Lung Volumes
Static volumes of the lung are measured with a spirometer (Table 51). Typically, the subject is sitting and breathes into and out of the spirometer, displacing a bell. The volume displaced is recorded on calibrated paper (Fig. 52).
Table 5–1 Abbreviations and Normal Values Associated with Respiratory Physiology
Abbreviation 
Meaning 
Normal Value 
P 
Gas pressure or partial pressure 

Blood flow 

V 
Gas volume 

Gas flow rate 

F 
Fractional concentration of gas 

A 
Alveolar gas 

a 
Arterial blood 

V 
Venous blood 

E 
Expired gas 

I 
Inspired gas 

L 
Transpulmonary 

TM 
Transmural 

Arterial Blood 

Partial pressure of O2 in arterial blood 
100 mm Hg 

Partial pressure of CO2 in arterial blood 
40 mm Hg 

Mixed Venous Blood 

Partial pressure of O2 in venous blood 
40 mm Hg 

Partial pressure of CO2 in venous blood 
46 mm Hg 

Inspired Air 

Partial pressure of O2 in dry inspired air 
160 mm Hg 

Partial pressure of CO2 in dry inspired air 
0 mm Hg 

Alveolar Air 

Partial pressure of O2 in alveolar air 
100 mm Hg 

Partial pressure of CO2 in alveolar air 
40 mm Hg 

Respiratory Volumes and Rates 

TLC 
Total lung capacity 
6.0 L 
FRC 
Functional residual capacity 
2.4 L 
VC 
Vital capacity 
4.7 L 
VT 
Tidal volume 
0.5 L 
Alveolar ventilation 
— 

— 
Breathing rate 
15 breaths/min 
VD 
Physiologic dead space 
0.15 L 
FVC 
Forced vital capacity 
4.7 L 
FEV1 
Volume of forced vital capacity expired in 1 second 
— 
Constants 

Patm, or PB 
Atmospheric (barometric) pressure 
760 mm Hg (sea level) 
PH2o 
Water vapor pressure 
47 mm Hg (37°C) 
STPD 
Standard temperature, pressure, dry 
273 K, 760 mm Hg 
BTPS 
Body temperature, pressure, saturated 
310 K, 760 mm Hg, 47 mm Hg 
— 
Solubility of O2 in blood 
0.003 mL O2/100 mL blood/mm Hg 
— 
Solubility of CO2 in blood 
0.07 mL CO2/100 mL blood/mm Hg 
Other Values 

— 
Hemoglobin concentration 
15 g/100 mL blood 
— 
O2binding capacity of hemoglobin 
1.34 mL O2/g hemoglobin 
O2 consumption 
250 mL/min 

