biology Biology is the scientific study of life. It is a natural science with a broad scope but has several unifying themes that tie it together as a single, coherent field. For instance, all organisms are made up of cells that process hereditary i ...

, homeostasis (

British British may refer to: Peoples, culture, and language * British people, nationals or natives of the United Kingdom, British Overseas Territories, and Crown Dependencies. ** Britishness, the British identity and common culture * British English, ...

also homoeostasis) (/hɒmɪə(ʊ)ˈsteɪsɪs/) is the state of steady internal, physical, and

chemical A chemical substance is a form of matter having constant chemical composition and characteristic properties. Some references add that chemical substance cannot be separated into its constituent elements by physical separation methods, i.e., w ...

conditions maintained by

living systems Living systems are open self-organizing life forms that interact with their environment. These systems are maintained by flows of information, energy and matter. In the last few decades, some scientists have proposed that a general living syst ...

. This is the condition of optimal functioning for the organism and includes many variables, such as

body temperature Thermoregulation is the ability of an organism to keep its body temperature within certain boundaries, even when the surrounding temperature is very different. A thermoconforming organism, by contrast, simply adopts the surrounding temperature ...

and

fluid balance Fluid balance is an aspect of the homeostasis of organisms in which the amount of water in the organism needs to be controlled, via osmoregulation and behavior, such that the concentrations of electrolytes ( salts in solution) in the various b ...

, being kept within certain pre-set limits (homeostatic range). Other variables include the pH of

extracellular fluid In cell biology, extracellular fluid (ECF) denotes all body fluid outside the cells of any multicellular organism. Total body water in healthy adults is about 60% (range 45 to 75%) of total body weight; women and the obese typically have a low ...

, the concentrations of

sodium Sodium is a chemical element with the symbol Na (from Latin ''natrium'') and atomic number 11. It is a soft, silvery-white, highly reactive metal. Sodium is an alkali metal, being in group 1 of the periodic table. Its only stable ...

potassium Potassium is the chemical element with the symbol K (from Neo-Latin ''kalium'') and atomic number19. Potassium is a silvery-white metal that is soft enough to be cut with a knife with little force. Potassium metal reacts rapidly with atmosph ...

and

calcium Calcium is a chemical element with the symbol Ca and atomic number 20. As an alkaline earth metal, calcium is a reactive metal that forms a dark oxide-nitride layer when exposed to air. Its physical and chemical properties are most similar t ...

ion An ion () is an atom or molecule with a net electrical charge. The charge of an electron is considered to be negative by convention and this charge is equal and opposite to the charge of a proton, which is considered to be positive by conve ...

s, as well as that of the blood sugar level, and these need to be regulated despite changes in the environment, diet, or level of activity. Each of these variables is controlled by one or more regulators or homeostatic mechanisms, which together maintain life. Homeostasis is brought about by a natural resistance to change when already in the optimal conditions, 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. The receptor is the sensing component that monitors and responds to changes in the environment, either external or internal. Receptors include thermoreceptors, and mechanoreceptors. Control centers include the

respiratory center The respiratory center is located in the medulla oblongata and pons, in the brainstem. The respiratory center is made up of three major respiratory groups of neurons, two in the medulla and one in the pons. In the medulla they are the dorsal ...

, and the

renin–angiotensin system The renin–angiotensin system (RAS), or renin–angiotensin–aldosterone system (RAAS), is a hormone system that regulates blood pressure, fluid and electrolyte balance, and systemic vascular resistance. When renal blood flow is reduced, ...

. An effector is the target acted on, to bring about the change back to the normal state. At the cellular level, effectors include nuclear receptors that bring about changes in gene expression through up-regulation or down-regulation, and act in negative feedback mechanisms. An example of this is in the control of bile acids in the

liver The liver is a major organ only found in vertebrates which performs many essential biological functions such as detoxification of the organism, and the synthesis of proteins and biochemicals necessary for digestion and growth. In humans, it ...

. Some centers, such as the

, control more than one variable. When the receptor senses a stimulus, it reacts by sending action potentials to a control center. The control center sets the maintenance range—the acceptable upper and lower limits—for the particular variable, such as temperature. The control center responds to the signal by determining an appropriate response and sending signals to an

effector Effector may refer to: *Effector (biology), a molecule that binds to a protein and thereby alters the activity of that protein * ''Effector'' (album), a music album by the Experimental Techno group Download * ''EFFector'', a publication of the El ...

, which can be one or more muscles, an organ, or a gland. When the signal is received and acted on, negative feedback is provided to the receptor that stops the need for further signaling. The

cannabinoid receptor type 1 Cannabinoid receptor type 1 (CB1), also known as cannabinoid receptor 1, is a G protein-coupled cannabinoid receptor that in humans is encoded by the ''CNR1'' gene. The human CB1 receptor is expressed in the peripheral nervous system and centr ...

(CB1), located at the

presynaptic In the nervous system, a synapse is a structure that permits a neuron (or nerve cell) to pass an electrical or chemical signal to another neuron or to the target effector cell. Synapses are essential to the transmission of nervous impulses from ...

neuron A neuron, neurone, or nerve cell is an electrically excitable cell that communicates with other cells via specialized connections called synapses. The neuron is the main component of nervous tissue in all animals except sponges and placozoa. ...

, is a

receptor Receptor may refer to: * Sensory receptor, in physiology, any structure which, on receiving environmental stimuli, produces an informative nerve impulse *Receptor (biochemistry), in biochemistry, a protein molecule that receives and responds to a ...

that can stop stressful neurotransmitter release to the postsynaptic neuron; it is activated by

endocannabinoids Cannabinoids () are several structural classes of compounds found in the cannabis plant primarily and most animal organisms (although insects lack such receptors) or as synthetic compounds. The most notable cannabinoid is the phytocannabinoid tet ...

(ECs) such as

anandamide Anandamide (ANA), also known as ''N''-arachidonoylethanolamine (AEA), is a fatty acid neurotransmitter. Anandamide was the first endocannabinoid to be discovered: it participates in the body's endocannabinoid system by binding to cannabinoid r ...

(''N''-arachidonoylethanolamide; AEA) and

2-arachidonoylglycerol 2-Arachidonoylglycerol (2-AG) is an endocannabinoid, an endogenous agonist of the CB1 receptor and the primary endogenous ligand for the CB2 receptor. It is an ester formed from the omega-6 fatty acid arachidonic acid and glycerol. It is present ...

(2-AG) via a

retrograde signaling Retrograde signaling in biology is the process where a signal travels backwards from a target source to its original source. For example, the nucleus of a cell is the original source for creating signaling proteins. During retrograde signaling, ins ...

process in which these compounds are synthesized by and released from postsynaptic neurons, and travel back to the presynaptic terminal to bind to the CB1 receptor for modulation of neurotransmitter release to obtain homeostasis. The

polyunsaturated fatty acid Polyunsaturated fatty acids (PUFAs) are fatty acids that contain more than one double bond in their backbone. This class includes many important compounds, such as essential fatty acids and those that give drying oils their characteristic proper ...

s (PUFAs) are

lipid Lipids are a broad group of naturally-occurring molecules which includes fats, waxes, sterols, fat-soluble vitamins (such as vitamins A, D, E and K), monoglycerides, diglycerides, phospholipids, and others. The functions of lipids includ ...

derivatives of

omega-3 Omega−3 fatty acids, also called Omega-3 oils, ω−3 fatty acids or ''n''−3 fatty acids, are polyunsaturated fatty acids (PUFAs) characterized by the presence of a double bond, three atoms away from the terminal methyl group in their chem ...

(docosahexaenoic acid, DHA, and eicosapentaenoic acid,

EPA The Environmental Protection Agency (EPA) is an independent executive agency of the United States federal government tasked with environmental protection matters. President Richard Nixon proposed the establishment of EPA on July 9, 1970; it be ...

) or of

omega-6 Omega-6 fatty acids (also referred to as ω-6 fatty acids or ''n''-6 fatty acids) are a family of polyunsaturated fatty acids that have in common a final carbon-carbon double bond in the ''n''-6 position, that is, the sixth bond, counting from ...

(arachidonic acid,

ARA ARA may refer to: Media and the arts * American-Romanian Academy of Arts and Sciences * '' Artistička Radna Akcija'', compilation album released in former Yugoslavia * Associate of the Royal Academy, denoting membership in the British Royal Aca ...

) are synthesized from

membrane A membrane is a selective barrier; it allows some things to pass through but stops others. Such things may be molecules, ions, or other small particles. Membranes can be generally classified into synthetic membranes and biological membranes. ...

phospholipids and used as a precursor for endocannabinoids (ECs) mediate significant effects in the fine-tune adjustment of body homeostasis.

