Control of Ventilation Flashcards
Neural studies on animals show what about the brain’s control of breathing in the higher brain?
Early animal studies were largely aimed at anatomically locating the integrator. Some studies involved neural transection where portions of the brain of an anesthetized animal was systemically removed to determine whether breathing rate or depth was altered. These studies showed that removal of the cerebral cortex and cerebellum (transection # 1) had little or no effect upon the breathing rate or depth, as shown in the figure. However, cutting the vagi, either before or after this transection, resulted in a slower breathing rate and an increase in tidal volume (VT). Likewise, a transection between the lower midbrain and upper pons also had no effect upon breathing rate or depth (transection # 2). Again, cutting the vagi resulted in a slower breathing frequency and an increased VT. These findings suggest that some sensors send signals via vagal afferent nerves to influence breathing rate and depth. However, these vagal afferents apparently innervate the brain below midbrain level.
Explain animal studies on the lower brain relating to breathing?
If a transection is made along the upper one-third of the pons, (figure, transection #3), breathing rate is slowed and VT is increased provided the vagi are intact. A breathing pattern similar to that of cutting the vagi alone (transection #1) is observed. However, if vagi are severed along with this pontine transection, an apneustic breathing pattern results. Apneusis is defined as the termination of breathing at end-inspiration, often manifested by inspiratory spasms and gasps.
Explain animals studies revealing the pneumotaxic and apneustic centers?
Results from neural transection studies suggest that the lower two-thirds of the pons encourages inspiration because without input from vagal afferents or the upper pons, apneusis was observed. Thus, the lower two-thirds of the pons is designated as the Apneustic Center, while the upper one-third is called the Pneumotaxic Center. The transection studies suggest that both the pneumotaxic center and vagal afferent nerves innervate the apneustic center to diminish inspiratory drive. One idea suggests that the apneustic center appears to continuously promote inspiration and requires periodic inhibition from the pneumotaxic center and vagal afferents for expiration to occur. As such, the pneumotaxic center and vagal afferents collectively constitute a “cut-off” switch for the apneustic center. When inspiration is terminated, expiration can occur.
Explain the medullary center?
Spontaneous, but irregular breathing, occurs after the brain stem is transected between the lower border of the pons and the medulla (transection #4). After this transection, the breathing pattern is characterized by a variable tidal volume and rate. Cutting the vagi after this transection has little influence on the breathing pattern. This suggests that vagal afferents likely innervate the pons as opposed to the medullary region. However, a transection across the lower border of the medulla (transection #5) results in apnea, or the termination of breathing at end expiration. These findings indicate that the minimal neuronal pools necessary for spontaneous breathing reside in the medullary portion of the brain stem. This brain stem region is appropriately called the Medullary Center. Although neuronal pools of the medullary center alone appear sufficient to initiate and maintain sequences of inspiration and expiration, input from the pontine pneumotaxic and apneustic centers appear to be essential for rhythmic and coordinated breathing.
Explain the integrator connections?
Neural interconnections between the integrating centers of the brain stem have been further explored using techniques like electrical stimulation, recording of neuronal signals, lesions placed in specific brain stem sites, and a variety of other interventions. Within the medulla, some neuron groups are primarily active during inspiration and are called inspiratory neurons. Other medullary neurons fire mostly during expiration and are termed expiratory neurons. Most medullary neurons that discharge in synchrony with either inspiration or expiration are fairly intermingled but located primarily in two areas, identified as the dorsal respiratory group (DRG) and ventral respiratory group (VRG) (see top figure). Several different models of varying complexity have been proposed to show how respiratory neurons might interconnect to generate a breathing rhythm
Explain the model of how integrators work?
One simple model of proposed pontine-medullary connections is shown (see bottom figure). In this model, motor neurons from the medullary inspiratory neuron pool initiate contraction of the inspiratory muscles (i.e., diaphragm and external intercostals). When active, medullary inspiratory neurons also appear to diminish activity of expiratory neuron pools in the medulla while facilitating activity of neurons in the pneumotaxic center. As the lung inflates, stretch receptors or proprioceptors in the lung are stimulated. Activation of stretch receptors, along with enhanced pneumotaxic center activity, tends to inhibit the apneustic center. This diminishes inspiratory drive and expiration commences. The spontaneous rhythmicity of breathing, originating from the brain stem centers, can be voluntarily overridden by input from higher cortical centers. In fact, higher brain centers regularly modify the cycle of inspiration and expiration during such activities as speaking, singing, playing a wind instrument, sneezing, coughing and during emotional stress. However, the brain stem centers will eventually dominate the breathing pattern as dictated by the need for CO2, removal or O2 uptake, or acid-base balance ofextracellular fluids.
explain muscles for breathing and their innervation?
Output from the brain stem integrator descends the spinal cord and exits via motor neurons to innervate the diaphragm, intercostal, and abdominal muscles. The diaphragm, the primary effector of breathing, is innervated by the phrenic nerve formed by the union of motor nerves exiting the spinal cord from C3 to C6. The external intercostals are innervated by the intercostal nerves that leave the cord at T1 to T12. The respiratory muscles most important to expiration are the internal intercostals and the abdominal muscles, which are innervated by nerve fibers originating at T1 through T11 and T4 to L3, respectively.
