Mucociliary clearance

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Mucociliary clearance
Bronchiolar epithelium 1 - SEM.jpg
Ciliated epithelium in bronchus with short microvilli on non-ciliated cells
Details
System Respiratory system
Identifiers
MeSH D009079
Anatomical terminology

Mucociliary clearance (MCC), mucociliary transport, or the mucociliary escalator describes the self-clearing mechanism of the airways in the respiratory system. [1] It is one of the two protective processes for the lungs in removing inhaled particles including pathogens before they can reach the delicate tissue of the lungs. The other clearance mechanism is provided by the cough reflex. [2] Mucociliary clearance has a major role in pulmonary hygiene.

Contents

MCC effectiveness relies on the correct properties of the airway surface liquid produced, both of the periciliary sol layer and the overlying mucus gel layer, and of the number and quality of the cilia present in the lining of the airways. [3] An important factor is the rate of mucin secretion. The ion channels CFTR and ENaC work together to maintain the necessary hydration of the airway surface liquid. [4]

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. [5] Cigarette smoke exposure can cause shortening of the cilia. [6]

Function

In the upper part of the respiratory tract, the nasal hair in the nostrils traps large particles, and the sneeze reflex may also be triggered to expel them. The nasal mucosa 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. 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. 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. [2]

Mucociliary clearance also takes part in pulmonary elimination, which with exhalation removes substances discharged from the pulmonary capillaries into the alveolar space. [7]

Scanning electron micrograph of the cilia projecting from respiratory epithelium in the trachea involved in mucociliary clearance. Bronchiolar epithelium 3 - SEM.jpg
Scanning electron micrograph of the cilia projecting from respiratory epithelium in the trachea involved in mucociliary clearance.

Components

In the respiratory tract, from the trachea to the terminal bronchioles, the lining is of respiratory epithelium that is ciliated. [8] The cilia are hair-like, microtubular-based structures on the luminal surface of the epithelium. 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 are surrounded by a periciliary liquid layer (PCL), a sol layer that is overlain with the gel layer of mucus. [9] These two components make up the epithelial lining fluid (ELF), also known as the airway surface liquid (ASL), the composition of which is tightly regulated. The ion channels CFTR, and ENaC work together to maintain the necessary hydration of the airway surface liquid. [10] An important factor is the rate of mucin secretion. The mucus helps maintain epithelial moisture and traps particulate material and pathogens moving through the airway, and its composition determines how well mucociliary clearance works. [11] [12]

Mechanism

Within the thin periciliary liquid layer the cilia beat in a coordinated fashion directed to the pharynx 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. [8]

Each cilium is about 7 μm in length, [13] and is fixed at its base. Its beat has two parts the power stroke, or effector stroke, and the recovery stroke. [14] [15] 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. [14] [16] 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. [16] The returning cilia bend to immerse completely in the PCL which has the effect of reducing a reverse movement of mucus. [14]

Cilia movement in a metachronal wave. Metachronal.svg
Cilia movement in a metachronal wave.

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. [2] The wave produced is a metachronal wave that moves the mucus. [5] Many mathematical models 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. [14]

Clinical significance

Accumulated mucus in the airways resulting from impaired mucociliary clearance, that may involve mucus hypersecretion. Respiratory Tract.jpg
Accumulated mucus in the airways resulting from impaired mucociliary clearance, that may involve mucus hypersecretion.

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, temperature, and acidity.

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 is a consequence of imbalances in the PCL. [9] 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 diseases often result from impaired mucociliary clearance that can be associated with mucus hypersecretion and these are sometimes referred to as mucoobstructive lung diseases. [12] 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. [17]

Humidity

High humidity 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. [18] Two methods of supporting this, particularly in mechanical ventilation, are provided by active and passive respiratory gas humidifiers.

See also

Related Research Articles

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The lungs are the most important 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 the heart. Their function in the respiratory system is to extract oxygen from the air and transfer it into the bloodstream, and to release carbon dioxide from the bloodstream into the atmosphere, in a process of gas exchange. The pleurae, which are thin, smooth, and moist, serve to reduce friction between the lungs and chest wall during breathing, allowing for easy and effortless movements of the lungs.

<span class="mw-page-title-main">Cilium</span> Organelle found on eukaryotic cells

The cilium is a membrane-bound organelle found on most types of eukaryotic cell. Cilia are absent in bacteria and archaea. The cilium has the shape of a slender threadlike projection that extends from the surface of the much larger cell body. Eukaryotic flagella found on sperm cells and many protozoans have a similar structure to motile cilia that enables swimming through liquids; they are longer than cilia and have a different undulating motion.

