View source for Homeostasis

{{Short description|State of steady internal conditions maintained by living things}}
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In [[biology]], '''homeostasis''' ([[British English|British]] also '''homoeostasis'''; {{IPAc-en|ˌ|h|oʊ|m|i|ə|ˈ|s|t|eɪ|s|ɪ|s}} {{respell|HOH|mee|ə|STAY|sis}}) is the state of steady internal [[physics|physical]] and [[chemistry|chemical]] conditions maintained by [[organism|living systems]].<ref>{{cite book |title=Anatomy and physiology |last=Gordon |first=Betts, J. |others=DeSaix, Peter., Johnson, Eddie., Johnson, Jody E., Korol, Oksana., Kruse, Dean H., Poe, Brandon. |isbn=978-1-947172-04-3 |location=Houston, Texas |page=9 |oclc=1001472383}}</ref> This is the condition of optimal functioning for the organism and includes many variables, such as [[body temperature]] and [[fluid balance]], being kept within certain pre-set limits (homeostatic range). Other variables include the [[pH]] of [[extracellular fluid]], the concentrations of [[sodium]], [[potassium]], and [[calcium]] [[ion]]s, as well as the [[blood sugar level]], and these need to be regulated despite changes in the environment, diet, or level of activity. Each of these variables is controlled by one or more regulators or homeostatic mechanisms, which together maintain life.

Homeostasis is brought about by a natural resistance to change when already in optimal conditions,<ref name="EM">{{cite book |title=A dictionary of biology |last=Martin |first=Elizabeth |date=2008 |publisher=Oxford University Press |isbn=978-0-19-920462-5 |edition=6th |location=Oxford |pages=315–316}}</ref> and equilibrium is maintained by many regulatory mechanisms; it is thought to be the central motivation for all organic action. All homeostatic control mechanisms have at least three interdependent components for the variable being regulated: a receptor, a control center, and an effector.<ref>{{cite web |title=Homeostasis  |url=https://www.biologyonline.com/dictionary/homeostasis  |website=Biology Online |date=27 October 2019  |access-date=27 October 2019  |archive-date=12 August 2020  |archive-url=https://web.archive.org/web/20200812025400/https://www.biologyonline.com/dictionary/homeostasis  |url-status=live }}</ref> The receptor is the sensing component that monitors and responds to changes in the environment, either external or internal. Receptors include [[thermoreceptor]]s and [[mechanoreceptor]]s. Control centers include the [[respiratory center]] and the [[renin–angiotensin system|renin-angiotensin system]]. An effector is the target acted on, to bring about the change back to the normal state. At the cellular level, effectors include [[nuclear receptor]]s that bring about changes in [[gene expression]] through up-regulation or down-regulation and act in [[negative feedback]] mechanisms. An example of this is in the control of [[bile acid]]s in the [[liver]].<ref name="Kalaany">{{cite journal |last1=Kalaany |first1=NY |last2=Mangelsdorf |first2=DJ |title=LXRS and FXR: the yin and yang of cholesterol and fat metabolism. |journal=Annual Review of Physiology |date=2006 |volume=68 |pages=159–91 |doi=10.1146/annurev.physiol.68.033104.152158 |pmid=16460270}}</ref>

Some centers, such as the [[renin–angiotensin system]], control more than one variable. When the receptor senses a stimulus, it reacts by sending action potentials to a control center. The control center sets the maintenance range—the acceptable upper and lower limits—for the particular variable, such as temperature. The control center responds to the signal by determining an appropriate response and sending signals to an [[Effector cell|effector]], which can be one or more muscles, an organ, or a [[gland]]. When the signal is received and acted on, negative feedback is provided to the receptor that stops the need for further signaling.<ref name=Marieb/>

The [[cannabinoid receptor type 1]], located at the [[Synapse|presynaptic]] [[neuron]], is a [[Receptor (biochemistry)|receptor]] that can stop stressful [[neurotransmitter]] release to the postsynaptic neuron; it is activated by [[Cannabinoid|endocannabinoids]] such as [[anandamide]] (''N''-arachidonoylethanolamide) and [[2-Arachidonoylglycerol|2-arachidonoylglycerol]] via a [[retrograde signaling]] process in which these compounds are synthesized by and released from postsynaptic neurons, and travel back to the presynaptic terminal to bind to the CB1 receptor for modulation of neurotransmitter release to obtain homeostasis.<ref>{{Citation |last=Lovinger |first=David M. |chapter=Presynaptic Modulation by Endocannabinoids |date=2008 |pages=435–477 |editor-last=Südhof |editor-first=Thomas C. |series=Handbook of Experimental Pharmacology |publisher=Springer Berlin Heidelberg  |doi=10.1007/978-3-540-74805-2_14 |pmid=18064422  |isbn=978-3-540-74805-2  |editor2-last=Starke |editor2-first=Klaus |title=Pharmacology of Neurotransmitter Release |volume=184  |issue=184}}</ref>

The [[polyunsaturated fatty acid]]s are [[lipid]] derivatives of [[Omega-3 fatty acid|omega-3]] ([[docosahexaenoic acid]], and [[eicosapentaenoic acid]]) or of [[Omega-6 fatty acid|omega-6]] ([[arachidonic acid]]). They are synthesized from [[Cell membrane|membrane]] [[phospholipid]]s and used as precursors for endocannabinoids to mediate significant effects in the fine-tuning adjustment of body homeostasis.<ref>{{Cite journal |last1=Freitas |first1=Hércules Rezende |last2=Isaac |first2=Alinny Rosendo |last3=Malcher-Lopes |first3=Renato |last4=Diaz |first4=Bruno Lourenço |last5=Trevenzoli |first5=Isis Hara |last6=Reis |first6=Ricardo Augusto De Melo |date=26 November 2018 |title=Polyunsaturated fatty acids and endocannabinoids in health and disease |journal=Nutritional Neuroscience |volume=21 |issue=10 |pages=695–714 |doi=10.1080/1028415X.2017.1347373 |pmid=28686542 |s2cid=40659630}}</ref>

==Etymology==
The word ''homeostasis'' ({{IPAc-en|ˌ|h|oʊ|m|i|oʊ-|ˈ|s|t|eɪ|s|ᵻ|s}}{{refn|{{MerriamWebsterDictionary|Homeostasis}}}}{{refn|{{Dictionary.com|Homeostasis}}}} {{respell|hoh|mee|oh|STAY|sis}}<ref>{{cite book |last1=VanPutte |first1=Cinnamon L. |last2=Regan |first2=Jennifer L. |last3=Russo |first3=Andrew F. |title=Seeley's Essentials of Anatomy & Physiology |date=2022 |publisher=McGraw-Hill |isbn=978-1-264-99515-8 |page=16 |edition=11 |url=https://books.google.com/books?id=45PEzgEACAAJ |language=en}}</ref>) uses [[classical compound|combining forms]] of ''homeo-'' and ''-stasis'', [[Neo-Latin]] from [[Ancient Greek|Greek]]: ὅμοιος ''homoios'', "similar" and στάσις ''stasis'', "standing still", yielding the idea of "staying the same".

