What you'll learn
Homeostasis, excretion and osmoregulation covers the maintenance of a constant internal environment, focusing on the kidney as the principal organ of both excretion and water regulation. At CAPE level you must know the nephron in structural detail, explain ultrafiltration and selective reabsorption at the molecular level, account for the counter-current multiplier in the loop of Henle, and explain hormonal control of water and glucose. By the end of this topic you should be able to explain negative feedback, describe the structure of the kidney and nephron, explain each stage of urine formation, explain osmoregulation by ADH, describe the control of blood glucose, and relate loop length to habitat.
Key terms and definitions
Homeostasis — the maintenance of a constant internal environment within narrow limits
Negative feedback — a control mechanism in which a deviation triggers a response that reverses it
Excretion — the removal of the waste products of metabolism
Osmoregulation — the control of the water potential of body fluids
Deamination — the removal of the amino group from an amino acid, forming ammonia
Ultrafiltration — filtration under pressure, separating small molecules from blood
Glomerulus — the knot of capillaries within the Bowman's capsule
Podocyte — a specialised cell of the Bowman's capsule with gaps between its extensions
Selective reabsorption — the return of useful substances from the filtrate to the blood
Loop of Henle — the hairpin section of the nephron that establishes a salt gradient in the medulla
Counter-current multiplier — the mechanism by which the loop maintains a gradient along its length
Antidiuretic hormone — the hormone increasing water reabsorption, abbreviated ADH
Aquaporin — a water channel protein inserted into the collecting duct membrane
Core concepts
Homeostasis and negative feedback
Homeostasis maintains the internal environment within narrow limits despite external change. The conditions regulated include body temperature, blood glucose concentration, blood water potential, blood pH and carbon dioxide concentration.
It matters because enzymes function only within narrow ranges of temperature and pH, and because cells are damaged by osmotic movement of water if the water potential of body fluids departs from the normal value.
Every control system has the same components: a receptor detecting the change, a coordinator processing the information, an effector producing the response, and a return towards the set point.
Negative feedback reverses a deviation. A rise triggers a response that lowers the level, and a fall triggers a response that raises it, so the value oscillates around a norm rather than drifting. Separate mechanisms usually operate in each direction, which allows more precise and more rapid control than a single mechanism reversing itself.
Positive feedback, by contrast, amplifies a change and moves the system further from its original state. It is much less common but does occur, for example in the release of oxytocin during childbirth, where uterine contractions stimulate further oxytocin release and therefore stronger contractions.
Excretory products and deamination
Excretion removes the waste products of metabolism, which must be distinguished from egestion, the removal of undigested food that was never part of the body's metabolism.
The main excretory products are carbon dioxide from respiration, removed by the lungs; urea, removed by the kidneys; and excess water and salts.
Excess amino acids cannot be stored, so they are deaminated in the liver. The amino group is removed and converted to ammonia, which is highly toxic and very soluble. Ammonia enters the ornithine cycle and is converted to urea, which is far less toxic and can therefore be transported safely in the blood to the kidneys. The remaining carbon skeleton, a keto acid, enters respiration or is converted to glycogen or fat.
Kidney and nephron structure
The kidney has an outer cortex, an inner medulla, and a pelvis leading to the ureter.
Each kidney contains about a million nephrons. A nephron consists of the Bowman's capsule surrounding the glomerulus, the proximal convoluted tubule, the loop of Henle descending into the medulla and returning, the distal convoluted tubule, and the collecting duct.
The Bowman's capsule and both convoluted tubules lie in the cortex; the loop of Henle and collecting duct pass through the medulla. This arrangement matters, because the salt gradient on which water reabsorption depends exists in the medulla.
Blood enters the glomerulus through the afferent arteriole and leaves through the efferent arteriole, which is narrower. This difference in diameter is the origin of the high pressure that drives filtration.
Ultrafiltration
Blood in the glomerulus is under high hydrostatic pressure, because the efferent arteriole is narrower than the afferent arteriole, restricting outflow.
This pressure forces small molecules out of the capillary through three layers: the fenestrations between the capillary endothelial cells, the basement membrane, and the filtration slits between the extensions of the podocytes lining the capsule.
The basement membrane is the actual filter, and its pore size determines what passes. Water, glucose, amino acids, mineral ions, urea and other small solutes pass into the capsule. Blood cells and plasma proteins are too large and remain in the blood.
The resulting glomerular filtrate has the same composition as plasma except that it contains no cells and essentially no protein.
The retained plasma proteins give the blood a more negative water potential, which opposes filtration, and the hydrostatic pressure of the filtrate already in the capsule also opposes it. Filtration occurs because the glomerular hydrostatic pressure exceeds the sum of these opposing pressures.
Selective reabsorption
About 180 litres of filtrate are produced daily but only about 1.5 litres of urine, so the great majority is reabsorbed.
