Nonuniform ventilation of the alveoli can be caused by uneven resistance to airflow or nonuniform compliance in different parts of the lung. Uneven resistance to airflow may be a result of collapse of airways, as seen in emphysema; bronchoconstriction, as in asthma; decreased lumen diameter due to inflammation, as in bronchitis; obstruction by mucus, as in asthma or chronic bronchitis; or compression by tumors or edema. Uneven compliance may be a result of fibrosis, regional variations in surfactant production, pulmonary vascular congestion or edema, emphysema, diffuse or regional atelectasis, pneumothorax, or compression by tumors or cysts.
Nonuniform perfusion of the lung can be caused by embolization or thrombosis; compression of pulmonary vessels by high alveolar pressures, tumors, exudates, edema, pneumothorax, or hydrothorax; destruction or occlusion of pulmonary vessels by various disease processes; pulmonary vascular hypotension; or collapse or overexpansion of alveoli.
As already noted in Chapters 3 and 4, gravity, local factors, and regional differences in intrapleural pressure cause a degree of nonuniformity in the distribution of ventilation and perfusion in normal lungs. This will be discussed in detail later in this chapter.
The methods used for testing for nonuniform ventilation, nonuniform perfusion, and ventilation-perfusion mismatch are summarized in Table 5–1.
Testing for Nonuniform Distribution of Inspired Gas
Several methods can be used to demonstrate an abnormal distribution of ventilation in a patient.
A rising expired nitrogen concentration in phase III (the “alveolar plateau”) of the single-breath-of-oxygen test shown in Figure 3–14 indicates the possibility of a maldistribution of ventilation (see “The Closing Volume” section of Chapter 3).
The same equipment used in the single-breath-of-oxygen test mentioned above can be used in another test for nonuniform ventilation of the lungs. In this test, the subject breathes normally through a 1-way valve from a bag of 100% oxygen, and the expired nitrogen concentration is monitored over a number of breaths. With each successive inspiration of 100% oxygen and subsequent expiration, the expired end-tidal nitrogen concentration falls as nitrogen is washed out of the lung (Figure 5–3).
Illustration of a nitrogen-washout curve.
The rate of decrease of the expired end-tidal nitrogen concentration depends on several factors. A high functional residual capacity (FRC), a low tidal volume, a large dead space, or a low breathing frequency could each contribute to a slower washout of alveolar nitrogen. Nonetheless, subjects with a normal distribution of airways resistance will reduce their expired end-tidal nitrogen concentration to less than 2.5% within 7 minutes. Subjects breathing normally who take more than 7 minutes to reach an alveolar nitrogen concentration of less than 2.5% have high-resistance pathways, or “slow alveoli” (see section “Dynamic Compliance” in Chapter 2).
If the logarithms of the end-tidal nitrogen concentrations are plotted against the number of breaths taken (for a subject breathing regularly), a straight line results (Figure 5–4A). On the other hand, the log [N2] plotted for a patient with a maldistribution of airways resistance, such as that produced experimentally by inhaling a histamine aerosol (Figure 5–4B), displays a more complex curve. After a short period of relatively rapid nitrogen washout, a long period of extremely slow nitrogen washout occurs, indicating a population of poorly ventilated “slow alveoli.”
Expired nitrogen concentration versus number of breaths during a nitrogen washout. Note the logarithmic scale for the nitrogen concentration. A: Curve from a normal subject. B: Curve from a normal subject after inhalation of a histamine aerosol, which produces a marked nonuniformity of ventilation. (Reproduced with permission from Bouhuys A, Jonsson R, Lichtneckert S, et al. Effects of histamine on pulmonary ventilation in man. Clin Sci. 1960;19:79–94. © the Biochemical Society and the Medical Research Society.)
Differences between the FRC determined by the helium-dilution technique and the FRC determined using a body plethysmograph may indicate gas trapped in the alveoli because of airway closure (see Chapter 3). Furthermore, if a number of high-resistance pathways are present in the lung of the patient being tested, it may take an exceptionally long time for the patient’s expired end-tidal helium concentration to equilibrate with the helium concentration in the spirometer. The closing volume determination, discussed at the end of Chapter 3, can also demonstrate airway closure in the lung.