Neurogenic reflexes in the lungs stem from? how many are there?
A large number and variety of sensors are located in the lungs, the cardiovascular system, skeletal muscles, and the muscles and tendons of respiratory muscles. Each conveys information to the brain stem integratorto inform it of the effectiveness of respiratory muscle work or the adequacy of ventilation in terms of O2 uptake or CO2 removal. At least eight different sensor reflexes have been identified according to the receptor location, structure, or afferent pathway.
What are the hering-breuer reflexes?
Two reflexes discovered by Hering and Breuer in 1868 appear to help regulate the work of breathing on a breath-to-breath basis. The Hering-Breuer Inflation reflex (also called inhibito-inspiratory reflex) is initiated by stretch receptors (sensors) located in the smooth muscles surrounding both large and small airways. With lung inflation, these stretch receptors are stimulated and send neural signals via vagal afferents that appear to be inhibitory to the pontine apneustic center. Thus, they function to facilitate termination of inspiration, as previously noted in the neural transection studies. There is also a Hering-Breuer Deflation reflex (or excito-inspiratory reflex). This reflex is initiated either by decreased activity in the same airway stretch receptors involved in the inflation reflex or by stimulation of other proprioceptors that are activated by lung deflation. This information is also conveyed via vagal afferents to the brain stem respiratory centers to encourage inspiration. While Hering-Breuer reflexes are readily demonstrated in anesthetized animals, they are more difficult to demonstrate in humans, except at large tidal volumes. These reflexes are detectable in infants and are probably important in regulating the work of breathing.
what is the J-receptor reflex?
The Pulmonary Jreceptors, an abbreviated name for the pulmonary juxtapulmonary-capillary receptors, are located in, or near, the walls of pulmonary microvessels. They appear to be stimulated by vascular emboli, interstitial edema, and certain chemicals (phenyldiguanide or capsaicin). Information from the J-receptors is also delivered via vagal afferents in the brain stem. Their stimulation results in rapid shallow breathing (tachypnea). These receptors are thought to be responsible for the psychological sensation of “air hunger”, also known as dyspnea. Dyspnea is characterized by the sensation of labored breathing and “shortness” of breath.
List several other respiratory neurogenic reflexes?
Irritant receptorsin the upper airway are stimulated by deformation, dust, smoke, or toxic gases. Afferent signals from irritant receptors are transmitted via the vagus, trigeminal, or olfactory nerve to the integrator to initiate coughing or sneezing. The arterial baroreceptors (carotid sinus and aortic arch) also can reflexly alter breathing rate. A reduction in arterial blood pressure tends to stimulate breathing, while a rise in blood pressure decreases ventilation. Reflexes also arise from stretchor proprioceptorslocated in skeletal muscles, tendons, and joints. When stimulated by movement, these receptors increase ventilation. They may be important in stimulating the increase in ventilation associated with exercise and help in adjusting ventilation to the external work load. However, the arterial chemoreceptors are the most important sensors in regulating ventilation according to the metabolic needs for O2 uptake and CO2 excretion.
What are the chemoreceptor reflexes in the lungs?
The chemoreceptors are specialized cells capable of detecting changes in the concentration of physically dissolved O2, CO2, or hydrogen ion (H+) in the extracellular fluid immediately surrounding them. These chemosensitive cells are divided functionally, anatomically and geographically into the peripheral and central chemoreceptors. They function to regulate ventilation so CO2 is maintained nearly constant and at a level consistent with CO2 production and O2 consumption by the tissues of the body.
Explain the carotid and aortic bodies?
The peripheral chemoreceptors are located in discrete structures known as the carotid and aortic bodies. The carotid body is a small nodule (5 mm long) located on the bifurcation of the common carotid artery just above the carotid sinus baroreceptors (figure). The aortic bodies are located above and below the aortic arch. In man, the carotid bodies appear to be more important than the aortic bodies, although this may relate to their greater accessibility for study. The peripheral chemoreceptors have a high metabolic rate but also have an exceedingly high blood flow of about 2000 ml/100 g of tissue. As a result, its difficult to detect a PO2 difference between the blood entering and leaving the carotid body. The carotid bodies are comprised of several cell types, with glomus cells being the principal constituent.
Explain the stimulation of peripheral chemoreceptors?
Thecarotid and aortic bodies are able to monitor the physically dissolved O2 and CO2 and the H+ concentration of arterial blood. These chemoreceptors are stimulated by a decline in the PO2, especially when it falls below 60 Torr (figure). They are also stimulated by an increase in the arterial blood H+ concentration (decreased pH) or an increase in physically dissolved CO2 (or PCO2). While it is not clear precisely how increases in H+ or CO2 or decreases in the PO2 stimulate the chemoreceptors, the peripheral chemoreceptors are the only sensors capable of detecting a fall in the PO2. Thus, the peripheral chemoreceptors account for increases in ventilation resulting from hypoxemia. However, these chemoreceptors only detect levels of physically dissolved O2 and not the O2 that is chemically attached to hemoglobin.
