DEFINITION AND PHYSIOLOGY
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.
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)/V̇A, where V̇co2 represents the carbon dioxide production, k is a constant and V̇A is fresh gas alveolar ventilation (see Chap. 279). V̇A can be calculated as minute ventilation × (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 so does not contribute to alveolar ventilation. As such, all disturbances of Paco2 must reflect altered CO2 production, minute ventilation, or dead space fraction.
Diseases that alter V̇co2 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 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.