The methods described thus far can indicate the presence of poorly ventilated regions of the lung but not their location. Images of the whole lung taken with a scintillation counter, after the subject has taken a breath of a radioactive gas mixture such as 133Xe or 99mTc DTPA (technetium-labeled diethylene triamine pentaacetic acid) and oxygen, can indicate which regions of the lung are poorly ventilated.
Testing for Nonuniform Distribution of Pulmonary Blood Flow
These methods were all discussed briefly in Chapter 4. They include angiograms, lung scans after intravenous injection of radiolabeled (with radioactive iodine or technetium) macroaggregates of albumin, and lung scans after intravenous administration of dissolved 133Xe. Each of these methods can indicate the locations of relatively large regions of poor perfusion.
Testing for Mismatched Ventilation and Perfusion
Several methods can demonstrate the presence or location of areas of the lung with mismatched ventilation and perfusion. These methods include calculations of the physiologic shunt, the physiologic dead space, differences between the alveolar and arterial and between arterial and end-tidal (“alveolar”) , which can indicate the presence or quantity of ventilation-perfusion mismatch; and lung scans after inhaled and intravenously administered 133Xe or 99mTc, which can indicate the location of ventilation-perfusion mismatch.
Physiologic Shunts and the Shunt Equation
A right-to-left shunt is the mixing of venous blood that has not been oxygenated (or not fully oxygenated) into the arterial blood. The physiologic shunt, which corresponds to the physiologic dead space, consists of the anatomic shunts plus the intrapulmonary shunts. The intrapulmonary shunts can be absolute shunts, or they can be “shuntlike states,” that is, areas of low ventilation-perfusion ratios in which alveoli are underventilated and/or overperfused.
Anatomic shunts consist of systemic venous blood entering the left ventricle without having entered the pulmonary vasculature. In a normal healthy adult, about 2% to 5% of the cardiac output, including venous blood from the bronchial veins, the thebesian veins, and the pleural veins, enters the left side of the circulation directly without passing through the pulmonary capillaries. Therefore, the output of the left ventricle is normally greater than that of the right ventricle in adults. (This normal anatomic shunt is also occasionally referred to as the physiologic shunt because it does not represent a pathologic condition.) Pathologic anatomic shunts such as right-to-left intracardiac shunts can also occur, as in tetralogy of Fallot.
Absolute Intrapulmonary Shunts
Mixed venous blood perfusing pulmonary capillaries associated with totally unventilated or collapsed alveoli constitutes an absolute shunt (like the anatomic shunts) because no gas exchange occurs as the blood passes through the lung. Absolute shunts are sometimes also referred to as true shunts.
Alveolar-capillary units with low also act to lower the arterial oxygen content because blood draining these units has a lower than blood from units with well-matched ventilation and perfusion.
The shunt equation conceptually divides all alveolar-capillary units into two groups: those with well-matched ventilation and perfusion and those with ventilation-perfusion ratios of zero. Thus, the shunt equation combines the areas of absolute shunt (including the anatomic shunts) and the shuntlike areas into a single conceptual group. The resulting ratio of shunt flow to the cardiac output, often referred to as the venous admixture, is the part of the cardiac output that would have to be perfusing absolutely unventilated alveoli to cause the systemic arterial oxygen content obtained from a patient. A much larger portion of the cardiac output could be overperfusing poorly ventilated alveoli and yield the same ratio.
The total volume of oxygen per time entering the systemic arteries is therefore
where equals oxygen content of arterial blood in milliliters of oxygen per 100 mL of blood. This total amount of oxygen per time entering the systemic arteries is composed of the oxygen coming from the well-ventilated and well-perfused alveolar-capillary units:
The shunt fraction is usually multiplied by 100% so that the shunt flow is expressed as a percentage of the cardiac output.
The arterial and mixed venous oxygen contents can be determined if blood samples are obtained from a systemic artery and from the pulmonary artery (for mixed venous blood), but the oxygen content of the blood at the end of the pulmonary capillaries with well-matched ventilation and perfusion is, of course, impossible to measure directly. This must be calculated from the alveolar air equation, discussed in Chapter 3, and the patient’s hemoglobin concentration, which will be discussed in Chapter 7.
