人工肝血液净化机理及实验系统的研究

发布时间：2018-06-01 04:14

本文选题：传质 + 动力学模型　；参考：《东华大学》2015年博士论文

【摘要】：血液净化是指通过血液净化系统除去血液中某些有害物质,从而治疗患者疾病的一种方式,它主要包括血液透析、血液滤过、血液吸附、血浆分离等。血液净化系统经常用于各种因素造成的代谢器官功能障碍,器官功能损伤等疾病的治疗,长期以来一直是人们研究的焦点。人工肾血液净化系统,是目前技术较成熟且应用广泛的一种血液净化系统,但是,这种系统的毒素清除机理仅适用于清除水溶性小分子毒素,而对于肝病患者体内的与白蛋白结合的毒素并不适用。本文主要针对非生物型人工肝血液净化机理及其相关系统进行基础理论和实验研究。首先基于大量文献,对目前人工肝血液净化技术以及相关设备的现状进行概述。由于清除血液中与白蛋白结合毒素的机理更为复杂,且涉及到的领域较多,目前国外关于人工肝血液净化机理的研究相对较少,且不完善。国外的现有设备也在生物相容性、白蛋白损失和毒素清除效率等方面存在一些不足。而国内针对人工肝血液净化方面的研究起步较晚,研究主要是集中在医疗机构对现有系统应用的临床实验研究,在与白蛋白结合毒素清除机理的基础研究和系统的原理设计方面研究甚少。因此本文针对人工肝血液净化技术的机理和系统设计的研究,对我国自主开发研制人工肝血液净化系统具有重要意义和研究价值。针对人工肝血液净化系统存在的诸多问题,本文做了几方面研究工作,具体研究内容如下:1.人工肝血液净化透析机理的优化动力学模型综合了白蛋白与毒素结合平衡机理和透析对流传质机理。基于该动力学优化模型分别建立单向透析模式和浓缩透析模式系统的流体力学模型,并利用MATLAB软件对两种模式透析系统的清除效率进行仿真。通过实验研究,结果表明该透析动力学优化模型仿真结果更准确,与实验数据更吻合。透析模式和浓缩透析模式的对比实验结果发现,浓缩模式的透析系统不仅在体积、回收、成本方面明显优于单向模式,其清除效率较单向模式系统也具有一定优势。仅在一定条件下,浓缩透析模式的最终清除效率低于单向模式,但透析开始时清除毒素的速率要明显高于单向模式。2.针对人工肝血液净化吸附动力学传质机理的研究,本文根据分层吸附的现象,建立毒素吸附过程的动力学模型。并基于白蛋白吸附量,对毒素吸附传质系数进行修正。利用吸附传质动力学模型,针对“超滤”和“对流”两种吸附模式,分别建立两种吸附模式系统的流体力学模型,并利用MATLAB软件对系统的毒素清除效率进行仿真。两种吸附模式的工作效率进行比较,结果发现,超滤模式的毒素清除效率较对流模式要快,但是由于系统使用的吸附介质总量相同,两种模式的系统最终毒素清除效率也会趋于一致。3.本文建立了人工肝血液净化实验系统。根据人工肝血液净化机理的研究,对实验系统的血液净化原理进行设计。首先提出流速增强设计,解决系统血浆流速受限的问题。对该系统使用的硬件进行设计和选型;再根据血液净化系统的一些安全性原则,对整个实验系统的硬件进行合理布局。根据实验系统的功能和工作流程,利用单片机实现实验系统的电气控制。同时,考虑到系统可能发生的异常情况,针对系统在泵工作异常、血液凝固、血液流速异常等特殊情况下,各个压力监控点的压力变化,得出整个系统的安全逻辑控制关系,来确保系统的安全运行。4.利用实验系统验证了人工肝血液透析优化模型和浓缩透析模式的准确性和有效性。之后又对超滤吸附模式和对流吸附模式的比较结果进行实验验证,结果表明,本文推导的吸附动力学模型仿真结果与实验数据一致;在实验开始阶段超滤模式的清除效率高于对流模式。最后还对本文的实验系统进行了实验验证。综上所述,本文设计的人工肝血液净化实验系统合理、有效,且具有体积小,回收方便,白蛋白损失少等方面的优势。通过上述研究,本文取得的创新成果如下:1.优化了血液透析动力学模型,并提出了一种浓缩透析模式。本文考虑局部超滤不均匀分布的现象,提出一种基于局部超滤的人工肝血液透析动力学优化模型,解决了一般模型预测不够准确的问题;针对单向模式透析系统存在的成本高、回收难、体积大等不足,首次提出了一种系统体积轻便、有利于白蛋白再生、便于回收的浓缩透析模式。结果证明,浓缩透析模式在清除效率方面也具有优势。2.提出基于白蛋白吸附量的变化,对毒素吸附传质系数进行衰减修正,并首次将超滤和对流两种吸附模式的工作效率进行比较。该修正合理解释了毒素吸附过程中,毒素吸附速率减慢的问题。基于吸附传质模型的仿真,结果发现,超滤模式的毒素清除效率较对流模式要快。3.提出了一种流速增强设计方案。流速增强设计利用分流和并流的思想,将系统中吸附后的一部分血浆,并入吸附前的血浆中,有效解决了超滤吸附模式血浆流量受限的问题,提高了系统清除效率。4.设计了一种多功能吸附装置。多功能吸附装置长度可调,多种吸附介质集于一体。该设计有效解决了一般吸附装置需要多个串联,系统冗余,且吸附介质容积有限的问题。
[Abstract]:Blood purification is a way of removing some of the harmful substances in the blood through the blood purification system, and it is a way to treat the patient's disease. It mainly includes hemodialysis, hemofiltration, blood adsorption and plasma separation. The blood purification system is often used in various factors such as metabolic organ dysfunction, organ dysfunction and other diseases. The blood purification system of artificial kidney is a mature and widely used blood purification system. However, the mechanism of this system is only suitable for scavenging water soluble small molecular toxin, but it does not apply to albumin binding toxin in the body of liver disease patients. Based on a large number of literature, the current status of blood purification and related equipment of artificial liver were summarized based on a large number of literature. The mechanism of clearing blood with albumin in blood was more complex and involved more fields. At present, the research on the mechanism of artificial liver blood purification is relatively small and imperfect. There are some deficiencies in the existing equipment abroad, such as biocompatibility, albumin loss and toxin clearance efficiency. The clinical experimental research on the application of the system is very small in the basic research on the mechanism of albumin binding toxin clearance and the principle design of the system. Therefore, the research on the mechanism and system design of the artificial liver blood purification technology is of great significance and value for the development and development of the artificial liver blood purification system in our country. A number of research work has been done on the problems of artificial liver blood purification system. The specific research contents are as follows: 1. the optimal kinetic model of the mechanism of hemodialysis for artificial liver is integrated with the binding equilibrium mechanism of albumin to toxins and the mechanism of dialysis convection mass transfer. The model and the hydrodynamics model of the concentrated dialysis mode system are used to simulate the clearance efficiency of the two model dialysis systems. The experimental results show that the simulation results of the dialysis dynamic optimization model are more accurate and more consistent with the experimental data. The comparative experimental results of the dialysis mode type and the concentrated dialysis mode have been found to be found. The concentration mode dialysis system is obviously superior to the one-way mode in volume, recovery and cost, and its clearance efficiency is also superior to the one-way mode system. Under certain conditions, the final clearance efficiency of the concentrated dialysis mode is lower than the one-way mode, but