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Chapter 40 - Basic Principles of Animal Form and Function Overview: Diverse Forms, Common Challenges Animals inhabit almost

t every part of the biosphere. o Despite their great diversity, all animals must solve a common set of problems. o All animals must obtain oxygen, nourish themselves, excrete wastes, and move. Animals of diverse evolutionary histories and varying complexity must solve these general challenges of life. o Consider the long, tongue-like proboscis of a hawk moth, a structural adaptation for feeding. o Recoiled when not in use, the proboscis extends as a straw through which the moth can suck nectar from deep within tube-shaped flowers. Analyzing the hawk moths proboscis gives clues about what it does and how it functions. o Anatomy is the study of the structure of an organism. o Physiology is the study of the functions an organism performs. o Natural selection can fit structure to function by selecting, over many generations, the best of the available variations in a population. Searching for food, generating body heat and regulating internal temperature, sensing and responding to environmental stimuli, and all other animal activities require fuel in the form of chemical energy. The concept of bioenergeticshow organisms obtain, process, and use energy resourcesis a connecting theme in the comparative study of animals. Concept 40.1 Physical laws and the environment constrain animal size and shape An animals size and shape, features often called body plans or designs, are fundamental aspects of form and function that significantly affect the way an animal interacts with its environment. o The terms plan and design do not mean that animal body forms are products of conscious invention. o The body plan or design of an animal results from a pattern of development programmed by the genome, itself the product of millions of years of evolution due to natural selection. Physical requirements constrain what natural selection can invent. An animal such as the mythical winged dragon cannot exist. No animal as large as a dragon could generate enough lift to take off and fly. Similarly, the laws of hydrodynamics constrain the shapes that are possible for aquatic organisms that swim very fast. Tunas, sharks, penguins, dolphins, seals, and whales are all fast swimmers. o All have the same basic fusiform shape, tapered at both ends. This shape minimizes drag in water, which is about a thousand times denser than air. The similar forms of speedy fishes, birds, and marine mammals are a consequence of convergent evolution in the face of the universal laws of hydrodynamics. o Convergence occurs because natural selection shapes similar adaptations when diverse organisms face the same environmental challenge, such as the resistance of water to fast travel. Body size and shape affect interactions with the environment. An animals size and shape have a direct effect on how the animal exchanges energy and materials with its surroundings. As a requirement for maintaining the fluid integrity of the plasma membrane of its cells, an animals body must be arranged so that all of its living cells are bathed in an aqueous medium. Exchange with the environment occurs as dissolved substances diffuse and are transported across the plasma membranes between the cells and their aqueous surroundings. o For example, a single-celled protist living in water has a sufficient surface area of plasma membrane to service its entire volume of cytoplasm. o Surface-to-volume ratio is one of the physical constraints on the size of single-celled protists. Multicellular animals are composed of microscopic cells, each with its own plasma membrane that acts as a loading and unloading platform for a modest volume of cytoplasm. o This only works if all the cells of the animal have access to a suitable aqueous environment. o For example, a hydra, built as a sac, has a body wall only two cell layers thick. o Because its gastrovascular cavity opens to the exterior, both outer and inner layers of cells are bathed in water. Another way to maximize exposure to the surrounding medium is to have a flat body. o For instance, a parasitic tapeworm may be several meters long, but because it is very thin, most of its cells are bathed in the intestinal fluid of the worms vertebrate host from which it obtains nutrients. While two-layered sacs and flat shapes are designs that put a large surface area in contact with the environment, these solutions do not permit much complexity in internal organization. Most animals are more complex and are made up of compact masses of cells, producing outer surfaces that are relatively small compared to the animals volume. o Most organisms have extensively folded or branched internal surfaces specialized for exchange with the environment. o The circulatory system shuttles material among all the exchange surfaces within the animal.

Although exchange with the environment is a problem for animals whose cells are mostly internal, complex forms have distinct benefits. o A specialized outer covering can protect against predators; large muscles can enable rapid movement; and internal digestive organs can break down food gradually, controlling the release of stored energy. o Because the immediate environment for the cells is the internal body fluid, the animals organ systems can control the composition of the solution bathing its cells. o A complex body form is especially well suited to life on land, where the external environment may be variable. Concept 40.2 Animal form and function are correlated at all levels of organization Life is characterized by hierarchical levels of organization, each with emergent properties. Animals are multicellular organisms with their specialized cells grouped into tissues. In most animals, combinations of various tissues make up functional units called organs, and groups of organs work together as organ systems. o For example, the human digestive system consists of a stomach, small intestine, large intestine, and several other organs, each a composite of different tissues. Tissues are groups of cells with a common structure and function. o Different types of tissues have different structures that are suited to their functions. o A tissue may be held together by a sticky extracellular matrix that coats the cells or weaves them together in a fabric of fibers. The term tissue is from a Latin word meaning weave. Tissues are classified into four main categories: epithelial tissue, connective tissue, nervous tissue, and muscle tissue. Occurring in sheets of tightly packed cells, epithelial tissue covers the outside of the body and lines organs and cavities within the body. o The cells of an epithelium are closely joined and in many epithelia, the cells are riveted together by tight junctions. o The epithelium functions as a barrier protecting against mechanical injury, invasive microorganisms, and fluid loss. The cells at the base of an epithelial layer are attached to a basement membrane, a dense mat of extracellular matrix. o The free surface of the epithelium is exposed to air or fluid. Some epithelia, called glandular epithelia, absorb or secrete chemical solutions. o The glandular epithelia that line the lumen of the digestive and respiratory tracts form a mucous membrane that secretes a slimy solution called mucus that lubricates the surface and keeps it moist. Epithelia are classified by the number of cell layers and the shape of the cells on the free surface. o A simple epithelium has a single layer of cells, and a stratified epithelium has multiple tiers of cells. o A pseudostratified epithelium is single-layered but appears stratified because the cells vary in length. The shapes of cells on the exposed surface may be cuboidal (like dice), columnar (like bricks on end), or squamous (flat like floor tiles). Connective tissue functions mainly to bind and support other tissues. o Connective tissues have a sparse population of cells scattered through an extracellular matrix. o The matrix generally consists of a web of fibers embedding in a uniform foundation that may be liquid, jellylike, or solid. o In most cases, the connective tissue cells secrete the matrix. There are three kinds of connective tissue fibers, which are all proteins: collagenous fibers, elastic fibers, and reticular fibers. Collagenous fibers are made of collagen, the most abundant protein in the animal kingdom. o Collagenous fibers are nonelastic and do not tear easily when pulled lengthwise. Elastic fibers are long threads of elastin. o Elastin fiber provides a rubbery quality that complements the nonelastic strength of collagenous fibers. Reticular fibers are very thin and branched. o Composed of collagen and continuous with collagenous fibers, they form a tightly woven fabric that joins connective tissue to adjacent tissues. The major types of connective tissues in vertebrates are loose connective tissue, adipose tissue, fibrous connective tissue, cartilage, bone, and blood. o Each has a structure correlated with its specialized function. Loose connective tissue binds epithelia to underlying tissues and functions as packing material, holding organs in place. o Loose connective tissue has all three fiber types. Two cell types predominate in the fibrous mesh of loose connective tissue. o Fibroblasts secrete the protein ingredients of the extracellular fibers. o Macrophages are amoeboid cells that roam the maze of fibers, engulfing bacteria and the debris of dead cells by phagocytosis. Adipose tissue is a specialized form of loose connective tissue that stores fat in adipose cells distributed throughout the matrix. o Adipose tissue pads and insulates the body and stores fuel as fat molecules. o Each adipose cell contains a large fat droplet that swells when fat is stored and shrinks when the body uses fat as fuel.

Fibrous connective tissue is dense, due to its large number of collagenous fibers. o The fibers are organized into parallel bundles, an arrangement that maximizes nonelastic strength. o This type of connective tissue forms tendons, attaching muscles to bones, and ligaments, joining bones to bones at joints. Cartilage has an abundance of collagenous fibers embedded in a rubbery matrix made of a substance called chondroitin sulfate, a protein-carbohydrate complex. o Chondrocytes secrete collagen and chondroitin sulfate. o The composite of collagenous fibers and chondroitin sulfate makes cartilage a strong yet somewhat flexible support material. o The skeleton of a shark and the embryonic skeletons of many vertebrates are cartilaginous. o We retain cartilage as flexible supports in certain locations, such as the nose, ears, and intervertebral disks. The skeleton supporting most vertebrates is made of bone, a mineralized connective tissue. o Bone-forming cells called osteoblasts deposit a matrix of collagen. o Calcium, magnesium, and phosphate ions combine and harden within the matrix into the mineral hydroxyapatite. o The combination of hard mineral and flexible collagen makes bone harder than cartilage without being brittle. o The microscopic structure of hard mammalian bones consists of repeating units called osteons. Each osteon has concentric layers of mineralized matrix deposited around a central canal containing blood vessels and nerves that service the bone. Blood functions differently from other connective tissues, but it does have an extensive extracellular matrix. o The matrix is a liquid called plasma, consisting of water, salts, and a variety of dissolved proteins. o The liquid matrix enables rapid transport of blood cells, nutrients, and wastes. o Suspended in the plasma are erythrocytes (red blood cells), leukocytes (white blood cells), and cell fragments called platelets. Red cells carry oxygen. White cells function in defense against viruses, bacteria, and other invaders. Platelets aid in blood clotting. Muscle tissue is composed of long cells called muscle fibers that are capable of contracting when stimulated by nerve impulses. o Arranged in parallel within the cytoplasm of muscle fibers are large numbers of myofibrils made of the contractile proteins actin and myosin. o Muscle is the most abundant tissue in most animals, and muscle contraction accounts for most of the energyconsuming cellular work in active animals. There are three types of muscle tissue in the vertebrate body: skeletal muscle, cardiac muscle, and smooth muscle. Attached to bones by tendons, skeletal muscle is responsible for voluntary movements. o Skeletal muscle consists of bundles of long cells called fibers. Each fiber is a bundle of strands called myofibrils. o Skeletal muscle is also called striated muscle because the arrangement of contractile units, or sarcomeres, gives the cells a striped (striated) appearance under the microscope. Cardiac muscle forms the contractile wall of the heart. o It is striated like skeletal muscle, and its contractile properties are similar to those of skeletal muscle. o Unlike skeletal muscle, cardiac muscle carries out the unconscious task of contraction of the heart. o Cardiac muscle fibers branch and interconnect via intercalated disks, which relay signals from cell to cell during a heartbeat. Smooth muscle, which lacks striations, is found in the walls of the digestive tract, urinary bladder, arteries, and other internal organs. o The cells are spindle-shaped. o They contract more slowly than skeletal muscles but can remain contracted longer. o Controlled by different kinds of nerves than those controlling skeletal muscles, smooth muscles are responsible for involuntary body activities. These include churning of the stomach and constriction of arteries. Nervous tissue senses stimuli and transmits signals from one part of the animal to another. o The functional unit of nervous tissue is the neuron, or nerve cell, which is uniquely specialized to transmit nerve impulses. o A neuron consists of a cell body and two or more processes called dendrites and axons. Dendrites transmit impulses from their tips toward the rest of the neuron. Axons transmit impulses toward another neuron or toward an effector, such as a muscle cell that carries out a body response. o In many animals, nervous tissue is concentrated in the brain. The organ systems of an animal are interdependent. In all but the simplest animals (sponges and some cnidarians) different tissues are organized into organs. In some organs the tissues are arranged in layers.

For example, the vertebrate stomach has four major tissue layers. A thick epithelium lines the lumen and secretes mucus and digestive juices. Outside this layer is a zone of connective tissue, surrounded by a thick layer of smooth muscle. Another layer of connective tissue encases the entire stomach. Many vertebrate organs are suspended by sheets of connective tissues called mesenteries in body cavities moistened or filled with fluid. o Mammals have a thoracic cavity housing the lungs and heart that is separated from the lower abdominal cavity by a sheet of muscle called the diaphragm. Organ systems carry out the major body functions of most animals. o Each organ system consists of several organs and has specific functions. The efforts of all systems must be coordinated for the animal to survive. o For instance, nutrients absorbed from the digestive tract are distributed throughout the body by the circulatory system. o The heart that pumps blood through the circulatory system depends on nutrients absorbed by the digestive tract and also on oxygen obtained from the air or water by the respiratory system. Any organism, whether single-celled or an assembly of organ systems, is a coordinated living whole greater than the sum of its parts. Concept 40.3 Animals use the chemical energy in food to sustain form and function All organisms require chemical energy for growth, physiological processes, maintenance and repair, regulation, and reproduction. o Plants use light energy to build energy-rich organic molecules from water and CO2, and then they use those organic molecules for fuel. o In contrast, animals are heterotrophs and must obtain their chemical energy in food, which contains organic molecules synthesized by other organisms. The flow of energy through an animalits bioenergeticsultimately limits the animals behavior, growth, and reproduction and determines how much food it needs. o Studying an animals bioenergetics tells us a great deal about the animals adaptations. Food is digested by enzymatic hydrolysis, and energy-containing food molecules are absorbed by body cells. Most fuel molecules are used to generate ATP by the catabolic processes of cellular respiration and fermentation. o The chemical energy of ATP powers cellular work, enabling cells, organs, and organ systems to perform the many functions that keep an animal alive. o Since the production and use of ATP generates heat, an animal continuously loses heat to its surroundings. After energetic needs of staying alive are met, any remaining food molecules can be used in biosynthesis. o This includes body growth and repair; synthesis of storage material such as fat; and production of reproductive structures, including gametes. Biosynthesis requires both carbon skeletons for new structures and ATP to power their assembly. Metabolic rate provides clues to an animals bioenergetic strategy. The amount of energy an animal uses in a unit of time is called its metabolic ratethe sum of all the energy-requiring biochemical reactions occurring over a given time interval. Energy is measured in calories (cal) or kilocalories (kcal). o A kilocalorie is 1,000 calories. o The term Calorie, with a capital C, as used by many nutritionists, is actually a kilocalorie. Metabolic rate can be determined several ways. Because nearly all the chemical energy used in cellular respiration eventually appears as heat, metabolic rate can be measured by monitoring an animals heat loss. o A small animal can be placed in a calorimeter, which is a closed, insulated chamber equipped with a device that records the animals heat loss. A more indirect way to measure metabolic rate is to determine the amount of oxygen consumed or carbon dioxide produced by an animals cellular respiration. o These devices may measure changes in oxygen consumed or carbon dioxide produced as activity changes. Over long periods, the rate of food consumption and the energy content of food can be used to estimate metabolic rate. o A gram of protein or carbohydrate contains about 4.55 kcal, and a gram of fat contains 9 kcal. o This method must account for the energy in food that cannot be used by the animal (the energy lost in feces and urine). There are two basic bioenergetic strategies used by animals. o Birds and mammals are mainly endothermic, maintaining their body temperature within a narrow range by heat generated by metabolism. Endothermy is a high-energy strategy that permits intense, long-duration activity of a wide range of environmental temperatures. Most fishes, amphibians, reptiles, and invertebrates are ectothermic, meaning they gain their heat mostly from external sources.

The ectothermic strategy requires much less energy than is needed by endotherms, because of the energy cost of heating (or cooling) an endothermic body. o However, ectotherms are generally incapable of intense activity over long periods. In general, endotherms have higher metabolic rates than ectotherms. Body size influences metabolic rate. The metabolic rates of animals are affected by many factors besides whether the animal is an endotherm or an ectotherm. One of animal biologys most intriguing, but largely unanswered, questions has to do with the relationship between body size and metabolic rate. Physiologists have shown that the amount of energy it takes to maintain each gram of body weight is inversely related to body size. o For example, each gram of a mouse consumes about 20 times more calories than a gram of an elephant. The higher metabolic rate of a smaller animal demands a proportionately greater delivery rate of oxygen. o A smaller animal also has a higher breathing rate, blood volume (relative to size), and heart rate (pulse) and must eat much more food per unit of body mass. One hypothesis for the inverse relationship between metabolic rate and size is that the smaller the size of an endotherm, the greater the energy cost of maintaining a stable body temperature. o The smaller the animal, the greater its surface-to-volume ratio, and thus the greater loss of heat to (or gain from) the surroundings. However, this hypothesis fails to explain the inverse relationship between metabolism and size in ectotherms, which do not use metabolic heat to maintain body temperature. o Researchers continue to search for causes underlying this inverse relationship. Animals adjust their metabolic rates as conditions change. Every animal has a range of metabolic rates. o Minimal rates power the basic functions that support life, such as cell maintenance, breathing, and heartbeat. The metabolic rate of a nongrowing endotherm at rest, with an empty stomach and experiencing no stress, is called the basal metabolic rate (BMR). o The BMR for humans averages about 1,600 to 1,800 kcal per day for adult males and about 1,300 to 1,500 kcal per day for adult females. In ectotherms, body temperature changes with temperature of the surroundings, and so does metabolic rate. o Therefore, the minimal metabolic rate of an ectotherm must be determined at a specific temperature. o The metabolic rate of a resting, fasting, nonstressed ectotherm is called its standard metabolic rate (SMR). For both ectotherms and endotherms, activity has a large effect on metabolic rate. o Any behavior consumes energy beyond the BMR or SMR. o Maximal metabolic rates (the highest rates of ATP utilization) occur during peak activity, such as lifting heavy weights, all-out running, or high-speed swimming. In general, an animals maximum metabolic rate is inversely related to the duration of activity. o Both an alligator (ectotherm) and a human (endotherm) are capable of intense exercise in short spurts of a minute or less. These sprints are powered by the ATP present in muscle cells and ATP generated anaerobically by glycolysis. o Neither organism can maintain its maximum metabolic rate and peak activity level over longer periods of exercise, although the endotherm has an advantage in endurance tests. The BMR of a human is much higher than the SMR of an alligator. Both can reach high levels of maximum potential metabolic rates for short periods, but metabolic rate drops as the duration of the activity increases and the source of energy shifts toward aerobic respiration. Sustained activity depends on the aerobic process of cellular respiration for ATP supply. o An endotherms respiration rate is about 10 times greater than an ectotherms. o Only endotherms are capable of long-duration activities such as distance running. Between the extremes of BMR or SMR and maximal metabolic rate, many factors influence energy requirements. o These include age, sex, size, body and environmental temperatures, quality and quantity of food, activity level, oxygen availability, hormonal balance, and time of day. Diurnal organisms, such as birds, humans, and many insects, are usually active and have their highest metabolic rates during daylight hours. Nocturnal organisms, such as bats, mice, and many other mammals, are usually active at night or near dawn and dusk and have their highest metabolic rates then. Metabolic rates measured when animals are performing a variety of activities give a better idea of the energy costs of everyday life. o For most terrestrial animals, the average daily rate of energy consumption is 24 times BMR or SMR. Humans in most developed countries have an unusually low average daily metabolic rate of about 1.5 times BMRan indication of relatively sedentary lifestyles. Energy budgets reveal how animals use energy and materials.

Different species of animals use the energy and materials in food in different ways, depending on their environment, behavior, size, and basic energy strategy of endothermy or ectothermy. o For most animals, the majority of food is devoted to the production of ATP, and relatively little goes to growth or reproduction. o However, the amount of energy used for BMR (or SMR), activity, and temperature control varies considerably between species. For example, the typical annual energy budgets of four vertebrates reinforces two important concepts in bioenergetics. o First, a small animal has a much greater energy demand per kg than does a large animal of the same class. o Second, an ectotherm requires much less energy per kg than does an endotherm of equivalent size. o Further, size and energy strategy has a great influence on how the total annual energy expenditure is distributed among energetic needs. A human female spends a large fraction of her energy budget for BMR and relatively little for activity and body temperature regulation. o The cost of nine months of pregnancy and several months of breast feeding amounts to only 58% of the mothers annual energy requirements. o Growth amounts to about 1% of her annual energy budget. A male penguin spends a much larger fraction of his energy expenditures for activity because he must swim to catch his food. o Because the penguin is well insulated and fairly large, he has relatively low costs of temperature regulation despite living in the cold Antarctic environment. o His reproductive costs, about 6% of annual energy expenditures, mainly come from incubating eggs and bringing food to his chicks. o Penguins, like most birds, do not grow once they are adults. A female deer mouse spends a large fraction of her energy budget on temperature regulation. o Because of the high surface-to-volume ratio that goes with small size, mice lose body heat rapidly to the environment and must constantly generate metabolic heat to maintain body temperature. o Female deer mice spend about 12% of their energy budget on reproduction. In contrast to endotherms, the ectothermic python has no temperature regulation costs. o Like most reptiles, she grows continuously throughout life. o In one year, she can add 750 g of new body tissue and produce about 650 g of eggs. o Through the pythons economical ectothermic strategy, she expends only 1/40 of the energy expended by the samesized endothermic penguin. Concept 40.4 Many animals regulate their internal environment within relatively narrow limits More than a century ago, physiologist Claude Bernard made the distinction between external environments surrounding an animal and the internal environment in which the cells of the animal actually live. The internal environment of vertebrates is called the interstitial fluid. o This fluid exchanges nutrients and wastes with blood contained in microscopic vessels called capillaries. Bernard also recognized that many animals tend to maintain relatively constant conditions in their internal environment, even when the external environment changes. o While a pond-dwelling hydra is powerless to affect the temperature of the fluid that bathes its cells, the human body can maintain its internal pond at a more or less constant temperature of about 37C. o Similarly, our bodies control the pH of our blood and interstitial fluid to within a tenth of a pH unit of 7.4. o The amount of sugar in our blood does not fluctuate for long from a concentration of about 90 mg of glucose per 100 mL of blood. There are times during the course of the development of an animal when major changes in the internal environment are programmed to occur. o For example, the balance of hormones in human blood is altered radically during puberty and pregnancy. o Still, the stability of the internal environment is remarkable. Today, Bernards constant internal milieu is incorporated into the concept of homeostasis, which means steady state, or internal balance. o Actually the internal environment of an animal always fluctuates slightly. o Homeostasis is a dynamic state, an interplay between outside forces that tend to change the internal environment and internal control mechanisms that oppose such changes. Animals may be regulators or conformers for a particular environmental variable. Regulating and conforming are two extremes in how animals deal with environmental fluctuations. An animal is a regulator for a particular environmental variable if it uses internal control mechanisms to moderate internal change while external conditions fluctuate. o For example, a freshwater fish maintains a stable internal concentration of solutes in its blood that is higher than the water in which it lives. An animal is a conformer for a particular environmental variable if it allows its internal conditions to vary as external conditions fluctuate.

For example, many marine invertebrates live in environments where solute concentration (salinity) is relatively stable. o Unlike freshwater fishes, most marine invertebrates do not regulate their internal solute concentration, but rather conform to the external environment. No organism is a perfect regulator or conformer. An animal may maintain homeostasis while regulating some internal conditions and allowing others to conform to the environment. o For example, most freshwater fishes regulate their internal solute concentration but allow their internal temperature to conform to external water temperature. Homeostasis depends on feedback circuits. Any homeostatic control system has three functional components: a receptor, a control center, and an effector. o The receptor detects a change in some variable in the animals internal environment, such as a change in temperature. o The control center processes the information it receives from the receptor and directs an appropriate response by the effector. One type of control circuit, a negative-feedback system, can control the temperature in a room. o In this case, the control center, called a thermostat, also contains the receptor, a thermometer. o When room temperature falls, the thermostat switches on the heater, the effector. In such a negative-feedback system, a change in the variable being monitored triggers the control mechanism to counteract further change in the same direction. o Owing to a time lag between receptor and response, the variable drifts slightly above and below the set point, but fluctuations are moderate. o Negative-feedback mechanisms prevent small changes from becoming too large. Most homeostatic mechanisms in animals operate on this principle of negative feedback. o Human body temperature is kept close to a set point of 37C by the cooperation of several negative-feedback circuits. In contrast to negative feedback, positive feedback involves a change in some variable that triggers mechanisms that amplify rather than reverse the change. o For example, during childbirth, the pressure of the babys head against receptors near the opening of the uterus stimulates uterine contractions. o These cause greater pressure against the uterine opening, heightening the contractions, which cause still greater pressure. o Positive feedback brings childbirth to completion, a very different sort of process from maintaining a steady state. While some aspects of the internal environment are maintained at a set point, regulated change is essential to normal body functions. o In some cases, the changes are cyclical, such as the changes in hormone levels responsible for the menstrual cycle in women. o In other cases, a regulated change is a reaction to a challenge to the body. For example, the human body reacts to certain infections by raising the set point for temperature to a slightly higher level, and the resulting fever helps fight infection. Over the short term, homeostatic mechanisms can keep a process, such as body temperature, close to a set point, whatever it is at that particular time. Over the longer term, homeostasis allows regulated change in the bodys internal environment. Internal regulation is expensive. o Animals use a considerable portion of their energy from the food they eat to maintain favorable internal conditions. Concept 40.5 Thermoregulation contributes to homeostasis and involves anatomy, physiology, and behavior Thermoregulation is the process by which animals maintain an internal temperature within a tolerable range. This ability is critical to survival, because most biochemical and physiological processes are very sensitive to changes in body temperature. The rates of most enzyme-mediated reactions increase by a factor of 2 or 3 for every 10C temperature increase until temperature is high enough to begin to denature proteins. o The properties of membranes also change with temperature. Although different species of animals are adapted to different environmental temperatures, each species has an optimal temperature range. o Thermoregulation helps keep body temperature within the optimal range, enabling cells to function effectively as external temperature fluctuates. Ectotherms and endotherms manage their heat budgets very differently. One way to classify the thermal characteristics of animals is to emphasize the role of metabolic heat in determining body temperature. Ectotherms gain most of their heat from the environment.

An ectotherm has such a low metabolic rate that the amount of heat it generates is too small to have much effect on body temperature. Endotherms can use metabolic heat to regulate their body temperature. o In a cold environment, an endotherms high metabolic rate generates enough heat to keep its body substantially higher than its surroundings. Many ectotherms can thermoregulate by behavioral means, such as basking in the sun or seeking out shade. o In general, ectotherms tolerate greater variation in internal temperature than do endotherms. Animals are not classified as ectotherms or endotherms based on whether they have variable or constant body temperatures. o It is the source of heat used to maintain body temperature that distinguishes ectotherms from endotherms. A differentand largely outdatedset of terms can be used to imply variable or constant body temperature. o A poikilotherm is an animal whose internal temperature varies widely. o A homeotherm is an animal that maintains relatively stable internal temperatures. Another common misconception is the idea that ectotherms are cold-blooded and endotherms are warm-blooded. o Ectotherms do not necessarily have low body temperatures. o While sitting in the sun, many ectothermic lizards have higher body temperatures than mammals. o Biologists avoid the terms cold-blooded and warm-blooded because they are so misleading. Endothermy and ectothermy are not mutually exclusive thermoregulatory strategies. o A bird is an endotherm but may warm itself in the sun on a cold morning, just as a lizard does. Endothermy has several important advantages. o Being able to generate a large amount of metabolic heat enables endotherms to perform vigorous activity for much longer than is possible for most ectotherms. o Sustained intense exercise, such as long-distance running or powered flight, is usually only possible for endotherms. Terrestrial animals can maintain stable body temperatures despite temperature fluctuations, which are more severe on land than in water. o For example, no ectotherm can be active in below-freezing weather, but many endotherms function well in such conditions. Endothermic vertebrates also have mechanisms for cooling their bodies in hot environments, allowing them to withstand heat loads that would be intolerable for most ectotherms. However, ectotherms can tolerate larger fluctuations in their internal temperatures. Being endothermic is energetically expensive. o For example, at 20C, a human at rest has a BMR or 1,300 to 1,800 kcal per day. o An American alligator of similar weight has an SMR of only 60 kcal per day. As a result, ectotherms need to consume far more food than ectotherms of equivalent size. o This is a serious disadvantage if food supplies are limited. Ectothermy is an extremely effective and successful strategy in most of Earths environments, as is shown by the abundance and diversity of ectothermic animals. Animals regulate the exchange of heat with their environment. Animals exchange heat with their external environment by four physical processes: conduction, convection, radiation, and evaporation. o Heat is always transferred from a hotter object to a cooler object. Endotherms and thermoregulating ectotherms must manage their heat budgets so that rates of heat gain are equal to rates of heat loss. Five general categories of adaptations help animals thermoregulate. A major thermoregulatory adaptation in mammals and birds is insulation: hair, feathers, or fat layers. o Insulation reduces the flow of heat between an animal and its environment and lowers the energy cost of keeping warm. In mammals, the insulating material is associated with the integumentary system, the outer covering of the body. Skin is a key organ of the integumentary system. o Skin functions as a thermoregulatory organ by housing nerves, sweat glands, blood vessels, and hair follicles. o It also protects internal body parts from mechanical injury, infection, and desiccation. Skin consists of two layers, the epidermis and the dermis, underlain by a tissue layer called the hypodermis. o The epidermis is the outer layer of skin, composed largely of dead epithelial cells. o The dermis supports the epidermis and contains hair follicles, oil and sweat glands, muscles, nerves, and blood vessels. o Adipose tissue provides varying degrees of insulation, depending on the species. The insulating power of a layer of fur or feathers depends mostly on how much air the layer traps. o Hair loses most of its insulating power when wet. o Land mammals and birds react to cold by raising their fur or feathers to trap a thicker layer of air. o Human goose bumps are a vestige of our hair-raising ancestors. Marine mammals have a very thick layer of insulating blubber just under their skin. o The skin temperature of a marine mammal is close to water temperature.

o However, blubber insulation is so effective that marine mammals can maintain body core temperatures of 3638C. Many endotherms and ectotherms can alter the amount of blood flow between the body core and the skin. Elevated blood flow in the skin results from vasodilation, an increase in the diameter of superficial blood vessels near the body surface. o Vasodilation is triggered by nerve signals that relax the muscles of the vessel walls. o In endotherms, vasodilation usually warms the skin, increasing the transfer of body heat to a cool environment. The reverse process, vasoconstriction, reduces blood flow and heat transfer by decreasing the diameter of superficial vessels. Another circulatory adaptation is an arrangement of blood vessels called a countercurrent heat exchanger, which reduces heat loss. o In some species, blood can either go through the heat exchanger or bypass it. o The relative amount of blood that flows through the two paths varies, adjusting the rate of heat loss. Unlike most fishes, which are thermoconformers, some specialized endothermic bony fishes and sharks have circulatory adaptations to retain metabolic heat. o Endothermic fishes include bluefin tuna, swordfish, and great white sharks. o Large arteries convey most of the cold blood from the gills to tissues just under the skin. o Branches deliver blood to the deep muscles, where small vessels are arranged into a countercurrent heat exchanger. o Endothermy enables vigorous, sustained activity that is characteristic of these animals. Some reptiles also have physiological adaptations to regulate heat loss. o In the marine iguanas of the Galpagos Islands, body heat is conserved by vasoconstriction of superficial blood vessels. Many endothermic insects (bumblebees, honeybees, some moths) have a countercurrent heat exchanger that helps maintain a high temperature in the thorax, where the flight muscles are located. o In some insects, the countercurrent mechanism can be shut down to allow heat to be shed during hot weather. o A bumblebee queen uses this mechanism to incubate her eggs. She generates heat by shivering her flight muscles and then transfers the heat to her abdomen, which she presses against her eggs. Many mammals and birds live in places where thermoregulation requires cooling as well as warming. o If environmental temperature is above body temperature, evaporation is the only way to keep body temperature from rising. o Terrestrial animals lose water by evaporation across the skin and when they breathe. o Water absorbs considerable heat when it evaporates; it is 50 to 100 times more effective than air in transferring heat. Some animals have adaptations to augment evaporative cooling. o Panting is important in birds and many mammals. o Some birds have a pouch richly supplied with blood vessels in the floor of the mouth. Birds flutter the pouch to increase evaporation. o Sweating or bathing moistens the skin and enhances evaporative cooling. Many terrestrial mammals have sweat glands controlled by the nervous system. o Other mechanisms to promote evaporative cooling include spreading saliva on skin or regulating the amount of mucus secretion. Many endotherms and ectotherms use behavioral responses to control body temperature. o Many ectotherms can maintain a constant body temperature by simple behaviors. o Some animals hibernate or migrate to a more suitable climate. Amphibians regulate body temperature mainly by behavior, by moving to a location where solar heat is available or by seeking shade. Reptiles also thermoregulate behaviorally. o When cool, they seek warm places, orient themselves toward a heat source, and expand the body surface exposed to the heat source. o When hot, they move to cool places or turn away from the heat source. o Many terrestrial invertebrates use similar behavioral mechanisms. Honeybees use a thermoregulatory mechanism that depends on social behavior. o In cold weather, they increase heat production and huddle together to retain heat. o They maintain a relatively constant temperature by changing the density of the huddling, and moving individuals between the cooler outer edges of the cluster and the warmer center. Honeybees expend considerable energy to keep warm during long periods of cold weather. This is the main function of the honey stored in the hive. o Honeybees also cool the hive in hot weather by transporting water to it and fanning it with their wings to promote evaporation and convection. Endotherms vary heat production to counteract constant heat loss. o For example, heat production is increased by such muscle activity as moving or shivering. Certain mammalian hormones can cause mitochondria to increase their metabolic activity and produce heat instead of ATP. o This nonshivering thermogenesis (NST) takes place throughout the body.

o Some mammals have brown fat that is specialized for rapid heat production. Through shivering and NST, mammals and birds may increase their metabolic heat production to 5 or 10 times the minimal levels characteristic of warm weather. A few large reptiles can become endothermic in particular circumstances. o For example, female pythons that are incubating eggs increase their metabolic rate by shivering, generating enough heat to elevate egg temperatures by 57C during incubation. The smallest endotherms are flying insects such as bees and moths. o These insects elevate body temperature by shivering before taking off. o They contract their flight muscles in synchrony to produce only slight wing movements but considerable heat. The regulation of body temperature in humans is a complex system facilitated by feedback mechanisms. Nerve cells that control thermoregulation are concentrated in a brain region called the hypothalamus. o The hypothalamus contains a group of nerve cells that functions as a thermostat. o Nerve cells that sense temperature are in the skin, in the hypothalamus itself, and in other body regions. If the thermostat in the brain detects a decrease in the temperature of the blood below the set point, it inhibits heat loss mechanisms and activates heat-saving ones such as vasoconstriction of superficial vessels and erection of fur, while stimulating heat-generating mechanisms such as shivering. If the thermostat in the brain detects a rise in the temperature of the blood above the set point, it shuts down heat retention mechanisms and promotes body cooling by vasodilation, sweating, or panting. Animals can acclimatize to a new range of environmental temperatures. Many animals can adjust to a new range of environmental temperatures by a physiological response called acclimatization. o Ectotherms and endotherms acclimatize differently. o In birds and mammals, acclimatization includes adjusting the amount of insulation and varying the capacity for metabolic heat production. o Acclimatization in ectotherms involves compensating for temperature changes. o Acclimatization responses in ectotherms often include adjustments at the cellular level. Cells may increase the production of certain enzymes or produce enzyme variants with different temperature optima. Membranes also change the proportions of saturated and unsaturated lipids to keep membranes fluid at different temperatures. Some ectotherms produce antifreeze compounds, or cryoprotectants, to prevent ice formation in body cells. o These compounds allow overwintering ectotherms such as frogs and arthropods to withstand body temperatures well below zero. o Arctic and antarctic fishes also have cryoprotectants to protect body tissues. Cells can make rapid adjustments to temperature changes. o For example, mammalian cells grown in culture respond to increased temperature by producing and accumulating stress-induced proteins, including heat-shock proteins. o These molecules, found in bacteria, yeast, plants, and animals, help to maintain the integrity of other proteins that would otherwise be denatured by severe heat. o Stress-induced proteins help prevent cell death when an organism is challenged by severe changes in cellular environment. Animals may conserve energy through torpor. Some animals deal with severe conditions by an adaptation called torpor. o Torpor is a physiological state in which activity is low and metabolism decreases. Hibernation is long-term torpor that is an adaptation to winter cold and food scarcity. When vertebrate endotherms enter torpor or hibernation, their body temperatures decline. o Some hibernating mammals cool to 12C, and a few drop slightly below 0C in a supercooled, unfrozen state. Metabolic rates during hibernation may be several hundred times lower than if animals tried to maintain normal body temperatures. o Hibernators can survive for very long periods on limited supplies of energy stored in body tissues or as food cached in a burrow. Estivation, or summer torpor, is also characterized by slow metabolism or inactivity. o Estivation allows animals to survive long periods of high temperatures and scarce water supplies. Hibernation and estivation are often triggered by seasonal changes in the length of daylight. o Some hibernators prepare for winter by storing food in their burrows or by eating huge quantities of food. o Ground squirrels double their weight prior to hibernation. Many small mammals and birds exhibit a daily torpor that is adapted to their feeding patterns. o For example, most bats and shrews feed at night and go into torpor during daylight hours. o Chickadees and hummingbirds feed during the day and go into torpor on cold nights. The body temperature of a hummingbird may drop by 2530C at night. An animals daily cycle of activity and torpor appears to be a built-in rhythm controlled by its biological clock. o Even if food is made available to a shrew, it will go through daily torpor.

Chapter 41 - Animal Nutrition Overview: The Need to Feed All animals eat other organismsdead or alive, whole or by the piece (including parasites). In general, animals fit into one of three dietary categories. I. Herbivores, such as gorillas, cows, hares, and many snails, eat mainly autotrophs (plants and algae). II. Carnivores, such as sharks, hawks, spiders, and snakes, eat other animals. III. Omnivores, such as cockroaches, bears, raccoons, and humans, consume animal and plant or algal matter. o Humans evolved as hunters, scavengers, and gatherers. While the terms herbivore, carnivore, and omnivore represent the kinds of food that an animal usually eats, most animals are opportunistic, eating foods that are outside their main dietary category when these foods are available. o For example, cattle and deer, which are herbivores, may occasionally eat small animals or bird eggs. o Most carnivores obtain some nutrients from plant materials that remain in the digestive tract of the prey that they eat. o All animals consume bacteria along with other types of food. For any animal, a nutritionally adequate diet must satisfy three nutritional needs: . A balanced diet must provide fuel for cellular work. I. It must supply the organic raw materials needed to construct organic molecules. II. Essential nutrients that the animal cannot make from raw materials must be provided in its food. Concept 41.1 Homeostatic mechanisms manage an animals energy budget The flow of food energy into and out of an animal can be viewed as a budget, with the production of ATP accounting for the largest fraction by far of the energy budget of most animals. o ATP powers basal or resting metabolism, as well as activity and, in endothermic animals, thermoregulation. Nearly all ATP generation is based on the oxidation of organic fuel moleculescarbohydrates, proteins, and fatsin cellular respiration. o The monomers of any of these substances can be used as fuel. o Fats are especially rich in energy, liberating about twice the energy liberated from an equal amount of carbohydrate or protein during oxidation. When an animal takes in more calories than it needs to produce ATP, the excess can be used for biosynthesis. o This biosynthesis can be used to grow in size or for reproduction, or it can be stored in energy depots. o In humans, the liver and muscle cells store energy as glycogen, a polymer made up of many glucose units. Glucose is a major fuel molecule for cells, and its metabolism, regulated by hormone action, is an important aspect of homeostasis. If glycogen stores are full and caloric intake still exceeds caloric expenditure, the excess is usually stored as fat. When fewer calories are taken in than are expendedperhaps because of sustained heavy exercise or lack of foodfuel is taken out of storage depots and oxidized. The human body expends liver glycogen first and then draws on muscle glycogen and fat. o Most healthy peopleeven if they are not obesehave enough stored fat to sustain them through several weeks of starvation. The average humans energy needs can be fueled by the oxidation of only 0.3 kg of fat per day. Severe problems occur if the energy budget remains out of balance for long periods. o If the diet of a person or other animal is chronically deficient in calories, undernourishment results. o The stores of glycogen and fat are used up, the body begins breaking down its own proteins for fuel, muscles begin to decrease in size, and the brain can become protein-deficient. o If energy intake remains less than energy expenditure, death will eventually result, and even if a seriously undernourished person survives, some damage may be irreversible. Because a diet of a single staple such as rice or corn can often provide sufficient calories, undernourishment is generally common only where drought, war, or some other crisis has severely disrupted the food supply. Another cause of undernourishment is anorexia nervosa, an eating disorder associated with a compulsive aversion to body fat. Obesity is a global health problem. Overnourishment, or obesity, the result of excessive food intake, is a common problem in the United States and other affluent nations. o The human body tends to store any excess fat molecules obtained from food instead of using them for fuel. In contrast, when we eat an excess of carbohydrates, the body tends to increase its rate of carbohydrate oxidation. o Thus, the amount of fat in the diet can have a more direct effect on weight gain than the amount of dietary carbohydrates. o While fat hoarding can be a liability today, it probably provided a fitness advantage for our hunting-and-gathering ancestors, enabling individuals with genes promoting the storage of high-energy molecules during feasts to survive the eventual famines.

