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gingiva and anterior part of the hard palate Serous minor glands=von Ebner below the sulci of the circumvallate and folliate papillae of the tongue Glands of Blandin-Nuhn: ventral tongue Palatine, glossopalatine glands are pure mucus Weber glands
Embryology The major salivary glands develop from the 6th-8th weeks of gestation as outpouchings of oral ectoderm into the surrounding mesenchyme. The parotid develops first, growing posteriorly as the facial nerve advances anteriorly; eventually, the fully developed parotid surrounds VII. However, the Parotid is the last to become encapsulated, after the lymphatics develop, resulting in its unique anatomy with entrapment of lymphatics in the parenchyma of the gland
the intercalated duct cells and myoepithelial cells oncocytic tumors originate from the striated duct cells acinous cell tumors originate from the acinar cells, Mucoepidermoid tumors and squamous cell carcinomas develop in the excretory duct cells
Salivary epithelial cells are often included within these lymph nodes, leading to development of Warthin s tumors and Lymphoepithelial cysts within the Parotid gland. The other major salivary glands do NOT have intraparenchymal lymph nodes.
Normal Histology
Mucous cells
Production, storage, and secretion of proteinaceous material; smaller enzymatic component -more carbohydrates-->mucins=more prominent Golgi -less prominent (conspicuous) rough endoplasmic reticulum, mitochondria -less interdigitations
Serous cells
Seromucus cells=secrete also polysaccharides They have all the features of a cell specialized for
Serous cells
The secretory process is continuous but cyclic There are complex foldings of cytoplasmic
Myoepithelial cells
One, two or even three myoepithelial cells in each salivary and piece body Four to eight processes Desmosomes between myoepithelial cells and secretory cells Myofilaments frequently aggregated to form dark bodies along the course of the process
Myoepithelial cells
The myoepithelial cells of the intercalated ducts
are more spindled-shaped and fewer processes Ultrastructurally very similar to that of smooth muscle cells Functions of myoepithelial cells
Support secretory cells Contract and widen the diameter of the intercalated ducts Contraction may aid in the rupture of acinar cells of epithelial origin
Macromolecular component
Synthesis of proteins RER, Golgi apparatus Ribosomes RER posttranslational
modification (N- & O-linked glycosylation) Golgi apparatus Secretory granules Exocytosis Endocytosis of the granule membrane
release of Ca2+
opening of channels K+, Cl- Na+ in K+ and Cl- in Also another electrolyte transport mechanism through HCO3-
Functions
Protection lubricant (glycoprotein) barrier against noxious stimuli;
microbial toxins and minor traumas washing non-adherent and acellular debris formation of salivary pellicle calcium-binding proteins: tooth protection; plaque
Functions
Buffering (phosphate ions and
bicarbonate) bacteria require specific pH conditions plaque microorganisms produce acids from sugars
Functions
Digestion
neutralizes esophageal contents dilutes gastric chyme forms food bolus brakes starch
Functions
Tissue repair
bleeding time of oral tissues shorter than other tissues resulting clot less solid than normal remineralization
Functions
Taste
solubilizing of food substances that can be sensed by receptors trophic effect on receptors
Function of Saliva
At least 8 major functions of saliva have been identified: 1) Moistens oral mucosa. Mucin layer is the most important nonimmune defense mechanism in the oral cavity. 2) Moistens dry food and cools hot food. 3) A medium for dissolved foods to stimulate the taste buds. 4) Buffers oral cavity contents due to high concentration of bicarbonate ions. 5) Digestion. Alpha-amylase, contained in saliva, breaks 1-4 glycoside bonds, while lingual lipase helps break down fats. 6) Controls bacterial flora of the oral cavity. 7) Mineralization of new teeth and repair of precarious enamel lesions. Saliva is high in calcium and phosphate. 8) Protects the teeth. This signifies a saliva protein coat on the teeth which contains antibacterial compounds. Thus, salivary hypofunction results in dental caries.
