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Файл:Ординатура / Хирургия / Библиотека им академика М.И. Перельмана / Книга_4507_Библиотеки_им_академика_М_И_Перельмана.pdf
3 Physiology ofthePeripheral andCentral Hearing System
Fig. 3.3 Anatomical location of the Eustachian tube
33
the Eustachian tube opens, allowing air to enter the middle ear and equalize the
middle ear pressure. Conversely, the external ear pressure increases and the
Eustachian tube opens to equalize the pressure. The function of the Eustachian tube
in the transmission of sound is important. Both positive and negative pressures in
the middle ear equally reduce the sensitivity of the middle ear to incoming stimuli.
In particular, it negatively affects low-frequency sound transmission by increasing
or decreasing TM tension. In addition to providing ventilation, the Eustachian tube
shields the middle ear from nasopharyngeal secretions and discharges these secretions into the nasopharynx via mucociliary activation in the tube [1, 19].
3.4.5 Impedance Matching
The sound stimulus transmitted from the outer ear moves the TM, allowing the
stimulus to pass into the middle ear. In middle ear sound transmission, the middle
ear provides impedance matching to the cochlea. Energy loss occurs during the
transfer of energy between different environments. As energy is transferred from the
air-lled middle ear to the uid-lled cochlea, the middle ear reduces the energy
loss of the sound stimulus. As a sound wave travels from one medium to another,
some of the sound energy is reected (e.g., on the surface of water) and some is
transmitted to the impulsive medium. The acoustic impedance of air is 41.5 ohms,
and the impedance of the uid in the inner ear is 143.000 ohms. The amount of
sound energy transferred to the second medium is explained by the difference
34
M. Baran et al.
between the acoustic impedances of the two media. The acoustic impedance of the
middle ear includes the tympanic membrane, ossicular chain, stapes base, and
Eustachian tube. Two approaches are used within the middle ear to match the TM
impedance to the acoustic impedance of the cochlea [1, 9, 11, 12, 19].
– The vibrating region of the TM is larger than the region of the oval window
where the base of the stapes sits within the cochlea. The forces concentrated on
the TM cause an increase in pressure on the oval window in a smaller region.
This is usually a signicant factor in the impedance transformation at the TM and
oval window. In humans, the vibrating TM area is 60mm2 and the oval window
area is 3.2mm2. The pressure at the stapes base increases 60/3.2=18.75 times.
– The second approach is the lever action seen in the middle ear ossicles. The fact
that the incus arm is shorter than the malleus reduces the velocity at the stapes
while increasing the force due to leverage. This is a relatively small but not neg-
ligible factor in impedance matching. Geometrically, the malleus is 2.1 times
longer than the incus, and, in lever action, it increases the force by 2.1 times and
decreases the velocity by 2.1 times. This lever action increases the impedance
(pressure/speed ratio) by 2.1×2.1=4.4 times.
Finally, when these transfer or impedance matching ratios are calculated with the
above two factors in mind, the sound transfer function of the middle ear is approximately 38–40dB.
3.5 The Inner Ear
The inner ear, which contains receptors for hearing and balance, is located in the
petrous part of the temporal bone. The entire inner ear is called the labyrinth because
it consists of complex pathways and channels that connect these pathways. It is connected to the middle ear by the round and oval windows and to intracranial structures by the cochlear and vestibular aqueducts [12].
The organ of Corti is an organ that converts the mobility of the stapes into neural
signals for hearing and also responds to neural signals. The organ of Corti is an
afferent structure in the spatial plane. It has both a receptor and an effector function
in the processing of sound or sound waves that reach the ear. It is the primary structure where frequency-specic coding takes place. The specicity of the reex elements (inner and outer hair cells and their associated structures) provides frequency
selectivity. The organ of Corti (Fig.3.4a), where energy conversion takes place, is
specialized with different structures to detect changes [20, 21]. Inner hair cells
(IHC); afferent transducer or primary receptor, outer hair cells (OHC); a secondary
receptor that provides efferent transducer, effector, and frequency specicity. They
are support cells that cauterize the isolated outer hair cell membrane structure and
membrane-penetrating effector motor proteins that provide membrane mobility.
