increased blood flow, swelling of the epithelial
lining, and contraction of the smooth muscle sur-
rounding the airways. Thus, there follow the symptoms
of congestion, running nose, sneezing, and difficulty in
breathing that characterize hay fever.
Allergic symptoms are usually localized to the site
of entry of the antigen. If very large amounts of the
chemicals released by the mast cells (or blood ba-
sophils) enter the circulation, however, systemic symp-
toms may result and cause severe hypotension and
bronchiolar constriction. This sequence of events,
termed anaphylaxis, can cause death due to circula-
tory and respiratory failure. It can be elicited in some
sensitized people by the antigen in a single bee sting.
The very rapid components of immediate hyper-
sensitivity often proceed to a late-phase reaction last-
ing many hours or days, during which large numbers
of leukocytes, particularly eosinophils, migrate into
the inflamed area. The chemoattractants involved are
particular cytokines released by mast cells and helper
T cells activated by the allergen. The eosinophils, once
in the area, secrete mediators that prolong the inflam-
mation and sensitize the tissues, so that less allergen
is needed the next time to evoke a response.

Given the inappropriateness of most immediate
hypersensitivity responses, how did such a system
evolve? The normal physiological function of the IgE–
mast cell–eosinophil pathways is to repel invasion by
multicellular parasites that cannot be phagocytized.
The mediators released by the mast cells stimulate the
inflammatory response against the parasites, and the
eosinophils serve as the major killer cells against them
by secreting several toxins. How this system also came
to be inducible by harmless agents is not clear.
Autoimmune Disease
While allergy is due to an inappropriate response to
an environmental antigen, autoimmune disease is due
to an inappropriate immune attack triggered by the
body’s own proteins acting as antigens. The immune
attack, mediated by autoantibodies and self-reactive
T cells, is directed specifically against the body’s own
cells that contain these proteins.
We explained earlier how the body is normally in
a state of immune tolerance toward its own cells.
Unfortunately, there are situations in which this toler-
ance breaks down and the body does in fact launch
antibody- or killer cell–mediated attacks against its
own cells and tissues. A growing number of human
diseases are being recognized as autoimmune in ori-
gin. Examples are multiple sclerosis, in which myelin
is attacked; myasthenia gravis, in which the receptors
for acetylcholine on skeletal-muscle cells are the tar-
get; rheumatoid arthritis, in which joints are damaged;
and insulin-dependent diabetes mellitus, in which the

insulin-producing cells of the pancreas are destroyed.
Some possible causes for the body’s failure to recog-
nize its own cells are summarized in Table 20–10.
Excessive Inflammatory Responses
Recall that complement, other inflammatory media-
tors, and the toxic chemicals secreted by neutrophils
and macrophages are not specific with regard to their
targets. Accordingly, sometimes during an inflamma-
tory response directed against microbes there can be
so much generation or release of these substances that
adjacent normal tissues may be damaged. These sub-
stances can also cause potentially lethal systemic
720
PART THREE Coordinated Body Functions
1. There may be failure of clonal deletion in the thymus or of clonal inactivation in the periphery. This is particularly true for
“sequestered antigens,” such as certain proteins that are unavailable to the immune system during critical early-life periods.
2. Normal body proteins may be altered by combination with drugs or environmental chemicals. This leads to an attack on the
cells bearing the now-”foreign” protein.
3. In immune attacks on virus-infected bodily cells, so many cells may be destroyed that disease results.
4. Genetic mutations in the body’s cells may yield new proteins that serve as antigens.
5. The body may encounter microbes whose antigens are so close in structure to certain of the body’s own proteins that the
antibodies or cytotoxic T cells produced against these microbial antigens also attack cells bearing the self proteins.
6. Proteins normally never encountered by lymphocytes may become exposed as a result of some other disease.
TABLE 20–10
Some Possible Causes of Autoimmune Attack
Vander et al.: Human
Physiology: The
Mechanism of Body
Function, Eighth Edition
III. Coordinated Body

Functions
20. Defense Mechanisms of
the Body
© The McGraw−Hill
Companies, 2001
responses. For example, macrophages release very
large amounts of IL-1 and TNF, both of which are pow-
erful inflammatory mediators (in addition to their
other effects) in response to an infection with certain
types of bacteria. These cytokines can cause profound
vasodilation throughout the body, precipitating a type
of hypotension termed septic shock. This is often ac-
companied by dangerously high fevers. In other
words, it is not the bacteria themselves that cause sep-
tic shock but rather the cytokines released in response
to the bacteria.
Another important example of damage produced
by excessive inflammation in response to microbes is
the dementia that occurs in AIDS. HIV does not itself
attack neurons but it does infect microglia. Such in-
vasion causes the microglia, which function as
macrophage-like cells, to produce very high levels of
inflammatory cytokines and other molecules that are
toxic to neurons. (Microglia are also implicated in non-
infectious brain disorders, like Alzheimer’s disease,
that are characterized by inflammation.)
Excessive long-standing inflammation can also oc-
cur in the absence of microbial infection. Thus, vari-
ous major diseases, including asthma, rheumatoid
arthritis, and inflammatory bowel disease, are cate-

gorized as chronic inflammatory diseases. The causes
of these diseases, and the interplay between genetic
and environmental factors, are still poorly understood.
Some, like rheumatoid arthritis, are mainly autoim-
mune in nature, but all are associated with a marked
positive-feedback increase in the production of cy-
tokines and other inflammatory mediators.
Yet another example of excessive inflammation in
a noninfectious state is the development of athero-
sclerotic plaques in blood vessels (Chapter 14). It is
likely that, in response to endothelial cell dysfunction,
the vessel wall releases inflammatory cytokines (IL-1,
for example) that promote all stages of atherosclero-
sis—excessive clotting, chemotaxis of various leuko-
cytes (as well as smooth-muscle cells), and so on. The
endothelial-cell dysfunction is caused by initially sub-
tle vessel-wall injury by lipoproteins and other factors,
including elevated blood pressure and homocysteine
(Chapter 14).
In summary, the various mediators of inflamma-
tion and immunity are a double-edged sword: In usual
amounts they are essential for normal resistance, but
in excessive amounts they can cause illness.
This completes the section on immunology. Table
20–11 presents a summary of immune mechanisms in
the form of a miniglossary of cells and chemical me-
diators involved in immune responses. All the mate-
rial in this table has been covered in this chapter.
721
Defense Mechanisms of the Body CHAPTER TWENTY

TABLE 20–11
A Miniglossary of Cells and Chemical Mediators Involved in Immune Functions
Cells
Activated macrophages Macrophages whose killing ability has been enhanced by cytokines, particularly IL-2 and interferon-
gamma.
Antigen-presenting cells (APC) Cells that present antigen, complexed with MHC proteins, on their surface to T cells.
B cells Lymphocytes that, upon activation, proliferate and differentiate into antibody-secreting plasma cells; provide major defense
against bacteria, viruses in the extracellular fluid, and toxins; can function as antigen-presenting cells for helper T cells.
Cytotoxic T cells The class of T lymphocytes that, upon activation by specific antigen, directly attacks the cells bearing that type
of antigen; are major killers of virus-infected cells and cancer cells; bind antigen associated with class I MHC proteins.
Eosinophils Leukocytes involved in destruction of parasites and in immediate hypersensitivity responses.
Helper T cells The class of T cells that, via secreted cytokines, plays a stimulatory role in the activation of B cells and cytotoxic
T cells; also can activate NK cells and macrophages; bind antigen associated with class II MHC proteins.
Lymphocytes The type of leukocyte responsible for specific immune defenses; categorized mainly as B cells, T cells, and NK cells.
Macrophages Cell type that (1) functions as phagocytes, (2) processes and presents antigen to helper T cells, and (3) secretes
cytokines involved in inflammation, activation of lymphocytes, and the systemic acute phase response to infection or injury.
Macrophage-like cells Several cell types that exert functions similar to those of macrophages (for example, microglia).
Mast cells Tissue cell that binds IgE and releases inflammatory mediators in response to parasites and immediate hypersensitivity
reactions.
Memory cells B cells and cytotoxic T cells that differentiate during an initial immune response and respond rapidly during a
subsequent exposure to the same antigen.
Monocytes A type of leukocyte; leaves the bloodstream and is transformed into a macrophage; has functions similar to those of
macrophages.
Natural killer (NK) cells Class of lymphocytes that binds to cells bearing foreign antigens without specific recognition and kills
them directly; major targets are virus-infected cells and cancer cells; participate in antibody-dependent cellular cytotoxicity (ADCC).
Neutrophils Leukocytes that function as phagocytes and also release chemicals involved in inflammation.
Plasma cells Cells that differentiate from activated B lymphocytes and secrete antibodies.
T cells Lymphocytes derived from precursors that differentiated in the thymus; see cytotoxic T cells and helper T cells.
Vander et al.: Human
Physiology: The

Mechanism of Body
Function, Eighth Edition
III. Coordinated Body
Functions
20. Defense Mechanisms of
the Body
© The McGraw−Hill
Companies, 2001
722
PART THREE Coordinated Body Functions
Chemical Mediators
Acute phase proteins Group of proteins secreted by the liver during systemic response to injury or infection; stimulus for their
secretion is IL-1, IL-6, and other cytokines.
Antibodies Immunoglobulins that are secreted by plasma cells; combine with the type of antigen that stimulated their production
and direct an attack against the antigen or a cell bearing it.
C1 The first protein in the classical complement pathway.
Chemoattractants A general name given to any chemical mediator that stimulates chemotaxis of neutrophils or other leukocytes.
Chemokines Any cytokine that functions as a chemoattractant.
Chemotaxin A synonym for chemoattractant.
Complement A group of plasma proteins that, upon activation, kills microbes directly and facilitates the various steps of the
inflammatory process, including phagocytosis; the classical complement pathway is triggered by antigen-antibody complexes,
whereas the alternate pathway can operate independently of antibody.
C-reactive protein One of several proteins that function as nonspecific opsonins; production by the liver is increased during the
acute phase response.
Cytokines General term for protein messengers that regulate immune responses; secreted by macrophages, monocytes,
lymphocytes, neutrophils, and several nonimmune cell types; function both locally and as hormones.
Eicosanoids General term for products of arachidonic acid metabolism (prostaglandins, thromboxanes, leukotrienes); function as
important inflammatory mediators.
Histamine An inflammatory mediator secreted mainly by mast cells; acts on microcirculation to cause vasodilation and increased
permeability to protein.

