Concept 31.3: The Mammalian Breathing System Is Anatomically and Functionally Elaborate

In mammals, air enters the lungs through the oral cavity and the nasal passages, which join together in the pharynx, or throat (FIGURE 31.11A). Below the pharynx, the esophagus, or food tube, directs food to the stomach, and the trachea, or windpipe, leads to the lungs. At the beginning of the trachea is the larynx, or voice box, which houses the vocal cords. The walls of the trachea and many further branches of the airways contain rings of cartilage, which help prevent airway collapse.

Figure 31.11: The Human Breathing System The hierarchy of human breathing structures extends from the nose and mouth to the minuscule alveoli. Because lung capillaries are a bit larger in diameter than systemic capillaries, red blood cells pass through as shown in (E).

The trachea branches into two primary bronchi, one leading to each lung. Each primary bronchus then branches more than 20 times to generate the treelike structure of progressively smaller airways we discussed earlier (FIGURE 31.11B). At the farthest reaches of the branching airways, each tiny branch ends blindly in an alveolar sac of epithelial tissue (FIGURE 31.11C). The wall of each alveolar sac consists of numerous semispherical pocket-like structures called alveoli (singular alveolus). These alveoli number about 300 million in the two lungs of an adult person, creating an enormous surface area (FIGURE 31.11D) where gas exchange occurs (FIGURE 31.11E).

Most branches of the airway system in a mammal are not involved in the exchange of O₂ and CO₂ between the air and blood. These branches—including the trachea, primary bronchi, and most of the succeeding branches—are called the conducting airways because their principal function is to conduct flowing air in and out of the lungs during inhalation and exhalation.

Exchange of O₂ and CO₂ between the air and blood occurs in the respiratory airways. These are the parts of the lungs where the membranes between air and blood are thin and perfused with blood at high rates. The respiratory airways include the last few branches of the branching airway system—termed respiratory bronchioles—and the alveolar sacs, including the alveoli. In healthy human lungs, blood and air are separated by only about 0.5 μm in the alveoli. Bulk air flow—inflow and outflow—takes place in the respiratory bronchioles as a person inhales and exhales. But the air inside the alveoli is motionless. This means that as O₂ and CO₂ travel to and from the gas exchange membranes, they must diffuse across the central cavities of the alveoli. Moreover, as we already discussed, O₂ and CO₂ must diffuse across the two thin epithelia that line the alveoli and the surrounding blood capillaries. Diffusion occurs rapidly because the distances to be covered are minute.

At rest, only a small portion of the lung volume is exchanged

The amount of air that moves in and out of the lungs per breath is called the tidal volume (FIGURE 31.12). When a person is at rest, it is called the resting tidal volume and amounts to about 0.5 liter. The maximal tidal volume—also called vital capacity—is the amount of air that moves in and out per breath when we inhale and exhale as vigorously as possible. It is about 5 liters. We use only about 10 percent of our maximal tidal volume when we breathe at rest.

RESEARCH TOOLS

Figure 31.12: Measuring Lung Ventilation A spirometer is a device that measures tidal volume: the volume of air a person breathes in and out per breath.

A person’s respiratory minute volume is the total volume of air that he or she inhales and exhales per minute. We calculate the minute volume by multiplying tidal volume (the volume exchanged per breath) by the number of breaths per minute. When people exercise and “breathe harder,” they increase their tidal volume above the resting tidal volume, and they also take more breaths per minute than they do at rest. These two factors can produce a large increase in minute volume. At rest we breathe about 12 times per minute. With a resting tidal volume of about 0.5 liter, our resting minute volume is about 6 liters per minute. Well-conditioned athletes can breathe at least 30 times per minute at a tidal volume of over 3 liters, meaning they can increase their minute volume by a factor of more than 15!

Mammals and other animals with tidally ventilated lungs do not empty their lungs completely when they exhale. Some air is always left behind in the lungs. The amount left after a maximum exhalation is called the residual volume (see Figure 31.12). During normal breathing, whenever a mammal inhales, the fresh air mixes with stale air from the previous breath that was not exhaled. This mixing lowers the O₂ partial pressure at the alveolar gas exchange membranes but ordinarily presents no problems.

The lungs are ventilated by expansion and contraction of the thoracic cavity

Mammalian lungs are suspended in the thoracic, or chest, cavity, which is bounded on the top by the bones of the shoulders, on the sides by the rib cage, and on the bottom by a sheet of muscle, unique to mammals, called the diaphragm. Any increase in volume of the thoracic cavity pulls on the walls of the lungs, thereby expanding the lungs and causing inflation.

Two muscles or sets of muscles are critical for breathing: the diaphragm and the intercostal (from the Latin costa, “rib”) muscles that run between adjacent ribs (see Figure 31.11A). The diaphragm is dome-shaped at rest, protruding upward from the abdomen into the thoracic cavity. It flattens when it contracts, so it protrudes less into the thoracic cavity, expanding it. There are two sets of intercostal muscles. One set enlarges the thoracic cavity when it contracts, and the other set makes it smaller when it contracts.