<span class="mw-page-title-main">Cystic fibrosis</span> Autosomal recessive disease mostly affecting the lungs

Cystic fibrosis (CF) is a rare genetic disorder that affects mostly the lungs, but also the pancreas, liver, kidneys, and intestine. The hallmark feature of CF is the accumulation of thick mucus in different organs. Long-term issues include difficulty breathing and coughing up mucus as a result of frequent lung infections. Other signs and symptoms may include sinus infections, poor growth, fatty stool, clubbing of the fingers and toes, and infertility in most males. Different people may have different degrees of symptoms.

<span class="mw-page-title-main">Respiratory tract</span> Organs involved in transmission of air to and from the point where gases diffuse into tissue

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.

<span class="mw-page-title-main">Bronchus</span> Airway in the respiratory tract

A bronchus is a passage or airway in the lower respiratory tract that conducts air into the lungs. The first or primary bronchi to branch from the trachea at the carina are the right main bronchus and the left main bronchus. These are the widest bronchi, and enter the right lung, and the left lung at each hilum. The main bronchi branch into narrower secondary bronchi or lobar bronchi, and these branch into narrower tertiary bronchi or segmental bronchi. Further divisions of the segmental bronchi are known as 4th order, 5th order, and 6th order segmental bronchi, or grouped together as subsegmental bronchi. The bronchi, when too narrow to be supported by cartilage, are known as bronchioles. No gas exchange takes place in the bronchi.

<span class="mw-page-title-main">Bronchiectasis</span> Disease of the lungs

Bronchiectasis is a disease in which there is permanent enlargement of parts of the airways of the lung. Symptoms typically include a chronic cough with mucus production. Other symptoms include shortness of breath, coughing up blood, and chest pain. Wheezing and nail clubbing may also occur. Those with the disease often get lung infections.

<span class="mw-page-title-main">Mucus</span> Secretion produced by mucous membranes

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 a viscous colloid containing inorganic salts, antimicrobial enzymes, immunoglobulins, and glycoproteins such as lactoferrin and mucins, which are produced by goblet cells in the mucous membranes and submucosal glands. Mucus serves to protect epithelial cells in the linings of the respiratory, digestive, and urogenital systems, and structures in the visual and auditory systems from pathogenic fungi, bacteria and viruses. Most of the mucus in the body is produced in the gastrointestinal tract.

<span class="mw-page-title-main">Primary ciliary dyskinesia</span> Medical condition

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<span class="mw-page-title-main">Cystic fibrosis transmembrane conductance regulator</span> Mammalian protein found in humans

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Mucoactive agents are a class of chemical agents that aid in the clearance of mucus or sputum from the upper and lower airways, including the lungs, bronchi, and trachea. Mucoactive drugs include expectorants, mucolytics, mucoregulators, and mucokinetics. These medications are used in the treatment of respiratory diseases that are complicated by the oversecretion or inspissation of mucus. These drugs can be further categorized by their mechanism of action.

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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 of the larynx, or the oropharynx and laryngopharynx, where instead the epithelium is stratified squamous. It also functions as a barrier to potential pathogens and foreign particles, preventing infection and tissue injury by the secretion of mucus and the action of mucociliary clearance.

<span class="mw-page-title-main">Epithelial sodium channel</span> Group of membrane proteins

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The lung microbiota is the pulmonary microbial community consisting of a complex variety of microorganisms found in the lower respiratory tract particularly on the mucous layer and the epithelial surfaces. These microorganisms include bacteria, fungi, viruses and bacteriophages. The bacterial part of the microbiota has been more closely studied. It consists of a core of nine genera: Prevotella, Sphingomonas, Pseudomonas, Acinetobacter, Fusobacterium, Megasphaera, Veillonella, Staphylococcus, and Streptococcus. They are aerobes as well as anaerobes and aerotolerant bacteria. The microbial communities are highly variable in particular individuals and compose of about 140 distinct families. The bronchial tree for instance contains a mean of 2000 bacterial genomes per cm2 surface. The harmful or potentially harmful bacteria are also detected routinely in respiratory specimens. The most significant are Moraxella catarrhalis, Haemophilus influenzae, and Streptococcus pneumoniae. They are known to cause respiratory disorders under particular conditions namely if the human immune system is impaired. The mechanism by which they persist in the lower airways in healthy individuals is unknown.

Airway basal cells are found deep in the respiratory epithelium, attached to, and lining the basement membrane.

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 impaired resulting in a build-up of mucus which obstructs breathing, and also affects the cough reflex. Mucus build-up can also cause infection, and inflammation, and repeated infections can result in damage to the airways, and the lung tissue.

