Objective 3: There are several mechanisms that underlie peripheral hearing
disorders
Our understanding of the cellular/molecular mechanisms that cause anatomical
changes in the organ of Corti after intense sound exposure is incomplete.
Two processes, mechanical and metabolic, have been suggested as the
principal mechanisms responsible for hair cell damage associated with acoustic
overstimulation. In general, mechanically induced injuries have a rapid
onset whereas those produced by "metabolic exhaustion" have
a more gradual onset. Mechanical factors related to excessive movements
of the cochlear partition would include disruption of the internal
structure of the cell. They might result in tears in the basilar membrane
or Reissner's membrane, which would result in the cytotoxic mixture
of endolymph and perilymph. Excess motion might also separate the organ
of Corti from the basilar membrane or from the tectorial membrane. The
synaptic junction between the hair cell and eighth nerve fiber could
be widened or the OHC stereocilia may lose their connections with the tectorial
membrane.
The long-term changes in hearing consequent to acoustic overstimulation
are believed to involve the hair cell metabolic machinery. Structural changes
in the endoplasmic reticular system and mitochondria suggest deficits
in fuel utilization, protein synthesis, and energy production. There may
be disruption in cellular enzyme systems critical to energy metabolism,
protein synthesis and ion transport. It is also suggested that acoustic
injury may involve regional ischemia, although there is little direct
support for this hypothesis. A third possibility has been suggested
that relates both to mechanical and metabolic hypotheses, namely
that damage results from changes in the cochlear vascular system.
Inner vs. Outer Hair Cells
Outer hair cells (OHCs) are more susceptible than inner hair cells
(IHCs) to acoustic over-stimulation. One reason may be that OHCs, because
of their greater distance from the fulcrum of the basilar membrane,
undergo greater velocity of motion and hence are at greater risk of
mechanical damage. Second, the direct mechanical linkage of OHC stereocilia
with the tectorial membrane may enhance this cell's susceptibility. Thirdly,
the difference may be metabolic, reflecting the differences in internal
organelle structure of the IHCs and OHCs. It is noted that OHCs are
also more susceptible to ototoxins. Also, the first row of OHCs seems
to be at greatest risk.
Damage to the Stereocilia
Recall that stereocilia act as rigid rods and that this rigidity is
imparted on them by compact bundles of microfilaments composed of actin strands
cross-bridged with another protein, possibly fibrin. The application of
scanning electron microscopy has revealed another dimension to
acoustic trauma to the organ of Corti: the disarray, collapse, fusing,
elongation, breaking, and/or elimination of sensory hairs. These observations
are accompanied by those showing that the crystalline fine-structure
of the stereocilia are altered by intense sound, a condition that could
reduce the rigidity of these hairs several-thousand-fold. Floppy stereocilia
occur when the crystalline lattice along the length of the sensory
hair is damaged. The disarray occurs after damage to the base of the hair
or its rootlet. The consequences of damage to these cytoskeletal
elements would be reduction in efficiency of coupling vibrational energy
to the hair and subsequent impairment of hair cell function. It
would appear that some forms of stereociliary damage are permanent.
Remembering that the tips of the hairs may be location of the ionic
current source of the receptor potential, damage to this membrane could
have profound effects on the transduction process itself. Fusion and
elongation of cilia are not specific to sound exposure and similar observations
have been made following ototoxic treatment with antibiotics.
Injury to the Auditory Nerve
Dendritic nerve endings beneath damaged IHCs and OHCs, including their
mitochondria, appear swollen after high-intensity noise exposure. Under
these sound conditions there may be signs of degeneration of spiral
ganglion neurons as well. The question of whether there can be nerve
damage or loss without hair cell destruction has not been answered.
The mechanisms of nerve damage may include degeneration secondary to
hair cell loss, direct mechanical injury, and/or metabolic dysfunction.
Changes in the central auditory system as a consequence of cochlear
damage
Injury to the receptor cells and auditory nerve can result in degenerative
changes in the cochlear nuclei of the brainstem and transneuronal atrophy in
the superior olivary complex and inferior colliculus. The available
evidence also supports the conclusion that the developing ear and brain is
more susceptible to acoustic injury than those of the adult. This has
been observed in a wide variety of mammalian species and thus there
is good reason to believe that it would hold for humans as well.
