Physiology 5th Ed.

INTEGRATIVE FUNCTIONS

As in the cardiovascular system, the coordinated functions of the respiratory system are best appreciated through examples. Two examples that illustrate many of the principles presented in this chapter are the responses to exercise and the adaptation to high altitude. A third example, chronic obstructive pulmonary disease, is discussed in Box 5-2.

BOX 5–2 Clinical Physiology: Chronic Obstructive Pulmonary Disease (COPD)

DESCRIPTION OF CASE. A 65-year-old man has smoked two packs of cigarettes a day for more than 40 years. He has a long history of producing morning sputum, cough, and progressive shortness of breath on exertion (dyspnea). For the past decade, each fall and winter he has had bouts of bronchitis with dyspnea and wheezing, which have gradually worsened over the years. When admitted to the hospital, he is short of breath and cyanotic. He is barrel-chested. His breathing rate is 25 breaths/min, and his tidal volume is 400 mL. His vital capacity is 80% of the normal value for a man his age and size, and FEV1 is 60% of normal. The following arterial blood values were measured (normal values are in parentheses):

image

image

image

image

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EXPLANATION OF CASE. The man’s history of smoking and bronchitis suggests severe lung disease. Of the arterial blood values, the one most notably abnormal is the image of 60 mm Hg. Hemoglobin concentration (14 g/L) is normal, and the percent saturation of hemoglobin of 90% is in the expected range for a image of 60 mm Hg (see Fig. 5-20).

The low value for image at 60 mm Hg can be explained in terms of a gas exchange defect in the lungs. This defect is best understood by comparing image (measured as 60 mm Hg) with image (calculated with the alveolar gas equation). If the two are equal, then gas exchange is normal and there is no defect. If image is less than image (i.e., there is an A − a difference), then there is a image defect, with insufficient amounts of O2 being added to pulmonary capillary blood.

The alveolar gas equation can be used to calculate image, if the imageimage, and respiratory quotient are known. image is calculated from the barometric pressure (corrected for water vapor pressure) and the percent O2 in inspired air (21%). image is equal to image, which is given. The respiratory quotient is assumed to be 0.8. Thus,

image

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Because the measured image (60 mm Hg) is much less than the calculated image (113 mm Hg), there must be a mismatch of ventilation and perfusion. Some blood is perfusing alveoli that are not ventilated, thereby diluting the oxygenated blood and reducing arterial PO2.

The man’s image is lower than normal because he is hyperventilating and blowing off more CO2 than his body is producing. He is hyperventilating because he is hypoxemic. His image is just low enough to stimulate peripheral chemoreceptors, which drive the medullary inspiratory center to increase the ventilation rate. His arterial pH is slightly alkaline because his hyperventilation has produced a mild respiratory alkalosis.

The man’s FEV1 is reduced more than his vital capacity; thus, FEV1/FVC is decreased, which is consistent with an obstructive lung disease in which airway resistance is increased. His barrel-shaped chest is a compensatory mechanism for the increased airway resistance: High lung volumes exert positive traction on the airways and decrease airway resistance; by breathing at a higher lung volume, he can partially offset the increased airway resistance from his disease.

TREATMENT. The man is advised to stop smoking immediately. He is given an antibiotic to treat a suspected infection and an inhalant form of albuterol (a β2 agonist) to dilate his airways.

Responses to Exercise

The response of the respiratory system to exercise is remarkable. As the body’s demand for O2 increases, more O2 is supplied by increasing the ventilation rate: Excellent matching occurs between O2consumption, CO2 production, and the ventilation rate.

For example, when a trained athlete is exercising, his O2 consumption may increase from its resting value of 250 mL/min to 4000 mL/min and his ventilation rate may increase from 7.5 L/min to 120 L/min. Both O2 consumption and ventilation rate increase more than 15 times the resting level! An interesting question is What factors ensure that the ventilation rate will match the need for O2? At this time, there is no completely satisfactory answer to this question. The responses of the respiratory system to exercise are summarized in Table 5-3 and Figure 5-34.

