Salivary Gland Hypofunction




1. The Salivary Glands
2.What is Salivary Gland Hypofunction?
3. Causes
4. Signs & Symptoms
5. Related Consequences of Salivary Gland Hypofunction



1. THE SALIVARY GLANDS



(Taken from YouTube: http://www.youtube.com/watch?v=3V0cyhoAZm0)


2. WHAT IS SALIVARY GLAND HYPOFUNCTION?

  • Salivary gland hypofunction refers to decreased saliva secretion due to dysfunction of the salivary glands
  • The key components of saliva related to mucosal lubrication include mucins, proline-rich glycoproteins and water
  • Loss of acini limits the ability of the gland to transport fluid and produce saliva
    • Occurs in a number of clinical conditions eg. Sjogren’s syndrome
  • Most common presentation of salivary gland disease : complaint of dry mouth, Xerostomia, which is a symptom rather than a diagnosis or disease (as dry mouth may be due to other causes not related to salivary dysfunction)
  • Dysfunction arising from the lack of saliva secretion leads to dryness, mucous membrane friability and altered oral sensation
  • Individuals with salivary gland dysfunction are at risk of a variety of oral and systemic complications
    • the absence of water and mucin will hinder formation of an adequate food bolus leading to swallowing difficulties (dysphagia)
    • an important aspect of salivary content relates to remineralisation secondary to the presence of anionic rich proteins as well as statherin. Absence of the aforementioned substances contributes to a much greater risk of development of dental caries and decay
  • Salivary hypofunction can be divided into two kinds, (depending on the cause):
    • Temporary
      • affects only resting (basal) secretion and patients retain their ability to respond normally to gustatory, masticatory, or olfactory stimuli
    • Chronic
      • long term potential to cause dental and oral mucosal disease and affect oral function
      • decrease in both resting and stimulated secretion rates
      • greater symptoms and less response to treatment
(http://www.cda.org/library/cda_member/pubs/journal/jour1200/xero.html)



3. CAUSES

Head and Neck radiation therapy used to be considered the most common cause of xerostomia and salivary gland hypofunction. However, in recent years, medication and drugs have emerged as the most common cause, especially in the geriatric patient population. Over 400 medications have been known to cause dry mouth as a potential adverse effect. Chronic xerostomia and salivary gland hypofunction can also be linked to a variety of medical conditions such as Sjögren’s syndrome, sarcoidosis, uncontrolled diabetes, depression, HIV infection and central nervous system disorders.
(http://jada.ada.org/cgi/content/full/134/5/619)

  1. Drugs

    • Prescription drug use is the most common cause of chronic salivary gland hypofunction
    • Over 500 medications which have xerostomia as a side effect (Table 1)
    table 1
    (Sandra F. Cassolato and Robert S. Turnbull. p4)
    • Most of these drugs cause xerostomia by inhibiting signalling pathways within salivary tissue and reducing salivary secretions of the glands.
    • 3 main areas of drug interference: parasympathetic neuroeffector junction, adrenergic effector junction, central connections of the autonomic nervous system (H. Mesee and R. Matsuo, 2007, p8)
    • From Formation of Saliva, we understand that salivary gland metabolism and growth are controlled by Autonomic Nervous System(ANS) and the control of salivation depends on neurotransmitter release from the nerve endings in the salivary glands
    • By disrupting the transmission of nerve impulses at the 3 main areas mentioned above, amount of salivary secretion is affected
    • The severity of xerostomia in each individual patient taking these drugs is also affected by the amount of drugs he or she is taking
    • Out of the drugs mentioned in Table 1, Antidepressants, Antipsychotics, Antihistamines, Anticholinergics are the main drugs that cause disruption to the signalling pathways within salivary tissue by blocking the action of the neurotransmitter, acetylcholine, at the parasympathetic neuroeffector junctions (Martin S. Greenberg, 2004, pp 2-3)
    • Diuretics are drugs that elevate rate of urination and thus increase excretion of water from bodies. They will affect the movement of water and/or electrolytes through cell membrane of salivary acinar cells.
    • Bronchodilators and Decongestants affect the sympathetic nervous stimulation of the salivary glands
    • As a general rule, the drying and hyposalivatory effects of drugs are transient - the removal of the drug would enable salivary function to return to the original pre-treatment level
  2. Ageing

