Endogenous and Exogenous Regulation and Control of Physiological Systems

Robert B. Northrop

• Publisher: CRC Press
• Year: 2020
• eBook ISBN: 9781000151800
• Topic: Medicine
• Subtopic: Physiology

From a biomedical engineering perspective, this book takes an analytic, quantitative approach to describing the basic components of physiological regulators and control systems (PRCs). In Endogenous and Exogenous Regulation and Control of Physiological Systems, the author provides grounding in the classical methods of designing linear and nonlinear systems. He also offers state-of-the-art material on the potential of PRCs to treat immune system ailments, most notably AIDS and cancer. The book focuses on certain "wet" physiological regulators, such as those using endocrine hormones as parametric control substances. Endogenous and Exogenous Regulation and Control of Physiological Systems includes simulations that illustrate model validations and the putative control of cancer and HIV proliferation. It explores novel, untried immunotherapies on the cutting-edge of PRC treatment and explores the latest technologies.

1 Introduction to Physiological Regulators and Control Systems

1.0 INTRODUCTION

Three major issues are addressed in this text: (1) how to accurately model and describe the dynamics of certain physiological regulators and control systems (PRCs) in order to predict their behavior when they are subject to unusual conditions caused by diseases, drugs, or physical damage; (2) how to use a validated model of a compartmental pharmacokinetic system to design a closed-loop drug administration system to maintain a desired concentration of a drug in a target organ; and (3) how to use a validated mathematical model of a compartmental pharmacokinetic system and a physiological system to design an effective closed-loop drug administration system in which the drug is used to manipulate a physiological parameter.

To accurately describe a physiological system in mathematical terms (as by a set of nonlinear ordinary differential equations), one must appreciate the enormous complexity of living systems. This complexity extends to the molecular level, where some expertise in biochemistry and cell and molecular biology is needed, as well as a knowledge of the physics of molecular diffusion and physical-chemical kinetics. In short, an interdisciplinary approach is necessary.

The horns of the dilemma created in trying to model a complex physiological system are complexity vs. reductionism. An accurate description of the behavior of a complex nonlinear system lies in its detailed parametric interactions. The inclusion of many states or parameters in a mathematical model is not as much of a challenge for today’s computers as it is for today’s bioengineers, physiologists, and biochemists. Most mathematical models of physiological systems require rate constants; many of them are unknown, as they have never been measured or, worse, are not now measurable. We are therefore forced to simplify or reduce the order and complexity of the model, thereby possibly missing interesting system behavior that is the result of nonlinear complexity.

Physiological systems are generally self-regulatory closed-loop systems. External physical or chemical factors or the presence of disease can destroy the “natural balance” of a physiological regulator, leading to a physiological parameter going out of its natural bounds. Such deviation can lead to malfunction in other PRCs or organs dependent on the out-of-bounds parameter (e.g., blood glucose in diabetes mellitus). By measuring certain critical physiological parameters, it is possible to design an external controller that will administer a drug that will allow a physiological parameter to be brought back into a “normal” range in a safe manner. As will be demonstrated, the design of closed-loop drug administration systems is made more challenging by the fact that the dynamics of how a drug is metabolized by the body and how it affects its target organ(s) change with time.

1.1 PHYSIOLOGY AND PHYSIOLOGICAL REGU...

Table of contents

• Cover
• Half Title
• Title Page
• Copyright Page
• Preface
• The Author
• Table of Contents
• Chapter 1 Introduction to Physiological Regulators and Control Systems
• Chapter 2 Physical and Chemical Factors Governing the Behavior of Physiological Regulators and Control Systems
• Chapter 3 Introduction to SISO Control Systems and Systems with Delays
• Chapter 4 Introduction to Compartmental Modeling and Pharmacokinetic Systems
• Chapter 5 Special Types of Closed-Loop Drug Input Controllers
• Chapter 6 Hormonal Regulation of Sodium, Potassium, Calcium, and Magnesium Ions
• Chapter 7 Regulation of Blood Glucose
• Chapter 8 Control of Mean Arterial Pressure by Sodium Nitroprusside Injection
• Chapter 9 Control of Postoperative Pain by Self-Administered Opioids
• Chapter 10 The Human Immune System Seen from a Biomedical Engineering Viewpoint
• Bibliography and References
• Appendix: Discussion of Simulation Languages for Physiological/Pharmacokinetic and Chemical Kinetic Systems
• Index