State of steady internal conditions maintained by living things
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Inbiology,homeostasis (British alsohomoeostasis;/ˌhoʊmiəˈsteɪsɪs/HOH-mee-ə-STAY-sis) is the state of steady internalphysical andchemical conditions maintained byliving systems.[1] This is the condition of optimal functioning for the organism and includes many variables, such asbody temperature andfluid balance, being kept within certain pre-set limits (homeostatic range). Other variables include thepH ofextracellular fluid, the concentrations ofsodium,potassium, andcalciumions, as well as theblood 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,[2] 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.[3] The receptor is the sensing component that monitors and responds to changes in the environment, either external or internal. Receptors includethermoreceptors andmechanoreceptors. Control centers include therespiratory center and therenin-angiotensin system. An effector is the target acted on, to bring about the change back to the normal state. At the cellular level, effectors includenuclear receptors that bring about changes ingene expression through up-regulation or down-regulation and act innegative feedback mechanisms. An example of this is in the control ofbile acids in theliver.[4]
Some centers, such as therenin–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 aneffector, which can be one or more muscles, an organ, or agland. When the signal is received and acted on, negative feedback is provided to the receptor that stops the need for further signaling.[5]
The concept of the regulation of the internal environment was described by French physiologistClaude Bernard in 1849, and the wordhomeostasis was coined byWalter Bradford Cannon in 1926.[11][12] In 1932,Joseph Barcroft, a British physiologist, was the first to say that higherbrain function required the most stable internal environment. Thus, to Barcroft homeostasis was not only organized by the brain—homeostasis served the brain.[13] 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.[11][12][14] The termcybernetics is applied to technologicalcontrol systems such asthermostats, which function as homeostatic mechanisms but are often defined much more broadly than the biological term of homeostasis.[5][15][16][17]
Themetabolic 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 thecell or in theinterstitial fluid bathing the cells. The best-known homeostatic mechanisms in humans and other mammals are regulators that keep the composition of theextracellular fluid (or the "internal environment") constant, especially with regard to thetemperature,pH,osmolality, and the concentrations ofsodium,potassium,glucose,carbon dioxide, andoxygen. However, a great many other homeostatic mechanisms, encompassing many aspects ofhuman physiology, control other entities in the body. Where the levels of variables are higher or lower than those needed, they are often prefixed withhyper- andhypo-, respectively such ashyperthermia andhypothermia orhypertension andhypotension.[citation needed]
Circadian variation in body temperature, ranging from about 37.5 °C from 10 a.m. to 6 p.m., and falling to about 36.4 °C from 2 a.m. to 6 a.m.
If an entity is homeostatically controlled it does not imply that its value is necessarily absolutely steady in health.Core body temperature is, for instance, regulated by a homeostatic mechanism with temperature sensors in, amongst others, thehypothalamus of thebrain.[18] However, theset point of the regulator is regularly reset.[19] For instance, core body temperature in humansvaries during the course of the day (i.e. has acircadian rhythm), with the lowest temperatures occurring at night, and the highest in the afternoons. Other normaltemperature variations include those related to themenstrual cycle.[20][21] The temperature regulator's set point is reset during infections to produce a fever.[18][22][23] Organisms are capable of adjusting somewhat to varied conditions such as temperature changes or oxygen levels at altitude, by a process ofacclimatisation.
