Carotid body
Encyclopedia
The carotid body is a small cluster of chemoreceptors and supporting cells located near the fork (bifurcation) of the carotid artery
(which runs along both sides of the throat).
The carotid body detects changes in the composition of arterial blood flowing through it, mainly the partial pressure of oxygen
, but also of carbon dioxide
. Furthermore, it is also sensitive to changes in pH
and temperature
.
The carotid body contains the most vascular tissue in the human body. The thyroid gland is very vascular, but not quite as much as the carotid body.
through the afferent fibers of the glossopharyngeal nerve, which relays the information to the central nervous system.
The output of the carotid bodies is low at an oxygen partial pressure
above about 100 mmHg (13,3 kPa
) (at normal physiological pH), but below this the activity of the type I (glomus) cells increases rapidly.
generation produced by cystathionine gamma-lyase
as hypoxia detection is reduced in mice in which this enzyme is knocked out or pharmacologically inhibited. The process of detection involves the interaction of cystathionine gamma-lyase with hemeoxygenase-2
and the production of carbon monoxide
.
Other theories suggest it may involve mitochondrial oxygen sensors and the haem-containing cytochromes that undergo reversible one-electron reduction during oxidative-phosphorylation. Haem reversibly binds O2 with an affinity similar to that of the carotid body, suggesting that haem containing proteins may have a role in O2, potentially this could be one of the complexes involved in oxidative-phosphorylation. This leads to increases in reactive oxygen species and rises in intracellular Ca2+. However, whether hypoxia leads to an increase or decrease in reactive oxygen species is unknown. The role of reactive oxygen species in hypoxia sensing is also under question.
The oxygen dependent enzyme haem-oxidase has also been put forward as a hypoxia sensor. In normoxia, haem-oxygenase generates carbon monoxide (CO), CO activates the large conductance calcium-activated potassium channel, BK. Falls in CO that occur as a consequence of hypoxia would lead to closure of this potassium channel and this would lead to membrane depolarisation and consequence activation of the carotid body. A role for the "energy sensor" AMP-activated protein kinase (AMPK) has also been proposed in hypoxia sensing. This enzyme is activated during times of net energy usage and metabolic stress, including hypoxia. AMPK has a number of targets and it appears that, in the carotid body, when AMPK is activated by hypoxia, it leads to downstream potassium channel closure of both O2-sentive TASK-like and BK channels
An increased PCO2 is detected because the CO2 diffuses
into the cell, where it increases the concentration of carbonic acid
and thus protons. The precise mechanism of CO2 sensing is unknown, however it has been demonstrated that CO2 and low pH inhibit a TASK-like potassium conductance, reducing potassium current. This leads to depolarisation of the cell membrane which leads to Ca2+ entry, excitation of glomus cells and consequent neurotransmitter release.
Arterial acidosis
(either metabolic
or from altered PCO2
) inhibits acid-base transporters (e.g. Na+-H+) which raise intracellular pH
, and activates transporters (e.g. Cl--HCO3-) which decrease it. Changes in proton concentration caused by acidosis (or the opposite from alkalosis
) inside the cell stimulates the same pathways involved in PCO2 sensing.
of the cell membrane
, and they affect this by blocking potassium
currents. This reduction in the membrane potential
opens voltage-gated calcium
channels, which causes a rise in intracellular calcium concentration. This causes exocytosis
of vesicles
containing a variety of neurotransmitters, including acetylcholine
, noradrenaline, dopamine
, adenosine, ATP
, substance P
, and met-enkephalin
. These act on receptors
on the afferent nerve fibres which lie in apposition to the glomus cell to cause an action potential.
via the afferent branches of the Glossopharyngeal nerve
. The efferent fibres of the aortic body
chemoreceptors are relayed by the Vagus nerve
. These centers, in turn, regulate breathing and blood pressure.
is a tumor that may involve the carotid body and is usually benign
. Rarely, a malignant neuroblastoma
may originate from the carotid body.
