In health the arterial level of carbon dioxide (PaCO2) is maintained between 37 and 43 mmHg at sea level. All disorders of ventilation result in abnormal measurements of PaCO2. This chapter reviews chronic ventilatory disorders that are reflected in abnormal PaCO2.
The continuous production of CO2 by cellular metabolism necessitates its efficient elimination by the respiratory system. The relationship between CO2 production and PaCO2 is described by the equation, PaCO2 = (k)(V̇CO2)/V̇ A, where V̇ CO2 represents the carbon dioxide production, k is a constant and V̇ A is fresh gas alveolar ventilation (Chap. 252). V̇ A can be calculated as minute ventilation x(1-Vd/Vt), where the dead space fraction Vd/Vt represents the portion of a tidal breath that remains within the conducting airways at the conclusion of inspiration and does not, therefore, contribute to alveolar ventilation. As such, all disturbances of PaCO2 must reflect altered CO2 production, minute ventilation, or dead space fraction.
Diseases that alter V̇ CO2 are often acute (sepsis, burns, or pyrexia, for example), and their contribution to ventilatory abnormalities and/or respiratory failure is reviewed elsewhere. Chronic ventilatory disorders typically involve inappropriate levels of minute ventilation or increased dead space fraction. Characterization of these disorders requires a review of the normal respiratory cycle.
The spontaneous cycle of inspiration and expiration is automatically generated in the brainstem. Two groups of neurons located within the medulla are particularly important: the dorsal respiratory group (DRG) and the ventral respiratory column (VRC). These neurons have widespread projections, including the descending projections into the contralateral spinal cord, where they perform many functions. They initiate activity in the phrenic nerve/diaphragm, project to the upper airway muscle groups and spinal respiratory neurons, and innervate the intercostal and abdominal muscles that participate in normal respiration. The DRG acts as the initial integration site for many of the afferent nerves relaying information about the partial pressure of arterial oxygen (PaO2), PaCO2, pH, and blood pressure from the carotid and aortic chemoreceptors and baroreceptors to the central nervous system (CNS). In addition, the vagus nerve relays information from stretch receptors and juxtapulmonary-capillary receptors in the lung parenchyma and chest wall to the DRG. The respiratory rhythm is generated within the VRC, as well as the more rostrally located parafacial respiratory group (pFRG), which is particularly important for the generation of active expiration. One particularly important area within the VRC is the so-called pre-Bötzinger complex. This area is responsible for the generation of various forms of inspiratory activity, and lesioning of the pre-Bötzinger complex leads to the complete cessation of breathing. The neural output of these medullary respiratory networks can be voluntarily suppressed or augmented by input from higher brain centers and the autonomic nervous system. During normal sleep there is an attenuated response to hypercapnia and hypoxemia resulting in mild nocturnal hypoventilation that corrects upon awakening.
Once neural input has been delivered to the respiratory pump muscles, normal gas exchange requires an adequate amount of respiratory muscle strength to overcome the elastic and resistive loads of the respiratory system (Fig. 264-1A, Chap. 252). In health, the strength of the respiratory muscles readily accomplishes this, and normal respiration continues indefinitely. Reduction in respiratory drive or neuromuscular competence or substantial increase in respiratory load can diminish minute ventilation, resulting in hypercapnia (Fig. 264-1B). Alternatively, if normal respiratory muscle strength is coupled with excessive respiratory drive, then alveolar hyperventilation ensues and leads to hypocapnia (Fig. 264-1C).
Examples of balance between respiratory system strength and load. A. Excess respiratory muscle strength in health. B. Load greater than strength. C. Increased drive with acceptable strength.
Diseases that reduce minute ventilation or increase dead space fall into four major categories: parenchymal lung and chest wall disease, sleep disordered breathing, neuromuscular disease, and respiratory drive disorders (Fig. 264-1B). The clinical manifestations of hypoventilation syndromes are nonspecific (Table 264-1) and vary depending on the severity of hypoventilation, the rate at which hypercapnia develops, the degree of compensation for respiratory acidosis, and the underlying disorder. Patients with parenchymal lung or chest wall disease typically present with shortness of breath and diminished exercise tolerance. Episodes of increased dyspnea and sputum production are hallmarks of obstructive lung diseases, such as chronic obstructive pulmonary disease (COPD), whereas progressive dyspnea and cough are common in interstitial lung diseases. Excessive daytime somnolence, poor quality sleep, and snoring are common among patients with sleep-disordered breathing. Sleep disturbance and orthopnea are also described in neuromuscular disorders. As neuromuscular weakness progresses, the respiratory muscles, including the diaphragm, are placed at a mechanical disadvantage in the supine position due to the upward movement of the abdominal contents. New-onset orthopnea is frequently a sign of reduced respiratory muscle force generation. More commonly, however, extremity weakness or bulbar symptoms develop prior to sleep disturbance in neuromuscular diseases, such as amyotrophic lateral sclerosis (ALS) or muscular dystrophy. Patients with respiratory drive disorders do not have symptoms distinguishable from other causes of chronic hypoventilation.
Table 264-1 Signs and Symptoms of Hypoventilation
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Table 264-1 Signs and Symptoms of Hypoventilation
|Dyspnea during activities of daily living|
|Orthopnea in diseases affecting diaphragm function|
|Poor quality sleep|
|Early morning headaches|
|Impaired cough in neuromuscular diseases|
The clinical course of patients with chronic hypoventilation from neuromuscular or chest wall disease follows a ...