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Measurement of Gas Exchange


Karen L. Wood

, MD, Grant Medical Center, Ohio Health

Reviewed/Revised Apr 2022 | Modified Sep 2022
Topic Resources

Gas exchange is measured through several means, including

  • Diffusing capacity for carbon monoxide

  • Pulse oximetry

  • 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 red blood cells. 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 carbon monoxide, hold their breath, and exhale. Measured DLCO should be adjusted for alveolar volume (which is estimated from dilution of helium Lung volume Lung volume ) and the patient’s hematocrit. DLCO is reported as mL/minute/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 Pulmonary Hypertension Pulmonary hypertension is increased pressure in the pulmonary circulation. It has many secondary causes; some cases are idiopathic. In pulmonary hypertension, pulmonary vessels may become constricted... read more and pulmonary embolism Pulmonary Embolism (PE) Pulmonary embolism (PE) is the occlusion of pulmonary arteries by thrombi that originate elsewhere, typically in the large veins of the legs or pelvis. Risk factors for pulmonary embolism are... read more Pulmonary Embolism (PE) , decrease DLCO. Conditions that affect the lung diffusely, such as emphysema Chronic Obstructive Pulmonary Disease (COPD) Chronic obstructive pulmonary disease (COPD) is airflow limitation caused by an inflammatory response to inhaled toxins, often cigarette smoke. Alpha-1 antitrypsin deficiency and various occupational... read more Chronic Obstructive Pulmonary Disease (COPD) and pulmonary fibrosis Idiopathic Pulmonary Fibrosis Idiopathic pulmonary fibrosis (IPF), the most common form of idiopathic interstitial pneumonia, causes progressive pulmonary fibrosis. Symptoms and signs develop over months to years and include... read more Idiopathic 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. Patients with anemia have lower DLCO values that correct when adjusted for hemoglobin values.

Conditions that increase DLCO

Conditions that cause DLCO to be higher than predicted include

The DLCO increase in heart failure presumably because the increased pulmonary venous and arterial pressure recruits additional pulmonary microvessels. In erythrocythemia, DLCO is increased because hematocrit is increased and because of the vascular recruitment that occurs with increased pulmonary pressures due to increased viscosity. In alveolar hemorrhage, red blood cells in the alveolar space can also bind carbon monoxide, increasing DLCO. In asthma, the increase in DLCO is attributed to presumed vascular recruitment; however, some data suggest it may also be due to growth factor–stimulated neovascularization.

Pulse Oximetry

Transcutaneous pulse oximetry estimates oxygen 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 oxygen saturation (SaO2). Results may be less accurate in patients with

  • Highly pigmented skin

  • Arrhythmias

  • Hypotension

  • Profound systemic vasoconstriction

Pulse oximetry results are also less accurate in patients wearing nail polish.

Pulse oximetry is able to detect only oxyhemoglobin or reduced hemoglobin but not other types of hemoglobin (eg, carboxyhemoglobin, methemoglobin); those types are assumed to be oxyhemoglobin and falsely elevate the SpO2 measurement.

Arterial Blood Gas (ABG) Sampling

ABG sampling is done to obtain accurate measures of arterial oxygen partial pressure (PaO2), arterial carbon dioxide partial pressure (PaCO2), and arterial pH; these variables adjusted for the patient’s temperature allow for calculation of bicarbonate 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 test may be done to assess adequacy of collateral circulation. With this maneuver, the radial and ulnar pulses are simultaneously occluded until the patient's hand becomes pale. The ulnar pulse is then released while pressure on the radial pulse is maintained. A blush across the entire hand within 7 seconds 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 heparin-treated 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 blood pressure is usually sufficient to push 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 oxygen consumption and carbon dioxide production by WBCs and is sent to the laboratory.


Hypoxemia is a decrease in the partial pressure of oxygen (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 hemoglobin (eg, methemoglobin), higher temperatures, lower pH, and higher levels of 2,3-diphosphoglycerate reduce hemoglobin SaO2 despite an adequate PaO2, as indicated by the oxyhemoglobin dissociation curve.

