NEUROLOGY OF PULMONOLOGY AND ACID-BASE DISTURBANCE

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CHAPTER 120 NEUROLOGY OF PULMONOLOGY AND ACIDBASE DISTURBANCE

Boby Varkey Maramattom, Eelco F.M. Wijdicks

Respiration is essential for cellular metabolism, and no other organ is more dependent on oxygen supply than is the brain. The consequences of disturbances in gas exchange are readily reflected in disturbance of neuronal function, in neuronal injury, or in death. The respiratory system is crucial for the gas exchange and plays a large part in acidbase homeostasis. Neuronal integrity and respiratory regulation are highly interdependent. A brief conceptualization of the neurological control of breathing is necessary for understanding various disordered respiratory patterns. Clinical respiratory abnormalities can be viewed in three contexts: disturbances in the neural control of respiration, in the respiratory apparatus, or in the carriage or composition of blood gases. This chapter describes abnormalities associated with neurological control of respiration and neurological consequences of respiratory dysfunction.

NEURAL CONTROL OF RESPIRATION

The nervous system is intricately connected to the mechanics of respiration at various levels. From the cerebral cortex via the brainstem to the level of the lower motor neurons, the nervous system regulates respiratory effort. It is aided by feedback from peripheral chemoreceptors and mechanoreceptors (Fig. 120-1).¹ The anterior horn cells controlling respiratory muscles represent the lower motor neurons, which control the actual mechanics of breathing. Inspiratory muscles generate subatmospheric pressures within the thorax and induce airflow and gas exchange at the alveolar level.

Figure 120-1 A representation of the neural control of breathing: the main systems involved in voluntary and involuntary breathing and their final activation of the respiratory muscles via the lateral corticospinal and reticulospinal pathways. CC, central chemoreceptors; DRG, dorsal respiratory group; NA, nucleus ambiguus; PRG, pontine respiratory group; V, sensory nucleus of V; VRG, ventral respiratory group.

(From Bolton C, Chen R, Wijdicks EFM, et al: Anatomy and physiology of the nervous system control of respiration. In Bolton C, Chen R, Wijdicks EFM, et al, eds: Neurology of Breathing. Philadelphia: Butterworth-Heinemann, 2004, pp 19-35.)

Respiratory activity takes place predominantly at an autonomic level. Modulation of this automatic control is also evident in various functions such as sneezing, vomiting, coughing, and swallowing. However, voluntary control of the respiratory and upper airway musculature is necessary for communication and speech.

Although respiration is a complex process involving pulmonary ventilation, gas exchange at the alveolar level, and gas transport to tissues, neurological conditions influencing respiration involve primarily abnormalities in pulmonary ventilation and air movement into and out of the respiratory tract. To better understand the neural control of breathing, it is essential to have an overview of the components and regulatory structures involved in this complex action.

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.

ABNORMAL RESPIRATORY PATTERNS IN NEUROLOGICAL DISEASES

Neurological illnesses can manifest with respiratory abnormalities involving the depth, rate, rhythm, or modulation of breathing. It is helpful to view these abnormalities in the context of dysfunction occurring at different levels of the neuraxis. Respiratory abnormalities can arise from dysfunction at the level of the lower motor neuron, mechanoreceptors and chemoreceptors, or higher centers of respiration. Patients can present with dyspnea, abnormal respiratory patterns, respiratory failure, or difficulty in weaning from a ventilator.

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

Muscle Diseases

Muscular dystrophies

Acid maltase deficiency

Myotonic dystrophy

Inflammatory myopathies

Mitochondrial myopathies

Hypokalemic myopathy

Hypophosphatemic myopathy

Critical illness–related myopathy

Neuromuscular Junction Disorders

Myasthenia gravis

Disorders induced by neuromuscular blocking agent

Organophosphorus poisoning

Snake/spider bite

Botulism

Lambert-Eaton myasthenic syndrome

Antibiotic-induced myasthenia

Tick paralysis

Congenital myasthenic syndromes

Peripheral Neuropathies

Acute inflammatory demyelinating polyneuropathy (AIDP)

Critical illness–related polyneuropathy

Phrenic neuropathies

Toxic neuropathies

Chronic idiopathic demyelinating polyneuropathy (CIDP)

