24_Physiology of the Respiratory System.pdf

bysiol theBes . . .

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

y iratory

LANGUAGE OF SCIENCE

Before reading the chapter, say each of these terms out loud. This will help you avoid stumbling over them as you read.

alveolar ventilation (al-VEE-oh-Iar ven-tiLAY-shun)

[alve- hollow, -ai-little, oar relating to, ventfan 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 POz (ar-TEER-ee-al) [arteri- airpipe (artery), -al relating to, Ppressure, O2 oxygen]

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-nohee-moh-GlOH-bin)

[carb-coal (carbon), -amino-ammonia compound (amino acid), -hemo- blood, -globball, -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]

compliance [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

RESPIRATORY PHYSIOLOGY 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 capillaries and cellular respiration

• Overall regulation of respiration

Figure 24-1 summarizes the essential processes of pulmonary 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 greater detail in Chapter 27.

PULMONARY VENTILATION 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 opposite direction. That is, air moves out of the lungs into the atmosphere. The pulmonary ventilation mechanism, therefore, must somehow establish these two gas pressure gradients-one in which alveolar pressure (PA, pressure within the alveoli of the lungs) is lower than atmospheric pressure (or barometric pressure, PB) to produce inspiration and one in

External respiration

Pulmonary ventilation

Pulmonary

gas { exchange

Transport

I FIGURE 24-1 1 Overview of respiratory physiology. This chapter is organized around the principle that respiratory function includes external respiration (ventilation and pulmonary gas exchange), transport of gases by blood, and internal respiration (systemic tissue gas exchange and cellular respiration). Cellular respiration is discussed 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

Internal respiration

Systemic I tissue gas-t

eXChang~ Cellular respi ration

.r--r--r-- O2 sensor r---r- CO2 sensor

~=---- pH sensor

802 UNIT 5 Respiration, Nutrition, and Excretion

which it is higher than atmospheric pressure to produce expiration . 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 contraction and relaxation of respiratory muscles . An understanding of Boyle 's law is important for understanding the pressure ehanges that occur in the lungs and thorax during the breathing 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 : expansion of the thorax (increase in volume) results in a decreased intrapleural (intrathoracic) pressure. This leads to a decreased intraalveolar pressure that causes air to move from the outside into the lungs.

The mechanics of ventilation are often modeled using a balloon 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 balloon represents the lungs. The space between the balloon and the jar represents the intrapleural space. Expanding the thorax by pulling the diaphragm downward increases thoracic volumethus 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. Temperature 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

s

Mediastinum Diaphragm R+L I

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 pressure (PB) is the air pressure of the atmosphere outside the body's airways. 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 visceral 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 (Po2) 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$$!!\ .. ~

INSPIRAnON

Higher pressure PB

EXPIRA110H

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. PB• Atmospheric [barometric) pressure; PA• alveolar pressure. (See Figure 24-2.)

BOYLE'S LAW: P x V = CONSTANT

A

~ ~ ~ Q ~ Q~ ~ Q ~ ~ QQ~ ~

Q~ ~ ~ ~ ~ ~ ~ Q ~ Q~ ~ ~ ~ ~ Q ~ Q ~ ~Q ~Q ~ ~ Q ~ ~

Total gas mixture C

1 Volume

decreases

Temperature Amount constant constant

~ Q Q ~ Q ~ + Q Q + ~ Q ~

~ Q Q

~ Q

~ QQQ

Temperature and volume constant

~

~

~

~

l Air

A

803

B 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 between 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.

CHARLES' LAW: VoT

B

~

~

~

~

Pressure constant ~ ~

~ ~ ~ ~~

~ ~ ~ ~ ~ ~ ~ ~ ~ ~

Temperature Amount increases constant

I Volume

increases

tIENR'rS LAW: CONCENTRATION OF GAS IN SOLUnON • X aouaurv OF GAS

Gas molecules 0 in gaseous phase

Water in beaker Q Q Q

o Q

Gas molecules in liquid phase

0 (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.


compliant (stretchable). the decrease in PIP causes a similar decrease in the balloon pressure (alveolar pressure, PA) . 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 respiratory cycle are outlined in the following sections and in Table 24-1.

INSPIRATION

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 stemocleidomastoid, pectoralis minor, and serratus anterior muscles can aid in elevation of the sternum and rib cage during forceful inspiration.

As the size of the thorax increases, the intrapleural (intrathoracic) and alveolar pressure decreases (Boyle's law) and inspiration 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 (frequently written -2 mm Hg). During normal quiet inspiration,

PB 760~mm Hg

Contraction of the diaphragm alone, or contraction of both the diaphragm and the external intercostal muscles, produces quiet inspiration. As the diaphragm 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 cohesion between the moist pleura

~

~

_.~JpB

; 760mm Hg

(IF'

, PA

\ ( i I :~pO mm Hg

\ ~ \, I 758mmHg

f--- -+-PIP

756 mm Hg

PA 760 mm Hg .... !-..:.--+--PIP

754 mm Hg ! ' I '.