CO2 production 
200 mL/min 

R 
Respiratory exchange quotient (CO2 production/O2 consumption) 
0.8 
Figure 5–2 Lung volumes and capacities. Measurements of lung volumes and capacities are made by spirometry. Residual volume cannot be measured by spirometry.
First, the subject is asked to breathe quietly. Normal, quiet breathing involves inspiration and expiration of a tidal volume (VT). Normal tidal volume is approximately 500 mL and includes the volume of air that fills the alveoli plus the volume of air that fills the airways.
Next, the subject is asked to take a maximal inspiration, followed by a maximal expiration. With this maneuver, additional lung volumes are revealed. The additional volume that can be inspired above tidal volume is called the inspiratory reserve volume, which is approximately 3000 mL. The additional volume that can be expired below tidal volume is called the expiratory reserve volume, which is approximately 1200 mL.
The volume of gas remaining in the lungs after a maximal forced expiration is the residual volume (RV), which is approximately 1200 mL and cannot be measured by spirometry.
Lung Capacities
In addition to these lung volumes, there are several lung capacities; each lung capacity includes two or more lung volumes. The inspiratory capacity (IC) is composed of the tidal volume plus the inspiratory reserve volume and is approximately 3500 mL (500 mL + 3000 mL). The functional residual capacity (FRC) is composed of the expiratory reserve volume (ERV) plus the residual volume, or approximately 2400 mL (1200 mL + 1200 mL). FRC is the volume remaining in the lungs after a normal tidal volume is expired and can be thought of as the equilibrium volume of the lungs. The vital capacity (VC) is composed of the inspiratory capacity plus the expiratory reserve volume, or approximately 4700 mL (3500 mL + 1200 mL). Vital capacity is the volume that can be expired after maximal inspiration. Its value increases with body size, male gender, and physical conditioning and decreases with age. Finally, as the terminology suggests, the total lung capacity (TLC) includes all of the lung volumes: It is the vital capacity plus the residual volume, or 5900 mL (4700 mL + 1200 mL).
Because residual volume cannot be measured by spirometry, lung capacities that include the residual volume also cannot be measured by spirometry (i.e., FRC and TLC). Of the lung capacities not measurable by spirometry, the FRC (the volume remaining in the lungs after a normal expiration) is of greatest interest because it is the resting or equilibrium volume of the lungs.
Two methods are used to measure FRC: helium dilution and the body plethysmograph.
In the helium dilution method, the subject breathes a known amount of helium, which has been added to the spirometer. Because helium is insoluble in blood, after a few breaths the helium concentration in the lungs becomes equal to that in the spirometer, which can be measured. The amount of helium that was added to the spirometer and its concentration in the lungs are used to “backcalculate” the lung volume. If this measurement is made after a normal tidal volume is expired, the lung volume being calculated is the FRC.
The body plethysmograph employs a variant of Boyle’s law, which states that for gases at constant temperature, gas pressure multiplied by gas volume is constant (P × V = constant). Therefore, if volume increases, pressure must decrease, and if volume decreases, pressure must increase. To measure FRC, the subject sits in a large airtight box called a plethysmograph. After expiring a normal tidal volume, the mouthpiece to the subject’s airway is closed. The subject then attempts to breathe. As the subject tries to inspire, the volume in the subject’s lungs increases and the pressure in his or her lungs decreases. Simultaneously, the volume in the box decreases, and the pressure in the box increases. The increase in pressure in the box can be measured and, from it, the preinspiratory volume in the lungs can be calculated, which is the FRC.
Dead Space
Dead space is the volume of the airways and lungs that does not participate in gas exchange. Dead space is a general term that refers to both the anatomic dead space of the conducting airways and a functional, or physiologic, dead space.
Anatomic Dead Space
The anatomic dead space is the volume of the conducting airways including the nose (and/or mouth), trachea, bronchi, and bronchioles. It does not include the respiratory bronchioles and alveoli. The volume of the conducting airways is approximately 150 mL. Thus, for example, when a tidal volume of 500 mL is inspired, the entire volume does not reach the alveoli for gas exchange. 150 mL fills the conducting airways (the anatomic dead space, where no gas exchange occurs), and 350 mL fills the alveoli. Figure 53 shows that at the end of expiration the conducting airways are filled with alveolar air; that is, they are filled with air that has already been in the alveoli and exchanged gases with pulmonary capillary blood. With the inspiration of the next tidal volume, this alveolar air is first to enter the alveoli, although it will not undergo further gas exchange (“already been there, done that”). The next air to enter the alveoli is fresh air from the inspired tidal volume (350 mL), which will undergo gas exchange. The rest of the tidal volume (150 mL) does not make it to the alveoli but remains in the conducting airways; this air will not participate in gas exchange and will be the first air expired. (A related point arises from this discussion: The first air expired is dead space air that has not undergone gas exchange. To sample alveolar air, one must sample endexpiratory air.)
Figure 5–3 Anatomic dead space. One third of each tidal volume fills the anatomic dead space. VT, Tidal volume.
Physiologic Dead Space
The concept of physiologic dead space is more abstract than the concept of anatomic dead space. By definition, the physiologic dead space is the total volume of the lungs that does not participate in gas exchange. Physiologic dead space includes the anatomic dead space of the conducting airways plus a functional dead space in the alveoli.
The functional dead space can be thought of as ventilated alveoli that do not participate in gas exchange. The most important reason that alveoli do not participate in gas exchange is a mismatch of ventilation and perfusion, or socalled ventilation/perfusion defect, in which ventilated alveoli are not perfused by pulmonary capillary blood.
In normal persons, the physiologic dead space is nearly equal to the anatomic dead space. In other words, alveolar ventilation and perfusion (blood flow) are normally well matched and functional dead space is small. In certain pathologic situations, however, the physiologic dead space can become larger than the anatomic dead space, suggesting a ventilation/perfusion defect. The ratio of physiologic dead space to tidal volume provides an estimate of how much ventilation is “wasted” (either in the conducting airways or in nonperfused alveoli).
The volume of the physiologic dead space is estimated with the following method, which is based on the measurement of the partial pressure of CO2 (PCO2) of mixed expired air () and the following three assumptions: (1) All of the CO2 in expired air comes from exchange of CO2 in functioning (ventilated and perfused) alveoli; (2) there is essentially no CO2 in inspired air; and (3) the physiologic dead space (nonfunctioning alveoli and airways) neither exchanges nor contributes any CO2. If physiologic dead space is zero, then will be equal to alveolar PCO2 (). However, if a physiologic dead space is present, then will be “diluted” by dead space air and will be less than by a dilution factor. Therefore, by comparing with , the dilution factor (i.e., volume of the physiologic dead space) can be measured. A potential problem in measuring physiologic dead space is that alveolar air cannot be sampled directly. This problem can be overcome, however, because alveolar air normally equilibrates with pulmonary capillary blood (which becomes systemic arterial blood). Thus, the PCO2 of systemic arterial blood () is equal to the PCO2 of alveolar air (). Using this assumption, the volume of physiologic dead space is calculated by the following equation:
where
VD 
= Physiologic dead space (mL) 
VT 
= Tidal volume (mL) 
= of arterial blood (mm Hg) 

