Block 4 Ear

Front 1

What are the clues for localization of sound in space?

Back 1

this is critical for the four F's of life:
brain uses 3 parameters to calculate localization:
1)time delay between the two ears
2)a dB decrease between the two ears (dB=20log(test mmHg/reference))
3)sound shadow created by auricles

to 1 degree sensitivity!

note: there is no space map in the brain of the sound world in contrast to the visual world

Front 2

Why is the tympanic membrane such a precise vibrator?

Back 2

between the outer and inner ear it forms with 3 layers:
1) the outer thick skin without epidermal pegs,
2) a stroma of very very organized fibers (outer radial inner circumferential - oh man where have I heard that before? muscles? ) and
3) inner layer of simple epithelium

it is vibrated by the malleus food plate inner surface of the tympanic membrane

precision comes form the amplification: the large tympanic membrane is translated to the much smaller oval window

Front 3

What are the ravages of otitis media on hearing?

Back 3

• Causes inflammation and scaring (epidermal pegs, irregular collagen) of the tympanic membrane so it does not vibrate so efficiently.

• Erodes the ossicles (reduces the efficiency of impedance matching)

• Destroys the synovial joints (reduces the efficiency of impedance matching)

• Causes early calcification and scaring of the annulus around the stapes foot process on the oval window (otosclerosis)

• Infection has easy access to the air filled cavities of the mastoid (and into the brain)

• Kids with immotile cilia syndrome or labile cilia syndrome have a higher risk of otitis media (cilia do not beat infection toward Eustachian tube (auditory tube).
• Very prevalent in kids because Eustachian tube is very horizontal in orientation as a child. With growth, the Eustachian tube assumes a greater angular drop for better middle ear drainage.

• Surgically can put a “tube” across the tympanic membrane for greater ventilation of the middle ear.

Front 4

Contrast conductive deafness versus sensorineural deafness.

Back 4

• Sensorineural Deafness – dysfunctional hair cells or damaged auditory nerve (CN VIII)

• Conductive Deafness – Compromised middle ear impedance matching

Front 5

Explain the results of the Weber and the Rinne tests.

Back 5

Weber: If lateralizes to one ear, either have sensorineural deafness in the silent ear or conductive deafness in the louder ear.

Rinne: Put tuning fork on the mastoid - if they hear nothing = seonsonurial. if they don't hear it MUCH louder once you get to the pinna/hear it again, they have conductive hearing loss.

Front 6

Explain the hearing changes described by a patient with Bell’s palsy.

Back 6

VII does not work, the ASR is absent, and the patient complains of hyperacusis (a very loud world).

Front 7

Why should a hunter hum before he/she pulls the trigger?

Back 7

Before you start to vocalize, CN VII contracts the stapedius muscle to pull on the stapes, and CN V contracts the tensor tympani to pull on the malleus which tightens the tympanic membrane, simultaneously. This dampens down the horrible noises created when a person speaks.

humming initiates this reflex, so the gun sound is not as damaging to the ear

Front 8

Define impedance matching

Back 8

Vibrations in these inner ear “fluids” cause depolarization of the hair cells which lead to the perception of hearing. This efficient process is called impedance matching and is the hearing caused by AIR CONDUCTION.

Front 9

presbycusis,

Back 9

The elderly thus loose their hearing sensitivity to high frequencies and the consonants. This normal age related deterioration of hearing acuity is called presbycusis.

The basal hair cells which are tuned to higher frequencies. There are five enzymes that maintain and repair hair cells throughout your entire life. But since all vowels pass over the consonants, the basal hair cells die in normal aging from constant, low grade, non-tonotopic use.

Front 10

hyperacusis

Back 10

When the Acoustic Stapedius Reflex - above 80dB (400x louder than threshold power at 3000Hz) doesn't work, the world seems really loud

Front 11

ASR

Back 11

Acoustic Stapedius Reflex (ASR) – Reflex activation of CN VII contracts the stapedius muscle which pulls on the stapes so that it pulsates less at the oval window and reduces high energy vibrations into the “fluids” of the inner ear which might damage hair cells. Responds to sounds louder than 80dB.

