XEROSTOMIA Physiology, Etiology, Epidemiology, Pathogenesis, Diagnosis, and Treatment Reviewed by:

XEROSTOMIA After viewing this lecture, attendees should be able to: describe the oral anatomy and physiology related to salivary function as well as the role of saliva in the oral cavity. discuss the etiology and epidemiology of xerostomia. relate treatment options for xerostomia.

DEFINITION OF XEROSTOMIA “Xero” = Dry & “Stomia” = Mouth Xerostomia can be defined as the subjective sensation of oral dryness that may or may not be associated with a reduction in salivary output.1,2 It can have profound negative effects on the quality of life.3 Subjective complaint of patient Diagnosis based on patient complaint and history Salivary flow can be measured but no normal limits have been established Xerostomia: The subjective sensation of oral dryness that may or may not be associated with a reduction in salivary output. Diagnosis based on patient complaint and history Salivary flow can be measured, but no normal limits have been established

XEROSTOMIA Production of Saliva Oral Glandular Tissue3 (saliva secreting) Begins development at 6 weeks gestation and is completed by about the 12th week The glandular tissue continues to enlarge until birth Saliva secreting oral glandular tissue begins development at 6 weeks gestation and is completed by about the 12th week. The glandular tissue continues to enlarge until birth.

NORMAL FUNCTION OF SALIVA3 Hydrating–moisturizing Cleansing Lubrication Digestion Remineralization of dentition (pH maintenance, buffering) Maintenance of mucosal integrity Immunity mediator Antimicrobial (antifungal, antibacterial) Stimulation of minor salivary glands Cellular maintenance Enables swallowing Enables tasting Enables speech articulation (Saliva secreting)

Cause one of two divisions Sympathetic Parasympathetic XEROSTOMIA Mechanisms of Salivary Production3 Salivary glands Neural innervation Cause one of two divisions Sympathetic Parasympathetic Sympathetic neural innervation causes very dry, thick, ropy saliva. Parasympathetic neural innervation causes thin, watery, profuse saliva. The two divisions work in opposition and have the ability to alter the quality as well as the quantity of saliva. Causes very dry, thick, ropy saliva Causes thin, watery, profuse salivation The two divisions work in opposition and have the ability to physiologically alter the quality as well as the quantity of the saliva

Salivary Gland Classifications by Secretion3 XEROSTOMIA Salivary Gland Classifications by Secretion3 Serous: very thin and watery Mucous: very thick and viscous Mixed secretions: mixture of the two

Salivary Gland Classifications by Secretion3 XEROSTOMIA Salivary Gland Classifications by Secretion3 Serous: very thin and watery parotid gland lingual glands of von Ebner (serous glands of von Ebner) Mucous: very thick and viscous Mixed secretions: mix of the two Serous secretions are very thin and watery. Secreted by the parotid gland, the lingual glands of von Ebner Serous acini

Salivary Gland Classifications by Secretion3 XEROSTOMIA Salivary Gland Classifications by Secretion3 Serous: very thin and watery Mucous: very thick and viscous palatine glands posterior lingual glands labial buccal glands Mixed secretions: mix of the two Mucous secretions are very thick and viscous. Secreted by the palatine glands, the posterior lingual glands, and the labial buccal glands. Mucous acini

Salivary Gland Classifications by Secretion3 XEROSTOMIA Salivary Gland Classifications by Secretion3 Serous: very thin and watery Mucous: very thick and viscous Mixed secretions: mix of the two Sublingual glands Mostly mucous with some serous Submandibular glands Mostly serous with some mucous Anterior lingual glands Mixed secretion Mixed secretions are a blend of serous and mucous secretions. The sublingual glands secrete a mix that is mostly mucous with some serous. The submandibular glands secrete a mix that is mostly serous with some mucous. The anterior lingual glands also secrete a mixed product. Mixed: mostly serous acini (dark), partially mucous acini (light cells)

Salivary Gland Classifications by Major or Minor Glands3 XEROSTOMIA Salivary Gland Classifications by Major or Minor Glands3 Major glands Secrete saliva intermittently Minor glands Secrete saliva continuously Major glands secrete saliva intermittently. Minor glands secrete saliva continuously.

