Centre for Heart, Lung and Vascular Health, School of Health and Exercise Sciences, University of British Columbia, Okanagan, Kelowna, Canada.
Cerebral Haemodynamics in Ageing and Stroke Medicine (CHiASM) Research Group, NIHR Leicester Biomedical Research Centre, University of Leicester, Leicester, UK.
J Physiol. 2021 Dec;599(24):5337-5359. doi: 10.1113/JP281517. Epub 2021 Nov 26.
The regulation and defence 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 (PCO ), bicarbonate (HCO ) 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 blood, extracellular fluid and intracellular brain tissue). We propose that alterations in arterial [HCO ] during acute respiratory acidosis/alkalosis contribute to cerebrovascular acid-base regulation; and (2) the regulation of CBF by direct changes in arterial vs. extravascular/interstitial PCO 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; and second, that the regulation of CBF is independent of arterial pH and that diffusion of CO across the blood-brain barrier is integral to altering perivascular extracellular pH. Overall, by realizing the integrative relationships between CBF, PCO , HCO and pH, experimental studies may provide insights to improve CBF regulation in clinical practice with treatment of systemic acid-base disorders.
细胞内 pH 值的调节和防御对于维持内环境稳定至关重要。事实上，脑血管酸碱平衡的改变直接影响脑血流量（CBF），这对人类健康和疾病都有影响。例如，在酸碱平衡紊乱期间，CBF 调节的变化在慢性阻塞性肺疾病和糖尿病酮症酸中毒等疾病中是明显的。过去 75 多年的经典实验研究被用来描述 CBF、二氧化碳分压（PCO ）、碳酸氢盐（HCO ）和 pH 值之间的综合关系。这些因素相互作用，影响（1）酸碱补偿变化的时间过程和各自的脑血管反应（由于动脉血、细胞外液和细胞内脑组织之间的快速交换动力学）。我们提出，在急性呼吸性酸中毒/碱中毒期间动脉[HCO ]的改变有助于脑血管酸碱调节；（2）通过直接改变动脉与血管外/间质 PCO 和 pH 值来调节 CBF-后者被认为是改变血管平滑肌细胞对 CBF 调节的近端隔室。总的来说，这些结果证实了两个关键观点：第一，CBF 的调节受到代谢/呼吸紊乱的严重程度的影响，包括部分/完全酸碱补偿的程度；第二，CBF 的调节独立于动脉 pH 值，CO 通过血脑屏障的扩散对于改变血管周围细胞外 pH 值是必不可少的。总的来说，通过认识到 CBF、PCO 、HCO 和 pH 值之间的综合关系，实验研究可以为改善临床实践中 CBF 调节提供见解，治疗全身酸碱紊乱。