the rate of removing toxin at the beginning of dialysis is obviously higher than that of the one-way mode.2. needle. In this paper, a kinetic model of the adsorption process of toxin was established based on the phenomenon of stratified adsorption. Based on the adsorption quantity of albumin, the adsorption mass transfer coefficient of the toxin was modified. The adsorption mass transfer kinetics model was used for the two adsorption modes of "ultrafiltration" and "convection", respectively. The hydrodynamics model of two kinds of adsorption mode system was established, and the MATLAB software was used to simulate the efficiency of the toxin clearance. The efficiency of the two adsorption modes was compared. The results showed that the ultrafiltration model was faster than the convective model, but the total amount of adsorption medium used in the system was the same, and the two models were the same. The final toxin clearance efficiency of the system will also be consistent with.3.. In this paper, an artificial liver blood purification experiment system is set up in this paper. According to the study of the mechanism of blood purification of artificial liver, the principle of blood purification in the experimental system is designed. First, a flow enhancement design is put forward to solve the problem of the limit of the blood flow velocity in the system. According to the safety principle of the blood purification system, the hardware of the whole experimental system is rationally arranged. According to the function and work flow of the experimental system, the electrical control of the experimental system is realized by the single chip microcomputer. At the same time, considering the possible abnormal conditions of the system, the blood coagulation of the system is abnormal in the pump and the blood is solidified. Under special conditions such as abnormal blood flow velocity and so on, the pressure change of each pressure monitoring point is changed, and the safety logic control relation of the whole system is obtained to ensure the safe operation of the system.4. to verify the accuracy and effectiveness of the artificial liver hemodialysis optimization model and the concentrated dialysis mode by the experimental system. After that, the ultrafiltration adsorption model and convection are also used. The results of the adsorption model are verified by experiments. The results show that the simulation results of the adsorption kinetics model are in agreement with the experimental data. At the beginning of the experiment, the clearance efficiency of the ultrafiltration model is higher than that of the convective model. Finally, the experimental verification of the experimental system is also carried out. In summary, the artificial liver blood is designed in this paper. The experimental system is reasonable, effective, and has the advantages of small size, convenient recovery and less loss of albumin. Through the above research, the achievements of this paper are as follows: 1. the dynamic model of hemodialysis is optimized and a concentrated dialysis mode is proposed. An artificial liver hemodialysis dynamic optimization model is used to solve the problem of inaccurate prediction of the general model. In view of the shortage of high cost, difficult recovery and large volume in the unidirectional mode dialysis system, a concentrated dialysis mode is proposed for the first time, which is convenient for the system volume and is beneficial to the rebirth of albumin, and is convenient for recovery. In terms of scavenging efficiency, the shrinkage mode also has the advantage of.2., which is based on the change of the adsorption amount of albumin, and the attenuation correction of the mass transfer coefficient of the toxin adsorption. The efficiency of the two adsorption modes of the ultrafiltration and convection is compared for the first time. This correction explains the problem of the slow adsorption rate of the toxin during the adsorption process. The simulation of adsorption mass transfer model shows that the removal efficiency of the ultrafiltration model is faster than that of the convective model..3. proposes a flow enhancement design. The flow enhancement design uses the idea of shunt and flow, and the absorption of a part of the plasma in the plasma into the plasma before the adsorption, effectively solving the ultrafiltration model plasma flow. A multi-functional adsorption device has been designed to improve the system clearance efficiency (.4.). The length of the multifunctional adsorption device is adjustable and a variety of adsorbents are integrated. The design effectively solves the problem that the general adsorption device needs multiple series, system redundancy and the limited volume of adsorbed medium.
【学位授予单位】：东华大学
【学位级别】：博士
【学位授予年份】：2015
【分类号】：R459.5

【参考文献】