S3: The Vesibulo-Ocular System, Vertigo and Vomiting

Question 1

What two parts of membraneous labyrinthis is inside the vestibule?

Answer 1

• One part is called the utricle, the other the saccule these are two large chambers. Note the two are joined (the membranous labyrinth also includes the cochlear duct in the cochlea),
• The utricle and saccule together form what is known as the otolith system.

Question 2

What is the apullae?

Answer 2

In the semi-circular canals, the membranous labyrinth is called the semi-circular ducts, which become swollen at the ends close to where it joins to the utricle, these are called the ampullae.

Question 3

Describe cluster of hair cells in semicircular system and otolith system

Answer 3

The vestibular receptors are found in the utricle, saccule and the ampullae. Between the semi-circular system and otolith system, there are 5 separate clusters of hair cells.

• Within the utricle and saccule there are one each called macula.
• Within each ampullae there is a cluster of hair cells sitting in a supportive ridge.

Question 4

Describe how the hair cells that detect movement of the head (otolith) differ from the hair cells in auditory part of the ear

Answer 4

The hair cells that detect movement of the head are pretty much identical to those in the auditory part of the inner ear. The same biochemical mechanism is essentially used to transduce movement of the head and pick up sound waves.

• Tilting of the sterocilia towards the tallest one, it will pull on the tip links, K+ will enter into the hair cell and depolarise it, causing more release of glutamate and increased afferent firing.
• Tilt the stereocilia in the opposite direction and the mechanical channels will be pushed closed and this will stop K+ entering in and AP firing will decrease as the cell hyperpolarises.
• What causes them to respond to different things, is the mechanics and structure of the inner ear.

Question 5

What do hair cells in the otolith system respond to?

Answer 5

The patches of hair cells in the otolith system respond only to linear movements (acceleration) of the head, forward, backward, up-down and tilting of the head (non turning movements). It is also sensitive to direction of gravity.

Question 6

Describe the sensory epithelium of otolith

Answer 6

Both otolith organs contain a sensory epithelium called a macula which is vertically orientated in the saccule and horizontally orientated in the utricle. The vestibular macula contains hair cells which lay on a bed of supporting cells with their cilia projecting up, embedded in a gelatinous material.

Question 7

Describe structure of macula of otolith

Answer 7

• There are hair cells with their afferents below. Here we can see the hair cells with their afferents below. Further underneath would be the other canals, as remember this otolith system is separated as it is membrane bound.
• The hair cells stereocilia project up towards the endolymph and are embedded in the gelatinous material called otolith.
• The gelatinous material is weighed down by tiny crystals called otoconia, together as a mass they are referred to as otolith (ear stones). By sitting on top of the gelatinous material they add extra weight, giving it inertia (resistance to change in state, tendency for objects to keep moving straight). The gelatinous substance will act like jelly!
• This system works on inertia - the tendency for an object to continue what it is doing so the mass in otolith helps with that e.g. If moving it wants to stay moving.

Question 8

Describe how the Otolith Organs Detect Linear Acceleration and Deceleration:

Answer 8

• The hair cells embedded in the macula and stereocilia in the gelatinous material. The stereocilia are in different directions in terms of height order.
• At rest the afferents fire streams of spontaneous action potentials.
• If we move the head towards the left, the main mass of jelly will lag behind the movement. So essentially the jelly will move partly but the otoconia cause part of the gelatinous mass to lag behind. This results in the sterocilia get tilted. This will depolarise the cell so more glutamate is released.
• When the head stops, the main mass of jelly will carry on moving with its inertia, which will cause the sterocilia to be tilted in the other direction!
• Thus we can see that it is not the literal movement that the hair cells are monitoring, rather it is changes in acceleration and deceleration (changes in velocity) that will cause the gelatinous substance to move.
• This is why when you accelerate or jerk forward in the car you can feel moving forward but not once moving at a constant speed as the gelatinous material has gone back to its resting position.

Question 9

How do the otolith organs also respond and detect changes in the direction of gravity?

Answer 9

This is because as we tilt our head, the direction of gravity on the hair cells and gelatinous mass changes. So the gelatinous cap will sag down in the direction of gravity which will pull on the sterocilia.

Question 10

Describe how the hair cells form an orderly pattern

Answer 10

• The hair cells go across the membrane vertically in saccule and horizontally in the utricle. Between the utricle and saccule, all directions of movements are covered.
• Even more clever, is the fact that the individual hair cells in the macula are orientated differently so every tallest sterocilia is facing a different direction so when moved in that direction it will be activated.
• So therefore each direction of movement will activate a unique group of hair cells in the saccule and utricle and these will fire messages to the brain via specific axons and the brain will be able to identify that as it was this patch of hair cells that moved, the movement must have been in x direction.

