SALIVA

Contents: Introduction Salivary gland anatomy Functions of saliva Secretion of saliva Composition of saliva Organic components Inorganic components Hypofunction of salivary glands Xerostomia Ptyalism Burning mouth syndrome Saliva:A diagnostic fluid Diagnostic imaging of salivary glands

Saliva lacks the drama of blood,the emotion of tears and toil of sweat but it still remains one of the most important fluids in the human body. Its status in the oral cavity is at par with that of blood i.e. to remove waste,supply nutrients and protect the cells

What is saliva? Saliva is composed of more than 99% water and less than 1% solids,mostly electrolytes and proteins,the latter giving saliva its characteristic viscosity The term saliva refers to the mixed fluid in the mouth in contact with the teeth and oral mucosa,which is often called ‘whole saliva’ Normally the daily production of whole saliva ranges from 0.5 to 1.0 litres

90% of the whole saliva is produced by three paired major salivary glands Parotid Gland Submandibular gland Sublingual gland

Secretions from many minor salivary glands in the oral mucosa (labial,lingual,palatal,buccal,glossopalatine and retromolar glands) also contribute (less than 10%) to the saliva secretion In addition,whole saliva contains contributions from non-glandular sources such as gingival crevicular fluid in an amount that depends on the periodontal status of the patient

Whole saliva,in contrast to glandular saliva,also contains vast amounts of epithelial cells from the oral mucosa and millions of bacteria. These components give whole saliva its cloudy appearance,which is different from glandular saliva, which is transparent like water.

Salivary gland anatomy Parotid gland: Largest of all the salivary glands Purely serous gland that produce thin,watery amylase rich saliva Superficial portion lies in front of external ear & deeper portion lies behind the ramus of mandible Stensen's Duct (Parotid Papilla) Opens out adjacent to maxillary second molar

Submandibular gland Second largest salivary gland Mixed gland Located in the posterior part of floor of mouth,adjacent to medial aspect of mandible & wrapping around the posterior border of mylohyoid muscle Wharton's Duct Opens beneath the tongue at sub-lingual caruncle lateral to the lingual frenum

Sublingual gland: Smallest salivary gland Mixed gland but mucous secretory cells predominate Located in anterior part of floor of mouth between the mucosa and mylohyoid muscle Opens through series of small ducts (ducts of rivinus) opening along the sub-lingual fold & often through a larger duct(bartholin’s duct) that opens with the wharton’s duct at the sub-lingual caruncle

Multifunctionality Amylases, Cystatins, Carbonic anhydrases, Histatins, Mucins, Peroxidases Carbonic anhydrases, Histatins Anti- Bacterial Buffering Amylases, Mucins, Lipase Cystatins, Mucins Anti- Viral Digestion Salivary Functions Mineral- ization Anti- Fungal Cystatins, Histatins, Proline- rich proteins, Statherins Histatins Lubricat- ion &Visco- elasticity Tissue Coating Amylases, Cystatins, Mucins, Proline-rich proteins, Statherins Mucins, Statherins

MAJOR FUNCTIONS OF SALIVA Fluid or Lubricant Saliva coats the mucosa & helps to protect against mechanical,chemical and thermal irritation. It also assists smooth airflow,speech & swallowing. Buffering Saliva helps to neutralise plaque pH after eating thus reducing time for demineralization caused by bacterial acids produced during sugar metabolism Remineralization Saliva is supersaturated with ions,which facilitate remineralization of teeth

Digestion Breakdown of starch-amylase Fat-lingual lipase Moistening and lubricative properties of saliva:allow the formation & swallowing of food bolus Anti-microbial action Lysozyme,lactoferrin,sialoperoxidase help against pathogenic microorganisms specifically Immunoglobulins and secretory IgA also act against microorganisms.

Cleansing Clears food and aids swallowing. Agglutination immunoglobulins and secretory IgA cause agglutination of specific microorganisms, preventing their adherence to oral tissues. Mucins as well as specific agglutinins also aggregate microorganisms.

Pellicle formation Derived from salivary proteins,it forms a protective diffusion barrier to acids from plaque. Taste Saliva has a low threshold concentration of sodium chloride,sugar,urea etc allowing perception of taste to occur. It acts as a solvent allowing mixing and interaction of food with taste buds

Water balance Osmoreceptors act as per state of hydration of the body to transmit information to the hypothalamus Tissue repair A variety of growth factors & other biologically active peptides and proteins are present in small quantities in saliva.under experimental conditions,many of these promote tissue growth & differentiation,wound healing and other beneficial effects.

Regulation of saliva secretion Afferent signals from sensory receptors in mouth Trigeminal,facial,glossopharyngeal nerves Salivary nuclei in the medulla oblongata of brain Parasympathetic nerve bundle sympathetic nerve bundle salivary glands

Innervation Parasympathetic innervation to major salivary glands Otic ganglion fibers supply Parotid Gland Submandibular ganglion supplies other major glands Sympathetic innervation promotes saliva flow Stimulates muscle contractions at salivary ducts

Saliva secretion is also controlled by the conditioned reflexes. Besides receiving impulses from the afferents,the salivary nuclei also receives impulses from higher centers of brain which leads to release of variety of neurotransmitters resulting in facilatory or inhibitory effects As a result of such control,unstimulated salivation is inhibited during sleep,fear & mental depression Stress may increase or decrease salivary flow

THE SECRETORY UNIT The basic building block of all salivary glands ACINI - water and ions derived from plasma Saliva formed in acini flows down DUCTS to empty into the oral cavity.

