Neuro Intro Physiology Flashcards
What occurs in gastrulation?
Gastrulation (3rd week development)
Ectoderm: skin, nervous system
Endoderm: epithelial lining of gut and respiratory system, liver, pancreas
Mesoderm: Notochord, muscular system
How does the spinal cord develop?
Ectoderm thickens in midline to form the neural plate
- Notochord forms from mesoderm cells soon after
gastrulation is complete - Signals from notochord cause inward folding of
ectoderm at the neural plate - Ends of neural plate fuse and disconnect to form an
autonomous neural tube
Up until end of 4th week
Where do the presumptive neural crest cells lie?
Lateral to the neural groove lie presumptive neural crest cells
When does the neural tube close?
The neural tube usually closes at the end of 4th embryonic week
What abnormalities of the spinal cord are related to neural tube?
Abnormalities of the spinal cord
Failure to close cephalic region – anencephaly
Failure to close spinal region – spina bifida
Collectively called – neural tube defects
What environmental factors contribute to neural tube defects?
Folic acid
Maternal diabetes
How does the brain develop?
4 weeks
Prosencephalon – cerebral hemispheres and thalamic structures
Mesencephalon – midbrain
Rhombencephalon – medulla, pons and cerebellum
How does the cererbal cortex form?
Formation of cwere
What are micro and macrocephaly?
Microcephaly – reduced head circumference
Macrocephaly – increased head circumference
What is Periventricular nodular heterotopia?
Periventricular nodular heterotopia – abnormal migration of neurons
What is the circulation of the CSF like?
CSF circulates through the subarachnoid spaces and through the ventricles
•CSF cushions the brain and helps circulate metabolites
• Around 120 mLs
•Produced as filtrate of blood at choroid plexuses in ventricules
•Absorbed via arachnoid granulations in superior sagittal sinus
What is hydrocephalus?
Hydrocephalus
•Accumulation of CSF with increased intracranial pressure
•Can cause macrocephaly in children (therefore always scan increasing head size)
•Obstructive (non-communicating): e.g. tumour, haemorrhage.
•Non-obstructive (communicating): e.g. increased CSF production
What are the basic types of muscle?
Skeletal (striated, voluntary)
•Smooth (visceral, involuntary)
•Cardiac
What is the basic structure of skeletal muscle?
Myofibres arranged in fascicles
•Connective tissue
•Epimysium
•Perimysium
•Endomysium
•Basement membrane
•Surrounds individual myofibres
•Collagen, glycoproteins and proteoglycans
•Roles in tensile strength, regeneration, development
•Vascular supply
•Innervation
•Myotendinous junction
What is the innervation of skeletal muscle?
Each fibre innervated by one nerve, with cell bodies in anterior horn of spinal cord or brainstem
•One neuron innervates multiple muscle fibres – motor unit
•Neuromuscular junction
•Synapse – rapid transmission of depolarising impulse
•Acetyl choline – binds post-synaptic AChR
•Proprioception – length and tension
•Muscle spindles – encapsulated intrafusal fibres. Mediate stretch reflexes and proprioception
•Golgi tendon organs - tension
Where is the control and sites of pathology in skeletal muscle?
Primary motor cortex - basal ganglia - cerebellar systems
Etc
What are the Sites of pathology affecting muscle and nerve?
MND
Peripheral neuropathies
Neuromuscular transmission defects
Primary muscle disease (myopathies)
What is skeletal muscle histology like?
Can be studied by muscle biopsy
•Requires the use of frozen sections and good orientation
•EM
•Molecular tests
How does Enzyme histochemistry reveals different fibre types
NADH
ATPase
What are the types of muscle fibres?
Slow twitch (red fibres) – type 1, oxidative, fatigue resistant
•Fast twitch – fatigue rapidly but generate a large peak of muscle tension
•2A – glycolytic and oxidative (intermediate)
•2B – glycolytic (white)
What is the motor unit like?
Motor neuron (lower) and the fibres it innervates
•Neuron and its fibres of same type
•Fibre type dependent on neuron
•Size of motor unit varies between muscles
How are motor units altered in denervating diseases?
