Respiratory Physiology Lectures

Respiratory Physiology 2010

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Respiratory Physiology 2010 Schedule

Lecture/Lab Day Date Time

Overview of Gas Exchange Friday Oct/7/2010 9:10-10:00

Gas Volumes & Ventilation Friday Oct/8/2010 10:10 –11:00

Mechanisms of Breathing Monday Oct/8/2010 11:10-Noon

Howard A. Rockman, M.D.

[email protected]

Lectures modified from Jo Rae Wright, Ph.D.


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Contents

Section Page

Symbols used in Respiratory Physiology 5

General abbreviations 5

Modifiers 5

Examples 6

Overview of Gas Exchange 7

Introduction 8

Major Functions of the Respiratory System 8

Respiration 8

Anatomy of the Respiratory System 9

Gross Anatomy 9

Airways 10

Alveolar-Capillary Unit 11

A Simple Model Of The Respiratory System 11

Lung Volumes and Capacities 12

Definitions of Standard Lung Volumes and Capacities 13

Indirect Measurement of Lung Volumes 14

Body Plethysmograph 14

Composition of Environmental and Alveolar Gas 15

Partial Pressure of Gases 15

Partial Pressure of Gases in Gases 15

Partial Pressures of Alveolar Gases 16

Non-Respiratory Functions of the Lung 17

Diffusion of Gases 19

Overview 19

Gases Diffuse from a Region of High Partial Pressure to a Region of

Low Partial Pressure 20

Diffusion of Gases in Gases 20

Diffusion of Gases in Liquids 20

Diffusion of Gases Across the Alveolar-Capillary Membrane 20

Fick’s Law for Diffusion 21

Transfer of O2 and CO2 between Alveolus and Capillary 21

Measurement of Diffusion Capacity 22

Single-Breath CO Method 22

Effects Of Exercise On Diffusing Capacity 22

Examples of Diseases that Affect Diffusion of Gases 23

Diseases Associated with Decrease Surface Area for Diffusion 23

Diseases that Affect “t” (“Thickness”) 23


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Contents (continued)

Section Page

Lung Mechanics 24

Overview 24

Pressures of the Respiratory System 25

Units of Pressure Measurements 25

Intrapleural Pressure 25

Transmural Pressure 26

Recoil of the Lungs 27

Collagen And Elastin Fibers 27

Surface Tension 27

Pressure-volume Curves of the Lung 28

Effects of Surfactant on Alveolar Stability 30

Lung Compliance & Disease 32

Elastic Recoil of the Chest Wall 32

Relaxation Pressure Volume Curve of The Respiratory System

(Lung + Chest Wall) 32

Airway Resistance 34

Factors that Influence Airway Resistance 34

Airway Diameter 34

Lung Volume 34

Elastic Recoil 35

Airway Smooth Muscle Tone 35

Measurement of Airway Resistance 35

Forced Expiratory Vital Capacity Curve 35

Dynamic Airway Compression 35-37


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List of Figures

Figure Page

Fig. 1.1 Schematic Representation Of External and Internal Respiration 8

Fig. 1.2 Model of the Airways 10

Fig. 1.3 Simplified Model of the Respiratory System 12

Fig. 1.4 Typical Volumes and Flows 12

Fig. 1.5 Spirometric Measurement of Lung Volumes and Capacities 13

Fig. 1.6 The approximate changes in partial pressure of O2 and CO2 in

alveolar gas 16

Fig. 1.7 Pulmonary Function test 18

Fig. 2.1 Time course for Transfer of Gas Between the Alveolus and the

Capillary Blood 21

Fig. 3.1 Transpulmonary Pressures in the Respiratory System 26

Fig. 3.2 Synthesis of Surfactant 28

Fig. 3.3 Pressure-volume Curve of the Lung 29

Fig. 3.4 Volume vs. inflation pressure during lung inflation with air and saline 29

Fig. 3.5 Laplace Law 31

Fig. 3.6 Deflation Pressure Curves of the “Normal” and Diseased Lung 33

Fig. 3.7 Intraorgan and Transorgan Pressure During Inspiration and End

of Expiration 33

Fig. 3.8 Forced Expiratory Vital Capacity Curve 36

Fig. 3.9 Dynamic Airway Compression 37


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Symbols used in Respiratory Physiology

These abbreviations are used not only in respiratory physiology but also in virtually all systems.

GENERAL ABBREVIATIONS

C Compliance

c Concentration, content

D Diffusing capacity

f Respiratory frequency

F Fraction concentration (dry gas)

P Gas pressure

R Resistance

R Respiratory exchange ratio

Q Volume of blood

V Gas volume

Q Volume of blood per unit time (blood flow)

V Gas volume per unit time (gas flow)

MODIFIERS

A Alveolar gas

B Barometric

D Dead space gas

E Expired gas

I Inspired gas

T Tidal gas

aw Airway

cw Chest wall

et End tidal

es Esophageal

pl Intrapleural

L Lung

rs Respiratory system

cw Transchestwall

L Transpulmonary

rs Transrespiratory system


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a Arterial blood

c Capillary blood

t Tissue

Mean value

Time derivative

EXAMPLES

PAO2 Partial pressure of oxygen in alveolar gas

PaO2 Partial pressure of oxygen in arterial blood

FECO2 Fraction of CO2 in dried, expired gas

PETCO2 Partial pressure of carbon dioxide in end tidal gas

VO2 Oxygen consumption per unit time

VA/Q Ventilation/perfusion ratio


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Overview of Gas Exchange

Objectives

• Relate the structural organization of the respiratory system to its function.

• Describe the functional importance of the intrapleural fluid and the parietal and

visceral pleura.

• Know the structural and functional features that distinguish the respiratory zone of the

airways from the conducting zone.

• Define and describe the alveolar-capillary unit.

• Know the major functions of type I cells, type II cells, and alveolar macrophages.

• Know the symbols that are commonly used in respiratory physiology.

• Know the definitions of fractional concentration (of a dry gas) and partial pressure of

a gas.

• Know the normal values for partial pressure of oxygen and carbon dioxide in arterial

and mixed venous blood.

Introduction The major functions of the respiratory system can be divided into two categories: respiratory

and non-respiratory. The first function, which will be emphasized in this course, is to carry out gas

exchange. Metabolizing tissues utilize oxygen and produce carbon dioxide. The respiratory system

must obtain oxygen from the environment and must eliminate CO2 that is produced by cellular

metabolism. These processes must be coordinated so that the demand for oxygen is met and so that

the CO2 that is produced is eliminated. It should be intuitive to most people that cells cannot live

without an adequate supply of oxygen. It may not be intuitive, however, that failure to eliminate CO2 adequately can also be harmful because changes in CO2 levels affect acid-base balance in the body.

The respiratory system, which includes the lungs, airways, the portion of the nervous system

involved in respiratory control, the chest wall, and muscles, is well designed to carry out gas

exchange in an expeditious manner.

