1. Animals get excess nitrogen, mostly the amino groups of amino acids, from foods and from the continuous breakdown of cellular proteins.

2. Animals use or store the carbon skeletons of amino acids and excrete the excess amino groups as ammonia, urea, or uric acid, depending on their way of life (Figure 46.1).

1. Lungfishes of Africa and South America excrete ammonia as long as water is plentiful.

2. They can survive the droughts that are common in their habitats by burrowing into the mud and forming a kind of cocoon (Figure 46.2).

3. They start to make urea, since accumulated ammonia would kill them.

4. Amphibians such as frogs typically begin their lives as aquatic larvae (tadpoles) that excrete ammonia, then start to make urea as they metamorphose into terrestrial adults.

1. Plants make unusual metabolites (such as pigments, hormones, and allomones), which may create interesting flavors but may also be quite toxic.

2. Animals eat these compounds, as well as many noxious materials made by bacteria and fungi.

3. Enzymes in organs such as the liver and kidneys partly break down many of these substances.

1. Extracellular fluid (blood plasma or hemolymph) is discharged into the lumen of a dead-end channel composed of a single layer of epithelial cells. It may be forced across in a process of ultrafiltration or it may be actively secreted into the channel by transport proteins.

2. Carefully regulated amounts of certain materials (such as glucose, water, and certain ions) are reabsorbed from the channel into the blood or hemolymph.

3. The remaining contents of the channel are excreted through an external pore.

1. Some epithelia are just protective surfaces, but others are specialized as glands for secreting enzymes or for moving ions and water.

2. In 1947 Hans Ussing used sodium isotopes to demonstrate that Na+ ions flow in one direction, from the outside surface of the skin to the inside, and he showed later that this flow can generate an electrical potential across the skin.

3. This mechanism is commonly called a sodium pump.

1. The movement of Na+ is clearly due to active transport, since it can be stopped by metabolic poisons such as cyanide and by specific poisons such as ouabain, which inhibits the Na+/K+ ATPase that transports K+ ions into cells and Na+ ions outward.

2. Na+/K+ ATPases maintain the high concentration of K+ ions in cytoplasm and are ultimately responsible for the voltage that cells maintain across their membranes.

3. When integrated into certain epithelia, these transport proteins create epithelial sodium pumps.

4. In frog skin, the Na+/K+ ATPases are confined to the inner surface of the epithelium (Figure 46.4), and K+ ions can leak out from this surface, creating the normal membrane voltage.

1. There are no cellular pumps for water, so water is transported by moving ions and letting the water passively follow by osmosis.

2. In water-pumping epithelia, deep clefts between the cells are closed at one end by tight junctions, which stop virtually all movement in that direction (Figure 46.5).

3. The adjacent cells pump ions into the base of the cleft; water follows osmotically and then moves out of the open end of the cleft (along with a gradual movement of the ions).

4. It is now clear that, in cells like these, water moves through specific water channels in proteins called aquaporins, which make plasma membranes 100-200 times more permeable to water than pure phospholipid-cholesterol membranes.

5. Substances will diffuse through surrounding interstitial fluid between the epithelium and the circulation (Figure 46.6).

6. When epithelium is operating normally, each substance will reach a steady-state concentration in the epithelium and interstitial fluid.

1. The system creates a concentrated fluid around a tubule such that water is drawn out of the tubule osmotically, and the material inside becomes more concentrated.

2. Since the hemolymph surrounding the tubules doesn't exert enough pressure to force wastes into the tubules, urine is actively secreted into them.

3. The tubules epithelium secretes K+ ions into the lumen of each tubule; Cl- ions and water then follow, carrying along nitrogenous wastes.

4. Water and ions are continually recycled through the gut, hemolymph, and tubules, while a very concentrated solution of wastes accumulates as urine in the gut.

1. The kidneys are paired, left and right (Figure 46.8).

2. Each one contains about a million tubules called nephrons, which filter the blood and regulate its composition.

3. Each nephron spans the kidney's outer cortex and inner medulla.

4. It only takes five minutes for the kidneys to filter the equivalent of all the blood in the body.

1. Under the high blood pressure in the renal artery, plasma is forced from a knot of capillaries, a glomerulus, through the surrounding Bowman's capsule into the lumen of the nephron to form a glomerular filtrate.

