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ANATOMY AND PHYSIOLOGY

Susan Blanchard, PhD

Chapter Contents

3.1 Introduction

3.2 Cellular Organization

3.2.1 Plasma Membrane

3.2.2 Cytoplasm and Organelles

3.2.3 DNA and Gene Expression

3.3 Tissues

3.4 Major Organ Systems

3.4.1 Circulatory System

3.4.2 Respiratory System

3.4.3 Nervous System

3.4.4 Skeletal System

3.4.5 Muscular System

3.5 Homeostasis Exercises Suggested Reading

At the conclusion of this chapter, the reader will be able to:

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Define anatomy and physiology and explain why they are important to biomedical engineering.

Define important anatomical terms.

Describe the cell theory.

List the major types of organic compounds and other elements found in cells.

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Explain how the plasma membrane maintains the volume and internal concentrations of a cell.

Calculate the internal osmolarity and ionic concentrations of a model cell at equilibrium. List and describe the functions of the major organelles found within mammalian cells. Describe the similarities, differences, and purposes of replication, transcription, and translation.

List and describe the major components and functions of five organ systems: Circulatory, respiratory, nervous, skeletal, and muscular.

Define homeostasis and describe how feedback mechanisms help maintain it.

3.1 INTRODUCTION

Since biomedical engineering is an interdisciplinary field based in both engineering and the life sciences, it is important for biomedical engineers to have knowledge about and be able to communicate in both areas. Biomedical engineers must understand the basic components of the body and how they function well enough to exchange ideas and information with physicians and life scientists. Two of the most basic terms and areas of study in the life sciences are anatomy and physiology. Anatomy refers to the internal and external structures of the body and their physical relationships, whereas physiology refers to the study of the functions of those structures.

Figure 3.1a shows a male body in anatomical position. In this position, the body is erect and facing forward with the arms hanging at the sides and the palms facing outward. This particular view shows the anterior (ventral) side of the body, whereas Figure 3.1c illustrates the posterior (dorsal) view of another male body that is also in anatomical position and Figure 3.1b presents the lateral view of the female body. In clinical practice, directional terms are used to describe the relative positions of various parts of the body. Proximal parts are nearer to the trunk of the body or to the attached end of a limb than are distal parts (Fig. 3.1a). Parts of the body that are located closer to the head than other parts when the body is in anatomical position are said to be superior (Fig. 3.1b), whereas those located closer to the feet than other parts are termed inferior. Medial implies that a part is toward the midline of the body, whereas lateral means away from the midline (Fig. 3.1c). Parts of the body that lie in the direction of the head are said to be in the cranial direction, whereas those parts that lie in the direction of the feet are said to be in the caudal direction (Fig. 3.2).

Anatomical locations can also be described in terms of planes. The plane that divides the body into two symmetric halves along its midline is called the midsaggital plane (Fig. 3.2). Planes that are parallel to the midsaggital plane but do not divide the body into symmetric halves are called sagittal planes. The frontal plane is perpendicular to the midsaggital plane and divides the body into asymmetric anterior and posterior portions. Planes that cut across the body and are perpendicular to the midsaggital and frontal planes are called transverse planes.

Human bodies are divided into two main regions, axial and appendicular. The axial part consists of the head, neck, thorax (chest), abdomen, and pelvis whereas the

appendicular part consists of the upper and lower extremities. The upper extremities, or limbs, include the shoulders, upper arms, forearms, wrists, and hands whereas the lower extremities include the hips, thighs, lower legs, ankles, and feet. The abdominal region can be further divided into nine regions or four quadrants.

The cavities of the body hold the internal organs. The major cavities are the dorsal and ventral body cavities and the smaller cavities include the nasal, oral, orbital (eye), tympanic (middle ear), and synovial (movable joint) cavities. The dorsal body cavity includes the cranial cavity that holds the brain and the spinal cavity that contains the spinal cord. The ventral body cavity contains the thoracic and abdominopelvic cavities that are separated by the diaphragm. The thoracic cavity contains the lungs and the mediastinum, which contains the heart and its attached blood vessels, the trachea, the esophagus, and all other organs in this region except for the lungs. The abdominopelvic cavity is divided by an imaginary line into the abdominal and pelvic cavities. The former is the largest cavity in the body and holds the stomach, small and large intestines, liver, spleen, pancreas, kidneys, and gall bladder. The latter contains the urinary bladder, the rectum, and the internal portions of the reproductive system.

The anatomical terms described previously are used by physicians, life scientists, and biomedical engineers when discussing the whole human body or its major parts. Correct use of these terms is vital for biomedical engineers to communicate with health care professionals and to understand the medical problem of concern or interest. Although it is important to be able to use the general terms that describe

the human body, it is also important for biomedical engineers to have a basic understanding of some of the more detailed aspects of human anatomy and physiology.

3.2 CELLULAR ORGANIZATION

Although there are many smaller units such as enzymes and organelles that perform physiological tasks or have definable structures, the smallest anatomical and physiological unit in the human body that can, under appropriate conditions, live and reproduce on its own is the cell. Cells were first discovered more than 300 years ago shortly after Antony van Leeuwenhoek, a Dutch optician, invented the microscope. With his microscope, van Leeuwenhoek was able to observe ‘‘many very small animalcules, the motions of which were very pleasing to behold’’ in tartar scrapings from his teeth. Following the efforts of van Leeuwenhoek, Robert Hooke, a Curator of Instruments for the Royal Society of England, in the late 1600s further described cells when he used one of the earliest microscopes to look at the plant cell walls that remain in cork. These observations and others led to the cell theory developed by

Theodor Schwann and Matthias Jakob Schleiden and formalized by Rudolf Virchow in the mid-1800s. The cell theory states that: (1) all organisms are composed of one or more cells, (2) the cell is the smallest unit of life, and (3) all cells come from previously existing cells. Thus, cells are the basic building blocks of life.

Cells are composed mostly of organic compounds and water with more than 60% of the weight in a human body coming from water. The organic compoundscarbohydrates, lipids, proteins, and nucleic acids—that cells synthesize are the molecules that are fundamental to sustaining life. These molecules function as energy packets, storehouses of energy and hereditary information, structural materials, and metabolic workers. The most common elements found in humans (in descending order based on percent of body weight) are oxygen, carbon, hydrogen, nitrogen, calcium, phosphorus, potassium, sodium, chlorine, magnesium, sulfur, iron, and iodine. Carbon, hydrogen, oxygen, and nitrogen contribute more than 99% of all the atoms in the body. Most of these elements are incorporated into organic compounds, but some exist in other forms, such as phosphate groups and ions.

Carbohydrates are used by cells not only as structural materials but also to transport and store energy. There are three classes of carbohydrates: monosaccharides (e.g., glucose), oligosaccharides (e.g., lactose, sucrose, maltose), and polysaccharides (e.g., glycogen). Lipids are greasy or oily compounds that will dissolve in each other but not in water. They form structural materials in cells and are the main reservoirs of stored energy. Proteins are the most diverse form of biological molecules. Specialized proteins called enzymes make metabolic reactions proceed at a faster rate than would occur if the enzymes were not available and enable cells to produce the organic compounds of life. Other proteins provide structural elements in the body, act as transport channels across plasma membranes, function as signals for changing activities, and provide chemical weapons against disease-carrying bacteria. These diverse proteins are built from a small number (20) of essential amino acids.

Nucleotides and nucleic acids make up the last category of important biological molecules. Nucleotides are small organic compounds that contain a five-carbon sugar (ribose or deoxyribose), a phosphate group, and a nitrogen-containing base that has a single or double carbon ring structure. Adenosine triphosphate (ATP) is the energy currency of the cell and plays a central role in metabolism. Other nucleotides are subunits of coenzymes which are enzyme helpers. The two nucleic acids are deoxyribonucleic acid (DNA) and ribonucleic acid (RNA). DNA (Fig. 3.3) is a unique, helical molecule that contains chains of paired nucleotides that run in opposite directions. Each nucleotide contains either a pyrimidine base—thymine (T) or cytosine (C)—with a single ring structure or a purine base—adenine (A) or guanine (G)with a double ring. In the double helix of DNA, thymine always pairs with adenine (T–A) and cytosine always pairs with guanine (C–G). RNA is similar to DNA except that it consists of a single helical strand, contains ribose instead of deoxyribose, and has uracil (U) instead of thymine.

All cells are surrounded by a plasma membrane that separates, but does not isolate, the cell’s interior from its environment. Animal cells, such as those found in humans, are eukaryotic cells. A generalized animal cell is shown in Figure 3.4. In addition to the plasma membrane, eukaryotic cells contain membrane-bound organelles and a

membrane-bound nucleus. Prokaryotic cells (e.g., bacteria) lack membrane-bound structures other than the plasma membrane. In addition to a plasma membrane, all cells have a region that contains DNA (which carries the hereditary instructions for the cell) and cytoplasm (which is a semifluid substance that includes everything inside the plasma membrane except for the DNA).

3.2.1 Plasma Membrane

The plasma membrane performs several functions for the cell. It gives mechanical strength, provides structure, helps with movement, and controls the cell’s volume and its activities by regulating the movement of chemicals in and out of the cell. The plasma membrane is composed of two layers of phospholipids interspersed with proteins and cholesterol (Fig. 3.5). The proteins in the plasma membranes of mammalian cells provide binding sites for hormones, recognition markers for identifying cells as one type or another, adhesive mechanisms for binding adjacent cells to each other, and channels for transporting materials across the plasma membrane. The phospholipids are arranged with their ‘‘water loving’’ (hydrophilic) heads pointing outward and their ‘‘water fearing’’ (hydrophobic) tails pointing inward. This doublelayer arrangement of phospholipids interspersed with protein channels helps maintain the internal environment of a cell by controlling the substances that move across the membrane, whereas the cholesterol molecules act as stabilizers to prevent extensive lateral movement of the lipid molecules.

