Homeostasis

Every objective in this topic is printed under "A Level subject content" in the 9700 syllabus, so all of it is A Level and none of it is AS. It is examined on Paper 4. Paper 1 is the AS multiple-choice paper and does not reach this topic, so no multiple-choice practice on this site is tagged to it.

Syllabus points

14.1 Homeostasis in mammals

• Explain what is meant by homeostasis and the importance of homeostasis in mammals.
• Explain the principles of homeostasis in terms of internal and external stimuli, receptors, coordination systems (nervous system and endocrine system), effectors (muscles and glands) and negative feedback.
• State that urea is produced in the liver from the deamination of excess amino acids.
• Describe the structure of the human kidney, limited to: fibrous capsule; cortex; medulla; renal pelvis; ureter; branches of the renal artery and renal vein.
• Identify, in diagrams, photomicrographs and electron micrographs, the parts of a nephron and its associated blood vessels and structures, limited to: glomerulus; Bowman's capsule; proximal convoluted tubule; loop of Henle; distal convoluted tubule; collecting duct.
• Describe and explain the formation of urine in the nephron, limited to: the formation of glomerular filtrate by ultrafiltration in the Bowman's capsule; selective reabsorption in the proximal convoluted tubule.
• Relate the detailed structure of the Bowman's capsule and proximal convoluted tubule to their functions in the formation of urine.
• Describe the roles of the hypothalamus, posterior pituitary gland, antidiuretic hormone (ADH), aquaporins and collecting ducts in osmoregulation.
• Describe the principles of cell signalling using the example of the control of blood glucose concentration by glucagon, limited to: binding of hormone to cell surface receptor causing conformational change; activation of G-protein leading to stimulation of adenylyl cyclase; formation of the second messenger, cyclic AMP (cAMP); activation of protein kinase A by cAMP leading to initiation of an enzyme cascade; amplification of the signal through the enzyme cascade as a result of activation of more and more enzymes by phosphorylation; cellular response in which the final enzyme in the pathway is activated, catalysing the breakdown of glycogen.
• Explain how negative feedback control mechanisms regulate blood glucose concentration, with reference to the effects of insulin on muscle cells and liver cells and the effect of glucagon on liver cells.
• Explain the principles of operation of test strips and biosensors for measuring the concentration of glucose in blood and urine, with reference to glucose oxidase and peroxidase enzymes.

14.2 Homeostasis in plants

• Explain that stomata respond to changes in environmental conditions by opening and closing and that regulation of stomatal aperture balances the need for carbon dioxide uptake by diffusion with the need to minimise water loss by transpiration.
• Explain that stomata have daily rhythms of opening and closing.
• Describe the structure and function of guard cells and explain the mechanism by which they open and close stomata.
• Describe the role of abscisic acid in the closure of stomata during times of water stress, including the role of calcium ions as a second messenger.

What homeostasis is, and why it matters

Homeostasis is the maintenance of a constant internal environment, within narrow limits, despite changes in external and internal conditions. Note the word constant, not fixed: the values fluctuate around a set point rather than sitting still.

It matters because enzymes are fussy. Temperature, pH and the concentration of solutes all affect enzyme activity, so a cell that let those drift would let every reaction in its metabolism drift with them. Constant water potential also keeps cells from bursting or shrivelling by osmosis, and a constant blood glucose concentration keeps respiratory substrate available to the brain, which cannot store glucose and cannot respire fatty acids.

The control loop

Every homeostatic mechanism has the same shape, and if you can name the parts you can answer almost any question of this type:

stimulus → receptor → coordination system → effector → response

• A stimulus is a change, internal or external.
• A receptor detects it. Osmoreceptors in the hypothalamus detect blood water potential; cells in the islets of Langerhans detect blood glucose.
• A coordination system carries the information: the nervous system as electrical impulses, or the endocrine system as hormones in the blood.
• An effector acts: a muscle or a gland.
• The response brings the value back towards the set point.

