Muscle Weakness Flashcards by Shalu James

The central dogma of information flow

DNA - rna - protein

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Journey from DNA to chromosome

DNA —> packaging around Huston’s proteins and so dna double helix is wrapped around beads —> beads can would around to increasingly complex structure to eventually give chromosomes

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What is the purpose of the long tail that points outside the Histone proteins?

At different stages you may need to vary the packaging of parts of chromosome - e.g the packaging maybe be relaxed so that chromosome can be used for transcription —> this requires energy which is facilitated by the histone tail

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2 types of repetitive DNA

Interspersed repeats
- sine and line often derived from retroviruses (can be short or long)

Tandem repeats 
- satellites e.g telomere TTAGGG 
- mini satalites 
- microsatelites 
(shorter segment but repeated adjacent to each other multiple times)

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Conditions associated with repetitive DNA

Myotonic dystrophy
- muscle disorder
Gets more serious as it’s passed through generations

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Mitochondrial DNA features

Circular: 
- different to nuclear DNA and shorter 
- May be multiple copies of mtDNA In each mitochondria 
- has a higher mutation rate 
Maternally inherited

maternally inherited

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Process of DNA replication

Semi conservative replication: each daughter molecule consists of one old strand (template) and one newly synthesised strand

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Steps of triggering muscle contraction

nerve impulse generated in CNS which stimulates motor neurone
AP generated in motor neurone and propagated along axon
AP reaches presynaptic bouton at the motor end plate of motor neurone
signal transmission through neurotransmitter executors
ACh in the synaptic cleft binds to the ACh receptors on post synaptic side of muscle cell

Muscle contraction

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What are the two types of synaptic transmission?

Electrical and chemical transmission through neurotransmitters

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Effects of sodium and chlorine on presynaptic

Influx of na causes EPSP + brings membrane closer to reaching AP threshold

Influx of cl causes IPSP + moves membrane potential away from AP threshold

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Differences between nicotinic and muscarinic

Nicotinic is found on the post synaptic muscle cell and is ionotropic

Muscarinic is metabotropic

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3 ways to block neurotransmitter transmission

Presynaptically by inhibiting ACh release (rate limiting step is choline uptake)

Presynaptically by inhibiting ACh synthesis

Postsynaptically (by interfering with the actions of ACh on the receptor)

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Effects of anti-cholinesterase

CNS:

initial excitation with convulsions
unconsciousness and respiratory failure

Autonomic nervous system:
SLUDGE
- salivation
- lacrimation 
- urination
- diaphoresis 
- Gastro-Intestinal upset 
- emesis

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Clinical uses of anticholineesterase

Anaesthesia

Myesthenia gravis (increase neuromuscular transmission)

Glaucoma (decrease intraocular pressure)

Alzheimer’s disease (enhance the cholinergic transmission in the CNS)

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Types of muscular dystrophy

Duchennes 
Fasciosccapulohumeral 
Becker
Limb-girdle 
Oculopharyngeal 
Emery-dreifuss

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Outline the mechanisms of cell signalling

Paracrine: cells communicate over relatively short distances by releasing chemical messengers

Endocrine: hormones are produced by specialised cells and released into the bloodstream, which carries them to target cells in distant parts of the body.

Holocrine: secretions are produced in the cytoplasm of the cell and released by the rupture of the plasma membrane, which destroys the cell and results in the secretion of the product into the lumen.

Define ligand and messenger

ligand: Often, a soluble molecule such as a hormone or neurotransmitter that binds to a receptor
messenger: an intracellular substance (as cyclic AMP) that mediates cell activity by relaying a signal from an extracellular molecule bound to the cell’s surface

Cellular components of the CNS

Neurones
Glial cells: 
- oligodendrocytes
- microglial cells
- astrocytes
- ependymal cells

Speed of neuronal transmission in regards to resistance

• The larger the diameter of the
axon, the lower the resistance is.
• Passive movement of charge along
the axon is easier with less
resistance
• Larger axons have faster passive charge movement

Speed of neuronal transmission in regards to capacitance

• The more surface area there is on
an axon, the higher its capacity to
store charge across its membrane
• The higher the capacitance the
harder it is for charge to cross over the membrane

Stages of synaptic signal transduction

action potential
voltage gated ca2+ channels open
ca2+ influx causes neurotransmitter filled vesicles to fuse with the cell membrane
neurotransmitter is released into the synaptic cleft and binds to receptors causing the iron channels to open. this results in ion influx into the post synaptic neurone.
depending on which ion flows in the postsynaptic cell moves closer to na+ or further away from cl- threshold.