I .' ~,j PA 761 mm Hg

~; i PIP 756 mm Hg

I'

PB 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. PA, Alveolar pressure; Pa, barometric pressure; PIP, intrapleural pressure .


TAB L E 2 4 - 1 I The Respiratory Cycle

Inspiration

758 760

756 759

754 760

Expiration

754 760

756 761

758 760

Pa

760

760

760

760

760

760

The diaphragm is relaxed, putting the thoracic cavity at low volume. At the beginning of inspiration PIP < PA , keeping alveoli open. Since PA = PB, no air is flowing yet.

The diaphragm contracts, increasing the thoracic volume and reducing Plf' A decrease in PIP causes a decrease in PA• Now PA < PB, and air flows down the pressure gradient (into the lungs).

Eventually, the alveoli fill with air and PA equilibrates with PB• Inward airflow stops. The cycle is now ready to shift to the expiration phase. Note that PIP is still dropping but PA has not yet "caught up" with the drop.

As expiration is about to begin, the diaphragm is contracted maximally. Since PA = PB, there is no airflow.

The diaphragm relaxes, and elastic recoil of the thoracic walls and alveoli increases PIP and PA• Now, PA > PB. Air moves (outward) down the pressure gradient.

The diaphragm eventually relaxes fully, so the decrease in volume stops. PA equilibrates with PB, and airflow ceases. The system is now ready for another inspiration phase.

P'P = Intrapleural pressure (air pressure in the intrapleural space); PA = alveolar pressure (air pressure inside the alveoli); PB = 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-typically a drop of about 1 to 3 mm Hg. The moment that alveolar 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 ventilation, 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 stops.

The ability of the lungs and thorax to stretch, referred to as compliance, is essential to normal respiration. If the compliance

B

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.


Sternocleidomastoid muscles contract _~-"I,----___ ---,

Pectoralis minor muscles contract I ~ ~,

External intercostal

muscles contract \ .. o~

S

Contraction of diaphragm

Relaxation of expiratory

muscles

Contraction of chest-elevating

muscles

I , Increase in vertical diameter of thorax

I , Decrease in intrapleural (intrathoracic) pressure

I ,

10

Expansion of lungs ,

l '{ Increase in anteroposterior and transverse dimensions of thorax

Cohesion of visceral and

parietal pleurae

I

I Compliance of

thorax and lungs

I

contracts P+ A Decrease in alveolar pressure

l 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 becomes 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.

EXPIRATION

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 always 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


Relaxation of inspiratory muscles

Contraction of expiratory muscles

I , I

Decrease in size of thorax

Increase in intrapleural (intrathoracic) pressure

Elastic recoil of lung tissue

Decrease in size of lungs

,...a:.--=:-:-:-----:~\--Internal intercostal

"" / muscles contract

/ I

I I

-1r,

'I-- - ----:---4 - Diaphragm relaxes

Increase in alveolar pressure

Pressure gradient from alveoli to atmosphere

Expiration

1 FIG U R E 24 - 81 Mechanism of expiration. Note that relaxation of the diaphragm plus contraction of chest-depressing muscles (internal intercostals) reduces thoracic volume, which increases pressure in the lungs and thus pushes air outward.

occurs as air flows outward through the respiratory passageways. In forced expiration, contraction of the abdominal and internal intercostal muscles can increase alveolar pressure tremendously-creating a very large air pressure gradient.

The tendency of the thorax and lungs to return to their preinspiration 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 transpulmonary pressure. Intrapleural pressure is always "negative" with respect to alveolar pressure. Transpulmonary pressure must be negative to maintain inflation of the lungs, as stated previously.

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 occur between alveolar air and pulmonary capillary blood.

PULMONARY VOLUMES

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 (PA) than larger alveoli would. Thus air would move from the smaller alveoli into larger alveoli. However, because the surfactant on

Without surfactant

Attractive forces~" ~ create high surface . . _ ,~

tension, pulling molecules together

~ a. • ... ~.

$~~~t:J ...... . ~ . Collapsed

Open

With surfactant ~ Surfactant

Attractive forces at surface disrupted, reducing surface tension

A ,-,...,vl l

the surface of the fluid that lines the smaller alveoli is more concentrated than that on larger alveoli, surface tension is reduced proportionally. 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

J~~ Young-LaPlace

Law

PA= 2T "T _ . r

~ ,. ,. ~ ~

:4 •• ,,"

PA = 1 • Pressure

PA= 2 B gradient

T=1 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 PA 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.

-,-~~,~ .,

Single respira~ory cycle


Inspiration Expi~ation Inspiration Expir:ation Inspir:ation ~,~--~~-----,~,~----~----~

Expi"!tion Insp~ation __ E_X_P __ ir:a .... t_io_n __ __

762-r--~--~--~--~--~--~------~--~--~--~--~--~--r---r---r---r---r---r-~ PA

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- 9 1 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 PA (negative transpulmonary pressure) , which helps keep the alveoli inflated. The lowest line shows the change in air volumes during the respiratory cycle.

SIMPLE SPIROMETER

A

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.