Salivary secretion:two step model Formation of primary saliva: Initiated by binding of neurotransmitters in the acinar cell membranes Acinar cell loses K⁺ to the interstitium & Cl⁻ to the lumen Gain of Cl⁻ creates negative potential in the lumen,driving interstitial Na⁺ into lumen thereby restoring electroneutrality Water flux follws the movement of salt into the lumen for osmotic reasons,resulting in acinar cell shrinkage Outcome is the formation of isotonic primary saliva

Ductal modification of primary saliva: Occurs principally through reabsorption & secretion of electrolytes The luminal & basolateral membrane have abundant transporters that function to produce a net reabsorption of Na⁺ & Cl⁻ resulting in formation of hypotonic final saliva The final electrolyte composition of saliva varies depending on the salivary flow rate

At high flow rates,saliva is in contact with the ductal epithelium for shorter time & Na⁺ & Cl⁻ concentration increase & K⁺ concentration decrease At low flow rates,the electrolyte concentration change in the opposite direction The HCO₃⁻ concentration increases with increased flow rates,reflecting the increased secretion of HCO₃⁻ by the acinar cells to drive fluid secretion

Hypotonic final saliva into mouth TWO STAGE HYPOTHESIS OF SALIVA FORMATION Most proteins Na+ Cl- resorbed Hypotonic final saliva into mouth Water & electrolytes Some proteins electrolytes K+ secreted Isotonic primary saliva

Saliva production Differential saliva production by glands Unstimulated salivation (Salivary gland at rest) 1.5 Liters produced per day (basal rate) Major salivary glands: 90% of saliva produced Submandibular and sublingual glands: 70% of saliva Stimulated salivation Saliva production increases 5 fold Parotid gland produces majority of saliva

Flow rate (ml/min) RESTING 0.2-0.4 0.04 0.1 STIMULATED 2.0-5.0 1.0-2.0 WHOLE PAROTID SUBMANDIBULAR RESTING 0.2-0.4 0.04 0.1 STIMULATED 2.0-5.0 1.0-2.0 0.8 pH 6.7-7.4 6.0-7.8

Testing of saliva production Unstimulated production – collection of saliva into container during 15 min Stimulated production – collection of saliva during 5 min of chewing 1g paraffin Unstimulated whole saliva flow rates of <0.1 ml/min. and stimulated whole saliva flow rate’s of <1.0 ml/min. are considered abnormally low& indicative of marked salivary hypofunction.

Recent work in Sjogren syndrome is beginning to identify changes in salivary cytokine & other protein levels that may have diagnostic significance . Saliva may play a greater diagnostic role in monitoring for the presence and concentrations of drugs of abuse and therapeutic agents.

COMPOSITION OF SALIVA

Inorganic components Saliva compositon

Calcium and phosphate Help to prevent dissolution of dental enamel 1.4 mmol/lt. (1.7 mmol/lt. in stimulated saliva) 50% in ionic form sublingual > submandibular > parotid Phosphate 6 mmol/lt. (4 mmol/lt. in stimulated saliva) 90% in ionic form pH around 6 - hydroxyapatite is unlikely to dissolve Increase of pH - precipitation of calcium salts => dental calculus

Hydrogen Bicarbonate Buffer Low in unstimulated saliva, increases with flow rate Pushes pH of stimulated saliva up to 8 pH 5.6 critical for dissolution of enamel Defence against acids produced by cariogenic bacteria Derived actively from CO2 by carbonic anhydrase

Other ions Fluoride Thiocyanate Sodium, potassium, chloride Low concentration, similar to plasma Thiocyanate Antibacterial (oxidated to hypothiocyanite OSCN- by active oxygen produced from bacterial peroxides by lactoperoxidase) Higher conc. => lower incidence of caries Smokers - increased conc. Sodium, potassium, chloride Lead, cadmium, copper May reflect systemic concentrations - diagnostics

Organic components Saliva composition

Organic components of saliva Mucins Proline-rich proteins Amylase Lipase Peroxidase Lysozyme Lactoferrin Secretory IgA Histatins Statherin Blood group substances, sugars, steroid hormones, amino acids, ammonia, urea

Mucins Products of acinar cells from submandibular,sublingual and some minor salivary glands. Asymmetrical molecule with open, randomly organized structure Glycoproteins - protein core with many oligosaccharide side chains attached by glycosidic bond Hydrophillic Unique rheological properties (e.g., high elasticity, adhesiveness, and low solubility)

