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Submandibular gland

The submandibular gland is one of the three major paired salivary glands in humans, ranking as the second largest after the , and is located within the of the neck, inferior to the and between the anterior and posterior bellies of the . It functions as a mixed , producing predominantly serous (about 90% of its acini) with some mucous components, contributing approximately 70% of total unstimulated secretion, which aids in lubricating the oral cavity, initiating starch digestion via , and facilitating swallowing and oral health. Structurally, the submandibular gland is encapsulated by a layer of deep cervical fascia and divided into a larger superficial lobe and a smaller deep lobe by the , with the superficial portion lying lateral to the muscle and the deep portion medial to it. Its main excretory duct, known as Wharton's duct, measures about 5 cm in length and 1.5 mm in diameter, traversing the floor of the mouth to open at the sublingual caruncle on the anterior floor of the oral cavity. The gland receives parasympathetic innervation primarily from the branch of the via the , which stimulates serous secretion, and sympathetic innervation from the , which promotes mucous secretion and . Blood supply is derived from branches of the , including the submental and sublingual arteries, with venous drainage into the facial and that empty into the . Embryologically, the submandibular gland develops from the oral between 6 and 8 weeks of through branching , becoming well-differentiated by 13 to 16 weeks with the appearance of acinar cells, myoepithelial cells, and ductal structures, and it achieves full functionality by birth. Clinically, it is prone to conditions such as (salivary stones, accounting for 80-90% of cases in the major glands due to its viscous secretions and long duct), (inflammation), and neoplasms (though rare, comprising less than 2% of head and neck cancers, with about 50% being malignant). These features underscore its critical role in salivary and its vulnerability to affecting oral and systemic .

Anatomy

Gross anatomy

The submandibular glands are paired exocrine glands situated in the of the , with each gland serving as the second largest of the major salivary glands. They are located inferior and posterior to the , within the digastric triangle bounded superiorly by the inferior border of the , anteriorly by the anterior belly of the , and posteriorly by the posterior belly of the and the . Each gland weighs approximately 15 g and is irregularly shaped, resembling a in size, with typical dimensions around 3 cm in length and 1.5 cm in width. The gland is divided into a superficial lobe and a deep lobe, connected by a narrow that allows it to hook around the posterior border of the . The superficial lobe, which constitutes the majority of the gland, lies lateral to the and occupies the , while the smaller deep lobe lies medial to the and extends into the sublingual space on the lateral aspect of the hyoglossus muscle. This U-shaped configuration positions the gland superficial to the hyoglossus and , anterior to the and posterior belly of the digastric, medial to the , and lateral to the . The gland is encapsulated by a thin layer derived from the deep . Saliva from the submandibular gland drains via the , also known as Wharton's duct, which measures approximately 5 cm in length and 1-3 mm in diameter. The duct originates at the hilum of the deep lobe, courses anteriorly between the mylohyoid and hyoglossus muscles, passes medial to the , and travels along the medial aspect of the before opening into the oral cavity at the sublingual caruncle on the floor of the mouth, lateral to the . The opening, or , exhibits variability classified into four sialoendoscopic types: Type A (estuary-like, open ), Type B (normal, evident papilla and ), Type C (narrow, difficult access), and Type D (substantially closed or stenotic, with high complication risk during procedures).

