Effect of varying CO2 equilibria on rates of HCO3- formation in cerebrospinal fluid

Abstract

The effects of elevated plasma CO2 partial pressure (PCO2) and [HCO3-] on cerebrospinal fluid (CSF) HCO3- accession have been reviewed in the context of the basal route of CSF HCO3- formation. The basal rate of 53 mM/h appears to be a consequence entirely of formation, via the reaction CO2 + OH- leads to HCO3-. Two-thirds of this rate is catalyzed by carbonic anhydrase, and the remainder uncatalyzed. The HCO3- accession matches 37% that of sodium, so that the HCO3- rate is involved with CSF turnover. When PCO2 is elevated twofold, the rate of HCO3- formation increase 10%, and results in elevation of CSF [HCO3-] by 5 mM in 1 h. Also, when plasma [HCO3-] is elevated 15 mM, CSF [HCO3-] rises about 5 mM/h; this is transfer of HCO3- “as such” by diffusion from plasma. The effects of hypercapnia and metabolic alkalosis on CSF HCO3- accumulation are additive, but they occur by separate processes. The effect of hypercapnia is an exaltation of the normal process due to increased substrate (CO2), but that of increased plasma HCO3- is due to imposition of an abnormal diffusion gradient for this ion between plasma and CSF. The effect of hypercapnia in elevating brain HCO3- operates to maintain brain pH and is also based on the formation of HCO3- from CO2. Brain HCO3- may also be a source of CSF HCO3-. Relations have been sought between the chemically calculated rates of HCO3- formation in CSF and those observed. The chemically calculated catalytic rate is 1,600 times greater than that observed, agreeing with the fact that more than 99.9% of choroid plexus carbonic anhydrase must be inhibited to yield a decrease in fluid formation or ion transport from plasma to CSF. The calculated uncatalyzed rate agrees closely with what is observed after complete inhibition of the enzyme. These considerations support the idea that all the HCO3- reaching the CSF is formed from CO2, rather than by transfer of the ion from plasma to CSF.