BALANCE

Vestibular system Vestibular apparatus:

utricle, saccule and semicircular ducts.

Sensory cells of vestibular apparatus lie in the ampular cristaeof canals and maculaein the utricle and saccule.

Both types of organs- hair cells- special stereocilia over the apical surface and one kinocilium:

In the utricle and saccule, the receptor organ is called macula- stereocillia and kinocilium are embedded in cuticular plate with otoliths (CaCO3 crystals)

In the semicircular ducts, the receptor organs are calledampular cristae- hairs are covered by cupulae, composed of a gelatinous material similar to otolithic membrane but lacking otoliths.

Macula (utricular and saccular)

Cristae ampullaris (semicircular canals)

- Utricle and saccule:

– Linear acceleration detection

– Head position (gravity)

- Semicircular canals

Angular motion

Function of the maculae detect head position and linear acceleration

otoliths (small calcium carbonate particles) drag on the stereocilia when the head changes position

when the body is in anatomical position: the patch of hair cells in the UTRICLE is nearly horizontal, with the stereocilia oriented vertically

the sensory epithelium is vertical in the SACCULE, with the stereocilia oriented horizontally

when the body is in anatomical position: the patch of hair cells in the UTRICLE is nearly horizontal, with the stereociliaoriented vertically

the sensory epithelium is vertical in the SACCULE, with the stereociliaoriented horizontally

K+ TRPA channels + tip- links

Depolarisation- lean towards the kinocillium- K+ ch open

Hyperpolarisation- lean towards the stereocillia- K+ ch close

orientation of the stereocilia within the sensory epithelium is determined by the STRIOLA, a curved dividing ridge that runs through the middle of the MACULA – in the UTRICLE, the kinociliaare oriented TOWARDthe striola, and in the SACCULE they are oriented AWAY from it

in any position, some hair cells will be depolarized and others hyperpolarized in BOTH otolith organs

Signal transduction

Semicircular canals- coding of rotation Three semicircular canals in each ear

Each canal is oriented in a different plane

Each canal is maximally sensitive to rotations perpendicular to the canal plane

Anterior (superior)- anterior and 45 degrees with the AP plane

Posterior- post and 45 degreees with the AP plane

Horizontal

Function of the cristae detect the rate of head

rotation when the head is initially

moved, the endolymphand ampulla (and therefore the hair cells) turn with it in a direction oposing rotation

DEPOLARISATION IN THE KINOCILUM DIRECTION

HYPERPOLARISATION IN THE STEREOCILLIUM DIRECTION

HORIZONTAL CANALS (“no”)

depolarization occurs in the SAME direction as the head movement (LEFT head turnproduces depolarization in the LEFT horizontal canal)

ANTERIOR (SUPERIOR) (“YES”) AND POSTERIOR CANALS anterior canals are located at ~90o to

each other posterior canals are also located at

~90o to each other the directionality of the stereocilia is

different in the anterior and posterior canals the anterior canals have their

kinocilium anterior to the stereocilia the posterior canals have their

kinocilium posterior to the stereocilia

the natural pairing of A/P canals is:LEFT ANTERIOR with RIGHT POSTERIORRIGHT ANTERIOR with LEFT POSTERIOR

Signal transduction K+ channels in the cillia

When stereocilia are bent towards the kinocilum K+ ch open

Depolarisation of the receptor cell= receptor potential

Ca2+ channels opening mediator release in the synaptic cleft

Action potential on the vestibular pathway

Vestibular pathway 1st order neuron= Scarpa ganglion- axons form the

vestibular branch of the VIIIth cranial nerve

2nd order neuron- vestibular nuclei in the medulla oblongata

3rd order neuron- thalamus

Cortical projection= superior temporal gyrus

1. to the thalamus (3rd order neuron)

2. to the paleocerebellum

3. to the spinal chord (vestibulospinal)

4. to the motor nuclei of cranial nerves III,IV,VI

Chemical senses Olfaction and taste

Both have receptors that sense the differences of concentration of a substance dissolved in the mucus/ saliva

So- the odorant/sapide molecules have to be soluble

Interaction of molecules with receptor cells

Both project to cerebral cortex & limbic system

evokes strong emotional reactions

Olfaction

Anatomy of olfactory receptors The receptors for olfaction, which are bipolar

neurons, are in the nasal epithelium in the superior portion of the nasal cavity

The only neurons to come into contact with the external enviroment

They are first-order neurons of the olfactory pathway.

