Homeostasis

Homeostasis or homoeostasis is the property of a system in which a variable (for example, the concentration of a substance in solution, or its temperature) is actively regulated to remain very nearly constant. This regulation occurs inside a defined environment (mostly within a living organism's body). Examples of homeostasis include the regulation of the body temperature of an animal, the pH of its extracellular fluids, or the concentrations of sodium (Na+) and calcium (Ca2+) ions or of glucose in the blood plasma, despite changes in the animal’s environment, or what it has eaten, or what it is doing (for example, resting or exercising). Each of these variables (for example, body temperature, the pH, or the Na+, Ca2+ and glucose concentrations) is controlled by a separate “homeostat” (or regulator), which, together, maintain life. Homeostats are energy-consuming physiological mechanisms.

The concept was described by French physiologist Claude Bernard in 1865 and the word was coined by Walter Bradford Cannon in 1926.

Although the term was originally used to refer to processes within living organisms, it is frequently applied to technological control systems such as thermostats. A homeostat has an absolute requirement for a sensor to detect changes in the controlled entity's value, as well as an effector mechanism that reverses any detected deviation from the desired value (or “setpoint”) of the regulated entity. Since the correction of any error detected by the sensor is always in the opposite direction to the error, a homeostat relies on what is known as a negative feedback connection between the sensor and effector. The effector's corrective effects are monitored by the sensor, which turns the corrective measures off when setpoint conditions have been restored. Negative feedback systems are therefore referred to as "closed loop", or "negative feedback loops", to distinguish them from "open loop" systems where a stimulus (acting on a sensor) results in an, often, all-or-none response that is not subject to modification once it has been set in motion.

Biological

The metabolic processes of all living organisms can only take place in very specific physical and chemical environments. The conditions vary with each organism, and with whether the chemical processes take place inside the cell or in the fluids bathing the cells in multicellular creatures. The best known homeostats in human and other mammalian bodies are regulators that keep the composition of the extracellular fluids (or the ”internal environment”) constant, especially with regard to the temperature, pH, osmolality, and the concentrations of Na+, K+, Ca2+, glucose and CO2 and O2. However, a great many other homeostats, encompassing many aspects of human physiology, control other entities in the body. On the other hand, it should be noted that not everything in the body is homeostatically controlled. For instance the signal (be it via neurons or hormones) from the sensor to the effector is, of necessity, highly variable in order to convey information about the direction and magnitude of the error detected by the sensor. Similarly the effector’s response needs to be highly adjustable to reverse the error – in fact it should be very nearly in proportion (but in the opposite direction) to the error that is threatening the internal environment. For instance, the arterial blood pressure in mammals is homeostatically controlled, and measured by sensors in the aorta and carotid arteries. The sensors send messages via sensory nerves to the medulla oblongata of the brain indicating whether the blood pressure has fallen or risen, and by how much. The medulla oblongata then distributes messages along motor or efferent nerves belonging to the autonomic nervous system to a wide variety of effector organs, whose activity is consequently changed to reverse the error in the blood pressure. One of the effector organs is the heart whose rate is stimulated to rise (tachycardia) when the arterial blood pressure falls, or to slow down (bradycardia) when the pressure rises above set point. Thus the heart rate (for which there is no sensor in the body) is not homeostatically controlled, but is one of effector responses to errors in the arterial blood pressure. Another example is the rate of sweating. This is one of the effectors in the homeostatic control of body temperature, and therefore highly variable in rough proportion to the heat load that threatens to destabilize the body’s core temperature, for which there is a sensor in the hypothalamus of the brain.

Apart from the entities that are homeostatically controlled in the internal environment of the body, and the mechanisms that are responsible for this regulation, there are variables that are neither homeostatically controlled nor involved in the operation of homeostats. The blood urea concentration is an example. Mammals do not have “urea sensors”. Instead the concentration of urea is determined by a dynamic equilibrium, in much the same way that the water level in a river at any particular point along its course is determined. The level of a river is simply dependent on the rate at which water flows into a particular section and how fast it flows away from there. It therefore varies with the rainfall in the catchment area and obstructions or otherwise to the flow down stream – there is no energy consuming “regulation”. The blood urea concentration is comparable to the water level in a natural river. It is manufactured by the liver from the amino groups of the amino acids of proteins that are being degraded in this organ. It is then excreted by the kidneys which simply pass most of the urea in the glomerular filtrate on into the urine without active resorption or excretion by the renal tubules (a relatively small proportion of the urea in the tubules diffuses passively back into the blood as its concentration in the tubules rises when water, without urea, is removed from the tubular fluid). A high protein diet therefore produces high blood urea concentrations, and a protein-poor diet produced low blood plasma urea concentrations, without any physiological attempt to correct or mitigate these fluctuations in the level of urea in the extracellular fluids.

Homeostatic breakdown

Many diseases are the result of the failure of one or more homeostat(s). Almost any functional component of any homeostat can malfunction, either as a result of an inherited defect, or an acquired disease. Some of the homeostats have inbuilt redundancies, which insures that life is not immediately threatened if a component malfunctions; but in other cases malfunction of a homeostat causes severe disease, which can be fatal if not treated. Here only a few well known examples of homeostat dysfunction are described.

Type 1 diabetes mellitus is probably the best known example. Here the blood glucose homeostat ceases to function because the beta cells of the pancreatic islets are destroyed. This means that the glucose sensor is absent, and its effector pathway (the insulin level in the blood) remains unchanged at zero. The blood glucose concentration therefore rises to very high levels, while the body’s proteins are degraded into amino acids which are turned at a very high rate into glucose, via gluconeogenesis, by the liver. The condition is fatal if not treated.

The plasma ionized calcium homeostat can be disrupted by the constant, unchanging, over-production of parathyroid hormone by a parathyroid adenoma resulting in the typically features of hyperparathyroidism, namely high plasma ionized Ca2+ levels and the resorption of bone, which can lead to spontaneous fractures. The abnormally high plasma ionized calcium concentrations cause conformational changes in many cell-surface proteins (especially ion channels and hormone or neurotransmitter receptors) giving rise to lethargy, muscle weakness, anorexia, constipation and labile emotions.

The body water homeostat can be compromised by the inability to secrete ADH in response to even the normal daily water losses via the exhaled air, the feces, and insensible sweating. On receiving a zero blood ADH signal, the kidneys produce huge unchanging volumes of very dilute urine, causing dehydration and death if not treated.

As organisms age, the efficiency of their control systems becomes reduced. The inefficiencies gradually result in an unstable internal environment that increases the risk of illness, and leads to the physical changes associated with aging.

Chronic disease compensation and decompensation

Various chronic diseases are kept under control by homeostatic compensation, which masks a problem by compensating for it (making up for it) in another way. However, the compensating mechanisms eventually wear out or are disrupted by a new complicating factor (such as the advent of a concurrent acute viral infection), which sends the body reeling through a new cascade of events. Such decompensation unmasks the underlying disease, worsening its symptoms. Common examples include decompensated heart failure, kidney failure, and liver failure.