Major salivary mucins are: MG1-adsorbs tightly to the tooth surface contributing to the enamel pellicle formation, thereby protecting the tooth surface from chemical & physical attack including acidic challenges MG2-also binds to the tooth surface but is easily displaced, however it promotes clearance of oral bacteria by aggregation

Mucin Functions Tissue Coating Lubrication Protective coating about hard and soft tissues Primary role in formation of acquired pellicle Concentrates anti-microbial molecules at mucosal interface Lubrication Align themselves with direction of flow (characteristic of asymmetric molecules) Increases lubricating qualities (film strength) Film strength determines how effectively opposed moving surfaces are kept apart

Aggregation of bacterial cells Bacteria adhere to mucins-result in surface attachment, or Mucin-coated bacteria may be unable to attach to surface Bacterial adhesion Mucin oligosaccharides mimic those on mucosal cell surface React with bacterial adhesins, thereby blocking them

Amylases Produced by acinar cells of major salivary glands Metabolizes starch and other polysaccharides into glucose & maltose Calcium metalloenzyme Parotid; 30% of total protein in parotid saliva “Appears” to have digestive function - inactivated in stomach, provides disaccharides for acid- producing bacteria It is also present in tears, serum, bronchial, and male and female urogenital secretions A role in modulating bacterial adherence

Lingual Lipase Secreted by sublingual gland and parotid gland Involved in first phase of fat digestion Hydrolyzes medium to long chain triglycerides Important in digestion of milk fat in newborn Unlike other mammalian lipases, it is highly hydrophobic and readily enters fat globules

Statherins Produced by acinar cells in salivary glands Acidic peptide containing relatively high levels of proline,tyrosine and phosphoserine Inhibits spontaneous precipitation of calcium phosphate salts from supersaturated saliva & favours remineralization Calcium phosphate salts of dental enamel are soluble under typical conditions of pH and ionic strength

Supersaturation of calcium phosphates maintain enamel integrity Also an effective lubricant for the tooth surface thus protecting it from physical forces

Proline-rich Proteins (PRPs) Like statherin, PRPs are also highly asymmetrical Present in the initially formed enamel pellicle and in “mature” pellicles 2 types: Basic Acidic Both are secretory products of major salivary glands Acidic proline-rich protein binds tightly to hydroxyapatite and prevents precipitation of calcium phosphate and thereby protecting the enamel surface & preventing demineralization Also bind to oral bacteria including mutans streptococcci

Role of PRPs in enamel pellicle formation Acquired enamel pellicle is 0.1-1.0 µm thick layer of macromolecular material on the dental mineral surface Pellicle is formed by selective adsorption of hydroxyapatite-reactive salivary proteins, serum proteins and microbial products such as glucans and glucosyl-transferase Pellicle acts as a diffusion barrier, slowing both attacks by bacterial acids and loss of dissolved calcium and phosphate ions

Remineralization of enamel and calcium phosphate inhibitors Early caries are repaired despite presence of mineralization inhibitors in saliva Sound surface layer of early carious lesion forms impermeable barrier to diffusion of high mol.wt. inhibitors. Still permeable to calcium and phosphate ions Inhibitors may encourage mineralization by preventing crystal growth on the surface of lesion by keeping pores open

Calculus formation and calcium phosphate inhibitors Calculus forms in plaque despite inhibitory action of statherin and PRPs in saliva May be due to failure to diffuse into calcifying plaque Proteolytic enzymes of oral bacteria or lysed leukocytes may destroy inhibitory proteins Plaque bacteria may produce their own inhibitors

Interaction of oral bacteria with PRPs and other pellicle proteins Several salivary proteins appear to be involved in preventing or promoting bacterial adhesion to oral soft and hard tissues PRPs are strong promoters of bacterial adhesion Amino terminal: control calcium phosphate chemistry Carboxy terminal: interaction with oral bacteria Interactions are highly specific

Lactoferrin Iron-binding protein Prevents iron from being used by microorganism that require it for metabolism Nutritional immunity (iron starvation) Some microorganisms (e.g., E. coli) have adapted to this mechanism by producing enterochelins. bind iron more effectively than lactoferrin iron-rich enterochelins are then reabsorbed by bacteria Lactoferrin, with or without iron, can be degraded by some bacterial proteases.

Lysozyme Positively charged enzymatic protein which binds to salivary anions of various types (bicarbonate,fluoride,iodide,nitrate) and forms a complex which binds to cell wall of bacteria & destabilizes the cell wall Present in numerous organs and most body fluids Also called muramidase Alters glucose metabolism in sensitive bacteria Causes aggregation,contributing to clearance of bacteria from the oral cavity

Histatins A group of histidine-rich proteins The major form in the oral cavity are histatin 1,histatin 3 and histatin 5 Binds to hydroxyapatite and prevent calcium phosphate precipitation from a supersaturated saliva and favour remineralization Potent inhibitors of Candida albicans growth

Cystatins Are inhibitors of cysteine-proteases Are present in many body fluids Prevent the action of potentially harmful proteases on the soft tissue of oral cavity Considered to be protective against unwanted proteolysis bacterial proteases lysed leukocytes Also inhibits calcium phosphate precipitation Promotes supersaturation of saliva with calcium and phosphate,thus protecting the tooth surface