Question 11

Describe role of the lateral vestibulospinal tract in aiding the otolith system

Answer 11

• A large part of the afferents carrying information from the otolith system is sent to the lateral vestibulospinal tract.
• These afferents target the ipsilateral (same side of body) anti-gravity muscles in the legs that enable control of posture when there is change in velocity.
• For example on the tube, it the velocity slows down your otolith system detects your head is moving forward fast so it puts down your leg to stop you falling.

Question 12

What do hair cells of semi-circular ducts respond to?

Answer 12

• These circular structures are designed so that the hair cells in the ampullae will only respond to rotating movements of the head.
• For example nodding, shaking the head.
• Remember that we are talking about accelerating and decelerating rotation of the head as the system only responds to changes. If you keep it constant it will soon reset itself.

Question 13

Describe how canals in semi -circular ducts detect angular acceleration and deceleration

Answer 13

• Within the ampulla is a hill of supporting cells called the ampullary crest, which contain the hair cells. The hair cell stereocilia project into the endolymph compartment and are embedded in a big a gelatinous membrane called the cupula. The cupula pretty much closes off the duct, spanning the duct.
• Using the left horizontal canal as example.
• The sterocilia in the cupula are all facing the same way, with the tallest all on the same side towards the utricle. If we turn our head to the left, then as we start to turn it, the fluid lags behind and this pushes back against the cupula causing it to bend towards the utricle.
• This will therefore tilt the hair cells and excite their afferents - depolarisation of hair cells and increase of activity L horizontal canal nerve.
• On the right horizontal canal is a mirror image and would hyperpolarise as the fluid moves in the same direction but as the canal is switched around the cupula will be pushed forward.
• When the head decelerates and stops moving, the fluid will carry on moving for a bit, this will cause the cupula to bow forward, this will close up the mechanical channels in the sterocilia and it will stop firing. In the right horizontal canal the opposite will occur - R and L horizontal canal act as mirror image pairs (push pull system)!

Question 14

Describe the axis of rotation the three canals cover

Answer 14

• Between the three canals, anterior, posterior and horizontal they can cover all axes of rotation. Each pair of canals responds to only movement in one plane e.g. left horizontal when head moves left, left anterior when head moves forward tilting left.
• However most natural movements will cause a mixture of activation in more than one pair. Any rotation will produce a specific output of bending and thus afferent firing from the three canals.
• Finally remember that the semi-circular ducts also only respond to acceleration and deceleration, as once moving at a constant velocity the endolymph will catch up with the walls of the canal and stop pressing against the cupula.

Question 15

Describe role of the medial vestibulospinal tract in aiding the semicircular ducts

Answer 15

• The output from all vestibular apparatus but particularly the semicircular ducts goes to the medial vestibulospinal tract.
• Their target is muscles that move the head and reaching movements, accuracy of visually-guided movements. In particular compensating, if you are moving about yourself.

Question 16

Describe how the vestibulo-ocular reflex ensures stability of gaze using an example

Answer 16

• The vestibular system is very important in the control of eye movements.
• Example: We are looking at a skull from birds eye view, in particular the horizontal semi circular canal when the head is turned to the left. The eyes need to turn to the right in order to maintain gaze at target.
• When the head turns to the left, the fluid in the ear will initially push against cupula and there will be a burst of AP firing. These afferents will terminate mainly in the vestibular nuclei in the brainstem.
• The vestibular nuclei is able to activate the motor neurones that control the extraocular muscles.
• In this case, the left canal input will be sent to the abducens nuclei on the contralateral side. This will give rise to CN VI which innervates lateral rectus. So this left rotating movement has activated CN VI contralaterally.
• The abducens nucleus at the same time sends a very rapid impulse to the oculomotor nucleus on the other side, in particular to the neurons that activate the medial rectus muscle (in the left eye).
• This is really important as allows us to keep our eyes fixated on a target even when our head is moving around (so at the same time head turns to the left, eyes turn to the right). The movements may be our own, as we bop our head to the beat or external as we are on a boat or a on a rickety bridge or branch.
• In order for this to be so efficient the pathways must be extremely fast.
  Indeed the axons that link both sides, so both eye muscles contract at the same time run through a pathway called the medial longitudinal fasiculus and they are really big and well myelinated to make them fast.
• There are inhibitory pathways also present which relax the opposing muscles in each eye.

Question 17

How does the cerebellum keep the vestibulo-ocular reflex accurate? Describe the cerebellar circuit

Answer 17

The floconodular lobe of the cerebellum interacts with the vestibular system and part of its job is to ensure the movements driven by the vestibular system are accurate.

