Homeostasis is the maintenance of a stable internal environment

In a nutshell

Homeostasis is the maintenance of a stable internal environment, so that cells work in conditions that stay close to their optimum.

This subtopic covers three things: the principle of negative feedback (and how it differs from positive feedback), the control of blood glucose concentration (insulin, glucagon, adrenaline, the second messenger model and diabetes), and the control of blood water potential by the kidney (osmoregulation, the nephron and ADH).

Assumed knowledge: Transport across cell membranes, Proteins, ATP.

Core content

What homeostasis is, and why it matters

Homeostasis is the maintenance of a constant internal environment within restricted limits. It relies on physiological control systems that keep conditions such as temperature, pH and glucose concentration close to a set point.

Three examples you must be able to justify:

• Stable core temperature. Enzymes have an optimum temperature. Too high and enzymes are denatured (the tertiary structure changes, so the substrate no longer fits the active site), so reactions slow or stop. Too low and molecules have less kinetic energy, so there are fewer successful collisions and fewer enzyme-substrate complexes form.
• Stable blood pH. Enzymes also have an optimum pH. A change in pH alters the ionic and hydrogen bonds holding the enzyme's tertiary structure, changing the shape of the active site so the substrate cannot bind.
• Stable blood glucose concentration. Glucose is the main respiratory substrate, so cells need a reliable supply to make ATP. Blood glucose also sets the water potential of the blood: if it rises too high the blood water potential falls, so water leaves cells by osmosis; if it falls too low, cells lack a respiratory substrate.

Negative feedback: the core principle

Negative feedback is a mechanism in which a change from the normal (set) level triggers a response that reverses the change and returns the system to its original level.

The general sequence is always the same:

1. A stimulus: a factor deviates from its set point.
2. A receptor detects the change.
3. A coordinator (for example the hypothalamus or a gland) processes the information.
4. An effector brings about a response.
5. The response reverses the original change, so the factor returns to the set point (and the correction is then switched off).

The key exam idea AQA credits: separate mechanisms control departures in different directions from the set point, and having two opposing mechanisms gives a greater degree of control. For example, one mechanism lowers blood glucose when it is too high and a different mechanism raises it when it is too low, so the value can be actively pushed back from either side rather than just left to drift.

Positive feedback (for comparison)

Positive feedback is a mechanism in which a change triggers a response that increases (amplifies) the original change, causing a greater deviation from the normal level. It does not restore a set point.

The phrase examiners look for is the idea of "more leads to more": the change produces a response, and that response makes the change even bigger. Examples you may be asked to interpret include the entry of sodium ions during an action potential (depolarisation opens more sodium ion channels) and oxytocin during childbirth (contractions stimulate more oxytocin, causing stronger contractions).

You are expected to interpret examples of negative and positive feedback, so read any data or diagram carefully and decide whether the response opposes the change (negative) or amplifies it (positive).

Control of blood glucose: the factors and the organs

The factors that change blood glucose concentration are simple:

• It rises when carbohydrate is eaten and glucose is absorbed from the gut into the blood.
• It falls when glucose is used in respiration, for example during exercise.

Blood glucose is monitored and controlled by the pancreas. Cells in the islets of Langerhans detect the concentration and secrete two antagonistic hormones:

• β (beta) cells secrete insulin when blood glucose is too high.
• α (alpha) cells secrete glucagon when blood glucose is too low.

After a meal (roughly 0 to 3 hours above) glucose rises, insulin is released and brings it back down. During fasting or exercise (roughly 5 to 7 hours) glucose falls, glucagon is released and brings it back up. The value fluctuates around, and is returned to, the set point.

The role of the liver

The liver stores and releases glucose through three processes you must be able to name and define:

• Glycogenesis: the conversion of glucose to glycogen (when blood glucose is high).
• Glycogenolysis: the breakdown of glycogen to glucose (when blood glucose is low).
• Gluconeogenesis: the production of glucose from non-carbohydrate sources such as glycerol and amino acids (when glycogen stores are low).

The action of insulin (lowers blood glucose)

When blood glucose is too high, insulin is secreted and acts by:

• attaching to receptors on the surfaces of target cells (liver, muscle and fat cells);
• increasing glucose uptake, by increasing the number of glucose channel / carrier (transport) proteins in the cell surface membranes, so more glucose enters the cells by facilitated diffusion;
• activating enzymes that convert glucose to glycogen (glycogenesis).

The net effect is that more glucose is taken out of the blood and stored or respired, so blood glucose falls back to normal.