XEROSTOMIA The Major Glands Parotid gland Parotid gland3,4 Largest of the 3 major glands Produces 30% of total saliva output Parotid duct is also known as Stenson’s duct Parotid/Stenson’s duct exits opposing the maxillary second molar Located anterior but inferior to the external auditory meatus Innervated by sympathetic and parasympathetic divisions Secretes serous type saliva The parotid gland is the largest of the 3 major glands. It produces 30% of total saliva output. The parotid duct is also known as Stenson’s duct. It exits opposing the maxillary second molar. The parotid gland is located anterior but inferior to the external auditory meatus. It is Innervated by sympathetic and parasympathetic divisions and secretes serous type saliva.

XEROSTOMIA The Major Glands Submandibular gland Submandibular gland3,4 Second largest salivary gland Produces 65-70% of total saliva output The duct is called Wharton’s duct Wharton’s duct exits on the floor of the mouth opposing the lingual surface of the tongue Located in a depression on the lingual side of the mandibular body Innervated by parasympathetic nerve endings and possesses NO sympathetic receptors The parasympathetic fibers arrive through the facial and glossopharyngeal nerves Mixed secretion – mostly serous The submandibular gland is the second largest salivary gland. It produces 65-70% of total saliva output. The duct is called Wharton’s duct; it exits on the floor of the mouth opposing the lingual surface of the tongue. The submandibular gland is located in a depression the lingual side of the mandibular body. It is innervated by parasympathetic nerve endings and possesses NO sympathetic receptors. The parasympathetic fibers arrive through the facial and glossopharyngeal nerves. The submandibular gland produces mixed secretion – mostly serous. Submandibular gland

XEROSTOMIA The Major Glands Sublingual glands3,4 Smallest of the major glands Produce less than 5% of total saliva output Saliva delivered via the ducts of Bartholin The Bartholin ducts exit on the base of the lingual surface of the tongue Innervated by parasympathetic fibers Little or no sympathetic influence Mixed secretion – mostly mucous The sublingual glands are the smallest of the major glands. They produce less than 5% of total saliva output. Saliva is delivered via the ducts of Bartholin, which exit on the base of the lingual surface of the tongue. The sublingual glands are Innervated by parasympathetic fibers and have little or no sympathetic influence. They secrete a mixed secretion – mostly mucous. Sublingual gland

XEROSTOMIA The Minor Salivary Glands3 Minor salivary glands are found throughout the mouth: Lips Buccal mucosa (cheeks) Alveolar mucosa (palate) Tongue dorsum and ventrum Floor of the mouth Together, they play a large role in salivary production. Minor salivary glands are found on the lips, buccal mucosa, alveolar mucosa, tongue, and the floor of the mouth. Together, they play a large role in salivary production.

XEROSTOMIA Salivary Flow3 Unstimulated Flow (resting salivary flow―no external stimulus) Typically 0.2 mL – 0.3 mL per minute Less than 0.1 mL per minute means the person has hyposalivation Hyposalivation – not producing enough saliva Stimulated Flow (response to a stimulus, usually taste, chewing, or medication [eg, at mealtime]) Typically 1.5 mL – 2 mL per minute Less than 0.7 mL per minute is considered hyposalivation Unstimulated salivary flow is salivation with no external stimulus. Typically 0.2 mL to 0.3 mL per minute. Less than 0.1 mL per minute is hyposalivation (not producing enough saliva). Stimulated salivary flow is salivation in response to a stimulus (usually taste, chewing food). Typically 1.5 mL to 2 mL per minute. Less than 0.7 mL per minute is hyposalivation.

XEROSTOMIA Salivary Flow3 The average person produces approximately 0.5 L – 1.5 L per day Salivary flow peaks in the afternoon Salivary flow decreases at night when the parotid gland shuts down There is a difference in the quality between stimulated and unstimulated saliva Salivary flow tracks a circadian rhythm and increases in the springtime. The average person produces approximately 0.5 L – 1.5 L per day. Salivary flow peaks in the afternoon and decreases at night when the parotid gland shuts down. There is a difference in the quality between stimulated and unstimulated saliva

XEROSTOMIA Salivary Composition1 90% of saliva is water 10% is composed of inorganic and organic ions, and cellular components sodium, potassium, and calcium are positive ions (cations) chloride, bicarbonate, and phosphates are negative ions (anions) The cationic and anionic components play an important role in the function of saliva Saliva is 90% water, 10% inorganic and organic ions and cellular components. Sodium, potassium, and calcium are cations (positive charge). Chloride, bicarbonate, and phosphates are anions (negative charge).

