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Oral cavity
• Entrance door of the gastrointestinal tract;
• Beginning of the digestive function;
• Provides security of the body against food and drink;
• Prior to the adoption act two strong evolutionary verified sensory
systems:
– Appearance;
– Flavor;
• When they enter in the mouth triggers the umbrella of the immune
system:
– Cell-associated protection:
– Phagocytes and lymphocytes;
• Secretory immunity system mainly protects mucous with secretory
IgA.
Additional protection in the mouth
• Taste - taste buds;
• Tactile sense - proprioception ;
• Saliva.
Liquid oral environment
• This is the liquid into the oral cavity, washing
mucosa and dental enamel;
• It consists of:
– Saliva;
– Gingival sulcus fluid;
– Peeling epithelial cells and their degradation
products;
– Microorganisms and their products.
Saliva
• Saliva is a complex fluid that in health almost
continually bathes the parts of the tooth
exposed within the oral cavity;
• Consequently, saliva represents the
immediate environment of the tooth.
Production
• Saliva is produced by three paired sets of
major salivary glands:
– Parotid;
– Submandibular;
– Sublingual glands;
– and by the many minor salivary glands scattered
throughout the oral cavity.
Account of the composition
• A precise account of the composition of saliva
is difficult because not only are the secretions
of each of the major and minor salivary glands
is different, but their volume may vary at any
given time.
• In recognition of this variability, the term
mixed saliva has been used to describe the
fluid of the oral cavity.
Saliva has several functions
• Saliva moistens the mouth;
• Facilitates speech;
• Lubricates food;
• Helps with taste by acting as a solvent for food molecules;
• Saliva also contains a digestive enzyme (amylase);
• Saliva dilutes noxious material mistakenly taken into the
mouth;
• Cleanses the mouth;
• Furthermore, it contains antibodies and antimicrobial
substances;
• Its buffering capacity plays an important role in
maintaining the pH of the oral cavity.
There are three major pairs of salivary glands that differ
in the type of secretion they produce:
Parotid duct
Parotid
gland
Branches of facial nerve
Sublingual ducts
Sublingual gland
Submandibular gland
HCO3−
DUCTAL • Release of water by the cells of the
secretory end pieces is regulated
MODIFICATION OF principally by the parasympathetic
innervation.
SALIVA • The next step – Ca2+ is released from
intracellular stores.
Interstitum
• The increased Ca2+ concentration opens
Cl– channels in the apical cell membrane
Na+
Na+ H+ K+ Cl− and K+ channels in the basolateral
membrane.
ATP
• The apical Cl– efflux draws extracellular
K+ Na+ into the lumen,through the tight
junctions, to balance the electrochemical
Striated duct cell gradient.
Cl− • It results in the movement of water into
Na+ Cl− Na+ the lumen via water channels in the apical
TJ membrane and through the tight
junctions.
H+ • Thus fluid secretion by the salivary glands
H2O Lumen is driven by the active transport of
electrolytes.
HCO3−
Electrolyte composition of saliva and
salivary flow rate
• The final electrolyte composition of saliva varies, depending on the
salivary flow rate.
• At high flow rates, saliva is in contact with the ductal epithelium for
a shorter time, and Na+ and Cl– concentrations rise and the K+
concentration decreases.
• At low flow rates the electrolyte concentrations change in the
opposite direction.
• The HCO3− concentration, however, increases with increasing flow
rates, reflecting the increased secretion of HCO3− by the acinar cells
to drive fluid secretion.
• Electrolyte reabsorption and secretion by the striated and excretory
ducts is regulated by the autonomic nervous system and by
mineralocorticoids produced by the adrenal cortex.
Macromolecular Components
• The cells of the secretory end pieces have abundant rough
endoplasmic reticula and a large Golgi complex, and they store
their products in membrane-bound granules in the apical
cytoplasm.
• The secretory granules are stored in the apical cytoplasm until
the cell receives an appropriate secretory stimulus.
• The granule membranes fuse with the cell membrane at the
apical (luminal) surface, and the contents are released into the
lumen by the process of exocytosis;
• The fusion of the granule membrane with the cell membrane is
mediated by the formation of a protein complex involving
proteins of the granule membrane, proteins of the cell
membrane, and proteins in the cytoplasm.
• Following release of the granule content, the granule
membrane is internalized by the cell as small vesicles, which
may be recycled or degraded.
• Myoepithelial cells are
MYOEPITHELIAL contractile cells
associated with the
CELLS secretory end pieces and
intercalated ducts of the
salivary glands;
• These cells are located
between the basal lamina
and the secretory or duct
cells and are joined to the
cells by desmosomes;
• Myoepithelial cells have
many similarities to
smooth muscle cells but
are derived from
epithelium.