Carotid artery
Carotid artery can refer to:* Common carotid artery* External carotid artery* Internal carotid artery...
(which runs along both sides of the throat).
The carotid body detects changes in the composition of arterial blood flowing through it, mainly the partial pressure of oxygen
Oxygen
Oxygen is the element with atomic number 8 and represented by the symbol O. Its name derives from the Greek roots ὀξύς and -γενής , because at the time of naming, it was mistakenly thought that all acids required oxygen in their composition...
, but also of carbon dioxide
Carbon dioxide
Carbon dioxide is a naturally occurring chemical compound composed of two oxygen atoms covalently bonded to a single carbon atom...
. Furthermore, it is also sensitive to changes in pH
PH
In chemistry, pH is a measure of the acidity or basicity of an aqueous solution. Pure water is said to be neutral, with a pH close to 7.0 at . Solutions with a pH less than 7 are said to be acidic and solutions with a pH greater than 7 are basic or alkaline...
and temperature
Temperature
Temperature is a physical property of matter that quantitatively expresses the common notions of hot and cold. Objects of low temperature are cold, while various degrees of higher temperatures are referred to as warm or hot...
.
Composition
The carotid body is made up of two types of cells, called glomus cells: glomus type I (chief) cells, and glomus type II (sustentacular) cells.- Glomus type I/chief cells are derived from neural crestNeural crestNeural crest cells are a transient, multipotent, migratory cell population unique to vertebrates that gives rise to a diverse cell lineage including melanocytes, craniofacial cartilage and bone, smooth muscle, peripheral and enteric neurons and glia....
, which, in turn are derived from neuroectodermNeuroectodermNeuroectoderm is the term for ectoderm which receives Bone Morphogenetic Protein-inhibiting signals from proteins such as noggin, which leads to the development of the nervous system from this tissue....
. They release a variety of neurotransmitterNeurotransmitterNeurotransmitters are endogenous chemicals that transmit signals from a neuron to a target cell across a synapse. Neurotransmitters are packaged into synaptic vesicles clustered beneath the membrane on the presynaptic side of a synapse, and are released into the synaptic cleft, where they bind to...
s, including acetylcholineAcetylcholineThe chemical compound acetylcholine is a neurotransmitter in both the peripheral nervous system and central nervous system in many organisms including humans...
, ATPAdenosine triphosphateAdenosine-5'-triphosphate is a multifunctional nucleoside triphosphate used in cells as a coenzyme. It is often called the "molecular unit of currency" of intracellular energy transfer. ATP transports chemical energy within cells for metabolism...
, and dopamineDopamineDopamine is a catecholamine neurotransmitter present in a wide variety of animals, including both vertebrates and invertebrates. In the brain, this substituted phenethylamine functions as a neurotransmitter, activating the five known types of dopamine receptors—D1, D2, D3, D4, and D5—and their...
that trigger EPSPs in synapsed neurons leading to the respiratory center.
- Glomus type II/sustentacular cells resemble gliaGlial cellGlial cells, sometimes called neuroglia or simply glia , are non-neuronal cells that maintain homeostasis, form myelin, and provide support and protection for neurons in the brain, and for neurons in other parts of the nervous system such as in the autonomous nervous system...
, express the glial marker S100S100S100 or S-100 can refer to:* S-100 bus, a type of computer bus* S-100 protein, a family of cellular antigens proteins* Hondata s100, a engine tuning system for Honda and Acura cars* QTEK S100, a re-badged HTC Magician Pocket PC phone...
and act as supporting cells.
The carotid body contains the most vascular tissue in the human body. The thyroid gland is very vascular, but not quite as much as the carotid body.
