Invited Topical Review: Acid-base balance and cerebrovascular regulation.

The regulation and defense of intracellular pH is essential for homeostasis. Indeed, alterations in cerebrovascular acid-base balance directly affect cerebral blood flow (CBF) which has implications for human health and disease. For example, changes in CBF regulation during acid-base disturbances are evident in conditions such as chronic obstructive pulmonary disease and diabetic ketoacidosis. The classic experimental studies from the past 75+ years are utilized to describe the integrative relationships between CBF, carbon dioxide tension (PCO2 ), bicarbonate (HCO3 - ), and pH. These factors interact to influence 1) the time course of acid-base compensatory changes and the respective cerebrovascular responses (due to rapid exchange kinetics between arterial, extracellular fluid, and intracellular brain tissue). We propose that alterations in arterial [HCO3 - ] during acute respiratory acidosis/alkalosis contribute to cerebrovascular acid-base regulation; and 2) the regulation of CBF by direct changes in arterial versus extravascular/ interstitial PCO2 and pH - the latter recognized as the proximal compartment which alters vascular smooth muscle cell regulation of CBF. Taken together, these results substantiate two key ideas: first, that the regulation of CBF is affected by the severity of metabolic/respiratory disturbances, including the extent of partial/full acid-base compensation. Second, that the regulation of CBF is independent of arterial pH and that diffusion of CO2 across the blood-brain barrier is integral to altering perivascular extracellular pH. Overall, by realizing the integrative relationships between CBF, PCO2 , HCO3 - , and pH, experimental studies may provide insights to improve CBF regulation in clinical practice with treatment of systemic acid-base disorders. This article is protected by copyright. All rights reserved.