Saliva as a Diagnostic Fluid

Dennis E. Lopatin, Ph.D.Dennis E. Lopatin, Ph.D.Page no. Page no. 11

Saliva as a Diagnostic FluidSaliva as a Diagnostic Fluid

Dennis E. Lopatin, Ph.D.Dennis E. Lopatin, Ph.D.University of MichiganUniversity of Michigan


Overview of LectureOverview of Lecture

Applications of SialochemistryApplications of Sialochemistry Collection of SalivaCollection of Saliva Examples of Clinical ConditionsExamples of Clinical Conditions Gingival Crevicular Fluid (GCF)Gingival Crevicular Fluid (GCF)


Historical Background: Historical Background: Diagnostic TestingDiagnostic Testing

Rice Test (anxiety=dry mouth=guilt)Rice Test (anxiety=dry mouth=guilt)


Saliva as a Mirror of the BodySaliva as a Mirror of the Body

Tissue fluid levels of natural substances, as well Tissue fluid levels of natural substances, as well as molecules introduced for therapeutic, as molecules introduced for therapeutic, dependency or recreational purposesdependency or recreational purposes

Emotional statusEmotional status Hormonal statusHormonal status Immunological statusImmunological status Neurological statusNeurological status Nutritional and metabolic influencesNutritional and metabolic influences


Applications of SialochemistryApplications of Sialochemistry

Diseases of the salivary glandsDiseases of the salivary glands Systemic diseases where salivary glands are Systemic diseases where salivary glands are

involvedinvolved Clinical situations in which salivary flow Clinical situations in which salivary flow

and chemistry are helpful in diagnosis or and chemistry are helpful in diagnosis or monitoring patient progressmonitoring patient progress


Local DiseasesLocal Diseases

Obstructive- neoplastic, mucus plugs, Obstructive- neoplastic, mucus plugs, stonesstones

Inflammatory- acute viral or bacterial, Inflammatory- acute viral or bacterial, chronic recurrent bacterial, allergicchronic recurrent bacterial, allergic

IrradiationIrradiation Functional hyper- or hypoactivityFunctional hyper- or hypoactivity


Systemic DiseasesSystemic Diseases Sjögren’s syndrome- lymphoepithelial lesionsSjögren’s syndrome- lymphoepithelial lesions Cystic fibrosisCystic fibrosis Hormonal dysfunction- diabetes, pancreatitis, adrenal-cortex disease, Hormonal dysfunction- diabetes, pancreatitis, adrenal-cortex disease,

thyroid disease, acromegaly, menopausethyroid disease, acromegaly, menopause HypertensionHypertension Obesity and hyperlipidemiaObesity and hyperlipidemia Alcoholic cirrhosisAlcoholic cirrhosis MalnutritionMalnutrition Neurologic diseases- Parkinson’s disease, Bell’s and cerebralNeurologic diseases- Parkinson’s disease, Bell’s and cerebral Psychogenic diseasesPsychogenic diseases


Access to Saliva from BloodAccess to Saliva from Blood


Clinical Situations Affecting Clinical Situations Affecting Salivary SecretionsSalivary Secretions

Digitalis toxicityDigitalis toxicity Drug monitoringDrug monitoring Environmental pollutantsEnvironmental pollutants OvulationOvulation ImmunodeficiencyImmunodeficiency Pharmacological agentsPharmacological agents

– ““Dry mouth” side effects, drugs with parasympathetic, sympathetic Dry mouth” side effects, drugs with parasympathetic, sympathetic and ganglionic blocking effectsand ganglionic blocking effects

– Direct effects- hypersensitivity or idiosyncratic reactionDirect effects- hypersensitivity or idiosyncratic reaction


Methods of Collection of Methods of Collection of SalivaSaliva

Whole SalivaWhole Saliva CatheterizationCatheterization Parotid SalivaParotid Saliva Submandibular (Submaxillary) SalivaSubmandibular (Submaxillary) Saliva


Limitations in Use of Whole SalivaLimitations in Use of Whole Saliva An admixture of parotid, submandibular and minor An admixture of parotid, submandibular and minor

gland secretions mixed with food debris, bacteria, shed gland secretions mixed with food debris, bacteria, shed cells, leukocytes and other particulate matter.cells, leukocytes and other particulate matter.

Compositional studies are affected by proportions of Compositional studies are affected by proportions of secretions from different glands, as well as chemistry of secretions from different glands, as well as chemistry of non-salivary elementsnon-salivary elements

In studies examining non-salivary components, must In studies examining non-salivary components, must take care to exclude GCF, especially where take care to exclude GCF, especially where inflammation is present.inflammation is present.