Evolved to the crashing sound of lightening. No protection to the noise generated when shooting a gun held adjacent to the shoulder and face when aiming. Useless during rock concerts with amplification for hours greater than 160 dB. With the inflammation of CN VII in Bell’s palsy, VII does not work, the ASR is absent, and the patient complains of hyperacusis (a very loud world).

Front 12

prevocalization reflex

Back 12

Tensor tympani (VII) contracts and pulls stapes off the oval window before you vocalize

Front 13

pitch,

Back 13

measured in Hz.
Range in humans (20 to 20,000 Hz), expressed in cycles per second, sensed as pitch, consonants are 2000 to 5000 Hz, vowels are 500-800 Hz

• In the human, 3000 Hz has the greatest sensitivity (least distortion) and depends upon the auditory canal passing through cartilage (outer 1/3) and then bone (inner 2/3). If this ratio is altered, hearing acuity decreases.

Front 14

dB

Back 14

loudness, the amplitude.
it's a comparison to a reference power,
if we take 0dB = threshold at 3000Hz - the most quiet sound - then dB=20log10(test/reference power)
180dB = 10^9 x louder than threshold = damage!

Front 15

bone conduction vs air conduction

Back 15

bone is inefficient

Front 16

otosclerosis

Back 16

calcification and scaring of the annulus around the stapes foot process on the oval window

Front 17

mastoid cavities

Back 17

??

Front 18

boundaries of the middle ear

Back 18

tympanic membrane, mastoid processes, bony wall of inner ear containing the oval and round windows, Eustachian tube (auditory tube), and a bony floor.

Front 19

protective mechanisms within the outer ear canal (external auditory meatus)

Back 19

sigmoid shape, hairs, cerumin

Front 20

four sites in the human body where the dermis of skin has NO adipose tissue

Back 20

eyelids, penis, scrotum, ear pinna,

Front 21

the “four F’s of life.”

Back 21

food, fuck, ??

Front 22

Compare perilymph and endolymph (sites of synthesis, flow pathways, and release mechanisms).

Back 22

perilymph is continuous with CSF in the subarachnoid space via the perilymphatic duct
• Perilymph flow is called bulk transport or bulk flow. CSF pressure abnormalities never have a clinical impact on the inner ear which is explained physically by the bore diameter of the perilymphatic duct

Endolymph in the membranous labyrinth:
• a complex system of tubes and sacs limited by a single layer of epithelial cells with tight junctions that floats in the bony caves
• within its lumen, contains a unique fluid called endolymph which is very very high in K+ (very unusual extracellular fluid)
• The apical surface of these epithelial cells faces the lumen which is filled with endolymph, while their basal surfaces (with a basement membrane) face the perilymph.
• The two fluids never mix.

Endolymph is secreted by cells at the base of the cristae in each ampulla of each semicircular canal and by a very specialized epithelium (stria vascularis) within the scala media of the cochlea.
• Endolymph freely diffuses throughout the membranous labyrinth. Its release occurs across the epithelial cells of the endolymphatic sac at a highly vascularized site within the subdural space. Endolymph release depends upon vacuolar uptake of endolymph by these epithelial cells, transcytosis of these vacuoles across the cell, and finally exocytosis and release of endolymph across the basal plasma membrane. This contrasts with the bulk flow of perilymph which involves no endocytosis/exocytosis.

Front 23

What are the six sites where the membranous labyrinth is differentiated into hair cells and give the function of each.

Back 23

1-3) On the cristae (7000 hair cells) across each ampulla in each semicircular canal to detect angular accelerations and decelerations.

Accessory structure called the cupula (gelatinous) totally closing off the canal.

Concept is that with low energy endolymph vectors, only the hair cells at the tip of the crista are impacted. In contrast, with high energy endolymph vectors, the total cupula is deformed, and all the hair cells “on the mountain” are impacted. Cells at the bottom of the cristae (dark cells because of their high mitochondrial content) secrete endolymph.


4) On the horizontal wall (1000 hair cells) of the utricle as the 2mm kidney shaped macula to detect linear accelerations in the horizontal plane (standing up in a moving bus)

5) and on the vertical wall (1000 hair cells) of the saccule as the 2mm hooked shaped macula to detect linear accelerations in the vertical plane (going up and down in an elevator).

