Core temperature Mammals regulate their
core temperature using input from
thermoreceptors in the
hypothalamus, brain, When the core temperature falls, the blood supply to the skin is reduced by intense
vasoconstriction. This acts as a
counter-current exchange system that short-circuits the warmth from the arterial blood directly into the venous blood returning into the trunk, causing minimal heat loss from the extremities in cold weather. The subcutaneous limb veins are tightly constricted, followed by
shivering thermogenesis if the earlier reactions are insufficient to correct the
hypothermia. When core temperature rises are detected by
thermoreceptors, the
sweat glands in the skin are stimulated via
cholinergic sympathetic nerves to secrete
sweat onto the skin, which, when it evaporates, cools the skin and the blood flowing through it. Panting is an alternative effector in many vertebrates, which cools the body also by the evaporation of water, but this time from the
mucous membranes of the throat and mouth.
Blood glucose at work in the regulation of blood sugar. Flat line is the set-point of glucose level and sine wave the fluctuations of glucose.
Blood sugar levels are
regulated within fairly narrow limits. In mammals, the primary sensors for this are the
beta cells of the
pancreatic islets. The beta cells respond to a rise in the blood sugar level by secreting
insulin into the blood and simultaneously inhibiting their neighboring
alpha cells from secreting
glucagon into the blood. 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). The glycogen stored in muscles remains in the muscles, and is only broken down, during exercise, to
glucose-6-phosphate and thence to
pyruvate to be fed into the
citric acid cycle 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 Iron homeostasis is a crucial physiological process that regulates iron levels in the body, ensuring that this essential nutrient is available for vital functions while preventing potential toxicity from excess iron. The primary site for iron absorption is the
duodenum, where dietary iron exists in two forms: heme iron, sourced from animal products, and
non-heme iron, found in plant foods. Heme iron is more efficiently absorbed than non-heme iron, which requires factors like
vitamin C for optimal uptake. Once absorbed, iron enters the bloodstream bound to
transferrin, a transport protein that delivers it to various tissues and organs. Cells uptake iron through transferrin receptors, making it available for critical processes such as oxygen transport and DNA synthesis. Excess iron is stored in the liver, spleen, and bone marrow as
ferritin and hemosiderin. The regulation of iron levels is primarily controlled by the hormone
hepcidin, produced by the liver, which adjusts intestinal absorption and the release of stored iron based on the body's needs. Disruptions in iron homeostasis can lead to conditions such as iron deficiency
anemia or iron overload disorders like
hemochromatosis, highlighting the importance of maintaining the delicate balance of this vital nutrient for overall health.
Copper regulation Copper is absorbed, transported, distributed, stored, and excreted in the body according to complex
homeostatic processes which ensure a constant and sufficient supply of the micronutrient while simultaneously avoiding excess levels. 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) and Cu2+ (
cupric). As a component of about a dozen
cuproenzymes, copper is involved in key
redox (i.e., oxidation-reduction) reactions in essential metabolic processes such as
mitochondrial respiration, synthesis of
melanin, 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
respiratory center, in the
brainstem where they are regulated. The
partial pressure of
oxygen and
carbon dioxide in the
arterial blood is monitored by the
peripheral chemoreceptors (
PNS) in the
carotid artery and
aortic arch. A change in the
partial pressure of carbon dioxide is detected as altered pH in the
cerebrospinal fluid by
central chemoreceptors (
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. An increased level of carbon dioxide in the blood, or a decreased level of oxygen, will result in a deeper breathing pattern and increased
respiratory rate to bring the blood gases back to equilibrium. Too little carbon dioxide, and, to a lesser extent, too much oxygen in the blood can temporarily halt breathing, a condition known as
apnea, which
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
acclimatization to high altitude.
Blood oxygen content The
kidneys measure the oxygen content rather than the
partial pressure of oxygen 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 cells (RBCs, also called ). The increase in RBCs leads to an increased
hematocrit in the blood, and a subsequent increase in
hemoglobin that increases the oxygen carrying capacity. This is the mechanism whereby high altitude dwellers have higher hematocrits than sea-level residents, and also why persons with
pulmonary insufficiency or
right-to-left shunts 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, but the hemoglobin content will be insufficient and subsequently as will be the oxygen content. Given enough supply of iron,
vitamin B12 and
folic acid, EPO can stimulate RBC production, and hemoglobin and oxygen content restored to normal.
