Stewart Physicochemical Interpretation of Cerebrospinal Fluid Acid--Base Physiology in Critical Illness

Abstract

Cerebrospinal fluid (CSF) constitutes the physicochemical milieu bathing the brain and brainstem and can diverge from arterial blood in both magnitude and time course during critical illness. This review synthesizes human and experimental evidence relevant to a Stewart physicochemical interpretation of CSF acid-base physiology, emphasizing compartmental kinetics, blood–CSF barrier and choroid plexus transport, and methodological constraints that complicate measurement. Because CSF contains minimal weak-acid buffering under physiological conditions, CSF pH is often dominated by PCO2 and strong ion difference (SID), making CSF a tractable compartment for compartment-aware physicochemical reasoning. Classical clinical observations and modern simultaneous CSF–arterial datasets in pregnancy and aneurysmal subarachnoid hemorrhage illustrate paired shifts in SID and PCO2 that are not inferable from arterial blood gases alone. Transporter-dependent recovery from hypercapnia, pH-sensitive ion fluxes, and chloride-linked transport perturbation studies support that CSF acid-base homeostasis is actively regulated and plausibly vulnerable in neuroinflammation and brain injury. We outline ICU implications, focusing on why arterial normalization may not ensure central normalization and why time-resolved ventricular datasets are the key prerequisite for bedside translation.