Homeostasis does not govern every activity in the body.[24][25] For instance, the signal (be it vianeurons orhormones) from the sensor to the effector is, of necessity, highly variable in order to conveyinformation about the direction and magnitude of the error detected by the sensor.[26][27][28] 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.[16][17] For instance,arterial blood pressure in mammals is homeostatically controlled and measured bystretch receptors in the walls of theaortic arch andcarotid sinuses at the beginnings of theinternal carotid arteries.[18] The sensors send messages viasensory nerves to themedulla oblongata of the brain indicating whether theblood pressure has fallen or risen, and by how much. The medulla oblongata then distributes messages alongmotor or efferent nerves belonging to theautonomic 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.[18] 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 ofsweating. 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 thehypothalamus of the brain.[citation needed]
Mammals regulate theircore temperature using input fromthermoreceptors in thehypothalamus, brain,[18][29]spinal cord,internal organs, and great veins.[30][31] Apart from the internal regulation of temperature, a process calledallostasis can come into play that adjusts behaviour to adapt to the challenge of very hot or cold extremes (and to other challenges).[32] These adjustments may include seeking shade and reducing activity, seeking warmer conditions and increasing activity, or huddling.[33]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.[34]
When the core temperature falls, the blood supply to the skin is reduced by intensevasoconstriction.[18] 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 (formingvenae comitantes).[29][33][35] This acts as acounter-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.[29][33][36] The subcutaneous limb veins are tightly constricted,[18] not only reducing heat loss from this source but also forcing the venous blood into the counter-current system in the depths of the limbs.
When core temperature rises are detected bythermoreceptors, thesweat glands in the skin are stimulated viacholinergicsympathetic nerves to secretesweat 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 themucous membranes of the throat and mouth.[38]
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 areregulated within fairly narrow limits.[39] In mammals, the primary sensors for this are thebeta cells of thepancreatic islets.[40][41] The beta cells respond to a rise in the blood sugar level by secretinginsulin into the blood and simultaneously inhibiting their neighboringalpha cells from secretingglucagon into the blood.[40] This combination (high blood insulin levels and low glucagon levels) act on effector tissues, the chief of which is theliver,fat cells, andmuscle cells. The liver is inhibited from producingglucose, taking it up instead, and converting it toglycogen andtriglycerides. The glycogen is stored in the liver, but the triglycerides are secreted into the blood asvery low-density lipoprotein (VLDL) particles which are taken up byadipose 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.[42]
A fall in blood glucose, causes insulin secretion to be stopped, andglucagon 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 (throughglycogenolysis) and from non-carbohydrate sources (such aslactate and de-aminatedamino acids) using a process known asgluconeogenesis.[43] 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, toglucose-6-phosphate and thence topyruvate to be fed into thecitric acid cycle or turned intolactate. 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-consuminggluconeogenesis, convert it back to glucose.[citation needed]
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.[44] The primary site for iron absorption is theduodenum, where dietary iron exists in two forms: heme iron, sourced from animal products, andnon-heme iron, found in plant foods. Heme iron is more efficiently absorbed than non-heme iron, which requires factors likevitamin C for optimal uptake. Once absorbed, iron enters the bloodstream bound totransferrin, 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 asferritin and hemosiderin. The regulation of iron levels is primarily controlled by the hormonehepcidin, 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 deficiencyanemia or iron overload disorders likehemochromatosis, highlighting the importance of maintaining the delicate balance of this vital nutrient for overall health.
Copper is absorbed, transported, distributed, stored, and excreted in the body according to complexhomeostatic processes which ensure a constant and sufficient supply of the micronutrient while simultaneously avoiding excess levels.[45] 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.[46]
Many aspects of copper homeostasis are known at the molecular level.[47] Copper's essentiality is due to its ability to act as an electron donor or acceptor as its oxidation state fluxes between Cu1+ (cuprous) and Cu2+ (cupric). As a component of about a dozencuproenzymes, copper is involved in keyredox (i.e., oxidation-reduction) reactions in essential metabolic processes such asmitochondrial respiration, synthesis ofmelanin, and cross-linking ofcollagen.[48] 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]
Too little carbon dioxide, and, to a lesser extent, too much oxygen in the blood can temporarily halt breathing, a condition known asapnea, whichfreedivers use to prolong the time they can stay underwater.
