Illustration depicting the movement of mucus in the respiratory tract
In the humanrespiratory system, mucus is part of theairway surface liquid (ASL), also known asepithelial lining fluid (ELF), that lines most of therespiratory tract. The airway surface liquid consists of asol layer termed thepericiliary liquid layer and an overlyinggel layer termed the mucus layer. The periciliary liquid layer is so named as it surrounds thecilia and lies on top of the surface epithelium.[5][6][7] The periciliary liquid layer surrounding the cilia consists of a gel meshwork of cell-tethered mucins and polysaccharides.[8] The mucus blanket aids in the protection of thelungs by trapping foreign particles before they can enter them, in particular through the nose during normal breathing.[9]
Mucus is made up of a fluid component of around 95% water, themucin secretions from the goblet cells, and the submucosal glands (2–3% glycoproteins), proteoglycans (0.1–0.5%), lipids (0.3–0.5%), proteins, and DNA.[8] The major mucins secreted –MUC5AC andMUC5B - are large polymers that give the mucus itsrheologic orviscoelastic properties.[8][5] MUC5AC is the main gel-forming mucin secreted by goblet cells, in the form of threads and thin sheets. MUC5B is a polymeric protein secreted from submucosal glands and some goblet cells, and this is in the form of strands.[10][11]
In the airways—thetrachea,bronchi, andbronchioles—the lining of mucus is produced by specialized airway epithelial cells calledgoblet cells, andsubmucosal glands. Small particles such as dust, particulatepollutants, andallergens, as well asinfectious agents andbacteria are caught in the viscous nasal or airway mucus and prevented from entering the system. This process, together with the continual movement of thecilia on therespiratory epithelium toward theoropharynx (mucociliary clearance), helps prevent foreign objects from entering the lungs during breathing. This explains why coughing often occurs in those who smoke cigarettes. The body's natural reaction is to increase mucus production. In addition, mucus aids in moisturizing the inhaled air and preventstissues such as thenasal andairway epithelia from drying out.[12]
Mucus is produced continuously in therespiratory tract. Mucociliary action carries it down from the nasal passages and up from the rest of the tract to the pharynx, with most of it being swallowed subconsciously. Sometimes in times of respiratory illness or inflammation, mucus can become thickened with cell debris, bacteria, and inflammatory cells. It is then known asphlegm which may becoughed up assputum to clear the airway.[13][14]
Increased mucus production in theupper respiratory tract is a symptom of many common ailments, such as thecommon cold, andinfluenza. Nasal mucus may be removed by blowing the nose or by usingnasal irrigation. Excess nasal mucus, as with a cold orallergies, due to vascular engorgement associated with vasodilation and increased capillary permeability caused byhistamines,[15] may be treated cautiously withdecongestant medications. Thickening of mucus as a "rebound" effect following overuse of decongestants may produce nasal or sinus drainage problems and circumstances that promote infection.
During cold, dry seasons, the mucus lining nasal passages tends to dry out, meaning that mucous membranes must work harder, producing more mucus to keep the cavity lined. As a result, the nasal cavity can fill up with mucus. At the same time, when air is exhaled, water vapor in breath condenses as the warm air meets the colder outside temperature near the nostrils. This causes an excess amount of water to build up inside nasal cavities. In these cases, the excess fluid usually spills out externally through the nostrils.[16]
3D render showing accumulated mucus in the airways
In thelower respiratory tract impairedmucociliary clearance due to conditions such asprimary ciliary dyskinesia may result in mucus accumulation in the bronchi.[17] The dysregulation of mucus homeostasis is the fundamental characteristic ofcystic fibrosis, an inherited disease caused by mutations in theCFTR gene, which encodes achloride channel. This defect leads to the altered electrolyte composition of mucus, which triggers its hyperabsorption and dehydration. Such low-volume, viscous, acidic mucus has a reduced antimicrobial function, which facilitates bacterial colonisation.[18] The thinning of the mucus layer ultimately affects the periciliary liquid layer, which becomes dehydrated, compromising ciliary function, and impairing mucociliary clearance.[17][18] Arespiratory therapist can recommendairway clearance therapy which uses a number of clearance techniques to help with the clearance of mucus.[19]
In thelower respiratory tract excessive mucus production in the bronchi and bronchioles is known asmucus hypersecretion.[11] Chronic mucus hypersecretion results in the chronic productive cough ofchronic bronchitis,[20] and is generally synonymous with this.[21] Excessive mucus can narrow the airways, limit airflow, and accelerate a decline in lung function.[11]
Gastric glands are composed of epithelial cells (B),chief cells (D), andparietal cells (E). The chief and parietal cells produce and secrete mucus (F) to protect the lining of the stomach (C) against the harsh pH of stomach acid. The mucus is basic, while the stomach acid (A) is acidic.
