When is expiration active

Ventilation , or breathing, is the movement of air through the conducting passages between the atmosphere and the lungs. The air moves through the passages because of pressure gradients that are produced by contraction of the diaphragm and thoracic muscles. Pulmonary ventilation is commonly referred to as breathing.

It is the process of air flowing into the lungs during inspiration inhalation and out of the lungs during expiration exhalation. Air flows because of pressure differences between the atmosphere and the gases inside the lungs.

Air, like other gases, flows from a region with higher pressure to a region with lower pressure. Ventilation is generally expressed as volume of air times a respiratory rate. The volume of air can refer to tidal volume the amount inhaled in an average breath or something more specific, such as the volume of dead space in the airways. The three main types of ventilation rates used in respiratory physiology are:.

Additionally, minute ventilation can be described as the sum of alveolar and dead space ventilation, provided that the respiratory rate used to derive them is in terms of breaths per minute. The three types of ventilation are mathematically linked to one another, so changes in one ventilation rate can cause the change of the other.

This is most apparent in changes of the dead space volume. Breathing through a snorkeling tube and having a pulmonary embolism both increase the amount of dead space volume through anatomical versus alveolar dead space respectively , which will reduce alveolar ventilation. Alveolar ventilation is the most important type of ventilation for measuring how much oxygen actually gets into the body, which can initiate negative feedback mechanisms to try and increase alveolar ventilation despite the increase in dead space.

In particular, the body will generally attempt to combat increased dead space by raising the frequency of breaths to try and maintain sufficient levels of alveolar ventilation. Gaseous Exchange in the Lungs: Diagram of gas exchange in the lungs. When gasses dissolve in the bloodstream during ventilation, they are generally described by the partial pressure of the gasses.

Partial pressure more specifically refers to the relative concentration of those gasses by the pressure they exert in a dissolved state. PaO 2 and PaCO 2 refer to the partial pressures of oxygen and carbon dioxide within arterial blood.

Differences in partial pressures of gasses between the alveolar air and the blood stream are the reason that gas exchange occurs by passive diffusion. Under normal conditions, PAO 2 is about mmHg, while PaO 2 is 80— mmHg in systemic arteries, but 40—50 mmHg in the deoxygenated blood of the pulmonary artery going to the lungs. Recall that gasses travel from areas of high pressure to areas of low pressure, so the greater pressure of oxygen in the alveoli compared to that of the deoxygenated blood explains why oxygen can passively diffuse into the bloodstream during gas exchange.

The partial pressure, and thus concentration of carbon dioxide, is greater in the in the capillaries of the alveoli compared to the alveolar air, so carbon dioxide will passively diffuse from the bloodstream into the alveoli during gas exchange. Additionally, because PaCO 2 is an indicator of the concentration of carbon dioxide in arterial blood, it can be used to measure blood pH and identify cases of respiratory acidosis and alkalkosis.

Inhalation is the flow of air into an organism that is due to a pressure difference between the atmosphere and alveolus. Inspiration refers to inhalation—it is the flow of the respiratory current into an organism.

In humans it is the movement of ambient air through the airways and into the alveoli of the lungs. Inspiration begins with the contraction of the diaphragm, which results in expansion of the thoracic cavity and the pleural cavity.

The pleural cavity normally has a lower pressure compared to ambient air —3 mmHg normally and typically —6 mmHg during inspiration , so when it expands, the pressure inside the lungs drops. Pressure and volume are inversely related to each other, so the drop in pressure inside the lung increases the volume of air inside the lung by drawing outside air into the lung.

As the volume of air inside the lung increases, the lung pushes back against the expanded pleural cavity as a result of the drop in intrapleural pressure pressure inside the pleural cavity. The force of the intrapleural pressure is even enough to hold the lungs open during inpiration despite the natural elastic recoil of the lung. The alveolar sacs also expand as a result of being filled with air during inspiration, which contributes to the expansion inside the lung.