XEROSTOMIA Ions and Salivary Flow3 As saliva passes through the salivary ducts, cations (sodium and chloride) are reabsorbed into the adjacent blood vessels. As saliva passes through the salivary ducts, cations (sodium and chloride) are reabsorbed into the adjacent blood vessels.

XEROSTOMIA Ions and Salivary Flow3 In exchange, the body releases bicarbonates and potassium. As saliva passes through the salivary ducts, cations (sodium and chloride) are reabsorbed into the adjacent blood vessels. In exchange, bicarbonates and potassium are transferred from the blood vessels into the salivary ducts.

XEROSTOMIA Ions and Salivary Flow3 Stimulated Salivary Flow Saliva passes through the salivary duct very rapidly (a negative result of fast flow) It impedes the exchange of sodium and chloride for potassium and bicarbonate Unstimulated Salivary Flow Has a high content of potassium and bicarbonate (a positive result of slow flow) The quality of unstimulated saliva will change when flow increases because of a stimulus (chewing gum, thinking about lemons, looking at a food you crave) Stimulated salivary flow causes rapid passage through the salivary duct and thus impedes the exchange of sodium and chloride for potassium and bicarbonate. Unstimulated salivary flow is slower and thus has a high content of potassium and bicarbonate. The quality of unstimulated saliva will change when flow increases because of a stimulus (chewing gum, thinking about lemons, looking at a food you crave).

XEROSTOMIA Fluoride and Saliva3 Fluoride is also secreted in saliva. Unlike the ions in saliva, the fluoride content (level) is not altered whether the salivary flow is simulated or unstimulated. Fluoride content is not altered regardless of stimulated or unstimulated salivary flow.

Organic Components of Saliva3 XEROSTOMIA Organic Components of Saliva3 Enzymes: Amylase – converting starch into glucose and fructose Lysozymes – prevents bacterial infections in the mouth Histatins – prevents fungal infections Secretory IgA – immunity mediator Lactoperoxidases – stimulation of minor salivary glands RNase and Dnase – cellular maintenance Lipase – initiates digestion of fat Kallikrein – vasoreactive substances Amylase – converting starch into glucose and fructose Lysozymes – prevents bacterial infections in the mouth Histatins – prevents fungal infections Secretory IgA - immunity mediator Lactoperoxidases - stimulation of minor salivary glands RNase and DNase - cellular maintenance Lipase – initiates digestion of fat Kallikrein- vasoreactive substances

Cellular Composition of Saliva3 XEROSTOMIA Cellular Composition of Saliva3 The cellular composition consists of: Epithelial cells Neutrophils Lymphocytes Bacterial flora Cellular components of saliva include epithelial cells, neutrophils, lymphocytes, bacterial flora. Neutrophils and lymphocytes are white cells that function in immune response

XEROSTOMIA: Epidemiology Factors that Affect Salivary Flow Medication Autoimmune disease (Sjogren’s syndrome, lupus)3 Systemic diseases (diabetes, asthma, kidney, sarcoidosis, HIV)3 Stress/anxiety/depression5 Radiation therapy to the head and neck3 30 Gy = glandular fibrosis (gland can still produce some saliva) 60-70 Gy = glandular destruction (gland can no longer produce saliva) Gender (70 % female, usually postmenopausal3) Sympathomimetic medications (stimulate the sympathetic nervous system)6 Parasympatholytic medications (inhibit the parasympathetic nervous system)6 Circadian rhythms (decreases in the fall and increases in the spring)

XEROSTOMIA: Epidemiology Factors that Affect Salivary Flow Over 400 Medications Can Produce the Side Effect of Xerostomia7 Antacid Antianxiety Anticholinergic Anticonvulsant Antidepressant Antiemetic Antihistamine Antihypertensive Antiparkinsonian Antipsychotic Bronchodilator Cholesterol reducing Decongestant Diet pills Diuretic Hormonal replacement therapy Muscle relaxant Narcotic analgesic Sedative

XEROSTOMIA: Epidemiology Factors that Affect Salivary Flow Age2,8 Studies show that among non-institutionalized people not taking medication, neither the quantity or quality of saliva change significantly with age Studies show a positive correlation between the number of drugs taken and the incidence and severity of xerostomia Studies show that among non-institutionalized people not taking medication, neither the quantity or quality of saliva change significantly with age. Studies show a positive correlation between the number of drugs taken and the incidence and severity of xerostomia.