Difference between spatial and temporal summation

Spatial summation:
multiple synapses from different neurons stimulating the same post-synaptic cell

Temporal summation:
The same synapse repeatedly stimulating the same post-synaptic cell

Methods of inhibiting ACh release

local anaesthetics
general inhalation of anaesthetics
inhibitors/competitors of calcium (magnesium ions and some antibiotics)
neurotoxins (e.g. botulinum toxin)

What are the clinical uses of neuromuscular blocking drugs?

endotracheal intubation
during surgical procedures
infrequently in intensive care
during electroconvulsive therapy

Describe the structure of nicotinic acetylcholine receptors

5 proteins make up the receptor and ACh binding to the alpha helices causes a conformational change which therefore allows ions to flow through.

Examples of nicotinic ACh receptor agonists and antagonists.

Agonist: nicotine, suxamethonium Antagonist: tubocurarine, atracurium

Describe the process of competitive antagonists of nicotinic ACh receptors at NMJ

e.g. tubocurarine, atracurium 1. Prevents ACh binding to receptor by occupying site 2. Decreases the motor end plate potential (EPP) 3. Decreases depolarisation of the motor end plate region 4. No activation of the muscle action potential

Describe the process of agonists of nicotinic ACh receptors at NMJ

e.g. suxamethonium, nicotine 1. Persistent depolarisation of the motor end plate 2. Prolonged EPP 3. Prolonged depolarisation of the muscle membrane 4. Membrane potential above the threshold for the resetting of the voltage-gated sodium channels 5. Sodium channels remain refractory 6. No more muscle action potentials generated

What are the two phases of depolarising block at a nicotinic ACh receptor?

phase 1: – Muscle fasciculations observed, then blocked – Repolarisation inhibited • K+ leaks from cells (hyperkalemia) – Voltage-gated Na+ channels kept inactivated phase 2: – Prolonged / increased exposure to drug – “Desensitisation blockade” • Depolarisation cannot occur, even in absence of drug

Function of anticholinesterase drugs

– ↑ availability of ACh at NMJ by ↓ degrada tion – Increases duration of activity of ACh at NMJ – More ACh to compete with non-depolarising blockers

What is sugammadex?

Selective relaxant binding agent (SRBA): | reverses effects of rocuronium and vecuronium

Describe the medical model

* The emphasis is on deficits, problems, things that are lacking, things that are wanting, wrong, need to be fixed, are not ‘normal’ * These messages are conveyed powerfully to young people and shape their sense of self, their identities and limiting their future potentialities * Defining people solely in terms of their impairments lowers expectations * Leads to people losing choice, control, independence

Describe the social model of disability

“In our view, it is society which disables physically impaired people. Disability is something imposed on top of our impairments by the way we are unnecessarily isolated and excluded from full participation in society. Disabled people are therefore an oppressed group in society."

What are the advantages and disadvantages of the social model?

``` Advantages: • Barrier removal Socialchange Independent living Anti-discriminationlaw • Liberation Re-representing impairment ``` Disadvantages: • Can be divisive – policing language • Silence about impairment (compare with the Liberation Network of People with Disabilities: people with disabilities suffer inherent problems)

What is the inheritance pattern of duchenne muscular dystrophy?

autosomal recessive x-linked caused by defect in Xp21 dystrophin gene destruction of skeletal muscle leading to progressive weakness

What is the presentation of DMD?

gross motor delay (gower sign)

Diagnosis tests for DMD

Creatinine kinase elevated Muscle biopsy Genetic testing

what are the treatments for DMD?

Steroids Physiotherapy Gene/stem cell therapy