References

  1. ↑ Antunes, MB; Cohen, NA (February 2007). "Mucociliary clearance--a critical upper airway host defense mechanism and methods of assessment". Current Opinion in Allergy and Clinical Immunology. 7 (1): 5–10. doi:10.1097/aci.0b013e3280114eef. PMID   17218804. S2CID   9551913.
  2. 1 2 3 Weinberger, Steven (2019). Principles of Pulmonary Medicine. Elsevier. pp. 286–287. ISBN   9780323523714.
  3. ↑ Widdicombe, J (October 2002). "Regulation of the depth and composition of airway surface liquid". Journal of Anatomy. 201 (4): 313–318. doi:10.1046/j.1469-7580.2002.00098.x. PMC   1570918 . PMID   12430955.
  4. ↑ Ghosh, A (October 2015). "Airway hydration and COPD". Cellular and Molecular Life Sciences. 72 (19): 3637–52. doi:10.1007/s00018-015-1946-7. PMC   4567929 . PMID   26068443.
  5. 1 2 Horani, A; Ferkol, T (September 2018). "Advances in the Genetics of Primary Ciliary Dyskinesia: Clinical Implications". Chest. 154 (3): 645–652. doi:10.1016/j.chest.2018.05.007. PMC   6130327 . PMID   29800551.
  6. ↑ De Rose, V (April 2018). "Airway Epithelium Dysfunction in Cystic Fibrosis and COPD". Mediators of Inflammation. 8: 1309746. doi: 10.1155/2018/1309746 . PMC   5911336 . PMID   29849481.
  7. ↑ "Pulmonary elimination". mesh.nlm.nih.gov. Retrieved 26 September 2019.
  8. 1 2 Hall, John (2011). Guyton and Hall Medical Physiology. Saunders. p. 473. ISBN   9781416045748.
  9. 1 2 Derichs, Nico (July 2011). "Hyperviscous airway periciliary and mucous liquid layers in cystic fibrosis measured by confocal fluorescence photobleaching". FASEB Journal. 25 (7): 2325–2332. doi: 10.1096/fj.10-179549 . PMC   3114535 . PMID   21427214.
  10. ↑ Ghosh, A (October 2015). "Airway hydration and COPD". Cellular and Molecular Life Sciences. 72 (19): 3637–52. doi:10.1007/s00018-015-1946-7. PMC   4567929 . PMID   26068443.
  11. ↑ Stanke, F. (2015). "The Contribution of the Airway Epithelial Cell to Host Defense". Mediators of Inflammation. 2015: 463016. doi: 10.1155/2015/463016 . PMC   4491388 . PMID   26185361.
  12. 1 2 Lewis, Brandon; Patial, Sonika (July 2019). "Immunopathology of Airway Surface Liquid Dehydration Disease". Journal of Immunology Research. 2019: 2180409. doi: 10.1155/2019/2180409 . PMC   6664684 . PMID   31396541.
  13. ↑ Fahy, John; Dickey, Burton (December 2010). "Airway Mucus Function and Dysfunction". The New England Journal of Medicine. 363 (23): 2233–2247. doi:10.1056/NEJMra0910061. PMC   4048736 . PMID   21121836.
  14. 1 2 3 4 Xu, L; Jiang, Y (July 2019). "Mathematical Modeling of Mucociliary Clearance: A Mini-Review". Cells. 8 (7): 736. doi: 10.3390/cells8070736 . PMC   6678682 . PMID   31323757.
  15. ↑ Wan, KY (7 December 2018). "Coordination of eukaryotic cilia and flagella". Essays in Biochemistry. 62 (6): 829–838. doi:10.1042/EBC20180029. PMC   6281475 . PMID   30464007.
  16. 1 2 Benjamin Lewin (2007). Cells. Jones & Bartlett Learning. p. 357. ISBN   978-0-7637-3905-8 . Retrieved 28 August 2019.
  17. ↑ Mall, M (April 2016). "Unplugging Mucus in Cystic Fibrosis and Chronic Obstructive Pulmonary Disease". Annals of the American Thoracic Society. 13: S177-85. doi:10.1513/AnnalsATS.201509-641KV (inactive 31 January 2024). PMID   27115954.{{cite journal}}: CS1 maint: DOI inactive as of January 2024 (link)
  18. ↑ Pieterse, A; Hanekom, SD (2018). "Criteria for enhancing mucus transport: a systematic scoping review". Multidisciplinary Respiratory Medicine. 13: 22. doi: 10.1186/s40248-018-0127-6 . PMC   6034335 . PMID   29988934.

Genetic disorders of mucociliary clearance consortium

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