Some molecules (e.g., oxygen, carbon dioxide, and water) can easily cross the plasma membrane, whereas other substances (e.g., large molecules and ions) must move through the protein channels. Osmosis is the process by which substances move across a selectively permeable membrane such as a cell’s plasma membrane, whereas diffusion refers to the movement of molecules from an area of relatively high concentration to an area of relatively low concentration. Substances that can easily cross the plasma membrane achieve diffusion equilibrium when there is no net movement of these substances across the membrane (i.e., the concentration of the substance inside the cell equals the concentration of the substance outside of the cell). Active transport, which requires an input of energy, usually in the form of ATP, can be used to move ions and molecules across the plasma membrane and is often used to move them from areas of low concentration to areas of high concentration. This mechanism helps maintain concentrations of ions and molecules inside a cell that are different from the concentrations outside the cell. A typical mammalian cell has internal sodium ion (Na þ )

concentrations of 12 mM (12 moles of Na þ per 1000 liters of solution) and extracellular Na þ concentrations of 120 mM, whereas intracellular and extracellular potassium ion (K þ ) concentrations are on the order of 125 mM and 5 mM, respectively. In addition to positively charged ions (cations), cells also contain negatively charged ions (anions). A typical mammalian cell has intracellular and extracellular chloride ion (Cl À ) concentrations of 5 mM and 125 mM and internal anion (e.g., proteins, charged amino acids, sulfate ions, and phosphate ions) concentrations of 108 mM. These transmembrane ion gradients are used to make ATP, to drive various transport processes, and to generate electrical signals.

Example Problem 3.1

How many molecules of sodium and potassium ions would a cell that has a volume of 2 nl contain?

Solution

Assuming that the intracellular concentrations of Na þ and K þ are 12 mM and 125 mM, respectively, the number of molecules for each can be determined by using the volume of the cell and Avogadro’s number.

moles

molecules

Na þ : 12

K þ : 125

 6:023  1023 1000 liters

 2  10 À9 liters ¼ 1:45  10 13 molecules

mole

moles

molecules

 6:023  1023 1000 liters

 2  10 À9 liters ¼ 1:51  10 14 molecules

mole

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The plasma membrane plays an important role in regulating cell volume by controlling the internal osmolarity of the cell. Osmolarity is defined in terms of concentration of dissolved substances. A 1 osmolar (1 Osm) solution contains 1 mole of dissolved particles per liter of solution whereas a 1 milliosmolar (1 mOsm) solution has 1 mole of dissolved particles per 1000 liters of solution. Thus, solutions with high osmolarity have low concentrations of water or other solvents. For biological purposes, solutions with 0.1 Osm glucose and 0.1 Osm urea have essentially the same concentrations of water. It is important to note that a 0.1 M solution of sodium chloride (NaCl) will form a 0.2 Osm solution since NaCl dissociates into Na þ and Cl À ions and thus has twice as many dissolved particles as a solution of a substance (e.g., glucose) that does not dissociate into smaller units. Two solutions are isotonic if they have the same osmolarity. One solution is hypotonic to another if it has a lower osmolarity and hypertonic to another if it has a higher osmolarity. It is important to note that tonicity (isotonic, hypotonic, or hypertonic) is determined by only those molecules that cannot cross the plasma membrane since molecules that can freely cross will eventually reach equilibrium with the same concentration inside and outside of the cell.

Consider a simple model cell that consists of a plasma membrane and cytoplasm. The cytoplasm in this model cell contains proteins that cannot cross the plasma membrane and water which can. At equilibrium, the total osmolarity inside the cell

must equal the total osmolarity outside the cell. If the osmolarity inside and the osmolarity outside of the cell are out of balance, there will be a net movement of water from the side of the plasma membrane where it is more highly concentrated to the other side until equilibrium is achieved. For example, assume that a model cell (Fig. 3.6) contains 0.2 M protein and is placed in a hypotonic solution that contains 0.1 M sucrose. The plasma membrane of this model cell is impermeable to proteins and sucrose but freely permeable to water. The volume of the cell, 1 nl, is very small relative to the volume of the solution. In other words, changes in the cell’s volume have no measurable effect on the volume of the external solution. What will happen to the volume of the cell as it achieves equilibrium?

At equilibrium, the osmolarity inside the cell must equal the osmolarity outside the cell. The initial osmolarity inside the cell is 0.2 Osm since the proteins do not dissociate into smaller units. The osmolarity outside the cell is 0.1 Osm due to the sucrose solution. A 0.2 Osm solution has 0.2 moles of dissolved particles per liter of solution whereas a 0.1 Osm solution has half as many moles of dissolved particles per liter. The osmolarity inside the cell must decrease by a factor of 2 in order to achieve equilibrium. Since the plasma membrane will not allow any of the protein molecules to leave the cell, this can only be achieved by doubling the cell’s volume. Thus, there will be a net movement of water across the plasma membrane until the cell’s volume increases to 2 nl and the cell’s internal osmolarity is reduced to 0.1 Osm—the same as the

osmolarity of the external solution. The water moves down its concentration gradient by diffusing from where it is more highly concentrated in the 0.1 M sucrose solution to where it is less concentrated in the 0.2 M protein solution in the cell.

Example Problem 3.2

What would happen to the model cell in Figure 3.6 if it were placed in pure water?

Solution

Water can pass through the plasma membrane and would flow down its concentration gradient from where it is more concentrated (outside of the cell) to where it is less concentrated (inside of the cell). Eventually, enough water would move into the cell to rupture the plasma membrane since the concentration of water outside of the cell would be higher than the concentration of water inside of the cell as long as there were proteins trapped within the cell. &

Example Problem 3.3

Assume that the model cell in Figure 3.6 has an initial volume of 2 nl and contains 0.2 M protein. The cell is placed in a large volume of 0.2 M NaCl. In this model, neither Na þ nor Cl À can cross the plasma membrane and enter the cell. Is the 0.2 M NaCl solution hypotonic, isotonic, or hypertonic relative to the osmolarity inside the cell? Describe what happens to the cell as it achieves equilibrium in this new environment. What will be the final osmolarity of the cell? What will be its final volume?

Solution

The osmolarity inside the cell is 0.2 Osm. The osmolarity of the 0.2 M NaCl solution is 0.4 Osm (0:2 Osm Na þ þ 0:2 Osm Cl À ). Thus, the NaCl solution is hypertonic relative to the osmolarity inside the cell (osmolarity outside > osmolarity inside ). Since none of the particles (protein, Na þ , and Cl À ) can cross the membrane, water will move out of the cell until the osmolarity inside the cell is 0.4 Osm. This will be achieved when the volume inside the cell has been reduced from 2 nl to 1 nl.

C1 V1 ¼C2 V2

0:2 Osm

 2 nl ¼ V2 0:4 Osm

1 nl ¼ V2

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Real cells are much more complex than the simple model described here. In addition to achieving osmotic balance at equilibrium, real cells must also achieve electrical balance with regard to the ions that are present in the cytoplasm. The principle of electrical neutrality requires that the overall concentration of cations in a biological compartment (e.g., a cell) must equal the overall concentration of anions in that compartment. Consider another model cell (Fig. 3.7) with internal and external cation and anion concentrations similar to those of a typical mammalian cell. Is the cell at equilibrium if the plasma membrane is freely permeable to K þ and Cl À but

impermeable to Na þ and the internal anions? The total osmolarity inside the cell is 250 mOsm (12 mM Na þ , 125 mM K þ , 5 mM Cl À , 108 mM anions) while the total osmolarity outside the cell is also 250 mOsm (120 mM Na þ , 5 mM K þ , 125 mM Cl À ) so the cell is in osmotic balance (i.e., there will be no net movement of water across the plasma membrane). If the average charge per molecule of the anions inside the cell is considered to be À1:2, then the cell is also approximately in electrical equilibrium (12 þ 125 positive charges for Na þ and K þ ; 5 þ 1:2 Â 108 negative charges for ClÀ and the other anions). Real cells, however, cannot maintain this equilibrium without expending energy since real cells are slightly permeable to Na þ . In order to maintain equilibrium and keep Na þ from accumulating intracellularly, mammalian cells must actively pump Na þ out of the cell against its diffusion and electrical gradients. Since Na þ is pumped out through specialized protein channels at a rate equivalent to the rate at which it leaks in through other channels, it behaves osmotically as if it cannot cross the plasma membrane. Thus, mammalian cells exist in a steady state, rather than at equilibrium, since energy in the form of ATP must be used to prevent a net movement of ions across the plasma membrane.

Example Problem 3.4

Consider a simple model cell, such as the one in Figure 3.7, which has the following ion concentrations. Is the cell at equilibrium? Explain your answer.

Solution

Yes. The cell is both electrically and osmotically at equilibrium because the charges within the inside and outside compartments are equal and the osmolarity inside the cell equals the osmolarity outside of the cell.

Inside

Outside

Positive Negative Osmolarity

158 þ 20 ¼ 178 mM 52 þ 1:2 Â 104 ¼ 177 mM 158 þ 20 þ 52 þ 104 ¼ 334 mM

178 mM pos % 177 mMneg

4 þ 163 ¼ 167 mM 167 mM 4 þ 163 þ 167 ¼ 334 mM

167 mM pos ¼ 167 mMneg

334 mM inside ¼ 334 mMoutside

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One of the consequences of the distribution of charged particles in the intracellular and extracellular fluids is that an electrical potential exists across the plasma membrane. The value of this electrical potential depends on the intracellular and extracellular concentrations of ions that can cross the membrane and will be described more fully in Chapter 11.

In addition to controlling the cell’s volume, the plasma membrane also provides a route for moving large molecules and other materials into and out of the cell. Substances can be moved into the cell by means of endocytosis (Fig. 3.8a) and out of the cell by means of exocytosis (Fig. 3.8b). In endocytosis, material (e.g., a bacterium) outside of the cell is engulfed by a portion of the plasma membrane that encircles it to form a vesicle. The vesicle then pinches off from the plasma membrane and moves its contents to the inside of the cell. In exocytosis, material within the cell is surrounded by a membrane to form a vesicle. The vesicle then moves to the edge of the cell where its membrane fuses with the plasma membrane and its contents are released to the exterior of the cell.

3.2.2 Cytoplasm and Organelles

The cytoplasm contains fluid (cytosol) and organelles. Ions (such as Na þ , K þ , and Cl À ) and molecules (such as glucose) are distributed through the cytosol via diffusion. Membrane-bound organelles include the nucleus, rough and smooth endoplasmic reticulum, the Golgi apparatus, lysosomes, and mitochondria. Nonmembranous organelles include nucleoli, ribosomes, centrioles, microvilli, cilia, flagella, and the microtubules, intermediate filaments, and microfilaments of the cytoskeleton.

The nucleus (Fig. 3.4) consists of the nuclear envelope (a double membrane) and the nucleoplasm (a fluid that contains ions, enzymes, nucleotides, proteins, DNA, and small amounts of RNA). Within its DNA, the nucleus contains the instructions for life’s processes. Nuclear pores are protein channels that act as connections for ions and RNA, but not proteins or DNA, to leave the nucleus and enter the cytoplasm and for some proteins to enter the nucleoplasm. Most nuclei contain one or more nucleoli.

Each nucleolus contains DNA, RNA, and proteins and synthesizes the components of the ribosomes that cells use to make proteins.