Eventually, the pressure inside the lung becomes less negative as the volume inside the lung increases and, when pressure and volume stabilize, air movement stops, inspiration ends, and expiration exhalation will begin. Deeper breaths have higher tidal volumes and require a greater drop in intrapleural pressure compared to shallower breaths.

Respiratory System: Resistance in any part of the respiratory tract can cause problems. The diaphragm is the primary muscle involved in breathing, however several other muscles play a role in certain circumstances.

These muscles are referred to as accessory muscles of inhalation. The accessory muscles assist breathing by expanding the thoracic cavity in a similar way to the diaphragm.

However, they expand a much smaller part of the thoracic cavity compared to diaphragm. Therefore they should not be used as the primary mechanism of inhalation, because they take in much less air compared to the diaphragm resulting in a much lower tidal volume.

For example, singers need a lot of air to support the powerful voice production needed for singing. A common problem in novice singers is breathing with the accessory muscles of the neck, shoulder, and ribs instead of the diaphragm, which gives them a much smaller air supply than what is needed to sing properly. Expiration, also called exhalation, is the flow of the respiratory current out of the organism.

Therefore, our work may represent the first model of the closed-loop respiratory system incorporating both mechanical and chemical feedback that simulates the transition to breathing with active expiration during hypercapnia. We extended the previously published model of lung mechanics and gas exchange [15] by incorporating an additional pump to simulate the effects of abdominal muscle contractions during active expiration We then connected this model with the previously developed, well elaborated model of the respiratory network [18] , [37] with both mechanoreceptor and central chemoreceptor feedback.

To test our model in a normal metabolic state normocapnia we performed several modeling experiments that simulated well-known experimental procedures including vagotomy removing mechanoreceptor feedback , pontine transection, and phase-dependent brief and continuous stimulations of mechanoreceptor vagal feedback.

Removal of vagal feedback in the model caused increases in the durations of both inspiration and expiration and in the maximum lung volume V A and lung tidal volume, along with a corresponding reduction in breathing frequency Figure 2.

These changes fully correspond to experimental data concerning the effects of vagotomy on the pattern of breathing [1] , [41]. Our simulations of brief vagal stimulations lung inflation applied during inspiration Figure 3C confirmed that such stimulation could produce premature termination of inspiration and that the threshold for such inspiratory termination decreased during inspiration.

These modeling results are also consistent with the existing experimental data [1] , [40] and previous modeling studies [12]. Similarly, we showed that continuous vagal stimulation lung inflation produced shortened inspiration and prolonged expiration, and that increases in the strength of this stimulation lead to expiratory apnea, which is consistent with the existing experimental data as well [1] , [41] , [45] , [46].

The results of these benchmark simulations provide an important validation of our closed-loop respiratory model, including the organization of interactions within the respiratory network and the organization and role of mechanoreceptor feedback in the closed-loop control of respiration.

The recruitment and activation of abdominal muscles during active expiration evoked by hypercapnia or exercise and their involvement in the amplification of ventilation have been amply documented [21] — [23].

It appears that this study is the first to address these issues using a computer model of the closed-loop control of ventilation.

To perform these investigations, we first modified the biomechanical lung model to incorporate an additional pump simulating the effect of abdominal muscle contractions on lung volume and ventilation Figure 1B. Second, following previous models [32] , [33] we simulated central chemoreceptor feedback, including a nonlinear dependence of RTN excitatory drive to the respiratory network and to the late-E neuron in the pFRG on the partial pressure of CO 2 in blood and tissue, calculated in the model of the lungs with gas exchange and transport Figure 1B.

As a result, our model was able to simulate the behavior of the closed-loop respiratory system during hypercapnia and capture the transition to active expiration with an increase of CO 2 level. Our simulations of hypercapnia predict that with the development of hypercapnia associated with an increase in the external concentration of CO 2 the respiratory system goes through a gradual transition to the regime of active expiration via the mechanism of quantal acceleration of the late-E and abdominal motor activity [29] , [37].

