肾脏血液分配的耦合数学模型
摘要
肾血液流动的重要功能是肾小球滤过、肾小管重吸收和分泌等,其自身调节机制主要是肌源性调节MR(myogenic response)与管球反馈TGF(tubuloglomerular feedback)。肌源性调节与管球反馈机制都作用于入球小动脉,引起该肾单位肾小球滤过率SNGFR(Single Nephron Glomerular Filtration Rate)的改变。SNGFR决定了流入肾髓质直小血管和管周毛细血管网的血流量,其结果直接影响髓质逆流倍增器的形成,以及肾小管各段对水和溶质的重吸收和分泌。因此,肾脏皮质的滤过过程、肾小管的重吸收过程通过肌源性调节、管球反馈等机制紧密联系在一起,应当在数学模型中全面考虑。
本文以哈根—泊苏叶定律和对流-扩散方程为基础,应用正常生理及某些病理状态的血流灌注量、血管管径、肾小管溶质浓度等参数,构建了耦合肌源性调节、管球反馈机制和小管系统的数学模型。
论文主要工作:
1.构建了肾脏管球反馈、肌源性调节机制及肾小管系统的耦合数学模型。
在肾髓质,对小管系统水分和溶质的重吸收进行了一维扩散-传质模型的构建;髓袢、集合管、直小血管的流量计算基于水的守恒;模型的所有参数,包括渗透系数、小管与小血管内径和各小管入口处的流量都取自实验数据。
2.研究了正常状态下肾脏滤过功能自身调节、重吸收和血液分配。
由于入球小动脉肌源性调节响应的不同,本文对两种肾单位,浅表肾单位和近髓肾单位分别进行考虑。在正常循环血量/灌注量和血钠浓度条件下,模拟了当肾动脉压在较大范围内变化时的肾小球压、SNGFR、出球小动脉流量和血浆蛋白浓度。然后,分别得到了肾小管系统长袢、短袢、集合管内小管液的流量、Na~+浓度、尿素浓度和渗透浓度,并讨论了抗利尿状态下肾髓质各处渗透浓度的变化及其生理意义。最后模拟了肾单位在肾皮质-外髓质-内髓质-肾盂处的血流量。
在一定范围内,无论动脉压P_A和灌注量J_A相对偏大或偏小,入球小动脉的肌源性调节功能使肾小球压在相对较小范围内变化,维持了有效滤过压和SNGFR的相对稳定。肾单位的血流量可间接反映全肾血液分配:皮质约88.5%,髓质约10.3%,肾乳头部约1.2%,基本与实验结果定量地吻合。
3.进行了病理状态下的肾脏血流分配与其它重要参数的模拟。
对于病理生理状态,首先模拟了肾单位灌注量变化时的肾小球压和SNGFR,并讨论了相应的肾脏血液重分配。然后模拟了灌注量增加和血钠浓度降低,即水利尿状态的集合管小管液流量、Na~+浓度、尿素浓度和渗透浓度,讨论并与抗利尿状态进形比较。最后模拟了水利尿状态的肾脏血液重分配。
血流量的增加引起皮质相对充血,增加了直小血管与肾小管流量,降低了逆流倍增效应和肾髓质形成的渗透梯度,减小了由肾小管和小血管壁重吸收到间质组织水分的比例。水利尿状态尿液流量较大,其含有的钠盐和尿素浓度较低,渗透浓度也较低;皮质、外髓质、肾盂处血流分布为90.1%,8.0%和1.9%,皮质血液比例比正常时略有增加。
论文主要特色:
1.首次综合考虑了肾血流自身调节的肌源性调节(myogenic response,MR)与管球反馈(tubuloglomerular feedback,TGF)两种调节机制,构建了肾管球反馈、肌源性调节机制及肾小管系统的耦合数学模型。
2.应用所构建的耦合数学模型,分别研究了正常状态和病理状态下肾滤过功能自身调节、重吸收和血液分配。模型较好反映肾脏的自身调节功能和血流分配,为临床提供了可借鉴的肾功能定性、定量评价方法。
Renal blood circulation is significant for the physiological function of the kidney, filtration and re-absorption,which are modulated by myogenic response(MR) and the tubuloglomerular feedback(TGF).By modulating the afferent artery of the nephron, these mechanisms affect on single nephron glomerular filtration rate(SNGFR),which decides the blood flow of the vesa recta and the capillary system in the medulla,and, in turn,affect re-absorption of water and solutes in the tubules.In one word,filtration and re-absorption are closely connected with MR and TGF.These mechanisms are required to be comprehensively involved and coupled in mathematical models.A mathematical model is developed based on Hagan-Poiseuille law and mass transport, coupling mechanics of MR,TGF and the tubular system in the medulla.
