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. . .
before you begin to read the chapter, as a preview of how the concepts
Respiratory Physiology, 800
Pulmonary Ventilation, 800
Mechanism of Pulmonary
Ventilation, 800
Inspiration, 804
Expiration, 806
Pulmonary Volumes and Capacities, 807
Pulmonary Volumes, 807
Pulmonary Capacities, 810
Pulmonary Airflow, 813
Pulmonary Gas Exchange, 814
Partial Pressure, 814
Exchange of Gases in the Lungs, 815
How Blood Transports Gases, 817
Hemoglobin, 818
Transport of Oxygen, 818
Transport of Carbon Dioxide, 820
Dissolved Carbon Dioxide, 820
Carbamino Compounds, 820
Bicarbonate, 820
Carbon Dioxide and pH, 822
Systemic Gas Exchange, 822
Regulation of Pulmonary Function, 824
Respiratory Control Centers, 824
Factors That Influence Breathing, 825
Ventilation and Perfusion, 828
The Big Picture: Respiratory Physiology
and the Whole Body, 829
Mechanisms of Disease, 830
Case Study, 833
Before reading the chapter, say
each of these terms out loud.
This will help you avoid stum-
bling over them as you read.
alveolar ventilation (al-VEE-oh-Iar ven-ti-
[alve- hollow, -ai-little, oar relating to, vent-
fan or create wind, -tion process]
anatomical dead space (an-ah-TOM-i-kal)
[ana- apart, -tom- cut, -leal relating to]
apneustic center (ap-NYOO-stik)
[a- not, -pneus- breathing, -Ie relating to]
arterial blood PO
[arteri- airpipe (artery), -al relating to,
Ppressure, O
arterial blood pressure (ar-TEER-ee-al)
[arteri- airpipe (artery) , -al relating to]
bicarbonate (bye-KAR-boh-nayt)
[bl- two, -carbon, coal (carbon), -ate
oxygen compound]
Bohr effect (BOR)
[Christian Bohr Danish physiologist]
Boyle's law (boils law)
[Robert Boyle English scientist]
carbamino hemoglobin (kahr-bam-ih-no-
[carb-coal (carbon), -amino-ammonia
compound (amino acid), -hemo- blood,
-glob- ball, -in substance]
cerebral cortex (seh-REE-bral KOR-teks)
[cerebr- brain (cerebrum), -alrelating to,
cortex bark] pl., cortices
Charles' law (Gay-lussac's law) (charlz law
[gay lus-SAKS law]) [Jacques Alexandre
Cesar Char/es French physicist, Joseph L.
Gay-Lussac French physical scientist]
chloride shin (KLOR-ide)
[chlor- green, -ide chemical]
[compli- complete, -ance act of]
continued on p. 832
n Chapter 23 the anatomy of the respiratory sys-
tem was presented as a basis for understanding
the physiological principles that regulate air distri-
bution and gas exchange. This chapter deals with
respiratory physiology-a complex series of interact-
ing and coordinated processes that have a critical role
in maintaining the stability, or constancy, of our internal
environment. The proper functioning of the respiratory
system ensures the tissues of an adequate oxygen sup-
ply and prompt removal of carbon dioxide. This process
Functionally, the respiratory system is composed of an integrated
set of regulated processes that include the following:
• External respiration: pulmonary ventilation (breathing) and
gas exchange in the pulmonary capillaries of the lungs
• Transport of gases by the blood
• Internal respiration: gas exchange in the systemic blood cap-
illaries and cellular respiration
• Overall regulation of respiration
Figure 24-1 summarizes the essential processes of pulmo-
nary function. We will use this set of processes as a general
framework for this chapter. Cellular respiration has already
been covered in Chapter 4 and will be reviewed again in great-
er detail in Chapter 27.
Pulmonary ventilation is a technical term for what most of us call
breathing. One phase of it, inspiration, moves air into the lungs
and the other phase, expiration, moves air out of the lungs.
Mechanism of Pulmonary Ventilation
Air moves in and out of the lungs for the same basic reason that any
fluid (a liquid or a gas) moves from one place to another- briefly,
is complicated by the fact that control mechanisms
must permit maintenance of homeostasis throughout a
wide range of ever-changing environmental conditions
and body demands. Adequate and efficient regulation
of gas exchange between body cells and circulating
blood under changing conditions is the essence of re-
spiratory physiology. This complex function would not
be possible without integration of numerous physiologi-
cal control systems, including acid-base, water, and
electrolyte balance, circulation, and metabolism.
because its pressure in one place is different from that in the other
place. Or stated differently, the existence of a pressure gradient (a
pressure difference) causes fluids to move. A fluid always moves
down its pressure gradient. This means that a fluid moves from the
area where its pressure is higher to the area where its pressure is
lower. When applied to the flow of air in the pulmonary airways, we
can call this central idea the primary principle of ventilation.
Under standard conditions, air in the atmosphere exerts a
pressure of 760 mm Hg. Air in the alveoli at the end of one
expiration and before the beginning of another inspiration
also exerts a pressure of 760 mm Hg. This explains why, at that
moment, air is neither entering nor leaving the lungs. The
mechanism that produces pulmonary ventilation is one that
establishes a gas pressure gradient between the atmosphere and
the alveolar air.
When atmospheric pressure is greater than pressure within
the lung, air flows down this gas pressure gradient. Then air
moves from the atmosphere into the lungs. In other words,
inspiration occurs. When pressure in the lungs becomes
greater than atmospheric pressure, air again moves down a
gas pressure gradient. But this time, the air moves in the op-
posite direction. That is, air moves out of the lungs into the
atmosphere. The pulmonary ventilation mechanism, there-
fore, must somehow establish these two gas pressure gradi-
ents-one in which alveolar pressure (P
, pressure within the
alveoli of the lungs) is lower than atmospheric pressure (or
barometric pressure, PB) to produce inspiration and one in
gas {
I FIGURE 24-1 1
Overview of respiratory
physiology. This chapter is orga-
nized around the principle that
respiratory function includes ex-
ternal respiration (ventilation and
pulmonary gas exchange), trans-
port of gases by blood, and inter-
nal respiration (systemic tissue
gas exchange and cellular respira-
tion). Cellular respiration is dis-
cussed separately (see Chapters 4
and 27). Regulatory mechanisms
centered in the brainstem use
feedback from blood gas sensors
to regulate ventilation.
Chapter 24 Physiology of the Respiratory System 801
Systemic I
tissue gas-t

respi ration
.r--r--r-- O
r---r- CO
        pH sensor
802 UNIT 5 Respirati on, Nutrition, and Excretion
which it is higher than atmospheric pressure to produce expi-
ration. See Figures 24-2 and 24-3.
These pressure gradients are established by changes in the
size of the thoracic cavity, which in turn are produced by con-
traction and relaxation of respiratory muscles. An understand-
ing of Boyle's law is important for understanding the pressure
ehanges that occur in the lungs and thorax during the breath-
ing cycle. It is a familiar principle, stating that the volume of a
gas varies inversely with pressure at a constant temperature
(Box 24- 1). One application of this principle is as follows : ex-
pansion of the thorax (increase in volume) results in a de-
creased intrapleural (i ntrathoracic) pressure. This leads to a
decreased intraalveolar pressure that causes ai r to move from
the outside into the lungs.
The mechanics of ventilation are often modeled using a bal-
loon in a jar, as you can see in Figure 24-4. The bell-shaped jar
represents the rib cage (thoracic cavity), and a rubber sheet across
the open bottom of the bell jar represents the diaphragm. A bal-
loon represents the lungs. The space between the balloon and the
jar represents the intrapleural space. Expanding the thorax by
pull ing the diaphragm downward increases thoracic volume-
thus decreasing intrapleural pressure (PIP)' Because the balloon is
Box 24-1 1 Gas Laws
A true understanding of respiratory function requires some familiarity
with some of what physical scientists call the "gas laws." The gas
laws are simply statements of what we have come to understand
about the physical nature of gases. The gas laws are based on the
concept of an ideal gas, that is, a gas whose molecules are so far
apart that the molecules rarely collide with one another.
The gas laws are also based on the premise that gas molecules
continually collide with the walls of their container and thus produce a
force against it called the gas pressure. Pressure exerted by a gas
depends on several factors. One factor is the frequency of collisions,
which is proportional to the concentration of the gas: the higher the
gas concentration, the higher the number of collisions with the wall of
the container and thus the higher the gas pressure. Boyle's law sums
up this principle very neatly by stating that a gas's volume is inversely
proportional to its pressure (see figure, part A). When the volume of a
container increases, the pressure of the gas inside it decreases, and
when the volume decreases, the gas pressure increases. In this
chapter, Boyle's law has been applied to ventilation: when thoracic
volume increases, air pressure in the airways decreases (allowing air
to move inward), and when thoracic volume decreases, air pressure in
the airways increases (allowing air to move outward).
Another factor that affects an ideal gas is its temperature. Tempera-
ture is really a measurement of the motion of molecules. Thus an
increase in temperature signals an increase in the average velocity of
gas molecules. It follows that all other things remaining the same, an
increase in the temperature of a gas will increase its pressure.
However, if the container is expandable, as it is in part B of the figure,
and thus the pressure is held constant, the volume increases. This
principle is summed up in Charles' law, which states that volume is
directly proportional to temperature (V oc T) when pressure is held
-- Atmospheric
(Pa) pressure
. \ Alveolar
(PA) pressure
..... , '1 Intrapleural
(PIP) pressure
Mediastinum Diaphragm
1 FIG U R E 2 4 - 21 Pressures important in ventilation. This
diagram shows the locations of pressures involved in the pressure
gradients needed for ventilation (see Figure 24-3). Atmospheric pres-
sure (PB) is the air pressure of the atmosphere outside the body's air-
ways. Alveolar pressure (PA) is intrapulmonary pressure-the pressure
at the far end of the internal airways. Intrapleural pressure (PIP) is the
fluid pressure of the pleural fluid between the parietal pleura and vis-
ceral pleura-or intrathoracic pressure (pressure in the thorax) .
constant (see figure, part C). One could extend this notion to state that
pressure is proportional to temperature (P oc T) when volume is held
constant. One can assume, then, that during inspiration, air expands in
volume as it is warmed by the respiratory mucosa.
Dalton's law takes things a step further by stating the situation when
the gas in question is actually a mixture of different kinds of gas
molecules, as in air (part E of the figure). Dalton's law states that the total
pressure exerted by a mixture of gases is the sum of the pressure of
each individual gas. That is, the collision force created by all of one type
of molecule accounts for only a part of the total pressure-the collision
forces of all the other types of molecules in the mixture must be included
to arrive at the total gas pressure. Dalton's law, also known as the law of
partial pressures, is used to determine the partial pressure of oxygen
) in air, for example. Because the partial pressure of a gas is
determined by its relative concentration in the mixture of gases, partial
pressure values can be used in much the same way as concentration
values in determining the direction of net diffusion.
Another gas law, Henry's law, describes how the pressure of a
gas relates to the concentration of that gas in a liquid solution (part
F of the figure). If you have a beaker of water surrounded by air,
which contains the oxygen, the concentration of oxygen dissolved in
the water will be proportional by the partial pressure of oxygen in
the air. Henry's law further states that the concentration of the gas in
solution is also a function of the gas's solubility, or its relative
ability to dissolve. Thus Henry's law states that the concentration of
a gas in a solution depends on the partial pressure of the gas and
the solubility of the gas, as long as the temperature remains
constant. This principle explains how the plasma concentration of a
gas such as oxygen relates to its partial pressure.
Also see Box 24-6, which discusses Fick's law.
iEI$$!!\ ..  
I FIG U R E 2 4 - 3 I Primary principle of ventilation.
Put simply, air moves down its pressure gradient-that is, it always
moves from an area of high pressure to an area of lower pressure. To
achieve inspiration, the higher pressure must be outside the body.
To achieve expiration, the higher pressure must be inside the body's
airways. P
• Atmospheric [barometric) pressure; P
• alveolar pressure.
(See Figure 24-2.)
~ ~ ~   ~
  ~ ~   ~
~     ~ ~
  ~ ~ ~ ~
~ ~ ~   ~
  ~ ~ ~
~   ~   ~
~   ~   ~
~   ~ ~
Total gas mixture
Temperature Amount
constant constant

Temperature and volume constant
l Air
I FIG U 'R E 2 4 - 4 I Balloon model
of ventilation. The cartoons show a classic
model in which a jar represents the rib cage
(thoracic cavity), a rub-ber sheet represents the
diaphragm, and a balloon represents the alveoli of the lungs. The space be-
tween the jar and balloon represents the intrapleural space. A, Inspiration,
caused by downward movement of the diaphragm. B, Expiration, caused by
elastic recoil of the diaphragm upward.
constant ~ ~
~ ~ ~
~ ~
~ ~ ~
~ ~
~ ~ ~
~ ~
Temperature Amount
increases constant
IN SOLUnON • X aouaurv OF GAS
Gas molecules
0 in gaseous phase
Water in beaker
o Q
Gas molecules
in liquid phase
(At equilibrium, Pgas is equal
throughout the system)
The gas laws. A, Boyle's law. B, Charles' law. C, Dalton's law. D, Henry's law.
804 UNIT 5 Respiration, Nutrition, and Excretion
compliant (stretchable). the decrease in PIP causes a similar de-
crease in the balloon pressure (alveolar pressure, P
) . This creates
a pressure gradient that results in flow of air into the balloon. The
opposite occurs when the elastic diaphragm recoils, decreasing
internal air volumes (thus increasing internal air pressure) and
forcing air out of the balloon.
Figure 24-5 applies the same principles of the balloon model to
the human airways to demonstrate the mechanics of ventilation.
The constant alternation between inspiration and expiration is
called the respiratory cycle. The specific mechanics of the respira-
tory cycle are outlined in the following sections and in Table 24-1.
Contraction ofthe extemal intercostal muscles pulls the anterior end of
each rib up and out (Figure 24-6, A). This also elevates the attached
stemum and enlarges the thorax from front to back and from side to
side (Figure 24-6, B). In addition, contraction of the stemocleidomas-
toid, pectoralis minor, and serratus anterior muscles can aid in eleva-
tion of the sternum and rib cage during forceful inspiration.
As the size of the thorax increases, the intrapleural (intra-
thoracic) and alveolar pressure decreases (Boyle's law) and in-
spiration occurs.
At the beginning of each inspiration, intrapleural pressure
(PIP) is about 758 mm Hg. Thus the PIP is about 2 mm Hg less
than atmospheric pressure (fre-
quently written -2 mm Hg).
During normal quiet inspiration,
Contraction of the diaphragm alone,
or contraction of both the diaphragm
and the external intercostal muscles,
produces quiet inspiration. As the dia-
phragm contracts, it descends, and
this makes the thoracic cavity longer.
-.;. [ I p,
( ) '\' ' 759 mm Hg
PIP decreases further to 756 mm
Hg (-4 mm Hg) or less. As the
thorax enlarges, it pulls the lungs
along with it because of cohe-
sion between the moist pleura