Note the wording examiners insist on: insulin does not "turn glucose into glycogen" itself, and it does not simply "open" existing channels. It activates enzymes and causes more transport proteins to be added to the membrane.

The action of glucagon (raises blood glucose)

When blood glucose is too low, glucagon is secreted and acts by:

• attaching to receptors on the surfaces of target cells (liver cells);
• activating enzymes that convert glycogen to glucose (glycogenolysis);
• activating enzymes that convert glycerol and amino acids into glucose (gluconeogenesis).

The glucose then leaves the liver cells and enters the blood, raising blood glucose back to normal.

The role of adrenaline

Adrenaline is released in response to stress or exercise ("fight or flight") and raises blood glucose by:

• attaching to receptors on the surfaces of target cells;
• activating enzymes that convert glycogen to glucose (glycogenolysis).

This makes more glucose available for respiration when the body may need to be active.

The second messenger model (adrenaline and glucagon)

Adrenaline and glucagon are proteins, so they cannot cross the cell surface membrane to act inside the cell. They use a second messenger instead.

The cascade, in order:

1. The hormone (first messenger) binds to a specific receptor on the cell surface membrane.
2. This activates the membrane enzyme adenylate cyclase.
3. Adenylate cyclase converts ATP into cyclic AMP (cAMP), the second messenger.
4. cAMP activates protein kinase (an enzyme).
5. Protein kinase activates the enzymes that carry out glycogenolysis, releasing glucose.

Still don't get it? · why a "second messenger" is needed

Imagine you are outside a locked house and you need something done inside, but you cannot get in. You knock on the door (you stay outside), someone inside hears you, and they run around switching on the lights and appliances. You never entered, yet the whole house responds.

Now the cell version, one step at a time. The hormone is stuck outside the cell because it cannot cross the membrane, so it only "knocks" by binding to a receptor on the surface. That knock switches on adenylate cyclase in the membrane, which makes a messenger inside the cell, cyclic AMP. cAMP is the person running around inside: it switches on protein kinase, which switches on the enzymes that break glycogen down to glucose.

So the exam answer is a chain, and you must give it in order: hormone binds to receptor, activating adenylate cyclase, which converts ATP to cyclic AMP (the second messenger), which activates protein kinase, which activates the enzymes for glycogenolysis. The hormone itself never enters the cell.

Insulin also works by binding to receptors, but it does not use the cyclic AMP second messenger system.

Insulin, glucagon and adrenaline compared

Diabetes

Diabetes is the inability to control blood glucose concentration.

Evaluating the response to rising type II diabetes. You may be asked to weigh the positions of health advisers and the food industry:

• Health advisers argue for lower sugar and fat in foods, clearer labelling, more physical activity, and measures such as sugar taxes, because type II diabetes damages health and is costly to treat.
• The food industry may point to consumer choice and personal responsibility, and may be reluctant to bear the cost of reformulating products or clearer labelling.

A good answer presents evidence on both sides rather than simply blaming one party.

Required practical 11: measuring glucose with a calibration curve

This required practical uses quantitative colorimetry to find the glucose concentration of an unknown "urine" sample.

Method:

1. Make a dilution series of a glucose solution of known concentrations (a serial dilution).
2. Carry out a quantitative Benedict's test on each standard: heat with excess Benedict's solution. The more glucose there is, the more brick-red precipitate forms, so the less blue Benedict's solution is left.
3. Remove the precipitate (filter or centrifuge) and measure the absorbance of the remaining blue solution with a colorimeter (using a red filter).
4. Plot a calibration curve of absorbance against known glucose concentration.
5. Treat the unknown sample in the same way, measure its absorbance, and read its glucose concentration off the calibration curve.

Because more glucose leaves less blue solution, absorbance falls as glucose concentration rises. The known standards define the curve, and the unknown is read against it.

Osmoregulation: controlling the water potential of the blood

Osmoregulation is the control of the water potential of the blood. It is carried out by the kidney, which filters the blood and reabsorbs useful substances and water.

The functional unit of the kidney is the nephron.

