An overview of the anatomy and physiology of slowly adapting pulmonary stretch receptors
Introduction
Slowly adapting pulmonary stretch receptors are a category of neural afferent endings that innervate the tracheobronchial tree. Their original designation was based on the observation that an increase in airway wall tension increases receptor discharge, i.e. there is a rhythmic pattern of discharge during eupneic breathing (dynamic property) and that this increase in discharge slowly adapts as airway wall tension is maintained (static property). The rhythmic discharge of eupneic breathing is characterized by a mounting discharge during inspiration and a declining discharge during expiration. The pattern of slowly adapting stretch receptor discharge during eupneic breathing and lung inflation is a direct consequence of their anatomical location within the tracheobronchial tree and the orientation of the their receptor endings in relationship to airway wall structures. The first documented role for slowly adapting pulmonary stretch receptors was as the afferent ‘input’ for evoking the Hering–Breuer inflation reflexes. These reflexes are characterized by an early termination of inspiration when the lungs are inflated during inspiration and a prolongation of the expiratory pause when a prolonged inflation is applied at the end of inspiration (Fig. 1). In addition these receptors have been implicated in playing a role in the regulation of airway smooth muscle tone, in the regulation of systemic vascular tone and heart rate, in the regulation of breathing during exercise (CO2 loading) and in the pathophysiology of restrictive lung disease.
Previous reviews of the physiology of slowly adapting pulmonary stretch receptors (SARs) are both excellent and extensive (Widdicombe, 1954b, Coleridge and Coleridge, 1986, Paintal, 1973, Sant'Ambrogio, 1982). The purpose of the present paper is to summarize relevant findings previously reviewed and to bring these findings up to date. This is accomplished by emphasizing the structure-function relationships of SARs within the tracheobronchial tree and the possible consequences of the interactions of structure and function in the reflex control of breathing and airway smooth muscle tone.
Section snippets
Morphology and anatomical distribution
Bartlett et al. (1976a) combined single fiber afferent recording techniques with selective airway tissue resection in order to study the location of SARs in the extrathoracic trachea and mainstem and lobar bronchi. Receptors continued to function after the mucosa had been resected, but ceased to function when airway smooth muscle was removed. This is the best direct functional evidence that SARs are anatomically located within the airway smooth muscle layer and correspond to the myelinated
Receptor distribution
Elftman (1943) described receptors, with the characteristics of SARs, innervating the bronchial smooth muscle of the dog extending from the trachea to as far as smooth muscle extends down the airway, but did not provide a quantitative analysis of the distribution of these fibers along the tracheobronchial tree. Because of the desire to identify the specific receptors and stimuli that play a role in setting breathing pattern and evoking the Hering–Breuer inflation reflexes several investigators (
Pattern of discharge
Given their location in the tracheobronchial tree and the different forces acting upon them during the ventilatory cycle it is not surprising that extrathoracic, intrathoracic-extrapulmonary and intrapulmonary slowly adapting receptors have different patterns of discharge. In addition, these different populations of receptors respond differently to applied lung inflation and deflation. Intrathoracic slowly adapting receptors have a rhythmic pattern of discharge during eupneic breathing that is
Influence of altered SAR activity on tidal volume and inspiratory time
Following on the early work of Hering and Breuer, 1868a, Hering and Breuer, 1868b, and the subsequent characterization of the impulse activity of SARs during the ventilatory cycle by Adrian (Adrian, 1933, Sant'Ambrogio, 1982), most investigators now believe that central summation within the respiratory centers of the brain stem by SAR activity during inspiration acts as an ‘off-switch’ to terminate inspiration (Coleridge and Coleridge, 1986). If peak phasic SAR activity is increased during
Cardiovascular responses to lung inflation
The cardiovascular responses to lung inflation have been previously reviewed by Daly (1986) and Kaufman and Cassidy (1987). Briefly, lung inflation in anesthetized dogs has been shown to produce a consistent volume-dependent reduction in systemic vascular resistance that is abolished or markedly attenuated by sectioning of the pulmonary branch of the vagus nerve (Daly et al., 1967, Lloyd, 1978). The threshold for this response is 5 cmH2O which would be consistent with SARs being the vagal
Response to carbon dioxide
The possible existence in the lungs of a chemoreceptor that is sensitive to changes in mixed venous CO2 has been a subject of recurring interest and the source of much controversy, since Pi-Suner and Bellido postulated it in 1919 (Pi-Suner and Bellido, 1919). In the 1970s interest in a ‘mixed venous chemoreceptor’ was stimulated by the observations of Bartoli et al. (1974), who found that, in dogs with lungs isolated from the systemic circulation by cardiopulmonary bypass, delivery of CO2 to
Slowly adapting receptor-smooth muscle interactions
Numerous investigators have demonstrated an increase in peak inspiratory and/or mean expiratory discharge activity of SARs located below the trachea in several species following the administration of broncho constrictive agents (Widdicombe, 1954a, Bartlett et al., 1976a, Davenport et al., 1981b, Matsumoto et al., 1990) and vagal parasympathetic efferent stimulation (Matsumoto, 1996). These interventions have been shown to act through the contraction of airway smooth muscle and not by a direct
SARs and lung disease
The role that phasic activity of SARs plays in determining normal airway tone and how this may be altered in disease states, such as asthma, has become an area of active study. Recent studies suggest that SARs play important roles in the regulation of breathing pattern and/or airway tone in pathological conditions where their sensitivity to normal stimuli is increased due to bronchoconstriction (Widdicombe, 1954a, Bartlett et al., 1976a, Davenport et al., 1981b, Matsumoto et al., 1990), airway
Conclusion
Widdicombe (1964) in his chapter in the 1964 Handbook of Physiology points out the wide variation in threshold and potency of the Hering–Breuer inhibitory reflex in research animals and the perceived lack of influence of SAR discharge has on resting breathing pattern in man. While one has learned much in recent years, the knowledge is far from perfect. Most investigators now believe that in most species once a certain volume threshold is achieved the ‘inspiratory off-switch’ provided by stretch
Acknowledgements
The authors thank William Walby and Mario Alfaro for their assistance in preparing editing the manuscript. The authors would also like to thank Drs Laura Van Winkle and Charles Plopper from the Department of Anatomy, Physiology and Cell Biology, School of Veterinary Medicine, University of California, Davis for providing the confocal images of mouse airway smooth muscle.
References (96)
- et al.
The effect of varying tidal volume on the associated phrenic motor neurone output: studies of vagal and chemical feedback
Respir. Physiol.
(1975) - et al.
CO2-sensitivity of stretch receptors in the marsupial lung
Respir. Physiol.
(1980) Stimulus-response curves of the lung inflation cardiodepressor reflex
Respir. Physiol.
(1984)- et al.
Tonic vagal influences on inspiratory duration
Respir. Physiol.
(1975) Central and direct vagal dependent control of expiratory duration in anaesthetized rabbits
Respir. Physiol.
(1978)- et al.
The effect of the resistive loading of inspiration and expiration on pulmonary stretch receptor discharge
Respir. Physiol.
(1981) - et al.
Effect of bronchoconstriction on the firing behavior of pulmonary stretch receptors
Respir. Physiol.
(1981) - et al.
Location of pulmonary stretch receptors in the guinea-pig
Respir. Physiol.
(1989) - et al.
Discharge patterns of the lung stretch receptors and activation of deflation fibres in anaphylactic bronchial asthma
Respir. Physiol.
(1973) - et al.
Study of CO2 sensitive vagal afferents in the cat lung
Respir. Physiol.
(1976)