What percentage of saliva is produced by the minor salivary glands? When are the minor salivary glands most active?
The minor salivary glands produce 10% of saliva. The minor salivary glands produce saliva during the sleeping hours when major salivary gland production has decreased.
Which of the salivary glands is the first to develop embryologically?
The submandibular gland.
What are the stages of salivary gland development?
Prebud
Initial bud
Pseudoglandular
Canalicular
Terminal bud
What is the terminal end of the salivary gland called? This is where the secretory cells of the salivary gland are found.
The acinus.
What are the three types of ducts that a secretory product passes through as it moves from the acinus to the oral cavity?
1. Intercolated ducts
2. Striated ducts
3. Excretory ducts (a.k.a. Extralobular duct)
Ture or false:
Acinar secretions are modified by ductal cells before entering the oral cavity.
True. The ionic content of acinar secretions are modified by ductal cells.
Na+ and Cl- concentrations are decreased.
K+ and HCO3- concentrations are increased.
Ionizing radiation kills cells by producing __________.
Free radicals.
Salivary glands are highly sensitive to radiation damage even though they have a slow rate of proliferation. This may be due to the high content of __________ found in these cells.
Metal ions. Acinar cells have a high concentration of high molecular weight materials in their secretions. This is thought to be a possible reason why they are so sensitive to irradiation.
Dryness of mouth is also called ______.
Xerostomia.
What are some symptoms / effects of hyposalivation?
1. Dryness of mouth (xerostomia)
2. Taste disturbances / taste loss
3. Mechanical problems such as difficulty swollowing or difficulty wearing dentures.
4. Discomfort / burning sensation
5. Shift in oral microflora
6. Increased risk for caries or radiation caries
7. Perio disease
Which of the following glandular cells are most sensitive to radiation exposure?
a. Acinar cells
b. Ductal cells
c. Endothelial cells
d. All are equally sensitive to radiation
Acinar cells are the most sensitive to radiation and die by apoptosis or reproductive death following radiation exposure.
Which cells in a salivary gland are "stem cells" associated with?
Ductal cells.
DNA labeling studies indicate that the highest levels of cell division are concentrated in the intercalated ducts. However, to date, a defined population of cells that can be definitively identified as "stem cells" has not been isolated from the salivary gland.
What are three strategies to help patients with salivary gland damage.
1. Preventative or protection of oral tissues during radiation tx. (Radioprotectors)
2. Replacement of damaged tissue via stem cell therapy. Stem cell transplantation.
3. Repair of damaged tissue via gene therapy.
What are two radioprotectors that have been used to prevent damage to tissue during radiation tx?
1. Amifostine - A free radical scavenger that is delivered systemically during radiotherapy.
2. Tempol - can be used topically, i.p., i.v. or s.c. to reduce damage by irradiation.
What type of vectors are used to transfer genetic information to glandular cells in gene therapy?
Adenoviral vectors are used.
True or false.
Gene therapeutics are also being considered as a means of treating systemic single protein deficiency disorders.
True. Gene transfer to salivary glands, causing them to produce a systemically missing protein, is being considered as a treatment for single protein deficiency disorders.
How do chemical radiation protectors such as Amifostine work?
They neutralize free radicals produced by ionizing radiation.
Ture or false.
During the process of radiotherapy, significant reductions in salivary secretions are seen only after the death of acinar cells.
False. Reductions in salivary secretions are seen surprisingly quickly after beginning radiotherapy and long before the death of the glandular cells.
True or False.
Vitamin E and Vitamin A are lipid soluble antioxidants.
True. They have the ability to absorb free radicals.
The CNS regulates salivary secretion through the _______ nervous system.
Autonomic
What are the specific neurotransmitters, and the associated receptors, that are associated with the sympathetic and parasympathetic pathways?
How do the receptors function?
Sympathetic: norepinepherine is the neurotransmitter and the alpha-adrenergic receptor is the associated receptor that drives the production of the fluid phase of secretion, resulting in fast flow rate and low organic content.