; 760mm Hg
, PA
\ ( i I mm Hg
\ \, I 758mmHg
f--- -+-PIP
756 mm Hg
760 mm Hg .... !-..:.--+--
754 mm Hg ! ' I '.
I .'   PA
761 mm Hg
756 mm Hg
760 mm H9I

I FIG U R E 24 - 51 The respiratory cycle. During inspiration, the diaphragm contracts, increasing the volume of the thoracic cavity. This
increase in volume results in a decrease in pressure, which causes air to rush into the lungs. During expiration, the diaphragm returns to an upward
position, reducing the volume in the thoracic cavity. Air pressure thus increases, forcing air out of the lungs. See Table 24-1 for additional details.
, Alveolar pressure; P
, barometric pressure; PIP, intrapleural pressure.
Chapter 24 Physiology of the Respiratory System 805
TAB L E 2 4 - 1 I The Respiratory Cycle
758 760
756 759
754 760
754 760
756 761
758 760
The diaphragm is relaxed, putting the thoracic cavity at low volume. At the beginning of inspiration PIP < P
, keeping alveoli
open. Since P
= P
, no air is flowing yet.
The diaphragm contracts, increasing the thoracic volume and reducing Plf' A decrease in PIP causes a decrease in P
• Now
< P
, and air flows down the pressure gradient (into the lungs).
Eventually, the alveoli fill with air and P
equilibrates with P
• Inward airflow stops. The cycle is now ready to shift to the
expiration phase. Note that PIP is still dropping but P
has not yet "caught up" with the drop.
As expiration is about to begin, the diaphragm is contracted maximally. Since P
= P
, there is no airflow.
The diaphragm relaxes, and elastic recoil of the thoracic walls and alveoli increases PIP and P
• Now, P
> P
. Air moves
(outward) down the pressure gradient.
The diaphragm eventually relaxes fully, so the decrease in volume stops. P
equilibrates with P
, and airflow ceases. The
system is now ready for another inspiration phase.
P'P = Intrapleural pressure (air pressure in the intrapleural space); P
= alveolar pressure (air pressure inside the alveoli); P
= atmospheric (barometric) pressure (air pressure of the
external environment [atmosphere)).
All P values are expressed in mm Hg and are examples only.
covering the lungs and the moist pleura lining the thorax.
Thus the lungs expand and the pressure in their tubes and
alveoli necessarily decreases. Alveolar pressure decreases
from an atmospheric level to a subatmospheric level-typi-
cally a drop of about 1 to 3 mm Hg. The moment that alveo-
lar pressure becomes less than atmospheric pressure, a
pressure gradient exists between the atmosphere and the inte-
rior of the lungs. According to the primary principle of venti-
lation, air moves into the lungs. Eventually, enough air moves
out of the lungs to establish a pressure equilibrium between
the atmosphere and the alveoli - and the flow of air then
The ability of the lungs and thorax to stretch, referred to as
compliance, is essential to normal respiration. If the compliance
Superior and anterior
movement of sternum
I FIG U R E 2 4 - 6 I Movement of the rib cage during breathing. A, Inspiratory muscles pull the ribs upward and thus outward, as in a bucket
handle. B, Inspiratory muscles pull the sternum upward and thus outward, as when pulling upward on the handle of a water pump.
806 UNIT 5 Respiration, Nutrition, and Excretion
muscles contract _ ~ -   , - - - - ___ ---,
Pectoralis minor
muscles contract I ~ ~ ,
muscles contract \ .. ~
Contraction of
of expiratory
Contraction of
I ,
Increase in vertical
diameter of thorax
Decrease in intrapleural
(intrathoracic) pressure
Expansion of lungs
l '{
Increase in anteroposterior and
transverse dimensions of thorax
Cohesion of
visceral and
parietal pleurae
Compliance of
thorax and
contracts P+A
Decrease in alveolar pressure
Establishes pressure gradient
from atmosphere to alveoli
• Inspiration
I FIG U R E 24- 71 Mechanism of inspiration. Note the role of the diaphragm and the chest-elevating muscles (pectoraliS minor and
external intercostals) in increasing thoracic volume, which decreases pressure in the lungs and thus draws air inward.
of these structures is reduced by injury or disease, inspiration be-
comes difficult-or even impossible (Box 24-2 on p. 808).
For a summary of the mechanism of inspiration just described,
see Figures 24-5 and 24-7.
Quiet expiration is ordinarily a passive process that begins when
the pressure gradients that resulted in inspiration are reversed.
The inspiratory muscles relax, causing a decrease in the size of the
thorax and an increase in intrapleural pressure from about 754
mm Hg (-6 mm Hg) before expiration to about 756 mm Hg (-4
mm Hg) or more during respiration. It is important to understand
that this pressure between the parietal and visceral pleura is al-
ways negative, that is, less than atmospheric pressure and less than
alveolar pressure. The negative intrapleural pressure is required to
overcome the so-called "collapse tendency of the lungs" caused
by surface tension of the fluid lining the alveoli and the stretch of
elastic fibers that are constantly attempting to recoil.
As alveolar pressure increases, a positive-pressure gradient is
established from alveoli to atmosphere-and thus expiration
Chapter 24 Physiology of the Respiratory System 807
Relaxation of
inspiratory muscles
Contraction of
expiratory muscles
Decrease in size of thorax
Increase in intrapleural
(intrathoracic) pressure
Elastic recoil of lung tissue
Decrease in size of lungs
muscles contract
'I-- - ----:---4 - Diaphragm
Increase in alveolar pressure
Pressure gradient from
alveoli to atmosphere
1 FIG U R E 24 - 81 Mechanism of expiration. Note that relaxation of the diaphragm plus contraction of chest-depressing muscles (in-
ternal intercostals) reduces thoracic volume, which increases pressure in the lungs and thus pushes air outward.
occurs as air flows outward through the respiratory passage-
ways. In forced expiration, contraction of the abdominal and
internal intercostal muscles can increase alveolar pressure tre-
mendously-creating a very large air pressure gradient.
The tendency of the thorax and lungs to return to their prein-
spiration volume is a physical phenomenon called elastic recoil.
If a disease condition reduces the elasticity of pulmonary tissues,
expirations must become forced even at rest.
Figures 24-5 and 24-8 summarize the mechanism of expiration
just described.
Look for a moment at Figure 24-9. This figure shows the
repeating respiratory cycle mapped out as changes in pressures
and volumes. Note that intrapleural pressure is always less than
alveolar pressure. This difference (PIP - PAl is called the trans-
pulmonary pressure. Intrapleural pressure is always "negative"
with respect to alveolar pressure. Transpulmonary pressure
must be negative to maintain inflation of the lungs, as stated
1. What is meant by the term pulmonary ventilation?
2. What effect does enlargement of the thoracic cavity have on the
air pressure inside the lungs?
3. Which requires more expenditure of energy during normal, quiet
breathing-inspiration or expiration?
Pulmonary Volumes and Capacities
The volumes of air moved in and out of the lungs and remaining
in them are matters of great importance. They must be normal
so that normal exchange of oxygen and carbon dioxide can oc-
cur between alveolar air and pulmonary capillary blood.
An apparatus called a spirometer is used to measure the volume
of air exchanged in breathing (Figure 24-10) . A graphic recording
Box 24-2 \ Surfactant and Lung Compliance
As we have discussed already, inspiration cannot occur without the
lungs and thorax having the ability to stretch-a characteristic called
compliance. Of course, the natural "stretchiness" of the alveolar walls is
important in determining lung compliance. Conditions that cause
thickening, or fibrosis, of lung tissues reduce the ease of stretch and
thus reduce lung compliance. A greater impact on lung compliance is
made by surface tension in the fluid film that lines the alveoli.
Surface tension in an aqueous (water-based) solution results from the
attractive forces between water molecules in the solution. Recall from
Chapter 2 that water molecules are polar and thus are electrically attracted
to one another-as though they are weak magnets. Surface tension is high
as the water molecules try to move toward one another, thereby contracting
the fluid. The fluid lining of each alveolus would thus tend to collapse under
this contracting force. However, as we discussed in Chapter 23 (see
p. 787), the presence of surfactant prevents such collapse of alveoli.
Surfactant is formed from the protein and phospholipid secretions of type II
cells in the wall of each alveolus. Surfactant reduces surface tension and
thus prevents fluid contraction and alveolar collapse. The role of surfactant
in preventing alveolar collapse is illustrated in Figure A.
The pressure created by the force of surface tension is greater in
smaller alveoli than in larger alveoli, according to the Young-LaPlace
law. This means that smaller alveoli would tend to have a higher
pressure (P
) than larger alveoli would. Thus air would move from the
smaller alveoli into larger alveoli. However, because the surfactant on
Without surfactant
create high surface . .
tension, pulling
molecules together

a. •

. .
With surfactant

Attractive forces at
surface disrupted,
reducing surface tension
,-,...,vl l
the surface of the fluid that lines the smaller alveoli is more concen-
trated than that on larger alveoli, surface tension is reduced proportion-
ally. In this way, the pressure in large alveoli is equal to that in smaller
alveoli. In theory, all alveoli-no matter what their size-are ventilated
equally. Figure B summarizes the Young-LaPlace law.
Surfactant is present in most newboms. However, because surfactant
formation is not fully under way until the seventh or eighth month of
prenatal development, premature infants often do not have enough
surfactant. The deficiency of surfactant in premature infants is called
hyaline membrane disease (HMO). Because lack of surfactant decreases
lung compliance, a premature infant will try to inflate the alveoli by
increasing effort of the inspiratory muscles. Such great effort is needed to
maintain normal ventilation that the baby may die of exhaustion. The effects
of such alveolar collapse and ventilation difficulty are collectively called
respiratory distress syndrome (ROS). In infants, it is more specifically
called infant respiratory distress syndrome (IRDS). See Figure C.
One way to treat IRDS is to use a special type of mechanical
respirator with continuous positive airway pressure (CPAP,
pronounced "SEE-pap"). The respirator artificially inflates the baby's
lungs and then maintains enough pressure during expiration to
prevent collapse-thus relieving the baby's inspiratory muscles.
Synthetic surfactants are also used frequently to prevent or treat
IRDS. The surfactant is delivered through a tube directly into the
airways-a method called intratracheal injection.
Without surfactant

PA= 2T
"T _.

,. ,.

:4 •• ,,"
PA = 1 •
PA= 2
B gradient
With surfactant
No pressure
PA = 1
C PA = 1 gradient
A, Role of surfactant The surface of the water that lines the small alveoli tends to contract because of its high surface tension, thereby collapsing the entire
alveolus. Surfactant disrupts some of the attractive forces and thus reduces surface tension-and the risk of alveolar collapse. B, Young-laPlace law. Also
called the law of LaPlace, this principle states that alveolar pressure (PA) is directly proportional to surface tension (T) and inversely proportional to the radius
(r) of the alveolus. Without surfactant, the pressure gradient would cause air to flow from the small alveoli to the larger alveoli-thus triggering collapse of the
smaller alveoli. When surfactant is present, the concentration of the surfactant is higher as the alveolus gets smaller. Because small alveoli have less surface
tension than larger alveoli do (as a result of more concentrated surfactant), the effect of the Young-laPlace law is counterbalanced. Because P
thus remains
about the same in all alveoli, regardless of size, ventilation is not disrupted. C, Microscopic effects of respiratory distress syndrome (ROS). The light
micrograph on the left shows normal lung structure, with many open alveoli. The right image is from an infant who died of RDS. Note the collapse of the alveoli.

Chapter 24 Physiology of the Respiratory System 809
Inspiration Inspiration Expir:ation Inspir:ation
Expi"!tion __ E_X_P __ ir:a .... t_io_n __ __

o 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20
Time (sec)
1 FIG U R E 24- 91 Rhythm of ventilation. Respiratory cycles repeat continuously in normal, quiet breathing. Notice the rhythmic rise
and fall of the intrapleural pressure (PIP) and alveolar pressure {PAl. You can easily see that PIP is always lower than P
(negative transpulmonary
pressure) , which helps keep the alveoli inflated. The lowest line shows the change in air volumes during the respiratory cycle.
1 FIG U R E 24- 1 0 1 Spirometer. Spirometers are devices that measure the volume of gas that the lungs inhale and exhale, usually as a
function of time. A, Diagram of a classic spirometer design showing how the volume of air exhaled and inhaled is recorded as a rising and falling
line. B, A simple spirometer attached to a computerized recording device. This apparatus is used frequently for routine assessment of ventilation.
810 UNIT 5 Respiration, Nutrition, and Excretion
of the changing pulmonary volumes observed during breathing is
called a spirogram (Figure 24-11, A). The volume of air exhaled
normally after a typical inspiration is termed tidal volume (TV).
As you can see in Figure 24-11, the normal volume of tidal air for
an adult at rest is approximately 500 m} (or 0.5 L).
After expiration of tidal air, an individual can force still more
air out of the lungs. The largest additional volume of air that one
can forcibly expire after expiring tidal air is called the expiratory
reserve volume (ERV). An adult, as Figure 24-11 shows, nor-
mally has an ERV of between 1000 and 1200 ml (l.0 to l.2 L).
Inspiratory reserve volume (IRV) is the amount of air that can
be forcibly inspired over and above a normal inspiration. It is



Resting state
(normal breathing)
reserve volume (IRV)
(3000-3300 ml)
reserve volume (ERV)
(1000-1200 ml)
Residual volume (RV)
(1200 ml)
Time .....
Anatomical dead space
Residual volume
Greater activity
(forceful inspiration
plus forceful expiration)
A Tidal volume Vital .
-"""<'--- Inspiratory
Total lung
reserve volume