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, normally 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

E a a ~ 12 !e. g-!::. ~ u !l rl CI c .a ! ~

A

B

Resting state (normal breathing)

Inspiratory reserve volume (IRV)

(3000-3300 ml)

Expiratory reserve volume (ERV)

(1000-1200 ml)

Residual volume (RV) (1200 ml)

Time .....

Anatomical dead space

Residual volume

Greater activity (forceful inspiration

plus forceful expiration)

Inspiratory reserve volume

diminishes

~:~~~O~~lume} ?LA Tidal volume Vital .

capacity -"""<'--- Inspiratory

Total lung capacity

reserve volume

I I al ..s E

! ~ g ~ ~ rl j >

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 respirations, 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 volume (RV) and amounts to about 1200 ml (l.2 L). Between breaths, an exchange of oxygen and carbon dioxide occurs between 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 airways, as well as some of your residual volume. A few alveoli collapse 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.

PULMONARY CAPACITIES

A pulmonary "capacity" is the sum of two or more pulmonary "volumes." Notice in Figure 24-11 that vital capacity (VC) is the sum of

IRV +TV + ERV

The vital capacity represents the largest volume of air an individual can move in and out of the lungs. It is determined by measuring 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 capacity 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 decreases 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 expiration. 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 necessary 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

IC = TV + IRV

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

Pneumothorax

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. Air 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 operations. 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,

FRC =ERV + RV

Using the volumes given, the functional residual capacity is 2200 to 2400 ml (2.2 to 2.4 L). The total volume 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 disruption of visceral pleura

S R+L I

'-.\----=rChest wall

t t----I-Pleural space

Mediastinum

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 air exchanges some of its oxygen fo r some of the blood's carbon dioxide.) With every breath we take, part of the entering air necessarily fi lls our air passageways - nose, pharynx, larynx, trachea, and bronchi . T his portion of air does not descend into any alveoli and therefore cannot take part in gas exchange . In this sense, it is "dead air." Appropriately, the larger air

VOLUME DESCRIPTION TYPICAL VALUE CAPACITY FORMULA TYPICAL VALUE

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)


passageways it occupies are said to constitute the anatomical dead space. Figure 24-11, B, relates the volume of the anatomical 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 anatomical dead space as the same number of milliliters as the individual'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 recognized and designated by name (see figure) .

Eupnea is the term used to describe normal quiet breathing. During 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

Eupnea

Hyperventilation

Hypoventilation

Description

Normal breathing

Rapid, deep respirations

Slow, shallow respirations

Examples of breathing patterns and spirograms.

anatomical dead space. The amount of air reaching your alveoli - 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 decreases the amount of oxygen that can enter blood and the amount of carbon dioxide that can leave it. Inadequate air-blood gas exchange, therefore, is the inevitable result of inadequate alveolar ventilation. Stated differently, the alveoli must be adequately ventilated 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 ''''~,.tio",

Cheyne-Stokes respiration

,~~ ~'J'JIi"l!I!"!!'K", 3>Wfrii,,,i!'iM §l!4444MfJ ¥1fl ;;w'4'QWk, ~''''''; 4k4W;L 4F. ~

PULMONARY AIRFLOW

Various applications of spirometry can be used to generate additional 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 maximum 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). FEV2, the total volume expired during the first 2 seconds, is about 94% of the VC. By the end of the third second, FEV3, 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)

6000

5000

4000

-! ~3000 ;:,

~ 2000

1000

3sec-------------.. ; 2 sec • • • . 1 sec_; •

Normal . : FEV : • _ ._ -"'-________ - .. .. - ..-x.- __ • ___ ",""_ :;:_:::_~ ..... =___--T_ ... _I . .

O~------------~r_---r----r_--_+----~~

012 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 person 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.


SPORTS and @ Box 24-5 FITNESS

Maximum Oxygen Consumption

Exercise physiologists use maximum oxygen consumption (V02 max) as a predictor of a person's capacity to do aerobic exercise. An individual's V02 max represents the amount of oxygen taken up by the lungs, transported to the tissues, and used to do work. V02 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 V02 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 represented 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 spirometers. It is no wonder, then, that peak flow measurements are

8,--------------------=~~------------------_,

6

4

Expiratory

2

Airflow (Usec)

2

Inspiratory

4

: •• ------------ FVC -------.,: 6

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 (horizontally) . The bottom of the loop represents inspiratory flow and volume. Notice that a person with COPD (chronic obstructive pulmonary disease) will produce a smaller loop with a "scooped-out" shape at the end of the expiratory curve. FVC, Forced vital capacity.


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 "scoopedout" shape of the expiratory part of the loop. In obstructive disorders, the inspiratory portion of the loop has a normal curve, but is smaller than normal.

_.I'II[",~_",: I ~"'~_

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 during 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?

PULMONARY GAS EXCHANGE

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 exerted by anyone gas in a mixture of gases or in a liquid. According

Nitrogen (N2)

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 atmosphere. 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 POz = 21 % x 760 = 159.6 mm Hg

The symbol used to designate partial pressure is the capital letter P preceding the chemical symbol for the gas. Examples: alveolar air POz is about 100 mm Hg, arterial blood POz is also about 100 mm Hg, and venous blood POz is about 37 mm Hg. The word tension is often used as a synonym for the term partial pressureoxygen tension means the same thing as POz.