Basal stem cells produce new olfactory receptors.The only neurons that regenerate!

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Olfactory Epithelium

1 square inch of membrane holding 10-100 million receptors

Covers superior nasal cavity and cribriform plate

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Cells of the Olfactory Mucosa Olfactory receptors

bipolar neurons with cilia or olfactory hairs

Supporting cells

columnar epithelium

Basal cells = stem cells

replace receptors monthly

Olfactory glands (Bowmann)

produce mucus

Principles of Human Anatomy and Physiology, 11e 27

Olfaction: Sense of Smell

Odorants bind to receptors

Na+/ Ca2+/ Cl- channels open

Depolarization occurs

Nerve impulse is triggered

Principles of Human Anatomy and Physiology, 11e 28

Olfactory receptors use a G-protein coupled transduction mechanism similar to visual receptors

There are 1000 different genes in 4 families; each codes 7-transmembrane domain G-protein coupled receptor protein that is expressed in olfactory receptors in mice

About 350 of these are functional genes in humans; the rest are present as “pseudogenes”

Each receptor cell in the epithelium expresses only one receptor gene

Therefore, each receptor is best “tuned” to one of 1000 different chemical “types”

What these types are is still not clear, nor is how the code gets turned into a “smell”

RECEPTORS

There are, in the rat, about 1000 odorant receptor genes. Each olfactory receptor expresses only one of these genes. This is the first critical feature of olfactory coding. When an odorant binds to the olfactory receptor protein it stimulates a G-protein that activates adenylatecyclase; cAMP binds to and opens channels permeable to Na+/Ca2+ and Cl- channels. The resulting current flow depolarizes the receptor cell (receptor potential) causing it to spike. Its axon terminal in the OB then releases transmitter (glutamate) to excite the target mitral cells.

Bear et al.

OLFACTORY BULB

Olfactory receptor axons terminate on mitral cell dendrites in a restricted encapsulated structure called a glomerulus; a glomerulus contains the dendritic bush of one mitral cell but many olfactory receptor axons. All the OR axons ending in one glomerulus are from receptors expressing same olfactory binding protein. So each mitral cell codes for one kind of

odorant molecule. This is the primary basis of olfactory coding.

Bear et al.

Olfactory Pathway Axons from olfactory receptors form the olfactory nerves

(Cranial nerve I) that synapse in the olfactory bulb pass through 40 foramina in cribriform plate

Second-order neurons within the olfactory bulb form the olfactory tract that synapses on primary olfactory area of temporal lobe, in the paleocortex conscious awareness of smell begins

Other pathways lead to the frontal lobe (Brodmann area 11) where identification of the odor occurs

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Adaptation & Odor Thresholds Adaptation = decreasing sensitivity

Olfactory adaptation is rapid

50% in 1 second

complete in 1 minute

Low threshold

only a few molecules need to be present

methyl mercaptan added to natural gas as warning

Taste

Clustered in taste buds

Associated with lingual papillae

OR free in the pharynx, larynx, oesophagus

Contain basal cells which appear to be stem cells

Gustatory cells extend taste hairs through a narrow taste pore

Taste receptors

Primary taste sensations

Sweet, sour, salty, bitter, umami (aminoacid glutamate)

Taste sensitivity shows significant individual differences, some of which are inherited

The number of taste buds declines with age

Gustatory discrimination

Taste buds

Receptors for taste are modified epithelial cell present in taste buds located on the tongue, roof of the mouth and pharynx

Taste receptors

FLAVOR

SKIN

What are we aware of?

CONSCIOUS SUBCONSCIOUSSpecial Senses Somatic stimuli

Vision Muscle length and tension

Hearing

Taste Visceral stimuli

Smell Blood pressure

Equilibrium pH and O2 content of the blood

pH of cerebrospinal fluid

Somatic senses Lung inflation

Touch-pressure Osmolarity of body fluids

Temperature Temperature

Pain Blood glucose

Proprioception Distension of GIT

Classification of sensory receptorsReceptor type bystimulus modality

Generalclassification

Class based onlocation

Example

Mechanoreceptor Special senses

Muscle & Joints

Skin & viscera

Cardiovascular

Telereceptors

Interoreceptors

Proprioreceptors

Exteroreceptors

Interoreceptors

Cochlear hair cells

Vestibular system hair cells

Muscle spindles

Golgi tendon organs

Pacinian corpuscle

Bare nerve endings

Arterial baroreceptors

Atrial volume receptors

Chemoreceptor Special senses

Skin & viscera

Telereceptors

Exteroreceptors

Exteroreceptors

Interoreceptors

Olfactory receptors

Taste receptors

Nociceptors

Nociceptors

Glomus cells (carotid body PO2)

