SALIVA DR VANISHREE.M DEPARTMENT OF ORAL PATHOLOGY
Saliva
CONTENTS Introduction. Salivary glands and its main features. Blood supply and nerve supply of salivary glands. Composition of saliva. Factors affecting composition of saliva. Methods of collection of saliva. Properties of saliva. Secretion of saliva. Conditions that affect salivation. Formation of saliva. Functions of saliva.
Clinical considerations. Salivary substitutes. Interaction of salivary components with the bacterial surface. Effects of aging on salivary secretion. Sialography . Saliva As A Diagnostic Fluid. Conclusion. Refrences .
INTRODUCTION “ 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” IRWIN MANDEL (DDS)
What is saliva? 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’. Composed of more than 99% water and less than 1% solids,mostly electrolytes and proteins,the latter giving saliva its characteristic viscosity. Normally the daily production of whole saliva ranges from 0.5 to 1.0 litres .
SALIVARY GLANDS Exocrine glands Two types- Major salivary glands- - Parotid. - Submandibular . - Sublingual. Minor salivary glands- - Labial and buccal glands. - Glossopalatine glands. - Palatine glands. -Lingual glands.
DEVELOPMENT OF SALIVARY GLANDS Stages of Development Divided into 6 stages- Stage I – Bud formation. Stage II – Formation and growth of epithelial cord . Stage III – Initiation of branching in terminal parts of epithelial cord and continuation of glandular differentiation. Stage IV – Dichotomous branching of epithelial cord and lobule formation . Stage V – Canalization of presumptive ducts . Stage VI – Cytodifferentiation .
HISTOLOGY OF SALIVARY GLANDS Consists of several ducts, terminating in secretory end pieces- acini . Terminal secretory units are composed of serous , mucous and myoepithelial cells arranged into acini or secretory tubule . Composed of parenchymal elements supported by connective tissue. Terminal secretory units leading into ducts that open into oral cavity.
Connective tissue encapsulates glands and extends into it dividing groups of secretory units and ducts into lobes and lobules. The main excretory duct -> interlobar & interlobular duct. interlobular duct = striated duct – modification of primary saliva.
SALIVARY GLAND ACINI Serous Mucous Mixed SEROUS CELL - Pyramidal in shape - Nucleus is spherical
Mucous cells Specialized for synthesis , secretion and storage of secretory products Secrete a viscous Glycoprotein called ‘ mucin ’ a useful lubricant for food and also protects the oral mucosa.
Myoepithelial cells Closely related to the secretory and intercalated duct cells Considered to have a contractile function, helping to expel secretions from the Lumina of the secretory units and ducts.
DUCT SYSTEM CELLS Classified as Intercalated, Striated and excretory INTERCALATED DUCT CELLS - Connect acinar secretions to the rest of the gland - not involved in the modification of electrolytes STRIATED CELLS - electrolyte regulation in resorbing sodium EXCRETORY DUCT CELLS - sodium resorption and secreting potassium - last part of the duct network before the saliva reaches the oral cavity.
MAIN FEATURES OF SALIVARY GLANDS Gland type and weight Location Route of secretory duct Histology %age of total salivary secretion 1. Parotid gland 20-30 gm each In the groove between ramus of mandible and mastoid process i.e below the ear Secretions pass via Stenson’s duct which open opp. The upper second molar in Oral cavity Contains purely serous cells 25% 2.Submandibular or submaxillary 8-10gm each In submaxillary triangle behind and below the mylohyoid muscle, with a small extension lying above the muscle Its duct i.e. Wharton’s duct opens into floor of the mouth at canancula sublingualis , a papilla along the side of lingual frenum Mixed i.e. contains both serous and mucous cells in the ratio of 4:1 70% 3.Sublingual glands 2-3 gm each Between floor of the mouth and mylohyoid muscle Its secretions are discharged by 5-15 small ducts. Main duct is Bartholins duct Mixed but mainly mucous cells Ratio 4:1 S:M 5%
BLOOD SUPPLY OF SALIVARY GLANDS ARTERIAL SUPPLY Parotid gland – Facial and External carotid arteries Submandibular gland – Facial and Lingual arteries Sublingual gland – Submental and Sublingual arteries VENOUS DRAINAGE All glands – External jugular vein
INFLUENCE OF BLOOD SUPPLY ON SALIVARY SECRETION Extensive blood supply required for rapid salivary secretion. Salivation indirectly dilates blood vessels providing increased nutrition. Large increase in blood flow accompanies salivary secretion.