IgA The class of antibodies secreted by the lining of the body’s various “tracts.”
IgD A class of antibodies whose function is unknown.
IgE The class of antibodies that mediate immediate hypersensitivity and resistance to parasites.
IgG The most abundant class of plasma antibodies.
IgM A class of antibodies that, along with IgG, provides the bulk of specific humoral immunity against bacteria and viruses.
Immunoglobulin (Ig) Proteins that function as B-cell receptors and antibodies; the five major classes are IgA, IgD, IgE, IgG, and
IgM.
Interferon Group of cytokines that nonspecifically inhibits viral replication; interferon-gamma also stimulates the killing ability of
NK cells and macrophages.
Interferon-gamma (See Interferon)
Interleukin 1 (IL-1) Cytokine secreted by macrophages (and other cells) that activates helper T cells, exerts many inflammatory
effects, and mediates many of the systemic acute phase responses, including fever.
Interleukin 2 (IL-2) Cytokine secreted by activated helper T cells that causes helper T cells, cytotoxic T cells, and NK cells to
proliferate, and cause activation of macrophages.
Interleukin 6 (IL-6) Cytokine secreted by macrophages (and other cells) that exerts multiple effects on immune-system cells,
inflammation, and the acute phase response.
Kinins Peptides that split from kininogens in inflamed areas and facilitate the vascular changes associated with inflammation; they
also activate neuronal pain receptors.
Leukotrienes A class of eicosanoids that is generated by the lipoxygenase pathway and functions as inflammatory mediators.
Membrane attack complex (MAC) Group of complement proteins that form channels in the surface of a microbe, making it
leaky and killing it.
Natural antibodies Antibodies to the erythrocyte antigens (of the A or B type)
Opsonin General name given to any chemical mediator that promotes phagocytosis.
Perforin Protein secreted by cytotoxic T cells and NK cells that forms channels in the plasma membrane of the target cell, making
it leaky and killing it; its structure and function are similar to that of the MAC in the complement system.
Tumor necrosis factor (TNF) Cytokine that is secreted by macrophages (and other cells) and that has many of the same actions
as IL-1.
TABLE 20–11
A Miniglossary of Cells and Chemical Mediators Involved in Immune Functions (Cont.)
Cells Mediating Immune Defenses

I. Immune defenses may be nonspecific, in which the
identity of the target is not recognized, or it may be
specific, in which it is recognized.
II. The cells of the immune system are leukocytes
(neutrophils, eosinophils, basophils, monocytes, and
lymphocytes), plasma cells, macrophages,
macrophage-like cells, and mast cells. The leukocytes
use the blood for transportation but function mainly
in the tissues.
SECTION A SUMMARY
III. Cells of the immune system (as well as some other
cells) secrete protein messengers that regulate
immune responses and are collectively termed
cytokines.
Nonspecific Immune Defenses
I. External barriers to infection are the skin, the linings
of the respiratory, gastrointestinal, and genitourinary
tracts, the cilia of these linings, and antimicrobial
chemicals in glandular secretions.
II. Inflammation, the local response to injury or
infection, includes vasodilation, increased vascular
permeability to protein, phagocyte chemotaxis,
Vander et al.: Human
Physiology: The
Mechanism of Body
Function, Eighth Edition
III. Coordinated Body
Functions
20. Defense Mechanisms of
the Body

© The McGraw−Hill
Companies, 2001
destruction of the invader via phagocytosis or
extracellular killing, and tissue repair.
a. The mediators controlling these processes,
summarized in Table 20
–3, are either released
from cells in the area or generated extracellularly
from plasma proteins.
b. The main cells that function as phagocytes are the
neutrophils, monocytes, macrophages, and
macrophage-like cells. These cells also secrete
many inflammatory mediators.
c. One group of inflammatory mediators—the
complement family of plasma proteins activated
during nonspecific inflammation by the alternate
complement pathway—not only stimulates
many of the steps of inflammation but mediates
extracellular killing via the membrane attack complex.
d. The end result of infection or tissue damage is
tissue repair.
III. Interferon stimulates the production of intracellular
proteins that nonspecifically inhibit viral replication.
Specific Immune Defenses
I. Lymphocytes mediate specific immune responses.
II. Specific immune responses occur in three stages.
a. A lymphocyte programmed to recognize a specific
antigen encounters it and binds to it via plasma-
membrane receptors specific for the antigen.
b. The lymphocyte undergoes activation—a cycle of

cell divisions and differentiation.
c. The multiple active lymphocytes produced in this
manner launch an attack all over the body against
the specific antigens that stimulated their
production.
III. The lymphoid organs are categorized as primary
(bone marrow and thymus) or secondary (lymph
nodes, spleen, tonsils and lymphocyte collections in
the linings of the body’s tracts).
a. The primary lymphoid organs are the sites of
maturation of lymphocytes that will then be
carried to the secondary lymphoid organs, which
are the major sites of lymphocyte cell division
and specific immune responses.
b. Lymphocytes undergo a continuous recirculation
among the secondary lymphoid organs, lymph,
blood, and all the body’s organs and tissues.
IV. The three broad populations of lymphocytes are B, T,
and NK cells.
a. B cells mature in the bone marrow and are carried
to the secondary lymphoid organs, where
additional B cells arise by cell division.
b. T cells leave the bone marrow in an immature
state, are carried to the thymus, and undergo
maturation there. These cells then travel to the
secondary lymphoid organs and new T cells arise
from them by cell division.
c. NK cells originate in the bone marrow.
V. B cells and T cells have different functions.
a. B cells, upon activation, differentiate into plasma

cells, which secrete antibodies. Antibody-
mediated responses constitute the major defense
against bacteria, viruses, and toxins in the
extracellular fluid.
b. Cytotoxic T cells directly attack and kill virus-
infected cells and cancer cells, without the
participation of antibodies.
c. Helper T cells stimulate B cells and cytotoxic
T cells via the cytokines they secrete. With few
exceptions, this help is essential for activation of
the B cells and cytotoxic T cells.
VI. B-cell surface plasma-membrane receptors are copies
of the specific antibody (immunoglobulin) that the
cell is capable of producing.
a. Any given B cell or clone of B cells produces
antibodies that have a unique antigen binding site.
b. Antibodies are composed of four interlocking
polypeptide chains; the variable regions of the
antibodies are the sites that bind antigen.
VII. T-cell surface plasma-membrane receptors are not
immunoglobulins, but they do have specific antigen
binding sites that differ from one T-cell clone to
another.
a. The T-cell receptor binds antigen only when the
antigen is complexed to one of the body’s own
plasma-membrane MHC proteins.
b. Class I MHC proteins are found on all nucleated
cells of the body, whereas class II MHC proteins
are found only on macrophages, B cells, and
macrophage-like cells. Cytotoxic T cells require

antigen to be complexed to class I proteins,
whereas helper T cells require class II proteins.
VIII. Antigen presentation is required for T cell activation.
a. Only macrophages, B cells, and macrophage-like
cells function as antigen-presenting cells (APCs)
for helper T cells. The antigen is internalized by
the APC and hydrolyzed to peptide fragments,
which are complexed with class II MHC proteins.
This complex is then shuttled to the plasma
membrane of the APC, which also delivers a
nonspecific costimulus to the T cell and secretes
interleukin 1 (IL-1) and tumor necrosis factor
(TNF).
b. A virus-infected cell or cancer cell can function as
an APC for cytotoxic T cells. The viral antigen or
cancer-associated antigen is synthesized by the
cell itself and hydrolyzed to peptide fragments,
which are complexed to class I MHC proteins.
The complex is then shuttled to the plasma
membrane of the cell.
IX. NK cells have the same targets as cytotoxic T cells,
but they are not antigen-specific; most of their
mechanisms of target identification are not
understood.
X. Immune tolerance is the result of clonal deletion and
clonal inactivation.
XI. In antibody-mediated responses, the membrane
receptors of a B cell bind antigen, and at the same
time a helper T cell also binds antigen in association
with a class II MHC protein on a macrophage or

other APC.
a. The helper T cell, activated by the antigen, by a
nonantigenic protein costimulus, and by IL-1 and
TNF secreted by the APC, secretes IL-2, which
then causes the helper T cell to proliferate into a
clone of cells that secrete additional cytokines.
723
Defense Mechanisms of the Body CHAPTER TWENTY
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Physiology: The
Mechanism of Body
Function, Eighth Edition
III. Coordinated Body
Functions
20. Defense Mechanisms of
the Body
© The McGraw−Hill
Companies, 2001
b. These cytokines then stimulate the antigen-bound
B cell to proliferate and differentiate into plasma
cells, which secrete antibodies. Some of the
activated B cells become memory cells, which are
responsible for active immunity.
c. There are five major classes of secreted antibodies:
IgG, IgM, IgA, IgD, and IgE. The first two are the
major antibodies against bacterial and viral
infection.
d. The secreted antibodies are carried throughout
the body by the blood and combine with antigen.
The antigen-antibody complex enhances the

inflammatory response, in large part by activating
the complement system. Complement proteins
mediate many steps of inflammation, act as
opsonins, and directly kill antibody-bound cells
via the membrane attack complex.
e. Antibodies of the IgG class also act directly as
opsonins and link target cells to NK cells, which
directly kill the target cells.
f. Antibodies also neutralize toxins and extracellular
viruses.
XII. Virus-infected cells and cancer cells are killed by
cytotoxic T cells, NK cells, and activated
macrophages.
a. A cytotoxic T cell binds, via its membrane
receptor, to cells bearing a viral antigen or cancer-
associated antigen in association with a class I
MHC protein.
b. Activation of the cytotoxic T cell also requires
cytokines secreted by helper T cells, themselves
activated by antigen presented by a macrophage.
The cytotoxic T cell then releases perforin, which
kills the attached target cell by making it leaky.
c. NK cells and macrophages are also stimulated by
helper T cell cytokines, particularly IL-2 and
interferon-gamma, to attack and kill virus-infected
or cancer cells.
Systemic Manifestations of Infection
I. The acute phase response is summarized in Figure
20
–19.

II. The major mediators of this response are IL-1, TNF,
and IL-6.
Factors That Alter the Body’s
Resistance to Infection
I. The body’s capacity to resist infection is influenced
by nutritional status, the presence of other diseases,
psychological factors, and the intactness of the
immune system.
II. AIDS is caused by a retrovirus that destroys helper
T cells and therefore reduces the ability to resist
infection and cancer.
III. Antibiotics interfere with the synthesis of
macromolecules by bacteria.
Harmful Immune Responses
I. Rejection of tissue transplants is initiated by MHC
proteins on the transplanted cells and is mediated
mainly by cytotoxic T cells.
II. Transfusion reactions are mediated by antibodies.
a. Transfused erythrocytes will be destroyed if the
recipient has natural antibodies against the
antigens (type A or type B) on the cells.
b. Antibodies against Rh-positive erythrocytes can
be produced following exposure of an Rh-
negative person to such cells.
III. Allergy (hypersensitivity reactions), caused by
allergens, are of several types.
a. In delayed hypersensitivity, the inflammation is
due to the interplay of helper T cell cytokines and
macrophages. Immune complex hypersensitivity
is due to complement activation by antigen-

antibody complexes.
b. In immediate hypersensitivity, antigen binds to
IgE antibodies, which are themselves bound to
mast cells. The mast cells then release
inflammatory mediators such as histamine that
produce the symptoms of allergy. The late phase
of immediate hypersensitivity is mediated by
eosinophils.
IV. Autoimmune attacks are directed against the body’s
own proteins, acting as antigens. Reasons for the
failure of immune tolerance are summarized in Table
20
–
10.
V. Normal tissues can be damaged by excessive
inflammatory responses to microbes.
SECTION A KEY TERMS
724
PART THREE Coordinated Body Functions
immunology
immune surveillance
nonspecific immune defense
specific immune defense
immune system
leukocyte
plasma cell
macrophage
macrophage-like cell
mast cell
phagocyte

phagocytosis
cytokine
inflammation
chemotaxis
adhesion molecule
chemoattractant
chemotaxin
chemokine
opsonin
phagosome
phagolysosome
nitric oxide
hydrogen peroxide
complement
membrane attack complex
(MAC)
C3b
alternate complement
pathway
C-reactive protein
interferon
antigen
lymphocyte activation
lymphoid organ
primary lymphoid organ
secondary lymphoid organ
thymus
thymopoietin
lymph node
spleen

tonsil
B lymphocyte (B cell)
T lymphocyte (T cell)
natural killer cell (NK)
antibody
antibody-mediated responses
cytotoxic T cell
helper T cell
immunoglobulin
Fc
antigen binding site
major histocompatibility
complex (MHC)
MHC proteins (class I and
class II)
antigen presentation
antigen-presenting cell (APC)
epitope
costimulus
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_

1. What are the major cells of the immune system and
their general functions?
2. Describe the major anatomical and biochemical
barriers to infection.
3. Name the three cell types that function as
phagocytes.
4. List the sequence of events in an inflammatory
response and describe each.
5. Name the sources of the major inflammatory
mediators.
6. What triggers the alternate pathway for complement
activation? What roles does complement play in
inflammation and cell killing?
7. Describe the antiviral role of interferon.
8. Name the lymphoid organs. Contrast the functions
of the bone marrow and thymus with those of the
secondary lymphoid organs.
9. Name the various populations and subpopulations
of lymphocytes and state their roles in specific
immune responses.
10. Contrast the major targets of antibody-mediated
responses and responses mediated by cytotoxic
T cells and NK cells.
SECTION A REVIEW QUESTIONS
11. How do the Fc and combining-site portions of
antibodies differ?
12. What are the differences between B-cell receptors
and T-cell receptors? Between cytotoxic T-cell
receptors and helper T-cell receptors?
13. Compare and contrast antigen presentation to helper

T cells and cytotoxic T cells.
14. Compare and contrast cytotoxic T cells and NK cells.
15. What two processes contribute to immune tolerance?
16. Diagram the sequence of events in an antibody-
mediated response, including the role of helper
T cells, interleukin 1, and interleukin 2.
17. Contrast the general functions of the different
antibody classes.
18. How is complement activation triggered in the
classical complement pathway, and how does
complement “know” what cells to attack?
19. Name two ways in which the presence of antibodies
enhances phagocytosis.
20. How do NK cells “know” what cells to attack in
ADCC?
21. Diagram the sequence of events by which a virus-
infected cell is attacked and destroyed by cytotoxic
T cells. Include the roles of cytotoxic T cells, helper
T cells, interleukin 1, and interleukin 2.
22. Contrast the extracellular and intracellular phases of
immune responses to viruses, including the role of
interferon.
23. List the systemic responses to infection or injury and
the mediators responsible for them.
24. What factors influence the body’s resistance to
infection?
25. What is the major defect in AIDs, and what causes
it?
26. What is the major cell type involved in graft
rejection?