==History==
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.<ref name=wotb>{{cite book |first=W.B. |last=Cannon |author-link=Walter Bradford Cannon |title=The Wisdom of the Body |pages=177–201 |year=1932 |publisher=W. W. Norton |location=New York}}</ref><ref name=cannon>{{cite book |language=fr |first=W. B. |last=Cannon |author-link=Walter Bradford Cannon |chapter=Physiological regulation of normal states: some tentative postulates concerning biological homeostatics |editor=A. Pettit|title=A Charles Riches amis, ses collègues, ses élèves |page=91 |publisher=Paris: Les Éditions Médicales |year=1926}}</ref> 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.<ref>{{Cite journal|last=Smith|first=Gerard P.|date=2008|title=Unacknowledged contributions of Pavlov and Barcroft to Cannon's theory of homeostasis|journal=Appetite|language=en|volume=51|issue=3|pages=428–432|doi=10.1016/j.appet.2008.07.003|pmid=18675307|s2cid=43088475}}</ref> 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.<ref name=wotb /><ref name=cannon /><ref name="zorea">{{Cite book|title=Steroids (Health and Medical Issues Today)|last=Zorea|first=Aharon|publisher=Greenwood Press|year=2014|isbn=978-1-4408-0299-7|location=Westport, CT|page=10}}</ref> The term [[cybernetics]] is applied to technological [[control system]]s such as [[thermostat]]s, which function as homeostatic mechanisms but are often defined much more broadly than the biological term of homeostasis.<ref name=Marieb>{{cite book |vauthors = Marieb EN, Hoehn KN |title=Essentials of Human Anatomy & Physiology |edition= 9th |year=2009 |publisher=Pearson/Benjamin Cummings |location=San Francisco |isbn=978-0-321-51342-7}}</ref><ref>{{cite book |last1=Riggs |first1=D.S. |title=Control theory and physiological feedback mechanisms. |location=Baltimore |publisher=Williams & Wilkins |date=1970 }}</ref><ref name="Hall">{{cite book|last1=Hall|first1=John|title=Guyton and Hall textbook of medical physiology|date=2011|publisher=Saunders/bich er|location=Philadelphia, Pa.|isbn=978-1-4160-4574-8|pages=4–9|edition= 12th}}</ref><ref name=milsum>{{cite book |last1=Milsum |first1=J.H. |title=Biological control systems analysis.| location=New York |publisher=McGraw-Hill |date=1966 }}</ref>

==Overview==

The [[Metabolism|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 (biology)|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 [[Thermoregulation|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]].{{citation needed|date=April 2023}}

[[Image:Body Temp Variation.svg|class=skin-invert-image|thumb|250px|right|Circadian variation in body temperature, ranging from about 37.5&nbsp;°C from 10 a.m. to 6 p.m., and falling to about 36.4&nbsp;°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. [[Thermoregulation|Core body temperature]] is, for instance, regulated by a homeostatic mechanism with temperature sensors in, amongst others, the [[hypothalamus]] of the [[brain]].<ref name=tortora2>{{cite book |last1=Tortora |first1=Gerard J. | last2=Anagnostakos |first2=Nicholas P. | title=Principles of Anatomy and Physiology |url=https://archive.org/details/principlesofan1987tort |url-access=registration | edition= Fifth |location=New York |publisher=Harper & Row, Publishers |date=1987 |pages=[https://archive.org/details/principlesofan1987tort/page/315 315]–316, 475, 657–658 |isbn=978-0-06-350729-6 }}</ref> However, the [[Setpoint (control system)|set point]] of the regulator is regularly reset.<ref>{{cite web |last1=Khan Academy |title=Homeostasis |url=https://www.khanacademy.org/science/high-school-biology/hs-human-body-systems/hs-body-structure-and-homeostasis/a/homeostasis |website=Khan Academy |access-date=13 July 2018 |archive-date=20 October 2019 |archive-url=https://web.archive.org/web/20191020034655/https://www.khanacademy.org/science/high-school-biology/hs-human-body-systems/hs-body-structure-and-homeostasis/a/homeostasis |url-status=live }}</ref> For instance, core body temperature in humans [[Thermoregulation#Variations due to circadian rhythms|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 [[Human body temperature|temperature variations]] include those related to the [[menstrual cycle]].<ref>{{cite book |url=https://books.google.com/books?id=JZb0ibgYDCIC&pg=PA149 |title=Women's Sports Medicine and Rehabilitation |isbn=978-0-8342-1731-7 |publisher=Lippincott Williams & Wilkins |year=2001 |last=Swedan |first=Nadya Gabriele |page=149 |access-date=11 October 2019 |archive-date=10 May 2020 |archive-url=https://web.archive.org/web/20200510140218/https://books.google.com/books?id=JZb0ibgYDCIC&pg=PA149 |url-status=live }}</ref><ref name=tcoyf2>{{cite book | first=Toni | last=Weschler | year=2002 | title=Taking Charge of Your Fertility | url=https://archive.org/details/takingchargeofyo00toni | url-access=registration | pages=[https://archive.org/details/takingchargeofyo00toni/page/52 52], 316, 361–362 | publisher=HarperCollins | location=New York | isbn=978-0-06-093764-5 }}</ref> The temperature regulator's set point is reset during infections to produce a fever.<ref name=tortora2 /><ref>{{cite book|last=Kluge |first=Matthew J. |title=Fever: Its Biology, Evolution, and Function|date=2015|publisher=Princeton University Press |isbn=978-1-4008-6983-1|page=57 |url=https://books.google.com/books?id=gIF9BgAAQBAJ&pg=PA57}}</ref><ref name=Gar2012p375>{{cite book|last1=Garmel|first1=Gus M.|editor-last1=Mahadevan|editor-first1=S.V.|editor-last2=Garmel|editor-first2=Gus M.|title=An introduction to clinical emergency medicine|chapter=Fever in adults|date=2012|publisher=Cambridge University Press|location=Cambridge|isbn=978-0-521-74776-9|page=375|edition=2nd|chapter-url=https://books.google.com/books?id=pyAlcOfBhjIC&pg=PA375|access-date=11 October 2019|archive-date=30 December 2019|archive-url=https://web.archive.org/web/20191230070045/https://books.google.com/books?id=pyAlcOfBhjIC&pg=PA375|url-status=live}}</ref> Organisms are capable of adjusting somewhat to varied conditions such as temperature changes or oxygen levels at altitude, by a process of [[acclimatization|acclimatisation]].

Homeostasis does not govern every activity in the body.<ref>{{Cite book|title = Where Medicine Went Wrong: Rediscovering the Path to Complexity|publisher = World Scientific|location = New Jersey|series = Studies of Nonlinear Phenomena in Life Science|volume = 11|last = West|first = Bruce J|doi = 10.1142/6175|isbn = 978-981-256-883-0|url = https://books.google.com/books?id=qdZoDQAAQBAJ|date = 2006|access-date = 23 January 2019|archive-date = 6 March 2022|archive-url = https://web.archive.org/web/20220306112837/https://books.google.com/books?id=qdZoDQAAQBAJ|url-status = live}}</ref><ref>{{Cite book|title=Perspectives on Organisms |publisher= Springer |last1=Longo |first1=Giuseppe |last2=Montévil |first2=Maël |doi=10.1007/978-3-642-35938-5|series = Lecture Notes in Morphogenesis|year = 2014|isbn = 978-3-642-35937-8|s2cid= 27653540 }}</ref> For instance, the signal (be it via [[neuron]]s or [[hormone]]s) from the sensor to the effector is, of necessity, highly variable in order to convey [[Information theory|information]] about the direction and magnitude of the error detected by the sensor.<ref name="Shannon">{{cite book|last1= Shannon |first1=Claude E.|last2=Weaver|first2=Warren|title=The mathematical theory of communication|date=1963|publisher=University of Illinois Press|location=Urbana|isbn=978-0-252-72548-7|edition= 4. print.}}</ref><ref>{{cite book |last1=Rucker |first1=R. |title=Mind tools: the mathematics of information.|pages=25–30 |location=Harmondsworth|publisher=Penguin Books |date=1987 }}</ref><ref>{{cite journal |last1= Koeslag |first1=Johan H. |last2=Saunders |first2=Peter T. |last3=Wessels |first3=Jabus A. | title=The chromogranins and counter-regulatory hormones: do they make homeostatic sense? |journal= Journal of Physiology | publication-date=1999 |volume=517 |issue=3 |pages=643–649 |doi= 10.1111/j.1469-7793.1999.0643s.x|pmid=10358106 |year=1999 |pmc=2269385 }}</ref>  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.<ref name="Hall" /><ref name=milsum /> For instance, [[arterial blood pressure]] in mammals is homeostatically controlled and measured by [[stretch receptor]]s in the walls of the [[aortic arch]] and [[carotid sinus]]es at the beginnings of the [[internal carotid arteries]].<ref name=tortora2 /> The sensors send messages via [[sensory nerve]]s 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 neuron|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.<ref name=tortora2 /> 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.{{citation needed|date=April 2023}}

