Pathophysiology and phonation mechanisms of vocal folds (VF)

Laryngology seminar
Pathophysiology and phonation mechanisms of vocal folds (VF)
2003-02-12 R3 Kuo ST.
1. Cover and Body theory by Hirano: viscoelastic materials, stiffness: 1:7:10
a. Cover: compliant: longitudinal, horizontal and vertical movement of VC
a. Epithelium: 6-8 layers NK stratified squamous epithelium (attached by
desmosone) lubricated by mucociliary blankets (posterior, superior
beating of cilia TB laryngeal lesions most in the posterior glottis)
b. Basement membrane zone (BMZ): Basal cells-hemidesmosone (type IV
collagen anchoring to LP + anchoring fibers (type VII collagen) +
proteins (some population density are genetically determined) to resist
shearing/ mechanical forces during vibration.
c. Reinke’s space (SLLP): elastin, ECM
b. Transition (Vocal ligament): after age 1-4 y/o: balance tension in adjacent layers,
set the geometric shape of oscillated tissues, major bearer of stress in more
intense and high-pitched phonation
MLLP: more elastin
DLLP: more collagen
c. Body: vocalis/TA (medial: slow muscle for phonation, lateral: fast muscle for
adduction): stability, tonicity, mass
3. ECM:
Fibroblasts: control turnover, similar population density in all layers
Myofibroblsts: only present for repair of injured tissues, e.g. SLLP in normal VF
Macrophages (Mφ): many just below SLLP and BMZ, attack foreign agents
Age and gender affect distribution
Fibrous protein:
Elastin (SLLP, MLLP) (elasticity and flexibility):
3 froms: enaunin, oxytalan (less elastic, SLLP), elastin fibers (stain+, MLLP).
Collagen: type I, II and III: identified at LP (e.g. DLLP- fibroblast)
type IV and VII: BMZ- epithelium
Infant < Adult = Geriatric, F < M
Aging: decreased activities of fibroblasts
a. Collagen fibers increase and become irregular or twisted, cross-linking and reticular
fibers decreased. (esp. man)
b. Elastin concentration: Age> gender effect, cross-linking (+).
b. Interstitial proteins: Viscosity (e.g. hyaluronic acid)
1. Proteoglycan:
a. Versican: Mφ and fibroblasts in LP, bind/organize water
b. Decorin: LP specificity (ECM, SLLP): ? reduce fibrosis,
c. Fibromodulin: LP specificity (ECM, MLLP & DLLP): binding to collagen
fibers thinner,
d. Heparan sulfate proteoglycan (HSPG): Mφ and fibroblasts in LP, BMZ. Binds to
fibronectin, collagen IV, laminin. ? tissue morphogenesis
e. Hyaluronic acid: Mφ and fibroblasts in ECM of LP (e.g. MLLP): Male > Female,
control viscosity ( control Pth, increased by dehydration), layer thickness and
internal fluid content, size and density of collagen
2. Glycoprotein etc.
a. Fibronectin
1. extensive in ECM, cell adhesion, migration, differentiation, maintenance of
cell structure and blood clotting. ? wound healing
2. most abundant in ECM of regenerating, healing, and embryonic tissue.
b. Matrix metalloproteinase (MMP)
1. degrade ~ all matrix components
2. > 20 MMPs: MMP-1: collagenase 1, MMP-13: collagenase 3, MMP-2:
gelatinase A, MMP-9: gelatinase B, MMP-12: elastase
C. Tissue inhibitors of metalloproteinase (TIMP) -1, -2, -3, -4.
Inhibit MMPs, decrease with aging
D. Lysyl oxidase:
Enzymatic and non-enzymatic cross-linking of collagen and elastin
c. carbohydrates and lipids: less is known
Actions of laryngeal muscles: (Ballenger Table 25-2) (e.g. VT, TA etc.)
Vibration theory:
a. Aerodynamic-myoelastic (Van den Berg, 1959): Bernoulli principle. Three main
parameters: mass, viscoelasticity, subglottal pressure (glottal cycle)
b. Mucoviscoelastic-aerodynamic theory (Cover and body) (Hirano, 1966) 
c. Single mass-spring oscillation driven by lung airflow, (Flanagan, 1968)
d. Two-mass model (Ishizaka, et al. 1972) (independent movement of upper and
lower lips+ body  Three mass): closed and open phase (opening
phase-convergent, closing-divergent phase) 
e. Flow induced self-sustained oscillation by propagating mucosa wave based by
cover-and-body/three mass model (Cover: Two mass coupled by spring, Body: for
medial-lateral motion three mass model, further coupled to thyroid cartilage)
(Titze IR, 1988, 1995): similar to observed VF motion, measured vertical phase
difference, mucosal wave velocity and experimentally intraglottal pressure.
f. Chaos theory (Titze IR, et al. 1992): Coupling of cover and body by nonlinear
spring and damping element (contractions of CT and TA alter their stiffness), and
the mix of elastin and collagen, and asymmetry between left and right VC.