Effector structures cause basilar membrane (BM) motility. Excitation or inhibition
of two different cells of the organ increases the quality of our communication with
3 Physiology ofthePeripheral andCentral Hearing System
35
a
b
c d
Fig. 3.4 (a) The organ of Corti: hematoxylin and eosin (H&E)×200. IHC inner hair cell, OHC
outer hair cell, TM tectorial membrane, OoCT Corti tunnel, BM basilar membrane. (b) Magnication
of the modiolus: 15×1.5×11.2. (c) Magnication of cochlear scales: 15×1.5×11.6. (d) Border
lines of the scala media
the outside world [20]. Detailed information on the morphology of the cochlea has
lagged far behind that of other sensorineural systems because of the different morphological characteristics of the cochlear anatomy, cells and tissues, and the technical difculties of evaluation. The cochlea is a delicate network of membranous
tissues suspended in uid and located in the hardest bone tissue in the body.
Evaluation of inner ear tissues requires specialized methods of examination. The
two most useful are: dissection of the entire base, surface preparation of the organ
of Corti and the BM complex, and the more standard radial incision of the entire
spiral organ. Alfonse Corti made the rst surface preparations of this organ and
described it with radial sections. His drawings provide accurate details of most of
the important structures of the membranous labyrinth, although they may show
postmortem artifacts. Corti’s work inspired other investigators to conduct further
studies. When the drawings of Reissner, Deiter, Boettcher, Cladius, Hensen, and,
especially Retzius are compared with cochlear micrographs taken with current technology, it is clear that Alfonse Corti’s observations are largely correct [12, 22, 23].
36
M. Baran et al.
3.5.1 General Organization oftheCochlea
The Greek word cochlos means snail [24]. The temporal bone houses the cochlea,
which is covered by a thin layer of bone called the otic capsule [22]. In a few species, such as rats and guinea pigs, the cochlea protrudes into the middle ear cavity,
but, in other mammals, including humans, a small piece of the cochlea is visible at
the entrance to the middle ear. The human cochlea is about 35-mm-long and consists of 2.5 spirals around a bone called the modiolus. This number varies from
species to species (Fig.3.4b). The modiolus forms the central axis of the cochlea
and contains nerve bers, blood vessels, and connective tissue [12, 23]. The otic
capsule becomes thinner toward the middle ear cavity and is connected to the modiolus by canals [12]. It has two openings: an oval window and a round window.
Unlike the cochlea, the inside of the cochlea does not consist of a single canal.
When sectioned, the upper part of the cochlea is called the scala vestibuli (SV), the
middle part is called the scala media, and the lower part is called the scala tympani
(ST) (Fig.3.4c). The SV extends from the oval window to the apex of the cochlea.
It is connected to the ST by a narrow canal called the helicotrema, which extends
basally and terminates at the round window. These two scales contain perilymph.