==Controls of variables==
===Core temperature===
{{Main |Thermoregulation |Thermoregulation in humans}}
{{Further |Preoptic area}}
[[File: Smallhuddle.jpg|thumb|Birds huddling for warmth]]
[[Mammal]]s regulate their [[Human body temperature#Core temperature|core temperature]] using input from [[thermoreceptor]]s in the [[hypothalamus]], brain,<ref name=tortora2 /><ref name=grays>{{cite book |last1=Williams |first1=Peter L. |last2=Warwick |first2=Roger |last3=Dyson|first3=Mary |last4=Bannister |first4=Lawrence H. |title=Gray's Anatomy| pages=691–692, 791, 10011–10012 |location=Edinburgh |publisher=Churchill Livingstone | edition= Twenty-seventh
|date=1989|isbn= 0-443-04177-6 }}</ref> [[spinal cord]], [[organs#(anatomy)|internal organs]], and great veins.<ref>{{cite journal|last1=Tansey|first1=Etain A.|last2=Johnson|first2=Christopher D|date=2015|title=Recent advances in thermoregulation|journal=Advances in Physiology Education|volume=39|issue=3|pages=139–148|doi=10.1152/advan.00126.2014|issn=1043-4046|pmid=26330029|s2cid=11553866 |url=https://pure.qub.ac.uk/portal/en/publications/recent-advances-in-thermoregulation-review(c59df53e-4325-4c81-b52b-4e337891c0bb).html|access-date=26 January 2019|archive-date=10 May 2020|archive-url=https://web.archive.org/web/20200510225628/https://pure.qub.ac.uk/en/publications/recent-advances-in-thermoregulation-review|url-status=live}}</ref><ref name=":0">{{Cite book|title=Gray's anatomy: the anatomical basis of clinical practice|others=Standring, Susan|isbn=978-0-7020-6851-5|edition= 41st|location=[Philadelphia]|pages=141, 151–152|oclc=920806541|last1 = Standring|first1 = Susan|date=7 August 2015}}</ref> 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).<ref name="Purves">{{cite book|last1=Purves|first1=Dale|title=Neuroscience|date=2011|publisher=Sinauer|location=Sunderland, Mass.|isbn=978-0-87893-695-3|page=458|edition= 5th}}</ref> These adjustments may include seeking shade and reducing activity, seeking warmer conditions and increasing activity, or huddling.<ref name= biology>{{cite book|last1=Campbell |first1=Neil A. |title=Biology |edition=  Second |pages=897–898 |location=Redwood City, California  |publisher=The Benjamin/Cummings Publishing Company |date=1990 |isbn= 978-0-8053-1800-5}}</ref>
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.<ref name="Flouris">{{cite journal|last1=Flouris|first1=AD|title=Functional architecture of behavioural thermoregulation.|journal=European Journal of Applied Physiology|date=January 2011|volume=111|issue=1|pages=1–8|doi=10.1007/s00421-010-1602-8|pmid=20711785|s2cid=9109352}}</ref>

When the core temperature falls, the blood supply to the skin is reduced by intense [[vasoconstriction]].<ref name=tortora2 /> 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 [[vena comitans|venae comitantes]]).<ref name=grays /><ref name= biology /><ref>{{cite book |last1=Gilroy |first1=Anne M. |last2=MacPherson |first2=Brian R. |last3=Ross|first3=Lawrence M. |title=Atlas of Anatomy| pages=318, 349  |location=Stuttgart|publisher=Thieme Medical Publishers|date=2008|isbn= 978-1-60406-062-1 }}</ref> This acts as a [[Countercurrent exchange|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.<ref name=grays /><ref name= biology /><ref name="pmid7233149">{{cite journal |vauthors = Schmidt-Nielsen K |title = Countercurrent systems in animals |journal = Scientific American |volume = 244 |issue = 5 |pages = 118–28 |year = 1981 |pmid = 7233149 |doi=10.1038/scientificamerican0581-118|bibcode = 1981SciAm.244e.118S }}</ref> The subcutaneous limb veins are tightly constricted,<ref name=tortora2 /> 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.

The metabolic rate is increased, initially by non-shivering [[thermogenesis]],<ref>{{cite book |last1=Stuart |first1=I.R. |title=Human physiology.| page=667|location=New York|publisher=McGraw-Hill | edition= Twelfth |date=2011 }}</ref> followed by [[Shivering|shivering thermogenesis]] if the earlier reactions are insufficient to correct the [[hypothermia]].

When core temperature rises are detected by [[thermoreceptor]]s, the [[sweat gland]]s in the skin are stimulated via [[cholinergic]] [[Sympathetic nervous system|sympathetic nerves]] to secrete [[Sweat gland#Sweat|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.<ref>{{Cite journal |last=Robertshaw |first=David |date=August 2006 |title=Mechanisms for the control of respiratory evaporative heat loss in panting animals |journal=Journal of Applied Physiology |volume=101 |issue=2 |pages=664–668 |doi=10.1152/japplphysiol.01380.2005 |issn=8750-7587 |pmid=16675613 }}</ref>

===Blood glucose===
{{Main |Blood sugar regulation |Glycolysis#Regulation of the rate limiting enzymes}}
[[File:Negative Feedback Gif.gif|thumb|300px|[[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  [[Blood sugar regulation|regulated]] within fairly narrow limits.<ref>{{Cite book|last=Bhagavan|first=N. V.|title=Medical biochemistry|edition=4th|publisher=[[Academic Press]]|year=2002|page=499|url=https://books.google.com/books?id=vT9YttFTPi0C&pg=PA499|isbn=978-0-12-095440-7|access-date=21 October 2020|archive-date=6 March 2022|archive-url=https://web.archive.org/web/20220306112840/https://books.google.com/books?id=vT9YttFTPi0C&pg=PA499|url-status=live}}</ref> In mammals, the primary sensors for this are the [[beta cells]] of the [[pancreatic islets]].<ref name=koeslag>{{cite journal |last1=Koeslag |first1=Johan H. |last2=Saunders |first2=Peter T. |last3=Terblanche |first3=Elmarie | title=Topical Review: A reappraisal of the blood glucose homeostat which comprehensively explains the type 2 diabetes-syndrome X complex |journal=Journal of Physiology | publication-date=2003 |volume= 549|issue=Pt 2 |pages=333–346 |doi=10.1113/jphysiol.2002.037895 |pmid=12717005 |pmc=2342944 |year=2003}}</ref><ref name=stryer>{{cite book |last1= Stryer |first1= Lubert | title=Biochemistry. |edition=  Fourth |location= New York |publisher= W.H. Freeman and Company|date= 1995 |pages=164, 773–774|isbn= 0-7167-2009-4 }}</ref> 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.<ref name=koeslag /> 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.<ref>{{Cite journal |last1=Richter |first1=Erik A. |last2=Hargreaves |first2=Mark |date=July 2013 |title=Exercise, GLUT4, and Skeletal Muscle Glucose Uptake |url=https://www.physiology.org/doi/10.1152/physrev.00038.2012 |journal=Physiological Reviews |language=en |volume=93 |issue=3 |pages=993–1017 |doi=10.1152/physrev.00038.2012 |pmid=23899560 |issn=0031-9333|url-access=subscription }}</ref>

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 [[Lactic acid|lactate]] and de-aminated [[amino acids]]) using a process known as [[gluconeogenesis]].<ref>{{Cite journal|last1=Aronoff|first1=Stephen L.|last2=Berkowitz|first2=Kathy|last3=Shreiner|first3=Barb|last4=Want|first4=Laura|date=1 July 2004|title=Glucose Metabolism and Regulation: Beyond Insulin and Glucagon|url=https://spectrum.diabetesjournals.org/content/17/3/183|journal=Diabetes Spectrum|language=en|volume=17|issue=3|pages=183–190|doi=10.2337/diaspect.17.3.183|issn=1040-9165|doi-access=|access-date=19 July 2018|archive-date=3 January 2020|archive-url=https://web.archive.org/web/20200103090044/https://spectrum.diabetesjournals.org/content/17/3/183|url-status=live|url-access=subscription}}</ref> 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 [[pyruvic acid|pyruvate]] to be fed into the [[citric acid cycle]] or turned into [[lactic acid|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.{{citation needed|date=January 2024}}

