Evidence of active regulation of cerebrospinal fluid acid-base balance

Abstract

To test the passive transport hypothesis of cerebrospinal fluid (CSF) [H+] regulation, we altered the relationship between plasma [H+] and the electrical potential difference between CSF and blood (PD) by elevating plasma [K+] during 6-h systemic acid-base disturbances. In five groups of pentobarbital-anesthetized dogs, we increased plasma [K+] from 3.5 to an average of 7.8 meq/l. Hyperkalemia produced an increase in the PD of 6.3 mV by 6 h with normal plasma acid-base status (pHa 7.4), of 8.3 mV with isocapnic metabolic acidosis (pHa 7.2), of 5.3 mV with isocapnic metabolic alkalosis (pHa 7.6), of 9.2 mV with isobicarbonate respiratory acidosis (PaCO2 61 Torr) and of 5.7 mV with isobicarbonate respiratory alkalosis (PaCO2 25 Torr). The change in CSF [H+] at 6 h in each group was the same as that observed in normokalemic animals (Am. J. Physiol. 228: 1134-1154, 1975). This result is not consistent with the passive transport hypothesis. The CSF-blood PD is therefore not an important determinant of CSF [H+] CSF [H+] homeostasis must result from some form of active transport control.

Fluid and ion transfer across the blood–brain and blood–cerebrospinal fluid barriers; a comparative account of mechanisms and roles

“…Firstly a variation of the PD in the opposite direction to that seen in most species can occur in cats even though they still regulate pH CSF [189, 435, 436] (see pg 120 in [185]). Secondly by varying [K + ] plasma the PD can be changed by as much as 9 mV with no effect on the distribution of Na + , H + or Cl − [437–439]. This indicates that changes in the PD do not produce the changes in [HCO 3 − ] CSF and [H + ] CSF needed for regulation.…”

“…The PD changes with a slope of −32 mV (pH unit) −1 when pH is varied by making primary changes in pCO 2 of blood and −43 mV (pH unit) −1 when the primary changes are in [HCO 3 − ] arterial [286]. See [525] (discussion after [401]) [438, 439] and for many further references [185, 388]. From the similar effects of increasing pCO 2 and decreasing [HCO 3 − ] arterial , it is inferred that the variation in PD depends primarily on [H + ] arterial rather than on [HCO 3 − ] arterial or pCO 2 .…”

Regulation of cerebral blood flow by arterial PCO2 independent of metabolic acidosis at 5050 m

“…2). Pioneering work by Severinghaus and colleagues (1963) revealed tight regulation of CSF pH with chronic hypocapnia and arterial alkalosis following 8 days of acclimatization to 3800 m – although the capacity of CSF [HCO 3 − ] active transport is reportedly controversial, these data illustrate the importance of interstitial/extracellular pH regulation (Severinghaus et al ., 1963; Mitchell et al ., 1965; Severinghaus, 1965; Pappenheimer1970, 1970; Hasan & Kazemi, 1976; Kazemi & Choma, 1977; Bledsoe et al ., 1981). Overall, the hyperventilatory‐induced reductions in PaCO 2 (i.e.…”

Acid–base balance and cerebrovascular regulation

“…Figure and caption adapted from Bledsoe et al . (1981), Hladky & Barrand (2016) and Carr et al . (2021).…”