Salivary peroxidase systems Sialoperoxidase (SP, salivary peroxidase) Produced in acinar cells of parotid glands Also present in submandibular saliva Readily adsorbed to various surfaces of mouth Myeloperoxidase (MP) From leukocytes entering via gingival crevice 15-20% of total peroxidase in whole saliva

Hypofunction of salivary glands

Clinical evaluation Patient’s complaints: Oral dryness and soreness Burning sensation of oral mucosa and tongue Difficulties in speech Difficulty in chewing dry food Taste impairment and disturbances Difficulties in wearing removable dentures Dry lips Acid reflux,nausea,heart burn Sensation of thirst The oral symptoms are often associated with other symptoms such as dry skin,dry nose,dry eyes,dry vaginal mucosa,dry throat,dry cough and constipation

Signs: Mucosal dryness:dry glazed and red oral mucosa Lobulation and fissuring of the dorsal part of tongue Atrophy of filiform papillae Dry lips,angular cheilitis Increased caries experience Oral candidiasis

Xerostomia It is a clinical manifestation of salivary gland dysfunction and it does not represent a disease entity .Dry mouth varies from minimal viscous appearance of saliva to complete absence of any salivary flow. More prevalent in women. Can cause significant morbidity and a reduction in a patient’s perception of quality of life. When unstimulated salivary flow is less than 0.12 to 0.16 ml/minute, a diagnosis of hypofunction is established.

Etiology Aging Foods:alcohol, coffee, coco cola, smoke Drugs: Anti-depressants Anti-histamine Cimitidine Anti-cholinergic Anti-HTN (sympathomimetic drugs) Anti-inflammatory Systemic factors Emotions: nervousness , excitation, depression, stress.. Encephalitis, brain tumors, stroke, Parkinson’s disease Dehydration: diarrhea, vomiting, polyuria of diabetes … Anemia, nutrition deficiency.

Etiology Sjogren’s syndrome Other salivary gland diseases Radiotherapy Acini atrophy fibrosis or replaced by fatty tissue Serous acini: more sensitive to R/T Saliva: thickened, altered electrolytes, pH↓, secretion of immunoglobulins↓ >1000rad (2-3wk): felt oral dryness >4000rad: irreversible change Sjogren’s syndrome Other salivary gland diseases

Symptoms & Signs Symptoms: Oral dryness (most common) Halitosis Burning sensation Loss of sense of taste or bizarre taste Difficulty in swallowing Tongue tends to stick to the palate Decreased retention of denture

Signs: Saliva pool disappear Mucosa: dry or glossy Duct orifices: viscous and opaque saliva Tongue: glossitis  fissured  red with papilla atrophy Angular cheilitis Rampant caries: cervical or cusp tip Periodontitis Candidiasis

Clinical Appearance: Oral mucosa appears dry, pale, or atrophic. Tongue may be devoid of papillae with fissured and inflamed appearance. New and recurrent dental caries. Difficulty with chewing, swallowing, and tasting may occur. Fungal infections are common.

Pale Fisured Tongue Due To Severe Dry Mouth

Moderate Xerostomia

Severe Dry Mouth (Strawberry Tongue)

Diagnosis History taking Symptoms & clinical examination Special investigations Salivary flow rate, SFR Salivary scintiscanning Sialochemical analysis & laboratory values Labial biopsy Sialography

Management Dietary & environmental considerations Preventive Dental Care Measures Saliva stimulants Saliva substitutes

Dietary & Environmental Considerations Avoid drugs that may produce xerostomia Avoid dry & bulky foods High fluid intake & rinsing with water Avoid alcohol, smoking and sugar Take protein and vitamin supplements Environment: Maintain optimal air humidity in the home Use Vaseline to protect the lips

Preventive Dental Care Measures Smooth sharp cusps, occlusal grooves or fissures, irregular fillings. Check and adjust the denture. Fluoride rinses & chlorhexidine rinses. Antifungal medications: Denture: Miconazole gel,amphotericin or nystatin ointment Topical: Nystatin, amphotercin suspension or fluconazole..

Saliva Substitutes: Sodium carboxymethyl cellulose:0.5% aqueous solution Commercial oral moisturizing gels (OTC) includes: OralBalance. XERO-Lube Salivart Optimoist

Saliva Stimulants: The use of sugar free gum, lemon drops or mints are conservative methods to temporarily stimulate salivary flow in patients with medication xerostomia or with salivary gland dysfunction. Biotine chewing gum Pilocarpine HCl May need 2-3 months to determine effectiveness. Side effects include sweating and diarrhea. Avoid in patients with narrow angle glaucoma, severe asthma, pulmonary diseases.

