RESUMEN
Vagal afferent nerves are the primary communication pathways between the bronchopulmonary system and the central nervous system. Input from airway afferent nerves to the CNS is integrated in the brainstem and ultimately leads to sensations and various reflex outputs. Afferent nerves innervating the airways can be classified into various distinct phenotypes. However, there is no single classification scheme that takes all features, including conduction velocity, cell body diameter, ganglionic origin, and stimuli to which they respond (modality) into account. At present, bronchopulmonary afferent nerves are typically considered to belong to one of three general categories, namely C-fibres, rapidly adapting stretch receptors (RARs), and slowly adapting stretch receptors (SARs). As our understanding of bronchopulmonary afferent nerves continues to deepen, we are likely to see more sophisticated classification schemes emerge. It is clear that the function of afferent fibres can be substantively influenced by airway inflammation and remodelling. The perturbations and perversions of afferent nerve function that occur during these states almost certainly contributes to many of the signs and symptoms of inflammatory airway disease. A more lucid characterization of bronchopulmonary afferent nerves, and a better understanding of the mechanisms by which these nerves influence pulmonary physiology during health and disease anticipates future research.
Asunto(s)
Vías Aferentes/fisiología , Bronquios/inervación , Pulmón/inervación , Conducción Nerviosa/fisiología , Plasticidad Neuronal/fisiología , Receptores de Estiramiento Pulmonares/fisiología , Vías Aferentes/anatomía & histología , Humanos , Neurotransmisores/fisiología , Receptores de Estiramiento Pulmonares/anatomía & histología , Sistema Respiratorio/inervación , Estornudo/fisiologíaRESUMEN
Pulmonary sensory receptors are the initiating sites for lung reflexes; however, little is known about their structure, especially the relationship between the structure and function of these receptors. Using a novel approach (combining electrophysiological and morphological techniques), we examined the structures of the typical slowly adapting pulmonary stretch receptors (SARs) located in the lung periphery. We recorded SAR activities in the cervical vagus nerve, identified the receptive field, dissected the SARs in blocks, fixed and processed these blocks for immunohistochemical staining using anti-Na+/K+-ATPase, and examined the blocks under a confocal microscope. These SAR structures have multiple endings that have terminal knobs. Some structures that are located in the airway walls have terminal knobs buried in smooth muscle. Others are in the most peripheral part of the lung, and their terminal knobs have no obvious relation to smooth muscle, suggesting that muscle contraction may not be a direct factor for SAR activation.
Asunto(s)
Pulmón/anatomía & histología , Pulmón/fisiología , Receptores de Estiramiento Pulmonares/anatomía & histología , Receptores de Estiramiento Pulmonares/fisiología , Animales , Axones/fisiología , Estimulación Eléctrica , Electrofisiología , Inmunohistoquímica , Pulmón/inervación , Microscopía Confocal , Fibras Nerviosas Amielínicas/fisiología , Conejos , ATPasa Intercambiadora de Sodio-Potasio/metabolismoRESUMEN
Rapidly adapting receptors (RARs) in the airway mucosa are found from the nasopharynx to the bronchi. They have thin (Adelta) vagal afferent fibres and lie in and under the epithelium, but their morphology has not been defined. They are very sensitive to mechanical stimuli, and have a rapidly adapting irregular discharge. However, with in vitro preparations they are rather insensitive to chemical stimuli, apart from acid and nonisosmolar solutions. Their pattern of response varies with site. RARs in the nasopharynx, larynx, and trachea usually respond only during the onset of stimuli, while those in the trachea often have an off-response as well. Those in the bronchi are less rapidly adapting and more chemosensitive. Their membranes have mechanosensitive and acid-sensitive ion channels, but no vanilloid receptors. In vivo RARs are sensitive to a wide range of chemical irritants and mediators, and presumably are excited secondarily to mechanical changes in the mucosa and airway smooth muscle. In the central nervous system (CNS) they interact with other vagal afferent pathways. The reflexes they cause vary with site (inspiratory efforts from the nasopharynx, cough or expiratory efforts from the larynx and trachea, and deep breaths or tachypnoea from the bronchi). Pathways from RARs and other vagal reflexes show plasticity at the peripheral, ganglionic, and CNS levels.
Asunto(s)
Receptores de Estiramiento Pulmonares/anatomía & histología , Receptores de Estiramiento Pulmonares/fisiología , Adaptación Fisiológica , Vías Aferentes/fisiopatología , Animales , Bronquios/inervación , Bronquios/fisiopatología , Tos/fisiopatología , Humanos , Conducción Nerviosa/fisiología , Plasticidad Neuronal/fisiología , Reflejo , Fenómenos Fisiológicos Respiratorios , Sistema Respiratorio/inervaciónRESUMEN
Since the original work by Hering and Breuer (1868) on slowly adapting pulmonary stretch receptors (SARs), numerous studies have demonstrated that these receptors are the lung vagal afferents responsible for eliciting the reflexes evoked by moderate lung inflation. SARs play a role in controlling breathing pattern, airway smooth muscle tone, systemic vascular resistance, and heart rate. Both anatomical and physiological studies support the contention that SARs, by their close association with airway smooth muscle, continuously sense the tension within the myoelastic components of the airways caused by lung inflation, smooth muscle contraction, and/or tethering of small intrapulmonary airways to the lung parenchyma. As a result, the receptor field location within the tracheobronchial tree of a SAR plays an important role in its discharge pattern, with variations in airway transluminal pressure and airway smooth muscle orientation being important modulating factors. The disruption of airway myoelastic components in various pulmonary diseases would be expected to alter the discharge pattern of SARs, and contribute to changes in breathing pattern and airway smooth muscle tone.