Porphyric neuropathy

Diphtheria

Vasculitis: systemic lupus erythematosus (SLE)

Lymphoma

Anterior Horn Cell Disorders

Acute poliomyelitis

Amyotrophic lateral sclerosis (ALS)

Spinal muscular atrophies

Disorders of Spinal Cord

Transverse myelitis

Spinal cord infarction

High cervical cord trauma

Spinal cord tumors

Spinal arteriovenous malformations

Spinal cord hemorrhage

Syringomyelia

Abnormal Respiratory Patterns

Central causes uncommonly result in respiratory failure. Many supraspinal neurological disorders produce a “restrictive” pattern on pulmonary function tests, which is often clinically insignificant. Respiratory failure is not a major problem unless other medical complications occur. Rare exceptions to this caveat include central hypoventilation syndromes resulting from congenital or acquired disorders of medullary respiratory center or apneic seizures. By and large, central disorders produce certain characteristic respiratory patterns in the context of acute devastating neurological illnesses. Most of these patterns, such as Cheyne-Stokes respiration, central neurogenic hyperventilation, apneustic breathing, and ataxic breathing, affect primarily the rate and rhythm of breathing. A number of nonneurological conditions can also produce these respiratory patterns.

Cheyne-Stokes Respiration

This respiratory pattern is characterized by repeated cycles of incremental hyperventilation, decremental hypoventilation (in a waxing-and-waning pattern), followed by a short period of apnea. It may occur in a variety of conditions but is classically associated with diffuse bilateral hemispherical dysfunction (especially cerebrovascular disease) and is thought to be caused by a reduced central response to carbon dioxide. It is also associated with other medical conditions, notably congestive cardiac failure.

Central Neurogenic Hyperventilation

Central neurogenic hyperventilation is a specific disorder characterized by sustained hyperventilation, often resulting in PaCO₂ of less than 35 mmHg. It persists during sleep and is often associated with respiratory alkalosis. It should be differentiated from nonneurological causes of hyperventilation, including metabolic acidosis, organ failure, and other medical causes. Hence, it is often a diagnosis of exclusion or associated with characteristic neurological disorders. Central neurogenic hyperventilation is classically described with upper pontine lesions or with primary central nervous system lymphomas. It may also be present with pontine tumors. Nevertheless, lesions anywhere in the brainstem can be associated with central neurogenic hyperventilation.

Apneustic Breathing

This pattern is characterized by brief pauses at the end of inspiration or alternating pauses at the inspiration and expiration. It is often encountered with bilateral lesions of the pontine tegmentum affecting the pontine pneumotaxic center.⁵ This center is involved in sending inhibitory impulses to the apneustic center and medulla that terminate inspiration and initiate passive expiration. Although readily reproducible in laboratory animals through introduction of pontine lesions, it is rarely observed in clinical practice. Isolated case reports describe reversal of apneustic breathing after stroke with buspirone.⁶

Ataxic Breathing

This is an agonal pattern of breathing that often occurs before impending cardiac arrest. It is completely irregular and is observed with medullary lesions.

Hiccups

Although hiccups are by and large encountered in normal individuals in certain circumstances, they occasionally result from central nervous system lesions. The paradigm of such a lesion is a lateral medullary infarct. Hiccups are characterized by inspiratory movements in the diaphragm and external intercostal muscles, followed immediately by glottic closure. This results in ineffectual inspiration. It is more likely to supervene during inspiration than during expiration.

Disorders of Automatic Breathing

Automatic breathing may be selectively impaired in some disorders that affect the neurons of the medullary ventral respiratory group. During wakefulness, voluntary breathing may be able to sustain respiration. During slow-wave sleep, however, automatic breathing is essential for maintaining respiration. In these disorders, central apnea and hypoxemia supervene during sleep. This condition is termed Ondine’s curse, after the story of a mythical figure, Hans, who was cursed by his jilted lover, Ondine. He was doomed to lose all automatic functions and thus had to stay awake in order to ensure continued breathing. In the modern era, it was most commonly observed in bulbar poliomyelitis, in which the ventral respiratory group neurons were involved. Nowadays it is also observed after high anterior cervical lesions, which affect the reticulospinal tracts subserving automatic respiration. This is particularly common after fibrocartilaginous embolism to the C3-C4 segments of the spinal cord.⁷

During sleep, automatic centers rely on feedback from central chemoreceptors to regulate breathing. This can be impaired in patients with the rare syndrome of central congenital hypoventilation syndrome. Such patients have a defect in central and peripheral chemoreception that impairs automatic control of breathing. Marked cyanosis and apnea occur during sleep in infants with this syndrome.

