Although the history and physical examination are essential to the diagnostic process, pulmonary signs and symptoms often lack sufficient specificity to allow a definitive conclusion. Further information is often required, such as that acquired from assessments of physiologic function, imaging studies, and sampling procedures. Singly and in combination, these studies are important components of the clinical approach to respiratory disorders.
Assessment of Gas Exchange
The ultimate function of the lungs is to replenish the supply of oxygen in the blood and to eliminate the carbon dioxide produced by metabolic activity. Measurement of the partial pressure of oxygen and of carbon dioxide in arterial blood is central to the assessment of respiratory function. Arterial blood gases are obtained from a peripheral artery in a heparinized syringe. Care should be taken to avoid or expel air bubbles, and samples should be delivered to the laboratory on ice and should be processed promptly before cellular metabolism leads to an arti-factual decrease in arterial oxygen tension (PaO2) and pH and an increase in arterial carbon dioxide tension (PaCO2).
Oxygen
Abnormalities in oxygen exchange are commonly described in relation to the alveolar PO2 (PAO2) or inspired oxygen concentration. Using the alveolar gas equation and assuming a normal resting respiratory exchange ratio (R) of 0.8 and that PaCO2 equals PACO2, PAO2 can be estimated as follows:
where PIO2 represents the inspired oxygen tension at body temperature, saturated with water.
The measured value of PaO2 is subtracted from the calculated value of PAO2 to give the alveolar-arterial difference in oxygen (A-aDO2). Normal values for A-aDO2 increase linearly with age because of a fall in PaO2 with essentially unchanged PAO2. Average values for A-aDO2 range from approximately 9 mm Hg at 20 years of age to 15 mm Hg at 70 years of age. The A-aDO2 is a commonly employed measure of the efficiency of oxygen exchange. However, even in the absence of changes in pulmonary gas exchanging function, it will change as a function of inspired oxygen fraction (FIO2), and it varies directly with cardiac output. The arterial-alveolar oxygen ratio, PaO2/PAO2, is somewhat more stable over varying inspired oxygen concentrations. The arterial-inspired oxygen ratio, PaO2/FIO2, is now widely used to quantitate abnormalities of oxygenation in critical care unit patients. A PaO2/FIO2 ratio of less than 250 indicates the presence of mild acute lung injury, and a PaO2/Fp2 ratio of less than 100 indicates a severe disorder.
Abnormalities of oxygen exchange are most commonly caused by mismatching of pulmonary ventilation (V) and perfusion (Q) or by shunting. Impaired diffusion across the alveolar-capillary membrane generally does not cause abnormalities in oxygenation at rest but can cause abnormalities during exercise and at high a.ltit.udes. Abnormalities caused by diffusion impairment and V/Q mismatching can be corrected by increasing the Fp2 and can be completely abolished by 100% inspired oxygen. Hypoxemia caused by shunts, which may be pulmonary or intracardiac, is not corrected by the administration of 100% inspired oxygen. By contrast, other causes of hy-poxemia, such as hypoventilation and low inspired O2 concentration, do not cause an increase in A-aDO2.
Systemic Oxygen Transport
The total amount of O2 delivered to the systemic circulation is the product of the cardiac output and the O2 content per unit of arterial blood (CaO2). The CaO2 is determined by the concentration and characteristics of hemoglobin and the arterial oxygen saturation (SaO2), as indicated by the following equation:
The last term in the equation reflects the amount of oxygen that is normally bound to fully saturated hemoglobin, the so-called carrying capacity of normal hemoglobin. The arterial O2 saturation refers to the percentage of the total O2 binding sites on hemoglobin that is actually occupied by O2. The SaO2 is in turn determined by the PaO2 and the physicochemical properties of hemoglobin, as reflected by the oxygen-hemoglobin dissociation curve [see Figure 1]. In the presence of acidemia, fever, elevated concentrations of 2,3-diphosphoglycerate, and certain abnormal hemoglobin types (e.g., hemoglobin Kansas), the oxy-gen-hemoglobin dissociation curve shifts to the right, which gives a decreased affinity of hemoglobin for oxygen and increased availability of oxygen to tissues. Alkalemia, hypothermia, and other abnormal hemoglobin types (e.g., hemoglobin Chesapeake) have the opposite effect and shift the position of the curve to the left, reflecting an increased affinity of hemoglobin for oxygen and reduced availability of oxygen to tissues.
