Pathophysiology Salivary Glands

8/10/2019 Pathophysiology Salivary Glands

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Pathophysiology of

salivary glands

PRODI KG FK UMY

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Salivary glands - Anatomyn Minor salivary glands

p Hundreds throughout mouth

n Major salivary glands (3 on each side offace)

p Parotid Gland (cheek)

p Submandibular gland (under angle of thejaw)

p Sublingual gland (under tongue)



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Minor salivary glandso The minor salivary glands are shown to be

organs whose function is decisively involved insymptoms such as xerostomia, stomatodynia,

and what is known as "denture intolerance".o Moreover, proper secretion of the palatine

glands is of crucial importance for the physicalretention of maxillary full dentures.

o There are no connections between secretoryrates of major and minor salivary glands.

o The effect of certain drugs on salivaryproduction and thus on the symptoms ofhyposalivation seems to be considerable.



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Parotid Gland

n Largest salivary glandn Most prone to bacterial sialadenitis

p Neonatal sialadenitis

p Acute bacterial sialadenitisp Chronic sialadenitisn Facial nerve bisects gland

p Superficial lobep Deep lobe

n Lies over maxillary bonep Superior to mandiblep Anterior to angle of jaw and auricle

n Stensen's Duct (Parotid Papilla)p Opens out adjacent to maxillary second molarp Milking parotid gland will expel drop at duct



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Gl. parotis



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Submandibular gland

n Second largest salivary gland

n Located within submandibular trianglep Recessed immediately below mandiblep Overlies hypoglossus muscle

p Hypoglossal and lingual nerves overly gland

n Wharton's Duct

p Opens adjacent to lingual frenulum



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Gl. submandibularis



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Physiology and Function

n Saliva functionp Controls oral pH

p Assists with food intaken Lubricates food bolus

n Contains amylase for carbohydratedigestion

p Mouth cleansing and oral hygienen Saliva limits oral pathogen growth

n Reduces oral odor (halitosis)



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Saliva contento Water 99,4%

o Organic compounds mucin, amylase,

lysozym, immunoglobulin Ao Anorganic compounds HCO3-, I, K, Cl,

Na, Ca, phosphates and others.



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Saliva productionn Differential saliva production by glands

p Unstimulated salivation (Salivary gland at

rest)n 1.5 Liters produced per day (basal rate)

n Major salivary glands: 90% of salivaproduced

n Submandibular and sublingual glands: 70%of saliva

p Stimulated salivationn Saliva production increases 5 fold

n Parotid gland produces majority of saliva



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Regulation of secretionn Innervation

p Parasympathetic innervation to major

salivary glandsn Otic ganglion fibers supply Parotid Gland

n Submandibular ganglion supplies othermajor glands

p Sympathetic innervation promotes saliva

flown Stimulates muscle contractions at salivary

ducts



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Testing of saliva productionThe kach test

o Unstimulated production collection of saliva

into container during 15 mino Stimulated production collection of saliva

during 15 min of chewing parafine gum

o Measuring of both amounts during 2x15 min

o Normal levels: greater than 8-10 mlo Pathologic levels: under 8 ml



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Xerostomiao Definition

n Decreased saliva production

o Physiology: Saliva plays vital rolein dental health

n Re-mineralizes enamel

n Buffers cariogenic acids

n Removes food residue

n Inhibits bacterial growth



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Causes of Xerostomian Medications (anticholinergic affect)

p Tricyclic Antidepressants

p Antispasmodics

p Neuroleptics

p MAO inhibitors

p Antiparkinsonian agents

p Lithium

p Central Adrenergic Agonists (antihypertensives)

p Diuretics

p Decongestantsp Antihistamines

p Bronchodilators



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Other causesp Radiation therapy to head and neckp Salivary Gland surgeryp Sjogren's Syndromep Amyloidosisp Human Immunodeficiency Virus (HIV Infection)p Diabetes Mellitusp Major Depressionp Granulomatous Disease

n Sarcoidosisn Tuberculosisn Leprosy



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Sjgren's syo Sjgren's syndrome (SS) is a relatively common

autoimmune connective tissue disorder. It is

most frequent in middle-aged women. About30% of patients with autoimmune disorderssuch as RA, SLE, scleroderma, vasculitis,mixed connective tissue disease, Hashimoto'sthyroiditis, primary biliary cirrhosis, or chronic

autoimmune hepatitis develop SS. Geneticassociations have been found (eg, HLA-DR3antigens in whites with primary SS).



