Control of respiration pdf

Sensa- Traditional approaches to the study of respiratory regula- tion originates with the stimulation of receptors and receptor tion have focused on the automatic and involuntary control stimulation is transduced into neural electrical impulses that of breathing with an emphasis on chemical and neurome- are transmitted along afferent pathways to the central nerv- chanical reflex pathways.

Key to the study of the respiratory ous system. Central processing by higher brain centers in- adjustments to changes in the mechanical properties of the volving recapitulation, abstraction, and interpretation results ventilatory apparatus is an accurate and reliable measure of in some evoked expression.

With respect to the respiratory respiratory motor output. For studies in human subjects, the system, receptors that may subserve respiratory sensation airway occlusion pressure, a measure of the forces generated include mechanoreceptors in airways, lungs, respiratory by the respiratory muscles contracting isometrically against a muscles, tendons, joints [4].

In a series of studies we and others showed that respiratory motor Psychophysical Studies output as measured by the occlusion pressure increased with Psychophysics is the study of the functional relations between stimulus variables on a physical continuum and the corresponding conscious sensation [5].

Altose Experimental approaches include threshold detection that ratory muscles [11]. With lung volume increases to produce measure the smallest stimulus or smallest change in stimulus muscle shortening, forces perceived to be the same required intensity that can be perceived and magnitude scaling that greater drive as measured by the EMG; with decreases in involve having subjects attempt to quantify the intensities of lung volume to increase muscle resting length there was less a range of stimuli.

A popular approach involved the magni- drive for forces perceived to be the same. However, with tude scaling of added external ventilatory loads. Loads over changes in lung volume to alter resting muscle length, the at least a fold range are added to the breathing circuit for perception of muscle force closely followed muscle tension.

As the magni- In addition to the psychophysical studies, there is con- tude of the load increases, there is a proportional increase in vincing physiological evidence that afferent signals related the intensity of the response and the relationship between the to breathing are transmitted to higher brain centers.

Respira- physical magnitude of the load and the resulting sensation tory-related sensory projections to the cerebral cortex and follows the psychophysical power law [6]. Brief early and mid-inspiratory airway ventila- among changes in airflow, lung inflation, chest wall expan- tory loads produce respiratory-related evoked potentials. Furthermore, the psychophysical re- while longer latency components, from to msec rep- sponses to different kind of loads elastic loads, a function of resent cognitive processing by higher brain centers that are volume, as compared to resistive loads, a function of flow considerably influenced by alertness, experience and expec- are not the same.

Subsequent studies by Killian et al. The close relationship between the amplitude of the showed that load sensation is preferentially shaped by the short latency cortical-evoked potentials and the magnitude magnitude and duration of the forces generated by the respi- scaling of the load provides important physiological valida- ratory muscles during the loaded breath. A role for rib cage tion of the psychophysical studies and supports the idea of muscle receptors is suggested by the impaired ventilatory the respiratory-related evoked potentials as a neural measure load sensation in patients with low cervical spinal cord of cortical activity related to respiratory load sensation [15].

In patients following double-lung Other studies have also shown that subjects can sepa- transplantation the early latency components in response to rately quantitate respiratory force and respiratory displace- inspiratory occlusion are not significantly different from ment.

We have assessed the sensations of thoracic displace- normal but the late latency respiratory-related evoked poten- ment by magnitude scaling of breath volume and by the tial, P3, were delayed and of a smaller amplitude suggesting technique of matching the volume of control breaths with that vagal afferents are not essential to elicit the evoked re- test breaths [9].

In matching studies, provided the mechani- sponse but may contribute to the cognitive processing of cal conditions of both control and test breaths are the same, respiratory stimuli [16].

On the other hand, direct intramus- matching is highly accurate. However the error in matching cular microstimulation has demonstrated projections of low- increases when the mechanical conditions change between threshold afferents from human intercostal muscles to the control and test breaths.

The volume of a test breath taken cerebral cortex [17]. A variety of other studies support an important role of Similarly, others have shown that the perceived magnitude chest wall receptors in mediating respiratory sensation.