The smooth and rough endoplasmic reticulum (ER), Golgi apparatus, and assorted vesicles (Figs. 3.4, 3.9a, and 3.9b) make up the cytomembrane system which delivers proteins and lipids for manufacturing membranes and accumulates and stores proteins and lipids for specific uses. The ER also acts as a storage site for calcium ions. The rough ER differs from the smooth ER in that it has ribosomes attached to its exterior surface. Ribosomes provide the platforms for synthesizing proteins. Those that are synthesized on the rough ER are passed into its interior where nonproteinaceous side chains are attached to them. These modified proteins move to the smooth ER where they are packaged in vesicles. The smooth ER also manufactures and packages lipids into vesicles and is responsible for releasing stored calcium ions. The vesicles leave the smooth ER and become attached to the Golgi apparatus where their contents are released, modified, and repackaged into new vesicles. Some of these vesicles, called lysosomes, contain digestive enzymes which are used to break down materials that move into the cells via endocytosis. Other vesicles contain proteins such as hormones and neurotransmitters that are secreted from the cells by means of exocytosis.

The mitochondria (Figs. 3.9c and 3.10) contain two membranes: an outer membrane that surrounds the organelle and an inner membrane that divides the organelle’s interior into two compartments. Approximately 95% of the ATP required by the cell is produced in the mitochondria in a series of oxygen-requiring reactions which produce carbon dioxide as a byproduct. Mitochondria are different from most other organelles in that they contain their own DNA. The majority of the mitochondria in sexually reproducing organisms, such as humans, come from the mother’s egg cell because the father’s sperm contributes little more than the DNA in a haploid (half) set of chromosomes to the developing offspring.

Microtubules, intermediate filaments, and microfilaments provide structural support and assist with movement. Microtubules are long, hollow, cylindrical structures that radiate from microtubule organizing centers and, during cell division, from centrosomes, a specialized region of the cytoplasm that is located near the nucleus

and contains two centrioles (Figs. 3.4 and 3.11a) oriented at right angles to each other. Microtubules consist of spiraling subunits of a protein called tubulin, whereas centrioles consist of nine triplet microtubules that radiate from their centers like the spokes of a wheel. Intermediate filaments are hollow and provide structure to the plasma membrane and nuclear envelope. They also aid in cell-to-cell junctions and in maintaining the spatial organization of organelles. Myofilaments are found in most cells and are composed of strings of protein molecules. Cell movement can occur when actin and myosin, protein subunits of myofilaments, interact. Microvilli (Fig. 3.11b) are extensions of the plasma membrane that contain microfilaments. They increase the surface area of a cell to facilitate absorption of extracellular materials.

Cilia (Fig. 3.11c) and flagella are parts of the cytoskeleton that have shafts composed of nine pairs of outer microtubules and two single microtubules in the center. Both types of shafts are anchored by a basal body which has the same structure as a centriole. Flagella function as whiplike tails that propel cells such as sperm. Cilia are generally shorter and more profuse than flagella and can be found on specialized cells such as those that line the respiratory tract. The beating of the cilia helps move mucustrapped bacteria and particles out of the lungs.

3.2.3 DNA and Gene Expression

DNA (Fig. 3.3) is found in the nucleus and mitochondria of eukaryotic cells. In organisms that reproduce sexually, the DNA in the nucleus contains information from both parents whereas that in the mitochondria comes from the organism’s mother. In the nucleus, the DNA is wrapped around protein spools, called nucleosomes, and is organized into pairs of chromosomes. Humans have 22 pairs of autosomal chromosomes and two sex chromosomes, XX for females and XY for males (Fig. 3.12). If the DNA from all 46 chromosomes in a human somatic cell (i.e., any cell

that does not become an egg or sperm cell) was stretched out end to end, it would be about 2 nm wide and 2 m long. Each chromosome contains thousands of individual genes that are the units of information about heritable traits. Each gene has a particular location in a specific chromosome and contains the code for producing one of the three forms of RNA (ribosomal RNA, messenger RNA, and transfer RNA). The Human Genome Project was begun in 1990 and had as its goal to first identify the location of at least 3000 specific human genes and then to determine the sequence of nucleotides (about 3 billion!) in a complete set of haploid human chromosomes (one chromosome from each of the 23 pairs). See Chapter 13 for more information about the Human Genome Project.

DNA replication occurs during cell division (Fig. 3.13). During this semiconservative process, enzymes unzip the double helix, deliver complementary bases to the nucleotides, and bind the delivered nucleotides into the developing complementary strands. Following replication, each strand of DNA is duplicated so that two double helices now exist, each consisting of one strand of the original DNA and one new strand. In this way, each daughter cell gets the same hereditary information that was contained in the original dividing cell. During replication, some enzymes check for accuracy while others repair pairing mistakes so that the error rate is reduced to approximately one per billion.

Since DNA remains in the nucleus where it is protected from the action of the cell’s enzymes and proteins are made on ribosomes outside of the nucleus, a method (transcription) exists for transferring information from the DNA to the cytoplasm. During transcription (Fig. 3.14), the sequence of nucleotides in a gene that codes for a protein is transferred to messenger RNA (mRNA) through complementary base pairing of the nucleotide sequence in the gene. For example, a DNA sequence of TACGCTCCGATA would become AUGCGAGGCUAU in the mRNA. The process is somewhat more complicated since the transcript produced directly from the DNA contains sequences of nucleotides, called introns, that are removed before the final mRNA is produced. The mRNA also has a tail, called a poly-A tail, of about 100–200 adenine nucleotides attached to one end. A cap with a nucleotide that has a methyl group and phosphate groups bonded to it is attached at the other end of the mRNA. Transcription differs from replication in that (1) only a certain stretch of DNA acts as

the template and not the whole strand, (2) different enzymes are used, and (3) only a single strand is produced.

After being transcribed, the mRNA moves out into the cytoplasm through the nuclear pores and binds to specific sites on the surface of the two subunits that make up a ribosome (Fig. 3.15). In addition to the ribosomes, the cytoplasm contains amino acids and another form of RNA, transfer RNA (tRNA). Each tRNA contains a triplet of bases, called an anticodon, and binds at an area away from the triplet to an amino acid that is specific for that particular anticodon. The mRNA that was produced from the gene in the nucleus also contains bases in sets of three. Each triplet in mRNA is called a codon. The four possibilities for nucleotides (A, U, C, G) in each of the three

places give rise to 64 (4 3 ) possible codons. These 64 codons make up the genetic code. Each codon codes for a specific amino acid, but some amino acids are specified by more than one codon (see Table 3.1). For example, AUG is the only mRNA codon for methionine (the amino acid that always signals the starting place for translation—the process by which the information from a gene is used to produce a protein) whereas UUA, UUG, CUU, CUC, CUA, and CUG are all codons for leucine. The anticodon on the tRNA that delivers the methionine to the ribosome is UAC, whereas tRNAs with anticodons of AAU, AAC, GAA, GAG, GAU, and GAC deliver leucine.

During translation, the mRNA binds to a ribosome and tRNA delivers amino acids to the growing polypeptide chain in accordance with the codons specified by the mRNA. Peptide bonds are formed between each newly delivered amino acid and the previously delivered one. When the amino acid is bound to the growing chain, it is released from the tRNA, and the tRNA moves off into the cytoplasm where it joins with another amino acid that is specified by its anticodon. This process continues until a stop codon (UAA, UAG, or UGA) is reached on the mRNA.

The protein is then released into the cytoplasm or into the rough ER for further modifications.

Example Problem 3.5

Consider a protein that contains the amino acids asparagine, phenylalanine, histidine, and serine in sequence. Which nucleotide sequences on DNA (assuming that there were no introns) would result in this series of amino acids? What would be the anticodons for the tRNAs that delivered these amino acids to the ribosomes during translation?

Solution

The genetic code (Table 3.1) provides the sequence for the mRNA codons that specify these amino acids. The mRNA codons can be used to determine the sequence in the original DNA and the anticodons of the tRNA since the mRNA bases must pair with the bases in both DNA and tRNA. Note that DNA contains thymine (T) but no uracil (U) and that both mRNA and tRNA contain U and not T. See Figs. 3.3 and 3.14 for examples of base pairing.

3.3 TISSUES

Groups of cells and surrounding substances that function together to perform one or more specialized activities are called tissues (Fig. 3.16). There are four primary types of tissue in the human body: epithelial, connective, muscle, and nervous. Epithelial tissues are either composed of cells arranged in sheets that are one or more layers thick or are organized into glands that are adapted for secretion. They are also characterized by having a free surface (e.g., the inside surface of the intestines or the outside of the skin) and a basilar membrane. Typical functions of epithelial tissue include absorption (lining of the small intestine), secretion (glands), transport (kidney

tubules), excretion (sweat glands), protection (skin, Fig. 3.16a), and sensory reception (taste buds). Connective tissues are the most abundant and widely distributed. Connective tissue proper can be loose (loosely woven fibers found around and between organs), irregularly dense (protective capsules around organs), and regularly dense (ligaments and tendons), whereas specialized connective tissue includes blood (Fig. 3.16b), bone, cartilage, and adipose tissue. Muscle tissue provides movement for the body through its specialized cells that can shorten in response to stimulation and then return to their uncontracted state. Figure 3.16c shows the three types of muscle tissue: skeletal (attached to bones), smooth (found in the walls of blood vessels), and cardiac (found only in the heart). Nervous tissue consists of neurons (Fig. 3.16d) that conduct electrical impulses and glial cells that protect, support, and nourish neurons.

3.4 MAJOR ORGAN SYSTEMS

CHAPTER 3

ANATOMY AND PHYSIOLOGY

Combinations of tissues that perform complex tasks are called organs, and organs that function together form organ systems. The human body has 11 major organ systems: integumentary, endocrine, lymphatic, digestive, urinary, reproductive, circulatory, respiratory, nervous, skeletal, and muscular. The integumentary system (skin, hair, nails, and various glands) provides protection for the body. The endocrine system (ductless glands such as the thyroid and adrenals) secretes hormones that regulate many chemical actions within cells. The lymphatic system (glands, lymph nodes, lymph, lymphatic vessels) returns excess fluid and protein to the blood and helps defend the body against infection and tissue damage. The digestive system (stomach, intestines, and other structures) ingests food and water, breaks food down into small molecules that can be absorbed and used by cells, and removes solid wastes. The urinary system (kidneys, ureters, urinary bladder, and urethra) maintains the fluid volume of the body, eliminates metabolic wastes, and helps regulate blood pressure and acid–base and water–salt balances. The reproductive system (ovaries, testes, reproductive cells, and accessory glands and ducts) produces eggs or sperm and provides a mechanism for the production and nourishment of offspring. The circulatory system (heart, blood, and blood vessels) serves as a distribution system for the body. The respiratory system (airways and lungs) delivers oxygen to the blood from the air and carries away carbon dioxide. The nervous system (brain, spinal cord, peripheral nerves, and sensory organs) regulates most of the body’s activities by detecting and responding to internal and external stimuli. The skeletal system (bones and cartilage) provides protection and support as well as sites for muscle attachments, the production of blood cells, and calcium and phosphorus storage. The muscular system (skeletal muscle) moves the body and its internal parts, maintains posture, and produces heat. Although biomedical engineers have made major contributions to understanding, maintaining, and/or replacing components in each of the eleven major organ systems, only the last five in the preceding list will be examined in greater detail.

