Physiology of Breathing.
In order to keep living our cells need the oxygen, available in the air we breath and that the body takes constantly and cycle-wise through breathing. Each cycle is made of two steps: inhalation, when the air gets into the body full of oxygen, and exhalation, when the air gets out of the body full of carbon dioxide produced through our metabolic process. The air we breath gets out of our body with an average rate of 13/16 cycles per minute. The alternation between inhalation and exhalation is controlled by the respiratory centre, that is located in the medulla oblongata at the base of the skull.
The centre gets signals by the chemoreceptors about the level of carbon dioxide in our body: when such a level increases over a certain amount it gives the impulse to the respiratory apparatus to inhale and exhale again. Let’s briefly see which are the components of the respiratory apparatus following the path of the incoming air.
I. Common characteristic of breathing. The respiratory system is divided into a respiratory zone, which is the site of gas exchange between air and blood, and a conducting zone, which conducts the air to the respiratory zone. The exchange of gases between air and blood occurs across the walls of tiny air sacs called alveoli, which are only a single cell layer thick to permit very rapid rates of gas diffusion.
The term respiration includes three separate but related functions:
(1) ventilation (breathing);
(2) gas exchange, which occurs between the air and blood in the lungs and between the blood and other tissues of the body; and (3) oxygen utilization by the tissues in the energy – liberating reactions of cell respiration. Ventilation and the exchange of gases (oxygen and carbon dioxide) between the air and blood are collectively called external respiration. Gas exchange between the blood and other tissues and oxygen utilization by the tissues are collectively known as internal respiration.
Ventilation is the mechanical process that moves air into and out of the lungs. Since the oxygen concentration of air is higher in the lungs than in the blood, oxygen diffuses from air to blood. Carbon dioxide conversely moves from the blood to the air within the lungs by diffusing down its concentration gradient. As a result of this gas exchange, the inspired air contains more oxygen and less carbon dioxide than the expired air. More importantly blood leaving the lungs (in the pulmonary veins) has a higher oxygen and lower carbon dioxide concentration than the blood delivered to the lungs in the pulmonary arteries. This result bring the fact that lungs function is to give gaseous equilibrium between blood and the air.
Intrapulmonary and Intrapleural Pressures
The visceral and parietal pleurae are stuck to each other like two wet pieces of glass. The intrapleural space between them contains only a thin layer of fluid, secreted by the parietal pleura. This fluid is like the interstitial fluid in other organs; it is formed as a filtrate from blood capillaries in the parietal pleura, and it is drained into lymphatic capillaries. The major function of the liquid in the intrapleural space is to serve as a lubricant so that the lungs can slide relative to the
chest during breathing. Since the lungs normally are stuck to the thoracic wall, for reasons described shortly, they expand and contract with the thoracic wall during breathing. The intrapleural space is thus more a potential space than a real
one; it becomes real only if the lungs collapse.
Air enters the lungs during inspiration because the atmospheric pressure is greater than the intrapulmonary, or intraalveolar, pressure. Because the atmospheric pressure does not usually change, the intrapulmonary pressure must fall below
atmospheric pressure to cause inspiration. A pressure below that of the atmosphere is called a subatmospheric pressure, or negative pressure. During quiet inspiration, for example, the intrapulmonary pressure may decrease to 3 mmHg below the
pressure of the atmosphere. This subatmospheric pressure is shown as − 3 mmHg. Expiration, conversely, occurs when the intrapulmonary pressure is greater than the atmospheric pressure.
During quiet expiration, for example, the intrapulmonary pressure may rise to at least + 3 mmHg over the atmospheric pressure . Because of the elastic tension of the lungs (discussed shortly) and the thoracic wall on each other, the lungs pull
in one direction (they “try” to collapse) while the thoracic wall pulls in the opposite direction (it “tries” to expand). The opposing elastic recoil of the lungs and the chest wall produces a subatmospheric pressure in the intrapleural space
between these two structures. This pressure is called the intra pleural pressure. The intrapleural pressure is lower (more negative) during inspiration because of the expansion of the thoracic cavity than it is during expiration. However, the
intrapleural pressure is normally lower than the intrapulmonary pressure during both inspiration and expiration.