= of mixed expired air (mm Hg) 
In words, the equation states that the volume of the physiologic dead space is the tidal volume (volume inspired with a single breath) multiplied by a fraction. The fraction represents the dilution of alveolar PCO2 by dead space air (which contributes no CO2).
To better appreciate the equation and its application, consider two extreme examples. In the first example, assume that physiologic dead space is zero; in the second example, assume that physiologic dead space is equal to the entire tidal volume. In the first example, in which dead space is zero, the PCO2 of expired air () will be the same as the PCO2 of alveolar gas () and arterial blood () because there is no “wasted” ventilation: The fraction in the equation is equal to zero, and thus the calculated value of VD is zero. In the second example, in which dead space is equal to the entire tidal volume, there is no gas exchange: Therefore, will be zero, the fraction will be 1.0, and VD will be equal to VT.
Ventilation Rates
Ventilation rate is the volume of air moved into and out of the lungs per unit time. Ventilation rate can be expressed either as the minute ventilation, which is the total rate of air movement into and out of the lungs, or as alveolarventilation, which corrects for the physiologic dead space. To calculate alveolar ventilation, the physiologic dead space first must be measured, which involves sampling systemic arterial blood, as described in the preceding section.
Minute ventilation is given by the following equation:
Alveolar ventilation is minute ventilation corrected for the physiologic dead space and is given by the following equation:
where
= Alveolar ventilation (mL/min) 

