Cover of the Nazi propaganda brochure "Der Untermensch" ("The Subhuman"), 1942. The SS booklet depicted the natives of the Soviet Union as "subhumans".
The term "under man" was introduced by the American author and Ku Klux Klan member Lothrop Stoddard in his 1922 book The Revolt Against Civilization: The Menace of the Under-man. Stoddard applies the term to those whom he considers unable to flourish in civilization due to their inferior heredity ("The word inferior has, however, been so often employed as a synonym for degenerate that it tends to produce confusion of thought, and to avoid this I have coined a term which seems to describe collectively all those kinds of persons whom I have just discussed. This term is The Under-Man—the
man who measures under the standards of capacity and adaptability imposed by the social order in which he lives". (p.23)). Therefore, the term has no racial connotations. Indeed, in his book Stoddard maintains that without eugenics any and all civilizations—irrespective of race, time and geography—have been, are and inevitably will be prone to gradual degradation. The Nazi Party later used the term in propaganda, possibly influenced in part from the title of the book's German edition Der Kulturumsturz: Die Drohung des Untermenschen (1925).
Austro-Hungarian postcard made in 1914 which features the rhyming slogan "Serbia must die!" Such images were representative of the social attitudes underlying the concept of untermensch.
The German word Untermensch had been used in earlier periods, but it had not been used in a racial sense; for example, it was used in the 1899 novel Der Stechlin by Theodor Fontane. Since most writers who employed the term did not address the question of when and how the word entered the German language, in English, Untermensch is usually translated as "subhuman". The leading Nazi who attributed the concept of the East-European "under man" to Stoddard was Alfred Rosenberg who, referring to communists of the Soviet Russia, wrote in his Der Mythus des zwanzigsten Jahrhunderts (1930) that "this is the kind of human being that Lothrop Stoddard has called the 'under man.'" ["...den Lothrop Stoddard als 'Untermenschen' bezeichnete."] Despite Nazi official support for The Myth of the Twentieth Century and Rosenberg's prominent role in promoting Nazi ideology, Adolf Hitler declared that it was not to be considered the official ideology of the Nazi Party, and he privately described the book as "mysticism" and "nonsense". Albert Speer claimed that Goebbels mocked Alfred Rosenberg. Goebbels also called the book a "philosophical belch".
It is possible that Stoddard constructed his "under man" as an opposite of Friedrich Nietzsche's Übermensch (superman) concept. Stoddard does not explicitly say this, but he critically refers to the "superman" idea at the end of his book (p.262). Wordplays with Nietzsche's term seem to have been used repeatedly as early as the 19th century and, due to the German linguistic trait of being able to combine prefixes and roots almost at will in order to create new words, this development can be considered logical. For instance, German author Theodor Fontane contrasts the Übermensch/Untermensch word pair in chapter 33 of his novel Der Stechlin. Nietzsche used the term Untermensch at least once in contrast to Übermensch in Die fröhliche Wissenschaft (1882). Earlier examples of Untermensch include Romanticist Jean Paul using the term in his novel Hesperus (1795) in reference to an Orangutan (Chapter "8. Hundposttag").
It happened at the time of the [Bavarian] Soviet Republic: When the unleashed subhumans rambled murdering through the streets, the deputies hid behind a chimney in the Bavarian parliament.
A chart used to illustrate the Nazi Nuremberg Laws introduced in 1935
The Nazi party and thereafter also the regime (1933–1945) repeatedly used the term Untermensch in writings and speeches which they directed against the Jews. In the pamphlet "The SS as an Anti-Bolshevist Fighting Organization", published in 1936, Himmler wrote:
We shall take care that never again in Germany, the heart of Europe, will the Jewish-Bolshevik revolution of subhumans be able to be kindled either from within or through emissaries from without.
In his speech "Weltgefahr des Bolschewismus" ("World danger of Bolshevism") in 1936, Joseph Goebbels said that "subhumans exist in every people as a leavening agent". At the 1935 Nazi party congress rally at Nuremberg, Goebbels also declared that, “Bolshevism is the declaration of war by Jewish-led international subhumans against culture itself."
The most notorious example of the usage of the term Untermensch by the Nazis is a Schutzstaffel (SS) brochure entitled "Der Untermensch[de]", distributed by the Reich Security Main Office under the directives of Heinrich Himmler. Published in 1942 after the start of Operation Barbarossa, it is around 50 pages long and consists, for the most part, of photos portraying the natives of Eastern Europe in an extremely negative way. Nearly four million copies of the pamphlet were printed in the German language and distributed across German-occupied territories. The contents of the "Der Untermensch" brochure extensively emphasized Himmler's racist demonization of Russians as "bestial untermenschen" and Jews as "the decisive leader of untermenschen". It was translated into Greek, French, Dutch, Danish, Bulgarian, Hungarian, Czech and seven other languages. It gives the following definition of an Untermensch:
The subhuman is a biological creature, crafted by nature, which has hands, legs, eyes and mouth, even the semblance of a brain. Nevertheless, this terrible creature is only a partial human being. Although it has features similar to a human, the subhuman is lower on the spiritual and psychological scale than any animal. Inside this being is a cruel chaos of wild, unrestrained passions, nameless desire for destruction, the most primitive desires, the most naked meanness.
Spanish Falangism
In Spain, in addition to the term underman, the terms subhuman and degenerate are frequent in speeches and articles, especially from the 1930s. These are words used naturally in the newspapers, without explanations of the specific meaning, so it can be deduced that they were general knowledge. They are terms that increase in intensity during the October Events, and during the civil war.
As the civil war approaches or takes place, there is a divergence in the meaning of subhuman, on the rebel side it acquires a racial/eugenic meaning, beside ideologic, while on the republican side it is more of a cultural type.
"We have to kill, kill, you know? They are like animals, you know, and we cannot expect them to get rid of the virus of Bolshevism. After all, rats and lice are the carriers of the plague. Now I hope you understand what we mean by the regeneration of Spain... Our programme consists... of exterminating one third of the male population of Spain. That would cleanse the country and get rid of the proletariat. And it is also economically convenient. There will be no more unemployment in Spain, do you understand?"
Policies of Nazi Germany
When faced with increasing military manpower shortages, the Nazi regime used soldiers from some Slavic countries, firstly from the Reich's allies Croatia and Slovakia as well as within occupied territories. The concept of the Slavs in particular being Untermenschen served the Nazis' political goals; it was used to justify their expansionist policy and especially their aggression against Poland and the Soviet Union in order to achieve Lebensraum, particularly in Ukraine. Early plans of the Nazi officials (summarized as Generalplan Ost) envisioned the ethnic cleansing and extermination of no fewer than 50 million people, who were not considered fit for Germanization, from territories it wanted to conquer in Europe. Nazi planners considered Ukraine's chernozem ("black earth") soil as a particularly desirable zone for colonization.