Obstructive Sleep Apnea

At this juncture, it is appropriate to consider vascular lesions in areas of the brainstem adjoining the respiratory center. Involvement of the motor nuclei of the lower cranial nerves (especially nucleus ambiguous) in the medulla leads to weakness of the upper airway structures and obstructive sleep apnea. In addition, dysphagia predisposes to aspiration of oropharyngeal secretions and to pulmonary infections.

Disorders of Voluntary Breathing

Voluntary control of breathing is mediated primarily via the corticospinal and corticobulbar tracts and is important in activities such as speech, singing, and voluntary breath holding. Disorders involving this mechanism occur mainly in bilateral pontine infarctions and lesions involving the pontine tegmentum that interrupt the descending motor pathways. The classical situation is that of patients with a “locked-in” syndrome. Such patients have a constant unvarying respiratory rhythm that cannot be modulated voluntarily. Thus, they are unable to hold their breath, breathe in deeply, or cough voluntarily. Reflex responses and responses to chemoreceptors remain intact. Partial lesions of the high cervical cord that selectively involve the corticospinal tracts at the C3-C4 segments can also produce a similar condition.⁷

An analogous disorder occurs in patients with bilateral hemispherical disorders (especially elderly patients with diffuse cerebrovascular disease). Such patients can have a respiratory “apraxia” in which they are unable to voluntarily hold their breath or take a deep breath on command. Swallowing on command is also impaired, although automatic swallowing is preserved. These patients commonly also display other “release reflexes” such as frontal release reflexes and gegenhalten.

Assorted Disorders of Breathing

A number of uncommon disorders of breathing also merit mention. Some of these are subclinical entities detected on examination or investigations. Others manifest with a variety of clinical problems and may be mistaken for anxiety-induced hyperventilation or panic attacks.

Hemiplegic patients can display reduced diaphragmatic and chest wall excursions on the weak side. More often than not, they are clinically insignificant. The basal ganglia also play an important role in motor control and are involved in a wide variety of neurological disorders. Dystonia can involve muscles of the diaphragm, as well as those of the upper airway, producing subjective dyspnea.⁸ Chorea and dyskinesias (notably levodopa-induced dyskinesias) can interfere with breathing and produce subjective dyspnea.

Diaphragmatic flutter is a rare condition characterized by dyspnea, epigastric pulsations, abdominal pain, hyperventilation, and repetitive diaphragmatic contraction at a rate of approximately 3Hz.⁹ It is considered to be a form of myoclonus and, as such, responds to a number of antiepileptic drugs (phenytoin, carbamazepine, and benzodiazepines), as well as to phrenic nerve crush. It can be unilateral or bilateral and may occur after encephalitis or lesions impinging on the phrenic nerve roots. Other pulmonary disorders such as neurogenic pulmonary edema are sometimes associated with devastating neurological illnesses such as subarachnoid hemorrhage or intracerebral hemorrhage.¹⁰ These disorders, however, are outside the scope of this chapter.

NEUROLOGICAL CONSEQUENCES OF RESPIRATORY INSUFFICIENCY

Although in the following discussion each condition is described as a separate entity, it should be realized that “isolated” clinical gas abnormalities are uncommon.