3.4.1 Circulatory System

The circulatory system (Fig. 3.17) delivers nutrients and hormones throughout the body, removes waste products from tissues, and provides a mechanism for regulating temperature and removing the heat generated by the metabolic activities of the body’s internal organs. Every living cell in the body is no more than 10–100 mm from a capillary (small blood vessels with walls only one cell thick that are 8 mm in diameter, approximately the same size as a red blood cell). This close proximity allows oxygen, carbon dioxide, and most other small solutes to diffuse from the cells into the capillary or from the capillary into the cells with the direction of diffusion determined by concentration and partial pressure gradients.

The heart (Fig. 3.18), the pumping station that moves blood through the blood vessels, consists of two pumps—the right side and the left side. Each side has one

chamber (the atrium) that receives blood and another chamber (the ventricle) that pumps the blood away from the heart. The right side moves deoxygenated blood that is loaded with carbon dioxide from the body to the lungs, and the left side receives oxygenated blood that has had most of its carbon dioxide removed from the lungs and pumps it to the body. The vessels that lead to and from the lungs make up the pulmonary circulation, and those that lead to and from the rest of the tissues in the body make up the systemic circulation (Fig. 3.19). Blood vessels that carry blood away from the heart are called arteries and those that carry blood toward the heart are called veins. The pulmonary artery is the only artery that carries deoxygenated blood, and the pulmonary vein is the only vein that carries oxygenated blood. The average adult has about 5 L of blood with 80–90% in the systemic circulation at any one time; 75% of the blood is in the systemic circulation in the veins, 20% in the arteries, and 5% in the capillaries. Cardiac output is the product of the heart rate and the volume of blood pumped from the heart with each beat (i.e., the stroke volume). Each time the heart beats, about 80 ml of blood leave the heart. Thus, it takes about 60 beats for the average red blood cell to make one complete cycle of the body.

In the normal heart, the cardiac cycle, which refers to the repeating pattern of contraction (systole) and relaxation (diastole) of the chambers of the heart, begins with a self-generating electrical pulse in the pacemaker cells of the sinoatrial node

(Fig. 3.20). This rapid electrical change in the cells is the result of the movement of ions across their plasma membranes. The permeability of the plasma membrane to Na þ changes dramatically and allows these ions to rush into the cell. This change in the electrical potential across the plasma membrane from one in which the interior of the cell is more negative than the extracellular fluid (approximately À90 mV) to one in which the interior of the cell is more positive than the extracellular fluid (approximately 20 mV) is called depolarization. After a very short period of time (<0.3 s), changes in the membrane and activation of the sodium–potassium pumps result in repolarization, the restoration of the original ionic balance in the cells. The entire electrical event in which the polarity of the potential across the plasma membrane rapidly reverses and then becomes reestablished is called an action potential. The cells in the sinoatrial node depolarize on the average of every 0.83 s in a typical adult at rest. This gives a resting heart rate of 72 beats per minute with about 8 5 of each beat spent in diastole and 8 3 in systole.

Cardiac cells are linked and tightly coupled so that action potentials spread from one cell to the next. Activation wavefronts move across the atria at a rate of about 1 m/s. When cardiac cells depolarize, they also contract. The contraction process in the atria (atrial systole) moves blood from the right atrium to the right ventricle and from the left atrium to the left ventricle (Fig. 3.21). The activation wavefront then moves to the atrioventricular (AV) node where it slows to a rate of about 0.05 m/s to allow time for the ventricles to completely fill with the blood from the atria. After leaving the AV node, the activation wavefront moves to specialized conduction tissue, the Purkinje system, which spreads the wavefront very rapidly (at about 3 m/s) to many cells in both venricles. The activation wavefront spreads through ventricular tissue at about

0.5 m/s. This results in the simultaneous contraction of both ventricles (ventricular systole) so that blood is forced from the heart into the pulmonary artery from the right ventricle and into the aorta from the left ventricle.

The electrocardiogram (ECG; Fig. 3.22) is an electrical measure of the sum of these ionic changes within the heart. The P wave represents the depolarization of the atria and the QRS represents the depolarization of the ventricles. Ventricular repolarization shows up as the T wave and atrial repolarization is masked by ventricular depolarization. Changes in the amplitude and duration of the different parts of the

ECG provide diagnostic information for physicians. Many biomedical engineers have worked on methods for recording and analyzing ECGs.

Example Problem 3.6

What would be the heart rate given by an ECG in which 10 R-waves occurred in 6.4 s?

Solution

A sequence of 10 R-waves represents 9 R–R intervals (see Fig. 3.22) or beats of the heart.

9 beats

6:4 s

60 s

1 min

¼ 84 bpm

&

Example Problem 3.7

What would be the cardiac output of the heart in Example Problem 3.6 if the stroke volume were 75 ml?

Solution

The cardiac output (given in liters per minute) is the product of the heart rate and the stroke volume.

beats ml ml liters  CO ¼ 84 75 ¼ 6300 ¼ 6:3 min beat min min

&

During atrial and ventricular systole, special one-way valves (Fig. 3.23a) keep the blood moving in the correct direction. When the atria contract, the atrioventricular valves (tricuspid and mitral) open to allow blood to pass into the ventricles. During ventricular systole, the semilunar valves (aortic and pulmonary) open to allow blood to leave the heart while the atrioventricular valves close and prevent blood from flowing backwards from the ventricles to the atria. The aortic and pulmonary valves prevent blood from flowing back from the pulmonary artery and aorta into the right and left ventricles, respectively. If a valve becomes calcified or diseased or is not properly formed during embryonic development, it can be replaced by an artificial valve (Fig. 3.23b), a device that has been developed by cooperative work between biomedical engineers and physicians.

Blood pressure can be measured directly or indirectly (noninvasively). Direct blood pressure measurements are made by introducing a catheter or needle that is coupled to a pressure transducer into a vein or artery. Indirect methods include sphygmomanometry, in which a cuff is used to apply sufficient pressure to an artery, usually in the arm, to prevent the flow of blood through the artery, and a stethoscope is used to listen to the change in sounds as the cuff is slowly deflated. The first Korotkoff sounds occur when the systolic pressure, the highest pressure reached when the ventricles contract and eject blood, first exceeds the pressure in the cuff so that blood once again flows through the artery beneath the stethoscope. The Korotkoff sounds become muffled and disappear when the pressure in the cuff drops below the diastolic

pressure, the minimum pressure that occurs at the end of ventricular relaxation. Another indirect measurement is the oscillometric method, which uses a microprocessor to periodically inflate and slowly deflate a cuff. When blood breaks through the occlusion caused by the cuff, the walls of the artery begin to vibrate slightly due to the turbulent nature of the blood flow. The onset of these oscillations in pressure correlates with the systolic pressure. The oscillations decrease in amplitude over time with the diastolic pressure event corresponding to the point at which the rate of amplitude decrease suddenly changes slope. A third indirect measurement, the ultrasonic method, depends on the Doppler shift of sound waves that hit red blood cells that are flowing with the blood.

Blood in the systemic circulation leaves the heart through the aorta with an average internalpressureofabout100 mmHg(maximumsystolicpressureofabout120 mmHg with a diastolic pressure of about 80 mm Hg in a normal adult) and moves to medium-sized arteries (Fig. 3.17a) and arterioles. Arterioles lead to capillaries (average internal pressure of about 30 mm Hg), which are followed by venules. Venules lead to medium-sized veins, then to large veins, and finally to the venae cavae (average internal pressure of about 10 mm Hg) which return blood to the heart at the right atrium. Blood in the pulmonary circulation (Fig. 3.19) leaves the pulmonary artery and moves to arterioles and then the capillary beds within the lungs. It returns to the heart through the left atrium. Blood flow is highest in the large arteries and veins (3040 cm/s in the aorta; 5 cm/s in the venae cavae) and slowest in the capillary beds (1 mm/s) where the exchange of nutrients, metabolic wastes, gases, and hormones takes place. Pressures in the pulmonary circulation are lower (25 mm Hg/10 mm Hg) than in the systemic circulation due to the decreased pumping power of the smaller right ventricle as compared to the left and to the lower resistance of blood vessels in the lungs.

Example Problem 3.8

What would be the pulse pressure and the mean arterial pressure for a person with a blood pressure reading of 118 mm Hg/79 mm Hg?

Solution

The pulse pressure is defined as the difference between the systolic (118 mm Hg) and disastolic (79 mm Hg) pressures, which would be 39 mm Hg in this case.

Mean arterial pressure is the average blood pressure in the arteries and is estimated as the diastolic pressure plus one-third of the pulse pressure, which would be 92 mm Hg in this example. &

3.4.2 Respiratory System

The respiratory system (Fig. 3.24a) moves air to and from the gas exchange surfaces in the body where diffusion can occur between air and the circulating blood. It includes the conduction zone and the respiratory zone. In the conduction zone (mouth, nose, sinuses, pharynx, trachea, bronchi, and bronchioles), the air that enters the body is warmed, humidified, filtered, and cleaned. Mucus is secreted by cells in the conduction zone and traps small particles (> 6 mm) before they can reach the respiratory zone. Epithelial cells that line the trachea and bronchi have cilia that beat in a coordinated fashion to move mucus toward the pharynx where it can be swallowed or expectorated. The respiratory zone, consisting of respiratory bronchioles with outpouchings of alveoli and terminal clusters of alveolar sacs, is where gas exchange

between air and blood occurs (Fig. 3.24b). The respiratory zone comprises most of the mass of the lungs.