During the war, Nazi propaganda instructed Wehrmacht officers to tell their soldiers to target people whom they considered "Jewish Bolshevik subhumans". In addition, Nazi Germany conducted its warfare against the Soviet Union as a racial war targeting Jews, Romanis, Slavs, and various indigenous inhabitants of Eastern Europe who were categorized as "untermenschen" in the Nazi ideology. Nazis viewed Russians as animalistic sub-humans who were incapable of mounting any form of collective resistance against a German invasion. Nazi anti-Slavism was also tied to the Judeo-Bolshevik conspiracy theory; which claimed that Slavs were inferior people controlled by Jews as pawns in their plots against Aryans.
Prior to the launch of Operation Barbarossa, the Wehrmacht's High Command began issuing orders to enable German soldiers to indiscriminately target the inhabitants of Eastern Europe and unleash systematic violence against entire populations. German Army was instructed to grant carte blanche to the anti-Jewish massacres carried out by the Einsatzgruppen death squads in German-occupied territories. “Guidelines for the Conduct of the Troops in Russia” issued by the German High Command on 19 May 1941, ordered German troops to target Jews, partisans, Bolsheviks, etc. and described the war in Eastern Europe as a "historic task to liberate the German people once forever from the Asiatic-Jewish danger". In 1943 Himmler issued a secret order for the destruction of the Warsaw Ghetto in order to eliminate the "living space" of 500,000 Untermenschen, unsuitable for the Germans.
Sub-human types
The Nazis divided the people who they considered the sub-humans into different types; they placed priority on the extermination of the Jews, and Roma, and the exploitation of others as slaves.
Historian Robert Jan van Pelt writes that for the Nazis, "it was only a small step to a rhetoric pitting the European Mensch against the Soviet Untermensch, which had come to mean a Russian in the clutches of Judeo-Bolshevism."
The Untermensch concept included Jews, Roma and Sinti (Gypsies), and Slavic peoples such as Poles, Ukrainians, and Russians. Slavs were regarded as Untermenschen, barely fit for exploitation as slaves. Hitler and Goebbels compared them to the "rabbit family" or to "stolid animals" that were "idle" and "disorganized" and spread like a "wave of filth". However, some among the Slavs who happened to have Nordic racial features were deemed to have distant Germanic descent which meant partially "Aryan" origin, and if under 10 years old, they were to be Germanized (see: kidnapping of children by Nazi Germany).
A 1940 poster listing the obligations imposed on Polish workers in Germany under the Polish decrees, including the death penalty for sexual relations with a German.
The Nazis were utterly contemptuous of the Slavs, as even prior to World War II, Slavs – particularly the Poles – were deemed to be inferior to Germans and other Aryans. After Adolf Hitler gained political power in Germany, the concept of non-Aryan "sub-human slave-material" was developed and started to be used also towards other Slavic peoples. Poles were at the bottom of the Slavic "racial hierarchy" established by the Nazis. Soon after the Molotov–Ribbentrop Pact expired, Russians also started to be seen as "subhumans". Similarly, Belarusians, Czechs, Slovaks, and Ukrainians were considered to be inferior. Nonetheless, there were Slavs such as Bosniaks, Bulgarians, and Croats who collaborated with Nazi Germany that were still being perceived as not racially "pure" enough to reach the status of Germanic peoples, yet they were eventually considered ethnically better than other Slavs, mostly due to theories about these nations having a minimal amount of Slavic genes and considerable admixtures of Germanic and Turkic blood.
In order to forge a strategic alliance with the Independent State of Croatia—a puppet state created after the invasion of Yugoslavia and the Kingdom of Bulgaria, the Nazis deviated from a strict interpretation of their racial ideology, and Croats were officially described as "more Germanic than Slav", a notion supported by Croatia's fascist (Ustashe) dictator Ante Pavelić who maintained that the "Croats were descendants of the ancient Goths" and "had the Panslav idea forced upon them as something artificial".Hitler also deemed the Bulgarians to be "Turkoman" in origin.
This poster (from around 1938) reads: "60,000 Reichsmark is what this person suffering from a hereditary defect costs the People's community during his lifetime. Fellow citizen, that is your money too. Read the Neues Volk, the monthly magazine of the Office of Racial Policy of the NSDAP."
While the Nazis were inconsistent in the implementation of their policy – for instance, mostly implementing the Final Solution while also implementing Generalplan Ost– the democidal death toll was in the range of tens of millions of victims. It is related to the concept of "life unworthy of life", a more specific term which originally referred to the severely disabled who were involuntarily euthanised in Aktion T4, and was eventually applied to the extermination of the Jews. That policy of euthanasia started officially on 1 September 1939 when Hitler signed an edict to the effect, and carbon monoxide was first used to murder disabled patients. The same gas was used in the death camps such as Treblinka, although they used engine exhaust gases to achieve the same end. In directive No. 1306 by Reich Ministry of Public Enlightenment and Propaganda from 24 October 1939, the term "Untermensch" is used in reference to Polish ethnicity and culture, as follows:
It must become clear to everybody in Germany, even to the last milkmaid, that Polishness is equal to subhumanity. Poles, Jews and Gypsies are on the same inferior level. This must be clearly outlined [...] until every citizen of Germany has it encoded in his subconsciousness that every Pole, whether a farm worker or intellectual, should be treated like vermin.
Biology classes in Nazi-era Germany schools taught about differences between the race of Nordic German "Übermenschen" and "ignoble" Jewish and Slavic "subhumans". The view that Slavs were subhuman was widespread among the German masses, and chiefly applied to the Poles. It continued to find support after the war.
Chronobiology is a field of biology that examines timing processes, including periodic (cyclic) phenomena in living organisms, such as their adaptation to solar- and lunar-related rhythms. These cycles are known as biological rhythms. Chronobiology comes from the ancient Greek χρόνος (chrónos, meaning "time"), and biology, which pertains to the study, or science, of life. The related terms chronomics and chronome have been used in some cases to describe either the molecular mechanisms involved in chronobiological phenomena or the more quantitative aspects of chronobiology, particularly where comparison of cycles between organisms is required.
Chronobiology studies variations of the timing and duration of biological activity in living organisms which occur for many essential biological processes. These occur in animals (eating, sleeping, mating, hibernating, migration, cellular regeneration, etc.), in plants (leaf movements, photosynthetic reactions, etc.), as well as in microbial organisms such as fungi and protozoa. They have also been found in bacteria, especially among the cyanobacteria (blue-green algae). The best studied rhythm in chronobiology is the circadian rhythm, a roughly 24-hour cycle shown by physiological processes in all these organisms. The term circadian comes from the Latincirca, meaning "around" and dies, "day", meaning "approximately a day." The circadian rhythm is regulated by circadian clocks, which are biochemical mechanisms that regulate physiological processes based on time of day.
The circadian rhythm regulates behaviour including timing of the activity phase. Depending on their innate active phase, organisms can be classified into one of three categories:
Diurnal, which describes organisms active during daytime
Nocturnal, which describes organisms active in the night
Crepuscular, which describes animals primarily active during the dawn and dusk hours (ex: domestic cats, white-tailed deer, some bats)
While circadian rhythms are generated by endogenous processes, they can be regulated by both endogenous and exogenous signals. Other biological cycles may be regulated by exogenous signals, such as lunar rhythms in marine life being dictated by the lunar cycle.