27. Diagram the sequences of events in immediate
hypersensitivity.
725
Defense Mechanisms of the Body CHAPTER TWENTY
interleukin 1 (IL-1)
tumor necrosis factor (TNF)
oncogene
immune tolerance
clonal deletion
clonal inactivation
interleukin 2 (IL-2)
memory cell
IgG
gamma globulin
IgM
IgE
IgA
IgD
classical complement
pathway
antibody-dependent cellular
cytotoxicity (ADCC)
active immunity
passive immunity
perforin
interferon-gamma
activated macrophage
acute phase response
acute phase protein
interleukin 6 (IL-6)

Rh factor
histamine
TOXICOLOGY: THE METABOLISM
OF ENVIRONMENTAL CHEMICALS
SECTION B
The body is exposed to a huge number of nonnutrient
chemicals in the environment, many of which can be
toxic. We shall refer to all these chemicals simply as
“foreign” chemicals. Some are products of the natural
world (lead, for example), but most are made by hu-
mans. There are now more than 10,000 chemicals be-
ing commercially synthesized, and over 1 million have
been synthesized at one time or another. Virtually all
foreign chemicals find their way into the body because
they are in the air, water, and food we use, or because
they are purposely taken, as drugs.
As described in Section A of this chapter, foreign
materials can induce inflammation and specific im-
mune responses. These defenses do not, however,
constitute the major defense mechanisms against most
foreign chemicals. Rather, metabolism—molecular
alteration, or biotransformation, and excretion—does.
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The body’s metabolism of foreign chemicals is
summarized in Figure 20–21. First, the chemical gains
entry to the body through the gastrointestinal tract,
lungs, skin, or placenta in the case of a fetus. Once
in the blood, the chemical may become bound re-
versibly to plasma proteins or to erythrocytes. Such
binding lowers its free concentration and thereby its
ability to alter cell function. It may accumulate in stor-
age depots—for example, DDT in fat tissue—or it may
undergo enzyme-mediated biotransformation in vari-
ous organs and tissues. The metabolites resulting from
biotransformation may enter the blood and follow the
same pathways as the parent molecules. Finally, the
chemical and its metabolites may be eliminated from
the body in urine, expired air, skin secretions, or feces.
The blood concentration of any foreign chemical
is determined by the interplay of all these metabolic
pathways. For example, kidney function and bio-
transformation both tend to decrease with age, which
explains why a particular dose of a drug often pro-
duces much higher blood concentrations in elderly
people than in young people.
726
PART THREE Coordinated Body Functions
Free chemical
and its
metabolites
Bound chemical

Exposure to chemical
Skin, GI tract, lungs
Absorption
Body
Blood
Sites of action
Tissue storage depots
Biotransformation sites
Metabolites
Excretory sites
Kidneys
GI tract
Skin
Lungs
Excretion
Chemical and its metabolites
FIGURE 20–21
Metabolic pathways for foreign chemicals.
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Function, Eighth Edition
III. Coordinated Body
Functions
20. Defense Mechanisms of
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Absorption
In practice, most foreign molecules move through the

lining of some portion of the gastrointestinal tract
fairly readily, either by diffusion or by carrier-mediated
transport. This should not be surprising since the
gastrointestinal tract evolved to favor absorption of the
wide variety of nutrient molecules in the environment.
Foreign chemicals are the beneficiaries of these rela-
tively nondiscriminating transport mechanisms.
The lung alveoli are highly permeable to most for-
eign chemicals and therefore offer an easy entrance
route for those that are airborne. Lipid solubility is all-
important for entry through the skin, so that this route
is of little importance for charged molecules but can
be used by oils, steroids, and other lipids.
The penetration of the placental membranes by
foreign chemicals is important since the effects of en-
vironmental agents on the fetus during critical periods
of development may be quite marked and, in many
cases, irreversible. Diffusion across the placenta occurs
for lipid-soluble substances, and carrier-mediated sys-
tems, which evolved for the movement of endogenous
nutrients, may be usurped by foreign chemicals to gain
entry into the fetus.
Storage Sites
The major storage sites for foreign chemicals are cell
proteins, bone matrix, and fat. A chemical bound to
cell proteins or bone or dissolved in the fat is in equi-
librium with the free chemical in the blood, so that an
increase in blood concentration causes more move-
ment into storage, up to the point of saturation. Con-
versely, as the chemical is eliminated from the body

and its blood concentration falls, movement occurs out
of storage sites.
These storage sites are a source of protection, but
it sometimes happens that the storage sites accumu-
late so much chemical that they become damaged. An
example of this is lead toxicity to the kidney cells that
bind lead.
Excretion
As described in Chapter 16, to appear in the urine, a
chemical must either be filtered through the renal cor-
puscle or secreted across the tubular epithelium.
Glomerular filtration is a bulk-flow process, so that all
low-molecular-weight substances in plasma undergo
filtration. Accordingly, there is considerable filtration
of most foreign chemicals, except those bound to
plasma proteins or erythrocytes. In contrast, tubular
secretion is by discrete transport processes, and many
foreign chemicals—penicillin, for example—utilize
the mediated transport systems available for naturally
occurring substances.
Once in the tubular lumen, the foreign chemical
will still not be excreted if it is reabsorbed across the
tubular epithelium into the blood. As the filtered fluid
moves along the renal tubules, molecules that are lipid-
soluble passively diffuse along with reabsorbed water
through the tubular epithelium and back into the
blood. The net result is that little is excreted in the
urine, and the chemical is retained in the body. If these
chemicals could be transformed into more polar and
therefore less lipid-soluble molecules, their passive re-

absorption from the tubule would be retarded and they
would be excreted more readily. This type of transfor-
mation is precisely what occurs in the liver, as de-
scribed in the next section.
An analogous problem exists for foreign molecules
secreted in the bile. Many of these substances, having
reached the lumen of the small intestine, are absorbed
back into the blood, thereby escaping excretion in the
feces. This cyclic enterohepatic circulation is described
in Chapter 17.
Biotransformation
The metabolic alteration—biotransformation—of for-
eign molecules occurs mainly in the liver, but to some
extent also in the kidneys, skin, placenta, and other or-
gans. A large number of distinct enzymes and path-
ways are involved, but the common denominator of
most of them is that they transform chemicals into
more polar, less lipid-soluble substances. One conse-
quence of this transformation is that the chemical may
be rendered less toxic, but this is not always so. The
second, more important, consequence is that the chem-
ical’s tubular reabsorption is diminished and urinary
excretion facilitated, as described in the previous sec-
tion. Similarly, for substances handled by biliary se-
cretion, gut absorption of the metabolite is less likely
so that fecal excretion is also enhanced.
The hepatic enzymes that perform these transfor-
mations are called the microsomal enzyme system
(MES) and are located mainly in the smooth endo-
plasmic reticulum. One of the most important features

of this enzyme system is that it is easily inducible; that
is, the number of these enzymes can be greatly in-
creased by exposure to a chemical that acts as a sub-
strate for the system. For example, chronic overuse of
alcohol results in an increased rate of alcohol catabo-
lism because of induction of the microsomal enzymes.
This accounts for much of the tolerance to alcohol—
that is, the fact that increasing doses must be taken to
achieve a given magnitude of effect.
727
Defense Mechanisms of the Body CHAPTER TWENTY
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Physiology: The
Mechanism of Body
Function, Eighth Edition
III. Coordinated Body
Functions
20. Defense Mechanisms of
the Body
© The McGraw−Hill
Companies, 2001
_
The hepatic biotransformation mechanisms vividly
demonstrate how an adaptive response may, under
some circumstances, turn out to be maladaptive. These
enzymes all too frequently “toxify” rather than “detox-
ify” a drug or pollutant. In fact, many foreign chemi-
cals are quite nontoxic until the liver enzymes bio-
transform them. Of particular importance is the fact
that many chemicals that cause cancer do so only after

biotransformation. For example, a major component of
cigarette smoke is transformed by the MES into a car-
cinogenic compound. Individuals with a very highly
inducible MES have a twenty- to fortyfold higher risk
of developing lung cancer from smoking.
The MES can also cause problems in another way
because it evolved primarily not to defend against
foreign chemicals, which were much less prevalent
during our evolution, but rather to metabolize endoge-
nous substances, particularly steroids and other lipid-
soluble molecules. Therefore, the induction of these en-
zymes by a drug or pollutant increases metabolism not
only of that drug or pollutant but of the endogenous
substances as well. The result is a decreased concen-
tration in the body of the normal substance, resulting
in its possible deficiency.
Another important fact about the MES is that
whereas certain chemicals induce it, others inhibit it.
The presence of such chemicals in the environment
could have deleterious effects on the system’s capac-
ity to protect against those chemicals that it transforms.
Just to illustrate how complex this picture can be, note
that any chemical that inhibits the microsomal enzyme
system may actually confer protection against those
other chemicals that must undergo transformation in
order to become toxic.
I. The concentration of a foreign chemical in the body
depends upon the degree of exposure to the
chemical, its rate of absorption across the GI tract,
lung, skin, or placenta, and its rates of storage,

biotransformation, and excretion.
II. Biotransformation occurs in the liver and other
tissues and is mediated by multiple enzymes,
notably the microsomal enzyme system (MES). The
major function of the MES is to make lipid-soluble
substances more polar (less lipid-soluble), thereby
decreasing renal tubular reabsorption and increasing
excretion.
a. The MES can be induced or inhibited by the
chemicals it processes and by other chemicals.
b. It detoxifies some chemicals but toxifies others,
notably carcinogens.
biotransformation
microsomal enzyme system (MES)
1. Why is the urinary excretion of lipid-soluble
substances generally very low?
2. What are two functions of biotransformation
mechanisms?
3. What are two ways in which activation of
biotransformation mechanisms may actually cause
malfunction?
SECTION B REVIEW QUESTIONS
SECTION B KEY TERMS
SECTION B SUMMARY
728
PART THREE Coordinated Body Functions
RESISTANCE TO STRESS
SECTION C
Much of this book has been concerned with the body’s
response to stress in its broadest meaning of an envi-