Oxyhemoglobin dissociation curve

Arterial oxyhemoglobin saturation is related to PO2. PO2 at 50% saturation (P50) is normally 27 mm Hg.

The dissociation curve is shifted to the right by increased hydrogen ion (H+) concentration, increased red blood cell 2,3-diphosphoglycerate (DPG), increased temperature (T), and increased PCO2.

Decreased levels of H+, DPG, temperature, and PCO2 shift the curve to the left.

Hemoglobin characterized by a rightward shifting of the curve has a decreased affinity for oxygen, and Hemoglobin characterized by a leftward shifting of the curve has an increased affinity for oxygen.

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 oxygen tension (PAO2) and PaO2, is elevated or normal. PAO2 is calculated as follows:


where FIO2 is the fraction of inspired oxygen (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 carbon dioxide, 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 hemoglobin becomes 100% saturated at a PaO2 of about 150 mm Hg, oxygen is soluble in blood, and the oxygen 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 while breathing room air; < 30 on 30% FIO2) correct for these effects.

Hypoxemia with increased (A-a)DO2

Hypoxemia with increased (A-a)DO2 is caused by

  • Low ventilation/perfusion (V/Q) ratio (a type of V/Q mismatch)

  • Right-to-left shunting

  • Severely impaired diffusing capacity

Low V/Q ratio is one of the more common reasons for hypoxemia and contributes to the hypoxemia occurring in COPD Chronic Obstructive Pulmonary Disease (COPD) Chronic obstructive pulmonary disease (COPD) is airflow limitation caused by an inflammatory response to inhaled toxins, often cigarette smoke. Alpha-1 antitrypsin deficiency and various occupational... read more Chronic Obstructive Pulmonary Disease (COPD) and asthma Asthma Asthma is a disease of diffuse airway inflammation caused by a variety of triggering stimuli resulting in partially or completely reversible bronchoconstriction. Symptoms and signs include dyspnea... read more . In normal lungs, regional perfusion closely matches regional ventilation because arteriolar vasoconstriction 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. V/Q mismatch can also occur when there is increased blood flow even when ventilation is normal, as in liver disease. Supplemental oxygen can correct hypoxemia due to low V/Q ratio by increasing the PAO2, although the increased (A-a)DO2 persists.

Right-to-left shunting is an extreme example of low V/Q ratio. 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 oxygen.

Impaired diffusing capacity only rarely occurs in isolation; usually it is accompanied by low V/Q ratio. Because oxygen completely saturates hemoglobin 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, during exercise), when barometric pressure is low (eg, at high altitudes), or when > 50% of the pulmonary parenchyma is destroyed. As with low V/Q ratio, the (A-a)DO2 is increased, but PaO2 can be increased by increasing the FIO2. Hypoxemia due to impaired diffusing capacity responds to supplemental oxygen.

Hypoxemia with normal (A-a)DO2

Hypoxemia with normal (A-a)DO2 is caused by

  • Hypoventilation

  • Low partial pressures of inspired oxygen (PIO2)

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 Obesity Obesity is a chronic, multifactorial, relapsing disorder characterized by excess body weight and defined as a body mass index (BMI) of ≥ 30 kg/m2. Complications include cardiovascular disorders... read more , or drug overdose, or in compensation for metabolic alkalosis Metabolic Alkalosis Metabolic alkalosis is primary increase in bicarbonate (HCO3) with or without compensatory increase in carbon dioxide partial pressure (Pco2); pH may be high or nearly normal. Common... read more ) or an increase in the fraction of dead space ventilation in patients already at their maximal ventilatory limit (eg, an exacerbation of severe COPD Chronic Obstructive Pulmonary Disease (COPD) Chronic obstructive pulmonary disease (COPD) is airflow limitation caused by an inflammatory response to inhaled toxins, often cigarette smoke. Alpha-1 antitrypsin deficiency and various occupational... read more Chronic Obstructive Pulmonary Disease (COPD) ). Hypoventilatory hypoxemia responds to supplemental oxygen.

