Excretory Products and Their Elimination

Living cells are chemical factories that never shut down, and every factory produces waste. Carbohydrates and fats burn cleanly enough, leaving carbon dioxide and water behind. Proteins and nucleic acids are different, because they carry nitrogen. When an amino acid is broken down for energy, the amino group is stripped off first, and that nitrogen leaves the cell as ammonia (NH₃). Ammonia is the cheapest nitrogenous waste an animal can produce, because the cell spends nothing extra to make it. It is also by far the most toxic. Even a small rise in the ammonia level of body fluids interferes with the nervous system, so an animal that excretes ammonia must get rid of it the moment it is formed, and washing it out takes a great deal of water. Ammonia is very soluble, so a large volume of water can carry it away easily; but a land animal simply does not have that much water to throw away.

This one trade-off, the cost of making the waste against the water needed to remove it, is what produces the three excretory patterns you have to know. The first is ammonotelism, the direct excretion of ammonia. Many bony fishes, aquatic amphibians and aquatic insects are ammonotelic. In these animals ammonia is not really a job for the kidney at all: because it is so soluble and diffuses so readily, most of it leaves straight across the general body surface or across the gill surfaces, usually in the form of ammonium ions. The animal is surrounded by fresh water, so the water bill is effectively zero, and it saves the energy that other animals spend on converting ammonia into something safer.

The second pattern is ureotelism. Mammals, many terrestrial amphibians and marine fishes are ureotelic. Here the ammonia produced by cellular metabolism is converted into urea, and in humans that conversion happens in the liver. This is the point students most often get wrong: the liver makes the urea, the kidney only removes it. Urea is released from the liver into the blood, travels to the kidneys, and is filtered out there. Because urea is far less toxic than ammonia, the blood can carry it safely and the body does not have to excrete it instantly, which means a moderate amount of water is enough. Notice that marine fishes are ureotelic even though they live in water, while the bony fishes listed as ammonotelic are the fresh water ones. The difference is not water in the surroundings but usable water: sea water is saltier than a fish's body fluids, so fresh water is constantly being pulled out of a marine fish across its gills. For it, water is scarce in exactly the way it is scarce for a desert animal, and a shark is the standard example of a ureotelic fish.

The third pattern is uricotelism. Reptiles, birds, land snails and insects excrete nitrogen mainly as uric acid, in the form of a pellet or a thick paste, with very little loss of water. Uric acid is almost insoluble, so it can be dumped in a semi-solid form. Making it costs the most energy of the three, but for an animal living on dry land, or developing inside a shelled egg where the waste has to be stored harmlessly until hatching, that energy is worth spending.

Excretion is not carried out by kidneys everywhere in the animal kingdom. Simpler animals use simpler structures, and the chapter lists them in order of increasing complexity. Protonephridia or flame cells are found in Platyhelminthes such as flatworms, in rotifers, in some annelids and in the cephalochordate Amphioxus; their main job is osmoregulation, that is, control of water and salt balance, rather than waste removal. Nephridia are the tubular excretory structures of earthworms and other annelids, and they help remove nitrogenous wastes as well as maintain fluid balance. Malpighian tubules in insects such as cockroaches remove nitrogenous wastes and are also responsible for osmoregulation, while antennal glands or green glands do the job in crustaceans like prawns.

The human excretory system is made of a pair of kidneys, a pair of ureters, a urinary bladder and a urethra. The kidneys are reddish brown and bean shaped, and they lie close to the dorsal inner wall of the abdominal cavity, one on each side of the vertebral column, roughly between the level of the last thoracic and the third lumbar vertebra. Each kidney of an adult human is about 10 to 12 cm long, 5 to 7 cm wide and 2 to 3 cm thick, weighing on average 120 to 170 grams. On the inner concave side of each kidney there is a notch called the hilum. The ureter, the blood vessels and the nerves enter and leave the kidney through this notch. Just inside the hilum is a funnel shaped space called the renal pelvis, and projecting into it are cup like extensions called calyces. Urine collected in the calyces drains into the pelvis, leaves through the ureter, is stored in the urinary bladder and is finally passed out through the urethra.