Perilymph is similar in composition to extracellular uid and contains high concentrations of Na+ and low concentrations of K+ ions. The scala media, on the other
hand, contains endolymph, which is similar to intracellular uid, with low concentrations of Na+ and high concentrations of K+ ions. This channel closes at the
cochlear apex but connects to the saccule via the ductus reuniens and opens into the
subdural space with the endolymphatic sac, which terminates at a blind end in the
vestibular system. This structure, which is a diverticulum of the saccule, is a specialized sound receptor. At the base of the cochlea, the ST connects to the subarachnoid
space via the cochlear aqueduct and opens into cerebrospinal uid (CSF) [11, 12,
22, 23]. The anatomical boundaries of scales are not necessary for uid boundaries
(perilymph, endolymph). The uid boundaries of endolymph include tight junctions
between adjacent epithelial cells that prevent their free diffusion. The boundaries of
the uid compartment containing endolymph are shown in Fig.3.4d. Endolymph is
separated from perilymph by tight junctions between Reissner’s membrane cells in
the SV.A second boundary is located in the reticular lamina and is formed by tight
junctions on the apical surface of sensory and supporting cells. In this way, perilymph spreads across the BM in the ST.There is always an electrical potential difference of about +80 mV between endolymph and perilymph. This potential is
called endocochlear potential (EP). Thus, the inside of the scala media is positive
and the outside is negative. This potential decreases as one moves from the basal to
the apical part of the cochlea. In guinea pigs, EP typically ranges from 93mV in the
rst round of the cochlea (basal round), 88mV in the second round, 82mV in the
third round, and 74mV in the fourth round (apical round) [11, 12, 22, 25]. The
dense network of junctions on the endolymphatic surface of the cells in the SM
allows the continuity of this electrical potential. These connections prevent the paracellular exchange of some ions and macromolecules between the endolymphatic
and perilymphatic spaces. The concentrations of Na+, K+, Ca++, Cl−, and HC3− are
3 Physiology ofthePeripheral andCentral Hearing System
37
149, 3.7, 0.7, 127, and 19 and 140, 8, 0.6, 125, and 18mmol/L in perilymph of the
scala vestibuli and scala tympani, respectively. These are 146, 3.2, 1.2, 131, and
19mmol/L in CSF and 1, 158, 0.02, 136, and 21mmol/L in cochlear endolymph,
respectively. Endolymph of the saccule and endolymphatic sac contains Na+, K+,
Ca++, and Cl− at 3, 150, 0.09, and 119 and 108, 14, 0.47, 98mmol/L, respectively.
The osmolality (milliosmoles) is 293, 294, and 304 for perilymph of the scala vestibuli, perilymph of the scala tympani, and endolymph of the cochlea, respectively.
The pH is 7.28, 7.26, 7.28, and 7.37 for perilymph of the scala vestibuli, perilymph
of the scala tympani, perilymph of cerebrospinal uid, and endolymph of the
cochlea, respectively. The electrical potentials (millivolt) are 0 for perilymph of the
scala vestibuli and cerebrospinal uid, 5 for perilymph of the scala tympani and
endolymph of the saccule, 85 for endolymph of the cochlea, and 13 for endolymph
of the endolymphatic sac [26]. The volumes of human endolymph and perilymph of
the cochlea and endolymph of the endolymphatic sac are 7.7, 75.9, and 3.926μl,
respectively [26].
The apical part of hair cells is located in endolymph and the basolateral part in
perilymph. It is an electrical potential that is present even when the cochlea is not
stimulated. There are two types of resting potentials in the cochlea, one of which is
the intracellular potential. This potential, as measured by hair cells, is −60mV.In
other words, the organ of Corti has a negative value of 60mV compared to the surrounding uid. The second potential is EP, and the endolymph in the scala media
has a different voltage of +80mV compared to the perilymph. Thus, there is a
potential difference of approximately 140mV across the hair cell membrane. It has
been suggested that the generation of both potentials depends on oxidative metabolism. Although the function of the resting potential is not fully understood, it is most
likely an energy sink for the cochlear action potential. Researchers have suggested
that EPs are present even in the presence of total hearing loss, and, therefore, these
electrical potentials cannot be used to interpret hearing test data [11, 12, 22, 25].
Within the membranous tissue of the scala media is the most specialized tissue
of the cochlea and the location of neurosensory cells. This membrane is also called
the cochlear duct. The cochlear duct is triangular in shape and can be divided into
three regions [11, 12].
– The lateral wall, which contains the spiral ligament, the stria vascularis, the spi-
ral prominence, and the outer sulcus.
– Reissner’s membrane (RM), which borders the scala media and SV.
– The basilar membrane, which forms the border between the SM and ST, and the
spiral lamina of the osseus.
3.5.1.1 Lateral Wall
The lateral wall is dened as the lateral view of the scala media, including the
medial stria vascularis and the lateral spiral ligament.
Stria Vascularis: The endolymphatic border of the cochlear duct is formed by the
stria vascularis. It extends from where the RM joins the spiral prominence (Fig.3.5).
