Case 22- Physiology

Question 1

Smell and taste

Answer 1

Cassified as visceral senses (Special Visceral Afferent, SVA), they are physiologically related to each other. Receptors for both are activated by external chemical. Both link to and stimulate the limbic system and are explicitly linked to memory and emotion.

• People with dementia can have blunting of their sense of smell and taste
• The stimuli are chemicals, they are detected by chemoreceptors which are specific for a stimulus or group of stimuli

Question 2

The tongue

Answer 2

• The tongue is a mass of skeletal muscle, covered in a mucous membrane of stratified squamous and keratinised epithelium with a midline fibrous septum separating the two muscular halves.
• It has a dorsum, tip, inferior surface and root.
• The ant 2/3 faces forwards and towards the hard palate, and the posterior 1/3 backwards towards the oropharynx. In the anterior 2/3 the facial nerve is responsible for taste sensation, in the posterior third the Glossopharyngeal nerve provides taste sensation

Question 3

5 types of taste sensation

Answer 3

• Salt taste for electrolyte balance.- most sensitive at the front of the mouth
• Sweet taste for energy- most sensitive at the tip of the tongue
• Bitter taste for poisonous compound- most sensitive at the back of the tongue
• Sour taste for acidity- most sensitive at the side of the tongue
• Umami for essential amino acids- equal all over the tongue
We taste the different stimuli all over the tongue, however, they do differ in their threshold or sensitivity to the stimuli. Has dietary and safety importance

Question 4

Taste buds

Answer 4

There are scattered mucous and serous glands under the sides and tip of the tongue. Forms saliva which helps with the interactions of the chemicals in the food with the taste buds. There are 4 types of papillae: filiform, fungiform, vallate and foliate.
Taste buds are also found in the palate, pharyngeal arches and pharyngeal wall

Question 5

The three types of papillae on the tongue surface which contain taste buds

Answer 5

• Circumvallate – at the rear of the tongue, most abundant (50% of total taste buds). Largest in size, in front of the sulcus terminalis
• Fungiform – At the tip of the tongue (anterior 2/3 of the tongue), ~25%. Mainly on margins and tips, mushroom shaped
• Foliate – at the posterolateral side of the tongue, ~25%. Leaf like ridges, present on margins near the sulcus terminalis

Question 6

Structure of taste buds

Answer 6

Taste hairs (microvilli), taste pore, taste cell, basal cell, supporting cell, synapse, sensory neurone.
• Taste hairs- finger like projections of the taste cells, they contain the taste receptors that interact with chemicals in food
• Taste pore- the taste hairs converge in an opening called the taste pore, an entry point for the chemicals contained in the saliva so that they can interact with the taste receptors in the taste hairs
• Taste cell- transduce the chemical signals into electrical impulses or action potentials
• Basal cell- replaces taste cells which die
• Supporting cell- nourishes the taste cell

Question 7

What supplies the sense of taste in the pharyngeal arches

Answer 7

The Vagus nerve

Question 8

Function of taste

Answer 8

• Helps to tell us if a substance is palatable or poisonus
• In childhood it helps us to make sense of the environment
• Chemical constituents of food interact with receptors
• Taste cells transduce this information to electrical signals- identity, concentration

Question 9

Taste types and their threshold

Answer 9

• HCL- sour- 100umol/l
• NaCl- salt- 2000umol/l
• Strychnine Hydrochloride- bitter- 1.6umol/l
• Glucose- sweet- 80,000umol/l
• Sucrose- sweet- 10,000umol/l
• Saccharin- sweet- 23umol/l

Question 10

Transduction of taste

Answer 10

• Gustation can identify & quantify a taste with respect to memory. If you remember you like the taste of some food you will be more receptive to it. If you remember not liking a substance you will need to try it multiple times before you can be receptive to it again
• Saliva: dissolve tastants (chemicals in food) so that it can bind to receptor found on taste cells
• Receptors: ion channel-coupled (salt and acid) or G protein-coupled (sweet, bitter, umami)
• Binding causes depolarization of the taste cells which opens voltage-gated calcium channels, resulting in exocytosis of neurotransmitters.
• Basolateral side of taste cells synapse with primary sensory neuron (cranial nerves)
• There will be generation of action potential which is passed on till it reaches the primary taste centre in the brain where it will be interpreted

Question 11

Transduction- Bitter compounds, sugar (sweet) compounds, amino acids (umami)