FUNDAMENTALS OF BIOMECHANICS
The cyclic alternation of inhalation and exhalation takes place tank to the activity of several muscles working right for the same aim. The most important one is the diaphragm, sinergically working with the ribcage muscles ant not only. The lungs in fact, per definition are passive organs, they cannot move autonomously to let air in and out, but they are expanded during inhalation, by the action of the diaphragm and the thorax inhalation muscles, or they are compressed by the exhalation muscles and by the abdominal muscles in case of forced exhalations.
The diaphragm is essentially an inhalation muscle: when its fibres contract, they lower it taking with them the lower portions of the lungs that expand and let air in.
Just to have an idea of what happens we can think the diaphragm as the piston of a syringe, while it goes down it sucks the air through the respiratory tract that in this example would represent the structure of the syringe.
The diaphragm however does not work alone. During inhalation (fig: 2) it works together with the external and middle intercostal muscles that in synergy with other thorax muscles (scalenus, sternocleidomastoideus) are destined to the expansion and the contraction of the ribcage, increasing the thorax volume and by consequence the quantity of air within the lungs.
The rib motions are essentially two: one called “bucket handle”, expanding the thorax, and the other called “pump lever”, raising the ribcage. In the exhalation phase the diaphragm de-contracts going back its original cupola shape, the thorax muscles relax, the ribs lower and the thorax gets back to its original volume (fig. 3). During the exhalation there should not be a massive muscle action as it all happens by relaxation.
However there are some exhalation muscles playing a key role in case of forced exhalation or activities for which an increased air volume is needed. In particular the abdominals during the exhalation can help diaphragm to raise more, compressing the lower portion of the lungs while the thorax muscles (inner intercostals) get the ribs closer reducing the ribcage volume and further compressing the lungs, this way a larger quantity of air gets out during exhalation
Main process of the external respiration. The passage air respiratory systems are divided into two functional zones. The respiratory zone is the region where gas exchange occurs, it includes the respiratory bronchioles (which contain separate outpouchings of alveoli) and the terminal cluster of alveolar sacs.
Gas exchange between the air and blood occurs entirely by diffusion through lung tissue. This diffusion occurs very rapid because there is a large surface area within the lungs and a very short diffusion distance between blood and air.
Phases of respiratory act. Inspiration & Expiration
Pulmonary ventilation consists of two phases: inspiration and expiration. Inspiration (inhalation) and expiration (exhalation) are accomplished by alternately increasing and decreasing the volume of the thorax and lungs.
The thorax must be sufficiently rigid so that it can protect vital organs and provide attachments for many short and powerful muscles. Breathing, or pulmonary ventilation, requires the flexibility of the thorax to function as a bellow during the ventilation cycle. The rigidity and the surfaces for muscle attachment are provided by the bony composition of the rib cage. The rib cage is pliable, because the ribs are separate from one another and most of the ribs (upper ten of the twelve pairs) are attached to the sternum by resilient costal cartilages. The vertebral attachments also provide considerable mobility. The structure of the rib cage and associated cartilages provides continuous elastic tension, so that after stretched by muscle contraction during inspiration, the rib cage can return passively to its resting dimension when the muscles relax. This elastic recoil is greatly aided by the elasticity of the lungs.
Respiratory muscles cause passage of air into the Lung. Between the bony portions of the rib cage are two layers of intercostals muscles: the external intercostal muscles and internal intercostal muscles. Between the costal cartilages, there is only one muscle layer, which its fibers oriented in the same manner to those of the internal intercostal muscle. These muscles may called as the interchondral part of the internal intercostal muscle or parasternal intercostal muscle.
An unforced, or quiet, inspiration primarily results from contraction of the dome– shaped diaphragm, which become lowered and flattened. This increases thoracic volume in a vertical direction. Inspiration is also aided by the parasternal and external intercostal muscles, which raise the ribs when they contract and increase thoracic volume laterally. Other thoracic muscles involved in forced (deep) inspiration. The most important of these is the scalenus muscle, followed by the pectoralis minor muscle, and in extreme cases the sternocleidomastoid muscle. Contraction of these muscles elevates the ribs in an anteroposterior direction; simultaneously, the upper rib cage is stabilized so that the intercostal muscles become more effective.
