LEARNING OBJECTIVES

After reading this chapter, you should:

• Understand the concepts of primary, secondary, tertiary, and quaternary structure in proteins.

• Understand the contribution of amino acid ionization to the structure of proteins.

• Understand the role of disulfide bonds in stabilizing protein structure.

• Recognize some of the methods used to determine the structure of proteins.

• Understand how post-translational modifications such as glycosylation and myristoylation contribute to protein structure and function.

• Understand the kinetics of enzyme action.

Prelude

Proteins are the workhorses of the cell (Figure 4.1): They provide structural support in the cytoskeleton, facilitate communication with other cells by acting as receptors, neutralize foreign pathogens, generate contraction forces in muscle, and most ubiquitously catalyze chemical reactions. Proteins are abundant in biological systems, such as eggs (Figure 4.2). Proteins are one of the major macronutrients in the human diet (Figure 4.3).

Some recombinant proteins now serve as therapeutic drugs for treatment or prevention of disease. Biomedical engineers also use recombinant proteins, such as growth factors, to promote growth and differentiation of cells in engineered tissues. Some biomedical engineers have been using techniques of protein engineering to design new biomaterials for use in tissue engineering, drug-delivery systems, or other medical applications.

This chapter describes the structure and function of proteins and also includes a brief introduction to some of the techniques used to determine protein structure, chiefly nuclear magnetic resonance (NMR) and x-ray crystallography. Researchers in the pharmaceutical industry use these protein structures in structure-guided drug design.

LEARNING OBJECTIVES

After reading this chapter, you should:

• Understand the concepts of an engineering system, system boundaries, and the differences between open and closed systems.

• Be familiar with the concepts of homeostasis and steady state and be able to distinguish equilibrium from steady state.

• Understand the concepts of external and internal respiration.

• Be familiar with air volumes and flow rates in the lungs.

• Understand how oxygen is carried by blood and the quantitative relationships describing oxygen concentration.

• Understand the relationship between carbon dioxide, bicarbonate ion, and pH in body fluids.

• Understand the diffusing capacity of the lung and how it relates to the properties of the respiratory membrane.

• Understand how the structure of the digestive organs (stomach, small intestine, large intestine, pancreas, and liver) is related to their functions in digestion.

• Understand the role of enzymes in digestion, and the importance of enzyme activation after secretion (i.e., the value of zymogens).

• Understand the role of reactor models in understanding digestion and absorption of nutrients.

Prelude

Humans eat, drink, and breathe to bring into their bodies the raw materials for growth, repair, and generation of the energy necessary for life and the actions that bring pleasure to life. This chapter provides an overview of human nutrition and respiration from the perspective of biomedical engineering (BME). The human body is an elegant machine that requires inputs for sustained operation. What are the processes responsible for input of nutrients and raw materials? How are molecular nutrients extracted from ingested materials? How are these processes controlled?

LEARNING OBJECTIVES

After reading this chapter, you should:

• Understand that the circulatory system consists of a circulating fluid, a system of vessels, and a pump.

• Know the composition of blood and the role of cells in determining blood's physical properties.

• Understand the general structure of the vascular system.

• Understand the relationship between vessel radius, resistance to flow, and pressure drop.

• Understand the function of capillaries in the distribution of flow throughout tissues and transport of molecules.

• Understand the anatomy of the heart and the electrical system that generates coordinated contractions.

• Understand the events in the cardiac cycle and how pressure is generated within the chambers and the aorta.

Prelude

Our bodies appear, from the outside, to be solid masses that are slow to change but, just beneath the surface, the body's fluids are in constant motion. Blood moves at high velocity throughout the body within an interconnected and highly branched network of vessels (Figure 8.1). The human circulatory system is responsible for the movement of fluid (and therefore vital nutrients contained in the fluid) throughout the body.

The purpose of the circulatory system is a familiar one to engineers and bakers; it provides mixing, and good mixing is an essential element of many successful enterprises. Cakes are made from flour, eggs, sugar, and milk (among other things); your birthday will be ruined (or at least a bit tarnished) if the chef does not mix these ingredients well. But why must humans be mixed?

LEARNING OBJECTIVES

After reading this chapter, you should:

• Describe the common components of a measurement system.

• Understand the different types of sensors and the mechanism by which each converts its detected signals into electrical signals.

• Describe the principle of operation of instruments used to monitor patient body temperature, blood pressure, oxygen saturation, cardiac function, and blood glucose levels.

