Regulating the Internal Environment

REGULATING THE INTERNAL ENVIRONMENT Introduction One of the most remarkable characteristics of animals is homeostasis, the ability to maintain physiologically favorable internal environments even as external conditions undergo dramatic shifts that would be lethal to individual cells. For example, humans will survive exposure to substantial changes in outside temperature but will die if their internal temperatures drift more than a few degrees above or below 37oC. Another mammal, the arctic wolf, can regulate body temperature even in winter when temperatures drop as low as -50oC. Three ways in which an organism maintains a physiological favorable environment include: Thermoregulation, maintaining body temperature within a tolerable range Osmoregulation, regulating solute balance and the gain and loss of water Excretion, the removal of nitrogen-containing waste products of metabolism such as urea. A. An Overview of Homeostasis 1. Regulating and conforming are the two extremes of how animals cope with environmental fluctuations An animal is said to be a regulator for a particular environmental variable if it uses mechanisms of homeostasis to moderate internal change in the face of external fluctuations. For example, endothermic animals such as mammals and birds are thermoregulators, keeping their body temperatures within narrow limits in spite of changes in environmental temperature. In contrast to regulators, many other animals, especially those that live in relatively stable environments, are conformers in their relationship to certain environmental changes. Such conformers allow some conditions within their bodies to vary with external changes. Many invertebrates, such as spider crabs of the genus Libinia, live in environments where salinity is relatively stable. These organisms do not osmoregulate, and if placed in water of varying salinity, they will lose or gain water to conform to the external environment even when this internal adjustment is extreme enough to cause death. Conforming and regulating represent extremes on a continuum. No organisms are perfect regulators or conformers. For example, salmon, which live part of their lives in fresh water and part in salt water, use osmoregulation to maintain a constant concentration of solutes in their blood and interstitial fluids, while conforming to external temperatures. Even for a particular environmental variable, a species may conform in one situation and regulate in another. Regulation requires the expenditure of energy, and in some environments that cost of regulation may outweigh the benefits of homeostasis. For example, temperature regulation may require a forest-dwelling lizard to travel long distances (and risk capture by a predator) to find an exposed sunny perch. However, this same lizard may use behavioral adaptations to bask in open habitats. 2. Homeostasis balances an animal’s gains versus losses for energy and materials Like all organisms, animals are open systems that must exchange energy and materials with their environment. These inward and outward flows of energy and materials are frequently rapid and often variable, but as they occur animals also need to maintain reasonably constant internal conditions. Normally, an animal’s input of energy and materials only exceeds its output where there is a net increase in organic matter due to growth or reproduction. Consider some exchanges during ten years in the life of a typical woman weighing 60 kg. Over the decade, she will eat about 2 tons of food, drink 6 to 10 tons of water, use almost two tons of oxygen, and metabolically generate more than 7 million kilocalories of heat. This same quantity of material and heat must be lost from the woman’s body to maintain its size, temperature, and chemical composition. If the woman produces two children (and breast-feeds each for two years) during this ten year span, she will need to increase the total flow of energy and materials by only 4-5% compared to her basic maintenance needs. Reproduction is a larger part of the energy and material flow in many other species. For example, a female mouse rearing two litters per year invests 10-15% of its annual energy budget on reproduction. Regardless of reproductive costs, every animal’s survival depends on accurate control of materials and energy exchange. Because homeostasis requires such a careful balance of materials and energy, it can be viewed as a set of budgets of gains and losses. These may include a heat budget, an energy budget, a water budget, and so on. Most energy and materials budgets are interconnected, with changes in the flux of one component affecting the exchanges of other components. For example, when terrestrial animals exchange gases with air by breathing, they also lose water by evaporation from the moist lung surfaces. This loss must be compensated by intake (in food or drink) of an equal amount of water. B. Regulation of Body Temperature Most biochemical and physiological processes are very sensitive to changes in body temperature. The rates for most enzyme-mediated reactions increase by a factor of 2-3 for every 10oC temperature increase, until temperature is high enough to denature proteins. This is known as the Q10 effect, a measure of the multiple by which a particular enzymatic reaction or overall metabolic process increases with a 10oC increase in body temperature. For example, if the rate of glycogen hydrolysis in a frog is 2.5 times greater at 30oC than at 20oC, then the Q10 for that reaction is 2.5. Because enzymatic reactions and the properties of membranes are strongly influenced by temperature, thermal effects influence animal function and performance. For example, because the power and speed of a muscle contraction is strongly temperature dependent, a body temperature change of only a few degrees may have a very large impact on an animal’s ability to run, jump, or fly. Although, different species of animals are adapted to different environmental temperatures, each animal has an optimal temperature range. Within that range, many animals maintain nearly constant internal temperatures as the external temperature fluctuates. This thermoregulation helps keep body temperature within a range that enables cells to function most effectively. An animal that thermoregulates balances its heat budget over time in such a way that the rate of heat gain exactly matches the rate of heat loss. 1. Four physical processes account for heat gain or loss An organism, like any object, exchanges heat by four physical processes called conduction, convection, radiation, and evaporation. Conduction is the direct transfer of thermal motion (heat) between molecules in direct contact with each other. For example, a lizard can elevate a low body temperature with heat conducted from a warm rock. Heat