HNS31 Salivary And Nasal Secretion Flashcards

1
Q

Salivary glands

A

Exocrine glands: produce saliva through system of ducts

3 Major pairs

  1. Parotid gland (15-20% resting salivary content in oral cavity)
    —> Parotid duct
    —> Opening at upper 2nd molar teeth
  2. Submandibular gland (65-70% of resting salivary content in oral cavity)
    —> Wharton duct
    —> Opening at area beneath tongue
  3. Sublingual gland (3-5% resting salivary content in oral cavity)
    —> Sublingual ducts
    —> Several openings at area beneath tongue

Function:

  1. Lubricating
  2. Protective

Minor gland (800-1000):

  • Bucca
  • Labia
  • Lingual mucosa
  • Soft palate
  • Floor of mouth

Function:
1. Hydrating mucosal surface

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2
Q

High salivary flow vs Low salivary flow region

A

High salivary flow region (Salivary highway):

  • Maxillary
  • Mandibular

Low salivary flow region (Salivary byway) —> Dental caries formation:
- Maxillary anterior

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3
Q

***Salivary glands secretion

A

Parotid:

  • Serous (contain enzymes) (watery)
  • Acini: Serous acinus

Submandibular:
- Mixed serous + mucous

Sublingual:

  • Mucous
  • Acini: Gianuzzi demilune
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4
Q

Serous vs Mucous

A

Serous:

  • **Zymogen granules (inactive enzyme) —> stain **darkly by eosin
  • ***Round nuclei
  • Secrete proteins in ***isotonic watery fluid

Mucous:

  • Stain ***lightly, appears empty
  • Bubbly shape
  • ***Flattened nuclei lie against basement membrane
  • Secrete ***mucin (mucoglycoprotein) (lubricant) —> squeeze nuclei to one side
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5
Q

Myoepithelial cells

A

Surround:

  • End of secretory piece (acini)
  • Ducts

Function:

  1. Prevent distension of end secretory piece
  2. Contract when gland is stimulated —> aid expulsion of saliva
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6
Q

***Salivary ducts

A

Intercalated duct (先):

  • Cuboidal cell: secrete
    1. Lactoferrin
    2. Lysozyme

Striated duct (後):
- Cuboidal cell with **deep infoldings of basal plasma membrane (with **numerous mitochondria within)
—> deep infoldings: for ***Reabsorption of NaCl
—> mitochondria: energy used for electrolyte transport

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7
Q

Saliva composition

A

pH 6.2-7.4 (mainly alkaline unless acid production due to ingestion)
—> ***Alkaline: Re-mineralisation of enamel + Neutralise acid byproducts by microbes

***Hypotonic —> allow taste for salt

  1. Water (99.5%)
  2. Solids (0.5%)
  • Organic substances
    —> Enzymes (Amylase, Lipase, Lysozyme)
    —> Others (Mucin, Lactoferrin, Agglutinin, IgA/G/M, Nitrogenous products e.g. urea, ammonia)
  • Inorganic substances
    —> Na, K, HCO3, Cl, Ca, PO4, F
    —> Ca, PO4: re-mineralisation
    —> F: Fluoroapatite coat teeth to prevent caries formation
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8
Q

***Saliva functions

A
  1. Hydration and lubrication of oral tissues
    - mucin
    - water
  2. Facilitate mastication and deglutition
    - mucin (highly adhesive)
    - water
  3. Solubilisation of food —> enhancement of taste
    - water
    - hypotonicity
  4. Initiating digestive process
    - **Amylase
    - **
    Lipase
    - NO protease
  5. Anti-bacterial —> oral hygiene and health of teeth
    - **Lysozyme
    - **
    Lactoferrin —> remove iron (iron-binding) which is required by bacteria
    - Agglutinin —> aggregate pathogens
    - IgA, G, M —> facilitate phagocytosis
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9
Q

***Salivary production - Electrolyte and Water

A

Water and electrolyte secretion: Energy consuming 2-stage process:

Stage 1 (in **Acini): **NaCl + **H2O secretion —> Isotonic primary saliva (~plasma fluid)
- **
G protein coupled receptor (muscarinic receptor by PNS) stimulated
—> Ca signaling pathway
—> Ca-activated Cl channels (apical membrane of acinar cells)
—> Cl move into lumen
—> Na paracellular transport into lumen via leaky tight junctions
—> H2O paracellular transport into lumen via leaky tight junctions / Transcellular H2O transport via Aquaporin 5 (AQP5) (apical)

Cl from:
- Na/K-ATPase —> pump out Na —> Na go back via NKCC channel —> bring along Cl
(K go out by Ca-activated K channel on basolateral)

