Human homeostasis
Encyclopedia
Human homeostasis is derived from the Greek, homeo or "same", and stasis or "stable" and means remaining stable or remaining the same.

The human body manages a multitude of highly complex interactions to maintain balance or return systems to functioning within a normal range. These interactions within the body facilitate compensatory changes supportive of physical and psychological functioning. This process is essential to the survival of the person and to our species. The liver
Liver
The liver is a vital organ present in vertebrates and some other animals. It has a wide range of functions, including detoxification, protein synthesis, and production of biochemicals necessary for digestion...

, the kidneys, and the brain (hypothalamus
Hypothalamus
The Hypothalamus is a portion of the brain that contains a number of small nuclei with a variety of functions...

, the autonomic nervous system
Autonomic nervous system
The autonomic nervous system is the part of the peripheral nervous system that acts as a control system functioning largely below the level of consciousness, and controls visceral functions. The ANS affects heart rate, digestion, respiration rate, salivation, perspiration, diameter of the pupils,...

 and the endocrine system
Endocrine system
In physiology, the endocrine system is a system of glands, each of which secretes a type of hormone directly into the bloodstream to regulate the body. The endocrine system is in contrast to the exocrine system, which secretes its chemicals using ducts. It derives from the Greek words "endo"...

) help maintain homeostasis. The liver is responsible for metabolizing toxic substances
Drug metabolism
Drug metabolism is the biochemical modification of pharmaceutical substances by living organisms, usually through specialized enzymatic systems. This is a form of xenobiotic metabolism. Drug metabolism often converts lipophilic chemical compounds into more readily excreted polar products...

 and maintaining carbohydrate metabolism
Carbohydrate metabolism
Carbohydrate metabolism denotes the various biochemical processes responsible for the formation, breakdown and interconversion of carbohydrates in living organisms....

. The kidneys are responsible for regulating blood water levels, re-absorption of substances into the blood, maintenance of salt and ion levels in the blood, regulation of blood pH
Acid-base imbalance
Acid–base imbalance is an abnormality of the human body's normal balance of acids and bases that causes the plasma pH to deviate out of the normal range . In the fetus, the normal range differs based on which umbilical vessel is sampled...

, and excretion of urea
Urea
Urea or carbamide is an organic compound with the chemical formula CO2. The molecule has two —NH2 groups joined by a carbonyl functional group....

 and other wastes.

An inability to maintain homeostasis may lead to death or a disease, a condition known as homeostatic imbalance. For instance, heart failure may occur when negative feedback mechanisms become overwhelmed and destructive positive feedback mechanisms take over. Other diseases which result from a homeostatic imbalance include diabetes, dehydration
Dehydration
In physiology and medicine, dehydration is defined as the excessive loss of body fluid. It is literally the removal of water from an object; however, in physiological terms, it entails a deficiency of fluid within an organism...

, hypoglycemia
Hypoglycemia
Hypoglycemia or hypoglycæmia is the medical term for a state produced by a lower than normal level of blood glucose. The term literally means "under-sweet blood"...

, hyperglycemia
Hyperglycemia
Hyperglycemia or Hyperglycæmia, or high blood sugar, is a condition in which an excessive amount of glucose circulates in the blood plasma. This is generally a glucose level higher than 13.5mmol/l , but symptoms may not start to become noticeable until even higher values such as 15-20 mmol/l...

, gout
Gout
Gout is a medical condition usually characterized by recurrent attacks of acute inflammatory arthritis—a red, tender, hot, swollen joint. The metatarsal-phalangeal joint at the base of the big toe is the most commonly affected . However, it may also present as tophi, kidney stones, or urate...

 and any disease caused by the presence of a toxin
Toxicology
Toxicology is a branch of biology, chemistry, and medicine concerned with the study of the adverse effects of chemicals on living organisms...

 in the bloodstream. Medical intervention can help restore homeostasis and possibly prevent permanent damage to the organs.

Temperature

Humans are warm-blooded
Warm-blooded
The term warm-blooded is a colloquial term to describe animal species which have a relatively higher blood temperature, and maintain thermal homeostasis primarily through internal metabolic processes...