The World Health Organization now recognizes obesity as a major global health problem. o The increased availability of fattening foods in many countries combines with more sedentary lifestyles to put excess weight on bodies. o In the United States, the percentage of obese people has doubled to 30% over the past 20 years, and another 35% are overweight. Obesity contributes to health problems, including diabetes, cancer of the colon and breast, and cardiovascular disease. Research on the causes and possible treatments for weight-control problems continues. o Over the long term, feedback circuits control the bodys storage and metabolism of fat. o Several hormones regulate long-term and short-term appetite by affecting a satiety center in the brain. Inheritance is a major factor in obesity. o Most of the weight-regulating hormones are polypeptides. o Dozens of genes that code for these hormones have been identified. In mammals, a hormone called leptin, produced by adipose cells, is a key player in a complex feedback mechanism regulating fat storage and use. o As adipose tissue increases, high leptin levels cue the brain to depress appetite and to increase energy-consuming muscular activity and body-heat production. o Conversely, loss of body fat decreases leptin levels in the blood, signaling the brain to increase appetite and weight gain. o Mice that inherit a defective gene for leptin become very obese. These mice can be treated by injection with leptin. o However, very few obese people have defective leptin production. In fact, most obese humans have abnormally high leptin levels, due to their large amounts of adipose tissue. o For some reason, the brains satiety center does not respond to the high leptin levels in many obese people. o One hypothesis is that in humans, in contrast to other mammals, the leptin system functions to stimulate appetite and prevent weight loss rather than to prevent weight gain. Most humans crave fatty foods. Although fat hoarding is a health liability today, it may have been advantageous in our evolutionary past. Our ancestors on the African savanna were hunter-gatherers who probably survived mainly on plant materials, occasionally supplemented by meat. o Natural selection may have favored those individuals with a physiology that induced them to gorge on fatty foods on the rare occasions that they were available. o Perhaps these individuals were more likely to survive famine. Obesity may be beneficial in certain species. o Small seabirds called petrels fly long distances to find food that is rich in lipids. o By bringing lipid-rich food to their chicks, the parents minimize the weight of food that they must carry. o However, because these foods are low in protein, young petrels have to consume more calories than they burn in metabolismand consequently they become obese. o In some petrel species, chicks at the end of the growth period weigh much more their parents, are too heavy to fly, and need to starve for several days to fly. o The fat reserves help growing chicks to survive periods when parents are unable to find food. Concept 41.2 An animals diet must supply carbon skeletons and essential nutrients In addition to fuel for ATP production, an animals diet must supply all the raw materials for biosynthesis. o This requires organic precursors (carbon skeletons) from its food. o Given a source of organic carbon (such as sugar) and a source of organic nitrogen (usually in amino acids from the digestion of proteins), animals can fabricate a great variety of organic moleculescarbohydrates, proteins, and lipids. Besides fuel and carbon skeletons, an animals diet must also supply essential nutrients. o These are materials that must be obtained in preassembled form because the animals cells cannot make them from any raw material. o Some materials are essential for all animals, but others are needed only by certain species. For example, ascorbic acid (vitamin C) is an essential nutrient for humans and other primates, guinea pigs, and some birds and snakes, but not for most other animals. An animal whose diet is missing one or more essential nutrients is said to be malnourished. o For example, many herbivores living where soils and plants are deficient in phosphorus eat bones to obtain this essential nutrient. o Malnutrition is much more common than undernourishment in human populations, and it is even possible for an overnourished individual to be malnourished. There are four classes of essential nutrients: essential amino acids, essential fatty acids, vitamins, and minerals. Animals require 20 amino acids to make proteins. o Most animals can synthesize half of these if their diet includes organic nitrogen. The remaining essential amino acids must be obtained from food in prefabricated form.

o Eight amino acids are essential in the adult human with a ninth, histidine, being essential for infants. o The same amino acids are essential for most animals. A diet that provides insufficient amounts of one or more essential amino acids causes a form of malnutrition known as protein deficiency. o This is the most common type of malnutrition among humans. o The victims are usually children, who, if they survive infancy, are likely to be retarded in physical and perhaps mental development. In one variation of protein malnutrition, called kwashiorkor, the diet provides enough calories but is severely deficient in protein. The protein in animal products, such as meat, eggs, and cheese, are complete, which means that they provide all the essential amino acids in their proper proportions. Most plant proteins are incomplete, being deficient in one or more essential amino acid. o For example, corn is deficient in the amino acid lysine. o Individuals who are forced by economic necessity or other circumstances to obtain nearly all their calories from corn would show symptoms of protein deficiency. This is true from any diet limited to a single plant source, including rice, wheat, and potatoes. Protein deficiency from a vegetarian diet can be avoided by eating a combination of plant foods that complement one another to supply all essential amino acids. o For example, beans supply the lysine that is missing in corn, and corn provides the methionine that is deficient in beans. Because the body cannot easily store amino acids, a diet with all essential amino acids must be eaten each day, or protein synthesis is retarded. Some animals have special adaptations that get them through periods where their bodies demand extraordinary amounts of protein. o For example, penguins use muscle proteins as a source of amino acids to make new proteins during molting. While animals can synthesize most of the fatty acids they need, they cannot synthesize essential fatty acids. o These are certain unsaturated fatty acids, including linoleic acids, which are required by humans. o Most diets furnish ample quantities of essential fatty acids, and thus deficiencies are rare. Vitamins are organic molecules required in the diet in quantities that are quite small compared with the relatively large quantities of essential amino acids and fatty acids animals need. o While vitamins are required in tiny amountsfrom about 0.01 mg to 100 mg per daydepending on the vitamin, vitamin deficiency (or overdose in some cases) can cause serious problems. So far, 13 vitamins essential to humans have been identified. o These can be grouped into water-soluble vitamins and fat-soluble vitamins, with extremely diverse physiological functions. The water-soluble vitamins include the B complex, which consists of several compounds that function as coenzymes in key metabolic processes. o Vitamin C, also water soluble, is required for the production of connective tissue. o Excessive amounts of water-soluble vitamins are excreted in urine, and moderate overdoses are probably harmless. The fat-soluble vitamins are A, D, E, and K. o They have a wide variety of functions. o Vitamin A is incorporated in the visual pigments of the eye. o Vitamin D aids in calcium absorption and bone formation. o Vitamin E seems to protect membrane phospholipids from oxidation. o Vitamin K is required for blood clotting. o Excess amounts of fat-soluble vitamins are not excreted but are deposited in body fat. Overconsumption may lead to toxic accumulations of these compounds. The subject of vitamin dosage has aroused heated scientific and popular debate. o Some believe that it is sufficient to meet recommended daily allowances (RDAs), the nutrient intake proposed by nutritionists to maintain health. o Others argue that RDAs are set too low for some vitamins, and a fraction of these people believe, probably mistakenly, that massive doses of vitamins confer health benefits. o Debate centers on the optimal doses of vitamins C and E. o While research is ongoing, all that can be said with any certainty is that people who eat a balanced diet are not likely to develop symptoms of vitamin deficiency. Minerals are simple inorganic nutrients, usually required in small amountsfrom less than 1 mg to about 2,500 mg per day. o Mineral requirements vary with animal species. o Humans and other vertebrates require relatively large quantities of calcium and phosphorus for the construction and maintenance of bone. Calcium is also necessary for the normal functioning of nerves and muscles. Phosphorus is a component of the cytochromes that function in cellular respiration.

Iron is a component of the cytochromes that function in cellular respiration and of hemoglobin, the oxygen-binding protein of red blood cells. o Magnesium, iron, zinc, copper, manganese, selenium, and molybdenum are cofactors built into the structure of certain enzymes. Magnesium, for example, is present in enzymes that split ATP. o Iodine is required for thyroid hormones, which regulate metabolic rate. Sodium, potassium, and chloride are important in nerve function and have a major influence on the osmotic balance between cells and the interstitial fluids. Excess consumption of salt (sodium chloride) is harmful. o The average U.S. citizen eats enough salt to provide about 20 times the required amount of sodium. o Excess consumption of salt or several other minerals can upset homeostatic balance and cause toxic side effects. o For example, too much sodium is associated with high blood pressure, and excess iron causes liver damage. Concept 41.3 The main stages of food processing are ingestion, digestion, absorption, and elimination Ingestion, the act of eating, is only the first stage of food processing. o Food is packaged in bulk form and contains very complex arrays of molecules, including large polymers and various substances that may be difficult to process or even toxic. Animals cannot use macromolecules like proteins, fats, and carbohydrates in the form of starch or other polysaccharides. o First, polymers are too large to pass through membranes and enter the cells of the animal. o Second, the macromolecules that make up an animal are not identical to those of its food. In building their macromolecules, however, all organisms use common monomers. For example, soybeans, fruit flies, and humans all assemble their proteins from the same 20 amino acids. Digestion, the second stage of food processing, is the process of breaking food down into molecules small enough for the body to absorb. o Digestion cleaves macromolecules into their component monomers, which the animal then uses to make its own molecules or as fuel for ATP production. o Polysaccharides and disaccharides are split into simple sugars. o Fats are digested to glycerol and fatty acids. o Proteins are broken down into amino acids. o Nucleic acids are cleaved into nucleotides. Digestion reverses the process that a cell uses to link together monomers to form macromolecules. o Rather than removing a molecule of water for each new covalent bond formed, digestion breaks bonds with the addition of water via enzymatic hydrolysis. o A variety of hydrolytic enzymes catalyze the digestion of each of the classes of macromolecules found in food. Chemical digestion is usually preceded by mechanical fragmentation of the foodby chewing, for instance. o Breaking food into smaller pieces increases the surface area exposed to digestive juices containing hydrolytic enzymes. After the food is digested, the animals cells take up small molecules such as amino acids and simple sugars from the digestive compartment, a process called absorption. During elimination, undigested material passes out of the digestive compartment. Digestion occurs in specialized compartments. To avoid digesting their own cells and tissues, most organisms conduct digestion in specialized compartments. The simplest digestive compartments are food vacuoles, organelles in which hydrolytic enzymes break down food without digesting the cells own cytoplasm, a process termed intracellular digestion. This process begins after a cell has engulfed food by phagocytosis or pinocytosis. Newly formed food vacuoles fuse with lysosomes, which are organelles containing hydrolytic enzymes. Later the vacuole fuses with an anal pore, and its contents are eliminated. In most animals, at least some hydrolysis occurs by extracellular digestion, the breakdown of food outside cells. o Extracellular digestion occurs within compartments that are continuous with the outside of the animals body. o This enables organisms to devour much larger prey than can be ingested by phagocytosis and digested intracellularly. Many animals with simple body plans, such as cnidarians and flatworms, have digestive sacs with single openings, called gastrovascular cavities. o These cavities function in both digestion and distribution of nutrients throughout the body. o For example, the cnidarians called hydras capture their prey with nematocysts and use tentacles to stuff the prey through the mouth into the gastrovascular cavity. The prey is then partially digested by enzymes secreted by specialized gland cells of the gastrodermis. o Nutritive muscular cells in the gastrodermis engulf the food particles. Most of the actual hydrolysis of macromolecules occurs intracellularly. o Undigested materials are eliminated through the mouth. In contrast to cnidarians and flatworms, most animals have digestive tubes extending between a mouth and anus. These tubes are called complete digestive tracts or alimentary canals.

Because food moves in one direction, the tube can be organized into specialized regions that carry out digestion and nutrient absorption in a stepwise fashion. o In addition, animals with alimentary canals can eat more food before the earlier meal is completely digested. Concept 41.4 Each organ of the mammalian digestive system has specialized food-processing functions The general principles of food processing are similar for a diversity of animals, including the mammalian system that we will use as a representative example. The mammalian digestive system consists of the alimentary canal and various accessory glands that secrete digestive juices into the canal through ducts. o Peristalsis, rhythmic waves of contraction by smooth muscles in the walls of the canal, pushes food along. o Sphincters, muscular ring-like valves, regulate the passage of material between specialized chambers of the canal. o The accessory glands include the salivary glands, the pancreas, the liver, and the gallbladder. After chewing and swallowing, it takes 5 to 10 seconds for food to pass down the esophagus to the stomach, where it spends 2 to 6 hours being partially digested. Final digestion and nutrient absorption occur in the small intestine over a period of 5 to 6 hours. In 12 to 24 hours, any undigested material passes through the large intestine, and feces are expelled through the anus. The oral cavity, pharynx, and esophagus initiate food processing. Both physical and chemical digestion of food begins in the mouth. o During chewing, teeth of various shapes cut, smash, and grind food, making it easier to swallow and increasing its surface area. o The presence of food in the oral cavity triggers a nervous reflex that causes the salivary glands to deliver saliva through ducts to the oral cavity. o Salivation may occur in anticipation because of learned associations between eating and the time of day, cooking odors, or other stimuli. Saliva contains a slippery glycoprotein called mucin, which protects the soft lining of the mouth from abrasion and lubricates the food for easier swallowing. o Saliva also contains buffers that help prevent tooth decay by neutralizing acid in the mouth. o Antibacterial agents in saliva kill many bacteria that enter the mouth with food. Chemical digestion of carbohydrates, a main source of chemical energy, begins in the oral cavity. o Saliva contains salivary amylase, an enzyme that hydrolyzes starch and glycogen into smaller polysaccharides and the disaccharide maltose. The tongue tastes food, manipulates it during chewing, and helps shape the food into a ball called a bolus. o During swallowing, the tongue pushes a bolus back into the oral cavity and into the pharynx. The pharynx, also called the throat, is a junction that opens to both the esophagus and the trachea (windpipe). o When we swallow, the top of the windpipe moves up so that its opening, the glottis, is blocked by a cartilaginous flap, the epiglottis. o This mechanism normally ensures that a bolus will be guided into the entrance of the esophagus and not directed down the windpipe. o When not swallowing, the esophageal sphincter muscles are contracted, the epiglottis is up, and the glottis is open, allowing airflow to the lungs. o When a food bolus reaches the pharynx, the larynx moves upward and the epiglottis tips over the glottis, closing off the trachea. o The esophageal sphincter relaxes and the bolus enters the esophagus. o In the meantime, the larynx moves downward and the trachea is opened, and peristalsis moves the bolus down the esophagus to the stomach. The esophagus conducts food from the pharynx down to the stomach by peristalsis. o The muscles at the very top of the esophagus are striated and, therefore, under voluntary control. o Involuntary waves of contraction by smooth muscles in the rest of the esophagus then take over. The stomach stores food and performs preliminary digestion. The stomach is located in the upper abdominal cavity, just below the diaphragm. o With accordion-like folds and a very elastic wall, the stomach can stretch to accommodate about 2 L of food and fluid, storing an entire meal. o The stomach also secretes a digestive fluid called gastric juice and mixes this secretion with the food by the churning action of the smooth muscles in the stomach wall. Gastric juice is secreted by the epithelium lining numerous deep pits in the stomach wall. o With a high concentration of hydrochloric acid, the pH of the gastric juice is about 2acidic enough to digest iron nails. This acid disrupts the extracellular matrix that binds cells together. It kills most bacteria that are swallowed with food. o Also present in gastric juice is pepsin, an enzyme that begins the hydrolysis of proteins. Pepsin, which works well in strongly acidic environments, breaks peptide bonds adjacent to specific amino acids, producing smaller polypeptides.

Pepsin is secreted in an inactive form called pepsinogen by specialized chief cells in gastric pits. Parietal cells, also in the pits, secrete hydrochloric acid that converts pepsinogen to the active pepsin only when both reach the lumen of the stomach, minimizing self-digestion. In a positive-feedback system, activated pepsin can activate more pepsinogen molecules. The stomachs second line of defense against self-digestion is a coating of mucus, secreted by epithelial cells, that protects the stomach lining. o Still, the epithelium is continually eroded, and the epithelium is completely replaced by mitosis every three days. o Gastric ulcers, lesions in the stomach lining, are caused by the acid-tolerant bacterium Heliobacter pylori. Ulcers are often treated with antibiotics. About every 20 seconds, the stomach contents are mixed by the churning action of smooth muscles. o You may feel hunger pangs when your empty stomach churns. Sensations of hunger are also associated with brain centers that monitor the bloods nutritional status and the levels of appetite-controlling hormones. o As a result of mixing and enzyme action, what begins in the stomach as a recently swallowed meal becomes a nutrient-rich broth known as acid chyme. Most of the time the stomach is closed off at either end. o The opening from the esophagus to the stomach, the cardiac orifice, normally dilates only when a bolus driven by peristalsis arrives. The occasional backflow of acid chyme from the stomach into the lower esophagus causes heartburn. o At the opening from the stomach to the small intestine is the pyloric sphincter, which helps regulate the passage of chyme into the intestine. A squirt at a time, it takes about 2 to 6 hours after a meal for the stomach to empty. The small intestine is the major organ of digestion and absorption. With a length of more than 6 m in humans, the small intestine is the longest section of the alimentary canal. Most of the enzymatic hydrolysis of food macromolecules and most of the absorption of nutrients into the blood occurs in the small intestine. In the first 25 cm or so of the small intestine, the duodenum, acid chyme from the stomach mixes with digestive juices from the pancreas, liver, gall bladder, and gland cells of the intestinal wall. o The pancreas produces several hydrolytic enzymes and an alkaline solution rich in bicarbonate that buffers the acidity of the chyme from the stomach. o Pancreatic enzymes include protein-digesting enzymes (proteases) that are secreted into the duodenum in inactive form. The pancreatic proteases are activated once they are in the extracellular space within the duodenum. The liver performs a wide variety of important functions in the body, including the production of bile. o Bile is stored in the gallbladder until needed. o It contains bile salts that act as detergents that aid in the digestion and absorption of fats. o Bile also contains pigments that are by-products of red blood cell destruction in the liver. These bile pigments are eliminated from the body with the feces. The brush border of the epithelial lining of the duodenum produces several digestive enzymes. o Several enzymes are secreted into the lumen, while others are bound to the surface of the epithelial cells. Enzymatic digestion is completed as peristalsis moves the mixture of chyme and digestive juices along the small intestine. Most digestion is completed while the chyme is still in the duodenum. The remaining regions of the small intestine, the jejunum and ileum, function mainly in the absorption of nutrients and water. To enter the body, nutrients in the lumen must pass the lining of the digestive tract. A few nutrients are absorbed in the stomach and large intestine, but most absorption takes place in the small intestine. o The small intestine has a huge surface area300 m2, roughly the size of a tennis court. The enormous surface of the small intestine is an adaptation that greatly increases the rate of nutrient absorption. o Large circular folds in the lining bear fingerlike projections called villi, and each epithelial cell of a villus has many microscopic appendages called microvilli that are exposed to the intestinal lumen. o The microvilli are the basis of the term brush border for the intestinal epithelium. Penetrating the core of each villus is a net of microscopic blood vessels (capillaries) and a single vessel of the lymphatic system called a lacteal. o Nutrients are absorbed across the intestinal epithelium and then across the unicellular epithelium of capillaries or lacteals. o Only these two single layers of epithelial cells separate nutrients in the lumen of the intestine from the bloodstream. In some cases, transport of nutrients across the epithelial cells is passive, as molecules move down their concentration gradients from the lumen of the intestine into the epithelial cells, and then into capillaries. o Fructose, a simple sugar, moves by diffusion alone down its concentration gradient from the lumen of the intestine into the epithelial cells and then into capillaries. Amino acids and sugars pass through the epithelium, enter capillaries, and are carried away from the intestine by the bloodstream. o

Glycerol and fatty acids absorbed by epithelial cells are recombined into fats. o The fats are mixed with cholesterol and coated with special proteins to form small globules called chylomicrons. o Chylomicrons are transported by exocytosis out of epithelial cells and into lacteals. o The lacteals converge into the larger vessels of the lymphatic system, eventually draining into large veins that return blood to the heart. o The capillaries and veins that drain nutrients away from the villi converge into the hepatic portal vein, which leads directly to the liver. Therefore, the liver, which has the metabolic versatility to interconvert various organic molecules, has first access to amino acids and sugars absorbed after a meal is digested. The liver modifies and regulates this varied mix before releasing materials back into the bloodstream. o For example, the liver helps regulate the levels of glucose in the blood, ensuring that blood exiting the liver usually has a glucose concentration very close to 0.1%, regardless of carbohydrate content of the meal. From the liver, blood travels to the heart, which pumps the blood and nutrients to all parts of the body. Reclaiming water is a major function of the large intestine. The large intestine, or colon, is connected to the small intestine at a T-shaped junction where a sphincter controls the movement of materials. o One arm of the T is a pouch called the cecum. o The relatively small cecum of humans has a fingerlike extension, the appendix, which makes a minor contribution to body defense. o The main branch of the human colon is shaped like an upside-down U, about 1.5 m long. A major function of the colon is to recover water that has entered the alimentary canal as the solvent to various digestive juices. o About 7 L of fluid are secreted into the lumen of the digestive tract of a person each day. o More than 90% of the water is reabsorbed, most in the small intestine, the rest in the colon. o Digestive wastes, the feces, become more solid as they are moved along the colon by peristalsis. o Movement in the colon is sluggish, requiring 12 to 24 hours for material to travel the length of the organ. o If the lining of the colon is irritated by a bacterial infection, less water than usual is resorbed, resulting in diarrhea. If insufficient water is absorbed because peristalsis moves the feces too slowly, the result is constipation. Living in the large intestine is a rich flora of mostly harmless bacteria. o One of the most common inhabitants of the human colon is Escherichia coli, a favorite research organism. o As a by-product of their metabolism, many colon bacteria generate gases, including methane and hydrogen sulfide. o Some bacteria produce vitamins, including biotin, folic acid, vitamin K, and several B vitamins, which supplement our dietary intake of vitamins. Feces contain masses of bacteria and undigested materials including cellulose. o Although cellulose fibers have no caloric value to humans, their presence in the diet helps move food along the digestive tract. The terminal portion of the colon is called the rectum, where feces are stored until they can be eliminated. o Between the rectum and the anus are two sphincters, one involuntary and one voluntary. o Once or more each day, strong contractions of the colon create an urge to defecate. Concept 41.5 Evolutionary adaptations of vertebrate digestive systems are often associated with diet The digestive systems of mammals and other vertebrates are variations on a common plan. However, there are many intriguing variations, often associated with the animals diet. Dentition, an animals assortment of teeth, is one example of structural variation reflecting diet. o Particularly in mammals, evolutionary adaptation of teeth for processing different kinds of food is one of the major reasons that mammals have been so successful. Nonmammalian vertebrates generally have less specialized dentition, but there are exceptions. o For example, poisonous snakes, such as rattlesnakes, have fangs, modified teeth that inject venom into prey. Some snakes have hollow fangs, like syringes, while others drip poison along grooves in the tooth surface. All snakes have another important anatomic adaptation for feeding, the ability swallow large prey whole. o The lower jaw is loosely hinged to the skull by an elastic ligament that permits the mouth and throat to open very wide for swallowing. Large, expandable stomachs are common in carnivores, which may go for a long time between meals and, therefore, must eat as much as they can when they do catch prey. o For example, a 200-kg African lion can consume 40 kg of meat in one meal. The length of the vertebrate digestive system is also correlated with diet. In general, herbivores and omnivores have longer alimentary canals relative to their body sizes than do carnivores, providing more time for digestion and more surface areas for absorption of nutrients. Vegetation is more difficult to digest than meat because it contains cells walls. Symbiotic microorganisms help nourish many vertebrates. Much of the chemical energy in the diet of herbivorous animals is contained in the cellulose of plant cell walls. o However, animals do not produce enzymes that hydrolyze cellulose.

Many vertebrates (and termites) solve this problem by housing large populations of symbiotic bacteria and protists in special fermentation chambers in their alimentary canals. o These microorganisms do have enzymes that can digest cellulose to simple sugars that the animal can absorb. The location of symbiotic microbes in herbivores digestive tracts varies depending on the species. o The hoatzin, an herbivorous bird that lives in South American rain forests, has a large, muscular crop that houses symbiotic microorganisms. o Many herbivorous mammals, including horses, house symbiotic microorganisms in a large cecum, the pouch where the small and large intestines connect. o The symbiotic bacteria of rabbits and some rodents live in the large intestine and cecum. Since most nutrients are absorbed in the small intestine, these organisms recover nutrients from fermentation in the large intestine by eating some of their feces and passing food through a second time. o The koala also has an enlarged cecum, where symbiotic bacteria ferment finely shredded eucalyptus leaves. The most elaborate adaptations for a herbivorous diet have evolved in the ruminants, which include deer, cattle, and sheep. o When the cow first chews and swallows a mouthful of grass, boluses enter the rumen and the reticulum. Symbiotic bacteria and protists digest this cellulose-rich meal, secreting fatty acids. Periodically, the cow regurgitates and rechews the cud, which further breaks down the cellulose fibers. o The cow then reswallows the cud to the omasum, where water is removed. o The cud, with many microorganisms, passes to the abomasum for digestion by the cows enzymes.

Chapter 42 - Circulation and Gas Exchange Overview: Trading with the Environment Every organism must exchange materials and energy with its environment, and this exchange ultimately occurs at the cellular level. o Cells live in aqueous environments. o The resources that they need, such as nutrients and oxygen, move across the plasma membrane to the cytoplasm. o Metabolic wastes, such as carbon dioxide, move out of the cell. Most animals have organ systems specialized for exchanging materials with the environment, and many have an internal transport system that conveys fluid (blood or interstitial fluid) throughout the body. o For aquatic organisms, structures such as gills present an expansive surface area to the outside environment. o Oxygen dissolved in the surrounding water diffuses across the thin epithelium covering the gills and into a network of tiny blood vessels (capillaries). o At the same time, carbon dioxide diffuses out into the water. Concept 42.1 Circulatory systems reflect phylogeny Diffusion alone is not adequate for transporting substances over long distances in animalsfor example, for moving glucose from the digestive tract and oxygen from the lungs to the brain of a mammal. Diffusion is insufficient over distances of more than a few millimeters, because the time it takes for a substance to diffuse from one place to another is proportional to the square of the distance. o For example, if it takes 1 second for a given quantity of glucose to diffuse 100 microns, it will take 100 seconds for it to diffuse 1 mm and almost three hours to diffuse 1 cm. The circulatory system solves this problem by ensuring that no substance must diffuse very far to enter or leave a cell. The bulk transport of fluids throughout the body functionally connects the aqueous environment of the body cells to the organs that exchange gases, absorb nutrients, and dispose of wastes. o For example, in the mammalian lung, oxygen from inhaled air diffuses across a thin epithelium and into the blood, while carbon dioxide diffuses out. o Bulk fluid movement in the circulatory system, powered by the heart, quickly carries the oxygen-rich blood to all parts of the body. o As the blood streams through the tissues within microscopic vessels called capillaries, chemicals are exchanged between blood and the interstitial fluid that bathes the cells. Most invertebrates have a gastrovascular cavity or a circulatory system for internal transport. The body plan of a hydra and other cnidarians makes a circulatory system unnecessary. o A body wall only two cells thick encloses a central gastrovascular cavity that serves for both digestion and for diffusion of substances throughout the body. The fluid inside the cavity is continuous with the water outside through a single opening, the mouth. Thus, both the inner and outer tissue layers are bathed in fluid. In cnidarians such as Aurelia, the mouth leads to an elaborate gastrovascular cavity that has branches radiating to and from the circular canal. o The products of digestion in the gastrovascular cavity are directly available to the cells of the inner layer, and it is only a short distance to diffuse to the cells of the outer layer. Planarians and most other flatworms also have gastrovascular cavities that exchange materials with the environment through a single opening.

The flat shape of the body and the branching of the gastrovascular cavity throughout the animal ensure that cells are bathed in a suitable medium and that diffusion distances are short. For animals with many cell layers, gastrovascular cavities are insufficient for internal distances because the diffusion transports are too great. In more complex animals, two types of circulatory systems that overcome the limitations of diffusion have evolved: open circulatory systems and closed circulatory systems. o Both have a circulatory fluid (blood), a set of tubes (blood vessels), and a muscular pump (the heart). The heart powers circulation by using metabolic power to elevate the hydrostatic pressure of the blood (blood pressure), which then flows down a pressure gradient through its circuit back to the heart. In insects, other arthropods, and most molluscs, blood bathes organs directly in an open circulatory system. There is no distinction between blood and interstitial fluid, collectively called hemolymph. One or more hearts pump the hemolymph into interconnected sinuses surrounding the organs, allowing exchange between hemolymph and body cells. In insects and other arthropods, the heart is an elongated dorsal tube. o When the heart contracts, it pumps hemolymph through vessels out into sinuses. o When the heart relaxes, it draws hemolymph into the circulatory system through pores called ostia. o Body movements that squeeze the sinuses help circulate the hemolymph. In a closed circulatory system, found in earthworms, squid, octopuses, and vertebrates, blood is confined to vessels and is distinct from interstitial fluid. o One or more hearts pump blood into large vessels that branch into smaller ones coursing through organs. o Materials are exchanged by diffusion between the blood and the interstitial fluid bathing the cells. The fact that open and closed circulatory systems are both widespread in the animal kingdom suggests that both systems offer advantages. o The lower hydrostatic pressures associated with open circulatory systems make them less costly than closed circulatory systems. o Because they lack an extensive system of blood vessels, open systems require less energy to build and maintain. o In molluscs and freshly molted aquatic arthropods, the open circulatory system functions as a hydrostatic skeleton. What advantages are associated with closed circulatory systems? o Closed systems with their higher blood pressure are more effective at transporting circulatory fluids to meet the high metabolic demands of the tissues and cells of larger and more active animals. o Among the molluscs, only the large and active squid and octopuses have closed circulatory systems. Vertebrate phylogeny is reflected in adaptations of the cardiovascular system. The closed circulatory system of humans and other vertebrates is often called the cardiovascular system. The heart consists of one atrium or two atria, the chambers that receive blood returning to the heart, and one or two ventricles, the chambers that pump blood out of the heart. Arteries, veins, and capillaries are the three main kinds of blood vessels. o Arteries carry blood away from the heart to organs. o Within organs, arteries branch into arterioles, small vessels that convey blood to capillaries. o Capillaries with very thin, porous walls form networks called capillary beds, which infiltrate each tissue. o Chemicals, including dissolved gases, are exchanged across the thin walls of the capillaries between the blood and interstitial fluid. o At their downstream end, capillaries converge into venules, and venules converge into veins, which (usually) return blood to the heart. Arteries and veins are distinguished by the direction in which they carry blood, not by the characteristics of the blood they carry. o All arteries carry blood from the heart toward capillaries. o Veins return blood to the heart from capillaries. A significant exception is the hepatic portal vein that carries blood from capillary beds in the digestive system to capillary beds in the liver. Metabolic rate is an important factor in the evolution of cardiovascular systems. o In general, animals with high metabolic rates have more complex circulatory systems and more powerful hearts than animals with low metabolic rates. o Similarly, the complexity and number of blood vessels in a particular organ are correlated with that organs metabolic requirements. o Perhaps the most fundamental differences in cardiovascular adaptations are associated with gill breathing in aquatic vertebrates compared with lung breathing in terrestrial vertebrates. A fish heart has two main chambers, one atrium and one ventricle. Blood is pumped from the ventricle to the gills (the gill circulation) where it picks up oxygen and disposes of carbon dioxide across the capillary walls. The gill capillaries converge into a vessel that carries oxygenated blood to capillary beds in the other organs (the systemic circulation) and back via veins to the atrium of the heart.

In fish, blood must pass through two capillary beds, the gill capillaries and systemic capillaries. o When blood flows through a capillary bed, blood pressurethe motive force for circulationdrops substantially. o Therefore, oxygen-rich blood leaving the gills flows to the systemic circulation quite slowly (although the process is aided by body movements during swimming). o This constrains the delivery of oxygen to body tissues and, hence, the maximum aerobic metabolic rate of fishes. Frogs and other amphibians have a three-chambered heart with two atria and one ventricle. o The ventricle pumps blood into a forked artery that splits the ventricles output into the pulmocutaneous and systemic circulations. The pulmocutaneous circulation leads to capillaries in the gas-exchange organs (the lungs and skin of a frog), where the blood picks up O2 and releases CO2 before returning to the hearts left atrium. o Most of the returning oxygen-rich blood is pumped into the systemic circulation, which supplies all body organs and then returns oxygen-poor blood to the right atrium via the veins. o This scheme, called double circulation, provides a vigorous flow of blood to the brain, muscles, and other organs because the blood is pumped a second time after it loses pressure in the capillary beds of the lung or skin. In the ventricle of the frog, some oxygen-rich blood from the lungs mixes with oxygen-poor blood that has returned from the rest of the body. o However, a ridge within the ventricle diverts most of the oxygen-rich blood from the left atrium into the systemic circuit and most of the oxygen-poor blood from the right atrium into the pulmocutaneous circuit. Nonbird reptiles also have double circulation with a pulmonary circuit (lungs) and a systemic circuit. o Turtles, snakes, and lizards have a three-chambered heart, although the ventricle is partially blocked by a septum, which results in even less mixing of oxygen-rich and oxygen-poor blood than in amphibians. o All reptiles except birds have two arteries leading from the heart to the systemic circuit, and arterial valves allow them to divert most of their blood from the pulmonary circuit to the systemic circuit. In crocodilians, birds, and mammals, the ventricle is completely divided into separate right and left chambers. o In this arrangement, the left side of the heart receives and pumps only oxygen-rich blood, while the right side handles only oxygen-poor blood. Double circulation restores pressure to the systemic circuit after blood has passed through the lung capillaries and prevents mixing of oxygen-rich and oxygen-poor blood. The evolution of a powerful four-chambered heart was an essential adaptation to support the endothermic way of life characteristic of birds and mammals. o Endotherms use about ten times as much energy as ectotherms of the same size. o Therefore, the endotherm circulatory system needs to deliver about ten times as much fuel and O2 to their tissues and remove ten times as much wastes and CO2. o Birds and mammals evolved from different reptilian ancestors, and their powerful four-chambered hearts evolved independentlyan example of convergent evolution. Concept 42.2 Double circulation in mammals depends on the anatomy and pumping cycle of the heart In the mammalian cardiovascular system, the pulmonary and system circuits operate simultaneously. o The two ventricles pump almost in unison. o While some blood is traveling in the pulmonary circuit, the rest of the blood is flowing in the systemic circuit. To trace the double circulation pattern of the mammalian cardiovascular system, well start with the pulmonary (lung) circuit. The pulmonary circuit carries blood from the heart to the lungs and back again. o The right ventricle pumps blood to the lungs via the pulmonary arteries. o As blood flows through capillary beds in the right and left lungs, it loads O2 and unloads CO2. o Oxygen-rich blood returns from the lungs via the pulmonary veins to the left atrium of the heart. o Next, the oxygen-rich blood flows to the left ventricle, as the ventricle opens and the atrium contracts. The left ventricle pumps oxygen-rich blood out to the body tissues through the systemic circuit. o Blood leaves the left ventricle via the aorta, which conveys blood to arteries leading throughout the body. The first branches from the aorta are the coronary arteries, which supply blood to the heart muscle. o The next branches lead to capillary beds in the head and arms. The aorta continues in a posterior direction, supplying oxygen-rich blood to arteries leading to arterioles and capillary beds in the abdominal organs and legs. Within the capillaries, blood gives up much of its O2 and picks up CO2 produced by cellular respiration. Venous return to the right side of the heart begins as capillaries rejoin to form venules and then veins. o Oxygen-poor blood from the head, neck, and forelimbs is channeled into a large vein called the anterior (or superior) vena cava. o Another large vein called the posterior (or inferior) vena cava drains blood from the trunk and hind limbs. o The two venae cavae empty their blood into the right atrium, from which the oxygen-poor blood flows into the right ventricle. The mammalian heart is located beneath the breastbone (sternum) and consists mostly of cardiac muscle. o The two atria have relatively thin walls and function as collection chambers for blood returning to the heart.

o The ventricles have thicker walls and contract much more strongly than the atria. A cardiac cycle is one complete sequence of pumping, as the heart contracts, and filling, as it relaxes and its chambers fill with blood. o The contraction phase is called systole, and the relaxation phase is called diastole. For a human at rest with a pulse of about 75 beats per minute, one complete cardiac cycle takes about 0.8 sec. o During the relaxation phase (atria and ventricles in diastole) lasting about 0.4 sec, blood returning from the large veins flows into atria and ventricles. o A brief period (about 0.1 sec) of atrial systole forces all the remaining blood out of the atria and into the ventricles. o During the remaining 0.3 sec of the cycle, ventricular systole pumps blood into the large arteries. Cardiac output is the volume of blood pumped per minute, and it depends on two factors: the rate of contraction or heart rate (number of beats per second) and stroke volume, the amount of blood pumped by the left ventricle in each contraction. o The average stroke volume for a human is about 75 mL. o The typical resting cardiac output, about 5.25 L/min, is equivalent to the total volume of blood in the human body. o Cardiac output can increase about fivefold during heavy exercise. o Heart rate can be measured indirectly by measuring your pulsethe rhythmic stretching of arteries caused by the pressure of blood pumped by the ventricles. Four valves in the heart, each consisting of flaps of connective tissue, prevent backflow and keep blood moving in the correct direction. o Between each atrium and ventricle is an atrioventricular (AV) valve, which keeps blood from flowing back into the atria when the ventricles contract. o The AV valves are anchored by strong fibers that prevent them from turning inside out. o Two sets of semilunar valves, one between the left ventricle and the aorta and the other between the right ventricle and the pulmonary artery, prevent backflow from these vessels into the ventricles while they are relaxing. The heart sounds we can hear with a stethoscope are caused by the closing of the valves. o The sound pattern is lub-dup, lub-dup, lub-dup. o The first heart sound (lub) is created by the recoil of blood against the closed AV valves. o The second sound (dup) is the recoil of blood against the semilunar valves. A defect in one or more of the valves causes a heart murmur, which may be detectable as a hissing sound when a stream of blood squirts backward through a valve. o Some people are born with heart murmurs. o Other murmurs are due to damage to the valves by infection. o Most heart murmurs do not reduce the efficiency of blood flow enough to warrant surgery. Because the timely delivery of oxygen to the bodys organs is critical for survival, several mechanisms have evolved to assure continuity and control of the heartbeat. o Certain cells of vertebrate cardiac muscle are self-excitable, meaning they contract without any signal from the nervous system. o Each cell has its own intrinsic contraction rhythm. o However, these cells are synchronized by the sinoatrial (SA) node, or pacemaker, which sets the rate and timing at which all cardiac muscle cells contract. o The SA node is located in the wall of the right atrium. Because the vertebrate heart has a pacemaker made up of specialized muscle tissues located within the heart itself, it is referred to as a myogenic heart. o In contrast, the pacemakers of most arthropod hearts originate in motor nerves arising from the outside, an arrangement called a neurogenic heart. The cardiac cycle is regulated by electrical impulses that radiate throughout the heart. o Cardiac muscle cells are electrically coupled by intercalated disks between adjacent cells. o The SA node generates electrical impulses, much like those produced by nerves that spread rapidly through the wall of the atria, making them contract in unison. The impulse from the SA node is delayed by about 0.1 sec at the atrioventricular (AV) node, the relay point to the ventricle, allowing the atria to empty completely before the ventricles contract. o Specialized muscle fibers called bundle branches and Purkinje fibers conduct the signals to the apex of the heart and throughout the ventricular walls. o This stimulates the ventricles to contract from the apex toward the atria, driving blood into the large arteries. The impulses generated during the heart cycle produce electrical currents that are conducted through body fluids to the skin. o Here, the currents can be detected by electrodes and recorded as an electrocardiogram (ECG or EKG). While the SA node sets the tempo for the entire heart, it is influenced by a variety of physiological cues. o Two sets of nerves affect heart rate, with one set speeding up the pacemaker and the other set slowing it down. Heart rate is a compromise regulated by the opposing actions of these two sets of nerves. o The pacemaker is also influenced by hormones. For example, epinephrine from the adrenal glands increases heart rate.

The rate of impulse generation by the pacemaker increases in response to increases in body temperature and with exercise. Concept 42.3 Physical principles govern blood circulation All blood vessels are built of similar tissues. The walls of both arteries and veins have three similar layers. o On the outside, a layer of connective tissue with elastic fibers allows the vessel to stretch and recoil. o A middle layer has smooth muscle and more elastic fibers. o Lining the lumen of all blood vessels, including capillaries, is an endothelium, a single layer of flattened cells that minimizes resistance to blood flow. Structural differences correlate with the different functions of arteries, veins, and capillaries. o Capillaries lack the two outer layers, and their very thin walls consist only of endothelium and its basement membrane, thus enhancing exchange. Arteries have thicker middle and outer layers than veins. o The thicker walls of arteries provide strength to accommodate blood pumped rapidly and at high pressure by the heart. o Their elasticity (elastic recoil) helps maintain blood pressure even when the heart relaxes. The thinner-walled veins convey blood back to the heart at low velocity and pressure. o Blood flows through the veins mainly because skeletal muscle contractions squeeze blood in veins. o Within larger veins, flaps of tissues act as one-way valves that allow blood to flow only toward the heart. Physical laws governing the movement of fluids through pipes affect blood flow and blood pressure. The observation that blood travels more than a thousand times faster in the aorta than in capillaries follows from the law of continuity, describing fluid movement through pipes. o If a pipes diameter changes over its length, a fluid will flow through narrower segments faster than it flows through wider segments because the volume of flow per second must be constant throughout the entire pipe. Each artery conveys blood to such an enormous number of capillaries that the total cross-sectional area is much greater in capillary beds than in any other part of the circulatory system. The resulting slow flow rate and thin capillary walls enhance the exchange of substances between the blood and interstitial fluid. As blood leaves the capillary beds and passes to venules and veins, it speeds up again as a result of the reduction in total cross-sectional area. Fluids exert a force called hydrostatic pressure against surfaces they contact, and it is that pressure that drives fluids through pipes. o Fluids always flow from areas of high pressure to areas of lower pressure. o Blood pressure, the hydrostatic force that blood exerts against vessel walls, is much greater in arteries than in veins and is highest in arteries when the heart contracts during ventricular systole, creating the systolic pressure. When you take your pulse by placing your fingers on your wrist, you can feel an artery bulge with each heartbeat. o The surge of pressure is partly due to the narrow openings of arterioles impeding the exit of blood from the arteries, the peripheral resistance. o Thus, when the heart contracts, blood enters the arteries faster than it can leave, and the vessels stretch from the pressure. o The elastic walls of the arteries snap back during diastole, but the heart contracts again before enough blood has flowed into the arterioles to completely relieve pressure in the arteries. o As a consequence of the elastic arteries working against peripheral resistance, there is substantial diastolic pressure even during diastole. Blood flows into arterioles and capillaries continuously. The arterial blood pressure of a healthy human oscillates between about 120 mm Hg at systole and less than 80 mm Hg at diastole. Blood pressure is determined partly by cardiac output and partly by peripheral resistance. o Contraction of smooth muscles in walls of arterioles constricts these vessels, increasing peripheral resistance and increasing blood pressure upstream in the arteries. o When the smooth muscles relax, the arterioles dilate, blood flow through arterioles increases, and pressure in the arteries falls. o Nerve impulses, hormones, and other signals control the arteriole wall muscles. o Stress, both physical and emotional, can raise blood pressure by triggering nervous and hormonal responses that will constrict blood vessels. Cardiac output is adjusted in concert with changes in peripheral resistance. o This coordination maintains adequate blood flow as the demands on the circulatory system change. o For example, during heavy exercise, arterioles in the working muscles dilate, admitting a greater flow of oxygenrich blood to the muscles and decreasing peripheral resistance. o At the same time, cardiac output increases, maintaining blood pressure and supporting the necessary increase in blood flow.

In large land animals, blood pressure is also affected by gravity. o In addition to the peripheral resistance, additional pressure is necessary to push blood to the level of the heart. o In a standing human, it takes an extra 27 mm of Hg pressure to move blood from the heart to the brain. o In an organism like a giraffe, this extra force is about 190 mm Hg (for a total of 250 mm Hg). o Special check valves and sinuses, as well as feedback mechanisms that reduce cardiac output, prevent this high pressure from damaging the giraffes brain when it puts its head down. By the time blood reaches the veins, its pressure is not affected much by the action of the heart. o The resistance of tiny arterioles and capillaries has dissipated the pressure generated by the pumping heart. o Rhythmic contractions of smooth muscles in the walls of veins and venules account for some movement of blood. o More important, the activity of skeletal muscles during exercise squeezes blood through the veins. o Also, inhalation changes pressure in the thoracic (chest) cavity, causing the venae cavae and other large veins near the heart to expand and fill with blood. Transfer of substances between the blood and the interstitial fluid occurs across the thin walls of capillaries. At any given time, only about 510% of the bodys capillaries have blood flowing through them. o Capillaries in the brain, heart, kidneys, and liver are usually filled to capacity, but in many other sites, the blood supply varies over times as blood is diverted. For example, after a meal, blood supply to the digestive tract increases. During strenuous exercise, blood is diverted from the digestive tract and supplied to skeletal muscles. Two mechanisms, both dependent on smooth muscles controlled by nerve signals and hormones, regulate the distribution of blood in capillary beds. o In one mechanism, contraction of the smooth muscle layer in the wall of an arteriole constricts the vessel, decreasing blood flow through it to a capillary bed. When the muscle layer relaxes, the arteriole dilates, allowing blood to enter the capillaries. o In the other mechanism, rings of smooth muscles, called precapillary sphincters because they are located at the entrance to capillary beds, control the flow of blood between arterioles and venules. o Some blood flows directly from arterioles to venules through thoroughfare channels that are always open. The exchange of substances between the blood and interstitial fluid that bathes the cells takes place across the thin endothelial walls of the capillaries. o Some substances are carried across endothelial cells in vesicles that form by endocytosis on one side and then release their contents by exocytosis on the other side. o Others simply diffuse between the blood and the interstitial fluid across cells or through the clefts between adjoining cells. Transport through these clefts occurs mainly by bulk flow due to fluid pressure. o Blood pressure within the capillary pushes fluid, containing water and small solutes, through the capillary clefts. This causes a net loss of fluid at the upstream end of the capillary. o Blood cells and most proteins in the blood are too large and remain in the capillaries. As blood proceeds along the capillary, blood pressure continues to drop and the capillary becomes hyperosmotic compared to the interstitial fluids. o The resulting osmotic gradient pulls water into the capillary by osmosis near the downstream end. o About 85% of the fluid that leaves the blood at the arterial end of the capillary bed reenters from the interstitial fluid at the venous end. o The remaining 15% is eventually returned to the blood by the vessels of the lymphatic system. The lymphatic system returns fluid to the blood and aids in body defense. Fluids and some blood proteins that leak from the capillaries into the interstitial fluid are returned to the blood via the lymphatic system. o Fluid enters this system by diffusing into tiny lymph capillaries intermingled among capillaries of the cardiovascular system. o Once inside the lymphatic system, the fluid is called lymph, with a composition similar to the interstitial fluid. o The lymphatic system drains into the circulatory system near the junction of the venae cavae with the right atrium. Lymph vessels, like veins, have valves that prevent the backflow of fluid toward the capillaries. o Rhythmic contraction of the vessel walls helps draw fluid into lymphatic capillaries. o Like veins, lymph vessels depend mainly on the movement of skeletal muscle to squeeze fluid toward the heart. Along lymph vessels are organs called lymph nodes. o The lymph nodes filter the lymph and attack viruses and bacteria. o Inside a lymph node is a honeycomb of connective tissue with spaces filled with white blood cells specialized for defense. When the body is fighting an infection, these cells multiply, and the lymph nodes become swollen. In addition to defending against infection and maintaining the volume and protein concentration of the blood, the lymphatic system transports fats from the digestive tract to the circulatory system. Concept 42.4 Blood is a connective tissue with cells suspended in plasma In invertebrates with open circulation, blood (hemolymph) is not different from interstitial fluid.