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2) Oral Lichen Planus (usually painful) 3) Burning Mouth Syndrome (normal appearing oral mucosa with a subjective sensation of burning) 4) Recurrent aphthous ulcers 5) Dental caries. The best way to evaluate salivary function is to measure the salivary flow rate in stimulated (e.g., by using a parasympathomimetic as pilocarpine) and unstimulated states. Xerostomia is NOT a reliable indicator of salivary hypofunction. There is a hierarchy of sensory stimuli such that swallow>mastication>taste>smell>sight>thought. Stimulation results in an increase in total salivary flow from 0.3 cc/min to >1 cc/min. The salivary response is directly related to a subject s state of hunger
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Structures at the Angle of the Mandible Medial relations of the parotid: the styloid process and its muscles separate the gland from the internal jugular vein Internal carotid artery The last four cranial nerves Lateral wall of the pharynx
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Parotid Bed
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Fascia
The parotid is enclosed in a split in the investing fascia The parotid lymph nodes lie both on and below the parotid gland Antero-inferiorly, the fascia is thickened to form the stylomandibular ligament; the only structure that separates the parotid from the submandibular glands
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Relation of the Facial Nerve and Parotid The parotid develops in the crotch formed by the 2 divisions of the facial nerve As it enlarges it overlaps the nerve trunks, the superficial and deep parts fuse and the nerve becomes buried within the gland It is not a sandwich
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Facial Nerve
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Nerve Injury
Clinical examination of the Parotid should include examination of the Facial nerve Malignant tumors of the parotid may involve VII and cause facial palsy, while benign tumors never affect VII During Superficial Parotidectomy, the nerve is exposed posteriorly in the space bet the bony canal of external auditory meatus and the mastoid process It is then traced anteriorly into the gland to excise the gland superficial to nerve branches
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Submandibular Gland
Large superficial lobe and a small deep lobe, that connect around the mylohyoid Superficial lobe lies at the angle of the Jaw, wedged bet the mandible and mylohyoid and overlapping the digastric
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Facial artery
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Clinical Applications
Submandibular LN are adherent to the gland and partly between it and the mandible Differentiating bet submandibular LN and Salivary gland: The salivary gland can be palpated bimanually as it extends into the floor of the mouth. The Lymph Nodes are only felt below the mandible. LN may be multiple and a space separates them from the mandible
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Clinical Applications
A stone in the submandibular duct can be felt bimanually in the floor of the mouth and can be seen if large The presence of LN adherent to the gland makes removal of the gland part of block neck dissection
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Autonomic Innervations
Parasympathetic Stimulation results in abundant, watery saliva with a decrease in [amylase] in saliva and an increase in [amylase] in the serum. Acetylcholine is the active neurotransmitter, binding at muscarinic receptors in the salivary glands. The parasympathetic nervous system is the primary instigator of salivary secretion. Parasympathetic Interruption to salivary glands results in atrophy, while sympathetic interruption doesn t cause a significant change. It was once thought that the sympathetic nervous system antagonizes the parasympathetic nervous system, but this is now known not to be true
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Autonomic Innervation
In the case of the parotid, parasympathetic fibers originate from CN IX In the case of the Submandibular and Sublingual glands, the parasympathetic fibers originate in CN VII
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Sympathetic Innervation
Stimulation by the sympathetic nervous system results in a scant, viscous saliva rich in solutes with an increase in [amylase] in the saliva and no change in [amylase] in the serum. For all of the salivary glands, these fibers originate in the Superior Cervical ganglion and travel with arteries to reach the glands: 1) External Carotid artery for the Parotid 2) Lingual artery for the Submandibular, and 3) Facial artery in the case of the Sublingual.
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History
Determine if solitary parotid or more generalized salivary gland involvement Progression of enlargement Inciting factors for enlargement Nature and duration of symptoms Pain: character, severity, frequency
Associated Symptoms - Head and Neck - Systemic Review of Systems Medications Past Medical History Social History (eg. alcohol use) Family History
Physical Examination
Complete Head and Neck Exam Inspection / Palpation of Salivary Glands - enlargement (unilateral/bilateral) - consistency - tenderness - mobility Differentiate diffuse gland enlargement from discrete mass or anatomic anomaly
Parotid gland: Inspect the pre- and infra-auricular region, observing for symmetry. Palpate the parotid gland. Lacrimal gland: Have the patient close their eyes and observe the upper and outer aspect of the upper lid. The lid is normally smooth and symmetrical. Gently retract the upper lid and have the patient gaze to the opposite side. The lacrimal gland is located under the lid near the outer angle. Submandibular gland: Observe the submandibular region. Tilt the patient's head forward and gently roll your fingers over the inner surface of the mandible.