Many other important cycles are also studied, including:
Infradian rhythms, which are cycles longer than a day. Examples include circannual or annual cycles that govern migration or reproduction cycles in many plants and animals, or the human menstrual cycle.
Tidal rhythms, commonly observed in marine life, which follow the roughly 12.4-hour transition from high to low tide and back.
Lunar rhythms, which follow the lunar month (29.5 days). They are relevant e.g. for marine life, as the level of the tides is modulated across the lunar cycle.
Within each cycle, the time period during which the process is more active is called the acrophase. When the process is less active, the cycle is in its bathyphase or trough phase. The particular moment of highest activity is the peak or maximum; the lowest point is the nadir.
History
A circadian cycle was first observed in the 18th century in the movement of plant leaves by the French scientist Jean-Jacques d'Ortous de Mairan. In 1751, Swedish botanist and naturalistCarl Linnaeus (Carl von Linné) designed a flower clock using certain species of flowering plants. By arranging the selected species in a circular pattern, he designed a clock that indicated the time of day by the flowers that were open at each given hour. For example, among members of the daisy family, he used the hawk's beard plant which opened its flowers at 6:30 am and the hawkbit which did not open its flowers until 7 am.
It was also in 1960 that Patricia DeCoursey invented the phase response curve while studying light response in rodents, one of the major tools used in the field since.
Franz Halberg of the University of Minnesota, who coined the word circadian, is widely considered the "father of American chronobiology." However, it was Colin Pittendrigh and not Halberg who was elected to lead the Society for Research in Biological Rhythms in the 1970s. Halberg wanted more emphasis on the human and medical issues while Pittendrigh had his background more in evolution and ecology. With Pittendrigh as leader, the Society members did basic research on all types of organisms, plants as well as animals. More recently it has been difficult to get funding for such research on any other organisms than mice, rats, humans and fruit flies.
The role of Retinal Ganglion cells
Melanopsin as a circadian photopigment
In 2002, Hattar and his colleagues showed that melanopsin plays a key role in a variety of photic responses, including pupillary light reflex, and synchronization of the biological clock to daily light-dark cycles. He also described the role of melanopsin in ipRGCs. Using a rat melanopsin gene, a melanopsin-specific antibody, and fluorescent immunocytochemistry, the team concluded that melanopsin is expressed in some RGCs. Using a Beta-galactosidase assay, they found that these RGC axons exit the eyes together with the optic nerve and project to the suprachiasmatic nucleus (SCN), the primary circadian pacemaker in mammals. They also demonstrated that the RGCs containing melanopsin were intrinsically photosensitive. Hattar concluded that melanopsin is the photopigment in a small subset of RGCs that contributes to the intrinsic photosensitivity of these cells and is involved in their non-image forming functions, such as photic entrainment and pupillary light reflex.
Melanopsin cells relay inputs from rods and cones
Light enters the eye and hits the retinal pigmented epithelium (maroon). This excites rods (grey) and cones (blue/red). These cells synapse onto bipolar cells (pink), which stimulate ipRGCs (green) and RGCs (orange). Both RGCs and ipRGCs transmit information to the brain through the optic nerve. Furthermore, light can directly stimulate the ipRGCs through its melanopsin photopigment. The ipRGCs uniquely project to the superchiasmatic nucleus, allowing the organism to entrain to light-dark cycles.
Hattar, armed with the knowledge that melanopsin was the photopigment responsible for the photosensitivity of ipRGCs, set out to study the exact role of the ipRGC in photoentrainment. In 2008, Hattar and his research team transplanted diphtheria toxin genes into the mouse melanopsin gene locus to create mutant mice that lacked ipRGCs. The research team found that while the mutants had little difficulty identifying visual targets, they could not entrain to light-dark cycles. These results led Hattar and his team to conclude that ipRGCs do not affect image-forming vision, but significantly affect non-image forming functions such as photoentrainment.
Distinct ipRGCs
Further research has shown that ipRGCs project to different brain nuclei to control both non-image forming and image forming functions. These brain regions include the SCN, where input from ipRGCs is necessary to photoentrain circadian rhythms, and the olivary pretectal nucleus (OPN), where input from ipRGCs control the pupillary light reflex. Hattar and colleagues conducted research that demonstrated that ipRGCs project to hypothalamic, thalamic, stratal, brainstem and limbic structures. Although ipRGCs were initially viewed as a uniform population, further research revealed that there are several subtypes with distinct morphology and physiology. Since 2011, Hattar's laboratory has contributed to these findings and has successfully distinguished subtypes of ipRGCs.
Diversity of ipRGCs
Hattar and colleges utilized Cre-based strategies for labeling ipRGCs to reveal that there are at least five ipRGC subtypes that project to a number of central targets. Five classes of ipRGCs, M1 through M5, have been characterized to date in rodents. These classes differ in morphology, dendritic localization, melanopsin content, electrophysiological profiles, and projections.
Diversity in M1 cells
Hattar and his co-workers discovered that, even among the subtypes of ipRGC, there can be designated sets that differentially control circadian versus pupillary behavior. In experiments with M1 ipRGCs, they discovered that the transcription factor Brn3b is expressed by M1 ipRGCs that target the OPN, but not by ones that target the SCN. Using this knowledge, they designed an experiment to cross Melanopsin-Cre mice with mice that conditionally expressed a toxin from the Brn3b locus. This allowed them to selectively ablate only the OPN projecting M1 ipRGCS, resulting in a loss of pupil reflexes. However, this did not impair circadian photo entrainment. This demonstrated that the M1 ipRGC consist of molecularly distinct subpopulations that innervate different brain regions and execute specific light-induced functions. This isolation of a 'labeled line' consisting of differing molecular and functional properties in a highly specific ipRGC subtype was an important first for the field. It also underscored the extent to which molecular signatures can be used to distinguish between RGC populations that would otherwise appear the same, which in turn facilitates further investigation into their specific contributions to visual processing.
Psychological impact of light exposure
Previous studies in circadian biology have established that exposure to light during abnormal hours leads to sleep deprivation and disruption of the circadian system, which affect mood and cognitive functioning. While this indirect relationship had been corroborated, not much work had been done to examine whether there was a direct relationship between irregular light exposure, aberrant mood, cognitive function, normal sleep patterns and circadian oscillations. In a study published in 2012, the Hattar Laboratory was able to show that deviant light cycles directly induce depression-like symptoms and lead to impaired learning in mice, independent of sleep and circadian oscillations.
Effect on mood
ipRGCs project to areas of the brain that are important for regulating circadian rhythmicity and sleep, most notably the SCN, subparaventricular nucleus, and the ventrolateral preoptic area. In addition, ipRGCs transmit information to many areas in the limbic system, which is strongly tied to emotion and memory. To examine the relationship between deviant light exposure and behavior, Hattar and his colleagues studied mice exposed to alternating 3.5-hour light and dark periods (T7 mice) and compared them with mice exposed to alternating 12-hour light and dark periods (T24 mice). Compared to a T24 cycle, the T7 mice got the same amount of total sleep and their circadian expression of PER2, an element of the SCN pacemaker, was not disrupted. Through the T7 cycle, the mice were exposed to light at all circadian phases. Light pulses presented at night lead to expression of the transcription factor c-Fos in the amygdala, lateral habenula, and subparaventricular nucleus further implicating light's possible influence on mood and other cognitive functions.
