Further Understanding of the Human Machine

The following sections are included:

• DEDICATION
• ACKNOWLEDGMENTS
• CONTRIBUTORS
• CONTENTS
• PREFACE

Bioengineering has evolved steadily and increasingly over the last two or three decades, but especially when it crossed the centuries dividing line, as if the millennium transition meant a unique omen leap. In the beginning, it was a simple mixture of a few ingredients, and people talked of Medical Electronics (ME) as a multidiscipline. Step by step, the link became more intimate, and it was called an interdiscipline, because there was free crossing from one area into the other. Nowadays, new disciplines show up, reminding of transgenic organisms, where the very deoxyribonucleic acid (DNA) is modified. Thus, we should speak of transdiscipline. Far off is the naïve 1950s idea of putting together in a room a bunch of engineers, biologists, and physicians to produce ME!

The basic concepts are briefly reviewed, for nerves, muscles, and heart (resting potential, action potential, and conduction velocity), as they are essential source of information. The ion channels and their most recent concepts are also covered succinctly since, for transport efficiency, channels have an advantage over carriers in that up to 100 million ions can pass through one open channel each second, a rate 10⁵ times greater than the fastest rate of transport mediated by any known carrier protein. Besides, the relationship to the Maxwell and Kirchhoff equations is given as the strongest theoretical ground electrophysiology may have.

Muscle contraction is the mechanical event, triggered by an electrical pulse, which in the end produces useful force, be it to lift a weight or to push a burst of blood forward. Basic laws, principles, and concepts govern such mechanical activity and they are revisited attempting to offer better mathematical background.

A quick review of the physiology of respiration is made assuming that the reader is acquainted with the subject to proceed, thereafter, to more challenging subareas of this essential function. After clearly defining what normal respiration is, high altitudes and deep sea responses are visited trying to update as much as possible. The theoretical side of the problem is also reviewed. This approach may help in a better understanding of respiratory distress and also in the design of ventilators.

First, we recall our aquatic origin showing how, steadily and very slowly, evolution brought us to the present state, where the intellect has become the central core — the kernel — governing all our steps immersed in the internal sea. The renal functions take place within it, giving us freedom to move about and beyond. Convolution and deconvolution are thereafter introduced, as mathematical tools, to find the renal retention function, essential physiological concept derived from renography. Finally, the renin–angiotensin–cardionatrine system is dealt with, even though some reader may complain it had better belong to the endocrine area.

After food ingestion and the digestion process in the stomach, the intestinal contents move from the duodenum through the rest of the small intestine, while more and more micronutrients are given off by the food. They must be absorbed into the surrounding cells and distributed to all the body tissues. Most absorption takes place by diffusion, so the available surface area and the concentration gradient determine the rate of absorption across the cell membrane. The intestine is specialized to maximize both. Absorption is an essential function for life maintenance. Malabsorption implies defective entrance of a dietary constituent resulting from interference with its digestion or absorption. In small animals, it is typically due to exocrine pancreatic insufficiency, whereas most cases of absorption failure are caused by small intestinal disease. This chapter will try to go deeper in it while devoting also space to the hepatic exchanger.

Who really knows, but many of the unknowns still hidden in the endocrine system (ES) may contain the answers to the flows and ebbs of human behavioral misfortunes and states of elation. It is a system with a high “engineering content”. In it, control is omnipotent, showing delicate high sensitivities all over, with extremely low concentrations of hormones in many cases. Its derangements lead always to unhappy endings. Its functional subsystems include the hypothalamic – hypophyseal axis, the catecholamine system (adrenal medulla, its central gland), the thyroid – parathyroid system for calcium regulation, the insulin – glucagon system (pancreas), the renin – angiotensin – cardionatrine system, and the relatively recently revisited pineal gland and associated Biological Clock, the two latter systems dealt with in other chapters of this book. Deconvolution is once more used, this time in a quite physiological ingenious way. The ES controls, coordinates, and regulates different functions in the organism, many times in conjunction with the nervous system. Its actions are relatively slow to take place because the hormones — with their messages — are released into the blood stream by the internal secretion glands. Hormones are highly specific and only trigger effects on well-determined targets (cells or organs). The elicited response is usually proportional to the stimulating hormonal concentration.

In a mechanistic-like oversimplification, the brain shows some similarities to a computer handling logical information, but, in fact, they are very different. In the brain, pattern recognition is an adaptive process that makes use of neural circuit changes, principally, by adjusting the strength of certain neural connections. Biological evolution “chose” the way to adjust them in order to improve individual survival. The brain has a population of hundreds of billions of neurons; hence, the interconnection of this neural circuitry is huge, so much, that it allows the brain to make each individual unique, with the ability to create art and science. In spite of such enormous and interconnected size, it has an organization that, in a way, makes easier to theorize how the brain works. Moreover, it is possible to find experimentally how neural populations encode information, and to simulate it with computational theories in an effort to find hypotheses to explain brain higher functions, such as learning and behavior.