, maintaining a near-constant body temperature. Thermoregulation is an important aspect of human homeostasis
Homeostasis
Homeostasis is the property of a system that regulates its internal environment and tends to maintain a stable, constant condition of properties like temperature or pH...

. Heat is mainly produced by the liver and muscle contractions. Humans have been able to adapt to a great diversity of climates, including hot humid and hot arid. High temperatures pose serious stresses for the human body, placing it in great danger of injury or even death. In order to deal with these climatic conditions, humans have developed physiologic and cultural modes of adaptation.

Temperature may enter a circle of positive feedback
Positive feedback
Positive feedback is a process in which the effects of a small disturbance on a system include an increase in the magnitude of the perturbation. That is, A produces more of B which in turn produces more of A. In contrast, a system that responds to a perturbation in a way that reduces its effect is...

, when temperature reaches extremes of 45°C (113°F), at which cellular proteins denature, causing the active site in proteins to change, thus causing metabolism stop and ultimately death.

Iron

Iron
Iron
Iron is a chemical element with the symbol Fe and atomic number 26. It is a metal in the first transition series. It is the most common element forming the planet Earth as a whole, forming much of Earth's outer and inner core. It is the fourth most common element in the Earth's crust...

 is an essential element for human beings. The control of this necessary but potentially toxic substance is an important part of many aspects of human health
Health
Health is the level of functional or metabolic efficiency of a living being. In humans, it is the general condition of a person's mind, body and spirit, usually meaning to be free from illness, injury or pain...

 and disease
Disease
A disease is an abnormal condition affecting the body of an organism. It is often construed to be a medical condition associated with specific symptoms and signs. It may be caused by external factors, such as infectious disease, or it may be caused by internal dysfunctions, such as autoimmune...

. Hematologists have been especially interested in the system of iron metabolism
Metabolism
Metabolism is the set of chemical reactions that happen in the cells of living organisms to sustain life. These processes allow organisms to grow and reproduce, maintain their structures, and respond to their environments. Metabolism is usually divided into two categories...

 because iron is essential to red blood cells. In fact, most of the human body
Human body
The human body is the entire structure of a human organism, and consists of a head, neck, torso, two arms and two legs.By the time the human reaches adulthood, the body consists of close to 100 trillion cells, the basic unit of life...

's iron is contained in red blood cells' hemoglobin
Hemoglobin
Hemoglobin is the iron-containing oxygen-transport metalloprotein in the red blood cells of all vertebrates, with the exception of the fish family Channichthyidae, as well as the tissues of some invertebrates...

, and iron deficiency is the most common cause of anemia
Anemia
Anemia is a decrease in number of red blood cells or less than the normal quantity of hemoglobin in the blood. However, it can include decreased oxygen-binding ability of each hemoglobin molecule due to deformity or lack in numerical development as in some other types of hemoglobin...

.

When body levels of iron are too low, then hepcidin
Hepcidin
Hepcidin is a peptide hormone produced by the liver. It was discovered in 2000, and appears to be the master regulator of iron homeostasis in humans and other mammals. In humans, HAMP is the gene that encodes for hepcidin.-Structure:...

 in the duodenal
Duodenum
The duodenum is the first section of the small intestine in most higher vertebrates, including mammals, reptiles, and birds. In fish, the divisions of the small intestine are not as clear and the terms anterior intestine or proximal intestine may be used instead of duodenum...

 epithelium is decreased. This causes an increase in ferroportin
Ferroportin
Ferroportin is a transmembrane protein that transports iron from the inside of a cell to the outside of it. It is found on the surface of cells that store or transport iron, including:*Enterocytes in the duodenum*Hepatocytes...

 activity, stimulating iron uptake in the digestive system. An iron surplus will stimulate the reverse of this process.

In individual cells, an iron deficiency causes responsive element binding protein (IRE-BP) to bind to iron responsive elements (IRE) on mRNAs for transferrin receptors, resulting in increased production of transferrin receptors. These receptors increase binding of transferrin
Transferrin
Transferrins are iron-binding blood plasma glycoproteins that control the level of free iron in biological fluids. In humans, it is encoded by the TF gene.Transferrin is a glycoprotein that binds iron very tightly but reversibly...

 to cells, and therefore stimulating iron uptake.