Arterial blood pressure The brain can regulate blood flow over a range of blood pressure values by
vasoconstriction and
vasodilation of the arteries. High pressure receptors called
baroreceptors in the walls of the
aortic arch 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 to secrete the hormone
atrial natriuretic peptide (ANP) into the blood. This acts on the kidneys to inhibit the secretion of renin and aldosterone causing the release of sodium, and accompanying water into the urine, thereby reducing the blood volume. This information is then conveyed, via
afferent nerve fibers, to the
solitary nucleus 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. The arterioles are the main resistance vessels in the
arterial tree, and small changes in diameter cause large changes in the resistance to flow through them. When the arterial blood pressure rises the arterioles are stimulated to
dilate making it easier for blood to leave the arteries, thus deflating them, and bringing the blood pressure down, back to normal. At the same time, the heart is stimulated via
cholinergic parasympathetic nerves to beat more slowly (called
bradycardia), ensuring that the inflow of blood into the arteries is reduced, thus adding to the reduction in pressure, and correcting the original error. Low pressure in the arteries, causes the opposite reflex of constriction of the arterioles, and a speeding up of the heart rate (called
tachycardia). If the drop in blood pressure is very rapid or excessive, the medulla oblongata stimulates the
adrenal medulla, via "preganglionic"
sympathetic nerves, to secrete
epinephrine (adrenaline) into the blood. This hormone enhances the tachycardia and causes severe
vasoconstriction of the arterioles to all but the essential organs in the body (especially the heart, lungs, and brain). These reactions usually correct the low arterial blood pressure (
hypotension) very effectively.
Calcium levels 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 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 (PTH) in response to a fall in the plasma ionized calcium level; the parafollicular cells of the thyroid gland secrete
calcitonin in response to a rise in the plasma ionized calcium level. The
effector organs of the first homeostatic mechanism are the
bones, the
kidney, and, via a hormone released into the blood by the kidney in response to high PTH levels in the blood, the
duodenum and
jejunum. Parathyroid hormone (in high concentrations in the blood) causes
bone resorption, releasing calcium into the plasma. This is a very rapid action which can correct a threatening
hypocalcemia within minutes. High PTH concentrations cause the excretion of
phosphate ions via the urine. Since phosphates combine with calcium ions to form insoluble salts (see also
bone mineral), a decrease in the level of phosphates in the blood, releases free calcium ions into the plasma ionized calcium pool. PTH has a second action on the kidneys. It stimulates the manufacture and release, by the kidneys, of
calcitriol into the blood. This
steroid hormone acts on the epithelial cells of the upper small intestine, increasing their capacity to absorb calcium from the gut contents into the blood. 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
endocannabinoids like
anandamide (
N-arachidonoylethanolamide; AEA) and
2-arachidonoylglycerol (2-AG), whose synthesis occurs through the action of a series of
intracellular enzymes activated in response to a rise in intracellular calcium levels to introduce homeostasis and prevention of
tumor development through putative protective mechanisms that prevent
cell growth and
migration by activation of
CB1 and/or
CB2 and adjoining
receptors.
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 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 cells, 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 and
loop of Henle. These cells also respond to rate of blood flow through the juxtaglomerular apparatus, which, under normal circumstances, is directly proportional to the
arterial blood pressure, making this tissue an ancillary arterial blood pressure sensor. In response to a lowering of the plasma sodium concentration, or to a fall in the arterial blood pressure, the juxtaglomerular cells release
renin into the blood. Renin is an enzyme which cleaves a
decapeptide (a short protein chain, 10 amino acids long) from a plasma
α-2-globulin called
angiotensinogen. This decapeptide is known as
angiotensin I. The reabsorption of sodium ions from the renal tubular fluid halts further sodium ion losses from the body, and therefore preventing the worsening of
hyponatremia. The hyponatremia can only be
corrected by the consumption of salt in the diet. However, it is not certain whether a "salt hunger" can be initiated by hyponatremia, or by what mechanism this might come about. When the plasma sodium ion concentration is higher than normal (
hypernatremia), the release of renin from the juxtaglomerular apparatus is halted, ceasing the production of angiotensin II, and its consequent aldosterone-release into the blood. The kidneys respond by excreting sodium ions into the urine, thereby normalizing the plasma sodium ion concentration. The low angiotensin II levels in the blood lower the arterial blood pressure as an inevitable concomitant response. The reabsorption of sodium ions from the tubular fluid as a result of high aldosterone levels in the blood does not, of itself, cause renal tubular water to be returned to the blood from the
distal convoluted tubules or
collecting ducts. This is because sodium is reabsorbed in exchange for potassium and therefore causes only a modest change in the
osmotic gradient between the blood and the tubular fluid. Furthermore, the epithelium of the distal convoluted tubules and collecting ducts is impermeable to water in the absence of
antidiuretic hormone (ADH) in the blood. ADH is part of the control of
fluid balance. Its levels in the blood vary with the
osmolality of the plasma, which is measured in the
hypothalamus of the brain. Aldosterone's action on the kidney tubules prevents sodium loss to the
extracellular fluid (ECF). So there is no change in the osmolality of the ECF, and therefore no change in the ADH concentration of the plasma. However, low aldosterone levels cause a loss of sodium ions from the ECF, which could potentially cause a change in extracellular osmolality and therefore of ADH levels in the blood.
