saliva - biochemistry Flashcards
1
Q
what things happen in the oral cavity that saliva is involved in
A
EVERYTHING
1) diseases of soft and calcified hard tissues
2) Interactions between oral cavity and restorative procedures + materials AND prostheses + prosthetic materials
3) role in surgical procedures and wound healing
4) Interactions with food and oral therapeutics
2
Q
what is resting saliva
A
when salivary flow NOT being stimulated (by smells, eating, chewing, swallowing)
3
Q
what does salivary volume differ between
A
males and females
4
Q
what range is normal daily saliva secretion
A
0.5 - 1.5 litres
5
Q
what is flow rate of unstimulated saliva per minute
A
0.3-0.4ml
6
Q
what does flow rate of unstimulated saliva per minute change to during…
a) sleep
b) stimulating activities (smells, eating, chewing, swallowing)
A
a) 0.1ml
b) 4ml (0-5)
7
Q
list the 3 major salivary gland pairs, their makeup and what %s they contribute
A
parotid = serous, 20% of resting, 50-60% stimulated
submandibular = seromucin, 65% resting
sublingual = mucous, 5-7% resting
8
Q
where do the minor salivary glands exist and what %s do they contribute
A
in hundreds in the soft palate, buccal + labial mucosa and all over oral cavity
8-10% of resting
9
Q
what is gingival crevicular fluid exudate (GCF)
A
- comes from major and minor glands
- secreted into + contributes to composition of saliva
- collects in gingival crevice and pockets
10
Q
what do relative contributions from salivary glands vary with
A
1) time of day
2) age
3) health status
4) medication
5) flow rate (circadian rythm; stimulus’ nature)
11
Q
what is the result of chemical stimulation on the contribution from different salivary glands when compared to resting
A
parotid = 20% resting, increases to 50-60% after stimulation
submandibular = 65% at BOTH resting and after chemical stimulation
sublingual = lowest contribution, resting contribution more than stimulated
12
Q
what is the result of sialogogues (drugs promoting saliva secretion) on salivary flow rate using
a) NaCl
b) Sucrose
A
sucrose (0.9ml at 1 mole) stimulates salivary flow BUT less than NaCl (1.5ml at 1 mole)
13
Q
what is the most potent stimulus of salivation
A
acid
ie citrus fruit / fruit juices
14
Q
what does the circadian rhythm curve (24 hr period) tell us about salivary flow rates
A
- lowest during sleep
- highest at midday and late aft (6pm)
15
Q
what are the 2 main categories of function of saliva, explain these
A
1) mechanical
- lubrication (of mucosa, food bolus during swallowing, of oral cavity for speech)
- dissolve food (helps it reach tastebuds for taste and wash it away for new taste)
2) chemical
- protective buffering (remin so anti-carious, due to Ca^2+ , [PO ₄]³⁻ and HCO3^-)
- antimicrobial
- protection + repair (due to growth factors and salivary proteins)
16
Q
which antimicrobials are contained in saliva
A
1) lysozyme
2) immunoglobulins
3) lactoferrin
4) complement factors
(also self-defence peptides + salivary proteins)
17
Q
how is saliva able to protect hard tissues
A
- buffer content
- HCO3^- = maintains salivary pH
- F- = replace Ca2+ in HAP (strengthens teeth)
- pellicle proteins = 2 types of pellicle
1) mucosal - protects mucosa
2) acquired enamel - protects hard tissue (teeth) - pH rising factors (sialin)
- Ca^2+ + [PO ₄]³⁻ = maintain mineral content of teeth
- antibacterial factors
18
Q
how is saliva able to protect soft tissues
A
- growth factors = help it heal in ulcer / injuries
- lactoperoxidase = antibacterial role
19
Q
what are the 7 protective functions of saliva
A
1) airway maintenance
2) speech
3) eating, swallowing, mastication
4) control of bacteria, fungi
5) digestion / GIT
6) protection / repair of oral mucosa
7) protection / repair of dentition
20
Q
what is the protective mechanism for airway maintenance
A
- antibacterials
- water retaining glycoproteins - play an agglutination role (stick to bacteria, aggluting them, prevents them attaching to tissues of oral mucosa and airway of mouth) also maintain moisture of oral mucosa and airways
21
Q
what clinical problems occur in airway maintenance because of lack of saliva
A
- increased air-borne microorganisms in airway
- dehydration
22
Q
what is the protective mechanism for speech
A
lubrication
23
Q
what clinical problems occur due in speech because of lack of saliva
A
- dehydration
- difficulty of speech
24
Q
what is the protective mechanism for eating, swallowing, mastication
A
(aids in this function because of 2 effects)
1) antibacterials
2) lubrication
25
what clinical problems occur due in eating, swallowing, mastication because of lack of saliva
- food-borne microorganisms
- abrasion of oral mucosa and ulceration (by debris or large food)
- due to lack of lubrication of food + lack of formation of food bolus
26
what is the protective mechanism for control of bacteria, fungi (the antimicrobial effect)
- antibacterials
- immunoglobulins (esp IgA)
- lactoferrin
- histidine