NERVE SUPLY Salivary gland secretion is regulated by both sympathetic and parasympathetic autonomic nerves Major Salivary Glands
Minor Salivary Glands Sympathetic : Labial and Buccal Glands via plexus on Facial Artery Lingual Glands via plexus on Lingual Artery Palatine Glands via plexus on Palatine Artery
Parasympathetic : Ant.Lingual Glands - superior salivatory nucleus Glands present in Palate, Upper Lip and Upper part of the Vestibule - post gang.fibres from the Pterygopalatine Gang. through the Palatine vessels. Glands of the Lower Lip and Lower part of the Vestibule - post gang. fibers from Otic gang.through Inf.Alv . And Buccal Nerves.
COMPOSITION OF SALIVA Dilute aqueous solution present in the oral environment. 99% of this hypotonic fluid is Water Remaining 1% consists of dissolved organic and inorganic constituents
ORGANIC CONSTITUENTS
PROTIENS consists only 3% of protein concentration present in plasma i.e., about 200 mg/100 ml. Salivary enzymes Alpha amylase(ptyalin) -parotid saliva- 60-120 mg/100ml, - submandibular saliva-25mg/100ml. Antibacterial substance - Lysozyme , Lactoferrin,Peroxidase system,Sialoperoxidase . Kallikrein , Dextranases , Invertase . Miscellaneous enzymes- Acid phosphatase, cholinesterase,ribonuclease,lipase,proteases , carboxypeptidases,urease,aminopeptidase etc.
Immunoglobulins - IgA , IgG , IgM . Proteins synthesized within the glands - Factor VII ( Pro-activator ) - Factor VIII ( Anti haemophilic globulin ) - Factor IX ( Christmas factor ) - Platelet factor Glycoproteins - MG1 and MG2 ( Submandibular and Sublingual saliva) - Proline rich glycoproteins ( Parotid saliva) Other Polypeptides - Statherin - Sialin
II . BLOOD GROUP SUBSTANCES III . HORMONES - Parotin - Nerve growth factor IV. CARBOHYDRATES -glucose, 0.5-1 mg/100 ml in parotid saliva - hexose , small amounts of hexosamine and sialic acid in submandibular saliva V. LIPIDS - diglycerides , triglycerides cholesterol and cholesterol esters - phospholipids - corticosteroids VI. NITROGEN CONTAINING COMPOUNDS VII. UREA - 12-20 mg/100ml VIII. WATER-SOLUBLE VITAMINS
INORGANIC CONSTITUENTS Sodium (0-80mg/100ml) Potassium (60-100mg/100ml) Calcium (2-11mg/100ml) Phosphate (6-71mg/100ml) Chloride (50-100mg/100ml) Fluoride (.01-.04mg/100ml) Bicarbonate (0-40mg/100ml) Thiocyanate ( 2mg ) Hydrogen ion (Ph range is 5.0-8.0)
FACTORS AFFECTING COMPOSITION Flow rate Differential gland contributions Duration of the stimulus Nature of the stimulus Diet Hormones Fatigue Plasma concentration Other factors - pregnancy , genetic polymorphism , antigenic stimulus , exercise, drugs and various diseases.