Standardization of CollectionStandardization of Collection Resting secretionsResting secretions

– need an accommodation period of at least 5 minutes. need an accommodation period of at least 5 minutes. (Influence of collection procedure as stimulus) (Influence of collection procedure as stimulus)

Stimulated salivaStimulated saliva– Consistent gustatory stimulant throughout the studyConsistent gustatory stimulant throughout the study

Flow rateFlow rate– Timed, focus on specific glandTimed, focus on specific gland

Time of dayTime of day– Circadian rhythm, time of collection is importantCircadian rhythm, time of collection is important


Salivary Studies in Cystic Fibrosis (CF)Salivary Studies in Cystic Fibrosis (CF)

CF gene cloned in 1991CF gene cloned in 1991 The gene product is a cyclic AMP-regulated chloride ion The gene product is a cyclic AMP-regulated chloride ion

channel named CFTRchannel named CFTR Cystic Fibrosis Transmembrane Conductance RegulatorCystic Fibrosis Transmembrane Conductance Regulator Most investigators felt that chloride and water secretion Most investigators felt that chloride and water secretion

was the unifying key to explain the abnormalities and was the unifying key to explain the abnormalities and consequences of CF.consequences of CF.

A disease of all exocrine glands.A disease of all exocrine glands.


Sialochemistry Studies of CFSialochemistry Studies of CF Marked increase in calcium, proteins and phosphate, Marked increase in calcium, proteins and phosphate,

most evident in submandibular glandsmost evident in submandibular glands Turbidity of the submandibular saliva probably due to Turbidity of the submandibular saliva probably due to

precipitation of calcium-binding proteinsprecipitation of calcium-binding proteins Too much overlap in calcium levels between CF and Too much overlap in calcium levels between CF and

asthmatics to serve as screening testasthmatics to serve as screening test Flow rate of saliva from labial salivary glands virtually Flow rate of saliva from labial salivary glands virtually

absent in 90% of CF children, probably due to turbidity absent in 90% of CF children, probably due to turbidity and blockage of ductand blockage of duct


Diagnostic Aids in Clinical SituationsDiagnostic Aids in Clinical Situations Digitalis toxicity (calcium and potassium)Digitalis toxicity (calcium and potassium) Affective disorders (prostaglandin)Affective disorders (prostaglandin) Immunodeficiency (sIgA)Immunodeficiency (sIgA) Stomatitis in chemotherapy (albumin)Stomatitis in chemotherapy (albumin) Cigarette usage (cotinine)Cigarette usage (cotinine) Gastric cancer (nitrates and nitrites)Gastric cancer (nitrates and nitrites) Forensic medicine (blood group substance)Forensic medicine (blood group substance) Coeliac disease (anti-IgA gliadin)Coeliac disease (anti-IgA gliadin) Liver function (caffeine clearance)Liver function (caffeine clearance)


MalignancyMalignancy P53 Tumor suppressor antigen P53 Tumor suppressor antigen

– inactivation in certain cancers leads to accumulation. inactivation in certain cancers leads to accumulation. Oral squamous cell carcinoma leads to anti-p53 Oral squamous cell carcinoma leads to anti-p53 antibodies in salivaantibodies in saliva

Salivary Defensin-1 levels elevated in oral SCC Salivary Defensin-1 levels elevated in oral SCC (made by PMN’s).(made by PMN’s).

C-erbB-2 (erb) Tumor marker associated with breast C-erbB-2 (erb) Tumor marker associated with breast carcinoma.carcinoma.

CA 125 (ovarian cancer marker) associated with CA 125 (ovarian cancer marker) associated with elevated salivary levelselevated salivary levels


Drug and Hormone MonitoringDrug and Hormone Monitoring Psychiatrists studying methadone: advantages Psychiatrists studying methadone: advantages

using salivausing saliva– humanitarian- less discomforthumanitarian- less discomfort– clinical- patient acceptance of repeated testingclinical- patient acceptance of repeated testing– children and patients with limiting coping abilitieschildren and patients with limiting coping abilities– economic (do it yourself tests)economic (do it yourself tests)

HIV therapyHIV therapy EpilepsyEpilepsy


DrugsDrugs


Salivary Antibodies and AntigensSalivary Antibodies and Antigens Advantages in large scale studiesAdvantages in large scale studies Viral ScreeningViral Screening Antigen DetectionAntigen Detection

– H. pyloriH. pylori (PCR of saliva) (PCR of saliva) Antibody ScreeningAntibody Screening

– rubellarubella– hepatitis A and Bhepatitis A and B– ShigellaShigella


Gingival Crevicular Fluid Gingival Crevicular Fluid (GCF)(GCF)

(E) Cervical enamel(E) Cervical enamel

(OSE) Oral sulcular epithelium(OSE) Oral sulcular epithelium

(JE) Junctional epithelium(JE) Junctional epithelium

(OE) Keratinized oral epithelium(OE) Keratinized oral epithelium


Collection of GCFCollection of GCF

Static fluidStatic fluid Timed crevicular fluid flowTimed crevicular fluid flow


GCF Flow and InflammationGCF Flow and Inflammation


GCF Flow and Probing DepthGCF Flow and Probing Depth


GCF Flow and Menstrual CycleGCF Flow and Menstrual Cycle

GCF flow GCF flow highest at highest at ovulationovulation


GCF and Tetracycline LevelsGCF and Tetracycline Levels

Blood by finger Blood by finger puncturepuncture

Maximum GCFMaximum GCF

Minimum GCFMinimum GCF


ConclusionsConclusions

Sialochemistry provides important information in Sialochemistry provides important information in a variety of clinical and disease statesa variety of clinical and disease states

Greater acceptance by patientsGreater acceptance by patients Non-invasive in most casesNon-invasive in most cases

Saliva as a Diagnostic Fluid

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