• Describe the principle of operation of instruments used in the laboratory such as a pH meter and spectrophotometer.

• Understand the importance of the emerging areas of biosensors and microelectromechanical systems (MEMS).

Prelude

Modern health care has benefited enormously from the work of biomedical engineers to create instruments that are used in clinical monitoring and laboratory analysis. Hospital operating rooms, emergency rooms, and doctors' offices each contain an array of instruments used to measure and record a patient's vital signs such as temperature, blood pressure, pulse, and oxygen saturation (Figure 11.1). Many of the most popular instruments enable non-invasive monitoring of vital signs of patient health: The stethoscope allows doctors to listen reliably to the beating heart, the sphygmomanometer allows them to estimate pressure within vessels deep in the body (Figure 11.2), and the ophthalmoscope allows them to see structures on the retina. It is impossible to estimate the number of lives that have been lengthened or improved by these devices.

The medical device industry—the constellation of large and small companies that design, manufacture, and sell medical devices and instruments—is one of the largest and most rapidly growing sectors of the U.S. economy.

LEARNING OBJECTIVES

After reading this chapter, you should:

• Be familiar with how changes in medicine have enhanced life span and quality of life.

• Understand a few examples of the role of engineering in defining medical treatments.

• Have developed your own definition of biomedical engineering.

• Understand some of the subdisciplines that are included in biomedical engineering.

• Understand the relationship between the study of biomedical engineering and the study of human physiology.

• Be familiar with the structure of this book, and have developed a plan for using it that fits your needs.

Prelude

The practice of medicine has changed dramatically since you were born. Consider a few of these changes, some of which have undoubtedly affected your own life: Couples can test for pregnancy in their homes, a new vaccine is available for chicken pox, inexpensive contact lenses provide clear vision, artificial hips allow recipients to walk and run, ultrasound imaging follows the progress of pregnancy, and small reliable pumps administer insulin continuously for diabetics. For your parents, the changes have been even more sweeping. Overall life expectancy—that is, the span of years that people born in a given year are expected to live—increased from 50 in 1900 to almost 80 by 2000 (Figure 1.1). You can expect to live 30 years longer than your great-grandparents; you can also expect to be healthier and more active during all the years of your life.

LEARNING OBJECTIVES

After reading this chapter, you should:

• Understand the stress–strain curve and how properties of materials can be evaluated by examining their deformations under applied loads.

• Understand the concept of elasticity in materials, and how it can be described by the Young's modulus.

• Understand the importance of the relationship between structure, function, and material properties in human tissues.

• Understand the intracellular structures that contribute to mechanical properties of cells.

Prelude

Humans can hold their bodies erect, vertically above the earth, because their bodies are solid objects capable of supporting their own weight. The human skeletal system is a collection of 206 bones, connected by soft tissues—cartilage, ligaments, tendons, and muscles—that together provide a mechanical support system for the human body.

Humans are also capable of movement. Muscles—connected to the solid bone framework—contract to generate forces that result in motion. Dancers, high jumpers, and surgeons learn to control these movements precisely to accomplish tasks and transport their bodies with precision (Figure 10.1). Strength, agility, and stamina can all be enhanced by training and, as a species, our understanding of the effects of training improves each year. As a result, humans continually improve performance on certain tasks, such as Olympic events (Figure 10.2).

This chapter describes some of the elements of human body structure and mechanics. To aid in description, the chapter begins with some basic concepts about the mechanical properties of materials.

LEARNING OBJECTIVES

After reading this chapter, you should:

• Understand the various types of biomaterials that are available and their common uses.

• Understand coagulation response to biomaterials in contact with blood and the foreign body response (FBR) to implanted biomaterials.

• Understand the importance of hemodialysis in the treatment of kidney disease and the materials and methods that are used to achieve hemodialysis.

• Describe, in quantitative terms, the efficiency of hemodialysis, as well as the changes in blood and dialysate composition that occur during hemodialysis.

• Understand the functions of membrane oxygenators and their role in open heart surgery.

• Learn about the range of medical devices—from artificial hearts and valves to drug-eluting stents—that are now used to treat heart disease.

• Understand the principles of biohybrid organs, which are similar to those used for tissue engineering, but usually applied for the creation of devices that treat blood outside the body.