The respiratory system is also involved in non-respiratory functions. It participates in

maintaining acid-base balance in the body since increases in CO2 concentrations in the body lead to

increased hydrogen ion concentrations. The lungs also metabolize naturally occurring compounds

such as angiotensin I, some prostaglandins, and norepinephrine. The lungs are also responsible for

protecting the body from inhaled particles.


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Figure 1.1: Schematic Representation Of External and Internal Respiration

Oxygen consumption is abbreviated ( 2VO ) and carbon dioxide production is abbreviated

( 2V

CO ). The dot ( ) indicates a time derivative. Thus, the units for 2VO and are ml/min.

Major Functions of the Respiratory System

Respiration

The term respiration encompasses all of the processes that are involved with supplying the

tissues with oxygen and removing the carbon dioxide that is produced during cellular metabolism.

“External” Respiration

“External” respiration is the movement of oxygen from the atmosphere to the cells of the body

and the movement of carbon dioxide from the cells to the atmosphere. The exchange of carbon

dioxide and oxygen takes place in the lungs. Upon command from the central nervous system, the

inspiratory muscles contract, the chest wall expands, and fresh air flows into the lungs.


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Simultaneously, venous blood, from which oxygen has been removed by metabolizing tissues and to

which carbon dioxide has been added, flows from the tissues to the lungs. In the pulmonary

capillaries, oxygen diffuses into the blood and carbon dioxide diffuses out. This blood which now

has a high concentration of oxygen and a low concentration of carbon dioxide flows to the tissues.

When the muscles of the respiratory system finally relax, expiration occurs and the gas that is

enriched in carbon dioxide is expelled from the lungs.

“Internal” Respiration

“Internal” respiration is the utilization of oxygen by the cells of the body to produce energy and

the by-product of metabolism, carbon dioxide. A general formula for this process is

O2 + Food CO2 + H2O + Energy (ATP) (1.1)

Because the chemical composition of different foodstuffs differs (i.e., carbohydrates, fat, and

proteins), the amount of oxygen that is utilized and the amount of carbon dioxide that is produced

when they are metabolized differs.

Anatomy of the Respiratory System

Gross Anatomy

The right and left lungs are housed in the thoracic cavity. The right lung has three lobes and the

left lung has two. The right and left lungs are separated by the mediastinum. The thoracic cavity is

lined by the parietal pleura and the lungs are covered by the visceral pleura. Between the two pleurae

is a thin film of fluid, called the intrapleural fluid. The pleural fluid functions as a lubricant and

serves to functionally connect the lungs and chest wall. Inspiration begins when the diaphragm and

the muscles of the chest wall contract. Contraction of the diaphragm causes it to descend and

contraction of the intercostal muscles of the chest wall raises the ribs. The muscles contract in

response to neural impulses from the brainstem. As a result of the muscle contraction, the thoracic

cavity is enlarged. Because the lungs are functionally connected to the chest wall by the visceral and

parietal pleura (which cover the lungs and the chest wall, respectively), the lungs are also expanded.

This increase in volume results in reduction of the pressure of the gases in the terminal airspaces

(alveolar ducts and alveoli, see below). Air is like water in that it flows from a region of high total

pressure to a region of low total pressure. This type of airflow is called bulk flow. When the pressure

in the alveoli (PA) becomes less than the pressure at the mouth, which is ordinarily atmospheric

pressure (PB), air flows in until PA = PB.

Expiration occurs when the muscles of inspiration relax. The lung is elastic and will return

passively to its pre-inspiratory volume. This reduction in volume raises the pressure in the lung and

gas will therefore flow out of the lung.


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Airways

Upon inhalation, air moves into the respiratory system through the nose and mouth. The air is

heated, warmed to body temperature, and humidified as it enters the airways. The airways are a

series of branching tubes that become narrower, shorter, and increase in number from the single tube

that is the trachea to the several hundred thousand bronchioles. The airways are not rigid tubes, but

are flexible. All together, the airways divide a total of 23 times. The airways are divided into two

parts: conducting zone and respiratory zone.

Figure 1.2: Model of the Airways

CONDUCTING ZONE includes all of the branchings down to and including the terminal bronchioles.

The function of the conducting zone is to lead inspired gas to the gas exchanging regions. The

conducting zone is ideally suited to its function because it has a small diameter, a small surface area,

and a small total volume (about 150 ml). These factors minimize the volume of inspired air that is

“wasted” or that does not participate in gas exchange. Since no gas exchange occurs in the

conducting zone, it is often called the anatomical dead space.

RESPIRATORY ZONE is the region of the lung where gas exchange occurs. The respiratory bronchioles

(generations 17-19) have a few alveoli budding off their walls. Alveoli are small sac-like structures

with very thin walls. Generations 20-22 are called alveolar ducts and they are completely lined with

alveoli. The branching terminates with the blind alveolar sacs. The volume of the respiratory zone is

much larger than the conducting zone (about 3000 ml.)


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Alveolar-Capillary Unit

Gas exchange is a two way street involving uptake of oxygen and elimination of carbon dioxide.

The site of gas exchange is the alveolar-capillary unit. The 300 million alveoli are virtually

surrounded by pulmonary capillaries. The resulting area of contact between gas and blood is about

the size of a tennis court. The distance that gas has to diffuse is very short. The alveolar capillary

membrane is about 0.2 microns thick or about 1/50 the thickness of a piece of airmail stationery. The

large surface area and short distance for diffusion make the alveolar-capillary unit ideally suited for

gas exchange.

Type I Cells

Type I cells line about 90% of the surface area of the alveoli. They are very thin squamous

epithelial cells and are considered to be the site of gas exchange.

Type II Cells

Type II cells are interspersed among the type I cells. Type II cells synthesize, secrete and

metabolize alveolar surfactant. Surfactant is a lipid-rich substance that lines the alveoli and helps

keep lungs from collapsing. This subject will be discussed in detail later.

Alveolar Macrophages

Alveolar macrophages are the third type of cell type found in the alveoli. Macrophages

phagocytose or engulf inspired particles such as bacteria. The cells are mobile and are attracted to

areas of infection or trauma.

A Simple Model Of The Respiratory System

The diagram shown in Figure 1.3 is a convenient and simple way to view the respiratory system.

The many branching bronchi that make up the conducting airways are represented by a single tube

called the anatomical dead space or conducting zone. The multiple alveolar-capillary units, which

are the sites of gas exchange, are represented by a half-circle (the respiratory zone) in close

approximation to a tube through which blood flows. At the end of expiration, the volume of gas in

the conducting zone is approximately 150 ml. The volume of gas in the respiratory zone is

approximately 3000 ml.

The methods for measuring these volumes, which can change dramatically in diseases, will be

discussed in laboratory. The alveolar gas in the respiratory zone is in contact with approximately 70

ml of pulmonary capillary blood at any given moment.