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 environment 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 (C02), 0.03% Other gases, 0.97%

Vacuum

A

Total atmospheric pressure 760mm (100%)

PN2 + P02 + 592.8 mm + 159.6 mm + (78%) (21%)

Oxygen (02)

PC02 + 0.2 mm + (0.03%)

Pother

7.4 mm (0.97%)

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 concentrations of nitrogen, oxygen, carbon dioxide, and other gases. B, A mercury barometer. 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

B

Mercury (Hg) column

Air pressure

TABLE 24 - 3 I Oxygen and Carbon Dioxide Pressure Gradients*

SYSTEMIC SYSTEMIC ALVEOLAR ARTERIAL VENOUS

ATMOSPHERE AIR BLOOD BLOOD

P02 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 time blood leaves the pulmonary capillaries as arterial blood, diffusion and approximate equilibration of oxygen and carbon dioxide across the membranes have occurred. Arterial blood Paz and Peoz therefore usually equal or very nearly equal alveolar P02

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 realize 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

External environment

\ I FIG U R E 24- 1 5 1 External-internal barrier. The respiratory membranes of the lung represent an interface or barrier that gases must cross to enter or exit the body's internal environment. The pulmonary airway is merely an extension of the external environment.

Chapter 24 Physiol~gy of the Respiratory System 815

Capillary

l

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 gradient (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 dioxide continues diffusing as long as there is a pressure gradient. P02 and Pco2 remain relatively constant in a continually ventilated alveolus.

environment, these gases must cross the barrier between the external world and the internal world.

Gases move in both directions through the respiratory membrane (see Figure 23-16). Oxygen enters blood from the alveolar air because the Paz of alveolar air is greater than the Paz of incoming 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 deoxygenated 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


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 incoming pulmonary blood (alveolar P02 - blood Po2)

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 diffusion. Anything that decreases alveolar Po2, for instance, tends to decrease the alveolar-blood oxygen pressure gradient and therefore tends to decrease the amount of oxygen entering the blood. An application of this is as follows: Alveolar air P02 decreases as altitude increases, and thus less oxygen enters the blood at high altitudes. At a certain high altitude, alveolar air P02 equals the P02 of blood entering the pulmonary capillaries. How would this affect 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 emphysema the total functional area decreases and is one of the factors 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 volume (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 determines 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

400

~

~ I I -t:;' E .2-

! t 100% i f· o · .. iV t i ii a:

200 II u iV

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 7 1 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 concentration?

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 oxygen 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 (C02) and oxygen (02) 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 (Po2 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 proportional 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 CO2 and O2 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 removed). 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.)


Low PC02

I'hi~k ! I')Els

s (I)

Respiratory membrane

High PC02

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.

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HOW BLOOD TRANSPORTS GASES 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 form a chemical union with some other molecule-such as hemoglobin, a plasma protein, or water. Once gas molecules are bound to another molecule, their plasma concentration decreases and more gas can diffuse into the plasma. In this way, comparatively large volumes of the gases can be transported .

818 UNIT 5 Respiration. Nutrition. and Excretion

Hemoglobin Heme

CHl CH2CH2COOH .... #--

O2

CH2CH2COOH

CH l

0<2

H2=CH CHl

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 (02) can bind to the iron (Fe) of the heme group. or carbon dioxide (C02) can bind to amine groups of the amino acids in the polypeptide chains.

Hemoglobin Before we begin our discussion of transport of gases in the blood, we will pause and briefly review some facts about hemoglobin (Hb) (Figure 24-19). As we outlined in Chapter 17, hemoglobin 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 chainseach 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 solution. Notice also in this figure that carbon dioxide (COz) 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, hemoglobin 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 ofhemoglobin 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-carrying capacity of blood.

Perhaps a more common way of expressing blood oxygen content 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 O2 and CO2 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 O2 does. That means that CO "knocks out" O2 from Hb02 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 P02 can be driven so high that it "knocks off" the CO from the Hb. allowing O2 to form Hb02•

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 transported would be only about 0.3 ml of O2 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 O2 per 100 ml of blood.

decreases oxygen transport and may produce marked cellular hypoxia (inadequate oxygen supply).

To combine with hemoglobin, oxygen must, of course, diffuse from plasma into the red blood cells where millions of

100

90

80

~ 70 .D :l: 60 '0 c 0 50 ! ;:, 40 i

N 30 0

20

10


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 POz accelerates hemoglobin association with oxygen:

Increasing POz Hb + Oz )HbOz

Decreasing POz, on the other hand, accelerates oxygen dissociation from oxyhemoglobin, that is, the reverse of the preceding equation. Oxygen associates with hemoglobin rapidly-so rapidly, in fact, that about 97% of the blood's hemoglobin 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 hemoglobin (oxyhemoglobin) . Of these two forms of transport, oxyhemoglobin carries the vast majority of the total oxygen transported by the blood.