    • Observations and morphological changes have shown changes in structure of salivary glands with age. However, it has been difficult to make a definite relation between these changes in structure and the loss in salivary gland function.
    • Changes in structure of salivary gland with age
      • Relatively linear reduction in the proportional volume represented by acinar cells
      • Decrease is slightly larger for the submandicular gland (approximately 37%) than for parotid glands (approximately 32%) (Figure 1)
      • Similar observations have been found in minor glands as well
      Figure 1
      Figure 1: Proportional acinar volume of salivary glands in relation to age
      • Salivary glands in elderly have higher percentage of ductal elements versus acinar cells when compared to younger people (Figures 2 and 3)
      • Acinar cells have been replaced by fatty or connective tissue (Figure 3)
      Figure 2
      Figure 2: Minor salivary gland of a young individual showing close approximation of the acinar elements
      Figure 3
      Figure 3: Minor serous salivary gland from an elderly individual showing adipose replacement
      • Reduction in acinar cells is significant as they are the only cell type in salivary glands capable of transporting fluid.
      • Furthermore, acinar cells make about 85-90% of the secreted proteins found in saliva with key oral functions
    • However, studies have not shown any significant change in saliva flow rates with effect of age despite these changes in structure of salivary glands with age.
    • Thus, clinically significant diseases in flow rates and complaints of oral dryness in an olded adult are not normal and should not be considered a natural consequence of growing old.
    • If so, why does the prevalence of Xerostomia increase with age?
      • One possible reason suggested in Color Atlas and Text of DENTAL CARE OF THE ELDERLY is that young adults have substantial secretory reserve capacity which can be utilized later in life. Thus, despite the loss of acinar tissue throughout the adult lifespan, normal levels of secretory function can be achieved, as long as there is no further stress on the system. Thus, salivary glands of older people may be viewed as endogenously adequately functional but vulnerable to external factors. In presence of exogenous influences (eg. drugs, x-radiation), the lack of a secretory reserve in elders renders the glands unable to function satisfactorily with the associated disastrous consequences of salivary gland hypofunction (which will be elaborated further later)
      • Furthermore, the elderly are often associated with renal diseases, diabetes mellitus, hypertension, etc. The prescribed medications for these diseases often have salivary gland hypofunction as a side effect.
    • In conclusion, it would be reasonable to say that changes in salivary gland secretions are not age changes per se but rather, a result of the incremental effects of wear, diseases and other factors.

      (Drummond, John R; Newton, James P; Yemm, Robert. 1995. pp 44-47)
  3. Therapeutic irradiation to the head and neck region

    Therapeutic irradiation damages the salivary glands resulting in xerostomia and salivary gland hypofunction. Such dysfunction is caused by inflammation and degeneration of salivary gland parenchyma, especially that of serous acinar cells. Radiation damage causes a glandular inflammatory infiltrate and concomitant swelling, which can lead to an increase in periductal pressure and ductal constriction, hence causing decreases in salivary flow. Not only does salivary flow decrease, there may be salivary retention that develops and could increase pain and swelling.

    Salivary flow commonly decreases within one week after ionising radiation therapy starts. Xerostomia becomes apparent if doses exceed 10Gy and irreversible dysfunction is induced if doses are larger than 54Gy. The degree of dysfunction is generally related to the radiation dosage and the volume of glandular tissue in the radiation field. Since the effects of irradiation are asymmetric, some salivary glands can remain unaffected and continue to produce normal salivary volumes. Such salivary glands that have been excluded form the radiation field may also become hyperplastic, as a result of the body's compensatory mechanism to cope with the decrease in or cessation of salivary flow from the affected tissues.
    (http://www.cancer.gov/cancertopics/pdq/supportivecare/oralcomplications/HealthProfessional/page15/print)

    In general, there may be observable recovery of the salivary glands in the first 6 months of post-therapy, and maximum recovery may be obtained after 12 months. However, recovery is often incomplete and the severity of the problem may increase over time.