The stria vascularis is the vascularized epithelial tissue of the cochlear duct and
38
Fig. 3.5 General
appearance of the stria
vascularis: hematoxylin
and eosin (H&E)×200. Sv
stria vascularis, Sm scala
media, Sp spiral
prominence, Sl spiral
ligament
M. Baran et al.
lacks a basement membrane. K+ is secreted into the cochlear endolymph through
KCNQ1K+ channels. Autosomal recessive mutation of this channel results in congenital bilateral sensorineural hearing loss, known as Jervell and Lange-Nielsen
syndrome [27]. Thus, it specically contributes to EP.There is abundant Na+-K+ATPase within the striae. This part of the lateral wall is considered critical for
cochlear function. The length of the stria vascularis of chinchilla is approximately
25.22mm. Its width and thickness decrease slowly toward the base of the cochlea
[11, 12, 18, 25].
3.5.1.2 Reissner’s Membrane
Reissner’s membrane separates the SV from the SM, which has a three-layered
structure. The three-layered structure consists of two cell layers. These layers are
separated by a basal lamina. The RM is attached to the modiolar edge of the spiral
limbus on the medial side and to the spiral ligament at the apex of the stria vascularis on the lateral side. The cells facing the endolymph have a cuboidal shape and
contain numerous apical microvilli. Their lateral edges are closed by tight junctions.
The trilaminar basement membrane is located between two cell layers. The cells
facing perilymph are at cells derived from mesenchymal broblasts. They are
loosely interconnected. The cells within the membrane and the association complexes between them act as barriers to ionic transitions. They control the ionic
3 Physiology ofthePeripheral andCentral Hearing System
39
balance of uids with selective ion pumps. Tension-activated cation channels, Cl−
and K+ channels, have been identied in the apical membrane of epithelial cells
located in the RM.The RM allows free passage of water, but tight junctions limit
paracellular passage into the endolymphatic space. In pathological conditions such
as Meniere’s disease, the RM extends toward the SV.This temporal bone pathology
is called hydrops [12, 22, 23, 25].
3.5.1.3 The Basilar Membrane
The basilar membrane extends from the lateral edge of the bony semicircular canal
to the basilar apex of the semicircular canal [12]. The BM, on which the organ of
Corti is located, is a complex layer of connective tissue bers. It contains cellular
and extracellular substances. The BM is a mechanical analyzer. It detects the frequency of sound. The BM is a brous membrane. It separates the scala media from
the tympanic scale. This membrane contains approximately 20,000–30,000 basilar
bers. These bers are distributed from the modiolus, the bony center of the cochlea,
toward the outer wall. Although the BM was not originally thought to contain collagen, it has recently been shown to contain collagen types II and IX.Fibronectin
xes and binds connective tissue proteins to its structure [22, 24]. The BM is mainly
composed of connective tissue and is important for the tonotopy of the cochlea [11,
12, 22]. Its average length is 18.8mm in guinea pigs, and its width increases toward
the cochlear apex, from 150μm to 250μm in guinea pigs [28, 29]. In humans, its
average length is 31.55mm and its width ranges from 150μm to 450μm. In chinchilla, they are 18.3mm and 230μm to 370μm, respectively. The side of the BM
facing the ST is covered with spindle-shaped tympanic border cells that run in the
direction of their cochlear spiral axes. Desmosomes connect these cells, but they do
not separate during auditory vibration. The large intercellular space brings perilymph into contact with the BM.The passage of perilymph into the BM can be
demonstrated by the absence of tight junctions in this region and the separation of
basement membranes in ultrastructural studies. The cells of the organ of Corti
(Claudius, Boettcher cells) are separated from the BM by the basement membrane.
The stiffness and mass of the cochlear portion contribute to the BM structure. In
normal adult animals, its mass increases while its stiffness decreases toward the
cochlear apex. While there are narrow and thick bers at the base of the cochlea,
there are wide and thin bers at the apex. These changes along the cochlear segments cause the stiff, short bers near the oval window of the cochlea to vibrate best
at high frequencies and the long, exible bers near the apex of the cochlea to
vibrate best at low frequencies [24, 25, 30, 31]. The BM is attached medially to the
spiral lamina and laterally to the basilar crest in the spiral ligament. Its width is
divided into two parts: the pars arcuata medially and the pars pectinata laterally. The
pars arcuata is the section that covers the area under the outer pillar cells of the
tympanic part of the spiral limbus. Basically, the laments (20μm in diameter) are
arranged transversely and are not grouped into bundles. Because the pars arcuata is
partially covered by the bony spiral lamina, its ability to move with the soundinduced vibrations of the cochlear uids is limited. The pars pectinata, consisting of
bundles of radially oriented brils, extends from the bottom of the outer hair cells to