The proximal convoluted tubule reabsorbs all the glucose and amino acids, most mineral ions and about 85 per cent of the water.
The mechanism is co-transport. Sodium ions are actively pumped out of the tubule cell into the blood, lowering the sodium concentration inside the cell. Sodium ions then enter from the filtrate through co-transporter proteins, carrying glucose or amino acids with them against their own concentration gradients. Glucose then leaves the cell into the blood by facilitated diffusion.
Water follows by osmosis, because the reabsorption of solutes makes the water potential of the blood more negative than that of the filtrate.
The epithelial cells of the proximal convoluted tubule are adapted accordingly, and the adaptations are examinable: microvilli on the luminal surface provide a very large surface area for absorption; numerous mitochondria supply the ATP required for the active transport of sodium; and the cells contain many co-transporter and carrier proteins in their membranes.
The loop of Henle
The loop of Henle establishes a gradient of increasing salt concentration, and therefore of decreasing water potential, from the cortex down into the medulla. The purpose is to allow water to be reabsorbed from the collecting duct.
The mechanism is a counter-current multiplier and operates as follows.
The ascending limb is impermeable to water. Sodium and chloride ions are actively pumped out of it into the surrounding medulla tissue fluid. Because water cannot follow, the tissue fluid becomes increasingly concentrated and its water potential falls.
The descending limb is permeable to water but relatively impermeable to ions. As filtrate passes down it through the increasingly concentrated medulla, water leaves by osmosis, so the filtrate itself becomes more concentrated as it descends, reaching its most concentrated at the tip of the loop.
Because the filtrate entering the ascending limb is already concentrated, the pumps there can raise the surrounding concentration further than would otherwise be possible. The counter-current arrangement therefore multiplies the effect of the pumps, producing a far steeper gradient than a straight tubule could achieve, with the lowest water potential at the base of the medulla.
The collecting duct then passes back down through this gradient. As filtrate descends, water moves out by osmosis into the medulla and is carried away by the blood, concentrating the urine.
Loop length correlates with habitat, and this is a standard comparison question. A desert mammal such as the kangaroo rat has very long loops of Henle and a thick medulla, producing a very steep gradient and therefore very concentrated urine, conserving water. A mammal living in fresh water or a well-watered habitat, such as the beaver, has short loops and produces dilute urine. Humans are intermediate.
Osmoregulation and ADH
Osmoreceptors in the hypothalamus detect the water potential of the blood.
If the blood water potential falls, for example through sweating, insufficient drinking or a salty meal, water leaves the osmoreceptor cells by osmosis and they shrink. This stimulates the hypothalamus, and the posterior pituitary gland releases more antidiuretic hormone into the blood.
ADH travels to the kidney and binds to receptors on the cells of the collecting duct and distal convoluted tubule. This triggers the insertion of aquaporins, water channel proteins, into the cell surface membrane, making it far more permeable to water.
More water is therefore reabsorbed from the filtrate into the medulla and the blood as it passes down the concentration gradient. A small volume of concentrated urine is produced, and the blood water potential rises back towards normal.
If the blood water potential rises above normal, less ADH is released, fewer aquaporins are present, less water is reabsorbed and a large volume of dilute urine is produced.
The whole system is negative feedback, and the answer must include the receptor, the hormone, the effect on the collecting duct and the return towards the set point.
Alcohol inhibits ADH release, which explains the diuretic effect and the dehydration that follows.
Control of blood glucose
The pancreas contains islets of Langerhans with two relevant cell types: beta cells producing insulin, and alpha cells producing glucagon.
When blood glucose rises after a meal, beta cells detect the change and secrete insulin. Insulin binds to receptors on liver and muscle cells, increasing the number of glucose transporter proteins in their membranes so that more glucose is taken up, and activating enzymes that convert glucose to glycogen. Blood glucose concentration therefore falls.
When blood glucose falls, alpha cells secrete glucagon. Glucagon binds to receptors on liver cells and activates enzymes that hydrolyse glycogen to glucose and that form glucose from non-carbohydrate sources such as amino acids and glycerol. Glucose is released into the blood and the concentration rises.
Adrenaline also raises blood glucose by stimulating glycogen breakdown, preparing the body for activity.
In type 1 diabetes the beta cells are destroyed, usually by an autoimmune response, so little or no insulin is produced. It usually begins in childhood and is treated by insulin injection with monitoring of blood glucose and control of diet.
In type 2 diabetes the cells become less responsive to insulin, often through a reduction in receptor number or sensitivity. It is associated with obesity, diet and inactivity, usually develops later in life, and is managed primarily by diet and exercise, sometimes with medication.
Worked examples
Example 1: Explaining the composition of filtrate (4 marks)
Explain why glomerular filtrate contains glucose but no plasma protein, and why urine normally contains neither.