Mice subjected to the T7 cycle exhibited depression-like symptoms, exhibiting decreased preference for sucrose (sucrose anhedonia) and exhibiting more immobility than their T24 counterparts in the forced swim test (FST). Additionally, T7 mice maintained rhythmicity in serum corticosterone, however the levels were elevated compared to the T24 mice, a trend that is associated with depression. Chronic administration of the antidepressant Fluoxetine lowered corticosterone levels in T7 mice and reduced depression-like behavior while leaving their circadian rhythms unaffected.
Effect on learning
The hippocampus is a structure in the limbic system that receives projections from ipRGCs. It is required for the consolidation of short-term memories into long-term memories as well as spatial orientation and navigation. Depression and heightened serum corticosterone levels are linked to impaired hippocampal learning. Hattar and his team analyzed the T7 mice in the Morris water maze (MWM), a spatial learning task that places a mouse in a small pool of water and tests the mouse's ability to locate and remember the location of a rescue platform located just below the waterline. Compared to the T24 mice, the T7 mice took longer to find the platform in subsequent trials and did not exhibit a preference for the quadrant containing the platform. In addition, T7 mice exhibited impaired hippocampal long-term potentiation (LTP) when subjected to theta burst stimulation (TBS). Recognition memory was also affected, with T7 mice failing to show preference for novel objects in the novel object recognition test.
Necessity of ipRGCs
Mice without (Opn4aDTA/aDTA mice) are not susceptible to the negative effects of an aberrant light cycle, indicating that light information transmitted through these cells plays an important role in regulation of mood and cognitive functions such as learning and memory.
Research developments
Light and melatonin
More recently, light therapy and melatonin administration have been explored by Alfred J. Lewy (OHSU), Josephine Arendt (University of Surrey, UK) and other researchers as a means to reset animal and human circadian rhythms. Additionally, the presence of low-level light at night accelerates circadian re-entrainment of hamsters of all ages by 50%; this is thought to be related to simulation of moonlight.
In the second half of 20th century, substantial contributions and formalizations have been made by Europeans such as Jürgen Aschoff and Colin Pittendrigh, who pursued different but complementary views on the phenomenon of entrainment of the circadian system by light (parametric, continuous, tonic, gradual vs. nonparametric, discrete, phasic, instantaneous, respectively).
Chronotypes
Humans can have a propensity to be morning people or evening people; these behavioral preferences are called chronotypes for which there are various assessment questionnaires and biological marker correlations.
Mealtimes
There is also a food-entrainable biological clock, which is not confined to the suprachiasmatic nucleus. The location of this clock has been disputed. Working with mice, however, Fuller et al. concluded that the food-entrainable clock seems to be located in the dorsomedial hypothalamus. During restricted feeding, it takes over control of such functions as activity timing, increasing the chances of the animal successfully locating food resources.
Diurnal patterns on the Internet
In 2018 a study published in PLoS ONE showed how 73 psychometric indicators measured on Twitter Content follow a diurnal pattern.
A followup study appeared on Chronobiology International in 2021 showed that these patterns were not disrupted by the 2020 UK lockdown.
Modulators of circadian rhythms
In 2021, scientists reported the development of a light-responsive days-lasting modulator of circadian rhythms of tissues via Ck1 inhibition. Such modulators may be useful for chronobiology research and repair of organs that are "out of sync".
Neurological disorders
In 2021, scientists found that children with autism spectrum disorder are more likely to have disruptions in their sleep-wake cycle. Additionally, children with autism were also found more likely to have abnormal daily hormone cycles of cortisol, melatonin, and serotonin compared to the average person.
A 2017 study found that people with Attention deficit hyperactivity disorder (ADHD) often have a delayed sleep phase in their circadian rhythm, meaning that they go to sleep later than the average person. An earlier study from 2013 found similar results to the 2017 study, but also found a correlation between Seasonal affective disorder, ADHD, and sleeping problems.
Physical diseases and disorders
In 2015, a study on the frequency of gout attacks found that they occur over twice as often in the night and early morning than other times of day. A 2021 study on osteoporosis found that disruption of circadian rhythms (such as working night shifts) can lead to osteoporosis by disturbing bone remodeling that typically happens at night.
In biology, homeostasis (in British English also homoeostasis) is the process by which living organisms maintain relatively stable internal physical and chemical conditions despite changes in their internal or external environment. Body temperature, blood glucose, blood pressure, fluid balance, levels of oxygen and carbon dioxide in the blood, pH, and the concentrations of ions such as sodium, potassium, and calcium are all homeostatically regulated variables. These variables are generally maintained within physiological ranges rather than at absolutely constant values; set points for some regulated variables may also change, as occurs with circadian variation in body temperature or during fever.
Homeostatic regulation commonly operates through negative feedback. Sensors detect changes in a regulated variable, control mechanisms coordinate an appropriate response, and effectors act to counter the deviation. Regulation can involve the nervous system, endocrine system, and organs: the kidneys, lungs, liver, and pancreas, as well as cellular mechanisms such as the regulation of gene expression. Predictive homeostasis consists of anticipatory responses to expected changes, but these require feedback mechanisms to correct deviations. Together, homeostatic processes maintain conditions in which metabolism and other physiological functions can occur.
The concept of regulation of the internal environment was developed in the 19th century by the French physiologist Claude Bernard, and the term homeostasis was coined by the American physiologist Walter Bradford Cannon in 1926. Failure of homeostatic mechanisms can contribute to disease; examples include type 1 diabetes, disorders of calcium regulation, and disturbances of water balance. The effectiveness of homeostatic control can also decline with aging, and compensatory mechanisms may temporarily mask chronic disease.
Although primarily a biological concept, homeostasis has also been applied to the biosphere and, by analogy, in a range of other fields.
The concept of the regulation of the internal environment was described by French physiologist Claude Bernard in 1849, and the word homeostasis was coined by Walter Bradford Cannon in 1926. In 1932, Joseph Barcroft, a British physiologist, was the first to say that higher brain function required the most stable internal environment. Thus, to Barcroft homeostasis was not only organized by the brain—homeostasis served the brain. Homeostasis is an almost exclusively biological term, referring to the concepts described by Bernard and Cannon, concerning the constancy of the internal environment in which the cells of the body live and survive. The term cybernetics is applied to technological control systems such as thermostats, which function as homeostatic mechanisms but are often defined much more broadly than the biological term of homeostasis.