40
M. Baran et al.
the basilar crest of the spiral ligament. It continues with the spiral ligament and the
bers in the limbus of the spiral ligament [22, 32, 33]. Outer hair cells are located in
this part, and their ability to move with sound-induced vibrations of the pectinate
zone is not limited. Movement occurs under the inuence of active cochlear mechanics and the exibility and stiffness of the BM.The pars pectinata is thicker than the
pars arcuata, and this thickness decreases as one moves toward the cochlear apex.
The spiral limbus is the functional unit of the BM and the spiral ligament. It is
thought to control the tension of the BM through the movement of spiral ligament
type III brocytes, which contain cytoskeletal proteins specialized for contraction
[22, 25].
3.5.2 Organ ofCorti
The organ of Corti is an anatomical structure located in the SM of the cochlea,
which is located in the petrous part of the temporal bone. It lies on the BM of the
inner ear and is a receptor organ composed of hair cells and supporting cells [9, 11,
24]. Its primary function is to provide independence to the structures that allow
movement of the sensory epithelium in response to mechanical stimuli. While the
diameter of the cochlea decreases from the base to the apex, most structures in the
cochlear duct increase in size longitudinally. The cells of the organ of Corti are
larger at the apex than at the base, and stereocilia are longer and less rigid.
Enlargement of the BM and an increase in density of the tectorial membrane mass
are observed [11, 12, 22, 24, 25]. The organ of Corti is the last sensorineural organ
of hearing. This organ contains hair cells and supporting cells derived from the
membranous labyrinth, a specialized BM, the tectorial membrane, and nerve endings. The apical surfaces of all cells are connected to junctional complexes that form
the reticular lamina, and these junctions form a barrier between the perilymph, in
which the basolateral side of the cells reside, and the endolymph, on the SM side.
The reticular lamina is organized as a mosaic epithelium, with each hair cell surrounded by four supporting cells [22, 25, 33–36]. The organ of Corti has approximately 3500 IHCs in a single row and~12,000 outer hair cells in 3–4 rows. IHCs
are the actual sensory cells that transmit impulses through the auditory nerve. OHCs
are a type of cell that the cochlea uses to modify its performance, increasing selectivity (qualitative) and sensitivity (quantitative). The name hair cell was given
because there are bundles of stereocilia that extend in the apical part of each cell.
These stereocilia also appear as specialized microvilli. OHCs are supported at their
bases by phalangeal cells (Deiters). The space between IHCs and OHCs is lled
with pillar cells. The organ of Corti is covered by a gelatinous membrane. The stereocilia of the OHCs are tightly attached to the underside of the tectorial membrane.
The stereocilia of the IHCs do not touch the tectorial membrane. There are approximately 16,000 hair cells in each cochlea, and they are innervated by approximately
30,000 afferent nerve bers [12, 22, 23, 25].
Hearing begins with the ear receiving sound energy. Although the intensity is
low, increases and decreases in air pressure cause the TM to move either inward or
3 Physiology ofthePeripheral andCentral Hearing System
41
outward. In other words, the TM acts as a resonator that mimics sound waves.
Movement of the TM causes displacement of the malleus, which is attached to the
membrane. The movement of the ossicles behind the malleus depends on the frequency and intensity of the sound. In simple terms, the movement of the incus and
malleus can be compared to a lever with two connecting points. As the incus pushes
the stapes into the oval window, the stapes causes the cochlear uid to move back
and forth like a piston. The acoustic energy transmitted to the oval window causes
compression and rarefaction motion at the base of the stapes. This activity is transmitted directly to the perilymph in the SV, which eventually joins the ST via the
helicotrema. The sound energy is then discharged through the round window that is
the end point of the ST.The organ of Corti, located at the BM, is exposed to the
compression and rarefaction waves of the perilymph through Reissner’s membrane
and the BM.These are compression and rarefaction waves between the tectorial
membrane and the hair cells that provide the mechanotransduction of sound energy
into electrical energy and an auditory nerve impulse [11, 22, 25, 31].