A&P CONNECT

Variations of hemoglobin exist in the body to temporarily store or carry oxygen. Find out why we need more than one type of oxygen carrier in the body in Oxygen-binding Proteins online at A&P Connect.

10 20 30 40 50 60 70 80 90 100 110 Plasma P02 (mm Hg)

I FIG U R E 24 - 2 1 I Oxygen-hemoglobin dissociation curve. The graph represents the relationship between P02 and O2 saturation of hemoglobin (Hb-02 affinity) . The inset shows how the graphed curve relates to oxygen transport by the blood. Notice that at high plasma P02 values (point A), hemoglobin (Hb) is fully loaded with oxygen. At low plasma P02 values (point B), Hb is only partially loaded with oxygen.


Hb~N/H

Carbaminohemoglobin

+ H+

Hydrogen ion

I FIG U R E 2 4 - 2 2 I Carbon dioxide-hemoglobin reaction. Carbon dioxide can bind to an amine group (NH2) 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 important of which are described briefly in the following paragraphs.

DISSOLVED CARBON DIOXIDE

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.

CARBAMINO COMPOUNDS

One fifth to one quarter of the carbon dioxide in blood unites with the NHz (amine) groups of the amino acids that make up the polypeptide chains of hemoglobin and various plasma proteins . When carbon dioxide binds to amine groups, it forms carbamino compounds. 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 equation, amplified in Figure 24-22, shows how carbon dioxide combines with amine (NHz) in hemoglobin's polypeptide chains to produce carbaminohemoglobin (HbNCOOH-) and H+:

H H / /

Hb- N + CO2 E ) Hb-N + H+ \ \ H COO-

Notice that the arrows in this equilibrium point in both directions. This means that under any given conditions, some carbon dioxide 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 carbon 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 carbaminohemoglobin. 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 COrcarrying capacity of blood increases as plasma Peaz increases.

BICARBONATE

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 (HZC03). Once formed, some of the H ZC03 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 ZC03 ~ 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 plasma, more will be converted to carbonic acid. Because the carbonic 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 concentration increases as a result, "pulling" the system toward the bicarbonate 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 bicarbonate. 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 transport, shows that once bicarbonate ions are formed, they diffuse down their concentration gradient into the plasma. The exit of this negative ion (HC03-) 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.

i -..2 1:.0

EE °0 U o "' .... 0 ... ~8. as '" 00 1-0

:[

60

30 35 40 45 50 55

Plasma PC02 (mm Hg)

I FIG U R E 2 4 - 2 3 I Carbon dioxide dissociation

60

curve. The relationship between Pco2 and total CO2 content (ml CO2 per 100 ml blood) is graphed as a nearly straight line. Notice that the CO2-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 highlighted 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 CO2 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 CO2 becomes dominant. The declining concentration of carbonic acid then forces a shift in favor of the conversion of bicarbonate to carbonic acid. In short, CO2 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.


52

48

Arterial Venous blood blood

"~ 20% Q\ 7<l%

, 10%

D Carbaminohemoglobin DHC03" DC02

Difference

I FIG U R E 2 4 - 2 6 I Proportions of carbon dioxide transported 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 carried in the form of HC03" (bicarbonate) .

Body cell

! ----------- CO2 ---

10% transported as CO2 dissolved

in plasma 20% transported as HbC02

(carbaminohemoblogin)

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, CO2 dissolves in the plasma. Some of the dissolved CO2 enters red blood cells (RBCs) and combines with hemoglobin (Hb) to form carbaminohemoglobin (HbC02) . Some of the CO2 entering RBCs combines with H20 to form carbonic acid (H2C03), a process facilitated by the enzyme carbonic anhydrase (CA) present inside each cell. Carbonic acid then dissociates 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.


CARBON DIOXIDE AND pH

You may have noticed by now that when carbon dioxide enters the blood, most of it is converted to carbaminohemoglobin and hydrogen ions (H+) or to bicarbonate and hydrogen ions. In other words, have you noticed that increasing the carbon dioxide content of the blood also increases its H+ concentration? Thus an increase 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 form?

13. What is oxyhemoglobin? What is carbaminohemoglobin?

14. How does carbon dioxide affect the pH of blood?

SYSTEMIC GAS EXCHANGE Exchange of gases in tissues takes place between arterial blood flowing through tissue capillaries and cells (Figure 24-27). It occurs 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 P02 is about 100 mm Hg, interstitial fluid P02 is considerably lower, and intracellular fluid P02 is still lower. Although intersti-tial fluid and intracellular fluid P02 are not definitely established, 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 P02, 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 P02 decreases, and this accelerates oxyhemoglobin dissociation to release more oxygen into the plasma for diffusion out to cells, as indicated in Figure 24-28 and the following equation:

Decreasing P02 Hb02 )Hb + O2

Because of oxygen release to tissues from tissue capillary blood, P02, oxygen saturation, and total oxygen content are less in venous blood than in arterial blood, as shown in Table 24-4. Carbon dioxide exchange between tissues and blood takes place in the opposite direction from oxygen exchange. Catabolism produces large amounts of CO2 inside cells. Therefore, intracellular and interstitial Pe02 are higher than arterial blood Pe02' This means that the CO2 pressure gradient causes diffusion of CO2

from the tissues into the blood flowing along through tissue capillaries (see Figure 24-27). Consequently, the Pe02 of blood increases 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

SYSTEMIC VENOUS SYSTEMIC ARTERIAL BLOOD ., BLOOD

- -- ----P02 40mm Hg 100 mm Hg

-~---Oxygen 75% 97%

saturation

Oxygen 15 ml O2 per 100 ml 20 ml O2 per 100 ml blood' content blood

'Oxygen use by tissues = difference between the oxygen content of arterial and venous blood (20 - 15) = 5 ml O2 per 100 ml blood circulated per minute.

OXYGEN

Systemic tissue

Capillary , Systemic tissue


CARBON DIOXIDE

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 cap illary, O2 diffuses down its pressure gradient (out of the blood). O2 continues diffusing out of the blood until equilibration has occurred (or until the blood leaves the capillary). B, As blood enters a systemic capillary, CO2 diffuses dbwn its pressure gradient (into the blood) . As with O2, CO2 continues diffusing as long as there is a pressure gradient.


At rest During exercise

100

90

l 80

Jl 70 x: '0 60 c

50 i .. 40 :::I

= 30

N

0 20

10

0 0 10 20

t 30 40 50 60 70 80 90 100110 t Plasma P02 (mm Hg) t

(Exercising) (Resting) Pulmonary

Systemic

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 O2 load when it reaches the low-Po2 (40 mm Hg) environment in systemic tissues (left inset). During exercise, the tissue P02 is even lower (20 mm Hg)-thus causing fully saturated Hb to unload about 70% of its O2 load (right inset). As you can see in the graph, a slight drop in tissue Po2-from point B to point C-causes a large increase in O2 unloading.

This increasing Peoz and decreasing Paz together produce two effects-they favor oxygen dissociation from oxyhemoglobin and carbon dioxide association with hemoglobin to form carbaminohemoglobin. This reciprocal interrelationship between oxygen and carbon dioxide transport mechanisms is contrasted in Figure 24-29. Note that increased Peoz decreases the affinity between hemoglobin and oxygen - this is called a "right shift." A right shift of the oxygen-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

~ Jl x: '0

I c 0 ;:: I! :::I -:J N

0

10 20 30 40 50 60 70 80 90 100 110120 130 140 ! Plasma P~ (mm Hg)

~'I!l!I~!fj!f\!ffi!IA!iS€. __ #l¥$B __ ,r;ffl·'!ffi\,C"'. ~m-/t ----.-

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 phenomenon is named for its discoverer John Scott Haldane.

A&P CONNECT

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.

~ '0 .::. -C .!! c 0 u N

0 0

J Pulmonary

Plasma PC02 (mm Hg)

A B I FIG U R E 2 4 - 2 9 I Interaction of P02 and Pco2 on gas transport by the blood. A, The increased plasma PC02 in systemic tissues decreases the affinity between Hb and O2, 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 P02 commonly observed in systemic tissues increases the CO2 content of the blood, shown as a left shift of the CO2 dissociation curve. This phenomenon is known as the Haldane effect.


,I

QUICK CHECK

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?

REGULATION OF PULMONARY FUNCTION

Respiratory Control Centers Various mechanisms operate to maintain relative constancy of the blood P02 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 expiration seems to be generated by the medullary rhythmicity area.

s

Limbic system (emotional responses)

Apneustic center

Central chemoreceptors

area

A+ P Medullary

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 alternating patterns of stimulation and inhibition of motor neurons that signal the muscles of the diaphragm. The DRG integrates information 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 center 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 center), 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 thorax

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 medu llary rhythmicity area. The pontine respiratory group (PRG, or pneumotaxic center) and apneustic center of the pons influence 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 (limbic) and sensory input. Despite these subconscious reflexes, the cerebral cortex can override the "automatic" control of breathing to some extent to do such activities as sing or blow up a balloon. Green arrows show flow of information to the respiratory control centers. The purple arrow 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 bronchi. 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 temperature-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 reflexes 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


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 requirements 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 changes 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 stimulating effect, mainly on central chemoreceptors (present throughout the brainstem).

Large increases in arterial Peoz also stimulate peripheral chemoreceptors in the carotid bodies and aorta. Stimulation of chemoreceptors by increased arterial Peoz results in faster breathing,


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.

