Gas exchange is measured through several means, including diffusing capacity for carbon monoxide, pulse oximetry, and arterial blood gas sampling.
Diffusing Capacity for Carbon Monoxide
The diffusing capacity for carbon monoxide (DLco) is a measure of the ability of gas to transfer from the alveoli across the alveolar epithelium and the capillary endothelium to the RBCs. The DLco depends not only on the area and thickness of the blood-gas barrier but also on the volume of blood in the pulmonary capillaries. The distribution of alveolar volume and ventilation also affects the measurement.
DLco is measured by sampling end-expiratory gas for carbon monoxide (CO) after patients inspire a small amount of CO, hold their breath, and exhale. Measured DLco should be adjusted for alveolar volume (which is estimated from dilution of helium) and the patient's Hct. DLco is reported as mL/min/mm Hg and as a percentage of a predicted value.
Conditions that decrease DLco:
Conditions that primarily affect the pulmonary vasculature, such as primary pulmonary hypertension and pulmonary embolism, decrease DLco. Conditions that affect the lung diffusely, such as emphysema and pulmonary fibrosis, decrease both DLco and alveolar ventilation (VA). Reduced DLco also occurs in patients with previous lung resection because total lung volume is smaller, but DLco corrects to or even exceeds normal when adjusted for VA because increased additional vascular surface area is recruited in the remaining lung. Anemic patients have lower DLco values that correct when adjusted for Hb.
Conditions that increase DLco:
DLco may be higher than predicted in patients with heart failure, presumably because the increased pulmonary venous and arterial pressure recruits additional pulmonary microvessels. DLco is also increased in patients with erythrocythemia, in part because of increased Hct and because of the vascular recruitment that occurs with increased pulmonary pressures due to increased viscosity. DLco is increased in patients with alveolar hemorrhage because RBCs in the alveolar space can also bind CO. DLco is also increased in patients with asthma. Although this increase is attributed to presumed vascular recruitment, recent data suggest it may also be due to growth factor–stimulated neovascularization.
Transcutaneous pulse oximetry estimates O2 saturation (Spo2) of capillary blood based on the absorption of light from light-emitting diodes positioned in a finger clip or adhesive strip probe. The estimates are generally very accurate and correlate to within 5% of measured arterial O2 saturation (Sao2). Results may be less accurate in patients with highly pigmented skin; patients wearing nail polish; and patients with arrhythmias, hypotension, or profound systemic vasoconstriction, in whom the amplitude of the signal may be dampened. Also, pulse oximetry is able to detect only oxyhemoglobin or reduced Hb but not other types of Hb (eg, carboxyhemoglobin, methemoglobin); those types are assumed to be oxyhemoglobin and falsely elevate the Spo2 measurement.
Arterial Blood Gas Sampling
ABG sampling is done to obtain accurate measures of Pao2, Paco2, and blood pH; these variables combined with the patient's temperature allow for calculation of HCO3 level (which can also be measured directly from venous blood) and Sao2. ABG sampling can also accurately measure carboxyhemoglobin and methemoglobin.
The radial artery is usually used. Because arterial puncture in rare cases leads to thrombosis and impaired perfusion of distal tissue, Allen's test is first done to ensure adequate collateral circulation. With this maneuver, the radial and ulnar pulses are simultaneously occluded until the hand becomes pale. The ulnar pulse is then released while the pressure on the radial pulse is maintained. A blush across the entire hand within 7 sec of release of the ulnar pulse suggests adequate flow through the ulnar artery.
Under sterile conditions, a 22- to 25-gauge needle attached to a heparinized syringe is inserted just proximal to the maximal impulse of the radial arterial pulse and advanced slightly distally into the artery until pulsatile blood is returned. Systolic BP often pushes back the syringe plunger. After 3 to 5 mL of blood is collected, the needle is quickly withdrawn, and firm pressure is applied to the puncture site to facilitate hemostasis. Simultaneously, the ABG specimen is placed on ice to reduce O2 consumption and CO2 production by WBCs and is sent to the laboratory.