===Iron levels===

{{more citations needed section|date=March 2025}}
{{See also |Human iron metabolism}}
Iron homeostasis is a crucial physiological process that regulates iron levels in the body, ensuring that this essential nutrient is available for vital functions while preventing potential toxicity from excess iron.<ref>{{Cite journal |last1=Anderson |first1=Gregory J. |last2=Frazer |first2=David M. |date=July 2017 |title=Current understanding of iron homeostasis |journal=The American Journal of Clinical Nutrition |volume=106 |issue=Suppl 6 |pages=1559S–1566S |doi=10.3945/ajcn.117.155804 |issn=1938-3207 |pmc=5701707 |pmid=29070551}}</ref> The primary site for iron absorption is the [[duodenum]], where dietary iron exists in two forms: heme iron, sourced from animal products, and [[Non-heme iron protein|non-heme iron]], found in plant foods. Heme iron is more efficiently absorbed than non-heme iron, which requires factors like [[vitamin C]] for optimal uptake. Once absorbed, iron enters the bloodstream bound to [[transferrin]], a transport protein that delivers it to various tissues and organs. Cells uptake iron through transferrin receptors, making it available for critical processes such as oxygen transport and DNA synthesis. Excess iron is stored in the liver, spleen, and bone marrow as [[ferritin]] and hemosiderin. The regulation of iron levels is primarily controlled by the hormone [[hepcidin]], produced by the liver, which adjusts intestinal absorption and the release of stored iron based on the body's needs. Disruptions in iron homeostasis can lead to conditions such as iron deficiency [[anemia]] or iron overload disorders like [[hemochromatosis]], highlighting the importance of maintaining the delicate balance of this vital nutrient for overall health.

===Copper regulation===
{{Main |Copper in health#Homeostasis}}
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.<ref>{{Citation |last1=Scheiber |first1=Ivo |title=Copper: Effects of Deficiency and Overload |date=2013 |work=Interrelations between Essential Metal Ions and Human Diseases |pages=359–387 |editor-last=Sigel |editor-first=Astrid |place=Dordrecht |publisher=Springer Netherlands |language=en |doi=10.1007/978-94-007-7500-8_11 |isbn=978-94-007-7500-8 |last2=Dringen |first2=Ralf |last3=Mercer |first3=Julian F. B. |volume=13 |pmid=24470097 |editor2-last=Sigel |editor2-first=Helmut |editor3-last=Sigel |editor3-first=Roland K.O.}}</ref> 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.<ref>{{Cite journal |last1=Burkhead |first1=Jason L. |last2=Gogolin Reynolds |first2=Kathryn A. |last3=Abdel-Ghany |first3=Salah E. |last4=Cohu |first4=Christopher M. |last5=Pilon |first5=Marinus |date=June 2009 |title=Copper homeostasis |url=https://nph.onlinelibrary.wiley.com/doi/10.1111/j.1469-8137.2009.02846.x |journal=New Phytologist |language=en |volume=182 |issue=4 |pages=799–816 |doi=10.1111/j.1469-8137.2009.02846.x |pmid=19402880 |bibcode=2009NewPh.182..799B |issn=0028-646X|url-access=subscription }}</ref>

Many aspects of copper homeostasis are known at the molecular level.<ref>{{Cite journal |last1=Stern |first1=Bonnie Ransom |last2=Solioz |first2=Marc |last3=Krewski |first3=Daniel |last4=Aggett |first4=Peter |last5=Aw |first5=Tar-Ching |last6=Baker |first6=Scott |last7=Crump |first7=Kenny |last8=Dourson |first8=Michael |last9=Haber |first9=Lynne |last10=Hertzberg |first10=Rick |last11=Keen |first11=Carl |last12=Meek |first12=Bette |last13=Rudenko |first13=Larisa |last14=Schoeny |first14=Rita |last15=Slob |first15=Wout |date=2007-04-03 |title=Copper and Human Health: Biochemistry, Genetics, and Strategies for Modeling Dose-response Relationships |url=http://www.tandfonline.com/doi/abs/10.1080/10937400600755911 |journal=Journal of Toxicology and Environmental Health, Part B |language=en |volume=10 |issue=3 |pages=157–222 |doi=10.1080/10937400600755911 |pmid=17454552 |bibcode=2007JTEHB..10..157S |issn=1093-7404|url-access=subscription }}</ref> Copper's essentiality is due to its ability to act as an electron donor or acceptor as its oxidation state fluxes between Cu<sup>1+</sup> ([[cuprous]]) and Cu<sup>2+</sup> ([[cupric]]). As a component of about a dozen [[cuproenzyme]]s, copper is involved in key [[redox]] (i.e., oxidation-reduction) reactions in essential metabolic processes such as [[mitochondria]]l respiration, synthesis of [[melanin]], and cross-linking of [[collagen]].<ref>{{Cite book |last1=Dameron |first1=C. |title=Cooper |last2=Howe |first2=Paul |date=1998 |publisher=World health organization |others=Programme international sur la sécurité des substances chimiques |isbn=978-92-4-157200-2 |series=Environmental health criteria |location=Geneva}}</ref> 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.{{citation needed|date=March 2025}}

===Levels of blood gases===
{{main |Respiratory center |Gas exchange}}
{{Further |Blood gas tension}}
[[File: 2327 Respiratory Centers of the Brain.jpg|thumb|The respiratory center]]
Changes in the levels of oxygen, carbon dioxide, and plasma pH are sent to the [[respiratory center]], in the [[brainstem]] where they are regulated.
The [[partial pressure]] of [[oxygen]] and [[carbon dioxide]] in the [[arterial blood]] is monitored by the [[peripheral chemoreceptors]] ([[Peripheral nervous system|PNS]]) in the [[common carotid artery|carotid artery]] and [[aortic arch]]. A change in the [[PCO2|partial pressure of carbon dioxide]] is detected as altered pH in the [[cerebrospinal fluid]] by [[central chemoreceptors]] ([[Central nervous system|CNS]]) in the [[medulla oblongata]] of the [[brainstem]]. Information from these sets of sensors is sent to the respiratory center which activates the effector organs – the [[Thoracic diaphragm|diaphragm]] and other [[muscles of respiration]]. An increased level of carbon dioxide in the blood, or a decreased level of oxygen, will result in a deeper breathing pattern and increased [[respiratory rate]] to bring the blood gases back to equilibrium.

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 [[freediving|freedivers]] use to prolong the time they can stay underwater.

The [[PCO2|partial pressure of carbon dioxide]] is more of a deciding factor in the monitoring of pH.<ref name="Spyer">{{cite journal|last1=Spyer|first1=KM|last2=Gourine|first2=AV|title=Chemosensory pathways in the brainstem controlling cardiorespiratory activity.|journal=Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences|date=12 September 2009|volume=364|issue=1529|pages=2603–10|doi=10.1098/rstb.2009.0082|pmid=19651660|pmc=2865116}}</ref> However, at high altitude (above 2500&nbsp;m) 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.<ref name=pubmed>{{cite journal|title=Oxygen at high altitude|journal=British Medical Journal|first=Andrew J|last=Peacock|date=17 October 1998|volume=317|pages=1063–1066|pmid=9774298|issue=7165|pmc=1114067|doi=10.1136/bmj.317.7165.1063}}</ref><ref name=BordenHuman>{{cite book |last1=Young|first1=Andrew J|last2=Reeves|first2=John T. |chapter=Human Adaptation to High Terrestrial Altitude|title=Medical Aspects of Harsh Environments |volume=2 |location=Borden Institute, Washington, DC |year=2002 |citeseerx=10.1.1.175.3270|chapter-url=https://www.usariem.army.mil/Pages/download/harshenvironmentsvol2.pdf|archive-url=https://web.archive.org/web/20120916195023/https://www.usariem.army.mil/Pages/download/harshenvironmentsvol2.pdf |publisher=Office of The Surgeon General Department of the Army, United States of America |access-date=5 January 2009|archive-date=16 September 2012}}</ref> This is important in [[Effects of high altitude on humans#Acclimatization|acclimatization to high altitude]].<ref name=harris>{{cite journal|url=https://emedicine.medscape.com/article/768478-overview|journal=EMedicine Specialties &gt; Emergency Medicine &gt; Environmental|title=Altitude Illness – Cerebral Syndromes|first1=N Stuart|last1=Harris|first2=Sara W|last2=Nelson|date=16 April 2008|access-date=30 June 2016|archive-date=12 June 2016|archive-url=https://web.archive.org/web/20160612041149/https://emedicine.medscape.com/article/768478-overview|url-status=live}}</ref>

===Blood oxygen content===
The [[kidneys]] measure the oxygen content rather than the [[partial pressure of oxygen]] in the arterial blood. When the [[Oxygen saturation (medicine)|oxygen content of the blood]] is chronically low, oxygen-sensitive cells secrete [[erythropoietin]] (EPO) into the blood.<ref name="Alberts">{{cite book|last1=Alberts|first1=Bruce|title=Molecular biology of the cell|date=2002|publisher=Garland|location=New York [u.a.]|isbn=978-0-8153-4072-0|pages=1292–1293|edition= 4th}}</ref> The effector tissue is the [[Bone marrow|red bone marrow]] which produces [[red blood cell]]s (RBCs, also called {{lang|la|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 shunt]]s in the heart (through which venous blood by-passes the lungs and goes directly into the systemic circulation) have similarly high hematocrits.<ref name=tortora>{{cite book |last1= Tortora |first1= Gerard J. |last2=Anagnostakos|first2=Nicholas P.| title=Principles of anatomy and physiology |url= https://archive.org/details/principlesofanat05tort |url-access= registration |pages=[https://archive.org/details/principlesofanat05tort/page/444 444–445]|edition=  Fifth |location= New York |publisher= Harper & Row, Publishers|date= 1987 |isbn= 978-0-06-350729-6 }}</ref><ref name=Fisher1996>{{cite journal |vauthors=Fisher JW, Koury S, Ducey T, Mendel S |title=Erythropoietin production by interstitial cells of hypoxic monkey kidneys |journal=British Journal of Haematology |volume=95 |issue=1 |pages=27–32 |year=1996 |pmid=8857934 |doi=10.1046/j.1365-2141.1996.d01-1864.x |s2cid=38309595 }}</ref>

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.<ref name=tortora /><ref name=pmid17253966>{{cite journal |vauthors=Jelkmann W |title=Erythropoietin after a century of research: younger than ever |journal=European Journal of Haematology |volume=78 |issue=3 |pages=183–205 |year=2007 |pmid=17253966 |doi=10.1111/j.1600-0609.2007.00818.x |s2cid=37331032 |doi-access= }}</ref>

===Arterial blood pressure===
{{Main |Baroreflex |Renin–angiotensin system}}
The brain can regulate blood flow over a range of blood pressure values by [[vasoconstriction]] and [[vasodilation]] of the arteries.<ref>{{cite web|url=https://www.orlandoregional.org/pdf%20folder/overview%20adult%20brain%20injury.pdf|archive-url=https://web.archive.org/web/20080227162001/https://www.orlandoregional.org/pdf%20folder/overview%20adult%20brain%20injury.pdf|archive-date=27 February 2008|date=2004 |title=Overview of Adult Traumatic Brain Injuries: Self-Learning Packet |publisher=Orlando Regional Healthcare}}</ref>

High pressure receptors called [[baroreceptor]]s in the walls of the [[Aorta|aortic arch]] and [[carotid sinus]] (at the beginning of the [[internal carotid artery]]) monitor the arterial [[blood pressure]].<ref>{{cite book|last1=Pocock|first1=Gillian|last2=Richards|first2=Christopher D.|title=Human physiology: the basis of medicine|date=2006|publisher=Oxford University Press |isbn=978-0-19-856878-0|page=4|edition= 3rd}}</ref> Rising pressure is detected when the walls of the arteries stretch due to an increase in [[blood volume]]. This causes [[cardiomyocytes|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.<ref name=tortora7>{{cite book |last1= Tortora |first1= Gerard J. |last2=Anagnostakos|first2=Nicholas P.| title=Principles of anatomy and physiology |url= https://archive.org/details/principlesofanat05tort |url-access= registration |page=[https://archive.org/details/principlesofanat05tort/page/430 430]|edition= 5th |publisher= Harper & Row |date= 1987 |isbn= 978-0-06-350729-6 }}</ref>
This information is then conveyed, via [[afferent nerve fiber]]s, to the [[solitary nucleus]] in the [[medulla oblongata]].<ref name="OUP">{{cite book|last1=Pocock|first1=Gillian|last2=Richards|first2=Christopher D.|title=Human physiology: the basis of medicine|date=2006|publisher=Oxford University Press |isbn=978-0-19-856878-0|pages=299–302|edition= 3rd}}</ref> 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 [[vasodilation|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 [[cholinergic]] [[Parasympathetic nervous system|parasympathetic 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.

===Calcium levels===
{{main|Calcium metabolism#Regulation of calcium metabolism}}
[[File:625 Calcium Homeostasis.jpg|thumb|upright=1.4 |Calcium homeostasis]]
The plasma ionized calcium (Ca<sup>2+</sup>) concentration is very tightly controlled by a pair of homeostatic mechanisms.<ref name=Brini>{{cite book | first1 = Marisa | last1 = Brini | first2 = Denis | last2 = Ottolini | first3 = Tito | last3 = Calì | first4 = Ernesto | last4 = Carafoli | chapter = Calcium in Health and Disease | editor-first1 = Astrid | editor-last1 = Sigel  | editor-last2 = Helmut | editor-first2 = Roland K. O. | title = Interrelations between Essential Metal Ions and Human Diseases | series = Metal Ions in Life Sciences | volume = 13 | year = 2013 | publisher = Springer | pages = 81–137 | doi = 10.1007/978-94-007-7500-8_4 | pmid = 24470090 | isbn = 978-94-007-7499-5 }}</ref> The sensor for the first one is situated in the [[parathyroid glands]], where the [[Parathyroid gland#Histology|chief cells]] sense the Ca<sup>2+</sup> 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 (biology)|effector]] organs of the first homeostatic mechanism are the [[bone]]s, 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|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.<ref>{{cite book |last1= Stryer |first1= Lubert | title=In: Biochemistry. |chapter= Vitamin D is derived from cholesterol by the ring-splitting action of light.|page=707 |edition=  Fourth |location= New York |publisher= W.H. Freeman and Company|date= 1995 |isbn= 0-7167-2009-4 }}</ref>

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.<ref>{{Cite journal|last1=Felsenfeld|first1=A. J.|last2=Levine|first2=B. S.|date=2015-03-23|title=Calcitonin, the forgotten hormone: does it deserve to be forgotten?|journal=Clinical Kidney Journal|volume=8|issue=2|pages=180–187|doi=10.1093/ckj/sfv011|pmid=25815174|issn=2048-8505|pmc=4370311}}</ref>

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 1&nbsp;kg) compared with the plasma calcium store (about 180&nbsp;mg). Longer term regulation occurs through calcium absorption or loss from the gut.

Another example are the most well-characterised [[Cannabinoid|endocannabinoids]] like [[anandamide]] (''N''-arachidonoylethanolamide; AEA) and [[2-Arachidonoylglycerol|2-arachidonoylglycerol]] (2-AG), whose synthesis occurs through the action of a series of [[intracellular]] [[enzyme]]s activated in response to a rise in intracellular calcium levels to introduce homeostasis and prevention of [[Neoplasm|tumor]] development through putative protective mechanisms that prevent [[cell growth]] and [[Metastasis|migration]] by activation of [[Cannabinoid receptor type 1|CB1]] and/or [[Cannabinoid receptor type 2|CB2]] and adjoining [[Cannabinoid receptor#Other cannabinoid receptors|receptors]].<ref>{{Cite journal|last1=Ayakannu|first1=Thangesweran|last2=Taylor|first2=Anthony H.|last3=Marczylo|first3=Timothy H.|last4=Willets|first4=Jonathon M.|last5=Konje|first5=Justin C.|date=2013|title=The Endocannabinoid System and Sex Steroid Hormone-Dependent Cancers|journal=International Journal of Endocrinology|volume=2013|article-number=259676|doi=10.1155/2013/259676|issn=1687-8337|pmc=3863507|pmid=24369462|doi-access=free}}</ref>

===Sodium concentration===
{{Main |Renin–angiotensin system}} {{Further |Sodium in biology |Tubuloglomerular feedback |Sodium-calcium exchanger}}
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 cell]]s, these cells respond to the sodium concentration in the [[nephron|renal tubular fluid]] after it has already undergone a certain amount of modification in the [[proximal convoluted tubule]] and [[loop of Henle]].<ref name=tortora3>{{cite book |last1= Tortora |first1= Gerard J. |last2=Anagnostakos|first2=Nicholas P.| title=Principles of anatomy and physiology |url= https://archive.org/details/principlesofan1987tort |url-access= registration |pages=[https://archive.org/details/principlesofan1987tort/page/420 420–421]|edition=  Fifth |location= New York |publisher= Harper & Row, Publishers|date= 1987 |isbn= 978-0-06-350729-6 }}</ref> 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.<ref name=tortora3 /><ref>{{cite journal|title=JAMA Article Jan 2012|journal=JAMA|volume=280|issue=13|pages=1168–72|doi=10.1001/jama.280.13.1168|pmid=9777817|year=1998|last1=Preston|first1=Richard A.|last2=Materson|first2=B. J.|last3=Reda|first3=D. J.|last4=Williams|first4=D. W.|last5=Hamburger|first5=R. J.|last6=Cushman|first6=W. C.|last7=Anderson|first7=R. J.|doi-access=free}}</ref><ref name="isbn0-07-146633-9">{{cite book |veditors=Loscalzo J, Fauci AS, Braunwald E, Kasper DL, Hauser SL, Longo DL | title = Harrison's principles of internal medicine | publisher = McGraw-Hill Medical | location =New York | year = 2008 | isbn = 978-0-07-146633-2 |vauthors=Williams GH, Dluhy RG | chapter = Chapter 336: Disorders of the Adrenal Cortex }}</ref> Renin is an enzyme which cleaves a [[Peptide#Notes on terminology|decapeptide]] (a short protein chain, 10 amino acids long) from a plasma [[Alpha globulin|α-2-globulin]] called [[angiotensinogen]]. This decapeptide is known as [[Angiotensin#Angiotensin I|angiotensin I]].<ref name=tortora3 />  It has no known biological activity. However, when the blood circulates through the lungs a pulmonary capillary [[Endothelium|endothelial]] enzyme called [[angiotensin-converting enzyme]] (ACE) cleaves a further two amino acids from angiotensin I to form an octapeptide known as [[Angiotensin#Angiotensin II|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 [[Nephron|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.<ref name=tortora3 /><ref>{{cite journal |vauthors=Bauer JH, Gauntner WC |title=Effect of potassium chloride on plasma renin activity and plasma aldosterone during sodium restriction in normal man |journal=Kidney Int. |volume=15 |issue=3 |pages=286–93 |date=March 1979 |pmid=513492 |doi= 10.1038/ki.1979.37|doi-access=free }}</ref> 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 tubule]]s or [[collecting duct]]s. This is because sodium is reabsorbed in exchange for potassium and therefore causes only a modest change in the [[Osmotic pressure|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 [[Vasopressin|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.

===Potassium concentration===
{{Main |Potassium#Homeostasis |Potassium in biology}}
High potassium concentrations in the plasma cause [[depolarization]] of the [[zona glomerulosa]] cells' membranes in the outer layer of the [[adrenal cortex]].<ref name="pmid22546854">{{cite journal |vauthors=Hu C, Rusin CG, Tan Z, Guagliardo NA, Barrett PQ |title=Zona glomerulosa cells of the mouse adrenal cortex are intrinsic electrical oscillators. |journal=J Clin Invest |volume=122 |issue=6 |pages=2046–2053 |date=June 2012 |pmid=22546854 |doi=10.1172/JCI61996 |pmc=3966877}}</ref> This causes the release of [[aldosterone]] into the blood.

Aldosterone acts primarily on the [[distal convoluted tubule]]s and [[collecting duct]]s of the kidneys, stimulating the excretion of potassium ions into the urine.<ref name=tortora3 /> It does so, however, by activating the [[basolateral]] [[Na+/K+-ATPase|Na<sup>+</sup>/K<sup>+</sup> 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 [[electrochemical gradient#Ion gradients|ionic concentration gradient]] which results in the reabsorption of sodium (Na<sup>+</sup>) ions from the tubular fluid into the blood, and secreting potassium (K<sup>+</sup>) ions from the blood into the urine (lumen of collecting duct).<ref name="pmid10760062">{{cite journal|year=2000|last1=Palmer|first1=LG|last2=Frindt|first2=G|title=Aldosterone and potassium secretion by the cortical collecting duct|journal=Kidney International|volume=57|issue=4|pages=1324–8|pmid=10760062|doi=10.1046/j.1523-1755.2000.00970.x|doi-access=free}}</ref><ref>{{cite journal |vauthors=Linas SL, Peterson LN, Anderson RJ, Aisenbrey GA, Simon FR, Berl T |title=Mechanism of renal potassium conservation in the rat |journal=Kidney International |volume=15 |issue=6 |pages=601–11 |date=June 1979 |pmid=222934 |doi= 10.1038/ki.1979.79|doi-access=free }}</ref>

===Fluid balance===
{{Main |Osmoregulation |Thirst}}
The [[body water|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 [[electrolyte]]s in the extracellular fluid stable. Fluid balance is maintained by the process of [[osmoregulation]] and by behavior. [[Osmotic pressure]] is detected by [[osmoreceptor]]s 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 [[Transepidermal water loss|unavoidable water loss through the skin]] which is not entirely waterproof and therefore always slightly moist, [[Breathing#Upper airways|water vapor in the exhaled air]], [[Perspiration|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 [[Tonicity#Hypertonic solution|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 tubule]]s and [[Collecting duct system|collecting ducts]], thus preventing aggravation of the water loss via the urine. The hypothalamus simultaneously stimulates the nearby [[Thirst|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 [[Tonicity#Hypertonic solution|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.

===Blood pH===
[[File:2714 Respiratory Regulation of Blood.jpg|class=skin-invert-image|border|right|364x364px]]
{{Main|Acid–base homeostasis |Acid-base imbalance}}
The [[pH#Living systems|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 [[PCO2|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.{{citation needed |date=November 2017}} The metabolism of these cells produces carbon dioxide, which is rapidly converted to hydrogen and bicarbonate through the action of [[carbonic anhydrase]].<ref name=tortora1 /> 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 decreases the carbonic acid, and consequently raises the plasma pH.<ref name=tortora1>{{cite book |last1= Tortora |first1= Gerard J. |last2=Anagnostakos|first2=Nicholas P.| title=Principles of anatomy and physiology |url= https://archive.org/details/principlesofan1987tort |url-access= registration |pages=[https://archive.org/details/principlesofan1987tort/page/581 581]–582, 675–676|edition=  Fifth |location= New York |publisher= Harper & Row, Publishers|date= 1987 |isbn= 978-0-06-350729-6 }}</ref>  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,<ref>{{cite journal|last1=Sakka|first1=L.|last2=Coll|first2=G.|last3=Chazal|first3=J.|title=Anatomy and physiology of cerebrospinal fluid|journal=European Annals of Otorhinolaryngology, Head and Neck Diseases|date=December 2011|volume=128|issue=6|pages=309–316|doi=10.1016/j.anorl.2011.03.002|pmid=22100360|doi-access=free}}</ref> and [[neuroendocrine]] factors, to which slight changes can cause problems or damage to the nervous system. For example, high [[glycine]] [[concentration]] disrupts [[temperature]] and [[blood pressure]] control, and high CSF [[pH]] causes [[dizziness]] and [[Syncope (medicine)|syncope]].<ref>{{cite book |last1=Saladin |first1=Kenneth |title=Anatomy and Physiology |edition= 6th |publisher=McGraw Hill |year=2012 |pages=519–20}}</ref>

===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.<ref name="Flores">{{cite journal|last1=Flores|first1=CE|last2=Méndez|first2=P|title=Shaping inhibition: activity dependent structural plasticity of GABAergic synapses.|journal=Frontiers in Cellular Neuroscience|date=2014|volume=8|page=327|doi=10.3389/fncel.2014.00327|pmid=25386117|pmc=4209871|doi-access=free}}</ref> An imbalance between excitation and inhibition is seen to be implicated in a number of [[neuropsychiatry|neuropsychiatric disorders]].<ref name="Um">{{cite journal|last1=Um|first1=Ji Won|title=Roles of Glial Cells in Sculpting Inhibitory Synapses and Neural Circuits|journal=Frontiers in Molecular Neuroscience|date=13 November 2017|volume=10|article-number=381|doi=10.3389/fnmol.2017.00381|pmid=29180953|pmc=5694142|doi-access=free}}</ref>

===Neuroendocrine system===
{{Further |Metabolism |Enterohepatic circulation |Metabolic pathway}}
{{See also |Enzyme#Regulation}}

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 regulation of metabolism, is carried out by [[hypothalamus|hypothalamic]] interconnections to other glands.<ref name="J o E">{{cite journal|last1=Toni|first1=R|title=The neuroendocrine system: organization and homeostatic role.|journal=[[Journal of Endocrinological Investigation]]|date=2004|volume=27|issue=6 Suppl|pages=35–47|pmid=15481802}}</ref>
Three [[endocrine gland]]s of the [[hypothalamic–pituitary–gonadal axis]] (HPG axis) often work together and have important regulatory functions. Two other regulatory endocrine axes are the [[hypothalamic–pituitary–adrenal axis]] (HPA axis) and the [[hypothalamic–pituitary–thyroid axis]] (HPT axis).

The [[liver]] also has many regulatory functions of the metabolism. An important function is the production and control of [[bile acid]]s. Too much bile acid can be toxic to cells and its synthesis can be inhibited by activation of [[Farnesoid X receptor|FXR]] a [[nuclear receptor]].<ref name=Kalaany/>

===Gene regulation===
{{Main |Regulation of gene expression}}
At the cellular level, homeostasis is carried out by several mechanisms including [[transcriptional regulation]] that can [[regulation of gene expression|alter the activity of genes]] in response to changes.

===Energy balance===
{{Main |Energy homeostasis}}
The amount of energy consumed through dietary intake must align closely with the amount of energy expended by the body in order to maintain overall energy balance, a state known as energy homeostasis. This critical process is managed through the regulation of appetite, which is influenced by two key hormones: [[ghrelin]] and [[leptin]]. Ghrelin is known as the '''hunger hormone''', as it plays a significant role in stimulating feelings of hunger, thereby prompting individuals to seek out and consume food. On the other hand, leptin serves a different function; it signals satiety, or the feeling of fullness, telling the body that it has consumed enough food.

In a comprehensive review conducted in 2019 that examined various weight-change interventions—including dieting, exercise, and instances of overeating—it was determined that the body's mechanisms for regulating weight homeostasis are not capable of precisely correcting for '''energetic errors'''. These energetic errors refer to the notable loss or gain of calories that can occur in the short term. This research highlights the complexity of energy balance, showing that the body may struggle to adjust rapidly to fluctuations in calorie intake or expenditure, thereby complicating the process of maintaining a stable body weight in response to immediate changes in energy consumption and usage.<ref>{{cite journal |last1=Levitsky |first1=DA |last2=Sewall |first2=A |last3=Zhong |first3=Y |last4=Barre |first4=L |last5=Shoen |first5=S |last6=Agaronnik |first6=N |last7=LeClair |first7=JL |last8=Zhuo |first8=W |last9=Pacanowski |first9=C |date=1 February 2019 |title=Quantifying the imprecision of energy intake of humans to compensate for imposed energetic errors: A challenge to the physiological control of human food intake. |journal=Appetite |volume=133 |pages=337–343 |doi=10.1016/j.appet.2018.11.017 |pmid=30476522 |s2cid=53712116}}</ref>

==Clinical significance==
Many diseases are the result of a homeostatic failure. Almost any homeostatic component can malfunction either as a result of an [[genetic disorder|inherited defect]], an [[inborn error of metabolism]], or an acquired disease. Some homeostatic mechanisms have inbuilt redundancies, {{which?|date=August 2025}} 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 [[Diabetes mellitus type 1|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]].<ref>{{Citation |last1=Mouri |first1=MIchelle |title=Hyperglycemia |date=2023-04-24 |work=StatPearls |url=https://www.ncbi.nlm.nih.gov/books/NBK430900/ |access-date=2025-01-11 |place=Treasure Island (FL) |publisher=StatPearls Publishing |pmid=28613650 |last2=Badireddy |first2=Madhu |archive-date=31 December 2024 |archive-url=https://web.archive.org/web/20241231211058/https://www.ncbi.nlm.nih.gov/books/NBK430900/ |url-status=live }}</ref>

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 Ca<sup>2+</sup> 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)<ref name=CMArmstrong1999>{{cite journal | vauthors = Armstrong CM, Cota G | title = Calcium block of Na<sup>+</sup> channels and its effect on closing rate | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 96 | issue = 7 | pages = 4154–7 | date = Mar 1999 | pmid = 10097179 | pmc = 22436 | doi = 10.1073/pnas.96.7.4154 | bibcode = 1999PNAS...96.4154A | doi-access = free }}</ref> giving rise to lethargy, muscle weakness, anorexia, constipation and labile emotions.<ref name=harrison>{{cite book | last1 = Harrison|first1= T.R. | title =Principles of Internal Medicine | edition=  third | pages = 170, 571–579 | location = New York | publisher =  McGraw-Hill Book Company}}</ref>

The body water homeostat can be compromised by the inability to secrete [[Antidiuretic hormone|ADH]] in response to even the normal daily water losses via the exhaled air, the [[feces]], and [[Dehydration#Cause|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.<ref name=Marieb/>

Various [[chronic (medicine)|chronic]] diseases are kept under control by homeostatic compensation, which masks a problem by compensating for it (making up for it) in another way. {{source?|date=August 2025}} However, the compensating mechanisms eventually wear out {{vague|date=August 2025}} 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. {{vague|date=August 2025}} 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).<ref>{{Cite journal |last1=Fan |first1=Xiu-Juan |last2=Yu |first2=Hao |last3=Ren |first3=Jun |date=February 2011 |title=Homeostasis and compensatory homeostasis: bridging Western medicine and traditional chinese medicine |journal=Current Cardiology Reviews |volume=7 |issue=1 |pages=43–46 |doi=10.2174/157340311795677671 |issn=1875-6557 |pmc=3131715 |pmid=22294974}}</ref>

==Biosphere==
In the [[Gaia hypothesis]], [[James Lovelock]]<ref>{{cite book |last1=Lovelock |first1=James | title=Healing Gaia: Practical Medicine for the Planet|url=https://archive.org/details/healinggaiaprac00love |url-access=registration |location=New York |publisher=Harmony Books |date=1991|isbn= 978-0-517-57848-3}}</ref> 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.<ref name=koeslag /> 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.<ref>{{cite book | first1 = Walter F. | last1 = Boron | first2 = Emile L. | last2 = Boulpaep | title = Medical physiology: a cellular and molecular approach | year = 2009 | publisher = Saunders/Elsevier | location = Philadelphia, PA | isbn = 978-1-4160-3115-4 | edition=  2nd International }}</ref> Such anticipatory reactions are open loop systems which are based, essentially, on "guess work", and are not self-correcting.<ref>{{cite journal |last1=Koeslag |first1=J.H. |last2=Saunders |first2=P.T. |last3=Wessels |first3=J.A. | title=Glucose homeostasis with infinite gain: further lessons from the Daisyworld parable? |journal= Journal of Endocrinology | date=1997 |volume=134 |issue=2 |pages=187–192  |doi=10.1677/joe.0.1540187 |pmid=9291828 }}</ref> 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:

===Risk===
{{Main|Risk homeostasis}}
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.<ref name="Risk">{{cite book|last1=Spencer|first1=Laci|title=Flotation: A Guide for Sensory Deprivation, Relaxation, & Isolation Tanks|date=2015|publisher=Lulu.com|isbn=978-1-329-17375-0 |page=29}}{{self-published source|date=February 2020}}</ref>{{self-published inline|date=February 2020}}

===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 (biology)|stress]], often generating artificial stresses if the "natural" level of stress is not enough.<ref>{{Cite book|url=https://books.google.com/books?id=z6TXCQAAQBAJ&pg=PA29|title=Flotation: A Guide for Sensory Deprivation, Relaxation, & Isolation Tanks|last=Spencer|first=Laci|date=29 May 2015|publisher=Lulu.com|isbn=978-1-329-17375-0|language=en|access-date=11 October 2019|archive-date=3 January 2020|archive-url=https://web.archive.org/web/20200103045858/https://books.google.com/books?id=z6TXCQAAQBAJ&pg=PA29|url-status=live}}{{self-published source|date=February 2020}}</ref>{{self-published inline|date=February 2020}}

[[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.