However, blood in the closed circulatory systems of vertebrates is a specialized connective tissue consisting of several kinds of cells suspended in a liquid matrix called plasma. The plasma includes the cellular elements (cells and cell fragments), which occupy about 45% of the blood volume, and transparent, straw-colored plasma. Plasma, about 55% of the blood volume, consists of water, ions, various plasma proteins, nutrients, waste products, respiratory gases, and hormones, while the cellular elements include red and white blood cells and platelets. o Blood plasma is about 90% water. Dissolved in the plasma are a variety of ions, sometimes referred to as blood electrolytes. o These are important in maintaining osmotic balance of the blood and help buffer the blood at a pH of about 7.4. o Also, proper functioning of muscles and nerves depends on the concentrations of key ions in the interstitial fluid, which reflects concentrations in the plasma. Bloods plasma proteins have many functions. o Collectively, they act as buffers against pH changes, help maintain osmotic balance, and contribute to the bloods viscosity. o Some specific proteins transport otherwise insoluble lipids in the blood. o Other proteinsthe immunoglobulins, or antibodieshelp combat viruses and other foreign agents that invade the body. o Fibrinogen proteins help plug leaks when blood vessels are injured. Blood plasma with clotting factors removed is called serum. Plasma carries a wide variety of substances in transit from one part of the body to another, including nutrients, metabolic wastes, respiratory gases, and hormones. Suspended in blood plasma are two classes of cells: red blood cells, which transport oxygen, and white blood cells, which function in defense. o A third cellular element, platelets, are pieces of cells that are involved in clotting. Red blood cells, or erythrocytes, are by far the most numerous blood cells. o Each cubic millimeter of blood contains 5 to 6 million red cells, 5,000 to 10,000 white blood cells, and 250,000 to 400,000 platelets. o There are about 25 trillion red blood cells in the bodys 5 L of blood. The main function of red blood cells, oxygen transport, depends on rapid diffusion of oxygen across the red blood cells plasma membranes. o Human erythrocytes are small biconcave disks, presenting a large surface area. o Mammalian erythrocytes lack nuclei, an unusual characteristic that leaves more space in the tiny cells for hemoglobin, the iron-containing protein that transports oxygen. o Red blood cells also lack mitochondria and generate ATP exclusively by anaerobic metabolism. An erythrocyte contains about 250 million molecules of hemoglobin. o Each hemoglobin molecule binds up to four molecules of O2, so one erythrocyte can transport a billion O2 molecules. As red blood cells pass through the capillary beds of lungs, gills, or other respiratory organs, oxygen diffuses into the erythrocytes and hemoglobin binds O2 and NO. o In the systemic capillaries, hemoglobin unloads oxygen, which then diffuses into body cells. o NO relaxes the capillary walls, allowing them to expand and helping deliver O2 to the cells. There are five major types of white blood cells, or leukocytes: monocytes, neutrophils, basophils, eosinophils, and lymphocytes. Their collective function is to fight infection. o For example, monocytes and neutrophils are phagocytes, which engulf and digest bacteria and debris from the bodys dead cells. o Lymphocytes develop into specialized B cells and T cells, which produce the immune response against foreign substances. o White blood cells spend most of their time outside the circulatory system, patrolling through interstitial fluid and the lymphatic system, fighting pathogens. o A microliter of human blood normally has about 5,000 to 10,000 leukocytes, but their numbers increase temporarily when the body is fighting infection. The third cellular element of blood, platelets, are fragments of cells about 2 to 3 microns in diameter. o They have no nuclei and originate as pinched-off cytoplasmic fragments of large cells in the bone marrow. o Platelets function in blood clotting. The cellular elements of blood wear out and are replaced constantly throughout a persons life. o For example, erythrocytes usually circulate for only about 3 to 4 months and are then destroyed by phagocytic cells in the liver and spleen. o Enzymes digest the old cells macromolecules, and the monomers are recycled. o Many of the iron atoms derived from hemoglobin in old red blood cells are incorporated into new hemoglobin molecules.

Erythrocytes, leukocytes, and platelets all develop from a single population of cells, pluripotent stem cells, in the red marrow of bones, particularly the ribs, vertebrae, breastbone, and pelvis. o Pluripotent means that these cells have the potential to differentiate into any type of blood cells or cells that produce platelets. o This population arises in the early embryo and renews itself while replenishing the blood with cellular elements. A negative-feedback mechanism, sensitive to the amount of oxygen reaching the tissues via the blood, controls erythrocyte production. o If the tissues do not produce enough oxygen, the kidney synthesizes and secretes a hormone called erythropoietin (EPO), which stimulates production of erythrocytes. o If blood is delivering more oxygen than the tissues can use, the level of erythropoietin is reduced, and erythrocyte production slows. Physicians use synthetic EPO to treat people with anemia, a condition of low hemoglobin levels. o Some athletes abuse EPO by injecting themselves with the drug to increase their erythrocyte levels. o This practice is known as blood doping. It is banned by the International Olympic Committee and other sports federations. Through a recent breakthrough in isolating and culturing pluripotent stem cells, researchers may soon have effective treatments for a number of human diseases, such as leukemia. o Individuals with leukemia have a cancerous line of stem cells that produce leukocytes. These cancerous cells crowd out cells that make red blood cells and produce an unusually high number of leukocytes, many of which are abnormal. o One strategy now being used experimentally for treating leukemia is to remove pluripotent stem cells from a patient, destroy the patients bone marrow, and restock it with noncancerous pluripotent cells. o As few as 30 of these cells can repopulate the bone marrow. Blood contains a self-sealing material that plugs leaks from cuts and scrapes. o A clot forms when the inactive form of the plasma protein fibrinogen is converted to fibrin, which aggregates into threads that form the framework of the clot. o The clotting mechanism begins with the release of clotting factors from platelets. o An inherited defect in any step of the clotting process causes hemophilia, a disease characterized by excessive bleeding from even minor cuts and bruises. o The clotting process begins when the endothelium of a vessel is damaged and connective tissue in the wall is exposed to blood. Platelets adhere to collagen fibers and release a substance that makes nearby platelets sticky. o The platelets form a plug. o The seal is reinforced by a clot of fibrin when vessel damage is severe. More than a dozen clotting factors have been discovered, and the mechanism is still not fully understood. A genetic mutation that affects any step of the clotting process causes hemophilia, a disease characterized by excessive bleeding from even minor cuts. Anticlotting factors in the blood normally prevent spontaneous clotting in the absence of injury. o Sometimes, platelets clump and fibrin coagulates within a blood vessel, forming a clot called a thrombus, and blocking the flow of blood. o These potentially dangerous clots are more likely to form in individuals with cardiovascular diseases, diseases of the heart and blood vessels. Cardiovascular diseases are the leading cause of death in the United States and most other developed nations. More than half of the deaths in the United States are caused by cardiovascular diseases, diseases of the heart and blood vessels. The tendency to develop cardiovascular disease is inherited to some extent, but lifestyle also plays a important role. o Nongenetic factors include smoking, lack of exercise, a diet rich in animal fat, and high levels of cholesterol in the blood. One measure of an individuals cardiovascular health or risk of arterial plaques can be gauged by the ratio of low-density lipoproteins (LDLs) to high-density lipoproteins (HDLs) in the blood. o LDL is associated with depositing of cholesterol in arterial plaques. o HDL may reduce cholesterol deposition. Exercise increases HDL concentration, while smoking increases LDL:HDL ratio. Healthy arteries have smooth inner linings that permit unimpeded blood flow. Deposition of cholesterol thickens and roughens this smooth lining. o Growths called plaques develop in the inner wall of the arteries, narrowing their bore and leading to a chronic cardiovascular disease known as atherosclerosis. o At plaque sites, the smooth muscle layer of an artery thickens abnormally and becomes infiltrated with fibrous connective tissue and lipids such as cholesterol. o The rough lining of an atherosclerotic artery encourages the adhesion of platelets, triggering the clotting process, and interfering with circulation.

Hypertension (high blood pressure) promotes atherosclerosis and increases the risk of heart disease and stroke. o Atherosclerosis raises blood pressure by narrowing the vessels and reducing their elasticity. o According to one hypothesis, high blood pressure causes chronic damage to the endothelium that lines the arteries, promoting plaque formation. o Hypertension is simple to diagnose and can usually be controlled by diet, exercise, medication, or a combination of these. A diastolic pressure over 90 is cause for concern, and extreme hypertension (200/100) courts disaster. As atherosclerosis progresses, arteries become more and more clogged and the threat of heart attack or stroke becomes much greater, but there may be warnings of this impending threat. o For example, if a coronary artery is partially blocked, a person may feel occasional chest pains, a condition known as angina pectoris. o This is a signal that part of the heart is not receiving enough blood, especially when the heart is laboring because of physical or emotional stress. However, many people with atherosclerosis experience no warning signs and are unaware of their disease until catastrophe strikes. o The final blow is usually a heart attack or stroke. o A heart attack is the death of cardiac muscle tissue resulting from prolonged blockage of one or more coronary arteries, the vessels that supply oxygen-rich blood to the heart. o A stroke is the death of nervous tissue in the brain. Heart attacks and strokes frequently result from a thrombus that clogs a coronary artery or an artery in the brain. A key process leading to the clogging of an artery is an inflammatory response triggered by the accumulation of LDLs in the inner lining of an artery. Such an inflammation can cause plaques to rupture, releasing fragments that form a thrombus. o The thrombus may originate at the site of blockage or it may develop elsewhere and be transported (now called an embolus) until it becomes lodged in an artery too narrow for it to pass. o Cardiac or brain tissue downstream of the blockage may die from oxygen deprivation. o If damage in the heart interrupts the conduction of electrical impulses through cardiac muscle, heart rate may change drastically or the heart may stop beating altogether. Still, the victim may survive if a heartbeat is restored by cardiopulmonary resuscitation (CPR) within a few minutes of the attack. The effects of a stroke and the individuals chance of survival depend on the extent and location of the damaged brain tissue. Concept 42.5 Gas exchange occurs across specialized respiratory surfaces Gas exchange is the uptake of molecular oxygen (O2) from the environment and the discharge of carbon dioxide (CO2) to the environment. o While often called respiration, this process is distinct from, but linked to, the production of ATP in cellular respiration. Gas exchange, in concert with the circulatory system, provides the oxygen necessary for aerobic cellular respiration and removes the waste product, carbon dioxide. The source of oxygen, the respiratory medium, is air for terrestrial animals and water for aquatic animals. o The atmosphere is about 21% O2 (by volume). o Dissolved oxygen levels in lakes, oceans, and other bodies of water vary considerably, but are always much less than an equivalent volume of air. The part of an animal where gases are exchanged with the environment is the respiratory surface. o Movements of CO2 and O2 across the respiratory surface occur entirely by diffusion. o The rate of diffusion is proportional to the surface area across which diffusion occurs, and inversely proportional to the square of the distance through which molecules must move. o Therefore, respiratory surfaces tend to be thin and have large areas, maximizing the rate of gas exchange. o In addition, the respiratory surface of terrestrial and aquatic animals must be moist to maintain the cell membranes. As a result, gases must dissolve in water before diffusing across respiratory surfaces. Because the respiratory surface must supply O2 and expel CO2 for the entire body, the structure of a respiratory surface depends mainly on the size of the organism, whether it lives in water or on land, and on its metabolic demands. o An endotherm requires a larger area of respiratory surface than a similar-sized ectotherm. Gas exchange occurs over the entire surface area of protists and other unicellular organisms. Similarly, for some relatively simple animals, such as sponges, cnidarians, and flatworms, the plasma membrane of every cell in the body is close enough to the outside environment for gases to diffuse in and out. However, in most animals, the bulk of the body lacks direct access to the respiratory medium. o The respiratory surface is a thin, moist epithelium, separating the respiratory medium from the blood or capillaries, which transport gases to and from the rest of the body. Some animals, such as earthworms and some amphibians, use the entire outer skin as a respiratory organ. o Just below the moist skin is a dense net of capillaries.

However, because the respiratory surface must be moist, the possible habitats of these animals are limited to water or damp places. o Animals that use their moist skin as their only respiratory organ are usually small and are either long and thin or flat in shape, with a high ratio of surface area to volume. For most other animals, the general body surface lacks sufficient area to exchange gases for the entire body. o The solution is a respiratory organ that is extensively folded or branched, enlarging the surface area for gas exchange. o Gills, tracheae, and lungs are the three most common respiratory organs. Gills are respiratory adaptations of most aquatic animals. Gills are outfoldings of the body surface that are suspended in water. In some invertebrates, such as sea stars, gills have a simple shape and are distributed over much of the body. Many segmented worms have flap-like gills that extend from each body segment, or long feathery gills clustered at the head or tail. The gills of clams, crayfish, and many other animals are restricted to a local body region. o The total surface area of gills is often much greater than that of the rest of the body. Water has both advantages and disadvantages as a respiratory medium. o There is no problem keeping the cell membranes of the respiratory surface moist, since the gills are surrounded by the aqueous environment. o However, O2 concentrations in water are low, especially in warmer and saltier environments. o Thus, gills must be very effective to obtain enough oxygen. Ventilation, which increases the flow of the respiratory medium over the respiratory surface, ensures that there is a strong diffusion gradient between the gill surface and the environment. o Without ventilation, a region of low O2 and high CO2 concentrations can form around the gill as it exchanges gas with the environment. o Crayfish and lobsters have paddle-like appendages that drive a current of water over their gills. o Fish gills are ventilated by a current of water that enters the mouth, passes through slits in the pharynx, flows over the gills, and exits the body. Because water is dense and contains little oxygen per unit volume, fishes must expend considerable energy in ventilating their gills. Gas exchange at the gill surface is enhanced by the opposing flows of water and blood at the gills. o This flow pattern is countercurrent exchange. o As blood moves through a gill capillary, it becomes more and more loaded with oxygen, but it simultaneously encounters water with even higher oxygen concentrations because it is just beginning its passage over the gills. o All along the gill capillary, there is a diffusion gradient favoring the transfer of oxygen from water to blood. o The countercurrent exchange mechanism is so efficient that the gills can remove more than 80% of the oxygen from water to blood. Gills are generally unsuited for an animal living on land. o An expansive surface of wet membrane exposed to air would lose too much water by evaporation. o In addition, the gills would collapse as their fine filaments, no longer supported by water, cling together, reducing surface area for exchange. o Most terrestrial animals have their respiratory surfaces within the body, opening to the atmosphere through narrow tubes. Tracheal systems and lungs are respiratory adaptations of terrestrial animals. As a respiratory medium, air has many advantages over water. o Air has a much higher concentration of oxygen. o Also, since O2 and CO2 diffuse much faster in air than in water, respiratory surfaces exposed to air do not have to be ventilated as thoroughly as gills. o When a terrestrial animal does ventilate, less energy is needed because air is far lighter and much easier to pump than water and much less volume needs to be breathed to obtain an equal amount of O2. Air does have problems as a respiratory medium. o The respiratory surface, which must be large and moist, continuously loses water to the air by evaporation. o This problem is greatly reduced by a respiratory surface folded into the body. The tracheal system of insects is composed of air tubes that branch throughout the body. o The largest tubes, called tracheae, open to the outside, and the finest branches extend to the surface of nearly every cell where gas is exchanged by diffusion across the moist epithelium that lines the terminal ends. o The open circulatory system does not transport oxygen and carbon dioxide. For a small insect, diffusion through the trachea brings in enough O2 and removes enough CO2 to support cellular respiration. o Larger insects with higher energy demands ventilate their tracheal systems with rhythmic body movements that compress and expand the air tubes like bellows. o An insect in flight has a very high metabolic rate, consuming 10 to 200 times more O2 than it does at rest.

Alternating contraction and relaxation of flight muscles compresses and expands the body, rapidly pumping air through the tracheal system. o The flight muscles are packed with mitochondria, and the tracheal tubes supply each with ample oxygen. Unlike branching tracheal systems, lungs are restricted to one location. o Because the respiratory surface of the lung is not in direct contact with all other parts of the body, the circulatory system transports gases between the lungs and the rest of the body. o Lungs have a dense net of capillaries just under the epithelium that forms the respiratory surface. o Lungs have evolved in spiders, terrestrial snails, and vertebrates. Among the vertebrates, amphibians have relatively small lungs that do not provide a large surface, and many lack lungs altogether. o They rely heavily on diffusion across other body surfaces, especially their moist skin, for gas exchange. In contrast, most reptiles (including all birds) and all mammals rely entirely on lungs for gas exchange. o Turtles may supplement lung breathing with gas exchange across moist epithelial surfaces in their mouth and anus. o Lungs and air-breathing have evolved in a few fish species (lungfishes) as adaptations to living in oxygen-poor water or to spending time exposed to air. In general, the size and complexity of lungs are correlated with an animals metabolic rate (and hence rate of gas exchange). o For example, the lungs of endotherms have a greater area of exchange surface than the lungs of similar-sized ectotherms. Located in the thoracic (chest) cavity, the lungs of mammals have a spongy texture and are honeycombed with a moist epithelium that functions as the respiratory surface. A system of branching ducts conveys air to the lungs. Air enters through the nostrils and is then filtered by hairs, warmed and humidified, and sampled for odors as it flows through the nasal cavity. o The nasal cavity leads to the pharynx, an intersection where the paths for air and food cross. o When food is swallowed, the larynx moves upward and tips the epiglottis over the glottis. o The rest of the time, the glottis is open, and air enters the upper part of the respiratory tract. The wall of the larynx is reinforced by cartilage. In most mammals, the larynx is adapted as a voice box in which vibrations of a pair of vocal cords produce sounds. These sounds are high-pitched when the vocal cords are stretched tight and vibrate rapidly and low-pitched when the cords are less tense and vibrate slowly. From the larynx, air passes into the trachea, or windpipe, whose shape is maintained by rings of cartilage. o The trachea forks into two bronchi, one leading into each lung. o Within the lung, each bronchus branches repeatedly into finer and finer tubes, called bronchioles. The epithelium lining the major branches of the respiratory tree is covered by cilia and a thin film of mucus. o The mucus traps dust, pollen, and other particulate contaminants, and the beating cilia move the mucus upward to the pharynx, where it is swallowed. At their tips, the tiniest bronchioles dead-end as a cluster of air sacs called alveoli. o Gas exchange occurs across the thin epithelium of the lungs millions of alveoli. o These have a total surface area of about 100 m2 in humans, sufficient to carry out gas exchange for the whole body. o Oxygen in the air entering the alveoli dissolves in the moist film and rapidly diffuses across the epithelium into a web of capillaries that surrounds each alveolus. o Carbon dioxide diffuses in the opposite direction. Concept 42.6 Breathing ventilates the lungs The process of breathing, the alternate inhalation and exhalation of air, ventilates lungs. A frog ventilates its lungs by positive pressure breathing. o During a breathing cycle, muscles lower the floor of the oral cavity, enlarging it and drawing in air through the nostrils. o With the nostrils and mouth closed, the floor of the oral cavity rises and air is forced down the trachea. o Elastic recoil of the lungs, together with compression of the muscular body wall, forces air back out of the lungs during exhalation. In contrast, mammals ventilate their lungs by negative pressure breathing. This works like a suction pump, pulling air instead of pushing it into the lungs. Muscle action changes the volume of the rib cage and the chest cavity, and the lungs follow suit. The lungs are enclosed by a double-walled sac, with the inner layer of the sac adhering to the outside of the lungs and the outer layer adhering to the wall of the chest cavity. o A thin space filled with fluid separates the two layers. o Because of surface tension, the two layers behave like two plates of glass stuck together by the adhesion and cohesion of a film of water. o The layers can slide smoothly past each other, but they cannot be pulled apart easily. o Surface tension couples movements of the lungs to movements of the rib cage.

Lung volume increases as a result of the contraction of the rib muscles and diaphragm, a sheet of skeletal muscle that forms the bottom wall of the chest cavity. o Contraction of the rib muscles expands the rib cage by pulling the ribs upward and the breastbone outward. o At the same time, the diaphragm contracts and descends like a piston. o These changes increase the lung volume, and as a result, air pressure within the alveoli becomes lower than atmospheric pressure. o Because air flows from higher pressure to lower pressure, air rushes into the respiratory system. During exhalation, the rib muscles and diaphragm relax. o This reduces lung volume and increases air pressure within the alveoli. o This forces air up the breathing tubes and out through the nostrils. Actions of the rib muscles and diaphragm account for changes in lung volume during shallow breathing, when a mammal is at rest. During vigorous exercise, other muscles of the neck, back, and chest further increase ventilation volume by raising the rib cage even more. In some species, rhythmic movements during running cause visceral organs, including the stomach and liver, to slide forward and backward in the body cavity with each stride. o This visceral pump further increases ventilation volume by adding to the piston-like action of the diaphragm. The volume of air an animal inhales and exhales with each breath is called tidal volume. o It averages about 500 mL in resting humans. The maximum tidal volume during forced breathing is the vital capacity, which is about 3.4 L and 4.8 L for college-age females and males, respectively. o The lungs hold more air than the vital capacity, but some air, the residual volume, remains in the lungs because the alveoli do not completely collapse. Since the lungs do not completely empty and refill with each breath cycle, newly inhaled air is mixed with oxygen-depleted residual air. o Therefore, the maximum oxygen concentration in the alveoli is considerably less than in the atmosphere. o Although this limits the effectiveness of gas exchange, the carbon dioxide in residual air is critical for regulating the pH of blood and breathing rate in mammals. Ventilation is much more complex in birds than in mammals. o Besides lungs, birds have eight or nine air sacs that do not function directly in gas exchange, but act as bellows that keep air flowing through the lungs. The entire systemlungs and air sacsis ventilated when the bird breathes. o Air flows through the interconnected system in a circuit that passes through the lungs in one direction only, regardless of whether the bird is inhaling or exhaling. o Instead of alveoli, which are dead ends, the sites of gas exchange in bird lungs are tiny channels called parabronchi, through which air flows in one direction. This system completely exchanges the air in the lungs with every breath. o Therefore, the maximum lung oxygen concentrations are higher in birds than in mammals. o Partly because of this efficiency advantage, birds perform much better than mammals at high altitude. For example, while human mountaineers experience tremendous difficulty obtaining oxygen when climbing Earths highest peaks, several species of birds easily fly over the same mountains during migration at altitudes of 9,000 m or more. Control centers in the brain regulate the rate and depth of breathing. While we can voluntarily hold our breath or breathe faster and deeper, most of the time autonomic mechanisms regulate our breathing. This ensures that the work of the respiratory system is coordinated with that of the cardiovascular system, and with the bodys metabolic demands for gas exchange. Our breathing control centers are located in two brain regions, the medulla oblongata and the pons. o Aided by the control center in the pons, the medullas center sets basic breathing rhythm, triggering contraction of the diaphragm and rib muscles. o A negative-feedback mechanism via stretch receptors prevents our lungs from overexpanding by inhibiting the breathing center in the medulla. The medullas control center monitors the CO2 level of the blood and regulates breathing activity appropriately. o Its main cues about CO2 concentration come from slight changes in the pH of the blood and cerebrospinal fluid bathing the brain. Carbon dioxide reacts with water to form carbonic acid, which lowers the pH. When the control center registers a slight drop in pH, it increases the depth and rate of breathing, and the excess CO2 is eliminated in exhaled air. Oxygen concentrations in the blood usually have little effect of the breathing control centers.

However, when the O2 level is severely depressedat high altitudes, for exampleO2 sensors in the aorta and carotid arteries in the neck send alarm signals to the breathing control centers, which respond by increasing breathing rate. o Normally, a rise in CO2 concentration is a good indicator of a fall in O2 concentrations because these are linked by the same process, cellular respiration. o However, deep, rapid breathing (hyperventilation) purges the blood of so much CO2 that the breathing center temporarily ceases sending impulses to the rib muscles and diaphragm. The breathing center responds to a variety of nervous and chemical signals and adjusts the rate and depth of breathing to meet the changing demands of the body. o However, breathing control is only effective if it is coordinated with control of the circulatory system, so that there is a good match between lung ventilation and the amount of blood flowing through alveolar capillaries. o For example, during exercise, cardiac output is matched to the increased breathing rate, which enhances O2 uptake and CO2 removal as blood flows through the lungs. Concept 42.7 Respiratory pigments bind and transport gases Gases diffuse down pressure gradients in the lungs and other organs. For a gas, whether present in air or dissolved in water, diffusion depends on differences in a quantity called partial pressure, the contribution of a particular gas to the overall total. o At sea level, the atmosphere exerts a total pressure of 760 mm Hg. o Since the atmosphere is 21% oxygen (by volume), the partial pressure of oxygen is 0.21 760, or about 160 mm Hg. o The partial pressure of CO2 is only 0.23 mm Hg. When water is exposed to air, the amount of a gas that dissolves in water is proportional to its partial pressure in the air and its solubility in water. o An equilibrium is eventually reached when gas molecules enter and leave the solution at the same rate. o At this point, the gas is said to have the same partial pressure in the solution as it does in the air. o Thus, in a glass of water exposed to air at sea-level air pressure, the partial pressure of O2 is 160 mm Hg and the partial pressure of CO2 is 0.23 mm Hg. A gas will always diffuse from a region of higher partial pressure to a region of lower partial pressure. Blood arriving at the lungs via the pulmonary arteries has a lower partial pressure of O2 and a higher partial pressure of CO2 than the air in the alveoli. o As blood enters the alveolar capillaries, CO2 diffuses from blood to the air within the alveoli, and oxygen in the alveolar air dissolves in the fluid that coats the epithelium and diffuses across the surface into the blood. o By the time blood leaves the lungs in the pulmonary veins, its partial pressure of O2 has been raised and its partial pressure of CO2 has been lowered. In the tissue capillaries, gradients of partial pressure favor the diffusion of oxygen out of the blood and carbon dioxide into the blood. o Cellular respiration removes oxygen from and adds carbon dioxide to the interstitial fluid by diffusion. o After the blood unloads oxygen and loads carbon dioxide, it is returned to the heart and pumped to the lungs again, where it exchanges gases with air in the alveoli. The low solubility of oxygen in water is a fundamental problem for animals that rely on the circulatory systems for oxygen delivery. o For example, a person exercising consumes almost 2 L of O2 per minute, but at normal body temperature and air pressure, only 4.5 mL of O2 can dissolve in a liter of blood in the lungs. o If 80% of the dissolved O2 were delivered to the tissues (an unrealistically high percentage), the heart would need to pump 500 L of blood per minutea ton every 2 minutes. In fact, most animals transport most of the O2 bound to special proteins called respiratory pigments instead of dissolved in solution. o Respiratory pigments, often contained within specialized cells, circulate with the blood. o The presence of respiratory pigments increases the amount of oxygen that can be carried in the blood to about 200 mL of O2 per liter of blood. o For our exercising individual, the cardiac output would need to be a manageable 12.5 L of blood per minute to meet the oxygen demands of the systemic system. A diversity of respiratory pigments has evolved in various animal taxa to support their normal energy metabolism. o One example, hemocyanin, found in the hemolymph of arthropods and many molluscs, has copper as its oxygenbinding component, coloring the blood bluish. o The respiratory pigment of almost all vertebrates is the protein hemoglobin, contained within red blood cells. Hemoglobin consists of four subunits, each with a cofactor called a heme group that has an iron atom at its center. Because iron actually binds the O2, each hemoglobin molecule can carry four molecules of O2. o Like all respiratory pigments, hemoglobin must bind oxygen reversibly, loading oxygen at the lungs or gills and unloading it in other parts of the body. Loading and unloading depend on cooperation among the subunits of the hemoglobin molecule.

The binding of O2 to one subunit induces the remaining subunits to change their shape slightly such that their affinity for oxygen increases. When one subunit releases O2, the other three quickly follow suit as a conformational change lowers their affinity for oxygen. o Cooperative oxygen binding and release is evident in the dissociation curve for hemoglobin. o Where the dissociation curve has a steep slope, even a slight change in PO2 causes hemoglobin to load or unload a substantial amount of O2. This steep part corresponds to the range of partial pressures found in body tissues. Because of the effect of subunit cooperativity, a slight drop in PO2 causes a relatively large increase in the amount of oxygen the blood unloads. o As in all proteins, hemoglobins conformation is sensitive to a variety of factors. o For example, a drop in pH lowers the affinity of hemoglobin for O2, an effect called the Bohr shift. o Because CO2 reacts with water to form carbonic acid, an active tissue will lower the pH of its surroundings and induce hemoglobin to release more oxygen. o In addition to oxygen transport, hemoglobin also helps transport carbon dioxide and assists in buffering blood pH. About 7% of the CO2 released by respiring cells is transported in solution. Another 23% binds to amino groups of hemoglobin. About 70% is transported as bicarbonate ions. o Carbon dioxide from respiring cells diffuses into the blood plasma and then into red blood cells. The CO2 first reacts with water, assisted by the enzyme carbonic anhydrase, to form H2CO3, which then dissociates into a hydrogen ion H+ and a bicarbonate ion (HCO3?) Most of the H+ attaches to hemoglobin and other proteins, minimizing the change in blood pH. The HCO3? diffuses into the plasma. o As blood flows through the lungs, the process is rapidly reversed as diffusion of CO2 out of the blood shifts the chemical equilibrium in favor of the conversion of HCO3? to CO2. Elite animal athletes have adaptations that allow them to meet extreme oxygen demands. o The elite animal marathon runner may be the antelope-like pronghorn that has roamed the grasslands of North America for 4 million years. Pronghorns can run as fast as 100 km/hr, a speed second only to the cheetah. Pronghorns can sustain high speeds over long distances, unlike the cheetah. o Stan Lindstedt and colleagues at the University of Wyoming and University of Bern explored how pronghorns sustain their combination of great speed and great endurance: through enhancements that supply increased oxygen to muscles, or through greater energetic efficiency? o Pronghorns consume O2 at a rate three times the rate expected for an animal of their size. o The rate of O2 consumption per gram of tissue by a pronghorn is the same as a mouse. The research team compared various physiological characteristics of pronghorns with similar-sized domestic goats, which are adapted to climbing rather than running. The maximum rate of O2 consumption by pronghorns is five times that of goats. o Why? Pronghorns have a larger surface area for diffusion in the lungs, nearly five times the cardiac output, much higher muscle mass, and a higher volume and density of mitochondria than goats. o In addition, pronghorns maintain higher muscle temperatures. The pronghorns extreme O2 consumption rate, which underlies their ability to run at high speeds over long distances, results from enhancements of the normal physiological mechanisms present in other animals. o These enhancements are the result of natural selection, perhaps exerted by the predators that chased pronghorns on the open plains of North America for millions of years. When an air-breathing animal swims underwater, it lacks access to its normal respiratory medium. o Most humans can hold their breath for only 2 to 3 minutes and swim to depths of 20 m or so. o However, a variety of seals, sea turtles, and whales can stay submerged for much longer times and reach much greater depths. The Weddell seal of Antarctica can plunge to depths of 200500 m and remain there from 20 minutes to more than an hour. o Elephant seals can dive to 1,500 m and stay submerged for up to 2 hours. One adaptation of these deep-divers, such as the Weddell seal, is an ability to store large amounts of O2 in the tissues. o Compared to a human, a seal can store about twice as much O2 per kilogram of body weight, mostly in the blood and muscles. o About 36% of our total O2 is in our lungs, and 51% is in our blood. o In contrast, the Weddell seal holds only about 5% of its O2 in its small lungs and stockpiles 70% in the blood. Several adaptations create these physiological differences between the seal and other deep-divers in comparison to humans. o First, the seal has about twice the volume of blood per kilogram of body weight as a human. o Second, the seal can store a large quantity of oxygenated blood in its huge spleen, releasing this blood after the dive begins. The spleen can store about 24 L of blood. o Third, diving mammals have a high concentration of an oxygen-storing protein called myoglobin in their muscles.

This enables a Weddell seal to store about 25% of its O2 in muscle, compared to only 13% in humans. Diving vertebrates not only start a dive with a relatively large O2 stockpile, but they also have adaptations that conserve O2. o They swim with little muscular effort and often use buoyancy changes to glide passively upward or downward. o Their heart rate and O2 consumption rate decrease during the dive, and most blood is routed to the brain, spinal cord, eyes, adrenal glands, and placenta (in pregnant seals). o Blood supply is restricted or even shut off to the muscles, and the muscles can continue to derive ATP from fermentation after their internal O2 stores are depleted. o During dives of more than 20 minutes, a Weddell seals muscles deplete the O2 stored in myoglobin and then derive ATP from fermentation instead of respiration.

Chapter 43 - The Immune System Overview: Reconnaissance, Recognition, and Response An animal must defend itself against unwelcome intrudersthe many potentially dangerous viruses, bacteria, and other pathogens it encounters in the air, in food, and in water. It must also deal with abnormal body cells, which, in some cases, may develop into cancer. Two major kinds of defense have evolved to counter these threats. The first kind of defense is innate immunity. o Innate defenses are largely nonspecific, responding to a broad range of microbes. o Innate immunity consists of external barriers formed by the skin and mucous membranes, plus a set of internal cellular and chemical defenses that defend against microbes that breach the external barriers. o The internal defenses include macrophages and other phagocytic cells that ingest and destroy pathogens. A second kind of defense is acquired immunity. o Acquired immunity develops only after exposure to microbes, abnormal body cells, or other foreign substances. o Acquired defenses are highly specific and can distinguish one inducing agent from another. o This recognition is achieved by white blood cells called lymphocytes, which produce two general types of immune responses. In the humoral response, cells derived from B-lymphocytes secrete defensive proteins called antibodies that bind to microbes and target them for elimination. In the cell-mediated response, cytotoxic lymphocytes directly destroy infected body cells, cancer cells, or foreign tissue. Concept 43.1 Innate immunity provides broad defenses against infection An invading microbe must penetrate the external barrier formed by the skin and mucous membranes, which cover the surface and line the openings of an animals body. If it succeeds, the pathogen encounters the second line of nonspecific defense, innate cellular and chemical mechanisms that defend against the attacking foreign cell. The skin and mucous membrane provide first-line barriers to infection. Intact skin is a barrier that cannot normally be penetrated by bacteria or viruses, although even minute abrasions may allow their passage. Likewise, the mucous membranes that line the digestive, respiratory, and genitourinary tracts bar the entry of potentially harmful microbes. o Cells of these mucous membranes produce mucus, a viscous fluid that traps microbes and other particles. o In the trachea, ciliated epithelial cells sweep out mucus with its trapped microbes, preventing them from entering the lungs. Beyond their role as a physical barrier, the skin and mucous membranes counter pathogens with chemical defenses. o In humans, for example, secretions from sebaceous and sweat glands give the skin a pH ranging from 3 to 5, which is acidic enough to prevent colonization by many microbes. o Microbial colonization is also inhibited by the washing action of saliva, tears, and mucous secretions that continually bathe the exposed epithelium. All these secretions contain antimicrobial proteins. One of these, the enzyme lysozyme, digests the cell walls of many bacteria, destroying them. Microbes present in food or water, or those in swallowed mucus, must contend with the highly acidic environment of the stomach. o The acid destroys many microbes before they can enter the intestinal tract. o One exception, the virus hepatitis A, can survive gastric acidity and gain access to the body via the digestive tract. Phagocytic cells and antimicrobial proteins function early in infection. Microbes that penetrate the first line of defense face the second line of defense, which depends mainly on phagocytosis, the ingestion of invading organisms by certain types of white cells. Phagocyte function is intimately associated with an effective inflammatory response and also with certain antimicrobial proteins. Phagocytes attach to their prey via surface receptors found on microbes but not normal body cells.

After attaching to the microbe, a phagocyte engulfs it, forming a vacuole that fuses with a lysosome. o Microbes are destroyed within lysosomes in two ways. Lysosomes contain nitric oxide and other toxic forms of oxygen, which act as potent antimicrobial agents. Lysozymes and other enzymes degrade mitochondrial components. Some microbes have adaptations that allow them to evade destruction by phagocytes. o The outer capsule of some bacterial cells hides their surface polysaccharides and prevents phagocytes from attaching to them. o Other bacteria are engulfed by phagocytes but resist digestion, growing and reproducing within the cells. Four types of white blood cells are phagocytic. The phagocytic cells called neutrophils constitute about 6070% of all white blood cells (leukocytes). o Cells damaged by invading microbes release chemical signals that attract neutrophils from the blood. o The neutrophils enter the infected tissue, engulfing and destroying microbes there. o Neutrophils tend to self-destruct as they destroy foreign invaders, and their average life span is only a few days. Monocytes, about 5% of leukocytes, provide an even more effective phagocytic defense. o After a few hours in the blood, they migrate into tissues and develop into macrophages, which are large, long-lived phagocytes. o Some macrophages migrate throughout the body, while others reside permanently in certain tissues, including the lungs, liver, kidneys, connective tissues, brain, and especially in lymph nodes and the spleen. The fixed macrophages in the spleen, lymph nodes, and other lymphatic tissues are particularly well located to contact infectious agents. o Microbes that enter the blood become trapped in the spleen, while microbes in interstitial fluid flow into lymph and are trapped in lymph nodes. o In either location, microbes soon encounter resident macrophages. Eosinophils, about 1.5% of all leukocytes, contribute to defense against large parasitic invaders, such as the blood fluke, Schistosoma mansoni. o Eosinophils position themselves against the external wall of a parasite and discharge destructive enzymes from cytoplasmic granules. Dendritic cells can ingest microbes like macrophages. However, their primary role is to stimulate the development of acquired immunity. A variety of proteins function in innate defense either by attacking microbes directly or by impeding their reproduction. o In addition to lysozyme, other antimicrobial agents include about 30 serum proteins, known collectively as the complement system. Substances on the surface of many microbes can trigger a cascade of steps that activate the complement system, leading to lysis of microbes. Another set of proteins that provide innate defenses are the interferons, which defend against viral infection. o These proteins are secreted by virus-infected body cells and induce uninfected neighboring cells to produce substances that inhibit viral reproduction. o Interferon limits cell-to-cell spread of viruses, helping to control viral infection. o Because they are nonspecific, interferons produced in response to one virus may confer short-term resistance to unrelated viruses. o One type of interferon activates phagocytes. o Interferons can be produced by recombinant DNA technology and are being tested for the treatment of viral infections and cancer. Damage to tissue by a physical injury or the entry of microbes leads to the release of chemical signals that trigger a localized inflammatory response. One of the chemical signals of the inflammatory response is histamine, which is stored in mast cells in connective tissues. o When injured, mast cells release their histamine. o Histamine triggers both dilation and increased permeability of nearby capillaries. o Leukocytes and damaged tissue cells also discharge prostaglandins and other substances that promote blood flow to the site of injury. o Increased local blood supply leads to the characteristic swelling, redness, and heat of inflammation. o Blood-engorged leak fluid into neighboring tissue, causing swelling. Enhanced blood flow and vessel permeability have several effects. o First, they aid in delivering clotting elements to the injured area. Clotting marks the beginning of the repair process and helps block the spread of microbes elsewhere. o Second, increased blood flow and vessel permeability increase the migration of phagocytic cells from the blood into the injured tissues. Phagocyte migration usually begins within an hour after injury. Chemokines secreted by many cells, including blood vessel endothelial cells and monocytes, attract phagocytes to the area. The body may also mount a systemic response to severe tissue damage or infection. o Injured cells secrete chemicals that stimulate the release of additional neutrophils from the bone marrow.

In a severe infection, the number of white blood cells may increase significantly within hours of the initial inflammation. o Another systemic response to infection is fever, which may occur when substances released by activated macrophages set the bodys thermostat at a higher temperature. Moderate fever may facilitate phagocytosis and hasten tissue repair. Certain bacterial infections can induce an overwhelming systemic inflammatory response leading to a condition known as septic shock. o Characterized by high fever and low blood pressure, septic shock is the most common cause of death in U.S. critical care units. o Clearly, while local inflammation is an essential step toward healing, widespread inflammation can be devastating. Natural killer (NK) cells do not attack microorganisms directly but destroy virus-infected body cells. o They also attack abnormal body cells that could become cancerous. o NK cells attach to a target cell and release chemicals that bring about apoptosis, or programmed cell death. To summarize the nonspecific defense systems, the first line of defense, the skin and mucous membranes, prevents most microbes from entering the body. The second line of defense uses phagocytes, natural killer cells, inflammation, and antimicrobial proteins to defend against microbes that have managed to enter the body. These two lines of defense are nonspecific in that they do not distinguish among pathogens. Invertebrates also have highly effective innate defenses. Insect hemolymph contains circulating cells called hemocytes. o Some hemocytes can phagocytose microbes, while others can form a cellular capsule around large parasites. o Other hemocytes secrete antimicrobial peptides that bind to and destroy pathogens. Current evidence suggests that invertebrates lack cells analogous to lymphocytes, the white blood cells responsible for acquired, specific immunity in vertebrates. Certain invertebrate defenses do exhibit some features characteristic of acquired immunity. o Sponge cells can distinguish self from nonself cells. o Phagocytic cells of earthworms show immunological memory, responding more quickly to a particular foreign tissue the second time it is encountered. Concept 43.2 In acquired immunity, lymphocytes provide specific defenses against infection While microorganisms are under assault by phagocytic cells, the inflammatory response, and antimicrobial proteins, they inevitably encounter lymphocytes, the key cells of acquired immunity, the bodys second major kind of defense. As macrophages and dendritic cells phagocytose microbes, they secrete certain cytokines that help activate lymphocytes and other cells of the immune system. o Thus the innate and acquired defenses interact and cooperate with each other. Any foreign molecule that is recognized by and elicits a response from lymphocytes is called an antigen. o Most antigens are large molecules such as proteins or polysaccharides. o Most are cell-associated molecules that protrude from the surface of pathogens or transplanted cells. o A lymphocyte actually recognizes and binds to a small portion of an antigen called an epitope. Lymphocytes provide the specificity and diversity of the immune system. The vertebrate body is populated by two main types of lymphocytes: B lymphocytes (B cells) and T lymphocytes (T cells). o Both types of lymphocytes circulate throughout the blood and lymph and are concentrated in the spleen, lymph nodes, and other lymphatic tissue. B and T cells recognize antigens by means of antigen-specific receptors embedded in their plasma membranes. o A single B or T cell bears about 100,000 identical antigen receptors. Because lymphocytes recognize and respond to particular microbes and foreign molecules, they are said to display specificity for a particular epitope on an antigen. Each B cell receptor for an antigen is a Y-shaped molecule consisting of four polypeptide chains: two identical heavy chains and two identical light chains linked by disulfide bridges. o A region in the tail portion of the molecule, the transmembrane region, anchors the receptor in the cells plasma membrane. o A short region at the end of the tail extends into the cytoplasm. At the two tips of the Y-shaped molecules are the light- and heavy-chain variable (V) regions whose amino acid sequences vary from one B cell to another. The remainder of the molecule is made up of the constant (C) regions, which do not vary from cell to cell. Each B cell receptor has two identical antigen-binding sites formed from part of a heavy-chain V region and part of a lightchain V region. The interaction between an antigen-binding site and its corresponding antigen is stabilized by multiple noncovalent bonds. Secreted antibodies, or immunoglobulins, are structurally similar to B cell receptors but lack the transmembrane regions that anchor receptors in the cell membrane. o B cell receptors are often called membrane antibodies or membrane immunoglobulins.