With each inspiration, approximately 500 ml of gas enters the lungs. The volume of air entering

the nose or mouth per breath is called the tidal volume. (NOTE: The “normal” values traditionally

provided in physiology text books generally apply to a 70 kg adult male. “Normal” lung volumes are

usually about 20-25% lower in females. The values are only approximations and will, of course, vary

from patient to patient.)


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In Figure 1.4, the volumes shown on the left side of the diagram below are static values; typical

flows and how they are calculated are shown on the right hand side of the diagram of lung volumes

is an important diagnostic tool since pathological states often alter both lung volumes and their

relationships to one another. There are many accepted protocols for measurement of lung volumes.

The methods can be subdivided into two categories: direct and indirect. A few of the most

commonly used methods are discussed below.

Figure 1.3: Simplified Model of the Respiratory System

Figure 1.4: Typical Volumes and Flows

Lung Volumes & Capacities

There are two types of conditions under which volumes are measured: dynamic and static.

Dynamic volumes refer to measurements made when volumes are changing, i.e., during gas flow.

Static volumes can be measured between two points where there is no flow, for example before and

after inspiration. We will discuss static lung volumes first.

2500 ml


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There are four standard lung volumes. There are also four standard lung capacities, which consist

of a combination of two or more volumes. Accepted “normal” values are included below. Note:

“Normal” values may vary from text to text or hospital to hospital.

Definitions of Standard Lung Volumes and Capacities

• Tidal volume (VT): volume of air inhaled or exhaled with each breath (in adult

males about 500ml; in general, lung volumes in females are usually about 20-

25% less).

• Inspiratory reserve volume (IRV): Volume of air that can be inspired after a

normal inspiration (about 3.0 L in males).

• Expiratory reserve volume (ERV): Maximal volume of air that can be expired

from resting expiratory level (about 1.0 L in males).

• Residual volume (RV): Volume of air in lungs at end of maximal expiration

(about 1.5 L males)

• Inspiratory capacity (IC=VT+IRV): Maximal volume of air that can be inspired

from resting expiratory level (about 3.5 L in males)

• Functional residual capacity: (FRC=RV+ERV): Volume of air in lungs at end

of a normal expiration. (approximately 2.5 L in males)

• Vital capacity (VC=ERV+VT+IRV): Volume of air that can be expired after

maximal inspiration (approximately 4.5 L)

• Total lung capacity (TLC=RV+ERV+VT+IRV): Volume of air in lungs at end

of maximal inspiration (about 6 L).

Figure 1.5: Spirometric Measurement of Lung Volumes and Capacities

IRV

ERV


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A spirometer is a simple volume recorder. It consists of two metal cans, one being larger than

the other. The larger can is filled with water and sits right-side up. The smaller can is immersed

upside down. A pulley is attached to the smaller can so that when the can moves up and down its

excursions are recorded on paper. A tube into which the patient breathes is in contact with the air in

the upside down can. So, when air moves into or out of the can, the can moves up and down and the

pen records this movement. (See diagram above.)

To determine lung volumes, the subject is usually seated and breathes quietly into the spirometer.

Volume is plotted on the y-axis and time on the x-axis. Note: although time is recorded in these

measurements, it is not relevant. Upon inspiration the pen moves up; upon expiration it moves

down. An idealized recording with the standard lung volumes and capacities and their definitions is

shown above in Figure 4.1.

The fact that the volume that a given amount of gas occupies varies with the temperature, and

pressure of the gas is a concept that is taught in introductory physics. This concept is important in

the measurement of lung volumes. As explained above, lung volumes are often measured with a

spirometer. The gas in the spirometer is at room (or ambient) temperature and pressure and is

saturated (ATPS). In order to calculate the actual volume that the gas occupied in the lungs, its

volume must be converted to body temperature, pressure and saturated with water vapor (BTPS).

The ideal gas law can be used to convert measurement made at ATPS to BTPS. Lung volumes are

reprinted at BTPS.

Indirect Measurement of Lung Volumes

Although the spirometer is a useful tool for measuring lung volumes it has some disadvantages.

First it can only measure the lung volumes that the subject can exchange with the gas in the

spirometer. Second, the patient must be awake and cooperative. The “indirect” methods of body

plethysmography is often used to determine functional residual capacity. The residual volume and

total lung capacity can then be calculated from the functional residual capacity measurement and the

volumes measured by spirometry.

Body Plethysmograph

The body plethysmograph is an air tight box that looks like a phone booth. The patient is hooked

up to an apparatus that measures the pressure at the patient’s airways (The pressure at the mouth

(airway pressure) will be equal to the pressure in the alveoli if there is no airflow). The patient’s

airflow is monitored by a pneumotachograph. The respiratory therapist can briefly block airflow at

the end of an expiration and measure the pressure at that time (P1). The patient is then instructed to

make an inspiratory effort against the closed airway and the pressure at the end of the inspiratory

effort is measured (P2). As a result of this inspiratory effort, the patient’s lungs expand (increase in

volume) which results in compression of the gas in the airtight chamber. Therefore, the pressure of

the gas in the chamber will rise and this change in box air pressure is recorded. The chamber is

calibrated so that a known change in box pressure is produced by a known change in volume (∆V).

Therefore the lung volume (V) can be estimated from the change in the volume of gas in the box

according to the equation: P1V = P2 (V + ∆V). One advantage of the method of plethysmography is

that any trapped gas that is not in communication with the airways will still be included in the

measurement.


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Composition of Environmental and Alveolar Gas

In order to perform its function of providing cells with oxygen and removing the carbon dioxide

that is produced, the pulmonary system must increase the amount of oxygen in the alveoli above that

found in the mixed venous blood. It must also lower the carbon dioxide in the alveoli below that of

mixed venous blood. Gases move by diffusion from regions of high partial pressure to regions of

low partial pressure.

Partial Pressure of Gases

The partial pressure of a gas is designated by the symbol “P” followed by a subscript designating

the gas in question. Thus, PO2 is the partial pressure of oxygen.

Partial Pressure of Gases in Gases

Gas molecules behave like individual particles that are in a constant state of motion. When the

particles collide with one another or the sides of the container they exert a pressure. The pressure

exerted will depend on the number of collisions. The more particles there are, the more collisions

there will be and therefore, the pressure exerted by the particles will be higher. At a given

temperature, the pressure of a gas is a measure of its concentration.

At sea level, the pressure exerted by gases found in the atmosphere is sufficient to support a

column of mercury 760 mm high (in average weather) in a sealed tube placed in a dish of mercury

open to the atmosphere. Therefore, a pressure of 1 atmosphere = 760 mm Hg. A container of pure

oxygen (or any other gas) at sea level will have a partial pressure of 760 mm Hg (i.e., PO2= 760 mm

Hg).