The blood is processed in stages along the nephron:

• Ultrafiltration (glomerulus and Bowman's capsule). Blood enters the glomerulus through a wide afferent arteriole and leaves through a narrower efferent arteriole, creating a high hydrostatic pressure. This forces small molecules (water, glucose, amino acids, ions and urea) out of the blood, through the basement membrane (which acts as the filter), into the Bowman's capsule. Large molecules such as plasma proteins, and blood cells, are too big to pass and stay in the blood. The fluid formed is the glomerular filtrate.
• Reabsorption in the proximal convoluted tubule (PCT). All of the glucose, plus some ions and water, is reabsorbed back into the blood here. Glucose is reabsorbed by active transport (co-transported with sodium ions), and water follows by osmosis. The PCT cells are adapted with microvilli (large surface area), many mitochondria (ATP for active transport) and carrier and channel proteins.
• Maintaining a sodium ion gradient in the medulla (loop of Henle). The loop acts as a countercurrent multiplier that gives the medulla a very low water potential, as set out below.
• Water reabsorption (distal convoluted tubule and collecting duct). As filtrate flows down the collecting duct through the low water potential medulla, water leaves by osmosis and is reabsorbed into the blood. How much is reabsorbed is controlled by ADH.

The loop of Henle

Pumping sodium ions out of the ascending limb lowers the water potential of the medulla (the surrounding tissue fluid). The longer the loop, and the deeper into the medulla, the lower the water potential becomes. This low water potential is what draws water out of the collecting duct later.

Still don't get it? · the loop of Henle and why the medulla matters

Think of the medulla as a very salty swimming pool, and the collecting duct as a thin water pipe running through the bottom of it. Water always moves from the pipe out into the saltier pool. The saltier the pool, the more water is pulled out of the pipe. The loop of Henle's whole job is to keep that pool salty.

Now step through how it does that. The ascending limb pumps sodium ions out into the surrounding tissue (the "pool"), and because the ascending limb is waterproof, the water cannot follow, so the tissue just gets saltier and its water potential drops. Because the loop is long and hairpin-shaped, this salty region builds up more and more towards the bottom of the medulla (this is why a longer loop makes a more concentrated urine).

So the exam answer joins the two ideas: the loop pumps sodium ions out of the ascending limb (by active transport) and keeps water in, giving the medulla a low water potential; then, as filtrate runs down the collecting duct through that low water potential, water is reabsorbed by osmosis. Always say "water potential", never "water concentration", and always say the ions are moved by active transport.

The role of the hypothalamus, posterior pituitary and ADH

Water reabsorption is fine-tuned by antidiuretic hormone (ADH) through negative feedback.

When the water potential of the blood is too low (for example after sweating or not drinking):

1. Osmoreceptors in the hypothalamus detect the fall in water potential.
2. The posterior pituitary releases more ADH into the blood.
3. ADH makes the walls of the distal convoluted tubule and collecting duct more permeable to water, by causing aquaporins (water channel proteins) to be inserted into the cell surface membranes.
4. More water is reabsorbed into the blood by osmosis.
5. A smaller volume of more concentrated urine is produced, and the water potential of the blood rises back to normal.

When the water potential of the blood is too high, the converse happens: less ADH is released, the walls are less permeable to water, less water is reabsorbed, and a larger volume of dilute urine is produced.

Worked examples

Model 5-mark answer: "Explain how a rise in blood glucose concentration after a meal is returned to normal by negative feedback."

1. The rise in blood glucose is detected by the β cells in the islets of Langerhans in the pancreas.
2. The β cells secrete insulin, which binds to receptors on target cells (liver, muscle and fat cells).
3. Insulin causes more glucose transport (channel/carrier) proteins to be added to the cell surface membranes, so more glucose enters cells by facilitated diffusion.
4. Insulin also activates enzymes that convert glucose to glycogen (glycogenesis) in the liver.
5. Blood glucose therefore falls back to the set point, and this reverses the original change, which is negative feedback.

The lesson: a five-mark "explain" answer needs five distinct, linked points, and it must name the detector, the hormone, the two actions and the idea that the change is reversed.

Data-handling example: reading the calibration curve.

An unknown "urine" sample is tested by the same method and gives an absorbance of 0.58.

• Find 0.58 on the absorbance (y) axis of the calibration curve.
• Read across to the curve, then down to the glucose axis.
• 0.58 lies halfway between the standards at 2 mmol dm⁻³ (absorbance 0.66) and 3 mmol dm⁻³ (absorbance 0.50), so the sample contains approximately 2.5 mmol dm⁻³ glucose.

Always read the unknown against the curve built from the known standards, and quote the units.

