Aging and Diseases of the Salivary Glands

Biology of Salivary Glands

Domenica G. Sweier DDS

June 4, 2003

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Saliva

Frustrating for the dental team yet necessary for the patient!

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When there is not Enough

Too little saliva can significantly alter a person’s quality of life and the morbidity associated with multiple systemic conditions• How little is too little? • What affects the quality and quantity of saliva

production and flow?

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Objective vs Subjective

Objective• Major gland secretions

Resting flow rate with a Carlson-Crittenden Cup

• Minor gland secretions

• Whole saliva Stimulated flow rate

with citric acid, wax

Subjective• Complaints of dry

mouth (xerostomia)

• Questionnaire

• Thirst

• The “cracker” test

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Xerostomia

Commonly referred to as “dry mouth” Diminished salivary flow rate, typically

accepted as a 50% decrease in the clinically determined rate in healthy individuals not taking medications• Resting Flow Rate 0.3-0.4 ml/min• Stimulated Flow Rate 1-2 ml/min

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Clinical Signs/Symptoms of Xerostomia

Dryness of mucous membranes

Tongue fissuring and lobulation (scrotal tongue)

Angular cheilosis/cheilitis Fungal infections Prosthesis-induced

stomatitis Amputation caries Thick, ropey saliva

Dysphagia Dysgeusia Difficulty eating/speaking/

wearing prosthesis Swelling of the salivary

glands Difficulty expressing

saliva Cheek biting Persistent need for fluids Burning tongue

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What Contributes to Xerostomia?

Aging• Hormonal Changes/Menopause

Disease• Local• Systemic

Environmental Insults/Trauma Medications

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Aging

Salivary Quantity in Health• No changes in major

secretions (parotid, submandibular)

• No changes in minor secretions

Salivary Quality in Health• No general changes in

salivary constituents

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Aging

If the quality and quantity of saliva doesn’t change with age, then what accounts for the increased incidence of xerostomia and associated morbidity among the elderly?• Medications, diseases, and other environmental

insults affect both the quality and quantity of saliva An increase in incidence of these insults generally

associated with an increase in age

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Menopause Average age of onset of menopause in USA is 50

years Oral symptoms common, particularly among those

with systemic complaints Cross-sectional and longitudinal studies have failed

to provide significant and reproducible evidence that salivary flow is affected by menopause• Oral complaints most likely the result of the types and

numbers of xerostomic medications taken Anti-hypertensives, anti-depressants, and anti-histamines are

common in this group

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Diseases/Environmental Factors

Diseases• Local• Systemic

Environmental Factors• Head and Neck Radiation• Chemotherapy• Medications

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Local Diseases

Tumors/Growths• Benign

• Malignant

Obstructive Diseases• Calculi, mucus plugs

• Unusual anatomy

Inflammatory Diseases• Acute viral sialadenitis

• Acute and recurrent bacterial sialadenitis

• Inflammation/Infection secondary to systemic disease

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Tumors/Growths

Primary benign and malignant tumors• Determine whether

benign or malignant since they are treated differently

• Incisional biopsy for definitive diagnosis

• Smaller the involved gland, more likely malignant

Malignant• Seek medical attention for

swelling under the chin or around the jawbone, if the face becomes numb, facial muscles do not move, or there is persistent pain

• Usually treated with a combination of surgery and radiation

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Obstruction: Sialolithiasis

Calculi form in the duct, blocking the egress of saliva• Majority in submandibular gland

Painful swelling which increases at meal time Bi-manual palpation in submandibular gland X-ray, sialography, CT, ultrasound Analgesics, try to push stone out, may need to

dilate orifice to remove

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Submandibular Calculi

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Unusual Anatomy

Unusual anatomy in the gland manifested as strictures in the duct system• Recurrent obstruction with associated pain and

inflammation of glands• Pooling of saliva leading to secondary infection

May need surgery to remove affected area of gland or entire gland

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Inflammation/Infection: Viral

Mumps is the most frequent diagnosis of acute viral sialadenitis• Member of the paramyxoviridae• Mostly in parotid• The incubation period is 2-3 weeks• Acute painful swelling and enlargement• Fever, headache, loss of appetite• Most common in children• Very effective vaccine

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Inflammation/Infection: Bacterial

Types• Acute suppurative bacterial sialadenitis

Commonly S. aureus, S. viridans, H. influenzae, E. coli

• Chronic recurrent sialadenitis May be secondary to some type of obstruction or unusual

anatomy May be due to resistant organism; culture to determine

Treatment• Antibiotics and analgesics• Rehydrate and stimulate saliva• May need open drainage/surgery

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Bacterial Parotiditis

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Systemic Diseases Sjögren’s Syndrome Sarcoidosis Cystic Fibrosis Diabetes Alzheimer’s Disease AIDS Graft vs Host Disease Dehydration

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Sjögren’s Syndrome

Autoimmune disorder affecting lacrimal and salivary glands• Xerostomia and keratoconjunctivitis sicca

Primary and Secondary disease• The latter associated with another autoimmune disorder

such as RA, SLE, etc. Dense inflammatory infiltrate with destruction of

glandular tissue Treatment is palliative

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Sarcoidosis

Unknown cause; believed to be alteration in cellular immune function and involvement of some allergen

Any organ but most often the lungs; can affect the parotid gland

Granulomatous inflammation Most often drugs of choice are

corticosteroids

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Cystic Fibrosis

Faulty transport of sodium and chloride from within cells lining lungs and pancreas to their outer surface