I FIG U R E 2 4 - 1 1 I Pulmonary ventilation volumes and
capacities. A, Spirogram. B, Pulmonary volumes (at rest) represented as
relative proportions of an inflated balloon. During normal, quiet respira-
tions, the atmosphere and lungs exchange about 500 ml of air (TV). With
forcible inspiration, about 3300 ml more air can be inhaled (IRV). After a
normal inspiration and normal expiration, approximately 1000 ml more air
can be forcibly expired (ERV) . Vital capacity is the amount of air that can
be forcibly expired after a maximal inspiration and therefore indicates the
largest amount of air that can enter and leave the lungs during respiration.
Residual volume is the air that remains trapped in the alveoli.
measured by having the individual exhale normally after a forced
inspiration. The normal IRV is about 3300 ml (3.3 L). No matter
how forcefully one exhales, one cannot squeeze all the air out of
the lungs. Some of it remains trapped in the alveoli. This amount
of air that cannot be forcibly expired is known as residual vol-
ume (RV) and amounts to about 1200 ml (l.2 L). Between
breaths, an exchange of oxygen and carbon dioxide occurs be-
tween the trapped residual air in the alveoli and the blood. This
process helps "level off" the amounts-or maintain the set point
values-of oxygen and carbon dioxide in the blood during the
breathing cycle. Have you ever had "the wind knocked out of
you" by a sudden impact to the thorax or a series of deep coughs?
In such a case, your expiratory reserve is forced out of your air-
ways, as well as some of your residual volume. A few alveoli col-
lapse as a result. It may take a moment or two, and some effort
on your part, to reinflate the collapsed alveoli and reestablish
normal breathing.
In pneumothorax (Box 24-3), the RV is eliminated when the
lung collapses. Even after the RV is forced out, the collapsed lung
has a porous, spongy texture and floats in water because of trapped
air called the minimal volume, which is about 40% of the RY.
A pulmonary "capacity" is the sum of two or more pulmonary "vol-
umes." Notice in Figure 24-11 that vital capacity (VC) is the sum of
The vital capacity represents the largest volume of air an indi-
vidual can move in and out of the lungs. It is determined by mea-
suring the largest possible expiration after the largest possible
inspiration. How large a vital capacity a person has depends on
many factors-the size of the thoracic cavity, posture, and various
other factors. In general, a larger person has a larger vital capacity
than a smaller person does. An individual has a larger vital capac-
ity when standing erect than when stooped over or lying down.
The volume of blood in the lungs also affects the vital capacity. If
the lungs contain more blood than normal, the alveolar air space
is encroached on and vital capacity accordingly decreases. This
becomes a very important factor in congestive heart disease.
Excess fluid in the pleural or abdominal cavities also decreas-
es vital capacity. So, too, does the disease emphysema. In the
latter condition, the alveolar walls become stretched - that is,
lose their elasticity-and are unable to recoil normally for expi-
ration. This leads to an increased RY. In severe emphysema, the
RV may increase so much that the chest occupies the inspiratory
position even at rest. Excessive muscular effort is therefore nec-
essary for inspiration, and because of the loss of elasticity of lung
tissue, greater effort is required, too, for expiration.
In diagnosing lung disorders a physician may need to know the
inspiratory capacity and the functional residual capacity of the
patient's lungs. Inspiratory capacity (IC) is the maximal amount
of air an individual can inspire after a normal expiration. From
Figure 24-11, you can deduce that
Using the volumes given in the figure, how many milliliters is
the IC? Check your answer in Table 24-2, which summarizes pul-
CJl Box 24-3 1 HEALTH matters
Air in the pleural space may accumulate when the visceral pleura ruptures
and air from the lung rushes out or when atmospheric air rushes in
through a wound in the chest wall and parietal pleura. In either case, the
lung collapses and normal respiration is impaired. Ai r in the thoracic cavity
is a condition known as pneumothorax (see figure). To apply some of the
information you have learned about the respiratory mechanism, let us
suppose that a surgeon makes an incision through the chest wall into the
pleural space, as is done in one of the dramatic, modern open-chest opera-
tions. What change, if any, can you deduce takes place in respirations?
Compare your deductions with those in the next paragraph.
Intrathoracic pressure, of course, immediately increases from its
normal subatmospheric level to the atmospheric level. More pressure
than normal is therefore exerted on the outer surface of the lung and
causes it to collapse. It could even collapse the other lung. Why?
Because the mediastinum is a mobile rather than a rigid partition
between the two pleural sacs. This anatomical fact allows the
increased pressure in the side of the chest that is open to push the
heart and other mediastinal structures over toward the intact side,
where they would exert pressure on the other lung. Pneumothorax
can also result from disruption of the visceral pleura and the
resulting flow of pulmonary air into the pleural space.
monary volumes and capacities. Functional residual capacity
(FRC) is the amount of air left in the lungs at the end of a normal
expiration. Therefore, as Figure 24-11 implies,
Using the volumes given, the functional residual capacity is
2200 to 2400 ml (2. 2 to 2.4 L). The total vol ume of air a lung can
hold is called the total lung capacity (TLC).lt is, as Figure 24- 11
indicates, the sum of all four lung volumes.
TABLE 24 - 2 I Pulmonary Volumes and Capacities
Chapter 24 Physiology of the Respiratory System 81 1
Pneumothorax results in many respiratory and Circulatory
changes. They are of great importance in determining medical and
nursing care but lie beyond the scope of this book.
Outside air rushes in due to
disruption of chest wall
and parietal pleura
Lung air
rushes out
due to
of visceral
t t----I-Pleural
Pneumothorax. Diagram showing air entering the thoracic
cavity, causing lung collapse.
The term alveolar ventilation means the volume of inspired
air that actually reaches, or "ventilates," the alveoli. Only this
volume of air takes part in the exchange of gases between air and
blood. (Alveolar ai r exchanges some of its oxygen for some of the
blood's carbon dioxi de.) Wi th every breath we take, part of the
enteri ng air necessarily fi lls our ai r passageways - nose, pharynx,
larynx, trachea, and bronchi . This portion of air does not de-
scend into any alveoli and therefore cannot take part in gas ex-
change. In this sense, it is "dead air." Appropriately, the larger air
Tidal volume (TV) Volume moved into or out of the 500 ml (0.5 L) Vital capacity TV+ IRV +ERV 4500-5000 ml
respiratory tract during a normal (VC) (4. 5-5.0 L)
respiratory cycle
Inspiratory reserve Maximum volume that can be moved 3000-3300 ml Inspiratory TV+ IRV 3500-3800 ml
volume (IRV) into the respiratory tract after a (3.0-3.3 L) capacity (IC) (3.5-3.8 L)
normal inspiration
Expiratory reserve Maximum volume that can be moved 1000-1200 ml Functional ERV + RV 2200-2400 ml
volume (ERV) out of the respiratory tract after a (1 .0-1 .2 L) residual capacity (2.2-2.4 L)
normal expiration (FRC)
Residual volume Volume remaining in the respiratory 1200 ml (1 .2 L) Total lung TV + IRV + ERV + RV 5700-6200 ml
(RV) tract after maximum expiration capacity (TLC) (5.7-6.2 L)
812 UNIT 5 Respiration, Nutrition, and Excretion
passageways it occupies are said to constitute the anatomical
dead space. Figure 24-11, B, relates the volume of the anatomi-
cal dead space to the major pulmonary volumes. In disorders
such as chronic obstructive pulmonary disease (COPD), some
alveoli are not able to perform gas exchange and are therefore
also "dead space." The anatomical dead space plus any alveolar
dead space together make up the physiological dead space.
One rule of thumb estimates the volume of air in the ana-
tomical dead space as the same number of milliliters as the indi-
vidual's weight in pounds. Another generalization says that the
anatomical dead space approximates 30% of the TV. TV - dead
space volume = alveolar ventilation volume. Suppose you have
a normal TV of 500 ml and that 30% of this, or 150 ml, fills the
Box 24-4 1 Types of Breathing
The alternate movement of air into and out of the lungs that we
call breathing can occur in distinctive patterns that can be recog-
nized and designated by name (see figure) .
Eupnea is the term used to describe normal quiet breathing. Dur-
ing eupnea, the need for oxygen and carbon dioxide exchange is
being met, and the individual is not usually conscious of the
breathing pattern. Ventilation occurs spontaneously at the rate of 12
to 17 breaths per minute.
Hyperpnea means increased breathing that is regulated to meet
an increased demand by the body for oxygen. During hyperpnea,
there is always an increase in pulmonary ventilation. The hyperpnea
caused by exercise may meet the need for increased oxygen by an
increase in tidal volume alone or by an increase in both tidal volume
and breathing frequency.
Hyperventilation is characterized by an increase in pulmonary
ventilation in excess of the need for oxygen. It sometimes results
from a conscious voluntary effort preceding exertion or from
psychogenic factors (hysterical hyperventilation). Hypoventilation is
a decrease in pulmonary ventilation that results in elevated blood
levels of carbon dioxide.
Name of pattern
Normal breathing
Rapid, deep respirations
Slow, shallow respirations
Examples of breathing patterns and spirograms.
anatomical dead space. The amount of air reaching your alveo-
li - your alveolar ventilation volume - is then 350 ml per breath,
or 70% of your TV.
Emphysema and certain other abnormal conditions, in effect,
increase the amount of dead space air or physiological dead space.
Consequently, alveolar ventilation decreases, and this in turn de-
creases the amount of oxygen that can enter blood and the amount
of carbon dioxide that can leave it. Inadequate air-blood gas ex-
change, therefore, is the inevitable result of inadequate alveolar
ventilation. Stated differently, the alveoli must be adequately ven-
tilated for an adequate gas exchange to take place in the lungs.
Box 24-4 summarizes some abnormal breathing patterns seen
in spirometry.
Dyspnea refers to labored or difficult breathing and is often
associated with hypoventilation. A person suffering from dyspnea is
aware, or conscious, of the breathing pattern and is generally
uncomfortable and in distress. Orthopnea refers to dyspnea while
lying down. It is relieved by sitting or standing up. This condition is
common in patients with heart disease.
Several terms are used to describe the cessation of breathing.
Apnea refers to the temporary cessation of breathing at the end of a
normal expiration. It may occur during sleep or when swallowing.
Apneusis is the cessation of breathing in the inspiratory position.
Failure to resume breathing following a period of apnea, or
apneusis, is called respiratory arrest.
I' Cheyne-Stokes respiration is a periodic type of abnormal breathing
often seen in terminally ill or brain-damaged patients. It is characterized
by cycles of gradually increasing tidal volume for several breaths
followed by several breaths with gradually decreasing tidal volume.
These cycles repeat in a type of crescendo-decrescendo pattern.
Biot breathing is characterized by repeated sequences of deep
gasps and apnea. This type of abnormal breathing pattern is seen in
individuals suffering from increased intracranial pressure.
Name of pattern Description
Ap"'"rv\ C,,,.Iio" of
        3>Wfrii,,,i!'iM §l!4444MfJ ¥1fl ;;w'4'QWk, 4k4W;L 4F.
Various applications of spirometry can be used to generate addi-
tional information about airflow in an individual. For example,
spirometry can be used to determine pulmonary airflow as the rate
of pulmonary ventilation, or total minute volume (volume moved
per minute) . Tidal volume (mllcycle) multiplied by respiration
rate (cycles per minute) yields the total minute volume (mllmin).
The total minute volume of a person at rest is about 6000 ml (500
mllcycle x 12 cycles/min) . Box 24-5 discusses the concept of max-
imum oxygen consumption.
Yet another application of spirometry is the forced expiratory
volume (FEV) test. The FEV test can determine the presence of
respiratory obstruction by measuring the volume of air expired per
second during forced expiration. The volume forcefully expired
during the first second, the FEV!> is normally about 83% of the
vital capacity (Figure 24-12). FEV
, the total volume expired dur-
ing the first 2 seconds, is about 94% of the VC. By the end of the
third second, FEV
, 97% of the vital capacity should have been
expired. The FEV test is also sometimes called the FVC (forced
vital capacity) test.
Some spirometers are capable of producing a graph called the
flow-volume loop. This type of graph shows a forced expiration
(forced vital capacity) as a loop rather than the peaks and valleys
of the classic spirogram. In Figure 24-13 you can see that the top
portion of the loop represents expiratory airflow (liters per second)


3sec-------------.. ;
2 sec • • •
1 sec_; •
Normal .
: FEV : •
_ ._-"'-________ - .. .. - ..-x.- __ • ___ ",""_ ..... =___--T_ ... _I
. .
Time (sec)
, __ roue
3 4
I FIG U R E 2 4 - 1 2 I Forced expiratory volume (FEV). A
normal individual forcefully exhales about 83% of the vital capacity
(VC) during the first second, 94% at the end of 2 seconds, and 97%
by the end of 3 seconds. The red line shows the results from a per-
son with COPD (chronic obstructive pulmonary disease) who cannot
forcefully exhale a large percentage of the vital capacity as quickly as
a person without pulmonary obstruction.
Chapter 24 Physiology of the Respiratory System 813
@ Box 24-5 FITNESS
Maximum Oxygen Consumption
Exercise physiologists use maximum oxygen consumption
max) as a predictor of a person's capacity to do aerobic
exercise. An individual's V0
max represents the amount of oxygen
taken up by the lungs, transported to the tissues, and used to do
work. V0
max is determined largely by hereditary factors, but
aerobic (endurance) training can increase it by as much as 35%.
Many endurance athletes are now using V0
max measurements to
help them determine and then maintain their peak condition.
along the vertical axis and expiratory volume (liters) along the
horizontal axis. The inspiratory airflow and volume are represent-
ed by the bottom portion of the loop.
Notice in Figure 24-13 that the top of the flow-volume loop
represents the peak expiratory flow, or more simply the peak flow.
The peak flow is easy to measure even with simple hand-held spi-
rometers. It is no wonder, then, that peak flow measurements are