Etymology

The word ''homeostasis'' () uses combining forms of ''homeo-'' and ''-stasis'',

New Latin New Latin (also called Neo-Latin or Modern Latin) is the revival of Literary Latin used in original, scholarly, and scientific works since about 1500. Modern scholarly and technical nomenclature, such as in zoological and botanical taxonomy ...

from

Greek Greek may refer to: Greece Anything of, from, or related to Greece, a country in Southern Europe: *Greeks, an ethnic group. *Greek language, a branch of the Indo-European language family. **Proto-Greek language, the assumed last common ancestor ...

: ὅμοιος ''homoios'', "similar" and στάσις ''stasis'', "standing still", yielding the idea of "staying the same".

History

The concept of the regulation of the internal environment was described by French physiologist

Claude Bernard Claude Bernard (; 12 July 1813 – 10 February 1878) was a French physiologist. Historian I. Bernard Cohen of Harvard University called Bernard "one of the greatest of all men of science". He originated the term '' milieu intérieur'', and the ...

in 1849, and the word ''homeostasis'' was coined by

Walter Bradford Cannon Walter Bradford Cannon (October 19, 1871 – October 1, 1945) was an American physiologist, professor and chairman of the Department of Physiology at Harvard Medical School. He coined the term "fight or flight response", and developed the theory ...

in 1926. In 1932, Joseph Barcroft a British physiologist, was the first to say that higher

brain A brain is an organ that serves as the center of the nervous system in all vertebrate and most invertebrate animals. It is located in the head, usually close to the sensory organs for senses such as vision. It is the most complex organ in a ve ...

function required the most stable internal environment. Thus, to Barcroft homeostasis was not only organized by the brain—homeostasis served the brain. Homeostasis is an almost exclusively biological term, referring to the concepts described by Bernard and Cannon, concerning the constancy of the internal environment in which the cells of the body live and survive. The term cybernetics is applied to technological control systems such as thermostats, which function as homeostatic mechanisms, but is often defined much more broadly than the biological term of homeostasis.

Overview

The metabolic processes of all organisms can only take place in very specific physical and chemical environments. The conditions vary with each organism, and with whether the chemical processes take place inside the

cell Cell most often refers to: * Cell (biology), the functional basic unit of life Cell may also refer to: Locations * Monastic cell, a small room, hut, or cave in which a religious recluse lives, alternatively the small precursor of a monastery ...

or in the

interstitial fluid In cell biology, extracellular fluid (ECF) denotes all body fluid outside the cells of any multicellular organism. Total body water in healthy adults is about 60% (range 45 to 75%) of total body weight; women and the obese typically have a lower ...

bathing the cells. The best known homeostatic mechanisms in humans and other mammals are regulators that keep the composition of the

(or the "internal environment") constant, especially with regard to the

temperature Temperature is a physical quantity that expresses quantitatively the perceptions of hotness and coldness. Temperature is measurement, measured with a thermometer. Thermometers are calibrated in various Conversion of units of temperature, temp ...

, pH,

osmolality Molality is a measure of the number of moles of solute in a solution corresponding to 1 kg or 1000 g of solvent. This contrasts with the definition of molarity which is based on a specified volume of solution. A commonly used unit for molali ...

, and the concentrations of

glucose Glucose is a simple sugar with the molecular formula . Glucose is overall the most abundant monosaccharide, a subcategory of carbohydrates. Glucose is mainly made by plants and most algae during photosynthesis from water and carbon dioxide, u ...

carbon dioxide Carbon dioxide ( chemical formula ) is a chemical compound made up of molecules that each have one carbon atom covalently double bonded to two oxygen atoms. It is found in the gas state at room temperature. In the air, carbon dioxide is trans ...

, and

oxygen Oxygen is the chemical element with the symbol O and atomic number 8. It is a member of the chalcogen group in the periodic table, a highly reactive nonmetal, and an oxidizing agent that readily forms oxides with most elements as ...

. However, a great many other homeostatic mechanisms, encompassing many aspects of

human physiology The human body is the structure of a human being. It is composed of many different types of cells that together create tissues and subsequently organ systems. They ensure homeostasis and the viability of the human body. It comprises a head ...

, control other entities in the body. Where the levels of variables are higher or lower than those needed, they are often prefixed with ''hyper-'' and ''hypo-'', respectively such as

hyperthermia Hyperthermia, also known simply as overheating, is a condition in which an individual's body temperature is elevated beyond normal due to failed thermoregulation. The person's body produces or absorbs more heat than it dissipates. When extreme ...

and

hypothermia Hypothermia is defined as a body core temperature below in humans. Symptoms depend on the temperature. In mild hypothermia, there is shivering and mental confusion. In moderate hypothermia, shivering stops and confusion increases. In severe ...

or hypertension and

hypotension Hypotension is low blood pressure. Blood pressure is the force of blood pushing against the walls of the arteries as the heart pumps out blood. Blood pressure is indicated by two numbers, the systolic blood pressure (the top number) and the dia ...

. If an entity is homeostatically controlled it does not imply that its value is necessarily absolutely steady in health.

Core body temperature Normal human body-temperature (normothermia, euthermia) is the typical temperature range found in humans. The normal human body temperature range is typically stated as . Human body temperature varies. It depends on sex, age, time of day, exert ...

is, for instance, regulated by a homeostatic mechanism with temperature sensors in, amongst others, the

hypothalamus The hypothalamus () is a part of the brain that contains a number of small nuclei with a variety of functions. One of the most important functions is to link the nervous system to the endocrine system via the pituitary gland. The hypothalamu ...

of the

. However, the set point of the regulator is regularly reset. For instance, core body temperature in humans varies during the course of the day (i.e. has a circadian rhythm), with the lowest temperatures occurring at night, and the highest in the afternoons. Other normal temperature variations include those related to the menstrual cycle. The temperature regulator's set point is reset during infections to produce a fever. Organisms are capable of adjusting somewhat to varied conditions such as temperature changes or oxygen levels at altitude, by a process of

acclimatisation Acclimatization or acclimatisation ( also called acclimation or acclimatation) is the process in which an individual organism adjusts to a change in its environment (such as a change in altitude, temperature, humidity, photoperiod, or pH), a ...

. Homeostasis does not govern every activity in the body. For instance the signal (be it via

s or

hormone A hormone (from the Greek participle , "setting in motion") is a class of signaling molecules in multicellular organisms that are sent to distant organs by complex biological processes to regulate physiology and behavior. Hormones are require ...

s) from the sensor to the effector is, of necessity, highly variable in order to convey

information Information is an abstract concept that refers to that which has the power to inform. At the most fundamental level information pertains to the interpretation of that which may be sensed. Any natural process that is not completely random ...

about the direction and magnitude of the error detected by the sensor. Similarly the effector's response needs to be highly adjustable to reverse the error – in fact it should be very nearly in proportion (but in the opposite direction) to the error that is threatening the internal environment. For instance, the

arterial blood pressure Blood pressure (BP) is the pressure of circulating blood against the walls of blood vessels. Most of this pressure results from the heart pumping blood through the circulatory system. When used without qualification, the term "blood pressure" r ...

in mammals is homeostatically controlled, and measured by

stretch receptor Stretch receptors are mechanoreceptors responsive to distention of various organs and muscles, and are neurologically linked to the Medulla oblongata, medulla in the brain stem via Afferent nerve fiber, afferent nerve fibers. Examples include stre ...

s in the walls of the

aortic arch The aortic arch, arch of the aorta, or transverse aortic arch () is the part of the aorta between the ascending and descending aorta. The arch travels backward, so that it ultimately runs to the left of the trachea. Structure The aorta begins ...

and carotid sinuses at beginnings of the

internal carotid arteries The internal carotid artery (Latin: arteria carotis interna) is an artery in the neck which supplies the anterior circulation of the brain. In human anatomy, the internal and external carotids arise from the common carotid arteries, where these ...

. The sensors send messages via

sensory nerve A sensory nerve, or afferent nerve, is a general anatomic term for a nerve which contains predominantly somatic afferent nerve fibers. Afferent nerve fibers in a sensory nerve carry sensory information toward the central nervous system (CNS) fro ...

s to the medulla oblongata of the brain indicating whether the blood pressure has fallen or risen, and by how much. The medulla oblongata then distributes messages along motor or efferent nerves belonging to the autonomic nervous system to a wide variety of effector organs, whose activity is consequently changed to reverse the error in the blood pressure. One of the effector organs is the heart whose rate is stimulated to rise (

tachycardia Tachycardia, also called tachyarrhythmia, is a heart rate that exceeds the normal resting rate. In general, a resting heart rate over 100 beats per minute is accepted as tachycardia in adults. Heart rates above the resting rate may be normal ( ...