Answer 11

• Interact with the G protein coupled receptor on the apical portion of the taste cell
• A second messenger is released which is Inositol triphosphate
• The second messenger will open the Ca+2 channels
• The increase of Ca+2 in the taste cell causes the movement of vesicles and exocytosis from the basolateral surface of the cell
• This causes an action potential from the post synaptic neuron

Question 12

Transduction methods- salt

Answer 12

• The Na+ ion channels are opened on the apical membrane of the taste cell
• Entry of Na+ causes depolarisation of the taste cell membrane
• Additional Na+ and Ca+2 channels are opened causing Na+ and Ca+2 to enter from the extracellular fluid
• This causes the movement of the vesicles and they fuse with the basolateral membrane
• Exocytosis of the neurotransmitter
• There is generation of an electrical impulse which is passed along the afferent nerve

Question 13

Transduction method- sour

Answer 13

• H+ ion channels are opened on the apical portion of the taste cells allowing entry of protons
• Causes depolarisation which opens the Na+ and Ca+2 channels allowing entry of the ions intracellularly
• This causes the movement and fusion of the vesicles containing the neurotransmitter into the basolateral portion of the taste cell and exocytosis.
• Generates action potential

Question 14

Receptors- taste

Answer 14

• Salt- amiloride sensitive Na+ channel
• Acids (sour)- H+ sensitive TRP channel (PKD variant)
• Sweet- T1R2, T1R3
• Amino acids- T1R1, T1R3
• Bitter- T24
In amino acids and bitter tastes IP3 is released from a PLC-beta2 receptor and the Ca+2 channel is TRPM3.
Signals go to the primary gustatory centre in the brain

Question 15

Cranial nerves that signal taste

Answer 15

• The Glossopharyngeal, Facial and Vagus nerve must pass through the solitary nucleus in the medulla oblongata (Nucleus of the solitary tract). These are second order neurones
• The nerve then goes through the Pons and decussates to the contralateral side
• The nerve synapses in the Thalamic nucleus (ventral posterior medial nucleus)
• Then goes to the Primary Gustatory cortex in the insular lobe of the brain

Question 16

Key points on olfaction

Answer 16

• Closely linked to memory- will like a smell more if its linked to a positive memory
• Organ-nose
• Stimuli: odorants
• Receptor cells: olfactory neurones (bipolar cells) which are found at the root of the aural cavity. They exit via the cribriform plate and synapse with neurones in the olfactory bulb
• First order neuron: CN I / Olfactory nerve- forms the olfactory bulb
• Centre: Primary olfactory cortex (temporal lobe)
• Smell must be converted to an action potential in order to be detected

Question 17

Olfactory mucosa

Answer 17

Made up of a superficial layer of mucous and an underlying layer of olfactory epithelium where the olfactory neurone is found. The superficial mucous is secreted by the Bowmans gland which is within the lamina propria of the olfactory epithelium. The mucous dissolves the odorants so it will be easier for them to interact with the olfactory receptor found in the olfactory cilia

Question 18

Structures within the Olfactory mucosa

Answer 18

• Olfactory ensheathing cell- protect neurones by rapidly clearing debris and secreting pro-survival neurotropins in the olfactory bulb of the cell mucosa
• Basal cell- differentiate into olfactory neurones by mitosis, the olfactory neurones have a turnover of 30-60 days
• Cribriform plate- under the olfactory mucosa, where the afferent neurones exit so it can synapse with neurones in the olfactory bulb
• Lamina propria
• Olfactory neuron (bipolar cell)
• Olfactory cilia- extensions on the apical surface of the olfactory neurone which contain the olfactory receptors
• Sustentacular cell- nuclei are found near the surface of the epithelium, provides olfactory support for the olfactory receptors and contribute secretions to the overlying mucous which plays a role in the binding of odorants
• Bowmans gland

Question 19

Odour cells

Answer 19

Can recognise multiple odorants, a singe odorant can also be recognised by multiple receptors. Whether we like a smell or not depends on the combination of odorants and receptors

Question 20

Combinatorial receptor codes for odours

Answer 20

• A single odorant can be recognized by multiple receptors and a single receptor can recognize multiple odorants.
• Odorant information is both structure and concentration dependent: a slight change in structure and concentration will change the perception about the odorant