Table 1 Categorization of Hypoxemia
|
Cause |
Example |
 |
 |
 |
 |
|
Low inspired oxygen tension |
Mountaineering |
 |
 |
Normal |
Good |
|
Hypoventilation |
Drug overdose |
 |
 |
Normal |
Good |
|
Diffusion impairment |
Pulmonary fibrosis plus exercise |
 |
 |
 |
Good |
|
Ventilation-perfusion imbalance |
Chronic obstructive pulmonary disease; pneumonia |
 |
 |
 |
Good |
|
Right-to-left shunt |
Pulmonary edema |
 |
 |
 |
Poor or none |
Figure 1 The relation between arterial oxygen tension (PaO2) and the percentage of oxygen binding sites on hemoglobin that are saturated by oxygen is shown by the oxygen-hemoglobin dissociation curve. The sigmoidal shape of the normal curve reflects the cooperative binding of oxygen by hemoglobin. An alteration in pH or body temperature, a change in the concentration of 2,3-diphosphoglycerate, or the presence of certain abnormal hemoglobin types shifts the curve to the left or right, so that at any given PaO2, the hemoglobin saturation will be correspondingly increased or decreased. Carboxyhemoglobinemia, in which the oxygen binding sites of hemoglobin are occupied by carbon monoxide, results in both a deformation of the shape of the dissociation curve and a reduction in the maximum number of binding sites that are available to oxygen.
Anemia does not alter PaO2 or SaO2. Anemia does, however, reduce the value for CaO2 and will decrease O2 delivery to the tissues if there is not a commensurate increase in cardiac output. A fixed change in PaO2 causes a considerably larger change in SaO2 over the steep portion of the oxygen-hemoglobin dissociation curve than it does over flatter portions of the curve. For instance, with a fall in PaO2 from 100 mm Hg to 90 mm Hg, SaO2 decreases from 97.4% to 96.8%, assuming that hemoglobin type is normal and physiologic conditions are standard—pH of 7.40 and body temperature of 37° C (98.6° F). In contrast, a 10 mm Hg decrement in PaO2 from 55 mm Hg to 45 mm Hg causes the SaO2 to decrease from 88.2% to 80.5%.
A profound reduction in arterial O2 content may be observed without a significant change in PaO2 if O2 binding to hemoglobin is acutely altered, as occurs in carbon monoxide intoxication. Because of the strong affinity of carbon monoxide for hemoglobin, an arterial carbon monoxide tension (PaCO) of less than 1 mm Hg is sufficient to cause a 50% saturation of hemoglobin with CO. Under these conditions, PaO2 may be 100 mm Hg, but severe tissue hypoxia may be present because SaO2 and CaO2 values have been reduced by half.1
Oximetry
Oxygenation can be monitored noninvasively by pulse oximetry. A pulse oximeter, placed on either a finger or an ear-lobe, measures the absorption of red (660 nM) and near infrared (940 nM) light through these tissue beds to estimate the ratio:
By assuming the pulsatile portion of the signal represents arterial blood and by comparing the ratio of the pulsatile portion to the nonpulsatile component to a calibration curve of known mixtures of oxyhemoglobin and reduced hemoglobin, the pulse oximeter is capable of estimating SaO2. Oximetric estimates are accurate to within ± 1% to 2% for true saturations above 90%. Accuracy deteriorates at saturations below 80%, with errors of ± 5% to 8%. Pulse oximetry is commonly used in emergency and critical care settings, for in-hospital patient transportation, and for assessing oxygenation during sleep. Medicare guidelines allow the use of resting pulse oximetry for determination of qualification for long-term oxygen therapy, but arterial blood gas measurements are still necessary for exercise evaluations for adjudication of disability under Social Security Administration regulations. Accuracy of pulse oximetry is reduced by carboxy-hemoglobin, methemoglobin, anemia, motion, bright ambient light, poor perfusion, nail polish, and darkly pigmented skin.2
Carbon Dioxide
Physiologic mechanisms normally act to maintain the PACO2 level within a narrow range (35 to 45 mm Hg) despite large changes in metabolic CO2 production. Elevated PACO2 levels (> 45 mm Hg) are termed hypoventilation, and low PACO2 values (< 35 mm Hg) are termed hyperventilation. Corresponding alterations in PaCO2 are termed hypercapnia and hypocapnia, respectively. The PaCO2 level is directly proportional to the ratio of carbon dioxide production to alveolar ventilation:
where Vco2 equals V x Feco2 and represents the amount of CO2 (in ml/min) produced by the body’s metabolism; and K is a constant (equal to 0.863) that reflects the fact that gas exchange occurs at normal body temperature under conditions of full saturation with water, assuming Paco2 is equal to Paco2. Thus, for any given level of Vco^ the alveolar (and arterial) Pco2 is determined by the level of alveolar ventilation. Hypercapnia is categorized according to causes [see Table 2].