3.5.2.1 Hair Cells
A hair cell is ~30-μm-long, while stereocilia are ~5-μm-wide. Hair cells are structures that open and close simultaneously with sound vibrations and convert mechanical energy into electrical energy with ion channels [12]. Hair bundles on the apical
surface of the cell are the receptor apparatus of the cell. Their length can vary from
1 to 100μm. These are 200–300 cylindrical structures organized in a hexagonal
order and are called stereocilia. The length of stereocilia varies from species to species. They have a frequency-specic morphology. At high frequencies, the length of
stereocilia shortens (long in the apical, short in the basal). In the human cochlea,
4-mm-long stereocilia respond to sounds at a frequency of 20kHz, while 7-mmlong stereocilia respond to sounds at a frequency of 20Hz. This relationship between
anatomical position and frequency is known as tonotopic mapping [11, 25, 31]. The
elastic structures between stereocilia are called “tip links.” These structures form a
lamentous connection between two stereocilia. Each terminal link is thought to be
a thin ber consisting of molecules arranged in two rows. It extends obliquely from
the distal end of one stereocilium to the adjacent stereocilium. Each stereocilium
has a skeleton of actin laments. The actin laments are cross-linked by brin.
Stereocilia are not true cilia but are long, tough microvilli that extend from the
cuticular layer of hair cells. The central two microtubule organization with nine
pairs of microtubules does not correspond to the true cilia structure. Stereocilia are
specialized microvilli. Stereocilia, the extensions of hair cells towards the endolymph, become thinner in their basal parts. This feature allows them to move away
from the basal junctions. Mature cochlear hair cells, unlike vestibular hair cells, do
not contain a kinocilium. However, the kinocilium remains in the cuticular layer of
the basal body. Applying a mechanical stimulus to hair cells causes an electrical
response in the cell. This is a receptor potential that occurs when ion channels sensitive to mechanical stimulation open. Ion channels involved in mechanoelectrical
transduction are opened and closed by elastic structures in the stereocilia. These
42
M. Baran et al.
elastic structures are referred to as gating springs. The channels in stereocilia are
known to be membrane-crossing proteins with cation-selective pores [12, 23, 31].
Moving stereocilia in the positive (+) direction, which is the direction of excitation,
increases the tension in the gate spring. Increasing the voltage causes the channel to
open and cations to ow in (Fig.3.6). The mechanoelectrical transformation of the
channels in hair cells is nonselective, and the conductance of these channels is ~100
pS [9, 22]. The most abundant cation in endolymph uid that hair cells come into
contact with is K+, which is responsible for the transduction current. The fact that
these channels are non-selective causes aminoglycoside antibiotics such as streptomycin and gentamicin to block the channels. High doses cause permanent damage to hair
cells. In an unstimulated cell, 15% of the ion channels are open. A positive stimulus
causes the stereocilia to move, allowing other closed channels to open (depolarization). A negative (−) stimulus—direction of inhibition—pushes the stereocilia to their
short side and causes the channels to close (hyperpolarization). Stimulation in the
opposite direction causes no change, and the cell remains at its resting potential. In
other words, the hair cell responds only to stimuli parallel to the stereocilia axis.
Oblique stimuli are stimulated only in proportion to their vectorial projections on this
axis. When the stimulus to the hair cell is large, the resulting receptor potential is also
large. The relationship between stereocilia deection and electrical response is sigmoidal. During normal stimulation, a hair bundle moves at an angle of ±1°. This
results in a distance of approximately 3nm. The major proteins identied in stereocilia are actin, myosin VI, myosin VIIa, myosin XV, and myosin V.Myosin VIIa,
recently discovered stereocilia defects are reported to cause deafness [9, 11, 22, 24].
Fig. 3.6 Neurotransmission of inner hair cells