Formation and composition of saliva/cosmetic dentistry courses

INDIAN DENTAL ACADEMY
Leader in continuing Dental Education
www.indiandentalacademy.com

 Ten Cate’s Oral Histology-Development,
Structure and Function 6th edition
 Orban’s Oral Histology and Embryology 10th
edition
 Review TheScientificWorldJOURNAL (2010) 10, 434–
456 Saliva: Physiology and Diagnostic Potential in
Health and Disease; Sebastien J.C. Farnaud
 Saliva in health and disease, chemical biology;
Tibor K. et al.
 Structure And Function of Human Salivary
Mucins:CROMB 1990.

 At the end of the seminar the learner should be
able to describe:
 Properties of saliva
 Organic contents of saliva
 Inorganic contents of saliva
 Alteration in saliva in disease state.

SALIVA
It is a complex fluid, produced by the salivary
glands that coats the teeth and mucosa and keeps
the oral cavity moist.

WHOLE SALIVA:
• It includes the secretions of the major glands, minor
glands, desquamated oral epithelial cells, microbes, their
products
food debris, serum
components and
inflammatory cells that
gain access through
the gingival crevice.

1)VOLUME-
 1000 to 1500 ml of saliva is
secreted per day at the rate of
approximately about 1 ml per
minute.
2)REACTION-
 Mixed saliva from all the glands
is slightly acidic with pH of 6.35
to 6.85 .

3)SPECIFIC GRAVITY-
 It ranges between 1.002 and 1.012.
4)TONICITY-
 Saliva is hypotonic to plasma.

 Mixed saliva contains 99.5% water and 0.5% solids.
 Solids are organic substance, inorganic substance
and gases.
0
20
40
60
80
100
WATER SOLIDwww.indiandentalacademy.com

 Salivary proteins-mucin ,albumin
 Salivary enzymes-amylase, lysozyme, peroxidase,
lipase, acid phosphatase, cholinesterase, ribonuclease.
 Kallikrein
 Blood group antigens
 Free amino acids
 Non protein nitrogenous substance-urea,uric acid ,
creatinine, xanthine and hypoxanthine.

 Sodium
 Potassium
 Chloride
 Bicarbonate
 Hydrogen ions
 Iodine
 Fluoride
 Calcium
 Phosphate
 Thiocynate www.indiandentalacademy.com

 Oxygen
 Carbondioxide
 Nitrogen

 Salivary mucin is a mixture of many glycoproteins.
 The viscous quality of whole saliva is attributed to
salivary mucin .
 The glycoproteins produced by submandibular
gland are mainly anionic, where as glycoproteins
produced by parotid gland are mostly cationic and
nonviscous in nature.

 Mucins are high-molecular-weight glycoproteins
 A peptide core (apomucin) enriched in serine,
threonine, and proline residues
 Carbohydrate side chains (oligosaccharides) are
linked to threonine or serine.

 The 0-linked oligosaccharides of human salivary
mucins may contain galactose (Gal), N-
acetylgalactosamine (GalNAc), N-acetylglucosamine
(GlcNAc), and sialic acids (SA).
 Sulfate, if present,is commonly linked to either Gal-
or GlcNAc.
 There is presence of a small number of asparagine-
linked (N-linked)oligosaccharides

 The first, characterized by uniform distribution of
oligosaccharides about the entire length of the
peptide core "BOTTLEBRUSH" CONFIGURATION
 These mucins that tend to be smaller in molecular
weight
 They form very large suprastructures via
noncovalent interactions.

 Second characterized by biased distribution of
oligosaccharides (with resultant longer stretches of
naked regions)
 Their suprastructure are formed via covalent
(disulfide) bonding of subunit structure.

MG2
 A low-molecular-weight species having bottle brush
configuration.
 Has a molecular weight of approximately 200 to
250,000.
 It consists of a single polypeptide chain, enriched in
threonine , serine, proline and alanine .

 The carbohydrate structures attached via O-glycosidic
linkage to this mucin consist of units that range from
two to seven sugars in length.
 There are approximately 170 oligosaccharide chains
per MG2 protein core.

 MGl consists of multiple subunits linked covalently.
 Molecular weight in excess of 1 million.
 The carbohydrate side chains of MGl range in size
from 4 to 16 sugar residues.
 There are an estimated 292 carbohydrate side
chains per MGl molecule.
 Some of these oligosaccharides are sulfated.