Each macula has a unique shape and various sized otoconia (calcium carbonate rocks that are 3 to 19 microns in diameter).

With endolymph vectors, these otoconia deform the proteinaceous “membrane” that impacts on the hair cells. A high energy endolymph vector can move the large and small otoconia. A low energy endolymph vector can only move the smallest otoconia.

With normal aging, the otoconia become uniformly homogenous (uniformly 6 microns at age 60 years) with less balance sensitivity. Often some of the otoconia become lose from the otolithic membrane of the macula of the utricle and become embedded in the cupula of the latera (horizontal) semicircular canals producing a common “positional vertigo” in the elderly when they roll to get out or into bed.

6) In the organ of Corti as one row of 3000 inner hair cells (flask shaped – type I - sitting on the bony protuberance of the tympanic lip of the osseous spiral lamina) and as three rows of outer hair cells (3000/row cylindrical shaped – type II - sitting on the basilar membrane spanning the distance between the tip of the tympanic lip of the osseous spiral lamina to the protuberance of the spiral ligament).

Front 24

Compare these hair cells with respect to the following:
Type I/type II distribution, nature of the hair bundle, presence of a kinocilium in the adult, only on-axis depolarization/hyperpolarization, potential for off-axis depolarization/hyperpolarization, somatic electromotility, and accessory structures.

-cristae in the ampulla of the semicircular canals

- macula of the utricle

- macula of the saccule

- inner hair cells of organ of Corti

- outer hair cells of organ of Corti

Back 24

THE SEMICIRCULAR CANALS

• All hair bundles (kinocilium) uniformly point toward the utricle in the horizontal canals.
• There is a mixture at every point (over the mountain of the crista in the ampulla) of type I and type II hair cells.
• There is a mixture or short/fat and tall/skinny hair bundles at every point (over the mountain of the crista in the ampulla).
• There is ONLY on-axis depolarization and on-axis hyperpolarization depending upon now the endolymph deforms the cupula.


THE MACULA OF THE SACCULE

• The hair bundles DIVERGE relative to the striola lina of the hook-shaped structure.
• Type I hair cells and the tinniest otoconia are enriched at the striola line.
• There is a mixture of short/fat and tall/skinny hair bundles at every point.
• Off-axis depolarization and off-axis hyperpolarization are operant and give the tremendous sensitivity of these 1000 hair cells to vertical linear accelerations.
• The striola line meanders so that at any given vector across the structure, there are unequal areas of hair cells.


THE MACULA OF THE UTRICLE

• The hair bundles CONVERGE relative to the striola lina of the kidney bean shaped structure.
• Type I hair cells and the tinniest otoconia are enriched at the striola line.
• There is a mixture of short/fat and tall/skinny hair bundles at every point.
• Off-axis depolarization and off-axis hyperpolarization are operant and give the tremendous sensitivity of these 1000 hair cells to horizontal linear accelerations.
• The striola line meanders so that at any given vector across the structure, there are unequal areas of hair cells.


THE ORGAN OF CORTI

• The one row of 3000 inner hair cells are pure segregated flask shaped (type I), sit on the tympanic lip of the osseous spiral lamina, at maturity have only a stereocilia bundle with the tallest stereocilia facing the stria vascularis, all bipolar afferents (30,000 neurons) contact the base of these inner hair cells. Their tallest stereocilia does NOT insert into the tectorial membrane. They depolarize on-axis in response to the endolymph jet. When depolarized by the endolymph jet, they secrete glutamate. They do not have a short/fat to tall/skinny morphologic gradient from the base to the apex of the cochlea. They display a uniform step-ladder wall function to receive the endolymph jet which causes on-axis depolarization.

• The three rows of outer hair cells are pure segregated cylindrical shaped (type II), sit on the basilar membrane, at maturity have only a stereocilia bundle with
the tallest stereocilia facing the stria vascularis, have a unique W configuration of the hair bundle, no bipolar afferents, post-synaptic to inhibitory efferents (to be probed in The Nervous System course in Block 5), have a gradation from short fat stereocilia bundles at the base which change linearly to tall skinny stereocilia bundles at the apex. With relative shear by the tectorial membrane they only depolarize on axis with a resultant somatic electromotility shortening.