Question 21

Transduction of smell

Answer 21

• Odorant binds to receptors on the surface of the bipolar cells
• Activates G-protein Golf
• Alpha subunit of the G-protein activates adenylyl cyclase
• Generates Camp
• Opens cation channel allowing entry of Na+ and potentially Ca+2
• Entry of cations and depolarisation, an action potential is generated
• Calcium opens chloride channels, Cl- leaves the cell
• The opening of Cl- leads to depolarisation that is transferred by the efferent nerve fibres that exit in the cribiform plate. Signal is sent to the olfactory bulb

Question 22

Olfactory receptor neurones to the olfactory bulb

Answer 22

• As the axons of ORNs leave the olfactory epithelium, they coalesce to form a large number of bundles that together make up the olfactory nerve (CN1).
• Olfactory nerve then projects ipsilaterally into the olfactory bulb and synapses with mitral cell at the glomerulus.
• Glutamate (excitatory) is the main neurotransmitter at the glomerulus.
• The mitral cells provide the only relay for olfactory information to the brain, wont pass through the thalamus
• The efferent fibres of the mitral cells coalesce to form the olfactory tract, at the base of the brain it divides into the Lateral olfactory tract and the Medial olfactory tract
• The lateral olfactory tract reaches the primary olfactory cortex, the medial olfactory tract synapse with the cells in the anterior commissure and the contralateral olfactory tract

Question 23

Lateral olfactory tract

Answer 23

1) Principle extension of the olfactory system. Most projections are ipsilateral and projects into the olfactory tubercle, the piriform cortex, the Amygdala, Peri-amygdaloid cortex and the para-hippocampus gyrus.
2) After reaching the primary olfactory cortex, olfactory information is projected to the Hypothalamic and other limbic structures such as the thalamus, hippocampus and the rest of the amygdala.
3) Information relayed from the hypothalamus to the orbital frontal cortex is used for interpretation of smell.
4) Those projected to the Hippocampus are responsible for olfactory memory, those projected to the Amydala help create an emotional response associated to a particular smell

Question 24

Structures int he Primary olfactory cortex

Answer 24

Piriform cortex, Periamygdaloid cortex and the Parahippocampal gyrus. The end point of the action potential from the olfactory receptor neurone

Question 25

Summary of olfaction

Answer 25

• Odorants are chemicals that act as stimuli in the sense of smell. They can interact with one or multiple receptors found in the cilia of the olfactory receptor neurons (ORN) or bipolar cells.
• Impulse generated by transduction is mediated by a Golf protein on the bipolar cells
• The impulse is conducted from the ORN to the olfactory bulb (mitral cells) then to the olfactory tract.
• The olfactory tract divides into medial and lateral olfactory tract.
• The lateral olfactory tract projects into the primary olfactory cortex.
• The primary olfactory cortex projects to the hypothalamus and the limbic system to interpret, memorize and associate emotion to an olfactory information.

Question 26

Prion disease

Answer 26

Characterised by accumulation of abnormal prion proteins within the CNS, Conditions are associated with a spongiform change and/or plaque accumulation at the microscopic level.

Question 27

CJD

Answer 27

Creutzfeldt-jakob disease

Question 28

Types of prion disease

Answer 28

• Idiopathic= Sporadic CJD- cause is unknown (idiopathic)
• Acquired= Latrogenic CJD, acquired via a medical procedure
- Kuru- confined to Papua New Guinea and associated with ritualistic canabilism
- Varient CJD- largely confined to individuals who have lived in the UK, linked to bovine spongiform encephalitis (BSE)
• Inherited= Familial CJD- associated with 30 different mutations in the prion protein gene and are dominantly inherited
- Gerstmann- Straussler- Scheinker syndrome
- Familial fatal insomnia

Question 29

Prions

Answer 29

Misfolded proteins, these are infectious proteins that induce a cells native proteins to fold incorrectly and impair cell function. Prions diseases are often celled transmissible spongiform encephalopathies (TSE). They are rare, progressive neurodegenerative disorders which affect both humans and animals. They are predominantly expressed in the CNS

Question 30

Prion proteins

Answer 30

PrPc or PrP or PRNP are predominantly expressed in the nervous system. A confirmational change occurs when PrPc changes to PrPsc. PrPsc is able to recruit PrPc and convert it to PrPsc.

Question 31

How prion proteins change

Answer 31

The normal prion protein is PrPc which has a higher percentage of Alpha helix and low percentage of beta sheet. The infectious prion protein is PrpSc, the alpha helix percentage drops and the beta sheet percentage increases.