Function
The carotid body functions as a sensor: it responds to a stimulus, primarily O2 partial pressure, which is detected by the type I (glomus) cells, and triggers an action potentialAction potential
In physiology, an action potential is a short-lasting event in which the electrical membrane potential of a cell rapidly rises and falls, following a consistent trajectory. Action potentials occur in several types of animal cells, called excitable cells, which include neurons, muscle cells, and...
through the afferent fibers of the glossopharyngeal nerve, which relays the information to the central nervous system.
Stimulus
While the central chemoreceptors in the brainstem are highly sensitive to CO2 the carotid body is a peripheral chemoreceptor that mainly provides afferent input to the respiratory center that is highly O2 dependent. However, the carotid body also senses increases in CO2 partial pressure and decreases in arterial pH, but to a lesser degree than for O2The output of the carotid bodies is low at an oxygen partial pressure
Partial pressure
In a mixture of ideal gases, each gas has a partial pressure which is the pressure which the gas would have if it alone occupied the volume. The total pressure of a gas mixture is the sum of the partial pressures of each individual gas in the mixture....
above about 100 mmHg (13,3 kPa
Pascal (unit)
The pascal is the SI derived unit of pressure, internal pressure, stress, Young's modulus and tensile strength, named after the French mathematician, physicist, inventor, writer, and philosopher Blaise Pascal. It is a measure of force per unit area, defined as one newton per square metre...
) (at normal physiological pH), but below this the activity of the type I (glomus) cells increases rapidly.
Detection
The mechanism for detecting reductions in PO2 has yet to be identified, there may be multiple mechanisms and could vary between species. Hypoxia detection has been shown to depend upon increased Hydrogen sulfideHydrogen sulfide
Hydrogen sulfide is the chemical compound with the formula . It is a colorless, very poisonous, flammable gas with the characteristic foul odor of expired eggs perceptible at concentrations as low as 0.00047 parts per million...
generation produced by cystathionine gamma-lyase
Cystathionine gamma-lyase
Cystathionine gamma-lyase is an enzyme which breaks down cystathionine into cysteine and α-ketobutyrate. Pyridoxal phosphate is a prosthetic group of this enzyme....
as hypoxia detection is reduced in mice in which this enzyme is knocked out or pharmacologically inhibited. The process of detection involves the interaction of cystathionine gamma-lyase with hemeoxygenase-2
HMOX2
Heme oxygenase 2 is an enzyme that in humans is encoded by the HMOX2 gene.- Function :Heme oxygenase, an essential enzyme in heme catabolism, cleaves heme to form biliverdin, which is subsequently converted to bilirubin by biliverdin reductase, and carbon monoxide, a putative neurotransmitter...
and the production of carbon monoxide
Carbon monoxide
Carbon monoxide , also called carbonous oxide, is a colorless, odorless, and tasteless gas that is slightly lighter than air. It is highly toxic to humans and animals in higher quantities, although it is also produced in normal animal metabolism in low quantities, and is thought to have some normal...
.
Other theories suggest it may involve mitochondrial oxygen sensors and the haem-containing cytochromes that undergo reversible one-electron reduction during oxidative-phosphorylation. Haem reversibly binds O2 with an affinity similar to that of the carotid body, suggesting that haem containing proteins may have a role in O2, potentially this could be one of the complexes involved in oxidative-phosphorylation. This leads to increases in reactive oxygen species and rises in intracellular Ca2+. However, whether hypoxia leads to an increase or decrease in reactive oxygen species is unknown. The role of reactive oxygen species in hypoxia sensing is also under question.