Microscopic anatomy

The submandibular gland is classified as a compound tubuloacinar (also known as branched acinar) , consisting primarily of serous acini with a smaller proportion of mucous acini. Approximately 90-95% of the acini are serous, while mucous acini constitute about 5-10%, reflecting its mixed secretory nature. Scattered myoepithelial cells, which are contractile and surround the acini and smaller ducts, aid in expelling secretions. Serous acinar cells are pyramidal in shape, featuring basophilic basal cytoplasm rich in rough , a central spherical , and an apical region packed with granules that contain enzymes such as for . In contrast, mucous acinar cells are cuboidal to low columnar, with pale-staining cytoplasm due to large mucinogen granules that produce viscous, glycoprotein-rich secretions for lubrication; these acini are often capped by cells, a fixation artifact highlighting the serous component. The ductal system comprises three main types: short intercalated ducts lined by low cuboidal , which connect acini to striated ducts and may serve as sites; striated ducts featuring tall columnar cells with basal infoldings and numerous mitochondria for active and modification of secretions; and excretory (or interlobular) ducts, which are larger, lined by stratified columnar to squamous near the oral , draining multiple lobules. Supporting structures include delicate septa that divide the into 20-40 lobes, providing structural support and housing blood vessels and nerves. Intralobular is present and increases with age through fatty infiltration originating from septal regions, contributing to glandular in the elderly. Additionally, the contains immune cells, including cells that produce secretory IgA for mucosal defense, transported via ductal cells. While pronounced is observed in models, submandibular glands show subtle variations, with potentially greater serous predominance in males, though this requires further confirmation.

Vascular supply

The arterial supply to the submandibular gland is primarily derived from the facial artery, a branch of the external carotid artery, which enters the gland after crossing the inferior border of the mandible. Specific branches include the submental artery, which supplies the inferior and anterior portions, and multiple glandular branches that penetrate the gland capsule to nourish the acinar and ductal structures. Additional contributions come from the sublingual artery, a branch of the lingual artery, which provides vascularization to the superior and posterior aspects, with occasional direct twigs from the external carotid or lingual artery. Venous drainage follows a parallel course to the arterial supply, with blood exiting via anterior and posterior glandular veins that converge at the gland's hilum. These veins primarily drain into the common vein and sublingual vein, with venae comitantes accompanying the , ultimately converging into the . Variability exists in the exact drainage patterns, but the anterior vein and a central hilum vein consistently handle the majority of outflow. Lymphatic drainage begins within the gland, where intraglandular vessels course along the ductal pathways, collecting interstitial fluid from acinar and connective tissues. Efferent lymphatics exit to the (level Ib), located superficially in the beneath the , typically numbering 3 to 6 nodes adjacent to but not encapsulated within the gland. From these level Ib nodes, proceeds to the chain, particularly levels II (upper jugular) and III (middle jugular), facilitating regional clearance. At the microscopic level, the submandibular gland features a dense network enveloping the serous and mucous acini as well as the intercalated, striated, and excretory ducts, ensuring efficient delivery and modification of salivary secretions. These fenestrated capillaries, derived from terminal arterioles, form sinusoidal plexuses around the striated ducts and portal venules connecting acinar regions, supporting high metabolic demands during secretion.

Innervation

The submandibular gland receives dual autonomic innervation that regulates its secretory and vascular functions. Parasympathetic fibers originate from the superior salivatory nucleus in the pontine tegmentum, traveling via the branch of the (cranial nerve VII). These preganglionic fibers exit the skull through the , join the (a branch of the mandibular division of the ), and synapse in the . Postganglionic parasympathetic fibers then innervate the glandular acini and ducts, releasing that binds to muscarinic receptors (primarily M3), stimulating watery serous secretion rich in enzymes such as . This innervation also promotes , increasing blood flow to support fluid production and enzyme release. Sympathetic innervation arises from the , with postganglionic fibers traveling via the external carotid plexus along branches of the , such as the . These fibers release norepinephrine, which acts on α-adrenergic receptors to induce , thereby reducing glandular blood flow. Norepinephrine further modulates toward a more viscous, protein-rich mucous composition by promoting of secretory granules. Sensory innervation to the submandibular gland is provided by the (mandibular division of cranial nerve V3), which supplies general somatic sensation, including and touch, to the ductal and surrounding tissues in the floor of the mouth. The , a parasympathetic containing the bodies of postganglionic neurons, is located superior to the deep lobe of the gland within the paralingual space, adjacent to the . It serves as the primary relay for parasympathetic fibers en route from the to the glandular , ensuring targeted secretomotor control.

