Respiratory Pathophysiology Cases Linda Costanzo Ph.D. I. Case of Pulmonary Fibrosis Susan was diagnosed 3 years ago with diffuse interstitial pulmonary fibrosis. She tries to continue normal activities, although it has become increasingly difficult. She tires easily and can no longer climb a flight of stairs without becoming short of breath. She is being closely followed by her pulmonologist. At a recent physical examination, her arterial blood gases were: Arterial Blood Gases Pa O2 76 mm Hg (Normal, 100mm Hg) Pa CO2 37 mm Hg ( Normal, 40mm Hg) % hemoglobin saturation 95% (Normal, 95-100%) 1. Susan had a decreased DL CO. What does this mean? 2. Diffuse interstitial fibrosis is characterized by thickening of alveolar membranes. Use this information to explain the decreased arterial P O2. 3. What was the total O 2 content her blood? Assume that the O 2 -binding capacity of her blood was 1.34 ml O 2 /g hemoglobin, that her hemoglobin concentration was 15 g/100 ml, and that the solubility of O 2 in blood is 0.003 ml O 2 /100 ml blood/mm Hg. 4. Susan was hypoxemic (i.e., she had a decreased Pa O2 ). However, she was not hypercapnic (i.e., she did not have CO 2 retention or an increased Pa CO2 ); in fact, her Pa CO2 was slightly below normal at 37 mm Hg. How can hypoxemia occur in the absence of hypercapnia? Answers and Explanations 1. Lung diffusing capacity (DL) is measured with carbon monoxide (CO). In the single-breath method, a subject maximally inspires air containing CO, holds her breath for ten seconds, then expires. The amount of CO transferred from alveolar gas into pulmonary capillary blood is measured to assess the diffusion characteristics of the alveolar-pulmonary capillary barrier. Susan s DL CO was decreased because of thickening of the alveolar walls. Such thickening increases the diffusion distance for gases such as CO (and O 2 ),
diminishing the total amount of gas that can be transferred across the alveolar wall. 2. Susan s Pa O2 was 76 mm Hg, which is lower than the normal value of 100 mm Hg. In normal lungs, there is equilibration of O 2 across the alveolar-pulmonary capillary barrier, such that the P O2 of the blood become equal to the P O2 of alveolar gas, or approximately 100 mm Hg. In Susan, equilibration of O 2 was impossible: thickening of her alveolar walls impaired O 2 diffusion (as detected in a decreased DlCO) and Pa O2 could not become equal to PA O2. 3. The total O 2 content of blood has two components free dissolved O 2 and O 2 - hemoglobin. By now you know that O 2 -hemoglobin is, by far, the greater contributor to total O 2 content. However, to be thorough, calculate both dissolved O 2 and bound O 2. 4. Although Susan has a problem with O 2 exchange and she is hypoxemic, she does not have a problem with CO 2 exchange (i.e., she is not hypercapnic). In fact, her Pa CO2 was slightly lower than the normal value of 40 mm Hg. This pattern is seen commonly in respiratory diseases: hypoxemia occurs without hypercapnia. But, why? Consider the sequence of events that created this pattern of arterial blood gases. The fibrotic disease affected some, but not all, regions of her lungs. In the diseased regions, there was thickening of alveolar walls and thickening of the diffusion barrier for both O 2 and CO 2. The diffusion problem caused hypoxemia (decreased Pa O2 ) and may have briefly caused hypercapnia (increased Pa CO2 ). However, because the central chemoreceptors are exquisitely sensitive to small changes in P CO2, they responded to the hypercapnia by increasing the ventilation rate. The increase in alveolar ventilation in healthy regions of the lungs ridded the body of excess CO 2 that was retained in unhealthy regions. In other words, by
increasing alveolar ventilation, healthy regions of the lungs compensated for unhealthy regions with respect to CO 2. As a result, P CO2 returned to normal. (Later in her disease, she may develop hypercapnia if there is not enough healthy lung tissue to compensate for the unhealthy tissue, or if the work of breathing becomes so great that she is unable to sufficiently increase her alveolar ventilation.) You may ask: If increased alveolar ventilation can rid the body of excess CO 2 retained in unhealthy regions of the lungs, why can t increased alveolar ventilation also correct the hypoxemia? The answer lies in the fact that welloxygenated blood from healthy lung regions is always mixing with, and being diluted by, poorly-oxygenated blood from unhealthy regions, and Pa O2 will always be lower than normal. Remember: O 2 added in healthy lung regions is largely in the form of dissolved O 2 (because hemoglobin will already be 100% saturated in those regions) and this dissolved O 2 does little to improve O 2 content or delivery. Is possible for the degree of hyperventilation to be so great