The oxygen dependent enzyme haem-oxidase has also been put forward as a hypoxia sensor. In normoxia, haem-oxygenase generates carbon monoxide (CO), CO activates the large conductance calcium-activated potassium channel, BK. Falls in CO that occur as a consequence of hypoxia would lead to closure of this potassium channel and this would lead to membrane depolarisation and consequence activation of the carotid body. A role for the "energy sensor" AMP-activated protein kinase (AMPK) has also been proposed in hypoxia sensing. This enzyme is activated during times of net energy usage and metabolic stress, including hypoxia. AMPK has a number of targets and it appears that, in the carotid body, when AMPK is activated by hypoxia, it leads to downstream potassium channel closure of both O2-sentive TASK-like and BK channels
An increased PCO2 is detected because the CO2 diffuses
Diffusion
Molecular diffusion, often called simply diffusion, is the thermal motion of all particles at temperatures above absolute zero. The rate of this movement is a function of temperature, viscosity of the fluid and the size of the particles...
into the cell, where it increases the concentration of carbonic acid
Carbonic acid
Carbonic acid is the inorganic compound with the formula H2CO3 . It is also a name sometimes given to solutions of carbon dioxide in water, because such solutions contain small amounts of H2CO3. Carbonic acid forms two kinds of salts, the carbonates and the bicarbonates...
and thus protons. The precise mechanism of CO2 sensing is unknown, however it has been demonstrated that CO2 and low pH inhibit a TASK-like potassium conductance, reducing potassium current. This leads to depolarisation of the cell membrane which leads to Ca2+ entry, excitation of glomus cells and consequent neurotransmitter release.
Arterial acidosis
Acidosis
Acidosis is an increased acidity in the blood and other body tissue . If not further qualified, it usually refers to acidity of the blood plasma....
(either metabolic
Metabolic acidosis
In medicine, metabolic acidosis is a condition that occurs when the body produces too much acid or when the kidneys are not removing enough acid from the body. If unchecked, metabolic acidosis leads to acidemia, i.e., blood pH is low due to increased production of hydrogen by the body or the...
or from altered PCO2
Respiratory acidosis
Respiratory acidosis is a medical condition in which decreased ventilation causes increased blood carbon dioxide concentration and decreased pH ....
) inhibits acid-base transporters (e.g. Na+-H+) which raise intracellular pH
Intracellular pH
All cells contain an intracellular fluid whose pH value is known as the intracellular pH . The pHi plays a critical role in the function of the cell, and close regulation is required for cells to survive...
, and activates transporters (e.g. Cl--HCO3-) which decrease it. Changes in proton concentration caused by acidosis (or the opposite from alkalosis
Alkalosis
Alkalosis refers to a condition reducing hydrogen ion concentration of arterial blood plasma . Generally, alkalosis is said to occur when pH of the blood exceeds 7.45. The opposite condition is acidosis .-Causes:...
) inside the cell stimulates the same pathways involved in PCO2 sensing.
Action potential
The type I (glomus) cells in the carotid (and aortic bodies) are derived from neuroectoderm and are thus electrically excitable. A decrease in oxygen partial pressure, an increase in carbon dioxide partial pressure, and a decrease in arterial pH can all cause depolarizationDepolarization
In biology, depolarization is a change in a cell's membrane potential, making it more positive, or less negative. In neurons and some other cells, a large enough depolarization may result in an action potential...
of the cell membrane
Cell membrane
The cell membrane or plasma membrane is a biological membrane that separates the interior of all cells from the outside environment. The cell membrane is selectively permeable to ions and organic molecules and controls the movement of substances in and out of cells. It basically protects the cell...
, and they affect this by blocking potassium
Potassium
Potassium is the chemical element with the symbol K and atomic number 19. Elemental potassium is a soft silvery-white alkali metal that oxidizes rapidly in air and is very reactive with water, generating sufficient heat to ignite the hydrogen emitted in the reaction.Potassium and sodium are...
currents. This reduction in the membrane potential
Membrane potential
Membrane potential is the difference in electrical potential between the interior and exterior of a biological cell. All animal cells are surrounded by a plasma membrane composed of a lipid bilayer with a variety of types of proteins embedded in it...
opens voltage-gated 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...
channels, which causes a rise in intracellular calcium concentration. This causes exocytosis
Exocytosis
Exocytosis , also known as 'The peni-cytosis', is the durable process by which a cell directs the contents of secretory vesicles out of the cell membrane...
of vesicles
Synaptic vesicle
In a neuron, synaptic vesicles store various neurotransmitters that are released at the synapse. The release is regulated by a voltage-dependent calcium channel. Vesicles are essential for propagating nerve impulses between neurons and are constantly recreated by the cell...
containing a variety of neurotransmitters, including acetylcholine
Acetylcholine
The chemical compound acetylcholine is a neurotransmitter in both the peripheral nervous system and central nervous system in many organisms including humans...