Energy

Energy balance
Energy balance (biology)
In biology, energy balance is the biological homeostasis of energy in living systems. It is measured with the following equation: Energy intake = internal heat produced + external work + storage. It is also an aspect of bioenergetics, concerning energy flow through living systems.It generally uses...

 is the homeostasis of energy
Energy
In physics, energy is an indirectly observed quantity. It is often understood as the ability a physical system has to do work on other physical systems...

 in living systems. It is measured with the following equation:
Energy intake = internal heat produced + external work + storage.

When calculating energy balances in the body, energy is often measured in calories, with the definitions of a calorie falling into two classes:
  • The small calorie or gram calorie (symbol: cal) approximates the energy needed to increase the temperature of 1 gram of water
    Water
    Water is a chemical substance with the chemical formula H2O. A water molecule contains one oxygen and two hydrogen atoms connected by covalent bonds. Water is a liquid at ambient conditions, but it often co-exists on Earth with its solid state, ice, and gaseous state . Water also exists in a...

     by 1 °C. This is about 4.2 joules.
  • The large calorie, kilogram calorie, dietary calorie or food calorie (symbol: Cal) approximates the energy needed to increase the temperature of 1 kilogram of water by 1 °C. This is exactly 1,000 small calories or about 4.2 kilojoules.

Blood composition

The balance of many blood solutes belongs to the scope of renal physiology
Renal physiology
Renal physiology is the study of the physiology of the kidney. This encompasses all functions of the kidney, including reabsorption of glucose, amino acids, and other small molecules; regulation of sodium, potassium, and other electrolytes; regulation of fluid balance and blood pressure;...

.

Sugar

Blood glucose is regulated with two hormones, insulin
Insulin
Insulin is a hormone central to regulating carbohydrate and fat metabolism in the body. Insulin causes cells in the liver, muscle, and fat tissue to take up glucose from the blood, storing it as glycogen in the liver and muscle....

 and glucagon
Glucagon
Glucagon, a hormone secreted by the pancreas, raises blood glucose levels. Its effect is opposite that of insulin, which lowers blood glucose levels. The pancreas releases glucagon when blood sugar levels fall too low. Glucagon causes the liver to convert stored glycogen into glucose, which is...

, both released from the pancreas
Pancreas
The pancreas is a gland organ in the digestive and endocrine system of vertebrates. It is both an endocrine gland producing several important hormones, including insulin, glucagon, and somatostatin, as well as a digestive organ, secreting pancreatic juice containing digestive enzymes that assist...

.

When blood sugar levels become too high, insulin is released from the pancreas. Conversely, when blood sugar levels become too low, glucagon is released. It promotes the release of glycogen, converted back into glucose. This increases blood sugar levels.

If the pancreas is for any reason unable to produce enough of these two hormones, diabetes results.

Osmoregulation

Osmoregulation is the active regulation of the osmotic pressure
Osmotic pressure
Osmotic pressure is the pressure which needs to be applied to a solution to prevent the inward flow of water across a semipermeable membrane....

 of bodily fluids to maintain the homeostasis of the body's water
Water
Water is a chemical substance with the chemical formula H2O. A water molecule contains one oxygen and two hydrogen atoms connected by covalent bonds. Water is a liquid at ambient conditions, but it often co-exists on Earth with its solid state, ice, and gaseous state . Water also exists in a...

 content; that is it keeps the body's fluids from becoming too dilute or too concentrated. Osmotic pressure is a measure of the tendency of water to move into one solution
Solution
In chemistry, a solution is a homogeneous mixture composed of only one phase. In such a mixture, a solute is dissolved in another substance, known as a solvent. The solvent does the dissolving.- Types of solutions :...

 from another by osmosis
Osmosis
Osmosis is the movement of solvent molecules through a selectively permeable membrane into a region of higher solute concentration, aiming to equalize the solute concentrations on the two sides...

