Mucociliary Escalator
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Mucociliary clearance (MCC), mucociliary transport, or the mucociliary escalator, describes the self-clearing mechanism of the airways in the
respiratory system The respiratory system (also respiratory apparatus, ventilatory system) is a biological system consisting of specific organs and structures used for gas exchange in animals and plants. The anatomy and physiology that make this happen varies grea ...
. It is one of the two protective processes for the
lung The lungs are the primary organs of the respiratory system in humans and most other animals, including some snails and a small number of fish. In mammals and most other vertebrates, two lungs are located near the backbone on either side of t ...
s in removing inhaled
particles In the physical sciences, a particle (or corpuscule in older texts) is a small localized object which can be described by several physical or chemical properties, such as volume, density, or mass. They vary greatly in size or quantity, from su ...
including
pathogen In biology, a pathogen ( el, πάθος, "suffering", "passion" and , "producer of") in the oldest and broadest sense, is any organism or agent that can produce disease. A pathogen may also be referred to as an infectious agent, or simply a germ ...
s before they can reach the delicate tissue of the lungs. The other clearance mechanism is provided by the
cough reflex The cough reflex occurs when stimulation of cough receptors in the respiratory tract by dust or other foreign particles produces a cough, which causes rapidly moving air which usually remove the foreign material before it reaches the lungs. This ty ...
. Mucociliary clearance has a major role in
pulmonary hygiene Pulmonary hygiene, formerly referred to as pulmonary toilet, is a set of methods used to clear mucus and secretions from the airways. The word ''pulmonary'' refers to the lungs. The word ''toilet'', related to the French ''toilette'', refers to b ...
. MCC effectiveness relies on the correct properties of the
airway surface liquid Mucus ( ) is a slippery aqueous secretion produced by, and covering, mucous membranes. It is typically produced from cells found in mucous glands, although it may also originate from mixed glands, which contain both serous and mucous cells. It is ...
produced, both of the periciliary sol layer and the overlying mucus gel layer, and of the number and quality of the
cilia The cilium, plural cilia (), is a membrane-bound organelle found on most types of eukaryotic cell, and certain microorganisms known as ciliates. Cilia are absent in bacteria and archaea. The cilium has the shape of a slender threadlike projecti ...
present in the lining of the airways. An important factor is the rate of
mucin Mucins () are a family of high molecular weight, heavily glycosylated proteins (glycoconjugates) produced by epithelial tissues in most animals. Mucins' key characteristic is their ability to form gels; therefore they are a key component in most ...
secretion. The
ion channel Ion channels are pore-forming membrane proteins that allow ions to pass through the channel pore. Their functions include establishing a resting membrane potential, shaping action potentials and other electrical signals by gating the flow of io ...
s
CFTR Cystic fibrosis transmembrane conductance regulator (CFTR) is a membrane protein and anion channel in vertebrates that is encoded by the ''CFTR'' gene. Geneticist Lap-Chee Tsui and his team identified the CFTR gene in 1989 as the gene linked wit ...
and
ENaC The epithelial sodium channel (ENaC), (also known as amiloride-sensitive sodium channel) is a membrane-bound ion channel that is selectively permeable to sodium ions (). It is assembled as a heterotrimer composed of three homologous subunits α ...
work together to maintain the necessary hydration of the airway surface liquid. Any disturbance in the closely regulated functioning of the cilia can cause a disease. Disturbances in the structural formation of the cilia can cause a number of ciliopathies, notably
primary ciliary dyskinesia Primary ciliary dyskinesia (PCD) is a rare, autosomal recessive genetic ciliopathy, that causes defects in the action of cilia lining the upper and lower respiratory tract, sinuses, Eustachian tube, middle ear, Fallopian tube, and flagella of ...
. Cigarette smoke exposure can cause shortening of the cilia.