Modes of vibration:
a. control by preglottal geometry (viscoelasticity, adduction etc.), airflow and
subglottal pressure etc.
b. dominated by the first 2-3 modes (Berry, 1994): simultaneous multiple 1-0, 1-1
modes in normal VC movement (finite element model, some modes with higher
shearing force and viscosity VF injury), a greater number of higher modes in
pathological voices (e.g. asymmetry of left and right VC)
a. Viscoelastisity: dependent interaction of mass, stiffness/tension and viscosity
b. F0: depends on VF vibration (not by vocal tract), decreases as mass increases and
tension decreases, interaction of intrinsic/ extrinsic laryngeal muscles.
c. F0 α 1/2L* √(T /σ) (L: length, σ: tissue density, T: stress/tension)
d. True VF: nonlinear tissues, the mix of elastin/spring performance and
collagen/resistance (e.g. break point). Collagen performance lead to Log
stress-strain curve (stress >> strain effect) large dynamic pitch range.
e. Most of the daily voice: dominated by elastin fiber performance.
f. Voice: glottal periodic sound wave: composed of F0 and harmonics (analysis by
Fourier transformation)
PL: threshold pressure of phonation
Small amplitude oscillation: Pth ≧ (2K/T) (BC) (01ξ2/01ξ + 02ξ)
K: constant
T: Vertical thickness (e.g. TA contraction)
B: viscosity damping coefficient of VF (e.g. ECM, hydration, hemorrhage)
C: propagating velocity of mucosa wave (increase with stiff cover, greater
airflow/subglottal pressure and increased F0)
ξ: Pre-phonatory glottal half-width: 01ξ: inferior, 02ξ: superior
a. In convergent VF, 01ξ >02ξ, and Pth > that of rectangular glottis (01ξ
b. In divergent VF, 01ξ < 02ξ, Pth < rectangular glottis. But more complicated in true VF
due to nonlinearities, e.g. Flow separation increases with glottal divergence more
asymmetrical driving force higher Pth than theory is needed in divergent VF
e. Offset /sustained Pth < onset Pth (e.g. when increased thickness and viscosity)
e. A nearly rectangular prephonatory glottal geometry is easier for phonation, e.g. in
phonosurgery, as Pth (true data results) in convergent and divergent VF is higher.
Pitch depends F0 : Man:100 Hz, F: 200 Hz, Newborn: 450-500 Hz
a. Increased subglottal phonation pressure increased F0
b. Tension: major muscle: CT contraction (decrease the Pth effect).
c. TA contraction: body > cover effect in low tone increased F0, cover > body effect
in high tone decreased F0 (imbalance between body - cover tension)
Intensity (loudness): Sum of F0 and harmonics
Supra-, sub- and glottal level control
a. Subglottal pressure: 2 X  increase 6 dB (e.g. low Hz), airflow affects high Hz
b. F0: 2X increase 2 dB.
c. Glottal shape and vibratory pattern: Narrower glottis louder due to decreased
roll-over rate of harmonics: increased closing phase/decreased conduction velocity
of mucosal wave etc.
d. Supraglottal resonance of vocal tract (shape/length): filtering effect of acoustic
output to affect distribution and shaping of format. Ring (2500-3000 Hz) and closer
format (F1) to F0  louder. Training of singers.
f. Acoustic output depends on intensity, F0, phonation modes, efficiency and
endurance, register etc.
a. 3 types: Pulsed voice (vocal fry)- modal (chest)- loft (falsetto): low- middle -high
F0 ranges, prolonged- middle- short/no closed phase
b. Periodicity register transition: Increased F0  pulsed/vocal fry to non-pulsed voice,
(decreased cognition of pulse).
c. Timbre register transition: (Roll-over-rate Vs chest and falsetto voice), e.g.
increased roll-over rate of harmonics Chest to falsetto voice (decreased cognition
of chest voice).
d. High F0: chest sound: CT directly proportional to TA contraction,
Low F0: falsetto: decrease TA contraction relative to CT contraction.
dDx of vocal nodules, polyps, Reinke’s edema, cysts: lesions in BMZ, SLLP with ?
altered action of fibroblast
1. Histology: Considerable overlap between vocal nodules, polyps, Reinke’s edema.
a. Nodules: disorganized & thickened BMZ ( chronic repetitive tissue injury),
dense deposition of type IV collagen/ fibronectin throughout LP
b. Polyps: Unaltered BMZ width, clustered fibronectin around neovascularity, less
type-IV collagen in BMZ of surface epithelium than in BMZ of neovascularity
c. Reinke’s edema: (similar in polypoid corditis): neovascularity, increased fibrin and
decreased fibronectin deposition
d. Cysts (same between mucosa retention and epithelium inclusion):decreased
mucosal wave in videostroboscopy (Vs the other 3 lesions), normal or slightly
thickened BMZ, normal fibronectin distribution in LP
2. Polyps Vs Reinke’s edema:
a. Different genotypes:
Polyps  high level of gene expression of MMPs and proteoglycans etc. (Increase
in fibronectin and decrease in fibromodulin)
Reinke’s edema: low level of gene expression
b. Different phenotypes:
Different ECM regulation pattern between polyps and Reinke’s edema
 better diagnostic and management strategies
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