Question 32

How misfolded prion proteins cause damage

Answer 32

When infectious prion proteins are injected they enter the circulatory system and travel to the brain they recruit normal prion proteins and convert them into the infectious form, the Heterodimer becomes a Homodimer. These infectious prion proteins aggregate to form the infectious form called amyloid which damages the brain
In the cortex of a patient with CJD you get a spongiform change, there is mild parenchymal vacuolation with prominent astrocytosis

Question 33

Human prion diseases

Answer 33

• Creutzfeldt-Jakob disease (CJD)- Sporadic CJD, Familial CJD, Latrogenic, Varient CJD
• Gerstmann-Straussler-Scheinker syndrome (GSS), fatal familial insomnia and familial CJD- familial, rare and due to inheritance of a mutation in the PrP gene
• Fatal familial insomnia (FFI)
• Kuru

Question 34

Animal prion disease

Answer 34

• Scrapie (sheep, goats, mice, hamsters)
• Bovine spongiform encephalopathy (cattle)
• Feline spongiform encephalopathy (cats)

Question 35

Pathogenesis- Prion disease

Answer 35

• Variant CJD- consumption of contaminated food (BSE or made cow disease)
• Sporadic CJD- spontaneous Prpc proteins to PrPsc conversion or somatic hypermutation
• Latrogenic CJD- transmitted accidently by contaminated growth hormone preparations from human cadaver pituitary glands, by corneal transplant, by contaminated surgical instruments and by cadaveric human dure mater grafts used for surgical repair of head injuries

Question 36

Bovine spongiform encephalopathy (BSE)

Answer 36

Also called mad cow disease, emerged in the UK and Europe in the 1980’s. The outbreak is traced to the use of cattle feed that contained contaminated bone meal from scrapie infected sheep and BSE infected cattle carcasses The epidemic peaked in the UK in 1993. The new variant form of CJD and BSE are caused by a common agent, indicating that the BSE agent had infected humans. The new varient form of CJD emerged shortly after the BSE epidemic.

Question 37

Basic features of prion disease

Answer 37

• Rapidly developing neurodegeneration and spongiform changes
• Amyloid plaques may be present in the brain
• Long incubation period from months to decades followed by chronic progressive disease (weeks to years)
• Prion diseases are always fatal, no known case of remission or recovery
• The host shows no inflammatory or immune response, the agents do not appear to be antigenic. No production of interferon is elicted and there is no effect on B-cell or T-cell function
• Immunosuppression of the host has no effect on pathogenesis

Question 38

Clinical features of prion disease

Answer 38

• Rapidly progressive multifocal neurological dysfunction
• Monoclonal jerks
• Severe cognitive impairment (rapidly progressive)
• Cerebellar dysfunction
• Behavioural abnormalities
• Death, usually a year after the onset of symptoms

Question 39

Probable and Possible CJD

Answer 39

Probable CJD- progressive dementia, typical findings on EEG
Possible CJD- progressive dementia, atypical findings on EEG. At least 2 of the following- myoclonus, visual impairment, cerebellar signs, pyramidal or extrapyramidal signs or akinetic mutism.

Question 40

Diagnostic interventions of CJD

Answer 40

• Co-ordinated through National CJD Surveillance Centre
• Lumbar puncture – test CSF for protein 14-3-3. Predictive value in sporadic CJD – good. Predictive value in vCJD (variant CJD) – poor
• EEG- Useful in sporadic CJD but not in vCJD
• MRI scan= Useful in sporadic CJD but not in vCJD. Pulvinar sign in posterior thalamus (vCJD)
• Tonsil biopsy – vCJD
• Brain biopsy (ante-mortem / post mortem) – confirmation for all CJD, lots of risks involved
• Genetic testing (familial types of CJD e.g. GSS)

Question 41

Treatment and prevention of CJD

Answer 41

• Currently no proven treatment exists for CJD/vCJD

* Conventional vaccine approaches unlikely to be successful due to poor immunogenicity of prions.

Question 42

Precautions of CJD

Answer 42

• These agents are unusually resistant to standard means of inactivation.
• Resistant to treatment with formaldehyde, urea, dry heat, boiling, ethanol, proteases, deoxycholate, and ionizing radiation.
• However, they are sensitive to phenol, household bleach, ether, NaOH, strong detergents (10% sodium dodecyl sulfate), and autoclaving (1 hour, 121’ C).
• Guanidine thiocyanate is highly effective in decontaminating medical supplies and instruments.