Ventilation
Alveolar ventilation (V) is that portion of the minute ventilation (VE) that comes into equilibrium with alveolar gas and represents the difference between VE and dead space ventilation (VD). A decrease in V results from either a reduction in VE or an increase in VD.
Minute ventilation is the volume of gas that moves in and out of the lung. The minute ventilation can be calculated by multiplying the respiratory frequency (f) and the tidal volume (VT), which is the volume of air expired with each breath. Typical resting values in the adult are as follows: respiratory frequency,14 breaths/min; tidal volume, 400 ml/breath; and minute ventilation, 5.6 L/min. However, there is considerable variability in these values among normal persons and in the same person throughout the day.
Table 2 Categorization of Hypercapnia
|
Cause |
Example |
 |
 |
 |
 |
|
Defective central control of breathing |
Drug overdose |
 |
 |
 |
 |
|
Neuromuscular disease |
Amyotrophic lateral sclerosis |
 |
 |
 |
 |
|
Chest wall disease |
Kyphoscoliosis |
 |
 |
 |
 |
|
Primary lung disease |
Chronic obstructive pulmonary disease |
 |
 |
 |
 |
Dead space consists of two types: anatomic and functional (also called physiologic). Anatomic dead space is the portion of inspired tidal volume that does not communicate with perfused alveoli and therefore does not participate in gas exchange. Anatomic dead space consists of the tracheobronchial tree from the oropharynx and nasopharynx down through the nonalveo-lated terminal bronchioles. The volume of the anatomic dead space in milliliters is roughly equal to a person’s lean body weight in pounds. Functional dead space ventilation is the sum of the excess ventilation relative to perfusio.n f.or all lung units where the ratio of ventilation to perfusion (V/Q) is significantly greater than 1.
A fixed volume of gas from each breath is required to fill the anatomic dead space. For any VE, fast and shallow breathing wastes a greater percentage of the minute ventilation because the anatomic dead space is proportionately greater as tidal volume decreases. Conversely, the alveolar ventilation at any VE is greatest when breathing is slow and deep [see Figure 2]. Additionally, dead space ventilation can be caused by inequalities in the distribution of alveolar ventilation and perfusion. Certain lung regions have greater ventilation than perfusion. The excess of regional ventilation to blood flow can be thought of as wasted, although in most disease states, the mismatch is caused by regional deficits in perfusion rather than excessive ventilation.
Dead space can be assessed by measuring the fractional concentration of CO2 in exhaled gas (Feco2) and by estimating the fractional concentration of CO2 in alveolar gas (Faco2). The Faco2 is estimated by assuming ideal alveolar air conditions, in which Paco2 values are equal to Paco2 values. VD/VT, the so-called dead space fraction, is calculated as follows:
The normal value for VD/VT is less than 0.4. The increased work demands imposed by a high VD/VT contribute significantly to dyspnea and often to respiratory failure in clinical lung disease.
Pulmonary Function Tests
Pulmonary function testing is used to categorize the nature and severity of pathophysiologic disturbances, to follow the progression of known cardiopulmonary disorders, and to measure the response to therapy. Pulmonary function is often used as the basis for the definition of disability for insurance purposes. Lung resection is the only indication for preoperative pulmonary function testing for which a consensus currently exists.otherwise, such testing offers little additional benefit over clinical parameters in assessing the risk for postoperative pulmonary complications, and prohibitive thresholds cannot be reliably established. A review reported that abnormal pulmonary function predicted a significantly increased relative risk for postoperative pulmonary complications in only four of 11 studies.3
The most commonly used pulmonary function tests are based on the forced vital capacity maneuver, measurements of lung volumes, and pulmonary diffusion capacity. Recording of the forced vital capacity maneuver produces a record of volume versus time, flow versus volume, or both during a forced exhalation from total lung capacity (TLC) to residual volume (RV). Forced vital capacity (FVC) is measured with a spirometer and is the most basic and useful lung function test. The test is simple and highly reproducible. However, valid values require maximal efforts by the patient, and these efforts may be compromised by pain or debilitation. The forced vital capacity maneuver shows whether obstruction is present and, if present, quan-titates the severity. If there is no obstruction, a reduced vital capacity indicates restriction. In the absence of obstruction, the severity of restriction is defined by comparing vital capacity with the value predicted according to the patient’s height, sex, age, and race.