is always conducted from an object of higher temperature to one of lower temperature. However, the rate and amount of heat transfer varies with different materials. Water is 50 to 100 times more effective than air in conducting heat. Convection is the transfer of heat by the movement of air or liquid past a surface. Convection occurs when a breeze contributes to heat loss from the surface of animal with dry skin. It also occurs when circulating blood moves heat from an animal’s warm body core to the cooler extremities such as legs. The familiar “wind-chill factor” is an example of how convection compounds the harshness of low temperatures by increasing the rate of heat transfer. Radiation is the emission of electromagnetic waves by all objects warmer than absolute zero, including an animal’s body, the environment, and the sun. Radiation can transfer heat between objects that are not in direct contact, as when an animal absorbs heat radiating from the sun. Evaporation is the removal of heat from the surface of a liquid that is losing some of its molecules as gas. Evaporation of water from an animal has a strong cooling effect. However, this can only occur if the surrounding air is not saturated with water molecules (that is, if the relative humidity is less than 100%). “It’s not the heat, it’s the humidity.” 2. Ectotherms have body temperatures close to environmental temperature; endotherms can use metabolic heat to keep body temperature warmer than their surroundings Although all animals exchange heat by some combination of the four mechanisms discussed in the previous section, there are important differences in how various species manage their heat budgets. An ectotherm has such a low metabolic rate that the amount of heat that it generates is too small to have much effect on body temperature. Consequently, ectotherm body temperatures are almost entirely determined by the temperature of the surrounding environment. Most invertebrates, fishes, amphibians, and reptiles are ectotherms. In contrast, an endotherm’s high metabolic rate generates enough heat to keep its body temperature substantially warmer than the environment. Mammals, birds, some fishes, a few reptiles, and numerous insect species are endotherms. Many endotherms, including humans, maintain a high and very stable internal temperature even as the temperature of their surroundings fluctuates. However, it is not constant body temperatures that distinguish endotherms from ectotherms. For example, many ectothermic marine fishes and invertebrates inhabit water with such stable temperatures that their body temperatures vary less than that of humans and other endotherms. Also, many endotherms maintain high body temperatures only part of the time. In addition, not all ectotherms have low body temperatures. While sitting in the sun, many ectothermic lizards have higher body temperatures than mammals. Endothermy has several important advantages. High and stable body temperatures, along with other biochemical and physiological adaptations, give these animals very high levels of aerobic metabolism. This allows endotherms to perform vigorous activity for much longer than is possible for ectotherms. Sustained intense activity, such as long distance running or powered flight, is usually only feasible for animals with an endothermic way of life. Endothermy also solves certain thermal problems of living of land, enabling terrestrial animals to maintain stable body temperatures in the face of environmental temperature fluctuations that are generally more severe than in aquatic habitats. For example, no ectotherm can be active in the below-freezing weather that prevails during winter over much of the Earth’s surface, but many endotherms function very well under these conditions. Endotherms also have mechanisms for cooling the body in a hot environment. Being an endotherm is liberating, but it is also energetically expensive, especially in a cold environment. For example, at 200C, a human at rest has a metabolic rate of 1,300 to 1,800 kcal per day. In contrast, a resting ectotherm of similar weight, such as an American alligator, has a metabolic rate of only about 60 kcal per day at 200C. Thus, endotherms generally need to consume much more food than ectotherms of similar size - a serious disadvantage for endotherms if food is limited. Ectothermy is an extremely effective and successful “strategy” in many terrestrial environments. 3. Thermoregulation involves physiological and behavioral adjustments that balance heat gain and loss For endotherms and for those ectotherms that thermoregulate, the essence of thermoregulation is management of the heat budget so that rates of heat gain are equal to rates of heat loss. If the heat budget gets out of balance, the animal will either become warmer or colder. There are four general categories of adaptations for thermoregulation. • (1) Adjusting the rate of heat exchange between the animal and its surroundings. Insulation, such as hair, feathers, and fat, reduces the flow of heat between an animal and its environment. Other mechanisms usually involve adaptations of the circulatory system. Vasodilation, expansion of the diameter of superficial blood vessels, elevates blood flow in the skin and typically increases heat transfer to a cool environment. Vasoconstriction reduces blood flow and heat transfer by decreasing the diameter of superficial vessels. Another circulatory adaptation is a special arrangement of blood vessels called a countercurrent heat exchanger that helps trap heat in the body core and reduces heat loss. For example, marine mammals and many birds living in cold environments face the problem of losing large amounts of heat from their extremities as warm arterial blood flows to the skin. However, arteries carrying warm blood are in close contact with veins conveying cool blood back toward the trunk. This countercurrent arrangement facilitates heat transfer from arteries to veins along the entire length of the blood vessels. By the end of the extremity, the arterial blood has cooled far below the core temperature, and the venous blood has warmed close to core temperature as it nears the core. In essence, heat in the arterial blood emerging from the core is transferred directly to the returning venous blood, instead of being lost to the environment. In some species, blood can either go through the heat exchanger or bypass it in other blood vessels. The relative amount of blood that flows through the two different paths varies, adjusting the rate of heat loss as an animal’s physiological state or environment changes. Circulatory adaptations that reduce heat loss enable some endotherms to survive the most extreme winter conditions. For example, arctic wolves remain active even when environmental temperatures drop as low as -500C. Thick fur coats keep