Potassium concentration High potassium concentrations in the plasma cause
depolarization of the
zona glomerulosa cells' membranes in the outer layer of the
adrenal cortex. This causes the release of
aldosterone into the blood. Aldosterone acts primarily on the
distal convoluted tubules and
collecting ducts of the kidneys, stimulating the excretion of potassium ions into the urine.
Fluid balance The
total amount of water in the body needs to be kept in balance.
Fluid balance involves keeping the fluid volume stabilized, and also keeping the levels of
electrolytes in the extracellular fluid stable. Fluid balance is maintained by the process of
osmoregulation and by behavior.
Osmotic pressure is detected by
osmoreceptors in the
median preoptic nucleus in the
hypothalamus. Measurement of the plasma
osmolality to give an indication of the water content of the body, relies on the fact that water losses from the body, (through
unavoidable water loss through the skin which is not entirely waterproof and therefore always slightly moist,
water vapor in the exhaled air,
sweating,
vomiting, normal
feces and especially
diarrhea) are all
hypotonic, meaning that they are less salty than the body fluids (compare, for instance, the taste of saliva with that of tears. The latter has almost the same salt content as the extracellular fluid, whereas the former is hypotonic with respect to the plasma. Saliva does not taste salty, whereas tears are decidedly salty). Nearly all normal and abnormal losses of
body water therefore cause the extracellular fluid to become
hypertonic. Conversely, excessive fluid intake dilutes the extracellular fluid causing the hypothalamus to register
hypotonic hyponatremia conditions. When the
hypothalamus detects a hypertonic extracellular environment, it causes the secretion of an antidiuretic hormone (ADH) called
vasopressin which acts on the effector organ, which in this case is the
kidney. The effect of vasopressin on the kidney tubules is to reabsorb water from the
distal convoluted tubules 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 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 regulates the ratio of carbonic acid to bicarbonate to be equal to 1:20, at which ratio the blood pH is 7.4 (as explained in the
Henderson–Hasselbalch equation). A change in the plasma pH gives an
acid–base imbalance. In
acid–base homeostasis there are two mechanisms that can help regulate the pH.
Respiratory compensation a mechanism of the
respiratory center, adjusts the
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. 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 factors, to which slight changes can cause problems or damage to the nervous system. For example, high
glycine concentration disrupts
temperature and
blood pressure control, and high CSF
pH causes
dizziness and
syncope.
Neurotransmission Inhibitory neurons in the
central nervous system play a homeostatic role in the balance of neuronal activity between excitation and inhibition. Inhibitory neurons using
GABA, make compensating changes in the neuronal networks preventing runaway levels of excitation. An imbalance between excitation and inhibition is seen to be implicated in a number of
neuropsychiatric disorders.
Neuroendocrine system The
neuroendocrine system is the mechanism by which the hypothalamus maintains homeostasis, regulating
metabolism, reproduction, eating and drinking behaviour, energy utilization, osmolarity and blood pressure. The regulation of metabolism, is carried out by
hypothalamic interconnections to other glands. Three
endocrine glands of the
hypothalamic–pituitary–gonadal axis (HPG axis) often work together and have important regulatory functions. Two other regulatory endocrine axes are the
hypothalamic–pituitary–adrenal axis (HPA axis) and the
hypothalamic–pituitary–thyroid axis (HPT axis). The
liver also has many regulatory functions of the metabolism. An important function is the production and control of
bile acids. Too much bile acid can be toxic to cells and its synthesis can be inhibited by activation of
FXR a
nuclear receptor. ==Clinical significance==