~ .. -" ~oV

Diaphragm contracts and

relaxes

Respiratory muscles

Respiration rate increases

C""ect;O"~ via nerves to ~~

thoracic muscles and diaphragm

Integrator

Recall that increases in the COz content of plasma are accompanied by a proportional

decrease in plasma pH. A decrease in arterial blood pH (increase in acid), within

certain limits, has a stimulating effect Disturbance on chemoreceptors located in the ca-

I'""·"'"

rotid and aortic bodies. Central chemoreceptors are more sensitive to changes in pH than are peripheral chemoreceptors. This increased sensitivity results from the fact that

BIOOdPC02,

Variable "" Detected by

Carotid chemoreceptors -CNIX

CNX

Aortic chemoreceptors

Feed information via nervous

pathways back to

Central chemoreceptors

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 central 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 increases, the rate of CO2 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 present in the blood. Thus, when blood Peo2 increases in the blood, it is partially buffered in the blood-but the CO2 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. Respirations then decrease or fail entirely. This principle has important clinical significance. For example, the respiratory centers cannot respond to stimulation by an increasing blood CO2 if, at the same time, blood P02 falls below a critical level-a fact that may become life or death important during anesthesia.

However, a decrease in arterial blood P02 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 constitutes an emergency respiratory control mechanism. It does not

50

40

30

C'20

~ -5 ~10 i i c 5

7.15

" "- o 3pendence of entilation on CSF pH

'\

I'" '\ \.

'\ r\.

'\ , 7.20 7.25

pHofCSF 7.30 7.35

I FIG U R E 2 4 - 3 2 I Regulatory effect of pH of cerebrospinal 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 CO2 loss from the body, eventually returning the body to a homeostatic balance.


help regulate respirations under usual conditions when arterial blood P02 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 pressure, by acting on aortic and carotid baroreceptors, results in reflex 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 volume 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 neuron, 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 inspiration to start again-the Hering-Breuer inspiratory reflex. Recent 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 respirations. In other words, an individual may voluntarily speed up or slow down the breathing rate. This voluntary control of respirations, 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 CO2 content of the blood because it is not being removed by respirations. CO2 is a powerful respiratory stimulant. So when arterial blood Peo2 increases to a certain level, it stimulates the inspiratory neuron (directly and reflexively) to send motor impulses to the respiratory muscles, and breathing is resumed, even though the individual 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 continued 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 reflex, a valuable protective device. It operates, for example, to prevent aspiration of food or liquids during swallowing.


The major fac tors that influence breathing are sum marized in Figure 24-30. Some factors that affect breathing during exercise are mentioned in Box 24-9.

Ventilation and Perfusion Alveolar ventilation, as we already know, is airflow to the alveoli (see Figure 24-1 ). Alveolar perfu sion is blood flow to the alveoli (see Figure 24-1 8). Matching ventilation and perfusion is important for efficient gas exchange in the lungs. If a poorly ventilated alveolus is well perfused, blood flow is being "wasted" on an inefficient alveolus. It is more effici ent to detour some of th e blood flow away from the poorly ventilated alveolus and toward a well-ventilated alveolus.

F igure 24-33 shows that perfusion can be matched- within very limited boundaries - to the ventilation status of indi-

vidual groups of alveoli . As yo u have probably already deduced, this is accomplish ed th rough vasoconstriction (narrowing) of certa in pulmonary arterioles to reduce perfusion to poorly ventila ted alveoli . Su ch ventila tion-perfusion matching in various region s of each lung can increase the overall effi ciency of gas exchange.

17. Where are the chief regulatory centers of the respiratory function 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 Pc02, P02, 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.

.-.

1401 L/~~~- 1- Exercise - Resting

.5 120 • Normal

S ~ 100

i 80J

~ , , , -c:: CD > 60 .. as "0

40 CD > <

20

0 20 30 40 50 60 80 100

Arterial PC02 (mm Hg)

Normal effects of maximum exercise in an athlete. 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 (Pc02) (horizontal axis) . As you can see at the normal points of a Pc02 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 .

1

1 2

1 3

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 perfusion-thus efficiently matching the perfusion to the ventilation.

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.


(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 respiratory 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, pathogens 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).


Mechanisms of Disease DISORDERS ASSOCIATED WITH RESPIRATORY FUNCTION Many things can interfere with the functions of gas exchange and ventilation and cause respiratory failure. A few of the more important 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 hallmark 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; immunological diseases, as in rheumatoid lung; obesity; and metabolic disorders 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 reduces their ability to work or perform normal daily activities. Therapy 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. Exposure to cigarette smoke and other common air pollutants can trigger a reflexive constriction of bronchial airways. Obstructive disorders may obstruct inspiration and expiration, whereas restrictive 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 hyperinflated chests. Figures 24-12 and 24-13 (p. 813) show the effects 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. However, 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 obstruction caused by foreign material. Learn about how these procedures can help choking victims in Heimlich Maneuver online at A&P Connect.

Bronchitis In chronic bronchitis, the person produces excessive tracheobronchial secretions that obstruct airflow, and the bronchial mucous glands are enlarged (Figure 24-34, B). Risk factors include cigarette smoking (accounting for 80% to 90% of the risk of developing CaPO), a normal decline in pulmonary function as a result of age, and environmental exposure to dust and chemicals. With impairment of the alveoli and loss of capillary beds, gas exchange is inefficient, which in turn produces hypoxia.