 Tissue coating of oral hard and soft tissues
 Lubrication
 Modulation of oral flora

AMYLASE
• Approximately 30% of the protein found in saliva is
α-amylase.
• The concentration of α-Amylase increases with the
rate of salivary secretion.

 There are two kinds of α-amylases in humans,
salivary and pancreatic amylase, which are
isoenzymes.
 Salivary amylases are encoded AMY1A, AMY1B,
AMY1C genes.
 AMY2A and AMY2B for pancreatic amylase .
 In humans, α-amylase is encoded by a multigene
family located on chromosome 1 .

 Salivary α-amylase is found to
have 496 amino-acid residues,
one calcium ion, one chloride
ion and 170 water molecules.
 Salivary amylase folds into a
multidomain structure
consisting of three domains, A,
B, and C.

 Enzyme works in a slightly acidic Ph.
 It can digest starch quickly because they can bind
anywhere on the substrate.
 Salivary amylase provides partial digestion.
 It breaks down polymeric starch into shorter
oligomers including maltose and dextrin.

 When the partially digested starch reaches the gut,
it is then extensively hydrolyzed into smaller
oligosaccharides, like glucose, by the pancreatic
amylase.
 Calcium and chloride are essential for both
amylases in order to enhance stability of the
molecule.
 Chloride, in particular appears to be vital for
amylase to function because it is located near the
active site of the enzyme

 Lysozyme is a protein that is found in tears, saliva,
and other secretions.
 Lysozyme is also found in egg white and is one of
the major egg white proteins that contributes to
egg allergy.
 It was the first antibacterial substance discovered.

 In humans, the gene encoding lysozyme is known as
the LYZ gene.
 Another term for the enzyme is muramidase,
because it cleaves the bond that connects N-
acetylmuramic acid to its adjoining sugar molecule.
 The technical name for the enzyme is N-
acetylmuramide glycanhydrolyase

 Lysozyme act on the ß(1-4) bond between N-acetyl-
muramic acid and N-acetyl-glucosamine in the
Gram-positive bacterial cell wall component leading
to its subsequent disruption and microbial death.

 The bacteria have polysaccharides in their cell walls
with side chains of amine groups.
 Lysozyme add a molecule of water to the sugar
linkage, causing it to break open.
 This is known as glycoside hydrolase, or water
breakdown of sugar.
 Once the polysaccharide chain is disrupted, the
bacterial cells burst.

 Lactoperoxidase is a member of the heme
peroxidase family of enzymes.
 In humans, lactoperoxidase is encoded by the LPO gene
 Lactoperoxidase together with its inorganic ion
substrates, hydrogen peroxide, and oxidized products is
known as the lactoperoxidase system.

 The structure of lactoperoxidase consists mainly
of alpha-helices plus two short antiparallel beta-
strands .
 A heme cofactor is bound near the center of the
protein.

 Lactoperoxidase catalyzes the hydrogen
peroxide (H2O2) oxidation of several acceptor
molecules.
reduced acceptor + H2O2 → oxidized acceptor + H2O
 Enzymes such as lysozyme and lactoperoxidase
are transferred from the tooth pastes to the pellicle.

 As part of tooth pastes, the lactoperoxidase system
has a beneficial influence to avoid early
childhood caries by reducing the number of
colonies formed by the cariogenic microflora while
increasing the thiocyanate concentration.

 In xerostomia patients, tooth pastes with the LPS
are seemingly superior to fluoride containing tooth
pastes with respect to plaque formation
and gingivitis

 Kallikreins are a group of serine proteases
 They are found in glandular cells, neutrophils,
and biological fluids.
 The best-known activity of these enzymes is
the cleavage of kininogen into kinin.
 Genes for kallikrein: hRKALL, hGGK-1, and
PSA .

 Kallikrein has a well-documented role in blood
coagulation, via the activation of the Hageman
factor.
 In saliva some hydrolysis of proline-rich
proteins occurs by kallikrein.
 It has been implicated in the regulation of local
blood flow in salivary glands

 Approximately 80% of the population exhibit the
antigens corresponding to their blood groups
(A,B,AB) or the glycoprotein H substance, in their
saliva.

 Hormone-like substance that have been described
in saliva: -Parotin.

 Parotin is composed of subunit (parotin-
subunit) which showed molecular weight of
45,000.
 Parotin, one of the salivary gland hormones,
was found to have several biological activities:
 Decreasing serum calcium level .