their bodies warm. By adjusting blood flow through countercurrent exchangers and other vessels in the legs, wolves can keep their foot temperatures just above 00C - cool enough to reduce heat loss but warm enough to prevent frostbite. At the same time, wolves can lose large quantities of heat through their feet after long-distance running. • (2) Cooling by evaporative heat loss. Terrestrial animals lose water by evaporation across the skin and when they breathe. Water absorbs considerable heat when it evaporates. Some organisms can augment this cooling effect. For example, most mammals and birds can increase evaporation from the lungs by panting. Sweating or bathing to make the skin wet also enhances evaporative cooling. • (3) Behavioral responses. Both endotherms and ectotherms use behavioral responses, such as changes in posture or moving about in their environment, to control body temperature. Many terrestrial animals will bask in the sun or on warm rocks when cold and find cool, shaded, or damp areas when hot. Many ectotherms can maintain a very constant body temperature by these simple behaviors. More extreme behavioral adaptations in some animals include hibernation or migration to a more suitable climate. • (4) Changing the rate of metabolic heat production. Many species of birds and mammals can greatly increase their metabolic heat production when exposed to cold. 4. Most animals are ectothermic, but endothermy is widespread Mammals and birds generally maintain body temperatures within a narrow range that is usually considerably warmer than the environment. Body temperature is 36-38oC for most mammals and 39-42oC for most birds. Because heat always flows from a warm object to cooler surroundings, birds and mammals must counteract the constant heat loss. This maintenance of warm body temperatures depends on several key adaptations. The most basic mechanism is the high metabolic rate of endothermy itself. Endotherms can produce large amounts of metabolic heat that replaces the flow of heat to the environment. They can vary heat production to match changing rates of heat loss. Heat production is increased by muscle activity during moving or shivering. In some mammals, nonshivering thermogenesis (NST) is induced by certain hormones to increase their metabolic activity and produce heat instead of ATP. Some mammals also have a tissue called brown fat in the neck and between the shoulders that is specialized for rapid heat production. In cold environments, mammals and birds can increase their metabolic heat production by as much as 5 to 10 times minimal levels under warm conditions. Another major thermoregulatory adaptation that evolved in mammals and birds is insulation (hair, feathers, and fat layers). This reduces the flow of heat and lowers the energy cost of keeping warm. The insulating power of a layer of fur or feathers mainly depends on how much still air the layer traps. Humans rely more on a layer of fat just beneath the skin as insulation. Vasodilation and vasocontriction also regulate heat exchange and may contribute to regional temperature differences within the animal. For example, heat loss from a human is reduced when arms and legs cool to several degrees below the temperature of the body core, where most vital organs are located. Marine mammals such as whales and seals have a very thick layer of insulating fat called blubber, just under the skin. Even though the loss of heat to water occurs 50 to 100 times more rapidly than heat loss in air, the blubber insulation is so effective that marine mammals maintain core body temperatures of about 36-38oC with metabolic rates about the same as those of land mammals. In areas such as the flippers or tail which lack insulation, countercurrent heat exchangers greatly reduce heat loss. Through metabolic heat production, insulation, and vascular adjustments, birds and mammals are capable of astonishing feats of thermoregulation. For example, a small chickadee, weighing only 20 grams, can remain active and hold body temperature nearly constant at 40oC in environmental temperatures as low as -40oC. Of course, this requires a large amount of food to supply the large amount of energy necessary for heat production. Many mammals and birds live in places where thermoregulation requires cooling as well as warming. For example, when a marine mammal moves into warm seas, as many whales do when they reproduce, excess metabolic heat is removed by vasodilation of numerous blood vessels in the outer layer of the skin. Many terrestrial mammals and birds may allow body temperatures to rise several degrees in hot climates or during vigorous exercise. Evaporative cooling often plays a key role in dissipating body heat. If environmental temperature is above body temperature, animals gain heat from the environment and by metabolic activity. Evaporation is the only way to keep body temperature from rising rapidly. Mechanisms to enhance evaporative cooling include panting, sweating, bathing, and using saliva as a water source. All amphibians and most reptiles are ectothermic, and their low metabolic rates have little influence on normal body temperature. The optimal temperature range for amphibians varies substantially with species. Most amphibians lose heat rapidly by evaporation from their moist body surfaces. However, behavioral adaptations help these animals maintain a satisfactory temperature most of time. When the surroundings are too warm, amphibians seek cooler microhabitats, such as shaded areas, and when the surroundings are too cool, they seek sites with solar heat. Like amphibians, reptiles control body temperature mainly by behavior. When cold, they seek warm places, orienting themselves toward heat sources and expanding the body surface exposed to a heat source. When hot, they move to cool areas or turn in another direct, reducing surface area exposed to the sun. Many reptiles keep their body temperatures very stable over the course of a day by shuttling between warm and cool spots. Some reptiles have physiological adaptations that regulate heat loss. For example, the marine iguana from the Galapagos Islands conserves body heat by vasoconstriction of superficial blood vessels when swimming in the cold ocean, reducing heat loss. When incubating eggs, female pythons increase their metabolic rate by shivering, generating enough heat to keep their body (and egg) temperatures warmer than the surrounding air for weeks at a time. Researchers continue to debate whether certain groups of dinosaurs were endothermic. Most fishes are thermoconformers as any metabolic heat generated by swimming muscles is lost to the surrounding water when blood passes through the gills. However, some specialized endothermic fishes, mainly large, powerful swimmers such as bluefin tuna, swordfish, and great white sharks, use