If we have a mixture of gases, the pressure exerted by each is the same as it would be if that gas

alone occupied the entire container (this is Dalton’s law). One way to think about this concept is that

the gas molecules are far enough apart that they do not interfere with each other so that they behave

as if there were no other gases around. To calculate the partial pressure of a gas “X”, PX = PB x FX,,

where PB is the barometric pressure (at sea level PB = 760 mm Hg), and FX is the fractional

concentration of gas X. Fractional concentration is simply the fraction of the dry gas molecules

which are gas X (i.e., FO2 = PO2/(PB-PH2O)). For simplicities sake, respiratory physiologists and

physicians generally assume that room air is always dry. Since 21% of dry room air is oxygen, the

PO2 of room air = FO2 x PB = 0.21 X 760mm Hg = 160 mm Hg. The concentration of carbon

dioxide in room air is so low (0.04%), it is generally considered to be zero. Once gas is inhaled it

becomes saturated with water vapor and warmed to body temperature. Even on a very cold, dry day

all of the inspired air will become saturated with water vapor and warmed to 37oC. At 37oC, the

partial pressure of water (PH2O)= 47 mm Hg. Recall, the PO2 of dry room air = FO2 x PB = 0.21 X

760mm Hg = 160 mm Hg. When this gas is warmed to 37oC, and becomes humidified as it passes

through the nasal passages, water vaporizes into the gas until the PH2O = 47 mm Hg. What this

means is that only 760 - 47 mm Hg or 713 mm Hg is available for other gases besides water.

Therefore, the PO2 of tracheal or inspired gas (abbreviated PIO2) = (760-47 mm Hg) X 0.21 = 150

mmHg.


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Partial Pressures of Alveolar Gases

Obviously the partial pressure of oxygen and carbon dioxide will vary during the respiratory

cycle. As fresh air, which is rich in oxygen and poor in carbon dioxide, enters the respiratory zone

during inspiration, the alveolar partial pressure of oxygen will rise and the alveolar partial pressure

of carbon dioxide will fall. As gas exchange occurs, the alveolar partial pressure of carbon dioxide

will rise and the alveolar partial pressure of oxygen will fall. Because these fluctuations are small (a

few mm Hg), they are generally ignored and only mean values PO2 and PCO2 are considered.

Figure 1.6: The approximate changes in partial pressure of O2 and CO2in alveolar gas.

The mean PO2 and PCO2(approximately 100 and 40 mm Hg, respectively) is

indicated by the horizontal line.

(Note: the fluctuations are small since 350 ml of gas entering the respiratory zone

with each breath is small compared to the 3000 ml there at the end of expiration).

Normal values for mean alveolar partial pressures are PO2 = 100 mm Hg and PCO2=

40 mm Hg. You should memorize these values.

Another important concept that must be conveyed is that at sea level and when there is no flow of

gas, the sum of all partial pressures of gases must be equal to barometric pressure which is close to

760 mmHg. For example, the partial pressures of gases in dry air are: PO2 = 160 mm Hg; PN2= 600

mmHg; PCO2 = 0 mm Hg. The partial pressure of gases in alveolar gas are: PO2 = 100 mm Hg;

PN2= 573 mm Hg; PCO2= 40 mm Hg; PH2O = 47 mm Hg. In both cases when there is no flow

Ptotal = 760 mm Hg.


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The total and partial pressure of respiratory gases in “ideal” alveolar gas and blood (at sea level) are

shown below.

Ambient air Moist tracheal Alveolar gas Systemic Mixed venous

(dry) air (R = 0.80) arterial blood blood

PO2 160 150 100 100 40

PCO2 0 0 40 40 46

PH2O, 37°C 0 47 47 47 47

PN2 600 563 573 † 573 573

P total 760 760 760 760 706 ‡

† PN2 is increased in alveolar gas because R < 1 normally

‡ Ptotal in venous blood is reduced because PO2 has decreased more than PCO2 has increased.

Non-Respiratory Functions of the Lung

Note: This topic will not be covered in lecture. This information is included for completeness.

The lung carries out several non-respiratory functions. Several vasoactive substances are

metabolized in the lung including prostaglandins. Approximately 30% of the norepinephrine in

mixed venous blood is removed by the lung. On the other hand epinephrine and isoproterenol are not

metabolized by the lung. It may be worthwhile to consider that the response of a patient to an

injection of norepinephrine would be quite different if it were injected through an arterial or venous

catheter.

The lung also plays an important role in host defense against infection. We inspire all sorts of

noxious particles and gases, as well as bacteria. Some of the material is trapped in the small airways

and is eventually removed from the lung by the action of the cilia of the airway epithelial cells. In

addition, the alveolar macrophage can engulf and inactivate invading foreign particles and bacteria.

This is only a partial list of the non-respiratory functions of the lung. This subject is a relatively

new one and it is likely that as our ability to isolate and purify the 40 some different cell types found

in the lung improves, our understanding of their metabolic functions will also improve.


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Figure 1.7: Sample Pulmonary Function Test


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Diffusion of Gases Objectives

• Know the factors that determine rates of diffusion of gases in gases and gases in liquids.

• Know how diffusion differs from bulk flow.

• Be able to state Fick’s law for diffusion.

• Describe the rate of diffusion of oxygen across the alveolar capillary membrane.

• Describe the rate of diffusion of carbon dioxide across the alveolar capillary membrane.

• Know why CO is most often used to measure diffusing capacity.

• Describe the effects of exercise on diffusing capacity.

• Know that it is very rare that impaired diffusion exists as a single physiological abnormality.

The process that causes the thickening of the membrane or the decrease in surface area almost

always leads to uneven ventilation, uneven capillary blood flow and therefore, uneven matching of

gas and blood (ventilation/perfusion).

Overview

The previous chapter dealt with how gas is moved into and out of the lungs and the volumes that

are normally involved. The next subject deals with the movement of gas from the alveolar air into

the blood and from the blood into alveolar air. The process of movement is a passive one that is

governed by the laws of diffusion. In order to understand the subject of diffusion of gases, we will

discuss some of the physical laws that govern the diffusion of gases, consider the properties of the

blood-gas barrier across which gas must diffuse, talk about some limitations to diffusion and

perfusion, and finally discuss the measurement of diffusing capacity.

Gases Diffuse from a Region of High Partial Pressure to a Region of Low Partial Pressure

Because of their random motion, gases will distribute themselves throughout a given space until

the partial pressure is the same everywhere. This process is diffusion and differs from movement of

gas by bulk flow. Bulk flow is mass movement of gases as a result of differences in their total

pressure. Molecules of different gases move from a region of high total pressure gradient to a region

of low total pressure. During diffusion, each individual gas moves according to its own partial

pressure gradient.


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Diffusion of Gases in Gases

The rate of diffusion of gases in a gaseous phase is dependent on the size of the gas molecules.