Each T cell receptor for an antigen consists of two different polypeptide chains: an alpha chain and a beta chain, linked by a disulfide bridge. Near the base of the molecule is a transmembrane region that anchors the molecule in the cells plasma membrane. At the outer tip of the molecule, the alpha and beta chain variable (V) regions form a single antigen-binding site. The remainder of the molecule is made up of the constant (C) regions. T cell receptors recognize and bind with antigens with the same specificity as B cell receptors. However, while the receptors on B cells recognize intact antigens, the receptors on T cells recognize small fragments of antigens that are bound to normal cell-surface proteins called MHC molecules. MHC molecules are encoded by a family of genes called the major histocompatibility complex (MHC). As a newly synthesized MHC molecule is transported toward the plasma membrane, it binds with a fragment of antigen within the cell and brings it to the cell surface, a process called antigen presentation. There are two ways in which foreign antigens can end up inside cells of the body. o Depending on their source, peptide antigens are handled by a different class of MHC molecule and recognized by a particular subgroup of T cells. Class I MHC molecules, found on almost all nucleated cells of the body, bind peptides derived from foreign antigens that have been synthesized within the cell. ? Any body cell that becomes infected or cancerous can display such peptide antigens by virtue of its class I MHC molecules. ? Class I MHC molecules displaying bound peptide antigens are recognized by a subgroup of T cells called cytotoxic T cells. o Class II MHC molecules are made by dendritic cells, macrophages, and B cells. In these cells, class II MHC molecules bind peptides derived from foreign materials that have been internalized and fragmented by phagocytosis. For each vertebrate species, there are numerous different alleles for each class I and class II MHC gene, producing the most polymorphic proteins known. o As a result of the large number of different alleles in the human population, most of us are heterozygous for every one of our MHC genes. o Moreover, it is unlikely that any two people, except identical twins, will have exactly the same set of MHC molecules. o The MHC provides a biochemical fingerprint virtually unique to each individual that marks body cells as self. Lymphocyte development gives rise to an immune system that distinguishes self from nonself. Lymphocytes, like all blood cells, originate from pluripotent stem cells in the bone marrow or liver of a developing fetus. Early lymphocytes are all alike, but they later develop into T cells or B cells, depending on where they continue their maturation. Lymphocytes that migrate from the bone marrow to the thymus develop into T cells. Lymphocytes that remain in the bone marrow and continue their maturation there become B cells. There are three key events in the life of a lymphocyte. o The first two events take place as a lymphocyte matures, before it has contact with any antigen. o The third event occurs when a mature lymphocyte encounters and binds a specific antigen, leading to its activation, proliferation, and differentiationa process called clonal selection. The variable regions at the tip of each antigen receptor chain, which form the antigen-binding site, account for the diversity of lymphocytes. o The variability of these regions is enormous. o Each person has as many as a million different B cells and 10 million different T cells, each with a specific antigenbinding ability. At the core of lymphocyte diversity are the unique genes that encode the antigen receptor chains. o These genes consist of numerous coding gene segments that undergo random, permanent rearrangement, forming functional genes that can be expressed as receptor chains. o Genes for the light chain of the B cell receptor and for the alpha and beta chains of the T cell receptor undergo similar rearrangements, but we will consider only the gene coding for the light chain of the B cell receptor. o The immunoglobulin light-chain gene contains a series of 40 variable (V) gene segments separated by a long stretch of DNA from 5 joining (J) gene segments. o Beyond the J gene segments is an intron, followed by a single exon that codes for the constant region of the light chain. o In this state, the light-chain gene is not functional. o However, early in B cell development, a set of enzymes called recombinase link one V gene segment to one J gene segment, forming a single exon that is part V and part J. Recombinase acts randomly and can link any one of 40 V gene segments to any one of 5 J gene segments. For the light-chain gene, there are 200 possible gene products (20 V 5 J).

Once V-J rearrangement has occurred, the gene is transcribed and translated into a light chain with a variable and constant region. The light chains combine randomly with the heavy chains that are similarly produced. o The random rearrangements of antigen receptor genes may produce antigen receptors that are specific for the bodys own molecules. o As B and T cells mature, their antigen receptors are tested for potential self-reactivity. o Lymphocytes bearing receptors specific for molecules present in the body are either destroyed by apoptosis or rendered nonfunctional. Failure to do this can lead to autoimmune diseases such as multiple sclerosis. Antigens interact with specific lymphocytes, inducing immune responses and immunological memory. Although it encounters a large repertoire of B cells and T cells, a microorganism interacts only with lymphocytes bearing receptors specific for its various antigenic molecules. A lymphocyte is selected when it encounters a microbe with epitopes matching its receptors. o Selection activates the lymphocyte, stimulating it to divide and differentiate, and eventually to produce two clones of cells. o One clone consists of a large number of effector cells, short-lived cells that combat the same antigen. o The other clone consists of memory cells, long-lived cells bearing receptors for the same antigen. This antigen-driven cloning of lymphocytes is called clonal selection and is fundamental to acquired immunity. o Each antigen, by binding selectively to specific receptors, activates a tiny fraction of cells from the bodys diverse pool of lymphocytes. o This relatively small number of selected cells gives rise to clones of thousands of cells, all specific for and dedicated to eliminating that antigen. The selective proliferation and differentiation of lymphocytes that occur the first time the body is exposed to an antigen is the primary immune response. o About 10 to 17 days are required from the initial exposure for the maximum effector cell response. o During this period, selected B cells and T cells generate antibody-producing effector B cells called plasma cells, and effector T cells, respectively. o While this response is developing, a stricken individual may become ill, but symptoms of the illness diminish and disappear as antibodies and effector T cells clear the antigen from the body. A second exposure to the same antigen at some later time elicits the secondary immune response. o This response is faster (only 2 to 7 days), of greater magnitude, and more prolonged. o In addition, the antibodies produced in the secondary response tend to have greater affinity for the antigen than those secreted in the primary response. Measures of antibody concentrations in the blood serum over time show the difference between primary and secondary immune responses. o The immune systems capacity to generate secondary immune responses is called immunological memory, based not only on effector cells, but also on clones of long-lived T and B memory cells. These memory cells proliferate and differentiate rapidly when they later contact the same antigen. Concept 43.3 Humoral and cell-mediated immunity defend against different types of threats The immune system can mount two types of responses to antigens: a humoral response and a cell-mediated response. o Humoral immunity involves B cell activation and clonal selection and results in the production of antibodies that circulate in the blood plasma and lymph. Circulating antibodies defend mainly against free bacteria, toxins, and viruses in the body fluids. o In cell-mediated immunity, activation and clonal selection of cytotoxic T lymphocytes allows these cells to directly destroy certain target cells, including nonself cancer and transplant cells. The humoral and cell-mediated immune responses are linked by cell-signaling interactions, especially via helper T cells. Helper T lymphocytes function in both humoral and cell-mediated immunity. When a helper T cell recognizes a class II MHC molecule-antigen complex on an antigen-presenting cell, the helper T cell proliferates and differentiates into a clone of activated helper T cells and memory helper T cells. A surface protein called CD4 binds the side of the class II MHC molecule. This interaction helps keep the helper T cell and the antigen-presenting cell joined while activation of the helper T cell proceeds. Activated helper T cells secrete several different cytokines that stimulate other lymphocytes, thereby promoting cell-mediated and humoral responses. Dendritic cells are important in triggering a primary immune response. o They capture antigens, migrate to the lymphoid tissues, and present antigens, via class II MHC molecules, to helper T cells. Macrophages present antigens to memory helper T cells, while B cells primarily present antigens to helper T cells in the course of the humoral response. In the cell-mediated response, cytotoxic T cells counter intracellular pathogens. Antigen-activated cytotoxic T lymphocytes kill cancer cells and cells infected by viruses and other intracellular pathogens.

Fragments of nonself proteins synthesized in such target cells associate with class I MHC molecules and are displayed on the cell surface, where they can be recognized by cytotoxic T cells. o This interaction is greatly enhanced by the T surface protein CD8 that helps keep the cells together while the cytotoxic T cell is activated. When a cytotoxic T cell is activated by specific contacts with class I MHC-antigen complexes on an infected cell, the activated cytotoxic T cell differentiates into an active killer, which kills its target cellthe antigen-presenting cellprimarily by secreting proteins that act on the bound cell. o The death of the infected cell not only deprives the pathogen of a place to reproduce, but also exposes it to circulating antibodies, which mark it for disposal. o Once activated, cytotoxic T cells kill other cells infected with the same pathogen. In the same way, cytotoxic T cells defend against malignant tumors. o Because tumor cells carry distinctive molecules not found on normal cells, they are identified as foreign by the immune system. o Class I MHC molecules on a tumor cell present fragments of tumor antigens to cytotoxic T cells. o Interestingly, certain cancers and viruses actively reduce the amount of class I MHC protein on affected cells so that they escape detection by cytotoxic T cells. o The body has a backup defense in the form of natural killer cells, part of the nonspecific defenses, which lyse virusinfected and cancer cells. In the humoral response, B cells make antibodies against extracellular pathogens. Antigens that elicit a humoral immune response are typically proteins and polysaccharides present on the surface of bacteria or transplanted tissue. The activation of B cells is aided by cytokines secreted by helper T cells activated by the same antigen. o These B cells proliferate and differentiate into a clone of antibody-secreting plasma cells and a clone of memory B cells. When antigen first binds to receptors on the surface of a B cell, the cell takes in a few of the foreign molecules by receptormediated endocytosis. The B cell then presents antigen fragments to a helper B cell. Many antigens (primarily proteins), called T-dependent antigens, can trigger a humoral immune response by B cells only with the participation of helper T cells. Other antigens, such as polysaccharides and proteins with many identical polypeptides, function as T-independent antigens. o These include the polysaccharides of many bacterial capsules and the proteins of the bacterial flagella. o These antigens bind simultaneously to a number of membrane antibodies on the B cell surface. o This stimulates the B cell to generate antibody-secreting plasma cells without the help of cytokines. o While this response is an important defense against many bacteria, it generates a weaker response than T-dependent antigens and generates no memory cells. Any given humoral response stimulates a variety of different B cells, with each giving rise to a clone of thousands of plasma cells. o Each plasma cell is estimated to secrete about 2,000 antibody molecules per second over the cells 4- to 5-day life span. o A secreted antibody has the same general Y-shaped structure as a B cell receptor, but lacks a transmembrane region that would anchor it to a plasma membrane. Antigens that elicit a humoral immune response are typically the protein and polysaccharide surface components of microbes, incompatible transplanted tissues, or incompatible transfused cells. o In addition, for some humans, the proteins of foreign substances such as pollen or bee venom act as antigens that induce an allergic, or hypersensitive, humoral response. Antibodies constitute a group of globular serum proteins called immunoglobins (Igs). There are five major types of heavy-chain constant regions, determining the five major classes of antibodies. o Two classes exist primarily as polymers of the basic antibody molecule: IgM as a pentamer and IgA as a dimmer. o The other three classesIgG, IgE, and IgDexist exclusively as monomers, The power of antibody specificity and antigen-antibody binding has been applied in laboratory research, clinical diagnosis, and disease treatment. o Some antibody tools are polyclonal, the products of many different clones of B cells, each specific for a different epitope. o Others are monoclonal, prepared from a single clone of B cells grown in culture. These cells produce monoclonal antibodies, specific for the same epitope on an antigen. These have been used to tag specific molecules. For example, toxin-linked antibodies search and destroy tumor cells. The binding of antibodies to antigens is also the basis of several antigen disposal mechanisms. o In viral neutralization, antibodies bind to proteins on the surface of a virus, blocking the viruss ability to infect a host cell.

In opsonization, the bound antibodies enhance macrophage attachment to and phagocytosis of the microbes. Neither the B cell receptor for an antigen nor the secreted antibody actually binds to an entire antigen molecule. Antibody-mediated agglutination of bacteria or viruses effectively neutralizes and opsonizes the microbes. o Agglutination is possible because each antibody molecule has at least two antigen-binding sites. o IgM can link together five or more viruses or bacteria. o These large complexes are readily phagocytosed by macrophages. In precipitation, the cross-linking of soluble antigen moleculesmolecules dissolved in body fluidsforms immobile precipitates that are disposed of by phagocytosis. The complement system participates in the antibody-mediated disposal of microbes and transplanted body cells. The pathway begins when IgM or IgG antibodies bind to a pathogen, such as a bacterium. o The first complement component links two bound antibodies and is activated, initiating the cascade. Ultimately, complement proteins generate a membrane attack complex (MAC), which forms a pore in the bacterial membrane, resulting in cell lysis. o Whether activated as part of innate or acquired defenses, the complement cascade results in the lysis of microbes and produces activated complement proteins that promote inflammation or stimulate phagocytosis. Immunity can be achieved naturally or artificially. Immunity conferred by recovering from an infectious disease such as chicken pox is called active immunity because it depends on the response of the infected persons own immune system. o Active immunity can be acquired naturally or artificially, by immunization, also known as vaccination. o Vaccines include inactivated bacterial toxins, killed microbes, parts of microbes, viable but weakened microbes, and even genes encoding microbial proteins. o These agents can act as antigens, stimulating an immune response and, more important, producing immunological memory. A vaccinated person who encounters the actual pathogen will have the same quick secondary response based on memory cells as a person who has had the disease. o Routine immunization of infants and children has dramatically reduced the incidence of infectious diseases such as measles and whooping cough, and has led to the eradication of smallpox, a viral disease. o Unfortunately, not all infectious agents are easily managed by vaccination. For example, the emergence of new strains of pathogens with slightly altered surface antigens complicates development of vaccines against some microbes, such as the parasite that causes malaria. Antibodies can be transferred from one individual to another, providing passive immunity. o This occurs naturally when IgG antibodies of a pregnant woman cross the placenta to her fetus. o In addition, IgA antibodies are passed from mother to nursing infant in breast milk. o Passive immunity persists as long as these antibodies last, a few weeks to a few months. This protects the infant from infections until the babys own immune system has matured. Passive immunity can be transferred artificially by injecting antibodies from an animal that is already immune to a disease into another animal. o This confers short-term, but immediate, protection against that disease. o For example, a person bitten by a rabid animal may be injected with antibodies against rabies virus because rabies may progress rapidly, and the response to an active immunization could take too long to save the life of the victim. Most people infected with rabies virus are given both passive immunizations (the immediate defense) and active immunizations (a longer-term defense). Concept 43.4 The immune systems ability to distinguish self from nonself limits tissue transplantation In addition to attacking pathogens, the immune system will also attack cells from other individuals. o For example, a skin graft from one person to a nonidentical individual will look healthy for a day or two, but it will then be destroyed by immune responses. o Interestingly, a pregnant woman does not reject the fetus as a foreign body. Apparently, the structure of the placenta is the key to this acceptance. One source of potential problems with blood transfusions is an immune reaction from individuals with incompatible blood types. o In the ABO blood groups, an individual with type A blood has A antigens on the surface of red blood cells. This is not recognized as an antigen by the owner, but it can be identified as foreign if placed in the body of another individual. o B antigens are found on type B red blood cells. o Both A and B antigens are found on type AB red blood cells. o Neither antigen is found on type O red blood cells. A person with type A blood already has antibodies to the B antigen, even if the person has never been exposed to type B blood. o These antibodies arise in response to bacteria (normal flora) that have epitopes very similar to blood group antigens. o Thus, an individual with type A blood does not make antibodies to A-like bacterial epitopesthese are considered selfbut that person does make antibodies to B-like bacterial epitopes.

If a person with type A blood receives a transfusion of type B blood, the preexisting anti-B antibodies will induce an immediate and devastating transfusion reaction. Because blood group antigens are polysaccharides, they induce T-independent responses, which elicit no memory cells. o Each response is like a primary response, and it generates IgM anti-blood-group antibodies, not IgG. o This is fortunate, because IgM antibodies do not cross the placenta, where they may harm a developing fetus with a blood type different from its mothers. However, another blood group antigen, the Rh factor, can cause mother-fetus problems because antibodies produced for it are IgG. o This situation arises when a mother that is Rh-negative (lacks the Rh factor) has a fetus that is Rh-positive, having inherited the factor from the father. o If small amounts of fetal blood cross the placenta late in pregnancy or during delivery, the mother mounts a humoral response against the Rh factor. o The danger occurs in subsequent Rh-positive pregnancies, when the mothers Rh-specific memory B cells produce IgG antibodies that can cross the placenta and destroy the red blood cells of the fetus. To prevent this, the mother is injected with anti-Rh antibodies after delivering her first Rh-positive baby. o She is, in effect, passively immunized (artificially) to eliminate the Rh antigen before her own immune system responds and generates immunological memory against the Rh factor, endangering her future Rh-positive babies. Major histocompatibility complex (MHC) molecules are responsible for stimulating rejection of tissue grafts and organ transplants. o Because MHC creates a unique protein fingerprint for each individual, foreign MHC molecules are antigenic, inducing immune responses against the donated tissue or organ. o To minimize rejection, attempts are made to match MHC of tissue donor and recipient as closely as possible. In the absence of identical twins, siblings usually provide the closest tissue-type match. In addition to MHC matching, various medicines are used to suppress the immune response to the transplant. o However, this strategy leaves the recipient more susceptible to infection and cancer during the course of treatment. o More selective drugs, which suppress helper T cell activation without crippling nonspecific defense or Tindependent humoral responses, have greatly improved the success of organ transplants. In bone marrow transplants, it is the graft itself, rather than the recipient, which is the source of potential immune rejection. o Bone marrow transplants are used to treat leukemia and other cancers as well as various hematological diseases. o Prior to the transplant, the recipient is typically treated with irradiation to eliminate the recipients immune system, eliminating all abnormal cells and leaving little chance of graft rejection. o However, the donated marrow, containing lymphocytes, may react against the recipient, producing graft versus host reaction, unless well matched. Concept 43.5 Exaggerated, self-directed, or diminished immune responses can cause disease Malfunctions of the immune system can produce effects ranging from the minor inconvenience of some allergies to the serious and often fatal consequences of certain autoimmune and immunodeficiency diseases. Allergies are hypersensitive (exaggerated) responses to certain environmental antigens, called allergens. o One hypothesis to explain the origin of allergies is that they are evolutionary remnants of the immune systems response to parasitic worms. o The humoral mechanism that combats worms is similar to the allergic response that causes such disorders as hay fever and allergic asthma. The most common allergies involve antibodies of the IgE class. o Hay fever, for example, occurs when plasma cells secrete IgE specific for pollen allergens. o Some IgE antibodies attach by their tails to mast cells present in connective tissue, without binding to the pollen. o Later, when pollen grains enter the body, they attach to the antigen-binding sites of mast cell-associated IgE, crosslinking adjacent antibody molecules. This event triggers the mast cell to degranulatethat is, to release histamines and other inflammatory agents from vesicles called granules. High levels of histamines cause dilation and increased permeability of small blood vessels. o These inflammatory events lead to typical allergy symptoms: sneezing, runny nose, tearing eyes, and smooth muscle contractions that can result in breathing difficulty. o Antihistamines diminish allergy symptoms by blocking receptors for histamine. Sometimes, an acute allergic response can result in anaphylactic shock, a life-threatening reaction to injected or ingested allergens. o Anaphylactic shock results when widespread mast cell degranulation triggers abrupt dilation of peripheral blood vessels, causing a precipitous drop in blood pressure. Death may occur within minutes. o Triggers of anaphylactic shock in susceptible individuals include bee venom, penicillin, or foods such as peanuts or fish. o Some hypersensitive individuals carry syringes with epinephrine, which counteracts this allergic response.

Sometimes the immune system loses tolerance for self and turns against certain molecules of the body, causing one of many autoimmune diseases. o In systemic lupus erythematosus (lupus), the immune system generates antibodies against various self-molecules, including histones and DNA released by the normal breakdown of body cells. Lupus is characterized by skin rashes, fever, arthritis, and kidney dysfunction. o Rheumatoid arthritis leads to damage and painful inflammation of the cartilage and bone of joints. o In insulin-dependent diabetes mellitus, the insulin-producing beta cells of the pancreas are the targets of autoimmune cytotoxic T cells. Multiple sclerosis (MS) is the most common chronic neurological disease in developed countries. o In MS, T cells reactive against myelin infiltrate the central nervous system and destroy the myelin sheath that surrounds some neurons. o People with MS experience a number of serious neurological abnormalities. The mechanisms that lead to autoimmunity are not fully understood. o It was thought that people with autoimmune diseases had self-reactive lymphocytes that escaped elimination during their development. o We now know that healthy people also have lymphocytes with the capacity to react against self, but these cells are inhibited from inducing an autoimmune reaction by several regulatory mechanisms. o Autoimmune disease likely arises from some failure in immune regulation, perhaps linked with particular MHC alleles. In immunodeficiency diseases, the function of either the humoral or cell-mediated immune defense is compromised. An immunodeficiency disease caused by a genetic or developmental defect in the immune system is called an inborn or primary immunodeficiency. An immunodeficiency defect in the immune system that develops later in life, following exposure to a chemical or biological agent, is called an acquired or secondary immunodeficiency. In severe combined immunodeficiency (SCID), both branches of the immune system fail to function. o For individuals with this disease, long-term survival requires a bone marrow transplant that will continue to supply functional lymphocytes. o Several gene therapy approaches are in clinical trials to attempt to reverse SCID. o Recent successes include a child with SCID who received gene therapy in 2002 when she was 2 years old. In 2004, her T cells and B cells were still functioning normally. Immunodeficiency may also develop later in life. o For example, certain cancers suppress the immune system. An example is Hodgkins disease, which damages the lymphatic system. AIDS is another acquired immune deficiency. Healthy immune system function appears to depend on both the endocrine system and the nervous system. o For example, hormones secreted by the adrenal glands during stress affect the number of white blood cells and may suppress the immune system in other ways. o Similarly, some neurotransmitters secreted when we are relaxed and happy may enhance immunity. o Physiological evidence also points to an immune systemnervous system link based on the presence of neurotransmitter receptors on the surfaces of lymphocytes and a network of nerve fibers that penetrates deep into the thymus. AIDS is an immunodeficiency disease caused by a virus. In 1981, increased rates of two rare diseases, Kaposis sarcoma, a cancer of the skin and blood vessels, and pneumonia caused by the protozoan Pneumocystis carinii, were the first signals to the medical community of a new threat to humans, later known as acquired immunodeficiency syndrome, or AIDS. o Both conditions were previously known to occur mainly in severely immunosuppressed individuals. o People with AIDS are susceptible to opportunistic diseases. o Because AIDS arises from the loss of helper T cells, both humoral and cell-mediated immune responses are impaired. In 1983, a retrovirus, now called human immunodeficiency virus (HIV), was identified as the causative agent of AIDS. HIV gains entry into cells by making use of proteins that participate in normal immune responses. o The main receptor for HIV on helper T cells is the cells CD4 molecule. o In addition to CD4, HIV requires a second cell-surface protein, a coreceptor. Once inside the cell, the HIV RNA is reverse-transcribed, and the product DNA is integrated into the host cells genome. In this form, the viral genome can direct the production of new viral particles. The death of helper T cells in HIV infection is due to the damaging effects of viral reproduction, coupled with inappropriately timed apoptosis triggered by the virus. HIV infection cannot yet be cured, although certain drugs slow HIV reproduction and the progression to AIDS. o However, these drugs are very expensive and not available to all infected people, especially in developing countries. o In addition, the mutational changes that occur with each round of virus reproduction can generate drug-resistant strains of HIV.

o o

Transmission of HIV requires the transfer of body fluids containing infected cells, such as semen or blood, from person to person. In December 2003, the Joint UN Program on AIDS estimated that 40 million people worldwide are living with HIV/AIDS. The best approach for slowing the spread of HIV is to educate people about the practices that lead to transmission, such as using dirty needles or having unprotected intercourse.

Chapter 44 - Osmoregulation and Excretion Overview: A Balancing Act The physiological systems of animals operate within a fluid environment. o The relative concentrations of water and solutes must be maintained within narrow limits, despite variations in the animals external environment. Metabolism also poses the problem of disposal of wastes. o The breakdown of proteins and nucleic acids is problematic because ammonia, the primary metabolic waste from breakdown of these molecules, is very toxic. An organism maintains a physiological favorable environment by osmoregulation, regulating solute balance and the gain and loss of water and excretion, the removal of nitrogen-containing waste products of metabolism. Concept 44.1 Osmoregulation balances the uptake and loss of water and solutes All animals face the same central problem of osmoregulation. o Over time, the rates of water uptake and loss must balance. o Animal cellswhich lack cell wallsswell and burst if there is a continuous net uptake of water, or shrivel and die if there is a substantial net loss of water. Water enters and leaves cells by osmosis, the movement of water across a selectively permeable membrane. o Osmosis occurs whenever two solutions separated by a membrane differ in osmotic pressure, or osmolarity (moles of solute per liter of solution). o The unit of measurement of osmolarity is milliosmoles per liter (mosm/L). 1 mosm/L is equivalent to a total solute concentration of 10-3 M. The osmolarity of human blood is about 300 mosm/L, while seawater has an osmolarity of about 1,000 mosm/L. If two solutions separated by a selectively permeable membrane have the same osmolarity, they are said to be isoosmotic. There is no net movement of water by osmosis between isoosmotic solutions, although water molecules do cross at equal rates in both directions. o When two solutions differ in osmolarity, the one with the greater concentration of solutes is referred to as hyperosmotic, and the more dilute solution is hypoosmotic. o Water flows by osmosis from a hypoosmotic solution to a hyperosmotic one. Osmoregulators expend energy to control their internal osmolarity; osmoconformers are isoosmotic with their surroundings. There are two basic solutions to the problem of balancing water gain with water loss. o Oneavailable only to marine animalsis to be isoosmotic to the surroundings as an osmoconformer. Although they do not compensate for changes in external osmolarity, osmoconformers often live in water that has a very stable composition and, hence, they have a very constant internal osmolarity. In contrast, an osmoregulator is an animal that must control its internal osmolarity because its body fluids are not isoosmotic with the outside environment. o An osmoregulator must discharge excess water if it lives in a hypoosmotic environment or take in water to offset osmotic loss if it inhabits a hyperosmotic environment. o Osmoregulation enables animals to live in environments that are uninhabitable to osmoconformers, such as freshwater and terrestrial habitats. o It also enables many marine animals to maintain internal osmolarities different from that of seawater. Whenever animals maintain an osmolarity difference between the body and the external environment, osmoregulation has an energy cost. o Because diffusion tends to equalize concentrations in a system, osmoregulators must expend energy to maintain the osmotic gradients via active transport. o The energy costs depend mainly on how different an animals osmolarity is from its surroundings, how easily water and solutes can move across the animals surface, and how much membrane-transport work is required to pump solutes. o Osmoregulation accounts for nearly 5% of the resting metabolic rate of many marine and freshwater bony fishes. Most animals, whether osmoconformers or osmoregulators, cannot tolerate substantial changes in external osmolarity and are said to be stenohaline. o In contrast, euryhaline animalswhich include both some osmoregulators and osmoconformerscan survive large fluctuations in external osmolarity. o For example, various species of salmon migrate back and forth between freshwater and marine environments.

The food fish, tilapia, is an extreme example, capable of adjusting to any salt concentration between freshwater and 2,000 mosm/L, twice that of seawater. Most marine invertebrates are osmoconformers. o Their osmolarity is the same as seawater. o However, they differ considerably from seawater in their concentrations of most specific solutes. o Thus, even an animal that conforms to the osmolarity of its surroundings does regulate its internal composition. Marine vertebrates and some marine invertebrates are osmoregulators. o For most of these animals, the ocean is a strongly dehydrating environment because it is much saltier than internal fluids, and water is lost from their bodies by osmosis. o Marine bony fishes, such as cod, are hypoosmotic to seawater and constantly lose water by osmosis and gain salt by diffusion and from the food they eat. o The fishes balance water loss by drinking seawater and actively transporting chloride ions out through their skin and gills. Sodium ions follow passively. o They produce very little urine. Marine sharks and most other cartilaginous fishes (chondrichthyans) use a different osmoregulatory strategy. o Like bony fishes, salts diffuse into the body from seawater, and these salts are removed by the kidneys, a special organ called the rectal gland, or in feces. o Unlike bony fishes, marine sharks do not experience a continuous osmotic loss because high concentrations of urea and trimethylamine oxide (TMAO) in body fluids leads to an osmolarity slightly higher than seawater. TMAO protects proteins from damage by urea. o Consequently, water slowly enters the sharks body by osmosis and in food, and is removed in urine. In contrast to marine organisms, freshwater animals are constantly gaining water by osmosis and losing salts by diffusion. o This happens because the osmolarity of their internal fluids is much higher than that of their surroundings. o However, the body fluids of most freshwater animals have lower solute concentrations than those of marine animals, an adaptation to their low-salinity freshwater habitat. o Many freshwater animals, including fish such as perch, maintain water balance by excreting large amounts of very dilute urine, and regaining lost salts in food and by active uptake of salts from their surroundings. Salmon and other euryhaline fishes that migrate between seawater and freshwater undergo dramatic and rapid changes in osmoregulatory status. o While in the ocean, salmon osmoregulate as other marine fishes do, by drinking seawater and excreting excess salt from the gills. o When they migrate to fresh water, salmon cease drinking, begin to produce lots of dilute urine, and their gills start taking up salt from the dilute environmentthe same as fishes that spend their entire lives in fresh water. Dehydration dooms most animals, but some aquatic invertebrates living in temporary ponds and films of water around soil particles can lose almost all their body water and survive in a dormant state, called anhydrobiosis, when their habitats dry up. o For example, tardigrades, or water bears, contain about 85% of their weight in water when hydrated but can dehydrate to less than 2% water and survive in an inactive state for a decade until revived by water. Anhydrobiotic animals must have adaptations that keep their cell membranes intact. o While the mechanism that tardigrades use is still under investigation, researchers do know that anhydrobiotic nematodes contain large amounts of sugars, especially the disaccharide trehalose. o Trehalose, a dimer of glucose, seems to protect cells by replacing water associated with membranes and proteins. o Many insects that survive freezing in the winter also use trehalose as a membrane protectant. The threat of desiccation is perhaps the largest regulatory problem confronting terrestrial plants and animals. o Humans die if they lose about 12% of their body water. o Camels can withstand twice that level of dehydration. Adaptations that reduce water loss are key to survival on land. o Most terrestrial animals have body coverings that help prevent dehydration. o These include waxy layers in insect exoskeletons, the shells of land snails, and the multiple layers of dead, keratinized skin cells of most terrestrial vertebrates. o Being nocturnal also reduces evaporative water loss. Despite these adaptations, most terrestrial animals lose considerable water from moist surfaces in their gas exchange organs, in urine and feces, and across the skin. o Land animals balance their water budgets by drinking and eating moist foods and by using metabolic water from aerobic respiration. Some animals are so well adapted for minimizing water loss that they can survive in deserts without drinking. o For example, kangaroo rats lose so little water that they can recover 90% of the loss from metabolic water and gain the remaining 10% in their diet of seeds. o These and many other desert animals do not drink. Water balance and waste disposal depend on transport epithelia.

The ultimate function of osmoregulation is to maintain the composition of cellular cytoplasm, but most animals do this indirectly by managing the composition of an internal body fluid that bathes the cells. o In animals with an open circulatory system, this fluid is hemolymph. o In vertebrates and other animals with a closed circulatory system, the cells are bathed in an interstitial fluid that is controlled through the composition of the blood. o The maintenance of fluid composition depends on specialized structures ranging from cells that regulate solute movement to complex organs such as the vertebrate kidney. In most animals, osmotic regulation and metabolic waste disposal depend on the ability of a layer or layers of transport epithelium to move specific solutes in controlled amounts in specific directions. o Some transport epithelia directly face the outside environment, while others line channels connected to the outside by an opening on the body surface. o The cells of the epithelium are joined by impermeable tight junctions that form a barrier at the tissue-environment barrier. In most animals, transport epithelia are arranged into complex tubular networks with extensive surface area. o For example, the salt-secreting glands of some marine birds, such as the albatross, secrete an excretory fluid that is much more salty than the ocean. o The counter-current system in these glands removes salt from the blood, allowing these organisms to drink seawater during their months at sea. The molecular structure of plasma membranes determines the kinds and directions of solutes that move across the transport epithelium. o For example, the salt-excreting glands of the albatross remove excess sodium chloride from the blood. o By contrast, transport epithelia in the gills of freshwater fishes actively pump salts from the dilute water passing by the gill filaments into the blood. o Transport epithelia in excretory organs often have the dual functions of maintaining water balance and disposing of metabolic wastes. Concept 44.2 An animals nitrogenous wastes reflect its phylogeny and habitat Because most metabolic wastes must be dissolved in water when they are removed from the body, the type and quantity of waste products may have a large impact on water balance. Nitrogenous breakdown products of proteins and nucleic acids are among the most important wastes in terms of their effect on osmoregulation. o During their breakdown, enzymes remove nitrogen in the form of ammonia, a small and very toxic molecule. o Some animals excrete ammonia directly, but many species first convert the ammonia to other compounds that are less toxic but costly to produce. Animals that excrete nitrogenous wastes as ammonia need access to lots of water. o This is because ammonia is very soluble but can be tolerated only at very low concentrations. o Therefore, ammonia excretion is most common in aquatic species. o Many invertebrates release ammonia across the whole body surface. o In fishes, most of the ammonia is lost as ammonium ions (NH4+) at the gill epithelium. Freshwater fishes are able to exchange NH4+ for Na+ from the environment, which helps maintain Na+ concentrations in body fluids. Ammonia excretion is much less suitable for land animals. o Because ammonia is so toxic, it can be transported and excreted only in large volumes of very dilute solutions. o Most terrestrial animals and many marine organisms (which tend to lose water to their environment by osmosis) do not have access to sufficient water. Instead, mammals, most adult amphibians, sharks, and some marine bony fishes and turtles excrete mainly urea. o Urea is synthesized in the liver by combining ammonia with carbon dioxide and is excreted by the kidneys. The main advantage of urea is its low toxicity, about 100,000 times less than that of ammonia. o Urea can be transported and stored safely at high concentrations. o This reduces the amount of water needed for nitrogen excretion when releasing a concentrated solution of urea rather than a dilute solution of ammonia. The main disadvantage of urea is that animals must expend energy to produce it from ammonia. o In weighing the relative advantages of urea versus ammonia as the form of nitrogenous waste, it makes sense that many amphibians excrete mainly ammonia when they are aquatic tadpoles. They switch largely to urea when they are land-dwelling adults. Land snails, insects, birds, and many reptiles excrete uric acid as the main nitrogenous waste. o Like urea, uric acid is relatively nontoxic. o But unlike either ammonia or urea, uric acid is largely insoluble in water and can be excreted as a semisolid paste with very little water loss. o While saving even more water than urea, it is even more energetically expensive to produce. Uric acid and urea represent different adaptations for excreting nitrogenous wastes with minimal water loss. Mode of reproduction appears to have been important in choosing among these alternatives.

Soluble wastes can diffuse out of a shell-less amphibian egg (ammonia) or be carried away by the mothers blood in a mammalian embryo (urea). o However, the shelled eggs of birds and reptiles are not permeable to liquids, which means that soluble nitrogenous wastes trapped within the egg could accumulate to dangerous levels. Even urea is toxic at very high concentrations. o Uric acid precipitates out of solution and can be stored within the egg as a harmless solid left behind when the animal hatches. The type of nitrogenous waste also depends on habitat. o For example, terrestrial turtles (which often live in dry areas) excrete mainly uric acid, while aquatic turtles excrete both urea and ammonia. o In some species, individuals can change their nitrogenous wastes when environmental conditions change. For example, certain tortoises that usually produce urea shift to uric acid when temperature increases and water becomes less available. Excretion of nitrogenous wastes is a good illustration of how response to the environment occurs on two levels. o Over generations, evolution determines the limits of physiological responses for a species. o During their lives, individual organisms make adjustments within these evolutionary constraints. The amount of nitrogenous waste produced is coupled to the energy budget and depends on how much and what kind of food an animal eats. o Because they use energy at high rates, endotherms eat more foodand thus produce more nitrogenous wastesper unit volume than ectotherms. o Carnivores (which derive much of their energy from dietary proteins) excrete more nitrogen than animals that obtain most of their energy from lipids or carbohydrates. Concept 44.3 Diverse excretory systems are variations on a tubular theme Although the problems of water balance on land or in salt water or fresh water are very different, the solutions all depend on the regulation of solute movements between internal fluids and the external environment. o Much of this is handled by excretory systems, which are central to homeostasis because they dispose of metabolic wastes and control body fluid composition by adjusting the rates of loss of particular solutes. Most excretory systems produce urine by refining a filtrate derived from body fluids. While excretory systems are diverse, nearly all produce urine in a process that involves several steps. o First, body fluid (blood, coelomic fluid, or hemolymph) is collected. The initial fluid collection usually involves filtration through selectively permeable membranes consisting of a single layer of transport epithelium. Hydrostatic pressure forces water and small solutes into the excretory system. This fluid is called the filtrate. o Filtration is largely nonselective. It is important to recover small molecules from the filtrate and return them to the body fluids. Excretory systems use active transport to reabsorb valuable solutes in a process of selective reabsorption. Nonessential solutes and wastes are left in the filtrate or added to it by selective secretion, which also uses active transport. o The pumping of various solutes also adjusts the osmotic movement of water into or out of the filtrate. The processed filtrate is excreted as urine. Flatworms have an excretory system called protonephridia, consisting of a branching network of dead-end tubules. o These are capped by a flame bulb with a tuft of cilia that draws water and solutes from the interstitial fluid, through the flame bulb, and into the tubule system. The urine in the tubules exits through openings called nephridiopores. o Excreted urine is very dilute in freshwater flatworms. o Apparently, the tubules reabsorb most solutes before the urine exits the body. o In these freshwater flatworms, the major function of the flame-bulb system is osmoregulation, while most metabolic wastes diffuse across the body surface or are excreted into the gastrovascular cavity. o However, in some parasitic flatworms, protonephridia do dispose of nitrogenous wastes. o Protonephridia are also found in rotifers, some annelids, larval molluscs, and lancelets. Metanephridia, another tubular excretory system, consist of internal openings that collect body fluids from the coelom through a ciliated funnel, the nephrostome, and release the fluid to the outside through the nephridiopore. o Each segment of an annelid worm has a pair of metanephridia. An earthworms metanephridia have both excretory and osmoregulatory functions. o As urine moves along the tubule, the transport epithelium bordering the lumen reabsorbs most solutes and returns them to the blood in the capillaries. o Nitrogenous wastes remain in the tubule and are dumped outside. o Because earthworms experience a net uptake of water from damp soil, their metanephridia balance water influx by producing dilute urine. o

Insects and other terrestrial arthropods have organs called Malpighian tubules that remove nitrogenous wastes and also function in osmoregulation. o These open into the digestive system and dead-end at tips that are immersed in the hemolymph. The transport epithelium lining the tubules secretes certain solutes, including nitrogenous wastes, from the hemolymph into the lumen of the tubule. o Water follows the solutes into the tubule by osmosis, and the fluid then passes back to the rectum, where most of the solutes are pumped back into the hemolymph. o Water again follows the solutes, and the nitrogenous wastes, primarily insoluble uric acid, are eliminated along with the feces. This system is highly effective in conserving water and is one of several key adaptations contributing to the tremendous success of insects on land. The kidneys of vertebrates usually function in both osmoregulation and excretion. o Like the excretory organs of most animal phyla, kidneys are built of tubules. o The osmoconforming hagfishes, which are not vertebrates but are among the most primitive living chordates, have kidneys with segmentally arranged excretory tubules. This suggests that the excretory segments of vertebrate ancestors were segmented. o However, the kidneys of most vertebrates are compact, nonsegmented organs containing numerous tubules arranged in a highly organized manner. o The vertebrate excretory system includes a dense network of capillaries intimately associated with the tubules, along with ducts and other structures that carry urine out of the tubules and kidney and eventually out of the body. Concept 44.4 Nephrons and associated blood vessels are the functional units of the mammalian kidney Mammals have a pair of bean-shaped kidneys. o Each kidney is supplied with blood by a renal artery and drained by a renal vein. o In humans, the kidneys account for less than 1% of body weight, but they receive about 20% of resting cardiac output. Urine exits each kidney through a duct called the ureter, and both ureters drain through a common urinary bladder. o During urination, urine is expelled from the urinary bladder through a tube called the urethra, which empties to the outside near the vagina in females or through the penis in males. o Sphincter muscles near the junction of the urethra and the bladder control urination. The mammalian kidney has two distinct regions, an outer renal cortex and an inner renal medulla. o Both regions are packed with microscopic excretory tubules, nephrons, and their associated blood vessels. o Each nephron consists of a single long tubule and a ball of capillaries, called the glomerulus. o The blind end of the tubule forms a cup-shaped swelling, called Bowmans capsule, that surrounds the glomerulus. o Each human kidney contains about a million nephrons, with a total tubule length of 80 km. Filtration occurs as blood pressure forces fluid from the blood in the glomerulus into the lumen of Bowmans capsule. o The porous capillaries, along with specialized capsule cells called podocytes, are permeable to water and small solutes but not to blood cells or large molecules such as plasma proteins. o The filtrate in Bowmans capsule contains salt, glucose, amino acids, vitamins, nitrogenous wastes such as urea, and other small molecules. From Bowmans capsule, the filtrate passes through three regions of the nephron: the proximal tubule; the loop of Henle, a hairpin turn with a descending limb and an ascending limb; and the distal tubule. o The distal tubule empties into a collecting duct, which receives processed filtrate from many nephrons. o The many collecting ducts empty into the renal pelvis, which is drained by the ureter. In the human kidney, about 80% of the nephrons, the cortical nephrons, have reduced loops of Henle and are almost entirely confined to the renal cortex. o The other 20%, the juxtamedullary nephrons, have well-developed loops that extend deeply into the renal medulla. o Only mammals and birds have juxtamedullary nephrons; the nephrons of other vertebrates lack loops of Henle. o It is the juxtamedullary nephrons that enable mammals to produce urine that is hyperosmotic to body fluids, conserving water. The nephron and the collecting duct are lined by a transport epithelium that processes the filtrate to form the urine. o Their most important task is to reabsorb solutes and water. o The nephrons and collecting ducts reabsorb nearly all of the sugar, vitamins, and other organic nutrients from the initial filtrate and about 99% of the water. o This reduces 180 L of initial filtrate to about 1.5 L of urine to be voided. Each nephron is supplied with blood by an afferent arteriole, a branch of the renal artery that subdivides into the capillaries of the glomerulus. o The capillaries converge as they leave the glomerulus, forming an efferent arteriole. o This vessel subdivides again into the peritubular capillaries, which surround the proximal and distal tubules. o Additional capillaries extend downward to form the vasa recta, a loop of capillaries that serves the loop of Henle. o The tubules and capillaries are immersed in interstitial fluid, through which substances diffuse.