. The higher the osmotic pressure of a solution the more water wants to go into the solution.

The kidneys are used to remove excess ions from the blood, thus affecting the osmotic pressure. These are then expelled as urine
Urine
Urine is a typically sterile liquid by-product of the body that is secreted by the kidneys through a process called urination and excreted through the urethra. Cellular metabolism generates numerous by-products, many rich in nitrogen, that require elimination from the bloodstream...

.

Pressure

The renin-angiotensin system (RAS) is a hormone system that helps regulate long-term blood pressure
Blood pressure
Blood pressure is the pressure exerted by circulating blood upon the walls of blood vessels, and is one of the principal vital signs. When used without further specification, "blood pressure" usually refers to the arterial pressure of the systemic circulation. During each heartbeat, BP varies...

 and extracellular volume
Extracellular fluid
Extracellular fluid usually denotes all body fluid outside of cells. The remainder is called intracellular fluid.In some animals, including mammals, the extracellular fluid can be divided into two major subcompartments, interstitial fluid and blood plasma...

 in the body.

Calcium

When blood calcium
Calcium
Calcium is the chemical element with the symbol Ca and atomic number 20. It has an atomic mass of 40.078 amu. Calcium is a soft gray alkaline earth metal, and is the fifth-most-abundant element by mass in the Earth's crust...

 becomes too low, calcium-sensing receptors in the parathyroid gland
Parathyroid gland
The parathyroid glands are small endocrine glands in the neck that produce parathyroid hormone. Humans usually have four parathyroid glands, which are usually located on the rear surface of the thyroid gland, or, in rare cases, within the thyroid gland itself or in the chest...

 become activated. This results in the release of PTH
Parathyroid hormone
Parathyroid hormone , parathormone or parathyrin, is secreted by the chief cells of the parathyroid glands as a polypeptide containing 84 amino acids...

, which acts to increase blood calcium, e.g. by release from bone
Bone
Bones are rigid organs that constitute part of the endoskeleton of vertebrates. They support, and protect the various organs of the body, produce red and white blood cells and store minerals. Bone tissue is a type of dense connective tissue...

s (increasing the activity of bone-degrading cells called osteoclasts). This hormone also causes calcium to be reabsorbed from urine and the GI tract.

Calcitonin
Calcitonin
Calcitonin is a 32-amino acid linear polypeptide hormone that is producedin humans primarily by the parafollicular cells of the thyroid, and in many other animals in the ultimobranchial body. It acts to reduce blood calcium , opposing the effects of parathyroid hormone . Calcitonin has been found...

, released from the C cells in the thyroid gland, works the opposite way, decreasing calcium levels in the blood by causing more calcium to be fixed in bone.

Acid-base

The kidneys maintain acid-base homeostasis by regulating the pH of the blood plasma
Blood plasma
Blood plasma is the straw-colored liquid component of blood in which the blood cells in whole blood are normally suspended. It makes up about 55% of the total blood volume. It is the intravascular fluid part of extracellular fluid...

. Gains and losses of acid and base must be balanced. The study of the acid-base reactions in the body is acid base physiology.

Volume

The body's homeostatic control mechanisms, which maintain a constant internal environment, ensure that a balance between fluid gain and fluid loss is maintained. The hormones ADH (Anti-diuretic Hormone, also known as vasopressin) and Aldosterone
Aldosterone
Aldosterone is a hormone that increases the reabsorption of sodium ions and water and the release of potassium in the collecting ducts and distal convoluted tubule of the kidneys' functional unit, the nephron. This increases blood volume and, therefore, increases blood pressure. Drugs that...

 play a major role in this.
  • If the body is becoming fluid-deficient, there will be an increase in the secretion of these hormones (ADH), causing fluid to be retained by the kidneys and urine output to be reduced.
  • Conversely, if fluid levels are excessive, secretion of these hormones (aldosterone) is suppressed, resulting in less retention of fluid by the kidneys and a subsequent increase in the volume of urine produced.
  • If there is too much Carbon dioxide(CO2) in the blood, it can cause the blood to become acidic. People respirate heavily not due to low oxygen(O2) content in the blood, but because they have too much CO2.