Ptyalism Pathophysiology Normal Submandibular Saliva production 0.10-0.15 ml/min Ptyalism may result in 1-2 L/day of Saliva loss Mechanisms of excessive Saliva Decreased Saliva swallowing and clearance Excessive Saliva production Neuromuscular disease Anatomic abnormalities

Causes Saliva Overproduction Pregnancy (Ptyalism Gravidarum) Excessive starch intake Gastrointestinal causes Gastric distention or irritation Gastroesophageal Reflux Acute Gastritis or Gastric Ulcer Pancreatitis Liver disease

Medications and toxins Clozapine(Clozaril) Potassium Chlorate Pilocarpine Mercury Poisoning Copper Arsenic poisoning Antimony (used to treat parasitic infections) Iodide Bromide Aconite (derived from Aconitum napellus root) Cantharides

Stomatitis and localized oral lesions Aphthous Ulcers Oral chemical burns Oral suppurative lesions Alveolar abscess Epulis Oral infectious Lesions Dental Caries Diphtheria Syphilis Tuberculosis Small Pox

Difficulty Swallowing Saliva Infections Tonsillitis Retropharyngeal Abscess Peritonsillar Abscess Epiglottitis Mumps Chancre Actinomycosis Bone Lesions Jaw fracture or dislocation Ankylosis of the temporomandibular joint Sarcoma of the jaw

Neuromuscular disorders Cerebral Palsy Mental retardation Bulbar Paralysis Pseudobulbar paralysis Bilateral Facial Nerve Palsy Cerebrovascular Accident Myasthenia Gravis Hypoglossal Nerve palsy Rabies Botulism Miscellaneous Causes Radiation therapy Macroglossia Dental malocclusion

Management Non-specific Treat specific causes as below General measures to reduce Saliva Tooth brushing and mouthwash has drying effect Reduce starch intake from diet Orthodontic appliances that aid swallowing Upper plate to cover palate with movable beads Aids lip closure Directs Saliva toward pharynx Anticholinergic Medications Glycopyrrolate

Advanced procedures in severe and refractory cases Botulinum toxin A Salivary Gland injection Performed under ultrasound guidance Radiation therapy Surgery Submandibular Gland excision or duct relocation Parotid duct relocation or ligation Salivary denervation (transtympanic neurectomy)

Specific measures Treat Nausea with Antiemetics Treat Gastroesophageal Reflux Neuromuscular causes Speech pathology (e.g. swallowing mechanism) Neurology consultation Oral diseases including dental malocclusion Dentist or orthodontist

Burning Mouth Syndrome Painful,frustating condition often described as a scalding sensation in tongue,lips,palate or throughout the mouth Can affect anyone but occurs most commonly in middle-aged or older women occurs with a range of medical and dental conditions, from nutritional deficiencies and menopause to dry mouth and allergies the exact cause of burning mouth syndrome cannot always be identified with certainty.

SIGNS AND SYMPTOMS Moderate to severe burning in the mouth is the main symptom of BMS and can persist for months or years the burning sensation begins in late morning, builds to a peak by evening, and often subsides at night Some feel constant pain; for others, pain comes and goes Anxiety and depression are common in people with burning mouth syndrome and may result from their chronic pain.

Other symptoms of BMS include: tingling or numbness on the tip of the tongue or in the mouth bitter or metallic changes in taste dry or sore mouth

Causes: damage to nerves that control pain and taste hormonal changes dry mouth, which can be caused by many medicines and disorders such as Sjögren’s syndrome or diabetes nutritional deficiencies oral candidiasis, a fungal infection in the mouth acid reflux poorly-fitting dentures or allergies to denture materials anxiety and depression. In some people, burning mouth syndrome may have more than one cause. But for many, the exact cause of their symptoms cannot be found

Diagnosis: A review of medical history, a thorough oral examination, and a general medical examination may help identify the source of burning mouth. Tests may include: • blood work to look for infection, nutritional deficiencies, and disorders associated with BMS such as diabetes or thyroid problems • oral swab to check for oral candidiasis • allergy testing for denture materials, certain foods, or other substances that may be causing symptoms.

Treatment: Treatment should be tailored to individual needs. Depending on the cause of BMS symptoms, possible treatments may include: adjusting or replacing irritating dentures treating existing disorders such as diabetes, Sjögren’s syndrome, or a thyroid problem to improve burning mouth symptoms recommending supplements for nutritional deficiencies

switching medicine, where possible, if a drug is causing burning mouth • prescribing medications to — relieve dry mouth — treat oral candidiasis — help control pain from nerve damage — relieve anxiety and depression. When no underlying cause can be found, treatment is aimed at the symptoms to try to reduce the pain associated with burning mouth syndrome.

Helpful tips: Sip water frequently. Suck on ice chips. Avoid irritating substances like hot, spicy foods; mouthwashes that contain alcohol; and products high in acid, like citrus fruits and juices. Chew sugarless gum. Brush teeth/dentures with baking soda and water. Avoid alcohol and tobacco products.

Clinical implications: Difficulties in chewing tasting swallowing speaking Increased chances of developing dental decay & other infections in mouth Mouth sores Difficult for operator to work when saliva pools in mouth (in case of sialorrhea) uncoordinated swallowing poorly synchronized lip closure abnormal increase in tone of the muscles that open the mouth

Inflammatory diseases of the salivary glands: Acute bacterial sialadenitis Chronic sialadenitis Recurrent sialadenitis Mumps Post operative usually parotid Autoimmune diseases

SALIVARY GLAND TUMORS: Tumors of the salivary glands are commonest in the parotid much less common in the submandibular gland and very rare in the sublingual and minor salivary glands.