Emphysema In emphysema, the air spaces distal to the terminal bronchioles are enlarged as a result of damage to lung connective tissue. As the bronchioles 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 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 inflammation (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 leukotriene modifiers to reduce the inflammation associated with asthma. (Recall from Chapter 21 that leukotrienes are immune cells to regulate the inflammation response

A

c

ASTHMA

Smooth muscle

Edema of respiratory mucosa and excessive mucus production obstruct airways.

Mucus

D


CHRONIC BRONCHITIS

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 elimination 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 Respiration, Nutrit ion, 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, -globball, -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 bend]

ideal gas inspiration (in-spih-RAY-shun)

[in- in, -spir- breathe, -ation process]

law of partial pressures medullary rhythmicity area (MEO-eh-Iair-ee rithMIH-sih-tee)

[medulla- middle, -ary relating to, rhythm- rhythm, -ic relating to, -ity condition]

oxygen-hemoglobin dissociation curve (AHKsih-jen hee-moh-GLOH-bin)

[oxy- sharp, -gen produce, hemo- blood, -globball, -in substance, dis- reverse, -socia- unite, -ation process]

oxyhemoglobin (ahk-see-hee-moh-GLOH-bin) [oxy- sharp (oxygen), -hemo- blood, -globball, -in substance]

partial pressure (pAR-shal) physiological dead space (tiz-ee-oh-LOJ-i-kal)

[physionature, -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, ventfan or create wind, -tion process]

LANGUAGE OF MEDICINE adult respiratory distress syndrome (AROS)

[re- again, -spir- breathe, -tory relating to syntogether, -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 respih-RAY-shun)

[John Cheyne Scots physician, William Stokes Irish physician]

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-rahtor-eel

[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, -ventfan or create wind, -tion process]

hypoventilation (hye-poh-ven-ti-LAY-shun) [hypo- below, -vent-fan or create wind, -tion process]

inspiratory capacity (IC) (in-SPY-rah-tor-ee kahPASS-I-tee)

[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 inJEK-shun)

[intra- within, -trache- rough duct, -al relating to]

pulmonary ventilation (PUL -moh-nair-ee ventih- LAY-shun)

(pulmon-Iung , -ary relating to, ventfan 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 tizee-OL-oh-jee)

[re- again, -spir- breathe, -tory relating to, physionature, -Iog- words (study), -y process]

solubility (sol-yoo-BI L -i-tee) [solubili- able to dissolve, -ity state]

surface tension 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 lahPLAHS)

[Thomas Young English physician, Pierre Simon de LaPlace French physicist]

maximum oxygen consumption (V02 mil) [maximum greatest, oxy- sharp, -gen produce, conwith 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 ah-REST)

[re- again, -spir- breathe, -tory relating to]

respiratory distress syndrome (ROS) (RES-pihrah- tor-ee di-STRESS SIN-drohm)

[re- again, -spir- breathe, -tory relating to, syntogether, -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 [yawn gape]

CASE STUDY

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 inhalations? 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 CO2 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

I I To download an MP3 version of the chapter summary for use with your iPod or portable media player, access the Audio

© Chapter Summaries online at http://evolve.elsevier.com.

Scan this summary after reading the chapter to help you reinforce the key concepts. Later, use the summary as a quick review before your class or before a test.

RESPIRATORY PHYSIOLOGY (FIGURE 24-1) 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

PULMONARY VENTILATION 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)

833

a. One in which the pressure within the alveoli of the lungs is lower than atmospheric pressure to produce inspiration


b. One in which the pressure in the alveoli of the lungs is higher than atmospheric pressure to produce expiration

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 (PA)

b. Air moves into the lungs when alveolar pressure (PA) 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

inspiration 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 volumes 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 pulmonary disease)

9. Alveoli must be properly ventilated for adequate gas exchange

E. Pulmonary airflow - rates of airflow int%ut of the pulmonary airways l. Total minute volume - volume moved per minute

(mllmin) 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 relationships (Figure 24-13)

PULMONARY GAS EXCHANGE 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 P02 and Peo2 equal alveolar P02 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

blood b. The total functional surface area of the respiratory

membrane 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)

HOW BLOOD TRANSPORTS GASES 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 O2

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 O2 in plasma and

as being associated with hemoglobin (oxyhemoglobin) a. Increasing blood P02 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 CO2 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 accelerated 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)

SYSTEMIC GAS EXCHANGE 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 P02 de

creases, which accelerates oxyhemoglobin dissociation to release more oxygen to plasma for diffusion to cells (Figure 24-28)

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 P02 (Figure 24-29, B)

REGULATION OF PULMONARY FUNCTION 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)


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 overinflation 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 Po2, 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 breathing; if it decreases, the result is slower breathing

b. A decrease in blood pH stimulates peripheral chemoreceptors 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 P02 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 alveoli 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 wellventilated alveoli

THE BIG PICTURE: RESPIRATORY PHYSIOLOGY AND THE WHOLE BODY

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 conversIOn

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


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

importance. 12. Describe four other unusual reflexes that indirectly

affect breathing. 13. Describe the changes in respirations during a period of

exercise.

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 syndromes.

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?

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