Ion channels related:

  1. ***Na/K-ATPase (basolateral)
  2. ***NKCC (basolateral)
  3. Ca-activated K channel (basolateral)
  4. ***Ca-activated Cl channel (apical)
  5. ***AQP5 (apical)
  6. ***Paracellular route (Na + H2O)

Stage 2 (in **Ducts): **NaCl reabsorption + ***KHCO3 secretion by ductal cells —> Hypotonic final saliva

  • Ducts: impermeable to H2O (H2O cannot go back to interstitial space)
  • Na reabsorption via ENaC (epithelial Na channels) (apical membrane of striated duct + excretory duct)
  • Na/HCO3 co-transporter (NBC) (basolateral)
    —> Na / HCO3 into cell
    —> HCO3 exit into lumen via Cl/HCO3 exchanger (apical)
    —> Cl into cell
    —> Cl goes into interstitial space via electrogenic Cl channel (basolateral)
  • Na/K-ATPase (basolateral) —> K accumulation in cell —> K efflux into lumen via K channel (apical)

Ion channels related:

  1. ***ENaC (apical)
  2. ***Cl/HCO3 exchanger (apical)
  3. K channel (apical)
  4. Na/K-ATPase (basolateral)
  5. ***Na/HCO3 co-transporter (basolateral)
  6. Electrogenic Cl channel (basolateral)
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10
Q

Protein secretion from Salivary glands

A

3 main modes of vesicular protein secretion

  1. Regulated secretion (80-90%, 要有stimulation先release)
    - stimulation of SNARE (SNAP receptor) (PKA cAMP pathway)
    —> membrane fusion
    —> secretion by secretory granule via exocytosis
  2. Constitutive secretion (傳統, 不受stimulation影響)
    - transcription + translation —> packaging in Golgi —> exocytosis
  3. Transcytosis
    - only for secretion of ***Ig complexes (produced by plasma cells around CT surrounding ducts)
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11
Q

Transcytosis mechanism

A
  1. Dimeric IgA released by plasma cells into interstitial matrix of salivary glands
  2. Dimeric IgA bind to polymeric Ig receptor (pIgR) (basolateral membrane of ductal epithelial cells)
  3. Internalisation and transport to luminal surface (dimeric IgA + pIgR)
  4. pIgR is cleaved and secretory IgA released into saliva
    - secretory IgA still has part of pIgR —> prevent digestion in acidic environment
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12
Q

***Regulation of salivary secretion

A

Unstimulated rate: ~0.3 ml/min (majority by submandibular gland)
Stimulated rate: ~7 ml/min (majority by parotid gland)

3 specific triggers:
1. Mechanical (chewing)
2. Gustatory
3. Olfactory
—> control salivary secretion via Autonomic NS (regulate both Volume + Type of saliva)

**Parasympathetic stimulation (rest and digest)
—> via ACh muscarinic M3 receptors (GPCR —> PLC —> IP3 —> Ca signaling pathway)
—> **
watery saliva secretion (Fluid + Electrolyte)

**Sympathetic stimulation
—> via β adrenergic receptors by NA (GPCR —> cAMP —> PKA pathway)
—> **
protein-rich saliva secretion (Mucin)
—> ↑ viscosity —> dry mouth

BOTH stimulation causes ***myoepithelial cell contraction
—> BOTH facilitate saliva secretion

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13
Q

***Nerve supply to salivary gland

A

SNS (“Thoracolumbar outflow”):
- Preganglionic neurons: T1-T4 of Intermediolateral cell column (i.e. Lateral horn)
—> **Superior cervical ganglion
—> Postganglion neurons pass through **
External carotid artery plexus and its branches
—> ALL 3 salivary glands

PNS (“Craniosacral outflow”):
1. Superior salivatory nucleus (medulla) (記: CLS)
—> Preganglionic neuron (CN7)
—> Intermediate nerve
—> ***Chorda tympani
—> ***Lingual nerve (branch of CNV3)
—> ***Submandibular ganglion
—> Submandibular, Sublingual gland, Minor salivary glands of mouth, pharynx, nasopharynx
2. Inferior salivatory nucleus (記: LOA)
—> Preganglionic neuron (CN9)
—> Tympanic nerve plexus
—> ***Lesser petrosal nerve
—> ***Otic ganglion
—> ***Auriculotemporal nerve (Postganglionic cell) (branch of CNV3)
—> Parotid gland
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14
Q