- lysozyme (bactericidal - degrades bacterial cell wall by piercing it)
27
what is the role of immunoglobulin A (IgA) in control of bacteria, fungi
antiviral, antibacterial, attaches with glycoproteins and when secreted helps agglutination of bacteria to inhibit it attaching to mucosa or tooth surface
then the bacteria is swallowed and killed by gastric acid
28
what is the role of lactoferrin in control of bacteria, fungi
- enzyme containing iron
- needs iron for its function
- takes on all iron in environment
- bacteriocidal effect
- bacteria need iron to grow (prevents growth + multiplication of facultative + aerobic bacteria depriving them of the iron needed for O2 transport)
29
what is the role of histidine in control of bacteria, fungi
- salivay protein
- a self defense peptide = potent antimicrobial effects
- exist in saliva and other bodily fluids
- ie deficins, histatin 1,3,5 and stetherin
- histatin 3 = antifungal and antiopportunistic infection
30
what clinical problems occur due in control of bacteria, fungi because of lack of saliva
- infection rate increased
| - maintenance of commensals affected
31
what is the protective mechanism for digestion/GIT
- amylase = starts carbohydrate digestion in mouth but minimal effect, stops once reaches stomach (acidic)
- specific antibacterial effect
32
what clinical problems occur due in digestion/GIT because of lack of saliva
NONE
- digestion not affected
- mouth only accounts for 17% of carb digestion
- rest = small intestine
33
what is the protective mechanism for protection / repair of oral mucosa
- mucin film (mucosal pellicle) = covers oral mucosa, helps lubrication + inhibition of microbial attachment to it. made up of salivary proteins (mustin, histitin, statherin)
- growth factors
1) epidermal growth factor EGF = repairs epithelial tissues and starts their regeneration = prevents + heals apthous ulcers + wounds
2) vascular growth factor = repair mucosa after ulceration / abrasion and protective effect against toxins, carcinogens etc
34
what clinical problems occur due in protection / repair of oral mucosa because of lack of saliva
- toxins, carcinogenesis
| - cause tissue damage and non-healing ulcers
35
what is the protective mechanism for protection / repair of dentition
- Ca^2+, [PO ₄]³⁻ = maintain mineralised tooth tissue
- HCO3^- = raises acidic ph, maintains pH thus remineralisation
- pellicle protein (histatin 3 and stetherin)
- F- = replaces Ca2+ in HAP if enters tooth surface, calcium hydroxide becomes fluoride hydroxide (stronger mineral formation + crystals) so anticarious
36
which pellicle aids protection / repair of dentition and how
acquired enamel pellicle (transparent membrane)
1) forms within 5 minutes of cleaning teeth
2) made of mainly salivary proteins (esp histitin 3 + stetherin) = maintain Ca^2+ , PO4^3-, inside the tooth surface protecting it
3) directs plaque forming bacteria to allow only favourable (NOT carcinogenic bacteria)
37
what is the clinical significance of the acquired enamel pellicle in composite or resin fillings
- enamel surface acid etched to make micropores that hold the restoration
- have to keep enamel dry (not in contact with saliva) before restoration placed to ensure pellicle is NOT formed (would close the micropores, resin cant properly attach, restoration fails)
38
what clinical problems occur due in protection / repair of dentition because of lack of saliva
increased incidence of
- caries
- periodontal disease
- erosion
39
how is oesophogeal mucosa repaired and healed and why may this be necessary
- by external and vascular growth factors in saliva
| - damage may be caused to it in people who vomit a lot (GORD, acid reflux, bulimia)
40
what is the name for the condition of dry mouth
xerostomia
41
when is saliva considered to be absent / extremely lacking
if flow rate decreases to 0.1ml/min or less
42
list 9 clinical consequences of xerostomia
1) rapid destruction of teeth and gums
2) mucosal damage
3) glossitis (cracking of tongue)
4) candida infections (oral thrush - glossitis makes good environment for its growth)
5) taste problems
6) difficulties with mastication, swallowing, speech
7) rampant caries
8) periodontal disease
9) cracked lips
43
how does glossitis appear and what does it cause
- inflamed, cracked tongue
| - contributes to infection - cracks harbour fungus or bacteria leading to halitosis
44
what are rampant caries, where can they be most dangerous
- rapidly progressing caries (produce rapid damage to teeth)
| - v detrimental to dentition in people who also have high caries index
45
what are local causes of xerostomia
1) sialolithiasis
2) salivary gland tumour
3) sialadentitis
46
what are systemic causes of xerostomia
1) sjogrens syndrome (SS)
2) medication
3) cancer therapies
4) undiagnosed / uncontrolled diabetes
5) neurological conditions (bells palsy, cerebral palsy, trauma)
6) sialotrophic infections (Hep C, HIV)
47
local causes