Temporal bone fractures
Fractures may occur along the longitudinal axis of the temporal bone
or transversely to this long axis. Transverse fractures are usually
more serious because they extend into the labyrinth resulting in a
total loss of hearing and destruction of the vestibular function.
Both kinds of fractures may injure the facial nerve resulting in a
facial nerve paralysis.
Cochlear concussion
A cochlear concussion results from a blow to the head not severe enough
to cause a fracture. It may however, produce a mild-to-total hearing
loss. This is because of tears of the membranous labyrinth which may
involve the vestibular structures as well as the cochlea. In such cases,
an individual may also experience vertigo.
Presbycusis
The term "presbycusis" has been traditionally applied to the hearing
loss that normally accompanies aging. Although it commonly refers
to hearing loss resulting from degenerative changes in the cochlea
alone, it is now clear that the aging process affects the whole auditory
system and that hearing loss of old age probably involves changes in
the middle ear, inner ear and central auditory pathways. Although there
is no clear relationship between age-related changes in the middle
ear and the audiographic findings, there are documented cases of ossicular
fixation and arthritic changes in ossicular joints with fibrous and calcific
changes. The correlation between the types and patterns of cochlear lesions
and the patterns of hearing loss has long been recognized. While there may
be wide variations in these patterns, in general, the common finding
is a high frequency sensorineural hearing loss associated with degeneration
of the organ of Corti in the base of the cochlea. Hearing loss may
progress over time to lower frequencies. Figure VIII-1 shows audiograms
taken at decade intervals. Note here the gradual and progressive loss
of sensitivity at high frequencies. Presbycustic individuals
may also have central nervous system involvement in their hearing disorder.
Within the cochlear nuclei, for example, the injury may range from little
or no alteration in cellular structure to complete destruction of cells.
Whether this occurs independently of a cochlear lesion is currently
not known.
Ototoxicity
It has long been known that certain drugs and chemicals can have strong
effects on the auditory and vestibular receptors of the inner ear.
The clinical signs of ototoxicity are variable but include one or
more of the following symptoms: sensorineural hearing loss, tinnitus,
"dizziness" of one description or another, and depressed
vestibular function with or without nystagmus. Over the past 40 years,
there has been a steady accumulation of data, from both the clinic
and the laboratory, on the mechanisms of action of various ototoxins.
With current understanding of the normal cellular-molecular mechanisms of receptor
cell action, we are on the threshold of understanding the mechanisms
of many of the disorders that affect hair cells. A brief description
is given a few of some of the more common agents and their actions.
Aminoglycoside antibiotics
Most of the antibiotics recognized as having ototoxic properties belong
to the family of aminoglycosides. The primary ones that require respect
are streptomycin, dihydrostreptomycin, neomycin, kanamycin, gentamicin
and tobramycin. Figure VIII-2 shows the audiograms from the left and right ears
of an individual treated with kanamycin for severe renal failure. Below
the audiogram are plots of hair cell and spiral ganglion cell loss
in each of the ears taken after postmortem histological preparation
of the temporal bones. Note the correspondence between hair cell loss
in the basal half of the cochlea and the high frequency hearing loss
which is typical of aminoglycoside ototoxicity.
Clinical and experimental evidence collected from human and animal
studies over many years has given a picture of the pathophysiological
mechanisms which underlie the damage inflicted by these agents. First,
the toxic substances must reach the labyrinthine fluid either via the
blood stream or, when applied topically to the middle ear, by direct penetration
of the oval and/or round windows. Second, primary damage is to the
hair cell; auditory nerve fibers may degenerate secondary to sensory
cell degeneration. Both kanamycin and neomycin affect first the outer
hair cells of the cochlea base; over time the lesion progresses to the cochlear
apex. Inner hair cells seem less vulnerable to these agents. In cases where
permanent damage is to outer hair cell regions alone, the physiology
of auditory nerve fiber innervating the inner hair cells in the region
of the lesion is clearly abnormal. A primary effect is to greatly alter
the frequency selectivity of an auditory nerve fiber. Third, at the
cellular-molecular level, the action of aminoglycosides seems to alter plasma
membrane permeability for there is microscopic evidence for the swelling
of sensory hairs with the deformation of the cell surface. This may
involve several processes upon which cellular integrity depends. Two
of them are the cellular metabolic and protein synthesizing machinery, for
there is also evidence that mitochondria and ribosomes are damaged.
