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The carotid body is a small cluster of chemoreceptor cells, and supporting sustentacular cells. The carotid body is located in the adventitia, in the bifurcation (fork) of the
common carotid artery In anatomy, the left and right common carotid arteries (carotids) (Entry "carotid"
in
neck The neck is the part of the body on many vertebrates that connects the head with the torso. The neck supports the weight of the head and protects the nerves that carry sensory and motor information from the brain down to the rest of the body. In ...
. The carotid body detects changes in the composition of arterial blood flowing through it, mainly the partial pressure of arterial oxygen, but also of
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 t ...
. It is also sensitive to changes in blood pH, and
temperature Temperature is a physical quantity that expresses quantitatively the perceptions of hotness and coldness. Temperature is measured with a thermometer. Thermometers are calibrated in various temperature scales that historically have relied o ...
.


Structure

The carotid body is made up of two types of cells, called glomus cells: glomus type I cells are
peripheral chemoreceptor 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 v ...
s, and glomus type II cells are sustentacular supportive cells. * Glomus type I cells are derived from the
neural crest Neural crest cells are a temporary group of cells unique to vertebrates that arise from the embryonic ectoderm germ layer, and in turn give rise to a diverse cell lineage—including melanocytes, craniofacial cartilage and bone, smooth muscle, per ...
. They release a variety of
neurotransmitter A neurotransmitter is a signaling molecule secreted by a neuron to affect another cell across a synapse. The cell receiving the signal, any main body part or target cell, may be another neuron, but could also be a gland or muscle cell. Neu ...
s, including
acetylcholine Acetylcholine (ACh) is an organic chemical that functions in the brain and body of many types of animals (including humans) as a neurotransmitter. Its name is derived from its chemical structure: it is an ester of acetic acid and choline. Par ...
, ATP, and
dopamine Dopamine (DA, a contraction of 3,4-dihydroxyphenethylamine) is a neuromodulatory molecule that plays several important roles in cells. It is an organic chemical of the catecholamine and phenethylamine families. Dopamine constitutes about 80% o ...
that trigger EPSPs in synapsed neurons leading to 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 ...
. They are innervated by axons of the glossopharyngeal nerve which collectively are called the carotid sinus nerve. * Glomus type II cells resemble
glial cells Glia, also called glial cells (gliocytes) or neuroglia, are non-neuronal cells in the central nervous system (brain and spinal cord) and the peripheral nervous system that do not produce electrical impulses. They maintain homeostasis, form myel ...
, express the glial marker S100 and act as supporting cells.


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 potential An action potential occurs when the membrane potential of a specific cell location rapidly rises and falls. This depolarization then causes adjacent locations to similarly depolarize. Action potentials occur in several types of animal cells ...
through the afferent fibers of the
glossopharyngeal nerve The glossopharyngeal nerve (), also known as the ninth cranial nerve, cranial nerve IX, or simply CN IX, is a cranial nerve that exits the brainstem from the sides of the upper medulla, just anterior (closer to the nose) to the vagus nerve. ...
, which relays the information to the central nervous system.


Stimulus

The carotid body peripheral chemoreceptors are primarily sensitive to decreases in the partial pressure of oxygen (PO2). This is in contrast to the central chemoreceptors in the
medulla oblongata The medulla oblongata or simply medulla is a long stem-like structure which makes up the lower part of the brainstem. It is anterior and partially inferior to the cerebellum. It is a cone-shaped neuronal mass responsible for autonomic (invol ...
that are primarily sensitive to changes in pH and PCO2 (a decrease in pH and an increase in PCO2). The carotid body chemoreceptors are also sensitive to pH and PCO2, but only secondarily. More specifically, the sensitivity of carotid body chemoreceptors to decreased PO2 is greater when pH is decreased and PCO2 is increased. Impulse rate for carotid bodies is particularly sensitive to changes in arterial PO2 in the range of 60 down to 30 mm Hg, a range in which hemoglobin saturation with oxygen decreases rapidly. The output of the carotid bodies is low at an oxygen
partial pressure In a mixture of gases, each constituent gas has a partial pressure which is the notional pressure of that constituent gas as if it alone occupied the entire volume of the original mixture at the same temperature. The total pressure of an ideal g ...
above about 100mmHg (13,3 k Pa) (at normal physiological pH), but below 60mmHg the activity of the type I (glomus) cells increases rapidly due to a decrease in hemoglobin-oxygen saturation below 90%.