This transition process is shown in Figures 5 and 6 for the intact and vagotomized cases, respectively. Specifically, abdominal motor outputs activate the abdominal pump and hence cause a reduction of basal lung volume and an increase in the amount of air expelled in each cycle in which they occur see Figures 4 — 6. Interestingly, the latter modeling-based conclusion is consistent with multiple experimental findings indicating that an increase in ventilation during hypercapnia in various preparations occurs mostly due to an increase in the breathing amplitude and that the respiratory rate does not significantly increase with hypercapnia after vagotomy [1] , [47] — [50].

This work represents the first attempt to computationally model the closed-loop neural control of respiration in mammals with a specific focus on active expiration under conditions of hypercapnia. The model, although greatly simplified relative to the full complexity present biologically, reproduces multiple experimental phenomena related to mechanoreceptor and central chemoreceptor feedback to the neural controller in the brainstem.

Based on our simulations we suggest that the closed-loop respiratory control system switches to active or forced expiration when a further increase of ventilation by a simple increase in the rate of breathing and phrenic amplitude defining the maximal lung inflation becomes insufficient or not effective enough to support gas homeostasis. The major limitation of the present model results from a lack of peripheral chemoreceptor pathways, which do not allow us to explicitly consider their role in control of breathing.

The model will be further extended by incorporating peripheral chemoreceptors and their pathways to study their role in closed-loop control of respiration under different conditions, including various respiratory disorders. All parameters in the model were based on studies on rats or tuned to match known observations from rats. The neuronal part of the model is an extended version of the model described by Rubin et al. The six neurons indicated in Figure 1 are modeled using a conductance-based description with non-spiking output.

In this framework, the membrane potential of neuron , is governed by the equation 1 where is a membrane capacitance, and are the conductance and the reversal potential of the leak current, , and , are the maximal conductances and reversal potentials of inhibitory and excitatory synaptic inputs, and , are the gating variables of inhibitory and excitatory synaptic channels, respectively.

The potassium rectifier current is described as 2 where is its maximal conductance, is the potassium reversal potential and specifies the voltage dependence of the potassium rectifier instantaneous activation.

The dynamics of the inactivation variable is governed by 4 where ms and are the voltage dependent time constant and steady state activation, respectively. For Early-I, Aug-E and Post-I neurons , , which is the potassium adaptive current given by 5 where is its maximal conductance, is the reversal potential for potassium, and is the inactivation gating variable governed by 6 where is a time constant, is a scaling parameter, and.

For Ramp-I ,. The gating variables for synaptic conductances are derived from the activity of presynaptic neurons and other input sources using the equations 8 9 where the function f V is defined in 7 , the constant drive comes from the pons, the drive D 2 is due to the RTN as defined in 27 below, and the non-zero synaptic weights a, b, c, e, f are provided in Table 1.

The lung and gas transport model represents an extended version of the model described by Ben-Tal and Smith [16] with certain parameters rescaled to represent the adult rat system. Diaphragm and abdominal effective displacements, and , are described by 10 11 These are dynamical variables that follow the activity of the ramp-I neuron, , and the late-E neuron, , with the parameters and representing muscle recoil while and represent a conversion from neural activity to velocity.

The mechanics and gas exchange in the lungs are taken from [15] , [39]. Specifically, diaphragm and abdominal muscles affect the pleural pressure through the relationship 12 where is the total pressure in the mouth, is the residual pressure, and are the conversion coefficients. Note that while. The alveolar pressure is a dynamical variable described by the differential equation 13 Here is the lung elastance and is the net flux of gas into the alveoli.

This flux consists of the flux from to the mouth and diffusion to from the blood: 14 where is the air flow from , inspiration or to , expiration the mouth, with airway resistance. The terms concerned with diffusion in 14 include the diffusion capacities , and differences of partial pressures in the blood and alveoli of carbon dioxide and oxygen, respectively.

Alveolar partial pressures are expressed in terms of the relative content of carbon dioxide and oxygen in the alveoli: 15 16 where is the water vapor pressure at Partial pressures of CO 2 and O 2 in the blood, , are dynamical variables that are reinitialized every heart beat i.

