Grotberg James B, Romanò Francesco, Grotberg John C
Department of Biomedical Engineering, University of Michigan, Ann Arbor, Michigan, United States of America.
Univ. Lille, CNRS, ONERA, Arts et Métiers Institute of Technology, Centrale Lille, UMR, LMFL - Laboratoire de Mécanique des Fluides de Lille - Kampé de Fériet, Lille, France.
PLoS Comput Biol. 2025 Apr 10;21(4):e1012917. doi: 10.1371/journal.pcbi.1012917. eCollection 2025 Apr.
The air-blood barrier protects the lung from blood/serum entering the air spaces, i.e., from "drowning in your own fluids". Failure leads to pulmonary edema, a regularly fatal complication during the Covid-19 pandemic which claimed 7 million lives worldwide. Finding no mathematical models for the underlying fluid mechanics, we created the first. Governing flow equations for alveolar capillary, interstitium, and alveolus are coupled by crossflows at the capillary and epithelial membranes and end-exit flows to the lymphatics. Case examples include normal/recovery, cardiogenic pulmonary edema, acute respiratory distress syndrome, effects of positive end expiratory pressure, and a wide range of parameter values for permeability of the membranes and interstitial matrix. Previously unknown membrane fluid shear stresses calculate to values that affect cell function in many systems. We add active epithelial reabsorption which has two effects: shifting streamlines to favor alveolar-lymphatic clearance and adding to the direct alveolar-capillary clearance. Simple algebraic equations are derived for the interstitial fluid pressure, pi, membrane crossflow velocities and the critical capillary pressure, pcrit, above which edema occurs. For validation, the pcrit predictions fit clinical definitions and flow calculations of lymphatic vs capillary clearance match animal experimental data. For decades the value of pi has been imposed as an input, whereas we calculate the value as an output. They don't agree. Since the space is too small for measurements, the ability to calculate pi and pcrit offers new insights, questions long-held beliefs, and opens applications from physiological studies to personalized clinical care.
气血屏障可保护肺部免受血液/血清进入气腔，即防止“溺于自身液体中”。功能失效会导致肺水肿，这是新冠疫情期间一种常致命的并发症，在全球造成了700万人死亡。由于未找到关于潜在流体力学的数学模型，我们创建了首个此类模型。肺泡毛细血管、间质和肺泡的控制流动方程通过毛细血管和上皮膜处的交叉流以及流向淋巴管的末端流出流耦合在一起。案例包括正常/恢复情况、心源性肺水肿、急性呼吸窘迫综合征、呼气末正压的影响以及膜和间质基质通透性的广泛参数值。此前未知的膜流体剪切应力经计算得出的值会影响许多系统中的细胞功能。我们加入了主动上皮重吸收，它有两个作用：使流线移动以利于肺泡 - 淋巴清除，并增加直接的肺泡 - 毛细血管清除。推导了间质液压力pi、膜交叉流速度和临界毛细血管压力pcrit（高于此值会发生水肿）的简单代数方程。为进行验证，pcrit预测符合临床定义，且淋巴与毛细血管清除的流量计算与动物实验数据相符。几十年来，pi的值一直作为输入值给定，而我们将其作为输出值进行计算。两者不一致。由于该空间太小无法进行测量，计算pi和pcrit的能力提供了新的见解，对长期以来的观念提出了质疑，并开启了从生理研究到个性化临床护理的应用。