Hypoxemia is a decrease in Po2 in arterial blood; hypoxia is a decrease in the Po2 in the tissue. ABGs accurately assess the presence of hypoxemia, which is generally defined as a Pao2 low enough to reduce the Sao2 below 90% (ie, Pao2 < 60 mm Hg). Abnormalities in Hb (eg, methemoglobin), higher temperatures, lower pH, and higher levels of 2,3-diphosphoglycerate reduce Hb O2 saturation despite an adequate Pao2, as indicated by the oxyhemoglobin dissociation curve (see Fig. 4: Oxyhemoglobin dissociation curve.).
Causes of hypoxemia can be classified based on whether the alveolar-arterial Po2 gradient [(A-a)Do2], defined as the difference between alveolar O2 tension (PAo2) and Pao2, is elevated or normal. PAo2 is calculated as follows:
where Fio2 is the fraction of inspired O2 (eg, 0.21 at room air), Patm is the ambient barometric pressure (eg, 760 mm Hg at sea level), PH2O is the partial pressure of water vapor (eg, usually 47 mm Hg), Paco2 is the measured partial pressure of arterial CO2, and R is the respiratory quotient, which is assumed to be 0.8 in a resting patient eating a normal diet.
For patients at sea level and breathing room air, Fio2 = 0.21, and the (A-a)Do2 can be simplified as follows:
where (A-a)Do2 is typically < 20 but increases with age (because of age-related decline in pulmonary function) and with increasing Fio2 (because, although Hb becomes 100% saturated at a Pao2 of about 150 mm Hg, O2 is soluble in blood, and the O2 content of plasma continues to increase at increasing Fio2). Estimations of normal (A-a)Do2 values as < (2.5 + [Fio2 × age in years]) or as less than the absolute value of the Fio2 (eg, < 21 on room air; < 30 on 30% Fio2) correct for these effects.
Hypoxemia with increased (A-a)Do2:
This situation is caused by
V/Q mismatch is one of the more common reasons for hypoxemia and contributes to the hypoxemia occurring with COPD and asthma. In normal lungs, regional perfusion closely matches regional ventilation because of the arteriolar vasoconstriction that occurs in response to alveolar hypoxia. In disease states, dysregulation leads to perfusion of alveolar units that are receiving less than complete ventilation (V/Q mismatch). As a result, systemic venous blood passes through the pulmonary capillaries without achieving normal levels of Pao2. Supplemental O2 can correct hypoxemia due to V/Q mismatch by increasing the Pao2, although the increased (A-a)Do2 persists.
Right-to-left shunting is an extreme example of V/Q mismatch. With shunting, deoxygenated pulmonary arterial blood arrives at the left side of the heart without having passed through ventilated lung segments. Shunting may occur through lung parenchyma, through abnormal connections between the pulmonary arterial and venous circulations, or through intracardiac communications (eg, patent foramen ovale). Hypoxemia due to right-to-left shunting does not respond to supplemental O2.
Impaired diffusing capacity only rarely occurs in isolation; usually it is accompanied by significant V/Q mismatch. Because O2 completely saturates Hb after only a fraction of the time that blood is in contact with alveolar gas, hypoxemia due to impaired diffusing capacity occurs only when cardiac output is increased (eg, with exercise), when barometric pressure is low (eg, at high altitudes), or when > 50% of the pulmonary parenchyma is destroyed. As with V/Q mismatch, the (A-a)Do2 is increased, but Pao2 can be increased by increasing the Fio2. Hypoxemia due to impaired diffusing capacity responds to supplemental O2.
Hypoxemia with normal (A-a)Do2:
This situation is caused by
Hypoventilation (reduced alveolar ventilation) decreases the Pao2 and increases the Paco2, thereby decreasing Pao2. In cases of pure hypoventilation, the (A-a)Do2 is normal. Causes of hypoventilation include decreased respiratory rate or depth (eg, due to neuromuscular disorders, severe obesity, or drug overdose) or an increase in the fraction of dead space ventilation in patients already at their maximal ventilatory limit (eg, an exacerbation of severe COPD). Hypoventilatory hypoxemia responds to supplemental O2.