Thepartial pressure of carbon dioxide is more of a deciding factor in the monitoring of pH.[49] However, at high altitude (above 2500 m) the monitoring of the partial pressure of oxygen takes priority, andhyperventilation 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.[50][51] This is important inacclimatization to high altitude.[52]
Thekidneys measure the oxygen content rather than thepartial pressure of oxygen in the arterial blood. When theoxygen content of the blood is chronically low, oxygen-sensitive cells secreteerythropoietin (EPO) into the blood.[53] The effector tissue is thered bone marrow which producesred blood cells (RBCs, also callederythrocytes). The increase in RBCs leads to an increasedhematocrit in the blood, and a subsequent increase inhemoglobin 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 withpulmonary insufficiency orright-to-left shunts in the heart (through which venous blood by-passes the lungs and goes directly into the systemic circulation) have similarly high hematocrits.[54][55]
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 inanemia, but the hemoglobin content will be insufficient and subsequently as will be the oxygen content. Given enough supply of iron,vitamin B12 andfolic acid, EPO can stimulate RBC production, and hemoglobin and oxygen content restored to normal.[54][56]
High pressure receptors calledbaroreceptors in the walls of theaortic arch andcarotid sinus (at the beginning of theinternal carotid artery) monitor the arterialblood pressure.[58] Rising pressure is detected when the walls of the arteries stretch due to an increase inblood volume. This causesheart muscle cells to secrete the hormoneatrial 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.[59]This information is then conveyed, viaafferent nerve fibers, to thesolitary nucleus in themedulla oblongata.[60] From heremotor nerves belonging to theautonomic nervous system are stimulated to influence the activity of chiefly the heart and the smallest diameter arteries, calledarterioles. The arterioles are the main resistance vessels in thearterial 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 todilate 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 viacholinergicparasympathetic nerves to beat more slowly (calledbradycardia), 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 (calledtachycardia). If the drop in blood pressure is very rapid or excessive, the medulla oblongata stimulates theadrenal medulla, via "preganglionic"sympathetic nerves, to secreteepinephrine (adrenaline) into the blood. This hormone enhances the tachycardia and causes severevasoconstriction of the arterioles to all but the essential organs in the body (especially the heart, lungs, and brain). These reactions usually correct the low arterial blood pressure (hypotension) very effectively.
The plasma ionized calcium (Ca2+) concentration is very tightly controlled by a pair of homeostatic mechanisms.[61] The sensor for the first one is situated in theparathyroid glands, where thechief cells sense the Ca2+ level by means of specialized calcium receptors in their membranes. The sensors for the second are theparafollicular cells in thethyroid gland. The parathyroid chief cells secreteparathyroid hormone (PTH) in response to a fall in the plasma ionized calcium level; the parafollicular cells of the thyroid gland secretecalcitonin in response to a rise in the plasma ionized calcium level.
Theeffector organs of the first homeostatic mechanism are thebones, thekidney, and, via a hormone released into the blood by the kidney in response to high PTH levels in the blood, theduodenum andjejunum. Parathyroid hormone (in high concentrations in the blood) causesbone resorption, releasing calcium into the plasma. This is a very rapid action which can correct a threateninghypocalcemia within minutes. High PTH concentrations cause the excretion ofphosphate ions via the urine. Since phosphates combine with calcium ions to form insoluble salts (see alsobone 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, ofcalcitriol into the blood. Thissteroid hormone acts on the epithelial cells of the upper small intestine, increasing their capacity to absorb calcium from the gut contents into the blood.[62]
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.[63]
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. Theskeleton acts as an extremely large calcium store (about 1 kg) compared with the plasma calcium store (about 180 mg). Longer term regulation occurs through calcium absorption or loss from the gut.
Another example are the most well-characterisedendocannabinoids likeanandamide (N-arachidonoylethanolamide; AEA) and2-arachidonoylglycerol (2-AG), whose synthesis occurs through the action of a series ofintracellularenzymes activated in response to a rise in intracellular calcium levels to introduce homeostasis and prevention oftumor development through putative protective mechanisms that preventcell growth andmigration by activation ofCB1 and/orCB2 and adjoiningreceptors.[64]
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 thejuxtaglomerular apparatus of kidneys, which senses the plasma sodium concentration in a surprisingly indirect manner. Instead of measuring it directly in the blood flowing past thejuxtaglomerular cells, these cells respond to the sodium concentration in therenal tubular fluid after it has already undergone a certain amount of modification in theproximal convoluted tubule andloop of Henle.[65] These cells also respond to rate of blood flow through the juxtaglomerular apparatus, which, under normal circumstances, is directly proportional to thearterial 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 releaserenin into the blood.[65][66][67] Renin is an enzyme which cleaves adecapeptide (a short protein chain, 10 amino acids long) from a plasmaα-2-globulin calledangiotensinogen. This decapeptide is known asangiotensin I.[65] It has no known biological activity. However, when the blood circulates through the lungs a pulmonary capillaryendothelial enzyme calledangiotensin-converting enzyme (ACE) cleaves a further two amino acids from angiotensin I to form an octapeptide known asangiotensin II. Angiotensin II is a hormone which acts on theadrenal cortex, causing the release into the blood of thesteroid 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, especiallyhypotension.