Certain physical properties—compliance, elasticity, and surface tension—are characteristic of lungs. Compliance refers to the ease with which lungs can expand under pressure. A normal lung is about 100 times more distensible than a toy balloon. Elasticity refers to the ease with which the lungs and other thoracic structures return to their initial sizes after being distended. This aids in pushing air out of the lungs during expiration. Surface tension is exerted by the thin film of fluid in the alveoli and acts to resist distention. It creates a force that is directed inward and creates pressure in the alveolus which is directly proportional to the surface tension and inversely proportional to the radius of the alveolus (Law of Laplace). Thus, the pressure inside an alveolus with a small radius would be higher than the pressure inside an adjacent alveolus with a larger radius and would result in air flowing from the smaller alveolus into the larger one. This could cause the smaller alveolus to collapse. This does not happen in normal lungs because the fluid inside the alveoli contains a phospholipid that acts as a surfactant. The surfactant lowers the surface tension in the alveoli and allows them to get smaller during expiration without collapsing. Premature babies often suffer from respiratory distress syndrome because their lungs lack sufficient surfactant to prevent their alveoli from collapsing. These babies can be kept alive with mechanical ventilators or surfactant sprays until their lungs mature enough to produce surfactant.

Breathing, or ventilation, is the mechanical process by which air is moved into (inspiration) and out of (expiration) the lungs. A normal adult takes about 15 to 20 breaths per minute. During inspiration, the inspiratory muscles contract and enlarge the thoracic cavity, the portion of the body where the lungs are located. This causes the alveoli to enlarge and the alveolar gas to expand. As the alveolar gas expands, the partial pressure within the respiratory system drops below atmospheric pressure by about 3 mm Hg so that air easily flows in (Boyle’s Law). During expiration, the inspiratory muscles relax and return the thoracic cavity to its original volume. Since the volume of the gas inside the respiratory system has decreased, its pressure increases to a value that is about 3 mm Hg above atmospheric pressure. Air now moves out of the lungs and into the atmosphere.

Lung mechanics refers to the study of the mechanical properties of the lung and chest wall, whereas lung statics refers to the mechanical properties of a lung in which the volume is held constant over time. Understanding lung mechanics requires knowledge about the volumes within the lungs. Lung capacities contain two or more volumes. The tidal volume (TV) is the amount of air that moves in and out of the lungs during normal breathing (Fig. 3.25). The total lung capacity (TLC) is the amount of gas contained within the lungs at the end of a maximum inspiration. The vital capacity (VC) is the maximum amount of air that can be exhaled from the lungs after inspiration to TLC. The residual volume (RV) is the amount of gas remaining in the lungs after maximum exhalation. The amount of gas that can be inhaled after inhaling during tidal breathing is called the inspiratory reserve volume (IRV). The amount of gas that can be expelled by a maximal exhalation after exhaling during tidal breathing is called the expiratory reserve volume (ERV). The inspiratory capacity (IC) is the

maximum amount of gas that can be inspired after a normal exhalation during tidal breathing, and the functional residual capacity (FRC) is the amount of gas that remains in the lungs at this time.

Allofthevolumesandcapacitiesexcept thosethatinclude theresidual volume canbe measured with a spirometer. The classic spirometer is an air-filled container that is constructed from two drums of different sizes. One drum contains water and the other air-filled drum is inverted over an air-filled tube and floats in the water. The tube is connectedtoamouthpieceusedbythepatient.Whenthepatientinhales,thelevelofthe floatingdrumdrops.Whenthepatientexhales,thelevelofthefloatingdrumrises.These changes in floating drum position can be recorded and used to measure lung volumes.

Example Problem 3.9

The total lung capacity of a patient is 5.9 liters. If the patient’s inspiratory capacity was found to be 3.3 liters using spirometry, what would be the patient’s functional residual capacity? What would you need to measure to determine the patient’s residual volume?

Solution

From Figure 3.25, total lung capacity (TLC) is equal to the sum of inspiratory capacity (IC) and functional residual capacity (FRC).

TLC ¼ IC þ FRC

5:9 liters ¼ 3:3 liters þ FRC

FRC ¼ 2:6 liters

TLC, which cannot be determined by means of spirometry, and vital capacity (VC), which can be measured using spirometry, must be known to determine residual volume (RV) since

TLC À VC ¼ RV

&

Because spirograms record changes in volume over time, flow rates can be determined for different maneuvers. For example, if a patient exhales as forcefully as possible to residual volume following inspiration to TLC, then the forced expiratory volume (FEV 1:0 ) is the total volume exhaled at the end of 1 s. The FEV 1:0 is normally about 80% of the vital capacity. Restrictive diseases, in which inspiration is limited by reduced compliance of the lung or chest wall or by weakness of the inspiratory muscles, result in reduced values for FEV 1:0 and vital capacity but their ratio remains about the same. In obstructive diseases, such as asthma, the FEV 1:0 is reduced much more than the vital capacity. In these diseases, the TLC is abnormally large but expiration ends prematurely. Another useful measurement is the forced expiratory flow rate (FEF25À À 75 % ), which is the average flow rate measured over the middle half of the expiration (i.e., from 25 to 75% of the vital capacity). Flow-volume loops provide another method for analyzing lung function by relating the rate of inspiration and expiration to the volume of air that is moved during each process.

The TLC can be measured using the gas dilution technique. In this method, patients inspire to TLC from a gas mixture containing a known amount of an inert tracer gas such as helium, and hold their breaths for 10 s. During this time, the inert gas becomes evenly distributed throughout the lungs and airways. Due to conservation of mass, the product of initial tracer gas concentration (which is known) times the amount inhaled (which is measured) equals the product of final tracer gas concentration (which is measured during expiration) times the TLC. Body plethysmography, which provides the most accurate method for measuring lung volumes, uses an airtight chamber in which the patient sits and breathes through a mouthpiece. This method makes use of Boyle’s Law, which states that the product of pressure and volume for gas in a chamber is constant under isothermal conditions. Changes in lung volume and pressure at the mouth when the patient pants against a closed shutter can be used to calculate the functional residual capacity. Since the expiratory reserve volume can be measured, the residual volume can be calculated by subtracting it from the functional residual capacity.

Example Problem 3.10

A patient is allowed to breathe a mixture from a 2-liter reservoir that contains 10% of an inert gas (i.e., one that will not cross from the lungs into the circulatory system). At the end of a period that is sufficient for the contents of the reservoir and the lungs to equilibrate, the concentration of the inert gas is measured and is found to be 2.7%. What is the patient’s total lung capacity?

Solution

The total amount of inert gas is the same at the beginning and end of the measurement, but its concentration has changed from 10% (C 1 ) to 2.7% (C 2 ). At the beginning, it is confined to a 2-liter reservoir (V 1 ). At the end, it is in both the reservoir and the patient’s lungs (V 2 ¼ V 1 þ TLC).

C1 V1 ¼C2 V2

(0:1) (2 liters) ¼ (0:027) (2 liters þ TLC)

0:2 liters À 0:054 liters ¼ 0:027 TLC

5:4 liters ¼ TLC

&

External respiration occurs in the lungs when gases are exchanged between the blood and the alveoli (Fig. 3.26). Each adult lung contains about 3:5 Â 10 8 alveoli, which results in a large surface area (60 – 70 m 2 ) for gas exchange to occur. Each alveolus is only one cell layer thick, making the air–blood barrier only two cells thick (an alveolar cell and a capillary endothelial cell) which is about 2 mm. The partial pressure of oxygen in the alveoli is higher than the partial pressure of oxygen in the blood so oxygen moves from the alveoli into the blood. The partial pressure of carbon dioxide in the alveoli is lower than the partial pressure of carbon dioxide in the blood so carbon dioxide moves from the blood into the alveoli. During internal respiration, carbon dioxide and oxygen move between the blood and the extracellular fluid surrounding the body’s cells. The direction and rate of movement of a gas depend

on the partial pressures of the gas in the blood and the extracellular fluid, the surface area available for diffusion, the thickness of the membrane that the gas must pass through, and a diffusion constant that is related to the solubility and molecular weight of the gas (Fick’s Law).

Mechanical ventilators can be used to deliver air or oxygen to a patient. They can be electrically or pneumatically powered and can be controlled by microprocessors. Negative pressure ventilators such as iron lungs surround the thoracic cavity and force air into the lungs by creating a negative pressure around the chest. This type of ventilator greatly limits access to the patient. Positive pressure ventilators apply high-pressure gas at the entrance to the patient’s lungs so that air or oxygen flows down a pressure gradient and into the patient. These ventilators can be operated in control mode to breathe for the patient at all times or in assist mode to help with ventilation when the patient initiates the breathing cycle. This type of ventilation changes the pressure within the thoracic cavity to positive during inspiration, which affects venous return to the heart and cardiac output (the amount of blood the heart moves with each beat). High frequency jet ventilators deliver very rapid (60–900 breaths per minute) low-volume bursts of air to the lungs. Oxygen and carbon dioxide are exchanged by molecular diffusion rather than by the mass movement of air. This method causes less interference with cardiac output than does positive pressure ventilation. Extracorporeal membrane oxygenation (ECMO) uses the technology that was developed for cardiopulmonary bypass machines. Blood is removed from the patient and passed through an artificial lung where oxygen and carbon dioxide are exchanged. It is warmed to body temperature before being returned to the patient. This technique allows the patient’s lungs to rest and heal themselves and has been used successfully on some cold-water drowning victims and on infants with reversible pulmonary disease.

3.4.3 Nervous System

The nervous system, which is responsible for the integration and control of all the body’s functions, has two major divisions: the central nervous system and the peripheral nervous system (Fig. 3.27). The former consists of all nervous tissue enclosed by bone (e.g., the brain and spinal cord), whereas the latter consists of all nervous tissue not enclosed by bone, which enables the body to detect and respond to both internal and external stimuli. The peripheral nervous system consists of the 12 pairs of cranial and 31 pairs of spinal nerves with afferent (sensory) and efferent (motor) neurons.

The nervous system has also been divided into the somatic and autonomic nervous systems. Each of these systems consists of components from both the central and peripheral nervous systems. For example, the somatic peripheral nervous system consists of the sensory neurons, which convey information from receptors for pain, temperature, and mechanical stimuli in the skin, muscles, and joints to the central nervous system, and the motor neurons, which return impulses from the central nervous system to these same areas of the body. The autonomic nervous system is concerned with the involuntary regulation of smooth muscle, cardiac muscle, and glands and consists of the sympathetic and parasympathetic divisions.

The sympathetic division causes blood vessels in the viscera and skin to constrict, vessels in the skeletal muscles to dilate, and heart rate to increase, whereas the parasympathetic division has the opposite effect on the vessels in the viscera and skin, provides no innervation to the skeletal muscles, and causes heart rate to decrease. Thus, the sympathetic division prepares the body for ‘‘fight or flight’’ and the parasympathetic division returns the body to normal operating conditions.