Classification: I. Benign: II. Malignant: a) Mixed salivary tumor or pleomorphic adenoma b) Adenolymphoma or warthin’s tumor c) Oncocytoma d) Monomorphic adenoma II. Malignant: a) Primary carcinoma b) Secondary carcinoma – direct invasion from skin or from secondarily involved lymph nodes

Typical Features of Benign & Malignant Salivary Gland Tumours Slow growing Soft or Rubbery Consistency Usually Encapsulated Does not ulcerate No associated nerve palsies Mainly affects the parotid gland. MALIGNANT At times Fast growing May be Hard Consistency Is not encapsulated. May ulcerate; invades bone May cause cranial nerve palsies depending on the site of involvement. Usually affects minor salivary glands.

Dental considerations: Present as swelling unilateral or bilateral painless or painful Slow growing or fast growing Associated symptoms: Trismus Pyrexia Tachycardia Purulent discharge from duct Difficulty in mastication Facial muscle weakness Nerve palsies-malignat tumours lymphadenopathy

Saliva and dental caries: THE CARIOGENIC CHALLENGE Although the etiology of dental caries is reasonably well established,the chemical- physical process that results in the demineralization of enamel and dentin often is less appreciated. The stage is set for the oral flora to metabolize the ingested carbohydrates leading to the production of acids that are capable of demineralizing enamel and dentin

The production of acids by microorganisms within the dental plaque continues until the carbohydrate substrate is metabolized The plaque’s pH goes from acidic to normal (or the resting level) within a few minutes This is due to the carbonate and phosphate pH buffering agents in saliva Saliva also serves as the host’s defense mechanism by repairing the demineralization that occurs when the plaque pH is below 5.5 to 6.0

CHEMICAL BENEFITS OF SALIVA STIMULATION Stimulating the flow of saliva alters its composition. Increases the concentration of protein, sodium, chloride and bicarbonate and decreases the concentration of magnesium and phosphorus. Perhaps of greatest importance is the increase in the concentration of bicarbonate, which increases progressively with the duration of stimulation. The increased concentration of bicarbonate diffuses into the plaque, neutralizes plaque acids, increases the pH of the plaque and favors the remineralization of damaged enamel and dentin

Studies have shown that chewing sugar-free gum after meals results in a significant decrease in the incidence of dental caries and that the benefit is due to stimulating salivary flow rather than any chewing gum ingredient. Stimulating salivary flow after meals reduces the incidence of dental caries so,its practical measures should be considered in caries prevention programs

Saliva & Age: With age, a generalized loss of salivary gland parenchymal tissue occurs. The lost salivary cells often are replaced by adipose tissue. Although decreased production of saliva often is produced in older persons,whether this is related directly to the decrease in parenchymal tissue is not clear. Some studies of healthy older individuals,in which the use of medication were carefully controlled,revealed little or no loss of salivary function. Other studies suggest that although resting salivary secretion is in the normal range,the volume of saliva produced during stimulated secretion is less than normal.

Saliva:A Diagnostic Fluid ADVANTAGES: non-invasive limited training no special equipment potentially valuable for children and older adults cost-effective eliminates the risk of infection screening of large populations

SALIVA COLLECTION: with or without stimulation Stimulated saliva-collected by masticatory action (i.e., from a subject chewing on paraffin) or by gustatory stimulation (i.e., application of citric acid on the subject's tongue) Unstimulated saliva is collected without exogenous gustatory, masticatory, or mechanical stimulation Unstimulated salivary flow rate is most affected by the degree of hydration,but also by olfactory stimulation, exposure to light, body positioning, and seasonal and diurnal factors Two ways: Draining method, in which saliva is allowed to drip off the lower lip Spitting method, in which the subject expectorates saliva into a test tube

Serum components may also reach the saliva through the crevicular fluid. This raises the prospect of using saliva in the diagnosis of certain pathologies The use of saliva in diagnosing caries risk is well-known, particularly in monitoring chemical treatments to control the disease,owing to the possibility of detecting the presence of S. mutans and Lactobacillus spp, as well as lactic acid which causes the sub-surface demineralisation that causes the onset of the caries lesion

Candidiasis-through the presence of Candida spp in the saliva The presence of periodontal pathogenic bacteria can also be diagnosed by this method-increasing the risk of cardiovascular and cerebrovascular diseases Cystic fibrosis-raised sodium chloride, calcium, phosphate, lipid and protein contents in the submaxillary saliva. An epidermal growth factor with low biological activity compared to that of healthy persons and raised prostaglandin E2 levels are also found in the saliva of these patients In 21-hydroxylase deficiency, a strong correlation has been found between 17- hydroxyprogesterone levels in saliva and in serum.