) when the arterial blood pressure falls, or to slow down ( bradycardia) when the pressure rises above set point. Thus the heart rate (for which there is no sensor in the body) is not homeostatically controlled, but is one of effector responses to errors in the arterial blood pressure. Another example is the rate of sweating. This is one of the effectors in the homeostatic control of body temperature, and therefore highly variable in rough proportion to the heat load that threatens to destabilize the body's core temperature, for which there is a sensor in the

of the brain.

Controls of variables

Core temperature

Mammals regulate their

core temperature Normal human body-temperature (normothermia, euthermia) is the typical temperature range found in humans. The normal human body temperature range is typically stated as . Human body temperature varies. It depends on sex, age, time of day, exert ...

using input from thermoreceptors in the

, brain,

spinal cord The spinal cord is a long, thin, tubular structure made up of nervous tissue, which extends from the medulla oblongata in the brainstem to the lumbar region of the vertebral column (backbone). The backbone encloses the central canal of the sp ...

internal organs In biology, an organ is a collection of tissues joined in a structural unit to serve a common function. In the hierarchy of life, an organ lies between tissue and an organ system. Tissues are formed from same type cells to act together in a ...

, and great veins. Apart from the internal regulation of temperature, a process called

allostasis Allostasis also known as “body budgeting” which Lisa Feldman Barret argues, proposes that efficient regulation requires preparing the body to satisfy the needs before they arise by budgeting those needed resources such as oxygen, insulin ...

can come into play that adjusts behaviour to adapt to the challenge of very hot or cold extremes (and to other challenges). These adjustments may include seeking shade and reducing activity, or seeking warmer conditions and increasing activity, or huddling. Behavioural thermoregulation takes precedence over physiological thermoregulation since necessary changes can be affected more quickly and physiological thermoregulation is limited in its capacity to respond to extreme temperatures. When core temperature falls, the blood supply to the skin is reduced by intense

vasoconstriction Vasoconstriction is the narrowing of the blood vessels resulting from contraction of the muscular wall of the vessels, in particular the large arteries and small arterioles. The process is the opposite of vasodilation, the widening of blood vess ...

. The blood flow to the limbs (which have a large surface area) is similarly reduced, and returned to the trunk via the deep veins which lie alongside the arteries (forming

venae comitantes Vena comitans is Latin for accompanying vein. It refers to a vein that is usually paired, with both veins lying on the sides of an artery. They are found in close proximity to arteries so that the pulsations of the artery aid venous return. B ...

). This acts as a counter-current exchange system which short-circuits the warmth from the arterial blood directly into the venous blood returning into the trunk, causing minimal heat loss from the extremities in cold weather. The subcutaneous limb veins are tightly constricted, not only reducing heat loss from this source, but also forcing the venous blood into the counter-current system in the depths of the limbs. The metabolic rate is increased, initially by non-shivering

thermogenesis Thermogenesis is the process of heat production in organisms. It occurs in all warm-blooded animals, and also in a few species of thermogenic plants such as the Eastern skunk cabbage, the Voodoo lily ('' Sauromatum venosum''), and the giant w ...

, followed by shivering thermogenesis if the earlier reactions are insufficient to correct the

. When core temperature rises are detected by thermoreceptors, the sweat glands in the skin are stimulated via

cholinergic Cholinergic agents are compounds which mimic the action of acetylcholine and/or butyrylcholine. In general, the word " choline" describes the various quaternary ammonium salts containing the ''N'',''N'',''N''-trimethylethanolammonium cati ...

sympathetic nerves to secrete

sweat Perspiration, also known as sweating, is the production of fluids secreted by the sweat glands in the skin of mammals. Two types of sweat glands can be found in humans: eccrine glands and apocrine glands. The eccrine sweat glands are distrib ...

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 A mucous membrane or mucosa is a membrane that lines various cavities in the body of an organism and covers the surface of internal organs. It consists of one or more layers of epithelial cells overlying a layer of loose connective tissue. It is ...

of the throat and mouth.

Blood glucose

Blood sugar Glycaemia, also known as blood sugar level, blood sugar concentration, or blood glucose level is the measure of glucose concentrated in the blood of humans or other animals. Approximately 4 grams of glucose, a simple sugar, is present in the blo ...

levels are

regulated Regulation is the management of complex systems according to a set of rules and trends. In systems theory, these types of rules exist in various fields of biology and society, but the term has slightly different meanings according to context. Fo ...

within fairly narrow limits. In mammals the primary sensors for this are the

beta cells Beta cells (β-cells) are a type of cell found in pancreatic islets that synthesize and secrete insulin and amylin. Beta cells make up 50–70% of the cells in human islets. In patients with Type 1 diabetes, beta-cell mass and function are dim ...

of the

pancreatic islets The pancreatic islets or islets of Langerhans are the regions of the pancreas that contain its endocrine (hormone-producing) cells, discovered in 1869 by German pathological anatomist Paul Langerhans. The pancreatic islets constitute 1–2% o ...

. 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 Alpha cells (α cells) are endocrine cells that are found in the Islets of Langerhans in the pancreas. Alpha cells secrete the peptide hormone glucagon in order to increase glucose levels in the blood stream. Discovery Islets of Langerhans were ...

from secreting glucagon into the blood. This combination (high blood insulin levels and low glucagon levels) act on effector tissues, chief of which are the

fat cells Adipocytes, also known as lipocytes and fat cells, are the cells that primarily compose adipose tissue, specialized in storing energy as fat. Adipocytes are derived from mesenchymal stem cells which give rise to adipocytes through adipogenesis. I ...

and

muscle cells A muscle cell is also known as a myocyte when referring to either a cardiac muscle cell (cardiomyocyte), or a smooth muscle cell as these are both small cells. A skeletal muscle cell is long and threadlike with many nuclei and is called a mus ...

. The liver is inhibited from producing

, taking it up instead, and converting it to glycogen and

triglycerides A triglyceride (TG, triacylglycerol, TAG, or triacylglyceride) is an ester derived from glycerol and three fatty acids (from ''tri-'' and ''glyceride''). Triglycerides are the main constituents of body fat in humans and other vertebrates, as we ...

. The glycogen is stored in the liver, but the triglycerides are secreted into the blood as

very low-density lipoprotein Very-low-density lipoprotein (VLDL), density relative to extracellular water, is a type of lipoprotein made by the liver. VLDL is one of the five major groups of lipoproteins ( chylomicrons, VLDL, intermediate-density lipoprotein, low-density l ...

(VLDL) particles which are taken up by

adipose tissue Adipose tissue, body fat, or simply fat is a loose connective tissue composed mostly of adipocytes. In addition to adipocytes, adipose tissue contains the stromal vascular fraction (SVF) of cells including preadipocytes, fibroblasts, vascular ...

, there to be stored as fats. The fat cells take up glucose through special glucose transporters (

GLUT4 Glucose transporter type 4 (GLUT4), also known as solute carrier family 2, facilitated glucose transporter member 4, is a protein encoded, in humans, by the ''SLC2A4'' gene. GLUT4 is the insulin-regulated glucose transporter found primarily in a ...

), whose numbers in the cell wall are increased as a direct effect of insulin acting on these cells. The glucose that enters the fat cells in this manner is converted into triglycerides (via the same metabolic pathways as are used by the liver) and then stored in those fat cells together with the VLDL-derived triglycerides that were made in the liver. Muscle cells also take glucose up through insulin-sensitive GLUT4 glucose channels, and convert it into muscle glycogen. A fall in blood glucose, causes insulin secretion to be stopped, and glucagon to be secreted from the alpha cells into the blood. This inhibits the uptake of glucose from the blood by the liver, fats cells and muscle. Instead the liver is strongly stimulated to manufacture glucose from glycogen (through glycogenolysis) and from non-carbohydrate sources (such as lactate and de-aminated amino acids) using a process known as gluconeogenesis. The glucose thus produced is discharged into the blood correcting the detected error (

hypoglycemia Hypoglycemia, also called low blood sugar, is a fall in blood sugar to levels below normal, typically below 70 mg/dL (3.9 mmol/L). Whipple's triad is used to properly identify hypoglycemic episodes. It is defined as blood glucose bel ...

). The glycogen stored in muscles remains in the muscles, and is only broken down, during exercise, to

glucose-6-phosphate Glucose 6-phosphate (G6P, sometimes called the Robison ester) is a glucose sugar phosphorylated at the hydroxy group on carbon 6. This dianion is very common in cells as the majority of glucose entering a cell will become phosphorylated in this wa ...

and thence to pyruvate to be fed into the

citric acid cycle The citric acid cycle (CAC)—also known as the Krebs cycle or the TCA cycle (tricarboxylic acid cycle)—is a series of chemical reactions to release stored energy through the oxidation of acetyl-CoA derived from carbohydrates, fats, and protein ...

or turned into lactate. It is only the lactate and the waste products of the citric acid cycle that are returned to the blood. The liver can take up only the lactate, and by the process of energy consuming gluconeogenesis convert it back to glucose.

