Respiration and cerebrospinal fluid pH in metabolic acidosis and alkalosis

¹ Department of Anesthesia, Cardiovascular Research Institute, University of California Medical Center, San Francisco, California

An acute base deficit of 5 mm/liter (metabolic acidosis) was induced in one normal man by an initial oral dose of 20 g NH₄Cl and sustained for 5 days by administering 3 g every 6 hr. pHa (arterial) decreased from 7.42 to 7.34 in 4 hr. Ve (minute ventilation) increased from 6.2 to 8.4 liters/min, Pa_COCO2 decreased from 40 to 37 mm Hg, CSF pH increased from 7.32 to 7.34, and the CO₂ response curve shifted –2.8 mm Hg Pco₂ without slope change. At 24 hr, CSF pH was 7.32, with CSF Pco₂ and HCO₃ ^– reduced to 42 mm Hg and 21.0 mEq/liter, respectively (control 49 mm Hg, 24 mEq/liter). Ve increased to 9.8 liters/min, arterial pH increased to 7.37, Pa_COCO2 fell to 36 mm Hg, and the CO₂ response curve was –5.0 mm Hg from control. After 6 days of acidosis, acute increase in pHa to 7.45 in 2 hr by NaHCO₃ ingestion decreased Ve to 6.8 liters/min, increased Pa_COCO2 to 39 mm Hg, decreased CSF pH to 7.30, and shifted the CO₂ response curve back to control. Results of this study are consistent with the hypothesis that the peripheral chemoreceptors initiate and sustain alterations in Ve in metabolic abnormalities in the following manner: 1) acute acidosis increases Ve by stimulating the peripheral chemoreceptors; 2) the Pa_COCO2 falls and CSF pH increases, decreasing medullary (H⁺) chemoreceptor activity; and 3) active transport across the blood-CSF barrier restores CSF pH and the medullary (H⁺) chemoreceptor activity to normal, causing a further increase in ventilation that partially compensates for the metabolic acidosis.

Submitted on July 27, 1964