In the work:
1.Model coupling MR,TGF and the tubular system is developed. Simulations of the blood and water flows of the loop of Henel,the collecting duct and vas rectum,are carried out by the model of the tubular system in the medulla,based on conservations of water and solutes of transmural transport.The model parameters, including the permeability coefficients,the vascular lumen radius and the solutes concentration at inlets of the tubes,are derived from the experimental results.
2.Autoregulation,reabsorption and blood distribution for normal condition Medium nephron and jaxelmedullary nephron are both involved in the model,because of their difference of afferent arteries in MR.Important parameters of the nephron, glomerular pressure,SNGFR,blood flow and plasma protein concentration of the efferent artery are simulated on normal blood intake and sodium concentration,fluxes and solutes concentration in the tubules,and renal blood distribution are attained as well.Osmolalities in the tubules on antidiuresis condition are discussed.The results predict the renal autoregulation on its blood pressure and flow that maintain glomerular pressure and SNGFR.The distribution in the cortex and the medulla is: 88.5%in the cortex,10.3%in the medulla,and 1.2%at papilla.
3.Blood distribution and other important parameters are simulated for pathological conditions.
For pathological conditions,nephron pressure and SNGFR on varied blood intake are simulated.On diuresis condition(higher blood intake and lower sodium concentration),water flux,solutes concentration and osmolality in the collecting duct are discussed,comparing to those of antidiuresis condition.Finally,the blood re-distributions of the kidney on the abnormal conditions are attained.
Percentage of blood distribution in the cortical is increased on higher blood intake, which rises the blood flow in the vesa recta and the tubules,lowers osmotic gradient in the medulla,as well as water re-absorption to the vesa recta.On diuresis condition, Urine flow is higher than normal but with lower sodium and urea concentration.The blood distribution in the cortical,medulla,and the pelvis is 90.1%,8.0%and 1.9%, indicating that the percentage of blood distributed in the cortical in higher than normal.
Advantages:
1.The important mechanisms,MR,TGF,are comprehensively involved in the present model,which is developed on autoregulation and the tubular system.
2.Filtration autoregulation,Reabsorption,and blood distribution are discussed for both normal and pathological conditions by the model.The present model could assess renal functions qualitatively and quantitatively,and provide a methodological approach for clinical research.
本文以哈根—泊苏叶定律和对流-扩散方程为基础,应用正常生理及某些病理状态的血流灌注量、血管管径、肾小管溶质浓度等参数,构建了耦合肌源性调节、管球反馈机制和小管系统的数学模型。
论文主要工作:
1.构建了肾脏管球反馈、肌源性调节机制及肾小管系统的耦合数学模型。
在肾髓质,对小管系统水分和溶质的重吸收进行了一维扩散-传质模型的构建;髓袢、集合管、直小血管的流量计算基于水的守恒;模型的所有参数,包括渗透系数、小管与小血管内径和各小管入口处的流量都取自实验数据。
2.研究了正常状态下肾脏滤过功能自身调节、重吸收和血液分配。
由于入球小动脉肌源性调节响应的不同,本文对两种肾单位,浅表肾单位和近髓肾单位分别进行考虑。在正常循环血量/灌注量和血钠浓度条件下,模拟了当肾动脉压在较大范围内变化时的肾小球压、SNGFR、出球小动脉流量和血浆蛋白浓度。然后,分别得到了肾小管系统长袢、短袢、集合管内小管液的流量、Na~+浓度、尿素浓度和渗透浓度,并讨论了抗利尿状态下肾髓质各处渗透浓度的变化及其生理意义。最后模拟了肾单位在肾皮质-外髓质-内髓质-肾盂处的血流量。
在一定范围内,无论动脉压P_A和灌注量J_A相对偏大或偏小,入球小动脉的肌源性调节功能使肾小球压在相对较小范围内变化,维持了有效滤过压和SNGFR的相对稳定。肾单位的血流量可间接反映全肾血液分配:皮质约88.5%,髓质约10.3%,肾乳头部约1.2%,基本与实验结果定量地吻合。
3.进行了病理状态下的肾脏血流分配与其它重要参数的模拟。
对于病理生理状态,首先模拟了肾单位灌注量变化时的肾小球压和SNGFR,并讨论了相应的肾脏血液重分配。然后模拟了灌注量增加和血钠浓度降低,即水利尿状态的集合管小管液流量、Na~+浓度、尿素浓度和渗透浓度,讨论并与抗利尿状态进形比较。最后模拟了水利尿状态的肾脏血液重分配。
血流量的增加引起皮质相对充血,增加了直小血管与肾小管流量,降低了逆流倍增效应和肾髓质形成的渗透梯度,减小了由肾小管和小血管壁重吸收到间质组织水分的比例。水利尿状态尿液流量较大,其含有的钠盐和尿素浓度较低,渗透浓度也较低;皮质、外髓质、肾盂处血流分布为90.1%,8.0%和1.9%,皮质血液比例比正常时略有增加。
论文主要特色:
1.首次综合考虑了肾血流自身调节的肌源性调节(myogenic response,MR)与管球反馈(tubuloglomerular feedback,TGF)两种调节机制,构建了肾管球反馈、肌源性调节机制及肾小管系统的耦合数学模型。