 Decreasing the number of circulating
leucocytes very rapidly within the first 2 or 3
hrs. after injection and subsequently increasing
the number of them in the next from 5 to 8 hrs.
 Decreasing the total serum protein level

SODIUM
 Sodium ions are present in acinar fluid at similar
concentrations to extracellular fluid.
 There is some resabsorbtion in the striated ducts.
 Resting saliva contains only traces of sodium ions,
although the concentration increases with salivary
secretion .

 The hypotonicity of saliva (low levels of glucose,
sodium, chloride, and urea) and its capacity to
provide the dissolution of substances allows the
gustatory buds to perceive different flavors.
 The taste detection threshold for NaCl is slightly
above the salivary sodium concentrations with
which the taste receptor is continuously stimulated.

 The level of bicarbonate in resting saliva is low but
markedly increases with glandular metabolic
activity.
 Bicarbonate is the principal salivary buffer.
 HCO3 has a marked effect on sweet taste
responses.
 The high salivary pH, which is maintained by the
buffering capacity of bicarbonate, increases sweet
taste response.

• Salivary pH is low in resting secretions, but rises
up to pH 8.0 in fast-flowing saliva, largely reflecting
the bicarbonate content.
• Maintains a low pH to facilitate the action of
salivary amylase.
• Equilibria between calcium phosphate in dental
hard tissue and surrounding liquid phase

 Hydrogen ions in saliva have several sources of
origin:
 secretion via glands as inorganic or organic acids.
 produced by oral microbes.
 taken into oral cavity in acidic drinks

IODINE
 Salivary glands actively transport iodine into saliva,
so the concentration is generally higher than that of
plasma.
 Saliva also tend to concentrate radioactive iodine
used for thyroid assays.

 The fluoride content of saliva is less than that of
serum, and is directly correlated with dietary
intake.
 It protects the teeth by the formation of fluoroaptite
crystals.

 The calcium content of submandibular saliva is
approximately double that of parotid saliva.
 The main factors controlling the stability of enamel
hydroxyapatite are the active concentrations of
calcium, phosphate and fluoride and the salivary
pH.
 The high concentrations of calcium and phosphate
in saliva guarantee ionic exchanges directed
towards the tooth surfaces that result in post-
eruptive maturation.www.indiandentalacademy.com

 Depending on pH, inorganic phosphate can be
complexed to inorganic ions or proteins.
 Less than 10% forms dimer pyrophosphoric
acid - an inhibitor of calcium phosphate
precipitation; and influences calculus formation.

 Functions of inorganic phosphate include:
 contributes to solubility product of calcium
phosphate, which is crucial in maintaining tooth
structure and is important as a buffer.

Ions
WATER
pH
HCO3
HPO3
Na
Cl
K
Ca
STIMULATED
94%
5.75-7.05
5-10mM/L
4-5mM/L
1-5mM/L
5mM/L
15mM/L
1mM/L
UNSTIMULATED
94%
Up to 8.0
40-60mM/L
4-5mM/L
Up to 100mM/L
up to 70mM/L
30-40mM/L
3-4mM/Lwww.indiandentalacademy.com

SUBMANDIBULAR
Na+:54.8mM
K+:13.7mM
Cl-:32.3mM
HCO3-:35.3mM
Mg2+:36.0mM
Ca2+:2.13mM
P(inorganic):1.57mM
pH:7.62
PAROTID
Na+:63.3mM
K+:18.7mM
Cl-:35.9mM
Hco3-:29.7mM
Mg2+:0.04mM
Ca2+:3.78mM
P(inorganic):9.7mM
pH:7.67

• Systemic Diseases (hereditary, autoimmune,
malignancy, and infectious)
• Viral Diseases
• Drug Monitoring
• The Monitoring of Hormone Levels

• Sjögren's syndrome (SS) is an autoimmune
exocrinopathy of unknown etiology.
• A reduction in lacrimal and salivary secretions is
observed.

• The presence of keratoconjunctivitis sicca and
xerostomia leads to a diagnosis of primary SS.
• In secondary SS, rheumatoid arthritis or systemic
lupus erythematosus are also present.
• A consistent finding is increased concentrations of
sodium and chloride.