Embryological development

The submandibular gland originates as an endodermal outgrowth from the epithelium of the floor of the primitive mouth, specifically from epithelial buds around the sublingual folds, beginning at the end of the sixth week of gestation. This initial thickening, observed during Carnegie Stage 16 (approximately 5.5 to early sixth week), forms the primordium in the medial paralingual groove, closely associated with the lingual nerve and developing parasympathetic ganglion. By the late sixth week (Carnegie Stage 17), the epithelial condensation proliferates and invaginates into the underlying mesenchyme to create a solid bud, marking the onset of glandular morphogenesis. Branching into primitive acinar structures occurs during the pseudoglandular stage around the seventh to eighth week (Carnegie Stages 18–23), with the bud extending and forming initial lobes dorsal to the parasympathetic ganglion. Ductal development proceeds through the canalization of these solid epithelial cords, initiating in the canalicular stage around the seventh to seventh-and-a-half week (Carnegie Stages 20–21), where the main begins to develop a that extends toward the oral epithelium. By the tenth week, the primary ducts are more defined, with further branching leading to the formation of intercalated and striated ducts distinguishable by the 16th week of gestation. The , derived from cells that migrate to form parasympathetic neurons, integrates with the gland during this period, with innervation of the and ducts evident by the eighth week as nerves extend from the ganglion into the . Maturation of the gland advances with the of acinar cells, where pre-acinar end buds form by the 16th week, and serous acini predominate by the 24th week, indicating the establishment of secretory capacity. Mucous acinar components emerge later, becoming more prominent from the 31st week onward, with secretory products observable in acini by approximately 28 weeks, though full maturation of mixed seromucous features completes around birth. The gland's size increases substantially postnatally, supporting its functional role in the infant. Developmental anomalies such as or ductal of the submandibular gland are rare and often associated with genetic factors, including in the gene, which disrupt epithelial-mesenchymal interactions essential for branching . These lead to or absence of the gland, as seen in conditions like aplasia of lacrimal and salivary glands. The submandibular gland develops in coordination with the other major salivary glands, following the parotid (initiation in the sixth week) and preceding or overlapping with the (around the seventh week), but it is uniquely positioned beneath the of the in the developing floor of the mouth.

Physiology

Saliva production

The submandibular gland plays a major role in production, contributing 60-70% of unstimulated whole and 20-30% during stimulated conditions. The total daily output of from all glands is approximately 0.5-1.5 L, with the submandibular gland accounting for about 300-500 mL of this volume. Saliva secretion originates in the acinar cells, which are primarily serous with some mucous elements, producing an initial primary fluid rich in + and Cl-. This fluid is subsequently modified in the striated ducts through + reabsorption via +/+-, coupled with active secretion of + and HCO3- and passive Cl- absorption, yielding a hypotonic final . The resulting saliva is serous-dominant, featuring enzymes like α-amylase for starch breakdown into maltose and dextrins, antibacterial agents such as lysozyme that hydrolyzes bacterial cell walls, and mucins that provide lubrication and mucosal protection. Its pH typically ranges from 6.5 to 7.5, buffered by bicarbonates and phosphates. Production is stimulated mainly by neural mechanisms, with parasympathetic input via acetylcholine on M3 muscarinic receptors dominating to increase watery saliva volume and flow, while sympathetic noradrenergic stimulation via α- and β-receptors primarily alters composition by boosting protein output. Gustatory triggers, such as food intake, activate these pathways through acetylcholine release. Regulation includes feedback from osmoreceptors that suppress flow during dehydration to maintain water balance, alongside age-related declines in output and gender differences, where females exhibit lower flow rates linked to smaller gland sizes.