XEROSTOMIA: Etiology “Dry Mouth” Xerostomia is the term used for the symptom of oral dryness. While oral dryness is most commonly associated with a reduction in salivary gland output (termed salivary gland hypofunction), the symptom may be reported by patients with apparently normal salivation who have changes in saliva composition.1 While oral dryness is most commonly associated with a reduction in salivary gland output (termed salivary gland hypofunction), the symptom may be reported by patients with apparently normal salivation who have changes in saliva composition.

XEROSTOMIA: Etiology Prevalence Xerostomia affects 25% of the population and is becoming one of the fastest-growing oral health problems in North America3,5 Medications are the cause of more than 90% of xerostomia cases 32 million Americans today take three or more medications daily Xerostomia was not a great problem in the past because people did not take as many medications as they do today5 Xerostomia affects 25% of the population and is becoming one of the fastest-growing oral health problems in North America1,9 Medications are the cause of more than 90% of xerostomia cases 32 million Americans today take three or more medications daily Xerostomia was not a great problem in the past because people did not take as many medications as they do today9

XEROSTOMIA: Etiology Global Prevalence The reported prevalence of dry mouth varies widely due to the methodological and population differences in various studies. Prevalence has been estimated to range from 10% to 38%,9-12 with 20% the most commonly reported figure2,3 Xerostomia is becoming increasingly common in developed countries where adults are living longer and poly-pharmacy is very common.13 The reported prevalence of dry mouth varies widely due to the methodological and population differences in various studies. Prevalence has been estimated to range from 10% to 38%, with 20% the most commonly reported figure. Xerostomia is becoming increasingly common in developed countries where adults are living longer and poly-pharmacy is very common.

XEROSTOMIA: Diagnosis “The approach to managing the patient has to follow a logical progression. It should be part of a comprehensive evaluation. Symptoms should be noted and signs should be recognized in order to properly diagnose the condition. Treatment should be based on all of that gathered information.”5 – Joseph L. Perno, DDS, FAGD Special Report – AGD Impact

XEROSTOMIA: Diagnosis Symptoms3,5 Viscous saliva Sticky saliva Difficulty speaking Difficulty swallowing Halitosis Altered taste Complaint of dryness Complaint of burning mouth, lips, or tongue Altered sense of smell

XEROSTOMIA: Diagnosis Signs3,5 Increased caries Food sticking to the oral structures Frothy saliva Gingivitis Absence of saliva Cracking and fissuring of the tongue Ulceration of oral mucosa No pooling of saliva in the floor of the mouth Recurrent candidal infections A toothbrush, mouth mirror, or instrument that sticks to the soft tissues Poorly fitting prostheses

XEROSTOMIA: Diagnosis Two Approaches Increase Salivary Flow Using drugs that mimic or stimulate the parasympathetic division of the autonomic nervous system3 These are typically only used for radiation therapy or Sjogrens’ syndrome-induced xerostomia They have adverse side effects including: sweating, urination, stuffy nose, lacrimation, and abdominal pain. Using citric acid–containing lozenges and candy that are sugar-free1,5 This approach may decrease the pH into an acidic range. Salivary pH is between 6.0 and 7.0. The critical pH where enamel erosion begins to be seen is reported to be below 5.5 Saliva Substitutes Over-the-counter products are indicated for medication-induced salivary hypofunction or xerostomia3,5 A. Increase Salivary Flow 1. Parasympathetomimetic drugs mimic or stimulate the parasympathetic division of the autonomic nervous system 1. Pilocarpine 2. Cevimeline These are typically only used for radiation therapy or Sjogrens’ syndrome-induced xerostomia Very effective so long as there is salivary gland tissue remaining, but they have adverse side effects including: sweating, urination, stuffy nose, and lacrimation. 2. Using citric acid–containing lozenges and candy that are sugar-free This approach may decrease the pH into an acidic range. Salivary pH is between 6.0 and 7.0. The critical pH is reported to be below 5.5 where you begin to see enamel erosion B. Saliva Substitutes Over-the-counter products are indicated for medication-induced salivary hypofunction or xerostomia. May be composed of several ingredients, including carboxymethylcellulose, sorbitol, xylitol, methylparaben, and citric acid.