Cut a kidney lengthwise and you see two clearly different zones. The outer zone is the cortex and the inner zone is the medulla. The medulla is not a single mass; it is divided into a few conical regions called medullary pyramids, whose tips project into the calyces. The cortex does not simply sit on top of the medulla either. It dips down between the pyramids as strips of tissue called renal columns or columns of Bertini. Keeping this geography in mind matters, because the fate of the filtrate depends on whether the tubule carrying it is sitting in the cortex or has dived deep into the medulla.

Each kidney contains nearly one million tubular units called nephrons. The nephron is the functional unit of the kidney, and it has two parts: a tuft of blood capillaries called the glomerulus, and a long twisted tube called the renal tubule. The glomerulus is formed by an afferent arteriole, a fine branch of the renal artery that breaks up into a knot of capillaries; the blood that has passed through this knot is collected by an efferent arteriole. The renal tubule begins with a double walled cup called Bowman's capsule, which wraps around the glomerulus the way a cupped palm wraps around a ball. The glomerulus together with Bowman's capsule is called the malpighian body or renal corpuscle.

Now walk along the tubule, because with no diagram on this page the order and the direction are what you must hold in your head. Filtrate leaves Bowman's capsule and enters the proximal convoluted tubule (PCT), a highly coiled segment lying in the cortex, lined by simple cuboidal epithelium whose inner surface carries a dense brush border of microvilli. The tubule then straightens and plunges downwards, out of the cortex and into the medulla, as the descending limb of the loop of Henle. Deep in the medulla it makes a hairpin bend and turns straight back up as the ascending limb, returning to the cortex. So the loop is a U turn, and the two limbs run side by side with fluid flowing in opposite directions in them. Back in the cortex the tubule coils again as the distal convoluted tubule (DCT). Several distal convoluted tubules from different nephrons then open into a single straight collecting duct, which runs back down through the medulla, passes through the medullary pyramid and opens into a calyx. The collecting duct is shared, which is why it is described as part of the kidney's ducts rather than as a private part of one nephron.

Nephrons are not all alike, and the difference decides how concentrated your urine can be. In cortical nephrons, which form the majority, the loop of Henle is very short and extends only a little way into the medulla, and the vasa recta (the fine capillary network that runs alongside the loop) is absent or highly reduced. In juxtamedullary nephrons, whose malpighian bodies sit close to the medulla, the loop of Henle is very long and runs deep into the medulla, and a well developed vasa recta accompanies it. Only the long looped juxtamedullary nephrons can set up the strong salt gradient in the medulla that makes concentrated urine possible. There is one more structure to note: at the point where the distal convoluted tubule comes into contact with the afferent arteriole of its own glomerulus, cells of both the tubule and the arteriole are modified to form the juxtaglomerular apparatus (JGA), a small sensor region that will matter when we come to regulation.

Urine formation happens in three steps: glomerular filtration, reabsorption and secretion, and they happen in different parts of the nephron.

Glomerular filtration. Blood is brought to the glomerulus by the afferent arteriole and leaves by the efferent arteriole, which is narrower. Because blood cannot escape easily, pressure builds inside the glomerular capillaries and plasma is squeezed out into Bowman's capsule. The kidneys receive an enormous share of the circulation: about 1100 to 1200 mL of blood flows through them every minute, which is roughly one fifth of the blood pumped out by the heart in that time. The filtering barrier has three layers, and you should be able to name them in order from blood to filtrate: the endothelium of the glomerular capillaries, a basement membrane, and the epithelium of Bowman's capsule. The cells of that inner epithelial layer are called podocytes, and they are arranged in an intricate interlocking manner that leaves tiny gaps between them called filtration slits or slit pores. Blood is filtered so finely through these three layers that essentially every constituent of the plasma except the proteins passes into the lumen of Bowman's capsule. That is why the process is called ultrafiltration.