countercurrent heat exchangers to trap heat in the muscles, digestive tract, eyes, or brain. While aquatic invertebrates are mainly thermoconformers, many terrestrial invertebrates can adjust internal temperature by the same behavioral mechanisms used by vertebrate ectotherms. On cold days, desert locusts orient in a direction that maximizes the absorption of sunlight. Many species of flying insects, such as bees and moths, are actually endothermic. The hawk moth uses a shivering-like mechanism to elevate body temperature as a pre-flight warmup. By contracting the flight muscles in synchrony, considerable heat is generated, but little movement. Chemical reactions, and hence cellular respiration, speed up in the warmed-up flight “motors.” These heat exchangers can keep the thorax of certain moths at about 300C during flight, even on a cold, snowy night. This can keep the thorax temperature of some insects at about 30oC even on a cold, snowy night. In contrast, insects flying in hot weather run the risk of overheating because of the heat generated by the flight muscles. In some species, the countercurrent mechanism can be shut down to allow heat to be lost from the thorax to the abdomen and then to the environment. Bumblebee queens can use this mechanism to transfer heat from flight muscles through the abdomen to eggs that they are incubating. Honeybees use an additional thermoregulatory mechanism that depends on social behavior. In cold weather they increase heat production and huddle together, thereby retaining heat. They can maintain a relatively constant temperature by changing the density of the huddle and the movement of individuals from the cooler areas to the warmer center. Even when huddling, honeybees must expend considerable energy to keep warm during long periods of cold weather, relying on the large quantities of honey (fuel) stored in the hive. In warm weather, fanning of their wings promotes evaporation and convection. The regulation of body temperature in humans and other mammals is a complex system facilitated by feedback mechanisms. Nerve cells that control thermoregulation, as well as those controlling other aspects of homeostasis, are concentrated in the hypothalamus of the brain. A group of neurons in the hypothalamus functions as a thermostat, responding to changes in body temperature above and below a set point by activating mechanisms that promote heat loss or gain. Temperature-sensing cells are located in the skin, the hypothalamus, and other body regions. Warm receptors signal the hypothalamic thermostat when temperatures increase and cold receptors indicate temperature decrease. When body temperature drops below normal, the thermostat inhibits heat-loss mechanisms and activates heat-saving ones such as vasoconstriction of superficial vessels and erection of fur, while stimulating heat-generating mechanisms. In response to elevated body temperature, the thermostat shuts down heat-retention mechanisms and promotes cooling by vasodilation, sweating, or panting. Many animals can adjust to a new range of environmental temperatures over a period of days or weeks, a response called acclimatization. In birds and mammals, acclimation often includes adjusting the amount of insulation—by growing a thicker fur coat in the winter and shedding it in the summer—and sometimes by varying the capacity for metabolic heat production seasonally. In contrast, acclimatization in ectotherms is a process of compensating for changes in body temperature through adjustments in physiology and temperature tolerance. For example, winter-acclimated catfish can only survive temperatures as high as 28oC, but summer-acclimated fish can survive temperatures to 36oC. Some ectotherms that experience subzero body temperatures protect themselves by producing “antifreeze” compounds (cryoprotectants) that prevent ice formation in the cells. In cold climates, cryoprotectants in the body fluids let overwintering ectotherms, such as some frogs and many arthropods and their eggs, withstand body temperatures considerably below zero. Cyroprotectants are also found in some Arctic and Antarctic fishes, where temperatures can drop below the freezing point of unprotected body fluids (about -0.7oC). Cells can often make rapid adjustments to temperature changes. For example, marked increases in temperature or other sources of stress induce cells grown in culture to produce stress-induced proteins, including heat-shock proteins, within minutes. These molecules help maintain the integrity of other proteins that would be denatured by severe heat. These proteins are also produced in bacteria, yeast, and plants cells, as well as in animals. These help prevent cell death when an organism is challenged by severe changes in the cellular environment. 5. Torpor reserves energy during environmental extremes Despite their many adaptations for homeostasis, animals may periodically encounter conditions that severely challenge their abilities to balance heat, energy, and materials budgets. For example, at certain seasons (or certain times of day) temperature may be extremely hot or cold, or food may be unavailable. One way that animals can save energy while avoiding difficult and dangerous conditions is to use torpor, a physiological state in which activity is low and metabolism decreases. Hibernation is long-term torpor that evolved as an adaptation to winter cold and food scarcity. During torpor or hibernation, body temperature declines, perhaps as low as 1-2oC or even lower. Because metabolic rates at these temperatures are so low, the energetic demands are tremendously reduced, allowing organisms to survive for long periods of time on energy, stored in body tissues or as food cached in a burrow. Ground squirrels, a favorite research animal for hibernation research, are active in the high mountains of California during spring and summer. They maintain a body temperature of about 37oC and have a metabolic rate of about 85 kcal per day. During the eight months the squirrel is in hibernation, its body temperature is only a few degrees above burrow temperature and its metabolic rate is very low. During hibernation, the ground squirrel rouses for a few hours every week or two, using metabolic heat to warm to about 37oC. By hibernation, the squirrels avoid severe cold and reduce the amount of energy they need to survive the winter, when their normal food of grasses and seeds is not available. Instead of having to spend 150 kcal per day to maintain body temperature in winter weather, a squirrel in its burrow spends an average of only 5-8 kcal per day (only about 1 kcal per day when hibernating) and live on stored fat for the entire hibernation season. Estivation, or summer torpor, also characterized by slow metabolism and inactivity, enables animals to survive long periods of high