Response to Co2, PaCO2 is most impoant factor in control of ventilation under normal conditions. PCo2 is most impoant input regulating magnitude of ventilation under resting conditions. Changes in alveolar ventilation have immediate, pronounced effect on aerial Pco2 (unlike Po2). Even slight alterations from normal Pco2 induce significant reflex. Increased Pco2 increases ventilation. Blood Brain Barrier is permeable to Co2, so increased aerial Pco2 increases brain ECF Pco2 and , it stimulates central chemoreceptors which increases ventilation by stimulating respiratory centers. Regulation of respiration: The rhythmic discharges from the brain that produce spontaneous respiration are regulated by alterations in aerial Po2, PCo2, and H+ concentration. There are numerous factors that affect and control ventilation. Chemical control Co2 ( CSF and brain interstitial fluid H+ concentration) o2 ( carotid and aoic bodies) H+ ( carotid and aoic bodies) Nonchemical control Vagal afferents from receptors in the airways and lungs Afferents from the pons, hypothalamus, and limbic system Afferents from proprioceptors Afferents from baroreceptors: aerial, atrial, ventricular, pulmonary Preipheral (Carotid & Aoic) Chemoreceptors: The carotid bodies are located at the bifurcation of common carotid aery. They send afferents in the carotid sinus nerve to the glossopharyngeal nerve (IX) the aoic bodies are located between the arch of aoa and pulmonary aery afferents ascend in the recurrent laryngeal nerves to the vagus (X). Stimulation results from a decrease in carotid and aoic body tissue PO2. Central Chemoreceptors: situated near (beneath) the ventral surface of the medulla, near the origins of the vagi and glossopharyngeal nerves these are anatomically separate from the respiratory centres, and are bathed in brain ECF. This is impermeable to both H+ and HCO3 -, however CO2 diffuses readily and decreases pH of CSF within a few minutes, which subsequently increases ventilation. Ref: A Concise Textbook Of Physiology, By S. And Kutty, K.M., Page 101.