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Pathophysiologyo Salivary, lacrimal, and other exocrine glands become

infiltrated with CD4+ T cells and with some B cells. The Tcells produce inflammatory cytokines (eg, IL-2,-interferon). Salivary duct cells also produce cytokines,eventually damaging the secretory ducts. Atrophy of thesecretory epithelium of the lacrimal glands causesdesiccation of the cornea and conjunctiva(keratoconjunctivitis sicca). Lymphocytic infiltration andintraductal cellular proliferation in the parotid gland causeluminal narrowing and in some cases formation ofcompact cellular structures termed myoepithelial islands;

atrophy of the gland can result. Dryness and GI mucosalor submucosal atrophy and diffuse infiltration by plasmacells and lymphocytes may cause symptoms (eg,dysphagia).



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Symptoms and Signso SS often affects the eyes or mouth initially and

sometimes exclusively. Dry eyes can produce irritationand photosensitivity. In advanced cases, the cornea isseverely damaged, epithelial strands hang from the

corneal surface (keratitis filiformis), and vision can beimpaired. Diminished saliva (xerostomia) results indifficulty chewing, swallowing, secondary Candidainfection, tooth decay, and calculi in the salivary ducts.Taste and smell may be diminished. Dryness may alsodevelop in the skin and in mucous membranes of thenose, throat, larynx, bronchi, vulva, and vagina. Dryness

of the respiratory tract may produce cough or lunginfections. Alopecia may occur. Parotid glands enlarge in1!3 of patients and are usually firm, smooth, and mildlytender. Chronic salivary gland enlargement is rarelypainful.



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o Arthritis occurs in about 1!3 of patients and is similar in

distribution and character to RA.o Other common extraglandular manifestations includegeneralized lymphadenopathy, Raynaud's phenomenon,parenchymal lung involvement (which is common butinfrequently serious), and vasculitis that can occasionallyaffect the peripheral nerves or CNS or cause skin rashes(including purpura), glomerulonephritis, or mononeuritismultiplex. Kidney involvement can produce renal tubularacidosis, impaired concentrating ability, kidney stones, orinterstitial nephritis. Pseudolymphoma, malignantlymphoma, or Waldenstrm's macroglobulinemia candevelop; patients develop non-Hodgkin lymphoma at 40times the normal rate and require careful follow-up.

Chronic hepatobiliary disease, pancreatitis (exocrinepancreatic tissue is similar to that of salivary glands), andfibrinous pericarditis may also occur.



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Diagnosiso SS should be suspected in patients with

scratchy or dry eyes or dry mouth, enlargedsalivary glands, purpura, or renal tubular

acidosis. Such patients should receivediagnostic tests that can include evaluation ofthe eyes and salivary glands and serologictests. Diagnosis is based on 6 criteria: eyesymptoms, oral symptoms, eye tests, salivary

gland involvement, autoantibodies, andhistopathology. SS is probable if" 3 criteria(including objective criteria) are positive anddefinite if" 4 criteria are positive.



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o Eye symptoms consist of" 3 mo ofeither dry eyes or use of tear substitutes

" 3 times/day; slit-lamp examination mayalso confirm dry eyes. Oral symptomsconsist of > 3 mo of daily dry mouthsensation, daily use of liquids to aid in

swallowing, or swollen salivary glands.



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Ceratoconjunctivitis sicca



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Candidasis oralis



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o The Schirmer test measures the quantity oftears secreted in 5 min after irritation from afilter paper strip placed under each lower eyelid.

A young person normally moistens 15 mm ofeach paper strip. Most people with SS moisten< 5 mm, although about 15% of test results are

false-positive and 15% are false-negative.Ocular staining with an eyedrop of rose bengalor lissamine green solution is highly specific.Slit-lamp examination showing a fluoresceintear breakup in < 10 sec is also suggestive.

o Salivary gland involvement can be confirmed by

abnormally low saliva production (# 1.5 mL/15min) as measured by salivary flow, sialography,or salivary scintiscanning, although these testsare less often used.



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o Serologic criteria have limited sensitivity and

specificity. They include antibodies to Ro (SS-A) or to nuclear antigens (termed La or SS-Bautoantibodies), antinuclear antibodies, or anelevated level of antibodies against -globulin.Rheumatoid factor is present in > 70% of

patients. ESR is elevated in 70%, 33% haveanemia, and up to 25% have leukopenia.

o Biopsy of minor salivary glands in the buccalmucosa should be performed if diagnosis is not

clear. Histopathologic involvement is confirmedif labial minor salivary glands show multiplelarge foci of lymphocytes with atrophy of acinartissue.