• In summary, hearing can be reduced to the electrical stimulation of the 30,000 bipolar cells of the spiral ganglion (cochlear branch of CN VIII) that are neural crest in origin and myelinated by Schwann cells. All second order afferents arise ONLY from the base of inner hair cells.

Front 25

What is meant by the statement that “vowels pass over the consonants in the traveling wave” along the tonotopic map of the organ of Corti?

Back 25

• Notice that the traveling wave of vowels travels over the tonotopic map of the consonants. Therefore, with the prevocalization reflex and the acoustic stapedius reflex (ASR), you always try to mask down the energy of vowels so that they do not mess up the very important consonant region where language is really transmitted. In a person with Bell’s palsy, this masking of vowels is not efficient, and the loud vowels “mess up” the consonant region. These patients then report that it is very difficult for them to understand what people are saying (along with a very noisy world – hyperacusis).

Front 26

How is a depression in Reissner’s membrane yoked to a depression of the basilar membrane which is yoked to a bulging of the round window out into the air filled middle ear.

Back 26

• 800 Hz vibrates the tympanic membrane
• the lever system of the middle ear ossicles transfers this 800 Hz vibration to the perilymph in the vestibule.
• The 800 Hz vibration travels up the scala vestibuli and continuously pushes on Reissner’s membrane. It passes right over the 5000 Hz spot.
• At some site more apical than the 5000 Hz, the basilar membrane has become more flaccid and floppy, and the 800 Hz can deform it. Then the depression of Reissner’s membrane is yolked to a depression of the basilar membrane which bows down into the scala tympani which causes the round window to bulge out into the middle ear. When this traveling wave maximally deforms this unique spot closer to the apex of the cochlea, the inner hair cells on the tympanic lip of the osseous spiral lamina are impacted and release more neurotransmitter which causes more action potentials in the second order afferent neurons which synapse on it.

Front 27

What are the two morphologic parameters that create the tonotopic map from the base to the apex of the organ of Corti?

Back 27

THE ORGAN OF CORTI

• The one row of 3000 inner hair cells are pure segregated flask shaped (type I), sit on the tympanic lip of the osseous spiral lamina, at maturity have only a stereocilia bundle with the tallest stereocilia facing the stria vascularis, all bipolar afferents (30,000 neurons) contact the base of these inner hair cells. Their tallest stereocilia does NOT insert into the tectorial membrane. They depolarize on-axis in response to the endolymph jet. When depolarized by the endolymph jet, they secrete glutamate. They do not have a short/fat to tall/skinny morphologic gradient from the base to the apex of the cochlea. They display a uniform step-ladder wall function to receive the endolymph jet which causes on-axis depolarization.

• The three rows of outer hair cells are pure segregated cylindrical shaped (type II), sit on the basilar membrane, at maturity have only a stereocilia bundle with
the tallest stereocilia facing the stria vascularis, have a unique W configuration of the hair bundle, no bipolar afferents, post-synaptic to inhibitory efferents (to be probed in The Nervous System course in Block 5), have a gradation from short fat stereocilia bundles at the base which change linearly to tall skinny stereocilia bundles at the apex. With relative shear by the tectorial membrane they only depolarize on axis with a resultant somatic electromotility shortening.

Front 28

Why does an albino have poor hearing?

Back 28

The scala media is 35mm long; the basilar membrane is 31mm long. The stria vascularis is a pseudostratified columnar epithelium uniquely invaded by melanocytes (essential for endolymph secretion and explains the hearing loss in albinos or people with neural crest suppression of melanocyte migration) and by capillaries (the only epithelium in the body where capillaries are not restricted to the lamina propria below the basal lamina).

Front 29

What are the causes of hair cell death?

Back 29

• They are post-mitotic, nonregenerating cells.