One of breath volume is greater during breathing against an approach involves chest wall vibration which is known to added ventilatory load and less during passive mechanical induce discharge from muscle spindles. Vibration of the ventilation [10]. These findings suggest that the sensations of chest wall to activate muscle spindles produces an illusion of displacement is shaped at least in part by the forces devel- chest movement. Chest wall vibration has also been shown oped by the contracting respiratory muscles.

Other sites can con- species of fish: trout Oncorhynchus mykiss , goldfish tribute to that response. The authors described innervated 24 and the spiracle or pseudobranch, innervated by nerves NEC at the filament tips in all species in a prime location to VII and IX 23 and maybe the brain The first gill arch sense PwO2, in agreement with physiological data. Activity the efferent filament artery.

Vagal Furthermore, the authors also described a group of non- afferent fibres also connect with the trigeminal complex that innervated NEC in the lamella that might have a paracrine receives inputs from proprioceptors in the respiratory pump role, acting directly on the pillar cells to enhance respiratory muscles innervated by the trigeminal Vth cranial nerve.

As surface area when exposed to aquatic hypoxia. Chemoreceptor stimulation transmitted in the to try to map locations and distribution as a function of vagus nerve, that affects ventilation, may be relayed via phylogeny, habitat and life history.

Short-term plasticity, the medulla. However, microinjection of glutamic acid into due to a previous history of exposure to hypoxia, may also identified areas of the vagal sensory projection in sculpin, lead to changes in responsiveness and even functionality identified by injection of a fluorescent tracer, elicited specific, of receptors The respiratory muscles in fish frequency and amplitude Glutamate has been identi- contain length and tension receptors, in common with other fied as the neurotransmitter for afferents into the nucleus vertebrate muscles, and the gill arches bear a number of tractus solitarii NTS in mammals.

Ventilation of the gills generates hydrostatic These mechanoreceptors will also be stimulated by the pressures, which fluctuate around, but predominantly above ventilatory movements of the gill arches and filaments and ambient levels. Arterial blood pressures in the branchial may be important in stabilising the respiratory rhythm.

When circulation of fish and the pressure difference across the gill gill arches of a lightly anaesthetised fish were artificially epithelia are relatively low, despite the fact that the highest moved the respiratory rhythm was regularly reset by the systolic pressures are generated in the ventral aorta, which imposed movements in a manner related to the phase of leaves the heart to supply the afferent branchial arteries.

However, in teleosts, injection of adrenaline, was close to the natural rhythm Central stimulation towards the brain of nerves in- yohimbine. These data imply active regulation of vasomotor nervating respiratory muscles in the carp with short trains tone and the balance of evidence indicates that functional of electrical stimuli also entrained the respiratory rhythm arterial baroreceptors may exist in the branchial circulation to the imposed stimuli The branchial branches of the IXth and Xth cranial nerves innervate a range of tonically and phasically ac- Aquatic surface respiration and air-breathing in fish tive mechanoreceptors as well as chemoreceptors on the It has generally been considered that hypoxia, conse- gill arches of fish and project directly to a dorsal sensory quent upon stagnation of tropical freshwater habitats, was nucleus lying above the equivalent motor nuclei in the the environmental spur for the evolution, in the Devonian medulla The sensory area in turn projects centrally era, of air-breathing in many bony fishes, which use a to the respiratory motor nuclei.

However, sensory fibres variety of different ABO, from modified swimbladders to from branchial receptors may terminate in different loca- diverticula of the branchial chambers There are also a tions within the brainstem and consequently have different large number of highly derived marine teleosts that occupy effects on integration. The selection pressures may have been loops, either directly or via the RF and may be involved an ability to tolerate emersion during low tide and to escape in the reflex contraction of adductor muscles on the gill extremes of salinity and hypoxia in tidepools.

These species filaments in response to mechanical stimulation of the gill typically use the skin, gills, and branchial chambers as ABO. Stronger stimulation may induce the However, it has been argued on the basis of fossil evidence www. Shingles et al. It has been suggested that true air-breathing evolved bradycardia, were elicited by chemoreceptors sensitive to from a behaviour known as aquatic surface respiration oxygen levels in the ventilatory water stream and the blood ASR As the name implies, ASR involves rising to the stream of flathead grey mullet Mugil cephalus.

Florindo et surface and ventilating the layer of water in contact with the al. Many teleost species have evolved and orobranchial cavity, innervated by cranial nerves VII, this behavioural response in both temperate and tropical IX, and X. These chemoreceptor sensory modalities and environments, freshwater and marine.