: •• ------------ FVC -------., :
Relative lung volume (L)
I FIG U R E 2 4 - 1 3 I Flow-volume loops. The top of the
loop represents expiratory flow (vertically) and volume (horizon-
tally) . The bottom of the loop represents inspiratory flow and vol-
ume. Notice that a person with COPD (chronic obstructive pulmo-
nary disease) will produce a smaller loop with a "scooped-out"
shape at the end of the expiratory curve. FVC, Forced vital capacity.
814 UNIT 5 Respiration, Nutrition, and Excretion
often used at home by asthma patients to keep a diary of airflow
function. The flow-volume loop is especially useful in assessing
such obstructive disorders because of the characteristic "scooped-
out" shape of the expiratory part of the loop. In obstructive disor-
ders, the inspiratory portion of the loop has a normal curve, but is
smaller than normal.
4. What is the difference between a pulmonary volume and a
pulmonary capacity?
5. The volume of air that is expired after a normal inspiration dur-
ing normal, quiet breathing goes by what name?
6. What is meant by the term vital capacity?
7. What is the total minute volume? How can it be calculated from
a spirogram?
Partial Pressure
Before discussing the exchange of gases across the respiratory
membranes, we need to understand the law of partial pressures
(Dalton's law) . The term partial pressure means the pressure ex-
erted by anyone gas in a mixture of gases or in a liquid. According
Nitrogen (N
to the law of partial pressures, the partial pressure of a gas in a
mixture of gases is directly related to the concentration of that gas
in the mixture and to the total pressure of the mixture. Figure 24-
14 shows how each gas in atmospheric air contributes to the total
atmospheric pressure. The partial pressure of each gas is directly
related to its concentration in the total mixture. Suppose we apply
this principle to compute the partial pressure of oxygen in the at-
mosphere. The concentration of oxygen in the atmosphere is
about 21 %, and the total pressure of the atmosphere is 760 mm
Hg under standard conditions. Therefore
Atmospheric PO
= 21 % x 760 = 159.6 mm Hg
The symbol used to designate partial pressure is the capital let-
ter P preceding the chemical symbol for the gas. Examples: alveo-
lar air PO
is about 100 mm Hg, arterial blood PO
is also about
100 mm Hg, and venous blood PO
is about 37 mm Hg. The word
tension is often used as a synonym for the term partial pressure-
oxygen tension means the same thing as PO
The partial pressure of a gas in a liquid is directly determined
by the amount of that gas dissolved in the liquid, which in turn
is determined by the partial pressure of the gas in the environ-
ment of the liquid. Gas molecules diffuse into a liquid from its
environment and dissolve in the liquid until the partial pressure
of the gas in solution becomes equal to its partial pressure in the
environment of the liquid. Alveolar air constitutes the environ-
Carbon dioxide (C0
), 0.03%
Other gases, 0.97%
PN2 + P0
592.8 mm + 159.6 mm +
(78%) (21%)
Oxygen (0
PC02 +
0.2 mm +
7.4 mm
I FIG U R E 2 4 - 1 4 I Partial pressure of gases in atmospheric air. A,
Composition of dry atmospheric air under standard conditions showing the concen-
trations of nitrogen, oxygen, carbon dioxide, and other gases. B, A mercury barom-
eter. The weight of air pressing down on the surface of the mercury in the open dish
pushes the mercury down into the dish and up the tube. The greater the air pressure
pushing down on the mercury surface, the farther up the tube the mercury will be
forced. Under standard conditions, air pressure causes the mercury column to rise
760 mm. A proportion of this pressure is exerted by each of the gases that comprise
air, according to their relative concentrations (see A). That is, the total atmospheric
air pressure is the sum of the partial pressures of nitrogen, oxygen, carbon dioxide,
water vapor, and other gases.
760 mm
Mercury (Hg)
TABLE 24 - 3 I Oxygen and Carbon Dioxide
Pressure Gradients*
160 100 100 40
PC02 0.2 40 40 46
'Values indicate approximate mm Hg pressure under usual conditions.
ment surrounding blood moving through pulmonary capillaries.
Standing between the blood and the air are only the very thin
alveolar and capillary membranes, and both of these membranes
are highly permeable to oxygen and carbon dioxide. By the ti me
blood leaves the pulmonary capillaries as arterial blood, diffu-
sion and approximate equilibration of oxygen and carbon diox-
ide across the membranes have occurred. Arterial blood Paz and
Peoz therefore usually equal or very nearly equal alveolar P0
and Peoz (Table 24-3).
Exchange of Gases in the Lungs
Exchange of gases in the lungs takes place between alveolar air
and blood flowing through lung capillaries. It is important to real-
ize that physiologically speaking, air in the lung is not part of our
body. That is, inspired air is not part of the internal environment.
As Figure 24-15 shows, the airways are merely inward extensions
of the external environment. Before oxygen can enter our internal
environment, and before carbon dioxide can leave our internal
I FIG U R E 24- 1 51 External-internal barrier. The respira-
tory membranes of the lung represent an interface or barrier that gas-
es must cross to enter or exit the body's internal environment. The
pulmonary airway is merely an extension of the external environment.
Chapter 24   of the Respiratory System 815
A Capillary B Capillary
i FIG U R E 2 4 - 1 6 I Pulmonary gas exchange. A, As blood
enters a pulmonary capillary, oxygen diffuses down its pressure gradi-
ent (into the blood). Oxygen continues diffusing into the blood until
equilibration has occurred (or until the blood leaves the capillary). B,
As blood enters a pulmonary capillary, carbon dioxide diffuses down
its pressure gradient (out of the blood). As with oxygen, carbon diox-
ide continues diffusing as long as there is a pressure gradient. P0
remain relatively constant in a continually ventilated alveolus.
environment, these gases must cross the barrier between the exter-
nal world and the internal world.
Gases move in both directions through the respiratory mem-
brane (see Figure 23-16). Oxygen enters blood from the alveolar
air because the Paz of alveolar air is greater than the Paz of incom-
ing blood. Another way of saying this is that oxygen diffuses "down"
its pressure gradient. Simultaneously, carbon dioxide molecules
exit from the blood by diffusing down the carbon dioxide pressure
gradient out into the alveolar air. The Peoz of venous blood is
much higher than the Peoz of alveolar air. This two-way exchange
of gases between alveolar air and pulmonary blood converts de-
oxygenated blood to oxygenated blood (Figure 24-16).
When you look at Figure 24-16, you might wonder why the
partial pressures of gases in the alveoli remain constant, whereas the
816 UNIT 5 Respiration, Nutrition, and Excretion
partial pressures of gases in the blood change to equilibrate with
alveolar partial pressures. The answer to this question lies in the fact
that the alveoli are more or less continually ventilated. That is, there
is always new air moving into the alveoli at a relatively low, stable
velocity (Figure 24-17). Therefore, the average partial pressures of
gases in the alveoli as a group are relatively constant.
The amount of oxygen that diffuses into blood each minute
depends on several factors, notably the following four:
1. The oxygen pressure gradient between alveolar air and in-
coming pulmonary blood (alveolar P0
- blood Po
2. The total functional surface area of the respiratory membrane
3. The respiratory minute volume (respiratory rate per minute
times volume of air inspired per respiration)
4. Alveolar ventilation (discussed on p. 811)
All four of these factors bear a direct relation to oxygen diffu-
sion. Anything that decreases alveolar Po
, for instance, tends to
decrease the alveolar-blood oxygen pressure gradient and there-
fore tends to decrease the amount of oxygen entering the blood.
An application of this is as follows: Alveolar air P0
decreases as
altitude increases, and thus less oxygen enters the blood at high
altitudes. At a certain high altitude, alveolar air P0
equals the P0
of blood entering the pulmonary capillaries. How would this af-
fect oxygen diffusion into blood?
Anything that decreases the total functional surface area of the
respiratory membrane also tends to decrease oxygen diffusion into
the blood (functional surface area is meant as that which is freely
permeable to oxygen). An application of this is as follows: In em-
physema the total functional area decreases and is one of the fac-
tors responsible for poor blood oxygenation in this condition.
Surfactant disorders (Box 24-2) and pneumothorax (Box 24-3) can
also decrease total functional area by collapsing alveoli.
Anything that decreases the respiratory minute volume also
tends to decrease blood oxygenation. Application: Morphine slows
respirations and therefore decreases the respiratory minute vol-
ume (volume of air inspired per minute) and tends to lessen the
amount of oxygen entering the blood.
Several times we have stated the principle that structure deter-
mines function. This principle applies to gas exchange in the
lungs. Several structural facts facilitate oxygen diffusion from the
alveolar air into the blood in lung capillaries:
• The walls of the alveoli and the capillaries together form a
very thin barrier for the gases to cross (estimated at not more
than 0.004 mm thick-see Figure 23-16, p. 788) .
• Alveolar and capillary surfaces are both extremely large
(Box 24-6) .
, 1600
200% I : Alveolar
Conducting airways
~ I
t 100% i f·
o · ..
0% I ii i ii =::;::=:y-- iii 0 ;2 I
o 2 4 6 8 10 12 14 16 18 20
Number of airway branches
",,,, "414 ~       ~ r
1 FIG U R E 24- 1 71 Airflow in airways. Air velocity
(speed of flow) is high in the upper respiratory tract, where the
total cross-sectional area is very low. As you can see on the left
of the graph, however, the airflow slows down considerably in the
alveolar airways because of the high total cross-sectional area of
all of the alveoli. This accounts for the fact that ventilation of the
alveoli is slow and relatively steady whereas ventilation of the
upper airways is characterized by high-speed, alternating rushes
of air.
• Lung capillaries accommodate a large amount of blood at
one time. The lung capillaries of a small individual - one
who has a body surface area of l.5 square meters - contain
about 90 ml of blood at one time under resting conditions
(Figure 24-18).
• Blood is distributed through the capillaries in a layer so thin
(equal only to the diameter of one red blood cell) that each
red blood cell comes close to alveolar air.
8. How does the partial pressure of a gas relate to its concentra-
9. What detennines the direction in which oxygen will diffuse
across the respiratory membrane?
10. List two of the four major factors that influence how much oxy-
gen diffuses into pulmonary blood per minute.
Box 24-6 1 Fick's Law
Fick's law is a principle that describes the diffusion of carbon
dioxide (C0
) and oxygen (0
) across the respiratory membrane,
including the fluid film on the surface of the alveoli. As you can
see in the figure, the principle illustrates common sense: each gas
diffuses more efficiently (faster) if the surface area (A) is large, if
the thickness of the membrane (t) is small, if the solubility of the
gas (5) is high, and if the partial pressure (Po
or PC02) gradient
is high. Another way of stating Fick's law is that the net gas
diffusion rate across a fluid membrane is proportional to the
membrane surface area (A), solubility of the gas in the membrane
(5) , and partial pressure (P) difference-and inversely propor-
tional to the membrane thickness (f).
The human respiratory system takes advantage of this principle
by improving what it can in the equation to maximize the rate of
gas diffusion. The body builds its respiratory membrane of material
with as much solubility to CO
and O
as possible and makes it as
thin as possible. The large number of alveoli in a fractal-like
arrangement ensure a very large surface area. And a high partial
pressure gradient is maintained across the respiratory membrane.
1 FIG U R E 2 4 - 1 81 Alveolar blood supply. Scanning electron
micrograph showing the rich blood supply to alveoli (which have been re-
moved). The numerous, narrow branches ensure that each red blood cell
is exposed to the alveolar air. (Black bar in lower left represents 10 J..lm.)
Chapter 24 Physiology of the Respiratory System 817
Low PC02
I   h i ~ k !
s (I)
High PC0
Rate of diffusion of a gas through a membrane. According
to Fick's law, the membrane diffusion rate is affected by surface
area (A), solubility (S) of the gas, membrane thickness (t) , and
the partial pressure (P) gradient.
A variety of conditions leave us feeling like we need more
oxygen-whether it is strenuous exercise or an abnormal respiratory
or cardiovascular condition. Getting extra oxygen for therapeutic,
sports, and even recreational use is explored in Oxygen Supple-
ments online at A&P Connect.
Blood transports oxygen and carbon dioxide either as solutes or
combined with other chemicals. Immediately on entering the
blood, both oxygen and carbon dioxide dissolve in the plasma, but
because fluids can hold only small amounts of gas in solution,
most of the oxygen and carbon dioxide rapidly for m a chemical
union with some other molecule-such as hemoglobin, a plasma
protein, or water. Once gas molecules are bound to another mol-
ecule, their plasma concentration decreases and more gas can dif-
fuse into the plasma. In this way, comparatively large volumes of
the gases can be transported.
818 UNIT 5 Respiration. Nutrition. and Excretion
Hemoglobin Heme
.... #--
1 FIG U R E 24 - 1 91 Hemoglobin. Sketch showing that hemoglobin is a quaternary protein consisting of four different tertiary (folded)
polypeptide chains-two alpha (a) chains and two beta   ~ ) chains. Each chain has an associated iron-containing heme group. as seen in detail in
the inset. Oxygen (0
) can bind to the iron (Fe) of the heme group. or carbon dioxide (C0
) can bind to amine groups of the amino acids in the
polypeptide chains.
Before we begin our discussion of transport of gases in the
blood, we will pause and briefly review some facts about hemo-
globin (Hb) (Figure 24-19). As we outlined in Chapter 17, he-
moglobin is a reddish protein pigment found only inside red
blood cells.
Hemoglobin is a quaternary protein made of four different
polypeptide chains-two alpha chains and two beta chains-
each associated with an iron-containing heme group. If you
look at Figure 24-19, you will see that an oxygen molecule (Oz)
can combine with the iron atom (Fe) in each heme group.
Thus hemoglobin can act as a kind of oxygen sponge that
chemically absorbs oxygen molecules from the surrounding so-
lution. Notice also in this figure that carbon dioxide (CO
molecules can combine with the amino acids of the alpha and
beta polypeptide chains. Thus hemoglobin can also act as a
carbon dioxide sponge and absorb carbon dioxide molecules
from a solution. Hemoglobin, then, has exactly the chemical
characteristics needed to pick up and transport gases that enter
the blood. As you will learn in the following paragraphs, hemo-
globin also has the chemical characteristics needed to unload
these gases. Box 24-7 explains how carbon monoxide interferes
with hemoglobin's function.
Transport of Oxygen
Because oxygenated blood has a POz of 100 mm Hg, it contains
only about 0.3 ml of dissolved Oz per 100 ml of blood. Many times
that amount, however, combines with the hemoglobin in 100 ml
of blood to form oxyhemoglobin. Because each gram ofhemoglo-
bin can unite with 1.34 ml of oxygen, the exact amount of oxygen
in blood depends mainly on the amount of hemoglobin present.
Normally, 100 ml of blood contains about 15 g of hemoglobin. If
100% of it combines with oxygen, 100 ml of blood will contain
15 x 1.34, or 20.1 ml, of oxygen in the form of oxyhemoglobin.
Figure 24-20 shows how hemoglobin increases the oxygen-carry-
ing capacity of blood.
Perhaps a more common way of expressing blood oxygen con-
tent is in terms of volume percent. Normal arterial blood, with a
POz of 100 mm Hg, contains about 20 vol% Oz (meaning 20 ml of
oxygen in each 100 ml of blood).
Blood that contains more hemoglobin can, of course, transport
more oxygen. Thus blood that contains less hemoglobin can
transport less oxygen. Therefore hemoglobin deficiency anemia
Carbon Monoxide
Box 24-7 I Poisoning
Gases other than O
and CO
can bind to the hemoglobin (Hb)
molecule. Carbon monoxide (CO) is a molecule produced by
incomplete combustion in furnaces. engines. and other
circumstances. This invisible. odorless gas binds to Hb more
than 200 times more strongly than O
does. That means that
CO "knocks out" O
from Hb0
and forms HbCO. As more and
more HbCO is formed. less and less oxygen is being carried
by your blood-a life-threatening situation. Because CO binds
so strongly. it is hard to remove it from Hb. One strategy to
remove CO is to place a person in a pressure chamber where
the P0
can be driven so high that it "knocks off" the CO from
the Hb. allowing O
to form Hb0

