Feedback & homeostasis

Set points and feedback loops

Homeostasis means keeping conditions inside the body within a narrow range. Each controlled variable, like body temperature or blood glucose, has a set point: the target value the body tries to hold. The value wobbles a little around it all the time, but it's pulled back.

The pulling back is done by a feedback loop, in which the result of a process affects the process itself. A homeostatic loop has three parts:

• A sensor (or receptor) detects the variable and any change in it.
• An integrator (or control centre) compares the reading with the set point and decides what to do. In many loops this is part of the brain, such as the hypothalamus.
• An effector, usually a muscle or gland, makes the change that brings the variable back.

Negative feedback: pushing back

In negative feedback, the response opposes the original change. If a variable rises, the response lowers it; if it falls, the response raises it. As the variable returns to the set point, the stimulus for the response fades, so the response switches itself off. Most homeostasis works this way.

Body temperature. Temperature sensors in the skin and in the brain report to the hypothalamus. If you get too hot, the hypothalamus triggers sweating and widens blood vessels in the skin, so more heat is lost. If you get too cold, it narrows those vessels and triggers shivering, which generates heat. Either way, the response moves temperature back towards about 37 °C.

Blood glucose. Here the pancreas is both sensor and integrator. After a meal, glucose rises. Beta (β) cells in the pancreas detect this and release insulin, which makes body cells take up glucose and makes the liver store it as glycogen. Blood glucose falls, and as it does, insulin release slows. Between meals, glucose falls, and alpha (α) cells release glucagon, which makes the liver break glycogen down and make new glucose. Blood glucose rises again, and glucagon release slows.

Glucose control uses two opposing hormones, like having both an accelerator and a brake. That gives tighter control than one hormone could manage.

Positive feedback: pushing further

In positive feedback, the response reinforces the original change, so it grows bigger and bigger. That would be a disaster for body temperature, but it's exactly right for a process that needs to go quickly to an end point and then stop.

• Childbirth. The baby's head pressing on the cervix triggers the release of the hormone oxytocin, which makes the uterus contract. The contractions push the head harder against the cervix, which releases more oxytocin, which causes stronger contractions. The loop ends when the baby is born and the stretching stops.
• Blood clotting. Platelets that stick to a damaged vessel release chemicals that attract and activate more platelets, and a cascade of clotting factors activates more of itself. The loop ends when the wound is sealed.
• Fruit ripening. Ripening fruit releases the plant hormone ethylene, which speeds ripening, which makes the fruit release more ethylene. It spreads to neighbouring fruit too: that's why one ripe banana speeds up the rest of the bunch.

Every positive-feedback loop needs a built-in end, because otherwise it would run away. That end is usually an external event, like the birth of the baby or the sealing of the wound.

When a loop breaks

Because a loop has separate parts, you can predict what goes wrong when one fails. The two main types of diabetes are a neat example: both give high blood glucose, but for different reasons.

• In type 1 diabetes, the body's immune system destroys the β cells. The signal is missing: little or no insulin is made. Giving insulin replaces the missing signal.
• In type 2 diabetes, insulin is made (at least early on), but the target cells respond to it less. This is insulin resistance. The signal is there; the effectors don't listen well.

A set point can also be moved on purpose. During an infection, substances called pyrogens reset the hypothalamus to a higher temperature. You shiver and feel cold even though your temperature is still normal, because the body is now defending the new, higher set point. That's a fever.

Feedback inside cells: end-product inhibition

The same logic works at the level of single enzymes. In a metabolic pathway, the final product often inhibits the enzyme that catalyses the first committed step, the first reaction that leads only to that product. This is end-product inhibition, also called feedback inhibition.

For example, bacteria make the amino acid isoleucine from threonine in a series of steps. When isoleucine builds up, it binds to the first enzyme of the pathway, threonine deaminase, at an allosteric site (a regulatory site away from the active site). The enzyme changes shape and slows down. When isoleucine is used up, the inhibition lifts and production resumes. The cell makes just as much as it needs, without wasting energy or raw materials.

Energy metabolism works similarly. ATP inhibits key enzymes of glucose breakdown, and ADP and AMP (which build up when ATP runs low) activate them. So when a cell is using ATP quickly, respiration speeds up, and when ATP is plentiful, it slows. This is negative feedback keeping the cell's energy supply steady: molecular homeostasis.

Key terms

Homeostasis

Keeping internal conditions within a narrow range despite changes outside.

Set point

The target value a feedback loop tries to maintain.

Sensor / integrator / effector

The parts of a loop that detect the change / compare it with the set point / make the correcting response.

Negative feedback

A response that opposes the change, bringing the variable back to its set point.

Positive feedback

A response that reinforces the change, driving a process to completion.

Insulin / glucagon

Pancreatic hormones that lower / raise blood glucose.

End-product (feedback) inhibition

The final product of a pathway inhibits an early enzyme in it.

Check yourself

Try answering in your head before you open each answer.

• 1.A drug blocks oxytocin receptors in the uterus. What would it do to labour, and why is this a clue that labour is driven by positive feedback?Show answerHide

  Contractions would weaken or stop, because the loop is broken at the effector: oxytocin can't make the uterus contract, so the cervix isn't stretched further and oxytocin release doesn't keep rising. In positive feedback each round depends on the one before, so breaking any link stops the whole escalation. (Drugs of this kind are used to delay premature labour.)

• 2.A person with type 2 diabetes has high blood glucose. Would you expect their insulin level to be low, normal or high, at least in the early stages? Explain using the feedback loop.Show answerHide

  Normal or high. The β cells still work and sense the high glucose, so they release plenty of insulin. The problem is that the target cells respond weakly, so glucose stays high, and the β cells keep being stimulated. In type 1 diabetes, by contrast, insulin would be low.

• 3.A bacterium's enzyme at the first step of an amino acid pathway is mutated so that the end product can no longer bind its allosteric site. Predict what happens when the bacterium is grown in a medium rich in that amino acid.Show answerHide

  The pathway keeps running at full speed even though the amino acid is already plentiful, because the brake has been removed. The cell overproduces the amino acid, wasting energy and raw materials, and may even excrete the excess.