• Ten reasons for deafness within the organ of Corti:

(1) death of hair cells by rubella,
(2) death of hair cells by CMV,
(3) death of hair cells by aminoglycosides
(4) death of hair cells by cis-platin
(5) mutated three proteins in the tectorial membrane
(6) mutated repair and maintenance enzymes of the hair bundle
(7) labile cilia syndromes (kinocilium falls apart before the hair bundle is formed along the gradient of short/fat to tall/skin - essence of mechanical tuning
(8) acoustic trauma
(9) episodic elevations of endolymph pressure as in Meniere’s disease (death of hair cells from apex to base)
(10) death of bipolar cells in spiral ganglion due to obstruction of internal auditory artery or proliferation of Schwann cells

Front 30

What is so exciting about the recent research breakthrough of the viral transvection of the gene that triggers hair cell differentiation from supporting cells of the membranous labyrinth of the inner ear? What are its shortcomings?

Back 30

• The kinocilium establishes the axis of bilateral symmetry of the hair bundle and the height of the hair bundle. The height of a hair bundle determines the diameter of its component stereocilia with the core of bundled actin that inserts into the cuticular plate. This is one important component of mechanical tuning of hair cells.

• This developmental event occurs only ONCE in a life time, although in guinea pigs, it is now possible to induce new hair cell development from the adjacent supporting cells if they are virus transvected with the single gene that causes the developmental sequence of hair cells. It is not known if these new hair cells are properly mechanically tuned, correctly display an organized axis of bilateral symmetry, or if second order afferent neurons synapse on the basal surface.

Front 31

Why do patients with Kartagener’s syndrome have no problems with hearing and balance?

Back 31

The kinocilium contains a core 9 + 2 non-motile axoneme (no dynein arms, no nexin links, no radial spokes, no radial spokeheads, no inner sheath, no central singlet bridges, and no projections from C1). So immotile cilia syndromes have no dysfunction within the inner ear hair cells. Kartagener’s syndrome patients have no hearing or balance disturbance.

Front 32

Why is the term stereocilia totally incorrect?

Back 32

stereocilia with the core of bundled actin that inserts into the cuticular plate

Highly modified microvilli (misnamed stereocilia and have nothing to do with axonemes). There is a constant renewal of their bundled actin filament core structure throughout life.

Front 33

Why must all hair bundles be some form of a truncated structure?

Back 33

Any given hair cell (type I or type II) can be a short/ fat rigid truncated cone. In contrast, another hair cell can be a tall/skinny flaccid truncated cone. All hair cells have a uniform stepladder configuration toward the kinocilium.

Front 34

What is the significance of hair bundles that are short and fat as compared with those that are tall and skinny?

Back 34

• The hair bundle moves as one viscoelastic unit because its component parts are linked together (basal links, lateral interdigitation of the glycocalyx, and
apically along the axis of bilateral symmetry by gating springs which control the opening and closing of the transduction channels).

• The gating springs span the distance from the patched transduction channel at the tip of one stereocilia to the side flank of a stereocilia in an adjacent row.

• There are between 30 and 150 stereocilia on each hair cell (we will say 100).

• All stereocilia in any GIVEN hair cell (type I or type II) have the same diameters (0.2u to 1u) where the 0.2u diameter population is found in the tallest hair bundles (100u) and the 1u diameter population is found in the shortest hair bundles (3u).

• The short (3u), fat (1u) stereocilia have many microfilaments which insert into the cuticular plate at the basal constriction point and give such a bundle great rigidity.

• In contrast, the tall (100u), skinny (.2u) stereocilia have very few microfilaments which insert into the cuticular plate at the basal constriction point and give such a bundle great flaccidity.

• All stereocilia in any given hair cell exists in rows of identical heights. The row of the shortest stereocilia is furthest from the kinocilium. Each progressive row of stereocilia is taller than the row in front of it. The final image is one of a truncated cone which is critical for the gating spring to function.

Front 35

When the hair bundle is deflected directly toward the kinocilium on the axis of bilateral symmetry....

Back 35

, maximal depolarization occurs.

Front 36

On axis, maximal depolarization is found in ...

Back 36

the semicircular canals, in the three rows of outer hair cells in the organ of Corti, and in the one row of inner hair cells in the organ of Corti.

Front 37

A graded off-axis depolarization occurs only in

Back 37

in the macula of the utricle and the macule of the saccule.