Decreased PIO2 is an 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 oxygen.

Carbon Dioxide

PCO2 normally is maintained between 35 and 45 mm Hg. A dissociation curve similar to that for oxygen exists for carbon dioxide but is nearly linear over the physiologic range of PaCO2. Abnormal PCO2 is almost always linked to disorders of ventilation (unless occurring in compensation for a metabolic abnormality) and is always associated with acid-base changes.


Hypercapnia is PCO2 > 45 mm Hg. Causes of hypercapnia are the same as those of hypoventilation Hypoxemia with normal (A-a)DO2 (eg, disorders that decrease respiratory rate or depth or increase the fraction of dead space ventilation in patients already at their maximal ventilatory limit). Disorders that increase carbon dioxide production (eg, hyperthyroidism Hyperthyroidism Hyperthyroidism is characterized by hypermetabolism and elevated serum levels of free thyroid hormones. Symptoms include palpitations, fatigue, weight loss, heat intolerance, anxiety, and tremor... read more Hyperthyroidism , fever) when combined with an inability to increase ventilation also cause hypercapnia.



Carbon monoxide binds to hemoglobin with an affinity 210 times that of oxygen and prevents oxygen 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 carbon monoxide poisoning Carbon Monoxide Poisoning Carbon monoxide (CO) poisoning causes acute symptoms such as headache, nausea, weakness, angina, dyspnea, loss of consciousness, seizures, and coma. Neuropsychiatric symptoms may develop weeks... read more 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 carbon monoxide poisoning and measure levels of carboxyhemoglobin when indicated. Carboxyhemoglobin can be directly measured from venous blood—an arterial sample is unnecessary. Oxygen saturation determined by pulse oximetry will be normal and cannot be used to screen for carbon monoxide poisoning. Carboxyhemoglobin can be measured by co-oximetry.

Treatment is the administration of 100% oxygen (which shortens the half-life of carboxyhemoglobin) and sometimes the use of a hyperbaric chamber.

Pearls & Pitfalls

  • Carboxyhemoglobin levels can be directly measured from venous blood—an arterial sample is unnecessary.


Methemoglobin is hemoglobin in which the iron is oxidized from its ferrous (Fe2+) to its ferric (Fe3+) state. Methemoglobin does not carry oxygen and shifts the normal oxyhemoglobin dissociation curve to the left, thereby limiting the release of oxygen 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, carboxyhemoglobin, hemoglobin, and oxyhemoglobin) or may be estimated by the difference between the oxygen saturation calculated from the measured PaO2 and the directly measured oxygen saturation. Oxygen saturation measured by pulse oximetry will be inaccurate in the presence of methemoglobinemia.

Patients with methemoglobinemia most often have asymptomatic cyanosis. In severe cases, oxygen delivery is reduced to such a degree that symptoms of tissue hypoxia, such as confusion, angina, and myalgias, result. 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.

Drugs Mentioned In This Article

Drug Name Select Trade
Anacin Adult Low Strength, Aspergum, Aspir-Low, Aspirtab , Aspir-Trin , Bayer Advanced Aspirin, Bayer Aspirin, Bayer Aspirin Extra Strength, Bayer Aspirin Plus, Bayer Aspirin Regimen, Bayer Children's Aspirin, Bayer Extra Strength, Bayer Extra Strength Plus, Bayer Genuine Aspirin, Bayer Low Dose Aspirin Regimen, Bayer Womens Aspirin , BeneHealth Aspirin, Bufferin, Bufferin Extra Strength, Bufferin Low Dose, DURLAZA, Easprin , Ecotrin, Ecotrin Low Strength, Genacote, Halfprin, MiniPrin, St. Joseph Adult Low Strength, St. Joseph Aspirin, VAZALORE, Zero Order Release Aspirin, ZORprin
Crinone, Endometrin , First - Progesterone MC 10, First - Progesterone MC 5, Prochieve, PROMETRIUM
PROVAYBLUE, Urolene Blue
NOTE: This is the Professional Version. CONSUMERS: View Consumer Version
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