Small molecules diffuse faster than large ones. The rates are proportional to the inverse of the square

roots of their molecular weights (Graham’s law). Thus, in gases, oxygen diffuses more rapidly than

does carbon dioxide. However, in the alveoli, it only takes a fraction of a second for newly inspired

gas to come into equilibrium with alveolar gas. Therefore, this difference in diffusion rates of

oxygen and carbon dioxide in gas is rarely a limiting factor. The equation below compares the rate

for transfer of CO2 and O2 through a barrier with pressure kept equal on both sides so that there is

no bulk flow.

Rate of transfer of CO2 MWO2

Rate of transfer of O2 MWCO2

32

44

5.66

6.63= = =

(2.2)

Diffusion of Gases in Liquids

Pulmonary physiologists must also be concerned about the rate at which gases diffuse in liquids,

such as blood or tissues. Henry’s law states that at any given temperature, the equilibrium

concentration of a gas that does not combine chemically with the liquid is directly proportional to the

partial pressure of the gas to which the liquid is exposed and directly proportional to the solubility of

the gas in the liquid. In water the solubility of CO2 at 37°C is (0.07 ml/100 ml plasma)/mm Hg. The

solubility of O2 is only about (0.003 ml/100 ml plasma)/mmHg. This difference of about 23 fold far

outweighs the 1.17-fold advantage of O2 over CO2 from molecular weights.

Rate

Solubility

MWα

(2.3)

Rate CO2

Rate O2

23

1=

(2.4)

However, the driving pressure for CO2 diffusion is lower (46-40 mm Hg = 6 mm Hg) than is the

driving pressure for oxygen diffusion (100-40 mm Hg = 60 mm Hg). Thus, even though the

solubility of carbon dioxide is much greater than the solubility of oxygen, the net result is that CO2

reaches equilibrium only slightly before O2 reaches equilibrium. Both oxygen and carbon dioxide

are very soluble in lipids, therefore, the barrier posed by cell membranes is small compared to the

barrier of aqueous layer to oxygen diffusion.

Diffusion of Gases Across the Alveolar-Capillary Membrane

In order to reach the blood, oxygen must diffuse through several layers including the alveolar

surfactant layer, the liquid beneath the surfactant, the alveolar epithelium, the capillary endothelium,

a layer of plasma in the pulmonary blood, the erythrocyte membrane, and finally through the

intracellular fluid of the erythrocyte. Carbon dioxide follows the reverse path. The distance across

the alveolar capillary membrane is very small (about 2 microns).


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Fick’s Law for Diffusion

The diffusion of gases across the blood-gas barrier by simple diffusion is described by Fick’s

law, which states that the volume of gas per unit time diffusing across a tissue is directly

proportional to surface area (A), a diffusion constant (D) (which is proportional to the solubility of

the gas in question and inversely proportional to the molecular weight of the gas) and the partial

pressure difference across the tissue (P1-P2) and is inversely proportional to the tissue thickness (t).

V

DA(P1-P2)

tα

(2.5)

Transfer of O2 and CO2 between Alveolus and Capillary

The time course for transfer of gas between the alveolus and the capillary blood is shown in

Figure 2.1. Even though a red blood cell spends only about 0.75 seconds passing through an

alveolus, the partial pressures of both carbon dioxide and oxygen normally reach equilibrium.

Equilibrium is reached by about 0.3 seconds. Even though the driving pressure for CO2 is lower

(PMVCO2-PACO2 = 46 mm Hg - 40 mm Hg = 6 mm Hg) than for O2 (PAO2 - PMVO2 = 100 - 40 = 60

mm Hg) the solubility of carbon dioxide is much greater. The net result is that the rates of diffusion

for carbon dioxide and oxygen are approximately equal.

Figure 2.1: Time Course for Transfer of Gas Between the Alveolus and the Capillary Blood


22

Measurement of Diffusing Capacity

The measurement of diffusing capacity is a valuable pulmonary function test. Early in the course

of interstitial disease, the diffusing capacity test may be the only one that shows abnormal values.

Measurement of diffusing capacity is also useful for following the course of a disease or its response

to treatment.

In order to accurately explain gas diffusion using Fick’s law, it is necessary to know the surface

area and membrane thickness of the alveolar-capillary membrane. However, these measurements

cannot be made in living subjects. Therefore, Fick’s equation is rearranged and terms of diffusivity,

thickness, and surface area are combined into DL,x, where X is the gas being used in the

measurement.

DL,x

V.

PA,x - Ppc,x=

(2.6)

It is very difficult to measure the diffusing capacity of the lung for oxygen, because the partial

pressure of oxygen increases along the pulmonary capillary. This problem does not occur with

carbon monoxide since its partial pressure remains essentially zero along the length of the

pulmonary capillary. The diffusing capacity of the lung for oxygen can be calculated from the

diffusing capacity of the lung for carbon monoxide by a correction factor (see below).

Single-Breath CO Method

Several techniques are used to measure diffusing capacity of the lung for carbon monoxide

(DL,CO). One of the most common tests is the single-breath CO method. Briefly, the patient rapidly

and maximally inhales a gas mixture containing a low concentration of CO and holds his/her breath

for a short period of time. The last part of the expired gas is collected and used to estimate the PACO and the uptake of CO (VCO). An advantage of this technique is that it is rapid. One disadvantage is

that some patients have difficulty holding their breath for even a short period of time. A detailed

discussion of the methodology is beyond the scope of this course. Interested readers are referred to

the chapter on diffusion (p398) in Laboratory Evaluation of Pulmonary Function, J.B. Lippincott

Company, Philadelphia. The diffusing capacity of the lung for oxygen can be calculated from the

DLCO according to DLO2 = DLCO x 1.23. This calculation takes into account the molecular weights

and solubilities of the two gases.

Effects of Exercise on Diffusing Capacity

DLCO increases with exercise. Capillaries that were previously closed or had low flow through

them are recruited; and pulmonary capillaries that were previously opened are dilated. Note: normal

subjects rarely exhibit diffusion impairment of oxygen transfer even with severe exercise except at

high altitudes, where it can be a major limitation.


23

Examples of Diseases that Affect Diffusion of Gases

Diseases Associated with Decrease Surface Area for Diffusion

Emphysema

Destruction of tissues results in destruction of alveolar walls so that a group of alveoli become

one air sac with less surface area for pulmonary blood.

Diseases that Affect “t” (“Thickness”)

Pulmonary Fibrosis

Deposition of fibrous tissue in alveolar walls.

Berylliosis

Associated with inhalation of berylium.

Asbestosis

Associated with inhalation of asbestos.

Sarcoidosis

Multiple granulomatous lesions.

Pulmonary Edema

Accumulation of fluid outside of capillaries.

IMPORTANT NOTE: It is very rare that impaired diffusion exists as a single physiological

abnormality. The process that causes the thickening of the membrane or the decrease in surface

area almost always leads to uneven ventilation, uneven capillary blood flow and therefore, uneven

matching of gas and blood.