METHODS OF COLLECTING SALIVA FROM DIFFERENT GLANDS Carlson- Crittendon cannula used for collecting parotid saliva A Segregator used for collecting saliva from submandibular and sublingual glands Most commonly used techniques for measuring unstimulated salivary flow rate are :- 1) Draining method 2) Spitting method 3) Suction method 4) Swab method
Two collection methods used to determine stimulated salivary flow rate :- 1) Masticatory method 2) Gustatory method
PROPERTIES OF SALIVA Consistency : Slightly cloudy Reaction : Usually slightly acidic PH : 5-8 Specific gravity : 1.0024 – 1.0061 Freezing point : 0.07 – 0.34 degree Celsius Flow rate : 0.02ml/minute at rest to 7ml/minute or more when stimulated. Buffering power of saliva -The carbonic acid/bicarbonate system - The phosphate buffer system - The salivary proteins
SECRETION OF SALIVA TOTAL VOLUME OF SALIVA SECRETED 500-750ml/day, May go up to 1litre/day Of this total volume of saliva :- 60% - Submandibular gland 30% - Parotid gland 3-5% - Sublingual gland 7% - Minor salivary glands These proportions vary with the intensity and type of stimulation.
CONTROL OF SALIVARY SECRETION Salivary glands are purely under nervous control Sympathetic nerve supply - secretory proteins like Amylase and Vasoconstrictors. Parasympathetic supply- Nerves innervate acinar cells, duct cells, blood vessels and myoepithelial cells. A ) AFFERENT PATHWAY I . RESTING FLOW a) Hydration b) Exercise and Stress c) Drugs d)Other factors like- gender , age ( above 15 years ) weight, gland size, psychic effects like thought/site of food , appetite and mental stress.
II. Psychic Flow III. Unconditional Reflexes ( Local stimuli ) a) Mastication b) Gustatory stimuli Factors Affecting The Flow Of Stimulated Saliva. - Nature of stimulus ( mechanical , gustatory ) - Vomiting, Smoking, Gland size, Gag reflex, Olfaction, Unilateral stimulation, Food intake. B . CENTRAL CONTROL C. EFFERENT PATHWAY
CONDITIONS THAT AFFECT SALIVATION Physiologic Taste, Surface texture, Dehydration, Age, Emotion Pathologic conditions that increase salivation Digestive tract irritants, Ill – fitting dentures / Inadequate interocclusal distance, Vitamin deficiency, Trauma from surgery. Pathologic conditions that decrease salivation Senile atrophy of the salivary glands, Irradiation therapy, Diseases of the brainstem, Diabetes mellitus / insipidus,Diarrhoea, Acute infectious diseases.
FORMATION OF SALIVA Saliva is formed in two stages:- A primary secretion occurs in the acini Then modified as it passes through the ducts MECHANISM OF ACTION Signal transduction - Phospholipase C Pathway - Adenyl cyclase pathway
Formation of granules Nucleus -> signaling-> mRNA-> ribosomes (synthesis protein molecules - preprotiens) -> NH2 signalling . Signal peptidase enzymes removes NH2 signalling -> preprotiens -> golgi bodies-> glycosylations ( serine,aspiragin + carbohydrates)-> glycoprotiens . vacuoles filled with granules are formed-> apical cytoplasmic end.
Mechanism of Formation of saliva Signal Transduction Stimulus Release of a neurotransmitter substance {Acetyl choline / Noradrenaline } Ext.surface of Secretory Cell membrane Stimulatory/Inhibitory Receptor intermediate protein GlycoProtein Inner cytoplasmic surface Phospholipase C/ Adenyl cyclase {Regulatory enzyme} Acetyl choline+muscarinic receptorsPhospholipase C Water & electrolytes Noradrenaline + adrenergic acinar receptorsAdenyl cyclase Exocytosis of secretory proteins .