VT 
= Tidal volume (mL) 
VD 
= Physiologic dead space (mL) 
SAMPLE PROBLEM. A man who has a tidal volume of 550 mL is breathing at a rate of 14 breaths/min. The Pco2 in his arterial blood is 40 mm Hg, and the Pco2 in his expired air is 30 mm Hg. What is his minute ventilation? What is his alveolar ventilation? What percentage of each tidal volume reaches functioning alveoli? What percentage of each tidal volume is dead space?
SOLUTION. Minute ventilation is tidal volume times breaths per minute, or:
Alveolar ventilation is minute ventilation corrected for the physiologic dead space, which must be calculated. This problem illustrates the usual method of assessing physiologic dead space, which represents structures that are ventilated but are not exchanging CO2.
Thus, alveolar ventilation () is
If tidal volume is 550 mL and physiologic dead space is 138 mL, then the volume of fresh air reaching functioning alveoli on each breath is 412 mL, or 75% of each tidal volume. Dead space is, accordingly, 25% of each tidal volume.
Alveolar Ventilation Equation
The alveolar ventilation equation is the fundamental relationship of respiratory physiology and describes the inverse relationship between alveolar ventilation and alveolar PCO2 (). The alveolar ventilation equation is expressed as follows:
or, rearranging,
where
The constant, K, equals 863 mm Hg for conditions of BTPS and when and are expressed in the same units (e.g., mL/min). BTPS means body temperature (310 K), ambient pressure (760 mm Hg), and gas saturated with water vapor.
Using the rearranged form of the equation, alveolar PCO2 can be predicted if two variables are known: (1) the rate of CO2 production from aerobic metabolism of the tissues and (2) alveolar ventilation,which excretes this CO2in expired air.
A critical point to be understood from the alveolar ventilation equation is that if CO2production is constant, then is determined by alveolar ventilation. For a constant level of CO2 production, there is a hyperbolic relationship between PACO2 and (Fig. 54). Increases in alveolar ventilation cause a decrease in ; conversely, decreases in alveolar ventilation cause an increase in .
Figure 5–4 Alveolar or arterial PCO2 as a function of alveolar ventilation. The relationship is described by the alveolar ventilation equation. When CO2 production doubles from 200 mL/min to 400 mL/min, alveolar ventilation also must double to maintain the and at 40 mm Hg.
An additional critical point, which is not immediately evident from the equation, is that because CO2 always equilibrates between pulmonary capillary blood and alveolar gas, the arterial () always equals the alveolar (). Consequently, , which can be measured, can be substituted for in the earlier discussion.
So, why does arterial (and alveolar) PCO2 vary inversely with alveolar ventilation? To understand the inverse relationship, first appreciate that alveolar ventilation is pulling CO2 out of pulmonary capillary blood. With each breath, CO2free air is brought into the lungs, which creates a driving force for CO2 diffusion from pulmonary capillary blood into the alveolar gas; the CO2 pulled out of pulmonary capillary blood will then be expired. The higher the alveolar ventilation, the more CO2 is pulled out of the blood and the lower the and the (because alveolar always equilibrates with arterial ). The lower the alveolar ventilation, the less CO2 is pulled out of the blood and the higher the and .
Another way to think about the alveolar ventilation equation is to consider how the relationship between and would be altered by changes in CO2 production. For example, if CO2 production, or , doubles (e.g., during strenuous exercise), the hyperbolic relationship between and shifts to the right (see Fig. 54). Under these conditions, the only way to maintain at its normal value (i.e., 40 mm Hg) is for alveolar ventilation to also double. The graph confirms that if CO2 production increases from 200 mL/min to 400 mL/min, is maintained at 40 mm Hg if, simultaneously, increases from 5 L/min to 10 L/min.
Alveolar Gas Equation
The alveolar ventilation equation describes the dependence of alveolar and arterial PCO2 on alveolar ventilation. A second equation, the alveolar gas equation, is used to predict the alveolar PO2, based on the alveolar PCO2, and is illustrated by the O2CO2 diagram in Figure 55. The alveolar gas equation is expressed as
Figure 5–5 PCO2 as a function of PO2. The relationship is described by the alveolar gas equation. The variations in PO2 between inspired air and mixed venous blood are much greater than the variations in PCO2.
where
= Alveolar (mm Hg) 