Asunto(s)
Receptores de Estiramiento Pulmonares/anatomía & histología , Receptores de Estiramiento Pulmonares/fisiología , Adaptación Fisiológica , Animales , Ácidos Araquidónicos/farmacología , Moduladores de Receptores de Cannabinoides/farmacología , Capsaicina/farmacología , Endocannabinoides , Humanos , Pulmón/inervación , Pulmón/fisiología , Conducción Nerviosa/efectos de los fármacos , Alcamidas Poliinsaturadas , Receptores de Estiramiento Pulmonares/efectos de los fármacos , Receptores de Droga/metabolismo , Reflejo , Nervio Vago/efectos de los fármacos , Nervio Vago/fisiologíaRESUMEN
Since the original work of by Hering and Breuer in 1868 numerous studies have demonstrated that slowly adapting pulmonary stretch receptors (SARs) are the lung vagal afferents responsible for eliciting the reflexes evoked by moderate lung inflation. SARs play a role in controlling breathing pattern, airway smooth muscle tone, systemic vascular resistance and heart rate. Both anatomical and physiological studies support the contention that SARs, by their close association with airway smooth muscle, continuously sense the tension within the myoelastic components of the airways caused by lung inflation, smooth muscle contraction and/or tethering of small intrapulmonary airways to the lung parenchyma. In addition, intrapulmonary SAR discharge activity is sensitive to changes in P(CO2) within the physiological range. Despite this extensive characterization of SARs, their role in determining breathing pattern and airway tone in individuals with respiratory diseases is only recently being appreciated.
Asunto(s)
Receptores de Estiramiento Pulmonares/anatomía & histología , Receptores de Estiramiento Pulmonares/fisiología , Adaptación Fisiológica/fisiología , Animales , HumanosRESUMEN
Rapidly adapting receptors (RARs) occur throughout the respiratory tract from the nose to the bronchi. They have thin myelinated nerve fibres, an irregular discharge and adapt rapidly to a maintained volume stimulus, but often slowly to a chemical stimulus. They are polymodal, responding to mechanical and chemical irritant stimuli, and to many inflammatory and immunological mediators. RARs show very varied sensitivities to different stimuli, and diverse reflex responses. Those in the larynx are usually called 'irritant' receptors. They probably cause cough, the expiration reflex and other laryngeal reflexes: cardiovascular, mucus secretion, bronchoconstrictor and laryngoconstrictor. Those in the trachea and larger bronchi are very mechanosensitive; they cause cough, bronchoconstriction and airway mucus secretion. Those in the larger bronchi are more chemosensitive; they may cause cough, but also stimulate hyperventilation, augmented breaths, mucus secretion, bronchoconstriction and laryngeal closure. Most of the stimuli to RARs also affect other airway receptors, especially those with C-fibre afferents, and the total reflex response will be the additive affect of all these reflexes.
Asunto(s)
Receptores de Estiramiento Pulmonares/anatomía & histología , Receptores de Estiramiento Pulmonares/fisiología , Reflejo/fisiología , Adaptación Fisiológica/fisiología , Animales , Bronquios/fisiología , Humanos , Laringe/fisiología , Pulmón/fisiologíaRESUMEN
The site of pulmonary slowly adapting stretch receptors (SRs) was investigated in anaesthetized, thoracotomized and artificially ventilated guinea-pigs. The location of SRs within the lungs and airways was determined by analyzing the changes of SR single fibres discharge patterns in response to (a) occlusion of the airways, (b) local probing, and (c) microinjection of the non-diffusible local anaesthetic cinchocaine into the presumed receptor site. The great majority (92%) of the 79 SRs examined was localized in small airways or in lung parenchyma ('peripheral SRs'), whereas only 8% were located in large airways, i.e., in the trachea, main bronchi and lobar bronchi ('central SRs'). The discharge responses to lung inflation and to ammonia inhalation slightly differed between these two SR groups. With the pronounced prevalence of peripheral SRs, the guinea-pig seems to take a unique position among the species examined hitherto.