24

Lung Mechanics

Objectives

• Know the definitions of lung volumes and capacities.

• Know the normal values for total lung capacity, functional residual capacity, tidal volume

and vital capacity.

• Know the formula for the ideal gas law and be able to convert a lung volume measured at

one set of conditions (e.g., BTPS, body temperature, pressure, saturated) to another set of

conditions (e.g., STPD, standard temperature, pressure, dry).

• Understand the measurement of lung volumes by the method of gas dilution and body

plethysmography.

• Describe how a pressure gradient is generated between the atmosphere and the alveoli.

• Know the definition of compliance, and how it is measured.

• Describe the factors involved in the elastic recoil of the lung.

• Describe the pressure-volume characteristics of the lung and chest wall. Understand the

concept of how the interaction of the lung and chest wall relates to the negative intrapleural

pressure.

• Define airways resistance. Be able to relate how airway diameter, lung volume and elastic

recoil properties of the lung affect airways resistance.

• Describe what happens during dynamic compression of the airways during a forced

ventilation.

• Predict how pathological conditions such as obstructive and restrictive lung disease affect

flow-volume curves.

NOTE: Objectives 1-4 (regarding lung volumes) will be covered in laboratory.

Overview

In order to study respiratory physiology, it is necessary to define the lung volumes and capacities

that are most commonly used to describe lung function. When the volumes are measured under

standard conditions used in pulmonary function laboratories, they can be compared between patients

or with time during the course of a disease in a single patient. Changes in these volumes and

capacities, which are the sum of more than one volume, are often indicative of lung disease.

Although it is important to know the definitions of the lung volumes and what “predicted” or normal


25

values are for these volumes, it is equally, if not more important, to understand the mechanical

factors that are involved in breathing. Taylor defines lung mechanics as the study of the pressures

acting on the respiratory system and the changes in volume that they produce. We will approach the

study of lung mechanics by:

• Defining lung volumes and capacities and how they are measured.

• Defining the pressures involved in normal breathing and how they are generated.

• Discussing the elastic recoil forces of the lung and chest wall and the pressures that must be

generated to overcome these forces in normal breathing (static behavior).

• Discuss resistances to airflow (dynamic process).

Pressures of the Respiratory System

Units of Pressure Measurements

Pressures in the cardiovascular system are usually measured in mm Hg. The units of pressure

measurement of gas tensions are also usually in mm Hg. However, when discussing lung mechanics

and ventilation, respiratory physiologists tend to measure pressure in and around the respiratory

system in cm H2O. Unless otherwise indicated, the pressure measurements are relative to

atmospheric pressure. The units of cm H2O are used because the relevant changes in pressure are

small and 760 mm Hg = 1,033 cm H2O. By convention, atmospheric pressure is referred to as 0 cm

H2O. Thus, the statement that alveolar pressure is 5 cm H2O really means that alveolar pressure is 5

cm greater than atmospheric pressure. If the measurement were made at sea level (760 mm Hg or

1,033 cm H2O), then the absolute pressure (compared to a vacuum with no pressure) would be

1,038cm H2O. Pulmonary physicians and physiologists are generally only concerned with pressures

relative to atmospheric. A pressure of -5 cm H2O means that the pressure is 5 cm H2O less than

atmospheric pressure.

Intrapleural Pressure

The pleural space is a true anatomic cavity. However, it is perhaps best to think of this space as a

tissue space. The cavity normally contains a small amount of incompressible liquid (about 0.1 to 0.3

ml/kg body weight) which probably has a low concentration of protein. There is normally no gas in

the pleural space. The fluid is spread out very thinly so that the visceral and parietal pleura do not

actually touch. But because the pleural fluid is just a small fixed volume, the lungs and the chest wall

must always change in volume by the same amount (unless a stab wound or lung rupture admits

some air into the pleural space). Pleural pressure is usually measured indirectly. The patient

swallows a soft-walled balloon attached to a pressure transducer. The balloon, which stays in the

lower part of the esophagus is in the thorax between the lungs and the chest wall. Since the

esophagus is thin-walled, changes in intrapleural pressure will be transmitted to the esophagus and to


26

the balloon inside it. For reasons that will be described later, the intrapleural pressure is normally 4

to 5 cm H2O lower than atmospheric or -4 to -5 cm H2O.

Transmural Pressures

The transmural or transwall pressure is the force that tends to distend a structure. Respiratory

physiologists are concerned with two “structures”, the lung and the chest wall and with three

transwall pressures as diagrammed above. The transpulmonary pressure (PL) is calculated by

subtracting intrapleural pressure (PPL) from alveolar pressure (PA). The transchest wall pressure is

calculated by subtracting pressure on the outside of the chest from intrapleural pressure. The

transtotal system pressure is calculated by subtracting the pressure on the outside of the chest from

alveolar pressure.


27

Recoil of the Lungs

If a person is stabbed in the chest with a knife admitting air to the pleural space, you would

observe that the lungs would collapse and the chest wall would expand. This condition is called a

pneumothorax. At normal lung volumes, the lung tends to collapse (“recoil”) and the chest wall

tends to expand. The lungs tend to collapse as a consequence of two factors:

• Collagen and elastin fibers

• Surface tension

Collagen And Elastin Fibers

The collagen and elastin fibers in the lung are functionally somewhat like nylon in nylon

stockings. Each individual fiber is not easily stretched, however, when stockings are manufactured,

the fibers are woven together in such a way that the stocking is easy to stretch or distend. Also, after

the stockings are stretched, they will return to their original size. When the inspiratory muscles

contract and expand the chest wall, the lungs are expanded. When the muscles relax, the lung tends

to “recoil” or return to its resting volume.

Surface Tension

The second force that contributes to the recoil properties of the lung is the surface tension which

exists at the alveolar gas-tissue interface. Surface tension is caused by the cohesive or attractant

force between water molecules. For example, water tends to form rounded drops due to the surface

tension generated by the attraction of water molecules to one another. The epithelium of the alveoli

is covered by a thin layer of liquid, the molecules of which will be attracted to one another making

the surface of the alveoli shrink to the smallest possible area. This tendency is offset by a unique

material called lung surfactant. Lung surfactant is synthesized by the alveolar type II cell and

secreted into the alveolar space (see Figure 3.2). Surfactant consists of both lipid and protein

components and is enriched in the lipid, dipalmitoylphosphatidylcholine (DPPC). It is generally

accepted that the DPPC is the component that is primarily responsible for reducing the surface

tension to very low levels. The DPPC is inserted perpendicularly into the gas-liquid interface so that

its non-polar, hydrophobic fatty acids (palmitate) are pointed toward the gas and its polar end is in

the liquid. The DPPC probably forms a monolayer that generates a film pressure that opposes the

surface tension. Also when the film is compressed (as the volume of the lungs is reduced) the film

pressure rises and surface tension falls even further. This property makes the lungs more stable.