ronmental change that must be adapted to if health
and life are to be maintained. Thus, any change in ex-
ternal temperature, water intake, and so on, sets into
motion mechanisms designed to prevent a significant
change in some physiological variable. In this section,
however, we describe the basic stereotyped response
to stress in the more limited sense of noxious or po-
tentially noxious stimuli. These stimuli comprise an
immense number of situations, including physical
trauma, prolonged exposure to cold, prolonged heavy
exercise, infection, shock, decreased oxygen supply,
sleep deprivation, pain, fright, and other emotional
stresses.
It is obvious that the response to cold exposure is
very different from that to infection or fright, but in
one respect the response to all these situations is the
same: Invariably, secretion of the glucocorticoid hor-
mone cortisol by the adrenal cortex is increased. In-
deed, to physiologists the term “stress” has come to
mean any event that elicits increased cortisol secretion.
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© The McGraw−Hill
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Activity of the sympathetic nervous system, including
release of the hormone epinephrine from the adrenal
medulla, is also usually increased in stress.
The increased cortisol secretion of stress is medi-
ated mainly by the hypothalamo-anterior pituitary
system described in Chapter 10. As illustrated in Fig-
ure 20–22, neural input to the hypothalamus from por-
tions of the nervous system responding to a particular
stress induces secretion of corticotropin releasing
hormone (CRH). This hormone is carried by the
hypothalamo-pituitary portal vessels to the anterior
pituitary and stimulates adrenocorticotropic hormone
(ACTH) release. ACTH in turn circulates to the adre-
nal cortex and stimulates cortisol release.
The secretion of ACTH, and therefore of cortisol,
is stimulated by several hormones in addition to hy-
pothalamic CRH. These include vasopressin and epi-
nephrine, both of which are usually increased in
stress. But the most interesting recent finding, men-
tioned in Section A, is that several of the cytokines, in-
cluding interleukin 1, also stimulate ACTH secretion
(both directly and by stimulating the secretion of
CRH). These cytokines provide a means for eliciting
a classical stress response when the immune system
is stimulated. The possible significance of this rela-
tionship for immune function is described on the fol-
lowing pages.
Functions of Cortisol in Stress
The major effects of increased cortisol during stress are
summarized in Table 20–12. The effects on organic me-

tabolism, as described in Chapter 18, are to mobilize
fuels—to increase the plasma concentrations of amino
acids, glucose, glycerol, and free fatty acids. These ef-
fects are ideally suited to meet a stressful situation.
First, an animal faced with a potential threat is usually
forced to forego eating, and these metabolic changes
are essential for survival during fasting. Second, the
amino acids liberated by catabolism of body protein
not only provide a source of glucose, via gluconeo-
genesis, but also constitute a potential source of amino
acids for tissue repair should injury occur.
A few of the medically important implications of
these cortisol-induced effects on organic metabolism
are as follows: (1) Any patient who is ill or is sub-
jected to surgery catabolizes considerable quantities
of body protein; (2) a diabetic who suffers an infec-
tion requires more insulin than usual; and (3) a child
subjected to severe stress of any kind manifests re-
tarded growth.
Cortisol has important effects during stress other
than those on organic metabolism. It enhances vascu-
lar reactivity; that is, it increases the ability of vascu-
lar smooth muscle to contract in response to stimuli
such as norepinephrine. Therefore, a patient with in-
sufficient cortisol faced with even a moderate stress,
which usually releases unknown vasodilators, may
develop hypotension, due primarily to a marked de-
crease in total peripheral resistance caused by the
vasodilators.
729

Defense Mechanisms of the Body CHAPTER TWENTY
Hypothalamus
CRH secretion
Anterior pituitary
Adrenal cortex
Target cells of cortisol
ACTH secretion
Cortisol secretion
Respond to increased cortisol
(See Table 20-12)
Input from various brain areas
Stress
Plasma CRH
(in hypothalamo-pituitary
portal vessels)
Plasma ACTH
Plasma cortisol
FIGURE 20–22
Pathway by which stressful stimuli elicit increased cortisol
secretion. Additional stimuli, not shown in the figure, for
ACTH release are vasopressin, epinephrine, and several
cytokines, including IL-1, released from immune cells.
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As denoted by item 3 in Table 20–12, we still do
not know the other reasons, in addition to the effect
on vascular smooth muscle, why increased cortisol is
so important for the body’s optimal response to
stress—that is, for its ability to resist the damaging in-
fluences of stress. What is clear is that persons exposed
to severe stresses can die, usually of circulatory fail-
ure, if their plasma cortisol concentration does not in-
crease above basal levels.
Effect 4 in the table stems originally from the
known fact that administration of very large amounts
of cortisol profoundly reduces the inflammatory re-
sponse to injury or infection. Cortisol can also reduce
the number of circulating lymphocytes and decrease
both antibody production and the activity of helper
T cells and cytotoxic T cells. Because of all these ef-
fects, cortisol is an invaluable tool in the treatment of
allergy, arthritis, other inflammatory diseases, and
graft rejection.
These anti-inflammatory and anti-immune effects
have generally been classified among the various phar-
macological effects of cortisol because it was assumed that
they could be achieved only by very large doses of cor-
tisol. It is now clear, however, that such effects also oc-
cur, albeit to a lesser degree, at the plasma concentra-
tions achieved during stress. Thus, the increased plasma
cortisol typical of infection or trauma exerts a dampen-
ing effect on the body’s immune responses, protecting

against possible damage from excessive inflammation.
This explains the significance of the fact, men-
tioned earlier, that several cytokines stimulate the se-
cretion of ACTH and thereby cortisol. Such stimula-
tion is part of a negative-feedback system in which the
increased cortisol then partially blocks the inflamma-
tory processes in which the cytokines participate.
Moreover, cortisol normally dampens the fever caused
by an infection.
It should not be assumed, however, that all the ef-
fects of stress on immune responses are due to cortisol.
Many of the other hormones released in increased quan-
tities during stress (see below) have important effects,
both inhibitory and stimulatory, on the immune system.
Functions of the Sympathetic
Nervous System in Stress
Activation of the sympathetic nervous system during
stress is often termed the fight-or-flight response, and
the name is appropriate. A list of the major effects of
increased sympathetic activity, including secretion of
epinephrine, almost constitutes a guide to how to meet
emergencies in which physical activity may be re-
quired and bodily damage may occur. Most of these
actions have been discussed in other sections of the
book, and they are listed in Table 20–13 with little or
no comment. Actions 6 and 7, however, have not been
mentioned before; they reflect stimulation by epi-
nephrine of the brain respiratory centers and of platelet
aggregation.
Also of considerable interest is the fact that the

stress of birth causes a huge increase in plasma cate-
cholamine concentrations in the newborn. They not
only help in the arousal of the newborn, but perform
a variety of other important functions, for example,
stimulation of fluid absorption from the lung alveoli
at birth.
Other Hormones Released
During Stress
Other hormones that are usually released during many
kinds of stress are aldosterone, vasopressin (ADH),
growth hormone, glucagon, and
␤
-endorphin (which
is coreleased from the anterior pituitary with ACTH).
Insulin secretion is usually decreased. The increases in
vasopressin and aldosterone ensure the retention of
730
PART THREE Coordinated Body Functions
TABLE 20–12
Effects of Increased Plasma Cortisol Concentration during Stress
1. Effects on organic metabolism
a. Stimulation of protein catabolism
b. Stimulation of liver uptake of amino acids and their conversion to glucose (gluconeogenesis)
c. Inhibition of glucose uptake and oxidation by many body cells (“insulin antagonism”) but not by the brain
d. Stimulation of triacylglycerol catabolism in adipose tissue, with release of glycerol and fatty acids into the blood
2. Enhanced vascular reactivity—that is, increased ability to maintain vasoconstriction in response to norepinephrine and other
stimuli
3. Unidentified protective effects against the damaging influences of stress
4. Inhibition of inflammation and specific immune responses
Vander et al.: Human

Physiology: The
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20. Defense Mechanisms of
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© The McGraw−Hill
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water and sodium within the body, an important adap-
tation in the face of potential losses by hemorrhage or
sweating. Vasopressin also stimulates the secretion of
ACTH, as we have seen, and may enhance learning.
As described in Chapter 18, the overall effects of the
changes in growth hormone, glucagon, and insulin are,
like those of cortisol and epinephrine, to mobilize en-
ergy stores. The role of
␤
-endorphin, if any, in stress,
is still unclear.
This list of hormones whose secretion rates are al-
tered by stress is by no means complete. It is likely
that the secretion of almost every known hormone
may be influenced by stress. For example, prolactin
and thyroid hormone are often increased, whereas the
pituitary gonadotropins and the sex steroids are de-
creased. The adaptive significance of many of these
changes is unclear.
Psychological Stress and Disease
Throughout this section we have emphasized the

adaptive value of the body’s various responses to
stress. It is now clear, however, that psychological
stress, particularly if chronic, can have deleterious ef-
fects on the body, constituting important links in the
mind-body interactions described on page 714. For ex-
ample, it is very likely that the increased plasma cor-
tisol associated with psychological stress can decrease
the activity of the immune system enough to reduce
the body’s resistance to infection and, perhaps, cancer.
It can also worsen the symptoms of diabetes because
of its anti-insulin effects, and it can cause increased rate
of death of neurons.
Similarly, it is possible that prolonged and re-
peated activation of the sympathetic nervous system
by psychological stress may enhance the development
of certain diseases, particularly atherosclerosis and
hypertension. For example, one can easily imagine that
the increased blood lipid concentration and cardiac
work could contribute to the former disease.
Thus, as we have seen in the case of cytokines, the
body’s adaptive stress responses, if excessive or inap-
propriate, may play a causal role in the development
of diseases. Conversely, stress-related neuroendocrine
responses probably play important roles in certain ben-
eficial responses, notably the placebo effect—the fre-
quent improvement or outright cure that occurs in
many diseases when patients are given a pharmaco-
logically inactive substance that they have reason to
believe will produce good results.
I. Classical responses to stress, whether physical or

psychological, are increased secretion of cortisol from
the adrenal cortex and activation of the sympathetic
nervous system, including release of epinephrine by
the adrenal medulla.
II. The functions of these responses, summarized in
Tables 20–12 and 20
–13, can be viewed both as a
preparation for fight or flight and for coping with
new situations.
III. Other hormones released during stress include
aldosterone, vasopressin, glucagon, growth hormone,
and prolactin. Insulin secretion is usually decreased.
IV. Psychological stress can have inappropriate and
deleterious effects on bodily functions and disease
processes.
SECTION C KEY TERMS
SECTION C SUMMARY
731
Defense Mechanisms of the Body CHAPTER TWENTY
1. Increased hepatic and muscle glycogenolysis (provides a quick source of glucose)
2. Increased breakdown of adipose tissue triacylglycerol (provides a supply of glycerol for gluconeogenesis and of fatty acids for
oxidation)
3. Decreased fatigue of skeletal muscle
4. Increased cardiac output secondary to increased cardiac contractility and heart rate
5. Diverting blood from viscera to skeletal muscles by means of vasoconstriction in the former beds and vasodilation in the latter
6. Increased ventilation
7. Increased coagulability of blood
TABLE 20–13
Actions of the Sympathetic Nervous System, Including Epinephrine Secreted
by the Adrenal Medulla, in Stress

stress
cortisol
epinephrine
corticotropin releasing
hormone (CRH)
adrenocorticotropic hormone
(ACTH)
fight-or-flight response
Vander et al.: Human
Physiology: The
Mechanism of Body
Function, Eighth Edition
III. Coordinated Body
Functions
20. Defense Mechanisms of
the Body
© The McGraw−Hill
Companies, 2001
1. Diagram the CRH-ACTH-cortisol pathway.
2. List the functions of cortisol in stress.
3. List the major effects of activation of the sympathetic
nervous system during stress.
4. List four hormones other than those listed in
previous questions that increase during stress and
one that decreases.
(Because of the subject matter of this chapter, it is difficult to
distinguish between “physiological” key terms and “clini-
cal” terms. This list is limited largely to disease-producing
agents and disease processes.)
CHAPTER 20 CLINICAL TERMS