K'. 44_ :;; ,Sj
Plasma Whole blood
I FIG U R E 2 4 - 2 0 I Oxygen-carrying capacity of blood. If
blood consisted only of plasma, the maximum oxygen that could be trans-
ported would be only about 0.3 ml of O
per 100 ml of blood. Because the red
blood cells contain hemoglobin molecules, which act as "oxygen sponges,"
the blood can actually carry up to 20 ml of dissolved O
per 100 ml of blood.
decreases oxygen transport and may produce marked cellular hy-
poxia (inadequate oxygen supply).
To combine with hemoglobin, oxygen must, of course, dif-
fuse from plasma into the red blood cells where millions of
0 50
Chapter 24 Physiology of the Respiratory System 819
hemoglobin molecules are located. Several factors influence
the rate at which hemoglobin combines with oxygen in lung
capillaries. For instance, as the following equation and the
oxygen-hemoglobin dissociation curve (Figure 24-21) show,
an increasing blood PO
accelerates hemoglobin association
with oxygen:
Increasing PO
Hb + Oz )HbO
Decreasing POz, on the other hand, accelerates oxygen dis-
sociation from oxyhemoglobin, that is, the reverse of the pre-
ceding equation. Oxygen associates with hemoglobin rap-
idly-so rapidly, in fact, that about 97% of the blood's hemo-
globin has united with oxygen by the time the blood leaves
the lung capillaries to return to the heart. In other words, the
average oxygen saturation of hemoglobin in oxygenated blood
is about 97%.
Summing up, we can say that oxygen travels in two forms: as
dissolved Oz in the plasma and as Oz associated with hemoglo-
bin (oxyhemoglobin) . Of these two forms of transport, oxyhemo-
globin carries the vast majority of the total oxygen transported by
the blood.
Variations of hemoglobin exist in the body to temporarily store
or carry oxygen. Find out why we need more than one type of oxy-
gen carrier in the body in Oxygen-binding Proteins online at A&P
10 20 30 40 50 60 70 80 90 100 110
Plasma P0
(mm Hg)
I FIG U R E 24 - 2 1 I Oxygen-hemoglobin dissociation curve. The graph represents the relationship between P0
and O
saturation of
hemoglobin (Hb-0
affinity) . The inset shows how the graphed curve relates to oxygen transport by the blood. Notice that at high plasma P0
values (point A), hemoglobin (Hb) is fully loaded with oxygen. At low plasma P0
values (point B), Hb is only partially loaded with oxygen.
820 UNIT 5 Respiration, Nutrition, and Excretion
H b ~ N / H
+ H+
I FIG U R E 2 4 - 2 2 I Carbon dioxide-hemoglobin
reaction. Carbon dioxide can bind to an amine group (NH
) in an amino
acid within a hemoglobin (Hb) molecule to form carbaminohemoglobin
(HbNCOOH-) and a hydrogen ion. The highlighted areas show where the
original carbon dioxide molecule is in each part of the equation.
Transport of Carbon Dioxide
Carbon dioxide is carried in the blood in several ways, the most im-
portant of which are described briefly in the following paragraphs.
A small amount of COz dissolves in plasma and is transported
as a solute. About 10% of the total amount of carbon dioxide
carried by the blood is carried in the dissolved form. It is this
dissolved COz that produces the Peaz of blood plasma.
One fifth to one quarter of the carbon dioxide in blood unites with
the NH
(amine) groups of the amino acids that make up the poly-
peptide chains of hemoglobin and various plasma proteins. When
carbon dioxide binds to amine groups, it forms carbamino com-
pounds. Because hemoglobin is the main protein that combines
with carbon dioxide, most carbamino molecules are formed and
transported in the red blood cells. The compound formed when
carbon dioxide combines with hemoglobin has a tongue-twisting
name - carbaminohemoglobin. The following chemical equa-
tion, amplified in Figure 24-22, shows how carbon dioxide com-
bines with amine (NH
) in hemoglobin's polypeptide chains to
produce carbaminohemoglobin (HbNCOOH-) and H+:
/ /
Hb- N + CO
E ) Hb-N + H+
\ \
Notice that the arrows in this equilibrium point in both direc-
tions. This means that under any given conditions, some carbon di-
oxide will be associated with hemoglobin and some will not-the
reaction is moving in both directions at the same time. The rate of
both forward and reverse reactions-carbon dioxide association with
and dissociation from hemoglobin- can shift with changes in car-
bon dioxide concentration. This principle is sometimes called the
rate law of chemistry. The addition of more carbon dioxide to blood,
therefore, will increase the rate of formation of carbaminohemoglo-
bin. Another way to state this principle is to say that the association
of carbon dioxide with hemoglobin is accelerated by an increase in
Peaz and is slowed by a decrease in Peaz. Figure 24-23, which shows
the carbon dioxide dissociation curve, illustrates that the COrcarry-
ing capacity of blood increases as plasma Peaz increases.
More than two thirds of the COz carried by blood is carried in the
form of bicarbonate ions (HCO"3) When COz dissolves in water
(as in blood plasma), some of the COz molecules associate with
HzO to form carbonic acid (H
). Once formed, some of the
molecules dissociate to form H+ and bicarbonate (HC03")
ions. This process, which is catalyzed by an enzyme present in red
blood cells called carbonic anhydrase (CA), is summarized by the
following chemical equation:
COz + HzO ~ H
~ H+ + HCO"3
Figure 24-24 amplifies this equation. According to the rate law
of chemistry we stated earlier, as more COz is added to the plas-
ma, more will be converted to carbonic acid. Because the car-
bonic anhydrase enzyme in the blood is facilitating the conversion
of carbon dioxide and water to carbonic acid, this reaction occurs
very rapidly as COz is added to the plasma. Carbonic acid concen-
tration increases as a result, "pulling" the system toward the bicar-
bonate side, thus increasing the rate of bicarbonate formation.
The end result is that COz molecules diffusing into plasma will
continually be removed from the solution and converted into bi-
carbonate. This allows room for even more COz to dissolve in the
plasma - thus increasing the COz-carrying capacity of the blood.
Figure 24-25, which summarizes all three forms of COz trans-
port, shows that once bicarbonate ions are formed, they diffuse
down their concentration gradient into the plasma. The exit of this
negative ion (HC0
-) from the red blood cell is balanced by the
inward transport of another negative ion, chloride (CI-). This COUI1-
tertransport of negative ions is often called the chloride shift.
°0 U
"' ....
0 ...
~ 8  
as '"
30 35 40 45 50 55
Plasma PC02 (mm Hg)
I FIG U R E 2 4 - 2 3 I Carbon dioxide dissociation
curve. The relationship between Pco
and total CO
content (ml CO
per 100 ml blood) is graphed as a nearly straight line. Notice that the
-carrying capacity of blood increases as the plasma PC02 increases.
_._ .... H+ +
Hydrogen Bicarbonate
ion ion
I FIG U R E 2 4 - 2 4 I Formation of bicarbonate. Carbon
dioxide can react with water to form carbonic acid, a reaction catalyzed
by the red blood cell (RBC) enzyme carbonic anhydrase. Carbonic acid
then dissociates to form bicarbonate and a hydrogen ion. The high-
lighted areas show where the original carbon dioxide molecule is in
each part of the equation. The double arrows show that each reaction is
reversible, the actual rate in each direction governed by the relative
concentration of each molecule.
According to the rate law of chemistry described earlier, when
is removed from the plasma, the entire system, illustrated in
Figures 24-24 and 24-25, shifts in the opposite direction. Thus the
reaction that converts carbonic acid to free CO
becomes domi-
nant. The declining concentration of carbonic acid then forces a
shift in favor of the conversion of bicarbonate to carbonic acid. In
short, CO
is unloaded from bicarbonate.
The relative proportions of the three different forms of carbon
dioxide carried in the blood are summarized in Figure 24-26.
Chapter 24 Physiology of the Respiratory System 821
Arterial Venous
blood blood
  ~ 2 0 %
Q\ 7<l%
, 10%
D Carbaminohemoglobin
I FIG U R E 2 4 - 2 6 I Proportions of carbon dioxide trans-
ported in the blood. This graph shows that systemic venous blood
carries more carbon dioxide than systemic arterial blood does. The
difference, shown in the upper left, represents the total amount of
carbon dioxide loaded into the blood in the systemic tissues. Or it
could be viewed as the total amount of carbon dioxide unloaded from
the blood in the lungs. Note that most of the carbon dioxide is car-
ried in the form of HC03" (bicarbonate) .
Body cell
----------- CO
10% transported
as CO
in plasma
20% transported
as HbC0
70% transported
as HC03" (bicarbonate)
dissolved in plasma
I FIG U R E 2 4 - 2 5 I Carbon dioxide transport in the blood. As the illustration shows, CO
dissolves in the plasma. Some of the dissolved
enters red blood cells (RBCs) and combines with hemoglobin (Hb) to form carbaminohemoglobin (HbC0
) . Some of the CO
entering RBCs combines
with H
0 to form carbonic acid (H
), a process facilitated by the enzyme carbonic anhydrase (CA) present inside each cell. Carbonic acid then dissoci-
ates to form H+ and bicarbonate (HC03"). The H+ combines with Hb, whereas the HC03" diffuses down its concentration gradient into the plasma. As HC03"
leaves each RBC, CI- enters and prevents an imbalance in charge-a phenomenon called the chloride shift, which is discussed in Chapter 30.
822 UNIT 5 Respiration, Nutrition, and Excretion
You may have noticed by now that when carbon dioxide enters the
blood, most of it is converted to carbaminohemoglobin and hy-
drogen ions (H+) or to bicarbonate and hydrogen ions. In other
words, have you noticed that increasing the carbon dioxide con-
tent of the blood also increases its H+ concentration? Thus an in-
crease in carbon dioxide in the blood causes an increase in the
acidity, or a drop in pH, in the blood. This is a very important
principle in understanding how and why respiration is regulated
in the manner that it is. We will discuss these matters later in this
chapter. This principle is also important to the understanding of
acid-base balance in the body-a topic discussed thoroughly in
Chapter 30.
11. Most oxygen carried by the blood is transported in what form?
12. Most carbon dioxide carried by the blood is transported in what
13. What is oxyhemoglobin? What is carbaminohemoglobin?
14. How does carbon dioxide affect the pH of blood?
Exchange of gases in tissues takes place between arterial blood
flowing through tissue capillaries and cells (Figure 24-27). It oc-
curs because of the principle already noted - that gases move down
a gas pressure gradient. More specifically, in the tissue capillaries,
oxygen diffuses out of arterial blood because the oxygen pressure
gradient favors its outward diffusion (see Figure 24-27). Arterial
blood P0
is about 100 mm Hg, interstitial fluid P0
is considerably
lower, and intracellular fluid P0
is still lower. Although intersti-
tial fluid and intracellular fluid P0
are not definitely estab-
lished, they are thought to vary considerably-perhaps from
around 60 mm Hg down to about 1 mm Hg.
As activity increases in any tissue, its cells necessarily
use oxygen more rapidly. This decreases intracellular and
interstitial P0
, which in turn tends to increase the oxygen
pressure gradient between blood and tissues and to accelerate
oxygen diffusion out of the tissue capillaries. In this way, the
rate of oxygen use by cells automatically tends to regulate the
rate of oxygen delivery to cells. As dissolved oxygen diffuses out
of arterial blood, blood P0
decreases, and this accelerates oxy-
hemoglobin dissociation to release more oxygen into the
plasma for diffusion out to cells, as indicated in Figure
24-28 and the following equation:
Decreasing P0
)Hb + O
Because of oxygen release to tissues from tissue capillary
blood, P0
, oxygen saturation, and total oxygen content are less in
venous blood than in arterial blood, as shown in Table 24-4. Car-
bon dioxide exchange between tissues and blood takes place in
the opposite direction from oxygen exchange. Catabolism pro-
duces large amounts of CO
inside cells. Therefore, intracellular
and interstitial Pe02 are higher than arterial blood Pe02' This
means that the CO
pressure gradient causes diffusion of CO
from the tissues into the blood flowing along through tissue capil-
laries (see Figure 24-27). Consequently, the Pe02 of blood in-
creases in tissue capillaries from its arterial level of about 40 mm
Hg to its venous level of about 46 mm Hg.
TAB L E 2 4 - 4 I Blood Oxygen
- -- ----
40mm Hg 100 mm Hg
Oxygen 75% 97%
Oxygen 15 ml O
per 100 ml 20 ml O
per 100 ml blood'
content blood
'Oxygen use by tissues = difference between the oxygen content of arterial and
venous blood (20 - 15) = 5 ml O
per 100 ml blood circulated per minute.
Systemic tissue
Systemic tissue
Systemic tissue
Systemic tissue
Systemic tissue
Systemic tissue
A Capillary B Capillary
I FIG U R E 2 4 - 2 7 I Systemic gas
exchange. A, As blood enters a systemic capillary, O
down its pressure gradient (out of the blood). O
continues diffus-
ing out of the blood until equilibration has occurred (or until the
blood leaves the capillary). B, As blood enters a systemic capillary,
diffuses dbwn its pressure gradient (into the blood) . As with
, CO
continues diffusing as long as there is a pressure gradient.
Chapter 24 Physiology of the Respiratory System 823
At rest During exercise
Jl 70
0 10 20
30 40 50 60 70 80 90 100110
t Plasma P02 (mm Hg) t
(Exercising) (Resting) Pulmonary
I FIG U R E 24 - 28 I Oxygen unloading at rest and during exercise. At rest, fully saturated Hb unloads almost 25% of its O
when it reaches the low-Po
(40 mm Hg) environment in systemic tissues (left inset). During exercise, the tissue P0
is even lower (20 mm
Hg)-thus causing fully saturated Hb to unload about 70% of its O
load (right inset). As you can see in the graph, a slight drop in tissue Po
from point B to point C-causes a large increase in O
This increasing Peoz and decreasing Paz together produce two
effects-they favor oxygen dissociation from oxyhemoglobin and
carbon dioxide association with hemoglobin to form carbaminohe-
moglobin. This reciprocal interrelationship between oxygen and
carbon dioxide transport mechanisms is contrasted in Figure 24-29.
Note that increased Peoz decreases the affinity between hemoglo-
bin and oxygen - this is called a "right shift." A right shift of the oxy-
gen-hemoglobin dissociation curve resulting from increased Peoz is
also known as the Bohr effect, named for Christian Bohr, who
along with other scientists, discovered this phenomenon in 1904. A

10 20 30 40 50 60 70 80 90 100 110120 130 140 !
Plasma (mm Hg)
            € __ #l¥$B__   ----.-
drop in plasma pH, which normally accompanies an increase in
blood Peoz, also causes a right shift. The Haldane effect refers to
the increased COz loading caused by a decrease in Paz. This phe-
nomenon is named for its discoverer John Scott Haldane.
If you are having trouble visualizing the essential process of
gas exchange, check out the simplified Summary of Gas Exchange
online at A&P Connect.