Iron levels

Copper regulation

Copper is absorbed, transported, distributed, stored, and excreted in the body according to complex

homeostatic In biology, homeostasis (British also homoeostasis) (/hɒmɪə(ʊ)ˈsteɪsɪs/) is the state of steady internal, physical, and chemical conditions maintained by living systems. This is the condition of optimal functioning for the organism and ...

processes which ensure a constant and sufficient supply of the micronutrient while simultaneously avoiding excess levels. If an insufficient amount of copper is ingested for a short period of time, copper stores in the liver will be depleted. Should this depletion continue, a copper health deficiency condition may develop. If too much copper is ingested, an excess condition can result. Both of these conditions, deficiency and excess, can lead to tissue injury and disease. However, due to homeostatic regulation, the human body is capable of balancing a wide range of copper intakes for the needs of healthy individuals. Many aspects of copper homeostasis are known at the molecular level. Copper's essentiality is due to its ability to act as an electron donor or acceptor as its oxidation state fluxes between Cu¹⁺(

cuprous Copper is a chemical element with the symbol Cu (from la, cuprum) and atomic number 29. It is a soft, malleable, and ductile metal with very high thermal and electrical conductivity. A freshly exposed surface of pure copper has a pinkish- ...

) and Cu²⁺ (

cupric Copper is a chemical element with the symbol Cu (from la, cuprum) and atomic number 29. It is a soft, malleable, and ductile metal with very high thermal and electrical conductivity. A freshly exposed surface of pure copper has a pinkish- ...

). As a component of about a dozen cuproenzymes, copper is involved in key

redox Redox (reduction–oxidation, , ) is a type of chemical reaction in which the oxidation states of substrate change. Oxidation is the loss of electrons or an increase in the oxidation state, while reduction is the gain of electrons or a ...

(i.e., oxidation-reduction) reactions in essential metabolic processes such as mitochondrial respiration, synthesis of

melanin Melanin (; from el, μέλας, melas, black, dark) is a broad term for a group of natural pigments found in most organisms. Eumelanin is produced through a multistage chemical process known as melanogenesis, where the oxidation of the amino ...

, and cross-linking of collagen. Copper is an integral part of the antioxidant enzyme copper-zinc superoxide dismutase, and has a role in iron homeostasis as a cofactor in ceruloplasmin.

Levels of blood gases

Changes in the levels of oxygen, carbon dioxide, and plasma pH are sent to the

, in the brainstem where they are regulated. The partial pressure of

and

in the

arterial blood Arterial blood is the oxygenated blood in the circulatory system found in the pulmonary vein, the left chambers of the heart, and in the artery, arteries. It is bright red in color, while venous blood is dark red in color (but looks purple through ...

is monitored by the

peripheral chemoreceptors Peripheral chemoreceptors (of the carotid and aortic bodies) are so named because they are sensory extensions of the peripheral nervous system into blood vessels where they detect changes in chemical concentrations. As transducers of patterns of va ...

( PNS) in the carotid artery and

. A change in the partial pressure of carbon dioxide is detected as altered pH in the

cerebrospinal fluid Cerebrospinal fluid (CSF) is a clear, colorless body fluid found within the tissue that surrounds the brain and spinal cord of all vertebrates. CSF is produced by specialised ependymal cells in the choroid plexus of the ventricles of the ...

central chemoreceptors Central chemoreceptors of the central nervous system, located on the ventrolateral medullary surface in the vicinity of the exit of the 9th and 10th cranial nerves, are sensitive to the pH of their environment. These act to detect the changes in ...

( 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 diaphragm and other

muscles of respiration The muscles of respiration are the muscles that contribute to inhalation and exhalation, by aiding in the expansion and contraction of the thoracic cavity. The diaphragm and, to a lesser extent, the intercostal muscles drive respiration during ...

. 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 The respiratory rate is the rate at which breathing occurs; it is set and controlled by the respiratory center of the brain. A person's respiratory rate is usually measured in breaths per minute. Measurement The respiratory rate in humans is me ...

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 freedivers use to prolong the time they can stay underwater. The partial pressure of carbon dioxide is more of a deciding factor in the monitoring of pH. However, at high altitude (above 2500 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. This is important in the

acclimatization to high altitude The effects of high altitude on humans are mostly the consequences of reduced partial pressure of oxygen in the atmosphere. The oxygen saturation of hemoglobin determines the content of oxygen in blood. After the human body reaches around above ...

Blood oxygen content

The kidneys measure the oxygen content rather than the

partial pressure of oxygen Blood gas tension refers to the partial pressure of gases in blood. There are several significant purposes for measuring gas tension. The most common gas tensions measured are oxygen tension (PxO2), carbon dioxide tension (PxCO2) and carbon monox ...

in the arterial blood. When the oxygen content of the blood is chronically low, oxygen-sensitive cells secrete erythropoietin (EPO) into the blood. The effector tissue is the red bone marrow which produces

red blood cell Red blood cells (RBCs), also referred to as red cells, red blood corpuscles (in humans or other animals not having nucleus in red blood cells), haematids, erythroid cells or erythrocytes (from Greek ''erythros'' for "red" and ''kytos'' for "holl ...

s (RBCs)(erythrocytes). The increase in RBCs leads to an increased

hematocrit The hematocrit () (Ht or HCT), also known by several other names, is the volume percentage (vol%) of red blood cells (RBCs) in blood, measured as part of a blood test. The measurement depends on the number and size of red blood cells. It is norm ...

in the blood, and subsequent increase in

hemoglobin Hemoglobin (haemoglobin BrE) (from the Greek word αἷμα, ''haîma'' 'blood' + Latin ''globus'' 'ball, sphere' + ''-in'') (), abbreviated Hb or Hgb, is the iron-containing oxygen-transport metalloprotein present in red blood cells (erythrocyt ...

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 Pulmonary (or pulmonic) insufficiency (or incompetence, or regurgitation) is a condition in which the pulmonary valve is incompetent and allows backflow from the pulmonary artery to the right ventricle of the heart during diastole. While a small ...

right-to-left shunt A right-to-left shunt is a cardiac shunt which allows blood to flow from the right heart to the left heart. This terminology is used both for the abnormal state in humans and for normal physiological shunts in reptiles. Clinical Significance A ...

s in the heart (through which venous blood by-passes the lungs and goes directly into the systemic circulation) have similarly high hematocrits. Regardless of the partial pressure of oxygen in the blood, the amount of oxygen that can be carried, depends on the hemoglobin content. The partial pressure of oxygen may be sufficient for example in

anemia Anemia or anaemia (British English) is a blood disorder in which the blood has a reduced ability to carry oxygen due to a lower than normal number of red blood cells, or a reduction in the amount of hemoglobin. When anemia comes on slowly, t ...

, but the hemoglobin content will be insufficient and subsequently as will be the oxygen content. Given enough supply of iron,

vitamin B12 Vitamin B12, also known as cobalamin, is a water-soluble vitamin involved in metabolism. It is one of eight B vitamins. It is required by animals, which use it as a cofactor in DNA synthesis, in both fatty acid and amino acid metabolism. ...

and

folic acid Folate, also known as vitamin B9 and folacin, is one of the B vitamins. Manufactured folic acid, which is converted into folate by the body, is used as a dietary supplement and in food fortification as it is more stable during processing and ...

, EPO can stimulate RBC production, and hemoglobin and oxygen content restored to normal.

Arterial blood pressure

The brain can regulate blood flow over a range of blood pressure values by

and

vasodilation Vasodilation is the widening of blood vessels. It results from relaxation of smooth muscle cells within the vessel walls, in particular in the large veins, large arteries, and smaller arterioles. The process is the opposite of vasoconstrictio ...

of the arteries. High pressure receptors called baroreceptors in the walls of the

and carotid sinus (at the beginning of the internal carotid artery) monitor the arterial blood pressure. Rising pressure is detected when the walls of the arteries stretch due to an increase in blood volume. This causes

heart muscle cells Cardiac muscle (also called heart muscle, myocardium, cardiomyocytes and cardiac myocytes) is one of three types of vertebrate muscle tissues, with the other two being skeletal muscle and smooth muscle. It is an involuntary, striated muscle th ...

to secrete the hormone

atrial natriuretic peptide Atrial natriuretic peptide (ANP) or atrial natriuretic factor (ANF) is a natriuretic peptide hormone secreted from the cardiac atria that in humans is encoded by the NPPA gene. Natriuretic peptides (ANP, BNP, and CNP) are a family of hormone/p ...