that the person actually becomes hypocapnic (has decreased Pa CO2 ). Yes, in fact, Susan s Pa CO2 is slightly less than normal. If the Pa O2 becomes low enough to stimulate the peripheral chemoreceptors (i.e., Pa O2 < 60 mm Hg), hyperventilation will be strongly stimulated, even greater amounts of CO 2 will be expired by healthy lung regions, and the Pa CO2 will fall below the normal value of 40 mm Hg. In summary, persons with lung disease may pass through three stages of arterial blood gases: (1) mild hypoxemia with normocapnia; (2) more severe hypoxemia (Pa O2 < 60 mm Hg) with hypocapnia, resulting in respiratory alkalosis; and (3) severe hypoxemia with hypercapnia, resulting in respiratory acidosis. Susan is somewhere between the first and the second stages. II. Case of chronic obstructive pulmonary disease (COPD) Clarence has smoked 4 packs a day for 45 years and has no intention of quitting. He fatigues easily, is short of breath, and sleeps on two pillows. In the physician s office, he had a prolonged expiratory phase, expiratory wheezes, increased chest (AP) diameter, and was cyanotic. The long history of smoking had caused chronic obstructive pulmonary disease. The following were results of pulmonary function tests and blood values: Vital Capacity FRC FEV 1 Hemoglobin Pa O2 Pa CO2 HCO 3 - decreased increased decreased 14.5 g/dl (normal) 48 mm Hg 69 mm Hg 34 meq/l
1. Why was Clarence s FEV 1 decreased? Why was his FRC increased? Why was his vital capacity decreased? 2. Why was his AP diameter increased? 3. Why did he have decreased Pa O2? Why was he cyanotic? 4. Why did he have increased Pa CO2? 5. What was his arterial ph, and what acid-base disorder does he have? 6. Why was his HCO 3 - concentration increased? Answers and Explanations 1. COPD, an obstructive disease, results in decreases in airflow especially during expiration. Because of the loss of elastic tissue, there is increased compliance of lung tissue. Normally, expiration is passive, driven by elastic recoil forces. With loss of elasticity, expiration is impaired. Also, airways are normally kept open by radial traction, which also depends on elasticity. With loss of elasticity, the airways may collapse, producing extra resistance to airflow, especially during expiration. For these two reasons, FEV 1 is decreased, and there was a prolonged expiratory phase and expiratory wheezes. Air that should have been expired is trapped in the lungs and increases residual volume and FRC. Vital capacity is decreased because the residual volume is increased (i.e., the volume that can be inspired above residual volume is compromised). 2. AP diameter was increased (barrel-shaped chest) because of air trapping and increased residual volume and FRC. 3. He was hypoxemic (decreased Pa O2 ) because of a V/Q defect caused by impaired ventilation. Regions of the lungs were perfused but not ventilated, resulting in decreased V/Q and even shunt. Blood perfusing those regions was not oxygenated in the lungs and mixed with oxygenated blood from well-ventilated regions. The overall P O2 of blood leaving the lungs was thereby decreased. He was cyanotic because there was an increased concentration of deoxyhemoglobin in blood; deoxyhemoglobin is blue (whereas oxyhemoglobin is red).
4. Pa CO2 was increased because of decreased alveolar ventilation. All of the CO 2 produced by his tissues could not be expired, leading to CO 2 retention. 5. Clarence had respiratory acidosis secondary to CO 2 retention. 6. The HCO 3 - concentration was increased as the renal compensation for chronic respiratory acidosis (aided by the increased P CO2 ). There is increased reabsorption of HCO 3 - by the kidneys, which increases the HCO 3 - concentration in blood tending to normalize the ratio of HCO 3 - / CO 2 and to normalize the ph. Thus, his ph was only slightly acidic, even though is P CO2 was markedly elevated.
III. Useful Abbreviations and Values for Respiratory Gases P pressure, or partial pressure (mm Hg) PB barometric pressure PH2O water vapor pressure Q blood flow (L/min) V gas flow (L/min) F fractional concentration (no units) A alveolar gas A arterial blood V venous blood E expired gas I inspired gas DL lung diffusing capacity % sat % saturation of hemoglobin respiratory exchange quotient (CO R 2 production/o 2 consumption Pa O2 Pa CO2 Pv O2 Pv CO2 PI O2 PI O2 PI CO2 PI N2 PI N2 PA O2 PA CO2 PB PH2O V O2 V CO2 R or R.Q. Solubility of O 2 in blood Solubility of CO 2 in blood Hemoglobin concentration O 2 -binding capacity Normal Value 100 mm Hg 40 mm Hg 40 mm Hg 46 mm Hg 160 mm Hg (dry) 150 mm Hg (humidified) 0 600 mm Hg (dry) 563 mm Hg (humidified) 100 mm Hg 40 mm Hg 760 mm Hg (sea level) 47 mm Hg 250 ml/min 200 ml/min 0.8 0.003 ml O 2 /100 ml blood/mm Hg 0.07 ml CO 2 /100 ml blood/mm Hg 15 g/100 ml 1.34 ml O 2 /g hemoglobin