2.应用所构建的耦合数学模型,分别研究了正常状态和病理状态下肾滤过功能自身调节、重吸收和血液分配。模型较好反映肾脏的自身调节功能和血流分配,为临床提供了可借鉴的肾功能定性、定量评价方法。
Renal blood circulation is significant for the physiological function of the kidney, filtration and re-absorption,which are modulated by myogenic response(MR) and the tubuloglomerular feedback(TGF).By modulating the afferent artery of the nephron, these mechanisms affect on single nephron glomerular filtration rate(SNGFR),which decides the blood flow of the vesa recta and the capillary system in the medulla,and, in turn,affect re-absorption of water and solutes in the tubules.In one word,filtration and re-absorption are closely connected with MR and TGF.These mechanisms are required to be comprehensively involved and coupled in mathematical models.A mathematical model is developed based on Hagan-Poiseuille law and mass transport, coupling mechanics of MR,TGF and the tubular system in the medulla.
In the work:
1.Model coupling MR,TGF and the tubular system is developed. Simulations of the blood and water flows of the loop of Henel,the collecting duct and vas rectum,are carried out by the model of the tubular system in the medulla,based on conservations of water and solutes of transmural transport.The model parameters, including the permeability coefficients,the vascular lumen radius and the solutes concentration at inlets of the tubes,are derived from the experimental results.
2.Autoregulation,reabsorption and blood distribution for normal condition Medium nephron and jaxelmedullary nephron are both involved in the model,because of their difference of afferent arteries in MR.Important parameters of the nephron, glomerular pressure,SNGFR,blood flow and plasma protein concentration of the efferent artery are simulated on normal blood intake and sodium concentration,fluxes and solutes concentration in the tubules,and renal blood distribution are attained as well.Osmolalities in the tubules on antidiuresis condition are discussed.The results predict the renal autoregulation on its blood pressure and flow that maintain glomerular pressure and SNGFR.The distribution in the cortex and the medulla is: 88.5%in the cortex,10.3%in the medulla,and 1.2%at papilla.
3.Blood distribution and other important parameters are simulated for pathological conditions.
For pathological conditions,nephron pressure and SNGFR on varied blood intake are simulated.On diuresis condition(higher blood intake and lower sodium concentration),water flux,solutes concentration and osmolality in the collecting duct are discussed,comparing to those of antidiuresis condition.Finally,the blood re-distributions of the kidney on the abnormal conditions are attained.
Percentage of blood distribution in the cortical is increased on higher blood intake, which rises the blood flow in the vesa recta and the tubules,lowers osmotic gradient in the medulla,as well as water re-absorption to the vesa recta.On diuresis condition, Urine flow is higher than normal but with lower sodium and urea concentration.The blood distribution in the cortical,medulla,and the pelvis is 90.1%,8.0%and 1.9%, indicating that the percentage of blood distributed in the cortical in higher than normal.
Advantages:
1.The important mechanisms,MR,TGF,are comprehensively involved in the present model,which is developed on autoregulation and the tubular system.
2.Filtration autoregulation,Reabsorption,and blood distribution are discussed for both normal and pathological conditions by the model.The present model could assess renal functions qualitatively and quantitatively,and provide a methodological approach for clinical research.
引文
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