In humans at rest, inhalation is active but exhalation is passive (FIGURE 31.13). During inhalation, the diaphragm and certain intercostal muscles contract, expanding the thoracic cavity and lungs, which fill by suction (a lower pressure in the lungs than in the atmosphere). During exhalation at rest, these muscles simply relax, allowing the elastic recoil of the lungs and thoracic cavity to restore the relaxed lung volume. During exercise, additional breathing muscles come into play. Inhalation is more forceful, and muscle contractions are employed to make exhalation faster and more forceful than it is at rest.

Figure 31.13: Resting Human Ventilation When a person is at rest, inhalation (A) is an active process driven by contraction of the diaphragm and some of the intercostal muscles. However, exhalation (B) is a passive process that occurs by elastic recoil; the thoracic cavity and lungs elastically return to their relaxed volume as soon as muscle contractions stop maintaining them in an expanded state.

The breathing rhythm depends on nervous stimulation of the breathing muscles

All the muscles involved in breathing require nervous stimulation to contract. The nerve impulses originate in the brain. These facts explain why a broken neck can kill a person rapidly. If the nerves carrying the breathing impulses from the brain to the breathing muscles are severed, the muscles stop contracting. Without artificial respiration, the person suffocates.

Physiologists have long sought the places in the brain where the breathing rhythm originates. Investigators recently identified these rhythm-generating (rhythmogenic) centers by studying thin slices of brain tissue taken from nestling rodents. Although these slices are cut off from all their normal connections with other parts of the nervous system, they remain functional for some time. Investigators have shown that two neural complexes in the medulla oblongata of the brain (a part of the brainstem) generate a breathing rhythm under these circumstances (FIGURE 31.14). These rhythm-generating centers, called the pre-Bötzinger complexes, are believed to be the beginning points for the nerve impulses that activate the muscles we use in breathing.

Figure 31.14: Where Does the Breathing Rhythm Originate? To find the neural tissue where the breathing rhythm starts, physiologists studied thin slices of living brain tissue from nestling mice. (A) This slice, cut from the medulla oblongata, has no connections to other parts of the nervous system. Its neural activity is therefore completely self-contained. (B) Electrical recordings were made from one of two clusters of nerve cells called the pre-Bötzinger complexes. The investigators found that these complexes generate electrical signals that control normal breathing. From simultaneous recordings from one of two other nerve cell clusters called the hypoglossal nuclei, the investigators found that the breathing rhythm that starts in the pre-Bötzinger complexes is relayed to the hypoglossal nuclei. In an intact mouse, the breathing rhythm would then be relayed to the breathing muscles via the hypoglossal nerves.

Breathing is under negative-feedback control by CO{sub}2{/sub}

You might expect that a mammal’s breathing would be regulated by the blood’s O₂ content. In fish, blood O₂ is indeed the primary feedback stimulus for gill ventilation. However, mammals are relatively insensitive to falling levels of O₂ in arterial blood. Instead they are very sensitive to changes in blood CO₂.

To fully understand control of breathing by CO₂, it is important to recognize that CO₂ dissolved in the blood reacts with blood H₂O. This reaction forms carbonic acid (H₂CO⁻), which dissociates almost completely into H⁺ ions and bicarbonate ions (HCO₃⁻).

What happens when the cells of your body increase their metabolism and therefore add CO₂ to the blood at an increased rate? There are two immediate consequences. First, the partial pressure of CO₂ in the blood rises. Second, the concentration of H⁺ in the blood also rises, meaning the blood becomes more acidic and its pH falls. Chemosensitive (chemical-sensing) neural centers located on the ventral surface of the medulla oblongata in the brain (see Figure 31.14) independently monitor the blood CO₂ partial pressure and H⁺ concentration. These centers detect the increases in CO₂ partial pressure and H⁺ concentration. This information is then used to control breathing in a negative-feedback manner. Breathing is stimulated so that the respiratory minute volume increases. This increased ventilation increases exhalation of CO₂, helping the body get rid of CO₂ at an accelerated rate when the cells have increased their rate of CO₂ production. The increased ventilation also tends to return both the blood CO₂ partial pressure and H⁺ concentration back toward their values that existed before CO₂ production increased.

What if, under different circumstances, your cells decrease the rate at which they add CO₂ to the blood? In this case, the blood CO₂ partial pressure and H⁺ concentration initially tend to fall. The chemosensitive centers detect these changes, leading again to negative-feedback control of breathing. In this instance, breathing is inhibited, lowering the rate of CO₂ exhalation and causing the blood CO₂ partial pressure and H⁺ concentration to rise.

These controls serve to adjust the respiratory minute volume so that the rate of CO₂ exhalation approximately matches the rate at which the cells of the body produce CO₂. The controls also stabilize the blood CO₂ partial pressure and H⁺ concentration, by tending to bring them down if they start to rise and tending to bring them up if they start to fall.