Hypothalamic osmoreceptors &

glucose receptors

Photoreceptor Special senses Telereceptors Retinal rods & cones

Thermoreceptor Skin

CNS

Exteroreceptors

Interoreceptors

Warm and cold receptors

Temperature–sensing

hypothalamic neurones

Sensory Systems - Peripheral Organisation Sensory unit = a single afferent neurone with all its receptor endings

distributed in a receptive field

The size of the receptive field varies inversely with the density of receptors. High receptor density gives rise to small receptive fields, which lead to greater acuity or discriminative ability of the input.

Overlapping receptive fields (of identical sensory receptors) allows interactions between sensory inputs and improves sensory discrimination.

adequatestimulus

sensory receptor

primary afferent neurone

synapse

2nd order neurone

graded receptor potential

threshold

generated action potentials

frequency coded action potentials conducted down

primary afferent neurone

synaptic integration

action potentials cause transmitter release & generate graded potentials

(EPSPs) in 2nd order neurone

reduced frequency ofaction potentials conducted

down 2nd order neurone

Transduction & Coding

related tostimulus intensity

and duration

transduction and generationof graded receptor potential

EPSPs

Sensory Coding for Intensity & Duration

amplitude 40mvduration 4ms

amplitude 65mvduration 7ms- note decay ofreceptor potential

small amounttransmitterreleased

large amounttransmitterreleased

exceeds threshold& generatesaction potentials

action potentialsconducted downsensory axon

generates higherfrequency of actionpotentials for longerperiod

more action potentialsconducted downsensory axon

recording arrangement from sensory unit

Receptive field Skin surface inervated by one neuron

Each nerve fiber- branches extensively in the skin- the more the branching, the wider the field and less sensitivity

Wide receptor field- trunck, abdomen, inferior limbs

Small receptor field- lips, tongue, hands (palms)- high tactile acuity

Two-point discrimination

Arms and legs: large receptive fields – up to 40 mm

Fingertips: smaller receptive fields – 2 mm

Adaptation Phasic R- rapid adaptation- moment modifications in

skin conditions- in time, they stop responding

Tonic R- slow adaptation- they keep discharging for a longer period of time (they stay active)- anouncing continuous stimulation

Adaptation Very rapid- 0.01 sec Pacini (vibrations)

Slow – 1-2 days- baroR in the circulatory system

Very slow- pain

Tactile receptors serve the sense of touch in the skin

Hairless skin (e.g., the palm of the hand): - Merkel disks (intensity rec, lowest layers of epidermis, slow

adaptation, respond to steady pressure),- Meissner corpuscles (velocity rec, adapt rapidly)- Pacinian corpuscles (very rapidly adapting/acceleration rec.,

sensitive to fast-changing stimuli as vibration)

Hairy skin:-hair-follicle receptors: mechanorec that adapt more slowly -Ruffini endings (in the dermis) are slowly adapting-also present: Merkel disks grouped in tactile disks, and Paciniancorpuscle to sense vibration in the hairy skin-non-myelinated nerve endings – limited tactile function, sense pain

Skin receptors signal transduction Nerve endings stimulation deflection mechanical

sensitive (stretch) channels Na+

Na+ influx is directly prop with the degree of deformation (respectively to the no of stimulated R)

AP if threshold

Nerve fibres of the first order neuron second order neuron (in spinal chord of the sensory nucleus of the trigeminal nerve) third order neuron in the thalamus

Merkel Disk- continuous pressure Epithelial cells synapsing with a free nerve ending

epidermal- dermal junction

Hairless skin

Small receptor field

Slow adaptation

Texture of examined object- in the tips of the fingers with high specificity (fine details)

Meissner corpuscule Hairless skin dermis

Incapsulated nerve endings

Detect stimuli with a low freqency (2-80 Hz)

Hand grip control

Rapid adaptation

Very small receptor field

Ruffini corpuscle Dermis of hairless skin and hairy skin

Adapt slowly

Detect stretching (continuous pressure) of the skin

Pacini receptor Largest mechanoR

Hypodermis

Incapsulated nerve ending- capsule is made of modified Schwann cells- flat and thin