In Sjögren’s syndrome, minor salivary gland biopsy is an accepted diagnostic procedure. A predominant inflammatory infiltrate composed of CD4 lymphocytes is found, together with lowered at rest and stimulated salivary flow rates. Quantitatively, there are raised concentrations of sodium, chloride, IgA, IgG, lactoferrin, albumin, microglobulin, cystatin C and S, lipids and inflammation mediators such as prostaglandin E2, thromboxane B2 and interleukin-6 In some malignant diseases, markers can be detected in the saliva, such as the presence of protein p53 antibodies in patients with oral squamous cell carcinoma

The presence of the c-erbB-2 tumour marker in the saliva and blood serum of breast cancer patients and its absence in healthy women is a promising tool for the early detection of this disease In ovarian cancer too, the CA 125 marker can be detected in the saliva with greater specificity and less sensitivity than in serum

PCR detection of Helicobacter pylori in the saliva shows high sensitivity The presence of antibodies to other infectious organisms such as Borrelia burdogferi, Shigella or Tenia Solium can also be detected through the saliva detection of hepatitis A antigen and hepatitis B surface antigen in the saliva has been used in epidemiological studies saliva has also been used to detect antibodies to the rubella, parotitis and rubeola viruses In neonates, the presence of IgA is an excellent marker of rotavirus infection

HIV antibody detection is as precise in saliva as in serum and is applicable in both clinical and epidemiological studies Salivary IgA levels to HIV decline as infected patients become symptomatic. It was suggested that detection of IgA antibody to HIV in saliva may, therefore, be a prognostic indicator for the progression of HIV infection Several salivary and oral fluid tests have been developed for HIV diagnosis Orasure® is a testing system that is commercially available in the United States and can be used for the diagnosis of HIV The test relies on the collection of an oral mucosal transudate (and therefore IgG antibody). IgG antibody to the virus is the predominant type of anti-HIV immunoglobulin

Certain drugs- lithium,carbamazepine, barbiturates, benzo- diazepines, phenytoin, theophylline and cyclosporine High correlation between ethanol concentrations in saliva and in serum. The presence of thiocyanate in the saliva is an excellent indicator of active or passive smoking Other drugs such as cocaine or opiates can also be detected in saliva

Consequently, the use of saliva as an alternative method of diagnosis or as a means to monitor the evolution of certain illnesses or the dosage of certain medicines is a promising path The earlier the diagnosis, the better the prognosis

DIAGNOSTIC IMAGING FOR SALIVARY GLANDS This procedure is done to differentiate inflammatory from neoplastic disease; diffuse from focal suppurative disease, identify and localize sialoliths, & demonstrate ductal morphology.

The methods employed are: - Plain Film Radiography - IntraOral Radiography - ExtraOral Radiography - Conventional Sialography - Computed Tomography (CT) - Magnetic Resonance Imaging - Scintigraphy - UltraSonography

CONVENTIONAL SIALOGRAPHY It is a radiographic technique wherein a radiopaque contrast agent is infused into the ductal system of a salivary gland before imaging. Imaging is done with plain films, flouoroscopy, panoramic radiography, CT. This technique is mainly used to study Parotid and SubMandibular glands. In this technique, a lacrimal or periodontal probe is used to dilate the sphincter at the ductal orifice before the passage of a cannula; blunt needle or catheter; which is connected to a syringe containing contrast agent.

SIALOGRAPHY INDICATIONS:- Detection of calculi or foreign bodies Determination of extent of destruction of salivary gland tissue Detection of fistulae, diverticuli & strictures Detection & diagnosis of recurrent swelling & inflammatory processes Demonstration of tumour, its size, location & origin

Selection of the site for biopsy Outline the plane of facial nerve as a guide in planning a biopsy or a dissection Detection of residual stones, residual tumour or a retention cyst

CONTRAINDICATIONS:- Patients with a known allergy or hypersenstivity to iodine compounds During the period of acute inflammation of salivary glands because:- 1. contrast media cause irritation 2. there is increased chance of rupture of duct & extravasation of contrast media into already inflamed gland

Patient scheduled for thyroid function tests in near future Patient scheduled for thyroid function tests in near future. absorption of iodine present in the contrast material, across the glandular mucosa may interfere with these studies.

PHASES OF SIALOGRAPHY Sialography can be divided into 3 phases:- Ductal phase Acinar phase Post-evacuation phase

DUCTAL PHASE Ductal phase of both parotid and submandibular sialogram starts with the reterograde injection of contrast medium & ends when glandular parenchyma starts to become “hazy” reflecting onset of acinar opacification Visualization of ducts draining accesory parotid gland often occur during this phase`

ACINAR PHASE It begins after the ductal system has become fully opacified with contrast and the gland parenchyma becomes filled subsequently

POST-EVACUATION PHASE It assesses normal secretory clearance function of the gland to determine whether any evidence of retention of contrast remains in the gland or ductal system after the sialogram

CONTRAST SIALOGRAPHY Contrast sialography can be performed either by :- A) lipid –soluble agents B) water –soluble agents

