title: An integrated model of the human ventilatory control system: the response to hypercapnia.
abstract: This work presents a mathematical model of the human respiratory control system, based on physiological knowledge. It includes three compartments for gas storage and exchange (lungs, brain tissue and other body tissues), and various kinds of feedback mechanisms. These comprehend peripheral chemoreceptors in the carotid body, central chemoreceptors in the medulla and a central ventilatory depression. The latter acts by reducing the response of the central neural system to the afferent peripheral chemoreceptor activity during prolonged hypoxia of the brain tissue. Furthermore, the model considers local blood flow adjustments in response to O2 and CO2 arterial pressure changes. In this study, the model has been validated by simulating the response to square changes in alveolar PCO2, performed at different constant levels of alveolar PO2. A good agreement with data reported in the literature has been checked. Subsequently, a sensitivity analysis on the role of the main feedback mechanisms on ventilation response to CO2 has been performed. The results suggest that the ventilatory response to CO2 challenges during hyperoxia can be almost completely ascribed to the central chemoreflex, while, during normoxia, the peripheral chemoreceptors provide a modest contribution too. By contrast, the response to hypercapnic stimuli during hypoxia involves a complex superimposition among different factors with disparate dynamics. Hence, results suggest that the ventilatory response to hypercapnia during hypoxia is more complex than that provided by simple empirical models, and that discrimination between the central and peripheral components based on time constants may be misleading.
authors.affiliation: Department of Electronics, Computer Science and Systems, University of Bologna, Bologna, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Ursino
authors.forename: E
authors.initials: E
authors.lastname: Magosso
authors.forename: G
authors.initials: G
authors.lastname: Avanzolini
mesh_terms: D002245:Carbon Dioxide / Q000097:blood; D002344:Carotid Body / Q000502:physiology; D002490:Central Nervous System / Q000502:physiology; D002628:Chemoreceptor Cells / Q000502:physiology*; D006801:Humans; D006935:Hypercapnia / Q000503:physiopathology*; D000860:Hypoxia / Q000503:physiopathology; D008962:Models, Theoretical; D010100:Oxygen / Q000097:blood; D011659:Pulmonary Gas Exchange; D012143:Respiratory Physiological Phenomena
chemical_list: D002245:Carbon Dioxide; D010100:Oxygen