Formation of Saliva
FUNCTIONS OF SALIVA PROTECTIVE PROPERTIES a) Lubrication b) Maintenance of mucous membrane integrity c) Soft tissue repair d) Maintenance of ecological balance e) Dilution and clearance f) Aggregation g) Direct Antibacterial activity h) Antifungal and antiviral activity i ) Maintenance of ph j) Maintenance of tooth integrity k) Salivary anticaries activity
ANOMALIES OF THE SALIVARY GLANDS I. Developmental Aberrant Salivary Glands Aplasia and Hyperplasia II.Obstructive conditions Sialolithiasis Mucocele Necrotizing Sialometaplasia iii. Inflammatory Diseases Viral: Mumps, H.I.V. Associated Bacterial : Sialadenitis
IV. Neoplastic Diseases Benign Malignant Epithelial Mesenchymal V. Degenerative Conditions Sjogren’s Syndrome Ionizing Radiation VI. Xerostomia
SIALOLITHIASIS occurrence of calcareous concentrations. It is form by deposition of calcium salts around central nidus which may be epithelial cells, foreign body or bacteria. Most commonly seen in Wharton’s duct.
MUCOCELE - the swelling caused due to the pooling of saliva at the site of damaged salivary duct due to trauma . -Lower lip followed by Floor Of the Mouth , tongue and palate . Two types : - Extravasation Type -Retention Type Clinical Appearance : - Characteristic blue swelling fluctuant on palpation.
RANULA Blue/Purplish Red enlargement occurring unilateral or occupying the whole floor of the mouth. Treatment Marsupialisation or Surgical removal
NECROTIZING SIALOMETAPLASIA -It is caused due to trauma resulting in ischemia of the salivary gland . Raised tumor like mass frequently with a deep surface ulcer. Treatment : Debridement of the lesion leads to healing in 6-12 weeks .
INFLAMMATORY DISORDERS Characterized by painful bilateral/unilateral swellings of the affected glands esp. while eating food or opening the mouth. Viral: Mumps- Paramyxovirus . H.I.V.Associated : Kaposi’s Sarcoma and Lymphoma. Bacterial Sialadenitis : Staph.aureus,Strep.viridans . Allergic Sialadenitis : Phenothiazine . TREATMENT : Symptomatic/Antibiotics/Surgical drainage.
CLINICAL FEATURES : Benign tumors : Slow growing masses Painless No ulceration No fixation Malignant tumors: Larger in size Painful Surface ulceration seen Fixation seen TREATMENT : Surgery/Radiotherapy
DEGENERATIVE CONDITIONS Ionizing radiation : Progressive fibrosis and parenchymal degeneration of the salivary gland . Sjogren’s syndrome :It is an immunologic disorder described as a triad of : - Keratoconjuctivitis sicca , Xerostomia , Rheumatoid arthritis Two types : - Primary & Secondary Treatment: Ocular lubricants and salivary substitutes, maintenance of oral hygiene, frequent fluoride application, sialogogues.
Saliva provides an easily available non-invasive diagnostic medium for a wide range of diseases and clinical situations. Diagnosis of salivary gland dysfunction can be made by Sialometry The most common subjective complaint resulting from salivary gland dysfunction is Xerostomia (dry mouth).
Causes :- Administration of drugs like antihypertensives , antidepressants etc. Local /Systemic conditions a) Fever b) Oral infections c) Diabetes Mellitus d) Thyroid disorders e) Hepatic disorders f) Depression Nutritional deficiency Deficiency of vitamin A , riboflavin and nicotinic acid Infection/Obstruction of the salivary glands Radiation
Management of Xerostomia It is mainly focused on relief of symptoms - Nutritious diet/Soft and moist food - Chewing non- cariogenic foods like raw vegetables or sugarless gums. - Frequent liquid intake - Fluoride application to prevent caries - Pilocarpine therapy - Lowering the dosage or changing the drug - Use of Salivary substitutes
Sialorrhoea/ Ptyalism an increased flow of blood through the salivary glands and their excessive stimulation Some psychological conditions in cerebral palsy and epilepsy As a manifestation of primary herpetic and other infections Halitosis The putrefactive action of microorganisms on proteinaceous substrates in saliva is the source of many volatiles found in mouth air The volatile sulphur compounds, H2S etc. are elevated in concentration in the mouth air of patients suffering from periodontal disease which causes bad breath
ARTIFICIAL SALIVA The salivary substitutes are useful agents for the palliative treatment of Xerostomia They are divided into 2 groups:- Carboxymethylcellulose (CMC) based - CMC is used to impart lubrication and viscosity. - Salts are added to mimic the electrolyte content of saliva. - Calcium , phosphate, fluoride ions are added to provide demineralization potential.