Hemostasis

Hemostasis is the process whereby bleeding is halted. A major part of this is coagulation
Coagulation
Coagulation is a complex process by which blood forms clots. It is an important part of hemostasis, the cessation of blood loss from a damaged vessel, wherein a damaged blood vessel wall is covered by a platelet and fibrin-containing clot to stop bleeding and begin repair of the damaged vessel...

.

Platelet
Platelet
Platelets, or thrombocytes , are small,irregularly shaped clear cell fragments , 2–3 µm in diameter, which are derived from fragmentation of precursor megakaryocytes.  The average lifespan of a platelet is normally just 5 to 9 days...

 accumulation causes blood clotting in response to a break or tear in the lining of blood vessels. Unlike the majority of control mechanisms in human body, the hemostasis utilizes positive feedback, for the more the clot grows, the more clotting occurs, until the blood stops. Another example of positive feedback is the release of oxytocin
Oxytocin
Oxytocin is a mammalian hormone that acts primarily as a neuromodulator in the brain.Oxytocin is best known for its roles in sexual reproduction, in particular during and after childbirth...

 to intensify the contractions that take place during childbirth.

Sleep

Sleep timing depends upon a balance between homeostatic sleep propensity, the need for sleep as a function of the amount of time elapsed since the last adequate sleep episode, and circadian rhythm
Circadian rhythm
A circadian rhythm, popularly referred to as body clock, is an endogenously driven , roughly 24-hour cycle in biochemical, physiological, or behavioural processes. Circadian rhythms have been widely observed in plants, animals, fungi and cyanobacteria...

s which determine the ideal timing of a correctly structured and restorative sleep episode.

Extracellular fluid


The kidneys, by regulating the blood composition, also controls the extracellular fluid homeostasis.

History of discovery

The conceptual origins of homeostasis
Homeostasis
Homeostasis is the property of a system that regulates its internal environment and tends to maintain a stable, constant condition of properties like temperature or pH...

 reach back to Greek concepts such as balance, harmony, equilibrium, and steady-state; all believed to be fundamental attributes of life and health. The Greek philosopher Heraclitus (540--480 BC) was the first to hypothesize that a static, unchanged state was not the natural human condition, and the ability to undergo constant change was intrinsic to all things. Thereafter, the philosopher Empedocles (495-435 BC) postulated the corollary that all matter consisted of elements and qualities that were in dynamic opposition or alliance to one another, and that balance or harmony was a necessary condition for the survival living organisms. Following these hypotheses, Hippocrates (460-375 BC) compared health to the harmonious balance of the elements, and illness and disease to the systematic disharmony of these elements.

Nearly 150 years ago, Claude Bernard published his seminal work, stating that the maintenance of the internal environment, the inner environment
Milieu interieur
Milieu intérieur or interior milieu, from the French, milieu intérieur, is a term coined by Claude Bernard to refer to the extra-cellular fluid environment, and its physiological capacity to ensure protective stability for the tissues and organs of multicellular living organisms.-Origin:Claude...

, surrounding the body's cells, was essential for the life of the organism. In 1929, Walter B. Cannon published an extrapolation from Bernard's 1865 work naming his theory "homeostasis". Cannon postulated that homeostasis was a process of synchronized adjustments in the internal environment resulting in the maintenance of specific physiological variables within defined parameters; and that these precise parameters included blood pressure, temperature, pH, and others; all with clearly defined "normal" ranges or steady-states. Cannon further posited that threats to homeostasis might originate from the external environment (e.g., tempurature extremes, traumatic injury) or the internal environment (e.g., pain, infection), and could be physical or psychological, as in emotional distress. Cannon's work outlined that maintenance of this internal physical and psychological balance, homeostasis, demands an internal network of communication, with sensors capable of identifying deviations from the acceptable ranges and effectors to return those deviations back within acceptable limits. Cannon identified these negative feedback systems and emphasized that, regardless of the nature of the danger to the maintenance of homeostasis, the response he mapped within the body would be the same.
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