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呼吸系统的数学模拟(作者译)

[Mathematical simulation of the respiratory system (author's transl)].

作者信息

Middendorf T, Loeschcke H H

出版信息

J Math Biol. 1976 Jun 30;3(2):149-77. doi: 10.1007/BF00276203.

Abstract

The respiratory system is described as a feedback control system. The controller consists of the peripheral chemoreceptors and the central chemosensitive structures, the respiratory centre in the medulla oblongata and the thorax-lung pump which they drive. The controlled system is comprised of three compartments (lung, brain and the remaining tissue) connected by the blood circulation. The controlled values are arterial pH and arterial O2 partial pressure and cerebral extracellular pH. Earlier models have been improved by: (1) the dead space description, (2) the thermodynamic formulation of the CO2 dissociation equation and the simple but accurate O2 dissociation equation of the blood, (3) the alteration of the CO2 dissociation equation for the brain and the remaining tissue to accommodate recent results, (4) the application of the one-receptor-theory of central chemosensitivity, (5) the pH dependence of brain circulation, (6) the bicarbonate exchange between blood and extracellular fluid of the brain and (7) the introduction of variable circulation times. Respiratory and metabolic disturbances of the respiratory system are analyzed. The mathematical formulation of the respiratory system is a differential difference equation system. In the steady state the experimental results are reproduced fairly well. A slight discrepancy is found in the simulation of metabolic acidosis. Apparently we have assumed the sensitivity of the peripheral chemoreceptors to be too large so that the respiratory response is not correctly predicted. In the numerical solution there is an overshoot in the on-transient and a damped oscillation in the off-transient of the alveolar CO2 partial pressure during respiratory acidosis. We have varied the parameters to make deviations small. The best agreement seems to result, if the central threshold is near the normal extracellular pH of the brain. A further deviation from experimental findings is that the cerebral CO2 and H+ concentration, the blood circulation of the brain, the alveolar O2 partial tension and the ventilation show a slight oscillation in the off-transient. Except for these discrepancies the experimental results, especially the stability of the extracellular pH of the brain, are reproduced fairly well. During hypoxia there are deviations form the experimental results if the central residual activity is constant and the central threshold deviates from the normal extracellular pH of the brain. But if the central residual activity is pH dependent and if the central threshold is equal to the normal extracellular pH of the brain, then the time course of VE and the other variables agree fairly well with experimental results. There is also a good correspondence between the theoretical and experimental data during hyperoxia. During metabolic acidosis the time constant of the bicarbonate exchange between blood and extracellular fluid of the brain is important. If a time constant of one minute is assumed, then the predicted and the experimental results correspond sufficiently well.

摘要

呼吸系统被描述为一个反馈控制系统。控制器由外周化学感受器和中枢化学敏感结构组成,延髓中的呼吸中枢以及由它们驱动的胸肺泵。受控系统由通过血液循环相连的三个部分(肺、脑和其余组织)组成。受控值是动脉pH值、动脉血氧分压和脑细胞外pH值。早期模型通过以下方面得到了改进:(1)死腔描述;(2)二氧化碳解离方程的热力学公式以及血液简单但准确的氧解离方程;(3)针对脑和其余组织的二氧化碳解离方程的改变,以适应最新结果;(4)中枢化学敏感性的单受体理论的应用;(5)脑循环对pH的依赖性;(6)血液与脑细胞外液之间的碳酸氢盐交换;(7)引入可变循环时间。对呼吸系统的呼吸和代谢紊乱进行了分析。呼吸系统的数学公式是一个微分差分方程组。在稳态下,实验结果得到了较好的再现。在代谢性酸中毒的模拟中发现了轻微差异。显然,我们假设外周化学感受器的敏感性过大,以至于呼吸反应没有得到正确预测。在数值解中,呼吸性酸中毒期间肺泡二氧化碳分压的上升瞬变存在过冲,下降瞬变存在阻尼振荡。我们通过改变参数使偏差变小。如果中枢阈值接近脑的正常细胞外pH值,似乎能得到最佳拟合。与实验结果的另一个偏差是,在下降瞬变中,脑二氧化碳和氢离子浓度、脑血液循环、肺泡氧分压和通气表现出轻微振荡。除了这些差异外,实验结果,尤其是脑细胞外pH值的稳定性,得到了较好的再现。在缺氧期间,如果中枢残余活性恒定且中枢阈值偏离脑的正常细胞外pH值,则与实验结果存在偏差。但是,如果中枢残余活性依赖于pH值且中枢阈值等于脑的正常细胞外pH值,那么VE和其他变量的时间进程与实验结果相当吻合。在高氧期间,理论数据和实验数据之间也有很好的对应关系。在代谢性酸中毒期间,血液与脑细胞外液之间碳酸氢盐交换的时间常数很重要。如果假设时间常数为一分钟,那么预测结果和实验结果就足够吻合。

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