Overview
The metabolic processes of all organisms can only take place in very specific physical and chemical environments. The conditions vary with each organism, and also with whether the chemical processes take place inside the cell or in the interstitial fluid bathing the cells. The best-known homeostatic mechanisms in humans and other mammals are regulators that keep the composition of the extracellular fluid (or the "internal environment") constant, especially with regard to the temperature, pH, osmolality, and the concentrations of sodium, potassium, glucose, carbon dioxide, and oxygen. However, a great many other homeostatic mechanisms, encompassing many aspects of human physiology, control other entities in the body. Where the levels of variables are higher or lower than those needed, they are often prefixed with hyper- and hypo-, respectively such as hyperthermia and hypothermia or hypertension and hypotension.
Circadian variation in body temperature, ranging from about 37.5°C from 10 a.m. to 6 p.m., and falling to about 36.4°C from 2 a.m. to 6 a.m.
If an entity is homeostatically controlled it does not imply that its value is necessarily absolutely steady in health. Core body temperature is, for instance, regulated by a homeostatic mechanism with temperature sensors in, amongst others, the hypothalamus of the brain. However, the set point of the regulator is regularly reset. For instance, core body temperature in humans varies during the course of the day (i.e. has a circadian rhythm), with the lowest temperatures occurring at night, and the highest in the afternoons. Other normal temperature variations include those related to the menstrual cycle. The temperature regulator's set point is reset during infections to produce a fever. Organisms are capable of adjusting somewhat to varied conditions such as temperature changes or oxygen levels at altitude, by a process of acclimatisation.
Homeostasis does not govern every activity in the body. 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, arterial blood pressure in mammals is homeostatically controlled and measured by stretch receptors in the walls of the aortic arch and carotid sinuses at the beginnings of the internal 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 the set point. Thus the heart rate (for which there is no sensor in the body) is not homeostatically controlled but is one of the effector responses to errors in 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.
Homeostasis is the body’s ability to maintain stable internal conditions despite changes in the environment.Birds huddling for warmth
Mammals regulate their core temperature using input from thermoreceptors in the hypothalamus, brain, spinal cord, internal organs, and great veins. Apart from the internal regulation of temperature, a process called allostasis can come into play that adjusts behaviour to adapt to the challenge of very hot or cold extremes (and to other challenges). These adjustments may include seeking shade and reducing activity, seeking warmer conditions and increasing activity, or huddling. Behavioral thermoregulation takes precedence over physiological thermoregulation since necessary changes can be affected more quickly and physiological thermoregulation is limited in its capacity to respond to extreme temperatures.
When the core temperature falls, the blood supply to the skin is reduced by intense vasoconstriction. The blood flow to the limbs (which have a large surface area) is similarly reduced and returned to the trunk via the deep veins which lie alongside the arteries (forming venae comitantes). This acts as a counter-current exchange system that short-circuits the warmth from the arterial blood directly into the venous blood returning into the trunk, causing minimal heat loss from the extremities in cold weather. The subcutaneous limb veins are tightly constricted, not only reducing heat loss from this source but also forcing the venous blood into the counter-current system in the depths of the limbs.
When core temperature rises are detected by thermoreceptors, the sweat glands in the skin are stimulated via cholinergicsympathetic nerves to secrete sweat onto the skin, which, when it evaporates, cools the skin and the blood flowing through it. Panting is an alternative effector in many vertebrates, which cools the body also by the evaporation of water, but this time from the mucous membranes of the throat and mouth.
Negative feedback at work in the regulation of blood sugar. Flat line is the set-point of glucose level and sine wave the fluctuations of glucose.
Blood sugar levels are regulated within fairly narrow limits. In mammals, the primary sensors for this are the beta cells of the pancreatic islets.The beta cells respond to a rise in the blood sugar level by secreting insulin into the blood and simultaneously inhibiting their neighboring alpha cells from secreting glucagon into the blood. This combination (high blood insulin levels and low glucagon levels) act on effector tissues, the chief of which is the liver, fat cells, and muscle cells. The liver is inhibited from producing glucose, taking it up instead, and converting it to glycogen and triglycerides. The glycogen is stored in the liver, but the triglycerides are secreted into the blood as very low-density lipoprotein (VLDL) particles which are taken up by adipose tissue, there to be stored as fats. The fat cells take up glucose through special glucose transporters (GLUT4), whose numbers in the cell wall are increased as a direct effect of insulin acting on these cells. The glucose that enters the fat cells in this manner is converted into triglycerides (via the same metabolic pathways as are used by the liver) and then stored in those fat cells together with the VLDL-derived triglycerides that were made in the liver. Muscle cells also take glucose up through insulin-sensitive GLUT4 glucose channels, and convert it into muscle glycogen.
A fall in blood glucose, causes insulin secretion to be stopped, and glucagon to be secreted from the alpha cells into the blood. This inhibits the uptake of glucose from the blood by the liver, fats cells, and muscle. Instead the liver is strongly stimulated to manufacture glucose from glycogen (through glycogenolysis) and from non-carbohydrate sources (such as lactate and de-aminated amino acids) using a process known as gluconeogenesis. The glucose thus produced is discharged into the blood correcting the detected error (hypoglycemia). The glycogen stored in muscles remains in the muscles, and is only broken down, during exercise, to glucose-6-phosphate and thence to pyruvate to be fed into the citric acid cycle or turned into lactate. It is only the lactate and the waste products of the citric acid cycle that are returned to the blood. The liver can take up only the lactate, and, by the process of energy-consuming gluconeogenesis, convert it back to glucose.
Controlling iron levels in the body is a critically important part of many aspects of human health and disease. There can be negative consequences on health if iron concentration is too high or too low.
Copper is absorbed, transported, distributed, stored, and excreted in the body according to complex homeostatic processes which ensure a constant and sufficient supply of the micronutrient while simultaneously avoiding excess levels. If an insufficient amount of copper is ingested for a short period of time, copper stores in the liver will be depleted. Should this depletion continue, a copper health deficiency condition may develop. If too much copper is ingested, an excess condition can result. Both of these conditions, deficiency and excess, can lead to tissue injury and disease. However, due to homeostatic regulation, the human body is capable of balancing a wide range of copper intakes for the needs of healthy individuals.
Many aspects of copper homeostasis are known at the molecular level. Copper's essentiality is due to its ability to act as an electron donor or acceptor as its oxidation state fluxes between Cu1+ (cuprous) and Cu2+ (cupric). As a component of about a dozen cuproenzymes, copper is involved in key redox (i.e., oxidation-reduction) reactions in essential metabolic processes such as mitochondrial respiration, synthesis of melanin, and cross-linking of collagen. Copper is an integral part of the antioxidant enzyme copper-zinc superoxide dismutase, and has a role in iron homeostasis as a cofactor in ceruloplasmin.
Too little carbon dioxide, and, to a lesser extent, too much oxygen in the blood can temporarily halt breathing, a condition known as apnea, which freedivers use to prolong the time they can stay underwater.
The partial pressure of carbon dioxide is more of a deciding factor in the monitoring of pH. However, at high altitude (above 2500m) the monitoring of the partial pressure of oxygen takes priority, and hyperventilation keeps the oxygen level constant. With the lower level of carbon dioxide, to keep the pH at 7.4 the kidneys secrete hydrogen ions into the blood and excrete bicarbonate into the urine. This is important in acclimatization to high altitude.