The amount of filtrate formed by all the nephrons of both kidneys per minute is the glomerular filtration rate (GFR), and in a healthy adult it is about 125 mL per minute, that is, roughly 180 litres per day. Compare that with the 1 to 1.5 litres of urine an adult actually passes in a day, and one fact becomes obvious: nearly 99 per cent of the filtrate has to be taken back into the blood. GFR is important because it is the number the kidney itself defends. The juxtaglomerular apparatus acts as a built in sensor, and a fall in GFR triggers the corrective response described in the section on regulation.

Reabsorption. Taking back 99 per cent of 180 litres is the tubule's main work, and it is selective, that is, useful substances are recovered and wastes are left behind. Reabsorption uses both active transport, which spends energy, and passive transport, which does not. Glucose, amino acids and sodium ions are reabsorbed actively; nitrogenous wastes are reabsorbed passively if at all; water moves passively, following the solutes. The PCT does the bulk of it. Its brush border of microvilli gives it a huge surface area, and here nearly all of the essential nutrients such as glucose and amino acids, and about 70 to 80 per cent of the electrolytes and water, are returned to the blood. The PCT also helps maintain the pH and the ionic balance of body fluids, by absorbing bicarbonate ions from the filtrate and by selectively secreting hydrogen ions, ammonia and potassium ions into it. In Henle's loop reabsorption is minimal; its real contribution is to build the concentration gradient in the medulla, which is dealt with separately. The DCT carries out conditional reabsorption of sodium ions and water, meaning it reabsorbs them only when hormones tell it to, and it can also reabsorb bicarbonate ions. In the collecting duct, large amounts of water can be reabsorbed to produce a concentrated urine, and small amounts of urea are allowed to pass out into the medullary interstitium, which helps keep the osmolarity there high.

Tubular secretion. Filtration alone is not fine enough, so the tubule cells also actively push certain substances from the surrounding blood into the filtrate. Hydrogen ions, potassium ions and ammonia are secreted in this way, mainly by the PCT, the DCT and the collecting duct. Secretion is how the kidney fine tunes the pH of the blood and the sodium potassium balance, and it is the reason your urine is normally slightly acidic.

The urine collected in the pelvis passes down the ureters and is stored in the urinary bladder until a voluntary signal comes from the central nervous system. Stretch receptors in the bladder wall report that it is filling; the CNS then sends motor signals that contract the smooth muscle of the bladder and simultaneously relax the urethral sphincter, releasing the urine. This release is called micturition, and the neural mechanism behind it is the micturition reflex. On average an adult passes 1 to 1.5 litres of urine a day. Normal human urine is a light yellow watery fluid, slightly acidic at about pH 6.0, with a characteristic odour, and it carries out on average 25 to 30 grams of urea per day.

To make urine more concentrated than blood, the kidney needs somewhere very salty to pull water into. It builds that salty region in the medulla, and the trick it uses is called the counter-current mechanism. Counter current simply means that two fluids run beside each other in opposite directions. In the kidney this happens twice over: the descending and ascending limbs of Henle's loop carry filtrate in opposite directions, and the descending and ascending portions of the vasa recta carry blood in opposite directions right alongside them. The loop and the vasa recta lie very close together, and it is that proximity plus the opposed flow that makes the whole thing work.

Start with the permeability of the two limbs, because everything follows from it. The descending limb is permeable to water but almost impermeable to electrolytes. As the filtrate travels down into a medulla that is getting saltier and saltier, water leaves it osmotically and salt does not enter, so the filtrate becomes progressively more concentrated as it approaches the hairpin bend. The ascending limb is impermeable to water but transports electrolytes out, actively or passively. So on the way up, sodium chloride leaves the filtrate while water is forced to stay behind, and the filtrate becomes progressively more dilute. Notice the elegance: the salt pumped out of the ascending limb is exactly what makes the medulla salty enough to draw water out of the descending limb.