Although the excretory tubules and their surrounding capillaries are closely associated, they do not exchange materials directly. o The tubules and capillaries are immersed in interstitial fluid, through which various materials diffuse between the plasma in the capillaries and the filtrate within the nephron tubule. Filtrate from Bowmans capsule flows through the nephron and collecting ducts as it becomes urine. Secretion and reabsorption in the proximal tubule substantially alter the volume and composition of filtrate. o For example, the cells of the transport epithelium help maintain a constant pH in body fluids by controlled secretions of hydrogen ions or ammonia. o The cells also synthesize and secrete ammonia, which neutralizes the acid. o The proximal tubules reabsorb about 90% of the important buffer bicarbonate (HCO3-). o Drugs and other poisons that have been processed in the liver pass from the peritubular capillaries into the interstitial fluid and then across the epithelium to the nephrons lumen. o Valuable nutrients, including glucose, amino acids, and K+, are actively or passively absorbed from filtrate. One of the most important functions of the proximal tubule is reabsorption of most of the NaCl and water from the initial filtrate volume. o Salt in the filtrate diffuses into the cells of the transport epithelium. o The epithelial cells actively transport Na+ into the interstitial fluid. o This transfer of positive charge is balanced by the passive transport of Cl- out of the tubule. o As salt moves from the filtrate to the interstitial fluid, water follows by osmosis. o The exterior side of the epithelium has a much smaller surface area than the side facing the lumen, which minimizes leakage of salt and water back into the tubule, and instead they diffuse into the peritubular capillaries. Reabsorption of water continues as the filtrate moves into the descending limb of the loop of Henle. o This transport epithelium is freely permeable to water but not very permeable to salt and other small solutes. o For water to move out of the tubule by osmosis, the interstitial fluid bathing the tubule must be hyperosmotic to the filtrate. o Because the osmolarity of the interstitial fluid becomes progressively greater from the outer cortex to the inner medulla, the filtrate moving within the descending loop of Henle continues to lose water. In contrast to the descending limb, the transport epithelium of the ascending limb of the loop of Henle is permeable to salt, not water. o As filtrate ascends the thin segment of the ascending limb, NaCl diffuses out of the permeable tubule into the interstitial fluid, increasing the osmolarity of the medulla. o The active transport of salt from the filtrate into the interstitial fluid continues in the thick segment of the ascending limb. o By losing salt without giving up water, the filtrate becomes progressively more dilute as it moves up to the cortex in the ascending limb of the loop. The distal tubule plays a key role in regulating the K+ and NaCl concentrations in body fluids by varying the amount of K+ that is secreted into the filtrate and the amount of NaCl reabsorbed from the filtrate. o Like the proximal tubule, the distal tubule also contributes to pH regulation by controlled secretion of H+ and the reabsorption of bicarbonate (HCO3-). By actively reabsorbing NaCl, the transport epithelium of the collecting duct plays a large role in determining how much salt is actually excreted in the urine. o Though the degree of its permeability is under hormonal control, the epithelium is permeable to water but not to salt or (in the renal cortex) to urea. o As the collecting duct traverses the gradient of osmolarity in the kidney, the filtrate becomes increasingly concentrated as it loses more and more water by osmosis to the hyperosmotic interstitial fluid. o In the inner medulla, the duct becomes permeable to urea. Because of the high urea concentration in the filtrate at this point, some urea diffuses out of the duct and into the interstitial fluid. Along with NaCl, this urea contributes to the high osmolarity of the interstitial fluid in the medulla. This high osmolarity enables the mammalian kidney to conserve water by excreting urine that is hyperosmotic to general body fluids. Concept 44.5 The mammalian kidneys ability to conserve water is a key terrestrial adaptation The osmolarity of human blood is about 300 mosm/L, but the kidney can excrete urine up to four times as concentrated about 1,200 mosm/L. o At an extreme of water conservation, Australian hopping mice, which live in desert regions, can produce urine concentrated to 9,300 mosm/L25 times as concentrated as their body fluid. In a mammalian kidney, the cooperative action and precise arrangement of the loops of Henle and the collecting ducts are largely responsible for the osmotic gradients that concentrate the urine. o In addition, the maintenance of osmotic differences and the production of hyperosmotic urine are only possible because considerable energy is expended by the active transport of solutes against concentration gradients.

In essence, the nephrons can be thought of as tiny energy-consuming machines whose function is to produce a region of high osmolarity in the kidney, which can then extract water from the urine in the collecting duct. o The two primary solutes in this osmolarity gradient are NaCl and urea. The juxtamedullary nephrons, which maintain an osmotic gradient in the kidney and use that gradient to excrete a hyperosmotic urine, are the key to understanding the physiology of the mammalian kidney as a water-conserving organ. o Filtrate passing from Bowmans capsule to the proximal tubule has an osmolarity of about 300 mosm/L. o As the filtrate flows through the proximal tubule in the renal cortex, large amounts of water and salt are reabsorbed. o The volume of the filtrate decreases substantially, but its osmolarity remains about the same. The ability of the mammalian kidney to convert interstitial fluid at 300 mosm/L to 1,200 mosm/L as urine depends on a countercurrent multiplier between the ascending and descending limbs of the loop of Henle. As the filtrate flows from the cortex to the medulla in the descending limb of the loop of Henle, water leaves the tubule by osmosis. o The osmolarity of the filtrate increases as solutes, including NaCl, become more concentrated. o The highest molarity occurs at the elbow of the loop of Henle. o This maximizes the diffusion of salt out of the tubule as the filtrate rounds the curve and enters the ascending limb, which is permeable to salt but not to water. o The descending limb produces progressively saltier filtrate, and the ascending limb exploits this concentration of NaCl to help maintain a high osmolarity in the interstitial fluid of the renal medulla. The loop of Henle has several qualities of a countercurrent system. o Although the two limbs of the loop are not in direct contact, they are close enough to exchange substances through the interstitial fluid. o The nephron can concentrate salt in the inner medulla largely because exchange between opposing flows in the descending and ascending limbs overcomes the tendency for diffusion to even out salt concentrations throughout the kidneys interstitial fluid. The vasa recta is also a countercurrent system, with descending and ascending vessels carrying blood in opposite directions through the kidneys osmolarity gradient. o As the descending vessel conveys blood toward the inner medulla, water is lost from the blood and NaCl diffuses into it. o These fluxes are reversed as blood flows back toward the cortex in the ascending vessel. o Thus, the vasa recta can supply the kidney with nutrients and other important substances without interfering with the osmolarity gradient necessary to excrete a hyperosmotic urine. The countercurrent-like characteristics of the loop of Henle and the vasa recta maintain the steep osmotic gradient between the medulla and the cortex. o This gradient is initially created by active transport of NaCl out of the thick segment of the ascending limb of the loop of Henle into the interstitial fluid. o This active transport and other active transport systems in the kidney consume considerable ATP, requiring the kidney to have one of the highest relative metabolic rates of any organ. By the time the filtrate reaches the distal tubule, it is actually hypoosmotic to body fluids because of active transport of NaCl out of the thick segment of the ascending limb. o As the filtrate descends again toward the medulla in the collecting duct, water is extracted by osmosis into the hyperosmotic interstitial fluids, but salts cannot diffuse in because the epithelium is impermeable to salt. o This concentrates salt, urea, and other solutes in the filtrate. o Some urea leaks out of the lower portion of the collecting duct, contributing to the high interstitial osmolarity of the inner medulla. Before leaving the kidney, the urine may obtain the osmolarity of the interstitial fluid in the inner medulla, which can be as high as 1,200 mosm/L. o Although isoosmotic to the inner medullas interstitial fluid, the urine is hyperosmotic to blood and interstitial fluid elsewhere in the body. o This high osmolarity allows the solutes remaining in the urine to be secreted from the body with minimal water loss. The juxtamedullary nephron is a key adaptation to terrestrial life, enabling mammals to get rid of salts and nitrogenous wastes without squandering water. o The remarkable ability of the mammalian kidney to produce hyperosmotic urine is completely dependent on the precise arrangement of the tubules and collecting ducts in the renal cortex and medulla. o The kidney is one of the clearest examples of how the function of an organ is inseparably linked to its structure. One important aspect of the mammalian kidney is its ability to adjust both the volume and osmolarity of urine, depending on the animals water and salt balance and the rate of urea production. o With high salt intake and low water availability, a mammal can excrete urea and salt with minimal water loss in small volumes of hyperosmotic urine. o If salt is scarce and fluid intake is high, the kidney can get rid of excess water with little salt loss by producing large volumes of hypoosmotic urine (as dilute as 70 mosm/L). o This versatility in osmoregulatory function is managed with a combination of nervous and hormonal controls.

Regulation of blood osmolarity is maintained by hormonal control of the kidney by negative feedback circuits. One hormone important in regulating water balance is antidiuretic hormone (ADH). o ADH is produced in the hypothalamus of the brain and stored in and released from the pituitary gland, which lies just below the hypothalamus. o Osmoreceptor cells in the hypothalamus monitor the osmolarity of the blood. When blood osmolarity rises above a set point of 300 mosm/L, more ADH is released into the bloodstream and reaches the kidney. o ADH induces the epithelium of the distal tubules and collecting ducts to become more permeable to water. o This amplifies water reabsorption. o This reduces urine volume and helps prevent further increase of blood osmolarity above the set point. By negative feedback, the subsiding osmolarity of the blood reduces the activity of osmoreceptor cells in the hypothalamus, and less ADH is secreted. o Only a gain of additional water in food and drink can bring osmolarity all the way back down to 300 mosm/L. o ADH alone only prevents further movements away from the set point. Conversely, if a large intake of water has reduced blood osmolarity below the set point, very little ADH is released. o This decreases the permeability of the distal tubules and collecting ducts, so water reabsorption is reduced, resulting in an increased discharge of dilute urine. o Alcohol can disturb water balance by inhibiting the release of ADH, causing excessive urinary water loss and dehydration (causing some symptoms of a hangover). o Normally, blood osmolarity, ADH release, and water reabsorption in the kidney are all linked in a feedback loop that contributes to homeostasis. A second regulatory mechanism involves a special tissue called the juxtaglomerular apparatus (JGA), located near the afferent arteriole that supplies blood to the glomerulus. o When blood pressure or blood volume in the afferent arteriole drops, the enzyme renin initiates chemical reactions that convert a plasma protein angiotensinogen to a peptide called angiotensin II. Acting as a hormone, angiotensin II increases blood pressure and blood volume in several ways. o It raises blood pressure by constricting arterioles, decreasing blood flow to many capillaries, including those of the kidney. o It also stimulates the proximal tubules to reabsorb more NaCl and water. This reduces the amount of salt and water excreted and, consequently, raises blood pressure and volume. o It also stimulates the adrenal glands, located atop the kidneys, to release a hormone called aldosterone. This acts on the distal tubules, which reabsorb Na+ and water, increasing blood volume and pressure. In summary, the renin-angiotensin-aldosterone system (RAAS) is part of a complex feedback circuit that functions in homeostasis. o A drop in blood pressure triggers a release of renin from the JGA. o In turn, the rise in blood pressure and volume resulting from the various actions of angiotensin II and aldosterone reduce the release of renin. While both ADH and RAAS increase water reabsorption, they counter different osmoregulatory problems. o The release of ADH is a response to an increase in the osmolarity of the blood, as when the body is dehydrated from excessive loss or inadequate intake of water. o However, a situation that causes excessive loss of salt and body fluidsan injury or severe diarrhea, for example will reduce blood volume without increasing osmolarity. o The RAAS will detect the fall in blood volume and pressure and respond by increasing water and Na+ reabsorption. Normally, ADH and the RAAS are partners in homeostasis. o ADH alone would lower blood Na+ concentration by stimulating water reabsorption in the kidney. o But the RAAS helps maintain balance by stimulating Na+ reabsorption. Still another hormone, atrial natriuretic factor (ANF), opposes the RAAS. o The walls of the atria release ANF in response to an increase in blood volume and pressure. o ANF inhibits the release of renin from the JGA, inhibits NaCl reabsorption by the collecting ducts, and reduces aldosterone release from the adrenal glands. o These actions lower blood pressure and volume. o Thus, the ADH, the RAAS, and ANF provide an elaborate system of checks and balances that regulates the kidneys ability to control the osmolarity, salt concentration, volume, and pressure of blood. The South American vampire bat, Desmodus rotundas, illustrates the flexibility of the mammalian kidney to adjust rapidly to contrasting osmoregulatory and excretory problems. o This species feeds on the blood of large birds and mammals by making an incision in the victims skin and then lapping up blood from the wound. Because they fly long distances to locate a suitable victim, they benefit from consuming as much blood as possible when they do find preyso much so that a bat would be too heavy to fly after feeding. o The bat uses its kidneys to offload much of the water absorbed from a blood meal by excreting large volumes of dilute urine as it feeds.

o Having lost enough water to fly, the bat returns to its roost in a cave or hollow tree, where it spends the day. In the roost, the bat faces a very different regulatory problem. o Its food is mostly protein, which generates large quantities of urea, but roosting bats dont have access to drinking water. o Their kidneys shift to producing small quantities of highly concentrated urine, disposing of the urea load while conserving as much water as possible. o The vampire bats ability to alternate rapidly between producing large amounts of dilute urine and small amounts of very hyperosmotic urine is an essential part of its adaptation to an unusual food source. Concept 44.6 Diverse adaptations of the vertebrate kidney have evolved in different environments Variations in nephron structure and function equip the kidneys of different vertebrates for osmoregulation in their various habitats. o Mammals that excrete the most hyperosmotic urine, such as hopping mice and other desert mammals, have exceptionally long loops of Henle. This maintains steep osmotic gradients, resulting in very concentrated urine. o In contrast, beavers, which rarely face problems of dehydration, have nephrons with short loops, resulting in a much lower ability to concentrate urine. Birds, like mammals, have kidneys with juxtamedullary nephrons that specialize in conserving water. o However, the nephrons of birds have much shorter loops of Henle than do mammalian nephrons. o Bird kidneys cannot concentrate urine to the osmolarities achieved by mammalian kidneys. o The main water conservation adaptation of birds is the use of uric acid as the nitrogen excretion molecule. The kidneys of other reptiles, having only cortical nephrons, produce urine that is, at most, isoosmotic to body fluids. o However, the epithelium of the cloaca helps conserve fluid by reabsorbing some of the water present in urine and feces. o Also, like birds, most other terrestrial reptiles excrete nitrogenous wastes as uric acid. In contrast to mammals and birds, a freshwater fish must excrete excess water because the animal is hyperosmotic to its surroundings. o Instead of conserving water, the nephrons produce a large volume of very dilute urine. o Freshwater fishes conserve salts by reabsorption of ions from the filtrate in the nephrons. Amphibian kidneys function much like those of freshwater fishes. o When in fresh water, the skin of the frog accumulates certain salts from the water by active transport, and the kidneys excrete dilute urine. o On land, where dehydration is the most pressing problem, frogs conserve body fluid by reabsorbing water across the epithelium of the urinary bladder. Marine bony fishes, being hypoosmotic to their surroundings, have the opposite problem of their freshwater relatives. o In many species, nephrons have small glomeruli or lack glomeruli altogether. o Concentrated urine is produced by secreting ions into excretory tubules. o The kidneys of marine fishes excrete very little urine and function mainly to get rid of divalent ions such as Ca2+, Mg2+, and SO42-, which the fish takes in by its incessant drinking of seawater. o Its gills excrete mainly monovalent ions such as Na+ and Cl- and the bulk of its nitrogenous wastes in the form of NH4+.

Chapter 45 - Hormones and the Endocrine System Overview: The Bodys Long-Distance Regulators An animal hormone is a chemical signal that is secreted into the circulatory system that communicates regulatory messages within the body. o A hormone may reach all parts of the body, but only specific target cells respond to specific hormones. o A given hormone traveling in the bloodstream elicits specific responses from its target cells, while other cell types ignore that particular hormone. Concept 45.1 The endocrine system and the nervous system act individually and together in regulating an animals physiology Animals have two systems of internal communication and regulation, the nervous system and the endocrine system. Collectively, all of an animals hormone-secreting cells constitute its endocrine system. o Hormones coordinate slow but long-acting responses to stimuli such as stress, dehydration, and low blood glucose levels. o Hormones also regulate long-term developmental processes such as growth and development of primary and secondary sexual characteristics. Hormone-secreting organs called endocrine glands secrete hormones directly into the extracellular fluid, where they diffuse into the blood. The nervous and endocrine systems overlap to some extent. o Certain specialized nerve cells known as neurosecretory cells release hormones into the blood. o The hormones produced by these cells are sometimes called neurohormones.

Chemicals such as epinephrine serve as both hormones of the endocrine system and neurotransmitters in the nervous system. The nervous system plays a role in certain sustained responsescontrolling day/night cycles and reproductive cycles in many animals, for exampleoften by increasing or decreasing secretions from endocrine glands. The fundamental concepts of biological control systems are important in regulation by hormones. o A receptor, or sensor, detects a stimulus and sends information to a control center. o After comparing the incoming information to a set point, the control center sends out a signal that directs an effector to respond. o In endocrine and neuroendocrine pathways, this outgoing signal, called an efferent system, is a hormone or neurohormone, which acts on particular effector tissues and elicits specific physiological or developmental changes. The three types of simple hormonal pathways (simple endocrine pathway, simple neurohormone pathway, and simple neuroendocrine pathway) include these basic functional components. A common feature of control pathways is a feedback loop connecting the response to the initial stimulus. In negative feedback, the effector response reduces the initial stimulus, and eventually the response ceases. o This prevents overreaction by the system. o Negative feedback regulates many endocrine and nervous mechanisms. Positive feedback reinforces the stimulus and leads to an even greater response. o The neurohormone pathway that regulates the release of milk by a nursing mother is an example of positive feedback. Suckling stimulates sensory nerve cells in the nipples, which send nervous signals that reach the hypothalamus, the control center. The hypothalamus triggers the release of the neurohormone oxytocin from the posterior pituitary gland. Oxytocin causes the mammary glands to secrete milk. The release of milk in turn leads to more suckling and stimulation of the pathway, until the baby is satisfied. Concept 45.2 Hormones and other chemical signals bind to target cell receptors, initiating pathways that culminate in specific cell responses Hormones convey information via the bloodstream to target cells throughout the body. o Other chemical signalslocal regulatorstransmit information to target cells near the secreting cells. o Pheromones carry messages to different individuals of a species. Three major classes of molecules function as hormones in vertebrates: proteins and peptides, amines, and steroids. o Most protein/peptides and amine hormones are water-soluble, unlike steroid hormones. Signaling by all hormones involves three key events: reception, signal transduction, and response. o Reception of the signal occurs when the signal molecule binds to a specific receptor protein in or on the target cell. o Binding of a signal molecule to a receptor protein triggers signal transduction within the target cell that results in a response, a change in the cells behavior. Cells that lack receptors for a particular chemical signal are unresponsive to that signal. Water-soluble hormones have cell-surface receptors. The receptors for water-soluble hormones are embedded in the plasma membrane. Binding of a hormone to its receptor initiates a signal transduction pathway, a series of changes in cellular proteins that converts an extracellular chemical signal to a specific intracellular response. o The response may be the activation of an enzyme, a change in uptake or secretion of specific molecules, or rearrangement of the cytoskeleton. o Signal transduction from some cell-surface receptors activates proteins in the cytoplasm that move into the nucleus and directly or indirectly regulate gene transcription. An example of the role of cell-surface receptors involves changes in a frogs skin color, an adaptation that helps camouflage the frog in changing light. o Skin cells called melanocytes contain the dark pigment melanin in cytoplasmic organelles called melanosomes. The frogs skin appears light when melanosomes cluster tightly around the cell nuclei and darker when they spread out in the cytoplasm. o A peptide hormone called melanocyte-stimulating hormone controls the arrangement of melanosomes and, thus, skin color. o Adding melanocyte-stimulating hormone to the interstitial fluid containing the pigment-containing cells causes the melanosomes to disperse. However, direct microinjection of melanocyte-stimulating hormone into individual melanocytes has no effect. o This provides evidence that interaction between the hormone and a surface receptor is required for hormone action. A particular hormone may cause diverse responses in target cells having different receptors for the hormone, different signal transduction pathways, and/or different proteins for carrying out the response. Lipid-soluble hormones have intracellular receptors. Evidence for intracellular receptors for steroid hormones came in the 1960s.

Researchers demonstrated that estrogen and progesterone accumulate within the nuclei of cells in the reproductive tract of female rats but not in the nuclei of cells in tissues that do not respond to estrogen. o These observations led to the hypothesis that cells sensitive to steroid hormones contain internal receptor molecules that bind the hormones. Researchers have since identified the intracellular protein receptors for steroid hormones, thyroid hormones, and the hormonal form of vitamin D. o All these hormones are small, nonpolar molecules that diffuse through the phospholipid interior of cell membranes. Intracellular receptors usually perform the entire task of transducing the signal within the target cell. o The chemical signal activates the receptor, which directly triggers the cells response. o In almost every case, the intracellular receptor activated by a lipid-soluble hormone is a transcription factor, and the response is a change in gene expression. Most intracellular receptors are located in the nucleus. o The hormone-receptor complexes bind to specific sites in the cells DNA and stimulate the transcription of specific genes. Some steroid hormone receptors are trapped in the cytoplasm when no hormone is present. o Binding of a steroid hormone to its cytoplasmic receptor forms a hormone-receptor complex that can move into the nucleus and stimulate transcription of specific genes. In both cases, mRNA produced in response to hormone stimulation is translated into new protein in the cytoplasm. o For example, estrogen induces cells in the reproductive system of a female bird to synthesize large amount of ovalbumin, the main protein of egg white. As with hormones that bind to cell-surface receptors, hormones that bind to intracellular receptors may exert different effects on different target cells. A variety of local regulators affect neighboring target cells. Local regulators convey messages between neighboring cells, a process referred to as paracrine signaling. o Local regulators can act on nearby target cells within seconds or milliseconds, eliciting responses more quickly than hormones can. o Some local regulators have cell-surface receptors; others have intracellular receptors. o Binding of local regulators to their receptors triggers events within target cells similar to those elicited by hormones. Several types of chemical compounds function as local regulators. o Among peptide/protein local regulators are cytokines, which play a role in immune responses, and most growth factors, which stimulate cell proliferation and differentiation. o Another important local regulator is the gas nitric oxide (NO). When blood oxygen level falls, endothelial cells synthesize and release NO. NO activates an enzyme that relaxes neighboring smooth muscle cells, dilating the walls of blood vessels and improving blood flow to tissues. Nitric oxide also plays a role in male sexual function, increasing blood flow to the penis to produce an erection. Highly reactive and potentially toxic, NO usually triggers changes in the target cell within a few seconds of contact and then breaks down. Viagra sustains an erection by interfering with the breakdown of NO. When secreted by neurons, NO acts as a neurotransmitter. When secreted by white blood cells, it kills bacteria and cancer cells. Local regulators called prostaglandins (PGs) are modified fatty acids derived from lipids in the plasma membrane. o Released by most types of cells into interstitial fluids, prostaglandins regulate nearby cells in various ways, depending on the tissue. o In semen that reaches the female reproductive tract, prostaglandins trigger the contraction of the smooth muscles of the uterine wall, helping sperm to reach the egg. o PGs secreted by the placenta cause the uterine muscles to become more excitable, helping to induce uterine contractions during childbirth. o Other PGs help induce fever and inflammation, and intensify the sensation of pain. These responses contribute to the bodys defense. The anti-inflammatory effects of aspirin and ibuprofen are due to the drugs inhibition of prostaglandin synthesis. o Prostaglandins also help regulate the aggregation of platelets, an early stage in the formation of blood clots. This is why people at risk for a heart attack may take daily low doses of aspirin. o In the respiratory system, two prostaglandins have opposite effects on the smooth muscle cells in the walls of blood vessels serving the lungs. Prostaglandin E signals the muscle cells to relax, dilating the blood vessels and promoting oxygenation of the blood. Prostaglandin F signals the muscle cells to contract, constricting the vessels and reducing blood flow through the lungs. Concept 45.3 The hypothalamus and pituitary integrate many functions of the vertebrate endocrine system

The hypothalamus integrates vertebrate endocrine and nervous function. This region of the lower brain receives information from nerves throughout the body and from other parts of the brain then initiates endocrine signals appropriate to environmental conditions. The hypothalamus contains two sets of neurosecretory cells whose hormonal secretions are stored in or regulate the activity of the pituitary gland, located at the base of the hypothalamus. The posterior pituitary (neurohypophysis) stores and secretes two hormones produced by the hypothalamus. o The long axons of these cells carry the hormones to the posterior pituitary. The anterior pituitary (adenohypophysis) consists of endocrine cells that synthesize and secrete at least six different hormones directly into the blood. o Several of these hormones have other endocrine glands as their targets. Hormones that regulate the function of endocrine glands are called tropic hormones. They are particularly important in coordinating endocrine signaling throughout the body. The anterior pituitary itself is regulated by tropic hormones produced by a set of neurosecretory cells in the hypothalamus. o Some hypothalamic tropic hormones (releasing hormones) stimulate the anterior pituitary to release its hormones. o Others (inhibiting hormones) inhibit hormone secretion. Hypothalamic releasing and inhibiting hormones are secreted into capillaries at the base of the hypothalamus. o The capillaries drain into portal vessels that subdivide into a second capillary bed within the anterior pituitary. Every anterior pituitary hormone is controlled by at least one releasing hormone. o Some have both a releasing hormone and an inhibiting hormone. The posterior pituitary releases two hormones, oxytocin and antidiuretic hormone. o Both are peptides made by neurosecretory cells in the hypothalamus and, thus, are neurohormones. Oxytocin induces contraction of the uterus during childbirth and causes mammary glands to eject milk during nursing. o Oxytocin signaling in both cases exhibits positive feedback. Antidiuretic hormone (ADH) promotes retention of water by the kidneys, decreasing urine volume. o ADH helps regulate osmolarity of the blood via negative feedback. Secretion is regulated by water/salt balance. The anterior pituitary produces many different hormones. o Four function as tropic hormones, stimulating the synthesis and release of hormones from the thyroid gland, adrenal glands, and gonads. o Several others exert only direct, nontropic effects on nonendocrine organs. o One, growth hormone, has both tropic and nontropic actions. Three of the tropic hormones secreted by the anterior pituitary are closely related in their chemical structures. o Follicle-stimulating hormone (FSH), luteinizing hormone (LH), and thyroid-stimulating hormone (TSH) are similar glycoproteins. FSH and LH are also called gonadotropins because they stimulate the activities of the gonads. TSH promotes normal development of the thyroid gland and the production of thyroid hormones. o Adrenocorticotropic hormone (ACTH) is a peptide hormone that stimulates the production and secretion of steroid hormones by the adrenal cortex. All four anterior pituitary tropic hormones participate in complex neuroendocrine pathways. o In each pathway, signals to the brain stimulate release of an anterior pituitary tropic hormone. o The tropic hormone then acts on its target endocrine tissue, stimulating secretion of a hormone that exerts systemic metabolic or developmental effects. Nontropic hormones produced by the anterior pituitary include prolactin, melanocyte-stimulating hormone (MSH), and endorphin. o These peptide/protein hormones, whose secretion is controlled by hypothalamic hormones, function in simple neuroendocrine pathways. o Prolactin (PRL) stimulates mammary gland growth and milk production and secretion in mammals. It regulates fat metabolism and reproduction in birds, delays metamorphosis in amphibians (where it may also function as a larval growth hormone), and regulates salt and water balance in freshwater fishes. This suggests that prolactin is an ancient hormone whose functions have diversified during the evolution of various vertebrate groups. Secretion is regulated by hypothalamic hormones. o Melanocyte-stimulating hormone (MSH) regulates the activity of pigment-containing cells in the skin of some fishes, amphibians, and reptiles. In mammals, MSH acts on neurons in the brain, inhibiting hunger. o -endorphin belongs to a class of chemical signals called endorphins. All the endorphins bind to receptors in the brain and dull the perception of pain. o Both MSH and -endorphin are formed by cleavage of the same precursor protein that gives rise to ACTH. Growth hormone (GH) is so similar structurally to prolactin that scientists hypothesize the genes directing their production evolved from the same ancestral gene. o GH acts on a wide variety of target tissues with both tropic and nontropic effects.

Its major tropic action is to signal the liver to release insulin-like growth factors (IGFs), which circulate in the blood and directly stimulate bone and cartilage growth. In the absence of GH, the skeleton of an immature animal stops growing. o GH also exerts diverse metabolic effects that raise blood glucose, opposing the effects of insulin. o Abnormal production of GH can produce several disorders. Gigantism is caused by excessive GH production during development. Acromegaly is caused by excessive GH production during adulthood. Pituitary dwarfism is caused by childhood GH deficiency, and can be treated by therapy with genetically engineered GH. Concept 45.4 Nonpituitary hormones help regulate metabolism, homeostasis, development, and behavior Thyroid hormones function in development, bioenergetics, and homeostasis. The thyroid gland of mammals consists of two lobes located on the ventral surface of the trachea. The thyroid gland produces two very similar hormones derived from the amino acid tyrosine: triiodothyronine (T3), which contains three iodine atoms, and thyroxin (T4), which contains four iodine atoms. o In mammals, the thyroid secretes mainly T4, but target cells convert most of it to T3 by removing one iodine atom. Although the same receptor molecule in the cell nucleus binds both hormones, the receptor has greater affinity for T3 than for T4. It is primarily T3 that brings about responses in target cells. o This process involves a complex neuroendocrine pathway with two negative feedback loops. The thyroid plays a crucial role in vertebrate development and maturation. o Thyroid controls metamorphosis of a tadpole into a frog, which involves massive reorganization of many different tissues. The thyroid is equally important in human development. o Cretinism, an inherited condition of thyroid deficiency, retards skeletal growth and mental development. The thyroid gland has important homeostatic functions. o In adult mammals, thyroid hormones help to maintain normal blood pressure, heart rate, muscle tone, digestion, and reproductive functions. Throughout the body, T3 and T4 are important in bioenergetics, increasing the rate of oxygen consumption and cellular metabolism. Too much or too little of these hormones can cause serious metabolic disorders. o Hyperthyroidism is the excessive secretion of thyroid hormones, leading to high body temperature, profuse sweating, weight loss, irritability, and high blood pressure. o An insufficient amount of thyroid hormones is known as hypothyroidism. This condition can cause cretinism in infants. Adult symptoms include weight gain, lethargy, and cold intolerance. o A deficiency of iodine in the diet can result in goiter, an enlargement of the thyroid gland. Without sufficient iodine, the thyroid gland cannot synthesize adequate amounts of T3 and T4. The resulting low blood levels of these hormones cannot exert negative feedback on the hypothalamus and anterior pituitary. The pituitary continues to secrete TSH, elevating TSH levels and enlarging the thyroid. In addition to cells that produce T3 and T4, the mammalian thyroid gland produces calcitonin. o This hormone acts in conjunction with parathyroid hormone to maintain calcium homeostasis. Parathyroid hormone and calcitonin balance blood calcium. Rigorous homeostatic control of blood calcium level is critical because calcium ions (Ca2+) are essential to the normal functioning of all cells. o If blood Ca2+ falls substantially, skeletal muscles begin to contract convulsively, a potentially fatal condition called tetany. o In mammals, parathyroid hormone and calcitonin play a major role in maintaining blood Ca2+ near a set point of about 10 mg/100 mL. When blood Ca2+ falls below the set point, parathyroid hormone (PTH) is released from four small structures, the parathyroid glands, embedded on the surface of the thyroid. PTH raises the level of blood Ca2+ by direct and indirect effects. o In bone, PTH induces specialized cells called osteoclasts to decompose the mineralized matrix of bone and release Ca2+ into the blood. o In the kidneys, it promotes the conversion of vitamin D to its active hormonal form. An inactive form of vitamin D is obtained from food or synthesized in the skin. o The active form of vitamin D acts directly on the intestines, stimulating the uptake of Ca2+ from food. o A rise in blood Ca2+ above the set point promotes release of calcitonin from the thyroid gland. o Calcitonin exerts effects on bone and kidneys opposite those of PTH and thus lowers blood Ca2+ levels. The regulation of blood Ca2+ levels illustrates how two hormones with opposite effects (PTH and calcitonin) balance each other, exerting tight regulation and maintaining homeostasis.

Each hormone functions in a simple endocrine pathway in which the hormone-secreting cells themselves monitor the variable being regulated. o In classic feedback, the response to one hormone triggers release of the antagonistic hormone, minimizing fluctuations in the concentration of Ca2+ levels in the blood. Endocrine tissues of the pancreas secrete insulin and glucagon, antagonistic hormones that regulate blood glucose. The pancreas has both endocrine and exocrine functions. o Its exocrine function is the secretion of bicarbonate ions and digestive enzymes, which are released into small ducts and carried to the small intestine via the pancreatic duct. o Tissues and glands that discharge secretions into ducts are described as exocrine. Clusters of endocrine cells, the islets of Langerhans, are scattered throughout the exocrine tissues of the pancreas. o Each islet has a population of alpha cells, which produce the hormone glucagon, and a population of beta cells, which produce the hormone insulin. o Both hormones are secreted directly into the circulatory system. Insulin and glucagon are antagonistic hormones that regulate the concentration of glucose in the blood. o This is a critical bioenergetic and homeostatic function, because glucose is a major fuel for cellular respiration and a key source of carbon skeletons for the synthesis of other organic compounds. Metabolic balance depends on maintaining blood glucose concentrations near a set point of about 90 mg/100 mL in humans. o When blood glucose exceeds this level, insulin is released and lowers blood glucose. o When blood glucose falls below this level, glucagon is released and its effects increase blood glucose concentration. o Each hormone operates in a simple endocrine pathway regulated by negative feedback. Insulin lowers blood glucose levels by stimulating all body cells (except brain cells) to take up glucose from the blood. o Brain cells can take up glucose without insulin and, thus, have access to circulating fuel at all times. Insulin also decreases blood glucose by slowing glycogen breakdown in the liver and inhibiting the conversion of amino acids and glycerol to glucose. The liver, skeletal muscles, and adipose tissues store large amounts of fuel and are especially important in bioenergetics. o The liver and muscles store sugar as glycogen, whereas adipose tissue cells convert sugars to fats. o The liver is a key fuel-processing center because only liver cells are sensitive to glucagon. The antagonistic effects of glucagon and insulin are vital to glucose homeostasis and regulation of fuel storage and fuel consumption by body cells. The livers ability to perform its vital roles in glucose homeostasis results from the metabolic versatility of its cells and its access to absorbed nutrients via the hepatic portal vein. Diabetes mellitus is perhaps the best-known endocrine disorder. o It is caused by a deficiency of insulin or a depressed response to insulin in target tissues. There are two types of diabetes mellitus with very different causes, but each is marked by high blood glucose. o In people with diabetes, elevated blood glucose exceeds the reabsorption capacity of the kidneys, causing them to excrete glucose. As glucose is concentrated in the urine, more water is excreted with it, resulting in excessive volumes of water and persistent thirst. o Without sufficient glucose to meet the needs of most body cells, fat becomes the main substrate for cellular respiration. o In severe cases of diabetes, acidic metabolites formed during fat breakdown accumulate in the blood, threatening life by lowering blood pH. Type I diabetes mellitus (insulin-dependent diabetes) is an autoimmune disorder in which the immune system destroys the beta cells of the pancreas. o Type I diabetes usually appears in childhood and destroys the persons ability to produce insulin. o The treatment is insulin injections, usually several times a day. o Human insulin is available from genetically engineered bacteria. Type II diabetes mellitus (non-insulin-dependent diabetes) is characterized by deficiency of insulin or, more commonly, by a decreased responsiveness to insulin in target cells, due to some change in insulin receptors. o This form of diabetes occurs after age 40, and the risk increases with age. o Although heredity can play a role in type II diabetes, excess body weight and lack of exercise significantly increase the risk. o Type II diabetes accounts for more than 90% of diabetes cases. Many type II diabetics can manage their blood glucose with regular exercise and a healthful diet, although some require insulin injections. The adrenal medulla and adrenal cortex help the body manage stress. The adrenal glands are located adjacent to the kidneys. In mammals, each adrenal gland is actually made up of two glands with different cell types, functions, and embryonic origins. o The adrenal cortex is the outer portion, and the adrenal medulla is the central portion.

Like the pituitary, the adrenal gland is a fused endocrine and neuroendocrine gland. o The adrenal cortex consists of true endocrine cells, while the secretory cells of the adrenal medulla derive from the neural crest during embryonic development. The adrenal medulla produces two hormones, epinephrine (adrenaline) and norepinephrine (noradrenaline). o These hormones are members of a class of hormones, the catecholamines, amines that are synthesized from the amino acid tyrosine. Both are also neurotransmitters in the nervous system. o Either positive or negative stress stimulates secretion of epinephrine and norepinephrine from the adrenal medulla. These hormones act directly on several target tissues to give the body a rapid bioenergetic boost. They increase the rate of glycogen breakdown in the liver and skeletal muscles, promote glucose release into the blood by liver cells, and stimulate the release of fatty acids from fat cells. The released glucose and fatty acids circulate in the blood and can be used by the body as fuel. o Epinephrine and norepinephrine also exert profound effects on the cardiovascular and respiratory systems. They increase heart rate and stroke volume of the heartbeat and dilate the bronchioles in the lungs to increase the rate of oxygen delivery to body cells. Catecholamines also act to shunt blood away from skin, digestive organs, and kidneys, and increase blood supply to the heart, brain, and skeletal muscles. Epinephrine generally has a greater effect on heart and metabolic rates, while the primary role of norepinephrine is in sustaining blood pressure. Secretion of these hormones by the adrenal medulla is stimulated by nerve signals carried from the brain via the sympathetic division of the autonomic nervous system. In response to a stressful situation, nerve impulses from the hypothalamus travel to the adrenal medulla, where they trigger the release of epinephrine. o Norepinephrine is released independently. The adrenal medulla hormones act in a simple neurohormone pathway. o The neurosecretory cells are modified peripheral nerve cells. Hormones from the adrenal cortex also function in the bodys response to stress. Stressful stimuli cause the hypothalamus to secrete a releasing hormone that stimulates the anterior pituitary to release the tropic hormone ACTH. When ACTH reaches the adrenal cortex via the bloodstream, it stimulates the endocrine cells to synthesize and secrete a family of steroids called corticosteroids. o Elevated levels of corticosteroids in the blood suppress the secretion of ACTH. The two main types of corticosteroids in humans are the glucocorticoids, such as cortisol, and the mineralocorticoids, such as aldosterone. o Both hormones help maintain homeostasis when stress is experienced over a long period of time. The primary effect of glucocorticoids is on bioenergetics, specifically on glucose metabolism. o Glucocorticoids make more glucose available as fuel. o They act on skeletal muscle, causing a breakdown of muscle proteins. o The synthesis of glucose from muscle proteins is a homeostatic mechanism providing circulating fuel when body activities require more than the liver can metabolize from its metabolic stores. Cortisol and other glucocorticoids also suppress certain components of the bodys immune system. o Because of their anti-inflammatory effect, glucocorticoids have been used to treat inflammatory diseases such as arthritis. o However, long-term use of these hormones can have serious side effects due to their metabolic actions and can also increase susceptibility to infection. Mineralocorticoids act principally on salt and water balance. o Aldosterone stimulates cells in the kidneys to reabsorb Na+ and water from filtrate, raising blood pressure and volume. o Aldosterone secretion is stimulated primarily by angiotensin II, as part of the regulatory pathway that controls the kidneys ability to maintain ion and water homeostasis of the blood. o When an individual is under severe stress, the resulting rise in blood ACTH levels can increase the rate at which the adrenal cortex secretes aldosterone as well as glucocorticoids. A third group of corticosteroids is composed of sex hormones. All the steroid hormones are secreted from cholesterol, and their structures differ in minor ways. o However, these differences are associated with major differences in their effects. The sex hormones produced by the adrenal cortex are mainly male hormones (androgens) with small amounts of female hormones (estrogens and progestins) o Androgens secreted by the adrenal cortex may account for the female sex drive. Gonadal steroids regulate growth, development, reproductive cycles, and sexual behavior. The gonads are the primary source of the sex hormones. The gonads produce and secrete three major categories of steroid hormones: androgens, estrogens, and progestins.

All three types are found in males and females but in different proportions. Sex hormones affect growth and development and regulate reproductive cycles and sexual behavior. The testes primarily synthesize androgens, the main one being testosterone. o Androgens promote development and maintenance of male sex characteristics. o Androgens produced early in development determine whether a fetus develops as a male or a female. o At puberty, high levels of androgens are responsible for the development of male secondary sex characteristics, including male patterns of hair growth, a low voice, and increased muscle mass and bone mass typical of males. o The muscle-building action of testosterone and other anabolic steroids has led some athletes to take them as supplements. Abuse of these hormones carries many health risks, and they are banned in most competitive sports. Estrogens, the most important of which is estradiol, are responsible for the development and maintenance of the female reproductive system and the development of female secondary sex characteristics. In mammals, progestins, which include progesterone, are involved in promoting uterine lining growth to support the growth and development of an embryo. Both estrogens and androgens are components of complex neuroendocrine pathways. o Their secretion is controlled by gonadotropins (FSH and LH) from the anterior pituitary gland. o FSH and LH production is controlled by a releasing hormone from the hypothalamus, GnRH (gonadotropinreleasing hormone). The pineal gland is involved in biorhythms. The pineal gland is a small mass of tissue near the center of the mammalian brain. o The pineal gland synthesizes and secretes the hormone melatonin, an amine. o Depending on the species, the pineal gland contains light-sensitive cells or has nervous connections from the eyes that control its secretory activity. o Melatonin regulates functions related to light and to seasons marked by changes in day length. o Its primary functions are related to biological rhythms associated with reproduction. Melatonin secretion is regulated by light/dark cycles. Melatonin is secreted at night, and the amount secreted depends on the length of the night. Thus, melatonin production is a link between a biological clock and daily or seasonal activities such as reproduction. o Recent evidence suggests that the main target cells of melatonin are the part of the brain called the suprachiasmatic nucleus (SCN), which functions as a biological clock. Melatonin seems to decrease the activity of neurons in the SCN, and this may be related to its role in mediating rhythms. o Much remains to be learned about the precise role of melatonin and about biological clocks in general. Concept 45.5 Invertebrate regulatory systems also involve endocrine and nervous system interactions Invertebrates produce a variety of hormones in endocrine and neurosecretory cells. Some invertebrate hormones have homeostatic functions, such as regulation of water balance. Others function in reproduction and development. o In hydras, one hormone functions in growth and budding (asexual reproduction) but prevents sexual reproduction. o In the mollusc Aplysia, specialized nerve cells secrete a neurohormone that stimulates the laying of thousands of eggs and inhibits feeding and locomotion, activities that interfere with reproduction. All groups of arthropods have extensive endocrine systems. o Crustaceans have hormones for growth and reproduction, water balance, movement of pigments in the integument and eyes, and regulation of metabolism. Crustaceans and insects grow in spurts, shedding the old exoskeleton and secreting a new one with each molt. o Insects acquire their adult characteristics in a single terminal molt. o In all arthropods with exoskeletons, molting is triggered by a hormone. The hormonal control of insect development is well understood. Brain hormone, produced by neurosecretory cells in the brain, stimulates the release of ecdysone from the prothoracic glands, a pair of endocrine glands behind the head. Ecdysone promotes molting and the development of adult characteristics. Brain hormone and ecdysone are balanced by juvenile hormone, secreted by the corpora allata, a pair of small endocrine glands that are somewhat analogous to the anterior pituitary of vertebrates. o As the name suggests, juvenile hormone promotes the retention of larval (juvenile) characteristics. In the presence of a high concentration of juvenile hormone, ecdysone still stimulates molting, but the product is simply a larger larva. Only when the level of juvenile hormone declines can ecdysone-induced molting produce a pupa. o Within the pupa, metamorphosis produces the adult form. o Synthetic juvenile hormone is used as insecticide to prevent insects from maturing to reproductive adults.