SECTION C REVIEW QUESTIONS
(Answers are given in Appendix A.)
1. If an individual failed to develop a thymus because
of a genetic defect, what would happen to the
immune responses mediated by antibodies and those
mediated by cytotoxic T cells?
2. What abnormalities would a person with a
neutrophil deficiency display? A person with a
monocyte deficiency?
3. An experimental animal is given a drug that blocks
phagocytosis. Will this drug prevent the animal’s
immune system from killing foreign cells via the
complement system?
4. If the Fc portion of a patient’s antibodies is
abnormal, what effects could this have on
antibody-mediated responses?
5. Would you predict that patients with AIDS would
develop fever in response to an infection? Explain.
6. A patient with symptoms of hyperthyroidism is
found to have circulating antibodies against the
receptors for the thyroid hormones. Can you deduce
the cause of hyperthyroidism?
7. Barbiturates and alcohol are normally metabolized
by the MES. Can you deduce why the actions of an
administered barbiturate last for a shorter time than
normal in persons who chronically consume large
quantities of alcohol?
CHAPTER 20 THOUGHT QUESTIONS
732
PART THREE Coordinated Body Functions

microbes
bacteria
viruses
oncogene
vaccine
combined immunodeficiency
acquired immune deficiency
syndrome (AIDS)
antibiotics
acyclovir
human immunodeficiency
virus (HIV)
graft rejection
cyclosporin
transfusion reaction
cross-matching
hemolytic disease of the
newborn
allergy (hypersensitivity)
allergen
delayed hypersensitivity
immune-complex
hypersensitivity
immediate hypersensitivity
IgE-mediated
hypersensitivity
anaphylaxis
late-phase reaction
autoimmune disease
multiple sclerosis

myasthenia gravis
insulin-dependent diabetes
mellitus
septic shock
Alzheimer’s disease
asthma
rheumatoid arthritis
inflammatory bowel disease
chronic inflammatory
diseases
placebo effect
Vander et al.: Human
Physiology: The
Mechanism of Body
Function, Eighth Edition
Back Matter Appendix A: Answers to
Thought Questions
© The McGraw−Hill
Companies, 2001
Chapter 4
4-1 A drug could decrease acid secretion by (1) binding to
the membrane sites that normally inhibit acid secretion,
which would produce the same effect as the body’s natural
messengers that inhibit acid secretion; (2) binding to a mem-
brane protein that normally stimulates acid secretion but not
itself triggering acid secretion, thereby preventing the body’s
natural messengers from binding (competition); or (3) hav-
ing an allosteric effect on the binding sites, which would in-
crease the affinity of the sites that normally bind inhibitor
messengers or decrease the affinity of those sites that nor-

mally bind stimulatory messengers.
4-2 The reason for a lack of insulin effect could be either
a decrease in the number of available binding sites to which
insulin can bind or a decrease in the affinity of the binding
sites for insulin so that less insulin is bound. A third possi-
bility, which does not involve insulin binding, would be a
defect in the way the binding site triggers a cell response
once it has bound insulin.
4-3 An increase in the concentration of compound A will
lead to a decrease in the concentration of compound H by
the route shown below. Sequential activations and inhibi-
tions of proteins of this general type are frequently encoun-
tered in physiological control systems.
4-5 Phosphoprotein phosphatase removes the phosphate
group from proteins that have been covalently modulated
by a protein kinase. Without phosphoprotein phosphatase,
the protein could not return to its unmodulated state and
would remain in its activated state. The ability to decrease
as well as increase protein activity is essential to the regula-
tion of physiological processes.
4-6 The reactant molecules have a combined energy con-
tent of 55 ϩ 93 ϭ 148 kcal/mol, and the products have 62 ϩ
87 ϭ 149. Thus, the energy content of the products exceeds
that of the reactants by 1 kcal/mol, and this amount of energy
must be added to A and B to form the products C and D.
The reaction is reversible since the difference in energy
content between the reactants and products is small. When
the reaction reaches chemical equilibrium, there will be a
slightly higher concentration of reactants than products.
4-7 The maximum rate at which the end product E can be

formed is 5 molecules per second, the rate of the slowest—
(rate-limiting)—reaction in the pathway.
4-8 Under normal conditions, the concentration of oxygen
at the level of the mitochondria in cells, including muscle at
rest, is sufficient to saturate the enzyme that combines oxy-
gen with hydrogen to form water. The rate-limiting reactions
in the electron transport chain depend on the available con-
centrations of ADP and P
i
, which are combined to form ATP.
Thus, increasing the oxygen concentration above nor-
mal levels will not increase ATP production. If a muscle is
contracting, it will break down ATP into ADP and P
i
, which
become the major rate-limiting substrates for increasing ATP
production. With intense muscle activity, the level of oxygen
may fall below saturating levels, limiting the rate of ATP
production, and intensely active muscles must use anaero-
bic glycolysis to provide additional ATP. Under these cir-
cumstances, increasing the oxygen concentration in the blood
will increase the rate of ATP production. As discussed in
Chapter 14, it is not the concentration of oxygen in the blood
that is increased during exercise but the rate of blood flow
to a muscle, resulting in greater quantities of oxygen deliv-
ery to the tissue.
4-9 During starvation, in the absence of ingested glucose,
the body’s stores of glycogen are rapidly depleted. Glucose,
which is the major fuel used by the brain, must now be syn-
thesized from other types of molecules. Most of this newly

formed glucose comes from the breakdown of proteins to
amino acids and their conversion to glucose. To a lesser ex-
tent, the glycerol portion of fat is converted to glucose. The
fatty acid portion of fat cannot be converted to glucose.
4-10 Fatty acids are broken down to acetyl coenzyme A
during beta oxidation, and acetyl coenzyme A enters the
Krebs cycle to be converted to carbon dioxide. Since the
Krebs cycle can function only during aerobic conditions, the
[A]
H
Allosteric
activation
Protein kinase B
activity
Enzyme C
Activity of enzyme C
D[E]
Allosteric
inhibition
Enzyme F activity
G
Decrease conversion of
G to H. Therefore,
[H]
appendix
Appendix A
ANSWERS TO THOUGHT QUESTIONS
4-4 (a) Acid secretion could be increased to 40 mmol/h
by (1) increasing the concentration of compound X from
2 pM to 8 pM, thereby increasing the number of binding sites

occupied; or (2) increasing the affinity of the binding sites
for compound X, thereby increasing the amount bound with-
out changing the concentration of compound X. (b) Increas-
ing the concentration of compound X from 18 to 28 pM will
not increase acid secretion because, at 18 pM, all the bind-
ing sites are occupied (the system is saturated), and there are
no further binding sites available.
733
Vander et al.: Human
Physiology: The
Mechanism of Body
Function, Eighth Edition
Back Matter Appendix A: Answers to
Thought Questions
© The McGraw−Hill
Companies, 2001
catabolism of fat is dependent on the presence of oxygen. In
the absence of oxygen, acetyl coenzyme A cannot be con-
verted to carbon dioxide, and the increased concentration of
acetyl coenzyme A inhibits the further beta oxidation of fatty
acids.
4-11 Ammonia is formed in most cells during the oxida-
tive deamination of amino acids and then travels to the liver
via the blood. The liver detoxifies the ammonia by convert-
ing it to the nontoxic compound urea. Since the liver is the
site in which ammonia is converted to urea, diseases that
damage the liver can lead to an accumulation of ammonia
in the blood, which is especially toxic to nerve cells. Note
that it is not the liver that produces the ammonia.
Chapter 5

5-1 Nucleotide bases in DNA pair A to T and G to C. Given
the base sequence of one DNA strand as:
A-G-T-G-C-A-A-G-T-C-T
a. The complementary strand of DNA would be:
T-C-A-C-G-T-T-C-A-G-A
b. The sequence in RNA transcribed from the first strand
would be:
U-C-A-C-G-U-U-C-A-G-A
Recall that uracil U replaces thymine T in RNA.
5-2 The triplet code G-T-A in DNA will be transcribed into
mRNA as C-A-U, and the anticodon in tRNA corresponding
to C-A-U is G-U-A.
5-3 If the gene were only composed of the triplet exon code
words, the gene would be 300 nucleotides in length since a
triplet of three nucleotides codes for one amino acid. How-
ever, because of the presence of intron segments in most genes,
which account for 75 to 90 percent of the nucleotides in a gene,
the gene would be between 1200 and 3000 nucleotides long;
moreover, there are also termination codons. Thus, the exact
size of a gene cannot be determined by knowing the number
of amino acids in the protein coded by the gene.
5-4 Tubulin is the protein that polymerizes to form micro-
tubules. The tubulin monomers become linked together in a
spiral that forms the walls of the hollow microtubules. With-
out microtubules to form the spindle apparatus, the chro-
mosomes will not separate during mitosis. There are chem-
ical agents in the cell that cause the polymerization of tubulin
at the time of mitosis and cause it to depolymerize follow-
ing cell division.
5-5 A drug that inhibits DNA replication will inhibit cell

division since a duplicate set of chromosomes is necessary
for this process. Since one of the characteristics of cancer cells
is their ability to undergo excessive uncontrolled division, a
drug that inhibits DNA replication will inhibit the multipli-
cation of cancer cells. Unfortunately, such drugs also inhibit
the division of normal cells, particularly those that divide at
a high rate. These include the cells that give rise to blood
cells and the epithelial lining of the gastrointestinal tract. The
use of such drugs must be carefully monitored to balance
the damage done to normal tissues against the inhibition of
tumor growth.
Chapter 6
6-1 (a) During diffusion, the net flux always occurs from
high to low concentration. Thus, it will be from 2 to 1 in A
and from 1 to 2 in B. (b) At equilibrium, the concentrations
of solute in the two compartments will be equal: 4 mM in
case A and 31 mM in case B. (c) Both will reach diffusion
equilibrium at the same rate since the difference in concen-
tration across the membrane is the same in each case, 2 mM
[(3 Ϫ 5) ϭϪ2, and (32 Ϫ 30) ϭ 2]. The two one-way fluxes
will be much larger in B than in A, but the net flux has the
same magnitude in both cases, although oriented in oppo-
site directions.
6-2 The ability of one amino acid to decrease the flux of a
second amino acid across a cell membrane is an example of
the competition of two molecules for the same binding site,
as explained in Chapter 4. The binding site for alanine on
the transport protein can also bind leucine. The higher the
concentration of alanine, the greater the number of binding
sites that it occupies, and the fewer available for binding

leucine. Thus, less leucine will be moved into the cell.
6-3 The net transport will be out of the cell in the direc-
tion from the higher-affinity site on the intracellular surface
to the lower-affinity site on the extracellular surface. More
molecules will be bound to the transporter on the higher-
affinity side of the membrane, and thus more will move out
of the cell than into it, until the concentration in the extra-
cellular fluid becomes large enough that the number of mol-
ecules bound to transporters at the extracellular surface is
equal to the number bound at the intracellular surface.
6-4 Although ATP is not used directly in secondary active
transport, it is necessary for the primary active transport of
sodium out of cells. Since it is the sodium concentration gra-
dient across the plasma membrane that provides the energy
for most secondary active-transport systems, a decrease in
ATP production will decrease primary active sodium trans-
port, leading to a decrease in the sodium concentration gra-
dient and thus to a decrease in secondary active transport.
6-5 The solution with the greatest osmolarity will have the
lowest water concentration. The osmolarities are:
A. 20 ϩ 30 ϩ (2 ϫ 150) ϩ (3 ϫ 10) ϭ 380 mOsm
B. 10 ϩ 100 ϩ (2 ϫ 20) ϩ (3 ϫ 50) ϭ 300 mOsm
C. 100 ϩ 200 ϩ (2 ϫ 10) ϩ (3 ϫ 20) ϭ 380 mOsm
D. 30 ϩ 10 ϩ (2 ϫ 60) ϩ (3 ϫ 100) ϭ 460 mOsm
Thus, solution D has the lowest water concentration. (Recall
that NaCl forms two ions in solution and CaCl
2
forms
three.)
Solution B is isosmotic since it has the same osmolarity