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Copyright 2003 BMJ Publishing Group Ltd.

Mason, G I et al. Mol Pathol 2003;56:52-59

Haematoxylin and eosin stained section of a labial gland from a patient withSjogren's syndrome showing (A) a periductal focus and (B) an area of more

extensive lymphocytic infiltration associated with a proliferating duct.



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Prognosis and Treatmento The disease is chronic, and death may

occasionally result from pulmonary infectionand, rarely, from renal failure or lymphoma.

Other connective tissue disorders usuallyworsen prognosis. There is no specifictreatment for the basic process.

o Dry eyes should be treated with OTC lubricatingeyedrops qid and prn. Skin and vaginal drynesscan be treated with lubricants.



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o Mouth dryness may be avoided by sippingfluids throughout the day, chewing sugarless

gum, and using a saliva substitute containingcarboxymethylcellulose as a mouthwash. Drugsthat decrease salivary secretion (eg,antihistamines, antidepressants, otheranticholinergics) should be avoided. Fastidiousoral hygiene and regular dental visits are

essential. Stones must be promptly removed,preserving viable salivary tissue. The pain ofsuddenly enlarged salivary glands is generallybest treated with warm compresses andanalgesics. Pilocarpine, 5 mg po tid to qid, orcevimeline HCl, 30 mg po tid, can stimulate

salivary production but should be avoided inpatients with bronchospasm and closed-angleglaucoma.



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Felty syo Young peopleo RA

o Splenomegaly

o Lymphadenopathy

o Anemia

o Thrombocytopenia

o Neutropenia

o Fever, loos of weight, tiredness

o Gramm/positive infections



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Management of xerostomia

o Management

n Consider stopping offending medication

n Commercial Saliva substituten Fluoride Supplementation

p Use 1.1% Fluoride gel daily

p Fluoride toothpaste

o Scrupulous dental care is essential



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Ptyalismo Pathophysiology

n Normal SubmandibularSaliva production 0.10-0.15 ml/min

n Ptyalism may result in 1-2 L/day ofSaliva loss

n Mechanisms of excessive Salivap Decreased Saliva swallowing and clearance

p Excessive Saliva production

p Neuromuscular diseasep Anatomic abnormalities



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Causes

o Saliva Overproduction

n Pregnancy (Ptyalism Gravidarum)

p Hyperemesis Gravidarumn Excessive starch intaken Gastrointestinal causes

p Gastric distention or irritationp Gastroesophageal Refluxp Acute Gastritis orGastric Ulcerp Pancreatitisp Liver disease



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n Medications and toxinsp Clozapine (Clozaril)p Potassium Chloratep Pilocarpinep Mercury Poisoning

p Copperp Arsenic poisoningp Antimony (used to treat parasitic infections)p Iodidep Bromidep Aconite (derived from Aconitum napellus root)p Cantharides



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n Stomatitis and localized oral lesionsp Aphthous Ulcersp Oral chemical burnsp Oral suppurative lesionsp Alveolar abscess

p Epulisn Oral infectious Lesions

p Dental Cariesp Diphtheriap Syphilis

p Tuberculosisp Small Pox



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o Difficulty Swallowing Salivan Infectionsp Tonsillitisp Retropharyngeal Abscessp Peritonsillar Abscessp Epiglottitis

p Mumpsp Chancrep Actinomycosis

n Bone Lesionsp Jaw fracture or dislocationp Ankylosis of the temporomandibular jointp Sarcoma of the jaw



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n Neuromuscular disordersp Cerebral Palsyp Mental retardationp Bulbar Paralysisp Pseudobulbar paralysisp Bilateral Facial Nerve Palsyp Cerebrovascular Accidentp Myasthenia Gravisp Hypoglossal Nerve palsyp Rabiesp Botulism

n Miscellaneous Causesp Radiation therapyp

Macroglossiap Dental malocclusion



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Managemento Non-specificn Treat specific causes as belown General measures to reduce Saliva

p Tooth brushing and mouthwash has drying effectp Reduce starch intake from diet

n Orthodontic appliances that aid swallowingp Upper plate to cover palate with movable beads

n Aids lip closuren Directs Saliva toward pharynx

n Anticholinergic Medications (if refractory to above)p Glycopyrrolate

n Adults: 0.5 to 2 mg PO qd to tid prnn Children: 0.04 mg/kg PO qd to tid prnn Scopolamine Patch 1.5 mg applied every 72 hours prn



