Saliva as a Diagnostic Fluid
Dennis E. Lopatin, Ph.D.
University of Michigan
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Dennis E. Lopatin, Ph.D.
Overview of Lecture
Applications of Sialochemistry
 Collection of Saliva
 Examples of Clinical Conditions
 Gingival Crevicular Fluid (GCF)
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Dennis E. Lopatin, Ph.D.
Historical Background:
Diagnostic Testing
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Rice Test (anxiety=dry mouth=guilt)
Dennis E. Lopatin, Ph.D.
Saliva as a Mirror of the Body
Tissue fluid levels of natural substances, as well
as molecules introduced for therapeutic,
dependency or recreational purposes
 Emotional status
 Hormonal status
 Immunological status
 Neurological status
 Nutritional and metabolic influences
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Dennis E. Lopatin, Ph.D.
Applications of Sialochemistry
Diseases of the salivary glands
 Systemic diseases where salivary glands are
involved
 Clinical situations in which salivary flow
and chemistry are helpful in diagnosis or
monitoring patient progress
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Dennis E. Lopatin, Ph.D.
Local Diseases
Obstructive- neoplastic, mucus plugs,
stones
 Inflammatory- acute viral or bacterial,
chronic recurrent bacterial, allergic
 Irradiation
 Functional hyper- or hypoactivity
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Dennis E. Lopatin, Ph.D.
Systemic Diseases
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Sjögren’s syndrome- lymphoepithelial lesions
Cystic fibrosis
Hormonal dysfunction- diabetes, pancreatitis, adrenal-cortex
disease, thyroid disease, acromegaly, menopause
Hypertension
Obesity and hyperlipidemia
Alcoholic cirrhosis
Malnutrition
Neurologic diseases- Parkinson’s disease, Bell’s and cerebral
Psychogenic diseases
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Dennis E. Lopatin, Ph.D.
Access to Saliva from Blood
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Dennis E. Lopatin, Ph.D.
Clinical Situations Affecting
Salivary Secretions
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Digitalis toxicity
Drug monitoring
Environmental pollutants
Ovulation
Immunodeficiency
Pharmacological agents
– “Dry mouth” side effects, drugs with parasympathetic, sympathetic
and ganglionic blocking effects
– Direct effects- hypersensitivity or idiosyncratic reaction
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Dennis E. Lopatin, Ph.D.
Methods of Collection of
Saliva
Whole Saliva
 Catheterization
 Parotid Saliva
 Submandibular (Submaxillary) Saliva
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Dennis E. Lopatin, Ph.D.
Limitations in Use of Whole Saliva
An admixture of parotid, submandibular and minor
gland secretions mixed with food debris, bacteria, shed
cells, leukocytes and other particulate matter.
 Compositional studies are affected by proportions of
secretions from different glands, as well as chemistry of
non-salivary elements
 In studies examining non-salivary components, must
take care to exclude GCF, especially where
inflammation is present.
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Dennis E. Lopatin, Ph.D.
Standardization of Collection
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Resting secretions
– need an accommodation period of at least 5 minutes.
(Influence of collection procedure as stimulus)
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Stimulated saliva
– Consistent gustatory stimulant throughout the study
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Flow rate
– Timed, focus on specific gland
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Time of day
– Circadian rhythm, time of collection is important
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Dennis E. Lopatin, Ph.D.
Salivary Studies in Cystic Fibrosis (CF)
CF gene cloned in 1991
 The gene product is a cyclic AMP-regulated chloride ion
channel named CFTR
 Cystic Fibrosis Transmembrane Conductance Regulator
 Most investigators felt that chloride and water secretion
was the unifying key to explain the abnormalities and
consequences of CF.
 A disease of all exocrine glands.
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Dennis E. Lopatin, Ph.D.
Sialochemistry Studies of CF
Marked increase in calcium, proteins and phosphate,
most evident in submandibular glands
 Turbidity of the submandibular saliva probably due to
precipitation of calcium-binding proteins
 Too much overlap in calcium levels between CF and
asthmatics to serve as screening test
 Flow rate of saliva from labial salivary glands virtually
absent in 90% of CF children, probably due to turbidity
and blockage of duct
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Dennis E. Lopatin, Ph.D.
Diagnostic Aids in Clinical Situations
Digitalis toxicity (calcium and potassium)
 Affective disorders (prostaglandin)
 Immunodeficiency (sIgA)
 Stomatitis in chemotherapy (albumin)
 Cigarette usage (cotinine)
 Gastric cancer (nitrates and nitrites)
 Forensic medicine (blood group substance)
 Coeliac disease (anti-IgA gliadin)
 Liver function (caffeine clearance)
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Dennis E. Lopatin, Ph.D.
Malignancy
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P53 Tumor suppressor antigen
– inactivation in certain cancers leads to accumulation.
Oral squamous cell carcinoma leads to anti-p53
antibodies in saliva
Salivary Defensin-1 levels elevated in oral SCC
(made by PMN’s).
 C-erbB-2 (erb) Tumor marker associated with breast
carcinoma.
 CA 125 (ovarian cancer marker) associated with
elevated salivary levels
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Dennis E. Lopatin, Ph.D.
Drug and Hormone Monitoring
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Psychiatrists studying methadone: advantages
using saliva
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humanitarian- less discomfort
clinical- patient acceptance of repeated testing
children and patients with limiting coping abilities
economic (do it yourself tests)
HIV therapy
 Epilepsy
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Dennis E. Lopatin, Ph.D.
Drugs
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Dennis E. Lopatin, Ph.D.
Salivary Antibodies and Antigens
Advantages in large scale studies
 Viral Screening
 Antigen Detection
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– H. pylori (PCR of saliva)
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Antibody Screening
– rubella
– hepatitis A and B
– Shigella
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Dennis E. Lopatin, Ph.D.
Gingival Crevicular Fluid
(GCF)
(E) Cervical enamel
(OSE) Oral sulcular epithelium
(JE) Junctional epithelium
(OE) Keratinized oral epithelium
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Dennis E. Lopatin, Ph.D.
Collection of GCF
Static fluid
 Timed crevicular fluid flow
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Dennis E. Lopatin, Ph.D.
GCF Flow and Inflammation
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Dennis E. Lopatin, Ph.D.
GCF Flow and Probing Depth
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Dennis E. Lopatin, Ph.D.
GCF Flow and Menstrual Cycle
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GCF flow
highest at
ovulation
Dennis E. Lopatin, Ph.D.
GCF and Tetracycline Levels
Maximum GCF
Minimum GCF
Blood by finger
puncture
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Dennis E. Lopatin, Ph.D.
Conclusions
Sialochemistry provides important information in
a variety of clinical and disease states
 Greater acceptance by patients
 Non-invasive in most cases
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Dennis E. Lopatin, Ph.D.