Liquid between lamelae homogenous distribution of pressure on the entire R

Pressure-mechanostimulationstretch sensitive Na+ ch receptor potential

If threshold voltage gated Na+ ch action potential

Intensity coding AP rate (50-500Hz)

Vibration

Fine texture by moving fingers

Krause corpuscles Incapsulated nerve endings

Skin/mucosae junction (lips)

Detect small pressure

Rapid adaptation

Hair follicle nerve endings

mecanoR

Sensitive to hair bending

Temperature sensation – thermoreceptors

Thermoreceptors= naked nerve endings

- thin myelinated fibers (cold rec, response peak at about 30º C) A delta – become insensitive below 8 degrees- nonmyelinated C fibres (warm rec, response peak at about 43ºC) with low conduction velocity-Phasic (rapidly adapting, responds only to temp changes) and tonic (depend on local temperature) components in their response-Diff densities on the body surface, cold>warm rec-comfort zone – no appreciable temperature sensation, 30-36ºC -at skin temperature <17ºC, cold pain is sensed by pain rec-at very high skin temperature (above 45ºC )- paradoxical cold caused by activation of some cold rec

ThermoR static/dinamic response Dinamic- changes in skin temp

Static- skin temperature- involved in thermoregulation

Body temp= balance between thermogenesis/ thermolysis

Pain

• Pain is a protective experience.

1. Somatic: - cutaneous sensation = superficial pain

- from muscles, joints, bones, connective tissue

= deep pain

2. Visceral pain: from internal organs (strong contraction, forcible

deformation…)

• Pain is sensed by Nociceptors (free nerve endings) of

unmyelinated C and A-fibres that transduce intense stimuli into

electrical events.

C-fibres (slow, chronic pain sickening burning sensation which

persists long after stimulus is removed).

A-fibres (fast, acute, abrupt sensation)

• Modalities

1) Heat/Cold, 2) Mechanical, 3) Polymodal (temperature, mechanical and

chemical).

Types of Pain and Their Qualities:Fast Pain and Slow Pain

Initial, fast pain (sharp pain, pricking pain, acute pain, electric pain)is felt within about 0.1 second after a pain stimulus is applied.

Fast pain is felt when a needle is stuck into the skin, when the skin is cut with a knife, or when the skin is acutely burned. It is also felt when the skin is subjected to electric shock.

Delayed, slow pain (slow burning pain, aching pain, chronic pain)begins only after 1 second or more and then increases slowly over many seconds and sometimes even minutes; it is usually associated with tissue destruction and can lead to prolonged, unbearable suffering.

Pain receptors and their stimulation Pain receptors are free nerve endings.

The pain receptors are widespread in the superficial layers of the skin as well as in certain internal tissues, such as the periosteum, the arterial walls and the joint surfaces.

Pain can be elicited by multiple types of stimuli. They are classified as mechanical, thermal, and chemical pain stimuli.

-In general, fast pain is elicited by the mechanical and thermal types of stimuli, whereas slow pain can be elicited by all three types.

-Some of the chemicals that excite the chemical type of pain are bradykinin, serotonin, histamine. The chemical substances are especially important in stimulating the slow type of pain that occurs after tissue injury.

In contrast to most other sensory receptors of the body, pain receptors adapt very little and sometimes not at all.

Pain steps Acute pain- direct injury

This leads to oversensitivity of the injured area or around it= primary hyperalgia

Phenomenon called facilitation in the posterior horns of the spinal chord

Initial stimulus leaves the interneurons slightly depolarized respond faster

“overreaction”

Pain steps Secondary hyperalgia

Inflammation cells release inflammatory factors

Vasodilation (PGI2, bradykinin, histamine)

Pain (bradikinin, hystamine, serotonin, K, PG)

In 20 min since injury occurs

Axon reflex

Nerve endings stimulation (polymodal)

Special endings release substance P

It amplifies inflammation higher vessel permeability , stimulates mast cells degranulation, lowers threshold of surrounding nerve endings

Types of painReferred Pain:

a person feels pain in a part of the body that is fairly remote from the tissue causing the pain: pain in one of the visceral organs often is referred to an area on the body surface.

Knowledge of the different types of referred pain is important in clinical diagnosis because in many visceral disorders the only clinical sign is referred pain.