temperatures and scarce water supplies. Hibernation and estivation are often triggered by seasonal changes in day length. As the days shorten, some animals store food in their burrows, while other eat huge quantities of food and fatten dramatically. Many small mammals and birds exhibit a daily torpor that seems to be adapted to their feeding patterns. For example, nocturnal mammals, such as most bats and shrews, feed at night and go into torpor when they are inactive during the day. Chickadees and hummingbirds feed during the day and often undergo torpor on cold nights. All endotherms that use daily torpor are relatively small, with high metabolic rates, and high energy consumption when active. An animal’s daily cycle of activity and torpor appears to be a built-in rhythm controlled by the biological clock. Even if food is made available to a shrew all day, it still goes through its daily torpor. The need for sleep in humans and the slight drop in body temperature that accompanies it may be an evolutionary remnant of a more pronounced daily torpor in our early mammalian ancestors. C. Water Balance and Waste Disposal Animals must also regulate the chemical composition of its body fluids by balancing the uptake and loss of water and fluids. Management of the body’s water content and solute composition, osmoregulation, is largely based on controlling movements of solutes between internal fluids and the external environment. This also regulates water movement, which follows solutes by osmosis. Animals must also remove metabolic waste products before they accumulate to harmful levels. While the ultimate goal of osmoregulation is to maintain the composition of body’s cells, this is primarily accomplished indirectly by managing the composition of the internal body fluid that bathes the cells. In insects and other organisms with an open circulatory system, this fluid is the hemolymph. Vertebrates and other animals with closed circulatory systems regulate the interstitial fluid indirectly by controlling the composition of blood. Animals often have complex organs, such as kidneys of vertebrates, that are specialized for the maintenance of fluid composition. 1. Water balance and waste disposal depend on transport epithelia 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 particular directions. Some transport epithelia directly face the outside environment, while others line channels connected to the outside by an opening on the body surface. 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. For example, the salt secreting glands of some marine birds, such as an albatross, secrete an excretory fluid that is much more salty than the ocean. 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. For example, the salt-excreting glands of the albatross remove excess sodium chloride from the blood. By contrast, transport epithelia in the gills of freshwater fishes actively pump salts from the dilute water passing by the gill filaments. Transport epithelia in excretory organs often have the dual functions of maintaining water balance and disposing of metabolic wastes. 2. An animal’s nitrogenous wastes are correlated with 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. During their breakdown, enzymes remove nitrogen in the form of ammonia, a small and very toxic molecule. In general, the kinds of nitrogenous wastes excreted depend on an animal’s evolutionary history and habitat—especially water availability. 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. Animals that excrete nitrogenous wastes as ammonia need access to lots of water. This is because ammonia is very soluble but can only be tolerated at very low concentrations. Therefore, ammonia excretion is most common in aquatic species. Many invertebrates release ammonia across the whole body surface. 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 and even for many marine fishes and turtles. Because ammonia is so toxic, it can only be transported and excreted in large volumes of very dilute solutions. 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, and many marine fishes and turtles excrete mainly urea. 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. Urea can be transported and stored safely at high concentrations. 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. 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. Like urea, uric acid is relatively nontoxic. But unlike either ammonia or urea, uric acid is largely insoluble in water and can be excreted as a semisolid paste with very small water loss. 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 between these alternatives. Soluble wastes can diffuse out of a shell-less amphibian egg (ammonia) or be carried away by the mother’s blood in a mammalian embryo (urea). 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). In these animals, 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. For example, terrestrial turtles (which often live in dry areas) excrete mainly uric acid, while aquatic turtles excrete both urea and ammonia. 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. Over generations, evolution determines the limits of physiological responses for a species. During their lives individual organisms make adjustments within these evolutionary constraints. 3. Cells require a balance between osmotic gain and loss of water All animals face the same central problem of osmoregulation. Over time, the rates of water uptake and loss must balance. Animal cells—which lack cell walls—swell 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. Osmosis occurs whenever two solutions separated by a membrane differ in osmotic pressure, or osmolarity (moles of solute per liter of solution). 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. There is no net movement of water by osmosis between isoosmotic solutions, although water molecules do cross at equal rates in both directions. 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. Water flows by osmosis from a hypoosmotic solution to a hyperosmotic one. 4. 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. One—available only to marine animals—is 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. 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. Osmoregulation enables animals to live in environments that are uninhabitable to osmoconformers, such as freshwater and terrestrial habitats. 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. Because diffusion tends to equalize concentrations in a system, osmoregulators must expend energy to maintain the osmotic gradients via active transport. The energy costs depend mainly on how different an animal’s osmolarity is from its surroundings, how easily water and solutes can move across the animal’s surface, and how much membrane-transport work is required to pump solutes. 