In thehuman digestive system, mucus is used as a lubricant for materials that must pass over membranes, such as food passing down theesophagus. Mucus is extremely important in thegastrointestinal tract. It forms an essential layer in the colon and in the small intestine that helps reduce intestinal inflammation by decreasing bacterial interaction with intestinal epithelial cells.[22] Thegastric glands in thegastric mucosa producegastric juice which contains digestive enzymes andgastric acid which can damage the stomach wall. A thick layer of protective mucus is secreted by some gastric glands. This alkaline mucus lines the stomach and helps to form the gastric mucosal barrier, vital in the protection of the stomach wall.[23]
In the human female reproductive system,cervical mucus prevents infection and provides lubrication during sexual intercourse. The consistency of cervical mucus varies depending on the stage of a woman's menstrual cycle. Atovulation cervical mucus is clear, runny, and conducive tosperm; post-ovulation, mucus becomes thicker and is more likely to block sperm. Severalfertility awareness methods rely on observation of cervical mucus, as one of three primary fertility signs, to identify a woman's fertile time at the mid-point of the cycle. Awareness of the woman's fertile time allows a couple to time intercourse to improve the odds of pregnancy. It is also proposed as a method to avoid pregnancy.[24]
In general, nasal mucus is clear and thin, serving to filter air during inhalation. During times of infection, mucus can change color to yellow or green either as a result of trappedbacteria[25] or due to the body's reaction toviral infection. For example,Staphylococcus aureus infection may turn the mucus yellow.[26] The green color of mucus comes from the heme group in the iron-containing enzymemyeloperoxidase secreted by white blood cells as a cytotoxic defense during arespiratory burst.
In the case of bacterial infection, the bacterium becomes trapped in already-cloggedsinuses, breeding in the moist, nutrient-rich environment.Sinusitis is an uncomfortable condition that may include congestion of mucus. A bacterial infection in sinusitis will cause discolored mucus and would respond to antibiotic treatment; viral infections typically resolve without treatment.[27] Almost all sinusitis infections are viral and antibiotics are ineffective and not recommended for treating typical cases.[28]
In the case of a viral infection such ascold orflu, the first stage and also the last stage of the infection cause the production of a clear, thin mucus in the nose or back of the throat. As the body begins to react to the virus (generally one to three days), mucus thickens and may turn yellow or green.
Obstructive lung diseases often result from impaired mucociliary clearance that can be associated with mucus hypersecretion, and these are sometimes referred to asmucoobstructive lung diseases.[29] Techniques ofairway clearance therapy can help to clear secretions, maintain respiratory health, and prevent inflammation in the airways.[19]
A uniqueumbilical cord lining epithelial stem cell expressesMUC1, termed (CLEC-muc). This has been shown to have good potential in the regeneration of thecornea.[30][31]
Mucus is able to absorb water or dehydrate throughpH variations. The swelling capacity of mucus stems from thebottlebrush structure[32] ofmucin within which hydrophilic segments provide a large surface area for water absorption. Moreover, the tunability of swelling effect is controlled by polyelectrolyte effect.