Mechanism of normal quiet inspiration and expiration. Quiet inspiration is an active process. The contraction of the inspiratory muscles and diaphragm increases intrathoracic volume. This stretch the thorax and lungs. Quiet expiration is a passive process. The thorax and lungs recoil when the respiratory muscles relax. due to their elastic tension
Control of Bronchial Tone
The walls of bronchi and bronchioles contain smooth muscle and they are innervated by the autonomic nervous system. In general, sympathetic discharge via Beta-2-adrenergic receptors causes the bronchi to dilate and parasympathetic discharge via the vagus nerves causes them to constrict.. It may be similar to the intrinsic enteric nervous system in the gastrointestinal tract and there is evidence that VIP (Vasoactive intestinal polypeptide) is the mediator secreted by its neurons.
The function of the bronchial muscles is still a matter of debate, but in general, they probably help to maintain an even distribution of ventilation. They also protect the bronchi during coughing. There is a circadian rhythm in bronchial tone, with maximal constriction at about
Lung Volumes. The amount of air that moves into the lungs with each inspiration (or the amount that moves out, with each expiration) is called the tidal volume. The air inspired with a maximal inspiratory effort in excess of the tidal volume is the inspiratory reserve volume. The volume expelled by an active expiration effort after passive expiration is the expiratory reserve volume, and the air left in the lungs after a maximal expiratory effort is the residual volume.
The space in the conducting zone of the airways occupied by gas that does not exchange with blood in the pulmonary vessels is the respiratory dead space. The vital capacity, the greatest amount of air that can be expired after a maximal inspiratory effort, is frequently measured clinically as an index of pulmonary function. The fraction of the vital capacity expired in 1 second (timed vital capacity; also called forced expired volume in 1 second, or FEV I”) gives additional valuable information. The vital capacity may be normal but the timed vital capacity can be greatly reduced in diseases such as asthma, in which the resistance of the airways is increased due to bronchial constriction. The amount of air inspired per minute (pulmonary ventilation, respiratory minute volume) is normally about
Alveolar Ventilation. Because of the dead space, the amount of air reaching the alveoli (alveolar ventilation) at a respiratory minute volume of 6 L/min is 500 minus 150 ml times 12 breath/min, or 4.2 L/min. because of the dead space, rapid, shallow respiration produces much less alveolar ventilation than slow, deep respiration at the same respiratory minute volume .
During quiet breathing, the intrapleural pressure, which is about –
Mechanism forced ventilation. Strong inspiratory efforts reduce the intrapleural pressure value as low as —30 mm Hg, producing correspondingly greater degrees of lung inflation. When forced ventilation is increased, the extent of lung deflation is also increased by active contraction of expiratory muscles that decrease intrathoracic volume.
Movement of the diaphragm accounts for 75% of the change in intrathoracic volume during quiet inspiration. This muscle attached around the bottom of the thoracic cage, and it arches over the liver and moves downward like a piston when it contracts.
The other important inspiratory muscles are the external intercostals muscles, which run obliquely downward and forward from rib to rib. The ribs pivot as if hinged at the back, so that when the external intercostals contract they elevate the lower ribs. This pushes the sternum outward and increases the anteroposterior diameter of the chest. The transverse diameter is actually changed little if at all. Either the diaphragm or the external intercostals muscles alone can maintain adequate ventilation at rest. Transaction of the spinal cord above the third cervical segment cause fatal without artificial respiration, but transaction below the origin of the phrenic nerves that innervate the diaphragm (third to fifth cervical segments) is not fatal; conversely, in patients with bilateral phrenic nerve palsy, respiration is somewhat labored, but adequate to maintain life. The scalene and sternocleidomastoid muscles in the neck are accessory inspiratory muscles that they help to elevate the thoracic cage during deep labored respiration.
A decrease in intrathoracic volume and forced expiration result when the expiratory muscles contract. The internal intercostals have this action because they pass obliquely downward and posterior from rib to rib and therefore pull the rib cage downward when they contract. Contractions of the muscles of the anterior abdominal wall also aid expiration by pulling the rib cage downward and inward and by increasing the intraabdominal pressure, which pushes the diaphragm upward.
Movement of blood on venous in correlation from phases of respiratory act.
Contraction of the diaphragm during inhalation also improves venous return. As the diaphragm contracts, it lowers to increase the thoracic volume and decrease the abdominal volume. This creates a partial vacuum in the thoracic cavity (negative intrathoracic pressure) and a higher pressure in the abdominal cavity. The pressure difference thus produced favors blood flow from abdominal to thoracic veins.