as intracellular fluid.
6-6 Initially the osmolarity of compartment 1 is
(2 ϫ 200) ϩ 100 ϭ 500 mOsm and that of 2 is (2 ϫ 100) ϩ
300 ϭ 500 mOsm. The two solutions thus have the same os-
molarity, and there is no difference in water concentration
across the membrane. Since the membrane is permeable to
urea, this substance will undergo net diffusion until it
reaches the same concentration (200 mM) on the two sides
of the membrane. In other words, in the steady state it will
not affect the volumes of the compartments. In contrast, the
higher initial NaCl concentration in compartment 1 than in
734
APPENDIX A Answers To Thought Questions
Vander et al.: Human
Physiology: The
Mechanism of Body
Function, Eighth Edition
Back Matter Appendix A: Answers to
Thought Questions
© The McGraw−Hill
Companies, 2001
compartment 2 will cause, by osmosis, the movement of wa-
ter from compartment 2 to compartment 1 until the concen-
tration of NaCl in both is 150 mM. Note that the same vol-
ume change would have occurred if there were no urea
present in either compartment. It is only the concentration
of nonpenetrating solutes (NaCl in this case) that determines
the volume change, regardless of the concentration of any
penetrating solutes that are present.
6-7 The osmolarities and nonpenetrating-solute concen-

trations are:
Only the concentration of nonpenetrating solutes (NaCl
in this case) will determine the change in cell volume. Since
the intracellular concentration of nonpenetrating solute is
300 mOsm, solution A will produce no change in cell vol-
ume. Solutions B and D will cause cells to swell since they
have a lower concentration of nonpenetrating solute (higher
water concentration) than the intracellular fluid. Solution C
will cause cells to shrink because it has a higher concentra-
tion of nonpenetrating solute than the intracellular fluid.
6-8 Solution A is isotonic because it has the same con-
centration of nonpenetrating solutes as intracellular fluid
(300 mOsm). Solution A is also hyperosmotic since its total
osmolarity is greater than 300 mOsm, as is also true for
solutions B and C. Solution B is hypotonic since its con-
centration of nonpenetrating solutes is less than 300 mOsm.
Solution C is hypertonic since its concentration of nonpen-
etrating solutes is greater than 300 mOsm. Solution D is hy-
potonic (less than 300 mOsm of nonpenetrating solutes) and
also hypoosmotic (having a total osmolarity of less than
300 mOsm).
6-9 Exocytosis is triggered by an increase in cytosolic cal-
cium concentration. Calcium ions are actively transported
out of cells, in part by secondary countertransport coupled
to the downhill entry of sodium ions on the same transporter.
If the intracellular concentration of sodium ions were in-
creased, the sodium concentration gradient across the mem-
brane would be decreased, and this would decrease the sec-
ondary active transport of calcium out of the cell. This would
lead to an increase in cytosolic calcium concentration, which

would trigger increased exocytosis.
Chapter 7
7-1 4.4 mmol/L. If you answered 8 mmol/L, you ignored
the fact that plasma potassium concentration is homeostati-
cally regulated so that the doubling of input will lead to
negative-feedback reflexes that oppose an equivalent in-
crease in plasma concentration. If you answered 4 mmol/L,
you ignored the fact that homeostatic control systems can-
not totally prevent changes in the regulated variable when a
perturbation occurs. Thus, there must be some rise in plasma
Nonpenetrating
Osmolarity, solute
Solution mOsm concentration, mOsm
A(2ϫ 150) ϩ 100 ϭ 400 2 ϫ 150 ϭ 300
B(2ϫ 100) ϩ 150 ϭ 350 2 ϫ 100 ϭ 200
C(2ϫ 200) ϩ 100 ϭ 500 2 ϫ 200 ϭ 400
D(2ϫ 100) ϩ 50 ϭ 250 2 ϫ 100 ϭ 200
potassium concentration in this situation (to serve as the
error signal for the compensating reflexes), and this is con-
sistent with the answer 4.4 mmol/L. (The actual rise would
have to be experimentally determined. There is no way you
could have predicted that the rise would be 10 percent. All
you could predict is that it would neither double nor stay
absolutely unchanged.)
7-2 No. There may in fact be one, but there is another pos-
sibility—that the altered skin blood flow in the cold repre-
sents an acclimatization undergone by each Eskimo during
his or her lifetime as a result of performing such work re-
peatedly.
7-3 Patient A’s drug very likely acts to block phospholi-

pase A
2
, whereas patient B’s drug blocks lipoxygenase (see
Figure 7–6).
7-4 The chronic loss of exposure of the heart’s receptors to
norepinephrine causes an up-regulation of this receptor type
(that is, more receptors in the heart for norepinephrine). The
drug, being an agonist of norepinephrine (that is, able to bind
to norepinephrine’s receptors and activate them) is now
more effective since there are more receptors for it to com-
bine with.
7-5 None. Since you are told that all six responses are me-
diated by the cAMP system, then blockage of any of the steps
listed in the question would eliminate all six of the responses.
This is because the cascade for all six responses is identical
from the receptor through the formation of cAMP and acti-
vation of cAMP-dependent protein kinase. Thus, the drug
must be acting at a point beyond this kinase (for example,
at the level of the phosphorylated protein mediating this re-
sponse).
7-6 Not in most cells, since there are other physiological
mechanisms by which signals impinging on the cell can in-
crease cytosolic calcium concentration. These include
(1) second-messenger–induced release of calcium from the
endoplasmic reticulum and (2) voltage-sensitive calcium
channels.
Chapter 8
8-1 Little change in the resting membrane potential would
occur when the pump first stops because the pump’s direct
contribution to charge separation is very small. With time,

however, the membrane potential would depolarize pro-
gressively toward zero because the sodium and potassium
concentration gradients, which depend on the Na,K-ATPase
pumps and which gives rise to the diffusion potentials that
constitute most of the membrane potential, run down.
8-2 The resting potential would decrease (that is, become
less negative) because the concentration gradient causing net
diffusion of this positively charged ion out of the cell would
be smaller. The action potential would fire more easily (that
is, with smaller stimuli) because the resting potential would
be closer to threshold. It would repolarize more slowly be-
cause repolarization depends on net potassium diffusion
from the cell, and the concentration gradient driving this dif-
fusion is lower. Also, the afterhyperpolarization would be
smaller.
8-3 The hypothalamus was probably damaged. It plays a
critical role in appetite, thirst, and sexual capacity.
735
Answers To Thought Questions APPENDIX A
Vander et al.: Human
Physiology: The
Mechanism of Body
Function, Eighth Edition
Back Matter Appendix A: Answers to
Thought Questions
© The McGraw−Hill
Companies, 2001
8-4 The drug probably blocks cholinergic muscarinic re-
ceptors. These receptors on effector cells mediate the actions
of parasympathetic nerves. Therefore, the drug would re-

move the slowing effect of these nerves on the heart, allow-
ing the heart to speed up. Blocking their effect on the sali-
vary glands would cause the dry mouth. We know that the
drug is not blocking cholinergic nicotinic receptors because
the skeletal muscles are not affected.
8-5 Since the membrane potential of the cells in question
depolarizes (that is, becomes less negative) when chloride
channels are blocked, one can predict that there was net chlo-
ride diffusion into the cells through these channels prior to
the drug. Therefore, one can also predict that this passive in-
ward movement was being exactly balanced by active trans-
port of chloride out of the cells.
8-6 Without acetylcholinesterase, acetylcholine would re-
main bound to the receptors, and all the actions normally
caused by acetylcholine would be accentuated. Thus, there
would be marked narrowing of the pupils, airway constric-
tion, stomach cramping and diarrhea, sweating, salivation,
slowing of the heart, and fall in blood pressure. On the other
hand, in skeletal muscles, which must repolarize after exci-
tation in order to be excited again, there would be weakness,
fatigue, and finally inability to contract. In fact, lethal poi-
soning by high doses of cholinesterase inhibitors occurs be-
cause of paralysis of the muscles involved in respiration. Low
doses of these compounds are used therapeutically.
8-7 These potassium channels, which open after a short
delay following the initiation of an action potential, increase
potassium diffusion out of the cell, hastening repolarization.
They also account for the increased potassium permeability
that causes the afterhyperpolarization. Therefore, the action
potential would be broader (that is, longer in duration), re-

turning to its resting level more slowly, and the afterhyper-
polarization would be absent.
Chapter 9
9-1 (a) Use drugs to block transmission in the pathways
that convey information about pain to the brain. For exam-
ple, if substance P is the neurotransmitter at the central end-
ings of the nociceptor afferent fibers, give a drug that blocks
the substance P receptors. (b) Cut the dorsal root at the level
of entry of the nociceptor fibers to prevent transmission of
their action potentials into the central nervous system. (c)
Give a drug that activates receptors in the descending path-
ways that block transmission of the incoming or ascending
pain information. (d) Stimulate the neurons in these same
descending pathways to increase their blocking activity
(stimulation-produced analgesia or, possibly, acupuncture).
(e) Cut the ascending pathways that transmit information
from the nociceptor afferents. (f) Deal with the emotions, at-
titudes, memories, and so on, to decrease the sensitivity to
the pain. (g) Stimulate nonpain, low-threshold afferent fibers
to block transmission through the pain pathways (TENS). (h)
Block transmission in the afferent nerve with a local anes-
thetic such as Novacaine or Lidocaine.
9-2 Information regarding temperature is carried via the
anterolateral system to the brain. Fibers of this system cross
to the opposite side of the body in the spinal cord at the level
of entry of the afferent fibers (see Figure 9–18b). Damage to
the left side of the spinal cord or any part of the left side of
the brain that contains fibers of the pathways for tempera-
ture would interfere with awareness of a heat stimulus on the
right. Thus, damage to the somatosensory cortex of the left

cerebral hemisphere (that is, opposite the stimulus) would in-
terfere with awareness of the stimulus. Injury to the spinal
cord at the point at which fibers of the anterolateral system
from the two halves of the spinal cord cross to the opposite
side would interfere with the awareness of heat applied to ei-
ther side of the body, as would the unlikely event that dam-
age occurred to relevant areas of both sides of the brain.
9-3 Vision would be restricted to the rods; therefore, it
would be normal at very low levels of illumination (when
the cones would not be stimulated anyway), but at higher
levels of illumination clear vision of fine details would be
lost, and everything would appear in shades of gray. There
would be no color vision. In very bright light, there would
be no vision because of bleaching of the rods’ rhodopsin.
9-4 (a) The individual lacks a functioning primary visual
cortex. (b) The individual lacks a functioning visual associ-
ation cortex.
Chapter 10
10-1 Epinephrine falls to very low levels during rest and
fails to increase during stress. The sympathetic preganglion-
ics provide the only major control of the adrenal medulla.
10-2 The increased concentration of binding protein
causes more TH to be bound, thereby lowering the plasma
concentration of free TH. This causes less negative-feedback
inhibition of TSH secretion by the anterior pituitary, and the
increased TSH causes the thyroid to secrete more TH until
the free concentration has returned to normal. The end re-
sult is an increased total plasma TH—most bound to the pro-
tein—but a normal free TH. There is no hyperthyroidism be-
cause it is only the free concentration that exerts effects on

