The ventilatory pump accomplishes bulk transfer of air to and from the alveoli. Accordingly, diseases that perturb the mechanical properties of any component of the ventilatory pump (i.e., the bony rib cage, the extra- and intrathoracic conducting airways, and the respiratory muscles) may interfere with CO2 elimination and O2 uptake. If disturbances in the function of the ventilatory pump are sufficiently severe, alveolar hypoventilation and respiratory acidosis may ensue. Hypercapnic respiratory failure is defined as a steady-state PaCO2 while awake at more than 45 mm Hg, the upper limit of normal. This definition is somewhat arbitrary but has proved clinically useful.
Conceptually, diseases that cause hypercapnic respiratory failure do so by deranging respiratory mechanics and lung dead space volume (e.g., chronic obstructive pulmonary disease [COPD], asthma, or kyphoscoliosis) or by impairing the contractile properties of the respiratory muscles (e.g., neuromuscular disease). Diseases that impair respiratory mechanics increase the elastic or resistive load against which the respiratory muscles must contract. On the other hand, neuromuscular diseases impair the strength or endurance properties of the respiratory muscles and impair their ability to generate swings in intrathoracic pressure sufficient to maintain ventilation.
The rhythmic act of breathing results from the activity of a central respiratory pattern generator (CRPG) comprises interacting networks of excitatory and inhibitory neurons in the pons and medulla oblongata.1,2 In turn, projections from the CRPG to bulbospinal motor neurons activate the respiratory skeletal muscles in the chest wall, abdomen, and upper airway and, hence, shape the neuromuscular drive to breathe. A variety of compensatory neural mechanisms located in the periphery that sense alterations in blood-gas tensions or ventilatory performance which project to the CRPG elicit increases in the neuromuscular drive to breathe and, in turn, help preserve alveolar ventilation.3–7 In fact, in most patients, rather marked abnormalities in ventilatory pump performance are required before hypercapnic respiratory failure ensues. Conceptually, the susceptibility to develop CO2 retention in the setting of lung, chest wall, or respiratory muscle dysfunction, therefore, depends on the balance between the severity of the derangement in ventilatory pump function and the intensity of the respiratory neuromuscular drive to breathe.5
This chapter deals with the pathogenic mechanisms at work in the development of CO2 retention in lung and chest wall diseases. The compensatory/adaptive mechanisms that help preserve ventilation (e.g., respiratory chemosensitivity, motor responses to alterations in the mechanics of breathing, and intrinsic changes in respiratory muscle strength and endurance) and the decompensating/maladaptive responses that predispose to CO2 retention (e.g., respiratory muscle wasting and fatigue and a rapid, shallow pattern of breathing) will be discussed.
The roles of compensatory or adaptive mechanisms in hypercapnic respiratory failure are considered with respect to respiratory chemosensitivity, blunted chemosensitivity, and alterations in respiratory structure.