Change of pressure in alveoli. The respiratory muscles cause pulmonary ventilation by alternatively compressing and distending the lungs, which in turn causes the pressure in the alveoli to rise and fall. During inspiration the intra-alveolar pressure becomes slightly negative with respect to atmospheric pressure, normally slightly less than
During maximum expiratory effort (with the glottis closed )the intra-alveolar pressure can be increased to as much as
Recoil Tendency of the Lungs, and the Intrapleural Pressure. The lungs have a continual elastic tendency to collapse and therefore to pull away from the chest wall. This is called the recoil tendency of the lungs, and it is caused by two different factors. First, throughout the lungs are many elastic fibers that are stretched by lung inflation and therefore attempt to shorten. Second, and even more important, the surface tension of the fluid lining the alveoli also causes a continual elastic tendency for the alveoli to collapse. This effect is caused by intermolecular attraction between the surface molecules of the alveolar fluid. That is, each molecule pulls on the next one so that the whole lining sheet of fluid on the alveolar surfaces acts like many small elastic balloons continuously trying to collapse the lung.
Ordinarily, the elastic fibers in the lungs account for about one third of the recoil tendency, and the surface tension phenomenon accounts for about two thirds.
The total recoil tendency of the lungs can be measured by the amount of negative pressure in the pleural space required to prevent collapse of the lungs; this pressure is called the pleural pressure or, occasionally, the lung recoil pressure. It is normally about –
NEURAL CONTROL OF BREATHING
Control Systems. Spontaneous respiration is produced by rhythmic discharge of the motor neurons that innervate the respiratory muscles. This discharge is totally dependent oerve impulses from the brain; breathing stops if the spinal cord is transected above the origin of the premix nerves.
Two separate neural mechanisms regulate respiration. One is responsible for voluntary control and the other for automatic control. The voluntary system is located in the cerebral cortex and sends impulses to the respiratory motor neurons via the corticospinal tracts. The automatic system is located in the pons and medulla, and the motor outflow from this system to the respiratory motor neurons is located in the lateral and ventral portions of the spinal cord.
The motor neurons to the expiratory muscles are inhibited when those supplying the inspiratory muscles are active, and vice versa. These reciprocal innervations are not due to spinal reflexes and in this regard differ from the reciprocal innervations of the limb flexors and extensors. Instead, impulses in descending pathways that excite agonists also inhibit antagonists, probably by exciting inhibitory interneurons.
Medullary Centers. Rhythmic discharge of neurons in the medulla oblongata produces automatic respiration. Respiratory neurons are of 2 types: those that discharge during inspiration (I neurons) and those that discharge during expiration (E neurons). Many of these discharge at increasing frequencies during inspiration, in the case of I neurons, or during expiration, in the case of E neurons. Some discharge at decreasing frequencies, and some discharge at the same high rate during inspiration or expiration. I neurons are actively inhibited during expiration, E neurons during inspiration.
The area in the medulla that is concerned with respiration has classically been called the respiratory center, but there are actually 2 groups of respiratory neurons. The dorsal group of neurons near the nucleus of the tracts solitaries is the source of rhythmic drive to the centra lateral premix motor neurons. These neurons also project to and drive the ventral group. This group has 2 divisions. The cranial division is made up of neurons in the nucleus ambiguous that innervate the ipsilateral accessory muscles of respiration, principally via the vagus nerves. The caudal division is made up of neurons in the nucleus retroambigualis that provide the inspiratory and expiratory drive to the motor neurons supplying the intercostal muscles. The paths from these neurons to expiratory motor neurons are crossed, but those to inspiratory motor neurons are both crossed and uncrossed.
Pontine & Vagal Influences. The rhythmic discharge of the neurons in the respiratory center is spontaneous, but it is modified by centers in the pons and by afferents in the vagus nerves from receptors in the lungs. The interactions of these components can be analyzed by evaluating the results of the experiments summarized diagrammatically in Fig -1.
Complete transaction of the brain stem below the medulla (section D in Fig -1) stops all respiration. When all of the cranial nerves (including the vagi) are cut and the brain stem is transected above the pons (section A in Fig -1), regular breathing continues. However, when an additional transaction is made in the inferior portion of the pons (section B in Fig -1), the inspiratory neurons discharge continuously and there is a sustained contraction of the inspiratory muscles. This arrest of respiration in inspiration is called apneusis. The area in the pons that prevents apneusis is called the pneumotaxic center and is located in the nucleus parabrachialis. The area in the caudal pons responsible for apneusis is called the apneustic center.