Function

In the upper part of the respiratory tract the
nasal hair Nasal hair or nose hair, is the hair in the human nose. Adult humans have hair in the nostrils. Nasal hair functions include filtering foreign particles from entering the nasal cavity, and collecting moisture. In support of the first function, the ...
in the
nostril A nostril (or naris , plural ''nares'' ) is either of the two orifices of the nose. They enable the entry and exit of air and other gasses through the nasal cavities. In birds and mammals, they contain branched bones or cartilages called turbi ...
s traps large particles, and the sneeze reflex may also be triggered to expel them. The
nasal mucosa The nasal mucosa lines the nasal cavity. It is part of the respiratory mucosa, the mucous membrane lining the respiratory tract. The nasal mucosa is intimately adherent to the periosteum or perichondrium of the nasal conchae. It is continuous wit ...
also traps particles preventing their entry further into the tract. In the rest of the respiratory tract, particles of different sizes become deposited along different parts of the airways. Larger particles are trapped higher up in the larger
bronchi A bronchus is a passage or airway in the lower respiratory tract that conducts air into the lungs. The first or primary bronchi pronounced (BRAN-KAI) to branch from the trachea at the carina are the right main bronchus and the left main bronchus. ...
. As the airways become narrower only smaller particles can pass. The branchings of the airways cause turbulence in the airflow at all of their junctions where particles can then be deposited and they never reach the
alveoli Alveolus (; pl. alveoli, adj. alveolar) is a general anatomical term for a concave cavity or pit. Uses in anatomy and zoology * Pulmonary alveolus, an air sac in the lungs ** Alveolar cell or pneumocyte ** Alveolar duct ** Alveolar macrophage * ...
. Only very small pathogens are able to gain entry to the alveoli. Mucociliary clearance functions to remove these particulates and also to trap and remove pathogens from the airways, in order to protect the delicate lung parenchyma, and also to provide protection and moisture to the airways. Mucociliary clearance also takes part in pulmonary elimination, which with
exhalation Exhalation (or expiration) is the flow of the breath out of an organism. In animals, it is the movement of air from the lungs out of the airways, to the external environment during breathing. This happens due to elastic properties of the lungs, ...
removes substances discharged from the
pulmonary capillaries A capillary is a small blood vessel from 5 to 10 micrometres (μm) in diameter. Capillaries are composed of only the tunica intima, consisting of a thin wall of simple squamous endothelial cells. They are the smallest blood vessels in the body: ...
into the alveolar space.