, noradrenaline, dopamine
Dopamine
Dopamine is a catecholamine neurotransmitter present in a wide variety of animals, including both vertebrates and invertebrates. In the brain, this substituted phenethylamine functions as a neurotransmitter, activating the five known types of dopamine receptors—D1, D2, D3, D4, and D5—and their...
, adenosine, ATP
Adenosine triphosphate
Adenosine-5'-triphosphate is a multifunctional nucleoside triphosphate used in cells as a coenzyme. It is often called the "molecular unit of currency" of intracellular energy transfer. ATP transports chemical energy within cells for metabolism...
, substance P
Substance P
In the field of neuroscience, substance P is a neuropeptide: an undecapeptide that functions as a neurotransmitter and as a neuromodulator. It belongs to the tachykinin neuropeptide family. Substance P and its closely related neuropeptide neurokinin A are produced from a polyprotein precursor...
, and met-enkephalin
Met-enkephalin
[Met]enkephalin, sometimes referred to as opioid growth factor , is a naturally-occurring, endogenous opioid peptide that has opioid effects of a relatively short duration. It is one of the two forms of enkephalin, the other being [leu]enkephalin...
. These act on receptors
Receptor (biochemistry)
In biochemistry, a receptor is a molecule found on the surface of a cell, which receives specific chemical signals from neighbouring cells or the wider environment within an organism...
on the afferent nerve fibres which lie in apposition to the glomus cell to cause an action potential.
Relay
The feedback from the carotid body is sent to the cardiorespiratory centers in the medulla oblongataMedulla oblongata
The medulla oblongata is the lower half of the brainstem. In discussions of neurology and similar contexts where no ambiguity will result, it is often referred to as simply the medulla...
via the afferent branches of the Glossopharyngeal nerve
Glossopharyngeal nerve
The glossopharyngeal nerve is the ninth of twelve pairs of cranial nerves . It exits the brainstem out from the sides of the upper medulla, just rostral to the vagus nerve...
. The efferent fibres of the aortic body
Aortic body
In the human heart, the aortic body is one of several small clusters of chemoreceptors, baroreceptors, and supporting cells located along the aortic arch.-Function:...
chemoreceptors are relayed by the Vagus nerve
Vagus nerve
The vagus nerve , also called pneumogastric nerve or cranial nerve X, is the tenth of twelve paired cranial nerves...
. These centers, in turn, regulate breathing and blood pressure.
Disorders
A paragangliomaParaganglioma
A paraganglioma is a rare neuroendocrine neoplasm that may develop at various body sites . About 97% are benign and cured by surgical removal; the remaining 3% are malignant because they are able to produce distant metastases...
is a tumor that may involve the carotid body and is usually benign
Benign
A benign tumor is a tumor that lacks the ability to metastasize. Common examples of benign tumors include moles and uterine fibroids.The term "benign" implies a mild and nonprogressive disease. Indeed, many kinds of benign tumors are harmless to human health...
. Rarely, a malignant neuroblastoma
Neuroblastoma
Neuroblastoma is the most common extracranial solid cancer in childhood and the most common cancer in infancy, with an annual incidence of about 650 cases per year in the US , and 100 cases per year in the UK . Close to 50 percent of neuroblastoma cases occur in children younger than two years old...
may originate from the carotid body.
External links
- Respiratory physiology notes at Kirksville College of Osteopathic Medicine