The distinction between mucus and phlegm
Mucus hypersecretion in response to pathophysiological stimulation
The regulation of mucus production and viscosity
References
Further reading
Phlegm is a form of respiratory mucus produced by the lungs. The airways between the larynx and the respiratory bronchioles are lined by columnar epithelium over which an airway surface liquid (ASL) lies. This layer is between 5 and 100 μm thick.
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The ASL is a tightly regulated liquid layer that protects the lung against infection. It is highly concentrated in secreted immunoglobulins, phospholipids, migratory cells, and signaling molecules. It comprises two distinct layers; the sol or periciliary liquid (PCL) layer, which interfaces the epithelial surface of the lungs and serves as a barrier between the second mucus layer. The primary function of the mucus layer is to entrap inhaled particles.
The mucus layer comprises high molecular weight, heavily glycosylated macromolecules comprising a tangled network of polymers. These polymeric glycoproteins are the products of the MUC5A and MUC5B genes; a protein core provides an anchor point for oligosaccharide side chains; the viscoelastic properties of mucus can be attributed to these oligosaccharides. Sulfhydryl bonds, formed between cysteine amino acids, contribute to the polymerization of the glycoprotein to result in the hallmark viscosity of the mucus.
The sol layer (periciliary liquid layer [PCL]) ensures that the mucus remains at an optimum distance (7 μm) from the underlying epithelia and affects the rate of mucosal clearance.
Collectively, the mucin and water contents, mono- and divalent ion concentrations, and pH of the ASL determine the properties of the mucin gel. The water content of the mucus is a tightly-regulated process driven by the movement of ions. Na+ reabsorption and Cl- secretion by the respiratory epithelial cells determine the passive movement of water across the epithelial layer.
The distinction between mucus and phlegm
Mucus and phlegm are considered to be two distinct forms of secretions. Mucus is considered to be a normal protective layering that exists in several areas of the body. These include the airway, eyes, nasal passages, and urogenital and gastrointestinal tracts. Mucus is an adhesive fiscal elastic gel produced in the airway by both the goblet cells and submucosal glands. High molecular weight mucus glycoproteins are responsible for forming linear polymers.
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Phlegm is produced in response to disease and can be difficult to clear from the body. It is often produced in response to inflammation and contains glycoprotein-based mucus alongside immunoglobulins, viruses, bacteria, and inflammatory cells. Phlegm is typically restricted in its definition, referring to the mucus produced by the respiratory system in response to inflammatory stimulation. Once phlegm is expectorated, it is referred to as sputum.
Mucus hypersecretion in response to pathophysiological stimulation
Mucus is considered to be part of the innate response to the respiratory tract; the mucus is created from goblet cells in the epithelium and submucosal glands. This secretion is an important feature of the inflammatory response. Several inflammatory mediators are responsible for stimulating mucus secretion and subsequent goblet cell hyperplasia (increased proliferation).
IL-3 is the most potent cytokine and is responsible for stimulating the MUC5AC and MUCB transcription, acting via the interleukin receptor IL-4Ra to activate the transcription factors Jak1 and STAT6. STAT6 subsequently switches on the MUC genes coma causing hyperplastic mucus production.
Several other cytokines also act in tandem to coordinate this response. The most potent stimulant of the secretion of mucus is ATP. Epidermal growth factor receptors are also responsible full regulating the hypersecretion of mucus.
The regulation of mucus production and viscosity
The amount of mucus produced is regulated predominantly by two mechanisms; the mucus-secreting cells and the mucociliary escalator. Goblet cells in the mucous membranes and submucosal glands in the respiratory, gastrointestinal, and reproductive systems govern mucus secretion. The mucociliary escalator is responsible for the clearance of the mucus towards the pharynx. Here, it is expelled by the cough reflex. In some incidences, however, dysregulation of mucus production and its viscosity.
This is notable in conditions such as chronic obstructive pulmonary disease and asthma. In these conditions, chronic irritation of the passage results in mucus hypersecretion. The excessive production of mucus overwhelms the mucociliary clearance mechanism. Consequently, excess mucin components MUC5AC and MUC5B in the airway accumulate, forming mucus plugs.
This further exacerbates the difficulty in clearing the airways; In response to this, an excess of inflammatory mediators is secreted. This augments mucous viscosity, resulting in further decreased clearance as well as the initiation of inflammation and fibrosis. The mucus is static and invaded by pathogenic bacteria; a positive feedback loop is initiated with an acute exacerbation of the condition.
This hypersecretion of airway mucus can obstruct the lumen, subsequently limiting the flow of air and accelerating the decline in lung function. Simultaneously, inflammatory responses compromise the rate of clearance by cilia, remove surfactants, and alter other biophysical properties of mucus.
Long term, this can result in recurrent airway infection, which further results in airway obstruction and remodeling by creating a continuous cycle. Evidence supports the causative role of chronic inflammation in mucus hypersecretion, which subsequently causes chronic airway inflammatory diseases.
While mucus production in the airways is normal, in excess, this causes phlegm production. This is considered abnormal, untypically an underlying pathological cause that typically results in the inflammatory response. In the absence of clearance of phlegm from the airways, a continuous cycle is created in which inflammation and lack of clearance exacerbate mucus production.
References
- Button BM, Button B. (2013) Structure and function of the mucus clearance system of the lung. Cold Spring Harb Perspect Med. doi:10.1101/cshperspect.a009720.
- Gupta R, Wadhwa R. Mucolytic Medications. [Updated 2021 Jul 10]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2021 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK559163/.
- Shen Y, Huang S, Kang J, et al. (2018) Management of airway mucus hypersecretion in chronic airway inflammatory disease: Chinese expert consensus (English edition). Int J Chron Obstruct Pulmon Dis. doi:10.2147/COPD.S144312.
- Tarran R. (2004) Regulation of airway surface liquid volume and mucus transport by active ion transport. Proc Am Thorac Soc. doi:10.1513/pats.2306014.