Components

In the
respiratory tract The respiratory tract is the subdivision of the respiratory system involved with the process of respiration in mammals. The respiratory tract is lined with respiratory epithelium as respiratory mucosa. Air is breathed in through the nose to th ...
, from the
trachea The trachea, also known as the windpipe, is a Cartilage, cartilaginous tube that connects the larynx to the bronchi of the lungs, allowing the passage of air, and so is present in almost all air-breathing animals with lungs. The trachea extends ...
to the
terminal bronchiole The bronchioles or bronchioli (pronounced ''bron-kee-oh-lee'') are the smaller branches of the bronchial airways in the lower respiratory tract. They include the terminal bronchioles, and finally the respiratory bronchioles that mark the start o ...
s, the lining is of
respiratory epithelium Respiratory epithelium, or airway epithelium, is a type of ciliated columnar epithelium found lining most of the respiratory tract as respiratory mucosa, where it serves to moisten and protect the airways. It is not present in the vocal cords o ...
that is
ciliated The cilium, plural cilia (), is a membrane-bound organelle found on most types of eukaryotic cell, and certain microorganisms known as ciliates. Cilia are absent in bacteria and archaea. The cilium has the shape of a slender threadlike projecti ...
. The
cilia The cilium, plural cilia (), is a membrane-bound organelle found on most types of eukaryotic cell, and certain microorganisms known as ciliates. Cilia are absent in bacteria and archaea. The cilium has the shape of a slender threadlike projecti ...
are hair-like, microtubular-based structures on the luminal surface of the
epithelium Epithelium or epithelial tissue is one of the four basic types of animal tissue, along with connective tissue, muscle tissue and nervous tissue. It is a thin, continuous, protective layer of compactly packed cells with a little intercellul ...
. On each epithelial cell there are around 200 cilia that beat constantly at a rate of between 10 and 20 times per second. The
cilia The cilium, plural cilia (), is a membrane-bound organelle found on most types of eukaryotic cell, and certain microorganisms known as ciliates. Cilia are absent in bacteria and archaea. The cilium has the shape of a slender threadlike projecti ...
are surrounded by a
periciliary liquid layer Mucus ( ) is a slippery aqueous secretion produced by, and covering, mucous membranes. It is typically produced from cells found in mucous glands, although it may also originate from mixed glands, which contain both serous and mucous cells. It is ...
(PCL), a ''sol'' layer that is overlain with the ''gel'' layer of
mucus Mucus ( ) is a slippery aqueous secretion produced by, and covering, mucous membranes. It is typically produced from cells found in mucous glands, although it may also originate from mixed glands, which contain both serous and mucous cells. It is ...
. These two components make up the
epithelial lining fluid Mucus ( ) is a slippery aqueous secretion produced by, and covering, mucous membranes. It is typically produced from cells found in mucous glands, although it may also originate from mixed glands, which contain both serous and mucous cells. It is ...
(ELF), also known as the
airway surface liquid Mucus ( ) is a slippery aqueous secretion produced by, and covering, mucous membranes. It is typically produced from cells found in mucous glands, although it may also originate from mixed glands, which contain both serous and mucous cells. It is ...
(ASL), the composition of which is tightly regulated. The
ion channel Ion channels are pore-forming membrane proteins that allow ions to pass through the channel pore. Their functions include establishing a resting membrane potential, shaping action potentials and other electrical signals by gating the flow of io ...
s
CFTR Cystic fibrosis transmembrane conductance regulator (CFTR) is a membrane protein and anion channel in vertebrates that is encoded by the ''CFTR'' gene. Geneticist Lap-Chee Tsui and his team identified the CFTR gene in 1989 as the gene linked wit ...
, and
ENaC The epithelial sodium channel (ENaC), (also known as amiloride-sensitive sodium channel) is a membrane-bound ion channel that is selectively permeable to sodium ions (). It is assembled as a heterotrimer composed of three homologous subunits α ...
work together to maintain the necessary hydration of the airway surface liquid. An important factor is the rate of
mucin Mucins () are a family of high molecular weight, heavily glycosylated proteins (glycoconjugates) produced by epithelial tissues in most animals. Mucins' key characteristic is their ability to form gels; therefore they are a key component in most ...
secretion. The mucus helps maintain epithelial moisture and traps particulate material and
pathogen In biology, a pathogen ( el, πάθος, "suffering", "passion" and , "producer of") in the oldest and broadest sense, is any organism or agent that can produce disease. A pathogen may also be referred to as an infectious agent, or simply a germ ...
s moving through the airway, and its composition determines how well mucociliary clearance works.