Asunto(s)
Cobayas/anatomía & histología , Mecanorreceptores/anatomía & histología , Receptores de Estiramiento Pulmonares/anatomía & histología , Sistema Respiratorio/inervación , Administración por Inhalación , Amoníaco/farmacología , Animales , Cobayas/fisiología , Pulmón/fisiología , Receptores de Estiramiento Pulmonares/efectos de los fármacos , Receptores de Estiramiento Pulmonares/fisiología , Respiración ArtificialRESUMEN
The distribution and location of slowly adapting pulmonary stretch receptors (PSRs) that affect respiratory and cardiovascular functions were investigated in anaesthetized, artificially ventilated and thoracotomized cats. The location of the receptors was done by punctate stimulation and local mechanical stimulation after occlusion of the trachea at end-expiration (Exp). 84% of the slowly adapting PSRs were found to be located in the lung parenchyma. The occlusion technique alone was found to be of help only for a limited population of stretch receptors. The intrapulmonary distribution of PSRs revealed a greater percentage of receptors in the diaphragmatic lobe. No correlation was found between conduction velocity and receptor location. Both the slowly and rapidly conducting receptors were found to be scattered throughout the entire lung parenchyma. However, it was observed that while the majority of low threshold (LT) PSRs were located closer to the hilum of the lung, many of the higher threshold (HT) receptors were located farther away. In addition, when veratrine was administered into the pulmonary circulation, 83% of HT PSRs studied were stimulated by the drug, while only 25% of LT PSRs under study could be stimulated this way. The significance of the above findings is discussed.
Asunto(s)
Adaptación Fisiológica , Pulmón/inervación , Mecanorreceptores/anatomía & histología , Receptores de Estiramiento Pulmonares/anatomía & histología , Obstrucción de las Vías Aéreas/fisiopatología , Animales , Gatos , Electrofisiología , Femenino , Inyecciones Intravenosas , Masculino , Conducción Nerviosa/efectos de los fármacos , Estimulación Física , Veratrina/administración & dosificaciónRESUMEN
Seven kittens age 5 to 8 days were anaesthetized with ketamine, tracheotomized, cannulated just below the larynx, paralyzed, and ventilated. The thorax was widely opened and an expiratory load equal to the transpulmonary pressure at functional residual capacity (PLFRC) added. Single vagal fibers were dissected from the peripheral cut end of the right vagus nerve. Thirty-eight receptor discharges modulated during the respiratory cycle (pulmonary stretch receptors, PSR) were studied; 4 (10.5%) were tonically active at PLFRC while the remaining 34 had a mean threshold at 3.2 cmH2O. All the receptors progressively increased their discharge frequency with higher pressures reaching a plateau between 8-10 cmH2O. By occluding the airways at different levels of the tracheobronchial tree 32 PSR were functionally localized: none were found in the extrathoracic trachea; 3 (9.5%) were located in the intrathoracic trachea, 12 (37.5%) at the carina, main bronchi, and lobar bronchi, and 17 (53%) inside the lobes. All three tracheal receptors were tonic PSR. Previously obtained data from adult mammals indicate that 27-60% of PSR are tonically active and most of these are located in the trachea. The low incidence of tonically active PSR in the kitten may suggest a delayed functional maturation of the tracheal receptors.
Asunto(s)
Bronquios/inervación , Mecanorreceptores/anatomía & histología , Receptores de Estiramiento Pulmonares/anatomía & histología , Tráquea/inervación , Animales , Animales Recién Nacidos , Gatos , Electrofisiología , Receptores de Estiramiento Pulmonares/fisiología , RespiraciónRESUMEN
Pulmonary stretch receptors are thought to mediate the breathing frequency (bf) response to changes in pulmonary CO2. However, the location and distribution of these receptors is disputed. The purpose of this study was to determine what contribution the extrapulmonary receptors make in the pulmonary CO2 bf response. Mongrel dogs were anesthetized and placed on cardiopulmonary bypass. The diaphragm electromyogram was used to monitor respiratory center output and to trigger a ventilator. Exposure of an upper airway segment to CO2 or positive end-expired pressure failed to produce changes in the bf. Denervation of the upper airway down to but not including the hilum caused similar insignificant changes in the CO2 bf response. Lungs collapsed by suction showed minimal Hering-Breuer inhibition when compared with inflated lungs. Bronchial arterial perfusion with hypocapnic followed by hypercapnic blood failed to produce changes in the bf while similar perfusion of the pulmonary arterial system resulted in significant increases in bf. It appears that the receptors mainly responsible for the pulmonary CO2 response are located in the more peripheral regions of the lung.
Asunto(s)
Dióxido de Carbono , Mecanorreceptores/fisiología , Receptores de Estiramiento Pulmonares/fisiología , Respiración , Animales , Perros , Pulmón/anatomía & histología , Pulmón/fisiología , Mediciones del Volumen Pulmonar , Receptores de Estiramiento Pulmonares/anatomía & histologíaRESUMEN
The localization of pulmonary stretch and deflation receptors was studied in anaesthetized, paralysed and artificially ventilated rabbits by recording the afferent activity in the vagus nerve while moving a double lumen balloon catheter along the tracheo-bronchial tree. The distributions of the two types of receptors were found to be parallel, with a proportion of 4 stretch receptors for 1 deflation receptor. A statistical analysis of the experimental results demonstrated that the distribution between stretch and deflation receptors was unbiased by the sampling procedure. However, in the localization of the stretch receptors along the tracheobronchial tree, there was a sampling bias, which constitutes a limit to the quantification of the results.