Parasympathetic: Acetylcholine is the neurotransmitter. Cholinergic receptors are associated and also drive the fluid phase of secretion resulting in fast flow rate and low organic content.
What are the principal intracellular messengers that affect salivary gland secretion? What processes do each of them regulate?
True or False.
The movement of water is mostly transcellular.
True
True or False.
The movement of Na is mostly transcellular.
False. The movement of sodium is mostly paracellular.
What vitamin directly regulates Ca absorption?
Vitamin D
What is the main biological function of PTH?
regulation of 1,25(OH)2D3 (active vitaminD) synthesis
What is the precursor to 1,25 and where is it found?
25 hydroxy D3 is made in the liver and is then converted into 1,25 hydroxy D3 in the kidney.
These cells surround the acinus and intercalated ducts and can contract, moving salivary secretions through the duct and toward the oral cavity.
Myoepithelial cells
True or False.
Because acinar cells have high metabolic activity and a tremendous need for O2, anini are surrounded by a capillary bed.
True.
Labial, buccal, palatine and lingual are the names of which kind of salivary glands?
Minor salivary glands
True or False.
Minor salivary glands are similar in structure to major salivary glands.
True. Minor salivary glands are very small and contain fewer acini but maintain a similar glandular structure to the major salivary glands.
Acetylcholine is the main driving force for the ________ pathway.
Parasympathetic
Norepinepherine is the main driving force for the __________ pathway.
Sympathetic
Fluid secretion is principally regulated by ______.
Calcium
Net water movement through acinar cells happens through this transmembranous protein.
Aquaporin
What is the normal range for saliva pH?
6.2 - 7.6
Unstimulated and stimulated flow rates for saliva are:
0.3-0.5 ml/min unstimulated
1-2 ml/min stimulated (or higher)
True or False.
The parasympathetic pathway leads to the secretion of primary secretory fluid (H2O and specific electrolites)
True.
True or False.
Stimulation of mechanical receptors around the teeth lead to exocytotic production by mucous and sirous cells via the Sympathetic pathway.
True.
True or false.
Bicarbonate production is much lower when salivation is stimulated.
False. Bicarbonate production is much higher when salivation is stimulated.
The principal regulatory molecule for exocytosis is __________.
Cyclic AMP. Beta-adrenergic receptor stimulation (sympathetic) increases cAMP and drives the secretion of macromolecules via exocytosis with low flow rate and high organic content.
What is the function of SNARE proteins?
Formation of a complex which mediates membrane fusion.
Reflex Arch consists of afferent signals via which nerves?
The trigeminal, facial and glossopharyngeal nerves.
What percentage of glandular mass is made up by acinar cells?
80%
What are the three types of ductal cells? What are the cells surrounding the acinus and ducts that promote saliva flow?
Intercalated, striated and excretory.
Myoepithelial cells
What are the two stages of fluid secretion?
1. Production of primary secretory fluid
2. Modification through ducts via reabsorption and secretion of electrolytes.
How does Ca regulate fluid secretion?
Intracellular Ca release is IP3 mediated. An increase in intracellular free Ca opens potassium and chloride channels on the basolateral membrane. Apical Cl efflux (going out of the cell) draws Na via paracellular channels into the lumen. Na and Cl concentrations result in water movement into the lumen via water channels (aquaporin).
What other ion do apical Cl channels also transport?
HCO3
True or False.
Movement of Cl is transcellular.
True
True or false.
Movement of Na is paracellular.
True
What maintains the intracellular pH during fluid secretion?
The basolateral Na/H exchanger does!
What receptors drive the fluid phase of secretion resulting in a fast flow rate and low organic content?
What receptor drives the secretion of macromolecules via exocytosis resulting in a low flow rate and high organic content?
Beta-adrenergic receptor stimulation drives this.