That last part is negative feedback: the response opposes the change that triggered it, so the value oscillates about the set point instead of running away. Contrast positive feedback, where the response amplifies the change. Positive feedback is not homeostatic and the examples in biology are events rather than states, such as the depolarisation of a neurone or the oxytocin loop of childbirth.

Excretion and urea

Amino acids cannot be stored. Excess ones are deaminated in the liver: the amino group is removed and converted, through the ornithine cycle, into urea, which is far less toxic than ammonia and is carried in solution in the blood plasma to the kidneys.

Note the division of labour, because questions test it: urea is made in the liver and excreted by the kidney. The kidney does not make it.

Structure of the kidney

From outside in: the fibrous capsule around the whole organ; the cortex, the darker outer region; the medulla beneath it; and the renal pelvis, the funnel that collects urine and leads to the ureter. The renal artery brings blood in and branches to supply every glomerulus; the renal vein takes it away.

A nephron straddles the two regions. Bowman's capsule, the proximal convoluted tubule and the distal convoluted tubule are in the cortex; the loop of Henle and the collecting duct run down into the medulla. That layout is what makes a section of kidney recognisable under a microscope: the cortex is full of round glomeruli and cut tubules, and the medulla shows long parallel tubes.

Along a nephron: glomerulus → Bowman's capsule → proximal convoluted tubule → loop of Henle → distal convoluted tubule → collecting duct.

Ultrafiltration

Blood arrives at the glomerulus through the afferent arteriole and leaves through the efferent arteriole, which is narrower. That difference is the whole mechanism: forcing the same volume out through a narrower exit raises the hydrostatic pressure inside the glomerular capillaries well above the pressure in the capsule.

The filter has three layers:

1. The capillary endothelium, which is fenestrated, meaning it is perforated by pores.
2. The basement membrane, a mesh of collagen and glycoproteins. This is the actual sieve, and it is the layer that decides what gets through.
3. The podocytes, cells with finger-like processes wrapped round the capillary, leaving gaps between them.

Water, glucose, amino acids, mineral ions, urea and other small solutes pass into the capsule. Plasma proteins and blood cells are held back, because they are too large to cross the basement membrane. So finding protein in the urine points at damage to the basement membrane, and finding blood cells points at damage further along.

Worked example. The renal arteries carry about 1200 cm³ of blood each minute, and roughly 125 cm³ of filtrate is formed each minute, yet urine is produced at about 1 cm³ per minute.

filtrate per day = 125 × 60 × 24 = 180000 cm³

urine per day = 1 × 60 × 24 = 1440 cm³

So about 99 per cent of the filtrate is reabsorbed:

(180000 - 1440) / 180000 × 100 = 99.2%

That figure is the reason reabsorption, not filtration, is the interesting half of the story. The kidney filters indiscriminately and then takes back what it wants.

Selective reabsorption in the proximal convoluted tubule

All the glucose and all the amino acids, most of the mineral ions and most of the water are reabsorbed here. The mechanism is worth reading as a chain rather than memorising as a list:

1. Sodium-potassium pumps on the basal membrane, the side facing the blood, actively pump sodium ions out of the tubule cell into the tissue fluid.
2. That lowers the sodium concentration inside the cell, so sodium diffuses into the cell from the tubule lumen through co-transporter proteins.
3. Each co-transporter carries a glucose or an amino acid molecule in with the sodium. This is facilitated diffusion of sodium coupled to the active transport of glucose against its gradient, and it is why glucose reabsorption ultimately depends on ATP even though the glucose carrier itself does not hydrolyse ATP.
4. Glucose then leaves the cell into the blood by facilitated diffusion.
5. All those solutes moving into the blood lower its water potential, so water follows by osmosis.

Structure matches this exactly:

• Microvilli on the luminal surface give a very large surface area for the carriers.
• Many mitochondria, because the sodium-potassium pumps run continuously and consume a great deal of ATP.
• Many carrier and co-transporter proteins in the membranes.
• Tight junctions between neighbouring cells, so substances must pass through the cells rather than between them, which is what makes the process selective.
• The cells sit against a dense capillary network that carries reabsorbed material away and keeps the gradient steep.

