The peripheral chemoreceptors also respond to CO2 and contribute about 20%–30% of the total ventilatory increase observed when CO2 is inhaled. Because peripheral chemoreceptors react rapidly to changes in CO2, peripheral chemoreceptor responses have been evaluated by measuring the immediate increase in ventilation caused by a few breaths of inspired CO2 or by measuring the immediate decrease in ventilation observed when CO2 is abruptly removed.
The response to hypoxia, like the response to hypercapnia, can be measured by either rebreathing or steady-state techniques. Because of the prominent effects of CO2 on breathing, it is important to keep the CO2 constant while the response to hypoxia is measured. Because O2 stores are small, the peripheral chemoreceptor response to O2 also can be evaluated by measuring the effect on ventilation of a few breaths of N2 or 100% O2.
No matter how it is measured, the ventilatory response to hypoxia is curvilinear, making quantitation difficult. The response can be made linear, however, by relating ventilation to the reciprocal of PO2 or to the arterial O2 saturation.
There are insufficient data to establish the range of normal values of the ventilatory response to hypoxia; however, available information indicates that it is closely related to the metabolic rate and is at least as variable as the CO2 response.
Prolonged periods of hypoxia, particularly early in life, are associated with depression of the chemoreceptor response to hypoxia. The ventilatory response to hypoxia is reduced in native residents of regions at high altitudes and in children with congenital cyanotic heart disease. The carotid body appears to be larger in native residents of high altitudes. The change in size may be caused by increased carotid body vascularity, which raises PO2 and decreases responsiveness.
In the newborn, hypoxia causes only a transient increase in ventilation, which then subsides to nearly prehypoxic levels. It has been recently appreciated that in adult humans, hypoxia lasting for as short a time as 5 minutes produces a gradual reduction in ventilation from its initial peak level.
The initial increase in ventilation is of course mediated by the carotid body. The subsequent decrease seems to represent a depressant effect of hypoxia on central respiratory neurons by hypoxia-induced increases in cerebral blood flow and probably the release of inhibitory neuromodulators, such as adenosine.
Lung disease or respiratory muscle weakness can depress ventilatory responses to chemical stimuli. The depressant effect seems to be greater for the response to CO2 than for the response to hypoxia. As a result of studies in which airway resistance was increased by requiring subjects to breathe through external resistance, either during inspiration or expiration, it was suggested that the inspiratory work of breathing at a given level of PCO2 is fixed, so that when the ratio of inspiratory muscle work to ventilation is increased by disease, ventilation decreases. The hypercapnia observed in severe obstructive lung disease was explained by the increase in flow-resistive work associated with chronic airway obstruction.
More recent studies have indicated that small increases in airway resistance have little effect on resting ventilation or CO2 response in normal subjects and may even heighten ventilation. The mechanisms responsible for the preservation of ventilation under these circumstances could include intrinsic properties of the respiratory muscles, increased inspiratory augmenting output from lung and chest-wall mechanoreceptors, readjustment in the sequence of contractions of the respiratory muscles so that mechanical advantage of the muscles and their coordination is improved, and increased inspiratory drive originating from the motor cortex. This last mechanism may depend on the conscious perception of changes in airway resistance. It is interesting that the ability to detect changes in airway resistance varies, decreasing with increasing airway resistance, and that it decreases further when airway obstruction is chronic than when it is acute.
Because mechanical changes may limit the ventilatory response to chemical stimuli, other methods of assessing the output of respiratory motor neurons have been devised. Two methods have been employed: measurement of occlusion pressure and EMG of the diaphragm. Neither is perfect, but both are useful under certain circumstances.
In the measurement of occlusion pressure, the force of contraction of the inspiratory muscles under quasi-isometric conditions is determined as follows: The airway is momentarily blocked at the beginning of inspiration, and the negative pressure developed during inspiration is measured. In conscious subjects, the reproducibility of the response is greater when the airways are occluded for just a fraction of a second. The occlusion pressure increases with hypercapnia and hypoxia and can be related to change in PCO2 and PO2 to estimate chemosensitivity.
Airway occlusion at FRC produces a no-flow state at the relaxed position of the respiratory system. The absence of air flow and prevention of significant volume change during inspiration prevent increases in airway resistance or decreases in compliance from affecting this index of respiratory output. In patients with mechanical abnormalities of the ventilatory pump caused by diseases of the lung or chest wall, occlusion pressure therefore more accurately reflects the neuromuscular drive to breathe than does ventilation.
Because the tensions developed by the inspiratory muscles theoretically depend on their initial length, the occlusion pressure in patients with lungs hyperinflated by disease may not reflect respiratory drive accurately. Increased FRC in animals reduces occlusion pressure responses. However, studies in conscious humans in whom FRC has been changed by altering body position show little effect on occlusion pressure, even when changes in FRC are fairly large (1000 mL). A conscious person apparently maintains constant muscle tension successfully, despite changes in initial muscle length, by altering neural output.
Measurement of the electrical activity of the diaphragm is probably the most direct way of evaluating respiratory neuronal output. This can be accomplished by passing a catheter containing electrodes down the esophagus and positioning the electrodes so that they straddle both surfaces of the diaphragm.
Various ways have been devised to quantitate diaphragmatic electrical activity measured this way. In the method most used currently, diaphragmatic activity is integrated over small intervals of time (100 to 200 ms), and the average activity per time limit is recorded (the so-called moving average). Electrical activity measured in this way depends on the exact positions of the electrodes in relation to the diaphragm during breathing, so that it is difficult to compare one individual with another. It is possible, however, to use this method to determine the effect of different therapeutic interventions in the same person.
No comments:
Post a Comment