Table 5–3 Summary of Respiratory Responses to Exercise

Parameter

Response to Exercise

O2 consumption

CO2 production

Ventilation rate

Arterial PO2 and PCO2

No change

Arterial pH

No change during moderate exercise

 

↓ During strenuous exercise

Venous Pco2

Pulmonary blood flow and cardiac output

image ratio

More evenly distributed throughout the lung

Physiologic dead space

O2-hemoglobin dissociation curve

Shifts to the right; ↑P50; decreased affinity

image

Figure 5–34 Responses of the respiratory system to exercise.

Arterial PO2 and PCO2

Remarkably, mean values for arterial PO2 and PCO2 do not change during exercise. An increased ventilation rate and increased efficiency of gas exchange ensure that there is neither a decrease in arterial PO2 nor an increase in arterial PCO2. (The arterial pH may decrease, however, during strenuous exercise because the exercising muscle produces lactic acid.) Recalling that the peripheral and central chemoreceptors respond, respectively, to changes in image and image, it is a mystery, therefore, how the ventilation rate can be altered so precisely to meet the increased demand when these parameters seem to remain constant. One hypothesis states that although mean values of arterial Po2 and Pco2 do not change, oscillations in their values do occur during the breathing cycle. These oscillatory changes may, via the chemoreceptors, produce such immediate adjustments in ventilation that mean values in arterial blood remain constant.

Venous Pco2

The PCO2 of mixed venous blood must increase during exercise because skeletal muscle is adding more CO2 than usual to venous blood. However, because mean arterial PCO2 does not increase, the ventilation rate must increase sufficiently to rid the body of this excess CO2 (i.e., the “extra” CO2 is expired by the lungs and never reaches systemic arterial blood).

Muscle and Joint Receptors

Muscle and joint receptors send information to the medullary inspiratory center and participate in the coordinated response to exercise. These receptors are activated early in exercise, and the inspiratory center is commanded to increase the ventilation rate.

Cardiac Output and Pulmonary Blood Flow

Cardiac output increases during exercise to meet the tissues’ demand for O2, as discussed in Chapter 4. Because pulmonary blood flow is the cardiac output of the right heart, pulmonary blood flow increases. There is a decrease in pulmonary resistance associated with perfusion of more pulmonary capillary beds, which also improves gas exchange. As a result, pulmonary blood flow becomes more evenly distributed throughout the lungs, and the image ratio becomes more “even,” producing a decrease in the physiologic dead space.

O2-Hemoglobin Dissociation Curve

During exercise, the O2-hemoglobin dissociation curve shifts to the right (see Fig. 5-22). There are multiple reasons for this shift including increased tissue PCO2, decreased tissue pH, and increased temperature. The shift to the right is advantageous, of course, because it is associated with an increase in P50 and decreased affinity of hemoglobin for O2, making it easier to unload O2 in the exercising skeletal muscle.

Adaptation to High Altitude

Ascent to high altitude is one of several causes of hypoxemia. The respiratory responses to high altitude are the adaptive adjustments a person must make to the decreased PO2 in inspired and alveolar air.

The decrease in PO2 at high altitudes is explained as follows: At sea level, the barometric pressure is 760 mm Hg; at 18,000 feet above sea level, the barometric pressure is one-half that value, or 380 mm Hg. To calculate the PO2 of humidified inspired air at 18,000 feet above sea level, correct the barometric pressure of dry air by the water vapor pressure of 47 mm Hg, then multiply by the fractional concentration of O2, which is 21%. Thus, at 18,000 feet, PO2 = 70 mm Hg ([380 mm Hg − 47 mm Hg] × 0.21 = 70 mm Hg). A similar calculation for pressures at the peak of Mount Everest yields a PO2 of inspired air of only 47 mm Hg!

Despite severe reductions in the PO2 of both inspired and alveolar air, it is possible to live at high altitudes if the following adaptive responses occur (Table 5-4 and Fig. 5-35).