XEROSTOMIA: Diagnosis Simple Management Strategies for Patients3,14 Perform oral hygiene at least 4 times daily, after each meal and before bedtimes Use fluoride toothpaste Rinse with a salt and baking soda solution 4 to 6 times daily Avoid citrus juices (oranges, grapefruit, tomatoes) Rinse and wipe oral cavity immediately after meals Keep water handy to moisten the mouth at all times Avoid liquids and foods with high sugar content Avoid rinses containing alcohol and salty foods Brush and rinse dentures after meals Apply prescription-strength fluoride get at bedtime as prescribed Use moisturizers regularly on the lips Try salivary substitutes or artificial saliva preparations

XEROSTOMIA: Management Treatment Challenges14 Some patients are predisposed to candidiasis because of the lack of salivary histatins Recommendation: Antifungal medication can be recommended to control fungal growth Denture patients also face challenges Dentures do not adhere to the tissues and are not retained as well Lack of lubrication increases the frictional forces between the dentures and the oral mucosa, causing sores Alveolar bone continues to resorb throughout life―dentures no longer fit properly Denture wearers are prone to inflamed tissues, called denture stomatitis (usually fungal) Be sure the denture correctly adapts to the denture-bearing tissues Optimize the patient’s tissue health Apply oral lubricants or saliva substitutes just before eating Candidiasis (thrush) is a fungal infection of the oral mucosa. Commonly referred to as a “yeast infection.” Antifungal medication can be recommended for treatment. Denture challenges include: Dentures don’t adhere to the tissues and are not retained as well Lack of lubrication increases the frictional forces between the dentures and the oral mucosa, causing sores Alveolar bone continues to resorb throughout life―dentures no longer fit properly Denture wearers are prone to inflamed tissues, called denture stomatitis (usually fungal) Treatment recommendations include: Be sure the denture correctly adapts to the denture-bearing tissues Optimize the patient’s tissue health Apply oral lubricants or saliva substitutes just before eating

XEROSTOMIA: Management Treatment of Xerostomia-Associated Problems14

XEROSTOMIA: Management Treatment of Xerostomia-Associated Problems14

XEROSTOMIA GETTING INVOLVED IN DIAGNOSING XEROSTOMIA CAN BE A WINDOW TO YOUR PATIENTS’ OVERALL HEALTH Diagnosing xerostomia is an important diagnostic tool for other systemic diseases. The signs and symptoms of xerostomia are often associated with and/or result from other conditions. Reformatted

XEROSTOMIA: References 1. Fox PC. Dry mouth: managing the symptoms and providing effective relief. J Clin Dent. 2006;17(2):27-29. 2. Nederfor T. Xerostomia: Prevalence and pharmacotherapy. Wed Dent J Suppl 116: 1-70, 1996 3. Crossley H. Unraveling the mysteries of saliva: its importance in maintaining oral health. Transcript of a lecture presented on August 6 at the 2006 AGD Annual Meeting & Exposition. Gen Dent. 2007;55)4):288-296. 4. Netter FH, Jansen JT. Atlas of Human Anatomy. 3rd ed. Teterboro, NJ: Icon Learning Systems; 2003. 5. Gater L. Understanding xerostomia. AGD Impact. 2008;June(Special Report):26-30. 6. Urquhart D, Fowler CE. Review of the use of polymers in saliva substitutes for symptomatic relief of xerostomia. J Clin Dent. 2006;17(2):29- 33. 7. Kroll B. Dry mouth. The pharmacist’s role in managing radiation-induced xerostomia. Pharma Pract. 1998;14:72-82. 8. Shirodaria S, Kilbourn T, Richardson M. Subjective assessment of a new moisturizing mouthwash for symptomatic management of dry mouth. J Clin Dent. 2006;17(2):45-51. 9. O’Grady NP: Incidence of dry mouth complaint in Cork Dental Hospital population. Stoma (Lisb). 1990;2(17): 55-56, 58. 10. Osterberg T, Birkhed D, Johnannson C, Svanborg A. Longintudinal study of stimulated whole saliva in an elderly population. Scand J Dent Res. 1992;100(6):340-345. 11. Thomson WM, Brown RH, Williams SM. Medication and perception of dry mouth in a population of institutionalized elderly people. NZ Med J 106: 219-221, 1993 12. Locker D: Xerostomia in older adults: A longitudinal study. Gerodontology. 12:18-25, 1985. 13. Edgar WM, O’Mullane DM. Saliva and Oral Health. 2nd ed. London: British Dental Journal Brooks; 1996. 14. Turner MD, Ship JA. Dry mouth and its effects on the oral health of elderly people. J Am Dent Assoc. 2009;138(September–Special Supplement):15S-20S.

XEROSTOMIA This IFDEA Educational Teaching Resource was underwritten by an unrestricted grant from: