Theory of gastric CO2 ventilation and its control during respiratory acidosis: Implications for central chemosensitivity, pH regulation, and diseases causing chronic CO2 retention

The theory of gastric CO2 ventilation describes a previously unrecognized reflex mechanism controlled by neurons in the caudal solitary complex (cSC) for non-alveolar elimination of systemic CO2 during respiratory acidosis. Neurons in the cSC, which is a site of CO2 chemosensitivity for cardiorespiratory control, also control various gastroesophageal reflexes that remove CO2 from blood. CO2 is consumed in the production of gastric acid and bicarbonate in the gastric epithelium and then reconstituted as CO2 in the stomach lumen from the reaction between H+ and HCO3−. Respiratory acidosis and gastric CO2 distension induce cSC/vagovagal mediated transient relaxations of the lower esophageal sphincter to vent gastric CO2 upwards by bulk flow along an abdominal-to-esophageal (= intrapleural) pressure gradient the magnitude of which increases during abdominal (gastric) compression caused by increased contractions of respiratory muscles. Esophageal distension induces cSC/nucleus ambiguus/vagovagal reflex relaxation of the upper esophageal sphincter and CO2 is vented into the pharynx and mixed with pulmonary gas during expiration or, alternatively, during eructation. It is proposed that gastric CO2 ventilation provides explanations for (1) the postprandial increase in expired CO2 and (2) the negative P(blood−expired)CO2P(blood−expired)CO2 difference that occurs with increased inspired CO2. Furthermore, it is postulated that gastric CO2 ventilation and alveolar CO2 ventilation are coordinated under dual control by CO2 chemosensitive neurons in the cSC. This new theory, therefore, presupposes a level of neural control and coordination between two previously presumed dissimilar organ systems and supports the notion that different sites of CO2 chemosensitivity address different aspects of whole body pH regulation. Consequently, not all sites of central chemosensitivity are equal regarding the mechanism(s) activated for CO2 elimination. A distributed CO2 chemosensitive network—at least nine different areas in the CNS, including the cSC, have been reported to date—may reflect the complexity and dynamic nature of the fundamental neural circuitry required to achieve CO2/pH regulation across multiple organ systems under various states of arousal, oxygenation, pH status, and redox state. Moreover, coordination of respiratory and digestive control networks through the cSC could also account for the frequent co-expression of pulmonary diseases that cause chronic respiratory acidosis (and overstimulation of cSC neurons) with peptic ulcer disease or gastroesophageal reflux disease.