Specialized cells that conduct electrical impulses (neurons) or protect, support, and nourish neurons (glial cells) make up the different parts of the nervous system. The cell body of the neuron (Fig. 3.16d) gives rise to and nourishes a single axon and multiple, branching dendrites. The dendrites are the main receptor portion of the neuron although the cell body can also receive inputs from other neurons. Dendrites usually receive signals from thousands of contact points (synapses) with other neurons. The axon extends a few millimeters (in the brain) to a meter (from the spinal cord to the foot) and carries nerve signals to other nerve cells in the brain or spinal cord or to glands and muscles in the periphery of the body. Some axons are surrounded by sheaths of myelin that are formed by specialized, nonneural cells called Schwann cells. Each axon has many branches, called presynaptic terminals, at its end. These knoblike protrusions contain synaptic vesicles that hold neurotransmitters. When the neuron is stimulated by receiving a signal at its dendrites, the permeability of the cell’s plasma membrane to sodium increases, as occurs in cardiac cells, and an

action potential moves from the dendrite to the cell body and then on to the axon. Gaps, called nodes of Ranvier, in the myelin sheaths of some axons allow the action potential to move more rapidly by essentially jumping from one node to the next. The vesicles in the presynaptic terminals release their neurotransmitter into the space between the axon and an adjacent neuron, muscle cell, or gland. The neurotransmitter diffuses across the synapse and causes a response (Fig. 3.28).

Neurons interconnect in several types of circuits. In a divergent circuit, each branch in the axon of the presynaptic neuron connects with the dendrite of a different postsynaptic neuron. In a convergent circuit, axons from several presynaptic neurons meet at the dendrite(s) of a single postsynaptic neuron. In a simple feedback circuit, the axon of a neuron connects with the dendrite of an interneuron that connects back with the dendrites of the first neuron. A two-neuron circuit is one in which a sensory neuron synapses directly with a motor neuron, whereas a three-neuron circuit consists of a sensory neuron, an interneuron in the spinal cord, and a motor neuron. Both of these circuits can be found in reflex arcs (Fig. 3.29). The reflex arc is a special type of neural circuit that begins with a sensory neuron at a receptor (e.g., a pain receptor in the fingertip) and ends with a motor neuron at an effector (e.g., a skeletal muscle). Withdrawal reflexes are elicited primarily by stimuli for pain and heat great enough to be painful and are also known as protective or escape reflexes. They allow the body to respond quickly to dangerous situations without taking additional time to send signals to and from the brain and to process the information.

The brain is a large soft mass of nervous tissue and has three major parts: (1) cerebrum, (2) diencephalon, and (3) brain stem and cerebellum. The cerebrum (Fig. 3.30), which is divided into two hemispheres, is the largest and most obvious portion of the brain and consists of many convoluted ridges (gyri), narrow grooves

(sulci), and deep fissures which result in a total surface area of about 2:25 m 2 . The outer layer of the cerebrum, the cerebral cortex, is composed of gray matter (neurons with unmyelinated axons) that is 2–4 mm thick and contains over 50 billion neurons and 250 billion glial cells called neuroglia. The thicker inner layer is the white matter that consists of interconnecting groups of myelinated axons that project from the cortex to other cortical areas or from the thalamus (part of the diencephalon) to the cortex. The connection between the two cerebral hemispheres is called the corpus callosum (Fig. 3.30b). The left side of the cortex controls motor and sensory functions from the right side of the body, whereas the right side controls the left side of the body. Association areas that interpret incoming data or coordinate a motor response are connected to the sensory and motor regions of the cortex.

Fissures divide each cerebral hemisphere into a series of lobes that have different functions. The functions of the frontal lobes include initiating voluntary movement of the skeletal muscles, analyzing sensory experiences, providing responses relating to personality, and mediating responses related to memory, emotions, reasoning, judgment, planning, and speaking. The parietal lobes respond to stimuli from cutaneous (skin) and muscle receptors throughout the body. The temporal lobes interpret some sensory experiences, store memories of auditory and visual experiences, and contain auditory centers that receive sensory neurons from the cochlea of the ear. The occipital lobes integrate eye movements by directing and focusing the eye and are responsible for correlating visual images with previous visual experiences and other sensory stimuli. The insula is a deep portion of the cerebrum that lies under the parietal, frontal, and temporal lobes. Little is known about its function, but it seems to be associated with gastrointestinal and other visceral activities.

The diencephalon is the deep part of the brain that connects the midbrain of the brain stem with the cerebral hemispheres. Its main parts are the thalamus, hypothalamus, and epithalamus (Fig. 3.30b). The thalamus is involved with sensory and motor systems, general neural background activity, and the expression of emotion and

uniquely human behaviors. Due to its two-way communication with areas of the cortex, it is linked with thought, creativity, interpretation and understanding of spoken and written words, and identification of objects sensed by touch. The hypothalamus is involved with integration within the autonomic nervous system, temperature regulation, water and electrolyte balance, sleep–wake patterns, food intake, behavioral responses associated with emotion, endocrine control, and sexual responses. The epithalamus contains the pineal body that is thought to have a neuroendocrine function.

The brain stem connects the brain with the spinal cord and automatically controls vital functions such as breathing. Its principal regions include the midbrain, pons, and medulla oblongota (Fig. 3.30b). The midbrain connects the pons and cerebellum with the cerebrum and is located at the upper end of the brain stem. It is involved with visual reflexes, the movement of eyes, focusing of the lenses, and the dilation of the pupils. The pons is a rounded bulge between the midbrain and medulla oblongata which functions with the medulla oblongata to control respiratory functions, acts as a relay station from the medulla oblongata to higher structures in the brain, and is the site of emergence of cranial nerve V. The medulla oblongata is the lowermost portion of the brain stem and connects the pons to the spinal cord. It contains vital centers that regulate heart rate, respiratory rate, constriction and dilation of blood vessels, blood pressure, swallowing, vomiting, sneezing, and coughing. The cerebellum is located behind the pons and is the second largest part of the brain. It processes sensory information that is used by the motor systems and is involved with coordinating skeletal muscle contractions and impulses for voluntary muscular movement that originate in the cerebral cortex. The cerebellum is a processing center that is involved with coordination of balance, body positions, and the precision and timing of movements.

3.4.4 Skeletal System

The average adult skeleton contains 206 bones, but the actual number varies from person to person and decreases with age as some bones become fused. Like the body, the skeletal system is divided into two parts: the axial skeleton and the appendicular skeleton (Fig. 3.31). The axial skeleton contains 80 bones (skull, hyoid bone, vertebral column, and thoracic cage), whereas the appendicular skeleton contains 126 (pectoral and pelvic girdles and upper and lower extremities). The skeletal system protects and supports the body, helps with movement, produces blood cells, and stores important minerals. It is made up of strong, rigid bones that are composed of specialized connective tissue, bear weight, and form the major supporting elements of the body. Some support also comes from cartilage which is a smooth, firm, resilient, nonvascular type of connective tissue. Since the bones of the skeleton are hard, they protect the organs, such as the brain and abdominal organs, that they surround.

There are 8 cranial bones that support, surround, and protect the brain. Fourteen facial bones form the face and serve as attachments for the facial muscles that primarily move skin rather than bone. The facial bones, except for the lower jaw (mandible), are joined with each other and with the cranial bones. There are 6 auditory ossicles, 3 in each ear, that transmit sound waves from the external environment to the inner ear. The hyoid bone, which is near the skull but not part

of it, is a small U-shaped bone that is located in the neck just below the lower jaw. It is attached to the skull and larynx (voice box) by muscles and ligaments and serves as the attachment for several important neck and tongue muscles.

The vertebral column starts out with approximately 34 bones, but only 26 independent ones are left in the average human adult. There are 7 cervical bones, including the axis which acts as a pivot around which the head rotates, and the atlas which sits on the axis and supports the ‘‘globe’’ of the head. These are followed by 5 cervical, 12 thoracic, and 5 lumbar vertebrae and then the sacrum and the coccyx. The last two consist of 5 fused vertebrae. The vertebral column supports the weight of and allows movement of the head and trunk, protects the spinal cord, and provides places for the spinal nerves to exit from the spinal cord. There are 4 major curves (cervical, thoracic, lumbar, and sacral/coccygeal) in the adult vertebral column which allow it to flex and absorb shock. Although movement between any 2 adjacent vertebrae is generally quite limited, the total amount of movement provided by the vertebral column can be extensive. The thoracic cage consists of 12 thoracic vertebrae (which are counted as part of the vertebral column), 12 pairs of ribs and their associated cartilage, and the sternum (breastbone). It protects vital organs and prevents the collapse of the thorax during ventilation.

Bones are classified as long, short, flat, or irregular according to their shape. Long bones, such as the femur and humerus, are longer than they are wide. Short bones, such as those found in the ankle and wrist, are as broad as they are long. Flat bones, such as the sternum and the bones of the skull, have a relatively thin and flattened shape. Irregular bones do not fit into the other categories and include the bones of the vertebral column and the pelvis.

Bones make up about 18% of the mass of the body and have a density of 1:9 g=cm3 . There are two types of bone: spongy and compact (cortical). Spongy bone forms the ends (epiphyses) of the long bones and the interior of other bones and is quite porous. Compact bone forms the shaft (diaphysis) and outer covering of bones and has a tensile strength of 120 N=mm2 , compressive strength of 170 N=mm2 , and Young’s modulus of 1:8 Â 104 N=mm2 . The medullary cavity, a hollow space inside the diaphysis, is filled with fatty, yellow marrow or red marrow that contains bloodforming cells.

Bone is a living organ that is constantly being remodeled. Old bone is removed by special cells called osteoclasts, and new bone is deposited by osteoblasts. Bone remodeling occurs during bone growth and to regulate calcium availability. The average skeleton is totally remodeled about three times during a person’s lifetime. Osteoporosis is a disorder in which old bone is broken down faster than new bone is produced so that the resulting bones are weak and brittle.

The bones of the skeletal system are attached to each other at fibrous, cartilaginous, or synovial joints (Fig. 3.32). The articulating bones of fibrous joints are bound tightly together by fibrous connective tissue. These joints can be rigid and relatively immovable to slightly movable. This type of joint includes the suture joints in the skull. Cartilage holds together the bones in cartilaginous joints. These joints allow limited motion in response to twisting or compression and include the joints of the vertebral system and the joints that attach the ribs to the vertebral column and to the sternum.

Synovial joints, such as the knee, are the most complex and varied and have fluid-filled joint cavities, cartilage that covers the articulating bones, and ligaments that help hold the joints together.