===Technology===
Familiar technological homeostatic mechanisms include:
* 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.<ref name="CarLife1965">{{cite journal |url=https://books.google.com/books?id=zO46AAAAMAAJ |page=46 |title=1966 American Motors |journal=Car Life |volume=12 |year=1965 |access-date=9 March 2015 |archive-date=2 January 2020 |archive-url=https://web.archive.org/web/20200102052736/https://books.google.com/books?id=zO46AAAAMAAJ |url-status=live }}</ref><ref>{{cite web |url=https://auto.howstuffworks.com/cruise-control2.htm |last=Nice |first=Karim |title=How Cruise Control Systems Work |date=15 January 2001 |publisher=HowStuffWorks |access-date=9 March 2015 |archive-date=6 March 2015 |archive-url=https://web.archive.org/web/20150306022245/https://auto.howstuffworks.com/cruise-control2.htm |url-status=live }}</ref>
* An [[autopilot]] operates the steering controls of an aircraft or ship in response to deviation from a pre-set compass bearing or route.<ref>{{cite web|last1=Harris|first1=William|title=How Autopilot Works|url=https://science.howstuffworks.com/transport/flight/modern/autopilot.htm|website=HowStuffWorks.com|access-date=14 April 2018|date=10 October 2007|archive-date=15 April 2018|archive-url=https://web.archive.org/web/20180415124936/https://science.howstuffworks.com/transport/flight/modern/autopilot.htm|url-status=live}}</ref>
* [[Process control]] systems in a [[chemical plant]] or [[oil refinery]] maintain fluid levels, pressures, temperature, chemical composition, etc. by controlling heaters, pumps and valves.<ref>{{cite web |last1=White |first1=Douglas |title=Advanced automation technology reduces refinery energy costs |url=https://www.ogj.com/articles/print/volume-103/issue-37/special-report/advanced-automation-technology-reduces-refinery-energy-costs.html |website=Oil and Gas Journal |access-date=13 July 2018 |date=3 October 2005 |archive-date=13 July 2018 |archive-url=https://web.archive.org/web/20180713074016/https://www.ogj.com/articles/print/volume-103/issue-37/special-report/advanced-automation-technology-reduces-refinery-energy-costs.html |url-status=live }}</ref>
* 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.<ref>{{cite journal|last=Maxwell|first=James Clerk|title=On Governors|journal=Proceedings of the Royal Society of London|volume= 16|year= 1868 |pages= 270–283 | doi = 10.1098/rspl.1867.0055 | jstor=112510|s2cid=51751195 |doi-access=}}</ref><ref name="ben93p48">{{Cite book| publisher = IET| isbn = 978-0-86341-299-8| last = Bennett| first = Stuart| title = A history of control engineering, 1930-1955| year = 1992| page = [https://books.google.com/books?id=VD_b81J3yFoC&pg=PA48 p. 48]
}}</ref>

===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.<ref>{{cite book |last1=Damasio|first1=Antonio |title=The Strange Order of Thinkgs: Life, Feeling, and the Making of Cultures  |date=2018 |publisher=Pantheon Books |page=27|isbn=978-0-307-90876-6|location=New York|edition=e-book|author1-link=Antonio Damasio}}</ref><ref>{{cite book |last1=Vaughan-Williams|first1=Nick  |title=The Routledge Handbook of Biopolitics  |date=2017 |publisher=Routledge- Taylor and Francis |chapter=Carl Schmitt, Giorgio Agamben and the ' nomos ' of contemporary political life |isbn=978-1-315-61275-1 |location=London |editor1-last=Prozorov |editor1-first=Sergei |editor2-last=Rentea |editor2-first=Simona|page=146}}</ref> Healthy [[The Civic Culture|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,<ref>{{cite journal |last1=Lim |first1=Tae-Seop |last2=Ahn |first2=Seokhoon |title=Dialectics of culture and dynamic balancing between individuality and collectivity  |journal=Journal of Asian Pacific Communication |volume=25 |issue=1 |doi=10.1075/japc.25.1.04lim |pages=63–77 |year=2015}}</ref> or that between governmental effectiveness and responsiveness to the interests of citizens.<ref>{{cite journal| title= Rethinking the Origins of Civic Culture and Why it Matters for the Study of the Arab World | last1= Wickham |first1=Carrie Rosefsky |date= 2020| journal= Government and Opposition|volume= 55|issue=1| doi= 10.1017/gov.2019.12 | pages= 1–20| s2cid= 151139202 | doi-access= free}}</ref><ref>{{cite web |last1=Pavone |first1=Tammaso |date=2014 |title=Political Culture and Democratic Homeostasis: A Critical Review of Gabriel Almond and Sidney Verba's The Civic Culture |publisher=Princeton University |url=https://scholar.princeton.edu/sites/default/files/tpavone/files/almond_verba-_the_civic_culture_critical_review_0.pdf |page=2 |access-date=2022-06-30 |archive-date=1 July 2022 |archive-url=https://web.archive.org/web/20220701235102/https://scholar.princeton.edu/sites/default/files/tpavone/files/almond_verba-_the_civic_culture_critical_review_0.pdf |url-status=live }}</ref>

==See also==
{{columns-list|
* {{annotated link|Apoptosis}}
* {{annotated link|Cerebral autoregulation}}
* {{annotated link|Chronobiology}}
* {{annotated link|Enantiostasis}}
* {{annotated link|Geophysiology}}
* {{annotated link|Glycobiology}}
* {{annotated link|Electrolyte imbalance}}
* {{annotated link|Homeorhesis}}
* {{annotated link|Homeostatic feeling}}
* {{annotated link|Homeostatic plasticity}}
* {{annotated link|Hormesis}}
* {{annotated link|Le Chatelier's principle}}
* {{annotated link|Lenz's law}}
* {{annotated link|Osmosis}}
* {{annotated link|Proteostasis}}
* {{annotated link|Senescence}}
* {{annotated link|Steady state (biochemistry)|Steady state}}
* {{annotated link|Systems biology}}
* {{annotated link|Vis medicatrix naturae}}
}}

==References==
{{reflist|30em}}

==Further reading==
{{refbegin |30em}}
* {{cite book
|editor1-first=Lucia |editor1-last=Banci |series=Metal Ions in Life Sciences |volume=12
|pages=41–67 |title=Metallomics and the Cell |year=2013 |publisher=Springer |isbn=978-94-007-5560-4|doi=10.1007/978-94-007-5561-1_3|pmid=23595670 |last1=Clausen |first1=M. J. |last2=Poulsen |first2=H. |chapter=Sodium/Potassium Homeostasis in the Cell }} electronic-book {{ISBN|978-94-007-5561-1}} {{issn|1559-0836}} electronic-{{issn|1868-0402}}
{{refend}}

==External links==
{{wiktionary}}

{{Commons category|Homeostasis}}
* [https://www.biology-innovation.co.uk/pages/human-biology/homeostasis/ Homeostasis] {{Webarchive|url=https://web.archive.org/web/20170815140048/https://www.biology-innovation.co.uk/pages/human-biology/homeostasis/ |date=15 August 2017 }}
* Walter Bradford Cannon, [https://www.panarchy.org/cannon/homeostasis.1932.html Homeostasis] (1932)
{{Biology nav|state=expanded}}
{{Water-electrolyte imbalance and acid-base imbalance}}
{{Human homeostasis}}
{{Authority control}}

[[Category:Homeostasis| ]]
[[Category:Physiology]]
[[Category:Biology terminology]]
[[Category:Cybernetics]]
[[Category:Change|*]]