Plasma PC02 (mm Hg)
I FIG U R E 2 4 - 2 9 I Interaction of P0
and Pco
on gas transport by the blood. A, The increased plasma PC02 in systemic tissues de-
creases the affinity between Hb and O
, shown as a right shift of the oxygen-hemoglobin dissociation curve. This phenomenon is known as the Bohr
effect. A right shift can also be caused by a decrease in plasma pH. B, At the same time, the decreased plasma P0
commonly observed in systemic
tissues increases the CO
content of the blood, shown as a left shift of the CO
dissociation curve. This phenomenon is known as the Haldane effect.
824 UNIT 5 Respiration, Nutrition, and Excretion
15. What factors can cause the attraction between hemoglobin and
oxygen to decrease?
16. What factors can cause an increase in the amount of carbon
dioxide loaded into the systemic blood?
Respiratory Control Centers
Various mechanisms operate to maintain relative constancy of the
blood P0
and PC02' This homeostasis of blood gases is maintained
primarily by means of changes in ventilation-the rate and depth of
breathing. The main integrators that control the nerves that affect the
inspiratory and expiratory muscles are located within the brainstem
and are together simply called the respiratory centers (Figure 24-30).
The basic rhythm of the respiratory cycle of inspiration and expi-
ration seems to be generated by the medullary rhythmicity area.
Limbic system
(emotional responses)
Apneustic center
Central chemoreceptors
rhythmicity -CDRG
VRG I ____
Medulla I -
This area of the medulla consists of two regions of interconnected
control centers: the dorsal respiratory group (DRG) and the ventral
respiratory group (VRG) . The VRG seems to be the basic rhythm
generator in animal models and thus may also serve this function in
human beings. Normal, quiet breathing rhythm is generated by al-
ternating patterns of stimulation and inhibition of motor neurons
that signal the muscles of the diaphragm. The DRG integrates in-
formation from chemoreceptors for PC02 and signals the VRG to
alter the breathing rhythm to restore homeostasis.
A current hypothesis suggests that the basic breathing
rhythm can be altered by different inputs to the medullary
rhythmicity area. For example, input from the apneustic cen-
ter in the pons regulates the length and depth of inspiration.
Damage to the nerves from the apneustic center results in
breathing characterized by abnormally long, deep inspirations,
which is sometimes called "apneustic breathing." The pontine
respiratory group (PRG; formerly called the pneumotaxic cen-
ter), also in the pons, normally regulates both the apneustic
center and the medullary rhythmicity area. Thus a network of
f::===-. Carotid chemoreceptors
and baroreceptors
Aortic chemoreceptors
and baroreceptors
Stretch receptors
in lungs and
I FIG 0 R E 24- 30 1 Regulation of breathing. The dorsal respiratory group (DRG) and ventral respiratory group (VRG) of the medulla
represent the medullary rhythmicity area. The pontine respiratory group (PRG, or pneumotaxic center) and apneustic center of the pons influ-
ence the basic respiratory rhythm by means of neural input to the medullary rhythmicity area. The brainstem also receives input from other parts
of the body; information from chemoreceptors, baroreceptors, and stretch receptors can alter the basic breathing pattern, as can emotional (lim-
bic) and sensory input. Despite these subconscious reflexes, the cerebral cortex can override the "automatic" control of breathing to some ex-
tent to do such activities as sing or blow up a balloon. Green arrows show flow of information to the respiratory control centers. The purple ar-
row shows the flow of information from the control centers to the respiratory muscles that drive breathing.
(Q) IBox 24-81 FYI
Unusual Breathing Reflexes
The cough reflex is stimulated by foreign matter in the trachea or bron-
chi. The epiglottis and glottis reflexively close, and contraction of the
expiratory muscles causes air pressure in the lungs to increase. The
epiglottis and glottis then open suddenly, resulting in an upward burst
of air that removes the offending contaminants-a cough.
The sneeze reflex is similar to the cough reflex, except that it is
stimulated by contaminants in the nasal cavity. A burst of air is directed
through the nose and mouth, forcing the contaminants (and mucus) out
of the respiratory tract. Droplets from a sneeze can travel more than 161
km/hr (100 miles/hr) and travel 3 m (12 ft). Research suggests that
many pathogenic microbes produce symptoms that trigger sneezing in
order to spread themselves to other people. Scientists call this altered
host behavior and identify it as a mechanism of microbes to effiCiently
spread themselves to additional human hosts.
The term hiccup is used to describe an involuntary, spasmodic
contraction of the diaphragm. When such a contraction occurs,
generally at the beginning of an inspiration, the glottis suddenly
closes, producing the characteristic sound. Hiccups lasting for
extended periods can be disabling. They may be produced by
irritation of the phrenic nerve or the sensory nerves in the
stomach or by direct injury or pressure on certain areas of the
brain. Fortunately, most cases of hiccups last only a few minutes
and are harmless.
A yawn is slow, deep inspiration through an unusually widened
mouth. Yawns were once thought to be reflexes that increase
ventilation when blood oxygen content is low, but newer evidence
suggests that this is unlikely. A current theory states that we yawn for
the same reason we occasionally stretch-to prepare our muscles and
our circulatory system for action. Recent alternate hypotheses suggest
that yawning cools the brain or otherwise regulates body tempera-
ture-or that yawning is triggered by neurotransmitters related to
mood. The variety of hypotheses show one thing for certain: we do not
currently understand the physiology of yawning!
interconnected centers in the brainstem regulates the rhythm
of breathing. Box 24-8 discusses some unusual breathing re-
flexes such as coughing and sneezing.
Factors That Influence Breathing
Feedback information to the medullary rhythmicity area comes
from sensors throughout the nervous system, as well as from other
control centers. For example, changes in the Peoz, Paz, and pH of
systemic arterial blood all influence the medullary rhythmicity
Chapter 24 Physiology of the Respiratory System 825
A protective physiological response called the diving reflex is
responsible for the astonishing recovery of apparent drowning
victimS-including some who may have been submerged for more
than 40 minutes! Survivors are most often preadolescent children
who have been immersed in water below 20°C (68°F). Apparently,
the colder the water, the better the chance of survival. Victims
initially appear dead when pulled from the water. Breathing has
stopped; they have fixed, dilated pupils; they are cyanotic; and their
pulse has stopped.
Studies have shown that when the head and face are immersed
in ice-cold water, there is immediate shunting of blood to the core
body areas with peripheral vasoconstriction and slowing of the
heart (bradycardia). Metabolism is slowed, and tissue require-
ments for oxygen and nutrients decrease. The diving reflex is a
protective response of the body to cold water immersion and is a
function of such physiological and environmental parameters as
water temperature, age, lung volume, and posture.
area. The Peoz acts on chemoreceptors located in the medulla.
Chemoreceptors, in this case, are cells that are sensitive to chang-
es in the COz and hydrogen ion concentration (pH) of arterial
blood. The normal range for arterial Peoz is about 38 to 40 mm
Hg. When it increases even slightly above this value, it has a stim-
ulating effect, mainly on central chemoreceptors (present through-
out the brainstem).
Large increases in arterial Peoz also stimulate peripheral che-
moreceptors in the carotid bodies and aorta. Stimulation of che-
moreceptors by increased arterial Peoz results in faster breathing,
826 UNIT 5 Respiration, Nutrition, and Excretion
with a greater volume of air moving in and out of the
lungs per minute. Figure 24-31 summarizes this
negative feedback response. Decreased arterial
Peoz produces opposite effects - it inhibits
central and peripheral chemoreceptors,
which leads to inhibition of the medullary
rhythmicity area and slower respirations.
In fact, breathing stops entirely for a few
moments (apnea) when arterial Peoz
drops moderately- to about 35 mm Hg,
for example.
.. -"