When the brain stem is transected in the inferior portion of the pons and the vagus nerves are left intact, regular respiration continues. In an apneustic animal, stimulation of the proximal stump of one of the cut vagi produces, after a moderate latent period, a relatively prolonged inhibition of inspiratory neuron discharge. There are stretch receptors in the lung parenchyma that relay to the medulla via afferents in the vagi, and rapid inflation of the lung inhibits inspiratory discharge (Hering-Breuer reflex). Thus, stretching of the lungs during inspiration reflexly inhibits inspiratory drive, reinforcing the action of the pneumotaxic center in producing intermittency of inspiratory neuron discharge. This is why the depth of inspiration is increased after vagotomy in otherwise intact experimental animals, although breathing continues as long as the pneumotaxic center is intact.
When all pontine tissue is separated from the medulla (section C in Fig 45-1), respiration continues whether or not the vagi are intact. This respiration is somewhat irregular and gasping, but it is rhythmic. Its occurrence demonstrates that the respiratory center neurons are capable of spontaneous rhythmic discharge.
The precise physiologic role of the pontine respiratory areas is uncertain, but they apparently make the rhythmic discharge of the medullary neurons smooth and regular. It appears that there are topically discharging neurons in the apneustic center which drive inspiratory neurons in the medulla, and these neurons are intermittently inhibited by impulses in afferents from the pneumotaxic center and vagal afferents.
REGULATION OF RESPIRATORY CENTER ACTIVITY
A rise in the P.CO2 or H+ concentration of arterial blood or a drop in its P.O2 increases the level of respiratory neuron activity, and changes in the opposite direction have a slight inhibitory effect. The effects of variations in blood chemistry on ventilation are mediated via respiratory chemoreceptors – receptor cells in the medulla and the carotid and aortic bodies sensitive to changes in the chemistry of the blood which initiate impulses that stimulate the respiratory center. Superimposed on this basic chemical control of respiration, other afferents provide nonchemical controls for the fine adjustments that affect breathing in particular situations held constant, the effects of excess in the blood are combated, and the P.O2; is raised when it falls to a potentially dangerous level. The respiratory minute volume is proportionate to the metabolic rate, but the link between metabolism and ventilation is CO2, not O2. The receptors in the carotid and aortic bodies are stimulated by a rise in the P CO2 or H+ concentration of arterial blood or a decline in its PO2. After denervation of the carotid chemoreceptors, the response to a drop in PO2; is abolished; the predominant effect of hypoxia after denervation of the carotid bodies is a direct depression of the respiratory center.
The response to changes in arterial blood H+ concentration in the pH 7.3-7.5 range is also abolished, although larger changes exert some effect. The response to changes in arterial P.CO2 is affected only slightly; it is reduced no more than 30-35%.
Carotid & Aortic Bodies.There is a carotid body near the carotid bifurcation on each side, and there are usually 2 or more aortic bodies near the arch of the aorta. Each carotid and aortic body (glomus) contains islands of 2 types of cells, type I and type II cells, surrounded by fenestrated sinusoidal capillaries.
NONCHEMICAL INFLUENCES ON RESPIRATION
Afferents from “Higher Centers”.
There are afferents from the neocortex to the motor neurons innervating the respiratory muscles, and even though breathing is not usually a conscious event, both inspiration and expiration are under voluntary control. Pain and emotional stimuli affect respiration, so there must also be afferents from the limbic system and hypothalamus.
Since voluntary and automatic control of respiration is separate, automatic control is sometimes disrupted without loss of voluntary control. The clinical condition that results has been called Ondine’s curse. In German legend, Ondine was a water nymph who had an unfaithful mortal lover. The king of the water nymphs punished the lover by casting a curse upon him that took away all his automatic functions. In this state, he could stay alive only by staying awake and remembering to breathe. He eventually fell asleep from sheer exhaustion and his respiration stopped. Patients with this intriguing condition generally have disease processes that compress the medulla or bulbar poliomyelitis. The condition has also been inadvertently produced in patients who have been subjected to bilateral anterolateral cervical cordotomy for pain. This cuts the pathways that bring about automatic respiration while leaving the voluntary efferent pathways in the corticospinal and rubrospinal tracts intact.