The alpha and beta pathways are associated with the sympathetic pathway and ensure that there is enough secretory fluid to cary the exocytotic products.
What is the membrane protein operative in salivary glands that is localized in lipid rafts and translocated to the apical membrane during stimulation?
AQP 5
Transcellular and paracellular water movement leads to production of primary secretory fluid.
True or False.
Water will only flow through aquaporin in one direction.
False. Water will flow either direction when the pore is open depending on the gradient.
How is a hypotonic saliva formed in the salivary gland?
Luminal and basolateral membranes of the ductal cells have abundant transporters that function to produce a net reabsorption of Na and Cl, resulting in formation of hypotonic final saliva.
Ducts also secrete K and HCO3
True or False.
Primary secretory fluid contains amylase.
True
Secretion by exocytosis is regulated by which two substances?
cAMP and Ca with cAMP as the primary intracellular messenger.
What is a zymogen granule?
Membrane bound bodies from the golgi containing zymogen. Zymogen is an inactive precursor to an enzyme.
What major proteins functions in the formation of a complex which mediates membrane fusion in exocytosis?
SNARE proteins
What acts in a priming step and in disassembly of SNARE complex?
SNARE cofactors
What does Rab regulate?
Rab regulates granule migration
What is the function of Ca-binding protein?
Ca-binding protein functions as a Ca sensor.
What is the residual volume of saliva in the mouth and what are the stagnant areas of the mouth?
Residual volume is 0.8 - 1.1 ml. The buccal, upper anterior and lower molars are areas with little saliva turnover.
What are secretory products of acinar cells?
Mucins
Proline-rich proteins
Histatins
Cystatins
Amylase
Statherin
What are ductal and stomal cell products?
Lactoferrin (binds iron - antimicrobial)
Lysozyme (antimicrobial)
Salivary peroxidase (antimicrobial)
Kallikrein (?)
Secretory IgA (host defense)
EGF
NGF
What is the most predominate protein in human saliva? In which gland is it mainly synthesized? What is its function?
Alpha-amylase. It is synthesized in teh parotid gland and functions to begin the process of carbohydrate digestion. Alpha-amylase also forms heterotypic complexes with other proteins, acts in tissue coating, lubrication and has a role in bacterial clearance.
Proline-rich proteins are secreted by which gland/s? They play a key role in the digestion of what substance?
Proline-rich proteins are secreted by both the parotid and submandibular glands and protect against the ingestion of tannins (polyphenolic acids produced by plants to keep things from eating them).
What are histatins? From what glands are they secreted?
Histatins are one of the smallest MW proteins in human saliva and are secreted by the parotid and submandibular glands. They have antifungal and antibacterial activity as well as salivary buffering and modulate Ca/P equilibrium.
This major salivary protein is a tyrosine-rich phosphopeptide containing 43 aa. It has a high affinity for Ca and hydroxyapatite and prevents Ca and phosphate precipitation. What protein is this?
Statherin.
What are cystatins?
A diverse group of thiol-protease inhibitors. There are at least 7 of these in saliva.
What is the difference between HMW mucins and LMW mucins?
High molecular weight mucins create a permeability barrier, coat oral tissues and protect from desiccation. They have a high concentration of protective molecules.
Low molecular weight mucins facilitate bacterial clearance via co-aggregation. They make a "sponge" that traps bacteria and viruses and keeps them from adhering to tooth or oral structures.
Salivary peroxidases are enzymes that do what?
Salivary peroxidases oxidize SCN by H2O2 generating highly reactive oxidative forms of thiocyanate.
Which beer did I choose to drink while making these flashcards?
Breckenridge Vanilla Porter
How are oral bacteria in plaque able to function as a coordinated, spatially organized and fully metabolically integrated microbial community?
Bacteria communicate via small diffusible signaling molecules.
The ____________ is an organic film that is primarily proteinaceous and formed by selective adsorption of salivary proteins.