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. In contrast, euryhaline animals—which include both some osmoregulators and osmoconformers—can survive large fluctuations in external osmolarity. 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, as are the hagfishes. Their osmolarity is the same as seawater. However, they differ considerably from seawater in their concentrations of most specific solutes. Thus, even an animal that conforms to the osmolarity of its surroundings does regulate its internal composition. Except for hagfishes, marine vertebrates are osmoregulators. Marine fishes (class Osteichthys) constantly lose water through their skin and gills. To balance this, these fishes obtain water in food and by drinking large amounts of seawater and they excrete ions by active transport out of the gills. They produce very little urine. Marine sharks and most other cartilaginous fishes (class Chondrichthys) use a different osmoregulatory “strategy.” 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. Unlike bony fishes, marine sharks do not experience a continuous osmotic loss because high concentrations of urea and trimethylamine oxide (TMAO) in body fluids lead to an osmolarity slightly higher than seawater. TMAO protects proteins from damage by urea. Consequently, water slowly enters the shark’s 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. Freshwater protists such as Amoeba and Paramecium have contractile vacuoles that pump out excess water. Many freshwater animals, including fishes, maintain water balance by excreting large amounts of very dilute urine, 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. While in the ocean, salmon osmoregulate like other marine fishes by drinking seawater and excreting excess salt from the gills. When they migrate to freshwater, salmon cease drinking, begin to produce lots of dilute urine, and their gills start taking up salt from the dilute environment—just like fishes that spend their entire lives in freshwater. 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. 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. While the mechanism that tardigrades use is still under investigation, researchers do know that anhydrobiotic nematodes contain large amount of sugars, especially the disaccharide trehalose. Trehalose, a dimer of glucose, seems to protect cells by replacing water associated with membranes and proteins. Many insects that that survive freezing in the winter also utilize trehalose as a membrane protectant. The threat of desiccation is perhaps the largest regulatory problem confronting terrestrial plants and animals. Humans die if they lose about 12% of their body water. Adaptations that reduce water loss are key to survival on land. Most terrestrial animals have body coverings that help prevent dehydration. 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. 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. 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. 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. These and many other desert animals do not drink. D. Excretory Systems Although the problems of water balance on land or in salt water or fresh water are very different, their solutions all depend on the regulations of solute movements between internal fluids and the external environment. 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. 1. Most excretory systems produce urine by refining a filtrate derived from body fluids: an overview While excretory systems are diverse, nearly all produce urine by a two-step process. First, body fluid (blood, coelomic fluid, or hemolymph) is collected. Second, the composition of the collected fluid is adjusted by selective reabsorption or secretion of solutes. Most excretory systems produce a filtrate by pressure-filtering body fluids into tubules. This filtrate is then modified by the transport epithelium which reabsorbs valuable substances, secretes other substances, like toxins and excess ion, and then excretes the contents of the tubule. The initial fluid collection usually involves filtration through the selectively permeable membranes of transport epithelia. These membranes retain cells as well as proteins and other large molecules from the body fluids. Hydrostatic pressure forces water and small solutes, such as salts, sugars, amino acids, and nitrogenous wastes, collectively called the filtrate, into the excretory system. Fluid collection is largely nonselective. Excretory systems use active transport to selectively reabsorb valuable solutes such as glucose, certain salts, and amino acids. Nonessential solutes and wastes are left in the filtrate or added to it by selective secretion. The pumping of various solutes also adjusts the osmotic movement of water into or out of the filtrate. 2. Diverse excretory systems are variations on a tubular theme Flatworms have an excretory system called protonephridia, consisting of a branching network of dead-end tubules. 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. Excreted urine is very dilute in freshwater flatworms. Apparently, the tubules reabsorb most solutes before the urine exits the body. 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. However, in some parasitic flatworms, protonephridia mainly dispose of nitrogenous wastes. Protonephridia are also found in rotifers, some annelids, larval mollusks, and lancelets. Metanephridium, another tubular excretory system, consists of internal openings that collect body fluids from the coelom through a ciliated funnel, the nephrostome, and release the fluid through the nephridiopore. Found in most annelids, each segment of a worm has a pair of metanephridia. An earthworm’s metanephridia have both excretory and osmoregulatory functions. As urine moves along the tubule, the transport epithelium bordering the lumen reabsorbs most solutes and returns them to the blood in the capillaries. Nitrogenous wastes remain in the tubule and are dumped outside. Because earthworms experience a net uptake of water from damp soil, their metanephridia balances water influx by producing dilute urine. Insects and other terrestrial arthropods have organs called Malpighian tubules that remove nitrogenous wastes and also function in osmoregulation. 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. 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. 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. The osmoconforming hagfishes, among the most primitive living vertebrates, have kidneys with segmentally arranged excretory tubules. However, the kidneys of most vertebrates are compact, nonsegmented organs containing numerous tubules arranged in a highly organized manner. 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. 3. Nephrons and associated blood vessels are the functional units of the mammalian kidney Mammals have a pair of bean-shaped kidneys. These are supplied with blood by a renal artery and a renal vein. 