Form and Function: The Physiological Implications of the Anatomy of the Respiratory System

The Respiratory Controller

The respiratory controller is the term used to denote the various elements of the system responsible for producing the neurological output of the brain that determines the rate and depth of breathing. Information is collected from a number of receptors and processed to lead ultimately to the neural information conducted by peripheral nerves to the ventilatory muscles (Fig. 2-1).

Requirements of the Controller ↑

To ensure adequate oxygen for metabolism 24 hours a day, including the hours that we are asleep, we need to have an automatic breathing center, meaning one that operates regardless of whether we are conscious and thinking about breathing. Imagine what would happen, however, if you were about to swallow some food and the diaphragm was suddenly stimulated to contract by the automatic control center, thereby generating a negative pressure in the thorax and movement of air into the lungs; food might well be sucked into the lungs as well. To avoid this misfortune and to allow us to speak, swim, and, on occasion, use our ventilatory muscles to support activities such as lifting heavy objects, we must also be able to modify or override the activity of the automatic center. Finally, the control system must be designed to monitor and respond to acidemia, a decrease in the normal pH of the blood.

Automatic Control: The Central Pattern Generator ↑

The primary source of automatic respiratory rhythm appears to reside with neurons located in the region of the brainstem called the medulla. These neurons have both inspiratory and expiratory activity, and we refer to this area of the brain as the central pattern generator. Within the medulla, the respiratory neurons appear to be collected into two regions: the dorsal respiratory group (DRG) and the ventral respiratory group (VRG). Information from receptors in the lungs and vascular system may be processed in the DRG. Most of the activity within the DRG, based on animal studies, is inspiratory in nature. The VRG contains both inspiratory and expiratory neurons, as well as cells that innervate muscles that control the larynx and pharynx. Axons from these neurons descend into the cervical spinal cord and ultimately project to the phrenic and intercostal nerves as well as accessory muscles, such as the sternocleidomastoid and the abdominal muscles. The accessory muscles are not primarily ventilatory muscles, but they do participate in ventilation when the body's metabolic needs are increased or if a mechanical problem exists with the ventilatory pump. As already noted, the motor neurons that activate the motion of the larynx are located within the VRG adjacent to inspiratory neurons. Thus, when these neurons send signals to initiate a breath, the muscles of the larynx are stimulated and the vocal cords abduct or move laterally outward, thereby decreasing the resistance of the upper airway and facilitating movement of air into the lungs.

Respiratory related neurons have also been identified in the pons, the portion of the brainstem superior to the medulla, although their function is not well delineated. These neurons are collected in a structure called the pontine respiratory group (PRG). Researchers speculate that the PRG assists the body in making a smooth transition from inspiration to expiration during the respiratory cycle, and they may serve to coordinate information from higher centers with the activity of the central pattern generator. Injuries to the PRG, as may occur with a stroke, can lead to apneustic breathing, a respiratory pattern characterized by breaths with a very long inspiratory phase followed by a rapid exhalation and a brief pause before the next inspiration.

The central pattern generator, while creating the inherent rhythm of breathing, does not act in isolation. Afferent information, a term that denotes neurological sensory messages arising in peripheral nerves and transmitted to the central nervous system (CNS), comes from a variety of sources. Within the lungs, flow, pressure, stretch, and irritant receptors provide data on the movement of gas and distention of the lung (Table 2-1). Chapter 6 discusses the function of these receptors in more detail.

Several specialized sensory bodies called chemoreceptors monitor oxygen and carbon dioxide levels as well as the pH of the blood, and the chemoreceptors have fibers that extend to the medulla in the region where the inspiratory neurons are located. The peripheral chemoreceptors are located in the aortic arch and in the carotid bodies at the bifurcation of the common carotid artery (note that, in humans, the carotid chemoreceptors appear to have a much more important role than the aortic chemoreceptor). The peripheral chemoreceptors respond to hypoxemia (low partial pressure of oxygen in the blood), hypercapnia (elevated levels of carbon dioxide), and changes in pH in the blood. The central chemoreceptors, located in the brainstem, are sensitive to changes in arterial carbon dioxide levels and pH (Chapter 6 discusses the physiology of these structures more fully). You might view this arrangement as a way for the automatic center to monitor the activity of the entire respiratory system at any given time and to make adjustments accordingly without the need for conscious intervention.

Behavioral Control ↑

In contrast to the cardiovascular and gastrointestinal systems, which are under only automatic control, the respiratory system is also under conscious control. You can instantly double the size of a breath or the rate at which you are breathing, Alternatively. you can hold your breath. Imagine trying to talk, sing, or swim without the ability to exert some influence on the central pattern generator. Of course, the automatic center cannot be inhibited indefinitely; the gas exchange abnormalities associated with breathholding stimulate the chemoreceptors to the point that your ability to hold your breath is limited.

Volitional efforts to initiate or increase breathing are generated in the motor cortex and descend directly to the relevant ventilatory muscles; these signals are not processed through the respiratory centers in the medulla. The role of this pathway can be seen in individuals with a rare congenital abnormality, congenital central hypoventilation syndrome (CCHS). In this condition, which is estimated to affect approximately 200 individuals worldwide, the central pattern generator is inoperative; there is no automatic control of breathing. Despite the absence of a functioning central pattern generator, however, people with CCHS are able to voluntarily initiate breaths.

Patients with CCHS provide an example of the independence of the automatic and volitional control of breathing. Breathholding offers an example of the integration of the two control mechanisms. Based on a unique experiment in which cats were trained to hold their breath, we believe that a breathhold is achieved by inhibiting the activity of the inspiratory neurons in the medulla (Orem J, Netick A: Behavioral control of breathing in the cat. Brain Research 1986, 366:238-253).