contracts and
rate increases
via nerves to
thoracic muscles and diaphragm
Recall that increases in the COz content of
plasma are accompanied by a proportional
decrease in plasma pH. A decrease in arte-
rial blood pH (increase in acid), within
certain limits, has a stimulating effect
Disturbance on chemoreceptors located in the ca-
rotid and aortic bodies. Central che-
moreceptors are more sensitive to
changes in pH than are peripheral
chemoreceptors. This increased
sensitivity results from the fact that
Variable "" Detected by
Feed information
via nervous
pathways back to
in brain
I FIG U R E 24- 3 1 I Negative feedback control of respiration. This diagram summarizes the feedback loop that operates to increase the
respiratory rate in response to high plasma PC02. Increased cellular respiration during exercise causes a rise in plasma Pc02-which is detected by cen-
tral chemoreceptors in the brain and perhaps peripheral chemoreceptors in the carotid sinus and aorta. Feedback information is relayed to integrators in
the brainstem that respond to the increase in PC02 above the set point value by sending nervous correction signals to the respiratory muscles, which act
as effectors. The effector muscles increase their alternate contraction and relaxation, thus increasing the rate of respiration. As the respiration rate in-
creases, the rate of CO
loss from the body increases and PC02 drops accordingly. This brings the plasma PC02 back to its set point value.
cerebrospinal fluid (CSF) and interstitial fluid (IF) of the brain is
protected by the BBB (blood-brain barrier) from the buffers pres-
ent in the blood. Thus, when blood Peo2 increases in the blood,
it is partially buffered in the blood-but the CO
is not buffered
in the brain's CSF and IF. The brain then senses unbuffered
changes in pH (Figure 24-32).
The role of arterial blood Paz in controlling respirations is not
entirely clear. Presumably, it has little influence as long as it stays
above a certain level. But neurons of the respiratory centers, like
all body cells, require adequate amounts of oxygen to function
optimally. Consequently, if they become hypoxic, they become
depressed and send fewer impulses to respiratory muscles. Respi-
rations then decrease or fail entirely. This principle has important
clinical significance. For example, the respiratory centers cannot
respond to stimulation by an increasing blood CO
if, at the same
time, blood P0
falls below a critical level-a fact that may be-
come life or death important during anesthesia.
However, a decrease in arterial blood P0
below 70 mm Hg,
but not so low as the critical level, stimulates chemoreceptors in
the carotid and aortic bodies and causes reflex stimulation of the
inspiratory neurons of the medullary rhythmicity area. This con-
stitutes an emergency respiratory control mechanism. It does not
~ 1  
c 5
o 3pendence of entilation on CSF pH
7.20 7.25
7.30 7.35
I FIG U R E 2 4 - 3 2 I Regulatory effect of pH of cerebrospi-
nal fluid. As PC02 of arterial blood increases, the pH of the cerebrospinal
fluid (CSF) decreases, as does the brainstem's interstitial fluid (IF) . As the
graph shows, the lower the pH goes, the higher the ventilation rate rises.
Higher ventilation results in increased rate of CO
loss from the body,
eventually returning the body to a homeostatic balance.
Chapter 24 Physiology of the Respiratory System 827
help regulate respirations under usual conditions when arterial
blood P0
remains considerably higher than 70 mm Hg, which is
the level necessary to stimulate the chemoreceptors.
Arterial blood pressure helps control breathing through the
respiratory pressoreflex mechanism. A sudden rise in arterial pres-
sure, by acting on aortic and carotid baroreceptors, results in re-
flex slowing of respirations. A sudden drop in arterial pressure
brings about a reflex increase in the rate and depth of respirations.
The pressoreflex mechanism is probably not of great importance
in the control of respirations. It is, however, of major importance
in the control of circulation.
The Hering-Breuer reflexes also help control respirations,
particularly their depth and rhythmicity when the tidal volume
is high. It is believed they regulate the depth of respirations
(extent of lung expansion)-and therefore the volume of tidal
air-in the following way. Presumably, when a large tidal vol-
ume of air has been inspired, the lungs are expanded enough
to stimulate stretch receptors located within them. The stretch
receptors then send inhibitory impulses to the inspiratory neu-
ron, relaxation of inspiratory muscles occurs, and expiration
follows the Hering-Breuer expiratory reflex. Then, when a large
tidal volume of air has been expired, the lungs are sufficiently
deflated to inhibit the lung stretch receptors and allow inspira-
tion to start again-the Hering-Breuer inspiratory reflex. Re-
cent evidence suggests that these reflexes do not play a
significant role in resting (low tidal volume) breathing, except
perhaps in newborns.
The cerebral cortex also influences breathing. Impulses to
the respiratory center from the motor area of the cerebrum
may either increase or decrease the rate and strength of respira-
tions. In other words, an individual may voluntarily speed up
or slow down the breathing rate. This voluntary control of res-
pirations, however, has certain limitations. For example, one
may stop breathing and do so for a few minutes, but holding
the breath results in an increase in the CO
content of the
blood because it is not being removed by respirations. CO
is a
powerful respiratory stimulant. So when arterial blood Peo2 in-
creases to a certain level, it stimulates the inspiratory neuron
(directly and reflexively) to send motor impulses to the respira-
tory muscles, and breathing is resumed, even though the indi-
vidual may still will contrarily.
Miscellaneous factors may also influence breathing. Among
these are blood temperature and sensory impulses from skin
thermal receptors and from superficial or deep pain receptors:
Sudden painful stimulation produces a reflex apnea, but contin-
ued painful stimuli cause faster and deeper respirations.
Sudden cold stimuli applied to the skin cause reflex apnea.
Stimulation of the pharynx or larynx by irritating chemicals or
by touch causes a temporary apnea. This is the choking re-
flex, a valuable protective device. It operates, for example, to
prevent aspiration of food or liquids during swallowing.
828 UNIT 5 Respi rati on, Nutrition, and Excretion
The major factors that infl uence breathi ng are summarized
in Figure 24-30. Some factors that affect breathing during ex-
ercise are mentioned in Box 24-9.
Ventilation and Perfusion
Alveolar venti lation, as we already know, is airflow to the al-
veoli (see Figure 24-1 ). Alveolar perfusion is blood flow to the
alveoli (see Figure 24-1 8). Matchi ng ventilation and perfu-
sion is import ant for efficient gas exchange in the lungs. If a
poorl y ventilated alveolus is well perfused, blood flow is being
"wasted" on an ineffi cient alveolus. It is more effici ent to de-
tour some of the bl ood fl ow away from the poorl y ventil ated
alveolus and toward a well-ventilated alveolus.
Figure 24-33 shows that perfusion can be matched- wi th-
in very li mited boundari es - to the ventil ation status of indi-
vidual groups of alveoli . As you have probably already
deduced, thi s is accomplished through vasoconstri cti on (nar-
rowing) of certain pulmonary arterioles to reduce perfusion
to poorl y ventilated alveoli . Such ventil ation-perfusion match-
ing in various regions of each lung can increase the overall
effi ciency of gas exchange.
17. Where are the chief regulatory centers of the respiratory func-
tion located?
18. Name several factors that can influence the breathing rate of an
individual; tell whether each triggers an increase or a decrease
in breathing rate.
@ 1 Box 24-91 SPORTS and FITNESS
Control of Respirations During Exercise
Respirations increase abruptly at the beginning of
exercise and decrease even more markedly as it ends.
This much is known. The mechanism that accomplishes
this increased ventilation rate, however, is not known. It is
not identical to the one that produces moderate increases
in breathing. Numerous studies have shown that arterial
blood Pc0
, P0
, and pH do not change enough during
exercise to produce the degree of hyperpnea (faster,
deeper respirations) observed. Presumably, many
chemical and nervous factors and temperature changes
operate as a complex, but still unknown, mechanism for
regulating respirations during exercise.
L / ~ ~ ~  
- Resting
.5 120
• Normal
~ 100
i 80J
40 CD
20 30 40 50 60 80 100
Arterial PC0
(mm Hg)
Normal effects of maximum exercise in an at hl ete. This
graph shows that the breathing rate (vertical axis) is much
higher in an athlete exercising maximally than would be
expected for any given blood carbon dioxide pressure (Pc0
(horizontal axis) . As you can see at the normal points of a Pc0
of 40 mm Hg, the exercising athlete's breathing (ventilation)
rate is 120 L1min. However, at rest the athlete's breathing rate
is only about 5 or 6 L1min at the same Pc02-thus showing
that PC02 is not the major factor causing an increased rate of
breathing during exercise.
Each alveolus is well
ventilated with air and
well perfused with blood,
an efficient combination.
Ventilation to the left
alveolus becomes
obstructed, but blood
perfusion is unchanged- I·
an inefficient
arrangement because
blood going to the poorly
ventilated alveolus is not
being fully oxygenated.
Vasoconstriction of the
pulmonary arteriole in
the left (poorly ventilated)
alveolus reduces blood
efficiently matching the
perfusion to the
I FIG U R E 2 4 - 3 3 I Ventilation and perfusion of the
alveoli. Here, two alveoli represent typical alveoli in the lungs.
Chapter 24 Physiology of the Respiratory System 829
(i) I the BIG picture
Respiratory Physiology and the Whole Body
The homeostatic balance of the entire body, and thus the survival of each
and every cell, depends on the proper functioning of the respiratory
system. Because the mitochondria in each cell require oxygen for their
energy conversions, and because each cell produces toxic carbon
dioxide as a waste product of the very same energy conversions, the
internal environment must continually acquire new oxygen and discard
carbon dioxide. If each cell were immediately adjacent to the external
environment-that is, atmospheric air-this would require no special
system. However, because almost every one of the 100 trillion cells that
make up the body are far removed from the outside air, another method
of satisfying this condition must be employed-this is where the respira-
tory system comes in. By the process of ventilation, fresh external air
continually flows less than a hair's breadth away from the circulating
fluid of the body-the blood. By means of diffusion, oxygen enters the
internal environment and carbon dioxide leaves. The efficiency of this
process is enhanced by the presence of "oxygen sponges," called
hemoglobin molecules, which immediately take oxygen molecules out of
solution in the plasma so that more oxygen can rapidly diffuse into the
blood. The blood, the circulating fluid tissue of the cardiovascular
system, carries the blood gases throughout the body-picking up gases
where there is an excess and unloading them where there is a deficiency.
In this manner, each cell of the body is continually bathed in a fluid
environment that offers a constant supply of oxygen and an efficient
system for removing carbon dioxide.
Specific mechanisms involved in respiratory function show the
interdependence between body systems observed throughout our study of
the human body. For example, without blood and the maintenance of
blood flow by the cardiovascular system, blood gases could not be
transported between the gas exchange tissues of the lungs and the various
systemic tissues of the body. Without regulation by the nervous system,
ventilation could not be adjusted to compensate for changes in the oxygen
or carbon dioxide content of the internal environment. Without the skeletal
muscles of the thorax, the airways could not maintain the flow of fresh air
that is so vital to respiratory function. The skeleton itself provides a firm
outer housing for the lungs and has an arrangement of bones that
facilitates the expansion and recoil of the thorax, which is needed to
accomplish inspiration and expiration. Without the immune system, patho-
gens from the external environment could easily colonize the respiratory
tract and possibly cause a fatal infection.
Even more subtle interactions between the respiratory system and
other body systems can be found. For example, the language
function of the nervous system is limited without the speaking ability
provided by the larynx and other structures of the respiratory tract.
The homeostasis of pH, which is regulated by a variety of systems, is
influenced by the respiratory system's ability to adjust the body's
carbon dioxide levels (and thus the levels of carbonic acid).
830 UNIT 5 Respiration, Nutrition, and Excretion
Mechanisms of Disease
Many things can interfere with the functions of gas exchange and
ventilation and cause respiratory failure. A few of the more impor-
tant disorders are briefly described here.
Restrictive Pulmonary Disorders
Restrictive pulmonary disorders involve restriction of the alveoli, or
reduced compliance, leading to decreased lung inflation. The hall-
mark of these disorders, regardless of their cause, is decreased lung
volumes and capacities such as inspiratory reserve volume and vital
capacity. Factors that restrict breathing can originate either within
the lung or outside of it. Causes of restrictive lung disorders include
alveolar fibrosis (scarring) secondary to occupational exposure to
asbestos, toxic fumes, coal dust, or other contaminants; immuno-
logical diseases, as in rheumatoid lung; obesity; and metabolic dis-
orders such as uremia. Restriction of breathing can also be caused
by pain that accompanies pleurisy (inflammation of the pleurae) or
mechanical injuries (such as a fractured or bruised rib). Patients
with restrictive lung disease classically experience dyspnea (labored
breathing) and are not able to tolerate increased activity, which re-
duces their ability to work or perform normal daily activities. Ther-
apy involves eliminating the cause of the restriction, ensuring
adequate gas exchange, and improving exercise tolerance.
Obstructive Pulmonary Disorders
A variety of conditions may cause obstruction of the airways. Ex-
posure to cigarette smoke and other common air pollutants can
trigger a reflexive constriction of bronchial airways. Obstructive
disorders may obstruct inspiration and expiration, whereas restric-
tive disorders mainly restrict inspiration.
Chronic Obstructive Pulmonary Disease
Chronic obstructive pulmonary disease (CaPO) is a broad term
used to describe conditions of progressive irreversible obstruction
of expiratory airflow. People with capo have chronic difficulties
with breathing, mainly emptying their lungs, and have visibly hy-
perinflated chests. Figures 24-12 and 24-13 (p. 813) show the ef-
fects of capo compared to normal breathing patterns. Those
with capo often have a productive cough and intolerance of
activity. The major disorders observed in people with capo are
chronic bronchitis and emphysema.
In North America, tobacco use is the primary cause of capo, but
air pollution, asthma, and respiratory infections also playa role. capo
is a leading cause of death-one that has been increasing over recent
years! Until a few years ago, more men had capo than women. How-
ever, the increase of smoking among women is thought to account for
the fact that the rate for female capo is growing rapidly.
Acute respiratory failure can occur when any of the disorders that
produce capo become intense. Heart failure resulting from the
pulmonary disease and the vascular resistance that develops with
capo is another possible outcome. Although there is no cure for
chronic obstructive respiratory conditions, limiting symptoms can
improve quality oflife. Bronchodilators and corticosteroids have been
used to relieve some of the airway obstruction involved in capo.
Acute obstruction of the airways, as when a piece of food blocks
airflow, requires immediate action to avoid death from suffocation.
A&P CONNECT f - I - - - - - - - - - ~  
Knowledge of the physical principles of ventilation can have lifesav- r:
ing applications in medical emergencies involving acute airway obstruc-
tion caused by foreign material. Learn about how these procedures can
help choking victims in Heimlich Maneuver online at A&P Connect.
In chronic bronchitis, the person produces excessive tracheo-
bronchial secretions that obstruct airflow, and the bronchial mu-
cous glands are enlarged (Figure 24-34, B). Risk factors include
cigarette smoking (accounting for 80% to 90% of the risk of devel-
oping CaPO), a normal decline in pulmonary function as a re-
sult of age, and environmental exposure to dust and chemicals.
With impairment of the alveoli and loss of capillary beds, gas ex-
change is inefficient, which in turn produces hypoxia.
In emphysema, the air spaces distal to the terminal bronchioles are
enlarged as a result of damage to lung connective tissue. As the bron-
chioles collapse and the alveoli enlarge, the alveolar walls rupture and
fuse into large irregular spaces, and gas exchange units are destroyed
(Figure 24-34, D). Although the etiology is not fully understood, this
condition is believed to be caused by proteolytic enzymes that destroy
lung tissue. Hypoxia often develops in emphysema victims.
Asthma is an obstructive lung disorder characterized by recurring
inflammation of mucous membranes and spasms of the smooth
muscles in the walls of the bronchial air passages. The inflamma-
tion (edema and excessive mucus production) and contractions
narrow airways, making breathing difficult (Figure 24-34, C). Initial
onset of asthma can occur in children or adults. Acute episodes of
asthma - so-called "asthma attacks" - can be triggered by stress,
heavy exercise, infection, or exposure to allergens or other irritants
such as dust, vapor, or fumes. Many patients with asthma have a
family history of allergies.
Dyspnea is the major symptom of asthma, but hyperventilation,
headaches, numbness, and nausea can occur. One way to treat
asthma is by using inhaled or systemic bronchodilators that reduce
muscle spasms and thus open the airways. Other types of treahnent
involve the use of antiinflammatory medications including leukot-
riene modifiers to reduce the inflammation associated with asthma.
(Recall from Chapter 21 that leukotrienes are
immune cells to regulate the inflammation response
Edema of respiratory
mucosa and excessive
mucus production
obstruct airways.
Chapter 24 Physiology of the Respiratory System 831
Walls of alveoli are
damaged and cannot be
repaired. Alveoli fuse into
large air spaces.
I FIG U R E 24 - 3 4 I Obstructive pulmonary disorders. Examples of chronic disorders involving pulmonary obstruction.
Cl i HEALTH matters
Sudden Infant Death Syndrome (5105)
Sudden infant death syndrome (SIDS) is the third-ranking cause of
infant death and accounts for about 1 in 9 of the nearly 30,000
infant deaths reported each year in the United States. Sometimes
called "crib-death," SIDS occurs most frequently in babies with no
obvious medical problems who are younger than 3 months of age.
The exact cause of death can seldom be determined even after
extensive testing and autopsy.
SIDS occurs at a higher rate in African-American and Native
American babies than in white, Hispanic, or Asian infants,
although the reasons remain a mystery. Regardless of infant
ethnicity, recent data suggest that certain precautions, such as
having babies sleep only on their backs and keeping cribs free of
pillows or plush toys that might partially cover the nose or mouth,
may reduce the incidence of SIDS. Also important is the elimina-
tion of smoking during pregnancy and protecting infants from
exposure to "second-hand" cigarette smoke after birth .
Although the exact cause of SIDS remains unknown, genetic
defects involving the structure and function of the respiratory
system or unusual physiological responses to common flu or cold
