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Hypoxia is sensed at the carotid body a: The carotid bodies are located bilaterally in the neck, at the rostral end of the left and right common carotid arteries, i.e., at the bifurcation into the internal and external carotid arteries. b: Hypoxia closes potassium channels in the type I cell glomus cell in the carotid body, which induces cell depolarization and opens voltage-gated calcium channels. Elevated calcium ion concentration in the cells triggers the release of neurotransmitters. These neurotransmitters cause firing of the carotid sinus nerve that sends signals of hypoxia information to the medullary respiratory center. Excitatory neurotransmitters released from type I cells activate P2Y 2 receptors on type II cells sustentacular cell , which induces elevation in intracellular calcium ion and opens the pannexin-1 channels. Subsequently, the opened pannexin-1 channels cause the release of neurotransmitters.
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Dyspnea is defined as “a subjective experience of breathing discomfort that consists of qualitatively distinct sensations that vary in intensity”. In patients especially with pulmonary diseases, dyspnea reduces daily activity, which worsens the physical condition, and thereby further increases dyspnea, forming a vicious cycle. In clinical practice,...
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Context 1
... chemoreceptors, such as the carotid body, are also excited by hypercapnia. However, they are relatively less activated as compared to hypoxia 18 Figure 2 . Further investigation is necessary to determine whether or not afferent information from central and peripheral receptors, which are excited by hypercapnia and hypoxia, directly induces sensation of dyspnea. ...
Citations
... However the role of these factors as a primary determinant of dyspnea is unclear. The dyspnea could also result from a mismatch between the respiratory motor output developed by the neuronal respiratory network and the accomplished ventilatory motor activity (Fukushi and Okada, 2019;Fukushi et al., 2021). Indeed, higher brain centers compare the respiratory motor command corollary discharge to the information coming Potential mechanism at the origin of the pulmonary fibrosis-induced neuroplasticity leading to increase of the ventilatory drive. ...
Some patients with idiopathic pulmonary fibrosis present impaired ventilatory variables characterised by low forced vital capacity values associated with an increase in respiratory rate and a decrease in tidal volume which could be related to the increased pulmonary stiffness. The lung stiffness observed in pulmonary fibrosis may also have an effect on the functioning of the brainstem respiratory neural network, which could ultimately reinforce or accentuate ventilatory alterations. To this end, we sought to uncover the consequences of pulmonary fibrosis on ventilatory variables and how the modification of pulmonary rigidity could influence the functioning of the respiratory neuronal network. In a mouse model of pulmonary fibrosis obtained by 6 repeated intratracheal instillations of bleomycin (BLM), we first observed an increase in minute ventilation characterised by an increase in respiratory rate and tidal volume, a desaturation and a decrease in lung compliance. The changes in these ventilatory variables were correlated with the severity of the lung injury. The impact of lung fibrosis was also evaluated on the functioning of the medullary areas involved in the elaboration of the central respiratory drive. Thus, BLM-induced pulmonary fibrosis led to a change in the long-term activity of the medullary neuronal respiratory network, especially at the level of the nucleus of the solitary tract, the first central relay of the peripheral afferents, and the Pre-Bötzinger complex, the inspiratory rhythm generator. Our results showed that pulmonary fibrosis induced modifications not only of pulmonary architecture but also of central control of the respiratory neural network. KEYWORDS lung injury, central respiratory drive, neuroplasticity, IPF-idiopathic pulmonary fibrosis, FOSB
... The inflammatory environment in COPD affects the vagal sensory nerve activity via the stimulation of a group of vagal receptors such as C-fibers and irritant receptors. Irritant receptors are located around the epithelial cells of the bronchial walls while C-fibers innervate the airways and the lungs 41 . It has been postulated that oxidative stress causes a perturbation to these receptors that are capable to evoke dyspnea 42,43 . ...
Chronic obstructive pulmonary disease (COPD) is a respiratory disease with high prevalence. Many factors contribute to its development, and probably that leads to its various clinical pictures. Inflammation is the mechanism responsible for the structural alterations in the lungs. Despite its heterogeneity, there are a couple of primary symptoms characterizing it, which are chronic and productive cough and dyspnea. The understanding of dyspnea in COPD is based on theories deriving from the interaction of a network formed between the cardiorespiratory and the neuromuscular system and their receptors. Many factors contribute to its occurrence, making it complex and giving it a very subjective character for a person to perceive. Various methods are used to study COPD. Non-invasive ones seem to attract attention nowadays. One of them is the exhaled breath condensate. It is a biofluid with rich content, which can capture a picture of the pathological processes happening in the lungs. Its study has shown that some markers of inflammation and oxidative stress, such as 8-isoprostane and H2O2, are elevated and able to connect dyspnea and inflammation. Additionally, they seem to provide information of the ongoing inflammatory process in the lungs as well as a picture of the severity of the symptoms. This evidence may enhance the association of dyspnea with dysfunctional breathing. Despite these interesting findings, further research is necessary both in dyspnea and inflammation in COPD to clarify their mechanisms and connective pathways. The utility of non-invasive techniques such as the exhaled breath condensate could be of significant help, but its establishment in the medical field requires extra studies.
... A spate of receptors is involved in the continuous monitoring of respiration; these receptors provide information on the chemical composition of arterial blood, the mechanics of the respiratory pump, and the perception of dyspnea (Table 1) [7]. ...
Dyspnea is defined as a subjective experience of breathing discomfort that consists of qualitatively distinct sensations that vary in intensity. It is a common symptom among patients with respiratory diseases that reduces daily activities, induces deconditioning, and is self-perpetuating. Although clinical interventions are needed to reduce dyspnea, its underlying mechanism is poorly understood depending on the intertwined peripheral and central neural mechanisms as well as emotional factors. Nonetheless, experimental and clinical observations suggest that dyspnea results from dissociation or a mismatch between the intended respiratory motor output set caused by the respiratory neuronal network in the lower brainstem and the ventilatory output accomplished. The brain regions responsible for detecting the mismatch between the two are not established. The mechanism underlying the transmission of neural signals for dyspnea to higher sensory brain centers is not known. Further, information from central and peripheral chemoreceptors that control the milieu of body fluids is summated at higher brain centers, which modify dyspneic sensations. The mental status also affects the sensitivity to and the threshold of dyspnea perception. The currently used methods for relieving dyspnea are not necessarily fully effective. The search for more effective therapy requires further insights into the pathophysiology of dyspnea.