•This increase is evident in both whole and gland-
specific saliva.
•In addition, elevated levels of IgA, IgG, lactoferrin, and
albumin, and a decreased concentration of phosphate in
saliva of patients with SS.
•Normal level of K,Ca and amylase.
• Analysis of unstimulated whole saliva was more
sensitive.

•Salivary analysis may aid in the early detection of
certain malignant tumors
• p53 antibody can also be detected in the saliva of
patients diagnosed with oral squamous cell carcinoma .

• Elevated levels of salivary defensin-1 were found to
be indicative of the presence of oral SCC.
• It is found that five protein biomarkers– M2BP,
MRP14, CD59, Profilin and catalase – predicted oral
cancer 93% of time.

• Saliva was found to be a useful alternative to serum
for the diagnosis of viral hepatitis.
• Acute hepatitis A (HAV) and hepatitis B (HBV) were
diagnosed based on the presence of IgM antibodies in
saliva.
• Saliva may also be used for determining immunization
and detecting infection with measles, mumps, and
rubella.

•Antibody to HIV (IgG and IgA) in whole saliva of
infected individuals, which was detected by ELISA and
Western blot assay, correlated with serum antibody
levels.
•Viral transmission via saliva is unlikely,
since infectious virus is rarely isolated
from saliva.

DRUG MONITORING
• For monitoring patient compliance with psychiatric
medications.
• For the monitoring of anti-epileptic drugs.
• For monitoring levels of anti-cancer drugs.
• Recreational drugs that can be identified in saliva
are barbiturates, benzodiazepines, cocaine and
opioids.

•Saliva can be analyzed as part of the evaluation of
endocrine function.
•The majority of hormones enter saliva by passive
diffusion across the acinar cells.
•Most of these hormones are lipid-soluble (i.e.steroids).

•Salivary aldosterone levels demonstrated a high
correlation with serum aldosterone levels and increased
aldosterone levels were found in both the serum and
saliva of patients with primary aldosteronism.
•Progesterone can be detected in saliva in
concentrations that are only 1-2% of serum
concentrations.

• Insulin can be detected in saliva, and salivary
insulin levels have been evaluated as a means of
monitoring serum insulin levels.
• Testosterone : Salivary concentrations were found
to be 1.5-7.5% of the serum concentrations of this
hormones.

DETECTION OF IONS
 The pH value can be measured with hydrogen-
selective electrodes.
 The free form of sodium and calcium can also be
measured with ion selective electrodes.
 Photometric (colorimetric) methods can be used for
measuring the total amount of chloride, calcium,
bicarbonate, and phosphate

 Qualitative protein analysis is carried out with gel
electrophoresis in 1-D or 2-D.
 Similarly, 1-D and 2-D liquid chromatography is also
used widely.
 Besides, immunologic methods such as Westernblot,
enzyme linked immunoassay and radio immunoassay .
 Measurements of enzymatic activity are common methods
for determination of salivary amylase and lysozyme.

 Qualitative and quantitative analysis of the
carbohydrate chains is carried out after enzymatic
digestion .
 The standard chemical methods based on
colorimetry or gas-liquid chromatography are used.
 Besides, immunologic methods such as ELISA,
immunoblotting are used.

BIOMARKERS POTENTIAL APPLICATION
DNA Standard genotyping, bacterial
infection,
Cancer diagnosis, forensics
RNA Viral and bacterial infection , cancer
Diagnosis.
PROTEINS Periodontitis diagnosis, cancer
diagnosis,
Caries susceptibility.
MUCINS/ GLYCOPROTEINS Head and neck cancer diagnosis
Caries susceptibility
IMMUNOGLOBULINS Viral infection
METABOLITES Endocrine conditions,
stress,periodontitis
Diagnosis, cystic fibrosis diagnosis
.
BIOMARKERS IN SALIVA

DRUGS Monitor drug use, monitor patient
compliance to therapy
VIRUSES Herpes virus reactivation
BACTERIA Oral cancer diagnosis, Caries
susceptibility
CELLULAR MATERIAL Head and neck cancer diagnosis

 Saliva is a mixture of fluids secreted by the three
major salivary glands, i.e. parotid, submandibular and
sublingual glands, with a slight contribution from many
minor glands within the oral cavity.
 Human salivary glands secrete typically 0.5-1 liter
of saliva per day in response to sympathetic and
parasympathetic stimulation

 Fluid secretion and macromolecule secretion occurs by
separate processes.
 Both are under the control of autonomic nervous
system, both are stimulated by presence of food in
the mouth.