Synovial joints are classified into six types based on their structure and the type of motion they permit. Gliding joints (Fig. 3.33) are the simplest type of synovial joint, allow back-and-forth or side-to-side movement, and include the intercarpal articulations in the wrist. Hinge joints such as the elbow permit bending in only one plane and are the most common type of synovial joint. The atlas and axis provide an example of a pivot joint that permits rotation. In condyloid articulations, an oval, convex surface of one bone fits into a concave depression on another bone. Condyloid joints, which include the metacarpophalangeal joints (knuckles) of the fingers, permit flexion–extension and rotation and are considered to bebiaxial because rotation islimitedto two axes of movement. The saddle joint, represented by the joint at the base of the thumb, is a modifiedcondyloidjointthatpermitsmovement inseveraldirections(multiaxial). Balland-socket joints allow motion in many directions around a fixed center. In these joints, the ball-shaped head of one bone fits into a cuplike concavity of another bone. This multiaxialjointisthemostfreelymovableofallandincludestheshoulderandhipjoints. Biomedical engineers have helped develop artificial joints that are routinely used as replacements in diseased or injured hips, shoulders, and knees (Fig. 3.34).

3.4.5 Muscular System

The muscular system (Fig. 3.35) is composed of 600–700 skeletal muscles, depending on whether certain muscles are counted as separate or as pairs, and makes up 40% of the body’s mass. The axial musculature makes up about 60% of the skeletal muscles in the body and arises from the axial skeleton (Fig. 3.31). It positions the head and spinal column and moves the rib cage during breathing. The appendicular musculature moves or stabilizes components of the appendicular skeleton.

The skeletal muscles in the muscular system maintain posture, generate heat to maintain the body’s temperature, and provide the driving force that is used to move the bones and joints of the body and the skin of the face. Muscles that play a major

role in accomplishing a movement are called prime movers, or agonists. Muscles that act in opposition to a prime mover are called antagonists, whereas muscles that assist a prime mover in producing a movement are called synergists. The continual contraction of some skeletal muscles helps maintain the body’s posture. If all of these muscles relax, which happens when a person faints, the person collapses.

A system of levers, which consist of rigid lever arms that pivot around fixed points, is used to move skeletal muscle (Fig. 3.36). Two forces act on every lever: the weight to be moved (i.e., the resistance to be overcome) and the pull or effort applied (i.e., the applied force). Bones act as lever arms and joints provide a fulcrum. The resistance to be overcome is the weight of the body part that is moved and the applied force is generated by the contraction of a muscle or muscles at the insertion, the point of attachment of a muscle to the bone it moves. An example of a first-class lever, one in which the fulcrum is between the force and the weight, is the movement of the facial portion of the head when the face is tilted upwards. The fulcrum is formed by the joint between the atlas and the occipital bone of the skull and the vertebral muscles inserted at the back of the head generate the applied force that moves the weight, the facial portion of the head. A second-class lever is one in which the weight is between the force and the fulcrum. This can be found in the body when a person stands on ‘‘tip toe.’’ The ball of the foot is the fulcrum and the applied force is generated by the calf muscles on the back of the leg. The weight that is moved is that of the whole body. A third-class lever is one in which the force is between the weight and the fulcrum. When a person has a bent elbow and holds a ball in front of the body, the applied force is generated by the contraction of the biceps brachii muscle. The weight to be moved

includes the ball and the weight of the forearm and hand, and the elbow acts as the fulcrum.

The three types of muscle tissue—cardiac, skeletal, and smooth—share four important characteristics: (1) contractility, the ability to shorten; (2) excitability, the capacity to receive and respond to a stimulus; (3) extensibility, the ability to be stretched; (4) and elasticity, the ability to return to the original shape after being stretched or contracted. Cardiac muscle tissue is found only in the heart, whereas smooth muscle tissue is found within almost every other organ where it forms sheets, bundles, or sheaths around other tissues. Skeletal muscles are composed of skeletal muscle tissue, connective tissue, blood vessels, and nervous tissue.

Each skeletal muscle is surrounded by a layer of connective tissue (collagen fibers) that separates the muscle from surrounding tissues and organs. These fibers come together at the end of the muscle to form tendons which connect the skeletal muscle to bone, to skin (face), or to the tendons of other muscles (hand). Other connective tissue fibers divide the skeletal muscles into compartments called fascicles that contain bundles of muscle fibers. Within each fascicle, additional connective tissue surrounds each skeletal muscle fiber and ties adjacent ones together. Each skeletal muscle fiber has hundreds of nuclei just beneath the cell membrane. Multiple nuclei provide multiple copies of the genes that direct the production of enzymes and structural proteins needed for normal contraction so that contraction can occur faster.

In muscle fibers, the plasma membrane is called the sarcolemma and the cytoplasm is called the sarcoplasm (Fig. 3.37). Transverse tubules (T tubules) begin at the sarcolemma and extend into the sarcoplasm at right angles to the surface of the sarcolemma. The T tubules, which play a role in coordinating contraction, are filled with extracellular fluid and form passageways through the muscle fiber. They make close contact with expanded chambers, cisternae, of the sarcoplasmic reticulum, a specialized form of the ER. The cisternae contain high concentrations of calcium ions which are needed for contraction to occur.

The sarcoplasm contains cylinders 1 or 2 mm in diameter that are as long as the entire muscle fiber and are called myofibrils. The myofibrils are attached to the sarcolemma at each end of the cell and are responsible for muscle fiber contraction. Myofilaments—protein filaments consisting of thin filaments (primarily actin) and thick filaments (mostly myosin)—are bundled together to make up myofibrils. Repeating functional units of myofilaments are called sarcomeres (Fig. 3.38). The sarcomere is the smallest functional unit of the muscle fiber and has a resting length of about 2:6 mm. The thin filaments are attached to dark bands, called Z lines, which form the ends of each sarcomere. Thick filaments containing double-headed myosin molecules lie between the thin ones. It is this overlap of thin and thick filaments that gives skeletal muscle its banded, striated appearance. The I band is the area in a relaxed muscle fiber that just contains actin filaments, whereas the H zone is the area that just contains myosin filaments. The H zone and the area in which the actin and myosin overlap form the A band.

When a muscle contracts, myosin molecules in the thick filaments form crossbridges at active sites in the actin of the thin filaments and pull the thin filaments toward the center of the sarcomere. The cross-bridges are then released and reformed at a different active site further along the thin filament. This results in a motion that is similar to the hand-over-hand motion that is used to pull in a rope. This action, the sliding filament mechanism, is driven by ATP energy and results in shortening of the muscle. Shortening of the muscle components (contraction) results in bringing the muscle’s attachments (e.g., bones) closer together (Fig. 3.38).

Muscle fibers have connections with nerves. Sensory nerve endings are sensitive to length, tension, and pain in the muscle and send impulses to the brain via the spinal cord, whereas motor nerve endings receive impulses from the brain and spinal cord that lead to excitation and contraction of the muscle. Each motor axon branches and supplies several muscle fibers. Each of these axon branches loses its myelin sheath and splits up into a number of terminals that make contact with the surface of the muscle. When the nerve is stimulated, vesicles in the axon terminals release a neurotransmitter, acetylcholine, into the synapse between the neuron and the muscle. Acetylcholine diffuses across the synapse and binds to receptors in a special area, the motor end plate, of the sarcolemma. This causes the sodium channels in the sarcolemma to open up, and an action potential is produced in the muscle fiber. The resulting action potential spreads over the entire sarcolemmal surface and travels down all of the T tubules where it triggers a sudden massive release of calcium by the cisternae.

Calcium triggers the production of active sites on the thin filaments so that crossbridges with myosin can form and contraction occurs. Acetylcholinesterase breaks down the acetylcholine while the contraction process is underway so that the original relatively low permeability of the sarcolemma to sodium is restored.

A motor unit is a complex consisting of one motor neuron and the muscle fibers it innervates. All the muscle fibers in a single motor unit contract at the same time, whereas muscle fibers in the same muscle but belonging to different motor units may contract at different times. When a contracted muscle relaxes, it returns to its original (resting) length if another contracting muscle moves it or if it is acted upon by gravity. During relaxation, ATP is expended to move calcium back to the cisternae. The active sites that were needed for cross-bridge formation become covered so that actin and myosin can no longer interact. When the cross-bridges disappear, the muscle returns to its resting length (i.e., it relaxes).

The human body contains two types of skeletal muscle fibers: fast and slow. Fast fibers can contract in 10 ms or less following stimulation and make up most of the skeletal muscle fibers in the body. They are large in diameter and contain densely packed myofibrils, large glycogen reserves (used to produce ATP), and relatively few mitochondria. These fibers produce powerful contractions that use up massive amounts of ATP and fatigue (can no longer contract in spite of continued neural stimulation) rapidly. Slow fibers take about three times as long to contract as fast fibers. They can continue to contract for extended periods of time because they contain

1. a more extensive network of capillaries so that they can receive more oxygen,

(2) a special oxygen-binding molecule called myoglobin, and (3) more mitochondria which can produce more ATP than fast fibers. Muscles contain different amounts of slow and fast fibers. Those that are dominated by fast fibers (e.g., chicken breast muscles) appear white and those that are dominated by slow fibers (e.g., chicken legs) appear red. Most human muscles appear pink because they contain a mixture of both. Genes determine the percentage of fast and slow fibers in each muscle, but the ability of fast muscle fibers to resist fatigue can be increased through athletic training.

3.5 HOMEOSTASIS

Organ systems work together to maintain a constant internal environment within the body. Homeostasis is the process by which physical and chemical conditions within the internal environment of the body are maintained within tolerable ranges even when the external environment changes. Body temperature, blood pressure, and breathing and heart rates are some of the functions that are controlled by homeostatic mechanisms that involve several organ systems working together.

Extracellular fluid—the fluid that surrounds and bathes the body’s cells—plays an important role in maintaining homeostasis. It circulates throughout the body and carries materials to and from the cells. It also provides a mechanism for maintaining optimal temperature and pressure levels, the proper balance between acids and bases, and concentrations of oxygen, carbon dioxide, water, nutrients, and many of the chemicals that are found in the blood.

Three components—sensory receptors, integrators, and effectors—interact to maintain homeostasis (Fig. 3.39). Sensory receptors, which may be cells or cell parts, detect stimuli (i.e., changes to their environment) and send information about the stimuli to integrators. Integrators are control points that pull together information from one or more sensory receptors. Integrators then elicit a response from effectors. The brain is an integrator that can send messages to muscles or glands or both. The messages result in some type of response from the effectors. The brain receives information about how parts of the body are operating and can compare this to information about how parts of the body should be operating.