Many species also innervations would appear to be homologous, therefore, to hold an air bubble or bubbles in their mouth when they those that drive reflex gill hyperventilation in all fish groups perform ASR, which may have a dual role of increasing oxy- studied to date 1, Thus, ASR may use the pre-existing gen levels in the bucco-opercular cavity, and maintaining the sensory arm of such hypoxic ventilatory reflexes, integrating fish buoyant at the water surface 38 , and may have been a new motor output that involves rising to the water surface the behavioural antecedent to true air-breathing.

Indeed, to ventilate the surface layer. Presumably, cessation of this behaviour is also driven by information from the same chemoreceptors Clearly, ASR is a much more complex chemoreflex than A changes in gill ventilation, with a very large behavioural component, which must involve significant inputs from higher brain centres Teleost fish exhibit behavioural modulation of gill ventilation patterns, and such higher- order inputs to the respiratory medulla must, presumably, have been a prerequisite for the evolution of the complex motor responses of ASR and true air-breathing in fishes.

One major ecological cost to reflexes such as ASR and air-breathing is that they place fish at significantly greater risk from aerial predation by birds. Exposure of the grey mullet to a model avian predator B delayed the onset of ASR in hypoxia or in response to direct chemoreceptor stimulation with cyanide. Furthermore, the fish surfaced preferentially under a sheltered area in their experimental chamber or close to the walls Figure 5A. In turbid water, the fish could not see the model predator and it had no effect on the onset of ASR but, in turbidity, all the mullet preferentially surfaced around the walls of their chamber Figure 5B.

Thus, the behavioural component of the ASR reflex is plastic; it can be modulated by inputs from higher centres, in particular as a function of perceived risk of predation A number of species have morphological features, such as upturned mouths and flattened heads, which appear to Figure 5.

Aerial view of locations of aquatic surface respiration ASR events performed by flathead grey mullet Mugil cephalus improve the efficiency of ASR. In some species, the mor- in response to an external application of mg NaCN into the phological adaptations are very pronounced such as the ventilatory stream via a buccal cannula A or when exposed to dermal lip protuberances in various tropical teleosts.

For aquatic hypoxia B in clear water left panel or in turbid water example, in the Neotropical tambaqui, C. Open circles represent ASR events in the absence a funnel that skims the surface layer of water into the of a model avian predator; solid circles represent events in the presence of the model.

The outer lines at the top of the diagrams mouth Florindo et al. Braz J Med Biol Res 43 5 www. Stimuli for of the Florida gar Lepisosteus platyrhincus to a model avian air-breathing in fish include hypoxia and hypercapnia, both predator resulted in a decrease in air-breathing frequency modulated by increased temperature and exercise, which and an increase in gill ventilation effort.

Herbert and Wells increase oxygen demand and CO2 production 4, In 42 found that fear of predation reduced air-breathing fre- the bowfin, air-breathing was only stimulated by changes in quency by the blue gourami, Trichogaster trichopterus, an water or blood O2 status, but not by changes in plasma acid- obligate air breather, which compensated by reducing activ- base status 13 , and further evidence suggests that bowfin ity, presumably to conserve the O2 stored in the ABO.

Indeed, air-breathing is known ing in amphibious marine species. The giant mudskipper, to be a chemoreflex driven by oxygen-sensitive receptors Periopthalmodon schlosseri, lives on tidal mudflats, where The surfacing and gulping response in freshwater it builds a deep burrow, from which it emerges to forage air-breathing species can be stimulated by chemoreceptors between shallow puddles and the exposed mudflats. It is an that sense oxygen levels in either the ventilatory water or obligate air breather, which stores air in a highly vascular- the blood stream 13, The The sites for O2-chemoreception in these fishes regu- gills are only ventilated with water when the animal expires late not only air-breathing, but also changes in heart and the air from its orobranchial cavity, at which point it will gill ventilation.