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n Advanced procedures in severe and refractorycasesp Botulinum toxinA Salivary Gland injection

n Performed under ultrasound guidance

n Porta (2001) Psychiatry 70:538-40

p Radiation therapyn Borg (1998) Int J Radiat Oncol Biol Phys 41:1113-

9

p Surgeryn Submandibular Gland excision or duct relocation

n Parotid duct relocation or ligationn Salivary denervation (transtympanic neurectomy)



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o Specific measures

n Treat Nausea withAntiemeticsn Treat Gastroesophageal Refluxn Neuromuscular causes

p Speech pathology (e.g. swallowing mechanism)p Occupational therapy (e.g. head-back wheelchair)p

Neurology consultationp Biofeedback

n Oral diseases including dental malocclusionp Dentist or orthodontist

n Macroglossia orTonsillar Hypertrophyp Otolaryngology



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Sialadenitis

o Acute viral and bacterial infection

o Chronic bacterial, fibroproductive,post-actnic, specific (actinomycosis,syfylis, TBC), immunosialadenitis



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Acute viral sialadenitis

o Parotitis acuta

o Paramyxovirus

o Neurotrophic effect n.VIIIo Affection of gonadal tissues, pancreas,

central nervous systm

o Incubation: 18 days

o Whole life immunity



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Acute bacterial sialadenitis

o Ascendent ductal infection

o Dehydratation, diabetes, renal diseases,

wrong dental hygiene, inflammation inmouth and pharynx



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Chronic bacterial parotitis

o Predisposition ectasy of salivary ducts congenital, postinfectious, obstructive,

immunopatologicalo Sialography



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Chronic fibroproductivesialoadenitis of submandibularyglando Known as Kttner tumor

o Periductal sclerosis

o Extirpation of submandibular gland andhistological verification



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Sialolithiasis

o Stones composed of Ca salts often obstructsalivary glands, causing pain, swelling, andsometimes infection. Diagnosis is madeclinically or with CT, ultrasound, or sialogram.Treatment involves stone expression with salivastimulants, manual manipulation, a probe, orsurgery.



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o Eighty percent of stones originate in thesubmandibular glands and obstruct Wharton'sduct. Most of the rest originate in the parotidglands and block Stensen's duct. Only about1% originate in the sublingual glands. Multiplestones occur in about 25% of cases.

o Most salivary stones are composed of Caphosphate with small amounts of Mg andcarbonate. Patients with gout may have uricacid stones. Stone formation requires a niduson which salts can precipitate plus salivarystasis. Stasis occurs in patients who aredebilitated, dehydrated, have reduced foodintake, or take anticholinergics. Persisting orrecurrent stones predispose to infection of theinvolved gland (sialadenitis).



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Symptoms, Signs, and

Diagnosiso Stones cause glandular swelling and pain, particularly after

eating, which stimulates saliva flow. Symptoms may subsideafter a few hours. Relief may coincide with a gush of saliva.Some stones cause intermittent or no symptoms. If a stone islodged distally, it may be visible or palpable at the duct's outlet.

o If a stone is not apparent on examination, the patient can begiven a sialagogue (eg, lemon juice, hard candy, or some othersubstance that triggers saliva flow). Reproduction of symptomsis almost always diagnostic of a stone.

o CT, ultrasound, and sialography are highly sensitive and areused if clinical diagnosis is equivocal. Contrast sialography maybe performed through a catheter inserted into the duct and can

differentiate between stone, stenosis, and tumor. This techniqueis occasionally therapeutic.o Because 90% of submandibular calculi are radiopaque and

90% of parotid calculi are radiolucent, plain x-rays are notalways accurate. MRI is not indicated.