The result is a steady rise in osmolarity as you go deeper. In the cortex the interstitial fluid is about 300 mOsmol L^-1, the same as blood, while in the inner medulla it reaches about 1200 mOsmol L^-1. This gradient is produced mainly by two solutes: NaCl and urea. The NaCl is transported out by the ascending limb of Henle's loop and is handed over to the descending limb of the vasa recta; the ascending portion of the vasa recta returns it to the interstitium instead of carrying it away. The urea contribution works in a similar circuit: small amounts of urea enter the thin segment of the ascending limb of Henle's loop, and urea is transported back into the interstitium from the collecting duct. Because both solutes keep being recycled rather than washed out, the gradient is maintained.

The vasa recta deserves a second look, because it is the part students most often misread. Blood has to flow through the medulla to keep the tissue alive, and any ordinary straight capillary would simply pick up the salt and carry it off, flattening the gradient within minutes. The hairpin shape prevents this. Blood flowing down the descending portion picks up solute and loses water; blood flowing back up the ascending portion gives most of that solute back to the interstitium. The vasa recta therefore supplies the medulla with blood while acting almost as a solute trap. This is exactly why cortical nephrons, which have little or no vasa recta and a short loop, cannot build this gradient, and why the long looped juxtamedullary nephrons are the ones that make concentrated urine possible.

Finally, the payoff. The collecting duct runs straight down through this increasingly salty medulla on its way to the calyx. Wherever the duct is permeable to water, the surrounding gradient pulls water out of the urine passing through it and returns that water to the blood. The urine left behind gets steadily more concentrated as it descends. Through this arrangement the human kidney can produce urine that is nearly four times as concentrated as the initial filtrate. Whether the duct actually lets that water out is not automatic; it is under hormonal control, which brings us to regulation.

The kidney's output is not fixed. How much water and salt it keeps is adjusted continuously by the nervous system and by hormones, and the chapter describes three mechanisms that do this.

ADH and the osmoreceptors. Scattered in the body are osmoreceptors, receptors that are activated by changes in blood volume, body fluid volume and ionic concentration. Suppose you sweat heavily on a hot day and lose a lot of fluid. The osmoreceptors detect the change and stimulate the hypothalamus to release antidiuretic hormone (ADH), also called vasopressin, from the neurohypophysis, which is the posterior part of the pituitary. ADH acts on the later parts of the tubule, the distal convoluted tubule and the collecting duct, and makes them permeable to water, so water is reabsorbed from the filtrate instead of being lost. This is what prevents diuresis, the passing of large volumes of dilute urine. The name gives the function away: anti-diuretic, against the loss of water. Once body fluid volume rises again, the osmoreceptors are switched off and ADH release is suppressed. That switching off is the feedback half of the loop, and it is as much a part of the answer as the switching on. ADH has a second effect as well: it constricts blood vessels, which raises blood pressure, and an increase in blood pressure increases glomerular blood flow and hence GFR.

The renin-angiotensin-aldosterone system. The juxtaglomerular apparatus plays a significant role in regulating GFR, and it works as follows. A fall in glomerular blood flow, glomerular blood pressure or GFR activates the JG cells to release renin. Renin is an enzyme, not a hormone, and this is worth remembering. It converts angiotensinogen present in the blood into angiotensin I, which is then converted into angiotensin II. Angiotensin II is a powerful vasoconstrictor: it narrows blood vessels, raises glomerular blood pressure, and thereby restores GFR. Angiotensin II also acts on the adrenal cortex and makes it release aldosterone. Aldosterone causes reabsorption of sodium ions and water from the distal parts of the tubule. Because sodium takes water with it, blood volume rises, blood pressure rises, and GFR rises with them. The whole chain is called the renin-angiotensin mechanism. Two traps to avoid here: aldosterone comes from the adrenal cortex, not the kidney, and it is angiotensin II, not angiotensin I, that does the vasoconstriction and triggers aldosterone release.