Table 5–4 Summary of Adaptive Respiratory Responses to High Altitude

Parameter

Response to High Altitude

Alveolar PO2

↓ (due to decreased barometric pressure)

Arterial PO2

↓ (hypoxemia)

Ventilation rate

↑ (hyperventilation due to hypoxemia)

Arterial pH

↑ (respiratory alkalosis due to hyperventilation)

Hemoglobin concentration

↑ (increased red blood cell concentration)

2,3-DPG concentration

O2-hemoglobin dissociation curve

Shifts to right; increased P50; decreased affinity

Pulmonary vascular resistance

↑ (due to hypoxic vasoconstriction)

Pulmonary arterial pressure

↑ (secondary to increased pulmonary resistance)

image

Figure 5–35 Responses of the respiratory system to high altitude. EPO, Erythropoietin.

Hyperventilation

The most significant response to high altitude is hyperventilation, an increase in ventilation rate. For example, if the alveolar PO2 is 70 mm Hg, then arterial blood, which is almost perfectly equilibrated, also will have a PO2 of 70 mm Hg, which will not stimulate peripheral chemoreceptors. However, if alveolar PO2 is 60 mm Hg, then arterial blood will have a PO2 of 60 mm Hg, in which case the hypoxemia is severe enough to stimulate peripheral chemoreceptors in the carotid and aortic bodies. In turn, the chemoreceptors instruct the medullary inspiratory center to increase the breathing rate.

A consequence of the hyperventilation is that “extra” CO2 is expired by the lungs and arterial PCO2 decreases, producing respiratory alkalosis. However, the decrease in PCO2 and the resulting increase in pH will inhibit central and peripheral chemoreceptors and offset the increase in ventilation rate. These offsetting effects of CO2 and pH occur initially, but within several days HCO3 excretion increases, HCO3leaves the CSF, and the pH of the CSF decreases toward normal. Thus, within a few days, the offsetting effects are reduced and hyperventilation resumes.

The respiratory alkalosis that occurs as a result of ascent to high altitude can be treated with carbonic anhydrase inhibitors (e.g., acetazolamide). These drugs increase HCO3 excretion, creating a mild compensatory metabolic acidosis.

Polycythemia

Ascent to high altitude produces an increase in red blood cell concentration (polycythemia) and, as a consequence, an increase in hemoglobin concentration. The increase in hemoglobin concentration means that the O2-carrying capacity is increased, which increases the total O2 content of blood in spite of arterial PO2 being decreased. Polycythemia is advantageous in terms of O2 transport to the tissues, but it is disadvantageous in terms of blood viscosity. The increased concentration of red blood cells increases blood viscosity, which increases resistance to blood flow (see Chapter 4, the Poiseuille equation).

The stimulus for polycythemia is hypoxia, which increases the synthesis of erythropoietin (EPO) in the kidney. Erythropoietin acts on bone marrow to stimulate red blood cell production.

2,3-DPG and O2-Hemoglobin Dissociation Curve

One of the most interesting features of the body’s adaptation to high altitude is an increased synthesis of 2,3-DPG by red blood cells. The increased concentration of 2,3-DPG causes the O2-hemoglobin dissociation curve to shift to the right. This right shift is advantageous in the tissues because it is associated with increased P50, decreased affinity, and increased unloading of O2. However, the right shift is disadvantageous in the lungs because it becomes more difficult to load the pulmonary capillary blood with O2.

Pulmonary Vasoconstriction

At high altitude, alveolar gas has a low Po2, which has a direct vasoconstricting effect on the pulmonary vasculature (i.e., hypoxic vasoconstriction). As pulmonary vascular resistance increases, pulmonary arterial pressure also must increase to maintain a constant blood flow. The right ventricle must pump against this higher pulmonary arterial pressure and may hypertrophy in response to the increased afterload.

Acute Altitude Sickness

The initial phase of ascent to high altitude is associated with a constellation of complaints including headache, fatigue, dizziness, nausea, palpitations, and insomnia. The symptoms are attributable to the initial hypoxia and respiratory alkalosis, which abate when the adaptive responses are established.