Aquired enamel pellicle
What are attached and free-floating forms of dental plaque called?
Sessile (attached)
Planktonic (free-floating)
True or False.
90% of people affected by primary Sjogren's Syndrome are men.
False. 90% of those affected by Sjogren's are women.
What is the most common cause of salivary gland hypofunction?
Suppression of CNS due to the use of various medications.
What are causes of salivary hypofunction?
Pharmaceuticals - 3 or more
Radiotherapy or chemotherapy
Sjogren's Syndrome
Diabetes
Dehydration
Graft-vs-host disease
Age
Mucositis, hyposalivation, taste loss, osteoradionecrosis, caries and trismus are all common clinical consequences of what kind of treatment?
Head and neck radiotherapy
Parched mouth, accelerated dental decay, swollen salivary glands, difficulty chewing and swallowing foods, burning and cracking of lips at corners of the mouth, dry, parchment-like mucosa and loss of filiform papillae of the tongue are all symptoms of what?
Sjogren's
True or False.
RDIs are the new term for RDAs and reflect nutrient requirements for individuals and groups.
True
What are diet and nutrition?
Diet: What we eat.
Nutrition: How the foods we eat are used by our bodies.
What are the six classes of nutrients? What nutrient is most important?
Water (most important)
Proteins
Carbohydrates
Fats
Minerals
Vitamins
True or false.
Decreasing variety in diets reduces the probability of nutritional deficiencies.
False. One can reduce the probability of nutritional deficiencies by increasing dietary variety.
True or false.
Essential nutrients are needed throughout life, only amounts change.
True
Dietary guidelines for Americans:
Don't be a fat pig! But how do I do this when I'm lovin' my high fat, high salt, high sugar fast food diet?
Eat a variety of foods (food, not edible food-like substances)
Balance food with physical activity
Make sure you drink alcohol, just do it in moderation and watch out for the distilled varieties!
Which vitamin plays a role in specific gene expression for a hormone action required for epithelial differentiation?
Vitamin A
The active form of vitaminD (1,25 dihydroxyvitaminD3) is synthesized in what tissue under the regulation of what hormone?
The active form of vitaminD (1,25) is synthesized in the kidney under the regulation of PTH or low phosphate.
Which fat-soluble vitamin plays a role in night blindness?
Vitamin A
What are some effects of vitamin A toxicity? Vitamin A deficiency?
Toxicity:
Damage to cell membranes
Teratogenic effects - birth defects
Deficiency:
Blindness
Degeneration of epithelial cells
Enamel hypoplasia
Which three hormones regulate calcium and phosphate metabolism? Which three organ systems are involved in this complex regulatory system?
Parathyroid hormone (PTH)
Vitamin D
Calcitonin
Bone
Intestine
Kidney
What hormone/s cause blood Ca to go up? What hormone/s cause it to go down?
PTH and Vitamin D cause Ca stimulate an increase in Ca levels.
Calcitonin stimulates a drop in Ca levels.
What is the biological importance of Ca?
Muscle contractions
Nerve impulse transmission
Secretory response of endocrine and exocrine cells
Membrane stability
Blood clotting
Intracellular messenger
What has the following biological importance?
-Is an intermediate in carbohydrate, lipid and protein metabolism, ATP and creatine phosphate, cofactors - NADP, second messengers - cAMP, inositos triphosphate, DNA & RNA along with the phosphorylation of key regulatory proteins.
Phosphate
How do intracellular and extracellular calcium concentrations compare?
Intracellular is lower (10-7) than extracellular (10-3)
What are problems caused by increased and decreased levels of Ca?
Increased levels: Respiratory or cardiac failure
Decreased levels: Tetany
What is the major salt of calcium?
Calcium phosphate
True or False.
Most Ca salts are chelated by organic acids such as citrate, oxlate, phytic acid and bile salts to allow absorption.
True
What is the site of Ca transport and what vitamin does it depend on?