Chapter 46 - Animal Reproduction Overview: Doubling Up for Sexual Reproduction Concept 46.1 Both asexual and sexual reproduction occur in the animal kingdom Asexual reproduction involves the formation of individuals whose genes come from a single parent. o There is no fusion of sperm and egg. Sexual reproduction is the formation of offspring by the fusion of haploid gametes to form a diploid zygote. o The female gamete, the unfertilized egg, or ovum, is usually large and nonmotile. o The male gamete is the sperm, which is usually small and motile. o Sexual reproduction increases genetic variation among offspring by generating unique combinations of genes inherited from two parents. Diverse mechanisms of asexual reproduction enable animals to produce identical offspring rapidly. Many invertebrates can reproduce asexually by fission, in which a parent separates into two or more approximately equalsized individuals. o Budding is also common among invertebrates. This is a form of asexual reproduction in which new individuals split off from existing ones. o In fragmentation, the body breaks into several pieces, some or all of which develop into complete adults. Reproducing in this way requires regeneration of lost body parts. Many animals can also replace new appendages by regeneration. Asexual reproduction has a number of advantages. o It allows isolated animals to reproduce without needing to find a mate. o It can create numerous offspring in a short period of time. o In stable environments, it allows for the perpetuation of successful genotypes. Reproductive cycles and patterns vary extensively among mammals. Most animals exhibit cycles in reproductive activity, usually related to changing seasons. o This allows animals to conserve resources and reproduce when more energy is available and when environmental conditions favor the survival of offspring. Reproductive cycles are controlled by a combination of environmental and hormonal cues. o Environmental cues may include seasonal temperature, rainfall, day length, and lunar cycles. Animals may reproduce exclusively asexually or sexually or they may alternate between the two modes, depending on environmental conditions. o Daphnia reproduce by parthenogenesis under favorable conditions and sexually during times of environmental stress. Parthenogenesis is the process by which an unfertilized egg develops without being fertilized. o Parthenogenesis plays a role in the social organization of some bees, wasps, and ants. Male honeybees (drones) are haploid, and female honeybees (queens and workers) are diploid. o Several genera of fishes, amphibians, and lizards reproduce by a form of parthenogenesis that produces diploid zygotes. Fifteen species of whiptail lizards reproduce exclusively by parthenogenesis. There are no males in this species, but the lizards imitate courtship and mating behavior typical of sexual species of the same genus. Sexual reproduction presents a problem for sessile or burrowing animals or parasites that may have difficulty encountering a member of the opposite sex. o One solution is hermaphroditism, in which one individual functions as both a male and a female. Some hermaphrodites can self-fertilize, but most mate with another member of the same species. In such matings, each individual receives and donates sperm. This results in twice as many offspring as would be produced if only one set of eggs were fertilized. o In sequential hermaphroditism, an individual reverses its sex during its lifetime. In some species, the sequential hermaphrodite is female first. In other species, the sequential hermaphrodite is male first. Concept 46.2 Fertilization depends on mechanisms that help sperm meet eggs of the same species The mechanisms of fertilization, the union of sperm and egg, play an important part in sexual reproduction. o In external fertilization, eggs are released by the female into a wet environment, where they are fertilized by the male. o In species with internal fertilization, sperm are deposited in or near the female reproductive tract, and fertilization occurs within the tract. A moist habitat is almost always required for external fertilization, both to prevent gametes from drying out and to allow the sperm to swim to the eggs. In species with external fertilization, timing is crucial to ensure that mature sperm encounter ripe eggs. o Environmental cues such as temperature or day length may cause gamete release by the whole population. o Individuals may engage in courtship behavior that leads to fertilization of the eggs of one female by one male.

Internal fertilization is an adaptation to terrestrial life that enables sperm to reach an egg in a dry environment. o Internal fertilization requires sophisticated reproductive systems, including copulatory organs that deliver sperm and receptacles for their storage and transport to ripe eggs. Mating animals may use pheromones, chemical signals released by one organism that influence the behavior or physiology of other individuals of the same species. o Pheromones are small, volatile, or water-soluble molecules that disperse into the environment. o Like hormones, pheromones are active in minute amounts. o Many pheromones act as male attractants. All species produce more offspring than can survive to reproduce. Internal fertilization usually involves the production of fewer zygotes than does external fertilization. o However, the survival rate is higher for internal fertilization. o Major types of protection include tough eggshells, development of the embryo within the reproductive tract of the mother, and parental care of the eggs and offspring. Marsupial mammals retain their embryos for only a short period in the uterus. o The embryos crawl out and complete fetal development attached to a mammary gland in the mothers pouch. The embryos of eutherian mammals develop entirely within the uterus, nourished through the placenta. Parental care of offspring can occur regardless of whether fertilization is external or internal. Reproductive systems produce gametes and make them available to gametes of the opposite sex. The least complex reproductive systems lack gonads, the organs that produce gametes in most animals. o Polychaete worms lack gonads. Eggs and sperm develop from undifferentiated cells lining the coelom. o As the gametes mature, they are released from the body wall and fill the coelom. o In some species, the body splits open to release the gametes, killing the parent. Some reproductive systems, such as those of parasitic flatworms, are very complex. Most insects have separate sexes with complex reproductive systems. o In many species, the female reproductive system includes a spermatheca, a sac in which sperm may be stored for a year or more. The basic plan of all vertebrate reproductive systems is very similar. o However, there are variations. In many nonmammalian vertebrates, the digestive, excretory, and reproductive systems share a common opening to the outside, the cloaca. Mammals have separate openings for the digestive and reproductive systems. Female mammals also have separate openings for the excretory and reproductive systems. o The uterus of most vertebrates is partly or completely divided into two chambers. o Male reproductive systems differ mainly in copulatory organs. Many mammalian vertebrates do not have a well-developed penis and simply turn the cloaca inside out to ejaculate. Concept 46.3 Reproductive organs produce and transport gametes: focus on humans Human reproduction involves intricate anatomy and complex behavior. The reproductive anatomy of the human female includes external and internal reproductive structures. o External reproductive structures consist of two sets of labia surrounding the clitoris and vaginal opening. o Internal reproductive organs consist of a pair of gonads and a system of ducts and chambers. The role of the ducts and chambers is to conduct the gametes and house the embryo and fetus. The ovaries, the female gonads, lie in the abdominal cavity, attached to the uterus by a mesentery. o Each ovary is enclosed in a tough protective capsule and contains many follicles. o Each follicle consists of one egg cell surrounded by one or more layers of follicle cells. A woman is born with about 400,000 follicles. Only several hundred of these will release eggs during a females reproductive years. Follicles produce the primary female sex hormones, estrogens. Usually one follicle matures and releases its egg during each menstrual cycle in the process of ovulation. o After ovulation, the remaining follicular tissue develops into the corpus luteum. o The corpus luteum secretes additional estrogens and progesterone, hormones that help maintain the uterine lining during pregnancy. o If pregnancy does not occur, the corpus luteum disintegrates and a new follicle matures during the next cycle. At ovulation, the egg is released into the abdominal cavity near the opening of the oviduct. o The cilia-lined funnel-like opening of the oviduct draws in the egg. o Cilia convey the egg through the oviduct to the uterus. o The highly vascularized inner lining of the uterus is called the endometrium. o The neck of the uterus, the cervix, opens into the vagina. o The vagina is a thin-walled chamber that forms the birth canal and is the repository for sperm during copulation. o It opens to the outside at the vulva, the collective term for the external female genitalia. The vaginal opening is partially covered by a thin sheet of tissue called the hymen.

The vaginal and urethral openings are located within a recess called the vestibule. The vestibule is surrounded by a pair of slender folds called the labia minora. The labia majora enclose and protect the labia minora and vestibule. The clitoris is found at the front edge of the vestibule. During sexual arousal, the clitoris, vagina, and labia engorge with blood and enlarge. o During sexual arousal, Bartholins glands secrete mucus into the vestibule, providing lubrication and facilitating intercourse. Mammary glands are present in both males and females but normally function only in females. o They are not a component of the human reproductive system but are important to mammalian reproduction. o Within the glands, small sacs of epithelial tissue secrete milk, which drains into a series of ducts opening at the nipple. o Adipose tissue forms the main mass of the mammary gland of a nonlactating mammal. The low estrogen level in males prevents the development of the sensory apparatus and fat deposits, so that male breasts remain small, with nipples unconnected to the ducts. The males external reproductive organs consist of the scrotum and penis. The internal reproductive organs consist of gonads that produce sperm and hormones, accessory glands that secrete products essential to sperm movement, and ducts to carry the sperm and glandular secretions. o The male gonads, or testes, consist of highly coiled tubes surrounded by layers of connective tissue. o The tubes are seminiferous tubules, where sperm are produced. o Leydig cells scattered between the seminiferous tubules produce testosterone and other androgens. o The scrotum, a fold in the body wall, holds the testes outside the body cavity at a temperature about 2C below that of the abdomen. This keeps testicular temperature cooler than that in the body cavity. o The testes develop in the body cavity and descend into the scrotum just before birth. From the seminiferous tubules of the testes, the sperm pass through the coiled tubules of the epididymis. o As they pass through this duct, sperm become motile and gain the ability to fertilize an egg. Ejaculation propels sperm from the epididymis to the vas deferens. o The vas deferens run from the scrotum and behind the urinary bladder. o Each vas deferens joins with a duct from the seminal vesicle to form an ejaculatory duct. o The ejaculatory ducts open into the urethra. o The urethra drains both the excretory and reproductive systems. Accessory sex glands add secretions to semen. o A pair of seminal vesicles contributes about 60% of total semen volume. Seminal fluid is thick, yellowish, and alkaline. It contains mucus, fructose, a coagulating enzyme, ascorbic acid, and prostaglandins. The prostate gland secretes directly into the urethra. o Prostatic fluid is thin and milky. o This fluid contains anticoagulant enzymes and citrate. Prostate problems are common in males older than 40. o Benign prostate enlargement occurs in virtually all males older than 70. o Prostate cancer is one of the most common cancers in men. The bulbourethral glands are a pair of small glands along the urethra below the prostate. o Prior to ejaculation, they secrete clear mucus that neutralizes any acidic urine remaining in the urethra. o Bulbourethral fluid also carries some sperm released before ejaculation. o This is one of the reasons the withdrawal method of birth control has a high failure rate. A male usually ejaculates about 25 mL of semen, with each milliliter containing about 50130 million sperm. Once in the female reproductive tract, prostaglandins in semen thin the mucus at the opening of the uterus and stimulate uterine contractions that help move the semen. o When ejaculated, semen coagulates, making it easier for uterine contractions to move it along. Anticoagulants then liquefy the semen, and the sperm begin swimming. o The alkalinity of semen helps neutralize the acidic environment of the vagina, protecting the sperm and increasing their motility. The human penis is composed of three layers of spongy erectile tissue. o During sexual arousal, the erectile tissue fills with blood from arteries. The resultant increased pressure seals off the veins that drain the penis, causing it to engorge with blood. The engorgement of the penis with blood causes an erection, which is essential for the insertion of the penis into the vagina. The penis of some mammals possesses a baculum, a bone that helps stiffen the penis. Temporary impotence can result from the consumption of alcohol or other drugs, and from emotional problems. Irreversible impotence due to nervous system or circulatory problems can be treated with drugs and penile implant devices.

The oral drug Viagra acts by promoting the action of nitric oxide, enhancing relaxation of smooth muscles in the blood vessels of the penis. This allows blood to enter the erectile tissue and sustain an erection. The main shaft of the penis is covered by relatively thick skin. o The sensitive head, or glans penis, is covered by thinner skin. o The glans is covered by the foreskin, or prepuce, which may be removed by circumcision. o There is no verifiable health benefit to circumcision, which arose from religious tradition. Human sexual response is very complex. Human arousal involves a variety of psychological and physical factors. Human sexual response is characterized by a common physiological pattern. o Two types of physiological reaction predominate in both sexes: I. Vasocongestion, filling of tissue with blood, is caused by increased blood flow. II. Myotonia is increased muscle tension. Both smooth and skeletal muscle may show sustained or rhythmic contractions. The sexual response can be divided into four phases: excitement, plateau, orgasm, and resolution. Excitement prepares the vagina and penis for coitus. o Vasocongestion is evident in the erection of the penis and clitoris; the enlargement of the testes, labia, and breasts; and vaginal lubrication. o Myotonia may result in nipple erection or tension in the arms and legs. In the plateau phase, these responses continue. o Stimulation by the autonomic nervous system increases breathing and heart rate. o In females, plateau includes vasocongestion of the outer third of the vagina, expansion of the inner two-thirds of the vagina, and elevation of the uterus to form a depression that receives sperm at the back of the vagina. Orgasm is the shortest phase of the sexual response cycle. o It is characterized by rhythmic, involuntary contractions of the reproductive structures in both sexes. o In male orgasm, emission is the contraction of the glands and ducts of the reproductive tract, which forces semen into the urethra. o Ejaculation occurs with the contraction of the urethra and expulsion of semen. o In female orgasm, the uterus and outer vagina contract. Resolution completes the cycle and reverses the responses of earlier stages. o Vasocongested organs return to their normal sizes and colors; muscles relax. Concept 46.4 In humans and other mammals, a complex interplay of hormones regulates gametogenesis Spermatogenesis and oogenesis both involve meiosis but differ in three significant ways. Gametogenesis is based on meiosis. Spermatogenesis is the production of mature sperm cells from spermatogonia. o Spermatogenesis is a continuous and prolific process in the adult male. o Each ejaculation contains 100650 million sperm. Spermatogenesis occurs in seminiferous tubules. o Primordial germ cells of the embryonic testes differentiate into spermatogonia, the stem cells that give rise to sperm. o As spermatogonia differentiate into spermatocytes and then into spermatids, meiosis reduces the chromosome number from diploid to haploid. o As spermatogenesis progresses, the developing sperm cells move from the wall to the lumen of a seminiferous tubule and then to the epididymis, where they become motile. The structure of sperm fits its function. o A head containing the haploid nucleus is tipped with an acrosome, which contains enzymes that help the sperm penetrate to the egg. o Behind the head are a large number of mitochondria (or a single large one) that provide ATP to power the flagellum. Oogenesis is the production of ova from oogonia. o Oogenesis differs from spermatogenesis in three major ways. I. At birth an ovary may contain all of the primary oocytes it will ever have. However, in 2004, researchers reported that multiplying oogonia exist in the ovaries of adult mice. Researchers are looking for similar cells in human ovaries. Sperm are produced from spermatogonia throughout a mans life. II. Unequal cytokinesis during meiosis results in the formation of a single large secondary oocyte and three small polar bodies. The secondary oocyte becomes the ovum, while the polar bodies degenerate. In spermatogenesis, all four products of meiosis become mature sperm. III. Oogenesis has long resting periods. o Spermatogenesis produces mature sperm from spermatogonia in an uninterrupted sequence. Oogenesis begins in the female embryo with differentiation of primordial germ cells into oogonia, ovary-specific stem cells. o An oogonium multiplies by mitosis and begins meiosis, but the process stops at prophase I.

The primary oocytes remain quiescent within small follicles until puberty. Beginning at puberty, follicle-stimulating hormone (FSH) stimulates a follicle to grow and induces its primary oocyte to complete meiosis I and start meiosis II. It is arrested at metaphase II as a secondary oocyte. o The secondary oocyte is released when the follicle breaks open at ovulation. o Meiosis is completed when a sperm penetrates the oocyte. Oogenesis is completed, producing an ovum. o The haploid nuclei of the sperm and ovum fuse in fertilization. o The ruptured follicle develops into the corpus luteum. If the released oocyte is not fertilized, the corpus luteum degenerates. In females, the secretion of hormones and the reproductive events they regulate are cyclic. o Hormonal control of the female cycle is complex. Humans and many other primates have menstrual cycles. o If pregnancy does not occur, the endometrium is shed through the cervix and vagina in menstruation. Other mammals have estrous cycles. o If pregnancy does not occur, the uterus reabsorbs the endometrium. o Estrous cycles are associated with more pronounced behavioral cycles than are menstrual cycles. The period of sexual activity, estrus, is the only time the condition of the vagina permits mating. Human females may be sexually receptive throughout their menstrual cycle. The term menstrual cycle refers specifically to the changes that occur in the uterus, and is also called the uterine cycle. o It is caused by cyclic events that occur in the ovaries, the ovarian cycle. The cycle begins with the release from the hypothalamus of GnRH or gonadotropin-releasing hormone, which stimulates the pituitary to secrete small amounts of FSH and LH. o FSH stimulates follicle growth, aided by LH, or luteinizing hormone, and the cells of the growing follicles start to make estrogen. There is a slow rise in estrogen secreted during the follicular phase, the part of the ovarian cycle in which follicles are growing and oocytes maturing. The low level of estrogen inhibits secretion of the pituitary hormones, keeping FSH and LH levels low. o The levels of FSH and LH shoot up when the secretion of estrogen by the growing follicle rises sharply. The high concentration of estrogen stimulates the secretion of gonadotropins by acting on the hypothalamus to increase its output of GnRH. This stimulates the secretion of FSH and LH. LH secretion is especially high, because the high concentration of estrogen increases the sensitivity of LHreleasing cells in the pituitary to GnRH. LH induces the final maturation of the follicle and ovulation. The follicle and adjacent wall of the ovary rupture, releasing the secondary oocyte. Following ovulation, during the luteal phase of the ovarian cycle, LH stimulates the transformation of the follicle into the corpus luteum, a glandular structure. Under the continued stimulation by LH during this phase, the corpus luteum secretes progesterone and estrogen. o As the levels of these hormones rise, they exert negative feedback on the hypothalamus and pituitary, inhibiting the secretion of LH and FSH. Near the end of the luteal phase, the corpus luteum disintegrates, causing concentrations of estrogen and progesterone to decline. o The pituitary and hypothalamus are liberated from the inhibitory effects of these hormones. o The pituitary begins to secrete enough FSH to stimulate the growth of new follicles in the ovary, initiating the next ovarian cycle. The follicular phase of the ovarian cycle is coordinated with the proliferative phase of the menstrual cycle. o Secretion of estrogens during the follicular phase stimulates endometrial thickening. o The estrogen and progesterone of the luteal phase stimulate development and maintenance of the endometrium, including the enlargement of arteries and the growth of endometrial glands. The glands secrete a nutrient fluid that can sustain an early embryo before it implants in the uterine lining. Thus, the luteal phase of the ovarian cycle is coordinated with the secretory phase of the uterine cycle. The rapid drop in ovarian hormones as the corpus luteum disintegrates causes spasms in the uterine lining, depriving it of blood. The upper two-thirds of the endometrium disintegrates, resulting in menstruation, or the menstrual flow phase of the uterine cycle, and the beginning of a new cycle. During menstruation, new ovarian follicles begin to grow. o Estrogen is also responsible for female secondary sex characteristics, including deposition of fat in the breasts and hips, increased water retention, and stimulation of breast development. o It also influences sexual behavior. Menopause, the cessation of ovarian and menstrual cycles, usually occurs between ages 46 and 54.

o o

During these years, the ovaries lose their responsiveness to FSH and LH, and menopause results from a decline in estrogen production by the ovary. Menopause is an unusual phenomenon. o In most species, females and males retain their reproductive capacity throughout life. There might be an evolutionary explanation for menopause. o One hypothesis proposes that cessation of reproduction allowed a woman to provide better care for her children and grandchildren, increasing the survival of individuals bearing her genes and increasing her fitness. The principle sex hormones in the male are the androgens. The male sex hormones, androgens, are steroid hormones produced mainly by the Leydig cells of the testes, interstitial cells near the seminiferous tubules. Testosterone, the most important male androgen, and other androgens are responsible for the primary and secondary male sex characteristics. o Primary sex characteristics are associated with the development of the vas deferens and other ducts, development of the external reproductive structures, and sperm production. o Secondary sex characteristics are features not directly related to the reproductive system, including deepening of the voice, distribution of facial and pubic hair, and muscle growth. Androgens also affect behavior. o In addition to specific sexual behaviors and sex drive, androgens increase general aggressiveness. o They are responsible for vocal behavior, like singing in birds and calling by frogs. Hormones from the anterior pituitary and hypothalamus control androgen secretion and sperm production by the testes. Concept 46.5 In humans and other placental mammals, an embryo grows into a newborn in the mothers uterus In placental mammals, pregnancy or gestation is the condition of carrying one or more embryos. o A human pregnancy averages 266 days. o Many rodents have gestation periods of 21 days. Cows have a gestation of 27 days, and elephant gestation lasts 600 days. Fertilization or conception occurs in the oviduct. o Twenty-four hours later, cleavage begins. o Three to four days after fertilization, the embryo reaches the uterus as a ball of cells. o By one week past fertilization, the blastocyst forms as a sphere of cells containing a cavity. o After a few more days, the blastocyst implants in the endometrium. The embryo secretes hormones to signal its presence and control the mothers reproductive system. o Human chorionic gonadotropin (HCG) acts like pituitary LH to maintain secretion of progesterone and estrogens by the corpus luteum for the first few weeks of pregnancy. o Some HCG is excreted in the urine, where it is detected by pregnancy tests. Human gestation is divided into three trimesters of three months each. o For the first 24 weeks of development, the embryo obtains nutrients from the endometrium. o The outer layer of the blastocyst, called the trophoblast invades the endometrium, eventually helping to form the placenta. The placenta allows diffusion of material between maternal and embryonic circulations, providing nutrients, exchanging respiratory gases, and disposing of metabolic wastes for the embryo. o Blood from the embryo travels to the placenta and returns via the umbilical vein. o Organogenesis occurs during the first trimester. By the end of week four, the heart is beating. By the end of week eight, all the major structures of the adult are present in rudimentary form. The rapidity of development makes this a time when the embryo is especially sensitive to environmental insults such as radiation or drugs. o High levels of progesterone initiate changes in the maternal reproductive system. These include increased mucus in the cervix to form a protective plug, growth of the maternal part of the placenta, enlargement of the uterus, and cessation of ovarian and menstrual cycling. The breasts enlarge rapidly and may be very tender. During the second trimester, the fetus grows rapidly to 30 cm and is very active. o The mother may feel movements during the early part of the second trimester. o Hormonal levels stabilize as HCG declines, the corpus luteum deteriorates, and the placenta takes over the secretion of progesterone, which maintains the pregnancy. During the third trimester, the fetus grows rapidly to about 34 kg in weight and 50 cm in length. o Fetal activity may decrease as the fetus fills the space available to it. o Maternal abdominal organs become compressed and displaced, leading to frequent urination, digestive blockages, and back strain. A complex interplay of local regulators (prostaglandins) and hormones (estrogen and oxytocin) induces and regulates labor. The mechanism that triggers labor is not fully understood. o In one possible model, high levels of estrogen induce the formation of oxytocin receptors on the uterus.

Oxytocin, produced by the fetus and the mothers posterior pituitary, stimulates powerful contractions by the smooth muscles of the uterus. o Oxytocin also stimulates the placenta to secrete prostaglandins, which enhance the contractions. o The physical and emotional stress associated with the contractions stimulate the release of more oxytocin and prostaglandins, a positive feedback system that underlies the process of labor. Birth, or parturition, is brought about by strong, rhythmic uterine contractions. o The process of labor has three stages. The first stage is the opening up and thinning of the cervix, ending in complete dilation. The second stage is the expulsion of the baby as a result of strong uterine contractions. The third stage is the expulsion of the placenta. Lactation is unique to mammals. o After birth, decreasing levels of progesterone free the anterior pituitary from negative feedback and allow prolactin secretion. o Prolactin stimulates milk production 23 days after birth. o The release of milk from the mammary glands is controlled by oxytocin. Reproductive immunologists are working to understand why mammalian mothers do not reject the embryo as a foreign body, despite its paternal antigens. o The trophoblast may inhibit a maternal immune response against the embryo by releasing signal molecules with immunosuppressive effects. These include HCG, a variety of protein factors, a prostaglandin, several interleukins, and an interferon. Some combination of these substances may interfere with immune rejection by acting on the mothers T lymphocytes. o A different hypothesis suggests that the trophoblast and later the placenta secrete an enzyme that rapidly breaks down local supplies of tryptophan, an amino acid necessary for T cell survival and function. This enzyme is essential for maintaining pregnancy in mice. o Another possibility is the absence of certain histocompatibility antigens on placenta cells and the secretion of a hormone that induces synthesis of a death activator protein (FasL) on placental cells. Activated T cells have a complementary death receptor (Fas), and the binding of FasL to Fas causes the T cells to self-destruct by apoptosis. o Contraception can be achieved in several ways. Some methods prevent the release of mature secondary oocytes and sperm from gonads, others prevent fertilization by keeping sperm and egg apart, and still others prevent implantation of an embryo. o Fertilization can be prevented by abstinence from sexual intercourse or by any of several barriers that keep sperm and egg apart. Temporary abstinence is called the rhythm method of birth control. This means of natural family planning depends on refraining from intercourse when conception is most likely. Ovulation can be detected by noting changes in cervical mucus and body temperature during the menstrual cycle. Natural family planning brings a pregnancy rate of 1020%. o As a method of preventing fertilization, coitus interruptus, or withdrawal (removal of the penis from the vagina before ejaculation), is unreliable. Sperm may be present in secretions that precede ejaculation. The several barrier methods of contraception that block sperm from meeting the egg have pregnancy rates of less than 10%. o The condom used by the male is a thin latex or natural membrane sheath that fits over the penis to collect the semen. o The diaphragm is a dome-shaped rubber cap that fits into the upper portion of the vagina before intercourse. o Both methods are more effective when used in conjunction with a spermicide. Birth control pills are chemical contraceptives with a pregnancy rate of less than 1%. o The most commonly used birth control pills are a combination of a synthetic estrogen and progestin (progesteronelike hormone). o This combination acts by negative feedback to stop the release of GnRH by the hypothalamus and, thus, of FSH and LH by the pituitary. The prevention of LH release prevents ovulation. As a backup mechanism, the inhibition of FSH secretion by the low dose of estrogen in the pills prevents follicles from developing. o A second type of birth control pill, the minipill, contains only progestin. o It does not effectively block ovulation, and it is not as effective a contraceptive as the combination pill. The minipill prevents fertilization mainly by causing thickening of a womans cervical mucus so it blocks sperm from entering the uterus. It also causes changes in the endometrium that interfere with implantation. o Combination pills carry a slightly elevated risk of abnormal blood clotting, high blood pressure, heart attack, and stroke. o

However, they decrease the risk of ovarian and endometrial cancers. Sterilization is the permanent prevention of gamete release. Tubal ligation in women involves cauterization or ligation of a section of the oviducts to prevent the eggs from traveling into the uterus. Vasectomy in men is the cutting of each vas deferens to prevent sperm from entering the urethra. o Abortion is the termination of a pregnancy. Spontaneous abortion or miscarriage occurs in as many of one-third of all pregnancies. In addition, 1.5 million American women choose abortions performed by physicians each year. A drug called mifepristone, or RU-486, enables a woman to terminate pregnancy nonsurgically within the first seven weeks. An analogue of progesterone, RU-486 blocks progesterone reception in the uterus, preventing progesterone from maintaining pregnancy. It is taken with a small amount of prostaglandin to induce uterine contractions. Modern technology offers solutions for some reproductive problems. It is now possible to diagnose many genetic and congenital abnormalities while the fetus is in the uterus. Amniocentesis and chorionic villus sampling are invasive techniques in which amniotic fluid or fetal cells are obtained for genetic analysis. Commonly used noninvasive techniques use ultrasound imaging to detect fetal conditions. o A newer noninvasive method uses the fact that maternal blood contains fetal blood cells that can be tested. o A maternal blood sample yields fetal cells that can be identified by specific antibodies and tested for genetic disorders. Reproductive technology can help with infertility treatments. o Hormone therapy can increase sperm and egg production. o Surgery can correct blocked oviducts. Many infertile couples use assisted reproductive technology (ART). o These procedures involve surgical removal of secondary oocytes from a womans body, fertilizing them, and returning them to the womans body. With in vitro fertilization, the most common ART procedure, the oocytes are mixed with sperm in culture dishes and inserted in the womans uterus at the eight-cell stage or beyond. In ZIFT (zygote intrafallopian transfer), eggs are also fertilized in vitro, but zygotes are transferred immediately to the womans fallopian tubes. In GIFT (gamete intrafallopian transfer), the eggs are not fertilized in vitro. Instead, the eggs and sperm are placed in the womans oviducts in the hope that fertilization will occur there. These techniques are performed throughout the world and have resulted in thousands of children. o

Chapter 47 - Animal Development Overview: A Body-Building Plan for Animals From egg to organism, an animals form develops gradually. The question of how a zygote becomes an animal has been asked for centuries. As recently as the 18th century, the prevailing idea was preformation, the notion that an egg or sperm contains an embryo that is a preformed miniature adult. The competing theory is epigenesis, proposed 2,000 years earlier by Aristotle. o According to epigenesis, the form of an animal emerges from a relatively formless egg. As microscopy improved in the 19th century, biologists could see that embryos took shape in a series of progressive steps. o Epigenesis displaced preformation as the favored explanation among embryologists. Both preformation and epigenesis have some legitimacy. o Although the embryos form emerges gradually as it develops, aspects of the developmental plan are already in place in the eggs of many species. o An organisms development is primarily determined by the genome of the zygote and also by differences that arise between early embryonic cells. o These differences set the stage for the expression of different genes in different cells. In some species, early embryonic cells become different because of the uneven distribution within the unfertilized egg of maternal substances called cytoplasmic determinants. o These substances affect development of the cells that inherit them during the early mitotic divisions of the embryo. In other species, the differences between cells are due to their location in the developing embryo. Most species establish differences between early embryonic cells by a combination of these two mechanisms. As development continues, selective gene expression leads to cell differentiation, the specialization of cells in structure and function.

Along with cell division and differentiation, development involves morphogenesis, the process by which an animal takes shape. Concept 47.1 After fertilization, embryonic development proceeds through cleavage, gastrulation, and organogenesis Fertilization activates the egg and brings together the nuclei of sperm and egg. The gametes (egg and sperm) are both highly specialized cell types. Fertilization combines haploid sets of chromosomes from two individuals into a single diploid cell, the zygote. Another key function of fertilization is activation of the egg. o Contact of the sperm with the eggs surface initiates metabolic reactions within the egg that trigger the onset of embryonic development. Sea urchin fertilization has been extensively studied. Sea urchin egg and sperm encounter each other after the animals release their gametes into seawater. o The jelly coat of the egg attracts the sperm, which swims toward the egg. When the head of the sperm comes into contact with the jelly coat, the acrosomal reaction is triggered, and the acrosome, a specialized vesicle at the tip of the sperm, discharges its contents by exocytosis. o Hydrolytic enzymes enable the acrosomal process to penetrate the eggs jelly coat. o The tip of the acrosomal process adheres to special receptor proteins on the eggs surface. o These receptors extend through the vitelline layer, just external to the eggs plasma membrane. o This lock-and-key recognition ensures that eggs will be fertilized only by sperm of the same species. The sperm and egg plasma membranes fuse, and the sperm nucleus enters the eggs cytoplasm. o Na+ channels in the eggs plasma membrane open. Na+ flows into the egg, and the membrane depolarizes, changing the membrane potential of the egg. Such depolarization is common in animals. Occurring within 13 seconds after the sperm binds to the egg, depolarization prevents additional sperm from fusing with the eggs plasma membrane. o This fast block to polyspermy prevents polyspermy, the fertilization of the egg by multiple sperm. Fusion of egg and sperm plasma membranes triggers a signal-transduction pathway. o Ca2+ from the eggs endoplasmic reticulum is released into the cytosol and propagates as a wave across the fertilized egg. High concentrations of Ca2+ cause cortical granules to fuse with the plasma membrane and release their contents into the perivitelline space, the space between the plasma membrane and the vitelline layer. o The vitelline layer separates from the plasma membrane. o An osmotic gradient draws water into the perivitelline space, swelling it and pushing it away from the plasma membrane. o The vitelline layer hardens into a fertilization envelope, which resists the entry of additional sperm. o The fertilization envelope and other changes in the eggs surface function together as a long-term slow block to polyspermy. o The plasma membrane returns to normal, and the fast block to polyspermy no longer functions. High concentrations of Ca2+ in the egg stimulate an increase in the rates of cellular respiration and protein synthesis, activating the egg. Unfertilized eggs can be activated artificially by the injection of Ca2+ or by a variety of mildly injurious treatments, such as temperature shock. o It is even possible to activate an egg that has had its nucleus removed. o Evidently, proteins and mRNAs present in the cytoplasm of the unfertilized egg are sufficient for egg activation. As the metabolism of the activated egg increases, the sperm nucleus swells and merges with the egg nucleus, creating the diploid nucleus of the zygote. o DNA synthesis begins and the first cell division occurs about 90 minutes after fertilization. Fertilization in terrestrial animals, including mammals, is generally internal. Secretions in the mammalian female reproductive tract alter certain molecules on the surface of sperm cells and increase sperm motility. The mammalian egg is surrounded by follicle cells also released during ovulation. o A sperm must migrate through a layer of follicle cells before it reaches the zona pellucida, the extracellular matrix of the egg. o Binding of the sperm cell to a receptor on the zona pellucida induces an acrosomal reaction similar to that seen in the sea urchin. Enzymes from the acrosome enable the sperm cell to penetrate the zona pellucida and bind to the eggs plasma membrane. o The binding of the sperm cell to the egg triggers changes within the egg, leading to a cortical reaction, the release of enzymes from cortical granules to the outside via exocytosis. The released enzymes catalyze alteration of the zona pellucida, which functions as a slow block to polyspermy. o The entire sperm, tail and all, enters the egg. A centrosome forms around the centriole that acted as the basal body of the sperms flagellum.

This centrosome duplicates to form the two centrosomes of the zygote. These will generate the mitotic spindle for the first cell division. The envelopes of both egg and sperm nuclei disperse. o The chromosomes from the two gametes share a common spindle apparatus during the first mitotic division of the zygote. o Only after the first division, as diploid nuclei form in the two daughter cells, do the chromosomes from the two parents come together in a common nucleus. Fertilization is much slower in mammals than in the sea urchin. o The first cell division occurs 1236 hours after sperm binding in mammals. Cleavage partitions the zygote into many smaller cells. A succession of rapid cell divisions called cleavage follows fertilization. o During this period, cells go through the S (DNA synthesis) and M (mitosis) phases of the cell cycle but may skip the G1 and G2 phases. As a result, little or no protein synthesis occurs. The first five to seven divisions form a cluster of cells known as the morula. A fluid-filled cavity called the blastocoel forms within the morula, which becomes a hollow ball of cells called the blastula. o The zygote is partitioned into many smaller cells called blastomeres. Each blastomere contains different regions of the undivided cytoplasm and, thus, may contain different cytoplasmic determinants. Most animals have both eggs and zygotes with a definite polarity. o Thus, the planes of division follow a specific pattern relative to the poles of the zygote. o Polarity is defined by the heterogeneous distribution of substances such as mRNA, proteins, and yolk. Yolk is most concentrated at the vegetal pole and least concentrated at the animal pole. In amphibians, a rearrangement of the egg cytoplasm occurs at the time of fertilization. o The plasma membrane and cortex rotate toward the point of sperm entry. The gray crescent is exposed, marking the dorsal surface of the embryo. o Molecules in the vegetal cortex are now able to interact with inner cytoplasmic molecules in the animal hemisphere, leading to the formation of cytoplasmic determinants that will later initiate development of dorsal structures. o Thus, cortical rotation establishes the dorsal-ventral (back-belly) axis of the zygote. In frogs, the first two cleavages are vertical and result in four blastomeres of equal size. o The third division is horizontal, producing an eight-celled embryo with two tiers of four cells. o The unequal division of yolk displaces the mitotic apparatus and cytokinesis toward the animal end of the dividing cells in equatorial divisions. As a result, animal blastomeres are smaller than those in the vegetal hemisphere. Continued cleavage produces a morula and then a blastula. o Because of unequal cell division, the blastocoel is located in the animal hemisphere. Animals with less yolk (such as the sea urchin) also have an animal-vegetal axis. o However, the blastomeres are similar in size, and the blastocoel is centrally located. Yolk has its most pronounced effect on cleavage in the eggs of reptiles, many fishes, and insects. o The yolk of a chicken egg is actually an egg cell, swollen with yolk nutrients. Cleavage of a fertilized birds egg is restricted to a small disk of yolk-free cytoplasm, while yolk remains uncleaved. o The incomplete division of a yolk-rich egg is meroblastic cleavage. o It contrasts with holoblastic cleavage, the complete cleavage of eggs with little or moderate yolk. Early cleavage in a bird embryo produces a cap of cells called the blastoderm, which rests on undivided egg yolk. o The blastomeres sort into upper and lower layers, the epiblast and the hypoblast. o The cavity between these two layers is the avian version of the blastocoel. This stage is the avian equivalent of the blastula. In insects, the zygotes nucleus is located within the mass of yolk. Cleavage begins with the nucleus undergoing mitotic divisions, unaccompanied by cytokinesis. o These mitotic divisions produce several hundred nuclei, which migrate to the outer edge of the embryo. o After several more rounds of mitosis, plasma membranes form around each nucleus, and the embryo, the equivalent of a blastula, consists of a single layer of 6,000 cells surrounding a mass of yolk. Gastrulation rearranges the blastula to form a three-layered embryo with a primitive gut. Gastrulation rearranges the embryo into a triploblastic gastrula. o The embryonic germ layers are the ectoderm, the outer layer of the gastrula; the mesoderm, which fills the space between ectoderm and endoderm; and the endoderm, which lines the embryonic gut. Sea urchin gastrulation begins at the vegetal pole where individual cells detach from the blastula wall and enter the blastocoel as migratory mesenchyme cells. o The remaining cells flatten to form a vegetal plate that buckles inward in a process called invagination. The buckled vegetal plate undergoes extensive rearrangement of its cells, transforming the shallow invagination into a primitive gut, or archenteron.

The open end, the blastopore, will become the anus. An opening at the other end of the archenteron will form the mouth of the digestive tube. Frog gastrulation produces a triploblastic embryo with an archenteron. o Where the gray crescent was located, invagination forms the dorsal lip of the blastopore. o Cells on the dorsal surface roll over the edge of the dorsal lip and into the interior of the embryo, a process called involution. o Once inside the embryo, these cells move away from the blastopore and become organized into layers of endoderm and mesoderm, with endoderm on the inside. o As the process is completed, the lip of the blastopore encircles a yolk plug. Gastrulation in the chick is similar to frog gastrulation in that it involves cells moving from the surface of the embryo to an interior location. o In birds, the inward movement of cells is affected by the large mass of yolk. o All the cells that will form the embryo come from the epiblast. o During gastrulation, some epiblast cells move toward the midline of the blastoderm then detach and move inward toward the yolk. These cells produce a thickening called the primitive streak, which runs along what will become the birds anterior-posterior axis. The primitive steak is the functional equivalent of the frog blastopore. Some of the inward-moving epiblast cells displace hypoblast cells and form the endoderm. Other epiblast cells move laterally into the blastocoel, forming the mesoderm. The epiblast cells that remain on the surface form ectoderm. The hypoblast is required for normal development and seems to help direct the formation of the primitive streak. o Some hypoblast cells later form portions of the yolk sac. In organogenesis, the organs of the animal body form from the three embryonic germ layers. Various regions of the three embryonic germ layers develop into the rudiments of organs during the process of organogenesis. While gastrulation involves mass cell movements, organogenesis involves more localized morphogenetic changes in tissue and cell shape. The first organs to form in the frog are the neural tube and notochord. o The notochord is formed from dorsal mesoderm that condenses above the archenteron. Signals sent from the notochord to the overlying ectoderm cause that region of notochord to become neural plate. o This process is often seen in organogenesis: one germ layer signaling another to determine the fate of the second layer. The neural plate curves inward, rolling itself into a neural tube that runs along the anterior-posterior axis of the embryo. o The neural tube becomes the brain and spinal cord. Unique to vertebrate embryos is a band of cells called the neural crest, which develops along the border where the neural tube pinches off from the ectoderm. o Neural crest cells migrate throughout the embryo, forming many cell types. o Some have proposed calling neural crest cells the fourth germ layer. Somites form in strips of mesoderm lateral to the notochord. o The somites are arranged serially on both sides along the length of the notochord. o Mesenchyme cells migrate from the somites to new locations. o The notochord is the core around which the vertebrae form. Parts of the notochord persist into adulthood as the inner portions of vertebral disks. o Somite cells also form the muscles associated with the axial skeleton. o Lateral to the somites, the mesoderm splits into two layers that form the lining of the coelom. As organogenesis progresses, morphogenesis and cell differentiation refine the organs that form from the three germ layers. Embryonic development leads to an aquatic, herbivorous tadpole larva, which later metamorphoses into a terrestrial, carnivorous adult frog. The derivatives of the ectoderm germ layer include epidermis of skin and its derivatives, epithelial lining of the mouth and rectum, cornea and lens of the eyes, the nervous system, adrenal medulla, tooth enamel, and the epithelium of the pineal and pituitary glands. The endoderm germ layer contributes to the epithelial linings of the digestive tract (except the mouth and rectum), respiratory system, pancreas, thyroid, parathyroids, thymus, urethra, urinary bladder, and reproductive system. Derivatives of the mesoderm germ layer are the notochord, the skeletal and muscular systems, the circulatory and lymphatic systems, the excretory system, the reproductive system (except germ cells), the dermis of skin, the lining of the body cavity, and the adrenal cortex. Amniote embryos develop in a fluid-filled sac within a shell or uterus. The amniote embryo is the solution to reproduction in a dry environment. The shelled eggs of birds and other reptiles, as well as monotreme mammals, and the uterus of placental mammals provide an aqueous environment for development.

Within the shell or uterus, the embryos of these animals are surrounded by fluid within a sac formed by a membrane called the amnion. o Reptiles (including birds) and mammals are thus amniotes. Amniote development includes the formation of four extraembryonic membranes: yolk sac, amnion, chorion, and allantois. o The cells of the yolk sac digest yolk, providing nutrients to the embryo. o The amnion encloses the embryo in a fluid-filled amniotic sac that protects the embryo from drying out. o The chorion cushions the embryo against mechanical shocks and works with the allantois to exchange gases between the embryo and the surrounding air. o The allantois functions as a disposal sac for uric acid and functions with the chorion as a respiratory organ. Mammalian development has some unique features. The eggs of most mammals are very small, storing little food. Early cleavage is relatively slow in mammals. o In humans, the first division is complete after 36 hours, the second division after 60 hours, and the third division after 72 hours. o Relatively slow cleavage produces equal-sized blastomeres. o At the eight-cell stage, the blastomeres become tightly adhered to one another, causing the outer surface to appear smooth. o At completion of cleavage, the embryo has more than 100 cells arranged around a central cavity. The blastocyst travels down the oviduct to reach the uterus. o Clustered at one end of the blastocyst is a group of cells called the inner cell mass that develops into the embryo and contributes to all the extraembryonic membranes. The trophoblast, the outer epithelium of the blastocyst, secretes enzymes that break down the endometrium to facilitate implantation of the blastocyst. o The trophoblast thickens, projecting fingerlike projections into the surrounding maternal tissue, which is rich in vascular tissue. o Invasion by the trophoblast leads to erosion of the capillaries in the surrounding endometrium, causing the blood to spill out and bathe trophoblast tissue. o At the time of implantation, the inner cell mass forms a flat disk with an upper layer of cells, the epiblast, and a lower layer, the hypoblast. As in birds, the human embryo develops almost entirely from the epiblast. As implantation is completed, gastrulation begins. o Cells move inward from the epiblast through the primitive streak to form mesoderm and endoderm. At the same time, extraembryonic membranes develop. o The trophoblast continues to expand into the endometrium. o The invading trophoblast, mesodermal cells derived from the epiblast, and adjacent endometrial tissue all contribute to the formation of the placenta. The embryonic membranes of mammals are homologous with those of birds and other mammals. o The chorion, which completely surrounds the embryo and other embryonic membranes, functions in gas exchange. o The amnion encloses the embryo in a fluid-filled amniotic cavity. o The yolk sac encloses another fluid-filled cavity, which contains no yolk. The yolk sac membrane of mammals is the site of early formation of blood cells, which later migrate to the embryo. o The fourth extraembryonic membrane, the allantois, is incorporated into the umbilical cord, where it forms blood vessels that transport oxygen and nutrients from the placenta to the embryo and rid the embryo of carbon dioxide and nitrogenous wastes. The extraembryonic membranes of reptiles, where embryos are nourished with yolk, were conserved as mammals diverged in the course of evolution but with modifications adapted to development within the reproductive tract of the mother. The completion of gastrulation is followed by the first events of organogenesis: the formation of the neural tube, notochord, and somites. Concept 47.2 Morphogenesis in animals involves specific changes in cell shape, position, and adhesion Morphogenesis is a major aspect of development in plants and animals, but only in animals does it involve cell movement. Movement of parts of a cell can bring about changes in cell shape. o It can also enable a cell to migrate from one place to another within the embryo. Changes in cell shape and cell position are involved in cleavage, gastrulation, and organogenesis. Changes in the shape of a cell usually involve the reorganization of the cytoskeleton. o Consider how the cells of the neural plate form the neural tube. o First, the microtubules oriented parallel to the dorsal-ventral axis of the embryo help to lengthen the cells in that direction. o At the dorsal end of each cell is a parallel array of actin filaments oriented crosswise. These contract, giving the cells a wedge shape that bends the ectoderm inward.