Positive feedback mechanisms are ones in which the initial stimulus is reinforced by the response. There are very few examples of this in the human body since it disrupts homeostasis. Childbirth provides one example. Pressure from the baby’s head in the birth canal stimulates receptors in the cervix which send signals to the hypothalamus. The hypothalamus responds to the stimulus by releasing oxytocin which enhances uterine contractions. Uterine contractions increase in intensity and force the baby further into the birth canal which causes additional stretching of the receptors in the cervix. The process continues until the baby is born, the pressure on the cervical stretch receptors ends, and the hypothalamus is no longer stimulated to release oxytocin.

Negative feedback mechanisms result in a response that is opposite in direction to the initiating stimulus. For example, receptors in the skin and elsewhere in the body detect the body’s temperature. Temperature information is forwarded to the hypothalamus in the brain which compares the body’s current temperature to what the temperature should be (approximately 378C). If the body’s temperature is too low, messages are sent to contract the smooth muscles in blood vessels near the skin (reducing the diameter of the blood vessels and the heat transferred through the skin), to skeletal muscles to start contracting rapidly (shivering), and to the arrector pili muscles (Fig. 3.16a) to erect the hairs and form ‘‘goose bumps.’’ The metabolic activity of the muscle contractions generates heat and warms the body. If the body’s temperature is too high, messages are sent to relax the smooth muscles in

the blood vessels near the skin (increasing the diameter of the blood vessels and the amount of heat transferred through the skin) and to sweat glands to release moisture and thus increase evaporative cooling of the skin. When the temperature of circulating blood changes enough in the appropriate direction that it reaches the set point of the system, the hypothalamus stops sending signals to the effector muscles and glands.

Another example of a negative feedback mechanism in the body involves the regulation of glucose in the blood stream by clusters of cells, the pancreatic islets (Fig. 3.40). There are between 2 Â 10 5 and 2 Â 10 6 pancreatic islets scattered throughout the adult pancreas. When glucose levels are high, beta cells in the islets produce insulin which facilitates glucose transport across plasma membranes and into cells and enhances the conversion of glucose into glycogen which is stored in the liver. During periods of fasting or whenever the concentration of blood glucose drops below normal (70–110 mg/dl), alpha cells produce glucagon which stimulates the liver to convert glycogen into glucose and the formation of glucose from noncarbohydrate sources such as amino acids and lactic acid. When glucose levels return to normal, the effector cells in the pancreatic islets stop producing their respective hormone (i.e., insulin or glucagon). Some biomedical engineers are working on controlled drug delivery systems that can sense blood glucose levels and emulate the responses of the pancreatic islet cells, whereas other biomedical engineers are trying to develop an artificial pancreas that would effectively maintain appropriate blood glucose levels.

EXERCISES

1. Using as many appropriate anatomical terms as apply, write sentences which describe the positional relationship between your mouth and (1) your left ear, (2) your nose, and (3) the big toe on your right foot.

2. Using as many appropriate anatomical terms as apply, describe the position of the stomach in the body and its position relative to the heart.

3. Search the Internet to find a transverse section of the body that was imaged using computerized tomography (CT) or magnetic resonance imaging (MRI). Print the image and indicate its web address.

4. Search the Internet to find a frontal section of the body that was imaged using CT or MRI. Print the image and indicate its web address.

5. Name and give examples of the four classes of biologically important organic compounds. What are the major functions of each of these groups?

6. What are the molarity and osmolarity of a 1-liter solution that contains half a mole of calcium chloride? How many molecules of chloride would the solution contain?

7. Consider a simple model cell, such as the one in Figure 3.6, that consists of cytoplasm and a plasma membrane. The cell’s initial volume is 2 nl and contains 0.2 M protein. The cell is placed in a large volume of 0:05 M CaCl2 . Neither Ca þþ nor Cl À can cross the plasma membrane and enter the cell. Is the 0:05 M CaCl 2 solution hypotonic, isotonic, or hypertonic relative to the

osmolarity inside the cell? Describe what happens to the cell as it achieves equilibrium in this new environment. What will be the final osmolarity of the cell? What will be its final volume?

8. What does the principle of electrical neutrality mean in terms of the concentration of ions within a cell?

9. Consider the same model cell that was used in Exercise 7, but instead of being placed in 0:05 M CaCl 2 , the cell is placed in 0:2 M urea. Unlike Caþþ and Cl À , urea can cross the plasma membrane and enter the cell. Describe

what happens to the cell as it achieves equilibrium in this environment. What will be the final osmolarity of the cell? What will be its final volume?

10. Briefly describe the path that a protein (e.g., a hormone) which is manufactured on the rough ER would take in order to leave the cell.

11. What major role do mitochondria have in the cell? Why might it be important to have this process contained within an organelle?

12. List and briefly describe three organelles that provide structural support and assist with cell movement.

13. Find a location on the Internet that describes the Human Genome Project.

Print its home page and indicate its web address. Find and print an ideogram of a chromosome that shows a gene that causes cystic fibrosis.

14. Briefly describe the major differences between replication and transcription.

15. Describe how the hereditary information contained in genes within the cell’s DNA is expressed as proteins which direct the cell’s activities.

16. Six different codons code for leucine while only one codes for methionine. Why might this be important for regulating translation and producing proteins?

17. Insulin (Fig. 3.41) was the first protein to be sequenced biochemically.

Assuming that there were no introns involved in the process, what are the possible DNA sequences that produced the last four amino acids in the molecule?

18. Copy the title page and abstract of five peer-reviewed journal articles that discuss engineering applications for five different organ systems in the body (one article per organ system). Review articles, conference proceeding papers, copies of keynote addresses and other speeches, book chapters, articles from the popular press and newspapers, and editorials are not acceptable. Good places to look are the Annals of Biomedical Engineering, the IEEE Transactions on Biomedical Engineering, the IEEE Engineering in Medicine and Biology Magazine, and Medical and Biological Engineering and Computing. What information in the article indicates that it was peer-reviewed?

19. Trace the path of a single red blood cell from a capillary bed in your right hand to the capillary beds of your right lung and back. What gases are exchanged? Where are they exchanged during this process?

20. Draw and label a block diagram of pulmonary and systemic blood flow that includes the chambers of the heart, valves, major veins and arteries that enter and leave the heart, the lungs, and the capillary bed of the body. Use arrows to indicate the direction of flow through each component.

21. Find on the Internet an example of an ECG representing normal sinus rhythm and use it to demonstrate how heart rate is determined.

22. Why are R waves (Fig. 3.22) used to determine heart rate rather than T waves?

23. How can the stroke volume be determined if a thermal dilution technique is used to determine cardiac output?

24. What would be the pulse pressure and mean arterial pressure for a hypertensive person with a systolic pressure of 145 mm Hg and a diastolic pressure of 98 mm Hg?

25. The total lung capacity of a patient is 5.5 liters. Find the patient’s inspiratory reserve volume if the patient’s vital capacity was 4.2 liters, the tidal volume was 500 ml, and the expiratory reserve volume was 1.2 liters.

26. What would you need to know or measure to determine the residual volume of the patient described in Example Problem 3.10?

27. Briefly describe the functions and major components of the central, peripheral, somatic, automatic, sympathetic, and parasympathetic nervous systems. Which ones are subsets of others?

28. Explain how sarcomeres shorten and how that results in muscle contraction.

29. How do the muscular and skeletal systems interact to produce movement?

30. Draw a block diagram to show the negative feedback mechanisms that help regulate glucose levels in the blood. Label the inputs, sensors, integrators, effectors, and outputs.

SUGGESTED READING

Brown, B.H., Smallwood, R.H., Barber, D.C., Lawford, P.V. and Hose, D.R. (1999). Medical Physics and Biomedical Engineering. Institute of Physics Publishing, Bristol and Philadelphia. Cooper, G.M. (2000). The Cell—A Molecular Approach, 2nd Ed. ASM Press, Washington, D.C. Deutsch, S. and Deutsch, A. (1993). Understanding the Nervous System: An Engineering

Perspective. IEEE Press, New York.

Fox, S.I. (2004). Human Physiology, 8th Ed. McGraw-Hill, Boston.

Germann, W.J. and Stanfield, C.L. (2005). Principles of Human Physiology, 2nd Ed. Pearson

Benjamin Cummings, San Francisco.

Guyton, A.C. (1991). Basic Neuroscience: Anatomy & Physiology. W. B. Saunders, Philadelphia. Guyton, A.C. and Hall, J.E. (2000). Textbook of Medical Physiology, 10th Ed. W. B. Saunders,

Philadelphia.

Harold, F.M. (2001). The Way of the Cell: Molecules, Organisms and the Order of Life. Oxford

Univ. Press, New York.

Karp, G. (2002). Cell and Molecular Biology—Concepts and Experiments, 3rd Ed. Wiley, New

York.

Katz, A.M. (1986). Physiology of the Heart. Raven Press, New York.

Keynes, R.D. and Aidley, D.J. (1991). Nerve & Muscle, 2nd Ed. Cambridge Univ. Press,

Cambridge.

Leff, A.R. and Schumacker, P.T. (1993). Respiratory Physiology: Basics and Applications.

Saunders, Philadelphia.

Lodish, H., Berk, A., Zipursky, S.L., Matsudaira, P., Baltimore, D. and Darnell, J. (2000).

Molecular Cell Biology, 4th Ed. W. H. Freeman, New York.

Martini, F.H. (2001). Fundamentals of Anatomy & Physiology, 5th Ed. Prentice Hall, Upper

Saddle River, NJ.

Matthews, G.G. (1991). Cellular Physiology of Nerve and Muscle. Blackwell Scientific, Boston. Pollack, G.H. (2001). Cells, Gels and the Engines of Life—A New Unifying Approach to Cell

Function. Ebner & Sons, Seattle, WA.

Rhoades R. and Pflanzer, R. (2003). Human Physiology, 4th Ed. Thomson Learning, Pacific

Grove, CA.

Silverthorn, D.U. (2004). Human Physiology—An Integrated Approach, 3rd Ed. Pearson Benja-

min Cummings, San Francisco.

To¨zeren A. and Byers, S.W. (2004). New Biology for Engineers and Computer Scientists. Pearson

Education, Upper Saddle River, NJ.

Van De Graaff, K.M., Fox, S.I. and LaFleur, K.M. (1997). Synopsis of Human Anatomy &

Physiology. Wm. C. Brown, Dubuque, IA.

West, J.B. (1990). Respiratory Physiology—The Essentials, 4th Ed. Williams & Wilkins, Baltimore. Widmaier, E.P., Raff, H. and Strang, K.T. (2004). Vander, Sherman, & Luciano’s Human

Physiology—The Mechanisms of Body Function. McGraw-Hill, Boston.