BACKGROUND: The acidity of human body fluids, expressed by the pH, is physiologically regulated in a narrow range, which is required for the proper function of cellular metabolism. Acid-base disorders are common especially in intensive care, and the acid-base status is one of the vital clinical signs for the patient management. Because acid-base balance is connected to many bodily processes and regulations, complex mathematical models are needed to get insight into the mixed disorders and to act accordingly. The goal of this study is to develop a full-blood acid-base model, designed to be further integrated into more complex human physiology models. RESULTS: We have developed computationally simple and robust full-blood model, yet thorough enough to cover most of the common pathologies. Thanks to its simplicity and usage of Modelica language, it is suitable to be embedded within more elaborate systems. We achieved the simplification by a combination of behavioral Siggaard-Andersen's traditional approach for erythrocyte modeling and the mechanistic Stewart's physicochemical approach for plasma modeling. The resulting model is capable of providing variations in arterial pCO2, base excess, strong ion difference, hematocrit, plasma protein, phosphates and hemodilution/hemoconcentration, but insensitive to DPG and CO concentrations. CONCLUSIONS: This study presents a straightforward unification of Siggaard-Andersen's and Stewart's acid-base models. The resulting full-blood acid-base model is designed to be a core part of a complex dynamic whole-body acid-base and gas transfer model.

• Keywords
• Acid-base modeling, Behavioral acid-base, Modelica, Physicochemical acid-base, Physiolibrary, Physiology, Siggaard-Andersen,
• MeSH
• Acid-Base Equilibrium * physiology   MeSH
• Models, Biological * MeSH
• Models, Chemical * MeSH
• Hydrogen-Ion Concentration MeSH
• Humans MeSH
• Acid-Base Imbalance diagnosis   epidemiology   physiopathology   MeSH
• Models, Theoretical * MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH

BACKGROUND: Simulators used in teaching are interactive applications comprising a mathematical model of the system under study and a graphical user interface (GUI) that allows the user to control the model inputs and visualize the model results in an intuitive and educational way. Well-designed simulators promote active learning, enhance problem-solving skills, and encourage collaboration and small group discussion. However, creating simulators for teaching purposes is a challenging process that requires many contributors including educators, modelers, graphic designers, and programmers. The availability of a toolchain of user-friendly software tools for building simulators can facilitate this complex task. OBJECTIVE: This paper aimed to describe an open-source software toolchain termed Bodylight.js that facilitates the creation of browser-based client-side simulators for teaching purposes, which are platform independent, do not require any installation, and can work offline. The toolchain interconnects state-of-the-art modeling tools with current Web technologies and is designed to be resilient to future changes in the software ecosystem. METHODS: We used several open-source Web technologies, namely, WebAssembly and JavaScript, combined with the power of the Modelica modeling language and deployed them on the internet with interactive animations built using Adobe Animate. RESULTS: Models are implemented in the Modelica language using either OpenModelica or Dassault Systèmes Dymola and exported to a standardized Functional Mock-up Unit (FMU) to ensure future compatibility. The C code from the FMU is further compiled to WebAssembly using Emscripten. Industry-standard Adobe Animate is used to create interactive animations. A new tool called Bodylight.js Composer was developed for the toolchain that enables one to create the final simulator by composing the GUI using animations, plots, and control elements in a drag-and-drop style and binding them to the model variables. The resulting simulators are stand-alone HyperText Markup Language files including JavaScript and WebAssembly. Several simulators for physiology education were created using the Bodylight.js toolchain and have been received with general acclaim by teachers and students alike, thus validating our approach. The Nephron, Circulation, and Pressure-Volume Loop simulators are presented in this paper. Bodylight.js is licensed under General Public License 3.0 and is free for anyone to use. CONCLUSIONS: Bodylight.js enables us to effectively develop teaching simulators. Armed with this technology, we intend to focus on the development of new simulators and interactive textbooks for medical education. Bodylight.js usage is not limited to developing simulators for medical education and can facilitate the development of simulators for teaching complex topics in a variety of different fields.

• Keywords
• Web browser, Web technologies, computer simulation, education, modeling, physiology,
• MeSH
• Internet MeSH
• Humans MeSH
• Software standards   MeSH
• Education, Medical methods   MeSH
• User-Computer Interface * MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH

Blood flows and pressures throughout the human cardiovascular system are regulated in response to various dynamic perturbations, such as changes to peripheral demands in exercise, rapid changes in posture, or loss of blood from hemorrhage, via the coordinated action of the heart, the vasculature, and autonomic reflexes. To assess how the systemic and pulmonary arterial and venous circulation, the heart, and the baroreflex work together to effect the whole-body responses to these perturbations, we integrated an anatomically-based large-vessel arterial tree model with the TriSeg heart model, models capturing nonlinear characteristics of the large and small veins, and baroreflex-mediated regulation of vascular tone and cardiac chronotropy and inotropy. The model was identified by matching data from the Valsalva maneuver (VM), exercise, and head-up tilt (HUT). Thirty-one parameters were optimized using a custom parameter-fitting tool chain, resulting in an unique, high-fidelity whole-body human cardiovascular systems model. Because the model captures the effects of exercise and posture changes, it can be used to simulate numerous clinical assessments, such as HUT, the VM, and cardiopulmonary exercise stress testing. The model can also be applied as a framework for representing and simulating individual patients and pathologies. Moreover, it can serve as a framework for integrating multi-scale organ-level models, such as for the heart or the kidneys, into a whole-body model. Here, the model is used to analyze the relative importance of chronotropic, inotropic, and peripheral vascular contributions to the whole-body cardiovascular response to exercise. It is predicted that in normal physiological conditions chronotropy and inotropy make roughly equal contributions to increasing cardiac output and cardiac power output during exercise. Under upright exercise conditions, the nonlinear pressure-volume relationship of the large veins and sympathetic-mediated venous vasoconstriction are both required to maintain preload to achieve physiological exercise levels. The developed modeling framework is built using the open Modelica modeling language and is freely distributed.

• Keywords
• Baroreflex, Computational model, Exercise, Head-up tilt, Valsalva maneuver, Vascular network,
• MeSH
• Baroreflex * physiology   MeSH
• Exercise * MeSH
• Cardiovascular System * MeSH
• Blood Pressure physiology   MeSH
• Humans MeSH
• Posture physiology   MeSH
• Heart Rate physiology   MeSH
• Systems Analysis MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Research Support, N.I.H., Extramural MeSH