Only a small number of species have been submerge the mouth and perform a few cycles of gill ven- studied to date and there is a lack of information about the tilation McKenzie DJ, unpublished personal observations. Application of the O2 chemorecep- air breath causing a characteristic variation in heart rate that tor stimulant sodium cyanide NaCN into the ventilatory is observed in all air-breathing fishes, namely an expiration water stream of longnose gar Lepisosteus osseus inhibited bradycardia followed by an inspiration tachycardia A gill ventilation and elicited air-breathing, whereas NaCN representative trace of this is shown in Figure 6A.

In the bowfin, only ventral aortic blood pressure and heart rate in the same externally applied NaCN elicited air-breathing, whereas mudskipper, with a pronounced hypoxic bradycardia and a both external and internal NaCN stimulate gill ventilation large increase in air-breathing frequency.

Figure 6C shows In the obligate air breather the African lungfish, there the effects of cyanide gas, given as a bolus into the buccal were air-breathing responses to both internally and exter- cavity, on heart rate, blood pressure and air-breathing in a nally applied NaCN, whereas in the facultative air breather giant mudskipper.

There is a typical teleost bradycardia in Ancistrus, which possesses suprabranchial chambers, response to cyanide, followed by vigourous air-breathing hypoxia stimulated air-breathing but increased temperature responses. Cyanide given as a bolus into the bloodstream, and exercise did not. Exactly the same pat- uted in the gills and pseudobranch of the gar and bowfin, tern of responses to hypoxia and cyanide was observed in innervated by cranial nerves VII, IX and X.

Thus, this meagre data set demonstrates that pletely abolished air-breathing in normoxia and abolished the giant mudskipper possesses chemoreceptors, which responses to hypoxia and NaCN 13, Air-breathing elicit bradycardia and air-breathing, but that these appar- can also be stimulated by stretch receptors in the swim- ently monitor oxygen levels in the air held in the mouth, bladder, which in the spotted gar Lepisosteus oculatus with no sensitivity to blood oxygen levels.

Most air-breathing fish supply their chemoreceptors, innervated by the IXth cranial nerve, that various air-breathing organs from the systemic circulation. It is possible that those receptors would work in the ies and veins in association with true lungs, having highly air-breathing fish by stopping gill ventilation while the ABO permeable surfaces; the lungfish, Protopterus, has a dif- organ provided oxygen to the blood in hypoxic waters.

However, possibly because dence that air-breathing reflexes are significantly influenced they retain gills, lungfish have similar, relatively low blood by higher central processing, in particular a perceived risk pressures in the respiratory and systemic circuits and, as of predation. Smith and Kramer 41 reported that exposure a consequence, may not have a functional requirement www.

Responses oedema resulting from hypertension. It could of course be to hypoxia in larval bullfrogs were eliminated by ablation argued that control of blood pressure in a relatively low of the first gill arches, suggesting that they are the site of pressure system requires sensitive pressoreception. This the O2-sensitive chemoreceptors. A residual slow response remains to be demonstrated. Amphibians The rapid responses to hypoxia are blunted in later stage Chemoreceptors. A detailed review by West and Van bullfrog larvae, in which the lungs are developing and the Vliet 45 considered the roles of peripheral chemoreceptors gills degenerating.

In an earlier study of the bimodally and baroreceptors in cardiorespiratory control in amphib- breathing bullfrog tadpole, mild aquatic hypoxia was found to ians, while the factors influencing the progressive transition increase gill ventilation but more severe hypoxia promoted from water to air-breathing during amphibian metamorphosis high frequencies of lung ventilation and a suppression of gill ventilation 1,47 , which was in response both to lung inflation per se and to the resulting increase in PO2 In the neotenous, gill-bearing axolotl, Ambystoma mexicanum, both gill ventilation and air-breathing were stimulated by cyanide, infused either into the ventilatory water stream or into the blood stream 1.

Cardiac responses were com- plex with an initial bradycardia, presumably in response to stimulation of peripheral chemoreceptors, followed by a tachycardia at the first air breath, possibly in response to stimulation of lung stretch receptors, a situation comparable to the mammalian response to hypoxia 1. Heart rate in the bullfrog tadpole did not change during aquatic hypoxia, with access to air 1, While their larvae may retain functional oxygen receptors on the gill arches, the carotid labyrinths are the main putative sites for oxygen receptors in adult amphibians.

