Lower Motor Components of Respiration

The lower motor components are composed of neurons innervating the diaphragm, intercostal muscles, abdominal muscles, and other accessory muscles.¹ During quiet breathing, only the diaphragm is vigorously active, with some contribution from the abdominal and external intercostal muscles. These muscles work in conjunction with muscles of the upper airway to maintain a patent airway and ensure an uninterrupted passage to air. The diaphragm is the most important inspiratory muscle, and it derives its nerve supply via the phrenic nerve from spinal cord segments C3-C5. Other inspiratory muscles include the external intercostal muscles, the parasternal intercostal muscles, and the scalene muscles.

Inspiration is an active process by which air flow and lung expansion are achieved. During quiet inspiration, the diaphragm descends into the abdominal cavity and increases the vertical dimension of the thoracic cage. Simultaneously, the external intercostal muscles, parasternal intercostal muscles, and scalene muscles elevate the upper ribs and sternum, increasing the anteroposterior diameter of the thorax (pump-handle movement). As the thoracic cage expands, it reduces the intrapleural pressure. This generates subatmospheric pressures, inducing air flow and expansion of the lung parenchyma. However, during deep breathing (minute volume, ≥40L/minute) or when the resistive load of the respiratory system increases, as in asthma or chronic obstructive pulmonary disease, additional muscles are recruited for inspiration. These accessory muscles of inspiration include the sternocleidomastoid, pectoralis minor and major, serratus anterior, latissimus dorsi, and serratus posterior superior muscles.

Expiration, in contrast, is a passive process produced by elastic recoil of the thoracic cage. Active expiratory muscles such as the abdominal muscles and the internal intercostal muscles are called into action only during exercise and during vigorous and deep breathing.

Upper airway structures are crucial in maintaining the patency of airways. Dysfunction of these structures is readily evident in abnormalities of speech and swallowing, as well as in obstructive sleep apneas and other breathing disorders. The muscles of the nose, mouth, soft palate, pharynx, epiglottis, and larynx work in conjunction to ensure a free flow of air into the trachea and bronchi. Somatic innervation of these muscles is provided by the lower cranial nerves: V, VII, IX, X, and XII.

Chemical Regulation of Respiration

Breathing is influenced by input from peripheral and central chemoreceptors. Peripheral chemoreceptors located in the carotid bodies (at the common carotid bifurcations) and the aortic bodies are influenced primarily by hypoxia. Other, less important stimuli include hypercarbia, acidosis, and hypoperfusion. Central chemoreceptors in the pons (locus ceruleus) and medulla (raphe nuclei, ventrolateral nuclei, and nucleus of tractus solitarius) are influenced primarily by changes in carbon dioxide tension (PCO₂) concentrations. These neurons project their dendrites to the surface of the brainstem, where they abut the circulating cerebrospinal fluid. Arterial PCO₂ (PaCO₂) changes are reflected by changes in cerebrospinal fluid pH. The precise mechanisms by which these structures influence automatic breathing are still a subject of study. Although breathing in the awake human is not closely influenced by these structures, their feedback becomes vital during sleep. Although peripheral chemoreceptors can be removed or destroyed during carotid endarterectomy, they do not clinically affect respiration. Lesions of the central chemoreceptors, in contrast, lead to respiratory abnormalities and apnea during deep sleep. This is probably because peripheral inputs are overridden in favor of central chemoreceptor inputs during sleep.

Upper Motor Components of Respiration

Normal respiration is an automatic rhythmic subconscious function that is modulated during complex activities such as speech, singing, laughter, hiccups, and vomiting. Three parallel pathways influence these separate components of respiration. Automatic breathing is regulated primarily by lower brainstem nuclei. These consist of pontine and medullary groups of nuclei. The most vital structures are neurons in the ventral respiratory group of the medulla. A subcomponent of this group, the pre-Bötzinger region, probably performs a pacemaker or driving function that initiates inspiration. It is supported by the pontine respiratory group and components of the dorsal and ventral respiratory group neurons of the medulla. Collectively, these are termed the pontomedullary respiratory generator. This generator produces a resting respiratory rate of 12 to 15 breaths per minute. In humans, this generator is modified by pulmonary and cardiovascular reflexes. The pulmonary reflexes termed the Hering-Breuer reflex are of minimal importance in humans. However cardiovascular reflexes are closely interlinked with respiratory patterns. This is readily evident in the phenomenon of respiratory sinus arrhythmia, in which the heart rate speeds up during inspiration and slows down during expiration. The parasympathetic innervation of the cardiac pacemaker predominates over the sympathetic innervation, and sinus arrhythmia is generated by phasic inhibition of vagal output to the sinus node. Moreover, polysynaptic connections in the medulla mediate respiratory modulation during complex reflex responses such as vomiting. The proximity of neurons involved in respiration and those of the lower motor neuron nuclei result in close intermingling and intermodulation of activity.

Nevertheless, pathways that subserve higher order functions such as speech, singing, and voluntary control of breathing exist in parallel to the automatic pathways. As in motor control of limb muscles, activation of cortical networks between the motor area, premotor area, supplementary motor area, basal ganglia, and cerebellum influence and modify respiratory rhythms. These networks are normally silent and are called into action during speech and singing, during which they inhibit automatic breathing and modulate the upper airway and respiratory rhythms. The third pathway is postulated to arise from the limbic system and modulates respiratory rhythms in response to emotional stimuli. This pathway, however, is not as well understood as the automatic and voluntary pathways. Automatic respiration is mediated via the reticulospinal tract, which lies in the anterolateral funiculus of the spinal cord, and voluntary respiration is mediated via the corticospinal tracts.

Respiratory Failure

Neurological disorders can produce dyspnea or frank respiratory failure. Respiratory failure exists when arterial oxygen tension (PaO₂) is less than 60 mmHg or when PaCO₂ exceeds 50 mmHg when the patient is breathing air, and it is the end result of respiratory dysfunction. It can exist in acute and chronic forms. Acute respiratory failure manifests dramatically, and most patients are immediately intubated and ventilated. Nearly 300,000 cases of acute respiratory failure are encountered each year in the United States; the approximate incidence is 137 cases per 100,000 population.² The number of cases related to neurological disorders is not known. Nevertheless, even if it is assumed that only 0.5% to 1% of cases of acute respiratory failure are related to neurological causes, they add up to 1500 to 3000 cases per year in the United States alone.

In clinical practice, the neurologist is most often consulted about patients with respiratory failure in which a clear pulmonary or medical cause is not evident. Sometimes the neurologist is consulted when there is difficulty in weaning a patient from a ventilator. This is common in the intensive care unit with critically ill patients who may display a necrotizing myopathy.³ Alternatively, respiratory failure may supervene in patients with known neurological illness such as myasthenia gravis or Guillain-Barré syndrome. Examination reveals tachypnea, brow sweating, tachycardia, weak cough, paradoxical respiration, and diminished respiratory muscle strength on pulmonary function tests. Patients with chronic respiratory failure may present with an insidious onset of sensorial alteration and coma. The commonest neurological causes of respiratory failure are neuromuscular and spinal cord disorders.⁴ Peripheral disorders result in respiratory muscle weakness, alveolar hypoventilation, and type II respiratory failure. Table 120-1 lists some of the common neuromuscular and spinal disorders producing respiratory weakness. Most of these disorders can manifest with acute or chronic respiratory failure. Associated findings, pulmonary function test results, neurophysiological evaluation findings, and muscle/nerve biopsy findings help identify most of these peripheral or spinal causes of respiratory failure.

TABLE 120-1 Neuromuscular Conditions Resulting in Respiratory Failure