 Parasympathetic nerves release acetylcholine (Ach)
and stimulate fluid secretion.
 Sympathetic nerves ,release noradrenalin (NA) and
stimulate protein secretion

 The afferent pathways for taste are via the facial and
glossopharyngeal nerves to a solitary nucleus in the
medulla.
 The parasympathetic efferent pathway for the
sublingual and submandibular glands are from the
facial nerve via the submandibular ganglion.

 For the parotid gland they are from the
glossopharyngeal nerve via the otic ganglion.
 The sympathetic post ganglionic pathways are from
the cervical ganglion of the sympathetic chain

 One important determinant of epithelial cell
polarisation is the plasma membrane ,which is divided
into two parts-
 The apical (top) membrane faces into the lumen and
the basolateral (bottom and sides )membrane faces
the gap between adjacent cells and the blood
capillaries.

 In salivary gland striated ducts ,the tight junction
restrict the passage of all substances whereas the
acinar cell tight junctions prevent anions moving
across the epithelium.

 The channel consist of hydrophilic central domain
which permits the passage of Na+ when the gate is
open surrounded by a hydrophobic domain to allow the
channel to sit in the plasma membrane.
 Ion channels can be highly selective by virtue of their
geometry and the presence of fixed charges and also
gated.

 Active transport is accomplished by membrane bound
proteins which can utilize metabolic energy, either
directly or indirectly to move substrates against
their electrochemical gradient.

•The most widely occurring active transporter is the
Na+/K+ATPase (Na+ pump) which extrudes Na+ from
the cells in exchange for K+.
• The Na+ pump is always found on the basolateral
membrane of epithelial cells which explains how part of
the functional polarity of epithelial cells is achieved.

 Under resting condition Cl ¯ can not get out of the
cell ,but when stimulated to secrete, Cl ¯ channels in
the luminal membrane of the acinar cells open to
provide an exit for Cl ¯ which now has clear pathway
across the cell from blood to lumen .

 Sodium follows chloride to preserve electro-neutrality.
 Now there is luminal hypertonicity to drive water
transport.
 Thus Cl ¯ transport is the key to fluid secretion.

 One possibility is that Bicarbonate and Chloride
compete for the same channel (i.e. the Cl¯ channel is
also Bicarbonate permeable.)
 Protons are also produced by this reaction, they are
extruded from the cell across the basolateral
membrane by Na+/H+ exchange (counter-transport)
so that intracellular pH is maintained.

 The polypeptides and proteins are synthesized and
released by the salivary acinar cells .
 Whatever the protein, when it is fully synthesized, it
will be too much large to cross the cell membrane.
 Therefore it must be synthesized and stored within
a membrane-bound structure so that it may be
released from the cell by EXOCYTOSIS.

 Synthesis of secretory proteins begins with gene
transcription and manufacture of messenger RNA to
carry the sequence information from the nucleus to
ribosome in the cytoplasm.
 Secretary proteins starts with a signal sequence
which targets the developing polypeptide to the
endoplasmic reticulum where it is N -glycosylated and
folded into the correct three-dimensional structure.

 Small membrane vesicles carry proteins from the ER
through several layers of the Golgi apparatus for
additional processing and packaging for export.
 In response to a secretory stimulus, secretory
vesicles fuse with the plasma membrane and
discharge their contents outside the cell.

 There are two types of exocytosis pathways
associated with protein secretion in salivary acinar
cells.
 In addition to regulated exocytosis, there is also the
process of constitutive exocytosis.

 Activation of adrenergic nerves is not the only way in
which protein secretion can be stimulated.
 In addition to cholinergic and adrenergic neurons,
salivary glands also contain peptidergic neurons and
acinar cells, in particular mucous acinar cells have been
shown to possess peptide receptors.

 The concentration of ions in primary saliva are relatively
unaffected by changes in flow rate or the source of
stimulation.
 Secretion of primary saliva is modified as it flow down the
duct system.
 Duct seems to be impermeable to water but selectively
reabsorbed sodium and potassium across the duct wall.

 At a low flow rate sodium get removed from the saliva
before it enters the oral cavity.
 In contrast Potassium level increases.
 At high flow rate:-Increase amount of sodium appears in
the final saliva.
 In contrast Potassium level decreases.