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 sulfide Hydrogen sulfide is a chemical compound with the formula . It is a colorless chalcogen-hydride gas, and is poisonous, corrosive, and flammable, with trace amounts in ambient atmosphere having a characteristic foul odor of rotten eggs. The under ...
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 Carbon monoxide ( chemical formula CO) is a colorless, poisonous, odorless, tasteless, flammable gas that is slightly less dense than air. Carbon monoxide consists of one carbon atom and one oxygen atom connected by a triple bond. It is the simpl ...
.Peng Y-J, Nanduri J, Raghuraman G, Souvannakitti D, Gadalla M.M, Kumar GK, Snyder SH, Prabhakar NR. (2010). H2S mediates O2 sensing in the carotid body PNAS 107 (23) 10719-10724. Yet, some studies show that physiologic concentration of hydrogen sulfide may not be strong enough to trigger such responses. 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 A proton is a stable subatomic particle, symbol , H+, or 1H+ with a positive electric charge of +1 ''e'' elementary charge. Its mass is slightly less than that of a neutron and 1,836 times the mass of an electron (the proton–electron m ...
. 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 is a process causing increased acidity in the blood and other body tissues (i.e., an increase in hydrogen ion concentration). If not further qualified, it usually refers to acidity of the blood plasma. The term ''acidemia'' describe ...
(either
metabolic 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 cell ...
or from altered PCO2) inhibits acid-base transporters (e.g. Na+-H+) which raise
intracellular pH Intracellular pH (pHi) is the measure of the acidity or basicity (i.e., pH) of intracellular fluid. The pHi plays a critical role in membrane transport and other intracellular processes. In an environment with the improper pHi, biological cells m ...
, and activates transporters (e.g. Cl-HCO3) which decrease it. Changes in proton concentration caused by acidosis (or the opposite from
alkalosis Alkalosis is the result of a process reducing hydrogen ion concentration of arterial blood plasma (alkalemia). In contrast to acidemia (serum pH 7.35 or lower), alkalemia occurs when the serum pH is higher than normal (7.45 or higher). Alkalosi ...
) inside the cell stimulates the same pathways involved in PCO2 sensing. Another mechanism is through oxygen sensitive potassium channels. A drop in dissolved oxygen lead to closing of these channels which results in depolarization. This leads to release of the neurotransmitter dopamine in the glossopharyngeal and vagus afferente to the vasomotor area.


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
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
cell membrane 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 (t ...
, and they affect this by blocking
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 atmos ...
currents. This reduction in the
membrane potential Membrane potential (also transmembrane potential or membrane voltage) is the difference in electric potential between the interior and the exterior of a biological cell. That is, there is a difference in the energy required for electric charges ...
opens voltage-gated
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 ...
channels, which causes a rise in intracellular calcium concentration. This causes
exocytosis Exocytosis () is a form of active transport and bulk transport in which a cell transports molecules (e.g., neurotransmitters and proteins) out of the cell ('' exo-'' + ''cytosis''). As an active transport mechanism, exocytosis requires the use ...
of
vesicles Vesicle may refer to: ; In cellular biology or chemistry * Vesicle (biology and chemistry), a supramolecular assembly of lipid molecules, like a cell membrane * Synaptic vesicle ; In human embryology * Vesicle (embryology), bulge-like features o ...
containing a variety of neurotransmitters, including
acetylcholine Acetylcholine (ACh) is an organic chemical that functions in the brain and body of many types of animals (including humans) as a neurotransmitter. Its name is derived from its chemical structure: it is an ester of acetic acid and choline. Par ...
, noradrenaline,
dopamine Dopamine (DA, a contraction of 3,4-dihydroxyphenethylamine) is a neuromodulatory molecule that plays several important roles in cells. It is an organic chemical of the catecholamine and phenethylamine families. Dopamine constitutes about 80% o ...
,
adenosine Adenosine (symbol A) is an organic compound that occurs widely in nature in the form of diverse derivatives. The molecule consists of an adenine attached to a ribose via a β-N9- glycosidic bond. Adenosine is one of the four nucleoside building ...
, ATP,
substance P Substance P (SP) is an undecapeptide (a peptide composed of a chain of 11 amino acid residues) and a member of the tachykinin neuropeptide family. It is a neuropeptide, acting as a neurotransmitter and as a neuromodulator. Substance P and its clo ...
, and
met-enkephalin Met-enkephalin, also known as metenkefalin (INN), sometimes referred to as opioid growth factor (OGF), is a naturally occurring, endogenous opioid peptide that has opioid effects of a relatively short duration. It is one of the two forms of enk ...
. These act on receptors 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 oblongata The medulla oblongata or simply medulla is a long stem-like structure which makes up the lower part of the brainstem. It is anterior and partially inferior to the cerebellum. It is a cone-shaped neuronal mass responsible for autonomic (invol ...
via the afferent branches of the
glossopharyngeal nerve The glossopharyngeal nerve (), also known as the ninth cranial nerve, cranial nerve IX, or simply CN IX, is a cranial nerve that exits the brainstem from the sides of the upper medulla, just anterior (closer to the nose) to the vagus nerve. ...
. The efferent fibres of the aortic body chemoreceptors are relayed by the
vagus nerve The vagus nerve, also known as the tenth cranial nerve, cranial nerve X, or simply CN X, is a cranial nerve that interfaces with the parasympathetic control of the heart, lungs, and digestive tract. It comprises two nerves—the left and righ ...
. These centers, in turn, regulate breathing and blood pressure, with hypoxia causing an increase in ventilation.


Clinical significance


Paraganglioma

A paraganglioma is a tumor that may involve the carotid body and is usually benign. Rarely, a malignant
neuroblastoma Neuroblastoma (NB) is a type of cancer that forms in certain types of nerve tissue. It most frequently starts from one of the adrenal glands but can also develop in the neck, chest, abdomen, or spine. Symptoms may include bone pain, a lump in ...
may originate from the carotid body.


References


External links

* Javier Villadiego, Reposo Ramírez-Lorca, Fernando Cala, José L Labandeira-García, Mariano Esteban, Juan J Toledo-Aral, José López-Barneo
Is Carotid Body Infection Responsible for Silent Hypoxemia in COVID-19 Patients?
In: Function, Volume 2, Issue 1, 2021. Oxford Academic. Published: 23 November 2020. zqaa032 doi:10.1093/function/zqaa032. Along: :
A Frightening New Explanation for the Lack of Blood Oxygenation in Many COVID-19 Patients
On: SciTechDaily. December 29, 2020. Source: University of Seville :
An explanation for the lack of blood oxygenation detected in many COVID-19 patients
On: EurekAlert! 29-Dec-2020. Source: University of Seville {{DEFAULTSORT:Carotid Body Angiology Respiration