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. 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. 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. Both regions are packed with microscopic excretory tubules, nephrons, and their associated blood vessels. Each nephron consists of a single long tubule and a ball of capillaries, called the glomerulus. The blind end of the tubule forms a cup-shaped swelling, called Bowman’s capsule, that surrounds the glomerulus. Each human kidney packs about a million nephrons. Filtration occurs as blood pressure forces fluid from the blood in the glomerulus into the lumen of Bowman’s capsule. 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. The filtrate in Bowman’s capsule contains salt, glucose, vitamins, nitrogenous wastes, and other small molecules. From Bowman’s 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. The distal tubule empties into a collecting duct, which receives processed filtrate from many nephrons. 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. The other 20%, the juxtamedullary nephrons, have well-developed loops that extend deeply into the renal medulla. 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. Their most important task is to reabsorb solutes and water. 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. 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. The capillaries converge as they leave the glomerulus forming an efferent arteriole. This vessel subdivides again into the peritubular capillaries, which surround the proximal and distal tubules. Additional capillaries extend downward to form the vasa recta, a loop of capillaries that serves the loop of Henle. The tubules and capillaries are immersed in interstitial fluid, through which substances diffuse. Filtrate from Bowman’s capsule flows through the nephron and collecting ducts as it becomes urine. • Proximal tubule. Secretion and reabsorption in the proximal tubule substantially alter the volume and composition of filtrate. For example, the cells of the transport epithelium help maintain a constant pH in body fluids by controlled secretions of hydrogen ions or ammonia. (1) The proximal tubules reabsorb about 90% of the important buffer bicarbonate (HCO3-). Drugs and other poisons pass from the peritubular capillaries into the interstitial fluid and then across the epithelium to the nephron’s lumen. 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. The epithelial cells actively transport Na+ into the interstitial fluid. This transfer of positive charge is balanced by the passive transport of Cl- out of the tubule. As salt moves from the filtrate to the interstitial fluid, water follows by osmosis. 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. • (2) Descending limb of the loop of Henle. Reabsorption of water continues as the filtrate moves into the descending limb of the loop of Henle. This transport epithelium is freely permeable to water but not very permeable to salt and other small solutes. For water to move out of the tubule by osmosis, the interstitial fluid bathing the tubule must be hyperosmotic to the filtrate. Because the osmolarity of the interstitial fluid does become progressively greater from the outer cortex to the inner medulla, the filtrate moving within the descending loop of Henle continues to loose water. • (3) Ascending limb of the loop of Henle. In contrast to the descending limb, the transport epithelium of the ascending limb is permeable to salt, not water. 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. The active transport of salt from the filtrate into the interstitial fluid continues in the thick segment of the ascending limb. 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. • (4) Distal tubule. 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. Like the proximal tubule, the distal tubule also contributes to pH regulation by controlled secretion of H+ and the reabsorption of bicarbonate (HCO3-). • (5) Collecting duct. 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. The epithelium is permeable to water but not to salt or (in the renal cortex) to urea. 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. In the inner medulla, the duct becomes permeable to urea, contributing to hyperosmotic interstitial fluid and enabling the kidney to conserve water by excreting a hyperosmotic urine. 4. The mammalian kidney’s 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. At an extreme of water conservation, Australian hopping mice, which live in desert regions, can produce urine concentrated to 9,300 mosm/L—25 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 concentrates the urine. 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 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. The two primary solutes here 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. Filtrate passing from Bowman’s capsule to the proximal tubule has an osmolarity of about 300 mosm/L. As the filtrate flows through the proximal tubule in the renal cortex, a large amount of water and salt is reabsorbed. 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. The osmolarity of the filtrate increases as solutes, including NaCl, become more concentrated. The highest molarity occurs at the elbow of the loop of Henle. 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. 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. Although the two limbs of the loop are not in direct contact, they are close enough to exchange substances through the interstitial fluid. 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 kidney’s interstitial fluid. The vasa recta is also a countercurrent system, with descending and ascending vessels carrying blood in opposite directions through the kidney’s osmolarity gradient. As the descending vessel conveys blood toward the inner medulla, water is lost from the blood and NaCl diffuses into it. These fluxes are reversed as blood flows back toward the cortex in the ascending vessel. 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. 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. 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. 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. This concentrates salt, urea, and other solutes in the filtrate. 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. Although isoosmotic to the inner medulla’s interstitial fluid, the urine is hyperosmotic to blood and interstitial fluid elsewhere in the body. 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. 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. 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 animal’s water and salt balance and the rate of urea production. 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. 