The lungs of many premature babies are unable to produce adequate amounts of functional

surfactant. Approximately 50% of babies born before the 31st week of gestation will suffer from

Respiratory Distress Syndrome. Because of the lack of surfactant, the surface tension in their lungs

is high, which increases the tendency of the lungs to collapse. In addition, the babies tend to have

many other medical problems including pulmonary edema, acidosis and damage to the lung tissue

from being mechanically ventilated. New treatments with exogenous surfactants are currently being

used in hospitals world-wide and have reduced infant mortality by approximately 50%.


28

Pressure-Volume Curves of the Lung

The elastic recoil properties of the lungs can be assessed by measuring the change in lung

volume as a function of the change in transpulmonary pressure. Compliance is defined as the change

in volume divided by the change in pressure. (C = ∆V/ ∆P). Volume changes can be measured with a

spirometer. Intrapleural pressure is measured with an esophageal balloon, alveolar pressure is

measured as the pressure at the mouth when there is no airflow. The most common way to obtain a

compliance curve is to have a patient inspire to total lung capacity and then expire slowly in small

increments. When airflow is temporarily stopped, volume and transpulmonary pressure are recorded.

A pressure-volume curve such as that shown in Figure 3.3 is constructed. The slope of the pressure

volume curve at any given point is lung compliance at that point. The pressure-volume curve is not

linear, since at high lung volumes the lungs are almost maximally stretched and a large change in

pressure produces only a small change in volume. Therefore, compliance is usually measured in the

mid-range of the pressure volume curve during tidal volume breathing near the resting FRC. A

normal value for lung compliance at this point is 0.2 liter/cm H2O.

Compliance also varies with lung size. A small lung will have a smaller volume change per unit

change in transpulmonary pressure than will a large lung. Compliance is therefore usually

normalized by dividing by functional residual capacity to give specific compliance. Most

mammalian lungs have a specific compliance of 0.08/cm H2O.

Figure. 3.2: Synthesis of Surfactant

Surfactant is synthesized by type II cells and stored in unique intracellular organelles called

lamellar bodies. The lamellar body contents are secreted into the liquid covering the cells. a

monomolecular surface film of dipalmitoylphosphatidylcholine (DPPC) is formed which

lowers surface tension of the air-liquie interface. The DPPC is inserted with its fatty acids

oriented toward the air and its polar head group in the liquid.


29

Figure. 3.3: Pressure-Volume Curve of the Lung

An esophageal balloon attached to an external pressure transducer measures

changes in intrapleural pressure. Lung volume is measured with a spirometer.

Figure. 3.4: Volume vs. inflation pressure during lung inflation with air and

saline. Compliance is greater with saline.


30

Effects of Surfactant on Alveolar Stability

Alveolar stability is also affected by surface tension. Practically speaking, alveoli can be

considered to be spheres. In a sphere, surface tension creates a force that tends to pull inward and

create a pressure. The relationship between surface tension and pressure inside a sphere is shown in

Figure 3.5 and is defined by the law of Laplace. According to Laplace, transmural pressure is equal

to twice the surface tension divided by the radius (P=2T/r).

If surface tension were equal (50 dynes/cm in our example) in alveoli of different sizes, the

pressure in the smaller alveolus would be greater than the pressure in the large alveolus and the

smaller alveolus would collapse into the larger one. This alveolar collapse is known as atelectasis.

This does not normally happen because the surface tension in a lung with surfactant is not constant

at 50 dynes/cm. As described above, surfactant reduces surface tension is a nonlinear fashion; i.e., as

area is reduced, surface tension is reduced even further. Thus by lowering surface tension

proportionately more in smaller alveoli, surfactant makes it possible for alveoli of different radii to

coexist and to be stable at low lung volumes.

During normal tidal breathing, the surface area of the lung remains fairly constant and with time

the surfactant becomes “inactivated” through poorly understood mechanisms. A deep sigh or a yawn

will increase the surface area of the lungs and new surfactant will spread at the air-liquid interface.

For this reason, post-surgical patients who have had anesthesia are often encouraged to breath deeply

to enhance the spreading of surfactant and prevent lung collapse.


31

Figure. 3.5: Surfactant alters alveolar stability. In absence of surfactant, surface

tension remains constant (50 dynes/cm in this theoretical model). Alveoli of different

diameters cannot coexist because the pressure in the smaller alveolus is greater than

the pressure in the large alveolus which will cause air to flow from the small alveolus

into the large alveolus. Thus, at low lung volumes, the smaller alveolus tend to

collapse. Surfactant stabilizes the alveoli because surfactant lowers surface tension

proportionately more in the smaller alveolus. Therefore, the pressure in the two

different sized alveoli will be equal and therefore, the alveoli can coexist. T = tension,

r = radius (cm), Dynes = unit of tension


32

Lung Compliance & Disease

A very compliant lung is easy to stretch. A lung with low compliance is stiffer and

hard to stretch. Fibrosis and respiratory distress syndrome of the premature newborn are

examples of diseases which are associated with reduced lung compliance. Emphysema

destroys lung tissue and can increase lung compliance. (See Fig. 3.6)

Elastic Recoil of the Chest Wall

The chest wall also has elastic properties that are affected by the stiffness of the thoracic cage

and muscles. The elastic recoil properties of the chest wall can be affected by diseases that cause

spasticity of the abdominal or thoracic muscles. It is important to emphasize that compliance is a

meaningful term only in a passive structure. It is defined as a measure of the inherent recoil

properties of a structure. Therefore, when measuring the compliance of the chest wall it is important

that the muscles of the chest wall be relaxed.

Relaxation Pressure-Volume Curve Of The Respiratory System (Lung + Chest Wall)

Although the lungs and chest wall both have elastic properties that can be discussed separately,

in fact the two structures are connected and their functions are interdependent. As explained above a

pneumothorax causes the chest wall to spring out and the lungs to collapse. Normally the forces that

tend to collapse the lungs oppose the forces that tend to cause the chest wall to spring out. The

balance of these forces determines the resting lung volume. The relationship between the elastic

recoil of the chest wall and the elastic recoil of the lung at various lung volumes can be appreciated

by discussing a relaxation-pressure volume curve.

In order to construct a relaxation pressure-volume curve, the subject inspires or expires from a

spirometer and then relaxes her chest. Lung volume is measured with the spirometer. Intrapleural

pressure is estimated with an esophageal balloon. Alveolar pressure is estimated by measuring

pressure at the mouth during conditions of no flow. Therefore, changes in transpulmonary (PA-PPL),

trans chest wall (PPL-PB) and trans system (PA-PB) pressures can be calculated. The change in

volume of both the lungs and chest wall can be assumed to be approximately the same because the

lung and chest wall are coupled together by the cohesive forces of the fluid in the pleural space.

Remember, compliance is a property of a passive organ (no muscle contraction should be occurring).