Hypoxia

The paradigm of acute severe hypoxia is exemplified by altitude sickness. At high altitudes, mountain climbers experience a variety of symptoms such as headaches, delirium, hallucinations, ataxia, amnesia, gait disturbances, and seizures, which are readily reversible with oxygen therapy or descent to lower altitudes. Cerebral edema with resultant papilledema also occurs. Another commonly encountered clinical scenario is cardiac arrest. The brain is exceptionally dependent on oxygen, and patients become unconscious within 20 seconds of cardiac arrest. Neuronal adenosine triphosphate stores are depleted within seconds, and neuronal damage ensues. Neurons in selected areas such as the hippocampus, basal ganglia, cortical lamina, cerebellum, and spinal cord are particularly involved because of their lower capacity to withstand hypoxia. Nevertheless, it is believed that pure hypoxia alone is not responsible for neuronal injury unless it is accompanied by neuronal ischemia. In isolated hypoxia (PaO₂ < 20 mmHg), irreversible neuronal injury is prevented by a manifold increase in cerebral blood flow. Hypoxia also induces cerebral vasodilatation directly and indirectly through the production of vasoactive factors.¹¹ When ischemia coexists, there is a massive outpouring of excitatory neurotransmitters, such as glutamate. This activates α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptors and N-methyl-D-aspartate receptors, opens ion channels, and initiates enzymatic cascades that induce neuronal cell death. Neurological sequelae occurring after successful resuscitation from cardiac arrest vary from amnesia, motor and gait disturbances, and myoclonus to severe dementia.

Chronic hypoxia produces more insidious neurological damage. Patients with chronic obstructive pulmonary disease have an increased incidence of small-fiber peripheral neuropathy, which is linked to chronic hypoxia.^12,¹³ Likewise, an asymptomatic autonomic neuropathy is encountered in these patients, although the etiological link is weaker with this entity.

Hyperoxia

Hyperoxia is encountered in humans exposed to hyperbaric environments. Such situations occur in patients undergoing hyperbaric therapies and in deep sea divers. These people experience short-term myopia as a result of direct hyperoxia-induced ocular lens changes. Neurological manifestations are transient and limited to headache and, in rare cases, seizures.¹⁴ Hyperoxia is also frequently encountered in patients on ventilators, in whom inadvertent hyperventilation or high fractional inspired oxygen concentrations result in elevated PaO₂. The effect of hyperoxia in these clinical situations is unclear.

Nitrogen-Induced Narcosis

A discussion of the neurological aspects of respiration would be incomplete without mention of nitrogen-induced narcosis (inert gas narcosis), once known as the “raptures of the deep.” This condition was frequently encountered in the past by deep sea divers, who breathed air at high ambient pressure (≥4atm). Increasing partial pressures of nitrogen in the blood led to impaired cognition, incoordination, and disruption of the normal thought process. Prolonged or higher concentrations led to coma and death. The narcotic potential of inert gases such as nitrogen is related to their lipid solubility (the content of which is high in the central nervous system). Substitution of nitrogen with less lipid-soluble gases such as helium has resulted in a decreased incidence of nitrogen-induced narcosis.

Hypercarbia

Although hypoxia is considered more dangerous and harmful to the brain, hypercarbia also produces neurological and cardiorespiratory depression. Neurological involvement is dependent on the rate of rise of carbon dioxide. Acute hypercarbia can produce drowsiness, coma, tremors, asterixis, myoclonus, seizures, papilledema, and fatal cardiac arrhythmias. Carbon dioxide rapidly diffuses across the blood-brain barrier and reduces cerebrospinal fluid pH. This results in postsynaptic glutamate receptor inhibition and resultant depression of the central nervous system. Although hypercarbia is commonly encountered along with hypoxia, isolated carbon dioxide–induced narcosis can be encountered. This situation is typically encountered in elderly patients with chronic obstructive pulmonary disease to whom only supplemental oxygen is administered. Arterial blood gas analysis in these patients reveals normal PaO₂ levels with extremely high PaCO₂ levels. This concept can be understood by studying the alveolar gas equations:

During hypoventilation, the fall in alveolar oxygen tension (PO₂) can be overcome by an increase in inspired oxygen while the alveolar carbon dioxide tension continues to rise. This phenomenon is used to diagnostic advantage in the apnea test for brain death, in which supplemental high-flow oxygen is administered through a cannula placed at the level of the carina and the ventilator is disconnected. In the appropriate clinical context, the apnea test result is suggestive of brain death if a rise in PaCO₂ of more than 20 mmHg does not result in respiratory efforts. Chronic hypercarbia produces milder neurological dysfunction as a result of compensatory nervous system adaptation. Nevertheless, morning headaches, asterixis or tremulousness, inattention, and cognitive dysfunction are often encountered in such patients. Cerebral edema and papilledema are often encountered in these patients. An important caveat in the treatment of these patients is that correction of hypercarbia should be attempted gradually. Rapid correction induces cerebral vasoconstriction and worsens the encephalopathy.