Blood oxygen content
The kidneys measure the oxygen content rather than the partial pressure of oxygen in the arterial blood. When the oxygen content of the blood is chronically low, oxygen-sensitive cells secrete erythropoietin (EPO) into the blood. The effector tissue is the red bone marrow which produces red blood cells (RBCs, also called erythrocytes). The increase in RBCs leads to an increased hematocrit in the blood, and a subsequent increase in hemoglobin that increases the oxygen carrying capacity. This is the mechanism whereby high altitude dwellers have higher hematocrits than sea-level residents, and also why persons with pulmonary insufficiency or right-to-left shunts in the heart (through which venous blood by-passes the lungs and goes directly into the systemic circulation) have similarly high hematocrits.
Regardless of the partial pressure of oxygen in the blood, the amount of oxygen that can be carried, depends on the hemoglobin content. The partial pressure of oxygen may be sufficient for example in anemia, but the hemoglobin content will be insufficient and subsequently as will be the oxygen content. Given enough supply of iron, vitamin B12 and folic acid, EPO can stimulate RBC production, and hemoglobin and oxygen content restored to normal.
The brain can regulate blood flow over a range of blood pressure values by vasoconstriction and vasodilation of the arteries.
High pressure receptors called baroreceptors in the walls of the aortic arch and carotid sinus (at the beginning of the internal carotid artery) monitor the arterial blood pressure. Rising pressure is detected when the walls of the arteries stretch due to an increase in blood volume. This causes heart muscle cells to secrete the hormone atrial natriuretic peptide (ANP) into the blood. This acts on the kidneys to inhibit the secretion of renin and aldosterone causing the release of sodium, and accompanying water into the urine, thereby reducing the blood volume. This information is then conveyed, via afferent nerve fibers, to the solitary nucleus in the medulla oblongata. From here motor nerves belonging to the autonomic nervous system are stimulated to influence the activity of chiefly the heart and the smallest diameter arteries, called arterioles. The arterioles are the main resistance vessels in the arterial tree, and small changes in diameter cause large changes in the resistance to flow through them. When the arterial blood pressure rises the arterioles are stimulated to dilate making it easier for blood to leave the arteries, thus deflating them, and bringing the blood pressure down, back to normal. At the same time, the heart is stimulated via cholinergicparasympathetic nerves to beat more slowly (called bradycardia), ensuring that the inflow of blood into the arteries is reduced, thus adding to the reduction in pressure, and correcting the original error.
Low pressure in the arteries, causes the opposite reflex of constriction of the arterioles, and a speeding up of the heart rate (called tachycardia). If the drop in blood pressure is very rapid or excessive, the medulla oblongata stimulates the adrenal medulla, via "preganglionic" sympathetic nerves, to secrete epinephrine (adrenaline) into the blood. This hormone enhances the tachycardia and causes severe vasoconstriction of the arterioles to all but the essential organs in the body (especially the heart, lungs, and brain). These reactions usually correct the low arterial blood pressure (hypotension) very effectively.
The plasma ionized calcium (Ca2+) concentration is very tightly controlled by a pair of homeostatic mechanisms. The sensor for the first one is situated in the parathyroid glands, where the chief cells sense the Ca2+ level by means of specialized calcium receptors in their membranes. The sensors for the second are the parafollicular cells in the thyroid gland. The parathyroid chief cells secrete parathyroid hormone (PTH) in response to a fall in the plasma ionized calcium level; the parafollicular cells of the thyroid gland secrete calcitonin in response to a rise in the plasma ionized calcium level.
The effector organs of the first homeostatic mechanism are the bones, the kidney, and, via a hormone released into the blood by the kidney in response to high PTH levels in the blood, the duodenum and jejunum. Parathyroid hormone (in high concentrations in the blood) causes bone resorption, releasing calcium into the plasma. This is a very rapid action which can correct a threatening hypocalcemia within minutes. High PTH concentrations cause the excretion of phosphate ions via the urine. Since phosphates combine with calcium ions to form insoluble salts (see also bone mineral), a decrease in the level of phosphates in the blood, releases free calcium ions into the plasma ionized calcium pool. PTH has a second action on the kidneys. It stimulates the manufacture and release, by the kidneys, of calcitriol into the blood. This steroid hormone acts on the epithelial cells of the upper small intestine, increasing their capacity to absorb calcium from the gut contents into the blood.
The second homeostatic mechanism, with its sensors in the thyroid gland, releases calcitonin into the blood when the blood ionized calcium rises. This hormone acts primarily on bone, causing the rapid removal of calcium from the blood and depositing it, in insoluble form, in the bones.
The two homeostatic mechanisms working through PTH on the one hand, and calcitonin on the other can very rapidly correct any impending error in the plasma ionized calcium level by either removing calcium from the blood and depositing it in the skeleton, or by removing calcium from it. The skeleton acts as an extremely large calcium store (about 1kg) compared with the plasma calcium store (about 180mg). Longer term regulation occurs through calcium absorption or loss from the gut.
Another example are the most well-characterised endocannabinoids like anandamide (N-arachidonoylethanolamide; AEA) and 2-arachidonoylglycerol (2-AG), whose synthesis occurs through the action of a series of intracellularenzymes activated in response to a rise in intracellular calcium levels to introduce homeostasis and prevention of tumor development through putative protective mechanisms that prevent cell growth and migration by activation of CB1 and/or CB2 and adjoining receptors.
The homeostatic mechanism which controls the plasma sodium concentration is rather more complex than most of the other homeostatic mechanisms described on this page.
The sensor is situated in the juxtaglomerular apparatus of kidneys, which senses the plasma sodium concentration in a surprisingly indirect manner. Instead of measuring it directly in the blood flowing past the juxtaglomerular cells, these cells respond to the sodium concentration in the renal tubular fluid after it has already undergone a certain amount of modification in the proximal convoluted tubule and loop of Henle. These cells also respond to rate of blood flow through the juxtaglomerular apparatus, which, under normal circumstances, is directly proportional to the arterial blood pressure, making this tissue an ancillary arterial blood pressure sensor.
In response to a lowering of the plasma sodium concentration, or to a fall in the arterial blood pressure, the juxtaglomerular cells release renin into the blood. Renin is an enzyme which cleaves a decapeptide (a short protein chain, 10 amino acids long) from a plasma α-2-globulin called angiotensinogen. This decapeptide is known as angiotensin I. It has no known biological activity. However, when the blood circulates through the lungs a pulmonary capillary endothelial enzyme called angiotensin-converting enzyme (ACE) cleaves a further two amino acids from angiotensin I to form an octapeptide known as angiotensin II. Angiotensin II is a hormone which acts on the adrenal cortex, causing the release into the blood of the steroid hormone, aldosterone. Angiotensin II also acts on the smooth muscle in the walls of the arterioles causing these small diameter vessels to constrict, thereby restricting the outflow of blood from the arterial tree, causing the arterial blood pressure to rise. This, therefore, reinforces the measures described above (under the heading of "Arterial blood pressure"), which defend the arterial blood pressure against changes, especially hypotension.