Blood in the glomerulus is under high hydrostatic pressure because the efferent arteriole is narrower than the afferent arteriole. This forces small molecules through the capillary fenestrations, the basement membrane and the filtration slits between podocytes.
Glucose molecules are small enough to pass through the pores of the basement membrane and so enter the filtrate. Plasma proteins have a much larger molecular size and cannot pass through, so they remain in the blood.
Urine contains no glucose because all of it is reabsorbed in the proximal convoluted tubule by co-transport with sodium ions, followed by facilitated diffusion into the blood. It contains no protein because none entered the filtrate in the first place.
Example 2: Explaining loop length (5 marks)
Explain why a desert-dwelling mammal has longer loops of Henle than a mammal from a well-watered habitat.
The loop of Henle establishes a gradient of decreasing water potential from the cortex into the medulla, by actively pumping sodium and chloride ions out of the water-impermeable ascending limb while the descending limb loses water by osmosis, an arrangement that multiplies the gradient.
A longer loop extends deeper into the medulla, so ions are pumped out over a greater distance and the counter-current multiplier operates over a longer run. This produces a steeper gradient and a much lower water potential at the base of the medulla.
The collecting duct passes back down through this gradient, and the steeper it is, the more water moves out of the filtrate by osmosis.
A desert mammal therefore reabsorbs a greater proportion of the water in the filtrate and produces a small volume of highly concentrated urine, conserving water in an environment where it is scarce. A mammal with abundant water has no such need, so short loops and dilute urine are sufficient.
Example 3: Explaining the response to dehydration (5 marks)
Describe the response to a fall in blood water potential following heavy sweating.
Sweating removes water from the blood, so the water potential of the blood becomes more negative.
Osmoreceptors in the hypothalamus detect this. Water leaves these cells by osmosis and they shrink, which stimulates the hypothalamus.
The posterior pituitary gland releases more antidiuretic hormone into the blood, which travels to the kidney.
ADH binds to receptors on the cells of the collecting duct, causing aquaporins to be inserted into the cell surface membranes and greatly increasing their permeability to water.
More water therefore moves out of the filtrate by osmosis into the concentrated medulla and back into the blood, so a small volume of concentrated urine is produced and the blood water potential rises back towards normal. This is negative feedback, since the response reverses the original change.
Common mistakes and how to avoid them
The most frequent error is confusing excretion with egestion. Egested material has never been part of metabolism.
Students often state that ADH increases water reabsorption by pumping water. Water always moves by osmosis; ADH acts by increasing membrane permeability through aquaporins.
Another common slip is describing the ascending limb as permeable to water. It is impermeable, which is precisely why the surrounding tissue fluid becomes concentrated.
Many candidates say that glucose is reabsorbed by active transport directly. It is reabsorbed by co-transport with sodium, and it is sodium that is actively transported.
In negative feedback answers, candidates frequently describe only one direction. Both the response to a rise and to a fall are usually required.
Finally, candidates often confuse the two types of diabetes. Type 1 is a failure to produce insulin; type 2 is a failure of cells to respond to it.
Exam technique for "Homeostasis, excretion and osmoregulation"
Structure every control answer around receptor, coordinator, effector and response, and state explicitly that the change is reversed.
For nephron questions, name the region of the nephron before describing the process. Different processes occur in different regions and the mark often depends on the location.
When explaining the loop of Henle, describe the two limbs separately and state the permeability of each, since the difference is the whole mechanism.
Use the term water potential with its sign rather than talking about concentration, and state the direction of osmosis explicitly.
For adaptation questions, relate the structural feature to the process it serves: microvilli for surface area, mitochondria for ATP, long loops for a steeper gradient.
Quick revision summary
Homeostasis maintains temperature, blood glucose, water potential and pH within narrow limits by negative feedback, with separate mechanisms reversing rises and falls. Excess amino acids are deaminated in the liver, the ammonia converted to less toxic urea. In the nephron, the narrower efferent arteriole raises glomerular pressure, driving ultrafiltration through capillary fenestrations, the basement membrane and podocyte slits, so that filtrate contains glucose and urea but no cells or protein. The proximal convoluted tubule reabsorbs all glucose and amino acids by co-transport with sodium, aided by microvilli and numerous mitochondria, with water following by osmosis. The loop of Henle acts as a counter-current multiplier: ions are pumped from the water-impermeable ascending limb while water leaves the descending limb, creating a steep salt gradient in the medulla, and longer loops in desert mammals give more concentrated urine. Osmoreceptors in the hypothalamus detect falling water potential, the posterior pituitary releases ADH, and aquaporins inserted into the collecting duct increase water reabsorption. Insulin from beta cells lowers blood glucose by increasing uptake and glycogen formation; glucagon from alpha cells raises it by glycogen hydrolysis.