Common exam mistakes

• Confusing glucagon (the hormone) with glycogen (the storage polymer). The spellings are close and examiners reject ambiguous versions such as "glucogen"; the spelling of glucagon must be exact.
• Writing that insulin "converts glucose into glycogen" or acts as an enzyme. Insulin activates the enzymes that do the conversion and increases glucose uptake; it is not itself the catalyst.
• Saying insulin "opens channels" or forgetting the numbers. The credited idea is that more transport (channel/carrier) proteins are added to the membrane.
• Writing that glucose "only enters cells when insulin is present". Glucose is always taken up; insulin increases the rate of uptake.
• Saying "glucagon breaks down glycogen" (as if the hormone acts directly) or that "glucagon is broken down into glucose". Glucagon activates enzymes that carry out glycogenolysis.
• In the second messenger model, being unable to name adenylate cyclase, or thinking it acts directly on glycogen. Give the full chain: receptor, adenylate cyclase, cyclic AMP, protein kinase, glycogenolysis.
• Calling the hormone-receptor site an "active site". Hormones bind to a receptor (binding) site; a hormone is not an enzyme and has no substrate.
• Writing that "enzymes are denatured by extremes of temperature". A low temperature does not denature enzymes; it slows reactions by reducing kinetic energy and the frequency of collisions.
• Saying type II diabetes is "not genetic", or describing it only as "resistance/immunity to insulin". The credited idea is that the cells/receptors are less responsive to insulin (and there is a genetic component).
• Forgetting that all the glucose is reabsorbed in the PCT, or giving the wrong location for glucose reabsorption.
• Using "salts" instead of "ions", or "water concentration" instead of "water potential". AQA requires the precise terms.
• In the loop of Henle, saying ions "diffuse" out of the ascending limb. Sodium ions are removed by active transport, and the ascending limb is impermeable to water. Do not swap the descending and ascending limbs.
• Saying ADH is released from the hypothalamus. It is made in the hypothalamus but released from the posterior pituitary; and it acts on the collecting duct and DCT, where water is reabsorbed by osmosis.

Key definitions

• Homeostasis: the maintenance of a constant (stable) internal environment within restricted limits.
• Negative feedback: a mechanism in which a change from the normal (set) level triggers a response that reverses the change and returns the system to its original level.
• Positive feedback: a mechanism in which a change triggers a response that increases (amplifies) the original change, causing a greater deviation from the normal level.
• Glycogenesis: the conversion of glucose to glycogen.
• Glycogenolysis: the breakdown of glycogen to glucose.
• Gluconeogenesis: the production of glucose from non-carbohydrate sources such as glycerol and amino acids.
• Second messenger (cyclic AMP): a molecule produced inside a target cell (from ATP, by adenylate cyclase) when a hormone binds to a receptor on the cell surface, which activates protein kinase to bring about the cell's response.
• Osmoregulation: the control of the water potential of the blood.
• Ultrafiltration: filtration under high hydrostatic pressure, in which small molecules are forced out of the glomerular capillaries through the basement membrane into the renal (Bowman's) capsule, while large molecules such as proteins remain in the blood.
• Antidiuretic hormone (ADH): a hormone that increases the permeability of the distal convoluted tubule and collecting duct to water, increasing water reabsorption.

Specification

• I can state that homeostasis is the maintenance of a constant internal environment within restricted limits, using physiological control systems.
• I can explain the importance of a stable core temperature and stable blood pH in relation to enzyme activity.
• I can explain the importance of a stable blood glucose concentration in terms of a respiratory substrate and the water potential of the blood.
• I can explain how negative feedback restores a system to its original level.
• I can explain how separate mechanisms controlling departures in different directions give a greater degree of control, and interpret examples of negative and positive feedback.
• I can state the factors that influence blood glucose concentration.
• I can describe the role of the liver in glycogenesis, glycogenolysis and gluconeogenesis.
• I can describe the action of insulin, including receptor binding, regulating glucose uptake through channel proteins, and activating enzymes for glycogenesis.
• I can describe the action of glucagon, including glycogenolysis and gluconeogenesis.
• I can describe the role of adrenaline in activating glycogenolysis.
• I can describe the second messenger model of adrenaline and glucagon, involving adenylate cyclase, cyclic AMP and protein kinase.
• I can describe the causes of type I and type II diabetes and their control, and evaluate the positions of health advisers and the food industry.
• I can produce a dilution series and use colorimetry to make a calibration curve to find the glucose concentration of an unknown sample.
• I can explain osmoregulation as control of the water potential of the blood, and the roles of the hypothalamus, posterior pituitary and ADH.
• I can describe the structure of the nephron and its role in ultrafiltration, reabsorption in the PCT, the sodium ion gradient set up by the loop of Henle, and water reabsorption in the DCT and collecting duct.

Related notes

• Transport across cell membranes
• Proteins
• Survival and response to stimuli
• Nervous coordination