    The specific mechanisms that are responsible for damage to the salivary glands are not clear, but possible mechanisms include the following:
    • damage to the salivary parenchyma (particularly acinar cells)
    • mitotic and interphase cell death
    • direct DNA damage or effects of secondary metabolites
    • damage to progenitor cells
    • altered gene expression

    For most patients, their quality of life is almost irreparably impaired. The loss of saliva leads to rampant dental caries, mucositis, dysphagia, frequent infections, difficulties with eating, weight loss and often severe depression. Proper dental care given prior to the administration of radiative treatment can obviate or reduce some of the changes in the salivary gland secretions, although not many patients receive such care. Recent studies have shown, though, that with careful shielding, the effects of the radiation may be reduced. It has also been demonstrated that pilocarpine significantly reduces the effects of irradiation-induced xerostomia.
    (Sreebny, LM. 2000. pg 140-160.)
  4. Diseases
    • Sjogren's syndrome

      Sjogren's syndrome is a chronic, multisystem, autoimmune disorder involving the salivary and lacrimal glands. It is characterised by:
      • polyclonal B cell proliferation, probably as a result of loss of T cell regulation
      • generalised exocrine gland hypofunction
      • serologic abnormalities
      • organ system changes
        (Sreebny, LM. 2000. pg 140-160.)

      Sjogren's syndrome can have widespread manifestations and is classified into:
      • Primary Sjogren's syndrome: association of xerostomia (dry mouth) and xerophthalmia (dry eyes)
      • Secondary Sjogren's syndrome: association of either xerostomia or xerophthalmia and an autoimmune connective tissue disease.
      The lesion in Sjogren's syndrome is an immunologically mediated inflammatory exocrinopathy that starts with periductal infiltration of the salivary tissue by plasma cells and lymphocytes. Glandular acini atrophy will occur and progressively disappear, with a dense infiltrate of lymphocytes replacing the cells. Salivary duct autoantibodies are another characteristic finding in this disease, but this may be unrelated to duct damage.

      Salivary gland hypofunction can have a devastating effect on oral health and may be an indicator of systemic disease such as Sjögren's syndrome. A certain prospective study investigates the oral and non-oral signs and symptom in 120 patients with objective evidence of salivary gland hypofunction (ie, an unstimulated whole salivary flow of < 0.2 ml/min). Patients were questioned about symptoms associated with decreased oral function; non-oral symptoms were also noted. The underlying cause of salivary gland hypofunction was established on the basis of clinical and laboratory findings and further investigations. Eighty-five per cent of patients reported symptoms of decreased oral function in addition to oral dryness. Non-oral signs and symptoms were reported by 106 patients. Fifty-three per cent of patients were diagnosed as having Sjögren's syndrome. The prevalence of the following non-oral signs and symptoms were significantly higher in patients with Sjögren's syndrome, than in those without; a history of dry/irritated eyes, salivary gland swelling, dry skin and reduced lacrimal flow. Salivary gland hypofunction is associated with a wide range of oral and non-oral signs and symptoms. Several of these are of potential value as triggers for the clinician to identify patients with Sjögren's syndrome, and should serve to prompt referral for specialist investigation.

      Salivary Gland Hypofunction - Cariology
      (Sreebny, LM. 2000. pg 140-160.)


    • Human Immunodeficiency Virus (HIV) Infection

      [Untitled]
      (taken from: http://www.scielo.br/img/revistas/clin/v64n5/14t2.gif)
    Xerostomia and salivary gland hypofunction in HIV-infected patients are usually attributed to xerostomic medications (e.g HAART). In an experiment conducted by A.L. Lin in the Journal of Dental Research, titled Alteration in Salivary Function in Early HIV Infection, the analysis showed that unstimulated whole and stimulated saliva from each of the salivary glands decreased in the early stages of HIV infection. Secretory function of the glands were not the only reduced factor, but saliva composition was altered as well. The study suggests that salivary gland function is adversely affected during the early stage of the disease.