viruses may also playa role in this tragic problem.
832 UNIT 5 Respirati on, Nutrition, and Excretion
LAN G U AGE 0 F SCI E N C E (continued from p. 799)
Dalton's law (OAL-tenz law)
[John Dalton English chemist and physicist]
elastic recoil (eh-LAS-tik REE-koyl)
[elast- drive or propel , -ic relating to]
expiration (eks-pih-RAY-shun)
[ex- out, -pir- breathe, -tion process]
flow-volume loop
Haldane eHect (HAWL-dayne)
[John Scott Haldane Scots physiologist]
heme group (heem)
[heme blood]
hemoglobin (Hb) (hee-moh-GLOH-bin)
[hemo- blood, -glob- ball , -in substance]
Henry's law
[William Henry English chemist]
Hering-Breuer reflex (HER-ing BROO-er REE-tleks)
[Heinrich E. Hering German physiologist, Joseph
Breuer Austral ian physician, re- back or again, -f/fJX
ideal gas
inspiration (in-spih-RAY-shun)
[in- in, -spir- breathe, -ation process]
law of partial pressures
medullary rhythmicity area (MEO-eh-Iair-ee rith-
[medulla- middle, -ary relating to, rhythm- rhythm,
-ic relating to, -ity condition]
oxygen-hemoglobin dissociation curve (AHK-
sih-jen hee-moh-GLOH-bin)
[oxy- sharp, -gen produce, hemo- blood, -glob-
ball, -in substance, dis- reverse, -socia- unite,
-ation process]
oxyhemoglobin (ahk-see-hee-moh-GLOH-bin)
[oxy- sharp (oxygen), -hemo- blood, -glob- ball,
-in substance]
partial pressure (pAR-shal)
physiological dead space (tiz-ee-oh-LOJ-i-kal)
[physio- nature, -Iog- words (study), -ical relating to]
pontine respiratory group (PRG) (pahn-TEEN
RES-pih-rah-toh-ree groop)
[pont- bridge (pons) , -ine relating to]
primary principle of ventilation (ven-tih-LAY-shun)
[prim- first, -ary relating to, princip-foundation,
vent- fan or create wind, -tion process]
adult respiratory distress syndrome (AROS)
[re- again, -spir- breathe, -tory relating to syn-
together, -drome running or (race)course]
apnea (AP-nee-ah)
[a- not, -pne- breathe, -a condition]
apneusis (ap-NYOO-sis)
[a- not, -pneu- breathe, -sis condition]
asthma (AZ-mah)
[asthma panting]
Biot's breathing (bee-OHS)
[Camille Biot French physician]
bronchitis (brong-KYE-tis)
[branch- windpipe, -itis inflammation]
carbon monoxide (CO) (KAR-bon mon-OKS-ide)
[mono- single, -ox- sharp (oxygen) , -ide chemical]
Cheyne-Stokes respiration (chain stokes res-
[John Cheyne Scots physician, William Stokes Irish
chronic obstructive pulmonary disease (COPO)
(KRON-ik ob-STRUK-tiv PUL-moh-nair-ee)
[chron-time, -ic relating to, pulmon-Iung, -ary
relating to]
continuous positive airway pressure (CPAP)
cough reflex
[re- back or again, -f/fJX bend]
diving reflex
[re- back or again, -f/fJX bend]
dyspnea (OISP-nee-ah)
[dys- painful , -pne- breathe, -a condition]
emphysema (em-ti-SEE-mah)
[em- in, -physema blowing or puffing up]
eupnea (YOOP-nee-ah)
[eu- easily, -pne- breathe, -a condition]
expiratory reserve volume (ERV) (eks-PYE-rah-
[ex- out of, -[s]pir- breathe, -tory relating to]
forced expiratory volume (FEY) (eks-PYE-rah-tor-ee)
[ex- out of, -[s]pir- breathe, -tory relating to]
functional residual capacity (FRC)
Heimlich maneuver (HYME-lik mah-NOO-ver)
[Henry J. Heimlich American physician]
hiccup (HIK-up)
[imitation of hiccup sound]
hyaline membrane disease (HMO) (HYE-ah-lin)
[hyal- glass, -ine of or like]
hyperpnea (hye-PERP-nee-ah)
[hyper- excessive, -pne- breathe, -a condition]
hyperventilation (hye-per-ven-ti-LAY-shun)
[hyper- excessive, -vent- fan or create wind, -tion
hypoventilation (hye-poh-ven-ti-LAY-shun)
[hypo- below, -vent-fan or create wind, -tion process]
inspiratory capacity (IC) (in-SPY-rah-tor-ee kah-
[in- in, -spir- breathe, -tory relating to]
inspiratory reserve volume (IRV) (in-SPY-rah-tor-ee)
[in- in, -spir- breathe, -tory relating to]
intratracheal injection (in-trah-TRAY-kee-al in-
[intra- within, -trache- rough duct, -al relating to]
pulmonary ventilation (PUL -moh-nair-ee ven-
tih- LAY-shun)
(pulmon-Iung, -ary relating to, vent- fan or create
wind, -tion process]
rate law
respiratory cycle (RES-pih-rah-tor-ee)
[re- again, -spir- breathe, -tory relating to]
respiratory physiology (RES-pih-rah-tor-ee tiz-
[re- again, -spir- breathe, -tory relating to, physio-
nature, -Iog- words (study), -y process]
solubility (sol-yoo-BI L -i-tee)
[solubili- able to dissolve, -ity state]
surface tension
transpulmonary pressure (trans-PUHL-mohn-air-ee)
[trans- across, pulmon-Iung, -ary relating to]
type II cells
. [I/Roman numeral two]
Young-LaPlace law (law of LaPlace) (yung lah-
[Thomas Young English physician, Pierre Simon de
LaPlace French physicist]
maximum oxygen consumption (V0
[maximum greatest, oxy- sharp, -gen produce, con-
with or in, -sum- take, -tion process]
orthopnea (or-THOP-nee-ah)
[ortho- straight or upright, -pne- breathe,
-a condition]
pneumothorax (noo-moh-THOH-raks)
[pneumo- air or wind, -thorax chest]
residual volume (RV) (ree-ZIO-yoo-al)
respiratory arrest (RES-pih-rah-tor-ee
[re- again, -spir- breathe, -tory relating to]
respiratory distress syndrome (ROS) (RES-pih-
rah- tor-ee di-STRESS SIN-drohm)
[re- again, -spir- breathe, -tory relating to, syn-
together, -drame running or (race)course]
sneeze reflex (sneez REE-tleks)
[re- back or again, -f/fJX bend]
spirogram (SPY-roh-gram)
[spir- breathe, -gram drawing]
spirometer (spih-ROM-eh-ter)
[spir- breathe, -meter measurement]
tidal volume (TV) (TYE-dal)
[tid- time, -al relating to]
total lung capacity (TLC)
total minute volume
vital capacity (VC) (VYE-tal kah-PASS-i-tee)
[vita- life, -al relating to]
[yawn gape]
After having surgery to remove a stomach tumor, Derrick woke
up in the recovery room in extreme pain. It hurt to move; it hurt to
blink; it hurt to take even a little breath, and here was this nurse
demanding that he take a deep breath and cough. Was she crazy?
1. Which of these muscles would not contract when Derrick
complied with his nurse's instructions?
a. Diaphragm
b. Serratus anterior
c. Rectus abdominis
d. External intercostals
2. Which statement best describes the "mechanics" of Derrick's
a. The thoracic cavity decreases in size, lowering the alveolar
pressure, and air flows from high (atmosphere) pressure to
low (alveolar) pressure.
b. The thoracic cavity increases in size, lowering the alveolar
pressure, and air flows from high (atmospheric) pressure to
low (alveolar) pressure.
c. Air flows from high (atmospheric) pressure to low (alveolar)
pressure and expands the thoracic cavity.
d. Air flows from high (intrapleural) pressure to low (alveolar)
pressure and expands the thoracic cavity.
What Derrick didn't realize was that his shallow respirations were
not getting rid of as much carbon dioxide as usual. As a result, the
concentration of CO
in his bloodstream was building to a level that
would negatively affect homeostasis.
3. This increased carbon dioxide will make Derrick's blood
a. More acidic
b. More basic
c. More neutral
d. None of the above
Chapter Summary
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© Chapter Summaries online at
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before your class or before a test.
A. Definition-complex, coordinated processes that help
maintain homeostasis
B. External respiration
1. Pulmonary ventilation (breathing)
2. Pulmonary gas exchange
C. Transport of gases by the blood
Chapter 24 Physiology of the Respiratory System
4. How is carbon dioxide transported in Derrick's blood?
a. Dissolved in the plasma
b. Bound to hemoglobin
c. In the form of bicarbonate
d. All of the above
To solve a case study, you may have to refer to the glossary
or index, other chapters in this textbook, A&P Connect,
and other resources.
D. Internal respiration
1. Systemic tissue gas exchange
2. Cellular respiration
E. Regulation of respiration
A. Respiratory cycle (ventilation; breathing)
1. Inspiration-moves air into the lungs
2. Expiration- moves air out of the lungs
B. Mechanism of pulmonary ventilation
1. The pulmonary ventilation mechanism must establish
two gas pressure gradients (Figures 24-2 and 24-3)
a. One in which the pressure within the alveoli of the lungs
is lower than atmospheric pressure to produce inspiration
834 UNIT 5 Respiration, Nutrition, and Excretion
b. One in which the pressure in the alveoli of the lungs
is higher than atmospheric pressure to produce
2. Pressure gradients are established by changes in the size
of the thoracic cavity that are produced by contraction
and relaxation of muscles (Figures 24-4 and 24-5)
3. Boyle's law-the volume of gas varies inversely with
pressure at a constant temperature
4. Inspiration-contraction of the diaphragm produces
inspiration-as it contracts, it makes the thoracic cavity
larger (Figures 24-6 and 24-7)
a. Expansion of the thorax results in decreased intrapleu-
ral pressure (PIP), leading to decreased alveolar
pressure (P
b. Air moves into the lungs when alveolar pressure (P
drops below atmospheric pressure (PB)
c. Compliance-ability of pulmonary tissues to stretch,
thus making inspiration possible
5. Expiration-a passive process that begins when the
inspiratory muscles are relaxed, which decreases the size
of the thorax (Figures 24-8 and 24-9)
a. Increasing thoracic volume increases the intrapleural
pressure and thus increases alveolar pressure above the
atmospheric pressure
b. Air moves out of the lungs when alveolar pressure
exceeds the atmospheric pressure
c. The pressure between parietal and visceral pleura is
always less than alveolar pressure and less than
atmospheric pressure; the difference between PIP and
PAis called transpulmonary pressure
d. Elastic recoil- tendency of pulmonary tissues to
return to a smaller size after having been stretched;
occurs passively during expiration
C. Pulmonary volumes- normal exchange of oxygen and
carbon dioxide depends on the presence of normal
volumes of air moving in and out and the remaining
volume (Figure 24-11)
1. Spirometer-instrument used to measure the volume of
air (Figure 24-10)
2. Tidal volume (TV)-amount of air exhaled after normal
3. Expiratory reserve volume (ERV) - largest volume of
additional air that can be forcibly exhaled (between 1.0
and 1.2 liters is normal ERV)
4. Inspiratory reserve volume (IRV)-amount of air that can
be forcibly inhaled after normal inspiration (normal IRV
is 3.3 liters)
5. Residual volume-amount of air that cannot be forcibly
exhaled (1.2 liters)
D. Pulmonary capacities-the sum of two or more pulmonary
1. Vital capacity (VC) - the sum ofIRV + TV + ERV
2. Minimal volume-the amount of air remaining after RV
3. A person's vital capacity depends on many factors,
including the size of the thoracic cavity and posture
4. Functional residual capacity (FRC) - the amount of air
at the end of a normal respiration
5. Total lung capacity (TLC)-the sum of all four lung
volumes - the total amount of air a lung can hold
6. Alveolar ventilation- volume of inspired air that reaches
the alveoli
7. Anatomical dead space - air in passageways that do not
participate in gas exchange (Figure 24-6)
8. Physiological dead space- anatomical dead space plus
the volume of any nonfunctioning alveoli (as in pulmo-
nary disease)
9. Alveoli must be properly ventilated for adequate gas
E. Pulmonary airflow - rates of airflow int%ut of the pulmo-
nary airways
l. Total minute volume - volume moved per minute
2. Forced expiratory volume (FEV) or forced vital
capacity (FVC) - volume of air expired per second
during forced expiration (as a percentage ofVC)
(Figure 24-12)
3. Flow-volume loop-graph that shows flow (vertically)
and volume (horizontally), with the top of the loop
representing expiratory flow-volume and the bottom of
the loop representing inspiratory flow-volume relation-
ships (Figure 24-13)
A. Partial pressure of gases-pressure exerted by a gas in a
mixture of gases or a liquid (Figure 24-14)
l. Law of partial pressures (Dalton's law)-the partial
pressure of a gas in a mixture of gases is directly related to
the concentration of that gas in the mixture and to the
total pressure of the mixture
2. Arterial blood P0
and Peo2 equal alveolar P0
and Peo2
B. Exchange of gases in the lungs-takes place between
alveolar air and blood flowing through lung capillaries
(Figures 24-15, 24-16, and 24-17)
1. Four factors determine the amount of oxygen that diffuses
into blood
a. The oxygen pressure gradient between alveolar air and
b. The total functional surface area of the respiratory
c. The respiratory minute volume
d. Alveolar ventilation
2. Structural facts that facilitate oxygen diffusion from the
alveolar air to the blood
a. The walls of the alveoli and capillaries form only a
very thin barrier for gases to cross
b. The alveolar and capillary surfaces are large
c. The blood is distributed through the capillaries in a
thin layer so that each red blood cell comes close to
alveolar air (Figure 24-18)
A. Oxygen and carbon dioxide are transported as solutes and as
parts of molecules of certain chemical compounds
B. Hemoglobin (Hb)
1. Made up of four polypeptide chains (two alpha chains, two
beta chains), each with an iron-containing heme group
2. Carbon dioxide can bind to amino acids in the chains
and oxygen can bind to iron in the heme groups
(Figure 24-19)
C. Transport of oxygen
1. Oxygenated blood contains about 0.3 ml of dissolved O
per 100 ml of blood
2. Hemoglobin increases the oxygen-carrying capacity of
blood (Figure 24-20)
3. Oxygen travels in two forms: as dissolved O
in plasma and
as being associated with hemoglobin (oxyhemoglobin)
a. Increasing blood P0
accelerates hemoglobin associa-
tion with oxygen (Figure 24-21)
b. Oxyhemoglobin carries the majority of the total oxygen
transported by blood
D. Transport of carbon dioxide
1. A small amount of CO
dissolves in plasma and is
transported as a sol ute (10%)
2. Less than one fourth of blood carbon dioxide combines with
NH2 (amine) groups of hemoglobin and other proteins to
form carbaminohemoglobin (20%) (Figure 24-22)
3. Carbon dioxide's association with hemoglobin is acceler-
ated by an increase in blood Peo2 (Figure 24-23)
4. More than two thirds of the carbon dioxide is carried in plasma
as bicarbonate ions (70%) (Figures 24-24, 24-25, and 24-26)
A. Exchange of gases in tissues takes place between arterial blood
flowing through tissue capillaries and cells (Figure 24-27)
1. Oxygen diffuses out of arterial blood because the oxygen
pressure gradient favors its outward diffusion
2. As dissolved oxygen diffuses out of arterial blood, blood P0
creases, which accelerates oxyhemoglobin dissociation to
release more oxygen to plasma for diffusion to cells (Figure 24-
B. Carbon dioxide exchange between tissues and blood takes
place in the opposite direction from oxygen exchange
1. Bohr effect - increased Peo2 decreases the affinity
between oxygen and hemoglobin (Figure 24-29, A)
2. Haldane effect-increased carbon dioxide loading caused
by a decrease in P0
(Figure 24-29, B)
A. Respiratory control centers-the main integrators controlling
the nerves that affect the inspiratory and expiratory muscles
are located in the brainstem (Figure 24-30)
1. Medullary rhythmicity center-generates the basic
rhythm of the respiratory cycle
a. Consists of two interconnected control centers
(1) Dorsal respiratory group (DRG)-integrates
information from chemoreceptors to regulate the
VRG pattern
(2) Ventral respiratory group (VRG)-generates basic
pattern of breathing rhythm
2. The basic breathing rhythm can be altered by different
inputs to the medullary rhythmicity center (Figure 24-30)
Chapter 24 Physiology of the Respiratory System 835
a. Input from the apneustic center in the pons regulates
the medullary rhythmicity area
b. Pontine respiratory group (PRG, or pneumotaxic
center)-in the pons-inhibits the apneustic center
and medullary rhythmicity area to prevent overinfla-
tion of the lungs
B. Factors that influence breathing-sensors from the nervous
system provide feedback to the medullary rhythmicity center
(Figure 24-31)
1. Changes in the Po
, Peo2, and pH of arterial blood
influence the medullary rhythmicity area
a. Peo2 acts on central chemoreceptors throughout the
brainstem-if it increases, the result is faster breath-
ing; if it decreases, the result is slower breathing
b. A decrease in blood pH stimulates peripheral chemo-
receptors in the carotid and aortic bodies and, even
more so, stimulates the central chemoreceptors
(because they are surrounded by unbuffered fluid)
(Figure 24-32)
c. Arterial blood P0
presumably has little influence if it
stays above a certain level
2. Arterial blood pressure controls breathing through the
respiratory pressoreflex mechanism
3. Hering-Breuer reflexes help control respirations by
regulating depth of respirations and the volume of
tidal air
4. Cerebral cortex influences breathing by increasing or
decreasing the rate and strength of respirations
C. Ventilation and perfusion (Figure 24-33)
1. Alveolar ventilation - airflow to the alveoli
2. Alveolar perfusion - blood flow to the alveol i
3. Efficiency of gas exchange can be maintained by
limited ability to match perfusion to ventilation-for
example, vasoconstricting arterioles that supply poorly
ventilated alveoli and allow full blood flow to well-
ventilated alveoli
A. The internal system must continually acquire new oxygen
and rid itself of carbon dioxide because each cell requires
oxygen and produces carbon dioxide as a result of energy
B. Specific mechanisms involved in respiratory function
1. Blood gases need blood and the cardiovascular system to
be transported between gas exchange tissues of the lungs
and various systemic tissues of the body
2. Regulation by the nervous system adjusts ventilation to
compensate for changes in oxygen or carbon dioxide in
the internal environment
3. The skeletal muscles of the thorax aid the airways in
maintaining the flow of fresh air
4. The skeleton houses the lungs, and the arrangement of
bones facilitates the expansion and recoil of the thorax
5. The immune system prevents pathogens from colonizing
the respiratory tract and causing infection
836 UNIT 5 Respiration, Nutrition, and Excretion
Review Questions
,. Write out the answers to these questions after reading the chapter
Aarr and reviewing the Chapter Summary. If you simply think through
the answer without writing it down, you won't retain much of your
new learning.
1. Define respiratory physiology.
2. What is the main inspiratory muscle?
3. Identify the separate volumes that make up the total
lung capacity.
4. Normally, about what percentage of the tidal volume fills
the anatomical dead space?
5. Normally, about what percentage of the tidal volume is
useful air, that is, ventilates the alveoli?
6. One gram of hemoglobin combines with how many
milliliters of oxygen?
7. What factors influence the amount of oxygen that diffuses
into the blood from the alveoli?
8. Identify the major factors that influence breathing.
9. Orthopnea is a symptom of what type of disease?
10. Dyspnea is often associated with what type of breathing?
11 . Define the diving reflex and explain its physiological
12. Describe four other unusual reflexes that indirectly
affect breathing.
13. Describe the changes in respirations during a period of
Critical Thinking Questions
After finishing the Review Questions, write out the answers to
these items to help you apply your new knowledge. Go back to
sections of the chapter that relate to items that you find difficult.
1. The proper functioning of the respiratory system allows what
to occur in the body? What other control system has an
impact on this function?
2. Can you identify the various processes that allow the
respiratory system to accomplish its function?
3. What is pulmonary ventilation? What evidence can you find
to describe whether the lungs are active or passive during
this process?
4. How would you compare and contrast inspiration and
expiration? Include the importance of elastic recoil and
compliance to these processes.
5. How would you summarize the interaction of oxygen and
carbon dioxide on gas transport in the blood? Include the
Bohr and Haldane effects in your explanation.
6. Suppose your blood has a hemoglobin content of 15 gil 00
dl and an oxygen saturation of97%. How many milliliters of
oxygen would 100 ml of your arterial blood contain?
7. Compare and contrast infant and adult respiratory distress
8. After strenuous exercise, inexperienced athletes will quite
often attempt to recover and resume normal breathing by
bending over or sitting down. Using the mechanics of
ventilation, how would you modify the recovery practices of
these athletes?