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 at 70 mosm/L). 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). ADH is produced in hypothalamus of the brain and stored in and released from the pituitary gland, which lies just below the hypothalamus. 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 blood stream and reaches the kidney. ADH induces the epithelium of the distal tubules and collecting ducts to become more permeable to water. This amplifies water reabsorption. 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. But only a gain of additional water in food and drink can bring osmolarity all the way back down to 300 mosm/L. 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. This decreases the permeability of the distal tubules and collecting ducts, so water reabsorption is reduced, resulting in an increased discharge of dilute urine. Alcohol can disturb water balance by inhibiting the release of ADH, causing excessive urinary water loss and dehydration (causing some symptoms of a hangover). 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. 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. It raises blood pressure by constricting arterioles, decreasing blood flow to many capillaries, including those of the kidney. 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. It also stimulates the adrenal glands, organs 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. A drop in blood pressure triggers a release of renin from the JGA. 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 problems. 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. However, a situation that causes excessive loss of salt and body fluids —an injury or severe diarrhea, for example—will reduce blood volume without increasing osmolarity. 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. ADH alone would lower blood Na+ concentration by stimulating water reabsorption in the kidney. But the RAAS helps maintain balance by stimulating Na+ reabsorption. Still another hormone, atrial natriuretic factor (ANF), opposes the RAAS. The walls of the atria release ANF in response to an increase in blood volume and pressure. ANF inhibits the release of renin from the JGA, inhibits NaCl reabsorption by the collecting ducts, and reduces aldosterone release from the adrenal glands. These actions lower blood pressure and volume. Thus, the ADH, the RAAS, and ANF provide an elaborate system of checks and balances that regulates the kidney’s 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. This species feeds on the blood of large birds and mammals by making an incision in the victim’s 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 prey—so much so that a bat would be too heavy to fly after feeding. The bat uses its kidneys to offload much of the water absorbed from a blood meal by excreting large volume of dilute urine as it feeds. 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. Its food is mostly protein, which generates large quantities of urea, but roosting bats don’t have access to drinking water. Their kidneys shift to producing small quantities of highly concentrated urine, disposing of the urea load while conserving as much water as possible. The vampire bat’s 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. 5. Diverse adaptations of the vertebrate kidney have evolved in different habitats Variations in nephron structure and function equip the kidneys of different vertebrates for osmoregulation in their various habitats. 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 urine becoming very concentrated. In contrast, beavers, which rarely face problems of dehydration, have nephrons with short loops, resulting in much lower ability to concentrate urine. Birds, like mammals, have kidneys with juxtamedullary nephrons that specialize in conserving water. However, the nephrons of birds have much shorter loops of Henle than do mammalian nephrons. Bird kidneys cannot concentrate urine to the osmolarities achieved by mammalian kidneys. The main water conservation adaptation of birds is the use of uric acid as the nitrogen excretion molecule. The kidneys of reptiles, having only cortical nephrons, produce urine that is, at most, isoosmotic to body fluids. However, the epithelium of the cloaca helps conserve fluid by reabsorbing some of the water present in urine and feces. Also, like birds, most 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. Instead of conserving water, the nephrons produce a large volume of very dilute urine. Freshwater fishes conserve salts by reabsorption of ions from the filtrate in the nephrons. Amphibian kidneys function much like those of freshwater fishes. When in fresh water, the skin of the frog accumulates certain salts from the water by active transport, and the kidneys excrete dilute urine. 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. In many species, nephrons lack glomeruli and Bowman’s capsules, and concentrated urine is produced by secreting ions into excretory tubules. 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. Its gills excrete mainly monovalent ions such as Na+ and Cl- and the bulk of its nitrogenous wastes in the form of NH4+. 6. Interacting regulatory systems maintain homeostasis Numerous regulatory systems are involved in maintaining homeostasis in an animal’s internal environment. The mechanisms that rid the body of nitrogenous wastes operate hand in hand with those involved in osmoregulation and are often closely linked with energy budgets and temperature regulation. Similarly, the regulation of body temperature directly affects metabolic rate and exercise capacity and is closely associated with mechanisms controlling blood pressure, gas exchange, and energy balance. Under some conditions, usually at the physical extremes compatible with life, the demands of one system may come into conflict with those of other systems. For example, in hot, dry environments, water conservation often takes precedence over evaporative heat loss. However, if body temperature exceeds a critical upper limit, the animal will start vigorous evaporative cooling and risk dangerous dehydration. Normally, however, the various regulatory systems act together to maintain homeostasis in the internal environment. The liver, the vertebrate body’s most functionally diverse organ, is pivotal to homeostasis. For example, liver cells interact with the circulatory system in taking up glucose from the blood. The liver stores excess glucose as glycogen and, in response to the body’s demand for fuel, converts glycogen back to glucose, releasing glucose to the blood. The liver also synthesizes plasma proteins important in blood clotting and in maintaining osmotic balance in the blood. Liver cells detoxify many chemical poisons and prepare metabolic wastes for disposal.