Mechanism of Referred Pain

branches of visceral pain fibers synapse in the spinal cord on the same second-order neurons that receive pain signals from the skin.

when the visceral pain fibers are stimulated, pain signals from the viscera are conducted through at least some of the same neurons that conduct pain signals from the skin, and the person has the feeling that the sensations originate in the skin itself.

Visceral Pain

In clinical diagnosis, pain from the different viscera of the abdomen and chest is one of the few criteria that can be used for diagnosing visceral disorders.

Often, the viscera have sensory receptors for no other modalities of sensation besides pain.

Visceral pain differs from surface pain in several important aspects:

- highly localized types of damage to the viscera rarely cause severe pain,

- a stimulus that causes diffuse stimulation of pain nerve endings causes pain that can be severe (ischemia caused by occluding the blood supply to a large area of gut stimulates many diffuse pain fibers at the same time and can result in extreme pain).

Causes of Visceral Pain

Any stimulus that excites pain nerve endings in diffuse areas of the viscera can cause visceral pain.

- ischemia of visceral tissue

- chemical damage to the surfaces of the viscera,

- spasm of the smooth muscle, excess distention of a hollow viscus, and stretching of the connective tissue surrounding or within the viscus.

Essentially all visceral pain that originates in the thoracic and abdominal cavities is transmitted through small type C pain fibers and, therefore, can transmit only the chronic-aching-suffering type of pain.

Ischemia. Ischemia causes visceral pain in the same way that it does in other tissues: formation of acidic metabolic end products or tissue-degenerative products such as bradykinin, proteolytic enzymes, or others that stimulate pain nerve endings.

Chemical Stimuli. On occasion, damaging substances leak from the gastrointestinal tract into the peritoneal cavity. For instance, proteolytic acidic gastric juice often leaks through a ruptured gastric or duodenal ulcer. This juice causes widespread digestion of the visceral peritoneum, thus stimulating broad areas of pain fibers. The pain is usually extremely severe.

Spasm of a Hollow Viscera: a portion of the gut, the gallbladder, a bile duct, a ureter, can cause pain -mechanical and chemical stimulation of the pain nerve endings, as the spasm might cause diminished blood flow to the muscle. Often in the form of cramps, with the pain increasing to a high degree of severity and then subsiding. This process continues intermittently, once every few minutes. The cramping type of pain frequently occurs in appendicitis, gastroenteritis, constipation, menstruation, gallbladder disease, or ureteral obstruction.

Insensitive Viscera. A few visceral areas are almost completely insensitive to pain of any type: parenchyma of the liver and the alveoli of the lungs.

Yet the liver capsule is extremely sensitive to both direct trauma and stretch, and the bile ducts are also sensitive to pain. In the lungs, even though the alveoli are insensitive, both the bronchi and the parietal pleura are very sensitive to pain.

Causes of Visceral Pain

Mechanical, polymodal and visceral nociceptors. A visceral pain afferent synapses in the spinal cord with the neuron of the lateral spinothalamic tract on which the cutaneous group IV pain afferent terminates.

The spinothalamic tracts and their sensory function.

Acute pain Myenlinated fibres A delta

First order neuron synapses with a second order neuron in lamina I of the posterior horn

Lateral spinothalamic tract

Ventromedial thalamic nucleus- third order neuron

Projection in the primary sensory area in the parietal cortex

At the same timesynapse with the alpha somatomotor neuron in the anterior hornnociceptor reflex

Chronic pain Slow nonmyelinated C fibres

N1 synapse in the II and III lamina of the posterior horn

N1 releases substance P

N2- anterior spinothalamic tract

Thalamic posterolateral nuclei

Primary sensory area

Direct modulation of neuronal activity

• Drugs

• Surgery cut afferent pathways, cut tracts, stimulation of the Periaqueductal Grey (mid brain)

Changed emotional reaction to pain leading to modulation

• Joy

• Fear

• Stress

Modulation of pain sensation

Target sites for drugs which produce pain relief (Analgesia)

Central

Synapse

Sensory Neurone

1) Block synthesis, release or receptors

for proinflammatory / pronociceptive

agents.

2) Block action potentials 3) Block neurotransmitter

release.

4) Block pain pathways in the

CNS

Summary on pain

• Pain serves to protect against noxious agents

• Pain is transmitted via unmyelinated C (slow, <2 m/sec) or A -fibres (fast, 5-30 m/sec)

• Fibres are activated by tissue damage and the subsequent release of chemicals and other agents

• Pain may be modulated by blocking the detection or the transmission of the stimulus.