The first part of this chapter introduces the musculoskeletal system, from the perspective of bioengineering, tackling aspects of the osseous tissue, joints and muscles, tendons, and ligaments. The second part of the chapter focuses into human motion and the discussion and analysis of new means for acquiring and processing signals concerning human balance. As opposed to traditional means, accelerometry-based devices are especially described, as a promising alternative. Given the importance of risk of falls for the elderly population, basic components and signal analysis strategies on a study case are presented, in which an accelerometry-based device was used during clinical, qualitative assessments of risk of falls according to scales of performance. Finally, results from the definition of specific indexes through signal processing strategies are shown.

Life has evolved in a cyclic environment, and consequently, during evolution the time dimension was incorporated in the inner organization of every single biological structure. This incorporation is evident in the biological rhythms detected in the whole phylogenetic range, from unicellular organisms to humans, and at all organizational levels within an organism, from molecular to behavioral variables. “Doing the right thing at the right time” enhances reproduction, health, survival, and longevity. Biological clocks generate such rhythms, afferent pathways synchronize them with the cyclic environment, and efferent pathways convey this time information to the organism as a whole. In mammals, the main biological clocks are localized in the hypothalamus, the suprachiasmatic nuclei, which receive direct specialized inputs from the retinas allowing synchronization to the external night–day maintaining the organism in tune with its environment. A particular and refined set of photoreceptors allows this light perception. A network of peripheral clocks in other neural, as well as non-neural tissues throughout the organism, receives this time information assuring precise temporal relationship between every system within the organism, the so-called internal temporal order. When considering any biological system, time of sampling should always be tracked, and the use of basic and simple chronobiological methods considered so avoiding misinterpretations.

Biosensors, sensing systems that use biological recognition, physicochemical transduction, and companion instrumentation, have been widely used to analyze and quantify different analytes. The application of biological entities to develop selective sensors has grown exponentially since the late 1990s, and the worldwide biosensor industry is now worth billions of dollars and tens of thousands of papers have been published in the area. Biosensors can be applied in medicine, pharmacology, food and process control, environmental monitoring, defense, and security. The biggest market is in the medical area, particularly the glucose biosensors for people with diabetes. The latest trend is to apply biosensors for personalized medicine. The modification of electrode surfaces with biological molecules (enzymes, antibodies, nucleic acids, organelles, whole cells, tissues, etc.) has now evolved with the use of nanostructures. The emergence of nanotechnology promises to enhance the performance of biotransducers through interface engineering. Among the nano-enabled enhancements, we find preferential orientation of biomolecules onto device surfaces, improved bioelectrocatalytic performance, direct electron transfer, and the consequential increased sensitivity and miniaturization. Recently, it has been suggested that amyloids, a class of protein aggregates, originally associated with human diseases, could be used for the bio-nanotechnological applications, particularly in the development of biosensors.

This chapter introduces the concept of biomedical biosensors, discusses the various transduction principles, the various biological agents used in biorecognition, the engineering challenges in fabrication and systems applications, and the new frontier opportunities for both fabrication and applying biosensors.

Biopotentials are essential signals that are immersed in the body like underwater currents in an ionic ocean. Electrodes allow their detection by transducing these ionic phenomena into electrical signals, feasible to be processed by electronic circuits. Thus, we do not have direct access to biopotentials but through variable (and sometimes unpredictable) electrode–skin impedances. Because of this, when available as electrical signals, biopotentials become faint and vulnerable to noise and interference sources. One approach to bypass this problem is to use invasive techniques such as skin abrading or percutaneous needles insertion, which bring us closer to the electrical source, thus reducing the impedance. These solutions try to find out a solution compromising the patients’ comfort, instead of working on electronic design. It is a task for bioengineers to design bioamplifiers able to acquire high-quality signals using noninvasive techniques while dealing with high-electrode impedances. This chapter describes the characteristics of biomedical signals available at the electrodes, the influence of external interference sources, and the desired bioamplifiers’ features to deal with. Classic and current amplifier design and new tendencies are herein presented, showing circuits for both traditional wet electrodes and capacitive electrodes (CEs). The latter is an emerging technology that does not require electrolytes (gel, liquid, or paste), which allow picking up biopotentials without any skin preparation, even through dielectric films or cotton clothes. A note should be made about the term “bioamplifier” itself. When analog electronics were the predominantly available tool, biopotential measurements were improved by enhancing the amplifier design. This remains true, but in a time when digital electronics and integrated systems are ever cheaper and more efficient, we think about the bioamplifier in connection with a broader class of devices which encompass the digital domain. In this chapter we discuss biopotential acquisition systems, because the characteristics of data converters and mixed-signal devices have become an integral part of a “bioamplifier” design.

We intend here to offer an overview of how biology and medicine entered into a process of mathematization, starting with Leonardo until reaching our current days, pointing out some outstanding areas without forgetting essential concepts that remain as theoretical columns or pillars.

Let us begin this last chapter by more or less repeating what was said in a previous book (Valentinuzzi, 2010): The last chapter is the most difficult of all for it intends to play the magician, the Nostradamus, by watching in the crystal ball to signal possible new avenues for research, development and applications. During such endeavor, some references not given before will be brought up to better complete the list and partially compensate for ignorance and/or forgetfulness. Thus, the subject order tries to fill up possible gaps left in the main text but … definitely YES … the traditional pending questions are…

The following sections is included:

• Index