| what is sialolithiasis and how does it cause xerostomia
- stones of the salivary ducts
- highest incidence in submandibular gland (duct runs horizontally so not affected by gravity)
- 2nd highest in parotid
- can block the salivary duct preventing saliva secretion
48
local causes
| what are give an example of a salivary gland tumor, and how do they cause xerostomia
- pleomorphic adenoma (benign, large, mostly in parotid gland)
- cause blockage as it pressurises the duct preventing saliva secretion
49
local causes
| what is sialodentitis and how does it cause xerostomia
- infections (viral OR bacterial) of the salivary gland itself (NOT the ducts) which can affect salivary flow
50
what is sjogrens syndrome (SS)
- autoimmune disease
- leads to parotid and submandibular gland dysfunction as the body cannot recognise its own tissue
- SO parotid and submandibular acini recognised as foreign tissue
- theyre attacked by immune system, infiltrated with lymphocytes and acini completely destroyed (so no longer produce saliva)
51
what are the two types of sjogrens syndrome and who does it affect most
```
primary = NOT associated with other autoimmune disease
secondary = associated with other autoimmune disease (rheumatoid arthritis, lupus)
```
prevalent in females aged 40-60 (1 in 2500 women)
52
where else does sjogrens disease cause dryness
the eyes
| affects lacrimal glands
53
how many types of drugs can cause xerostomia and what are these mostly categorised as
OVER 500!
- anti-parasympathetic
- anti-cholinergic
54
where is medication causing xerostomia most important and dangerous
elderly patients
- complex medications
- synergistic affects when taking multiple medications raises incidence of xerostomia
55
why is parotid salivary gland most highly sensitive to radiation therapy used to treat oral carcinomas
- serous acinar cells = more sensitive than mucous cell types
- serous contain more heavy metal ions - absorb radiation energy promoting free radical release
- free radicals destroy the salivary glands of salivary ducts so destroy serous acini
56
what is the issue with xerostomia produced by radiation therapy
MOSTLY IRREVERSIBLE
- rarely recovers completely
- in some cases = reversible within 18 months and some recovery in first year
- if treatment 60+ rays = definitely irreversible (as little as 10 can be too)
- after 5 weeks of radiation = salivary flow greatly reduced
57
when doing radiation therapy what should we do if possible
spare a portion of the parotid gland from radiation
58
what increases to compensate for radiation damage
salivary flow from contralateral glands
59
what is important for residual lubrication following radiation damage
recovery of mucous glands (less radiosensitive than serous glands)
60
what changes are present after radiation therapy
- saliva more viscous
- saliva yellow-brown colour
- salivary buffering capacity reduced so pH decreases
- antimicrobial activities compromised
- increased incidence of oral disease
61
what drug can be given to patients undergoing radiation therapy that includes a significant portion of the parotid glands to reduce incidence of xerostomia
how does it work
AMIFOSTINE
- chemoprotective
- scavenger of free radicals
62
what does chemotherapy cause and result in
- systemic immunosuppression which affects salivary immunoglobulin content exacerbating the effects of a dry mouth
- this results in oral mucositis, progression of gingival disease, caries, opportunistic infection
63
which types of chemotherapeutic drugs cause xerostomia and how
antineoplastic drugs - degree of xerostomia caused is related to the total number of chemotherapeutic agents used
- we DO NOT know exact mechanism by which they damage tissue
64
what is observed in chemotherapy patients with low flow rates
- increased salivary drug concentration
| - prolonged contact of drug containing saliva with oral epithelium
65
what does high concentration of a biologically active drug result in
increased toxicity to oral tissues
66
why is amifostine used
detoxifies reactive metabolites of cisplatin (cancer drug)
67
how does diabetes cause xerostomia
- xerostomia + freq urination = 1st symptom of it
- HBA1C inversely proportional to salivary flow SO more blood glucose attached to haemoglobin = lower salivary flow (reported in type 2)
- type 1 = fasting blood sugar levels
68
how do neurological conditions cause xerostomia
affect neurological parasympathetic stimulation / control of salivary flow
69
how do sialotrophic infections cause xerostomia
- lead to autoimmune disease of salivary glands as infected cells become foreign
- causes sjogren-like syndrome
70
what causes parasympathetic outflow and what does it result in, how does this increase flow of watery saliva
- coordinated via centres in the medulla, innervation occurs via facial + glossopharyngeal nerves when afferent info from mouth is sent to brain
- release of acetylcholine (ACh) onto M3 muscarinic receptors
causing...