  5. Interference of Nervous Transmissions

    Interference with neural transmission affecting the salivar glands can result from:
    • certain medications
    • autonomic dysfunction
    • CNS conditions such as Alzheimer's desease
    • trauma
    • decrease in mastication resulting in salivary gland atrophy
    Hypoplasia of the parotid glands has also been reported in patienst with Melkersson-Rosenthal Syndrome (a rare neurological disorder) which classically produces a fissured tongue, salivary gland hypofunction, and facial hemiparesis.
    (http://www.mkdentalcare.com/DryMouth.htm)

    Decreased mastication saliva


    Mastication is the exercise of the oral apparatus. Chewing increases function, while lack of it induces atrophy of disuse. Impaired mastication is associated with:
    • a reduction in the width of the periodontal membrane
    • a loss of supporting alveolar bone
    • a decline in the function of muscles
    • a reduction in the mass of salivary glands and the decrease in the synthesis and secretion of saliva
    The salivary glands are particularly vulnerable to decreased mastication. Certain findings have related the partial or total loss of teeth, the presence of dentures, a decrease in bite force, temporomandibular joint dysfunction, extensive caries and periodontal disease, pain, immobilisation of the jaws, and other clinical conditions to a decrease in the flow of saliva and salivary gland hypofunction. These changes are not only the primary cause of salivary dysfunction, but may aggravate other conditions which may induce salivary gland disease.
    (Sreebny, LM. 2000. pg 140-160.)



4. SIGNS & SYMPTOMS
Symptoms are related to decreased fluid in oral cavity and effects it has on mucosal hydration and oral functions

ORAL
SALIVA:
  • Decrease in amount, foamy, viscous, ropy
  • Litlle or no pooled saliva in the mouth floor during examination
  • Thick or cloudy saliva expressible from parotid or submandibular gland ducts
TONGUE: Burning (glossopyrosis), pain (glossodynia), Fissuring, Lobulation, Appear smooth and reddened with loss of papillation
CHEEKS: Dry
SALIVARY GLANDS: Bilateral salivary gland enlargement and swelling, pain
THIRST: Frequent ingestion of fluids, especially while eating; keep water at bedside
MASTICATION: Difficulty with eating dry foods; difficulty with the use of a denture
SWALLOWING: Difficulty with (dysphagia)
SPEECH: Difficulty with (dysphonia)
TASTE: Difficulty with (dysgeusia)
DENTAL CARIES:
  • Frequent recurrent decay even in presence of vigilant oral hygiene (This is because with diminished salivary output, there is a tendency for greater accumulations of food debris in interproximal regions, especially where recession has occurred. Saliva acts as a buffer. With decreased salivary secretion, it results in a more acidic environment favourable for plaque development and caries growth.)
  • Present in oral sites not usually prone to decay e.g. lower anterior teeth, cervical areas
  • Multiple caries in cervical, incisal and marginal locations
ORAL MUCOSA: Dry, pale and corrugated in appearance OR sticky
INFECTIONS AND DISEASES:
Whole saliva is the principal protector of the oral tissues. As the saliva level drops, the mouth becomes more susceptible to infections and diseases.
For example,
Signs of erythematous candidiasis:
  • dorsal tongue with erythema, loss of flilliform papillae and fissured or cobblestoned appearance
  • angular cheilitis - inflammatory lesion at corner of mouth
  • patchy erythema on other mucosal surfaces
  • frequent fungal infection that appears as red patches on mucosa

Drymouth.info. Wm. Wrigley Jr. Company (2009)


5. RELATED CONSEQUENCES OF SALIVARY GLAND HYPOFUNCTION


Xerostomia
Xerostomia is the medical term for dry mouth. It is sometimes called pasties, cottonmouth, or doughmouth. It is common in smokers and is also a common symptom of salivary gland disease.