In the experiment in FIGURE 31.15, dogs ran on a treadmill at a constant speed. The slope of the treadmill could be tilted up at various angles, allowing the researchers to vary the dogs’ metabolic workload and thus their rates of CO₂ production. Negative-feedback systems rarely lead to complete stability. In this case, the CO₂ partial pressure in a dog’s arterial blood tended to vary a little (it would have varied much more without negative feedback). The results demonstrate that a dog’s respiratory minute volume is closely correlated with its blood CO₂ partial pressure. This evidence supports the idea that breathing is stimulated when the blood CO₂ partial pressure increases.

Investigation

HYPOTHESIS

Arterial CO₂ partial pressure is a feedback stimulus controlling ventilation.

METHOD

1. Dogs are trained to run on a treadmill.
2. The dogs are equipped with instruments that measure respiratory minute volume and with arterial catheters that enable sampling of blood.
3. As a dog runs at a constant speed, the slope of the treadmill is changed to modify the metabolic workload.
4. Minute volume is plotted as a function of arterial CO₂ partial pressure.

RESULTS

When the workload is altered by slowly changing the slope of the treadmill (no change in speed), the respiratory minute volume is a function of arterial CO₂ partial pressure.

Figure 31.15: The Respiratory Control System Detects Exercise What is the metabolic feedback signal that controls ventilation during exercise? In experiments with dogs running on a treadmill at a constant speed but at varying upward slopes, the respiratory minute volume increased as the CO₂ partial pressure in the arterial blood increased.^a

CONCLUSION

The data support the hypothesis that arterial CO₂ partial pressure is a metabolic feedback signal controlling ventilation in response to changes in workload.

ANALYZE THE DATA

Additional experiments were done in which the speed of the treadmill was changed instead of the slope to modify the metabolic workload. Again the respiratory minute volume (L/min) and arterial CO₂ partial pressure (PCO₂, in units of mm Hg) were measured. The average values when the dogs were running at 3 mph were CO₂ partial pressure = 39.0 mm Hg and L/min = 9. The data for the first seven breaths after the treadmill speed was increased to 6 mph are shown in the table. After the dogs had run at 6 mph for several minutes, the values averaged CO₂ partial pressure = 41.0 mm Hg and L/min = 15.0. Plot these data and use the information to answer the questions.

1. Do these data support the hypothesis that CO₂ partial pressure is the feedback signal controlling ventilation? Why or why not?
2. How do you explain the average values after the dogs had been running at the higher speed for a few minutes?
3. Relate these results to those obtained in the experiment in which the slope of the treadmill was varied. Explain the differences between the results.

Go to LaunchPad for discussion and relevant links for all INVESTIGATION figures.

^aC. R. Bainton. 1972. Journal of Applied Physiology 33: 778–787.

Breathing is also under control of factors in addition to CO{sub}2{/sub}

You may have noticed that when you start running, your breathing rate increases almost immediately—far sooner than your blood CO₂ partial pressure would be expected to change. This everyday observation suggests that the simple act of moving muscles and joints may serve to accelerate ventilation during exercise. Investigators studied this possibility in the experiments on dogs we’ve been discussing (see Analyze the Data in Figure 31.15). For this purpose the dogs ran on a horizontal treadmill, and investigators altered the dogs’ intensity of work by varying how fast they ran. When the dogs worked harder, respiratory minute volume sometimes increased to a greater extent than CO₂ partial pressure by itself would explain. According to the results of this study and other studies, information from receptors that detect motion in muscles and joints is used during exercise to help control the intensity of ventilation.

Blood O₂ partial pressure is also sometimes used in controlling the intensity of ventilation. O₂ partial pressure is not as influential as CO₂ partial pressure, and minor fluctuations in the O₂ partial pressure have little effect on ventilation. However, a large drop in blood O₂ partial pressure—such as might occur at high elevation—strongly stimulates ventilation.

In mammals, two sets of oxygen-sensing chemosensitive bodies detect the blood O₂ partial pressure. They are called peripheral chemoreceptors because they are not in the brain. They are positioned along the large arteries leaving the heart (see Figure 32.6). One set (by far the most important set in humans) is a pair of carotid bodies found along the carotid arteries in the neck. The second set consists of aortic bodies associated with the aorta. These bodies detect blood O₂ partial pressure and send information on it by way of nerves to the breathing control centers in the medulla oblongata.

ANSWER Any particular type of sustained, physical work demands a certain amount of sustained metabolic effort and thus a certain, fixed rate of O₂ consumption (regardless of elevation). Consequently a person’s maximal rate of O₂ consumption determines the maximal sustained work intensity of which he or she is capable. A person’s maximal rate of O₂ consumption decreases with elevation because O₂ becomes more dilute in the atmosphere as elevation increases (FIGURE 31.16). For this reason, maximal work intensity decreases with elevation. At the top of Mount Everest, hardly any work is possible. The maximal intensity of work is a slow walk.

Figure 31.16: A Person’s Maximal Rate of O₂ Consumption Decreases as Elevation Increases Each symbol represents one measurement on one person. Data from many studies were compiled to create this plot.