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Treatment

o Analgesics, hydration, and massage can relievesymptoms. Antistaphylococcal antibiotics can be used toprevent acute sialadenitis if started early. Stones maypass spontaneously or when salivary flow is stimulatedby sialagogues; patients are encouraged to suck a lemon

wedge or sour candy every 2 to 3 h.o Stones right at the duct orifice can sometimes beexpressed manually by squeezing with the fingertips.Dilation of the duct with a small probe may facilitateexpulsion.

o Surgical removal of stones succeeds if other methods

fail. Stones at or near the orifice of the duct may beremoved transorally, whereas those in the hilum of thegland often require complete excision of the salivarygland



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Enlargement of salivary glands

o Causes

n Unilateral Salivary enlargement

p Salivary Gland Tumorp Bacterial Sialadenitis

p Chronic Sialadenitis

p Sialolithiasis



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n Bilateral Salivary enlargement withhypofunctionp Viral Sialadenitis

p Sjogren's Syndrome

p Human Immunodeficiency Virus (HIV

Infection orAIDS)p Chronic granulomatous disease

n Sarcoidosis

n Tuberculosis

n Leprosy



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n Sialadenosis (asymptomatic parotid

enlargement)p Eating disorder (Anorexia, Bulimia)

p Cirrhosis

p Chronic Pancreatitis

p Endocrine Disordern Acromegaly

n Diabetes Mellitus

n Gonadal hypofunction



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Case report Bulimia nervosa (BN)

o case of a 22-year-old woman with BNwho had bilateral parotid gland swelling,

serum electrolyte alteration and nodental stigmata. Her principal concernwas the associated cosmetic deformity.



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o From the time of onset, the parotid glandswelling was persistent, painless and did notfluctuate in size. Palpation confirmed that theenlarged parotid glands were painless andnormal in tone. We did not see any cervicallymphadenopathy. Intraorally, the mucosa was

normally moist. All salivary ducts were patentwith a clear and adequate salivary flow exitingfrom each parotid orifice when the gland wasmanually milked. The patient was caries-free,and no restorations were present. There were

no signs of enamel erosion or periodontalabnormalities. The patient was excellent atfollowing an oral hygiene regimen.



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o Because she became increasingly alarmedabout the parotid gland swellings, she soughtmedical care in June 2002, without admitting tothe emetic problem. A computerizedtomography, or CT, scan was performed, andshe was told that the parotid glands wereenlarged and denser for unknown reasons butthat no pathology was present. She was notoffered any medical treatment.



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Figure 1. A. Right parotid

gland swelling (arrow). B. Left

parotid gland swelling (arrow).

Figure 2. Computerized

tomography scan with contrast

of moderately enlarged parotid

glands (arrows).



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o In December 2002, she visited anotherphysician, who performed a serologyevaluation. The patients serum potassium levelwas abnormally low (3.2 millimolar per liter;normal = 3.55.5 mmol/L).

o Hypokalemia was the only abnormalityuncovered by the physician. At this point, thepatient told her physician that she had BN.

o After potassium replacement therapy, she wasreferred to a psychiatrist and prescribed the

antidepressant paroxetine hydrochloride.



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o Bilateraland occasionally unilateralparotid glandswelling is not unusual in people with BN; the incidenceof parotid gland swelling has been reported to occur in 10

to 15 percent of people with BN.The submandibularsalivary gland is involved infrequently. The exactpathogenesis has not been determined.

o However, it generally is accepted that multiple emeticepisodes cause an autonomic neuropathy. With

sympathetic nerve impairment, individual acinar cellsenlarge because of zymogen granule engorgement.

o One explanation is that the sympathetic nerve supply tothe secreting acinar cell is concerned with the productionand secretion of zymogen, the precursor of amylase.

Because of sympathetic nerve dysfunction, there may bean increase in zymogen storage in the cell, owing toincreased production, decreased secretion of thegranules or both



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Benign tumors

n Benignp Mixed Tumor (Pleomorphic adenoma)

n Most Common benign Salivary Gland tumor

n May affect major Salivary Glandsn May also affect minorSalivary Glands (esp.

palate)

n Slow growing, nonulcerated painless tumor

n Occurs most commonly in women aged 30to 60 years

p Monomorphic Adenoma

p Warthin's Tumor



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Malignant tumors

n Malignantp Mucoepidermoid carcinoma (ages 20 to 50

years)

p Adenoid cystic carcinoma (age over 50years)



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o Locations: May affect any of

Salivary Glands

n Parotid Glandn Sublingual Gland

n Submandibular Gland

n MinorSalivary Glands

p Especially on posterolateral Hard Palatep Buccal mucosa and lips may also be

affected



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o Diagnosis

n Slow growing, painless massn Palpation reveals enlargement

n CT or MRI scan diagnostic

o Management

n Surgical biopsyo Prognosis

n Mucoepidermoid carcinoma

p Five year survival dependent on grading:50-90%

n Adenoid cystic carcinomap Five year survival: 65%

p Twenty year survival: 15%

Pathophysiology Salivary Glands

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