• The cerebellum receives input from the vestibular nuclei and the inner ear afferents themselves.
• The Purkinje cells in the cerebellum project down to the vestibular nuclei, it is an inhibitory pathway.
• So if you want to increase the power of the pathway then reduce the inhibition and if you want to decrease the power then increase the inhibition.
• This can happen on a moment to moment basis to ensure accurate movements are occurring in the eye. The cerebellum can compensate to loss of outputs from this system.

Question 18

Describe how visual input ‘fine tunes’ the cerebellar circuit

Answer 18

• Visual input ‘fine tunes’ the cerebellar circuit as there needs to be something feeding into the Purkinje cells to tell them if they need to increase or decrease the reflex, to correct the movement.
• The retinal ganglion cells in addition to projecting to the LGN and cortex they also project to the accessory optic system (involves a large number of nuclei in the brainstem!) providing an error signal. The accessory optic system feeds into the pontine nuclei and the olive.
  The pontine nuclei and olivary nuclei feed into the granule cells.
• The way this whole thing works is that if something we are watching starts to move out of our fovea, our accessory optic system will recognise this and send impulses, that through the pontine nuclei and olive and the granule cells will cause the Purkinje cell to modify the pathway to bring the eye back to the object. This is a fine-tuning a pathway!
• This is demonstrated by the fact the vestibulo-ocular reflex isn’t that accurate in the dark, as the visual input fine tunes eye movements in the light. This happens all the time.

Question 19

What can go wrong with the vestibular pathway?

Answer 19

• The vestibular pathway: The inner ear projecting to the vestibular nuclei, to the cranial nerve nuclei that control the extraocular muscles.
• Things that can go wrong:
• You can lose hair cells, as a natural consequence of ageing or disease.
• Loss of transmission through the pathways e.g. MS.
• May lose myocytes in the eye.
• Have to wear glasses.
• These things will de-calibrate eye movements and make them innacurate. This is where the cerebellum comes in, to make things accurate!

Question 20

How and why is our vestibular-optic system permanently modified?

Answer 20

• If you’ve had permanent damage to the pathway e.g. lost some hair cells.
  You don’t want to be massively tweaking the pathway every single time.
  It would be much better if the system was modified in a permanent way to compensate for the damage.
• This occurs through fibres projecting from the olivary nuclei to the Purkinje cells that have the ability to control and change the strength of that part of the pathway. They can potentiate or de-potentiate the synapses. This re-calibrates the cerebellum so it now has compensated for the previous issue and working at its new reality.

Question 21

Describe vertigo and how it affects vestibular system

Answer 21

Vertigo is the sensation of moving around in a space and/or having objects move around you. The individual can feel as if they are spinning in which case the vestibular afferents are reporting that the head is turning. Also, they can feel as if the world is spinning around them, in which case the brain thinks it is holding the eyes steady but the visual image is drifting across the retina (e.g. nystagmus!).

• Normally if head turns to the left, there is increase output from LHS canal and decreased output from RHS canal. The difference creates the sensation of turning left and causes eyes to turn to the right.
• If RHS canal is dysfunctional, the output of LHS canal can be normal but then output of RHS canal is deduced. The different creates the sensation of turning left and causes eyes to turn right despite head not turning.

Question 22

Describe nystagmus, effect and how it occurs

Answer 22

• It is defined as constant, involuntary cyclical, lateral movement of the eyeball. Where the eyes move side to side in a saw tooth pattern. Nystagmus is an eye movement designed to compensate to occur when head is moving but it occurs when head is still.
• Vestibular damage or damage to the cerebellum can lead to nystagmus (vestibular apparatus lesions, vestibular pathway lesions, cerebellar lesions). The eye drifts to the side then flicks back and does it again. It is the same movement if you were looking out a train
• The problem is caused because stable fixation on an object requires balanced inputs from both left and right vestibular systems.
  If there is damage to the vestibular pathways or cerebellum it can cause an imbalance in the signals being sent to the CN nuclei. This will cause eye drift, hence nystagmus. Because the drifting is involuntary it can make the person feel as if they are spinning and this can be very nauseating.

Question 23

Describe how nausea and vomiting occurs and effects

Answer 23

• Vestibular problems are often associated with nausea and vomiting, thus vertigo and nystagmus are often accompanied by nausea and vomiting.
• This may be because of the conflict between what the vestibular system is saying (that you’re spinning) and what the other senses are saying, esp. visual (that you’re not). This is a sensory conflict/mismatch.
• So this situation of feeling nauseas and vomiting can occur when there is vestibular dysfunction (either because it is nauseating in general or because of the conflict with the other senses). It may also occur in sensory environments that provoke motion sickness, this too is also believed to be linked with sensory mismatch.
• The cerebral cortex must be involved in the feeling of nausea but not needed in vomiting and other signs of nausea.

Question 24

What is motion sickness?