(ANP) into the blood. This acts on the kidneys to inhibit the secretion of renin and aldosterone causing the release of sodium, and accompanying water into the urine, thereby reducing the blood volume. This information is then conveyed, via afferent nerve fibers, to the

solitary nucleus In the human brainstem, the solitary nucleus, also called nucleus of the solitary tract, nucleus solitarius, and nucleus tractus solitarii, (SN or NTS) is a series of purely sensory nuclei (clusters of nerve cell bodies) forming a vertical column ...

in the medulla oblongata. From here motor nerves belonging to the autonomic nervous system are stimulated to influence the activity of chiefly the heart and the smallest diameter arteries, called

arterioles An arteriole is a small-diameter blood vessel in the microcirculation that extends and branches out from an artery and leads to capillaries. Arterioles have muscular walls (usually only one to two layers of smooth muscle cells) and are the primar ...

. The arterioles are the main resistance vessels in the

arterial tree In anatomy, arterial tree is used to refer to all arteries and/or the branching pattern of the arteries. This article regards the human arterial tree. Starting from the aorta: the following are the parts Ascending aorta It is a portion of the ...

, and small changes in diameter cause large changes in the resistance to flow through them. When the arterial blood pressure rises the arterioles are stimulated to

dilate Dilation (or dilatation) may refer to: Physiology or medicine * Cervical dilation, the widening of the cervix in childbirth, miscarriage etc. * Coronary dilation, or coronary reflex * Dilation and curettage, the opening of the cervix and surgic ...

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

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 correction of 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

). 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

of the arterioles to all but the essential organ in the body (especially the heart, lungs, and brain). These reactions usually correct the low arterial blood pressure (

) very effectively.

Calcium levels

The plasma ionized calcium (Ca²⁺) concentration is very tightly controlled by a pair of homeostatic mechanisms. The sensor for the first one is situated in the parathyroid glands, where the

chief cells In human anatomy, there are three types of chief cells, the gastric chief cell, the parathyroid chief cell, and the type 1 chief cells found in the carotid body. Cell types The gastric chief cell (also known as a zymogenic cell or peptic cell) is a ...

sense the Ca²⁺ level by means of specialized calcium receptors in their membranes. The sensors for the second are the parafollicular cells in the thyroid gland. The parathyroid chief cells secrete

parathyroid hormone Parathyroid hormone (PTH), also called parathormone or parathyrin, is a peptide hormone secreted by the parathyroid glands that regulates the serum calcium concentration through its effects on bone, kidney, and intestine. PTH influences bone ...

(PTH) in response to a fall in the plasma ionized calcium level; the parafollicular cells of the thyroid gland secrete

calcitonin Calcitonin is a 32 amino acid peptide hormone secreted by parafollicular cells (also known as C cells) of the thyroid (or endostyle) in humans and other chordates. in the ultimopharyngeal body. It acts to reduce blood calcium (Ca2+), opposing th ...

in response to a rise in the plasma ionized calcium level. The

organs of the first homeostatic mechanism are the

bone A bone is a rigid organ that constitutes part of the skeleton in most vertebrate animals. Bones protect the various other organs of the body, produce red and white blood cells, store minerals, provide structure and support for the body, ...

s, the

kidney The kidneys are two reddish-brown bean-shaped organs found in vertebrates. They are located on the left and right in the retroperitoneal space, and in adult humans are about in length. They receive blood from the paired renal arteries; blo ...

, and, via a hormone released into the blood by the kidney in response to high PTH levels in the blood, the duodenum and

jejunum The jejunum is the second part of the small intestine in humans and most higher vertebrates, including mammals, reptiles, and birds. Its lining is specialised for the absorption by enterocytes of small nutrient molecules which have been previou ...

. Parathyroid hormone (in high concentrations in the blood) causes

bone resorption Bone resorption is resorption of bone tissue, that is, the process by which osteoclasts break down the tissue in bones and release the minerals, resulting in a transfer of calcium from bone tissue to the blood. The osteoclasts are multi-nuclea ...

, releasing calcium into the plasma. This is a very rapid action which can correct a threatening

hypocalcemia Hypocalcemia is a medical condition characterized by low calcium levels in the blood serum. The normal range of blood calcium is typically between 2.1–2.6 mmol/L (8.8–10.7 mg/dL, 4.3–5.2 mEq/L) while levels less than 2.1 mm ...

within minutes. High PTH concentrations cause the excretion of phosphate ions via the urine. Since phosphates combine with calcium ions to form insoluble salts (see also

bone mineral Bone mineral (also called inorganic bone phase, bone salt, or bone apatite) is the inorganic component of bone tissue. It gives bones their compressive strength. Bone mineral is formed predominantly from carbonated hydroxyapatite with lower cry ...

), 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 Calcitriol is the active form of vitamin D, normally made in the kidney. It is also known as 1,25-dihydroxycholecalciferol. It is a hormone which binds to and activates the vitamin D receptor in the nucleus of the cell, which then increases the ...

into the blood. This steroid hormone acts on the epithelial cells of the upper small intestine, increasing their capacity to absorb calcium from the gut contents into the blood. The second homeostatic mechanism, with its sensors in the thyroid gland, releases calcitonin into the blood when the blood ionized calcium rises. This hormone acts primarily on bone, causing the rapid removal of calcium from the blood and depositing it, in insoluble form, in the bones. The two homeostatic mechanisms working through PTH on the one hand, and calcitonin on the other can very rapidly correct any impending error in the plasma ionized calcium level by either removing calcium from the blood and depositing it in the skeleton, or by removing calcium from it. The skeleton acts as an extremely large calcium store (about 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-characterised

(''N''-arachidonoylethanolamide; AEA) and

(2-AG), whose synthesis occurs through the action of a series of

intracellular This glossary of biology terms is a list of definitions of fundamental terms and concepts used in biology, the study of life and of living organisms. It is intended as introductory material for novices; for more specific and technical definitions ...

enzyme Enzymes () are proteins that act as biological catalysts by accelerating chemical reactions. The molecules upon which enzymes may act are called substrates, and the enzyme converts the substrates into different molecules known as products ...

s activated in response to a rise in intracellular calcium levels to introduce homeostasis and prevention of

tumor A neoplasm () is a type of abnormal and excessive growth of tissue. The process that occurs to form or produce a neoplasm is called neoplasia. The growth of a neoplasm is uncoordinated with that of the normal surrounding tissue, and persists ...

development through putative protective mechanisms that prevent cell growth and

migration Migration, migratory, or migrate may refer to: Human migration * Human migration, physical movement by humans from one region to another ** International migration, when peoples cross state boundaries and stay in the host state for some minimum le ...

by activation of CB1 and/or CB2 and adjoining

receptors Receptor may refer to: *Sensory receptor, in physiology, any structure which, on receiving environmental stimuli, produces an informative nerve impulse *Receptor (biochemistry), in biochemistry, a protein molecule that receives and responds to a n ...

Sodium concentration

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 The juxtaglomerular apparatus (also known as the juxtaglomerular complex) is a structure in the kidney that regulates the function of each nephron, the functional units of the kidney. The juxtaglomerular apparatus is named because it is next to ...

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 Juxtaglomerular cells (JG cells), also known as juxtaglomerular granular cells are cells in the kidney that synthesize, store, and secrete the enzyme renin. They are specialized smooth muscle cells mainly in the walls of the afferent arteriol ...

s, these cells respond to the sodium concentration in the renal tubular fluid after it has already undergone a certain amount of modification in the

proximal convoluted tubule The proximal tubule is the segment of the nephron in kidneys which begins from the renal pole of the Bowman's capsule to the beginning of loop of Henle. It can be further classified into the proximal convoluted tubule (PCT) and the proximal straig ...

and

loop of Henle In the kidney, the loop of Henle () (or Henle's loop, Henle loop, nephron loop or its Latin counterpart ''ansa nephroni'') is the portion of a nephron that leads from the proximal convoluted tubule to the distal convoluted tubule. Named after its ...

. These cells also respond to rate of blood flow through the juxtaglomerular apparatus, which, under normal circumstances, is directly proportional to the

, 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 Renin (etymology and pronunciation), also known as an angiotensinogenase, is an aspartic protease protein and enzyme secreted by the kidneys that participates in the body's renin–angiotensin–aldosterone system (RAAS)—also known as the r ...

into the blood. Renin is an enzyme which cleaves a

decapeptide Peptides (, ) are short chains of amino acids linked by peptide bonds. Long chains of amino acids are called proteins. Chains of fewer than twenty amino acids are called oligopeptides, and include dipeptides, tripeptides, and tetrapeptides. A p ...

(a short protein chain, 10 amino acids long) from a plasma α-2-globulin called

angiotensinogen Angiotensin is a peptide hormone that causes vasoconstriction and an increase in blood pressure. It is part of the renin–angiotensin system, which regulates blood pressure. Angiotensin also stimulates the release of aldosterone from the a ...