Similar changes in cell shape occur during other invaginations and evaginations of tissue layers throughout development. The cytoskeleton is also drives cell migration. o Cells crawl within the embryo by extending cytoplasmic fibers to form cellular protrusions, in a manner akin to amoeboid movement. The cellular protrusions of migrating embryonic cells are usually flat sheets (lamellipodia) or spikes (filopodia). o During gastrulation, invagination is initiated by the wedging of cells on the surface of the blastula, but the movement of cells deeper into the embryo involves the extension of filopodia by cells at the leading edge of the migrating tissue. The cells that first move through the blastopore and along the inside of the blastocoel drag others along behind them as a sheet of cells. This involuted sheet of cells forms the endoderm and mesoderm of the embryo. o Cell crawling is also involved in convergent extension, a type of morphogenetic movement in which the cells of a tissue layer rearrange themselves so the sheet converges and extends, becoming narrower but longer. Convergent extension allows the archenteron to elongate in the sea urchin and frog and is responsible for the change in shape of a frog embryo from spherical to submarine shaped. o The movements of convergent extension probably involve the extracellular matrix (ECM), a mixture of secreted glycoproteins lying outside the plasma membrane. ECM fibers may direct cell movement by functioning as tracks, directing migrating cells along particular routes. Some ECM substances, such as fibronectins, help cells migrate by providing anchorage for crawling. Other ECM substances may inhibit migration in certain directions. In frog gastrulation, fibronectin fibers line the roof of the blastocoel. o As the future mesoderm moves into the interior of the embryo, cells at the free edge of the mesodermal sheet migrate along these fibers. Researchers can prevent the attachment of cells to fibronectin (and prevent inward movement of the mesoderm) by injecting embryos with antifibronectin antibodies. As migrating cells move along specific paths through the embryo, receptor proteins on their surfaces pick up directional cues from the immediate environment. o Such signals from the ECM can direct the orientation of cytoskeletal elements to propel the cell in the proper direction. Cell adhesion molecules (CAMs), located on cell surfaces, bind to CAMs on other cells. o CAMs vary in amount and chemical identity with cell type. o These differences help to regulate morphogenetic movement and tissue binding. Cadherins are also involved in cell-to-cell adhesion. o Cadherins require the presence of calcium for proper function. o There are many cadherins, and the gene for each cadherin is expressed in specific locations at specific times during embryonic development. Concept 47.3 The developmental fate of cells depends on their history and on inductive signals Development requires the timely differentiation of cells in specific locations. Two general principles integrate the current understanding of the genetic and cellular mechanisms that underlie differentiation during embryonic development. First, during early cleavage divisions, embryonic cells must somehow become different from one another. o In many animal species, initial differences result from uneven distribution of cytoplasmic determinants (mRNAs, proteins, and other molecules) in the unfertilized egg. o The resulting differences in the cytoplasmic composition of cells help specify body axes and influence the expression of genes that affect the developmental fate of cells. For example, the cells of the inner cell mass are located internally in the early human embryo, while trophoblast cells are located on the outer surface of the blastocyst. The difference in cell environment determines the fate of these cells. Second, once initial cell asymmetries are set up, subsequent interactions among the embryonic cells influence their fate, usually by causing changes in gene expression. o This mechanism is termed induction. o Induction, which brings about the differentiation of many specialized cell types, is mediated by diffusible chemical signals or by cell-surface interactions. Fate mapping can reveal cell genealogies in chordate embryos. Fate maps illustrate the developmental history of cells. In classic experiments in the 1920s, German embryologist Vogt charted fate maps for different regions of early amphibian embryos.

His work provided evidence that the lineage of cells making up the three germ layers created by gastrulation is traceable to cells in the blastula, before gastrulation begins. Developmental biologists have combined fate-mapping studies with experimental manipulation of parts of embryos. o Two important conclusions have emerged. Founder cells give rise to specific tissues in older embryos. o As development proceeds, a cells developmental potential (the range of structures it can form) becomes restricted. The eggs of most vertebrates have cytoplasmic determinants that help establish the body axes. A bilaterally symmetrical animal has an anterior-posterior axis, a dorsal-ventral axis, and left and right sides. o Establishing this basic body plan is a first step in morphogenesis and a prerequisite for the development of tissues and organs. In frogs, locations of melanin and yolk define the animal and vegetal hemispheres respectively. o The animal-vegetal axis indirectly determines the anterior-posterior body axis. Fertilization in frogs triggers cortical rotation, which establishes the dorsal-ventral axis and leads to the appearance of the gray crescent, whose position marks the dorsal side. Once any two axes are established, the third (right-left) is specified by default. o Molecular mechanisms then carry out the program associated with that axis. In amniotes, body axes are not fully established until later. o In chicks, gravity is involved in establishing the anterior-posterior axis as the egg travels down the oviduct before being laid. o Later, pH differences between the two sides of the blastoderm establish the dorsal-ventral axis. In mammals, no polarity is obvious until after cleavage, although recent research suggests that the orientation of the egg and sperm nuclei before fusion may play a role in determining the axes. In many species with cytoplasmic determinants, only the zygote is totipotent, capable of developing into all cell types found in the adult. o The fate of embryonic cells is affected by both the distribution of cytoplasmic determinants and cleavage pattern. o In frogs, the first cleavage occurs along an axis that produces two identical blastomeres with identical developmental potential. The cells of the mammalian embryo remain totipotent until the 16-cell stage, when they become arranged into the precursors of the trophoblast and inner cell mass of the blastocyst. o At that time, location determines cell fate. o At the 8-cell stage, each of the blastomeres of the mammalian embryo can form a complete embryo if isolated. The progressive restriction of potency is a general feature of development in animals. o In some species, the cells of the early gastrula retain the capacity to give rise to more than one kind of cell, although they are no longer totipotent. o In general, the tissue-specific fates of cells in the late gastrula are fixed. Even if manipulated experimentally, they will give rise to the same type of cells as in a normal embryo. Inductive signals play an important role in cell fate determination and pattern formation. Once embryonic cell division creates cells that are different from one another, the cells begin to influence each others fates by induction. o At the molecular level, the effect of induction is usually the switching on of a set of genes that make the receiving cells differentiate into a specific tissue. In the 1920s, Hans Spemann and Hilde Mangold carried out a set of transplantation experiments. o These experiments showed that the dorsal lip of the blastopore in an early gastrula serves as an organizer of the embryo by initiating a chain of inductions that results in the formation of the notochord, neural tube, and other organs. Developmental biologists are working to identify the molecular basis of induction by Spemanns organizer (also called the gastrula organizer or simply the organizer). o A growth factor called bone morphogenetic protein 4 (BMP-4) is active exclusively in cells on the ventral side of the amphibian gastrula. BMP-4 induces those cells to form ventral structures. Organizer cells inactivate BMP-4 on the dorsal side of the embryo by producing proteins that bind to BMP4, rendering it unable to signal. This allows formation of dorsal structures such as the notochord and neural tube. Proteins related to BMP-4 and its inhibitors are also found in other animals, suggesting that they evolved long ago and may participate in development in many different organisms. Many inductions involve a sequence of inductive steps that progressively determine the fate of cells. o In late gastrula of the frog, ectoderm cells destined to form the lenses of the eyes receive inductive signals from the ectodermal cells that will form the neural plate. o Later, inductive signals from the optic cup, an outgrowth of the developing brain, complete the determination of lens-forming cells. Inductive signals play a major role in pattern formation, the development of an animals spatial information.

o Positional information, supplied by molecular cues, tells a cell where it is relative to the animals body axes. Limb development in chicks serves as a model of pattern formation. Wings and legs of chicks begin as bumps of tissue called limb buds. o Each component of a chick limb develops with a precise location and orientation relative to three axes, the proximaldistal axis (shoulder-to-fingertip), the anterior-posterior axis (thumb-to-little-finger), and the dorsal-ventral axis (knuckle-to-palm). A limb bud consists of a core of mesodermal tissue covered by a layer of ectoderm. Two critical organizer regions are present in all vertebrate limb buds. o The cells of these regions secrete proteins that provide key positional information to the other cells of the bud. One limb-bud organizer region is the apical ectodermal ridge (AER), a thickened area of ectoderm at the tip of the bud. o The AER is required for the outgrowth of the limb along the proximal-distal axis and for patterning along this axis. The cells of the AER produce several secreted protein signals, belonging to the fibroblast growth factor (FGF) family. These signals promote limb-bud outgrowth. o If the AER is surgically removed and beads soaked in FGF are put in its place, a nearly normal limb will develop. The AER (and other limb-bud ectoderms) also appears to guide pattern formation along the limbs dorsal-ventral axis. o If the ectoderm of the limb bud, including the AER, is detached from the mesoderm and rotated 180 back-to-front, the limb elements that form have reversed dorsal-ventral orientation. The second major limb-bud organizer region is the zone of polarizing activity (ZPA), a block of mesodermal tissue located underneath the ectoderm where the posterior side of the bud is attached to the body. o The ZPA is necessary for proper pattern formation along the anterior-posterior axis of the limb. o Cells nearest the ZPA give rise to posterior structures (such as our little finger); cells farthest from the ZPA form anterior structures (such as our thumb). o Tissue transplantation experiments support the hypothesis that the ZPA produces an inductive signal that conveys positional information indicating posterior. The cells of the ZPA secrete a protein growth factor called Sonic hedgehog. If cells genetically engineered to produce large amounts of Sonic hedgehog are implanted in the anterior region of a normal limb bud, a mirror-image limb bud results. Extra toes and fingers in mice (and maybe humans) result from the production of Sonic hedgehog in the wrong part of the limb bud. We can conclude from these experiments that pattern formation requires cells to receive and interpret environmental cues that vary with location. o These cues tell cells where they are in the 3-D realm of a developing organ. o Organizers such as the AER and the ZPA function as signaling centers. o The AER and ZPA also interact with each other via signaling molecules and signaling pathways, to influence each others developmental fates. What determines whether a limb bud develops into a forelimb or a hindlimb? o The cells receiving signals from the AER and ZPA respond according to their own developmental histories. o Earlier developmental signals have set up patterns of gene expression that distinguish future forelimbs from future hindlimbs. Construction of a fully formed animal involves a sequence of events that include many steps of signaling and differentiation. o Initial cell asymmetries allow different types of cells to influence each other to express specific sets of genes. o The products of these genes direct cells to differentiate into specific types. o Coordinated with morphogenesis, various pathways of pattern formation occur in all the different parts of the developing embryo. o These processes produce a complex arrangement of multiple tissues and organs, each functioning in the appropriate location to form a coordinated organism.

Chapter 48 - Nervous Systems Overview: Command and Control Center The human brain contains an estimated 1011 (100 billion) neurons. o Each neuron may communicate with thousands of other neurons in complex information-processing circuits. Recently developed technologies can record brain activity from outside the skull. o One technique is functional magnetic resonance imaging (fMRI), which reconstructs a 3-D map of the subjects brain activity. o The results of brain imaging and other research methods show that groups of neurons function in specialized circuits dedicated to different tasks. The ability of cells to respond to the environment has evolved over billions of years. The ability to sense and react originated billions of years ago with prokaryotes that could detect changes in their environment and respond in ways that enhanced their survival and reproductive success.

o Such cells could locate food sources by chemotaxis. Later, modification of this simple process provided multicellular organisms with a mechanism for communication between cells of the body. By the time of the Cambrian explosion, systems of neurons that allowed animals to sense and move rapidly had evolved in essentially modern form. Concept 48.1 Nervous systems consist of circuits of neurons and supporting cells Nervous systems show diverse patterns of organization. All animals except sponges have some type of nervous system. What distinguishes nervous systems of different animal groups is how the neurons are organized into circuits. Cnidarians have radially symmetrical bodies organized around a gastrovascular cavity. o In hydras, neurons controlling the contraction and expansion of the gastrovascular cavity are arranged in diffuse nerve nets. The nervous systems of more complex animals contain nerve nets, as well as nerves, which are bundles of fiberlike extensions of neurons. With cephalization come more complex nervous systems. o Neurons are clustered in a brain near the anterior end in animals with elongated, bilaterally symmetrical bodies. In simple cephalized animals such as the planarian, a small brain and longitudinal nerve cords form a simple central nervous system (CNS). In more complex invertebrates, such as annelids and arthropods, behavior is regulated by more complicated brains and ventral nerve cords containing segmentally arranged clusters of neurons called ganglia. o Nerves that connect the CNS with the rest of the animals body make up the peripheral nervous system (PNS). The nervous systems of molluscs correlate with lifestyle. o Clams and chitons have little or no cephalization and simple sense organs. o Squids and octopuses have the most sophisticated nervous systems of any invertebrates, rivaling those of some vertebrates. The large brain and image-forming eyes of cephalopods support an active, predatory lifestyle. Nervous systems consist of circuits of neurons and supporting cells. In general, there are three stages in the processing of information by nervous systems: sensory input, integration, and motor output. Sensory neurons transmit information from sensors that detect external stimuli (light, heat, touch) and internal conditions (blood pressure, muscle tension). o Sensory input is conveyed to the CNS, where interneurons integrate the sensory input. Motor output leaves the CNS via motor neurons, which communicate with effector cells (muscle or endocrine cells). o Effector cells carry out the bodys response to a stimulus. The stages of sensory input, integration, and motor output are easy to study in the simple nerve circuits that produce reflexes, the bodys automatic responses to stimuli. Networks of neurons with intricate connections form nervous systems. The neuron is the structural and functional unit of the nervous system. The neurons nucleus is located in the cell body. Arising from the cell body are two types of extensions: numerous dendrites and a single axon. o Dendrites are highly branched extensions that receive signals from other neurons. o An axon is a longer extension that transmits signals to neurons or effector cells. The axon joins the cell body at the axon hillock, where signals that travel down the axon are generated. o Many axons are enclosed in a myelin sheath. o Near its end, axons divide into several branches, each of which ends in a synaptic terminal. The site of communication between a synaptic terminal and another cell is called a synapse. o At most synapses, information is passed from the transmitting neuron (the presynaptic cell) to the receiving cell (the postsynaptic cell) by means of chemical messengers called neurotransmitters. Glia are supporting cells that are essential for the structural integrity of the nervous system and for the normal functioning of neurons. There are several types of glia in the brain and spinal cord. o Astrocytes are found within the CNS. They provide structural support for neurons and regulate the extracellular concentrations of ions and neurotransmitters. Some astrocytes respond to activity in neighboring neurons by facilitating information transfer at those neurons synapses. By inducing the formation of tight junctions between capillary cells, astrocytes help form the blood-brain barrier, which restricts the passage of substances into the CNS. o In an embryo, radial glia form tracks along which newly formed neurons migrate from the neural tube. Both radial glia and astrocytes can also act as stem cells, generating neurons and other glia.

Oligodendrocytes (in the CNS) and Schwann cells (in the PNS) are glia that form myelin sheaths around the axons of vertebrate neurons. These sheaths provide electrical insulation of the axon. In multiple sclerosis, myelin sheaths gradually deteriorate, resulting in a progressive loss of body function due to the disruption of nerve signal transmission. Concept 48.2 Ion pumps and ion channels maintain the resting potential of a neuron Every cell has a voltage, or membrane potential, across its plasma membrane. All cells have an electrical potential difference (voltage) across their plasma membrane). o This voltage is called the membrane potential. o In neurons, the membrane potential is typically between ?60 and ?80 mV when the cell is not transmitting signals. The membrane potential of a neuron that is not transmitting signals is called the resting potential. o In all neurons, the resting potential depends on the ionic gradients that exist across the plasma membrane. o In mammals, the extracellular fluid has a Na+ concentration of 150 millimolar (mM) and a K+ of 5 mM. In the cytosol, Na+ concentration is 15 mM, and K+ concentration is 150 mM. o These gradients are maintained by the sodium-potassium pump. The magnitude of the membrane voltage at equilibrium, called the equilibrium potential (Eion), is given by a formula called the Nernst equation. o For an ion with a net charge of +1, the Nernst equation is: Eion = 62mV (log [ion]outside/[ion]inside) o The Nernst equation applies to any membrane that is permeable to a single type of ion. o In our model, the membrane is only permeable to K+, and the Nernst equation can be used to calculate EK, the equilibrium potential for K+. With this K+ concentration gradient, K+ is at equilibrium when the inside of the membrane is 92 mV more negative than the outside. o Assume that the membrane is only permeable to Na+. ENa, the equilibrium potential for Na+, is +62 mV, indicating that, with this Na+ concentration gradient, Na+ is at equilibrium when the inside of the membrane is 62 mV more positive than the outside. How does a real mammalian neuron differ from these model neurons? The plasma membrane of a real neuron at rest has many open potassium channels, but it also has a relatively small number of open sodium channels. Consequently, the resting potential is around ?60 to ?80 mV, between EK and ENa. o Neither K+ nor Na + is at equilibrium, and there is a net flow of each ion (a current) across the membrane at rest. The resting membrane potential remains steady, which means that the K+ and Na+ currents are equal and opposite. The reason the resting potential is closer to EK than to ENa is that the membrane is more permeable to K+ than to Na+. If something causes the membranes permeability to Na+ to increase, the membrane potential will move toward ENa and away from EK. This is the basis of nearly all electrical signals in the nervous system. The membrane potential can change from its resting value when the membranes permeability to particular ions changes. Sodium and potassium play major roles, but there are also important roles for chloride and calcium ions. The resting potential results from the diffusion of K+ and Na+ through ion channels that are always open. These channels are ungated. Neurons also have gated ion channels, which open or close in response to one of three types of stimuli. o Stretch-gated ion channels are found in cells that sense stretch, and open when the membrane is mechanically deformed. o Ligand-gated ion channels are found at synapses and open or close when a specific chemical, such as a neurotransmitter, binds to the channel. o Voltage-gated ion channels are found in axons (and in the dendrites and cell bodies of some neurons, as well as in some other types of cells) and open or close in response to a change in membrane potential. Concept 48.3 Action potentials are the signals conducted by axons Gated ion channels are responsible for generating the signals of the nervous system. o If a cell has gated ion channels, its membrane potential may change in response to stimuli that open or close those channels. Some stimuli trigger a hyperpolarization, an increase in the magnitude of the membrane potential. o Gated K+ channels open, K+ diffuses out of the cell, and the inside of the membrane becomes more negative. Other stimuli trigger a depolarization, a reduction in the magnitude of the membrane potential. o Gated Na+ channels open, Na+ diffuses into the cell, and the inside of the membrane becomes less negative. These changes in membrane potential are called graded potentials because the magnitude of the changeeither hyperpolarization or depolarizationvaries with the strength of the stimulus. o A larger stimulus causes a larger change in membrane permeability and, thus, a larger change in membrane potential. In most neurons, depolarizations are graded only up to a certain membrane voltage, called the threshold.

A stimulus strong enough to produce a depolarization that reaches the threshold triggers a different type of response, called an action potential. An action potential is an all-or-none phenomenon. o Once triggered, it has a magnitude that is independent of the strength of the triggering stimulus. Action potentials of neurons are very briefonly 12 milliseconds in duration. o This allows a neuron to produce them at high frequency. Both voltage-gated Na+ channels and voltage-gated K+ channels are involved in the production of an action potential. o Both types of channels are opened by depolarizing the membrane, but they respond independently and sequentially: Na+ channels open before K+ channels. Each voltage-gated Na+ channel has two gates, an activation gate and an inactivation gate, and both must be open for Na+ to diffuse through the channel. o At the resting potential, the activation gate is closed and the inactivation gate is open on most Na+ channels. o Depolarization of the membrane rapidly opens the activation gate and slowly closes the inactivation gate. Each voltage-gated K+ channel has just one gate, an activation gate. o At the resting potential, the activation gate on most K+ channels is closed. o Depolarization of the membrane slowly opens the K+ channels activation gate. How do these channel properties contribute to the production of an action potential? o When a stimulus depolarizes the membrane, the activation gates on some Na+ channels open, allowing more Na+ to diffuse into the cell. The Na+ influx causes further depolarization, which opens the activation gates on still more Na+ channels, and so on. Once the threshold is crossed, this positive-feedback cycle rapidly brings the membrane potential close to ENa during the rising phase. However, two events prevent the membrane potential from actually reaching ENa. o The inactivation gates on most Na+ channels close, halting Na+ influx. o The activation gates on most K+ channels open, causing a rapid efflux of K+. Both events quickly bring the membrane potential back toward EK during the falling phase. o In fact, in the final phase of an action potential, called the undershoot, the membranes permeability to K+ is higher than at rest, so the membrane potential is closer to EK than it is at the resting potential. The K+ channels activation gates eventually close, and the membrane potential returns to the resting potential. The Na+ channels inactivation gates remain closed during the falling phase and the early part of the undershoot. o As a result, if a second depolarizing stimulus occurs during this refractory period, it will be unable to trigger an action potential. Nerve impulses propagate themselves along an axon. The action potential is repeatedly regenerated along the length of the axon. o An action potential achieved at one region of the membrane is sufficient to depolarize a neighboring region above the threshold level, thus triggering a new action potential. Immediately behind the traveling zone of depolarization due to Na+ influx is a zone of repolarization due to K+ efflux. o In the repolarized zone, the activation gates of Na+ channels are still closed. o Consequently, the inward current that depolarizes the axon membrane ahead of the action potential cannot produce another action potential behind it. Once an action potential starts, it normally moves in only one directiontoward the synaptic terminals. Several factors affect the speed at which action potentials are conducted along an axon. o One factor is the diameter of the axon: the larger the axons diameter, the faster the conduction. In the myelinated neurons of vertebrates, voltage-gated Na+ and K+ channels are concentrated at gaps in the myelin sheath called nodes of Ranvier. o Only these unmyelinated regions of the axon depolarize. o Thus, the impulse moves faster than in unmyelinated neurons. This mechanism is called saltatory conduction. Concept 48.4 Neurons communicate with other cells at synapses When an action potential reaches the terminal of the axon, it generally stops there. o However, information is transmitted from a neuron to another cell at the synapse. Some synapses, called electrical synapses, contain gap junctions that do allow electrical current to flow directly from cell to cell. o Action potentials travel directly from the presynaptic to the postsynaptic cell. o In both vertebrates and invertebrates, electrical synapses synchronize the activity of neurons responsible for rapid, stereotypical behaviors. The vast majority of synapses are chemical synapses, which involve the release of chemical neurotransmitter by the presynaptic neuron. o The presynaptic neuron synthesizes the neurotransmitter and packages it in synaptic vesicles, which are stored in the neurons synaptic terminals.

When an action potential reaches a terminal, it depolarizes the terminal membrane, opening voltage-gated calcium channels in the membrane. Calcium ions (Ca2+) then diffuse into the terminal, and the rise in Ca2+ concentration in the terminal causes some of the synaptic vesicles to fuse with the terminal membrane, releasing the neurotransmitter by exocytosis. The neurotransmitter diffuses across the narrow gap, called the synaptic cleft, which separates the presynaptic neuron from the postsynaptic cell. o The effect of the neurotransmitter on the postsynaptic cell may be direct or indirect. o Information transfer at the synapse can be modified in response to environmental conditions. o Such modification may form the basis for learning or memory. Neural integration occurs at the cellular level. At many chemical synapses, ligand-gated ion channels capable of binding to the neurotransmitter are clustered in the membrane of the postsynaptic cell, directly opposite the synaptic terminal. Binding of the neurotransmitter to the receptor opens the channel and allows specific ions to diffuse across the postsynaptic membrane. o This mechanism of information transfer is called direct synaptic transmission. o The result is generally a postsynaptic potential, a change in the membrane potential of the postsynaptic cell. Excitatory postsynaptic potentials (EPSPs) depolarize the postsynaptic neuron. o The binding of neurotransmitter to postsynaptic receptors opens gated channels that allow Na+ to diffuse into and K+ to diffuse out of the cell. Inhibitory postsynaptic potential (IPSP) hyperpolarizes the postsynaptic neuron. o The binding of neurotransmitter to postsynaptic receptors open gated channels that allow K+ to diffuse out of the cell and/or Cl? to diffuse into the cell. Various mechanisms end the effect of neurotransmitters on postsynaptic cells. o The neurotransmitter may simply diffuse out of the synaptic cleft. o The neurotransmitter may be taken up by the presynaptic neuron through active transport and repackaged into synaptic vesicles. o Glia actively take up the neurotransmitter at some synapses and metabolize it as fuel. o The neurotransmitter acetylcholine is degraded by acetylcholinesterase, an enzyme in the synaptic cleft. Postsynaptic potentials are graded; their magnitude varies with a number of factors, including the amount of neurotransmitter released by the presynaptic neuron. o Postsynaptic potentials do not regenerate but diminish with distance from the synapse. o Most synapses on a neuron are located on its dendrites or cell body, whereas action potentials are generally initiated at the axon hillock. Therefore, a single EPSP is usually too small to trigger an action potential in a postsynaptic neuron. Graded potentials (EPSPs and IPSPs) are summed to either depolarize or hyperpolarize a postsynaptic neuron. o Two EPSPs produced in rapid succession at the same synapse can be added in an effect called temporal summation. o Two EPSPs produced nearly simultaneously by different synapses on the same postsynaptic neuron can be added, in an effect called spatial summation. o Summation also applies to IPSPs. This interplay between multiple excitatory and inhibitory inputs is the essence of integration in the nervous system. o The axon hillock is the neurons integrating center, where the membrane potential at any instant represents the summed effect of all EPSPs and IPSPs. o Whenever the membrane potential at the axon hillock reaches the threshold, an action potential is generated and travels along the axon to its synaptic terminals. In indirect synaptic transmission, a neurotransmitter binds to a receptor that is not part of an ion channel. o This binding activates a signal transduction pathway involving a second messenger in the postsynaptic cell. o This form of transmission has a slower onset, but its effects have a longer duration. cAMP acts as a secondary messenger in indirect synaptic transmission. o When the neurotransmitter norepinephrine binds to its receptor, the neurotransmitter-receptor complex activates a G-protein, which in turn activates adenylyl cyclase, the enzyme that converts ATP to cAMP. o cAMP activates protein kinase A, which phosphorylates specific channel proteins in the postsynaptic membrane, causing them to open or close. o Because of the amplifying effect of the signal transduction pathway, the binding of a neurotransmitter to a single receptor can open or close many channels. The same neurotransmitter can produce different effects on different types of cells. Each of the known neurotransmitters binds to a specific group of receptors. o Some neurotransmitters have a dozen or more receptors, which can produce very different effects in postsynaptic cells. Acetylcholine is one of the most common neurotransmitters in both invertebrates and vertebrates. o In the vertebrate CNS, it can be inhibitory or excitatory, depending on the type of receptor.

At the vertebrate neuromuscular junction, acetylcholine released by the motor neuron binds to receptors on ligandgated channels in the muscle cell, producing an EPSP via direct synaptic transmission. o Nicotine binds to the same receptors. o Acetylcholine is inhibitory to cardiac muscle cell contraction. Biogenic amines are neurotransmitters derived from amino acids. v One group, known as catecholamines, consists of neurotransmitters produced from the amino acid tyrosine. This group includes epinephrine and norepinephrine and a closely related compound called dopamine. Another biogenic amine, serotonin, is synthesized from the amino acid tryptophan. The biogenic amines are usually involved in indirect synaptic transmission, most commonly in the CNS. Dopamine and serotonin affect sleep, mood, attention, and learning. Imbalances in these neurotransmitters are associated with several disorders. o Parkinsons disease is associated with a lack of dopamine in the brain. o LSD and mescaline produce hallucinations by binding to brain receptors for serotonin and dopamine. Depression is treated with drugs that increase the brain concentrations of biogenic amines such as norepinephrine and serotonin. o Prozac inhibits the uptake of serotonin after its release, increasing its effect. Four amino acids function as neurotransmitters in the CNS: gamma aminobutyric acid (GABA), glycine, glutamate, and aspartate. o GABA is the neurotransmitter at most inhibitory synapses in the brain, where it produces IPSPs. Several neuropeptides, relatively short chains of amino acids, serve as neurotransmitters. o Most neurons release one or more neuropeptides as well as a nonpeptide neurotransmitter. o Neuropeptides usually operate via signal transduction pathways. o The neuropeptide substance P is a key excitatory neurotransmitter that mediates our perception of pain. Other neuropeptides, endorphins, act as natural analgesics. Opiates such as morphine and heroin bind to receptors on brain neurons by mimicking endorphins, which are produced in the brain under times of physical or emotional stress. Some neurons of the vertebrate PNS and CNS release dissolved gases, especially nitric oxide and carbon monoxide, which act as local regulators. o During male sexual arousal, certain neurons release NO into the erectile tissue of the penis. o In response, smooth muscle cells in the blood vessel walls of the erectile tissue relax, allowing the blood vessels to dilate and fill the spongy erectile tissue with blood, producing an erection. Viagra inhibits an enzyme that slows the muscle-releasing effects of NO. Carbon monoxide is synthesized by the enzyme heme oxygenase. o In the brain, CO regulates the release of hypothalamic hormones. o In the PNS, it acts as an inhibitory neurotransmitter that hyperpolarizes intestinal smooth muscle cells. NO and CO are synthesized by cells as needed. o They diffuse into neighboring target cells, produce an effect, and are broken down, all within a few seconds. Concept 48.5 The vertebrate nervous system is regionally specialized Vertebrate nervous systems have central and peripheral components. In all vertebrates, the nervous system shows a high degree of cephalization and has distinct CNS and PNS components. o The brain provides integrative power that underlies the complex behavior of vertebrates. o The spinal cord integrates simple responses to certain kinds of stimuli and conveys information to and from the brain. The vertebrate CNS is derived from the dorsal embryonic nerve cord, which is hollow. o In the adult, this feature persists as the narrow central canal of the spinal cord and the four ventricles of the brain. o Both the canal and the ventricles are filled with cerebrospinal fluid, which is formed in the brain by filtration of the blood. o Cerebrospinal fluid circulates through the central canal and ventricles and then drains into the veins, assisting in the supply of nutrients and hormone and the removal of wastes. o In mammals, the fluid cushions the brain and spinal cord by circulating between two of the meninges, layers of connective tissue that surround the CNS. White matter of the CNS is composed of bundles of myelinated axons. o Gray matter consists of unmyelinated axons, nuclei, and dendrites. The divisions of the peripheral nervous system interact in maintaining homeostasis. The PNS transmits information to and from the CNS and plays an important role in regulating the movement and internal environment of a vertebrate. o The vertebrate PNS consists of left-right pairs of cranial and spinal nerves and their associated ganglia. o Paired cranial nerves originate in the brain and innervate the head and upper body. o Paired spinal nerves originate in the spinal cord and innervate the entire body. The PNS can be divided into two functional components: the somatic nervous system and the autonomic nervous system. The somatic nervous system carries signals to and from skeletal muscle, mainly in response to external stimuli.

It is subject to conscious control, but much skeletal muscle activity is actually controlled by reflexes mediated by the spinal cord or the brainstem. The autonomic nervous system regulates the internal environment by controlling smooth and cardiac muscles and the organs of the digestive, cardiovascular, excretory, and endocrine systems. o Three divisions make up the autonomic nervous system: sympathetic, parasympathetic, and enteric. Activation of the sympathetic division correlates with arousal and energy generationthe flight or fight response. Activation of the parasympathetic division generally promotes calming and a return to self-maintenance functionsrest and digest. When sympathetic and parasympathetic neurons innervate the same organ, they often have antagonistic effects. The enteric division consists of complex networks of neurons in the digestive tract, pancreas, and gallbladder. The enteric networks control the secretions of these organs as well as activity in the smooth muscles that produce peristalsis. The sympathetic and parasympathetic divisions normally regulate the enteric division. The somatic and autonomic nervous systems often cooperate in maintaining homeostasis. Embryonic development of the vertebrate brain reflects its evolution from three anterior bulges of the neural tube. In all vertebrates, three bilaterally symmetrical, anterior bulges of the neural tube form the forebrain, midbrain, and hindbrain during embryonic development. Over vertebrate evolution, the brain became further divided structurally and functionally, providing additional complex integration. o The forebrain is particularly enlarged in birds and mammals. Five brain regions form by the fifth week of human embryonic development. o The telencephalon and diencephalon develop from the forebrain. o The mesencephalon develops from the midbrain. o The metencephalon and myelencephalon develop from the hindbrain. The telencephalon gives rise to the cerebrum. o Rapid growth of the telencephalon during the second month of human development causes the outer portion of the cerebrum, the cerebral cortex, to extend over the rest of the brain. The adult brainstem consists of the midbrain (derived from the mesencephalon), the pons (derived from the metencephalon), and the medulla oblongata (derived from the myelencephalon). The metencephalon also gives rise to the cerebellum. Evolutionarily older structures of the vertebrate brain regulate essential automatic and integrative functions. The brainstem is one of the evolutionarily older parts of the brain. o Sometimes called the lower brain, it consists of the medulla oblongata, pons, and midbrain. o The brain stem functions in homeostasis, coordination of movement, and conduction of impulses to higher brain centers. Centers in the brainstem contain neuron cell bodies that send axons to many areas of the cerebral cortex and cerebellum, releasing neurotransmitters. o Signals in these pathways cause changes in attention, alertness, appetite, and motivation. The medulla oblongata contains centers that control visceral (autonomic, homeostatic) functions, including breathing, heart and blood vessel activity, swallowing, vomiting, and digestion. The pons also participates in some of these activities. o It regulates the breathing centers in the medulla. Information transmission to and from higher brain regions is one of the most important functions of the medulla and pons. The two regions also help coordinate large-scale body movements. o Axons carrying instructions about movement from the midbrain and forebrain to the spinal cord cross from one side of the CNS to the other in the medulla. o The right side of the brain controls the movement of the left side of the body, and vice versa. The midbrain contains centers involved in the receipt and integration of sensory information. o Superior colliculi are involved in the regulation of visual reflexes. o Inferior colliculi are involved in the regulation of auditory reflexes. The midbrain relays information to and from higher brain centers. The reticular activating system (RAS) of the reticular formation regulates sleep and arousal. o Acting as a sensory filter, the RAS selects which information reaches the cerebral cortex. o The more information the cortex receives, the more alert and aware the person is. o The brain can ignore some stimuli while actively processing other input. Sleep and wakefulness are regulated by specific parts of the brainstem. o The pons and medulla contain centers that cause sleep when stimulated, and the midbrain has a center that causes arousal.

Serotonin may be the neurotransmitter of the sleep-producing centers. All birds and mammals show characteristic sleep/wake cycles. Melatonin, a hormone produced by the pineal gland, appears to play an important role in these cycles. o The function of sleep is still not fully understood. One hypothesis is that sleep is involved in the consolidation of learning and memory, and experiments show that regions of the brain activated during a learning task can become active again during sleep. The cerebellum develops from part of the metencephalon. o It functions to error-check and coordinate motor activities, and perceptual and cognitive functions. The cerebellum is involved in learning and remembering motor skills. o It relays sensory information about joints, muscles, sight, and sound to the cerebrum. o The cerebellum also coordinates motor commands issued by the cerebrum. The embryonic diencephalon develops into three adult brain regions: the epithalamus, thalamus, and hypothalamus. o The epithalamus includes the pineal gland and the choroid plexus, one of several clusters of capillaries that produce cerebrospinal fluid from blood. o The thalamus relays all sensory information to the cerebrum and relays motor information from the cerebrum. Incoming information from all the senses is sorted in the thalamus and sent to the appropriate cerebral centers for further processing. The thalamus also receives input from the cerebrum and other parts of the brain that regulate emotion and arousal. o Although it weighs only a few grams, the hypothalamus is a crucial brain region for homeostatic regulation. It is the source of posterior pituitary hormones and releasing hormones that act on the anterior pituitary. The hypothalamus also contains centers involved in thermoregulation, hunger, thirst, sexual and mating behavior, and pleasure. Animals exhibit circadian rhythms, one being the sleep/wake cycle. o The biological clock is an internal timekeeper that regulates a variety of physiological phenomena, including hormone release, hunger, and sensitivity to external stimuli. o In mammals, the hypothalamic suprachiasmatic nuclei (SCN) function as a biological clock. The clocks rhythm requires external cues to remain synchronized with environmental cycles. Experiments in which humans have been deprived of external cues have shown that the human biological clock has a period of 24 hours and 11 minutes. The cerebrum is the most highly developed structure of the mammalian brain. The cerebrum is derived from the embryonic telencephalon and is divided into left and right cerebral hemispheres. Each hemisphere consists of an outer covering of gray matter, the cerebral cortex; internal white matter; and groups of neurons deep within the white matter called basal nuclei. o The basal nuclei are important centers for planning and learning movement sequences. In humans, the largest and most complex part of the brain is the cerebral cortex. o It is here that sensory information is analyzed, motor commands are issued, and language is generated. The cerebral cortex underwent a dramatic expansion when the ancestors of mammals diverged from reptiles. Mammals have a region of the cerebral cortex known as the neocortex. o The neocortex forms the outermost part of the mammalian cerebrum, consisting of six parallel layers of neurons running tangential to the brain surface. o The human neocortex is highly convoluted, allowing the region to have a large surface area and still fit inside the skull. Although less than 5 mm thick, the human neocortex has a surface area of about 0.5m2 and accounts for about 80% of the total brain mass. o Nonhuman primates and cetaceans also have exceptionally large, convoluted neocortices. The surface area relative to body size of a porpoises neocortex is second only to that of a human. The cerebral cortex is divided into right and left sides. o The left hemisphere is primarily responsible for the right side of the body. o The right hemisphere is primarily responsible for the left side of the body. A thick band of axons known as the corpus callosum is the major connection between the two hemispheres. Damage to one area of the cerebrum early in development can frequently cause redirection of its normal functions to other areas. Concept 48.6 The cerebral cortex controls voluntary movement and cognitive functions The cerebrum is divided into frontal, temporal, occipital, and parietal lobes. o Researchers have identified a number of functional areas within each lobe. o These areas include primary sensory areas, each of which receives and processes a specific type of sensory information, and association areas, which integrate the information from various parts of the brain. The major increase in the size of the neocortex that occurred during mammalian evolution was mostly an expansion of the association areas that integrate higher cognitive functions and make more complex behavior and learning possible.

o o

Most sensory information coming into the cortex is directed via the thalamus to primary sensory areas within the lobes: visual information to the occipital lobe; auditory input to the temporal lobe; and somatosensory information about touch, pain, pressure, temperature, and position of limbs and muscles to the parietal lobe. o In mammals, olfactory information is first sent to regions in the cortex that are similar in mammals and reptiles, and then via the thalamus to an interior part of the frontal lobe. o Based on the integrated sensory information, the cerebral cortex can generate motor commands that cause specific behaviors. o These commands consist of action potentials produced by neurons in the primary motor cortex, which lies at the rear of the frontal lobe. o The action potentials travel along axons to the brainstem and spinal cord, where they excite motor neurons, which in turn excite skeletal muscle cells. In both the somatosensory cortex and the motor cortex, neurons are distributed in an orderly fashion according to the part of the body that generates the sensory input or receives the motor command. o The cortical surface area devoted to each body part is not related to the size of the part. o Instead it is related to the number of sensory neurons that innervate that part (for the somatosensory cortex) or the amount of skill needed to control muscles in that part (for the motor cortex). During brain development, competing functions segregate and displace each other in the cortex of the left and right cerebral hemispheres, resulting in lateralization of brain function. o The left hemisphere specializes in language, math, logic operations, and the processing of serial sequences of information, and fine visual and auditory details. It specializes in detailed activities required for motor control. o The right hemisphere specializes in pattern recognition, spatial relationships, nonverbal ideation, emotional processing, and the parallel processing of information. Understanding and generating the stress and intonation patterns of speech that convey its emotional content is primarily a right-hemisphere function, as is musical appreciation. o The right hemisphere specializes in perceiving the relationship between images and the whole context in which they occur, whereas the left hemisphere is better at focused perception. o The two hemispheres work together, exchanging information through the fibers of the corpus callosum. Brocas area, located in the left hemispheres frontal lobe, is responsible for speech production. Wernickes area, located in the right hemispheres temporal lobe, is responsible for speech comprehension. o Studies of brain activity using fMRI and positron-emission tomography (PET) confirm that Brocas area is active during the generation of speech, while Wernickes area is active when speech is heard. o These areas are part of a larger network of brain regions involved in language, including the visual cortex (for reading) and frontal and temporal areas that are involved in generating verbs to match nouns and grouping together related words and concepts. Emotions are the result of a complex interplay of many regions of the brain. The limbic system is a ring of structures around the brainstem, including three parts of the cerebral cortexthe amygdala, hippocampus, and olfactory bulbalong with some inner portions of the cortexs lobes, and parts of the thalamus and hypothalamus. o These structures interact with sensory areas of the neocortex to mediate primary emotions that result in laughing or crying. o It also attaches emotional feelings to basic, survival-level functions controlled by the brainstem, including aggression, feeding, and sexuality. o The limbic system is central to crucial mammalian behaviors involved in emotional bonding and extended nurturing of infants. The amygdala, a structure in the temporal lobe, is central in recognizing the emotional content of facial expression and laying down emotional memories. o This emotional memory system seems to appear earlier in development than the system that supports explicit recall of events, which requires the hippocampus. As children develop, primary emotions such as pleasure and fear are associated with different situations in a process that requires portions of the neocortex, especially the prefrontal cortex. o Damage to regions of the frontal cortex may leave the patients intelligence and memories intact, but destroy their motivation, foresight, goal formation, and decision making. Frontal lobotomy was a widely performed surgical procedure in which the connection between the prefrontal cortex and the limbic system was disrupted. o This technique was used to treat severe emotional problems. o It resulted in docility and the loss of ability to concentrate, plan, and work toward goals. o Drug therapy has replaced frontal lobotomy. Short-term memories are stored in the frontal lobes and released as they become irrelevant. Should we wish to retain knowledge of short-term memories, long-term memories are established by mechanisms involving the hippocampus.