Polymers with charged molecules are calledpolyelectrolytes. Mucins, a kind of polyelectrolyteproteoglycans, are the main component of mucus, which provides the polyelectrolyte effect in mucus.[33] The process of inducing this effect comprises two steps: attraction of counter-ions and water compensation. When exposed in physiological ionic solution, the charged groups in the polyelectrolytes attract counter-ions with opposite charges, thereby leading to a solute concentration gradient. An osmotic pressure is introduced to equalize the concentration of solute throughout the system by driving water to flow from the low concentration areas to the high concentration areas. In short, the influx and outflux of water within mucus, managed by the polyelectrolyte effect, contribute to mucus' tunable swelling capacity.[34]
The ionic charges of mucin are mainly provided by acidic amino acids includingaspartic acid (pKa=3.9) andglutamic acid (pKa=4.2). The charges of acidic amino acids will change with environmental pH value due toacid dissociation and association. Aspartic acid, for example, has a negative side chain when the pH value is above 3.9, while a neutrally charged side chain will be introduced as pH value drops below 3.9. Thus, the number of negative charges in mucus is influenced by the pH value of surrounding environment. That is, the polyelectrolyte effect of mucus is largely affected by the pH value of solution due to the charge variation of acidic amino acid residues on the mucin backbone. For instance, the charged residue on mucin is protonated at a normal pH value of the stomach, approximately pH 2. In this case, there is scarcely polyelectrolyte effect, thereby causing compact mucus with little swelling capacity. However, a kind of bacteria,Helicobacter pylori, is prone to producing base to elevate the pH value in stomach, leading to the deprotonation of aspartic acids and glutamic acids, i.e., from neutral to negative-charged. The negative charges in the mucus greatly increase, thus inducing the polyelectrolyte effect and the swelling of the mucus. This swelling effect increases the pore size of the mucus and decreases mucus' viscosity, which allows bacteria to penetrate and migrate into the mucus and cause disease.[35]
The high selective permeability of mucus plays a crucial role in the healthy state of human beings by limiting the penetration of molecules, nutrients, pathogens, and drugs. The charge distribution within mucus serves as a charge selective diffusion barrier, thus significantly affecting the transportation of agents. Among particles with various surfacezeta potentials, cationic particles tend to have a low depth of penetration, neutral ones possess medium penetration, and anionic ones have the largest penetration depth. Furthermore, the effect of charge selectivity changes when the status of the mucus varies, i.e., native mucus has a threefold higher potential to limit agent penetration than purified mucus.[36]
Mucus is also produced by a number of other animals.[37] Allfish are covered in mucus secreted from glands all over their bodies.[38]Invertebrates such assnails andslugs secrete mucus calledsnail slime to enable movement, and to prevent their bodies from drying out. Theirreproductive systems also make use of mucus for example in the covering of theireggs. In the unique mating ritual ofLimax maximus the mating slugs lower themselves from elevated locations by a mucus thread. Mucus is an essential constituent ofhagfish slime used to deter predators.[39] Mucus is produced by theendostyle in sometunicates and larvallampreys to help in filter feeding.
^Althaus, M (March 2013). "ENaC inhibitors and airway re-hydration in cystic fibrosis: state of the art".Curr Mol Pharmacol.6 (1):3–12.doi:10.2174/18744672112059990025.PMID23547930.
^abMall, MA (March 2008). "Role of Cilia, Mucus, and Airway Surface Liquid in Mucociliary Dysfunction: Lessons from Mouse Models".Journal of Aerosol Medicine and Pulmonary Drug Delivery.21 (1):13–24.doi:10.1089/jamp.2007.0659.PMID18518828.S2CID18362681.
^Han, Leo; Taub, Rebecca; Jensen, Jeffrey T. (November 2017). "Cervical mucus and contraception: what we know and what we don't".Contraception.96 (5):310–321.doi:10.1016/j.contraception.2017.07.168.PMID28801053.
^Harding, S. E.; Creeth, J. M. (1983-07-28). "Polyelectrolyte behaviour in mucus glycoproteins".Biochimica et Biophysica Acta (BBA) - Protein Structure and Molecular Enzymology.746 (1–2):114–119.doi:10.1016/0167-4838(83)90017-1.ISSN0006-3002.PMID6871229.