Mucin based - They have the lowest contact angle and the best wetting properties on the oral mucosa - Their rheological properties are more comparable to that of natural saliva - These salivary substitutes are available in the form of sprays and lozenges.
SIALGOGUES AND ANTISIALGOGUES Sialgogues - Drugs which stimulate salivation - Also called as cholinergic drugs or parasympa - - thetomimetic drugs Classified as : Esters of choline i.e. acetyl choline , metacholine . Cholinomimetic alkaloid i.e. pilocarpine Cholinesterase inhibitors e.g., neostigmine , organophosphoric compounds Antisialgogues – They are parasympathetic or cholinergic blocking agents include atropine and its related alkaloids obtained from the plant.
INTERACTION OF SALIVARY COMPONENTS WITH THE BACTERIAL SURFACE Many studies have demonstrated that salivary components interact selectively with bacteria to form a “salivary-bacterial pellicle” More recently it has been realized that salivary components may block microbial adhesion to host surfaces. Considering the number of bacterial species in the oral cavity(>500) and the number of components in saliva(>70), the potential number of permutations of saliva-bacterium interactions is surprising.
The interaction of salivary molecules with bacteria may be of four kinds:- * Promotion of microbial clearance from the oral cavity by agglutination or steric hindrance * Promotion of adhesion to the host surface * Direct killing of microbes * Providing substrates for microbial nutrition and growth
HUMAN SALIVARY AGGLUTININS MOLECULE SP. OF BACTERIA AGGLUTINATED Mucins MG1 Streptococcus mutans Actinomycetes S.rattus MG2 S.sanguis S.gordonii S.mutans Elkenella corrodens Staphylococcus aureus Pseudomonas aeruginosa IgA Oral streptococci S.sanguis E . coli
MOLECULE SP . OF BACTERIA AGGLUTINATED Parotid agglutinin S.mutans Lactobacillus casei S.sanguis Actinomyces viscosus Lysozyme S.mutans S.sanguis Capnocytophaga gingivalis Actinobacillus actinomycetemcomitans Beta2-microglobulin S.mutans Other agglutinins S.mutans E.coli
EFFECTS OF AGING ON SALIVARY SECRETION Prevalence of oral dryness and difficulty in swallowing salivary flow is lowered with increasing age. Recent studies- No generalized change in salivary gland function during aging.
SIALOGRAPHY It is the radiographic evaluation of the ductal tree of the salivary glands by means of the intraductal injection of a radio-opaque contrast solution to delineate the ductal pattern which will be radiographically visible. VARIOUS RADIOGRAPHIC APPEARANCES- Normal Salivary gland – Branched leafless tree Parotid gland – Tree in winter Submandibular gland – Bush in winter Tumours – Ball in hand appearance Sjogren’s Syndrome – Cherry Blossom / Branchless fruit- laden tree
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
HISTORY Historical ‘background Diagnostic value of saliva was recognized by ancient judicial community who employed the absence of salivary flow as the basis of a lie detector test.
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 paraf f in Unstimulated whole saliva flow rates of <0.1 ml/min. Stimulated whole saliva flow rate ’ s of <1.0 ml/min Considered abnormally low & indicative of marked salivary hypofunction.
Two methods- a.measurement of whole saliva b.measurement of parotid saliva. Techniques for measurement of whole saliva unstimulated (resting) Draining method Spitting method Suction method Swab method
Techniques for collection stimulated whole saliva Masticatory method (standardized piece of paraffin used) Gustatory method(1% to 6% citric acid used ) The spitting method for estimating resting flow and masticatory method with paraffin chewing for stimulating saliva for measuring flow rates are reliable.
