Review of Medical Physiology - William F. Ganong 2002

Respiration
Regulation of Respiration
Nonchemical Influences on Respiration

Response Reactions Caused by Airways and Lung Receptors

Receptors within the airways and Lungs are innervated by myelinated and unmyelinated fibers of the Vagus nerve. The unmyelinated fibers consist of C-fibers. Receptors innervated by myelinated fibers are typically divided into two groups: slowly adapting receptors and rapidly adapting receptors. This division is supported by stimuli that induce prolonged or short-lasting impulse activity in their respective afferent nerve fibers (Table 36-2). Another group of receptors predominantly comprises C-fiber endings, which are classified as pulmonary or bronchial based on their Location. The shortening of inspiration induced by vagal afferent activity (see Fig. 36-3) is initiated by slowly adapting receptors. This shortening is known as the Hering-Breuer reflex. This reflex—consisting of the prolongation of expiration upon lung inflation and the Hering-Breuer deflation reflex—shortens the expiration phase triggered by the corresponding release of air from the lungs.

Class="center">Table 36-2. Airway and Lung Receptors¹

¹ Modified and reproduced with permission from Berger AJ, Hornbein TF: Control of Respiration. In: Textbook of Physiology, 21st ed. Vol. 2. Patton HD et al [editors]. Saunders, 1989.

Because rapidly adapting receptors are stimulated by chemical agents such as histamine, they are also referred to as irritant receptors. Activation of this receptor type in the Trachea causes coughing, bronchoconstriction, and mucus secretion, whereas in the lungs it may induce hyperventilation.

The C-fiber endings located close to the pulmonary vessels are called J-receptors (derived from juxtacapillary). They are stimulated by hyperventilation in the lungs and also respond to intravenous or intracardiac administration of chemical agents such as capsaicin. The reflex response is apnea followed by rapid breathing, bradycardia, and hypotension (pulmonary chemoreflex). A similar response is elicited by receptors in The Heart (Bezold-Jarisch reflex or coronary chemoreflex; see Chapter 31). The Physiological Role of this reflex remains incompletely understood, but it is partly observed during pathological conditions such as pulmonary edema or pulmonary artery embolization, and develops upon the release of endogenous substances.

Cough and Sneeze

A cough begins with a deep inspiration and is followed by a forceful expiration against a closed glottis. This increases intrapleural pressure to 100 mmHg or even higher. The glottis then suddenly opens, producing an explosive blast of air outward at speeds of up to 965 km/h. Sneezing is a similar expiratory maneuver with a prolonged open glottis (see Chapter 14). These Reflexes help eliminate irritants and keep the airways clean.

Responses in Patients with Cardiopulmonary Transplants

Heart-lung transplantation has moved past the experimental stage and is now an established Treatment for severe pulmonary diseases and certain other conditions. Specifically, in transplant recipients, the recipient's right atrium is connected to the donor heart; the donor heart is not reinnervated, so the resting heart rate is typically higher. The donor trachea is anastomosed to the recipient's trachea just above the carina, and afferent fibers from the lungs do not regenerate. Consequently, observing heart-lung transplant recipients provides an opportunity to assess The Role of pulmonary innervation in normal physiology. Irritant-induced cough responses occur normally in these patients because the trachea is innervated; however, irritation of the smaller airways does not elicit a cough. In heart-lung transplant recipients, the Bronchi tend to be more dilated than normal. Furthermore, they exhibit a normal frequency of yawns and sighs, indicating that these actions do not depend on pulmonary innervation. Transplant patients exhibit a loss of the Hering-Breuer reflexes, yet resting breathing remains normal, demonstrating that these reflexes do not play a critical role in regulating resting ventilation.

Afferent Pathways to Higher Centers

Painful and emotional stimuli affect respiration, implying the presence of afferent inputs from the Limbic System and Hypothalamus to the respiratory Neurons of the Brainstem. Furthermore, steady breathing is not always a conscious act. Both inspiration and expiration are under voluntary control. The pathways for voluntary regulation run from the neocortex directly to the motor neurons innervating the Respiratory Muscles, bypassing the medullary neurons.

Because voluntary and autonomic controls of breathing are separate, autonomic control can occasionally be interrupted without the loss of voluntary control. The clinical condition arising from this is known as Ondine's curse. In German legend, Ondine was a Water nymph who had a treacherous mortal lover. The King of the water nymphs severely punished the lover by stripping him of all autonomic Functions. As a result, he could stay alive only while awake by consciously remembering to breathe, but exhausted, he eventually fell asleep and his breathing ceased. This condition is seen in patients with bulbar encephalitis due to poliomyelitis or brainstem decompression.

Afferent Fibers from Proprioceptors

Precise studies have demonstrated that active and passive joint movements stimulate breathing, as impulses in afferent pathways from proprioceptors in muscles, tendons, and joints excite inspiratory neurons. This influence likely increases pulmonary ventilation during Physical Exercise.

Respiratory Components of Visceral Reflexes

The respiratory adjustments during vomiting, swallowing, and coughing are described in Chapters 14 and 26. The inhibition of respiration and closure of the glottis during these actions not only prevent the aspiration of food or vomitus into the trachea but also halt chest wall movements during vomiting so that abdominal muscle contractions can increase intra-abdominal pressure. Similarly, glottic closure and respiratory inhibition occur during voluntary and involuntary straining.

Hiccups are spasmodic contractions of the Diaphragm and other inspiratory muscles that produce an inspiration, during which the glottis abruptly closes. Glottic closure accounts for the characteristic sensation and sound. Hiccups occur in the fetus during intrauterine development and can manifest throughout a person's life. Their exact function remains unclear. Most episodes are short-lived and often correspond to breath-holding or other stimuli that increase P_CO2. Prolonged hiccups can be debilitating.

Yawning is a peculiar, contagious respiratory act whose physiological basis and significance remain unknown. Much like hiccups, yawning appears in the prenatal period and is also characteristic of fish, turtles, and mammals. Unventilated alveoli are prone to collapse; therefore, deep inspirations are thought to open them and prevent The Development of Atelectasis. Yawning also enhances venous return to the heart. Sighs perform similar functions. Moreover, recent experiments demonstrate the anti-atelectatic effect of sighing. It has also been suggested that sighing serves as a nonverbal signal for communication within animal groups, and some maintain that the same holds true for humans, albeit on a different level.

Respiratory Effects of Baroreceptor Stimulation

Afferent fibers from baroreceptors in the carotid sinus, aortic arch, atria, and ventricles transmit impulses to respiratory neurons as well as to vasomotor and cardioinhibitory neurons in the Medulla Oblongata. Impulses from these receptors inhibit respiration, but this effect is modest and its physiological significance is minor. Hyperventilation during Shock is caused by acidosis resulting from chemoreceptor stimulation and secondary Hypoxia due to local circulatory stagnation (occurring independently of baroreceptors). The activity of inspiratory neurons affects blood pressure and heart rate (see Chapters 28 and 31), whereas activity in the vasomotor and cardiac centers of the medulla can exert only a minor influence on respiration.

Effects of Sleep

Breathing during sleep is less tightly controlled than during wakefulness, and brief periods of apnea normally occur in sleeping adults. Various changes in pulmonary ventilation then develop in response to hypoxia. If P_CO2 drops during wakefulness, various proprioceptive and environmental stimuli maintain ventilation, but during sleep the efficacy of these stimuli is diminished, and a drop in P_CO2 may induce apnea. During REM sleep, breathing is irregular, and the response to CO₂ is highly variable.