It is caused by a decrease in the amount of saliva produced and/or an alteration in its chemical composition and can result in a significant decline in quality of life by decreasing taste sensation and impairing chewing ability. It can also cause difficulty in speech and halitosis, otherwise known as bad breath and contributes to increase in the number of dental caries.

Xerostomia is more prevalent in the elderly population, primarily due to their increased dependence and use of drugs, as well as their susceptibility to diseases. It can cause denture wearing to be very uncomfortable, exacerbating chewing difficulties. This is mainly due to reduced surface tension between denture and oral mucosa. Many drugs and drug classes have been linked to xerostomia and the xerostomic effect increases when many of the drugs are taken concurrently. (Refer to section on Drugs under Causes above)
(Sandra F. Cassolato and Robert S. Turnbull, p1)


Xerostomia produces certain changes in the mouth:
  • Salivary viscosity increases, with resultant impaired lubrication of oral tissues
  • Buffering capacity is compromised, with increased risk for dental caries
  • Oral flora becomes more pathogenic
  • Plaque levels accumulate due to the patient’s difficulty in maintaining oral hygiene
  • Acid production after sugar exposure results in further demineralization of the teeth and leads to dental decay
Salivary Gland Hypofunction - Cariology
(Sreebny, LM. 2000. pg 140-160.)





References

1. Practitioner portal:Diagnosis of Dry Mouth: Symptoms, signs, causes. Retrieved 29 October, 2009 from http://www.drymouth.info/practitioner/diagnosis.asp
2) Porter, S. R., Scully, C., & Hegarty, A. M. (2004). An update of the etiology and management of xerostomia. Oral Surg Oral Med Oral Pathol Oral Radiol Endod, 97(1), 28-46.
3) Cassolato, S. F., & Turnbull, R. S. (2003). Xerostomia: clinical aspects and treatment. Gerodontology, 20(2), 64-77.
4) Drummond, J.R. (1995). Colour Atlas and Text of Dental care of the Elderly. : Spain: Mosby-Wolfe.
5) Mese, H., & Matsuo, R. (2007). Salivary secretion, taste and hyposalivation. J Oral Rehabil, 34(10), 711-723.
6) National Cancer Institute: Conditions Affected By Both Chemotherapy and Head/Neck Radiation. Retreived October 30, 2009 from http://www.cancer.gov/cancertopics/pdq/supportivecare/oralcomplications/HealthProfessional/page15/print.
7)Oral complications of HIV disease. Retreived October 3o, 2009 from
http://www.scielo.br/scielo.php?script=sci_arttext&pid=S1807-59322009000500014.
8)Daniels, T (2000). Xerostomia -- Clinical Evaluation and Treatment in General Practice. Retreived October 30, 2009 from
http://www.cda.org/library/cda_member/pubs/journal/jour1200/xero.html.
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Last Accessed: 30/10/09
Used in: Causes
10) Coulthard, Paul; Horner, Keith; Sloan, Phillip; Theaker, Elizabeth; (year of publication); Oral and Maxillofacial Surgery, Radiology, Pathology and Oral Medicine; (pages)
Used in: Causes - Sjogren's Syndrome
11) http://www.mkdentalcare.com/DryMouth.htm.
Last Accessed: 22/10/09
Used in: Causes - Interference with Neurological Transmissions
12) http://grants.nih.gov/grants/guide/pa-files/PA-92-082.html.
Last Accessed: 23/10/09
Used in: Causes - Sjogren's Syndrome
13) Sreebny, Leo M.; Shwartz, Steven S.; (1986, updated 1997); Reference Guide to Drugs and Dry Mouth; Abstract
Used in: Xerostomia
14) Saliva in Health and Disease: An appraisal and update; LM Sreebny; www.fdiworldental.org/assets/pdf/commission/97_6_3.pdf.
Last Accessed: 23/10/09
Used in: Causes






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