The angiotensin II-stimulatedaldosterone released from thezona glomerulosa of theadrenal glands has an effect on particularly the epithelial cells of thedistal convoluted tubules andcollecting ducts of the kidneys. Here it causes the reabsorption of sodium ions from therenal 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.[65][68] The reabsorption of sodium ions from the renal tubular fluid halts further sodium ion losses from the body, and therefore preventing the worsening ofhyponatremia. The hyponatremia can only becorrected 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 thedistal convoluted tubules orcollecting ducts. This is because sodium is reabsorbed in exchange for potassium and therefore causes only a modest change in theosmotic 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 ofantidiuretic hormone (ADH) in the blood. ADH is part of the control offluid balance. Its levels in the blood vary with theosmolality of the plasma, which is measured in thehypothalamus of the brain. Aldosterone's action on the kidney tubules prevents sodium loss to theextracellular fluid (ECF). So there is no change in the osmolality of the ECF, and therefore no change in the ADH concentration of the plasma. However, low aldosterone levels cause a loss of sodium ions from the ECF, which could potentially cause a change in extracellular osmolality and therefore of ADH levels in the blood.
Aldosterone acts primarily on thedistal convoluted tubules andcollecting ducts of the kidneys, stimulating the excretion of potassium ions into the urine.[65] It does so, however, by activating thebasolateralNa+/K+ pumps of the tubular epithelial cells. These sodium/potassium exchangers pump three sodium ions out of the cell, into the interstitial fluid and two potassium ions into the cell from the interstitial fluid. This creates anionic concentration gradient which results in the reabsorption of sodium (Na+) ions from the tubular fluid into the blood, and secreting potassium (K+) ions from the blood into the urine (lumen of collecting duct).[70][71]
Thetotal 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 ofelectrolytes in the extracellular fluid stable. Fluid balance is maintained by the process ofosmoregulation and by behavior.Osmotic pressure is detected byosmoreceptors in themedian preoptic nucleus in thehypothalamus. Measurement of the plasmaosmolality to give an indication of the water content of the body, relies on the fact that water losses from the body, (throughunavoidable water loss through the skin which is not entirely waterproof and therefore always slightly moist,water vapor in the exhaled air,sweating,vomiting, normalfeces and especiallydiarrhea) are allhypotonic, 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 ofbody water therefore cause the extracellular fluid to becomehypertonic. Conversely, excessive fluid intake dilutes the extracellular fluid causing the hypothalamus to registerhypotonic hyponatremia conditions.
When thehypothalamus detects a hypertonic extracellular environment, it causes the secretion of an antidiuretic hormone (ADH) calledvasopressin which acts on the effector organ, which in this case is thekidney. The effect of vasopressin on the kidney tubules is to reabsorb water from thedistal convoluted tubules andcollecting ducts, thus preventing aggravation of the water loss via the urine. The hypothalamus simultaneously stimulates the nearbythirst center causing an almost irresistible (if the hypertonicity is severe enough) urge to drink water. The cessation of urine flow prevents thehypovolemia andhypertonicity 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 acompensatory 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.