Regulatory functions

The submandibular gland contributes to immunological homeostasis through the secretion of secretory immunoglobulin A (sIgA), which provides mucosal immunity in the oral cavity by neutralizing pathogens and modulating the microbiota. Additionally, it releases , an protein that binds iron to inhibit and supports innate immune responses. The gland also produces the SGP-T , a thymoactive factor that regulates T-cell maturation and exerts anti-inflammatory effects by modulating production during immune challenges. In maintaining oral health, submandibular saliva buffers acids via ions (HCO₃⁻), neutralizing fluctuations from dietary acids and bacterial metabolism to prevent enamel demineralization. It facilitates tooth remineralization by supplying calcium (Ca²⁺) and (PO₄³⁻) ions, which promote formation and repair early carious lesions. The mucous components provide , forming a protective that reduces friction and prevents -related mucosal damage. Systemically, the gland influences regulation through the release of kinins and vasoactive peptides during sympathetic stimulation, which induce and hypotensive effects. It also supports via (EGF), a potent that accelerates epithelial regeneration and tissue repair in the oral and gastrointestinal tracts upon swallowing. Hormonal integration modulates submandibular function, with androgens binding to receptors in acinar cells to enhance glandular and secretory capacity, particularly during . Salivary output exhibits circadian rhythms, driven by clock , with lower flow rates during nighttime phases but basal secretion supporting overnight mucosal protection. Evolutionarily, the submandibular gland's mixed seromucous composition represents an adaptation for terrestrial feeding in vertebrates, balancing enzymatic digestion from serous components with viscous lubrication from mucous elements to facilitate bolus formation and on land. This dual nature likely arose to meet the demands of diverse diets, from carnivorous to omnivorous, enhancing survival in varied environments.

Clinical significance

Disorders

The submandibular gland is highly susceptible to , with approximately 80% to 90% of all salivary stones occurring in this location due to its dependent anatomic position, the long and tortuous course of Wharton's duct, and the production of more viscous, alkaline that promotes stone formation. These sialoliths are primarily composed of inorganic material (70% to 80%), including and , along with organic components such as and glycoproteins (20% to 30%). Clinical presentation typically involves intermittent, painful swelling of the gland, often worsening during meals due to ductal obstruction, and may progress to colicky pain or secondary if untreated. Infections affecting the submandibular gland encompass both bacterial and viral forms. Acute bacterial , or suppurative inflammation, is most commonly caused by or streptococcal species, leading to rapid glandular swelling, tenderness, and fever; risk factors include , to the head and , poor , and salivary stasis from medications or postoperative states. Viral infections can also involve the submandibular gland, though less frequently than the parotid; causes epidemic but may lead to submandibular involvement with bilateral swelling, while HIV-associated salivary gland disease manifests as painless enlargement due to lymphocytic infiltration and is linked to sicca-like symptoms. Tumors of the submandibular gland are uncommon, comprising about 8% to 14% of all salivary gland neoplasms, with an overall incidence of salivary gland malignancies estimated at 1 to 2 per 100,000 population annually as of recent epidemiological data. Benign tumors predominate, with accounting for approximately 50% of cases in this gland, presenting as a slow-growing, painless mass that may cause mild discomfort if large. Malignant tumors, which represent 40% to 50% of submandibular neoplasms, include (the most frequent, characterized by and indolent growth) and (often low-grade with cystic features); emerging studies suggest limited but increasing associations with human papillomavirus (HPV) in certain salivary malignancies, though primarily in minor glands rather than submandibular sites. Autoimmune and inflammatory disorders frequently target the submandibular gland. In Sjögren's syndrome, a systemic autoimmune condition, lymphocytic infiltration leads to glandular atrophy and reduced saliva production, often presenting with and recurrent swelling; the degree of infiltration correlates with that observed in minor salivary glands. involves fibroinflammatory changes with dense IgG4-positive infiltration and storiform in the submandibular gland, accompanied by elevated serum IgG4 levels; recent studies from 2023 to 2025 highlight favorable responses to corticosteroid therapy, with remission in glandular swelling and function preservation in responsive cases. Other disorders include , a or arising from mucus extravasation, often from the but extending into the as a "plunging ranula," resulting in a fluctuant floor-of-mouth or neck mass. Congenital cysts, such as cystic dilatations or ranula-like lesions from imperforate submandibular ducts, present at birth as painless swellings and arise from developmental ductal anomalies. Additionally, induced by medications, such as antihistamines or antidepressants, impairs submandibular secretion via muscarinic receptor blockade, leading to subjective oral dryness and increased caries risk without structural glandular changes.