Question 43

Communication with a patient who has a cognitive impairement- FRAME

Answer 43

• F: Familiarize yourself with how your patient communicates before starting the medical interaction
• R: Reduce rate
• A: Assist patient with communication
• M: Mix communication methods
• E: Engage patient to respect their autonomy

Question 44

Other strategies to enhance communication with a patient who has a cognitive impairment- Preparation:

Answer 44

• Aim for a quiet, well-lit environment, avoiding distractions (TV, radio, other people).
• If they normally wear glasses, hearing aid or dentures, make sure these are available.
• Make sure the patient’s other needs are met before you start (e.g. they are not hungry or in pain).
• Choose the time of day when your patient communicates best

Question 45

Other strategies to enhance communication with a patient who has a cognitive impairment- How

Answer 45

• Sit close on the same level.
• Make eye contact and gain the person’s attention.
• Speak clearly and calmly with short, simple sentences.
• Speak at a slightly slower pace, and allow time between sentences for the person to process the information and respond.
• Try to communicate with the person in a conversational way, not question after question.
• Be patient, take extra time and show respect.

Question 46

Other strategies to enhance communication with a patient who has a cognitive impairement- what?

Answer 46

• Try to stick to one idea at a time - giving choice is important, but too many options can be confusing.
• If the person is finding it hard to understand, rephrase rather than repeat and consider:
• Breaking down what you’re saying into smaller chunks so that it is more manageable.
• Asking questions one at a time and phrase them in a way that allows for a ‘yes’ or ‘no’ answer
• Using non-verbal communication, pictures and pointing, as well as communication aids such as picture boards or pain scales

Question 47

Types of age

Answer 47

Chronological age- the number of years you have been alive
Biological age- how well the body is functioning comparative to age. Some people will age faster then others
Hard to study aging as can be influenced by conditions and people age in different ways. Need a large group of people in order to accurately measure it.

Question 48

Memory and ageing

Answer 48

• Sense organs decrease function during aging
• Decrease in encoding and recollection of declarative memory- normally in episodic memory such as names
• Decrease in working memory (short term)
• Decrease in attention span
• Decrease in task switching flexibility
• Difficulty laying down new associations- can affect motor and declerative knowledge
• More susceptible to distraction
• Slower processing speed

Question 49

Ageing and comorbidities

Answer 49

Symptoms of memory loss due to aging may be due to cardiovascular issues causing a decline to the blood supply of the brain. Neurones are less able to repair themselves and if the neurones are damaged they are unable to be replaced. Decline in metabolic function which affects neurones

Question 50

The ageing brain

Answer 50

• The average weight of a human brain decreases with age
• Number of neurons believed to be stable
• Dendritic complexity reduced, decreased number of dendrites and reduced distance that they reach
• Number of synapses decrease- which reduce the number of memories stored and the connections between the memories
• White matter tracts decrease- amount of myelin decreases so speed of action potentials is reduced
• Changes in neurotransmitter binding potential
• Changes in mood

Question 51

Default network

Answer 51

The areas of the brain which light up in an MRI scanner when the patient is doing nothing. Less lights up as the patients age, showing the reduced connectivity between the different brain regions, particularly the Posterior Cingular cortex and the Ventromedial Prefrontal Cortex. These are the regions most heavily associated with working memory and connections between them tend to decline the fastest. As you get older the rate of decline increases

Question 52

Ageing- Compensatory mechanisms

Answer 52

As you get older your brain can employ different coping mechanisms. For example, when recalling memories young people use the prefrontal cortex in one hemisphere but older people who have good recall use the prefrontal cortex in both hemispheres. This compensates for the reduction in visual processing systems. This is the posterior-anterior shift of ageing, so instead of using the back of the brain, older people are more reliant on the front of the brain.

Question 53

The types of memory to go first in ageing

Answer 53

Working memory is the first type of memory to decline in normal aging. The site of the working memory is the dorsolateral prefrontal cortex, which is used in rule based learning and can shift rapidly to changing goals. Lots of synaptic plasticity to adapt to these changing goals. In layer 1 and 3 of the pre-frontal cortex there is a massive decline in the number of synapses. In layer three there is synapses with other brain regions.

Question 54

Types of dendritic spines

Answer 54

Thin spines are particularly important for flexibility and new learning as they are the immature spines from which new connections grow. Whilst mushroom spines represent stable memories. The fewer thin spines you have the less well you will perform in a rule based learning task. The number of thin spines directly correlates with ability in a memory task.