Answer 24

Motion sickness is the induction of nausea (often accompanied by pallor and cold sweating) and vomiting by motion or perceived motion. Anyone can be made to feel sick by motion!
Most commonly it is due to things like boats, fairground rides etc.

Question 25

Who is more susceptible to motion sickness?

Answer 25

• Being female/
• Asian origin.
• Family history.
• Being a migraine sufferer.

Question 26

What may a history of motion sickness predict?

Answer 26

• Pregnancy sickness.
• Anticipatory emesis.
• Post operative emesis.
  Therefore when dealing with a patient it is important you find out if they have a history of motion sickness because it can be an important warning sign of other potential types of nausea and vomiting.

Question 27

Describe how motion sickness can be induced by travel/motion

Answer 27

• It can be induced by travelling in boats, cars, planes or tilting trains. The worst thing you can do in this situation is to start reading a book because your eyes are telling your brain that you are stable, but your vestibular system is telling you you’re in motion. This conflict = nausea.
• It can be induced by spacecraft due to the loss of gravity on the otolith system.
• Can be induced by violent movement in fairground rides.

Question 28

Describe how motion sickness can be induced by perceived motion

Answer 28

• An individual doesn’t even have to be moving to experience motion sickness, this is because it is the sensory conflict that causes it.
• If we shove someone in a drum with visual image and spin it, their visual system will be telling their brain they are spinning but their vestibular system will be telling them they aren’t.
• Also imaxx cinemas, virtual reality headsets, looking down a microscope the whole day can also induce motion sickness.

Question 29

Why does sensory conflict make us ill?

Answer 29

This sensory conflict response is present in many animals, including fish, frogs, birds, many mammals suggesting it has an evolutionary purpose.

• The best suggestion is that it is part of our natural defence against ingested toxins. This experience of motion sickness may be because poisoning can damage hair cells or produce aberrant activity in them, so when there is the sensory conflict the brain thinks this is due to aberrant activity in the vestibular system and you’ve been poisoned, so you feel motion sickness.
• It may be that if poisoned you start moving around oddly due to physiological disturbances of the poison, the vestibular system picks this up and the brain thinks you’ve been poisoned.

Question 30

Describe mechanism for motion sickness

Answer 30

• Sensory conflict can account for most forms of motion sickness! The vestibular system is essential for feeling motion sickness (either the semi-circular canal system or otolith organs).
• The visual system is frequently involved but isn’t essential! We know this as even blind people can be made motion sick.
• The simplest explanation is that it mimics the effects of poison on the vestibular apparatus.

Question 31

Describe mechanism for nausea and vomiting

Answer 31

• The most common way it happens is that the vestibular organs and visual system feed into the vestibular nuclei.
  Strong, unpredictable motion or sensory conflict between vestibular and visual will produce an output from the vestibular nuclei to the NTS telling it that there is a mismatch going on.
• The NTS will co-ordinate the nausea and vomiting.
  The NTS is responsible for the increase in vasopressin when nauseous and also links in with the distress and aversion pathways that prevent us from doing whatever we did again.
• On the vomiting side, the NTS signals increase in sympathetic activity and causes gut dysrhythmia, the precursors to vomiting.
• The NTS is the same centre that receives information from the area postrema about toxins in the blood and from the vagal afferents about toxins in the gut.
• Hence we see the vestibular system is plugging into the same pathway producing nausea and vomiting as these other ones to do with toxin ingestion.

Question 32

Describe pharmalogical treatment of nausea and vomiting (caused by vestibular dysfunction or motion sickness)

Answer 32

The main classes of pharmacological agents are mACh and or histamine H1 receptor antagonists.
They are also best used prophylactically (as a preventative measure, before feeling ill).
- Muscarinic receptor antagonists act in the vestibular nucleus e.g. Hyoscine hydrobromide (scopolamine).
- Histamine (H1) receptor antagonists may act in the vestibular nucleus as well, in part could be due to anti-muscarinic actions e.g. various drugs ending in –zine, diphenhydramine (Benadryl).
- Multiaction antagonist: Promethazine is a H1 and mACHR antagonist, it is a much stronger medication and has more sedative power than the more “clean” antihistamines.
- Multiaction antagonist: Prochlorperazine is used as an anti-psychotic medication at higher dosages. It is a dopamine D2 (also mACH and histamine) antagonist and used to treat very severe N+V caused by vertigo, motion sickness, migraine. Because it is so powerful it has lots of potential side-effects and only used if absolutely necessary.
- All of them have side effects! Both include drowsiness/sedation, dry mouth and or blurred vision!

Question 33

Alternative treatment to nausea and vomiting

Answer 33

• Ginger! Has a long history of being used to combat N+V, there is scientific evidence that they are good at treating N+V.
• Placebo travel bands.