Prelude

The search for artificial replacements for failing human organs is long and filled with great successes. Today, hemodialysis is routinely used to replace kidney function, artificial hip prostheses allow millions of people to walk, and artificial lenses provide cataract sufferers with clear vision. There are many disappointments as well; despite decades of serious effort, there is still no proven artificial heart, liver, or pancreas.

This chapter describes the success of several artificial organs, including hemodialysis for treating kidney failure and artificial hips. It also describes the efforts to build artificial hearts, livers, and pancreases, and the challenges that remain for these artificial organs.

LEARNING OBJECTIVES

After reading this chapter, you should:

• Be familiar with current biomedical imaging technology.

• Understand the principles behind x-ray, ultrasound, nuclear medicine, optical, and magnetic resonance imaging (MRI) techniques.

• Be familiar with some of the scientific and medical applications of these imaging modalities.

• Understand the basics of digital image processing and analysis.

Prelude

Biomedical imaging has revolutionized medicine and biology by allowing us to see inside the body and to visualize biological structure and function at microscopic levels. Images are representations of measurable properties that vary with spatial position (and often time). Images can provide exquisitely detailed information about biological structures; the most powerful imaging modalities provide functional information as well, allowing the recording of molecular or cellular processes, or physical properties (such as elasticity or temperature). Methods to visualize and quantify these properties are now available at the macroscopic (i.e., of a size visible to the human eye) and microscopic level. This information can be used clinically for diagnosis and monitoring of treatment as well as scientifically for understanding normal and abnormal structure and physiology.

Technology has brought about remarkable changes in imaging (Figure 12.1). Gene expression can now be imaged using positron emission tomography (PET) imaging—an image creation method that depends on injection of special radioisotopes—coupled with methods from genetics. The brain can be imaged at work on cognitive tasks with functional MRI (fMRI), and that information can be used to guide neurosurgery.

LEARNING OBJECTIVES

After reading this chapter, you should:

• Understand the basic components of eukaryotic cells and the differences between eukaryotic and prokaryotic cells.

• Understand the basic role of the cytoskeleton, ribosomes, endoplasmic reticulum (ER), Golgi apparatus, mitochondria, lysosomes, and genomic deoxyribonucleic acid (DNA) in cell function.

• Understand the structure of extracellular matrix (ECM) and its role in tissue function.

• Understand the role of membrane proteins in regulating transport through cell membranes and regulating cell adhesion.

• Understand the cell cycle and cell division by mitosis and meiosis.

• Understand the basic principles of stem cells and differentiation.

• Understand the basic elements of cell culture and its importance in modern biomedical science and engineering.

Prelude

The cell is the basic functional unit in the body. The human body is composed of more than 200 different types of cells (Figure 5.1). Each cell of an individual is genetically the same: They all share the same genetic information, but cell types within an individual differ with respect to size, shape, and constituent molecules (Figure 5.2); therefore, they have different properties. For example, liver cells have abundant enzymes for detoxification of chemicals whereas red blood cells instead have abundant hemoglobin for oxygen transport. These differences are important to the function of the cell in the context of the organ in which it resides.

Despite this diversity of cell composition and function, the trillions of cells in each person (most estimates range from 50 to 200 trillion cells in an average person) share common properties.

LEARNING OBJECTIVES

After reading this chapter, you should:

• Understand the relationship between biomolecular engineering and chemical engineering.

• Understand the concepts of drug effectiveness and toxicity, the limitations of some of the simplest methods of drug administration, and the need for controlled delivery systems that optimize therapy for a particular drug.

• Understand how polymeric materials with different physical properties can be fashioned into matrix, microsphere, transdermal, and other delivery systems.

• Understand how tissue engineering has emerged as a possible solution for organ replacement or healing.

• Understand the biological significance of materials with nanoscale dimensions and how material scientists are learning to assemble materials that use or mimic biological principles of self-assembly.

Prelude

The early chapters of this book introduce some of the chemicals that are important in human biology. In fact, it is possible to think of the human body as an elaborate bag of chemicals. In the subspecialty called biomolecular engineering (or biotechnology), biomedical engineers examine the changes in chemical components within a biological system and develop methods for modifying these chemicals or their interactions. The concept of introducing chemicals to induce a change in a biological system is familiar; for example, we all have some experience with taking purified chemicals such as acetaminophen or ibuprofen as drugs to relieve pain. But new biological tools now make it possible to consider more complex chemical interventions such as gene therapy (in which a new deoxyribonucleic acid [DNA] sequence is introduced to allow expression of a new genetic activity).