. This decapeptide is known as

angiotensin I Angiotensin is a peptide hormone that causes vasoconstriction and an increase in blood pressure. It is part of the renin–angiotensin system, which regulates blood pressure. Angiotensin also stimulates the release of aldosterone from the a ...

. It has no known biological activity. However, when the blood circulates through the lungs a pulmonary capillary

endothelial The endothelium is a single layer of squamous endothelial cells that line the interior surface of blood vessels and lymphatic vessels. The endothelium forms an interface between circulating blood or lymph in the lumen and the rest of the vessel ...

enzyme called angiotensin-converting enzyme (ACE) cleaves a further two amino acids from angiotensin I to form an octapeptide known as angiotensin II. Angiotensin II is a hormone which acts on the adrenal cortex, causing the release into the blood of the

steroid hormone A steroid hormone is a steroid that acts as a hormone. Steroid hormones can be grouped into two classes: corticosteroids (typically made in the adrenal cortex, hence ''cortico-'') and sex steroids (typically made in the gonads or placenta). Withi ...

, 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

. The angiotensin II-stimulated aldosterone released from the

zona glomerulosa The ''zona glomerulosa'' (sometimes, glomerular zone) of the adrenal gland is the most superficial layer of the adrenal cortex, lying directly beneath the renal capsule. Its cells are ovoid and arranged in clusters or arches (''glomus'' is Latin ...

of the

adrenal glands The adrenal glands (also known as suprarenal glands) are endocrine glands that produce a variety of hormones including adrenaline and the steroids aldosterone and cortisol. They are found above the kidneys. Each gland has an outer cortex whic ...

has an effect on particularly the epithelial cells of the

distal convoluted tubules The distal convoluted tubule (DCT) is a portion of kidney nephron between the loop of Henle and the collecting tubule. Physiology It is partly responsible for the regulation of potassium, sodium, calcium, and pH. On its apical surface (lumen ...

and collecting ducts of the kidneys. Here it causes the reabsorption of sodium ions from the renal tubular fluid, in exchange for potassium ions which are secreted from the blood plasma into the tubular fluid to exit the body via the urine. The reabsorption of sodium ions from the renal tubular fluid halts further sodium ion losses from the body, and therefore preventing the worsening of

hyponatremia Hyponatremia or hyponatraemia is a low concentration of sodium in the blood. It is generally defined as a sodium concentration of less than 135 mmol/L (135 mEq/L), with severe hyponatremia being below 120 mEq/L. Symptoms can be a ...

. 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 Hypernatremia, also spelled hypernatraemia, is a high concentration of sodium in the blood. Early symptoms may include a strong feeling of thirst, weakness, nausea, and loss of appetite. Severe symptoms include confusion, muscle twitching, and b ...

), 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 The distal convoluted tubule (DCT) is a portion of kidney nephron between the loop of Henle and the collecting tubule. Physiology It is partly responsible for the regulation of potassium, sodium, calcium, and pH. On its apical surface (lumen ...

s or

collecting duct The collecting duct system of the kidney consists of a series of tubules and ducts that physically connect nephrons to a minor calyx or directly to the renal pelvis. The collecting duct system is the last part of nephron and participates in elect ...

s. This is because sodium is reabsorbed in exchange for potassium and therefore causes only a modest change in the

osmotic gradient Osmosis (, ) is the spontaneous net movement or diffusion of solvent molecules through a selectively-permeable membrane from a region of high water potential (region of lower solute concentration) to a region of low water potential (region of ...

between the blood and the tubular fluid. Furthermore, the epithelium of the distal convoluted tubules and collecting ducts is impermeable to water in the absence of antidiuretic hormone (ADH) in the blood. ADH is part of the control of

. Its levels in the blood vary with the

of the plasma, which is measured in the

of the brain. Aldosterone's action on the kidney tubules prevents sodium loss to the

(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

High potassium concentrations in the plasma cause

depolarization In biology, depolarization or hypopolarization is a change within a cell, during which the cell undergoes a shift in electric charge distribution, resulting in less negative charge inside the cell compared to the outside. Depolarization is ess ...

of the

cells' membranes in the outer layer of the adrenal cortex. This causes the release of aldosterone into the blood. Aldosterone acts primarily on the

s and

s of the kidneys, stimulating the excretion of potassium ions into the urine. It does so, however, by activating the

basolateral The cell membrane (also known as the plasma membrane (PM) or cytoplasmic membrane, and historically referred to as the plasmalemma) is a biological membrane that separates and protects the interior of all cells from the outside environment (th ...

Na⁺/K⁺ pumps of the tubular epithelial cells. These sodium/potassium exchangers pump three sodium ions out of the cell, into the interstitial fluid and two potassium ions into the cell from the interstitial fluid. This creates an ionic concentration gradient which results in the reabsorption of sodium (Na⁺) ions from the tubular fluid into the blood, and secreting potassium (K⁺) ions from the blood into the urine (lumen of collecting duct).

Fluid balance

The total amount of water in the body needs to be kept in balance.

Fluid balance Fluid balance is an aspect of the homeostasis of organisms in which the amount of water in the organism needs to be controlled, via osmoregulation and behavior, such that the concentrations of electrolytes ( salts in solution) in the various b ...

involves keeping the fluid volume stabilized, and also keeping the levels of electrolytes in the extracellular fluid stable. Fluid balance is maintained by the process of

osmoregulation Osmoregulation is the active regulation of the osmotic pressure of an organism's body fluids, detected by osmoreceptors, to maintain the homeostasis of the organism's water content; that is, it maintains the fluid balance and the concentration o ...

and by behavior. Osmotic pressure is detected by

osmoreceptor An osmoreceptor is a sensory receptor primarily found in the hypothalamus of most homeothermic organisms that detects changes in osmotic pressure. Osmoreceptors can be found in several structures, including two of the circumventricular organs – ...

s in the median preoptic nucleus in the

. Measurement of the plasma

to give an indication of the water content of the body, relies on the fact that water losses from the body, (through unavoidable water loss through the skin which is not entirely waterproof and therefore always slightly moist, water vapor in the exhaled air, sweating,

vomiting Vomiting (also known as emesis and throwing up) is the involuntary, forceful expulsion of the contents of one's stomach through the mouth and sometimes the nose. Vomiting can be the result of ailments like food poisoning, gastroenteri ...

, normal feces and especially

diarrhea Diarrhea, also spelled diarrhoea, is the condition of having at least three loose, liquid, or watery bowel movements each day. It often lasts for a few days and can result in dehydration due to fluid loss. Signs of dehydration often begin w ...

) are all

hypotonic In chemical biology, tonicity is a measure of the effective osmotic pressure gradient; the water potential of two solutions separated by a partially-permeable cell membrane. Tonicity depends on the relative concentration of selective membrane-imp ...

, 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 In physiology, body water is the water content of an animal body that is contained in the tissues, the blood, the bones and elsewhere. The percentages of body water contained in various fluid compartments add up to total body water (TBW). This ...

therefore cause the extracellular fluid to become

hypertonic In chemical biology, tonicity is a measure of the effective osmotic pressure gradient; the water potential of two solutions separated by a partially-permeable cell membrane. Tonicity depends on the relative concentration of selective membrane- ...

. Conversely, excessive fluid intake dilutes the extracellular fluid causing the hypothalamus to register hypotonic hyponatremia conditions. When the

detects a hypertonic extracellular environment, it causes the secretion of an antidiuretic hormone (ADH) called

vasopressin Human vasopressin, also called antidiuretic hormone (ADH), arginine vasopressin (AVP) or argipressin, is a hormone synthesized from the AVP gene as a peptide prohormone in neurons in the hypothalamus, and is converted to AVP. It then trave ...

which acts on the effector organ, which in this case is the

. The effect of vasopressin on the kidney tubules is to reabsorb water from the

s and collecting ducts, thus preventing aggravation of the water loss via the urine. The hypothalamus simultaneously stimulates the nearby thirst center causing an almost irresistible (if the hypertonicity is severe enough) urge to drink water. The cessation of urine flow prevents the hypovolemia and

hypertonicity In chemical biology, tonicity is a measure of the effective osmotic pressure gradient; the water potential of two solutions separated by a partially-permeable cell membrane. Tonicity depends on the relative concentration of selective membrane- ...

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

The plasma pH can be altered by respiratory changes in the partial pressure of carbon dioxide; or altered by metabolic changes in the carbonic acid to bicarbonate ion ratio. The

bicarbonate buffer system The bicarbonate buffer system is an acid-base homeostatic mechanism involving the balance of carbonic acid (H2CO3), bicarbonate ion (HCO), and carbon dioxide (CO2) in order to maintain pH in the blood and duodenum, among other tissues, to sup ...