LIPID-SOLUBLE AGENTS These agents contain 37% iodine, e.g. ethiadol ADVANTAGES:- It is not diluted by saliva It is not absorbed across glandular mucosa DISADVANTAGES:- These are more viscous , hence higher injection pressure is required More pain & discomfort

Any calculus encounterd in the duct may be displaced backward Extravasated agents can cause foreign body reaction, & can induce inflammatory reactions and granuloma formation

WATER –BASED AGENTS These agents contain 28 to 38% iodine, e.g. hypaque50%, hypaque M 75%, renografin 60, isopaque, triosol & dionosil ADVANTAGES:- Low viscosity Low surface tension and more miscible with salivary secretions Residual contrast medium is absorbed and excreted through kidney

DISADVANTAGES:- Opacification is generally not as good as oil –based media as it is rapidly absorbed across glandular mucosa It is diluted by saliva The injection is accompanied by little pain & discomfort

TECHNIQUE EQUIPMENT:- Polythene tubing with a special blunt metallic tip with side holes for parotid gland injection A 5-10ml syringe Lacrimal dilator Contrast medium Lemon slices or artificial lemon extract

PROCEDURE:- 1) Identification of the location of duct orifices The parotid duct is located at the base of the papilla in the buccal mucosa opposite maxillary 1st and 2nd molar teeth The area of the mucosa in the vicinity of the orifice is dried with a small sponge The application of gentle pressure over the area would lead to expression of saliva The submandibular duct orifice is situated on the summit of papilla by side of lingual frenum

2)EXPLORATION OF THE DUCT WITH A LACRIMAL PROBE- In view of torturous course of the parotid duct, patient”s cheek must be turned outward prior to insertion of the probe into the duct. This eversion of cheek reduces the chances of penetration of duct at the sharp angles in its course.

In case of the submandibular duct, the probe should pass through the considerable length of the floor of the mouth to the level of posterior border of mylohyoid muscle, apx 5cm In both the ducts, the probe should slide easily back & forth and also rotate freely without dragging.

3) CANNULATION OF THE DUCTS:- The duct orifice is slightly enlarged, & the salivary cannula is inserted into the duct. The cannula is held in place by taping the tubing wrapped in sponge. INTRODUCTION OF THE RADIOGRAPHIC DYE:- The dye is slowly introduced into the duct

The amount used is best determined by flouroscopic observation. The patient is instructed to inform the operator when the gland area feels tight or full. The apx. Values of the dye required vary from 0.76ml to 1.0ml for parotid gland, & 0.5 to 0.75ml for submandibular gland

RADIOGRAPHIC PROJECTIONS 1)LATERAL OBLIQUE PROJECTION:- This projection is best to delineate the submandibular gland, as the image is projected below the ramus of the mandible 2)LATERAL PROJECTION:- This projection also shows ductal projection 3)OCCLUSAL PROJECTION:- This view is useful for sialolith located in the anterior part of the wharton’s duct

4)ANTERIOR-POSTERIOR PROJECTION:- This projection demonstrates medial and lateral gland structures 5)PANORAMIC PROJECTION:- This projection is made during the filling phase. It has following advantages:- Easier to expose Radiation dose is relatively low Satisfactory bony details

COMPUTED TOMOGRAPHY Less invasive than sialography Does not require the use of contrast material Used for assessment of mass lesions of the salivary glands Can demonstrate salivary gland calculi. Especially submandibular stones that are located posteriorly in the duct, at the hilum of the gland or in the substance of gland itself.

MAGNETIC RESONANCE IMAGING MRI is superior to CT scanning in delineating the soft tissue detail of the salivary gland lesions, esp. tumours With no radiation exposure to the patient or the neccesity of contrast enhancement

ULTRASONOGRAPHY It is a relatively simple, non-invasive imaging modality, with poor detail resolution. Useful in assessment of superficial structures to determine whether a mass lesion that is being evaluated is solid or cystic in nature.

SIALOENDOSCOPY It is a specialised procedure that uses a small video camera with a light at the end of a flexible cannula , which is introduced into the ductal orifice Can be used diagnostically and therapeutically Can demonstrate strictures and kinks in the ductal system , as well as mucous plugs and calcifications May be used to dilate small stictures and flush clear small mucous plugs

SIALOCHEMISTRY An examination of electrolyte composition of saliva of each gland may indicate a variety of salivary gland disorders. Principally, the concentrations of sodium and potassium, which normally change with salivary flow rate, are measured

REFERENCES: Textbook of medical physiology by guyton & hall Dental caries by Ole Fejerskov & Edwina Kidd Ten Cate’s Oral Histology Textbook of Pediatric Dentistry by Shobha Tandon Textbook of Oral Pathology by Shafer Preventive community dentistry by Soben Peter

Microbial composition of whole saliva:The Dental Clinics of North America Saliva:the precious body fluid:The Journal of the American Dental Association Burning mouth syndrome:NIDCR The diagnostic applications of saliva a review: published by SAGE Dry mouth:NIDCR The effect of saliva on dental caries:The Journal of the American Dental Association The role of saliva in maintaining oral health and as an aid to diagnosis:clinical dentistry

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