TH’s target cells.
10-3 Destruction of the anterior pituitary or hypothala-
mus. These symptoms reflect the absence of, in order, growth
hormone, the gonadotropins, and ACTH (the symptom is
due to the resulting decrease in cortisol secretion). The prob-
lem is either primary hyposecretion of anterior pituitary hor-
mones or secondary hyposecretion because the hypothala-
mus is not secreting hypophysiotropic hormones normally.
10-4 Vasopressin and oxytocin (that is, the major posterior
pituitary hormones). The anterior pituitary hormones would
not be affected because the influence of the hypothalamus
on these hormones is exerted not by connecting nerves but
via the hypophysiotropic hormones in the portal vascular
system.
10-5 The secretion of GH increases. Somatostatin, coming
from the hypothalamus, normally exerts an inhibitory effect
on the secretion of this hormone.
10-6 Norepinephrine and many other neurotransmitters
are released by neurons that terminate on the hypothala-
mic neurons that secrete the hypophysiotropic hormones.
Therefore, manipulation of these neurotransmitters will
736
APPENDIX A Answers To Thought Questions
Vander et al.: Human
Physiology: The
Mechanism of Body
Function, Eighth Edition
Back Matter Appendix A: Answers to
Thought Questions
© The McGraw−Hill

Companies, 2001
alter secretion of the hypophysiotropic hormones and
thereby the anterior pituitary hormones.
10-7 The high dose of the cortisol-like substance inhibits the
secretion of ACTH by feedback inhibition of (1) hypothalamic
corticotropin releasing hormone and (2) the response of the
anterior pituitary to this hypophysiotropic hormone. The lack
of ACTH causes the adrenal to atrophy and decrease its se-
cretion of cortisol.
10-8 The hypothalamus. The low basal TSH indicates ei-
ther that the pituitary is defective or that it is receiving in-
adequate stimulation (TRH) from the hypothalamus. If the
thyroid itself were defective, basal TSH would be elevated
because of less negative-feedback inhibition by TH. The TSH
increase in response to TRH shows that the pituitary is ca-
pable of responding to a stimulus and so is unlikely to be
defective. Therefore, the problem is that the hypothalamus
is secreting too little TRH.
Chapter 11
11-1 Under resting conditions, the myosin has already
bound and hydrolyzed a molecule of ATP, resulting in an en-
ergized molecule of myosin (M
*
и ADP и P
i
). Since ATP is nec-
essary to detach the myosin cross bridge from actin at the
end of cross-bridge movement, the absence of ATP will re-
sult in rigor mortis, in which case the cross bridges become
bound to actin but do not detach, leaving myosin bound to

actin (A и M).
11-2 No. The transverse tubules conduct the muscle ac-
tion potential from the plasma membrane into the interior of
the fiber, where it can trigger the release of calcium from the
sarcoplasmic reticulum. If the transverse tubules were not at-
tached to the plasma membrane, an action potential could
not be conducted to the sarcoplasmic reticulum and there
would be no release of calcium to initiate contraction.
11-3 The length-tension relationship states that the maxi-
mum tension developed by a muscle decreases at lengths be-
low l
o
. During normal shortening, as the sarcomere length
becomes shorter than the optimal length, the maximum ten-
sion that can be generated decreases. With a light load, the
muscle will continue to shorten until its maximal tension just
equals the load. No further shortening is possible since at
shorter sarcomere lengths the tension would be less than the
load. The heavier the load, the less the distance shortened
before reaching the isometric state.
11-4 Maximum tension is produced when the fiber is
(1) stimulated by an action potential frequency that is high
enough to produce a maximal tetanic tension, and (2) at its
optimum length l
o
, where the thick and thin filaments have
overlap sufficient to provide the greatest number of cross
bridges for tension production.
11-5 Moderate tension—for example, 50 percent of maxi-
mal tension—is accomplished by recruiting sufficient num-

bers of motor units to produce this degree of tension. If ac-
tivity is maintained at this level for prolonged periods, some
of the active fibers will begin to fatigue and their contribu-
tion to the total tension will decrease. The same level of to-
tal tension can be maintained, however, by recruiting new
motor units as some of the original ones fatigue. At this point,
for example, one might have 50 percent of the fibers active,
and 25 percent fatigued and 25 percent still unrecruited.
Eventually, when all the fibers have fatigued and there are
no additional motor units to recruit, the whole muscle will
fatigue.
11-6 The oxidative motor units, both fast and slow, will be
affected first by a decrease in blood flow since they depend
on blood flow to provide both the fuel—glucose and fatty
acids—and the oxygen required to metabolize the fuel. The
fast-glycolytic motor units will be affected more slowly since
they rely predominantly on internal stores of glycogen,
which is anaerobically metabolized by glycolysis.
11-7 Two factors lead to recovery of muscle force.
(1) Some new fibers can be formed by the fusion and devel-
opment of undifferentiated satellite cells. This will replace
some, but not all, of the fibers that were damaged. (2) Some
of the restored force results from hypertrophy of the surviv-
ing fibers. Because of the loss of fibers in the accident, the
remaining fibers must produce more force to move a given
load. The remaining fibers undergo increased synthesis of
actin and myosin, resulting in increases in fiber diameter and
thus their force of contraction.
11-8 In the absence of extracellular calcium ions, skeletal
muscle contracts normally in response to an action potential

generated in its plasma membrane because the calcium re-
quired to trigger contraction comes entirely from the sar-
coplasmic reticulum within the muscle fibers. If the motor
neuron to the muscle is stimulated in a calcium-free medium,
however, the muscle will not contract because the influx of
calcium from the extracellular fluid into the motor nerve ter-
minal is necessary to trigger the release of acetylcholine that
in turn triggers an action potential in the muscle.
In a calcium-free solution, smooth muscles of all types
would fail to respond to stimulation of the nerve supplying
the muscle. However, the response to direct stimulation of
the muscle’s plasma membrane would depend on the type
of smooth muscle. Smooth muscles that primarily depend
on calcium released from the sarcoplasmic reticulum will be-
have like skeletal muscle and respond to direct stimulation.
Smooth muscles that rely on the influx of calcium from the
extracellular fluid to trigger contraction will fail to contract
in response to stimulation of its plasma membrane.
11-9 The simplest model to explain the experimental ob-
servations is as follows. Upon parasympathetic nerve stim-
ulation, a neurotransmitter is released that binds to recep-
tors on the membranes of smooth-muscle cells and triggers
contraction. The substance released, however, is not acetyl-
choline (ACh) for the following reason.
Action potentials in the parasympathetic nerves are es-
sential for initiating nerve-induced contraction. When the
nerves were prevented from generating action potentials
by blockage of their voltage-gated sodium channels, there
was no response to nerve stimulation. ACh is the neuro-
transmitter released from most, but not all, parasympathetic

endings. When the muscarinic receptors for ACh were
blocked, however, stimulation of the parasympathetic nerves
still produced a contraction, providing evidence that some
substance other than ACh is being released by the neurons
and producing contraction.
737
Answers To Thought Questions APPENDIX A
Vander et al.: Human
Physiology: The
Mechanism of Body
Function, Eighth Edition
Back Matter Appendix A: Answers to
Thought Questions
© The McGraw−Hill
Companies, 2001
Chapter 12
12-1 None. The gamma motor neurons are important in
preventing the muscle-spindle stretch receptors from going
slack, but when testing this reflex, the intrafusal fibers are
not flaccid. The test is performed with a bent knee, which
stretches the extensor muscles in the thigh (and the intra-
fusal fibers within the stretch receptors). The stretch recep-
tors are therefore responsive.
12-2 The efferent pathway of the reflex arc (the alpha mo-
tor neurons) would not be activated, the effector cells (the
extrafusal muscle fibers) would not be activated, and there
would be no reflex response.
12-3 The drawing must have excitatory synapses on the
motor neurons of both ipsilateral extensor and ipsilateral
flexor muscles.

12-4 A toxin that interferes with the inhibitory synapses
on motor neurons would leave unbalanced the normal exci-
tatory input to these neurons. Thus, the otherwise normal
motor neurons would fire excessively, which would result in
increased muscle contraction. This is exactly what happens
in lockjaw as a result of the toxin produced by the tetanus
bacillus.
Chapter 13
13-1 Dopamine is depleted in the basal ganglia of people
with Parkinson’s disease, and they are therapeutically given
dopamine agonists, usually
L
-dopa. This treatment raises
dopamine levels in other parts of the brain, however, where
the dopamine levels were previously normal. Schizophrenia
is associated with increased brain dopamine levels, and
symptoms of this disease appear when dopamine levels are
high. The converse therapeutic problem can occur during the
treatment of schizophrenics with dopamine-lowering drugs,
which sometimes causes the symptoms of Parkinson’s dis-
ease to appear.
13-2 Experiments on anesthetized animals often involve
either stimulating a brain part to observe the effects of in-
creased neuronal activity or damaging (“lesioning”) an area
to observe resulting deficits. Such experiments on animals,
which lack the complex language mechanisms of people,
cannot help with language studies. Diseases sometimes
mimic these two experimental situations, and behavioral
studies of the resulting language deficits in people with
aphasia, coupled with study of their brains after death, have

provided a wealth of information.
Chapter 14
14-1 No. Decreased erythrocyte volume is certainly one
possible explanation, but there is a second: The person might
have a normal erythrocyte volume but an abnormally in-
creased plasma volume. Convince yourself of this by writ-
ing the hematocrit equation as: erythrocyte volume/(ery-
throcyte volume ϩ plasma volume).
14-2 A halving of tube radius. Resistance is directly pro-
portional to blood viscosity but inversely proportional to the
fourth power of tube radius.
14-3 The plateau of the action potential and the contrac-
tion would be absent. You might think that contraction
would persist since most calcium in excitation-contraction
coupling in the heart comes from the sarcoplasmic reticu-
lum. However, the signal for the release of this calcium is the
calcium entering across the plasma membrane.
14-4 The SA node is not functioning, and the ventricles
are being driven by a pacemaker in the AV node or the bun-
dle of His.
14-5 The person has a narrowed aortic valve. Normally,
the resistance across the aortic valve is so small that there is
only a tiny pressure difference between the left ventricle and
the aorta during ventricular ejection. In the example given
here, the large pressure difference indicates that resistance
across the valve must be very high.
14-6 This question is analogous to question 14-5 in that
the large pressure difference across a valve while the valve
is open indicates an abnormally narrowed valve—in this
case, the left AV valve.

14-7 Decreased heart rate and contractility. These are
effects mediated by the sympathetic nerves on beta-
adrenergic receptors in the heart.
14-8 120 mmHg. MAP ϭ DP ϩ 1/3 (SP Ϫ DP).
14-9 The drug must have caused the arterioles in the
kidneys to dilate enough to reduce their resistance by
50 percent. Blood flow to an organ is determined by mean
arterial pressure and the organ’s resistance to flow. Another
important point can be deduced here: If mean arterial pres-
sure has not changed even though renal resistance has
dropped 50 percent, then either the resistance of some other
organ or cardiac output has gone up.
14-10 The experiment suggests that acetylcholine causes
vasodilation by releasing nitric oxide or some other va-
sodilator from endothelial cells.
14-11 A low plasma protein concentration. Capillary pres-
sure is, if anything, lower than normal and so cannot be caus-
ing the edema. Another possibility is that capillary perme-
ability to plasma proteins has increased, as occurs in burns.
14-12 20 mmHg/L per minute. TPR ϭ MAP/CO.
14-13 Nothing. Cardiac output and TPR have remained
unchanged, and so their product, MAP, has also remained
unchanged. This question emphasizes that MAP depends on
cardiac output but not on the combination of heart rate and
stroke volume that produces the cardiac output.
14-14 It increases. There are a certain number of impulses
traveling up the nerves from the arterial baroreceptors. When
these nerves are cut, the number of impulses reaching the
medullary cardiovascular center goes to zero, just as it would
physiologically if the mean arterial pressure were to decrease