Bowman's capsule likewise matches its job: podocytes with gaps between their processes, a thin basement membrane and fenestrated capillaries, all of which make it a filter rather than a barrier.

Osmoregulation

The pathway is short and the marks are in stating it in order.

When blood water potential falls, for instance after sweating or after a salty meal:

1. Osmoreceptors in the hypothalamus shrink as water leaves them by osmosis, and this stimulates them.
2. The hypothalamus signals the posterior pituitary gland to release antidiuretic hormone (ADH) into the blood. ADH is made in the hypothalamus and stored in the posterior pituitary; the pituitary does not manufacture it.
3. ADH binds to receptors on the cells of the collecting duct and the distal convoluted tubule, triggering vesicles carrying aquaporins to fuse with the cell surface membrane.
4. More aquaporins means the collecting duct wall is more permeable to water, so more water is reabsorbed by osmosis into the concentrated tissue fluid of the medulla.
5. A small volume of concentrated urine is produced, and blood water potential rises back towards normal. That is the negative feedback.

When blood water potential rises, less ADH is released, the aquaporins are removed from the membrane by endocytosis, the collecting duct becomes less permeable, and a large volume of dilute urine is produced.

Two points that are regularly mishandled. ADH does not pump water; it changes permeability, and the water still moves by osmosis. And the gradient it exploits is set up by the loop of Henle, which makes the medulla tissue fluid progressively more concentrated with depth.

Cell signalling: glucagon and the second messenger

This is the syllabus's worked example of how a hormone that never enters a cell can change what that cell does. Glucagon is a peptide and cannot cross the phospholipid bilayer, so everything happens through a relay.

1. Glucagon binds to a receptor on the cell surface membrane of a liver cell. The receptor changes shape, a conformational change.
2. The changed receptor activates a G-protein.
3. The G-protein stimulates adenylyl cyclase, an enzyme on the inside of the membrane.
4. Adenylyl cyclase converts ATP into cyclic AMP (cAMP), the second messenger. The hormone was the first messenger; cAMP carries the signal on inside the cell.
5. cAMP activates protein kinase A, which begins an enzyme cascade: each kinase phosphorylates and thereby activates the next enzyme.
6. Because one enzyme activates many molecules of the next, the signal is amplified at every step. A handful of hormone molecules can end up mobilising a great deal of glucose.
7. The final enzyme in the cascade is activated and catalyses the breakdown of glycogen to glucose, which leaves the liver cell and raises blood glucose concentration.

The two ideas being examined are amplification and the fact that the same hormone can produce different responses in different cells, because what a cell does with cAMP depends on which enzymes it happens to contain.

Negative feedback and blood glucose

Normal blood glucose is around 90 mg per 100 cm³, or roughly 5 mmol dm⁻³.

Blood glucose rises after a meal. Beta cells in the islets of Langerhans detect this and secrete insulin. Insulin:

• causes vesicles carrying GLUT4 transporter proteins to fuse with the cell surface membranes of muscle and liver cells, so more glucose enters them by facilitated diffusion,
• activates enzymes that convert glucose to glycogen (glycogenesis) in liver and muscle cells,
• increases the rate at which cells respire glucose, and
• promotes conversion of glucose to fat.

Blood glucose falls, the beta cells detect the fall, and insulin secretion drops. Negative feedback.

Blood glucose falls during fasting or exercise. Alpha cells secrete glucagon, which acts on liver cells only, through the cascade above, to:

• break glycogen down to glucose (glycogenolysis), and
• form glucose from non-carbohydrate sources such as amino acids and glycerol (gluconeogenesis).

Blood glucose rises, and glucagon secretion drops.

The asymmetry is examinable: insulin acts on both liver and muscle; glucagon acts on the liver. Muscle glycogen has no glucagon receptors, which is why muscle glycogen serves only the muscle that stores it and never restores blood glucose directly.

Test strips and biosensors

Both rely on the same pair of enzymes, and both are specific to glucose because the enzyme is.