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 In chemistry and biochemistry, the Henderson–Hasselbalch equation :\ce = \ceK_\ce + \log_ \left( \frac \right) relates the pH of a chemical solution of a weak acid to the numerical value of the acid dissociation constant, ''K''a, of acid and th ...

). A change in the plasma pH gives an acid–base imbalance. In

acid–base homeostasis Acid–base homeostasis is the homeostatic regulation of the pH of the body's extracellular fluid (ECF). The proper balance between the acids and bases (i.e. the pH) in the ECF is crucial for the normal physiology of the body—and for cellu ...

there are two mechanisms that can help regulate the pH.

Respiratory compensation Respiratory compensation is the modulation by the brainstem respiratory centers, which involves altering alveolar ventilation to try and bring the plasma pH back to its normal value (7.4) in order to keep the acid-base balance in the body. It ...

a mechanism of the

, adjusts the partial pressure of carbon dioxide by changing the rate and depth of breathing, to bring the pH back to normal. The partial pressure of carbon dioxide also determines the concentration of carbonic acid, and the bicarbonate buffer system can also come into play. Renal compensation can help the bicarbonate buffer system. The sensor for the plasma bicarbonate concentration is not known for certain. It is very probable that the renal tubular cells of the distal convoluted tubules are themselves sensitive to the pH of the plasma. The metabolism of these cells produces carbon dioxide, which is rapidly converted to hydrogen and bicarbonate through the action of carbonic anhydrase. When the ECF pH falls (becoming more acidic) the renal tubular cells excrete hydrogen ions into the tubular fluid to leave the body via urine. Bicarbonate ions are simultaneously secreted into the blood that decreases the carbonic acid, and consequently raises the plasma pH. The converse happens when the plasma pH rises above normal: bicarbonate ions are excreted into the urine, and hydrogen ions released into the plasma. When hydrogen ions are excreted into the urine, and bicarbonate into the blood, the latter combines with the excess hydrogen ions in the plasma that stimulated the kidneys to perform this operation. The resulting reaction in the plasma is the formation of carbonic acid which is in equilibrium with the plasma partial pressure of carbon dioxide. This is tightly regulated to ensure that there is no excessive build-up of carbonic acid or bicarbonate. The overall effect is therefore that hydrogen ions are lost in the urine when the pH of the plasma falls. The concomitant rise in the plasma bicarbonate mops up the increased hydrogen ions (caused by the fall in plasma pH) and the resulting excess carbonic acid is disposed of in the lungs as carbon dioxide. This restores the normal ratio between bicarbonate and the partial pressure of carbon dioxide and therefore the plasma pH. The converse happens when a high plasma pH stimulates the kidneys to secrete hydrogen ions into the blood and to excrete bicarbonate into the urine. The hydrogen ions combine with the excess bicarbonate ions in the plasma, once again forming an excess of carbonic acid which can be exhaled, as carbon dioxide, in the lungs, keeping the plasma bicarbonate ion concentration, the partial pressure of carbon dioxide and, therefore, the plasma pH, constant.

Cerebrospinal fluid

Cerebrospinal fluid (CSF) allows for regulation of the distribution of substances between cells of the brain, and

neuroendocrine Neuroendocrine cells are cells that receive neuronal input (through neurotransmitters released by nerve cells or neurosecretory cells) and, as a consequence of this input, release messenger molecules (hormones) into the blood. In this way they bri ...

factors, to which slight changes can cause problems or damage to the nervous system. For example, high

glycine Glycine (symbol Gly or G; ) is an amino acid that has a single hydrogen atom as its side chain. It is the simplest stable amino acid ( carbamic acid is unstable), with the chemical formula NH2‐ CH2‐ COOH. Glycine is one of the proteinog ...

concentration In chemistry, concentration is the abundance of a constituent divided by the total volume of a mixture. Several types of mathematical description can be distinguished: '' mass concentration'', ''molar concentration'', '' number concentration'', ...

disrupts

and blood pressure control, and high CSF pH causes

dizziness Dizziness is an imprecise term that can refer to a sense of disorientation in space, vertigo, or lightheadedness. It can also refer to disequilibrium or a non-specific feeling, such as giddiness or foolishness. Dizziness is a common medical c ...

and syncope.

Neurotransmission

Inhibitory neurons in the

central nervous system The central nervous system (CNS) is the part of the nervous system consisting primarily of the brain and spinal cord. The CNS is so named because the brain integrates the received information and coordinates and influences the activity of all p ...

play a homeostatic role in the balance of neuronal activity between excitation and inhibition. Inhibitory neurons using GABA, make compensating changes in the neuronal networks preventing runaway levels of excitation. An imbalance between excitation and inhibition is seen to be implicated in a number of

neuropsychiatric disorders A mental disorder, also referred to as a mental illness or psychiatric disorder, is a behavioral or mental pattern that causes significant distress or impairment of personal functioning. Such features may be persistent, relapsing and remitti ...

Neuroendocrine system

The

neuroendocrine system Neuroendocrinology is the branch of biology (specifically of physiology) which studies the interaction between the nervous system and the endocrine system; i.e. how the brain regulates the hormonal activity in the body. The nervous and endocrine ...

is the mechanism by which the hypothalamus maintains homeostasis, regulating

metabolism Metabolism (, from el, μεταβολή ''metabolē'', "change") is the set of life-sustaining chemical reactions in organisms. The three main functions of metabolism are: the conversion of the energy in food to energy available to run c ...

, reproduction, eating and drinking behaviour, energy utilization, osmolarity and blood pressure. The regulation of metabolism, is carried out by hypothalamic interconnections to other glands. Three

endocrine gland Endocrine glands are ductless glands of the endocrine system that secrete their products, hormones, directly into the blood. The major glands of the endocrine system include the pineal gland, pituitary gland, pancreas, ovaries, testes, ...

s of the

hypothalamic–pituitary–gonadal axis The hypothalamic–pituitary–gonadal axis (HPG axis, also known as the hypothalamic–pituitary–ovarian/testicular axis) refers to the hypothalamus, pituitary gland, and gonadal glands as if these individual endocrine glands were a single en ...

(HPG axis) often work together and have important regulatory functions. Two other regulatory endocrine axes are the

hypothalamic–pituitary–adrenal axis The hypothalamic–pituitary–adrenal axis (HPA axis or HTPA axis) is a complex set of direct influences and feedback interactions among three components: the hypothalamus (a part of the brain located below the thalamus), the pituitary gland (a ...

(HPA axis) and the

hypothalamic–pituitary–thyroid axis The hypothalamic–pituitary–thyroid axis (HPT axis for short, a.k.a. thyroid homeostasis or thyrotropic feedback control) is part of the neuroendocrine system responsible for the regulation of metabolism and also responds to stress. As its na ...

(HPT axis). The

also has many regulatory functions of the metabolism. An important function is the production and control of bile acids. Too much bile acid can be toxic to cells and its synthesis can be inhibited by activation of FXR a nuclear receptor.

Gene regulation

At the cellular level, homeostasis is carried out by several mechanisms including

transcriptional regulation In molecular biology and genetics, transcriptional regulation is the means by which a cell regulates the conversion of DNA to RNA (transcription), thereby orchestrating gene activity. A single gene can be regulated in a range of ways, from al ...

that can alter the activity of genes in response to changes.

Energy balance

The amount of energy taken in through

nutrition Nutrition is the biochemical and physiological process by which an organism uses food to support its life. It provides organisms with nutrients, which can be metabolized to create energy and chemical structures. Failure to obtain sufficient ...

needs to match the amount of energy used. To achieve energy homeostasis appetite is regulated by two hormones, grehlin and leptin. Grehlin stimulates hunger and the intake of food and leptin acts to signal satiety (fullness). A 2019 review of weight-change interventions, including dieting, exercise and overeating, found that body weight homeostasis could not precisely correct for "energetic errors", the loss or gain of calories, in the short-term.

Clinical significance

Many diseases are the result of a homeostatic failure. Almost any homeostatic component can malfunction either as a result of an inherited defect, an

inborn error of metabolism Inborn errors of metabolism form a large class of genetic diseases involving congenital disorders of enzyme activities. The majority are due to defects of single genes that code for enzymes that facilitate conversion of various substances ( substr ...

, or an acquired disease. Some homeostatic mechanisms have inbuilt redundancies, which ensures that life is not immediately threatened if a component malfunctions; but sometimes a homeostatic malfunction can result in serious disease, which can be fatal if not treated. A well-known example of a homeostatic failure is shown in

type 1 diabetes mellitus Type 1 diabetes (T1D), formerly known as juvenile diabetes, is an autoimmune disease that originates when cells that make insulin (beta cells) are destroyed by the immune system. Insulin is a hormone required for the cells to use blood sugar f ...