Front 38

off-axis trick

Back 38

When the hair bundle is deflected on-axis away from the kinocilium, the nonspecific transduction channels are closed more of the time because the tension in the gating spring is lessened. The hair cell is maximally hyperpolarized with deflections on axis away from the kinocilium. With possible deflection of the hair bundle off axis away from the kinocilium, there is decreased hyperpolarization, until there is no hyperpolarization when the hair bundle is moved at right angles to the axis of bilateraly symmetry. This off-axis trick is found ONLY in the macula of the utricle and the macula of the saccule. With hyperpolarization, less glutamate is released, and the number of action potentials per unit time drops BELOW resting tonic levels. The hair cells in the organ of Corti ONLY depolarize on axis.

Front 39

production of endolymph

Back 39

stria vascularis of the cochlea and ampulla of the semicircular canals: dark cells with mitochondria making endolymph high in K+

melanocytes and vasculation of the stria vascularis allow the production of endolymph;

Front 40

bony canal lining

Back 40

1 cell thick

Front 41

saccule to cochlear duct

Back 41

ductus reunions

Front 42

duplicity

Back 42

type I and type II hair cells

Front 43

apical surface of the hair cells

Back 43

endolymph on apical surface

Front 44

hair cells are what order neuron?

Back 44

first order, secrete glutamate, still cytokeratin + !

Front 45

how many afferents on hair cell I vs II?

Back 45

one on type I
several on type II

Front 46

inhibitory neurons are where?

Back 46

onto the 2nd order in the type I
onto the type II directly

Front 47

Kinocilium

Back 47

never beats, (no spoke, spoke hear, nexin, dynein arms), 9+2 Microtubule
can be 100micron - 3micron long

Front 48

each hair bundle develop stereocilia - what is inside?

Back 48

actin; height depends on the height of the kinocilium - that also determines the thickness of the cilia;
1 transduction channel on each stereocilia and a gating spring - tension on the transduction channel ( open more of the time, normally only the Brownian motion) [kinocilium has no channel/spring like that]

gotta be ladder shaped for the on-axis depolarization maximum

Front 49

cupula

Back 49

mountain of mucopolysacharide structure - in the macula and saccule and semicircular canal;
either in one other other direction - endolymph never moves off axis or sideways; either maximal depolarization or maximal hyperpolarization;
the apex of the mountain is touched lightly - only the top cells activated;
more recruitment for more energy -specificity = that's why it's on a mountain!



mixture of type I and II at every point over the mountain. only the kinocilium is inserted into the cupula so the gating spring is not touched.

Front 50

kidney shaped horizontal...

Back 50

macule in the utricle,
heir cell polarity converges at the striola - imaginary - more type I on the striola with smaller otoliths,
1000hair cells

no matter how the movement, never same area on either side = never cancer each other out- depolarization and hyperpolarization on the other side of the striola line

endolymph of life is running over your otoconia and there are many different sizes hair cells - but then they go down and become uniformly short - less balance -

Front 51

pancreas shape

Back 51

saccule - is diverging because of the shape = hook shaped. 1000 cells,
polarity diverges at the striola

Front 52

= positional vertigo

Back 52

little weights on the cupula from the detached utricle and maccula - older people have added little weight moving the cupula - not just endolymph but additional stones moving the semicircular canals
= positional vertigo

bend over and smack on the head at 30o

Front 53

Ca induced toxicity

Back 53

tremendous overuse with noise toxicity kills the hair cell

Front 54

which hair cells do you use the most?

Back 54

high frequency at the base - loose the frequency of the consonants

Front 55

external auditory

Back 55

calcification of the mucus canal

Front 56

the louder the noise

Back 56

the broader the deflection of the basilar membrane so they can get the consonants = essence of speech interpretation

Front 57

spiral nerve

Back 57

from the internal hair cells

Front 58

spiral ligament>

Back 58

lateral to scala media and vestibuli, to the basilar membrane which goes to the lip = tympanic lip of osseus spinal lamina

Front 59

inner hair cell sits on ....

Back 59

bone of the tympanic lip of the osseus spiral ligament

Front 60

as the basilar membrane sink

Back 60

outer hair cells depolarize on axis

by shear relative to the tectorial membrane and they shrink - somatic electro motility - and then endolymph vector - the endolymph jet = that hits the inner hair cell to depolarize them and then there is an Action potential of the afferent 2o neurons