2. The glomerular filtrate must pass through large pores, 20-50 nm in diameter, through the basal lamina around the capillary endothelium, and through a barrier made by unique cells called podocytes (Figure 46.9).

3. Podocytes cover the capillaries with interdigitating extensions that leave only very narrow slits through which the glomerular filtrate can pass.

1. The GFR depends on the same factors of osmotic and hydrostatic pressure that determine the exchange of plasma and interstitial fluid.

2. Figure 46.10 shows that the hydrostatic pressure in a glomerulus, about 75 torr, is exerted against two back pressures: the hydrostatic pressure from the nephron and surrounding interstitial fluid (20 torr) and the total osmotic pressure (30 torr).

3. This pressure moves plasma from the glomerulus into the nephron.

1. Since only about one percent of the filtrate will become urine, a nephron recovers virtually all the water passing through it.

2. A nephron can actively secrete H+ and K+ ions and other materials into the filtrate, as needed for homeostasis.

3. The combination of filtration, reabsorption, and secretion, with hormonal and neural controls, maintains the proper balance of each substance in the extracellular fluid.

1. The form of the loop, with two thin, parallel tubes, suggests that it is a countercurrent exchange device.

2. The loop of Henle and vasa recta together create a strong concentration gradient of Na+ ions, Cl- ions, and urea throughout the interstitial fluid of the kidney, from a low concentration in the cortex to a high concentration in the medulla.

3. The vasa recta and loop of Henle both exchange salt and water between their ascending and descending limbs, thus establishing concentration gradients within themselves (Figure 46.11).

4. The vasa recta leaves a gradient of salt and urea in the interstitial fluid but constantly removes water from the region.

1. The thin descending limb is highly permeable to water and is slightly permeable to urea.

2. The thin ascending limb is highly permeable to NaCl and is slightly permeable to urea.

3. The thick ascending limb actively transports NaCl outward.

4. The outer medullary collecting duct is highly permeable to water.

5. The inner medullary collecting duct is variably permeable to water and highly permeable to urea.

1. Tissue cells are bathed in an interstitial fluid whose principal ion is Na+, and its Na+ ion concentration strongly influences the water flux in and out of cells.

2. This flux determines the intracellular and extracellular volumes.

3. In an animal that takes in too much Na+ without enough water, the osmolarity of its extracellular fluid will increase and water will flow out of its cells by osmosis; thus its intracellular volume will shrink, with possibly severe consequences.

1. These factors are monitored by two kinds of interoceptors: baroreceptors that measure blood pressure and osmoreceptors that measure the osmolarity of the plasma and interstitial fluid.

2. The kidneys regulate the volume and osmolarity of extracellular fluid through two systems of hormones that affect the balance between filtration through the glomerulus and reabsorption from the filtrate.

3. Most of the water and Na+ is withdrawn from the glomerular filtrate in the proximal region of the nephron and the loop of Henle; as the remainder passes through the distal convoluted tubule and collecting duct, its water and Na+ content are adjusted.

1. Diuresis means "producing urine," so antidiuresis means producing less urine.

2. Osmoreceptors in the hypothalamus monitor the osmolarity of the interstitial fluid, and once they detect osmotic pressure above a set point, they signal the secretion of ADH, which targets the collecting duct endothelium of the nephron (Figure 46.13).

3. Under the influence of ADH, the aquaporin-CDs of the endothelium open and let more water diffuse out of the glomerular filtrate.

1. In the kidney, the juxtaglomerular apparatus made of specialized cells next to each glomerulus monitors blood pressure.

2. If the juxtaglomerular apparatus detects a decrease in pressure, it secretes the enzyme renin.

3. Renin converts angiotensinogen to angiotensin I, which is then converted into the active hormone angiotensin II by converting enzymes in capillaries of the lung and other organs.

1. First, it causes general vasoconstriction in blood vessels throughout the circulatory system, thus raising the blood pressure.