Physical Examination
Oral Cavity -Moisture level -Dentition status -Salivary duct output amount character -Palpate for sialoliths, masses Salivary duct probing
LABORATORY
Chemical analysis of saliva
Anti-SS-A, anti-SS-B, and rheumatoid factor
may be present in autoimmune diseases. Saliva may be cultured, which is helpful, and it may be analyzed chemically, which is rarely helpful. Most laboratories cannot perform useful tests on saliva. Dental researchers had hopes for several decades that analysis of saliva would be of diagnostic importance. Saliva has such wide variations in composition that analysis has produced little of diagnostic value.
Laboratory Studies HIV test Angiotensin converting enzyme (Sarcoid) Autoantibodies (Sjogrens) - Rheumatoid factor - Antinuclear antibodies - Anti-SSA, Anti-SSB Antineutrophil cytoplasmic antibody;ANCA(Wegeners) Hormone levels (eg. TSH)
EXPLORATORI METHODS
1. X-rays without preparation. Plainfilm The views of the salivary glands are taken full face and profile of the parotid, or the submandibular gland, depending on the pathology. A 3/4 x-ray view of the submandibular gland is preferred. These different x-rays can show not only radio opaque stones in the salivary glands, but also old calcifications in a lymph node.
2. Regular occlusal x-rays of the floor of the mouth. These occlusal views are helpful in revealing an opaque stone in the submandibular gland, or in the duct. The procedure entails actually putting film in the mouth to obtain an x-ray image. Regular occlusal X-rays can only be made at the submandibular and sub-lingual glands levels. They either entail the positioning of an occlusal image source in an orthogonal position in relation to the mouth's floor, or scanning the ray to obtain a view of the forward sub-mandibular gland. This results in the visualisation of calcification in the glandular area. These are most frequently stones but may also be calcified lymph node
SIALOGRAPHY
3. Sialography Technique A cannula is introduced into the parotid or submandibular ducts and is used to inject contrast enhancing products (eg Lipiodol) to outline the ramifications of the ductal systems of these glands, showing their patterns and calibers. This examination can be performed on everyone, including children over the age of 4. The injection should be of no more than 0.5 to 1 cc, and injected very slowly. This examination is painless if done smoothly. The only contraindication is an allergic reaction to iodine.It must be know in such cases, pre-medication with corticosterods will permit the examination. Results Basically, sialography is prescribed each time there is a suspicion of an inflammatory syndrome, especially if there is the possibility of a lithiasis, in order to visualize the exact caliber of the duct and the position of the stone, as opposed to calcification within a lymph node.
Conventional sialography.
IMAGING
Simple ranula.
BIOPSY
Incisional biopsy -Under local anesthesia, a biopsy of the tail of the gland
may be obtained by an experienced surgeon without injury to the facial nerve. Fine-needle aspiration biopsy frequently is diagnostic for tumors and may be helpful to identify cell types and to obtain material for cultures when the clinical picture suggests infection. Excisional biopsy of a labial minor salivary gland may be diagnostic when the clinical picture suggests Sjgren syndrome.
PLUNGING RANULA
RANULA
Pleomorphic Adenoma
Pleomorphic Adenoma
SUBMAXILLECTOMY
Warthin's Tumor
Warthin's tumor (benign papillary cystadenoma lymphomatosum) the second most common benign tumor of the parotid gland It accounts for 2-10% of all parotid gland tumors Bilateral in 10% of the cases may contain mucoid brown fluid in FNA
Monomorphic Adenoma
Similar to Pleomorphic Adenoma except no mesenchymal stromal component Predominantly an epithelial component More common in minor salivary glands (upper lip) 12% bilateral Rare malignant potential Types: Basal Cell Adenoma Canicular Adenoma Myoepithelioma Adenoma Clear Cell Adenoma Membranous Adenoma Glycogen-Rich Adenoma
Malignant Tumors
Approximately 20-25% of parotid, 35-40% of submandibular tumors, 50% of palate tumors, and > 90% of sublingual gland tumors are malignant The most common benign salivary tumor is pleomorphic adenoma, comprising 50% of all salivary tumors and 65% of parotid gland tumors The most common malignant salivary tumor is the mucoepidermoid carcinoma, comprising 10% of all salivary gland neoplasms and 35% of malignant salivary gland neoplasms, occurring most often in the parotid gland.
