Homeostasis and homeostatic regulation. Control systems, negative feedback, and levels of physiological regulation

• Homeostasis is the maintenance of a constant internal environment (the extracellular fluid) by coordinated physiological mechanisms. Cells can function only while pH, temperature and chemical composition stay constant.
• Homeostatic control systems are closed-loop control systems with negative feedback. They need a sensor (receptor), a processor (integrative centre) that compares the actual value with the setpoint, and an effector that changes the parameter back.
• Negative feedback reverses the change and keeps the system stable. Positive feedback amplifies the change: it speeds up some normal processes (the action potential, childbirth) but can start vicious circles.
• Physiological regulation works at four levels: intracellular, local, organ or system, and whole body.
• Neural regulation is fast and precise; endocrine regulation is slower, more diffuse and controls long-term processes such as metabolism, growth and reproduction. The two interact in neuro-endocrine reflexes.

Physiology is the science of the normal functions of living organisms and their parts. Homeostasis refers to stability or balance in a system. In human biology it is the body's attempt to maintain a constant internal environment, which requires constant monitoring and adjustment. Homeostatic regulation involves three main mechanisms: the receptor, which receives information; the control centre, which takes the information and processes it; and the effector, which responds to the control centre's commands and changes the body. The effector changes the parameter of importance, which is then detected by the receptor again. Knowledge of normal function is needed to understand the adaptive responses to abnormal function, and so to understand and recognise disease. Knowledge of body functions is also essential for understanding how drugs act.

Homeostasis is the maintenance of a constant internal environment within the body by coordinated physiological mechanisms. Nearly every organ and tissue of the body performs functions that help keep that internal environment constant.

In multicellular organisms the cells do not communicate with the external world directly. They are surrounded by an internal environment, which is the extracellular fluid. Cells can live, grow and perform their special functions only if conditions such as pH, temperature and chemical composition stay constant in this internal milieu. In humans the body temperature that the cells work at is about 37 °C. Diseases or death may occur when homeostasis fails.

The concept was introduced by Claude Bernard (1813-1878), who wrote that the constancy of the internal environment is a condition of free life. The term "homeostasis" was coined by Walter Cannon (1871-1945) in 1926 to describe the body's capacity to regulate the parameters of the extracellular fluid.

A control system, in the sense of cybernetics, is a device or set of devices that manages, commands, directs or regulates the behaviour of other devices or systems. The body's control systems share the common characteristics of all control systems. The questions to answer are how they work and which structures are involved.

In an open-loop control system a desired output response goes to a controller and then to a process, and the output is not measured or compared with the target. In a closed-loop control system the output is measured, the measurement is compared with the desired value, and the controller corrects the process on the basis of that comparison.

Closed-loop systems can have negative or positive feedback. The homeostatic control systems are basically closed-loop systems with negative feedback.

Because the goal of homeostatic control is to keep the parameters of the internal environment constant, the homeostatic control systems are closed-loop systems with negative feedback. The effects of the disturbing factor are countered: the system responds so as to reverse the change. Negative feedback is therefore the mechanism that keeps the system stable.

The lecture diagram names five parts of a closed-loop system with negative feedback:

• the parameter that is controlled, for example temperature, pH or pO₂;
• the sensor (receptor), which measures the actual value of the parameter;
• the processor (integrative centre), which compares the actual value with the setpoint value and computes the difference;
• the effector, which acts on the parameter on the processor's command; and
• the disturbing factor, which pushes the parameter away from the setpoint and is opposed by the loop.

The actual value travels from the parameter to the sensor, from the sensor to the processor, and from the processor to the effector. The effector then changes the parameter, which is measured again.

Two examples match the lecture model:

• Carbon dioxide. If the level of CO₂ in the body rises, the body increases lung activity and expels more CO₂, which reverses the change.
• Body temperature. The skin acts as the receptor. The brain receives the signal from the skin and acts as the control centre. The sweat glands and blood vessels act as effectors on the brain's instruction. When the temperature is too high, the body sweats and the vessels dilate, which lowers the temperature. The change in temperature is then detected by the skin again.