. Here blood sugar regulation is unable to function because the

of the

are destroyed and cannot produce the necessary insulin. The blood sugar rises in a condition known as hyperglycemia. The plasma ionized calcium homeostat can be disrupted by the constant, unchanging, over-production of

by a parathyroid adenoma resulting in the typically features of

hyperparathyroidism Hyperparathyroidism is an increase in parathyroid hormone (PTH) levels in the blood. This occurs from a disorder either within the parathyroid glands (primary hyperparathyroidism) or as response to external stimuli (secondary hyperparathyroidism). ...

, namely high plasma ionized Ca²⁺ levels and the resorption of bone, which can lead to spontaneous fractures. The abnormally high plasma ionized calcium concentrations cause conformational changes in many cell-surface proteins (especially ion channels and hormone or neurotransmitter receptors) giving rise to lethargy, muscle weakness, anorexia, constipation and labile emotions. The body water homeostat can be compromised by the inability to secrete ADH in response to even the normal daily water losses via the exhaled air, the feces, and insensible sweating. On receiving a zero blood ADH signal, the kidneys produce huge unchanging volumes of very dilute urine, causing dehydration and death if not treated. As organisms age, the efficiency of their control systems becomes reduced. The inefficiencies gradually result in an unstable internal environment that increases the risk of illness, and leads to the physical changes associated with aging. Various chronic diseases are kept under control by homeostatic compensation, which masks a problem by compensating for it (making up for it) in another way. However, the compensating mechanisms eventually wear out or are disrupted by a new complicating factor (such as the advent of a concurrent acute viral infection), which sends the body reeling through a new cascade of events. Such decompensation unmasks the underlying disease, worsening its symptoms. Common examples include decompensated heart failure,

kidney failure Kidney failure, also known as end-stage kidney disease, is a medical condition in which the kidneys can no longer adequately filter waste products from the blood, functioning at less than 15% of normal levels. Kidney failure is classified as eit ...

, and liver failure.

Biosphere

In the Gaia hypothesis, James Lovelock stated that the entire mass of living matter on Earth (or any planet with life) functions as a vast homeostatic

superorganism A superorganism or supraorganism is a group of synergetically interacting organisms of the same species. A community of synergetically interacting organisms of different species is called a holobiont. Concept The term superorganism is used m ...

that actively modifies its planetary environment to produce the environmental conditions necessary for its own survival. In this view, the entire planet maintains several homeostasis (the primary one being temperature homeostasis). Whether this sort of system is present on Earth is open to debate. However, some relatively simple homeostatic mechanisms are generally accepted. For example, it is sometimes claimed that when atmospheric carbon dioxide levels rise, certain plants may be able to grow better and thus act to remove more carbon dioxide from the atmosphere. However, warming has exacerbated droughts, making water the actual

limiting factor A limiting factor is a variable of a system that causes a noticeable change in output or another measure of a type of system. The limiting factor is in a pyramid shape of organisms going up from the producers to consumers and so on. A factor not l ...

on land. When sunlight is plentiful and the atmospheric temperature climbs, it has been claimed that the phytoplankton of the ocean surface waters, acting as global sunshine, and therefore heat sensors, may thrive and produce more dimethyl sulfide (DMS). The DMS molecules act as cloud condensation nuclei, which produce more clouds, and thus increase the atmospheric

albedo Albedo (; ) is the measure of the diffuse reflection of solar radiation out of the total solar radiation and measured on a scale from 0, corresponding to a black body that absorbs all incident radiation, to 1, corresponding to a body that refl ...

, and this feeds back to lower the temperature of the atmosphere. However, rising sea temperature has stratified the oceans, separating warm, sunlit waters from cool, nutrient-rich waters. Thus, nutrients have become the limiting factor, and plankton levels have actually fallen over the past 50 years, not risen. As scientists discover more about Earth, vast numbers of positive and negative feedback loops are being discovered, that, together, maintain a metastable condition, sometimes within a very broad range of environmental conditions.

Predictive

Predictive homeostasis is an anticipatory response to an expected challenge in the future, such as the stimulation of insulin secretion by gut hormones which enter the blood in response to a meal. This insulin secretion occurs before the blood sugar level rises, lowering the blood sugar level in anticipation of a large influx into the blood of glucose resulting from the digestion of carbohydrates in the gut. Such anticipatory reactions are open loop systems which are based, essentially, on "guess work", and are not self-correcting. Anticipatory responses always require a closed loop negative feedback system to correct the 'over-shoots' and 'under-shoots' to which the anticipatory systems are prone.

Other fields

The term has come to be used in other fields, for example:

Risk

An actuary may refer to ''risk homeostasis'', where (for example) people who have anti-lock brakes have no better safety record than those without anti-lock brakes, because the former unconsciously compensate for the safer vehicle via less-safe driving habits. Previous to the innovation of anti-lock brakes, certain maneuvers involved minor skids, evoking fear and avoidance: Now the anti-lock system moves the boundary for such feedback, and behavior patterns expand into the no-longer punitive area. It has also been suggested that ecological crises are an instance of risk homeostasis in which a particular behavior continues until proven dangerous or dramatic consequences actually occur.

Stress

Sociologists and psychologists may refer to ''stress homeostasis'', the tendency of a population or an individual to stay at a certain level of

stress Stress may refer to: Science and medicine * Stress (biology), an organism's response to a stressor such as an environmental condition * Stress (linguistics), relative emphasis or prominence given to a syllable in a word, or to a word in a phrase ...

, often generating artificial stresses if the "natural" level of stress is not enough.

Jean-François Lyotard Jean-François Lyotard (; ; ; 10 August 1924 – 21 April 1998) was a French philosopher, sociologist, and literary theorist. His interdisciplinary discourse spans such topics as epistemology and communication, the human body, modern art and ...

, a postmodern theorist, has applied this term to societal 'power centers' that he describes in ''

The Postmodern Condition ''The Postmodern Condition: A Report on Knowledge'' (french: La condition postmoderne: rapport sur le savoir) is a 1979 book by the philosopher Jean-François Lyotard, in which the author analyzes the notion of knowledge in postmodern society as ...

'', as being 'governed by a principle of homeostasis,' for example, the scientific hierarchy, which will sometimes ignore a radical new discovery for years because it destabilizes previously accepted norms.

Technology

Familiar technological homeostatic mechanisms include: * A thermostat operates by switching heaters or air-conditioners on and off in response to the output of a temperature sensor. *

Cruise control Cruise control (also known as speed control, cruise command, autocruise, or tempomat) is a system that automatically controls the speed of a motor vehicle. The system is a servomechanism that takes over the throttle of the car to maintain a s ...

adjusts a car's throttle in response to changes in speed. * An

autopilot An autopilot is a system used to control the path of an aircraft, marine craft or spacecraft without requiring constant manual control by a human operator. Autopilots do not replace human operators. Instead, the autopilot assists the operator' ...

operates the steering controls of an aircraft or ship in response to deviation from a pre-set compass bearing or route. * Process control systems in a chemical plant or

oil refinery An oil refinery or petroleum refinery is an industrial process plant where petroleum (crude oil) is transformed and refined into useful products such as gasoline (petrol), diesel fuel, asphalt base, fuel oils, heating oil, kerosene, lique ...

maintain fluid levels, pressures, temperature, chemical composition, etc. by controlling heaters, pumps and valves. * The

centrifugal governor A centrifugal governor is a specific type of governor with a feedback system that controls the speed of an engine by regulating the flow of fuel or working fluid, so as to maintain a near-constant speed. It uses the principle of proportional con ...

of a steam engine, as designed by James Watt in 1788, reduces the throttle valve in response to increases in the engine speed, or opens the valve if the speed falls below the pre-set rate.

Society and Culture

The use of sovereign power, codes of conduct, religious and cultural practices and other dynamic processes in a society can be described as a part of an evolved homeostatic system of regularizing life and maintaining an overall equilibrium that protects the security of the whole from internal and external imbalances or dangers. Healthy civic cultures can be said to have achieved an optimal homeostatic balance between multiple contradictory concerns such as in the tension between respect for individual rights and concern for the public good, or that between governmental effectiveness and responsiveness to the interests of citizens.

References

External links

Homeostasis
* Walter Bradford Cannon

(1932) {{Authority control Physiology Biology terminology Cybernetics

Etymology

History

Overview

Controls of variables

Core temperature

Blood glucose

Iron levels

Copper regulation

Levels of blood gases

Blood oxygen content

Arterial blood pressure

Calcium levels

Sodium concentration

Potassium concentration

Fluid balance

Blood pH

Cerebrospinal fluid

Neurotransmission

Neuroendocrine system

Gene regulation

Energy balance

Clinical significance

Biosphere

Predictive

Other fields

Risk

Stress

Technology

Society and Culture

See also

References

Further reading

External links