The angiotensin II-stimulated aldosterone released from the zona glomerulosa of the adrenal glands has an effect on particularly the epithelial cells of the distal convoluted tubules and collecting ducts of the kidneys. Here it causes the reabsorption of sodium ions from the renal tubular fluid, in exchange for potassium ions which are secreted from the blood plasma into the tubular fluid to exit the body via the urine. The reabsorption of sodium ions from the renal tubular fluid halts further sodium ion losses from the body, and therefore preventing the worsening of hyponatremia. The hyponatremia can only be corrected by the consumption of salt in the diet. However, it is not certain whether a "salt hunger" can be initiated by hyponatremia, or by what mechanism this might come about.
When the plasma sodium ion concentration is higher than normal (hypernatremia), the release of renin from the juxtaglomerular apparatus is halted, ceasing the production of angiotensin II, and its consequent aldosterone-release into the blood. The kidneys respond by excreting sodium ions into the urine, thereby normalizing the plasma sodium ion concentration. The low angiotensin II levels in the blood lower the arterial blood pressure as an inevitable concomitant response.
The reabsorption of sodium ions from the tubular fluid as a result of high aldosterone levels in the blood does not, of itself, cause renal tubular water to be returned to the blood from the distal convoluted tubules or collecting ducts. This is because sodium is reabsorbed in exchange for potassium and therefore causes only a modest change in the osmotic gradient between the blood and the tubular fluid. Furthermore, the epithelium of the distal convoluted tubules and collecting ducts is impermeable to water in the absence of antidiuretic hormone (ADH) in the blood. ADH is part of the control of fluid balance. Its levels in the blood vary with the osmolality of the plasma, which is measured in the hypothalamus of the brain. Aldosterone's action on the kidney tubules prevents sodium loss to the extracellular fluid (ECF). So there is no change in the osmolality of the ECF, and therefore no change in the ADH concentration of the plasma. However, low aldosterone levels cause a loss of sodium ions from the ECF, which could potentially cause a change in extracellular osmolality and therefore of ADH levels in the blood.
Aldosterone acts primarily on the distal convoluted tubules and collecting ducts of the kidneys, stimulating the excretion of potassium ions into the urine. It does so, however, by activating the basolateralNa+/K+ pumps of the tubular epithelial cells. These sodium/potassium exchangers pump three sodium ions out of the cell, into the interstitial fluid and two potassium ions into the cell from the interstitial fluid. This creates an ionic concentration gradient which results in the reabsorption of sodium (Na+) ions from the tubular fluid into the blood, and secreting potassium (K+) ions from the blood into the urine (lumen of collecting duct).
The total amount of water in the body needs to be kept in balance. Fluid balance involves keeping the fluid volume stabilized, and also keeping the levels of electrolytes in the extracellular fluid stable. Fluid balance is maintained by the process of osmoregulation and by behavior. Osmotic pressure is detected by osmoreceptors in the median preoptic nucleus in the hypothalamus. Measurement of the plasma osmolality to give an indication of the water content of the body, relies on the fact that water losses from the body, (through unavoidable water loss through the skin which is not entirely waterproof and therefore always slightly moist, water vapor in the exhaled air, sweating, vomiting, normal feces and especially diarrhea) are all hypotonic, meaning that they are less salty than the body fluids (compare, for instance, the taste of saliva with that of tears. The latter has almost the same salt content as the extracellular fluid, whereas the former is hypotonic with respect to the plasma. Saliva does not taste salty, whereas tears are decidedly salty). Nearly all normal and abnormal losses of body water therefore cause the extracellular fluid to become hypertonic. Conversely, excessive fluid intake dilutes the extracellular fluid causing the hypothalamus to register hypotonic hyponatremia conditions.
When the hypothalamus detects a hypertonic extracellular environment, it causes the secretion of an antidiuretic hormone (ADH) called vasopressin which acts on the effector organ, which in this case is the kidney. The effect of vasopressin on the kidney tubules is to reabsorb water from the distal convoluted tubules and collecting ducts, thus preventing aggravation of the water loss via the urine. The hypothalamus simultaneously stimulates the nearby thirst center causing an almost irresistible (if the hypertonicity is severe enough) urge to drink water. The cessation of urine flow prevents the hypovolemia and hypertonicity from getting worse; the drinking of water corrects the defect.
Hypo-osmolality results in very low plasma ADH levels. This results in the inhibition of water reabsorption from the kidney tubules, causing high volumes of very dilute urine to be excreted, thus getting rid of the excess water in the body.
Urinary water loss, when the body water homeostat is intact, is a compensatory water loss, correcting any water excess in the body. However, since the kidneys cannot generate water, the thirst reflex is the all-important second effector mechanism of the body water homeostat, correcting any water deficit in the body.
The plasma pH can be altered by respiratory changes in the partial pressure of carbon dioxide; or altered by metabolic changes in the carbonic acid to bicarbonate ion ratio. The bicarbonate buffer system regulates the ratio of carbonic acid to bicarbonate to be equal to 1:20, at which ratio the blood pH is 7.4 (as explained in the Henderson–Hasselbalch equation). A change in the plasma pH gives an acid–base imbalance.
In acid–base homeostasis there are two mechanisms that can help regulate the pH. Respiratory compensation a mechanism of the respiratory center, adjusts the partial pressure of carbon dioxide by changing the rate and depth of breathing, to bring the pH back to normal. The partial pressure of carbon dioxide also determines the concentration of carbonic acid, and the bicarbonate buffer system can also come into play. Renal compensation can help the bicarbonate buffer system.
The sensor for the plasma bicarbonate concentration is not known for certain. It is very probable that the renal tubular cells of the distal convoluted tubules are themselves sensitive to the pH of the plasma. The metabolism of these cells produces carbon dioxide, which is rapidly converted to hydrogen and bicarbonate through the action of carbonic anhydrase. When the ECF pH falls (becoming more acidic) the renal tubular cells excrete hydrogen ions into the tubular fluid to leave the body via urine. Bicarbonate ions are simultaneously secreted into the blood that decrease the carbonic acid, and consequently raise the plasma pH. The converse happens when the plasma pH rises above normal: bicarbonate ions are excreted into the urine, and hydrogen ions released into the plasma.
When hydrogen ions are excreted into the urine, and bicarbonate into the blood, the latter combines with the excess hydrogen ions in the plasma that stimulated the kidneys to perform this operation. The resulting reaction in the plasma is the formation of carbonic acid which is in equilibrium with the plasma partial pressure of carbon dioxide. This is tightly regulated to ensure that there is no excessive build-up of carbonic acid or bicarbonate. The overall effect is therefore that hydrogen ions are lost in the urine when the pH of the plasma falls. The concomitant rise in the plasma bicarbonate mops up the increased hydrogen ions (caused by the fall in plasma pH) and the resulting excess carbonic acid is disposed of in the lungs as carbon dioxide. This restores the normal ratio between bicarbonate and the partial pressure of carbon dioxide and therefore the plasma pH.