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PAROTID CANCER
Mucoepidermoid Carcinoma
MECs contain two major elements: mucin-producing cells and epithelial cells of the epidermoid variety (Epidermoid and Mucinous components). MEC is divided into low-grade (well differentiated). High-grade (poorly differentiated).
benign histomorphologic picture but by occasional malignant behavior. These lesions are treated by surgical excision Bilateral involvement occurs in 3% of patients, making acinic cell carcinoma the second-most common neoplasm, after Warthin s tumor, to exhibit bilateral
Mucoepidermoid Carcinoma
Mucoepidermoid carcinoma (MEC) is the most common malignant tumor of the parotid gland and the second-most common malignancy (adenoid cystic carcinoma is more common) of the submandibular and minor salivary glands. Stained +ve by musicarmine. MECs constitute approximately 35% of salivary gland malignancy, and 80% to 90% of MECs occur in the parotid gland.
Hodgkin's Lymphoma
Hodgkin's disease
involving the parotid gland. Note the ReedSternberg cell. (Fine needle aspiration, Pap, 630x)
PARTIAL PAROTIDECTOMY
Inflammatory Enlargement
Acute Sialadenitis Viral Bacterial Radiation Medication Chronic Sialadenitis Obstructive Granulomatous Autoimmune HIV-associated
Sialadentitis
What is Sialadentitis?
Simply inflammation of the salivary glands Can be due to a number of factors including:
Mumps infection Coxackie Virus Parainfluenza Systemic Disease
Sialadentitis: Etiology
May be infectious: May be caused by bacterial or viral infections May be non-infectious: May be caused by systemic disease such as Sjogren s or Sarcoidosis or even by radiation therapy May be Post-Surgical: Called Surgical Mumps Pt kept without fluids and given atropine causes xerostomia predisposing to inflammation May be Pharmacological: Drugs causing xerostomia May be architectural: Block of the salivary gland due to a stone
SIALOLITHIASIS
Sialolithiasis
Recurrent painful parotid gland swelling Episodes of acute bacterial sialadenitis Abscess formation Chronic sialadenitis Gland atrophy
Parotitis
Definition:
Inflammation of the Parotid Gland
Parotitis
Definition:
Inflammation of the Parotid Gland
Will see rapid swelling of the parotids bilaterally Acute pain when salivating
Bacterial Saladenitis
Bacterial saladinitis usually occurs after surgery
most commonly abdominal surgery. The possible reason may be temporary lack of ductal flow which can develop while atropine sulphate is administered while delivering general anesthesia which allows ascending infections and thus pyogenic bacteria can inhibit the ducts. Due to this there is pain and swelling . Purulent exudate can be expressed from the orifice of the duct.