They are situated at the bifurcation of the internal and external carotid arteries and innervated by branches of the glossopharyngeal nerve, which projects its afferent fibres to the NTS in the brainstem These receptors are functionally similar to the mammalian carotid bodies, as they also respond to hypercapnia and their discharge can be modulated by sympathetic stimulation 1.

More recent studies have also shown that the receptors are sensitive to oxygen partial pressure, rather than content 45 ; a finding consistent with the results of whole animal study of the stimulus modality of the hypoxic ventilatory response in toads 1. The degree of shunting is likely to Figure 6. Representative traces of ventral aortic blood pressure be referred to input from peripheral chemoreceptors. The return of blood to the right side of 2 mg NaCN acidified to form gaseous HCN given as a bolus of the heart from the cutaneous circulation may specifically into the orobranchial cavity during an air-breath holding period serve to improve oxygen supply to the myocardium, which C , see text for details.

A similar response was recorded showed that lung inflation inhibited fictive breathing, as from the in vitro preparation of the bullfrog brainstem 1,4. Repeating sociation with periods of submersion, typically display large these experiments in unanesthetised animals indicated that increases in heart rate and pulmonary blood flow at the the contribution of peripheral receptors to respiratory drive onset of bouts of lung ventilation.

Whereas artificial lung inflation increased heart rate drive in the toad, a similar proportion to that observed in in anaesthetised toads, in conscious Xenopus laevis, mammals 1,4, PSR denervation did not abolish the increase in heart rate This dominant role for central chemoreceptors in the associated with lung inflation and in lightly anaesthetised generation of respiratory drive in amphibians appears at animals artificial lung inflation did not affect heart rate, metamorphosis.

An in vitro preparation of the isolated though pulmo-cutaneous blood flow increased 1. A similar brainstem from the bullfrog tadpole displayed co-ordinated, response was demonstrated in Bufo marinus In early stage larvae, variations in pH of the su- Chemoreceptors.

Scattered groups of glomus cells perfusate were without effect on gill or lung burst frequency. This area is profusely innervated by the superior pH The onset of episodic breathing patterns during laryngeal branch of the vagus nerve and possibly the metamorphosis was coincident with developmental changes glossopharyngeal nerve 1.

All primary afferent fibres of the in the nucleus isthmi in the bullfrog, and it seems possible glossopharyngeal and the majority of vagal afferent fibres, that this region of the brainstem is involved in integration enter the NTS in the monitor lizard. Although activity in these of central chemoreceptor information Pulmonary stretch receptors this area abolished the increase in ventilation shown by PSR constitute another important source of feedback, lizards when hypoxic or hypercapnic blood was injected contributing to the control of breathing in amphibians.

There into the carotid arch 1,4, These recep- division of the internal carotids, the external carotids having tors are innervated by afferent fibres in the pulmonary vagi atrophied during development Milsom 26 suggests 51,52 , which project to the solitary tract in the brainstem that due to this process the site homologous to the carotid The receptors are mostly slowly adapting and their bifurcation in amphibians and mammals is part of the aortic firing rates decrease when the intrapulmonary CO2 con- arch in turtles.

The largest aggregations of chemoreceptive centration is increased 47,52, There is evidence for tissue are found in this central cardiovascular area and are interactions between mechanoreceptor and chemoreceptor innervated by the superior and inferior branches of the vagus reflexes.

In the toad lung, inflation decreased the effect of nerve arising from the nodose ganglion. The inferior branch cyanide injection, while these same effects were increased also innervates chemoreceptors located on the pulmonary by hypercapnia Pulmonary afferent fibres play a key role in the termi- These receptor groups have been shown to respond nation of lung inflation in the adult and inhibition of buccal to changes in oxygen level but their roles in establishing oscillation in the pre-metamorphic tadpoles.

The evidence resting ventilatory drive or in reflex responses to hypoxia is that pulmonary deafferentation by vagotomy in Xeno- are unknown Peripheral oxygen receptors in reptiles pus results in an increase in the number of inspirations seem to respond to a reduction in oxygen content i. Similar characteristics ventilation in the bullfrog 1,55 , indicating that PSR feed- have been attributed to arterial chemoreceptors in fish and back modulates the breathing pattern; however, these data in birds and mammals This matter amphibians, have pulmonary and systemic circulations that remains unresolved as decerebrate paralysed anurans are incompletely separated, so that some systemic venous www.