Explain the stimulation of central chemoreceptors?
The central chemoreceptors have been located physiologically but not anatomically. Chemosensitive areas (CSA) are located along the ventrolateral surface of the medulla near the cerebral spinal fluid (CSF) of the 4th ventricle of the brain. At least three areas of the brain stem appear capable of chemodetection. Like the arterial chemoreceptors, the central chemoreceptors are stimulated by an increase in the PCO2 or H+ concentration, but not O2. These central chemosensitive areas appear to be more sensitive to changes in the H+ or PCO2 of CSF than of cerebral blood. The blood brain barrier (BBB), that separates blood from the CSF, limits access of certain blood constituents, such as HCO3- and H+ to the CSF. In contrast to the peripheral receptors, the central chemoreceptors are not sensitive to changes in the PO2 of cerebral blood or CSF.
Role of The Blood Brain Barrier in central chemoreceptors?
The BBB separating blood from brain tissue is freely permeable to O2 and CO2, but largely impermeable to charged ions, such as H+ or HCO3-. Thus, CO2 present in blood can readily diffuse into the CSF where, in the presence of carbonic anhydrase, it can undergo hydration to form H+ and HCO3-. It appears the central chemoreceptors are probably more sensitive to changes in the [H+] than the CO2 of CSF. Thus, chemoreceptor stimulation depends largely on the free entry of CO2 into the CSF and subsequent hydration to H+. The central chemoreceptors are not sensitive to changes in blood [H+] because entry of H+ into the CSF is limited by the BBB (figure).
what is the chemical composition of arterial blood and CSF?
Explain the contribution of central vs. arterial chemoreceptors?
The ventilatory response to changes in the inhaled CO2, O2, or an increase in blood [H+] (decrease pH) are compared in the figure. The most potent stimulus to ventilation is an increase in CO2. The PCO2 of arterial blood is closely maintained around 40 Torr by the medullary center via chemoreceptor input. In contrast, the PO2, monitored only by the peripheral arterial chemoreceptors, has to decline markedly (from 100 to 60 Torr) before ventilation is noticeably increased. This would correspond to a decrease in the inspired O2 from 21% to about 8%, as shown in the figure.
The central and peripheral chemoreceptors respond to changes in PCO2 of the CSF and arterial blood, respectively. This sensory input to the medullary integrator represents the most important component in regulating respiration on a breath-to-breath basis.
The peripheral receptors are more proficient in responding to abrupt changes in the PCO2, whereas the central receptors respond to changes in PCO2 over longer periods. If CO2 is voluntarily inhaled, ventilation will increase in proportion to the increase in the fractional composition of CO2 in the inspired gas mixture (figure). If neural afferents from the peripheral receptors are cut, the ventilatory response to CO2 is only slightly diminished (10% to 20%). Thus, the central chemoreceptors appear to account for a sizable portion of the ventilatory response to CO2. The increased ventilation that accompanies an elevation in arterial H+ concentration or a decline in PO2 are largely mediated via the peripheral receptors. The hydrogen ion does not readily traverse the BBB and the central chemoreceptors are incapable of detecting changes in oxygen tension
Explain the interaction between chemoreceptors?
The figure illustrates the interaction between central and peripheral receptors. The increase in ventilation to a fixed elevation in alveolar CO2 (42 to 47 Torr), resulting from inhaling a CO2 gas mixture, is potentiated when the arterial blood PO2 (in Torr on right of graph) is simultaneously decreased. Thus, the peripheral and central chemoreceptors interact in mediating ventilatory responses when the PCO2 and PO2 change simultaneously.
Summarize the control of breathing?
At first glance, it might seem more logical for the respiratory control system to closely monitor and regulate blood O2 rather than CO2 levels or the [H+] of CSF. After all, O2 is essential for aerobic metabolism, while CO2 and H+ are discardable metabolic endproducts.
However, the sigmoidal shape of the oxyhemoglobin dissociation curve insures adequate oxygenation of blood over a wide range of arterial PO2s, from 60 to 100 Torr or more. So, too closely regulate alveolar ventilation to maintain arterial blood PO2 around 100 Torr would have little effect on blood O2 content in as much as a fall in the PO2 to 60 Torr would only reduce blood O2 content from 19.8 to 18.4 vol%. Only when the arterial PO2 falls below 60 Torr, corresponding to the steep slope of the oxyhemoglobin curve, does hypoxemia result in a marked stimulation to ventilation.
Interestingly, the respiratory control system is designed to more closely regulate physically dissolved CO2 (i.e., PCO2). Since CO2 readily reacts with water to yield H+ and HCO3-, the control of CO2 by ventilation helps to maintain a proper acid-base environment that is essential for the proper enzyme function. Thus, the respiratory control system is geared towards the regulation of extracellular fluid CO2 and pH with secondary emphasis upon maintaining adequate blood oxygenation. When ventilation is sufficient to maintain a proper CO2 and pH of blood, the oxygenation of blood will in most instances also be adequate.
Had the respiratory control system been designed to regulate arterial PO2 within narrow limits, it would be of minimal benefit to blood O2 content and result is less of a fine control of acid-base balance.