Calcium is actively transported in the small intestine by a vitaminD dependent system.
Since PTH is sensitive to changes in plasma Ca and acts to increase plasma Ca levels, its rate of secretion is directly or inversely proportionsl to blood Ca concentrations?
Inversely
PTH acts on which tissues that regulate plasma Ca levels?
Bone and Kidney
Secretion of calcitonin is directly proportional to serum ionized Ca. Its function is to lower plasma levels of Ca and does so by targeting cells in which tissues?
Vitamin D stimulates absorption of calcium by increasing the number of calcium transport poumps in the basolateral membrane via gene regulation(Steroid Hormone). It also stimulates absorption of phosphate and magnesium.
True or False.
Vitamin E is a fat-soluble membrane antioxidant.
True.
What is the main function of vitamin K?
Blood clotting
What is the role of vitamin B1. What is the common name for B1?
Vitamin B1 is a coenzyme in pyruvate dehydrogenase complex. It is commonly known as Thiamine.
What is the physiological role of Vitamin B2? What is its common name?
Intracellular respiration, Flavoproteins, FADH2 and electron transport. It is also known as Riboflavin.
Deficiency of what vitamin leads to beriberi?
Vitamin B1
Vitamin B3 is known commonly as what? What is its physiological role and what are the symptoms of B3 deficiency?
Niacin. Electron transport: NAD, NADP. Deficiency in B3 leads to pellegra: dermatitis, diarrhea, dementia.
Vitamin B5 is part of coenzyme A structure and plays a central role in carbohydrate, lipid and amino acid metabolism. What is it commonly called?
Pantothenic Acid
How many freakin' B vitamins are there? What is caused by a vitamin B6 deficiency?
At least six so far. Vitamin B6 (Pyridoxine) is a coenzyme for transaminases, aa metabolism, neurotransmitters, serotonin and sphingolipids.
B6 deficiency leads to hyperirritability, convulsions and anemia.
What is the most common cause of Biotin deficiency?
Children in the tropics who have parasites.
Folic Acid/Folate acts in the synthesis of what proteins? What do folate deficiencies cause?
Folate has 5 coenzyme forms in the one-carbon transfer during synthesis of DNA and RNA. It acts in the synthesis of choline, serine and methionine.
A deficiency leads to neurotube defects in newborns and megalobastic anemia.
What role does vitamin B12 play?
It is a coenzyme in folate metabolism.
What is required for the absorption of vitamin B12?
Intrinsic Factor is a glycoprotein secreted in the stomach that is required for absorption of B12.
Vitamin C (Ascorbic Acid) aids in the biosynthesis of what type of tissue? It also aids in the absorption of what material?
Vitamin C aids in the biosynthesis of collagen and in the absorption of Iron. A deficiency in vitamin C leads to scurvy, gingivitis and cessation of bone growth.
What is the most abundant extracellular divalent cation?
Calcium
What is the most common intracellular divalent cation?
Magnesium.
Zinc is a mineral that aids in what?
It acts in over 120 enzymes, helps with cell growth and differentiation, fertility, reproduction and sexual development, immune defense system, taste and apetite, DNA, RNA and protein synthesis.
What are the two most abundant extracellular and intracellular monovalent cations?
Sodium (extracellular) and Potassium (intracellular). These regulate normal fluid volume and regulate acid-base balance.
This mineral is found in cytochromes and hemaglobin, aids in collagen synthesis, nucleic acid biosynthesis, lipid uptake, detoxification of drugs in liver, production of antibodies and is bound by lactoferrin in saliva. Deficiency leads to anemia.
Iron
Iodine helps to maintain the basal metabolic rate, aids in thyroxine synthesis and tissue specific gene expression. A deficiency in Iodine leads to what condition?
Goiter and hypothyroidism.
Chloride helps to maintain what?
Extracellular fluid balance, osmotic equilibrium and blood pH. It also plays a role in gastric secretion.