Omid's notes show the same loop as a graph: a disturbing factor pushes the variable away from its setpoint, and regulation pulls it back, so the curve settles around the setpoint.

Homeostasis is therefore best thought of as a dynamic equilibrium, created by the body and kept up by the nerves and the endocrine system. These two systems exert the ultimate control because they coordinate the functions of the body's systems.

Positive feedback amplifies the change in the variable, so it destabilises the system rather than restoring it. A positive feedback process can be useful, because it amplifies the impact of a biological phenomenon. Positive feedback is not homeostatic on its own, but it has two important roles, as the lecture puts it: it can speed up some normal physiological processes, and it can cause vicious circles and death.

The upstroke of the action potential is an example of this. Opening of voltage-gated Na⁺ channels increases the membrane's Na⁺ permeability. This increases the inflow of Na⁺ into the cell, which depolarises the membrane further and opens more voltage-gated Na⁺ channels. This sodium flow increases exponentially.

In normal childbirth positive feedback amplifies the stimulation of the cervix and the uterine contractions. The lecture shows normal vaginal delivery as an example of a process that is sped up by positive feedback. The same loop is described with the hormone oxytocin, which is released and amplifies the stimulation. In the lecture, oxytocin is released under the control of the hypothalamus, as the oxytocin reflex in section 8 shows.

Omid's notes show the same idea as a graph. Each disturbance is followed by a further rise rather than a return to the setpoint, so the curve climbs away from the dashed line.

A vicious circle is positive feedback that drives a process further in the harmful direction. The lecture uses a blocked coronary artery. A plaque builds up in the artery, a blood clot blocks it, and blood flow to the heart muscle stops, so the muscle dies. The same pattern is described as a clot that restricts flow, which causes further restriction, and so on.

The lecture slide that poses the question "what is the effect of a positive feedback?" shows the action-potential loop, childbirth, a coronary blockage and a skull-and-crossbones symbol for death. Read it as a summary of the three examples above.

Physiological regulation is present at every level of the body's systems. The lecture names four levels:

• intracellular, inside one cell;
• local, within a tissue or small region;
• organ or system; and
• whole body.

The lecture also lists four types of control: proportional control, derivative control, integral control and anticipatory control. It names them without defining them. Their meaning is given in the comparison table in the last note.

Neural regulation is involved in fast adaptation to changes in the external and the internal environment, and in the regulation of movements. It works with precise targeting and adaptation. The lecture uses the regulation of blood pressure as its example.

Neural regulation is fast, regulates movement and is known for precise targeting.

The endocrine system is characterised by slower responses and more diffuse influences. It is involved in the long-term regulation of metabolism, growth and reproduction. Hormones can reach every cell, whereas nerves cannot.

The lecture's example is the control of blood glucose by the pancreas. When blood glucose is low, the alpha cells of the pancreas release glucagon, which makes the liver release glucose into the blood. When blood glucose is high, the beta cells release insulin, which makes fat cells take up glucose from the blood. Both actions bring blood glucose back to its normal level.

Neural and endocrine control are linked. Both take part in neuro-endocrine reflexes. The endocrine glands are controlled by the hypothalamus and by the autonomic nerves, and hormones modulate neuronal activity.

The lecture's example is the oxytocin reflex. A sound, such as a baby's cry, reaches the higher brain centres, which act on the hypothalamus. Oxytocin neurones in the hypothalamus release oxytocin from the posterior pituitary. Oxytocin causes milk secretion and contraction of smooth muscle. Mechanoreceptors in the nipple, stimulated by the baby sucking, feed back into the reflex. The same reflex is described in a mother breastfeeding her baby.

Neural and endocrine regulation compared:

Negative and positive feedback compared:

The parts of a control system and their examples: