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The primary stimulus in the regulation of breathing patterns are the chemical changes in the blood such as the partial pressures of oxygen and carbon dioxide (PO2/PCO2) and hydrogen ion concentration (pH). Hydrogen ion concentration in the cerebrospinal fluid (CSF) has the earliest and greatest influence on respiratory activity. Hence, hypoventilation (as in breath holding) stimulates neurons of the inspiratory center in the medulla when the rising partial pressure of carbon dioxide decreases cerebrospinal fluid pH. Conversely, voluntary hyperventilation depresses the respiratory center via the decrease in partial pressure of carbon dioxide which raises cerebrospinal fluid pH.

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