MYOEPITHELIAL CELLS
Intercalated
Basal lamina duct
Secretory
end piece
Myoepithelial
cell
Secretory cell
Myoepithelial cells
• Myoepithelial cells
present around the
secretory end pieces have
a stellate shape;
• Numerous branching
processes extend from
the cell body to surround
and embrace the end
piece ;
• The processes are filled
with filaments of actin
and soluble myosin.
Control of the secretion
• Secretion of saliva is under control of the
autonomic nervous system, which controls both
the volume and type of saliva secreted.
• This is actually fairly interesting: a dog fed dry
dog food produces saliva that is predominantly
serous, while dogs on a meat diet secrete saliva
with much more mucus.
• Parasympathetic stimulation from the brain, as
was well demonstrated by Ivan Pavlov, results in
greatly enhanced secretion, as well as increased
blood flow to the salivary glands.
• Potent stimuli for increased salivation include
the presence of food or irritating substances in
the mouth, and thoughts of or the smell of
food.
• Knowing that salivation is controlled by the
brain will also help explain why many psychic
stimuli also induce excessive salivation - for
example, why some dogs salivate all over the
house when it's thundering.
Composition of the saliva
– proteins;
• calcium;
– amino acids;
– enzymes;
• phosphorus;
– immunoglobulins; • sodium;
– glucose; • potassium;
– lactates; • magnesium;
– citrate; • fluorine;
– ammonia; • chlorides;
– urea; • bicarbonates;
– creatinine; • Phosphates.
– Cholesterol.
Saliva
• Human saliva is 99.5% water, while the other
0.5% consists of electrolytes,
mucus, glycoproteins, enzymes,
and antibacterial compounds such as
secretory IgA and lysozyme.
Electrolytes:
• 2–21 mmol/L sodium (lower than blood plasma);
• 10–36 mmol/L potassium (higher than plasma);
• 1.2–2.8 mmol/L calcium (similar to plasma);
• 0.08–0.5 mmol/L magnesium;
• 5–40 mmol/L chloride (lower than plasma);
• 25 mmol/L bicarbonate (higher than plasma);
• 1.4–39 mmol/L phosphate;
• Iodine - usually higher than plasma, but
dependent variable according to dietary iodine
intake.
Organic components of Saliva
• Enzymes:
– Amylase – converting starch into glucose and
fructose;
– Lyzozymes – prevents bacterial infection in the
mouth;
– Histatins – prevents fungal infections;
– Secretory IgA – immunity mediator.
Mucus
• Mucus in saliva mainly consists
of mucopolysaccharides and glycoproteins;
Glycoprotein (Mucins)
• Lubricant;
• Types – MG1 and MG2;
• Polypeptide chain that stick together;
• Low solubility, high viscosity, strong
adhesiveness;
• Aids in mastication, speech, swallowing by
lubrication.
Glycoprotein (Mucins)
• Preserve mucosal integrity;
• Protective barrier by excessive wear;
• Antibacterial action by selective adhesion of
microbes to oral tissue surface;
• Barrier against acid penetration.
MG1
• High molecular wt;
• Adsorbs tightly to the tooth surface – enamel;
• Pellicle formation – protection from acid
challenges;
• High in caries susceptible patients.
MG2
• Low molecular wt;
• Binds to enamel but get displaces easily;
• Promotes the aggregation and clearance of
oral bacteria (S. mutans);
• High in caries resistant cases.
Antibacterial compounds and growth
factor
• Antibacterial compounds
(thiocyanate, hydrogen peroxide, and
secretory immunoglobulin A);
• Epidermal growth factor or EGF.
Antimicrobial enzymes that kill
bacteria
• Lysozyme;
• Salivary lactoperoxidase;
• Lactoferrin;
• Immunoglobulin A.
There are three major enzymes found
in saliva:
• α-amylase or ptyalin, secreted by the acinar cells
of the parotid and submandibular glands, starts
the digestion of starch before the food is even
swallowed. It has a pH optima of 7.4;
• Lingual lipase is secreted by the acinar cells of
the sublingual gland, has a pH optimum ~4.0 so it
is not activated until entering the acidic
environment of the stomach;
• Kallikrein is a vasodilator. It is secreted by the
acinar cells of all three major salivary glands.
ά-Amylase
• Present in parotid saliva at conc. of 60-120
mg/100ml; in submandibular saliva at approx.