2. Second, it stimulates thirst centers in the hypothalamus, thus stimulating drinking, which can increase the blood volume.

3. Third, it causes the adrenal cortex to release the steroid hormone aldosterone, whose target cells are in the distal convoluted tubule of the kidney.

1. Animal cells operate near neutrality; for instance, human plasma is normally pH 7.4, with a slight excess of OH- ions.

2. Acidosis (pH less than 7.4) or alkalosis (pH greater than 7.4) can result from functional disorders and can produce severe illness.

3. A human cannot tolerate a pH less than 7.0 or more than 7.8.

1. Metabolic CO2 that is converted to HCO3- and H+ ions.

2. Lactic and other acids being transported through the blood.

3. Sulfuric and phosphoric acids from the sulfide and phosphate groups released when proteins and nucleic acids are broken down.

1. Hemoglobin, for instance, takes care of a great deal of acid by picking up one H+ ion for each O2 it releases.

2. Additional H+ ions combine at other points on the hemoglobin molecule, primarily at histidine residues that are stronger bases in the non-oxygen-binding conformation than in the binding conformation.

3. Subtle structural changes make hemoglobin well adapted for its function of carrying O2 and CO2.

1. They respond to acidosis by pumping H+ or ammonium ions into the urine to acidify it (Figure 46.15).

2. In alkalosis, the kidneys can restore H+ ions to the plasma by actively secreting K+ ions into the glomerular filtrate (Figure 46.15).

3. Nephrons normally reabsorb HCO3- from the filtrate, and they can change the rate of reabsorption.

1. The composition of animals' body fluids reflects the general composition of those ancient seas.

2. Early animals could maintain a cytoplasm that was isotonic to seawater, so they had no need for rigid cell walls to keep from rupturing under the pressure of incoming water.

1. Many marine invertebrates are osmoconformers whose body fluids conform to the osmolarity of their surroundings (Figure 46.16).

2. Even though the overall ionic concentration of their fluids keeps them in osmotic balance with their surroundings, their specific ion pumps can maintain some ions at concentrations different from those of seawater.

3. Other animals are osmoregulators whose kidneys or other organs regulate the composition of their body fluids and maintain an osmotic pressure quite different from that of their surroundings.

1. The first fishes evolved kidneys that collect and excrete excess extracellular water.

2. The first kidneys were simply a series of nephron units along the back of the coelom, one per segment, with an opening (a coelomostome) to drain fluid from the coelom (Figure 46.18).

3. Fishes and amphibians have efficient kidneys; their nephrons are associated with glomeruli for filtering water from the blood at first rather loosely connected with a Bowman's capsule.

4. Freshwater fish excrete very dilute, hypoosmotic urine.

5. Freshwater fish replace the salts lost in their urine by absorbing extra salt through pumps in their gills.

1. One of their adaptations to life on land is to excrete urea or uric acid instead of ammonia.

2. They cannot conserve water nearly as well as birds and mammals do because their kidneys have no loop of Henle.

3. Both amphibians and reptiles have mechanisms for reabsorbing water from both their urinary bladder and cloaca.

4. It is only in birds and mammals that the loop of Henle evolved, allowing some species to become very well adapted to dry conditions and sometimes to live exclusively on their own metabolic water (Figure 46.19).

1. In addition to their kidneys, fishes have a unique osmoregulatory mechanism in the chloride cells of their gills, which stand directly between the blood on one side and the open water on the other (Figure 46.20).

2. In freshwater fishes, these cells pump Na+ and Cl- ions into the blood with antiport mechanisms.

3. In marine fishes, the chloride cells pump in the opposite direction.

4. Salmon and other fish that live part of their lives in freshwater and part in seawater can adapt to the different environments through a change in the pumps of their chloride cells.

1. These birds excrete massive amounts through a remarkable salt gland located in the corner of each eye, which creates an extremely concentrated brine that continuously runs down the beak (Figure 46.21).

2. Operating on the countercurrent exchange principle, these glands use ion pumps that move Na+ outward, with Cl- following passively.

3. Turtles, crocodilians, marine snakes, and lizards also have salt glands.