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A short summary of this paper. Respiratory Sensation and Control of Breathing. This led to studies of respiratory sensation using a variety of psy- chophysical approaches. These psychophysical studies revealed that respiratory-related physical changes are consciously appreciated and indicated that sensory information from the ventilatory apparatus does reach the cerebral cortex. This was further supported by physiological studies that demonstrated respiratory-related cortical-evoked potentials over somato- sensory regions of the brain.

Studies utilizing chest wall vibration support an important role for chest wall muscle spindles in mediating respiratory sensation. Our studies have also shown that voluntarily reducing the level of ventilation at a con- stant level of chemical drive results in a progressive proportional increase in the intensity of the unpleasant sensation of respiratory discomfort and the increase in respiratory sensation is predominantly a function of the degree to which tidal volume is reduced suggesting that limiting chest expansion or thoracic displacement is the proximate cause of the un- pleasant sensation.

Our observations that the sensation of dyspnea intensifies with increases in ventilation as well as when ventilation is reduced below the spontaneously adopted free breathing level can be simulated by mathematical models that suggest that respiratory drive integration depends not only on the direct effects of chemical and mechanical feedback but also on the perceptual consequences of these stimuli.

In the course of daily living, the body is challenged to ventilatory loading in conscious but not in anesthetized ani- maintain homeostasis by changes in metabolic, mechanical, mals and humans and the increase occurs even though and environmental conditions.

Challenges posed to the respi- chemical drive is held constant [2,3]. The dependence of this ratory system are greatest by diseases of the ventilatory ap- non-chemically mediated load compensation response on a paratus that affect the mechanical properties of the lung and state of wakefulness suggested that the mechanism was not chest wall and the mechanical advantage of the respiratory simply an automatic reflex but rather involved conscious muscles.

In the face of all of these perturbations, the respira- behavioral processing by higher brain centers. This raised tory system manages to make appropriate adjustments so as the question of whether the perception of the load or the con- to maintain ventilation at appropriate levels and preserve scious appreciation of the ventilatory consequences of the blood gas and acid-base homeostasis.

The initial focus of our loading is required in order that respiratory motor output be research was to identify the mechanisms of the respiratory increased. It has been long known that there are somatic sensations of position, movement and muscle tension. Sensa- Traditional approaches to the study of respiratory regula- tion originates with the stimulation of receptors and receptor tion have focused on the automatic and involuntary control stimulation is transduced into neural electrical impulses that of breathing with an emphasis on chemical and neurome- are transmitted along afferent pathways to the central nerv- chanical reflex pathways.

Key to the study of the respiratory ous system. Central processing by higher brain centers in- adjustments to changes in the mechanical properties of the volving recapitulation, abstraction, and interpretation results ventilatory apparatus is an accurate and reliable measure of in some evoked expression. With respect to the respiratory respiratory motor output. For studies in human subjects, the system, receptors that may subserve respiratory sensation airway occlusion pressure, a measure of the forces generated include mechanoreceptors in airways, lungs, respiratory by the respiratory muscles contracting isometrically against a muscles, tendons, joints [4].

In a series of studies we and others showed that respiratory motor Psychophysical Studies output as measured by the occlusion pressure increased with Psychophysics is the study of the functional relations between stimulus variables on a physical continuum and the corresponding conscious sensation [5].

Altose Experimental approaches include threshold detection that ratory muscles [11]. With lung volume increases to produce measure the smallest stimulus or smallest change in stimulus muscle shortening, forces perceived to be the same required intensity that can be perceived and magnitude scaling that greater drive as measured by the EMG; with decreases in involve having subjects attempt to quantify the intensities of lung volume to increase muscle resting length there was less a range of stimuli.

A popular approach involved the magni- drive for forces perceived to be the same. Tarasova, , published in Fiziologiya Cheloveka, , Vol. Reprints and Permissions. Nervous control of respiration. Hum Physiol 32, — Download citation. Received : 28 October Issue Date : July Anyone you share the following link with will be able to read this content:. Sorry, a shareable link is not currently available for this article.

Provided by the Springer Nature SharedIt content-sharing initiative. Skip to main content. Search SpringerLink Search. Abstract Century-old notions on and formulations of the principle of external respiration control are discussed.

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