Diagnosis

Diagnosis of submandibular gland disorders begins with a thorough clinical , which includes to assess for swelling, masses, or tenderness. The bimanual technique, involving simultaneous intraoral and external , allows for detailed evaluation of the gland and its duct, facilitating the detection of abnormalities such as calculi. Duct , a maneuver where gentle pressure is applied along the duct from posterior to anterior, can express or dislodge small stones, aiding in the identification of . Imaging modalities play a central role in confirming clinical findings and characterizing pathology. Ultrasound serves as the first-line imaging tool due to its non-invasiveness and ability to detect calculi greater than 2 mm with approximately 90% sensitivity, while Doppler assessment evaluates vascularity and inflammation. Computed tomography (CT) is particularly useful for identifying dense stones and assessing bony involvement, though it involves radiation exposure that must be weighed against benefits. Magnetic resonance imaging (MRI), often with sialographic contrast, excels in delineating soft tissue tumors, ductal anatomy, and perineural spread. Sialendoscopy represents a minimally invasive advancement in the , utilizing 1-2 mm endoscopes to visualize ductal structures, remove obstructions, and perform directly within the gland. This technique classifies papillae into types A-D based on morphology and accessibility, guiding procedural approaches and improving outcomes for obstructive diseases. techniques provide definitive histopathological diagnosis. (FNA) cytology offers about 80% accuracy in detecting malignancy, making it a standard for initial evaluation of masses. For suspected , core needle of the submandibular gland yields higher diagnostic yield by preserving tissue architecture for immunohistochemical analysis. Laboratory tests support diagnosis by identifying underlying causes. Elevated serum levels indicate glandular inflammation or obstruction, while microbial cultures from aspirated pus confirm bacterial infections such as . According to updated 2025 guidelines, tomography-computed tomography (PET-CT) is recommended for malignant tumors, offering superior assessment of metabolic activity and metastatic spread.

Treatment

Treatment of submandibular gland disorders begins with conservative measures for mild conditions such as , emphasizing hydration, warm compresses, and gentle gland massage to promote salivary flow and reduce inflammation. Sialagogues like lemon drops are often used to stimulate production and alleviate , while bacterial infections are managed with antibiotics such as amoxicillin-clavulanate. These approaches are effective for acute episodes and help avoid progression to more invasive interventions. For persistent issues like , interventional procedures such as sialendoscopy provide minimally invasive stone removal, often incorporating with success rates exceeding 95% in recent studies. Emerging updates in 2025 include robotic assistance to enhance precision during sialendoscopy, particularly for complex hilar stones in the submandibular gland. injections into the submandibular gland offer targeted relief for , reducing saliva production by up to 50-70% with effects lasting 3-6 months. Surgical options are reserved for neoplasms or cases, with submandibular gland excision performed via the approach to minimize risks to the marginal mandibular nerve. For malignant tumors, this may involve comprehensive resection akin to principles, combined with for involvement. In affecting the submandibular gland, initial treatment follows 2024 protocols with glucocorticoids (e.g., 0.5-1 mg/kg), followed by rituximab for steroid- or relapsing cases. Radiation and chemotherapy play key roles in salivary gland malignancies, with intensity-modulated radiation therapy (IMRT) employed to spare contralateral salivary structures and mitigate xerostomia. For advanced cases, systemic chemotherapy regimens like cisplatin-based protocols are integrated post-surgery. Emerging therapies focus on regenerative approaches for xerostomia and autoimmune damage, including phase II trials of gene therapy using AAV2-hAQP1 vectors to restore aquaporin expression and saliva production. Stem cell-based interventions, such as autologous mesenchymal stem cells enhanced with interferon-gamma, show promise in early 2025 trials for repairing radiation- or autoimmune-induced submandibular dysfunction, with initial data indicating improved salivary flow in pilot cohorts.

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