It is useful to consider the interactions of the lung and chest wall at a few selected lung volumes.

• At FRC, the forces tending to collapse the lungs are equal but opposite to the forces tending

to expand the chest wall. This is the equilibrium volume of the lung. At FRC, Prs = 0 because

PA = PB = 0.

• At TLC, the lungs and chest wall are both tending to recoil to smaller volumes. See Figure

3.7

• At residual volume, the chest wall is tending to pull outward. This outward pull is balanced

by large negative transchestwall pressures. The lungs are still tending to collapse, although

they are only slightly stretched. This tendency to collapse is balanced by a positive

transpulmonary pressure.


33

Figure. 3.6: Deflation Pressure Curves of the “Normal” and Diseased Lung


34

END EXPIRATION: At the end of expiration, the muscles of the chest wall are relaxed. The inward

elastic recoil of the lung is balanced by the outward elastic recoil of the chest wall. Recoil tendencies

are indicated by direction of the arrows. The relative recoil tendency is indicated by the thickness of

the arrows. A high recoil tendency is indicated by a thicker arrow. Intrapleural pressure (PPL) is –0.5

cm H2O; alveolar pressure (PA) = 0 cm H2O. The translung pressure difference (PL) = +5 cm H2O).

The elastic recoil of the lungs (arrows) is equal but opposite of the elastic recoil of the chest wall.

DURING INSPIRATION: Contraction of the muscles during inspiration causes the intrapleural

pressure to become more negative. The translung pressure gradient increases and the alveoli are

distended. The tendency of the lung to recoil is greater than at end expiration (above, darker arrows).

The alveolar pressure (PA) drops below atmospheric which results in airflow into the alveoli.

Airway Resistance

Thus far we have discussed the changes in pressure that are required to overcome only the elastic

recoil tendencies of the respiratory system. These measurements were made under conditions of no

air flow. An additional force that must be overcome during normal breathing is the resistance to

airflow. Changes in airway resistance accompany many lung diseases and measurement of it is an

extremely useful diagnostic tool. Flow will depend upon the driving pressure and the resistance

according to the equation:

Flow = Pressure/Resistance.

Therefore,

Resistance = Pressure difference (cm H2O)/flow (Liters/sec)

Resistance is a constant only if airflow is laminar, or smooth. In fact airflow in the airways is not

all laminar, but is also turbulent, in which air molecules are moving laterally and colliding with each

other. Airflow can also be transitional, which is a mixture between laminar and turbulent flow.

Factors that Influence Airway Resistance

Airway Diameter

It is probably intuitive that the more narrow the airway, the higher the resistance in that

individual airways will be. What may not be intuitive is that most of the resistance to air flow is

found in the mouth, trachea and large bronchi. The reason for this is that as the airways divide and

become narrower, they also become more numerous. The small airways divide more rapidly than

their diameter decreases, therefore, the resistance of each individual airway is relatively high, but

their total-cross sectional area is so great that their combined resistance is low. Even though

relatively little of the total resistance to breathing is found in the small airways, they are the most

susceptible to disease-induced changes in resistance to air flow.

Lung Volume

The diameter of the airway lumen is affected by lung volume. The airways are not rigid and are

capable of being distended and compressed. The bronchi and the smaller airways are intimately

connected with the lung parenchyma and functionally connected to the surrounding lung tissue. At

high lung volumes the airways are “pulled” open and their resistance is lower than at low lung

volumes.


35

Elastic Recoil

Airway resistance is also affected by elastic recoil properties of the lung tissue. Airway diameter

will be affected by the transmural pressure across them. Although the airways are embedded in the

parenchyma the pressure that they are exposed to on their outside wall is close to intrapleural

pressure. Thus their transmural pressure = Pin the airways - Ppl. If elastic recoil of the lung tissue is

reduced, then pleural pressure will be less negative than normal, since the tendency of the lungs to

recoil from the chest wall will be reduced. The transmural pressure across the airways will be lower,

the airway diameter will be smaller than normal, and resistance will be higher than normal. Patients

with emphysema often have destruction of lung tissue, decreased elastic recoil (increased

compliance), and increased airway resistance.

Airway Smooth Muscle Tone

Constriction of bronchial smooth muscle will decrease the diameter of the airways and also

increase airway resistance. Parasympathetic stimulation causes contraction; sympathetic stimulation

causes relaxation. Asthmatics often have hyperreactive airways and smooth muscle contraction.

Drugs which stimulate beta-adrenergic receptors in the bronchioles cause relaxation and are often

used to treat asthmatics.

Measurement of Airway Resistance

For practical purposes we can assume that flow through the airways is laminar and that airway

resistance can be approximated by the equation: R = driving pressure/ flow = PA-Pmouth/flow. Flow

can be easily measured with a pneumotachograph. The measurement of PA is difficult. Alveolar

pressure can be measured directly by a body plethysmograph. The details of this measurement are

beyond the scope of our discussion.

Forced Expiratory Vital Capacity Curve

Examples of a normal and forced expiratory vital capacity curve are shown in Figure 3.8. This is

a somewhat indirect but very valuable assessment of airway resistance. The advantages of this

technique are that the procedure is highly reproducible, easy to perform, and sensitive. The subject

simply inhales to total lung capacity, and then exhales into a spirometer as forcefully, rapidly, and as

completely as possible. The volume expired under these conditions is called the forced vital capacity

(FVC). The volume exhaled in 1 second is called the 1-second forced expiratory volume (FEV1). It

is useful to express this value as a % of FVC (FEV1/FVC). Normally FEV1 is at least 80% of FVC.

This value will be reduced in patients such as asthmatics who have obstructed airways. The forced

expiratory flow 25-75% (FEF25-75%) can also be estimated from the same data. The flow at these

two points is connected by a straight line. Thus, the slope of this line in a patient with obstructed

airways would be less than the slope of a line obtained from a patient with normal airways.

Dynamic Airway Compression

The airways close when the pressure outside them is greater than the pressure inside them (i.e.,

transmural pressure is negative). During forced expiration, the muscles of the chest wall generate a

positive intrapleural pressure. Alveolar pressure must also be positive in order for exhalation to

occur. As air flows out of the alveoli, the pressure in the airways drops due to the resistance to flow

along the airways. Eventually the pressure drops far enough so that the airway pressure becomes less

than the intrapleural pressure and the airways collapse. Further expiratory effort will only augment


36

the compression downstream and therefore, this portion of the flow-volume curve is effort

independent. When flow stops, the airway pressure increases to equal alveolar pressure which opens

the airways. This opening and closing of the airways produces the wheezing sound often heard in

asthmatics. See Figure 3.8.

Figure. 3.8: Forced Expiratory Vital Capacity Curve


37

Figure. 3.9: Dynamic airway compression.

A decrease in elastic recoil (increased compliance) results in decreased driving

pressure and airway collapse during forced expiration.

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