Chronic:
Eliminate causative agent:
Get rid of salivary stone/ other blockage
Warm Compresses Sialogogues Possible surgical resection Ligation of the duct in hopes of atrophy
Radiation Sialadenitis
Inflammatory process due to radiation effect on gland parenchyma, dose-related injury Serous glands and acini most susceptible External beam radiation Radioactive iodine Painful, tender glands; swelling; xerostomia Chronic injury can result Some benefit with sialendoscopy
Chronic Sialadenitis
Non-granulomatous chronic inflammatory condition Etiology may be unclear by history - primary obstruction / secondary infection - primary infection / secondary obstruction Recurrent painful gland enlargement common - exacerbation with eating Relief of duct obstruction, sialogogues, glandular massage, warm heat Gland resection for medical therapy failure
Sjogren s Syndrome
Sjogrens Syndrome
It is a group of autoimmune conditions with a
marked predilection for woman, it has an intense T lymphocyte mediated autoimmune process in salivary and the lacrimal glands as on of its most prominent component Sjogren s syndrome exhibits T cells infiltration and replaces the glandular parenchyma
Sjogrens Syndrome
Sjogren s Syndrome:
objective evidence of keratoconjunctivitis sicca characteristic pathologic features of the salivary glands 2 out of 3 of:
recurrent chronic idiopathic salivary gland swelling unexplained xerostomia connective tissue disease
% OF PATIENTS
35 30 25 20 15 10 5 0
Onset At diagnosis
AGE
Stomatitis Oral Ulcers Cracked, crocodile skin tongue Carious Teeth Parotid Gland Enlargement Certain Tests can be done
Tongue, Carious
% positive
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60 30 95
Tests and Studies: Scintigraphy administer radioactive substance Scintigraphy (Nuclear Medicine)
in order to show the physiology and state of the biological process:
Scintigraphy Moderate Marked Normal diagnosis involvement involvement Degree of None Mild Severe xerostomia Salivary flow 1.60 0.42 0.00 rate (ml/5min/gland)
Tests and Studies: Schirmer s Test of whether the eye has enough tears to keep moist A test
Procedure:
Piece of filter paper inserted for several minutes (usually 5) and moisture recorded <5 ml in 5 minutes is characteristic of Sjogren s Syndrome
Pathophysiology: Continued
Multifactorial disease SS is sometimes called autoimmune epithelitis in which there is apoptosis of epithelial cells leading to degradation products and leading to antinuclear autoantigens to the immune system Molecules within the TNF family play a big role in the polyclonal activation of B Cells. This, in turn leads to autoantibodies There is known inhibition of healthy glands and/or the muscarinic receptors (via antibodies) and also abnormal function of aquaporins leading to poor function of remaining healthy glandular structure There is prolonged/permanent activation of autoreactive B cells favoring oncogenic activity and possible development of B Lymphoma
Pathological
Kidney involvement
(Interstitial Nephritis/Glomerulonephritis)
To Treat Xerophthalmia:
Stimulation for tears:
Cyclosporin A Pilocarpine Cimeviline
Treatment: Continued
Treatment for Salivary Gland Enlargement:
Local moist heat Antibiotic Therapy NSAIDs Rule out a Lymphoma
SARCOIDOSIS
HEERFORD SDR
Sarcoidosis
Systemic granulomatous disease, unclear etiology < 1/3 patients - painless salivary gland swelling Nontender and multinodular glands; xerostomia ACE elevation (50-80%) Most patients have pulmonary involvement CXR- hilar nodes, adenopathy, parenchymal infiltrates Noncaseating granulomas on histopathology Treatment supportive; steroids in select patients
Non-Inflammatory Enlargement
Acute Enlargement Neoplasm Miscellaneous: Trauma Pneumoparotitis Anesthesia/ Endoscopy Chronic Enlargement Obesity Sialadenosis - Endocrine - Nutritional - Medication - Idiopathic Amyloidosis
Sialadenosis (Sialosis)
Non-inflammatory, non-neoplastic gland parenchyma enlargement Bilateral parotid enlargement most common Can be recurrent or persistent Wide variety of systemic conditions causative Unifying factor - neuropathic alteration of the autonomic innervation of salivary acini (Batsakis) Diagnosis primarily clinical, exclusion of others Complete metabolic and endocrine evaluation
Sialadenosis - Etiologies
Endocrine Disorders - Diabetes Mellitus (1/4) - Hypothyroidism Alcoholism (autonomic neuropathy) Nutritional Disorders - Bulimia (1/3) - Deficiency condition eg. protein (alcoholism) vitamin (niacin, thiamine, vit. A)
Sialadenosis - Etiologies
Medications - Direct effect on gland eg. iodine compounds - Drug side-effect (adrenergic, cholinergic) eg. antihypertensives (guanethidine) antiemetics (phenothiazine) antiepileptics (phenobarbital) bronchodilators (isoproterenol) Idiopathic - diagnosis of exclusion
SIALADENOSIS - Treatment
Correct underlying disorder Pilocarpine - Bulimia Consider parotidectomy only for unacceptable cosmetic deformity unresponsive to medical therapy