Afferent signals to Salivary nuclei

A
  1. Taste buds (gustatory-salivary reflex)
    - Anterior tongue (CN7)
    - Posterior tongue (CN9)
    —> Nucleus solitary tract
    —> Salivary nuclei
  2. Olfactory receptors (olfactory-salivary reflex)
    - CN1
    —> medial olfactory area
    —> descending pathways from cortical centres
    —> Salivary nuclei
  3. Mechanoreceptors (masticatory-salivary reflex)
    - CN5
    —> Trigeminal nucleus
    —> Salivary nuclei

After afferent signals received —> either PNS / SNS activated —> visceral motor output

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15
Q

3 major segments of Nasal cavity

A
  1. Squamous mucosa (stratified squamous) (入口)
  2. Respiratory mucosa (largest) (大部分)
  3. Olfactory mucosa (頂部)
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16
Q

***Respiratory mucosa

A

Ciliated Pseudostratified columnar epithelium with Goblet cells

  1. Ciliated columnar cells (mostly)
    - mucociliary clearance
  2. Non-ciliated ***goblet cells
    - mucin
  3. Basal cells
    - desmosomes for cell adhesion

Underneath BM:

  1. ***Submucosal (Seromucosal) gland
    - serous cells: Lactoferrin, Lysozyme
    - mucous cells: Mucoglycoprotein (Mucin)
    - with blood vessel supplying it (vasodilatation —> ↑ fluid in interstitial space —> squeeze submucosal gland —> ↑ nasal secretion)
17
Q

***Nasal secretion

A

Maintain hydration + Physicochemical barrier to protect underlying epithelium from pathogen / particles

Nasal mucosa semi-permeable —> Allow nasal route drug administration

Bilayered secretion film:

  1. Outer mucous layer (gel layer)
    - mainly by secretions from submucosal gland + goblet cell —> ***Mucin (aggregation of pathogens)
  2. Inner perciliary fluid layer (sol layer)
    - by ion transport through epithelium
    - ***Fluid —> for easier beating of cilia
    - thickness is crucial (too thick cilia cannot remove mucin that is too far; too thin cilia cannot beat viscous mucin)
18
Q

***Nasal secretions ion channels

A

Apical:

  • ENaC (Na into cell)
  • ***CFTR (Cl out of cell)
  • ***NHE (Na into cell, H out of cell) —> nasal secretion is acidic

—> HCl out, Na into cell

Basolateral:
- NKCC (Na, K, Cl into cell)
- Na/K-ATPase (Na out, K into cell)
- Na/HCO3 co-transporter (NBC) (Na, HCO3 out of cell)
(- K channel (K out of cell))

—> HCO3 out of cell

19
Q

***Nerve innervation and regulation of mucin secretion

A

Nasal mucosa richly innervated by

  1. Sensory (CN5)
    - Anterior wall: CNV1 (minor)
    - Posterior wall: CNV2 (majority)
    - activation of sensory pathway (irritant, allergen, chemosensory stimulus)
    —> Trigeminal ganglion —> cortex for interpretation
    OR
    —> perception of potential noxious stimuli
    —> protective reflexes
    —> neuropeptides (**Substance P, **CGRP)
    —> submucosal gland activation
    —> ↑ mucin secretion
    —> Nasal congestion
  2. Parasympathetic
    - CN7
    —> Superior salivatory nucleus
    —> **Greater petrosal nerve
    —> **
    Pterygopalatine ganglion
    —> Nasal cavity
    —> **ACh, **VIP (vasoactive intestinal polypeptide) as neurotransmitter
    —> Vasodilation, Sinusoidal engorgement, Glandular discharge
    —> Nasal congestion
  3. Sympathetic
    - **Superior cervical ganglion
    —> sympathetic plexus around **
    internal carotid artery
    —> **Deep petrosal nerve
    —> **
    Pterygopalatine ganglion
    —> Nasal cavity
    —> innervates mainly arterioles + arteriovenous anastomoses
    —> **NA, **neuropeptide Y as neurotransmitter
    —> Vasoconstriction + ↓ Secretion
    —> ↓ Nasal congestion
20
Q

Nerves at risk during submandibular salivary gland surgery

A
  1. Marginal Mandibular nerve of CN7
  2. Lingual nerve of CNV3 —> numbness of tongue
  3. CN12 —> only very rarely bruised —> ↓ tongue movement
21
Q

Epithelium summary

A

Respiratory mucosa:
- Ciliated Pseudostratified columnar epithelium with Goblet cells

Nasal squamous mucosa:
- Stratified squamous

Oral mucosa:
- Stratified squamous

Vocal cord:

  • Pseudostratified squamous epithelium (superior + inferiorly)
  • Non-keratinising squamous epithelium (contact surface of medial cord)