Causes production of an abnormally thick sticky mucus

Obstruction of pancreas leads to digestive problems; inability to digest and absorb nutrients

Gene has been identified and cloned No known “cure” therefore palliative treatment

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Diabetes

Uncontrolled blood glucose levels may contribute to xerostomia

Medications may induce xerostomia May get enlargement and inflammation of

parotid glands (common in endocrine diseases)

Difficulty to ward off infection: candidiasis, gingivitis, periodontitis, and caries

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Alzheimer’s Disease

A neurodegenerative disorder leading to a decrease in cognition and mobility

May affect the neurological component to salivary production and/or flow

Xerostomic medications• Complicated by behavior which makes it difficult to

maintain a healthy dentition Poor oral hygiene Poor cooperation for dental care and treatment in a

conventional setting

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AIDS

HIV-Associated Salivary Gland Disease (HIV-SGD)• Enlargement of the major salivary glands• Xerostomia• Some similarities to autoimmune diseases• HIV itself not consistently found to be in

glandular tissue Medications

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Graft vs Host Disease (GVHD)

Immune cells of an allogenic transplant attack recipient

Acute, < 100 days, and chronic > 100 days Major cause of morbidity and mortality Initial presentation as a red rash Salivary gland involvement with swelling and

inflammation Progresses quickly to life-threatening condition Treat by increasing immunosuppression

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Dehydration

Defined as the loss of water and essential body salts (electrolytes) needed for body function• Sweating, diarrhea, emesis, blood loss, etc.

Symptoms include flushed face, dry, warm skin, fatigue, cramping, reduced amount of urine

Oral signs/symptoms• Xerostomia, dry tongue• Thick, sticky saliva• Dry, cracked lips (cheilosis)

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Head and Neck Cancer: Radiation Therapy

Goal is to kill cancer cells Measured in Gray (Gy) units of absorbed

radiation: 1 Gy = 100 cGy = 100 rads Can be used alone or combined with surgery

and/or chemotherapy Three main routes

• External beam (most head and neck)• Brachytherapy (body cavities)• Interstitial

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Radiation Dose

Dependent on tumor tissue/type Average of 200 cGy daily for 5 consecutive

days with two days of rest Total cummulative dose ranges from 5000

cGy to 8000 cGy for advanced tumors Threshold of permanent destruction is

2100- 4000 cGy

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Tissue Response

25 Gy: Bone marrow, lymphocytes, GI epithelium, germinal cells

25-50 Gy: Oral epithelium, endothelium of blood cells, salivary glands, growing bone and cartilage, collagen

Doses > 50 Gy: bone and cartilage, skeletal muscle

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Tissue Changes

Irradiated tissue becomes hypocellular, hypovascular, and hypoxic resulting in fibrosis and vascular occlusion

The destruction is mostly permanent• Irradiated tissue does not re-vascularize with time

As a result, irradiated tissue does not heal well after injury

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Common Side Effects: Systemic

Nausea Vomiting Neutropenia Alopecia Fatigue

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Common Side Effects: Oral

Mucositis and Dermatitis Dysphagia Dysgeusia Trismus Osteo- and soft tissue necrosis Xerostomia

• Fungal infections

• Radiation Caries

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Radiation: Xerostomia

Parotid gland is more susceptible than the submandibular or sublingual glands

See a slight improvement after therapy but will soon plateau at a lower level than pre-therapy

Result is thick, ropey saliva, decreased in amount, with markedly diminished lubricating and protective qualities

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Radiation: Mucositis

The oral eipthelium will get a “sun burn” like inflammation

This will be exacerbated by the lack of the lubricating properties of saliva

The result will be a red, irritated, dry mucosa

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Saliva Post-Radiation

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Mucositis

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Radiation Caries

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Prosthesis-Induced Stomatitis

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Fungal Infections

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Scrotal Tongue

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Chemotherapy Is given orally, IV, by injection (SQ, IM, IL), or

topically in cycles depending on the treatment goals (type of cancer, how your body responds, how well you body recovers, etc.)

Affects all rapidly dividing cells• Many side effects in all body systems

Oral complications from direct damage to oral tissues secondary to chemotherapy and indirect damage due to regional or systemic toxicity• Frequency and severity related to systemic immune

compromise, i.e. myelosuppresion

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Chemotherapeutics

Drugs commonly associated with oral complications• Methotrexate• Doxorubicin• 5-Fluorouracil (5-FU)• Busulfan• Bleomycin• Platinum coordination complexes

Cisplatin Carboplatin

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Tissue Damage

The propensity of chemotherapy to damage tissue, specifically oral tissues, is dependent on each individual drug and its ability to induce myelosuppresion (neutropenia)

Drugs differ on the timing of myelosuppresion• Consider this when treating patients undergoing

chemotherapy Tissues, oral tissues, return to pre-chemotherapy

state when allowed time to heal after therapy

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Common Side Effects: Systemic

Fatigue Nausea Constipation Diarrhea Hemorrhage Anemia Neutropenia

Pain Alopecia Peripheral neuropathy CNS disturbances Fluid retention Bladder and kidney

problems

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Common Side Effects: Oral

Mucositis (ulcerative) Reactivation of HSV Dysgeusia Dysphagia Infections

• Fungal

• Periodontium

• periapices

Neuropathies Salivary gland

dysfunction/toxicity• xerostomia

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Summary While there appear to be many insults leading to

salivary hypofunction, healthy aging does not appear to be one of them

The main insults leading to salivary gland damage and/or hypofunction are• Disease

Local Systemic

• Environmental insults/trauma Radiation Chemotherapy

• Medications