Mechanism

Within the thin periciliary liquid layer the cilia beat in a coordinated fashion directed to the
pharynx The pharynx (plural: pharynges) is the part of the throat behind the mouth and nasal cavity, and above the oesophagus and trachea (the tubes going down to the stomach and the lungs). It is found in vertebrates and invertebrates, though its struc ...
where the transported mucus is either swallowed or coughed up. This movement towards the pharynx is either upward from the lower respiratory tract or downwards from the nasal structures clearing the mucus that is constantly produced. Each cilium is about 7 μm in length, and is fixed at its base. Its beat has two parts the power stroke, or effector stroke, and the recovery stroke. The movement of the cilia takes place in the periciliary liquid which is a little shorter in depth than the height of an extended cilium. This allows the cilia to penetrate the mucous layer during its full extension in the effector stroke, and to propel the mucus directionally, away from the cell surface. In the recovery stroke the cilium bends from one end to the other bringing it back to the starting point for the next power stroke. The returning cilia bend to immerse completely in the PCL which has the effect of reducing a reverse movement of mucus. The coordinated movement of the cilia on all the cells is carried out in a fashion that is not clear. This produces wave-like motions that in the trachea, move at a speed of between 6 and 20 mm per minute. The wave produced is a metachronal wave that moves the mucus. Many
mathematical model A mathematical model is a description of a system using mathematical concepts and language. The process of developing a mathematical model is termed mathematical modeling. Mathematical models are used in the natural sciences (such as physics, ...
s have been developed in order to study the mechanisms of ciliary beating. These include models to understand the generation and rhythm of the metachronal wave, and the generation of the force in the effective stroke of the cilium.


Clinical significance

Effective mucociliary clearance depends on a number of factors including the numbers of cilia, and their structure particularly their height, and the quality of the mucus produced that needs to be maintained at a correct
humidity Humidity is the concentration of water vapor present in the air. Water vapor, the gaseous state of water, is generally invisible to the human eye. Humidity indicates the likelihood for precipitation, dew, or fog to be present. Humidity depe ...
, temperature, and
acidity In computer science, ACID ( atomicity, consistency, isolation, durability) is a set of properties of database transactions intended to guarantee data validity despite errors, power failures, and other mishaps. In the context of databases, a sequ ...
. The cilia need to be able to move freely in the periciliary liquid layer and when this is impaired through damage to the cilia or by imbalances in the moisture or pH of the PCL, the mucus is unable to be cleared properly from the airways.
Cystic fibrosis Cystic fibrosis (CF) is a rare genetic disorder that affects mostly the lungs, but also the pancreas, liver, kidneys, and intestine. Long-term issues include difficulty breathing and coughing up mucus as a result of frequent lung infections. O ...
is a consequence of imbalances in the PCL. Accumulated mucus, apart from causing varying degrees of airflow obstruction, makes a breeding ground for bacteria that cause many respiratory infections that can seriously worsen existing lung disorders.
Obstructive lung disease Obstructive lung disease is a category of respiratory disease characterized by airway obstruction. Many obstructive diseases of the lung result from narrowing (obstruction) of the smaller bronchi and larger bronchioles, often because of excessive ...
s often result from impaired mucociliary clearance that can be associated with
mucus hypersecretion Mucus ( ) is a slippery aqueous secretion produced by, and covering, mucous membranes. It is typically produced from cells found in mucous glands, although it may also originate from mixed glands, which contain both serous and mucous cells. It is ...
and these are sometimes referred to as ''mucoobstructive lung diseases''. Studies have shown that the dehydration of airway surface liquid is enough to produce mucus obstruction even when there is no evidence of mucus hypersecretion.


Humidity

High
humidity Humidity is the concentration of water vapor present in the air. Water vapor, the gaseous state of water, is generally invisible to the human eye. Humidity indicates the likelihood for precipitation, dew, or fog to be present. Humidity depe ...
enhances mucociliary clearance. One study in dogs found that mucus transport was lower at an absolute humidity of 9 g water/m3 than at 30 g water/m3. Two methods of supporting this, particularly in
mechanical ventilation Mechanical ventilation, assisted ventilation or intermittent mandatory ventilation (IMV), is the medical term for using a machine called a ventilator to fully or partially provide artificial ventilation. Mechanical ventilation helps move air ...
, are provided by active and passive respiratory gas humidifiers.


See also

*
Airway clearance therapy Airway clearance therapy is treatment that uses a number of airway clearance techniques to clear the respiratory airways of mucus and other secretions. Several respiratory diseases cause the normal mucociliary clearance mechanism to become impair ...


References

{{Reflist


External links

Genetic disorders of mucociliary clearance consortium
Respiratory system Histology