Editing Homeostasis (section)

==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 |url=https://pubmed.ncbi.nlm.nih.gov/16675613 |journal=Journal of Applied Physiology |volume=101 |issue=2 |pages=664–668 |doi=10.1152/japplphysiol.01380.2005 |issn=8750-7587 |pmid=16675613 |archive-date=11 April 2024 |access-date=21 June 2024 |archive-url=https://web.archive.org/web/20240411232422/https://pubmed.ncbi.nlm.nih.gov/16675613 |url-status=live }}</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 |url=https://doi.org/10.1007/978-94-007-7500-8_11 |access-date=2024-08-11 |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.|url-access=subscription }}</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.{{cn|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|url-status=dead|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?|url=https://dx.doi.org/10.1093/ckj/sfv011|journal=Clinical Kidney Journal|volume=8|issue=2|pages=180–187|doi=10.1093/ckj/sfv011|pmid=25815174|issn=2048-8505|pmc=4370311|access-date=18 June 2021|archive-date=6 March 2022|archive-url=https://web.archive.org/web/20220306112843/https://academic.oup.com/ckj/article/8/2/180/471044|url-status=live}}</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|pages=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|pages=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|pages=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>