• Glucose oxidase catalyses the oxidation of glucose to gluconic acid and hydrogen peroxide.
• Peroxidase then catalyses a reaction between that hydrogen peroxide and a colourless chemical in the pad, producing a coloured product.

On a test strip, the depth of colour is compared with a chart, so the reading is semi-quantitative. In a biosensor, the strip sits in an electrode and the reaction generates a small current proportional to the glucose concentration, which is displayed as a number. The biosensor is quantitative and far more precise.

The specificity is the point. The enzyme binds glucose and not other sugars, so a positive result means glucose and nothing else. Benedict's solution, by contrast, responds to any reducing sugar.

Homeostasis in plants: stomata

A stoma is a compromise. Open, and carbon dioxide diffuses in for photosynthesis, but water vapour diffuses out. Closed, and water is conserved, but photosynthesis is starved. The plant regulates the aperture rather than choosing one or the other, and it does so continually as conditions change.

Stomata show a daily rhythm, opening around dawn and closing around dusk, and the rhythm persists for a while even in constant conditions, which shows it is driven by an internal clock and not only by the light itself.

How guard cells work

Guard cells are the only epidermal cells with chloroplasts, and their walls are unevenly thickened: thick and inelastic on the inner side facing the pore, thinner and elastic on the outer side. Cellulose microfibrils run round the cell in hoops, so the cell cannot expand in girth, only in length.

To open:

1. ATP-powered proton pumps in the guard cell membrane pump hydrogen ions out of the cell.
2. The inside becomes more negative, and this drives potassium ions in through voltage-gated channels.
3. The higher solute concentration lowers the water potential of the guard cell.
4. Water enters by osmosis and the cell becomes turgid.
5. Because the outer wall stretches more than the inner wall, the cell curves away from its partner and the pore opens.

To close, the pumping stops, potassium leaves, water potential rises, water leaves by osmosis, the cells become flaccid and the pore closes.

Abscisic acid and water stress

When a plant is short of water, abscisic acid (ABA) is produced, chiefly in the roots and leaves, and it closes stomata quickly, before wilting sets in.

1. ABA binds to receptors on the guard cell surface membrane.
2. This causes calcium ions to enter the cytoplasm, from outside the cell and from the vacuole. Calcium ions are the second messenger here, exactly as cAMP was in the glucagon example.
3. Calcium ions open channels that let negative ions out of the guard cell, and inhibit the proton pumps.
4. The loss of negative ions makes the inside less negative, so potassium ions leave too.
5. Water potential rises, water leaves by osmosis, the guard cells become flaccid, and the stoma closes.

Common mistakes

• Defining homeostasis as keeping conditions exactly the same, rather than within narrow limits about a set point.
• Describing a positive feedback loop and calling it negative feedback. Ask whether the response opposes or reinforces the change.
• Saying the kidney makes urea. The liver makes it by deamination; the kidney removes it.
• Explaining ultrafiltration without the narrower efferent arteriole, so the source of the high hydrostatic pressure is never given.
• Saying proteins are reabsorbed. They never enter the filtrate in the first place.
• Calling reabsorption in the proximal convoluted tubule simple diffusion, or forgetting that the sodium-potassium pump is what makes the co-transport of glucose possible.
• Saying ADH causes water to be pumped out of the collecting duct. It increases permeability by inserting aquaporins, and the water moves by osmosis.
• Saying ADH is made in the pituitary. It is made in the hypothalamus and released from the posterior pituitary.
• Writing that glucagon enters the liver cell. It binds to a surface receptor; cAMP carries the message inside.
• Saying glucagon acts on muscle cells. It acts on liver cells.
• Confusing glycogenesis, glycogenolysis and gluconeogenesis. Making glycogen, breaking glycogen, making new glucose.
• Saying a guard cell opens because water enters, without saying why the water potential fell, or without using the unequal wall thickening to explain the shape change.
• Naming ABA as the second messenger. ABA is the first messenger; calcium ions are the second.