markedly. Accordingly, the medullary cardiovascular center
responds to the absent impulses by reflexly increasing arte-
rial pressure.
14-15 It decreases. The hemorrhage causes no immediate
change in hematocrit since erythrocytes and plasma are lost
in the same proportion. As interstitial fluid starts entering
the capillaries, however, it expands the plasma volume and
decreases hematocrit. (This is too soon for any new erythro-
cytes to be synthesized.)
738
APPENDIX A Answers To Thought Questions
Vander et al.: Human
Physiology: The
Mechanism of Body
Function, Eighth Edition
Back Matter Appendix A: Answers to
Thought Questions
© The McGraw−Hill
Companies, 2001
Chapter 15
15-1 200 ml/mmHg.
Lung compliance ϭ ∆ lung volume/∆ (P
alv
Ϫ P
ip
)
ϭ 800 ml/[0 Ϫ (Ϫ8)] mmHg Ϫ
[0 Ϫ (Ϫ4)] mmHg
ϭ 800 ml/4 mmHg ϭ 200 ml/mmHg
15-2 More subatmospheric than normal. A decreased sur-

factant level causes the lungs to be less compliant (that is,
more difficult to expand). Therefore, a greater transpul-
monary pressure (P
alv
Ϫ P
ip
) is required to expand them a
given amount.
15-3 No.
Alveolar ventilation ϭ (tidal volume-dead space) ϫ
breathing rate
ϭ (250 ml Ϫ 150 ml) ϫ 20 breaths/min
ϭ 2000 ml/min
whereas normal alveolar ventilation is approximately 4000
ml/min.
15-4 The volume of the snorkel constitutes an additional
dead space, and so total pulmonary ventilation must be in-
creased if alveolar ventilation is to remain constant.
15-5 The alveolar P
O
2
will be higher than normal, and the
alveolar P
CO
2
will be lower. If you do not understand why,
review the factors that determine the alveolar gas pressures.
15-6 No. Hypoventilation reduces arterial P
O
2

but only be-
cause it reduces alveolar P
O
2
. That is, in hypoventilation, both
alveolar and arterial P
O
2
are decreased to essentially the same
degree. In this problem, alveolar P
O
2
is normal, and so the
person is not hypoventilating. The low arterial P
O
2
must
therefore represent a defect that causes a discrepancy be-
tween alveolar P
O
2
and arterial P
O
2
. Possibilities include im-
paired diffusion, a shunting of blood from the right side of
the heart to the left through a hole in the heart wall, and mis-
matching of airflow and blood flow in the alveoli.
15-7 Not at rest, if the defect is not too severe. Recall that
equilibration of alveolar air and pulmonary capillary blood

is normally so rapid that it occurs well before the end of the
capillaries. Therefore, even though diffusion may be re-
tarded, as in this problem, there may still be enough time for
equilibration to be reached. In contrast, the time for equili-
bration is decreased during exercise, and failure to equili-
brate is much more likely to occur, resulting in a lowered ar-
terial P
O
2
.
15-8 Only a few percent (specifically, from approximately
200 ml O
2
/L blood to approximately 215 ml O
2
/L blood).
The reason the increase is so small is that almost all the oxy-
gen in blood is carried bound to hemoglobin, and hemoglo-
bin is almost 100 percent saturated at the arterial P
O
2
achieved by breathing room air. The high arterial P
O
2
achieved by breathing 100 percent oxygen does cause a di-
rectly proportional increase in the amount of oxygen dissolved
in the blood (the additional 15 ml), but this still remains a
small fraction of the total oxygen in the blood. Review the
numbers given in the text.
15-9 All except plasma chloride concentration. The rea-

sons are all given in the text.
15-10 It would cease. Respiration depends on descending
input from the medulla to the nerves supplying the di-
aphragm and the inspiratory intercostal muscles.
15-11 The 10 percent oxygen mixture will markedly lower
alveolar and thus arterial P
O
2
, but no increase in ventilation
will occur because the reflex response to hypoxia is initiated
solely by the peripheral chemoreceptors. The 5 percent car-
bon dioxide mixture will markedly increase alveolar and ar-
terial P
CO
2
, and a large increase in ventilation will be elicited
reflexly via the central chemoreceptors. The increase will not
be as large as in a normal animal because the peripheral
chemoreceptors do play a role, albeit minor, in the reflex re-
sponse to elevated P
CO
2
.
15-12 These patients have profound hyperventilation,
with marked increases in both the depth and rate of venti-
lation. The stimulus, mainly via the peripheral chemorecep-
tors, is the marked increase in their arterial hydrogen-ion
concentration due to the acids produced. The hyperventila-
tion causes an increase in their arterial P
O

2
and a decrease in
their arterial P
CO
2
.
Chapter 16
16-1 No. These are possibilities, but there is another. Sub-
stance T may be secreted by the tubules.
16-2 No. It is a possibility, but there is another. Substance
V may be filtered and/or secreted, but the substance V en-
tering the lumen via these routes may be completely reab-
sorbed.
16-3 125 mg/min. The amount of any substance filtered
per unit time is given by the product of the GFR and the fil-
terable plasma concentration of the substance—in this case,
125 ml/min ϫ 100 mg/100 ml ϭ 125 mg/min.
16-4 The plasma concentration might be so high that the
T
m
for the amino acid is exceeded, and so all the filtered
amino acid is not reabsorbed. A second possibility is that
there is a specific defect in the tubular transport for this
amino acid. A third possibility is that some other amino acid
is present in the plasma in high concentration and is com-
peting for reabsorption.
16-5 No. Urea is filtered and then partially reabsorbed.
The reason its concentration in the tubule is higher than in
the plasma is that relatively more water is reabsorbed than
urea. Therefore, the urea in the tubule becomes concentrated.

Despite the fact that urea concentration in the urine is greater
than in the plasma, the amount excreted is less than the fil-
tered load (that is, net reabsorption has occurred).
16-6 They would all be decreased. The transport of all
these substances is coupled, in one way or another, to that
of sodium.
16-7 GFR would not go down as much, and renin secre-
tion would not go up as much as in a person not receiving
the drug. The sympathetic nerves are a major pathway for
both responses during hemorrhage.
16-8 There would be little if any increase in aldosterone se-
cretion. The major stimulus for increased aldosterone secre-
tion is angiotensin II, but this substance is formed from an-
giotensin I by the action of angiotensin-converting enzyme,
and so blockade of this enzyme would block the pathway.
739
Answers To Thought Questions APPENDIX A
Vander et al.: Human
Physiology: The
Mechanism of Body
Function, Eighth Edition
Back Matter Appendix A: Answers to
Thought Questions
© The McGraw−Hill
Companies, 2001
16-9 (b) Urinary excretion in the steady state must be less
than ingested sodium chloride by an amount equal to that
lost in the sweat and feces. This is normally quite small, less
than 1 g/day, so that urine excretion in this case equals ap-
proximately 11 g/day.

16-10 If the hypothalamus had been damaged, there
might be inadequate secretion of ADH. This would cause
loss of a large volume of urine, which would tend to dehy-
drate the person and make her thirsty. Of course, the area of
the brain involved in thirst might have suffered damage.
16-11 Because aldosterone stimulates sodium reabsorp-
tion and potassium secretion, there will be total-body reten-
tion of sodium and loss of potassium. Interestingly, the per-
son in this situation actually retains very little sodium
because urinary sodium excretion returns to normal after a
few days despite the continued presence of the high aldo-
sterone. One explanation for this is that GFR and atrial na-
triuretic factor both increase as a result of the initial sodium
retention.
16-12 Sodium and water balance would become negative
because of increased excretion of these substances in the
urine. The person would also develop a decreased plasma
bicarbonate concentration and metabolic acidosis because of
increased bicarbonate excretion. The effects on acid-base sta-
tus are explained by the fact that hydrogen-ion secretion—
blocked by the drug—is needed both for bicarbonate reab-
sorption and for the excretion of hydrogen ion (contribution
of new bicarbonate to the blood). The increased sodium ex-
cretion reflects the fact that much sodium reabsorption by
the proximal tubule is achieved by Na/H countertransport.
By blocking hydrogen-ion secretion, therefore, the drug also
partially blocks sodium reabsorption. The increased water
excretion occurs because the failure to reabsorb sodium and
bicarbonate decreases water reabsorption (remember that
water reabsorption is secondary to solute reabsorption), re-

sulting in an osmotic diuresis.
Chapter 17
17-1 If the salivary glands fail to secrete amylase, the undi-
gested starch that reaches the small intestine will still be di-
gested by the amylase secreted by the pancreas. Thus, starch
digestion is not significantly affected by the absence of sali-
vary amylase.
17-2 Alcohol can be absorbed across the stomach wall, but
absorption is much more rapid from the small intestine with
its larger surface area. Ingestion of foods containing fat re-
leases enterogastrones from the small intestine, and these
hormones inhibit gastric emptying and thus prolong the time
alcohol spends in the stomach before reaching the small in-
testine. Milk, contrary to popular belief, does not “protect”
the lining of the stomach from alcohol by coating it with a
fatty layer. Rather, the fat content of milk decreases the rate
of absorption of alcohol by decreasing the rate of gastric emp-
tying.
17-3 Vomiting results in the loss of fluid and acid from the
body. The fluid comes from the luminal contents of the stom-
ach and duodenum, most of which was secreted by the gas-
tric glands, pancreas, and liver and thus is derived from the
blood. The cardiovascular symptoms of this patient are the
result of the decrease in blood volume that accompanies
vomiting.
The secretion of acid by the stomach produces an equal
number of bicarbonate ions, which are released into the
blood. Normally these bicarbonate ions are neutralized by
hydrogen ions released into the blood by the pancreas when
this organ secretes bicarbonate ions. Because gastric acid is

lost during vomiting, the pancreas is not stimulated to se-
crete bicarbonate by the usual high-acidity signal from the
duodenum, and no corresponding hydrogen ions are formed
to neutralize the bicarbonate released into the blood by the
stomach. As a result, the acidity of the blood decreases.
17-4 Fat can be digested and absorbed in the absence of
bile salts but in greatly decreased amounts. Without ade-
quate emulsification of fat by bile salts and phospholipids,
only the fat at the surface of large lipid droplets is available
to pancreatic lipase, and the rate of fat digestion is very slow.
Without the formation of micelles with the aid of bile salts,
the products of fat digestion become dissolved in the large
lipid droplets, where they are not readily available for dif-
fusion into the epithelial cells. In the absence of bile salts,
only about 50 percent of the ingested fat is digested and ab-
sorbed. The undigested fat is passed on to the large intes-
tine, where the bacteria there produce compounds that in-
crease colonic motility and promote the secretion of fluid into
the lumen of the large intestine, leading to diarrhea.
17-5 Damage to the lower portion of the spinal cord pro-
duces a loss of voluntary control over defecation due to dis-
ruption of the somatic nerves to the skeletal muscle of the
external anal sphincter. Damage to the somatic nerves leaves
the external sphincter in a continuously relaxed state. Under
these conditions, defecation occurs whenever the rectum be-
comes distended and the defection reflex is initiated.
17-6 Vagotomy decreases the secretion of acid by the stom-
ach. Impulses in the parasympathetic nerves directly stimu-
late acid secretion by the parietal cells and also cause the re-
lease of gastrin, which in turn stimulates acid secretion.

Impulses in the vagus nerves are increased during both the
cephalic and gastric phases of digestion. Vagotomy, by de-
creasing the amount of acid secreted, decreases irritation of
existing ulcers, which promotes healing and decreases the
probability of acid contributing to the production of new
ulcers.
Chapter 18
18-1 The concentration in plasma would increase, and the
amount stored in adipose tissue would decrease. Lipopro-
tein lipase cleaves plasma triacylglycerols, so its blockade
would decrease the rate at which these molecules were
cleared from plasma and would decrease the availability of
the fatty acids in them for synthesis of intracellular triacyl-
glycerols. However, this would only reduce but not elimi-
nate such synthesis, since the adipose-tissue cells could still
synthesize their own fatty acids from glucose.
18-2 The person might be an insulin-dependent diabetic
or might be a normal fasting person; plasma glucose would
be increased in the first case but decreased in the second.
Plasma insulin concentration would be useful because it
would be decreased in both cases. The fact that the person
740
APPENDIX A Answers To Thought Questions