Week 11 - L1 - Saliva Composition, Function, and Regulation

This lecture shifts focus from gastrointestinal motility to secretions into the lumen of the gastrointestinal (GI) tract, beginning specifically with saliva.
The primary learning outcomes for this session include: - Discussing the detailed composition and various functions of saliva. - Describing the regulation of salivation via the autonomic nervous system. - Explaining the pharmacological treatment of tilism (excessive drooling) and xerostomia (dry mouth resulting from insufficient salivation).

Secretions throughout the gut vary in volume and acidity; however, most are neutral or alkaline to protect the lining and facilitate enzymatic activity.
Saliva: The first secretion encountered in the GI tract.
Gastric Secretions: Highly acidic, representing a major exception to the generally alkaline nature of other secretions.
Bile: Plays a critical role in digestion, to be covered in subsequent detail.
Pancreatic Secretions: Involved in neutralizing gastric acid and providing digestive enzymes.

Salivation is defined as the secretion or discharge of saliva.
Infant Salivation: Drooling or dribbling is considered normal in infants up to the age of $15 - 18$ months because they have not yet developed the voluntary control required to swallow their saliva.
Intrinsic Salivary Glands (Buccal Glands): These are small glands located within the mucosa (the lining of the mouth, also known as the buccal cavity). They secrete saliva continuously to ensure the mouth remains moist.
Extrinsic Salivary Glands: There are three pairs of large glands located outside of the mouth with ducts that lead into the buccal cavity: - Parotid Glands: The largest pair, situated anterior to the ear. The parotid duct enters the mouth through the cheek, specifically opposite the second molar. - Submandibular Glands: Located beneath the mandibular bone (lower jaw), with a duct that empties saliva directly beneath the tongue. - Sublingual Glands: A collection of small glands located beneath the tongue ("sublingual" meaning beneath the tongue). These possess multiple separate ducts that empty saliva under the tongue.

Daily Volume: Humans secrete between $800 - 1500\,mL$ of saliva daily, with an average secretion of approximately $1\,L$ .
Basal Rate (Sleep): During sleep, salivation is inhibited to a rate of approximately $0.05\,mL/min$ to prevent drooling onto pillows.
Waking Rate: When awake, the rate increases tenfold to approximately $0.5\,mL/min$ .
Stimulated Rate: Exposure to acid is a potent stimulus. For example, sucking on a lemon can increase the salivation rate to $7 - 8\,mL/min$ .

Water Content: Saliva is comprised of $97 - 99.5\%$ water.
Ions: Contains electrolytes in concentrations typically similar to those found in plasma, including: - Sodium ( $Na^+$ ) - Potassium ( $K^+$ ) - Calcium ( $Ca^{2+}$ ) - Magnesium ( $Mg^{2+}$ ) - Phosphate ( $PO_4^{3-}$ ) - Bicarbonate ( $HCO_3^-$ ) - Chloride ( $Cl^-$ )
Calcium Phosphates: These are critical for dental health as they prevent the demineralization of teeth.
Proteins and Enzymes: - Mucin: A glycoprotein that acts as a lubricant for ingested food. - Tylin (Salivary Amylase): An enzyme that initiates the chemical digestion of carbohydrates and starches. - Immunoglobulins: Proteins that limit the ability of microbes to colonize the oral cavity.

Lubrication: Mucin coats food to facilitate swallowing.
Digestion: Salivary amylase begins the breakdown of complex starches.
Oral Hygiene and Protection: Saliva rinses the teeth to remove food acids, protecting the health of both the teeth and gums.
Hydration Control: The moisture level of the mouth lining acts as a feedback mechanism for water intake; a dry mouth triggers the urge to hydrate.
Speech: Saliva facilitates the movement of the tongue within the mouth, which is essential for clear speech.
Drug Absorption: Certain medications can be absorbed sublingually (under the tongue) through the saliva. An example is nitrates, which are used for rapid treatment during a heart attack because they enter the bloodstream quickly.
Taste: Chemical "tastants" in food must be dissolved in a fluid to be detected by taste buds; saliva serves as this solvent.

The rate of salivation is predominantly controlled by the parasympathetic nervous system.
Stimuli for Salivation: - The thought, smell, sight, or sound of food (e.g., the sound of bacon frying or popcorn popping). - Physical actions such as chewing, touch, and the sensation of taste. - Nausea: The most potent stimulus for salivation. This is a protective mechanism; since vomit is highly acidic, a surge of alkaline saliva helps protect the mouth, teeth, and gums from acid damage.
The Neural Pathway: 1. Activation of sensory nerves (taste buds, stretch receptors). 2. Signal transmission to higher brain regions (auditory, visual, gustatory/taste, and olfactory/smell cortices). 3. Activation of the salivatory nucleus located in the brain stem (medulla). 4. Activation of parasympathetic nerves innervating the salivary glands, leading to increased secretion.
Inhibition of Salivation: - Occurs during sleep. - Occurs during states of intense fear, which often results in a "dry mouth" sensation. - Fear inhibits the salivatory nuclei, reducing parasympathetic output to the glands.

Tilism: Characterized by excessive salivation or drooling.
Mechanism for Treatment: Targeting muscarinic receptors on the salivary gland epithelium.
Normal Physiology: The parasympathetic nerve terminal releases acetylcholine (ACh), which binds to muscarinic receptors to increase saliva secretion.
Atropine: A muscarinic receptor inhibitor (antagonist) used to treat tilism. - It helps resolve hygienic problems and social barriers associated with excess salivation. - Warning: It must be used in low doses. High doses can cause systemic side effects, such as inhibiting gut motility by blocking muscarinic receptors in the smooth muscle cells of the gastrointestinal tract.

Xerostomia: A condition of dry mouth caused by insufficient salivary secretion.
Primary Causes: - Side effects of medications (affects approximately $20\%$ of people on prescriptions). - Tricyclic antidepressants are particularly known for causing dry mouth. - Radiotherapy, severe dehydration, shock, and renal failure.
Consequences of Untreated Xerostomia: - Oral diseases, dental cavities, and gum disease. - Halitosis (bad breath). - Constant sensation of thirst. - Altered taste sensations. - Difficulty in chewing, swallowing, and speaking.
Diagnosis: - Swabbing the tongue with $5\%$ citric acid to measure the resulting saliva volume. - Dry Cracker Test: A patient is asked to chew and swallow dry crackers without water; those with xerostomia find this task extremely difficult.
Treatment: - Use of muscarinic receptor agonists (activators) to increase secretion. - Removal or replacement of the drug causing the side effect.
Note on Artificial Saliva: Many commercially advertised artificial salivas are essentially water and are generally considered ineffective.