The transfer of information from short-term to long-term memory is enhanced by repetition (practice makes perfect), positive or negative emotional states mediated by the amygdala, and the association of the new data with previously stored information. Many sensory and motor association areas of the cerebral cortex outside Brocas area and Wernickes area are involved in storing and retrieving words and images. The memorization of information can be very rapid and may rely mainly on rapid changes in the strength of existing neural connections. o In contrast, the slow learning and remembering of skills and procedures appear to involve the formation of new connections between neurons, by cellular mechanisms similar to those responsible for brain growth and development. Motor skills are usually learned by repetition. o It is possible to perform such skills without consciously recalling the individual steps involved. Nobel laureate Eric Kandel and his colleagues at Columbia University studied the cellular basis of learning using the sea hare, Aplysia californica. o They were able to explain the mechanism of simple forms of learning in the mollusc in terms of changes in the strength of synaptic transmission between specific sensory and motor neurons. In the vertebrate brain, a form of learning called long-term potentiation (LTP) involves an increase in the strength of synaptic transmission that occurs when presynaptic neurons produce a brief, high-frequency series of action potentials. o LTP can last for days or weeks and may be a fundamental process by which memories are stored or learning takes place. The cellular mechanism of LTP has been studied most thoroughly at synapses in the hippocampus, where presynaptic neurons release the excitatory neurotransmitter glutamate. The postsynaptic neurons possess two types of glutamate receptors: AMPA receptors and NMDA receptors. o AMPA receptors are part of ligand-gated ion channels. When glutamate binds to them, Na+ and K+ diffuse through the channels, and the postsynaptic membrane depolarizes. o NMDA receptors are part of channels that are both ligand-gated and voltage-gated. The channels open only if glutamate is bound and the membrane is depolarized. The binding of glutamate to these two types of receptors can lead to LTP through changes in both the presynaptic and postsynaptic neurons. Neuroscientists have begun studying human consciousness using brain-imaging techniques such as fMRI. o Brain imaging can show neural activity associated with conscious perceptual choices and unconscious processing of sensory information. o Such studies offer an increasingly detailed picture of how neural activity correlates with conscious experience. There is a growing consensus that consciousness is an emergent property of the brain, one that recruits activities in many areas of the cerebral cortex. Several models suggest a scanning mechanism that repetitively sweeps across the brain, integrating widespread activity into a unified, conscious moment. Concept 48.7 CNS injuries and diseases are the focus of much research Unlike the PNS, the mammalian CNS does not have the ability to repair itself when damaged or injured by disease. Surviving neurons in the brain can make new connections and sometimes compensate for damage. o Generally speaking, brain and spinal cord injuries, strokes, and diseases that destroy CNS neurons have devastating effects. Research on nerve cell development and neural stem cells may be the future of treatment for damage to the CNS. Researchers are investigating how neurons find their way during CNS development. o To reach their target cells, axons must elongate from a few micrometers to a meter or more. o Molecular signposts along the way direct and redirect the growing axon in a series of mid-course connections that result in a meandering, but not random, elongation. o The responsive region at the leading edge of the neuron is called the growth cone. o Signal molecules released by cells along the growth route bind to receptors on the plasma membrane of the growth cone, triggering a signal transduction pathway. The axon may respond by growing toward the source of the signal molecules (attraction) or away from it (repulsion). o Cell adhesion molecules on the axons growth cone also play a role by attaching to complementary molecules on surrounding cells that provide tracks for the growing axon to follow. o Nerve growth factor released by astrocytes and growth-promoting proteins produced by the neurons themselves contribute to the process by simulating axonal elongation. o The growing axon expresses different genes as it develops, and it is influenced by surrounding cells that it moves away from. o

This complex process has been conserved during millions of years of evolution, for the genes, gene products, and mechanisms of axon guidance are remarkably similar in humans, nematode worms, and insects. o In 1998, it was discovered that a adult human brain does produce new neurons. New neurons have been found in the hippocampus. The function of these new neurons is not clear, but it is known that mice living in stimulating conditions have more new neurons in their hippocampus than those that receive little stimulation. Since mature human brain cells cannot undergo cell division, the new cells must have arisen from stem cells. In 2001, Fred Gage of the Salk Institute announced that they had cultured neural progenitor cells from adult human brains. The term progenitor means that these stem cells are committed to develop as neurons or glia. In culture, the cells divided 30 to 70 times and differentiated into neurons and astrocytes. The nervous system has a number of diseases and disorders. About 1% of the worlds population suffers from schizophrenia, a severe mental disturbance characterized by psychotic episodes. o The symptoms of schizophrenia include hallucinations and delusions, blunted emotions, distractibility, lack of initiative, and poverty of speech. The cause of schizophrenia is unknown, although the disease has a strong genetic component. o There is an active effort to find the mutant genes that predispose a person to schizophrenia. o Multiple genes must be involved because inheritance does not follow a simple Mendelian pattern. Available treatments for schizophrenia focus on the use of dopamine as a neurotransmitter. o Two lines of evidence suggest that this approach is suitable. First, amphetamine, which stimulates dopamine release, can produce symptoms identical to those of schizophrenia. Second, many of the drugs that alleviate the symptoms block dopamine receptors. Additional neurotransmitters may also be involved because other drugs successful in treating schizophrenia have stronger effects on serotonin and/or norepinephrine transmitters. There are other indications that glutamate receptors may play a role in schizophrenia. o The street drug PCP blocks glutamate receptors and induces strong schizophrenia-like symptoms. Many current schizophrenia medications have severe side effects. o Twenty-five percent of schizophrenics on chronic drug therapy develop tardive dyskinesia, in which the patient has uncontrolled facial writhing movements. Two broad forms of depressive illness are known: bipolar disorder and major depression. o Bipolar disorder involves swings in mood from high to low and affects about 1% of the worlds population. o People with major depression have a low mood most of time. o Five percent of the population suffers from major depression. In bipolar disorder, the manic phase is characterized by high self-esteem, increased energy, a flow of ideas, and risky behaviors such as promiscuity and reckless spending. o In the depressive phase, symptoms include lowered ability to feel pleasure, loss of interest, sleep disturbances, feelings of worthlessness, and risk of suicide. Both bipolar disorder and major depression have a genetic component, as identical twins have a 50% chance of sharing this mental illness. o It is likely that childhood stress is also an important factor. Several treatments for depression are available, including Prozac, electroconvulsive shock therapy, lithium administration, and talk therapy. Alzheimers disease is a mental deterioration or dementia. o It is characterized by confusion, memory loss, and a variety of other symptoms. o Its incidence is age related, rising from 10% at age 65 to 35% at age 85. The disease is progressive, with patients losing the ability to live alone and take care of themselves. o There are also personality changes, almost always for the worse. It is difficult to diagnose Alzheimers disease while the patient is still alive. However, it results in characteristic brain pathology. o Neurons die in huge areas of the brain, often leading to shrinkage of brain tissue. o The diagnostic features are neurofibrillary tangles and senile plaques in the remaining brain tissue. Neurofibrillary tangles are bundles of degenerated neuronal and glial processes. Senile plaques are aggregates of -amyloid, an insoluble peptide that is cleaved from a membrane protein normally found in neurons. Membrane enzymes, called secretases, catalyze the cleavage, causing -amyloid to accumulate outside the neurons and to aggregate in the form of plaques. The plaques seem to trigger the death of the surrounding neurons.

In 2004, a team of researchers at Northwestern University used genetic engineering to eliminate one of the secretases in a strain of mice prone to Alzheimers disease. o The genetically engineered mice accumulated less -amyloid and did not experience the age-related memory deficits typical of mice of that strain. o Other drugs are being developed to prevent the development of senile plaques, which form before overt symptoms of Alzheimers disease develop. Approximately 1 million people in the United States suffer from Parkinsons disease, a motor disease characterized by difficulty in initiating movement, slowness of movement, and rigidity. Like Alzheimers disease, Parkinsons disease results from death of neurons in a midbrain nucleus called the substantia nigra. o These neurons normally release dopamine from their synaptic terminals in the basal nuclei. o The degeneration of dopamine neurons is associated with the accumulation of protein aggregates containing a protein typically found in presynaptic nerve terminals. Most cases of Parkinsons disease lack a clearly identifiable cause. o The consensus among scientists is that it results from a combination of environmental and genetic factors. At present, there is no cure for Parkinsons disease, although various approaches are used to manage the symptoms, including brain surgery; deep-brain stimulation; and drugs such as L-dopa, a dopamine precursor that can cross the blood-brain barrier. o One potential cure is to implant dopamine-secreting neurons, either in the substantia nigra or in the basal ganglia. o Embryonic stem cells can be stimulated or genetically engineered to develop into dopamine-secreting neurons. Transplantation of these cells into rats with an experimentally induced condition that mimics Parkinsons disease has led to a recovery of motor control. It remains to be seen whether this kind of regenerative medicine will work in humans. Chapter 40 - Basic Principles of Animal Form and Function Chapter 40 Basic Principles of Animal Form and Function Lecture Outline Overview: Diverse Forms, Common Challenges Animals inhabit almost every part of the biosphere. o Despite their great diversity, all animals must solve a common set of problems. o All animals must obtain oxygen, nourish themselves, excrete wastes, and move. Animals of diverse evolutionary histories and varying complexity must solve these general challenges of life. o Consider the long, tongue-like proboscis of a hawk moth, a structural adaptation for feeding. o Recoiled when not in use, the proboscis extends as a straw through which the moth can suck nectar from deep within tube-shaped flowers. Analyzing the hawk moths proboscis gives clues about what it does and how it functions. o Anatomy is the study of the structure of an organism. o Physiology is the study of the functions an organism performs. o Natural selection can fit structure to function by selecting, over many generations, the best of the available variations in a population. Searching for food, generating body heat and regulating internal temperature, sensing and responding to environmental stimuli, and all other animal activities require fuel in the form of chemical energy. The concept of bioenergeticshow organisms obtain, process, and use energy resourcesis a connecting theme in the comparative study of animals. Concept 40.1 Physical laws and the environment constrain animal size and shape An animals size and shape, features often called body plans or designs, are fundamental aspects of form and function that significantly affect the way an animal interacts with its environment. o The terms plan and design do not mean that animal body forms are products of conscious invention. o The body plan or design of an animal results from a pattern of development programmed by the genome, itself the product of millions of years of evolution due to natural selection. Physical requirements constrain what natural selection can invent. An animal such as the mythical winged dragon cannot exist. No animal as large as a dragon could generate enough lift to take off and fly. Similarly, the laws of hydrodynamics constrain the shapes that are possible for aquatic organisms that swim very fast. Tunas, sharks, penguins, dolphins, seals, and whales are all fast swimmers. o All have the same basic fusiform shape, tapered at both ends. This shape minimizes drag in water, which is about a thousand times denser than air. The similar forms of speedy fishes, birds, and marine mammals are a consequence of convergent evolution in the face of the universal laws of hydrodynamics. o Convergence occurs because natural selection shapes similar adaptations when diverse organisms face the same environmental challenge, such as the resistance of water to fast travel. Body size and shape affect interactions with the environment. An animals size and shape have a direct effect on how the animal exchanges energy and materials with its surroundings.

As a requirement for maintaining the fluid integrity of the plasma membrane of its cells, an animals body must be arranged so that all of its living cells are bathed in an aqueous medium. Exchange with the environment occurs as dissolved substances diffuse and are transported across the plasma membranes between the cells and their aqueous surroundings. o For example, a single-celled protist living in water has a sufficient surface area of plasma membrane to service its entire volume of cytoplasm. o Surface-to-volume ratio is one of the physical constraints on the size of single-celled protists. Multicellular animals are composed of microscopic cells, each with its own plasma membrane that acts as a loading and unloading platform for a modest volume of cytoplasm. o This only works if all the cells of the animal have access to a suitable aqueous environment. o For example, a hydra, built as a sac, has a body wall only two cell layers thick. o Because its gastrovascular cavity opens to the exterior, both outer and inner layers of cells are bathed in water. Another way to maximize exposure to the surrounding medium is to have a flat body. o For instance, a parasitic tapeworm may be several meters long, but because it is very thin, most of its cells are bathed in the intestinal fluid of the worms vertebrate host from which it obtains nutrients. While two-layered sacs and flat shapes are designs that put a large surface area in contact with the environment, these solutions do not permit much complexity in internal organization. Most animals are more complex and are made up of compact masses of cells, producing outer surfaces that are relatively small compared to the animals volume. o Most organisms have extensively folded or branched internal surfaces specialized for exchange with the environment. o The circulatory system shuttles material among all the exchange surfaces within the animal. Although exchange with the environment is a problem for animals whose cells are mostly internal, complex forms have distinct benefits. o A specialized outer covering can protect against predators; large muscles can enable rapid movement; and internal digestive organs can break down food gradually, controlling the release of stored energy. o Because the immediate environment for the cells is the internal body fluid, the animals organ systems can control the composition of the solution bathing its cells. o A complex body form is especially well suited to life on land, where the external environment may be variable. Concept 40.2 Animal form and function are correlated at all levels of organization Life is characterized by hierarchical levels of organization, each with emergent properties. Animals are multicellular organisms with their specialized cells grouped into tissues. In most animals, combinations of various tissues make up functional units called organs, and groups of organs work together as organ systems. o For example, the human digestive system consists of a stomach, small intestine, large intestine, and several other organs, each a composite of different tissues. Tissues are groups of cells with a common structure and function. o Different types of tissues have different structures that are suited to their functions. o A tissue may be held together by a sticky extracellular matrix that coats the cells or weaves them together in a fabric of fibers. The term tissue is from a Latin word meaning weave. Tissues are classified into four main categories: epithelial tissue, connective tissue, nervous tissue, and muscle tissue. Occurring in sheets of tightly packed cells, epithelial tissue covers the outside of the body and lines organs and cavities within the body. o The cells of an epithelium are closely joined and in many epithelia, the cells are riveted together by tight junctions. o The epithelium functions as a barrier protecting against mechanical injury, invasive microorganisms, and fluid loss. The cells at the base of an epithelial layer are attached to a basement membrane, a dense mat of extracellular matrix. o The free surface of the epithelium is exposed to air or fluid. Some epithelia, called glandular epithelia, absorb or secrete chemical solutions. o The glandular epithelia that line the lumen of the digestive and respiratory tracts form a mucous membrane that secretes a slimy solution called mucus that lubricates the surface and keeps it moist. Epithelia are classified by the number of cell layers and the shape of the cells on the free surface. o A simple epithelium has a single layer of cells, and a stratified epithelium has multiple tiers of cells. o A pseudostratified epithelium is single-layered but appears stratified because the cells vary in length. The shapes of cells on the exposed surface may be cuboidal (like dice), columnar (like bricks on end), or squamous (flat like floor tiles). Connective tissue functions mainly to bind and support other tissues. o Connective tissues have a sparse population of cells scattered through an extracellular matrix. o The matrix generally consists of a web of fibers embedding in a uniform foundation that may be liquid, jellylike, or solid. o In most cases, the connective tissue cells secrete the matrix.

There are three kinds of connective tissue fibers, which are all proteins: collagenous fibers, elastic fibers, and reticular fibers. Collagenous fibers are made of collagen, the most abundant protein in the animal kingdom. o Collagenous fibers are nonelastic and do not tear easily when pulled lengthwise. Elastic fibers are long threads of elastin. o Elastin fiber provides a rubbery quality that complements the nonelastic strength of collagenous fibers. Reticular fibers are very thin and branched. o Composed of collagen and continuous with collagenous fibers, they form a tightly woven fabric that joins connective tissue to adjacent tissues. The major types of connective tissues in vertebrates are loose connective tissue, adipose tissue, fibrous connective tissue, cartilage, bone, and blood. o Each has a structure correlated with its specialized function. Loose connective tissue binds epithelia to underlying tissues and functions as packing material, holding organs in place. o Loose connective tissue has all three fiber types. Two cell types predominate in the fibrous mesh of loose connective tissue. o Fibroblasts secrete the protein ingredients of the extracellular fibers. o Macrophages are amoeboid cells that roam the maze of fibers, engulfing bacteria and the debris of dead cells by phagocytosis. Adipose tissue is a specialized form of loose connective tissue that stores fat in adipose cells distributed throughout the matrix. o Adipose tissue pads and insulates the body and stores fuel as fat molecules. o Each adipose cell contains a large fat droplet that swells when fat is stored and shrinks when the body uses fat as fuel. Fibrous connective tissue is dense, due to its large number of collagenous fibers. o The fibers are organized into parallel bundles, an arrangement that maximizes nonelastic strength. o This type of connective tissue forms tendons, attaching muscles to bones, and ligaments, joining bones to bones at joints. Cartilage has an abundance of collagenous fibers embedded in a rubbery matrix made of a substance called chondroitin sulfate, a protein-carbohydrate complex. o Chondrocytes secrete collagen and chondroitin sulfate. o The composite of collagenous fibers and chondroitin sulfate makes cartilage a strong yet somewhat flexible support material. o The skeleton of a shark and the embryonic skeletons of many vertebrates are cartilaginous. o We retain cartilage as flexible supports in certain locations, such as the nose, ears, and intervertebral disks. The skeleton supporting most vertebrates is made of bone, a mineralized connective tissue. o Bone-forming cells called osteoblasts deposit a matrix of collagen. o Calcium, magnesium, and phosphate ions combine and harden within the matrix into the mineral hydroxyapatite. o The combination of hard mineral and flexible collagen makes bone harder than cartilage without being brittle. o The microscopic structure of hard mammalian bones consists of repeating units called osteons. Each osteon has concentric layers of mineralized matrix deposited around a central canal containing blood vessels and nerves that service the bone. Blood functions differently from other connective tissues, but it does have an extensive extracellular matrix. o The matrix is a liquid called plasma, consisting of water, salts, and a variety of dissolved proteins. o The liquid matrix enables rapid transport of blood cells, nutrients, and wastes. o Suspended in the plasma are erythrocytes (red blood cells), leukocytes (white blood cells), and cell fragments called platelets. Red cells carry oxygen. White cells function in defense against viruses, bacteria, and other invaders. Platelets aid in blood clotting. Muscle tissue is composed of long cells called muscle fibers that are capable of contracting when stimulated by nerve impulses. o Arranged in parallel within the cytoplasm of muscle fibers are large numbers of myofibrils made of the contractile proteins actin and myosin. o Muscle is the most abundant tissue in most animals, and muscle contraction accounts for most of the energyconsuming cellular work in active animals. There are three types of muscle tissue in the vertebrate body: skeletal muscle, cardiac muscle, and smooth muscle. Attached to bones by tendons, skeletal muscle is responsible for voluntary movements. o Skeletal muscle consists of bundles of long cells called fibers. Each fiber is a bundle of strands called myofibrils. o Skeletal muscle is also called striated muscle because the arrangement of contractile units, or sarcomeres, gives the cells a striped (striated) appearance under the microscope. Cardiac muscle forms the contractile wall of the heart.

It is striated like skeletal muscle, and its contractile properties are similar to those of skeletal muscle. Unlike skeletal muscle, cardiac muscle carries out the unconscious task of contraction of the heart. Cardiac muscle fibers branch and interconnect via intercalated disks, which relay signals from cell to cell during a heartbeat. Smooth muscle, which lacks striations, is found in the walls of the digestive tract, urinary bladder, arteries, and other internal organs. o The cells are spindle-shaped. o They contract more slowly than skeletal muscles but can remain contracted longer. o Controlled by different kinds of nerves than those controlling skeletal muscles, smooth muscles are responsible for involuntary body activities. These include churning of the stomach and constriction of arteries. Nervous tissue senses stimuli and transmits signals from one part of the animal to another. o The functional unit of nervous tissue is the neuron, or nerve cell, which is uniquely specialized to transmit nerve impulses. o A neuron consists of a cell body and two or more processes called dendrites and axons. Dendrites transmit impulses from their tips toward the rest of the neuron. Axons transmit impulses toward another neuron or toward an effector, such as a muscle cell that carries out a body response. o In many animals, nervous tissue is concentrated in the brain. The organ systems of an animal are interdependent. In all but the simplest animals (sponges and some cnidarians) different tissues are organized into organs. In some organs the tissues are arranged in layers. o For example, the vertebrate stomach has four major tissue layers. A thick epithelium lines the lumen and secretes mucus and digestive juices. Outside this layer is a zone of connective tissue, surrounded by a thick layer of smooth muscle. Another layer of connective tissue encases the entire stomach. Many vertebrate organs are suspended by sheets of connective tissues called mesenteries in body cavities moistened or filled with fluid. o Mammals have a thoracic cavity housing the lungs and heart that is separated from the lower abdominal cavity by a sheet of muscle called the diaphragm. Organ systems carry out the major body functions of most animals. o Each organ system consists of several organs and has specific functions. The efforts of all systems must be coordinated for the animal to survive. o For instance, nutrients absorbed from the digestive tract are distributed throughout the body by the circulatory system. o The heart that pumps blood through the circulatory system depends on nutrients absorbed by the digestive tract and also on oxygen obtained from the air or water by the respiratory system. Any organism, whether single-celled or an assembly of organ systems, is a coordinated living whole greater than the sum of its parts. Concept 40.3 Animals use the chemical energy in food to sustain form and function All organisms require chemical energy for growth, physiological processes, maintenance and repair, regulation, and reproduction. o Plants use light energy to build energy-rich organic molecules from water and CO2, and then they use those organic molecules for fuel. o In contrast, animals are heterotrophs and must obtain their chemical energy in food, which contains organic molecules synthesized by other organisms. The flow of energy through an animalits bioenergeticsultimately limits the animals behavior, growth, and reproduction and determines how much food it needs. o Studying an animals bioenergetics tells us a great deal about the animals adaptations. Food is digested by enzymatic hydrolysis, and energy-containing food molecules are absorbed by body cells. Most fuel molecules are used to generate ATP by the catabolic processes of cellular respiration and fermentation. o The chemical energy of ATP powers cellular work, enabling cells, organs, and organ systems to perform the many functions that keep an animal alive. o Since the production and use of ATP generates heat, an animal continuously loses heat to its surroundings. After energetic needs of staying alive are met, any remaining food molecules can be used in biosynthesis. o This includes body growth and repair; synthesis of storage material such as fat; and production of reproductive structures, including gametes. Biosynthesis requires both carbon skeletons for new structures and ATP to power their assembly. Metabolic rate provides clues to an animals bioenergetic strategy. The amount of energy an animal uses in a unit of time is called its metabolic ratethe sum of all the energy-requiring biochemical reactions occurring over a given time interval.

o o o

Energy is measured in calories (cal) or kilocalories (kcal). o A kilocalorie is 1,000 calories. o The term Calorie, with a capital C, as used by many nutritionists, is actually a kilocalorie. Metabolic rate can be determined several ways. Because nearly all the chemical energy used in cellular respiration eventually appears as heat, metabolic rate can be measured by monitoring an animals heat loss. o A small animal can be placed in a calorimeter, which is a closed, insulated chamber equipped with a device that records the animals heat loss. A more indirect way to measure metabolic rate is to determine the amount of oxygen consumed or carbon dioxide produced by an animals cellular respiration. o These devices may measure changes in oxygen consumed or carbon dioxide produced as activity changes. Over long periods, the rate of food consumption and the energy content of food can be used to estimate metabolic rate. o A gram of protein or carbohydrate contains about 4.55 kcal, and a gram of fat contains 9 kcal. o This method must account for the energy in food that cannot be used by the animal (the energy lost in feces and urine). There are two basic bioenergetic strategies used by animals. o Birds and mammals are mainly endothermic, maintaining their body temperature within a narrow range by heat generated by metabolism. Endothermy is a high-energy strategy that permits intense, long-duration activity of a wide range of environmental temperatures. Most fishes, amphibians, reptiles, and invertebrates are ectothermic, meaning they gain their heat mostly from external sources. o The ectothermic strategy requires much less energy than is needed by endotherms, because of the energy cost of heating (or cooling) an endothermic body. o However, ectotherms are generally incapable of intense activity over long periods. In general, endotherms have higher metabolic rates than ectotherms. Body size influences metabolic rate. The metabolic rates of animals are affected by many factors besides whether the animal is an endotherm or an ectotherm. One of animal biologys most intriguing, but largely unanswered, questions has to do with the relationship between body size and metabolic rate. Physiologists have shown that the amount of energy it takes to maintain each gram of body weight is inversely related to body size. o For example, each gram of a mouse consumes about 20 times more calories than a gram of an elephant. The higher metabolic rate of a smaller animal demands a proportionately greater delivery rate of oxygen. o A smaller animal also has a higher breathing rate, blood volume (relative to size), and heart rate (pulse) and must eat much more food per unit of body mass. One hypothesis for the inverse relationship between metabolic rate and size is that the smaller the size of an endotherm, the greater the energy cost of maintaining a stable body temperature. o The smaller the animal, the greater its surface-to-volume ratio, and thus the greater loss of heat to (or gain from) the surroundings. However, this hypothesis fails to explain the inverse relationship between metabolism and size in ectotherms, which do not use metabolic heat to maintain body temperature. o Researchers continue to search for causes underlying this inverse relationship. Animals adjust their metabolic rates as conditions change. Every animal has a range of metabolic rates. o Minimal rates power the basic functions that support life, such as cell maintenance, breathing, and heartbeat. The metabolic rate of a nongrowing endotherm at rest, with an empty stomach and experiencing no stress, is called the basal metabolic rate (BMR). o The BMR for humans averages about 1,600 to 1,800 kcal per day for adult males and about 1,300 to 1,500 kcal per day for adult females. In ectotherms, body temperature changes with temperature of the surroundings, and so does metabolic rate. o Therefore, the minimal metabolic rate of an ectotherm must be determined at a specific temperature. o The metabolic rate of a resting, fasting, nonstressed ectotherm is called its standard metabolic rate (SMR). For both ectotherms and endotherms, activity has a large effect on metabolic rate. o Any behavior consumes energy beyond the BMR or SMR. o Maximal metabolic rates (the highest rates of ATP utilization) occur during peak activity, such as lifting heavy weights, all-out running, or high-speed swimming. In general, an animals maximum metabolic rate is inversely related to the duration of activity. o Both an alligator (ectotherm) and a human (endotherm) are capable of intense exercise in short spurts of a minute or less.

These sprints are powered by the ATP present in muscle cells and ATP generated anaerobically by glycolysis. o Neither organism can maintain its maximum metabolic rate and peak activity level over longer periods of exercise, although the endotherm has an advantage in endurance tests. The BMR of a human is much higher than the SMR of an alligator. Both can reach high levels of maximum potential metabolic rates for short periods, but metabolic rate drops as the duration of the activity increases and the source of energy shifts toward aerobic respiration. Sustained activity depends on the aerobic process of cellular respiration for ATP supply. o An endotherms respiration rate is about 10 times greater than an ectotherms. o Only endotherms are capable of long-duration activities such as distance running. Between the extremes of BMR or SMR and maximal metabolic rate, many factors influence energy requirements. o These include age, sex, size, body and environmental temperatures, quality and quantity of food, activity level, oxygen availability, hormonal balance, and time of day. Diurnal organisms, such as birds, humans, and many insects, are usually active and have their highest metabolic rates during daylight hours. Nocturnal organisms, such as bats, mice, and many other mammals, are usually active at night or near dawn and dusk and have their highest metabolic rates then. Metabolic rates measured when animals are performing a variety of activities give a better idea of the energy costs of everyday life. o For most terrestrial animals, the average daily rate of energy consumption is 24 times BMR or SMR. Humans in most developed countries have an unusually low average daily metabolic rate of about 1.5 times BMRan indication of relatively sedentary lifestyles. Energy budgets reveal how animals use energy and materials. Different species of animals use the energy and materials in food in different ways, depending on their environment, behavior, size, and basic energy strategy of endothermy or ectothermy. o For most animals, the majority of food is devoted to the production of ATP, and relatively little goes to growth or reproduction. o However, the amount of energy used for BMR (or SMR), activity, and temperature control varies considerably between species. For example, the typical annual energy budgets of four vertebrates reinforces two important concepts in bioenergetics. o First, a small animal has a much greater energy demand per kg than does a large animal of the same class. o Second, an ectotherm requires much less energy per kg than does an endotherm of equivalent size. o Further, size and energy strategy has a great influence on how the total annual energy expenditure is distributed among energetic needs. A human female spends a large fraction of her energy budget for BMR and relatively little for activity and body temperature regulation. o The cost of nine months of pregnancy and several months of breast feeding amounts to only 58% of the mothers annual energy requirements. o Growth amounts to about 1% of her annual energy budget. A male penguin spends a much larger fraction of his energy expenditures for activity because he must swim to catch his food. o Because the penguin is well insulated and fairly large, he has relatively low costs of temperature regulation despite living in the cold Antarctic environment. o His reproductive costs, about 6% of annual energy expenditures, mainly come from incubating eggs and bringing food to his chicks. o Penguins, like most birds, do not grow once they are adults. A female deer mouse spends a large fraction of her energy budget on temperature regulation. o Because of the high surface-to-volume ratio that goes with small size, mice lose body heat rapidly to the environment and must constantly generate metabolic heat to maintain body temperature. o Female deer mice spend about 12% of their energy budget on reproduction. In contrast to endotherms, the ectothermic python has no temperature regulation costs. o Like most reptiles, she grows continuously throughout life. o In one year, she can add 750 g of new body tissue and produce about 650 g of eggs. o Through the pythons economical ectothermic strategy, she expends only 1/40 of the energy expended by the samesized endothermic penguin. Concept 40.4 Many animals regulate their internal environment within relatively narrow limits More than a century ago, physiologist Claude Bernard made the distinction between external environments surrounding an animal and the internal environment in which the cells of the animal actually live. The internal environment of vertebrates is called the interstitial fluid. o This fluid exchanges nutrients and wastes with blood contained in microscopic vessels called capillaries. Bernard also recognized that many animals tend to maintain relatively constant conditions in their internal environment, even when the external environment changes.

While a pond-dwelling hydra is powerless to affect the temperature of the fluid that bathes its cells, the human body can maintain its internal pond at a more or less constant temperature of about 37C. o Similarly, our bodies control the pH of our blood and interstitial fluid to within a tenth of a pH unit of 7.4. o The amount of sugar in our blood does not fluctuate for long from a concentration of about 90 mg of glucose per 100 mL of blood. There are times during the course of the development of an animal when major changes in the internal environment are programmed to occur. o For example, the balance of hormones in human blood is altered radically during puberty and pregnancy. o Still, the stability of the internal environment is remarkable. Today, Bernards constant internal milieu is incorporated into the concept of homeostasis, which means steady state, or internal balance. o Actually the internal environment of an animal always fluctuates slightly. o Homeostasis is a dynamic state, an interplay between outside forces that tend to change the internal environment and internal control mechanisms that oppose such changes. Animals may be regulators or conformers for a particular environmental variable. Regulating and conforming are two extremes in how animals deal with environmental fluctuations. An animal is a regulator for a particular environmental variable if it uses internal control mechanisms to moderate internal change while external conditions fluctuate. o For example, a freshwater fish maintains a stable internal concentration of solutes in its blood that is higher than the water in which it lives. An animal is a conformer for a particular environmental variable if it allows its internal conditions to vary as external conditions fluctuate. o For example, many marine invertebrates live in environments where solute concentration (salinity) is relatively stable. o Unlike freshwater fishes, most marine invertebrates do not regulate their internal solute concentration, but rather conform to the external environment. No organism is a perfect regulator or conformer. An animal may maintain homeostasis while regulating some internal conditions and allowing others to conform to the environment. o For example, most freshwater fishes regulate their internal solute concentration but allow their internal temperature to conform to external water temperature. Homeostasis depends on feedback circuits. Any homeostatic control system has three functional components: a receptor, a control center, and an effector. o The receptor detects a change in some variable in the animals internal environment, such as a change in temperature. o The control center processes the information it receives from the receptor and directs an appropriate response by the effector. One type of control circuit, a negative-feedback system, can control the temperature in a room. o In this case, the control center, called a thermostat, also contains the receptor, a thermometer. o When room temperature falls, the thermostat switches on the heater, the effector. In such a negative-feedback system, a change in the variable being monitored triggers the control mechanism to counteract further change in the same direction. o Owing to a time lag between receptor and response, the variable drifts slightly above and below the set point, but fluctuations are moderate. o Negative-feedback mechanisms prevent small changes from becoming too large. Most homeostatic mechanisms in animals operate on this principle of negative feedback. o Human body temperature is kept close to a set point of 37C by the cooperation of several negative-feedback circuits. In contrast to negative feedback, positive feedback involves a change in some variable that triggers mechanisms that amplify rather than reverse the change. o For example, during childbirth, the pressure of the babys head against receptors near the opening of the uterus stimulates uterine contractions. o These cause greater pressure against the uterine opening, heightening the contractions, which cause still greater pressure. o Positive feedback brings childbirth to completion, a very different sort of process from maintaining a steady state. While some aspects of the internal environment are maintained at a set point, regulated change is essential to normal body functions. o In some cases, the changes are cyclical, such as the changes in hormone levels responsible for the menstrual cycle in women. o In other cases, a regulated change is a reaction to a challenge to the body.

For example, the human body reacts to certain infections by raising the set point for temperature to a slightly higher level, and the resulting fever helps fight infection. Over the short term, homeostatic mechanisms can keep a process, such as body temperature, close to a set point, whatever it is at that particular time. Over the longer term, homeostasis allows regulated change in the bodys internal environment. Internal regulation is expensive. o Animals use a considerable portion of their energy from the food they eat to maintain favorable internal conditions. Concept 40.5 Thermoregulation contributes to homeostasis and involves anatomy, physiology, and behavior Thermoregulation is the process by which animals maintain an internal temperature within a tolerable range. This ability is critical to survival, because most biochemical and physiological processes are very sensitive to changes in body temperature. The rates of most enzyme-mediated reactions increase by a factor of 2 or 3 for every 10C temperature increase until temperature is high enough to begin to denature proteins. o The properties of membranes also change with temperature. Although different species of animals are adapted to different environmental temperatures, each species has an optimal temperature range. o Thermoregulation helps keep body temperature within the optimal range, enabling cells to function effectively as external temperature fluctuates. Ectotherms and endotherms manage their heat budgets very differently. One way to classify the thermal characteristics of animals is to emphasize the role of metabolic heat in determining body temperature. Ectotherms gain most of their heat from the environment. o An ectotherm has such a low metabolic rate that the amount of heat it generates is too small to have much effect on body temperature. Endotherms can use metabolic heat to regulate their body temperature. o In a cold environment, an endotherms high metabolic rate generates enough heat to keep its body substantially higher than its surroundings. Many ectotherms can thermoregulate by behavioral means, such as basking in the sun or seeking out shade. o In general, ectotherms tolerate greater variation in internal temperature than do endotherms. Animals are not classified as ectotherms or endotherms based on whether they have variable or constant body temperatures. o It is the source of heat used to maintain body temperature that distinguishes ectotherms from endotherms. A differentand largely outdatedset of terms can be used to imply variable or constant body temperature. o A poikilotherm is an animal whose internal temperature varies widely. o A homeotherm is an animal that maintains relatively stable internal temperatures. Another common misconception is the idea that ectotherms are cold-blooded and endotherms are warm-blooded. o Ectotherms do not necessarily have low body temperatures. o While sitting in the sun, many ectothermic lizards have higher body temperatures than mammals. o Biologists avoid the terms cold-blooded and warm-blooded because they are so misleading. Endothermy and ectothermy are not mutually exclusive thermoregulatory strategies. o A bird is an endotherm but may warm itself in the sun on a cold morning, just as a lizard does. Endothermy has several important advantages. o Being able to generate a large amount of metabolic heat enables endotherms to perform vigorous activity for much longer than is possible for most ectotherms. o Sustained intense exercise, such as long-distance running or powered flight, is usually only possible for endotherms. Terrestrial animals can maintain stable body temperatures despite temperature fluctuations, which are more severe on land than in water. o For example, no ectotherm can be active in below-freezing weather, but many endotherms function well in such conditions. Endothermic vertebrates also have mechanisms for cooling their bodies in hot environments, allowing them to withstand heat loads that would be intolerable for most ectotherms. However, ectotherms can tolerate larger fluctuations in their internal temperatures. Being endothermic is energetically expensive. o For example, at 20C, a human at rest has a BMR or 1,300 to 1,800 kcal per day. o An American alligator of similar weight has an SMR of only 60 kcal per day. As a result, ectotherms need to consume far more food than ectotherms of equivalent size. o This is a serious disadvantage if food supplies are limited. Ectothermy is an extremely effective and successful strategy in most of Earths environments, as is shown by the abundance and diversity of ectothermic animals. Animals regulate the exchange of heat with their environment. Animals exchange heat with their external environment by four physical processes: conduction, convection, radiation, and evaporation.

o Heat is always transferred from a hotter object to a cooler object. Endotherms and thermoregulating ectotherms must manage their heat budgets so that rates of heat gain are equal to rates of heat loss. Five general categories of adaptations help animals thermoregulate. A major thermoregulatory adaptation in mammals and birds is insulation: hair, feathers, or fat layers. o Insulation reduces the flow of heat between an animal and its environment and lowers the energy cost of keeping warm. In mammals, the insulating material is associated with the integumentary system, the outer covering of the body. Skin is a key organ of the integumentary system. o Skin functions as a thermoregulatory organ by housing nerves, sweat glands, blood vessels, and hair follicles. o It also protects internal body parts from mechanical injury, infection, and desiccation. Skin consists of two layers, the epidermis and the dermis, underlain by a tissue layer called the hypodermis. o The epidermis is the outer layer of skin, composed largely of dead epithelial cells. o The dermis supports the epidermis and contains hair follicles, oil and sweat glands, muscles, nerves, and blood vessels. o Adipose tissue provides varying degrees of insulation, depending on the species. The insulating power of a layer of fur or feathers depends mostly on how much air the layer traps. o Hair loses most of its insulating power when wet. o Land mammals and birds react to cold by raising their fur or feathers to trap a thicker layer of air. o Human goose bumps are a vestige of our hair-raising ancestors. Marine mammals have a very thick layer of insulating blubber just under their skin. o The skin temperature of a marine mammal is close to water temperature. o However, blubber insulation is so effective that marine mammals can maintain body core temperatures of 3638C. Many endotherms and ectotherms can alter the amount of blood flow between the body core and the skin. Elevated blood flow in the skin results from vasodilation, an increase in the diameter of superficial blood vessels near the body surface. o Vasodilation is triggered by nerve signals that relax the muscles of the vessel walls. o In endotherms, vasodilation usually warms the skin, increasing the transfer of body heat to a cool environment. The reverse process, vasoconstriction, reduces blood flow and heat transfer by decreasing the diameter of superficial vessels. Another circulatory adaptation is an arrangement of blood vessels called a countercurrent heat exchanger, which reduces heat loss. o In some species, blood can either go through the heat exchanger or bypass it. o The relative amount of blood that flows through the two paths varies, adjusting the rate of heat loss. Unlike most fishes, which are thermoconformers, some specialized endothermic bony fishes and sharks have circulatory adaptations to retain metabolic heat. o Endothermic fishes include bluefin tuna, swordfish, and great white sharks. o Large arteries convey most of the cold blood from the gills to tissues just under the skin. o Branches deliver blood to the deep muscles, where small vessels are arranged into a countercurrent heat exchanger. o Endothermy enables vigorous, sustained activity that is characteristic of these animals. Some reptiles also have physiological adaptations to regulate heat loss. o In the marine iguanas of the Galpagos Islands, body heat is conserved by vasoconstriction of superficial blood vessels. Many endothermic insects (bumblebees, honeybees, some moths) have a countercurrent heat exchanger that helps maintain a high temperature in the thorax, where the flight muscles are located. o In some insects, the countercurrent mechanism can be shut down to allow heat to be shed during hot weather. o A bumblebee queen uses this mechanism to incubate her eggs. She generates heat by shivering her flight muscles and then transfers the heat to her abdomen, which she presses against her eggs. Many mammals and birds live in places where thermoregulation requires cooling as well as warming. o If environmental temperature is above body temperature, evaporation is the only way to keep body temperature from rising. o Terrestrial animals lose water by evaporation across the skin and when they breathe. o Water absorbs considerable heat when it evaporates; it is 50 to 100 times more effective than air in transferring heat. Some animals have adaptations to augment evaporative cooling. o Panting is important in birds and many mammals. o Some birds have a pouch richly supplied with blood vessels in the floor of the mouth. Birds flutter the pouch to increase evaporation. o Sweating or bathing moistens the skin and enhances evaporative cooling. Many terrestrial mammals have sweat glands controlled by the nervous system. o Other mechanisms to promote evaporative cooling include spreading saliva on skin or regulating the amount of mucus secretion.

Many endotherms and ectotherms use behavioral responses to control body temperature. o Many ectotherms can maintain a constant body temperature by simple behaviors. o Some animals hibernate or migrate to a more suitable climate. Amphibians regulate body temperature mainly by behavior, by moving to a location where solar heat is available or by seeking shade. Reptiles also thermoregulate behaviorally. o When cool, they seek warm places, orient themselves toward a heat source, and expand the body surface exposed to the heat source. o When hot, they move to cool places or turn away from the heat source. o Many terrestrial invertebrates use similar behavioral mechanisms. Honeybees use a thermoregulatory mechanism that depends on social behavior. o In cold weather, they increase heat production and huddle together to retain heat. o They maintain a relatively constant temperature by changing the density of the huddling, and moving individuals between the cooler outer edges of the cluster and the warmer center. Honeybees expend considerable energy to keep warm during long periods of cold weather. This is the main function of the honey stored in the hive. o Honeybees also cool the hive in hot weather by transporting water to it and fanning it with their wings to promote evaporation and convection. Endotherms vary heat production to counteract constant heat loss. o For example, heat production is increased by such muscle activity as moving or shivering. Certain mammalian hormones can cause mitochondria to increase their metabolic activity and produce heat instead of ATP. o This nonshivering thermogenesis (NST) takes place throughout the body. o Some mammals have brown fat that is specialized for rapid heat production. Through shivering and NST, mammals and birds may increase their metabolic heat production to 5 or 10 times the minimal levels characteristic of warm weather. A few large reptiles can become endothermic in particular circumstances. o For example, female pythons that are incubating eggs increase their metabolic rate by shivering, generating enough heat to elevate egg temperatures by 57C during incubation. The smallest endotherms are flying insects such as bees and moths. o These insects elevate body temperature by shivering before taking off. o They contract their flight muscles in synchrony to produce only slight wing movements but considerable heat. The regulation of body temperature in humans is a complex system facilitated by feedback mechanisms. Nerve cells that control thermoregulation are concentrated in a brain region called the hypothalamus. o The hypothalamus contains a group of nerve cells that functions as a thermostat. o Nerve cells that sense temperature are in the skin, in the hypothalamus itself, and in other body regions. If the thermostat in the brain detects a decrease in the temperature of the blood below the set point, it inhibits heat loss mechanisms and activates heat-saving ones such as vasoconstriction of superficial vessels and erection of fur, while stimulating heat-generating mechanisms such as shivering. If the thermostat in the brain detects a rise in the temperature of the blood above the set point, it shuts down heat retention mechanisms and promotes body cooling by vasodilation, sweating, or panting. Animals can acclimatize to a new range of environmental temperatures. Many animals can adjust to a new range of environmental temperatures by a physiological response called acclimatization. o Ectotherms and endotherms acclimatize differently. o In birds and mammals, acclimatization includes adjusting the amount of insulation and varying the capacity for metabolic heat production. o Acclimatization in ectotherms involves compensating for temperature changes. o Acclimatization responses in ectotherms often include adjustments at the cellular level. Cells may increase the production of certain enzymes or produce enzyme variants with different temperature optima. Membranes also change the proportions of saturated and unsaturated lipids to keep membranes fluid at different temperatures. Some ectotherms produce antifreeze compounds, or cryoprotectants, to prevent ice formation in body cells. o These compounds allow overwintering ectotherms such as frogs and arthropods to withstand body temperatures well below zero. o Arctic and antarctic fishes also have cryoprotectants to protect body tissues. Cells can make rapid adjustments to temperature changes. o For example, mammalian cells grown in culture respond to increased temperature by producing and accumulating stress-induced proteins, including heat-shock proteins. o These molecules, found in bacteria, yeast, plants, and animals, help to maintain the integrity of other proteins that would otherwise be denatured by severe heat.

Stress-induced proteins help prevent cell death when an organism is challenged by severe changes in cellular environment. Animals may conserve energy through torpor. Some animals deal with severe conditions by an adaptation called torpor. o Torpor is a physiological state in which activity is low and metabolism decreases. Hibernation is long-term torpor that is an adaptation to winter cold and food scarcity. When vertebrate endotherms enter torpor or hibernation, their body temperatures decline. o Some hibernating mammals cool to 12C, and a few drop slightly below 0C in a supercooled, unfrozen state. Metabolic rates during hibernation may be several hundred times lower than if animals tried to maintain normal body temperatures. o Hibernators can survive for very long periods on limited supplies of energy stored in body tissues or as food cached in a burrow. Estivation, or summer torpor, is also characterized by slow metabolism or inactivity. o Estivation allows animals to survive long periods of high temperatures and scarce water supplies. Hibernation and estivation are often triggered by seasonal changes in the length of daylight. o Some hibernators prepare for winter by storing food in their burrows or by eating huge quantities of food. o Ground squirrels double their weight prior to hibernation. Many small mammals and birds exhibit a daily torpor that is adapted to their feeding patterns. o For example, most bats and shrews feed at night and go into torpor during daylight hours. o Chickadees and hummingbirds feed during the day and go into torpor on cold nights. The body temperature of a hummingbird may drop by 2530C at night. An animals daily cycle of activity and torpor appears to be a built-in rhythm controlled by its biological clock. o Even if food is made available to a shrew, it will go through daily torpor.

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