Salivary production and secretion

• The parotid is the largest type of salivary gland and is located in front of the ear and behind the lower jaw
• Parotid gland contributes 15-20% of resting saliva
• The parotid ducts opens adjacent to the upper second molar
• The submandibular is a walnut-sized gland located beneath the floor of the mouth
• The submandibular gland contributes 65-70% of resting salivary content
• The sublingual is the smallest major salivary gland
• The sublingual gland contributes 3-5% of resting saliva
• The area beneath the tongue is an area of high saliva flow, so the maxillary anterior teeth has no direct flow of saliva, and thus has a higher chance of issues such as dental caries
• During eating, stimulated conditions yield different figures, for example the parotid contributes 50% stimulated saliva
• The parotid gland secretes serous, watery saliva
• The submandibular gland secretes mixed serous and mucous saliva
• The sublingual gland secretes mucous saliva
• Serous cells are darkly stained as they contain zymogen granules (inactive enzymes) and have round nuclei; they produce a lot of proteins in an isotonic watery fluid
• Mucous cells are lightly stained and contain mucin, they appear bubbly in shape and have flattened nuclei that are pushed up against the basement membrane
• The basic structural unit of saliva production is the acinus cell
• Acini, no matter serous or mucous, are surrounded by the myoepithelial cells
• Myoepithelial cells contract and relax to push the saliva along the duct so it can be secreted into the oral cavity, and prevents distension of the end pieces
• The first duct encountered by saliva as they leave the acini is the intercalated ducts, which produces lactoferrin and lysozymes
• After the intercalated ducts are the striated ducts, which consists of columnar cells with a lot of mitochondria and infolding of the basement membrane to increase surface area; it modifies electrolyte content of saliva
• The final duct reached is the excretory duct, which is surrounded by a lot of connective tisue; inside the connective tissue is a lot of plasma cells involved in producing immunoglobulins for the saliva
• Around 1-1.5L of saliva is produced everyday, and the majority of it (99%) is water, while other substances include enzymes, mucin, lactoferrin, lysozymes, electrolytes, etc.
• Saliva hydrates and lubricates (with water and mucin) the oral tissues to facilitate mastication and swallowing
• Saliva allows for the solubilisation of food so it can be tasted (it is hypotonic and contains little electrolytes, so the taste buds can sense even a small bit of salt)
• Lactoferrin can bind iron, which is a major food source for microorganisms, thereby depriving their food source and inhibiting their growth
• Saliva contains lysozymes that can lyse bacterial cells and mucin to cleanse and aggregate microorganisms
• Salivary production is a two-step process: firstly the isotonic primary saliva is formed by the acinus cells, and secondly the hypotonic secondary/final saliva is formed by the striated ducts
• Primary saliva production: production of saliva that contains isotonic fluid rich in sodium chloride
• Primary saliva production: stimulation increases intracellular calcium levels → calcium-activated potassium channels and calcium-activated chloride channels are activated → sodium-potassium ATPase pumps out three sodium ions and two potassium ions in → sodium re-enters via NKCC → water follows the movement of ions through paracellular transport or through aquaporin 5
• Transporters involved in primary saliva secretion: Na/K-ATPase (basolateral), Na/K/2Cl cotranspoter (NKCC) (basolateral), calcium-activated potassium channel (basolateral), calcium-activated chloride channel (apical), aquaporin 5 (apical)
• Secondary saliva production modifies salivary electrolyte content in the striated ducts to produce hypotonic saliva
• Sodium-potassium ATPase pumps out three sodiums and pumps in two potassium → potassium accumulates and effluxes through potassium channel → ENaC reabsorbs sodium ions to replenish those pumped out → sodium-bicarbonate cotransporter allows sodium to re-enter the cell with bicarbonate → chloride-bicarbonate exchanger pumps bicarbonate into saliva and reabsorbs chloride → chloride leaves cells via chloride channels
• Transporters involved in secondary saliva production: sodium/potassium ATPase (basoalteral), sodium-bicarbonate cotransporter (basolateral), chloride channel (basoalteral), ENaC (apical), chloride-bicarbonate exchanger (apical), potassium channel (apical)
• Protein secretion into the saliva involves three different pathways: regulatory secretion, constitutive secretion, and transcytosis
• Constitutive secretion occurs via the fusion of secretory vesicles into the membrane; proteins are directly secreted when they are made
• Regulatory secretion accounts for 80-90% of protein secretion and is driven by cAMP
• Transcytosis is only for immunoglobulins (plasma cells produce dimeric IgA which is cleaved in the duct cell)
• The unstimulated flow rate of saliva is around 0.3ml/min, while the stimulated rate is around 2ml
• There are three specific triggers for salivary secretion: mechanical (act of chewing), gustatory and olfactory; they control saliva secretion through the autonomic nervous system
• The parasympathetic system releases acetylcholine, which binds to cholinergic muscarinic M3 receptors and provokes the secretion of watery saliva
• The sympathetic system releases norepinephrine, which binds to beta-adrenergic receptors and leads to the production of more mucous/protein-rich saliva