25 mg/100 ml;
• Very little amylase activity in the sublingual
and minor glandular secretions;
• 6 isoenzyme forms exist. Alpha-amylase is Ca
dependent and readily inactivated by a pH of
4 or less’;
• The enzyme hydrolyses the alpha 1:4
glycosidic bond between glucose units in the
polysaccharide chain of starch.
Enzymes
• Lactoperoxidase – stimulation of minor
salivary glands;
• RNA and DNA – cellular maintenance;
• Lipase – iniciates digestion of fat;
Lyzozyme
• An antibacterial enzymes;
• The mean concentration in whole saliva:
– Resting – 22 mg/100ml;
– Stimulated – 11 mg/100 ml;
• Lyzozyme acts on the B(1-4) bond between N-
acetyl-muramic acid and N-acetyl glucosamin in
the Gram+ bacterial cell wall component;
• Lyzozyme may also be bactericidal;
• Inhibits mucosal colonization by microbial
aggregation.
Enzymes
• Kallikrein
– Splits serum beta-globulin into bradykinin;
– Functional vasodilatation to supply an actively
secreting gland;
• Dextranases
– Increased whole saliva dextranase levels may be
associated with impaired oral hygiene and over
consumption of sucrose and related fermentable
carbohydrates which support the growth of
organisms producing dextranases.
Invertases
• High invertase activity is based on the
involvement of several enzymes chiefly
derived from dental plaque S. Mutans and S.
Salivarius;
• High invertase activity – consume high sucrose
and it usually parallels with high lactobacillus
and streptococcus count of plaque.
Prolin-rich proteins
• Proline-rich proteins have function
in enamel formation, Ca2+-binding, microbe
killing and lubrication.
Minor enzymes
• Include:
– salivary acid phosphatases A+B;
– N-acetyl-alanine amidase;
– NAD(P)H dehydrogenase;
– superoxide dismutase;
– transferase;
– aldehyde dehydrogenase;
– glucose-6-phosphate isomerase,
– and tissue kallikrein (function unknown).
Cells:
• Possibly as many as 8 million human and 500
million bacterial cells per mL;
• The presence of bacterial products (small
organic acids, amines, and thiols) causes saliva
to sometimes exhibit foul odor.
Cellular Composition
• The cellular composition consists of:
– Epithelial cells;
– Neutrophils;
– Lymphocytes;
– Bacterial flora.
Opiorphin
• Opiorphin, a newly researched pain-killing
substance found in human saliva
Haptocorrin
• a protein which binds to Vitamin B12 to
protect it against degradation in the stomach,
before it binds to Intrinsic Factor
Individual Hydration
• The degree of individual hydration is the most
important factor that interferes in salivary
secretion;
• When the body water content is reduced by
8%, salivary flow virtually diminishes to zero,
whereas hyperhydration causes an increase in
salivary flow.
• During dehydration, the salivary glands cease
secretion to conserve water.
Factors Influencing Salivary Flow and
Composition
• Several factors may influence salivary flow and
its composition.
• As a result, these vary greatly among
individuals and in the same individual under
different circumstances.
Body Posture, Lighting, and Smoking
• Patients kept standing up or lying down present
higher and lower SF, respectively, than seated
patients.
• There is a decrease of 30% to 40% in SF of people
that are blindfolded or in the dark. However, the
flow is not less in blind people, when compared
with people with normal vision.
• This suggests that blind people adapt to the lack
of light that enters through the eyes.
• Olfactive stimulation and smoking cause a
temporary increase in unstimulated SF.
The Circadian and Circannual Cycle
• SF attains its peak at the end of the afternoon but goes
down to almost zero during sleep.
• Salivary composition is not constant and is related to the
Circadian cycle.
• The concentration of total proteins attains its peak at the
end of the afternoon, while the peak production levels of
sodium and chloride occur at the beginning of the morning.
• According to Edgar, the circannual rhythm also influences
salivar secretion.
• In the summer lower volumes of salivary flows from the
parotid gland, while in the winter there are peak volumes
of secretion.
Thinking of Food and Visual
Stimulation
• Thinking of food or looking at food are weak
salivation stimuli in humans.
• It may seem that people salivate simply
because of thinking of food, but in reality they
become more conscious of the saliva in the
floor of the mouth between swallows.
• Some researchers observed a small increase in
SF in the face of visual stimuli, while others
observed no effect whatever.
Medications
• Many classes of drugs, particularly those that
have anticholinergic action (antidepressants,
antipsychotics, antihistaminics, and
antihypertensives) may cause reduction in SF
and alter its composition.
Regular Stimulation of Salivary Flow
• There is evidence regular stimulation of SF
with the use of chewing gum leads to an
increase in stimulated SF.