Saliva in dental caries Saliva is important for health of both oral soft and hard tissues It influences the tooth structure by affecting the caries process Four imp tooth protective functions of saliva - Buffering ability - Cleansing effect - Antibacterial action - Saliva supersaturated in calcium phosphate maintains integrity of tooth structure
Saliva in periodontal disease Saliva contains Proteins of host origin : Enzymes Immunoglobulins Phenotypic markers : Epithelial keratin's Hormones : Cortisol Bacteria and bacteria products.
SALIVA IN VIRAL INFECTIONS Ig capture radio immune assay {GACRIA}of igA,igG and igM antibody level can also be used In viral diagnosis and screening. Parrt et al; {1990} have shown the application of this method for salivary monitoring of hepatitis A and B Infection and rubella. Saliva based test are used in diagnostic and epidemiological studies of herpes viruses .hepatitis B virus ,EB virus .and entamoeba histolytica infection
Saliva in oral cancer High salivary levels of nitrate and nitrite may predict oral cancer for epidemiological studies Boyle jo et al {1994} sequenced mutations in the P53gene recovered from head and neck squamous cell carcinomas and altered DNA sequence as tumor –specific genetic markers for cancer cells in the patients saliva.
Saliva in chronic heart failure Salivary endothelin I concentration is elevated in patients with chronic heart failure and can be used to assess disease severity. Measurement of endothelin in saliva may be simple ,non invasive method to assist in diagnosis and assessment of disease in patients with suspected and established CHF. Elevated levels of salivary calcium and K are an easy and sensitive means of identifying patients with digitalis toxicity.
Saliva in Sjogren’s syndrome Sialochemistry provides helpful screening procedures for Salivary Glucose. Decreased sodium and CL concentrations Elevated K concentrations Reduced flow rate Elevation in lactoferrin Elevation in B2-microglobulin Kallikrein
Saliva in down syndrome Saliva used as a model for studying mucosal immuno competence in down syndrome. Salivary total immunoglobulin secretions reflects a central compartment of the mucosal immune system. There will be decreased secretary rates of IgA and IgG seen in down syndrome.
Drugs currently monitored in saliva FDA approved orasure oral specimen collection system to be sensitive and specific kit. Detects any of the NIDA-5 drugs that is marijuana, cocaine, methamphetamine, opiates and phencyclidine hydrochloride using a single orasure specimen.
Role of saliva in smoking Salivary thiocyanate concentration is higher in smokers than in nonsmokers Using levels of nicotine in air and salivary nicotine levels, we can calculate risk level of passive smoking in the work place.
Role of saliva in alcohol The US department of transportation recently approved a versatile and alternative method with saliva to determine the immediate quantitative blood alcohol concentration An enzymatic reaction occurs based on the enzymatic oxidation of alcohol to acetaldehyde by alcohol dehydrogenase .
Saliva In elderly Studies of age related changes in the composition of salivary secretions suggest that there are slight changes In the protective capacity of salivary IgA antibodies which make elderly people more susceptible to oral bacterial and fungal infections, such as root caries and candidasis .
Saliva in forensic science DNA analysis has recently been introduced to forensic dentistry to identify the individuals. Always consider human bite marks as both physical and biological evidence DNA recovery in minute traces of saliva may be present ,even in situations involving bacteria –rich foods
Recent advances in diagnostic technology The development of micro electromechanical system{MEMS} and nanoelectromechanical system {NEMS} biosensors exhibit high levels of sensitivity and specificity for analyte detection , down to the single molecule level.
Oral fluid nanosensor test The OFNASET is a hand held automated ,easy to use integrated system that will enable simultaneous and rapid detection of multiple salivary protein and nucleic acid targets. Transcriptome markers offers the combined advantage of high Through put marker discovery via a non invasive biofluidic method and high patient compliance. Highly diagnostic salivary RNA have identified for oral cancer and for two other major human systemic disease.
CONCLUSION Saliva is a complex fluid produced by a number of specialized glands which discharge into the oral cavity. It plays a major role in the maintenance of the health of an individual. And it has many applications as a diagnostic fluid.
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