- acinar cells inc saliva secretion
- duct cells inc HCO3^- secretion
- co-transmitters cause inc'd blood flow to salivary glands
- myoepithelium contracts to inc rate of saliva expulsion
SO incd flow of saliva more watery in composition
71
what 4 methods are used to treat xerostomia and stimulate salivary flow
1) chewing sugar free gum or sweets
2) artificial salivary substitutes
3) water-based oral moisturising gels
4) medication
72
how does chewing sugar free gum or sucking sweets stimulate saliva
what else may help increase salivary flow in ss patients
- gum = mechanical stimulation
- sweets = chemical (gustatory) stimulation - esp if use citrus lozengers (vitamin c, lemon drops) but w caution due to its acidity
sonic toothbrushing
73
how do artificial salivary substitutes (ie oralube, xero-lube) help stimulate saliva
- short term relief
- common
- unpleasant SO low compliance - contain carboxymethylcellulose (mimics viscosity of natural saliva)
74
how do water-based oral moisturising gels help stimulate saliva
- used intraorally as a saliva substitute
| - used extraorally on lips to provide 8 hours of relief from symptoms
75
what is the medication used to increase serous secretion, give 2 examples
- cholinergic agonists which provide parasympathetic stimulation of exocrine glands
- PILOCARPINE (h+n cancer and ss pts)
- CEVIMELINE (ss pts)
- both fda approved
76
what is the problem with the cholinergic effect of these drugs clinically
where may this be of benefit
- systemic so affect ALL exocrine glands
- adverse effects (ie excessive sweating)
- SO use with caution in patients with cardiovascular disease, chronic respiratory conditions, kidney disease
relieving multiple symptoms of ss
77
in which patients is the use of these cholinergic systemic drugs contraindicated
- narrow angle glaucoma
- uncontrolled asthma
- liver disease
78
what is current research on xerostomia treatment investigating
- using other medication classes that may relieve dry mouth symptoms
- tissue engineering and regeneration technology
- salivary transplantation
79
why is the oral cavity considered to be compartmentalised
- positioning of major glands
| - oral conformation
80
what is the result of where the salivary glands are situated in the oral cavity + where their ducts open
- site specific retention and clearance (some areas retain food, debris, drugs more than others)
- limited transfer across mouth
81
what has leeds research discovered about salivary retention of fluoride (15 minutes after rinsing with 1000ppm F mouthwash)
- upper labial sulcus retains more than lower
- upper labial sulcus on RIGHT = highest retention
- posterior lhs + rhs = comparable, less retention
- least retention in the tongue (due to its movement)
- retention higher in upper, clearing higher in lower
82
research
what was measured after a patient wore a retainer containing some sterilised dentine particles for a period and then dissolved a fluoride tablet on upper right sulcus
fluoride retained in dentine particles measured
- RHS shows highest retention until 30 minutes
| - LHS much lower retention over time
83
how does different compartments of the oral cavity having different retention and clearance have clinical relevance
1) retention / clearance of sugars (areas retaining more = higher caries incidence)
2) areas retaining fluoride + therapeutics equally = respond to therapy better
3) areas retaining toxins / carcinogens more = damaged more
4) slow-release devices like ionomers (knowing how compartmentalisation works helps)
84
why do we analyse saliva
contains many marker of health + disease so analysing helps understand more about them
85
what do we need to know and control in order to analyse saliva for experiments
- nature of sample (from fixed or single gland)
control
1) time of day sampled
2) flow rate
3) nature of stimulant if used
- understand the method of collection (paper points, curby cup, cannulation, drooling)
86
how is site specific sampling using paper points carried out and what is this best for
1) weigh filter paper point prior to experiment
2) put it in labial sulcus to collect saliva from minor salivary glands
3) then weigh it after to find weight of saliva
4) put paper point into eppendorf tube
5) analyse nucleic acids
6) can extract proteins and buffers from the sample
BEST WAY FOR collecting saliva from minor salivary glands
87
how is collection carried out using curby cup and what is this specific for
1) inner chamber fits over parotid gland
2) outer chamber holds device in place through gentle suction applied by syringe attached to a tube
3) inner chamber exerts squeezing so parotid gland produces saliva
4) saliva collected from inner chamber via exit tube
SPECIFIC FOR collection of parotid saliva (collect single saliva from a single gland)
88
immediate analysis of saliva preferred - what are the consequences of freezing
1) loss of enzyme activity (denatured)
2) loss of CO2 by diffusion
3) pH changes
4) desquamated cells in saliva will be lysed on freezing
5) freeze-drying causes irreversible protein precipitation