Size of Salivary Glands and Body
Weight
• Stimulated SF is directly related to the size of
the salivary gland, contrary to unstimulated SF
which does not depend on its size;
65-70%
20%
parotid
Subman
dibular
Unstimulated flow
• Resting salivary flow – no external stimulus:
– Typically – 0.2ml – 0.3ml per min;
– Less then 0.1 ml per minute means the person has
hyposalivation;
– Hyposalivation – non produsing enough saliva.
Stimulated saliva
• Response to the stimulus, usually taste,
shewing, or medication, at mealtime;
– Tipically – 1,5 ml – 2,0 ml per minute;
– Les then 0,7 ml per minute is considered
hyposalivation
Stimulated Salivary Flow
• Saliva passes through the salivary duct very
rapidly;
– It impedes the exchange of sodium and chloride
for potassium and bicarbonate;
Unstimulated Salivary Flow
• Has high content of potassium and
bicarbonate;
– The quality of unstimulated saliva will change
when flow increases because of a stimulus
(chewing gum, thinking about lemons, looking at a
food you crave).
Average amount of saliva
• The average person produces approximately
• 0.5 to9 1,5 L per day.
Secretory leukocyte proteinase
inhibitor (SLPI)
• Proteinase inhibitory property;
• Antimicrobial and antiviral;
• Important role in wound healing
Tissue inhibitors of metalloproteinase
• Remodeling of extracellular matrix in
inflamation;
• Growth promoting activity;
• Stimulation of osteclastic bone resorption.
Immunoglobulins
• Secretory IgA is the predominant immunoglobulin –
20mg/100ml;
• 90% of the total parotid IgA;
• 85% of whole saliva IgA;
• 30-35% of which is derived from minor glands, IgG
(1.5mg/100ml)& IgM (0,2mg/100ml);
• Secretory IgA is syntesized by plasma cells within the
glands in addition to the mucosal epithelial cells;
• Secretory IgA – non-lymphoid-derived glycoprotein
designated as the secretory component.
Immunoglobulins
• This IgA exhibits 3 possible functions:
– Inhibition of bacterial colonization ,probably by
agglutination;
– Binding to specific bacterial antigens involved with
adherence;
– Affecting specific enzymes essential for bacterial
metabolism.
Strucural features of salivary proteins
• Proline – rich proteins;
• Statherins;
• Cystatins;
• Histatins
Prolin-rich protein (Glycoprotein)
• 70% of total secretory proteins;
• Acidic (Large), Basic (Small);
• Present in enamel pellicle;
• Larger PRP promote bacterial attachment;
• Smaler reduces the initial bacterial
attachment;
• Actinomyces viscosus, S. mutans, S.Gordoni.
Staterin (Phosphoprotein)
• Is a small phosphoprotein (12 000 daltons)
relatively rich in tyrosine and proline which
has the property of inhibiting Hydroxyapatite
crystal growth;
• Potential precursor of enamel pellicle;
• Inhibit spontaneous precipitation of Ca,
phosphate in saturated solution.
Cystatins
• Several cystatins are phosphorylated and bind
to HA;
• Inhibit crystal growth of Ca Phosphate salt.
Histatin
• Parotid and Submandibular saliva;
• Bind to HA, precursor of acquired pellicle;
• Kills C. Albican in yeast form and mycelia form;
• Bacteriostatic;
• Inhibit hem agglutination and thereby
colonization.
Other organic compounds
• Free Amino acids – (Below 0,1mg/100ml)
– Too low to provide nutrient source for bacterial
growth;
• Urea (12-20 mg/100ml)
– Hydrolized by bacteria with the release of
Ammonia – Rise in pH;
• Glucose (0,5-1,0mg/100ml)
– Too low for bacterial growth;
– Increase in DM
Lipids
– Cholesterol, fatty acid glycerides, phospholipids;
– Corticosteroids;
– Cortisol and cortisine;
– 1-2 mg/100ml
• Vitamins
– Water soluble vitamins.
Salivary Amylase Alpha Antibody
Functions of Saliva
Protection
EFFECT ACTIVE CONSTITUENTS
• Clearance • Water
• Lubrication • Mucins, glycoproteins
• Thermal/chemical insulation • Mucins
pH
Secretion Buffer
rate capacity
BUFFERING
• The bicarbonate and, to some extent, phosphate,
ions in saliva provide a buffering action that helps
to protect the teeth from demineralization
caused by bacterial acids produced during sugar
metabolism.
• Some basic salivary proteins also may contribute
to the buffering action of saliva.
• Additionally, the metabolism of salivary proteins
and peptides by bacteria produces urea and
ammonia, which help to increase the pH.
Tooth integrity
EFFECT ACTIVE CONSTITUENTS