Theplasma pH can be altered by respiratory changes in the partial pressure of carbon dioxide; or altered by metabolic changes in thecarbonic acid tobicarbonate ion ratio. Thebicarbonate 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 theHenderson–Hasselbalch equation). A change in the plasma pH gives anacid–base imbalance.Inacid–base homeostasis there are two mechanisms that can help regulate the pH.Respiratory compensation a mechanism of therespiratory center, adjusts thepartial 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] The metabolism of these cells produces carbon dioxide, which is rapidly converted to hydrogen and bicarbonate through the action ofcarbonic anhydrase.[72] 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.[72] 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 (CSF) allows for regulation of the distribution of substances between cells of the brain,[73] andneuroendocrine factors, to which slight changes can cause problems or damage to the nervous system. For example, highglycineconcentration disruptstemperature andblood pressure control, and high CSFpH causesdizziness andsyncope.[74]
Inhibitory neurons in thecentral nervous system play a homeostatic role in the balance of neuronal activity between excitation and inhibition. Inhibitory neurons usingGABA, make compensating changes in the neuronal networks preventing runaway levels of excitation.[75] An imbalance between excitation and inhibition is seen to be implicated in a number ofneuropsychiatric disorders.[76]
Theneuroendocrine system is the mechanism by which the hypothalamus maintains homeostasis, regulatingmetabolism, reproduction, eating and drinking behaviour, energy utilization, osmolarity and blood pressure.
Theliver also has many regulatory functions of the metabolism. An important function is the production and control ofbile acids. Too much bile acid can be toxic to cells and its synthesis can be inhibited by activation ofFXR anuclear receptor.[4]
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 andleptin. Ghrelin is known as thehunger 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 forenergetic 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.[78]
Many diseases are the result of a homeostatic failure. Almost any homeostatic component can malfunction either as a result of aninherited defect, aninborn error of metabolism, or an acquired disease. Some homeostatic mechanisms have inbuilt redundancies,[which?] 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 intype 1 diabetes mellitus. Hereblood sugar regulation is unable to function because thebeta cells of thepancreatic islets are destroyed and cannot produce the necessaryinsulin. The blood sugar rises in a condition known ashyperglycemia.[79]
The plasma ionized calcium homeostat can be disrupted by the constant, unchanging, over-production ofparathyroid hormone by a parathyroidadenoma resulting in the typically features ofhyperparathyroidism, namely high plasma ionized Ca2+ levels and the resorption of bone, which can lead to spontaneous fractures. The abnormally high plasma ionized calcium concentrations cause conformational changes in many cell-surface proteins (especially ion channels and hormone or neurotransmitter receptors)[80] giving rise to lethargy, muscle weakness, anorexia, constipation and labile emotions.[81]
The body water homeostat can be compromised by the inability to secreteADH in response to even the normal daily water losses via the exhaled air, thefeces, andinsensible 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.[5]
Variouschronic diseases are kept under control by homeostatic compensation, which masks a problem by compensating for it (making up for it) in another way.[citation needed] However, the compensating mechanisms eventually wear out[vague] 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] Such decompensation unmasks the underlying disease, worsening its symptoms. Common examples include decompensatedheart failure,kidney failure, andliver failure according to Fan et al. (2011).[82]
In theGaia hypothesis,James Lovelock[83] stated that the entire mass of living matter on Earth (or any planet with life) functions as a vast homeostaticsuperorganism 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 actuallimiting factor on land. When sunlight is plentiful and the atmospheric temperature climbs, it has been claimed that thephytoplankton of the ocean surface waters, acting as global sunshine, and therefore heat sensors, may thrive and produce moredimethyl sulfide (DMS). The DMS molecules act ascloud condensation nuclei, which produce more clouds, and thus increase the atmosphericalbedo, 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 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.[40] 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.[84] Such anticipatory reactions are open loop systems which are based, essentially, on "guess work", and are not self-correcting.[85] 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.
Anactuary may refer torisk 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.[86][self-published source?]
Sociologists and psychologists may refer tostress homeostasis, the tendency of a population or an individual to stay at a certain level ofstress, often generating artificial stresses if the "natural" level of stress is not enough.[87][self-published source?]
Jean-François Lyotard, a postmodern theorist, has applied this term to societal 'power centers' that he describes inThe 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.
Thecentrifugal governor of asteam engine, as designed byJames 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.[92][93]
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.[94][95] Healthycivic 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,[96] or that between governmental effectiveness and responsiveness to the interests of citizens.[97][98]
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