Loss of innervation causes fibre atrophy
•Collateral sprouting from adjacent motor units allows reinnervation
•Larger motor units result – this can be detected electrophysiologically
•Conversion of fibres results in fibre type grouping
What is denervation and re-innervation?
What are fibre type groupings?
What is the organisation of micro fibrils like?
Sarcomere – basic unit of contraction
Repeating arrangement of thick (myosin) and thin filaments (actin)
Other proteins include
At the Z-line
--actinin
-Titin
-Nebulin
-Desmin (links myofibrils to each other and the sarcolemma
Linked to actin
-Troponin/tropomyosin complex – Calcium regulation
Z disc
A-band
I-band
What is the sliding filament theory?
Myosin heads bind actin
•Binding of ATP allows release and hydrolysis to ADP allows movement of myosin head. ADP released during power stroke.
•Sarcomeric shortening due to sliding of the filaments NOT change in length of either actin or myosin
•Initiated by increased cytosolic Ca2+
•Accessory proteins
•Troponin/tropomyosin – mediate Ca2+
What is the energy requirement in muscle?
High energy requirement from ATP
•Creatine phosphate a short term energy store
•CP replenished by creatine kinase (CK)
•CK is released on muscle fibre damage
•Measurement of serum CK clinically useful
What are mitochondrial cytopathies?
Mitochondrial DNA - Circular ds DNA, Maternally inherited
•Diverse clinical presentations with an emphasis on CNS
•E.g. MERRF, MELAS, CPEO
•Mutations in either mitochondrial or nuclear DNA
•Mitochondrial mutations – maternal inheritance
•Heteroplasmy
How are Mitochondrial cytopathies diagnosed by muscle biopsy?
Ragged red fibres - gomori trichrome
•Electron transport chain deficits – cytochrome oxidase negative fibres
•Abnormal mitochondrial morphology
•Gene defects
What is the histochemistry of cytochrome oxidase and succinate dehydrogenase?
How is the Maintenance of Membrane Stability with Dystrophin and its Associated Proteins?
What are the dystophies of sacrolemmal related proteins?
Dystrophies are genetically determined, destructive and mainly progressive disorders of muscle
•There are many types of dystrophy
•Defects of proteins that confer stability to the sarcolemma are one group of causes.
What is dystrophin?
A large protein encoded by a 2.4 million bp gene on Xp21
•Confers stability to the muscle cell membrane
•Deletion resulting in disruption of the reading frame results in Duchenne
•In Becker’s, and in-frame deletion results in a truncated product
What occurs in neuromuscular transmission?
Nerve impulse results in the release of acetyl choline from synaptic vesicles
•ACh binds to its receptor
•Cation entry results in depolarisation, the end-plate potential
•An action potential travels across the muscle cell membrane and into the T-tubule system
•Calcium is released from the sarcoplasmic reticulum leading to activation of contraction
What are some disorders of neuromuscular transmission?
Myasthenia gravis – variable weakness, progressive with sustained effort, eye signs – ptosis
•Autoimmune disease
•Anti-AChR antibodies resulting in a reduction in ACh receptors
•Acetyl cholinesterase inhibitors can improve muscle function
What is the basic histology of peripheral nerves, nerve fascicles (cross section)?
What are myelinated fibres like?
In the PNS, the Schwann cell is responsible for the myelin sheath
•Each Schwann cell is responsible for one segment of myelin
•Nodes of Ranvier lie between adjacent myelin segments
•The node is where depolarisation of the membrane occurs
•Myelination allows saltatory conduction
What are peripheral neuropathies?
Damage to motor or sensory neurons – neuronopathies
•Damage to axons – axonopathies
•Selective damage to myelin sheaths - demyelination
What is axonal degeneration/regeneration/wallerian degeneration?
•Injury to axon – distal fragmentation
•Globules of myelin and axon debris form, initially within Schwann cell
•Axonal sprouts form from proximal part of damaged axon and grow along columns of proliferating Schwann cells
•Regenerated axons can remyelinate
What is demyelination?
Injuries primarily to Schwann cell or myelin sheath
•Demyelination segmental
•Remyelination begins with a thin myelin sheath
•Demyelination results in functional impairment with slowing of conduction velocity