Afferents from Proprioceptors. Carefully controlled experiments have shown that active and passive movements of joints stimulate respiration, presumably because impulses in afferent pathways from proprioceptors in muscles, tendons, and joints stimulate the inspiratory neuron. This effect probably helps increase ventilation during exercise.
Responses to Irritation of the Air Passages. Sneezing and coughing are reflex responses to irritation of receptors in the mucosa of the large respiratory passages. Irritation of the walls of the trachea or large bronchi produces coughing, which begins with a deep inspiration followed by forced expiration against a closed glottis. This increases intrapleural pressure to
Other Pulmonary Receptors. The vagally mediated inhibition of inspiration produced by inflation of the lung has been mentioned above. The response is due to stimulation of stretch receptors located in the smooth muscle of the airways. Pulmonary deflation receptors that trigger inflation have also been described, and the expiratory and inspiratory reflex responses to pulmonary inflation and deflation, respectively, have been known as the Hering-Breuer reflexes. However, the deflation receptors respond better to pulmonary congestion and embolization, producing shallow, rapid breathing, and they have come to be called J receptors instead, because of their juxtacapillary location. There are also lung irritant receptors located between the epithelial cells in the bronchi and bronchioles. When stimulated, they initiate hyperventilation and bronchoconstriction, but their function iormal breathing is not known.
Respiratory Components of Other Visceral Reflexes.
The respiratory adjustments during vomiting, swallowing and gagging; inhibition of respiration and closure of the glottis during these activities not only prevent the aspiration of food or vomitus into the trachea but, in the case of vomiting, fix the chest so that contraction of the abdominal muscles increases the intra-abdominal pressure. Similar glottis closure and inhibition of respiration occur during voluntary and involuntary straining.
Hiccup is a spasmodic contraction of the diaphragm that produces an inspiration during which the glottis suddenly closes. The glottis closure is responsible for the characteristic sensation and sound. Yawning is a peculiar “infectious” respiratory act the physiologic basis and significance of which are uncertain. However, under ventilated alveoli have a tendency to collapse, and it has been suggested that the deep inspiration and stretching open them alveoli and prevent the development of atelectasis. Yawning also increases venous return to the heart.
Respiratory Effects of Baroreceptor Stimulation. Afferent fibers from the baroreceptors in the carotid sinuses, aortic arch, atria, and ventricles relay to the respiratory center as well as the vasomotor and cardioinhibitory centers in the medulla. Impulses in them inhibit respiration, but the inhibitory effect is slight and of little physiologic importance. The hyperventilation in shock is due to chemoreceptor stimulation caused by acidosis and hypoxia secondary to local stagnation of blood flow and is not baroreceptor mediated. The activity of the inspiratory neurons affects the blood pressure and heart rate and activity in the vasomotor center and the cardiac centers in the medulla may have minor effects on respiration.
Effect of irritant receptors in the airways. The epithelium of the trachea, bronchi, and bronchioles is supplied with sensory nerve endings that are stimulated by irritants that enter the respiratory airways. These cause coughing and sneezing. They possibly also cause bronchial constriction in such diseases as asthma and emphysema.
Function of Lung “J” Receptors. A few sensory nerve endings occur in the alveolar walls in Juxtaposition to the pulmonary capillaries, from whence comes the name “J” receptors. They are stimulated when irritant chemicals are injected into the pulmonary blood, and they are also excited when the pulmonary capillaries become engorged with blood or when pulmonary edema occurs in such conditions as congestive heart failure. Though the functional role of the J receptors is not known, their excitation perhaps does give the person a feeling of dyspnea.
Limitation of Inspiration by Lung Inflation Signals – the Hering-Breuer Inflation Reflex
Located in the walls of the bronchi and bronchioles throughout the lungs are stretch receptors that transmit signals through the vagi into the dorsal respiratory group of neurons when the lungs become overstretched. These signals affect inspiration in much the same way as signals from the pneumotaxic center; that is, they limit the duration of
Therefore, when the lungs become overly inflated, the stretch receptors activate an appropriate feedback response that “switches off” the inspiratory ramp and thus limits further inspiration. This is called the Hering-Breuer inflation reflex. This reflex also increases the rate of respiration because of the reduced period of inspiration, the same as is true for signals from the pneumotoxic center.
However, in human beings, the Hering-Breuer reflex probably is not activated until the tidal volume increases to greater than approximately