Stage 1
 Acinar end pieces produce an isotonic plasma-like
primary saliva.
Stage 2
 This NaCl-rich fluid is modified during its passage
along the ductal epithelium, where most of the NaCl is
reabsorbed, while K+ is usually secreted.
 Because ductal epithelium is poorly permeable to
water, the final saliva is usually hypotonic.

 Secretion of the primary saliva fluid takes place in
the secretory endpieces, also called acinar cells.
 Ion channels and transporters expressed at the apical
and basolateral membranes of the secretory cells play
a key role in fluid secretion.

 Aquaporin 5 (Aqp5), the major water channel
expressed in the apical membrane of secretory acinar
cells.
 An osmotic gradient is established upon ion secretion,
thus promoting the transcellular movement of water
through aquaporin 5.
 Water movement in salivary glands requires Cl
secretion
 Cl is secreted transcellularly by acinar cells.

 The basolateral Na-K-Cl– cotransporter encoded by the
Nkcc1 gene (Slc12a2) is the main Cl concentrative
component.
 Acinar cell Cl-- influx across the basolateral membrane is
energized by the Na+ electrochemical gradient.
 The Na-K-ATPase, which is highly expressed in the
basolateral membrane of salivary glands secretory cells,
maintains an inward-directed Na+ electrochemical
gradient

 As a consequence of the coordinated Nkcc1 and the
Na+, K+ ATPase activities, Cl is concentrated in the
intracellular space above its equilibrium potential.
 A K+ channel located at the basolateral membrane of
secretory cells is necessary to complete the Cl
secretory molecular machinery.
 Two different K+ channels have been characterized in
salivary gland acinar cells, one of which is a Ca-
activated commonly named IK1.
 The second K+ channel is both Ca2+ - and voltage-
activated . It is named maxi K or Slo.

 The final ionic composition of saliva is the result of
transport processes in the acini as well as the ducts
system.
 Salivary gland ducts are composed of several different
cell types and their composition differs between
salivary glands.

 There are three main types of ducts in salivary glands
: intercalated, striated and excretory ducts.
 Intercalated and striated ducts are intralobular and
excretory ducts are primarily extralobular

 A comparison of the ion composition and osmolality of the
saliva collected in intralobular and extralobular ducts
suggests that the NaCl reabsorption takes place in both
intra and extralobular ducts.
 It has been proposed that the epithelial Na+ channel ENaC,
which is expressed in the apical membrane of salivary gland
ducts, plays a key role in ductal Na+ reabsorption.

 Cl is also actively reabsorbed in salivary gland ducts.
 Apical Cl channels and Cl/HCO3 exchangers have been
postulated to mediate Cl reabsorption in salivary gland
duct epithelium.
 The K+ concentration of saliva is higher than the
concentration found in plasma.

 K+ is secreted in response to secretagogues by intra
and extralobular salivary gland ducts .
 Apical K/H exchangers,K-HCO3 cotransporters have
been suggested to play a role in K+ secretion

CAUSES :
 Medications - Several hundred current medications
can cause xerostomia. These
include antihypertensives, antidepressants,
analgesics, tranquilizers, diuretics and antihistamines .
 Cancer Therapy - Chemotherapeutic drugs can change
the flow and composition of the saliva. Radiation
treatment that is focused on or near the salivary
gland can temporarily or permanently damage the
salivary glands

 Sjogren's syndrome - An autoimmune disease, causes
xerostomia and dry eyes.
 Nerve Damage - Trauma to the head and neck area
from surgery or wounds can damage the nerves that
supply sensation to the mouth. While the salivary
glands may be left intact, they cannot function
normally without the nerves that signal them to
produce saliva.

 Hypersalivation (ptyalism and sialorrhea) is excessive
production of saliva.
 It has also been defined as increased amount of saliva
in the mouth, which may also be caused by decreased
clearance of saliva.

 Gastroesophageal reflux disease
 Pregnancy
 Excessive starch intake
 Pancreatitis
 Liver disease
 Mouth ulcers
 Oral infections
 Medications like:clozapine,pilocarpine,ketamine.

 Toxins that can cause hypersalivation include:
 mercury
 copper
 organophosphates
 arsenic

 Infections such as tonsillitis and mumps.
 Problems with the jaw, e.g., fracture or dislocation
 Neurologic disorders such as myasthenia
gravis, Parkinson's disease, bilateral facial nerve
palsy and hypoglossal nerve palsy.

Formation and composition of saliva/cosmetic dentistry courses

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