Precise maintenance of acid-base homeostasis is fundamental for optimal functioning of physiological and cellular processes. The presence of an acid-base disturbance can affect clinical outcomes and is usually caused by an underlying disease. It is, therefore, important to assess the acid-base status of patients, and the extent to which various therapeutic treatments are effective in controlling these acid-base alterations. In this paper, we develop a dynamic model of the physiological regulation of an HCO₃^-/CO₂ buffering system, an abundant and powerful buffering system, using Henderson-Hasselbalch kinetics. We simulate the normal physiological state and four cardinal acidbase disorders: Metabolic acidosis and alkalosis and respiratory acidosis and alkalosis. We show that the model accurately predicts serum pH over a range of clinical conditions. In addition to qualitative validation, we compare the in silico results with clinical data on acid-base homeostasis and alterations, finding clear relationships between primary acid-base disturbances and the secondary adaptive compensatory responses. We also show that the predicted primary disturbances accurately resemble clinically observed compensatory responses. Furthermore, via sensitivity analysis, key parameters were identified which could be the most effective in regulating systemic pH in healthy individuals, and those with chronic kidney disease and distal and proximal renal tubular acidosis. The model presented here may provide pathophysiologic insights and can serve as a tool to assess the safety and efficacy of different therapeutic interventions to control or correct acid-base disorders.

中文翻译：

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四种主要的酸碱障碍的数学模型

酸碱稳态的精确维持对于生理和细胞过程的最佳功能至关重要。酸碱紊乱的存在会影响临床结果，通常是由潜在疾病引起的。因此，重要的是评估患者的酸碱状态，以及各种治疗方法可有效控制这些酸碱变化的程度。在本文中，我们开发一种HCO的生理调节的动态模型₃ ^- / CO ₂缓冲系统，使用Henderson-Hasselbalch动力学的丰富而强大的缓冲系统。我们模拟正常的生理状态和四种主要的酸碱失调：代谢性酸中毒和碱中毒以及呼吸性酸中毒和碱中毒。我们显示该模型可以在一系列临床条件下准确预测血清pH值。除了定性验证，我们还将计算机模拟结果与酸碱平衡和改变的临床数据进行了比较，发现原发酸碱紊乱与继发性适应性代偿反应之间存在明确的关系。我们还表明，预测的原发性疾病准确地类似于临床观察到的代偿反应。此外，通过敏感性分析，确定了对健康个体以及患有慢性肾脏疾病以及远端和近端肾小管酸中毒的个体最有效的调节全身pH的关键参数。本文介绍的模型可提供病理生理学见解，并可作为评估控制或纠正酸碱障碍的不同治疗干预措施的安全性和有效性的工具。