Another is that the ionic channels which are responsible for mechano-electric
transduction to occur may be blocked or otherwise affected.
A number of other antibiotics with differing molecular structure are
known to have ototoxic properties. These include viomycin (polypeptide),
polymyxins (polypeptides), vancomycin (contains both sugars and amino
acids) and minocycline (a tetracycline).
Diuretics - Two potent diuretics in general use have well-recognized
ototoxic effects. These are ethacrynic acid and furosemide. Rapid intravenous infusion
of either of these agents may produce a sensorineural hear loss which
is usually immediate in onset and transient, lasting a few hours to
several days. There may be vertigo. Severe and permanent hearing
loss is reported.
Animal studies have shown that intravenous injection of ethacrynic
acid or furosemide produces within seconds depression of the cochlear microphonic
potential (hair cell receptor potential) and auditory nerve action potentials and
a decrease in endocochlear potential which is necessary for normal
transduction and transmission in the inner ear receptor organs. Anatomical
changes include outer hair cell degeneration in basal and middle turns
of the cochlea. In those cells that survive there may be distortion
of the stereociliary bundle. Moreover, there are marked changes
in the stria vascularis, with intra- and extracellular edema and destruction
of the intermediate cell layer. Thus, it would appear that diuretic
ototoxicity involves changes in the transduction and transmission properties
of the hair cells and a breakdown in the intra-labyrinthine secretory
mechanisms of the stria vascularis.
Quinine derivatives - It has long been known that quinine derivatives produce
irreversible sensorineural hearing loss with tinnitus as the major
symptom. Administration to women in the first trimester of pregnancy
has resulted in severe abnormalities of the inner ear of the fetus.
There may be a complete absence of hair cells and supporting cells
throughout much of the organ of Corti.
Salicylates - High doses of salicylates predictably produce a bilaterally
symmetric, flat hearing loss up to about 40 dB with some reduction
in speech discrimination. The magnitude of the hearing loss is
directly related to the serum levels of the substance. The hearing loss
and accompanying tinnitus are completely reversible within 24-72 hours
after the drug is discontinued. There is no consistent morphological
change observed in the inner ears of humans or animals subjected to
high doses of salicylates. While biochemical changes of the perilymph
and endolymph have been noted along with consistently reduced electrical
activity of the cochlea and auditory nerve, the precise mechanisms of
this form of ototoxicity are not known.
Meniere's disease (idiopathic endolymphic hydrops)
The prototypic intra-labyrinthine auditory-vestibular disorder is Meniere's disease.
The classic description of the symptom complex was given more than
a century ago: (1) tinnitus, (2) spontaneous, episodic vertigo and (3)
hearing loss. Endolymphic hydrops (i.e. distention of scala media with
Reissner's membrane bulging into scala vestibuli) was clearly described
as the basic histopathologic lesion associated with the disease (hence
the clinical synonym) although a cause-and-effect relationship between
the hydrops and the clinical findings remains obscure. Vertigo
of Meniere's disease occurs in sudden attacks and may be accompanied
by spontaneous positional nystagmus. Hearing loss is characteristically
unilateral, fluctuating, and sensorineural in nature. Bilateral hearing
loss occurs in 10-20% of the cases although a figure as high as
40% has been reported. Subjectively, the hearing loss is frequently
accompanied by fullness and feelings of pressure in the affected ear. Tinnitus
may be roaring, buzzing, whistling or mixed in nature. Histopathologic
studies of temporal bones taken postmortem from Meniere's patients
usually show hydrops of the scala media and, less frequently, hydrops
of the utricle and/or one or more semicircular canal. In severe cases, secondary complications
such as rupture of membranes, herniation of the vestibular organs, and degeneration
of the organ of Corti may occur. Occasionally, there are noted changes other
than hydrops involving the endolymphic sac and its surrounding tissue
and the vestibular aqueduct and endolymphic duct. Traditionally, clinical experience
indicates that there may be a number of secondary factors that contribute
to the syndrome. These include metabolic, infectious, allergic
neurogenic and psychosomatic factors.