In 18 , is the derivative of the hemoglobin saturation function 20 with parameters , , and provided in Table 2 below. The dynamics of the relative content of gases in the alveoli is described as follows: 21 22 where are inspired concentrations of oxygen and carbon dioxide, respectively, defined by 23 are the relative concentrations of O 2 and CO 2 in the mouth, and is the lung volume given by The activity of the pulmonary stretch receptors PSR was taken to be equal to the inspired lung volume: 25 Chemoreceptor activity RTN drive was modeled as a saturating function of the smoothed partial pressure of carbon dioxide in the blood.

To this end, we used the equation 26 where is the value of the CO 2 partial pressure right before the most recent heart beat. The RTN drive was calculated using a simplified version of the expression suggested in [32] , 27 where is used to simulate RTN stimulation where applicable see text and is otherwise set to 0.

All model parameters for the lungs and gas transport are shown in Table 2. Differential equations were solved using the exponential Euler integration method with a time step of 0. Browse Subject Areas? Click through the PLOS taxonomy to find articles in your field.

Abstract Breathing is a vital process providing the exchange of gases between the lungs and atmosphere. Introduction The neural control of ventilation in mammals serves two major functions. Model The Closed-loop Control of Breathing: System Organization and Interactions We developed a mathematical model of the closed-loop system for the control of breathing, as illustrated in a general diagram in Figure 1A.

Download: PPT. Figure 2. Model performance in control conditions A and after vagotomy B. Lung Mechanics and Gas Exchange and Transport The lung and gas exchange sub-system in the model is based on the earlier models of Ben-Tal and Smith [15] , [16]. Feedforward and Feedback Connections For simplicity, the phrenic and abdominal motoneurons, and the premotor cVRG neurons have not been explicitly modeled. Figure 3. Perturbations of respiratory neural activity pattern by pontine removal and vagal stimulations.

Modeling Hypercapnia and Active Expiration As shown in many physiological studies, hypercapnia causes an increase of ventilation. Figure 4. Figure 5. Simulation of progressive hypercapnia in the intact model. Figure 6. Simulation of progressive hypercapnia in the vagotomized model. Figure 7. Changes in tidal volume, breathing rate, and ventilation relative to normocapnia with the development of hypercapnia in the intact panel A and vagotomized panel B models. Comparison of Model Simulations with Experimental Data In the closed-loop control system considered here, the RTN represents the major site of CO 2 central chemoreception [34] , [35] and the target for chemical feedback.

Figure 8. Comparison of model simulations with experimental data. Discussion Modeling the Closed-Loop Respiratory System We have developed a novel closed-loop model of the respiratory system with well elaborated neural and pulmonary components: the brainstem respiratory network and CPG, representing the neural controller, and the biomechanical model of lungs including gas exchange and transport mechanisms, representing the controlled subsystem and providing both mechanical and chemical feedback to the neural controller.

Modeling Hypercapnia and Active Expiration The recruitment and activation of abdominal muscles during active expiration evoked by hypercapnia or exercise and their involvement in the amplification of ventilation have been amply documented [21] — [23]. Conclusions Our simulations of hypercapnia predict that with the development of hypercapnia associated with an increase in the external concentration of CO 2 the respiratory system goes through a gradual transition to the regime of active expiration via the mechanism of quantal acceleration of the late-E and abdominal motor activity [29] , [37].

Methods Parameters All parameters in the model were based on studies on rats or tuned to match known observations from rats. Modeling the Pontine-Medullary Respiratory Network The neuronal part of the model is an extended version of the model described by Rubin et al.

Modeling the Lungs and Gas Transport The lung and gas transport model represents an extended version of the model described by Ben-Tal and Smith [16] with certain parameters rescaled to represent the adult rat system. Mechanoreceptor and Central Chemoreceptor Feedback The activity of the pulmonary stretch receptors PSR was taken to be equal to the inspired lung volume: 25 Chemoreceptor activity RTN drive was modeled as a saturating function of the smoothed partial pressure of carbon dioxide in the blood.

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