The converse happens when a high plasma pH stimulates the kidneys to secrete hydrogen ions into the blood and to excrete bicarbonate into the urine. The hydrogen ions combine with the excess bicarbonate ions in the plasma, once again forming an excess of carbonic acid which can be exhaled, as carbon dioxide, in the lungs, keeping the plasma bicarbonate ion concentration, the partial pressure of carbon dioxide and, therefore, the plasma pH, constant.
Cerebrospinal fluid
Cerebrospinal fluid (CSF) allows for regulation of the distribution of substances between cells of the brain, and neuroendocrine factors, to which slight changes can cause problems or damage to the nervous system. For example, high glycineconcentration disrupts temperature and blood pressure control, and high CSF pH causes dizziness and syncope.
Neurotransmission
Inhibitory neurons in the central nervous system play a homeostatic role in the balance of neuronal activity between excitation and inhibition. Inhibitory neurons using GABA, make compensating changes in the neuronal networks preventing runaway levels of excitation. An imbalance between excitation and inhibition is seen to be implicated in a number of neuropsychiatric disorders.
The neuroendocrine system is the mechanism by which the hypothalamus maintains homeostasis, regulating metabolism, reproduction, eating and drinking behaviour, energy utilization, osmolarity and blood pressure.
The liver also has many regulatory functions of the metabolism. An important function is the production and control of bile acids. Too much bile acid can be toxic to cells and its synthesis can be inhibited by activation of FXR a nuclear receptor.
The amount of energy taken in through nutrition needs to match the amount of energy used. To achieve energy homeostasis appetite is regulated by two hormones, grehlin and leptin. Grehlin stimulates hunger and the intake of food and leptin acts to signal satiety (fullness).
A 2019 review of weight-change interventions, including dieting, exercise and overeating, found that body weight homeostasis could not precisely correct for "energetic errors", the loss or gain of calories, in the short-term.
Clinical significance
Many diseases are the result of a homeostatic failure. Almost any homeostatic component can malfunction either as a result of an inherited defect, an inborn error of metabolism, or an acquired disease. Some homeostatic mechanisms have inbuilt redundancies, which ensures that life is not immediately threatened if a component malfunctions; but sometimes a homeostatic malfunction can result in serious disease, which can be fatal if not treated. A well-known example of a homeostatic failure is shown in type 1 diabetes mellitus. Here blood sugar regulation is unable to function because the beta cells of the pancreatic islets are destroyed and cannot produce the necessary insulin. The blood sugar rises in a condition known as hyperglycemia.
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 stable albeit larger volumes of very dilute urine, causing dehydration and death if left untreated.
As organisms age, the efficiency of their control systems decays. The inefficiencies gradually result in an unstable internal environment that increases the risk of illness, and leads to the physical changes associated with aging.
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 according to Fan et al. (2011).
Biosphere
In the Gaia hypothesis, James Lovelock stated that the entire mass of living matter on Earth (or any planet with life) functions as a vast homeostatic superorganism that actively modifies its planetary environment to produce the environmental conditions necessary for its own survival. In this view, the entire planet maintains several homeostasis (the primary one being temperature homeostasis). Whether this sort of system is present on Earth is open to debate. However, some relatively simple homeostatic mechanisms are generally accepted. For example, it is sometimes claimed that when atmospheric carbon dioxide levels rise, certain plants may be able to grow better and thus act to remove more carbon dioxide from the atmosphere. However, warming has exacerbated droughts, making water the actual limiting factor on land. When sunlight is plentiful and the atmospheric temperature climbs, it has been claimed that the phytoplankton of the ocean surface waters, acting as global sunshine, and therefore heat sensors, may thrive and produce more dimethyl sulfide (DMS). The DMS molecules act as cloud condensation nuclei, which produce more clouds, and thus increase the atmospheric albedo, and this feeds back to lower the temperature of the atmosphere. However, rising sea temperature has stratified the oceans, separating warm, sunlit waters from cool, nutrient-rich waters. Thus, nutrients have become the limiting factor, and plankton levels have actually fallen over the past 50 years, not risen. As scientists discover more about Earth, vast numbers of positive and negative feedback loops are being discovered,, that, together, maintain a metastable condition, sometimes within a very broad range of environmental conditions.
Predictive
Predictive homeostasis is an anticipatory response to an expected challenge in the future, such as the stimulation of insulin secretion by gut hormones which enter the blood in response to a meal. This insulin secretion occurs before the blood sugar level rises, lowering the blood sugar level in anticipation of a large influx into the blood of glucose resulting from the digestion of carbohydrates in the gut. Such anticipatory reactions are open loop systems which are based, essentially, on "guess work", and are not self-correcting. Anticipatory responses always require a closed loop negative feedback system to correct the 'over-shoots' and 'under-shoots' to which the anticipatory systems are prone.
Other fields
The term has come to be used in other fields, for example:
An actuary may refer to risk homeostasis, where (for example) people who have anti-lock brakes have no better safety record than those without anti-lock brakes, because the former unconsciously compensate for the safer vehicle via less-safe driving habits. Previous to the innovation of anti-lock brakes, certain maneuvers involved minor skids, evoking fear and avoidance: Now the anti-lock system moves the boundary for such feedback, and behavior patterns expand into the no-longer punitive area. It has also been suggested that ecological crises are an instance of risk homeostasis in which a particular behavior continues until proven dangerous or dramatic consequences actually occur.[self-published source?]
Stress
Sociologists and psychologists may refer to stress homeostasis, the tendency of a population or an individual to stay at a certain level of stress, often generating artificial stresses if the "natural" level of stress is not enough.
Jean-François Lyotard, a postmodern theorist, has applied this term to societal 'power centers' that he describes in The Postmodern Condition, as being 'governed by a principle of homeostasis,' for example, the scientific hierarchy, which will sometimes ignore a radical new discovery for years because it destabilizes previously accepted norms.
A thermostat operates by switching heaters or air-conditioners on and off in response to the output of a temperature sensor.
Cruise control adjusts a car's throttle in response to changes in speed.
An autopilot operates the steering controls of an aircraft or ship in response to deviation from a pre-set compass bearing or route.
Process control systems in a chemical plant or oil refinery maintain fluid levels, pressures, temperature, chemical composition, etc. by controlling heaters, pumps and valves.
The centrifugal governor of a steam engine, as designed by James Watt in 1788, reduces the throttle valve in response to increases in the engine speed, or opens the valve if the speed falls below the pre-set rate.
Society and culture
The use of sovereign power, codes of conduct, religious and cultural practices and other dynamic processes in a society can be described as a part of an evolved homeostatic system of regularizing life and maintaining an overall equilibrium that protects the security of the whole from internal and external imbalances or dangers. Healthy civic cultures can be said to have achieved an optimal homeostatic balance between multiple contradictory concerns such as in the tension between respect for individual rights and concern for the public good, or that between governmental effectiveness and responsiveness to the interests of citizens.
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