Labyrinthitis - Invasion of the labyrinth by inflammatory reaction is
manifested by vertigo, nystagmus, sensorineural hearing impairment,
nausea and vomiting. Serous (non-suppurative) labyrinthitis represents
a serous inflammation of the labyrinth secondary to an acute or chronic
infection of the surrounding bony labyrinth. There is not active invasion
of the labyrinth by the infecting organism. Normal vestibular and
auditory function returns. Suppurative labyrinthitis occurs secondary
to otitis media and mastoiditis and represents a direct extension of
the infection into the labyrinth. The symptoms include roaring
tinnitus, progressive sensorineural hearing loss to total deafness, and
violent vertigo with associated nausea and vomiting. Complications
of this disease are meningitis or epidural abscess.
Tumor of the VIIIth nerve - Lesions of the eight nerve are characterized
by tinnitus, sensorineural hearing loss, mild vertigo, and in some
patients, other cranial nerve signs. The classic lesion is the so-called
"acoustic neuroma", a benign tumor that is usually not of
auditory nerve origin nor is it a neuroma. The tumor is a schwannoma typically
arising from the vestibular nerve within the internal auditory meatus. The
growth of the tumor in the vestibular nerve does not typically produce vestibular
signs and it is not until the tumor compresses the auditory nerve that
it is noticed. The most common first symptom is unilateral tinnitus.
This may be followed by a high frequency hearing loss. The mechanism for
the hearing disorder probably involves the disruption of normal transmission
of action potentials in the fibers of the auditory nerve due to compression
by the tumor. Sudden occlusion of the internal auditory artery, which
supplies the organ of Corti, may produce a severe or total cochlear hearing
loss. Pressure from the growing tumor may eventually involve cranial
nerves VII, VI and V.
Tinnitus is a major disorder of the peripheral auditory system
What is tinnitus?
No doubt everyone has experienced sounds that do not originate from a source
or sources outside of the body. Instead, they originate 'within the head'.
These auditory sensations may take many forms, such as roaring noise, tones
and clicks, and they may be intermittent or continuous. They all are referred
to as tinnitus. Thus, tinnitus can be defined broadly as a conscious experience
of sound that originates within the head of its owner.
Tinnitus is not a disease per se, but is a symptom of a wide range of disorders.
Severity of tinnitus ranges widely, from being mildly irritating and hardly
noticed to being severely debilitating. The incidence of tinnitus is very
high. About 32% of all U.S. adults report having tinnitus at one time or
another, and about 6.2% of them report it to be severe or debilitating.
What are the causes of tinnitus?
Tinnitus may have a physical basis. That is, sound energy is produced somewhere
in the head, which is then heard by a subject. This could include such things
as vascular anomalies, muscular contraction, clicking jaws. Also, sounds
may be generated within the inner ear that are loud enough to be heard by
a subject (or a nearby listener), the so called otoacoustic emissions. In
all of these cases, the inner ear and central auditory pathways are normal
in their transmission and processing of the unwanted and often annoying
sounds.
Tinnitus may have no physical basis. In these cases it is the result of
abnormal physiological activity in the inner ear or in the central auditory
pathways, which gives rise to the perception of sound even though there
is no physical sound present.
Except for those cases for which there is a clear mechanical cause, the
physiological mechanisms that underlie tinnitus are unknown.
Because mechanisms are unknown and because tinnitus may arise from any of
a number sites in the ear and brain, it is not surprising that there is
no single treatment that works in all cases.
Tinnitus has multiple etiologies. It may be associated with:
a. blows to the head. Tinnitus may be transient or long-lasting.
b. drugs and general anesthetics used during surgery may initiate or exacerbate
a tinnitus.
c. tumors of the eighth nerve (schwannoma's), and is an early symptom in
a high percentage of such cases. Rarely does it go away after surgery.
d. sensorineural hearing loss. In cases of acoustic trauma and presbycusis
tinnitus is reported to be high pitched, matching the frequency in the transition
zone between regions of greater and lesser hearing loss.
e. otosclerosis, which may be associated with pregnancy.
f. Menier's disease.