Hypocarbia/Hyperventilation

Hypocarbia exists when the PaCO₂ concentration falls below the normal range of 35 to 45 mmHg. It is encountered in syndromes of hyperventilation. Such situations are encountered in voluntary or iatrogenic hyperventilation or are induced by systemic or central nervous system disorders. Patients present with a variety of neurological symptoms, including lightheadedness, tinnitus, cheiro-oral paresthesias, blurring of vision, tetany, and seizures. These symptoms are mediated by various mechanisms. Hyperventilation-induced respiratory alkalosis induces calcium shift and hypocalcemia, which is responsible for the peripheral paresthesia and tetany. Hypocarbia shifts the hemoglobin-oxygen dissociation curve to the left, reducing tissue delivery of oxygen and causing tissue hypoxia. Hypocarbia also induces cerebral vasoconstriction, reducing cerebral blood flow. This phenomenon is used to therapeutic advantage during hyperventilation for reduction of increased intracranial pressure.

Air Embolism and Decompression Sickness

All of the disorders just described involve abnormalities in the partial pressures of gases dissolved in the blood. In normal circumstances, gases dissolve in blood in proportion to their partial pressure (Henry’s law). However, there are other conditions in which this gas-blood equilibrium is disturbed and bubbles of gas form. The following discussion pertains to such phenomena. A discussion on respiration would be incomplete without a reference to these disorders. Arterial air embolism occurs with trauma, arterial cannulations, and surgical procedures. Exposure to extremely high atmospheric pressures during dives can cause rupture of pulmonary alveoli and entry of air into pulmonary veins. The resultant air bubbles act as embolic fragments and produce changes in mental status and focal neurological deficits. Similarly, when deep sea divers ascend too rapidly, there is no time for arterial gases to equilibrate, and nitrogen dissolved in adipose tissue bubbles out into the blood stream, causing decompression sickness (the “bends”). Again, gas bubbles cause neurological dysfunction in myriad ways. They can act as mechanical emboli, induce coagulation cascades at the bubble-blood interface, and cause mechanical compression and distention of vascular structures and tissues. Although cutaneous, musculoskeletal, and cardiopulmonary manifestations predominate, the nervous system is another favored site of injury. Visual symptoms, spinal cord injury, labyrinthine symptoms, focal neurological deficits, and altered mental status can occur. Although air embolism and decompression sickness produce similar neurological abnormalities, the underlying pathophysiological processes are different. Nevertheless, similar treatment protocols, involving recompression with 100% oxygen in hyperbaric chambers, are used for both conditions.¹⁴

ACIDBASE BALANCE AND RESPIRATION

The respiratory system works closely with the kidneys, the liver, and an effective circulation in maintaining homeostasis and acidbase balance. Nearly 15,000 mmol of carbon dioxide is produced every day and eliminated by the respiratory system. The pH of blood is immediately altered by respiratory changes, and vice versa.¹⁵ For clinical purposes, a linear relationship can be assumed to exist between pH and acute changes in PaCO₂. Hence, for every increase in PaCO₂ of 20 mmHg above normal, the pH falls by 0.1, and for every decrease of PaCO₂ of 10 mmHg below normal, the pH rises by 0.1.

Respiratory alkalosis can be produced by voluntary and involuntary hyperventilation. Respiratory acidosis occurs during respiratory failure.

Although metabolic acidbase disturbances are better understood with the newer concept of Stewart’s model,¹⁶ most clinicians rely on the simplified concept of anion gap and base excess. Stewart’s model postulates that acidbase balance depends on a number of factors, including PaCO₂ levels, strong ion difference, and concentrations of weak acids.^17,¹⁸ Metabolic acidosis from a variety of disorders results in compensatory respiratory changes. PaCO₂ is “blown off’” in an attempt to normalize pH, and patients display hyperventilation. Metabolic alkalosis may result in compensatory hypoventilation and respiratory acidosis but is less commonly observed.¹⁹ The PaCO₂ increases by 0.5 to 0.7 mmHg for every 1.0-mm increase in plasma HCO₃ concentration up to a maximum of 55 to 60 mmHg. If PaCO₂ fails to increase appropriately, a mixed acidbase disturbance such as additional respiratory alkalosis should be considered.²⁰ Such disorders manifest less frequently in neurological practice and are hence not considered in greater detail.