Atrial natriuretic factor. If every mechanism only pushed blood pressure up, there would be no brake. An increase in blood flow to the atria of the heart causes the release of atrial natriuretic factor (ANF). ANF causes vasodilation, the widening of blood vessels, and thereby decreases blood pressure. ANF therefore acts as a check on the renin-angiotensin mechanism. Think of the two as opposite ends of a see-saw: renin-angiotensin-aldosterone raises pressure and conserves sodium and water, ANF lowers pressure. The name is a hint too, since natriuretic refers to the loss of sodium.

Putting the three together, the pattern to remember is simple. If the problem is too little water, ADH is the answer, because ADH acts on water permeability. If the problem is too little pressure or too little filtration, the renin pathway is the answer, because it acts on vessel diameter and on sodium. If the problem is too much volume arriving at the heart, ANF is the answer. All three finally act on the same place, the later parts of the nephron and the arterioles supplying it.

Excretion is not the kidney's monopoly. Several other organs get rid of wastes as part of doing their own jobs, and the chapter treats them as accessory excretory organs.

The lungs remove large quantities of carbon dioxide, roughly 200 mL every minute, along with significant quantities of water in the exhaled air every day. Since carbon dioxide is produced by every respiring cell, a great deal of waste leaves this way, even though we rarely think of breathing as excretion. The liver, apart from making urea, secretes bile, and bile carries out substances such as bilirubin and biliverdin (pigments from the breakdown of haemoglobin), cholesterol, degraded steroid hormones, some vitamins and drugs. Most of these leave the body along with the digestive wastes. The skin contributes through two kinds of glands. Sweat glands produce sweat, a watery fluid containing sodium chloride and small amounts of urea, lactic acid and similar substances. The main function of sweat is to cool the body surface as it evaporates, but it also removes some of these wastes along the way. Sebaceous glands eliminate substances such as sterols, hydrocarbons and waxes through sebum, a secretion whose main role is to provide a protective oily covering for the skin. Small amounts of nitrogenous waste can also leave in saliva. Keep the emphasis right in an answer: these are supporting routes, and the bulk of nitrogenous waste still leaves through the kidneys.

The chapter closes with a short list of kidney conditions, and these are to be named and defined, nothing more. Uraemia is the accumulation of urea in the blood that results when the kidneys are not functioning properly; it is harmful and may lead to kidney failure. Renal failure is the condition in which the kidneys are no longer able to carry out filtration adequately. Renal calculi are stones, that is, insoluble masses of crystallised salts such as oxalates, formed within the kidney. Glomerulonephritis is inflammation of the glomeruli of the kidney; the name itself breaks up neatly into glomerulo, referring to the glomerulus, and nephritis, meaning inflammation of kidney tissue.

Two ways of dealing with failing kidneys are described. Haemodialysis is the removal of urea from the blood using an artificial kidney. Blood is drained from a convenient artery and, after an anticoagulant such as heparin is added, it is pumped into the dialysing unit. Inside that unit the blood passes through a coiled cellophane tube surrounded by dialysing fluid, whose composition is the same as that of plasma except that it contains no nitrogenous wastes. Movement of molecules across the cellophane membrane depends only on the concentration gradient, so because the nitrogenous wastes are absent from the dialysing fluid, they move freely out of the blood, while the useful plasma constituents, which are present at the same concentration on both sides, have no gradient to follow and stay put. The cleared blood is then pumped back into the body through a vein after adding anti-heparin. That single design choice, matching the fluid to plasma and leaving out only the wastes, is the whole idea of dialysis. Kidney transplantation is the ultimate method for correcting acute renal failure: a functioning kidney from a donor, preferably a close relative, is used, since a close match minimises the chances of the organ being rejected by the recipient's immune system.

None of this section is guidance for dealing with an illness. It is a set of definitions you should be able to state, and nothing about symptoms, testing or treatment belongs in an answer here.