Alveolar-Arterial Oxygen Difference
Throughout most of this book, the alveolar and arterial are treated as though they are equal. However, the arterial is normally a few mm Hg less than the alveolar . This normal alveolar-arterial oxygen difference, the (A-a), is caused by the normal anatomic shunt, some degree of ventilation-perfusion mismatch (see later in this chapter), and diffusion limitation (see Chapter 6) in some parts of the lung. Of these, mismatch is usually the most important, with a small contribution from shunts and very little from diffusion limitation. Larger-than-normal differences between the alveolar and arterial may indicate significant ventilation-perfusion mismatch; however, increased alveolar-arterial oxygen differences (Table 5–2) can also be caused by anatomic or intrapulmonary shunts, diffusion block, low mixed venous s, breathing higher than normal oxygen concentrations, or shifts of the oxyhemoglobin dissociation curve (also see Table 8–6).
Table 5–2. Causes of Increased Alveolar-Arterial Oxygen Difference |Favorite Table|Download (.pdf)
Table 5–2. Causes of Increased Alveolar-Arterial Oxygen Difference
- Increased right-to-left shunt
- Increased ventilation-perfusion mismatch
- Impaired diffusion
- Increased inspired partial pressure of oxygen
- Decreased mixed venous partial pressure of oxygen
- Shift of oxyhemoglobin dissociation curve
Single-Breath Carbon Dioxide Test
The expired concentration of carbon dioxide can be monitored by a rapid-response carbon dioxide meter in a manner similar to that used in the single-breath tests utilizing a nitrogen meter, as described in Chapter 3 (see Figure 3–9). The alveolar plateau phase of the expired carbon dioxide concentration may show signs of poorly matched ventilation and perfusion if such regions empty asynchronously with other regions of the lung.
Lung Scans after Inhaled and Infused Markers
Lung scans after both inhaled and injected markers can be used to inspect the location and amount of ventilation and perfusion to the various regions of the lung (see Chapters 3 and 4).
Multiple Inert Gas Elimination Technique
A more specific graphic method for assessing ventilation-perfusion relationships in human subjects is called the multiple inert gas elimination technique. This technique uses the concept that the elimination via the lungs of different gases dissolved in the mixed venous blood is affected differently by variations in the ventilation-perfusion ratios of alveolar-capillary units, according to the solubility of each gas in the blood. At a ventilation-perfusion ratio of 1.0, a greater volume of a relatively soluble gas would be retained in the blood than would be the case with a relatively insoluble gas. Thus, the retention of any particular gas by a single alveolar-capillary unit is dependent on the blood-gas partition coefficient of the gas and the ventilation-perfusion ratio of the unit. Gases with very low solubilities in the blood would be retained in the blood only by units with very low (or zero) . Gases with very high solubilities in the blood would be eliminated mainly in the expired air of units with very high .
In the standard multiple inert gas elimination technique for assessing relationships, a mixture of 6 gases dissolved in saline is infused into a peripheral arm vein at a constant rate of 2 to 5 mL/min until a steady state of gas exchange is established. This usually takes about 20 minutes. The 6 gases—sulfur hexafluoride, ethane, cyclopropane, halothane, diethyl ether, and acetone—were chosen to represent a wide range of solubilities in blood, with acetone the most soluble and sulfur hexafluoride the least soluble. Samples of expired air and arterial blood are analyzed by gas chromatography to determine the concentrations of each of the 6 gases. Other data usually obtained include cardiac output by indicator dilution, minute ventilation, and arterial and mixed venous blood gases.
Examples of distributions of ventilation-perfusion ratios in normal subjects. A: The results in a young subject. B: The results in an older man. Reproduced from Wagner PD, Laravuso RB, Uhl RR, West JB. Continuous distributions of ventilation-perfusion ratios in normal subjects breathing air and 100% O2. J Clin Invest. 1974;54:54–68 by copyright permission of The American Society for Clinical Investigation.