Decreased Pio2 is a final uncommon cause of hypoxemia that in most cases occurs only at high altitude. Although Fio2 does not change with altitude, ambient air pressure decreases exponentially; thus, Pio2 decreases as well. For example, Pio2 is only 43 mm Hg at the summit of Mt. Everest (altitude, 8848 m [29,028 ft]). The (A-a)Do2 remains normal. Hypoxic stimulation of respiratory drive increases alveolar ventilation and decreases Paco2 level. This type of hypoxemia responds to supplemental O2.
Pco2 normally is maintained between 35 and 45 mm Hg. A dissociation curve similar to that for O2 exists for CO2 but is nearly linear over the physiologic range of Paco2. Abnormal Pco2 is always linked to disorders of ventilation and is always associated with acid-base changes.
Hypercapnia is Pco2 > 45 mm Hg. Causes of hypercapnia are the same as those of hypoventilation (see Hypoxemia with normal (A-a)Do). Disorders that increase CO2 production (eg, hyperthyroidism, fever) when combined with an inability to increase ventilation also cause hypercapnia.
Hypocapnia is Pco2 < 35 mm Hg. Hypocapnia is always caused by hyperventilation due to pulmonary (eg, pulmonary edema or embolism), cardiac (eg, heart failure), metabolic (eg, acidosis), drug-induced (eg, aspirin, progesterone), CNS (eg, infection, tumor, bleeding, increased intracranial pressure), or physiologic (eg, pain, pregnancy) disorders or conditions. Hypocapnia is thought to directly increase bronchoconstriction and lower the threshold for cerebral and myocardial ischemia, perhaps through its effects on acid-base status.
CO binds to Hb with an affinity 210 times that of O2 and prevents O2 transport. Clinically toxic carboxyhemoglobin levels are most often the result of exposure to exhaust fumes or from smoke inhalation, although cigarette smokers have detectable levels. Patients with CO poisoning (see Carbon Monoxide Poisoning) may present with nonspecific symptoms such as malaise, headache, and nausea. Because poisoning often occurs during colder months (because of indoor use of combustible fuel heaters), symptoms may be confused with a viral syndrome such as influenza. Clinicians must be alert to the possibility of CO poisoning and measure levels of carboxyhemoglobin when indicated; COHb can be directly measured from venous blood—an arterial sample is unnecessary.
Treatment is the administration of 100% O2 (which shortens the half-life of carboxyhemoglobin) and sometimes the use of a hyperbaric chamber.
Methemoglobin is Hb in which the iron is oxidized from its ferrous (Fe2+) to its ferric (Fe3+) state. Methemoglobin does not carry O2 and shifts the normal HbO2 dissociation curve to the left, thereby limiting the release of O2 to the tissues. Methemoglobinemia is caused by certain drugs (eg, dapsone, local anesthetics, nitrates, primaquine, sulfonamides) or, less commonly, by certain chemicals (eg, aniline dyes, benzene derivatives). Methemoglobin level can be directly measured by co-oximetry (which emits 4 wavelengths of light and is capable of detecting methemoglobin, COHb, Hb, and HbO2) or may be estimated by the difference between the O2 saturation calculated from the measured PaO2 and the directly measured SaO2. Patients with methemoglobinemia most often have asymptomatic cyanosis. In severe cases, O2 delivery is reduced to such a degree that symptoms of tissue hypoxia result, such as confusion, angina, and myalgias. Stopping the causative drug or chemical exposure is often sufficient. Rarely, methylene blue (a reducing agent; a 1% solution is given 1 to 2 mg/kg slowly IV) or exchange transfusion is needed.
Last full review/revision May 2009 by James M. O'Brien, Jr., MD, MSc
Content last modified October 2013