= PO2 in inspired air (mm Hg) 

= Alveolar (mm Hg) 

R 
= Respiratory exchange ratio or respiratory quotient (CO2 production/O2 consumption) 
The correction factor is small and usually is ignored. In the steady state, R, the respiratory exchange ratio, equals the respiratory quotient. According to the earlier alveolar ventilation equation, when alveolar ventilation is halved, doubles (because less CO2 is removed from the alveoli). A second consequence of halving alveolar ventilation is that will decrease (a decrease in alveolar ventilation means that less O2 is brought into the alveoli). The alveolar gas equation predicts the change in that will occur for a given change in . Because the normal value for the respiratory exchange ratio is 0.8, when alveolar ventilation is halved, the decrease in will be slightly greater than the increase in . To summarize, when is halved, is doubled and is slightly more than halved.
Further inspection of the alveolar gas equation reveals that if for some reason the respiratory exchange ratio changes, the relationship between and also changes. As stated, the normal value of the respiratory exchange ratio is 0.8. However, if the rate of CO2 production decreases relative to the rate of O2 consumption (e.g., if the respiratory quotient and respiratory exchange ratio are 0.6 rather than 0.8), then would decrease relative to .
SAMPLE PROBLEM. A man has a rate of CO2 production that is 80% the rate of O2 consumption. If his arterial PCO2 is 40 mm Hg and the PO2 in humidified tracheal air is 150 mm Hg, what is his alveolar PO2?
SOLUTION. To solve this problem, a basic assumption is that CO2 equilibrates between arterial blood and alveolar air. Thus, (needed for the alveolar gas equation) equals (given in the problem). Using the alveolar gas equation, can be calculated from if the respiratory quotient and the PO2 of inspired air are known. It is stated that CO2 production is 80% of O2 consumption; thus, the respiratory quotient is 0.8, a normal value. is calculated as follows:
This calculated value for can be confirmed on the O2CO2 diagram shown in Figure 54. The graph indicates that alveolar gas or arterial blood with a PCO2 of 40 mm Hg will have a PO2 of 100 mm Hg when the respiratory quotient is 0.8—exactly the value calculated by the alveolar gas equation!
Forced Expiratory Volumes
Vital capacity is the volume that can be expired following a maximal inspiration. Forced vital capacity (FVC) is the total volume of air that can be forcibly expired after a maximal inspiration, as shown inFigure 56. The volume of air that can be forcibly expired in the first second is called FEV1. Likewise, the cumulative volume expired in 2 seconds is called FEV2, and the cumulative volume expired in 3 seconds is called FEV3. Normally, the entire vital capacity can be forcibly expired in 3 seconds, so there is no need for “FEV4.”
Figure 5–6 FVC and FEV1 in normal subjects and patients with lung disease. Subjects inspired maximally and then expired forcibly. A–C, The graphs show the phase of forced expiration. The total volume that is forcibly expired is called the forced vital capacity (FVC). The volume expired in the first second is called FEV1.
FVC and FEV1 are useful indices of lung disease. Specifically, the fraction of the vital capacity that can be expired in the first second, FEV1/FVC, can be used to differentiate among diseases. For example, in a normal person, FEV1/FVC is approximately 0.8, meaning that 80% of the vital capacity can be expired in the first second of forced expiration (see Fig. 56A). In a patient with an obstructive lung disease such as asthma, both FVC and FEV1 are decreased, but FEV1 is decreased more than FVC is. Thus, FEV1/FVC is also decreased, which is typical of airway obstruction with increased resistance to expiratory airflow (see Fig. 56B). In a patient with a restrictive lung disease such as fibrosis, both FVC and FEV1 are decreased but FEV1 is decreased less than FVC is. Thus, in fibrosis, FEV1/FVC is actually increased (see Fig. 56C).